Nephrology for General Practitioners - O.I. Bakaliuk 2003
Glomerulonephritis
The first mention of GN dates back to 1840 and is associated with the name of P. Bayer. In 1899, this Kidney disease was classified as a distinct nosological entity.
GN comprises bilateral immune-inflammatory renal diseases primarily affecting the glomeruli. However, this definition does not exclude the potential involvement of the renal tubules and interstitium in the pathological process. GN is a fairly widespread form of pathology with an upward trend (O.A. Borzykh, 2000). Unfortunately, to date, the detection of these diseases in Ukraine is far from being resolved, and statistical data vary significantly. For instance, according to L.A. Pyrih (2001), the incidence of acute GN increased from 6.7 to 8.2 cases per 100,000 population between 1995 and 2000, ranging from 4.7 cases in Kirovohrad Oblast to 14.6 cases in Volyn Oblast. At the same time, the incidence rates of chronic GN remained practically (!) unchanged (6.5 and 6.4 cases per 100,000 population, respectively), while the prevalence of the latter even decreased (89.3 and 80.0 per 100,000 population, respectively).
According to current understanding, GN is a heterogeneous group of conditions encompassing numerous pathological states that vary in Etiology, Pathogenesis, Morphology, and prognosis. In most cases, the term refers to an independent renal disease; however, GN quite frequently occurs as a secondary manifestation of Renal Involvement in other systemic disorders (such as collagenoses) or clinical states.
Despite various proposals, there is no universally accepted Classification of GN, just as there is no universally convenient classification of renal diseases in general. Nevertheless, the division of GN into acute, rapidly progressive (subacute, extracapillary), and chronic forms is widely accepted and rarely contested. In this light, we will present An Overview of GN, preceded by a brief outline of its morphology and mechanisms of progression.
Progress in our understanding of GN morphology is associated with the Introduction of vital percutaneous renal biopsy, light Cell/15.html">Microscopy, immunohistochemical, and electron microscopic techniques, as well as the contributions of V.V. Serov et al. (1970, 1987, 1995), B. Bell (1938, 1946), D. Earle (1970), J. Cameron (1972), R. Heptinstall (1974), and J. Churd and L. Sobin (1982). Notably, J. Churd and L. Sobin (1982) proposed a morphological classification of GN that largely satisfied clinicians and received a positive evaluation from the WHO.
According to this classification, glomerulonephritis is categorized into minimal change, focal segmental, and diffuse forms.
GN with minimal changes includes four forms: lipoid nephrosis, focal segmental glomerular hyalinosis, mesangioproliferative GN with deposits of IMMUNOGLOBULINS A, G, and the C3 Complement component, and mesangioproliferative GN without deposits of immunoglobulins A, G, and the C3 complement component.
Focal segmental changes are diagnosed when less than 60% of the glomeruli are affected by the pathological process (focal changes) or when the process involves individual capillary loops of a glomerulus or groups thereof (segmental changes).
Diffuse GN is represented by membranous, proliferative, and fibroplastic variants.
We share the viewpoint of the Kyiv school of nephrologists, as well as researchers from Russia (M. Ratner et al., 1996) and Great Britain, who believe that morphological changes are merely an important Supplement to the clinical characterization of individual GN nosological forms, and that clinical classification has a significantly higher prognostic value than morphological classification. Nevertheless, it should be emphasized that the evaluation of vital morphological renal data plays a crucial role not only in diagnosing the disease, assessing its activity and progression rate, but also in predicting Treatment efficacy—since it is known that out of 10 morphological variants of GN, complete recovery is possible in only three types, which can be identified as early as the first weeks of the disease (L.A. Pyrih, 2002).
Structure/19.html">The Importance of this research method increases substantially when correlated with clinical data. A successful example of such integration is the study by B.A. Zus et al. (1991), who formalized Changes in the glomeruli, tubules, and renal interstitium, developing a histological evaluation algorithm. This algorithm not only allows for the comparison of changes across different nephron segments but also standardizes parameters to compare biopsy specimens from different patients and researchers. Furthermore, it can be utilized for the mathematical Processing of clinical, laboratory, and instrumental data, enabling Conclusions to be drawn regarding the dynamics of morphological changes without The Need for repeat renal biopsies.
In Ukraine, the accepted classification of GN (A.P. Peleshchuk, 1980; L.A. Pyrih, 1995, 2002) distinguishes several clinical forms: acute (with a protracted course lasting over 4 months), rapidly progressive (subacute, with pre-azotemic and azotemic stages), and chronic GN; stages of chronic GN (pre-hypertensive, hypertensive, and four stages of chronic renal failure); and clinical variants (syndromes) of the disease course, such as urinary (currently proposed to be termed anephrotic, T.D. Nykula, 2000, 2001) and nephrotic. The course of chronic GN also comprises active and remission phases.
Recently, nephrologists have concluded that in the course of acute GN, alongside the urinary and nephrotic variants, an acute nephritic variant should also be distinguished (L.A. Pyrih, 2002).
The presence of microhematuria (exceeding 5–107/L red Blood Cells in the Nechyporenko test) across any clinical variant is designated as the hematuric component.
T.D. Nykula (1994, 2000, 2001), while noting certain shortcomings in this classification (such as the antithesis between urinary and nephrotic syndromes, the inclusion of Hypertension in only a single stage of chronic GN, and the lack of process activity criteria analogous to, for example, the classification of collagenoses), proposes his own classification variant for chronic GN: disease course (progressive, persistent, recurrent); activity (grades 0, I, II, III); clinical form (nephrotic, anephrotic); stage (absence of CRF [CRF 0], initial CRF [CRF stage I], pronounced CRF [CRF stage II], terminal CRF [CRF stage III]); and clinical groups (pre-hypertensive [CRF 0-A], hypertensive [CRF 0-B], pre-azotemic [CRF I-A], azotemic [CRF I-B], paucisymptomatic [CRF II-A], polysymptomatic [CRF II-B], uncomplicated [CRF III-A], complicated [CRF III-B]). Additionally, the Diagnosis characterizes manifestations such as renoparenchymal arterial hypertension (transitory, labile, stable, refractory), macrohematuria, transitory renal failure (caused, for example, by high disease activity), and extrarenal visceropathies. The advantages of this classification lie in the inclusion of categories that are absolutely essential for selecting therapeutic tactics and determining the degree of disability.
Acute glomerulonephritis is the most frequent clinical form of diffuse immune-inflammatory renal involvement. According to L.A. Pyrih (1992), patients with acute GN account for 0.5–3% of admissions in therapeutic hospitals; men aged 20–40 are affected more frequently (2:1), predominantly during the cold season.
Renal changes in this condition are caused by the deposition of heterologous immune complexes in the glomerular capillaries, manifesting as endocapillary proliferative GN with sequentially developing exudative, exudative-proliferative, proliferative phases, and a phase of residual symptoms (V.V. Serov et al., 1995).
Two mechanisms of acute GN development are recognized: autoimmune (damage to the glomerular capillary basement membrane [BM] by autoantibodies directed against the "classic" BM antigen—a glycoprotein) and immune-complex-mediated (injury to the glomerular capillary BM by immune complexes formed in the bloodstream or other Tissues and transported to renal structures via the blood). However, it has recently become clear that a strict division of immune-inflammatory renal diseases into those caused solely by autoantibodies against glomerular capillary BM (5–15%) and those associated with the deposition of circulating immune complexes on the BM (75–80%) is a somewhat oversimplified Concept of the immunological mechanisms driving acute GN. It has been proven that immune complex deposits can form in glomeruli *in situ* (M.L. Nanchikeeva et al., 1992; P.V. Peake et al., 1991); that is, an antigen is first deposited within the Capillary Wall, followed by an antibody, which subsequently bind to each other. The resulting immune complexes interact with The Complement System, activating it via the classical or alternative pathways. This process results in the release of specific complement fractions, such as C3a, C5a, and C5b–C9, which directly participate in BM injury (D.G. Matsell et al., 1991).
An important role in the onset of acute GN and glomerular injury is attributed to changes (increases) in The activity of mononuclear leukocytes, primarily T-cells and monocytes, general and local activation of the complement system by immune complexes or glomerular capillary BM Antibodies, and disturbances in renal blood flow, microcirculation, and hemorheological properties.
Among cellular mediators of immune inflammation, neutrophils and platelets play a pivotal role. Under certain conditions, neutrophils are capable of actively producing numerous damaging factors—Proteolytic Enzymes, free oxygen radicals, cationic Proteins, procoagulant factors, and platelet-activating factor (A. Otha, 1992). In turn, platelet activation promotes the release of various inflammatory mediators, including vasoactive amines, proteolytic enzymes, Prostaglandins, and chemotactic factors for neutrophils and monocytes (M.H. Wener, 1996). For instance, During the first week of the disease, high concentrations of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and other platelet-derived growth factors are observed in the blood, along with interleukin-8 (IL-8), which is actively produced by glomerular cells and monocytes (A. Harada et al., 1994). IL-8 promotes the release of lysosomal enzymes and oxygen radicals from neutrophils and potentiates the accumulation of T-cells in the inflammatory zone. Local (kinins, prostaglandins) and humoral (histamine, serotonin) inflammatory mediators contribute to alterations in glomerular capillary BM permeability by increasing efferent arteriolar resistance and intracapillary pressure. Concurrently, a mesangial cell reaction occurs, characterized by hyperfunction and expansion of the mesangial matrix aimed at isolating and eliminating immune complexes. Thus, glomerular hypercellularity in acute GN is represented primarily by resident glomerular cells, mesangial cells, intraglomerular polymorphonuclear leukocytes, monocytes, and T-lymphocytes.
Currently, significant attention in the pathogenesis and clinical course of GN is focused on integrin receptors—specifically ICAM-1 (intercellular adhesion molecule-1) and LFA-1 (lymphocyte function-associated molecule-1)—through which blood mononuclears and neutrophils infiltrate the glomerular tissue (H.S. Hillis et al., 1997; N.A. Rakityanskaya et al., 1998; Dal Canton, 1995). It has been proven that the adhesion mediated by these receptors plays a critical role in intercellular interactions involving antigen-presenting cells and cytotoxic T-cells and natural killer cells, thereby regulating the intensity of the Immune Response and the degree of nephron structural damage (M. Yagoub et al., 1996).
