Nephrology for the Family Physician - O.I. Bakaliuk 2003

Renal Pathology in Other Diseases
Kidneys and Systemic Vasculitides

Recently, with the advent of assays for antineutrophil cytoplasmic Antibodies (ANCA), the Pathogenesis of vasculitides and their overlapping clinical symptoms have become much better understood. Neutrophils fixed in alcohol and incubated with a patient's serum containing ANCA exhibit two distinct staining patterns: cytoplasmic (c-ANCA), which indicates antibodies directed against proteinase-3, and perinuclear (p-ANCA), indicating antibodies to myeloperoxidase (J.C. Jenette et al., 1994). The discovery of ANCA has advanced our understanding of the role humoral factors play in The Development of vasculitis. A strong correlation between ANCA titers and disease activity, alongside their high Specificity for vasculitides, points to a crucial pathogenetic role: the reaction of these antibodies with neutrophils triggers the degranulation of neutrophil Cytoplasm and the generation of free oxygen radicals (R. Falk et al., 1990, W.L. Gross et al., 1995) with all the ensuing pathological consequences. Furthermore, a potential link between HLA Class allotypes and ANCA-associated diseases cannot be ruled out. A new international Classification of Primary vasculitides has recently been proposed, based on the caliber of the affected vessels and ANCA positivity (J.C. Jenette et al., 1994).

The Role of the cellular Immune Response in vasculitis is driven by cytotoxic T-Cell reactivity against Antigens within the vascular wall, leading to necrosis and neutrophil infiltration. Endothelial Cells may also directly participate in this process, as they are capable of expressing class II Major Histocompatibility Complex antigens and adhesion molecules.

Thus, vascular endothelial injury in ANCA-associated vasculitis can be conceptualized as follows (J.C. Jenette et al., 1994): The impact of a triggering factor (