Recently, studies investigating The Role of apoptosis—programmed cell death—in the pathogenesis of GN have emerged. It has been demonstrated that the suppression of apoptosis (impaired clearance of hypercellularity residues) plays a crucial role in the chronification of GN (V.O. Moiseyenko, 2001; H. Soto et al., 1992, 1997; P. Mene et al., 1998). Apoptosis is essential for clearing both intrinsic glomerular cells and infiltrated lymphocytes, neutrophils, and monocytes from the glomerulus, which is a prerequisite for the restoration of damaged nephron structures.
Regarding the renal tubules, their overall structure does not undergo significant changes in acute GN. However, the appearance of hyaline droplet, vacuolar, or granular dystrophy, interstitial leukocyte infiltration, focal sclerosis, and tubular epithelial atrophy may serve as criteria indicating the Transition of acute GN into chronic GN (S.I. Ryabov et al., 1997).
Most researchers point to the streptococcus as the most frequent trigger of acute GN—more precisely, a preceding streptococcal infection (such as tonsillitis, rheumatic fever, chronic tonsillitis, pharyngitis, scarlet fever, furunculosis, or erysipelas). Despite the general downward trend in streptococcal-etiology diseases, epidemic outbreaks of such infections continue to be reported (J. Bisno et al., 1970; S. Holm, 1988). In these cases, acute GN typically develops 7 to 14 days later, which is the time required for antibody formation. In some instances, acute GN may result from Pneumonia, bacterial endocarditis (*Staphylococcus aureus*, *Streptococcus viridans*), meningitis (*Neisseria meningitidis*, *Mycoplasma* [M. Bonsdorff et al., 1984; M.H. Said et al., 1999]), abscesses, Osteomyelitis (*Staphylococcus aureus*, *Escherichia coli*, *Pseudomonas aeruginosa*, *Proteus mirabilis*), rheumatic fever, infectious diseases such as typhus, leptospirosis, and brucellosis, parasitic conditions like malaria and Toxoplasmosis (K.S. Hugh, 1986), animal-borne infections (rickettsioses), and fungal infections (*Candida albicans*, *Coccidioides immitis* [D. Michalk, 1989; D. Clotz et al., 1991]). Most frequently, however, the CAUSATIVE AGENT OF GN is specific (nephritogenic) strains of group A beta-hemolytic streptococcus—types 1, 2, 4, 12, 18, 25, 49, 55, 57, and 60 of the M-protein fraction (B. Rodriguez-Iturbe, 1998). Streptococcal Antigens may include proteins, teichoic acid, neuraminidase, cationic antigens, and streptococcal Bacteriophages (S.I. Ryabov et al., 1999, 2000; R. Zaum et al., 1987). It should be noted that certain streptococcal serotypes do not produce streptolysin, a factor that must be considered when determining serum antibody titers against this antigen.
The role of Viruses in the etiology of human acute GN remains insufficiently studied. Acute viral infections are rarely the cause of acute GN, with the exception of hemorrhagic fever with renal syndrome. Nevertheless, a potential etiological role cannot be entirely ruled out for hepatitis B virus, Epstein-Barr virus, Coxsackie virus, herpes simplex, measles, HIV, enteroviruses, oncoviruses, cytomegalovirus, Influenza, parainfluenza, and Adenoviruses (V.I. Bondarenko, 1992; V.V. Stavskaya, 1997; T. Okuno et al., 1990; S.I. Vas, 1991; G.A. Herrera et al., 1996). For instance, patients with GN exhibit an 8-fold increase in antibody titers against the measles virus compared to healthy individuals; measles virus RNA has been isolated from blood lymphocytes using dot Hybridization, with the detection frequency depending on the phase of the pathological process. Furthermore, HBsAg in leukocytes or blood serum is detected in 28.9% of patients with GN (V.V. Serov et al., 1991).
According to current concepts, three distinct mechanisms are thought to drive virus-induced glomerular injury: direct cytopathic effects of viruses on glomerular structures, the involvement of viral antigens in immune reactions leading to circulating immune complex (CIC) formation, and THE CONTRIBUTION OF viruses to autoimmune reactions (A.N. Shishkin, 2000). Other recognized factors include the ability of viruses to integrate with the cellular genome, alterations in the antigenic structure of renal tissue resulting from viral Replication within cells (R.G. Filimonova, 1995), and the suppression of serum and leukocyte interferon production (A. Sinha et al., 1990). As early as 1969, A.A. Smorodintsev noted that the renal epithelium can serve as a site for viral replication, while J.P. Utz (1964) emphasized that viruses do not simply pass "in transit" through an intact renal filter; rather, they become sequestered there, precipitating various pathological states (L.A. Zilber, 1958). Thus, acute GN may develop following virtually any bacterial or viral infection (I.A. Rakityanskaya et al., 2000).
Among non-infectious triggers, notable factors include alcohol consumption, hypothermia, antigenic agents (sera, Vaccines, chemicals, insect venom, and food products), and local venous congestion. The nephritogenic properties of alcohol are supported by clinical data—such as a clear link between GN and alcohol binges, favorable disease dynamics during abstinence—along with the detection of its markers, specifically Intermediate filaments, within the cells of renal structures (podocyte and nephrocyte Cytoplasm). Uric acid METABOLISM disorders are also implicated as an etiologic factor, with a distinct subset of patients presenting with hyperuricemia whose course of GN is marked by specific Clinical Features and prominent tubulo-stromal-vascular changes.
Beyond etiologic factors, genetic predisposition plays a pivotal role in the onset of acute GN. An associative link has been proven between GN and Major Histocompatibility Complex (HLA) antigens—specifically HLA-A26, the phenotypic antigen combination B5-B40, and the haplotypes A2-B18, A9-B5, and A9-B40 (S.I. Ryabov et al., 1999; K. Mori et al., 1996).
Clinical manifestations of acute GN are diverse. In the classic presentation, where the disease begins acutely and abruptly, a preceding infection (occurring 1 to 3 weeks prior) can usually be identified. According to S.I. Ryabov (2000), the duration of the incubation period is distributed as follows: up to 1 week in 29.2% of cases, 1–2 weeks in 19.8%, 2–3 weeks in 15.6%, and more than 3 weeks in 21.9% of cases.
Patients predominantly complain of edema, headache, fatigue, loss of appetite, shortness of breath, palpitations, pain in the precordial and lumbar regions, frequent and moderately painful urination, decreased daily urine output, and changes in urine color. Clinical examination reveals Skin pallor, edema, arterial hypertension, bradycardia (in 77–88% of cases) or tachycardia (in 12–23% of cases), and signs of Heart failure in a subset of patients.
The classic triad of acute GN signs includes edema, hypertension, and Hematuria.
Edema is the most typical symptom, affecting 70–90% of patients. Its predominant localization on the face, combined with skin pallor, is referred to as facies nephritica.
Edema may develop rapidly (within a matter of hours), manifest across all PARTS OF THE body—including large joint cavities—and subside fairly quickly if the course of GN is favorable.
The mechanisms underlying edema involve a complex interplay of renal factors (increased capillary wall permeability, enhanced tubular reabsorption of sodium and Water) and extrarenal factors (increased systemic vascular permeability, elevated secretion of aldosterone and antidiuretic hormone, heightened tissue hydrophilicity, and, somewhat later, a drop in blood oncotic pressure).
Acute hypervolemia leads to cardiac chamber dilation and changes in heart sound intensity, specifically a muffled first sound and an accentuated second sound. In severe cases, a systolic murmur may be auscultated at the apex due to relative mitral regurgitation, alongside a gallop rhythm.
The leading role in The Development of arterial hypertension belongs to sodium and water retention, an increase in circulating blood volume (CBV), and elevated Cardiac Output (a hyperkinetic hemodynamics variant) against a Background of unchanged or reduced peripheral vascular resistance (the latter increases in severe disease). Transient retinal vessel changes—such as arterial narrowing, venous dilatation, and punctate hemorrhages—typically develop in The Setting of severe and prolonged hypertension.
Other noteworthy symptoms include lumbar pain and oliguria.
Blood test abnormalities are non-specific and include moderate anemia due to hypervolemia, leukocytosis, an elevated ESR, markers of acute-phase inflammation, dysproteinemia (hyper-alpha2-globulinemia), hypercholesterolemia, and hyperlipidemia (all transient).
Renal function changes depend on the severity of the pathological process. Renal blood flow is either normal or increased, nitrogen-excreting function is typically preserved, and Acute Kidney Injury (AKI) develops rarely.
Urinary sediment is characterized by proteinuria (ranging from 1–35 g/L) and hematuria (most commonly microhematuria).
Proteinuria peaks at disease onset and persists for 1–2 weeks, while moderate proteinuria can be detected for up to 1–1.5 years.
Microhematuria is persistent, whereas macrohematuria occurs less frequently, giving the urine a characteristic "meat wash" appearance. In isolated cases—once arterial pressure has normalized, edema has resolved, and the general condition has improved—hematuria may paradoxically increase significantly over several days. This phenomenon is attributed to secondary hyperemic changes in the renal glomeruli and is referred to as "recovery hematuria."
Prolonged acute GN is diagnosed when the disease duration exceeds 3 months, with the defining criterion in this scenario being urinary syndrome rather than extrarenal signs (edema, hypertension).
A reliable sign of chronicity in prolonged acute GN is the persistence of proteinuria (exceeding 1 g/day) combined with hematuria (exceeding 5 ∙ 106/L), showing no tendency to decrease over the aforementioned timeframe. A tendency toward a protracted course is a hallmark of the modern evolution of acute GN (E.A. Movchan et al., 1990). Patient age, sex, race, and the presence or absence of hypertension during the acute phase hold no prognostic significance (P.S. Singhal et al., 1991). The likelihood of complete recovery in prolonged acute GN drops sharply, ranging from 30–33% for the paucisymptomatic and full-blown clinical variants down to just 1% for the nephrotic variant.
Thus, the potential trajectories for acute GN include spontaneous recovery or recovery induced by treatment (40–60% of cases), progression to chronic GN (39–80% of cases), or rapid progression to rapidly progressive GN (0.1–1%) (E.A. Movchan et al., 1990; L.A. Pyrih, 1995; D. Clotz et al., 1991).
Diagnostic challenges in acute GN arise when it presents with an atypical (latent) onset, characterized by symptoms that are brief, subtle, or entirely absent. In such situations, the only reliable diagnostic criterion is an isolated urinary syndrome, even though it may manifest solely as microhematuria without proteinuria ("nephritis without nephritis," E.M. Tareyev, 1958).
Diagnostic errors in acute GN reach up to 15.2% (B.B. Bondarenko, 1994). Cytology/practical/136.html">Differential diagnosis OF acute GN must be performed against exacerbations of chronic latent GN, renal involvement in Collagen Vascular Diseases, acute Pyelonephritis or exacerbations of Chronic Pyelonephritis, Renal Amyloidosis, cardiac disorders (congestive proteinuria), systemic vasculitis, tuberculosis, tumors of the Kidneys or Urinary Tract, and urolithiasis.
In severe cases, acute GN may be complicated by ACUTE RENAL FAILURE, left ventricular failure, or Eclampsia. Mortality does not exceed 0.1% in adults and 3.4% in children (V.I. Naumov et al., 1996). According to E.M. Tareyev (1983), the most frequent cause of death in acute GN is heart failure (64%), followed by eclampsia and stroke (21%), and pneumonia (15%). Recovery typically occurs within 2–4 weeks, though it may occasionally drag on for up to 1.5 years. If renal (urinary syndrome) or extrarenal (edema, hypertension) symptoms persist beyond this maximum timeframe, progression to chronic GN should be suspected. Recurrent episodes of acute GN are also possible (2–3%, L.A. Pyrih, N.Ya. Melman, 1982; S.I. Ryabov et al., 1999).
Clinical variants of acute GN include rapidly progressive GN (synonyms: subacute, malignant, extracapillary, fulminant GN) and minimal change GN (lipoid nephrosis).
The morphological foundation of rapidly progressive GN is proliferative glomerulonephritis characterized by fibrocellular crescents, total or segmental obliteration of Bowman's space, necrosis of glomerular capillaries, degeneration and Atrophy of the tubular epithelium, and interstitial sclerosis.
Rapidly progressive GN is characterized by the maximum severity of clinical and laboratory symptoms as early as the first week of the disease (oliguria, edema ranging up to anasarca, hypertension, retinopathy with retinal detachment, pronounced proteinuria, hematuria, anemia, hypercreatininemia, hyperlipidemia, hypercholesterolemia, and a rapid drop in relative urine density despite oliguria). Patients are most commonly 30–40 years of age.
Its pathogenesis is associated with The formation of crescents in at least 50% of glomeruli (the formation of antibodies to the glomerular basement membrane — type I crescentic GN, or the deposition of circulating immune complexes in glomerular structures — type II crescentic GN).
With this type of GN, antineutrophil cytoplasmic antibodies (ANCA, see below) are often detected in the blood, which can serve as an additional diagnostic criterion.
Definitive criteria for diagnosing rapidly progressive GN, In addition to severe clinical manifestations and the presence of antineutrophil cytoplasmic antibodies, include a rapid and sustained decline in renal function, alongside progressively worsening fundus changes. Pre-azotemic and azotemic stages are distinguished in this condition. Patient death occurs 6–18 months after disease onset, most frequently due to renal failure; only isolated cases of a favorable clinical course have been described (B.B. Bondarenko, 1980).
Minimal change GN is currently viewed as an independent disease with uniquely specific morphological features and clinical characteristics (A.I. Dyadyk et al., 1987, 1991; S. Oji et al., 1992). J. Churg (1982) referred to this condition as "podocyte FOOT process disease."
Minimal change GN is one of the "primary" glomerulopathies responsible for Nephrotic Syndrome in 75–80% of children and 10–15% of adults; the mean age of adult patients is 42.7 years (J.S. Cameron et al., 1989). Notably, this group also encompasses IgM nephropathy, focal segmental glomerulosclerosis/hyalinosiss, membranous, and membranoproliferative GN (A. Cohen et al., 1998).
This form of renal pathology is frequently combined with Hodgkin's disease, non-Hodgkin's lymphomas, chronic Lymphocytic Leukemia, mesothelioma, hypernephroma, or occurs following The Use of gold preparations, NSAIDs, or lithium carbonate (T. Nadasty et al., 1994).
The pathogenesis of the disease is not yet fully understood, although A number of facts indicate the involvement of immune mechanisms (elevated serum levels of alkaline phosphatase, classes M and E immunoglobulins, decreased Class G immunoglobulins, along with focal and segmental deposits of class M immunoglobulins and the C3 complement component in the mesangium and capillary walls (W.W. Bakker et al., 1986; S. Oji et al., 1992; E. Ritz, 1994).
The prevailing view is that of R. Stylhoub, put forward as early as 1974, according to which the underlying mechanism of the disease is a functional T-cell imbalance with increased activity of effector T cells, subsequent hyperproduction of lymphokines, and other factors capable of damaging the glomerular polyanion and increasing the permeability of the glomerular capillary basement membrane. Meanwhile, the glomerular capillary basement membrane itself remains unchanged or shows minor focal thickening; moderate mesangial cell proliferation, expansion of the mesangial matrix, and podocyte foot process lysis and proteinuria are sometimes observed, which are attributed to the presence of a specific blood protein factor (with a yet undetermined structure) that, when administered to experimental animals, reproduces the aforementioned picture (D. Donatti et al., 1998). According to the WHO classification, 5 variants of renal changes are distinguished in this condition:
- absence of glomerular changes;
- minimal focal glomerular collapse;
- minimal expansion of the mesangial matrix without changes in the glomerular cell count;
- focal tubular changes;
- minimal mesangial hypercellularity.
The disease has an acute onset and manifests with significant (predominantly selective) proteinuria, frequently exceeding 10 g/day, leading to the development of nephrotic syndrome. Edema is quite pronounced, and hypertension is detected in 40–50% of adults (10–15% of children), although it should be noted that hypertension is generally not characteristic of this type of GN, and persistent hypertension casts doubt on the accuracy of the diagnosis. Blood pressure is not elevated. Hypercreatininemia and a decrease in creatinine clearance are likely at the onset of the disease. Marked hypovolemia can trigger hypovologic Shock; acute renal failure, arterial, or venous thrombosis occur in some cases.
The prognosis for minimal change GN is somewhat better than for other morphological forms of acute GN — chronic renal failure develops in isolated cases, yet mortality reaches up to 10% due to complications. In most patients, treatment with prednisolone leads to the complete disappearance of proteinuria within several weeks. Even untreated minimal change GN frequently undergoes spontaneous remissions.
Chronic Glomerulonephritis is also classified among immune-inflammatory renal disorders. It is characterized by the involvement of not only glomerular, but also tubular structures and the interstitium in the pathological process. This form of pathology features relentless progression with the inevitable development of end-stage renal failure.
Chronic GN occurs 2–4 times more frequently than acute GN (L.A. Pyrih, 1995), with the lion's share of cases occurring between the ages of 20 and 50 years (S.I. Ryabov, 1992). Both seasonal and "baseline" components of morbidity are identified, alongside a growing number of proliferative, prognostically unfavorable forms (Yu.A. Ermakov et al., 1998).
It is generally accepted that the development and progression of chronic GN are based on immune (immune-inflammatory) mechanisms, associated hemocoagulation shifts, and non-immune (hormonal-hemodynamic) processes (I.E. Tareyeva et al., 1995). To be fair, determining the predominant contribution of each of these factors in a specific case of disease onset and progression is extremely difficult.
Among the causes of chronization, primary note is given to those accompanied by the continuous entry of antigen into the body (foci of infection, tumors, unfavorable working conditions [especially exposure to damp cold], trauma, alcohol, hyperuricemia, prolonged use of certain medications, etc.).
Until the 1970s, the dominant concept in the pathogenesis of chronic GN was the predominant role of humoral Immunity disorders involving the damaging action of antibodies or immune complexes; it was only from the mid-1980s that studies emerged highlighting the primary and leading significance of lymphoid cells and delayed-type hypersensitivity over serum factors in this process.
The main facts are summarized in the following provisions:
- mononuclear leukocytes (monocytes-macrophages, T cells) can infiltrate the glomeruli and interstitium in GN;
- Structural and functional changes in the kidneys are specifically linked to macrophage activity;
- glomerular damage by lymphocytes and macrophages can develop in the complete absence of a HUMORAL IMMUNE RESPONSE (E.M. Shilov et al., 1987, 1991).
Views on the glomerulus as a passive participant in pathological immune responses have also been revised. Accumulated data on The properties of glomerular cells, which form the biological basis for the development of cell-mediated immune reactions within them, have made it possible to conceptualize the glomerulus as an active participant in these processes.
THE SPECTRUM OF pathological changes in the nephron during its damage is exceptionally broad: glomerular hypertrophy and/or hypercellularity resulting from the proliferation of intrinsic glomerular cells, infiltration of the glomerulus by circulating blood cells, expansion of the mesangial matrix with the development of sclerosis and capillary loop obliteration, alterations in GBM permeability, hemodynamic disorders with an increase or decrease in renal blood flow and filtration fraction, focal local ischemia accompanied by the release of reactive oxygen species, vasoactive components, and cytokines, as well as tubular injury leading to impaired reabsorption and the development of secondary immunodeficiency (I.O. Dudar, 1999).
The most typical manifestations of the glomerular response to immunoinflammatory injury are proliferation (hypercellularity) and expansion of the mesangial matrix.
Hypercellularity is a common feature of many forms of glomerular inflammation. It results from two parallel processes: the infiltration of the glomerulus by circulating mononuclear and neutrophilic leukocytes (S.R. Holdsworth et al., 1991) and the enhanced proliferation of resident mesangial, epithelial, and endothelial Cells of the glomerulus (R. Sterzel et al., 1996).
The primary stimulators of glomerular cell proliferation are macrophages, peripheral blood mononuclear leukocytes, and platelets.
Macrophages secrete a number of pro-inflammatory mediators (P. Davies et al., 1995), among which interleukin-1 (IL-1) deserves the greatest attention. It is a low-molecular-weight polypeptide monokine that exhibits endogenous pyrogen properties. Its main effects are numerous: induction of interleukin-2 secretion by T cells (a T-lymphocyte growth factor), acting as a comitogen for B lymphocytes, stimulation of acute-phase protein secretion (J.J. Oppenheim et al., 1994), promotion of mesangial cell proliferation and collagen synthesis, and—importantly—neutral protease synthesis (D.H. Lovett et al., 1993; C. Melcion et al., 1994). Neutral protease is classified among enzymes capable of degrading normal GBM components, including type IV collagen. In addition, IL-1 activates the synthesis of colony-stimulating factors (CSFs) and/or acts as a CSF itself, driving the Bone Marrow response to inflammation. It also affects activated B lymphocytes (typically in conjunction with interleukin-2 and other lymphokines), subsequently inducing their proliferation and differentiation into immunoglobulin-secreting plasma cells. Incidentally, it should be noted that in addition to macrophages, Brain glial cells, skin epithelial cells, and renal glomerular mesangial cells also possess The ability to produce factors whose action resembles that of IL-1 (E.P. McCarthy et al., 1994).
A pivotal interleukin involved in the cytokine response within the nephron is interleukin-6. It is actively produced by tubular epithelial and mesangial cells. Its primary Mechanisms of action include a significant enhancement of mesangial cell proliferation, subsequently transforming them into active producers of the same interleukin.
The role of peripheral blood mononuclear leukocytes in the pathogenesis of chronic GN has been studied somewhat less extensively than that of macrophages. However, it has been proven that they produce substances that either stimulate (IL-1, TNF-alpha, platelet-derived growth factor, Insulin-like growth factor, transforming growth factors alpha and beta) or inhibit (prostaglandins, intermediate oxidation products, protein kinase C, IL-1 inhibitor) the growth of various cells (E.M. Shilov et al., 1991; A.A. Filchenko et al., 1994; O.F. Vozianov et al., 1999; M.P. Ruiz-Torres et al., 1998).
Another growth factor found in platelets is platelet-derived growth factor itself. This is a cytokine capable of stimulating the proliferation of various cell types of mesenchymal origin, particularly glomerular mesangial and endothelial cells (P. Bohov et al., 1992; P. Odetti et al., 1993).
Among the molecular mediators involved in the complex mechanisms of immune inflammation in the kidney, an important role is also assigned to Fibronectin, a glycoprotein containing binding sites for collagen, fibrin-fibrinogen, glycosaminoglycans, the C1q component of complement, and factor XIIIa; its receptors have been found on endothelial cells, platelets, fibroblasts, mesangial cells, and podocytes.
As a component of the mesangial matrix, fibronectin stimulates monocyte-macrophage chemotaxis, induces platelet aggregation and adhesion, activates phagocytosis and the macrophage "respiratory burst" (J.A. Bruijn et al., 1995), and, by binding to receptors on mesangial cells and fibroblasts, stimulates the proliferation of these cells. This leads to the accumulation of Extracellular matrix—a crucial condition for the development of renal fibrosis (P. Roy-Chaudhuri et al., 1996).
Chemokines also play a certain role in nephron structural damage in GN (R. Bing et al., 1998), with the predominant one being the C-X-C chemokine for neutrophils, which under these conditions are capable of actively producing interleukin-8, a potent proliferative factor.
An important role in the pathogenesis of chronic GN is also attributed to the reduction of the phagocytic properties of circulating and tissue cells (The phenomenon of impaired and incomplete phagocytosis). However, the role of cellular inflammatory reactions is not limited to this phenomenon: an imbalance is observed in the interaction between sensitized glomerular T lymphocytes (sensitized to GBM components or antigens within circulating immune complexes) and Blood Platelets, monocytes, neutrophils, and tissue macrophages. The activation of the latter by sensitized glomerular T lymphocytes is likewise accompanied by the hyperproduction of growth factors, proteases, collagenases, fibrinolysin, free oxygen radicals, etc., resulting in cell proliferation and the accumulation of the glomerular mesangial matrix. The involvement of humoral mediators (kinins, histamine, serotonin, prostaglandins) in immune inflammation, along with the development of local intravascular coagulation and microcirculatory disorders, potentiates these processes, which culminate in glomerular sclerosis and obliteration (secondary shrunken kidney).
It should be noted that changes in the activity of the cellular immunity link in chronic GN occur not only at the level of mature lymphocyte types, but also at the level of their precursors, the so-called precursor T lymphocytes.
The most striking changes in this component of immunity correlate with the degree of activity of chronic GN: high process activity is accompanied by an elevated serum content of precursor T Lymphocytes and T lymphocytes with helper Functions.
The inactive phase of chronic GN is characterized by a marked decrease in the number of precursor cells, which can be viewed as depletion of the precursor lymphocyte clone. However, The Nature of this deficit remains uncertain to this day. The fact is that pre-T cells are pluripotent forms that, upon maturation, can replenish populations of T lymphocytes with both helper and suppressor properties. Therefore, their reduction in the inactive phase of chronic GN may, on the one hand, be a consequence of enhanced transformation into T lymphocytes with helper functions that sustain the autoimmune process, or, on the other hand, reflect an intense functioning of compensatory mechanisms for T-cell generation that mark the onset of remission (V.I. Nekipelova et al., 1989).
Continuing research in this direction, S.I. Ryabov et al. (1998, 2000) demonstrated that the clinical course and frequency of chronic GN exacerbations may be associated with a decrease in the number of a specific T-lymphocyte population, the so-called TdT⁺ cells. These cells belong to early, poorly differentiated lymphocyte precursors (lymphopoietic stem cells) that bear a specific marker enzyme, terminal deoxynucleotidyl transferase. Interest in TdT⁺ cells is also driven by the experimentally proven property of these cells to acquire trophic and morphogenetic functions and participate in maintaining physiological and reparative tissue regeneration (A.G. Babaeva et al., 1993).
Thus, the role of immune mechanisms, inflammatory reactions, and hemostasis-Fibrinolysis disorders followed by glomerular sclerosis (the first mechanism) in the progression of GN is beyond doubt.
Subsequently, clinical and experimental studies proved that the progression of GN is also driven by non-immune (hormonal-hemodynamic) factors (the second mechanism), which are more closely associated with tubulointerstitial regions (M.Y. Ratner et al., 1998) and sustain the alterations triggered by immune mechanisms.
Among these, we should note the damaging effect of proteinuria itself on the tubular apparatus and interstitium, systemic hypertension, deterioration of renal hemodynamics with glomerular ischemia (I.E. Tareeva, 1988, 1995; K.T. Woo, 1997), and the development of interstitial renal edema. In the latter case, exceeding the drainage capacity of the straight Vessels of the inner medulla, which lacks lymphatic drainage, leads to an increase in intratubular hydrostatic pressure in the more proximal tubular segments, disruption of the Starling forces balance in the glomerular capillaries, and an elevation of intraglomerular pressure (I.O. Dudar, 1999).
The importance of hemodynamic mechanisms in the progression of chronic GN is confirmed by the fact that The rate of this progression slows down during prolonged adherence to a low-protein diet (0.5–0.6 g protein/kg body weight/day). Its renoprotective effect in this situation is attributed precisely to a hemodynamic effect—a reduction in the dilation of afferent and, possibly, dilation of efferent arterioles (I.G. Kayukov et al., 1998).
Researchers also discuss the potential role of metabolic and biochemical disorders in GN progression, such as Lipid Metabolism disorders (referring to lipid nephrotoxicity) (A.V. Smirnov, 1997; F.V. Ziad et al., 1999), alterations in the Lipid Composition of renal structural membranes due to the activation of Lipid Peroxidation processes (A.I. Kulikova et al., 2000), hormonal imbalances (especially THYROID Hormones), and hyperfiltration (A.V. Brenner, 1990).
Various morphological and clinical classifications of chronic GN exist.
It must be emphasized that the morphological classification of chronic GN reflects only separate phases of renal structural disorders, that one type of GN can transition into another, and that such Diagnostics are approximate because they are based on the examination of only a small fraction (5–30 out of 2–3 million) of nephrons (A.S. Chizh et al., 1988). Nevertheless, histological studies of biopsy material still make it possible to determine the Features of the disease course at a specific stage, which is extremely critical for selecting the optimal and most effective treatment strategy.
Below is the morphological classification of chronic GN according to V.V. Serov et al. (1995), which distinguishes: minimal change GN, membranous GN with variants (mesangiomembranous, mesangioproliferative, mesangiocapillary, lobular), proliferative GN (intra- and extracapillary), focal segmental glomerulosclerosis/hyalinosis, fibroplastic GN, and secondary shrunken kidney. Each of the mentioned forms of GN is, as mentioned above, relatively independent, with the exception of fibroplastic GN and secondary shrunken kidney, which represent The final stage of all variants.
Despite the lack of a universal consensus on classifying chronic glomerulonephritis (GN) into Primary and secondary forms, it should be noted that such a distinction has persisted until recently. The arguments against this division are, firstly, the impossibility of conclusively ruling out a prior history of acute GN (masked by another disease), and secondly, the morphological, clinical, and therapeutic similarities between both variants.
There are also various clinical classification systems for chronic GN.
E.M. Tareev (1965) described 6 main clinical courses: malignant (subacute, extracapillary), mixed, nephrotic, hypertensive (vascular, F. Volhard, 1931), latent, and terminal.
N.A. Ratner (1965), and later M.Ya. Ratner (1980), identified the following forms of chronic GN: latent, nephrotic, hypertensive, hematuric, and mixed.
Depending on the severity of urinary syndrome, M.Ya. Ratner (1980) distinguishes hematuric, proteinuric, proteinuric-hematuric, nephrotic, nephrotic-hematuric, and nephrotic-hypertensive (with or without urinary syndrome) forms.
Let us briefly characterize the main Clinical forms of chronic GN (according to N.A. Ratner, 1965; M.Ya. Ratner, 1980).
Latent GN manifests as a mildly pronounced urinary syndrome in the absence of extrarenal signs of the disease. Facial puffiness occurs only in isolated cases. Proteinuria does not exceed 1 g/day, hematuria ranges between 10-20 red blood cells per high-power field, and cylindruria is negligible. Renal function remains unaltered, as evidenced by a sufficiently high relative urine density in Zimnitsky's test, along with normal values of GFR and creatininemia. Patients retain their working capacity for a long time (decades), and this pathological form is quite often diagnosed either incidentally during routine preventive examinations or already at the stage of Chronic Kidney Disease (CKD).
The nephrotic form of chronic GN (lipoid nephrosis according to E. Munk, 1913) is relatively rare. Its characteristic clinical and laboratory features include edema, massive proteinuria exceeding 3.0 g/day, cylindruria (initially hyaline, followed by granular and waxy casts), hypo- and dysproteinemia, and hyperlipidemia—in other words, all components of nephrotic syndrome.
Azotemic excretion, filtration, and concentration Functions of the kidneys are unimpaired during the compensation period, blood pressure typically does not rise, and persistent arterial hypertension develops alongside renal failure. Such patients are prone to various intercurrent infections (pneumonia, erysipelas, Sepsis) that can become the direct cause of death; overall, the clinical course of the nephrotic form of chronic GN is less favorable than that of the latent or hematuric forms.
In the hypertensive form of chronic GN, the leading clinical syndrome is arterial hypertension. Hypertension is generally well tolerated by patients, and the duration of the compensated stage ranges from 10 to 30 years. Symptoms, objective findings, and data from supplementary examinations (ECG, echocardioscopy, rheovasography, funduscopy) are identical to those in Essential Hypertension.
Unlike essential hypertension, certain Specific features of this type of hypertension include a relatively lower incidence of crises, coronary artery disease, left ventricular failure, and strokes. However, these patients more frequently experience visual acuity impairments, up to and including blindness, resulting from retinal detachment, central retinal artery thrombosis, or hemorrhages. Blood pressure rises sharply upon the development of renal failure, at which point the hypertension acquires malignant features. The urinary sediment shows moderate changes (proteinuria is minimal—up to 1 g/day; red blood cell counts do not exceed 5-10 per high-power field; single hyaline casts are present).
The hematuric form of chronic GN is relatively rare in adults. In light of modern data, its primary progression mechanism is considered to be hemocoagulatory—or more precisely, inflammatory-coagulatory—viewing hemostasis as a bridging link between immunity and inflammation.
According to recent findings, the persistence of the hematuric form of chronic GN is sustained by a pathological vicious circle: the activation of platelet aggregation by factors produced by mesangioblasts and macrophages (E.M. Shilov et al., 1987), and The stimulation of mesangial cell proliferative and synthetic activity by platelet-derived growth factor (C. Melcion et al., 1997).
This form is characterized by persistent and pronounced hematuria ( urinary red blood cell loss reaching 50-100 ∙ 106/day) and moderate proteinuria (up to 1 g/day) in the absence of edema and arterial hypertension.
According to N.L. Tov et al. (1989), the Criteria for the hematuric form of chronic GN should be considered:
a) erythrocyturia that constantly or periodically reaches 50 ∙ 106/day;
b) gross hematuria with daily proteinuria not exceeding 1 g;
c) exacerbations manifesting as an increase in erythrocyturia rather than proteinuria, in the absence of signs of Acute Nephritic Syndrome, edema, and arterial hypertension.
Overall, its clinical course is characterized by rather slow progression.
The hematuric form of chronic GN is diagnosed only after ruling out all other conditions that may cause hematuria, specifically tumors (even in young patients), urolithiasis, tuberculosis, polyps, etc.
The mixed form of chronic GN is a combination of nephrotic and hypertensive syndromes. In some cases, they appear simultaneously; in others, one syndrome (more commonly the nephrotic) develops more rapidly.
Prognostically, this form of chronic GN is considered the most unfavorable—the life expectancy of such patients rarely exceeds 8 years.
Finally, I.E. Tareeva et al. (1995) distinguish terminal GN, which represents the end-stage of GN of any type. The authors justify classifying it as a separate form due to the feasibility of initiating active renal replacement therapy—such as hemodialysis or kidney transplantation—specifically during this period.
Complaints from patients with chronic GN are primarily caused by progressive uremic intoxication, arterial hypertension with the development of a hypertensive heart, anemia syndrome, acidosis, and electrolyte imbalances.
Overall, the clinical course of GN was described in such detail by R. Bright nearly 200 years ago that we deem it appropriate to present this description, as it remains nearly impossible to improve upon even today: ... "A child or an adult is seized with scarlatina, or some other acute disease; or has, for a month or upwards, been exposed to the undue influence of spirituous liquors:--he is exposed to some casual, or habitual suppression of perspiration;--he observes that his urine is scanty and high-coloured, or that it is tinged with blood;--or without these observations, he awakes in the morning with his face bloated, his ankles surcharged, or his hands oedematous."
If under these conditions the patient is examined by a physician, significant amounts of albumin are detected in the urine; the pulse is full and bounding, the skin is dry, and frequent headaches occur, sometimes accompanied by lower back pain.
With treatment—whether more or less active, or sometimes without any treatment at all—the most striking and unpleasant of these symptoms subside, intermittent or constant sweating ceases to be observed, and red particles are no longer found in the urine. Depending on the importance previously attributed to these symptoms, they are gradually overlooked or entirely forgotten.
However, from time to time, facial puffiness appears and headaches occur with unusual frequency. Painful urges to urinate disturb the patient's nocturnal rest.
Over time, the healthy complexion fades, weakness or lower back pain increases, and headaches—frequently accompanied by vomiting—add to the overall discomfort. Fatigue, lethargy, and depression gradually take hold of both mind and body.
If the Nature of the disease is suspected, a thorough urinalysis is performed, revealing albumin in almost every test. When bloodletting is performed to relieve the condition, the blood often appears "buffed" and the serum turbid or milky in appearance; careful examination frequently reveals a significant decrease in albumin, and occasionally the initial signs of urea."
One of the most pressing issues in nephrology is predicting the rate of progression of chronic glomerulonephritis (GN), as it inevitably leads to chronic renal failure (RF)—a highly undesirable outcome even with the use of modern replacement therapy. At the same time, the timeframe for the development of end-stage renal disease is substantial, ranging from 3 to 40 years (M.Ya. Ratner et al., 1989).
An analysis of numerous clinical and morphological observations has established that the most important predictors of chronic GN progression are its clinical types (maximal active and active nephritic, nephrotic-hypertensive), the Early Development of sclerotic changes in the form of fibroplastic transformation of the glomeruli, the involvement of the tubulointerstitial component, and the morphological type of GN (M.S. Komadenko et al., 1991; S.I. Ryabov et al., 1997). Unfavorable morphological types of chronic GN include mesangiocapillary GN and focal segmental glomerulosclerosis/hyalinosis (M.Ya. Ratner et al., 1999).
An important factor is also the sensitization of the Organism to medications, leading to immediate (immunoglobulin E-mediated reactions) or delayed-type hypersensitivity reactions. These reactions are caused by the direct interaction of the drug—secreted by the renal tubules—with sensitized T-lymphocytes and the subsequent release of delayed-type hypersensitivity factors.
According to M.Ya. Ratner et al. (1991), the involvement of the tubulointerstitial component in chronic GN can be diagnosed by assessing renal functions such as the capacity for maximal osmotic concentration and The excretion of hydrogen and ammonium ions (which decrease by 33–50%), as well as by determining the blood and urine levels of beta-2-microglobulin, which are elevated in such cases (O.E. Golovanova et al., 1996).
Insufficient knowledge of the clinical syndromes characteristic of chronic GN, as well as the misinterpretation of urinalysis findings, accounts for fairly frequent diagnostic errors—ranging from 7–10% in specialized departments to 20–25% in general therapeutic departments (L.A. Pyryg, N.Ya. Melman, 1982).
First of all, we should emphasize the necessity of differentiating physiological proteinuria (orthostatic, stress-induced, etc.) from pathological proteinuria.
An Exacerbation of chronic GN (most commonly presenting with an isolated urinary syndrome) may be mistaken for acute GN, especially when the disease manifestations arise following a recent streptococcal infection.
The core elements of differential diagnosis are a carefully taken medical history and an analysis of medical records. In the absence of such data, the functional state of the kidneys should be analyzed. Evidence favoring chronic GN includes a decrease in the Glomerular Filtration rate (GFR), impaired renal concentration function, and hypercreatininemia. In acute GN, reduced GFR and hypercreatininemia are generally transient and occur only in cases of a fulminant course accompanied by pronounced oliguria, edema, and hypertension, while the relative urine density remains elevated. Other data should also be taken into account, such as the sudden onset of nephrotic syndrome, uncorrected arterial hypertension, elevated serum levels of middle-molecule Peptides, an increase in daily proteinuria, hematuria in single urine portions (10-fold or more), dysproteinemia, hyperfibrinogenemia, enzymuria, and changes in immunological parameters.
The hypertensive form of chronic GN is most commonly differentiated from essential hypertension, latent renal failure, renovascular hypertension, Conn's syndrome, and pheochromocytoma. It should be noted that urinary sediment abnormalities (which are less pronounced than in chronic GN) occur in the late stages of essential hypertension. In essential hypertension, renal plasma flow decreases before the GFR, whereas in chronic GN, the opposite is true.
In the differential diagnosis of chronic GN and renovascular hypertension, the full range of instrumental and hardware Methods described above is utilized. Conditions such as renal amyloidosis (in the proteinuric stage), diabetic glomerulosclerosis, Preeclampsia, gouty nephropathy, renal involvement in collagenoses and systemic vasculitis, Polycystic Kidney Disease and Nephroptosis, urolithiasis, tumors, Renal tuberculosis, and renal vein thrombosis should also be kept in mind.
Differential diagnosis between chronic GN and chronic pyelonephritis in the phase of incomplete remission is also quite challenging, requiring the proper interpretation of bacteriological, radiological, ultrasound, and isotopic data.
To conclude this section, we present information on a fairly frequent form of primary GN—so-called IgA nephropathy (synonyms: Berger's disease, glomerulitis with diffuse IgA deposits in the mesangium, IgA-IgG nephropathy, mesangial IgA nephritis, primary IgA-IgG glomerulonephritis)—which has been the object of numerous studies over the past 20–30 years.
Since its original description (J. Berger et al., 1968), this form of pathology has attracted the attention of researchers and clinicians primarily due to its frequency, conflicting data regarding its pathogenesis, the difficulties in predicting outcomes, and the lack of universally accepted therapeutic tactics.
IgA glomerulonephritis occurs with a frequency of 6.2–60% (G.D. Doyle et al., 1986), with this rate varying by region: 2–4% in Great Britain, 30.2% in Australia, 39–60% in the USA and Europe, 66.7% in Russia, 18–22% in France, and 28–40% in Japan (S.I. Ryabov, 2000).
Among individuals with chronic renal failure, patients with IgA glomerulonephritis account for 10% (Yu. Nagy, 1991).
At present, a clear association is observed between the disease and certain human leukocyte antigen (HLA) alleles, specifically BW35, BW4, BW12, and CW1 at the HLA-A, B, C loci, and DR4, DQW7, and DQA2U at the HLA-DR loci. Additionally, certain peculiarities of immunoglobulin A metabolism are observed—such as their increased synthesis in the Tonsils, elevated levels in nasal and nasopharyngeal secretions, and intensive production under The Influence of dietary proteins, viral infections, and vaccine stimulation (M. Russel et al., 1998).
According to H. Sakai (1997), the leading factor in the pathogenesis of this condition is nevertheless a genetic predisposition to elevated blood levels of class A immunoglobulins and an immune response mediated by IgA antibodies, which, upon contact with various antigens, leads to the Development of the disease. These antigens are likewise considered to include Bacteria, viruses, dietary proteins, etc. (R. Coppo, 1995).
The most significant diagnostic (morphological) feature of IgA glomerulonephritis is the detection of class A immunoglobulin deposits in the mesangium of all glomeruli (M.C. Bene et al., 1981, 1994), frequently in combination with deposits of class G immunoglobulins, the C3 complement component, and fibrinogen/fibrin. In some glomeruli, subendothelial or subepithelial deposits are found, usually combined with alterations in the basement membrane—areas of thinning, reduced density, splitting, and ruptures. It is possible that these very changes lead to hematuria, while the fusion of podocyte foot processes results in proteinuria (S.N. Emancipator, 1992).
In the blood serum, factors that stimulate interleukin-1 production and enhanced proliferation of mesangial cells, autoantibodies against mesangial cells, anti-endothelial antibodies, and antibodies to cardiolipin, Laminin, and double-stranded DNA are identified, thereby demonstrating signs of marked B-cell hyperactivation.
Recently, in Addition to Isolated primary IgA glomerulonephritis, so-called secondary IgA glomerulonephritis has been described, wherein glomerular IgA deposits are found in systemic diseases, hemorrhagic vasculitis, alcoholic Liver and renal disease, and AIDS.
There are two hypotheses regarding the pathogenesis of IgA glomerulonephritis in humans.
One of them attributes the onset of the disease to the deposition in the mesangium of circulating immune complexes containing, alongside the mandatory class A immunoglobulins, immunoglobulins of classes M and G, as well as fibrin; the second links it to the formation of immune complexes in situ, meaning the initial 'implantation' of the antigen into the mesangium—likely due to an impairment of its 'garbage disposal' function—followed by the binding of specific IgA antibodies to it.
Individuals most vulnerable to IgA glomerulonephritis are males (with a male-to-female ratio of 2–5:1) aged 20–40 years. In childhood, IgA glomerulonephritis most commonly manifests after the age of 3 (in 50% of cases, between 6 and 12 years).
In approximately 50% of patients, the onset of the disease cannot be established, and it is diagnosed incidentally during routine check-ups or investigations for abdominal pain, arthralgia, frequent recurrent Upper Respiratory Tract infections, or hypertension.
Although the reported frequency of macroscopic hematuria varies, most authors consider it the hallmark symptom of the disease (37–60%, D.C. Battle, 1990; F. Schema, 1998). It may present as a single episode or as recurrent bouts. Recurrent macroscopic hematuria is detected in 30–60% of patients, lasting from 1 to 50 days with intervals ranging from several months to 2 years or more (A.R. Clarkson et al., 1990). Gross hematuria is the most frequent presentation in children (80% of cases). In one-third of cases, persistent microscopic hematuria is observed. Hematuria may be accompanied by a dull ache in the lumbar region and abdomen.
Hematuria is frequently preceded by sore throat, other upper respiratory or gastrointestinal infections (implicating antigens of bacterial or viral origin), physical overexertion, vaccination, asthma attacks, etc.
Selective proteinuria (seen in 50% of patients) typically does not exceed 1 g/day. Nephrotic syndrome rarely develops, and hypertension is not considered an obligatory symptom, although J. Berger himself described it in one-third of cases.
In a subset of patients (10%), IgA glomerulonephritis may present as acute glomerulonephritis, characterized by gross hematuria, proteinuria, edema, and hypertension. Significant and prolonged macroscopic hematuria combined with heavy proteinuria serves as a marker of an unfavorable disease course (P.S. Kincaid-Smith, 1985).
The definitive diagnosis of IgA glomerulonephritis relies on immunopathological examination of the kidneys, which reveals deposits of class A immunoglobulins (sometimes accompanied by class G immunoglobulin deposits) within renal structures, alongside features of diffuse mesangioproliferative (78%), focal proliferative (13.7%), diffuse membranoproliferative (3%), or diffuse extracapillary (2.3%) glomerulonephritis (Y. Nakamoto et al., 1990).
Literature data regarding serum IgA levels in this form of pathology are conflicting: some authors report elevated levels, while others find them normal. It is worth noting that as early as 1984, K. Nicholls et al. and J.L. Rodicio concluded that measuring blood IgA levels in this condition is pointless, as the deposition of these immunoglobulins in the mesangium does not correlate with their circulating blood levels.
Differential diagnosis is carried out with other conditions that are also accompanied by the deposition of class A immunoglobulins in the renal mesangium.
While differentiating the condition from dermatitis herpetiformis or alcoholic cirrhosis poses no difficulty, challenges arise in the presence of renal manifestations associated with hemorrhagic vasculitis, celiac disease, Crohn's disease, or systemic lupus erythematosus. Immunohistologically, these pathological entities are remarkably similar and can only be clinically distinguished when cutaneous signs of hemorrhagic vasculitis, systemic symptoms of lupus, Crohn's disease, or similar conditions appear. In lupus-associated glomerulonephritis, C1q deposits are identified, which are absent in both hemorrhagic vasculitis and IgA glomerulonephritis.
To date, no consensus has been reached on whether Berger's disease is a 'renal' manifestation of hemorrhagic vasculitis or a distinct nosological entity. Despite overlapping clinical, immunological, and histochemical features, most researchers favor viewing these conditions as independent nosological units (M.O. Kolesnyk et al., 2001; I.S. Davin et al., 1999; J. Floege et al., 2000).
Treatment of immuno-inflammatory kidney diseases. Typically, these conditions are managed in specialized inpatient settings upon initial presentation or during an acute flare. However, their subsequent management is carried out in outpatient clinics, which underscores the necessity of acquainting physicians with modern therapeutic approaches for these forms of pathology.
As previously mentioned, immuno-inflammatory kidney diseases primarily encompass acute and chronic glomerulonephritis, as well as renal involvement in systemic Connective Tissue diseases (L.A. Pyrih, 1998, 2001). Drawing upon these sources, as well as the works of M.Ya. Ratner (1992) and S.I. Ryabov (2000), we outline the core principles of treatment for these pathological conditions.
It should be noted at the outset that the overall outcomes of Pathogenetic Therapy for nephritis are undeniably disappointing, prompting skepticism from many nephrologists. For instance, as early as 1977, J.S. Cameron wrote that '...the successes achieved in the treatment of nephritis are more the result of good fortune than of a logical approach.'
One reason for the limited efficacy of such therapy lies in its lack of Specificity, given that the onset of glomerulonephritis can be driven by immuno-inflammatory disturbances, hemodynamic and hemocoagulatory disorders, genetic factors, and other mechanisms, the individual contributions of which are difficult to quantify in any given patient.
Immunosuppressive therapy generally fails to significantly improve the prognosis of primary glomerulonephritis—which constitutes the majority of nephrological pathology—while carrying considerable adverse effects and complications, both 'Major and minor' (L.R. Polyantseva et al., 1990).
Furthermore, it cannot be ruled out that drugs used in the pathogenetic therapy of glomerulonephritis may contribute to the development and progression of tubulointerstitial lesions (M. Ahuja et al., 1999). This view is shared by B.I. Shulutko et al. (1985), whose conclusions are based on data from 46 repeat renal biopsies, while J. Cameron et al. (1972) famously termed the successes of cytostatic therapy for childhood glomerulonephritis complicated by subsequent leukemia as a Pyrrhic victory.
A major challenge in pathogenetic therapy is the development of resistance. This resistance is practically independent of the morphological form of glomerulonephritis and may be primary or secondary in origin—meaning that for reasons unknown, the drug fails to elicit its pharmacological effect. It is well established that the positive outcomes achieved with glucocorticoids or cytostatics are inconsistent; in the same patients, a drug that proved effective at disease onset often becomes ineffective during subsequent relapses. The development of resistance is attributed to innate cellular receptor deficiencies for glucocorticoids, the Selection and proliferation of cell clones that differ from the original dominant subpopulation in chemosensitivity, the NEGATIVE IMPACT OF glucocorticoids on lymphoid tissue mass, reduced synthesis of T- and B-lymphocytes, and The production of defective antibodies by the latter. THE CONCEPT OF 'resistance' also applies to cytostatics (owing to their capacity to suppress cell proliferation via the blockade or destruction of nuclear DNA, thereby interrupting the replication necessary for Cell Division, an initial exacerbation of undifferentiated lymphoid progenitor depletion followed by bone marrow hyperregeneration, and an increased release of early lymphoid elements into the bloodstream, etc.) (I.A. Rakityanskaya, 1998).
Nevertheless, it should be noted that pathogenetic therapy can still improve the duration and quality of life in patients with nephrotic syndrome and so-called minimal change disease, or rapidly progressive glomerulonephritis within the context of systemic disease, where high or ultra-high doses of glucocorticoids and/or immunosuppressants, combined with anticoagulants and antiplatelet agents, can stall a fatal disease trajectory.
The Management of acute glomerulonephritis—whose natural course typically features a complete restoration of normal renal parenchymal structure—is largely symptomatic, aimed at preventing or reversing life-threatening emergencies at presentation, such as hypertensive encephalopathy, renal eclampsia, acute renal failure, and acute heart failure.
The Prevention of these conditions is closely linked to the administration of potent natriuretic therapy, prescribed early in the disease course upon the sudden onset of massive edema and hypertension.
Furosemide is the drug of choice. Depending on the severity of oliguria and the rate of progression of extrarenal manifestations, it is administered orally (40–120 mg/day) or intravenously (80–120 mg) when diuresis is 500–600 mL/day. If diuresis does not increase by 400 mL within the next 2 hours, a repeat dose of 400–600 mg of furosemide is recommended. The same dosage of furosemide is used from the outset when creatininemia exceeds 0.8–1.0 mmol/L; in select cases (oliguria or anuria lasting 12–24 hours), furosemide is administered intravenously at a dose of 800–2,000 mg.
Oliganuric acute renal failure lasting more than 2 days and refractory to natriuretic therapy requires rigorous monitoring of serum potassium levels. In the event of life-threatening hyperkalemia (exceeding 6.5–7 mmol/L), immediate correction is mandatory (see the section 'Management of Acute Renal Failure').
The presence of acute renal failure symptoms for 3-4 days or longer provides a strong rationale for hemodialysis.
Antibiotics (most commonly Semisynthetic Penicillins at standard therapeutic doses of 2-4 g/day) are prescribed for 2-3 weeks in cases of a clearly documented history linking acute nephritis to a prior streptococcal infection, or in the presence of high titers of antistreptococcal antibodies in the blood.
Anticoagulant or antiplatelet therapy is indicated if even minimal alterations are detected in the hemocoagulation system.
Glucocorticoids have become widely used in the treatment of acute glomerulonephritis. Their MECHANISM OF ACTION is primarily attributed to effects on the cellular immune response (increasing the blood population of T lymphocytes with helper functions and mature immunocompetent cells), reducing capillary permeability, inhibiting aldosterone secretion, and suppressing antibody production. Prednisolone is most frequently administered at a dosage of 1-1.5 mg/kg of body weight/day, or other agents at an equivalent dose, for 4-6 weeks. One tablet of prednisolone is equivalent to: methylprednisolone (Medrol) - 4.0 mg, triamcinolone (Kenacort) - 4.0 mg, dexamethasone - 0.75 mg, betamethasone - 0.64 mg, paramethasone - 2.0 mg. A gradual reduction of the drug dosage, especially starting from 40-30 mg/day, is continued over 2-6 months, and in cases of glomerulonephritis associated with systemic connective tissue diseases, for up to 6-8 months, followed by maintenance therapy (10-30 mg/day for 2-4 years). The lowest incidence of complications is observed with the administration of methylprednisolone, Medrol, and Metypred.
If the aforementioned therapy proves ineffective, pulse therapy is administered (up to 1000 mg of prednisolone/day, every 1-2 days, with a course of 3-6 sessions). Steroid sensitivity can also be enhanced through the combined or prior use of hemosorption or plasmapheresis (4-6 sessions every 1-3 days).
Glucocorticoid therapy is highly effective (achieving complete remission in 85–97% of cases) in minimal change glomerulonephritis, and its efficacy in adults is no lower than in children. In the event of disease relapse following achieved remission or steroid resistance, alkylating cytostatics are used (cyclophosphamide at a dose of 1 mg/kg of body weight/day; A.I. Dyadyk et al., 1991).
The desire to enhance the efficacy of immunosuppressants as early as the 1960s–1980s led to the development of various treatment regimens: combining cytostatics with different mechanisms of action (T. Orłowski et al., 1982), alternating administration of cytostatics and prednisolone (C. Ponticelli et al., 1984), combining a cytostatic with an anticoagulant and an antiplatelet agent (P. Cincaid-Smith et al., 1986), combining a cytostatic with a corticosteroid, an anticoagulant, and an antiplatelet agent (L.D. Sidorova et al., 1986; C.B. Brown et al., 1974), and cytostatic pulse therapy (H.J. Dinant et al., 1982).
Among cytostatic agents, azathioprine (Imuran), cyclophosphamide, and 6-mercaptopurine are used at a daily dose of 1.5-4.0 mg/kg of body weight, chlorambucil (Leukeran) at a daily dose of 0.1-0.2 mg/kg of body weight, and methotrexate at 5-10 mg/week.
Cytostatics are frequently combined with corticosteroids, which allows for a reduction in the daily doses of the latter. Such combination therapy is particularly indicated for glomerulopathies associated with systemic connective tissue diseases and systemic vasculitis.
In cases where the aforementioned therapy is ineffective or if there are contraindications to prednisolone pulse therapy, cyclophosphamide pulse therapy is recommended (1000 mg/day, once a month, for 4-6 months, followed by maintenance therapy once every 6 months; A.I. Taran, 1999). Literature data (G.M. Shilov et al., 1995) describe the use of ultra-high-dose cyclophosphamide therapy (20 mg/kg of body weight/day once every 4 weeks); however, according to the same researchers, worsening of the condition was recorded in 39% of patients.
In steroid-resistant patients, particularly those with lupus nephritis, cyclosporine A (Sandimmune, 3-5 mg/kg of body weight/day) is administered for 6 months to 3-5 years. A newer formulation, Sandimmun Neoral (Novartis, Switzerland), based on microemulsion technology, allows for more reliable dose titration for oral administration (D.C. Cattran et al., 1999).
The simultaneous administration of calcium channel blockers reduces the risk of cyclosporine-induced nephropathy.
In cases of primary lupus glomerulonephritis developing against the background of hemorrhagic vasculitis, a novel cytostatic, mycophenolate mofetil, is employed at a daily dose of 1-2 g for 3-8 months (R. Nowak et al., 1997; L.A. Pyrih, 1999, 2000; I.A. Hauser et al., 1999; S.K. Fujinaka et al., 2000). In incomplete remission of such nephropathy or when immunosuppressive therapy proves ineffective, ketotifen hydrogen fumarate (Zaditen, Broniten) is introduced into the treatment regimen at a daily dose of 4 mg for the first 10 days, followed by 2 mg/day for 3 months.
Thus, the indications for cytostatic-anticoagulant-antiplatelet therapy, regardless of the morphological type of glomerulonephritis, include a prolonged (exceeding 1 year) pronounced nephrotic syndrome accompanied by fibroplastic transformation, acute nephritic syndrome persisting for more than 1 month, and the relapse phase of chronic glomerulonephritis manifested by a significant increase in proteinuria combined with hematuria, edema, and/or arterial hypertension.
A combination of anticoagulants, cytostatics, and corticosteroids is recommended for patients with rapidly progressive and lupus glomerulonephritis, as well as early forms of membranoproliferative and diffuse mesangioproliferative glomerulonephritis. In focal segmental glomerulosclerosis/hyalinosis and mesangial IgA glomerulonephritis, anticoagulants, corticosteroids, and immunosuppressants do not significantly affect the Clinical presentation or the progression of chronic renal failure.
It must be stated, however, that The problem of determining the optimal duration of immunosuppressive therapy for each individual case of glomerulonephritis remains far from resolved.
An absolute indication for continuing, and potentially intensifying, such therapy is the persistence of recognized symptoms of glomerulonephritis activity.
It is more challenging to determine the management strategy when clinical and laboratory symptoms improve or completely disappear. It should be kept in mind that immunological remission develops significantly later than clinical remission; therefore, attempting to discontinue immunosuppressive therapy while immunological activity persists will inevitably lead to a disease relapse. Consequently, immunological monitoring is the optimal method for assessing disease activity, although it remains largely inaccessible in routine clinical practice.
Heparin therapy is an essential component in the treatment of immune-mediated renal diseases due to heparin's anticoagulant, lipolytic, and natriuretic properties.
Heparin is administered at a daily dose of 20,000 IU for 3-4 weeks (subcutaneously into the anterior abdominal wall twice daily). Heparin therapy may be supplemented with infusions of fresh frozen plasma.
Recently, low-molecular-weight heparins have been successfully used instead of standard heparin, as discussed below.
Among antiplatelet agents, dipyridamole (Persantine) has gained widespread use (200-400 mg/day for prolonged periods, often years), alongside ticlopidine (0.25 mg twice daily for 2-6 months), aspirin (0.25 g/day for 4-6 months), complamin (2-6 ml of a 15% solution intravenously by drip infusion for 10-15 days), and pentoxifylline (Trental, 300-1000 mg intravenously by drip infusion for 10-15 days). Subsequently, oral administration of complamin or pentoxifylline (300-600 mg/day) is recommended for 2-4 months (O.M. Karamzina et al., 1999; L.A. Pyrih, 1999). Combined use of dipyridamole with aspirin and enalapril (Renitec) can also be recommended (O.I. Bakalyuk et al., 1998). Antiplatelet agents, particularly pentoxifylline, are utilized as monotherapy for the latent and hypertensive variants of chronic glomerulonephritis.
Membrane-stabilizing therapy is administered to patients with acute glomerulonephritis presenting with a hematuric component.
This approach involves the inpatient administration for 1 month of unithiol (5% solution, 5 ml daily intramuscularly), tocopherol acetate (200-250 mg/day), dimephosphone (100 mg/kg of body weight/day), and chloroquine (Delagil, 0.25 g twice daily), followed by outpatient administration of tocopherol acetate (200 mg/day) combined with chloroquine (0.25 g/day) for 5 months. According to L.A. Pyrih et al. (1999), this therapy is most indicated for younger patients; in middle-aged patients, preference should be given to Hyperbaric Oxygenation, whereas in elderly patients, dipyridamole is preferred.
Quercetin (80-100 mg/day) and canaflazin (100-150 mg/day) in three-week cycles are used as Vitamin P Donors (I. Ishikawa et al., 2000). To reduce capillary permeability, escin (aescin) is recommended (10-20 drops three times daily) (V.O. Kaluhin et al., 1997).
Hypolipidemic therapy requires prescribing an appropriate diet and/or Cholesterol-lowering medications (preferably from the statin group (Lipitor) or micronized fenofibrate (Lipanthyl 200M)).
There are reports in literature regarding the efficacy of systemic enzyme therapy (Wobenzym) in patients with chronic GN (I.V. Mukhin, 2000; E.D. Egudina et al., 2000).
Hyperbaric Oxygen therapy is indicated for patients with acute and chronic GN, anephrotic syndrome or NS, with a hematuric component, in the pre-hypertensive or hypertensive stages of chronic GN.
In recent years, plasmapheresis has been used for the treatment of chronic GN; studies on its efficacy are associated with the names of C.M. Lockwood et al. (1977),
C.S. Rosenblatt et al. (1979).
Indications for its use include the hypertensive (mixed) form of GN resistant to corticosteroid and cytostatic therapy, or the impossibility of using the latter to their full extent; GN with rapidly progressive CRF, and severe renal involvement in systemic vasculitis and collagenoses (M.B. Velychko, 1996).
At the same time, the contribution of plasmapheresis to the overall treatment efficacy of these forms of GN remains not fully understood (Yu.E. Malakhovsky et al., 1991; S.B. Dorofeev et al., 1991).
ACE inhibitors have become widely used in the treatment of immuno-inflammatory renal diseases. They are used as monotherapy and in combination therapy for GN (L.A. Pyrih, 1999).
Monotherapy with ACE inhibitors is used:
- in patients with chronic GN and urinary syndrome in the pre-hypertensive stage (with or without a hematuric component);
- in patients with chronic GN and urinary syndrome in the hypertensive stage (with or without a hematuric component) provided there is an adequate antihypertensive effect;
- in patients with chronic GN, urinary and nephrotic syndromes in stage I CRF, provided there is adequate correction of hypertension and control of blood creatinine and potassium levels.
The dose of the ACE inhibitor is selected individually; the criterion for its sufficiency is a diastolic BP level of 80 mmHg or lower, or its decrease by 10 mmHg or more compared to baseline data.
ACE inhibitors are used in the combination treatment of:
- patients with chronic GN and urinary syndrome in the pre-hypertensive stage (with or without a hematuric component) along with membrane-stabilizing therapy and dipyridamole (200-300 mg/day);
- patients with chronic GN and urinary syndrome in the hypertensive stage (with or without a hematuric component) along with membrane-stabilizing therapy and dipyridamole;
- patients with chronic GN and urinary syndrome in the hypertensive stage (with or without a hematuric component) along with other antihypertensive agents, provided there is no adequate antihypertensive effect with ACE inhibitor monotherapy;
- patients with chronic GN, urinary and nephrotic syndromes in stage I CRF along with treatment using dipyridamole, pentoxifylline, xanthinol nicotinate, and enterosorbents;
- patients with chronic GN and NS along with the administration of prednisolone (1 mg/kg body weight/day) and cyclophosphamide (3 mg/kg body weight/day);
- patients with chronic GN and NS along with pulse therapy with cyclophosphamide.
ACE inhibitors are also a promising group of drugs for the combination treatment of lupus GN due to their positive effect on intrarenal hemodynamics (I.E. Tareeva et al., 1998).
As for attempts to use calcium channel blockers to slow the progression rate of chronic GN, the obtained data are mixed. It is emphasized that a slowdown in the progression rate of chronic GN can only be expected under the condition of prolonged normalization (!) of systemic BP levels; otherwise (only lowering systemic BP), The Effect of calcium channel blockers on renal function may become negative.
New approaches to the treatment of chronic GN are based on the administration of immunomodulators. A complete regimen of cytostatics and immunomodulators may look as follows (S.I. Ryabov, 2000):
- plasmapheresis, 3-5 sessions;
- thymalin and/or T-activin, vilozen calculated per 1 kg of body weight for 10-12 days;
- glucocorticoids or cytostatics in the aforementioned doses.
Physiotherapeutic treatment methods for acute GN are used to a limited extent: inductothermy (in the absence of ARF), UHF therapy, microwave therapy, solux, infrared therapy, general calcium Electrophoresis according to Vermel's method, and paraffin-ozokerite Applications (E.M. Neiko, 2000).
In chronic GN, the issue of prescribing physiotherapeutic Procedures is resolved individually, depending on the patient's condition and the leading syndrome. For the nephrotic variant, to improve the Excretory Function of the skin and kidneys, electric light baths, paraffin or ozokerite applications, Hauffe baths, general (sitting) fresh or low-mineralized baths at a Temperature of 36.5–37 °C for 10–30 minutes are prescribed; for the hypertensive variant, inductothermy to the renal area, microwave therapy, Hauffe baths, carbon dioxide baths at 36.5–37 °C for 10–12 minutes; for uremia and skin pruritus, fresh baths at 36–38 °C followed by dry wrapping for 30–40 minutes, conifer baths, and bran baths (A.N. Obrosov, 1976).
Patients with chronic GN also undergo intravascular laser therapy (T.S. Ignatenko et al., 2000), UHF therapy, inductothermy, Microwave Resonance therapy (provided there is no ARF) (V.S. Karpenko et al., 1995), corporal acupuncture, and auriculotherapy (T.I. Holub, 1999).
It is believed (E.M. Neiko, 2000) that there are no contraindications to phytotherapy in acute GN. In such cases, the following are recommended:
- to achieve a diuretic and hypotensive effect: a) black currant leaves, oregano herb, marigold flowers (1 part each) + lemon balm herb (1 part) – pour 1 cup of boiling water over 1 tablespoon of the mixture overnight, infuse for 12 hours, add 1 cup of boiled water, boil for 3–4 minutes, strain, add 1–2 tablespoons of honey, and take the entire mixture in 4–5 divided doses; b) hawthorn leaves, motherwort herb (2 parts each) + hops cones (1 part) + bearberry herb, parsley ROOT (3 parts each) – preparation method is the same as for the previous mixture;
- for hematuria: a) kidney tea herb, St. John's wort herb, nettle leaves, arnica flowers (1 part each) + bistort root (2 parts) + white dead-nettle flowers (3 parts) – preparation method is the same as for the previous mixture; b) kidney tea herb, yarrow leaves, wild strawberry leaves (1 part each) + beggarticks herb (2 parts) + marigold flowers (3 parts) – preparation method is the same as for the previous mixture.
In chronic GN at the pre-hypertensive stage without impaired nitrogen-excreting renal function and with urinary syndrome, herbal mixtures may be prescribed, which can include woolly-flower milkvetch herb, barberry, St. John's wort herb, centaury herb, medical burnet, common thyme, rose hips, betony herb, lemon balm herb, yarrow herb, tricolor violet flowers, marigold flowers, linden flowers, common comfrey root; to improve Blood Circulation and renal excretory function – Icelandic moss, elecampane root, black elderberry flowers, garden parsley root, lingonberry leaves, St. John's wort herb, motherwort herb, wormwood herb, turnip herb, celandine herb, centaury herb, flax seeds (M.O. Harbarets et al., 1981).
Patients with chronic GN at the hypertensive stage are prescribed an infusion of marigold flowers, shepherd's purse herb, sage herb, and motherwort herb; in cases of chronic renal failure – an infusion of kidney tea leaves, bogbean, St. John's wort, meadowsweet flowers, elderberry bark, dandelion root, comfrey root, restharrow root, and bean husks.
The treatment of IgA nephropathy remains an unresolved issue, with about 33% of adult patients over 20 years and 11% of children over 15 years of follow-up dying from chronic renal failure.
In this disease, the therapeutic approach is implemented taking into account potential pathogenetic mechanisms of development, clinical and morphological manifestations, and includes: targeting the exogenous (bacterial, viral, dietary) antigen to eliminate it; suppressing the Antigen-Antibody Reaction considering the immune-complex nature of the disease; and acting on secondary pathogenetic links (blood clotting system, microcirculation).
Recently, considerable attention in the treatment of IgA nephropathy has been paid to a gluten-free diet (E.L. Panchenko et al., 1994; R. Coppo et al., 1990), prophylactic antibiotic administration, and tonsillectomy (K. Koichi et al., 1993).
Combined immunosuppressive and anticoagulant therapy (K.T. Woo et al., 1991), D-penicillamine (K.M. Bannister et al., 1992), plasmapheresis (J. Chalopin et al., 1990), danazol (L. Fry et al., 1980; J.A. Sheyman, 1999), phenytoin (J. Egilo et al., 1994), fish oil and its derived preparations (eicosapentaenoic acid, docosahexaenoic acid) (L. Pyrih, 2001; J.V. Donadio et al., 1991), nonsteroidal anti-inflammatory drugs (G. Lagrue et al., 1995), and kidney transplantation (J. Bignon et al., 1996) have also been proposed; however, none of these methods has a pronounced positive effect on the disease course and its prognosis. It should be noted that mesangial IgA deposits "recur" in the transplant, but they are clinically insignificant and rarely lead to renal failure (J. Berger, 1988).
Last update: 08/08/2026
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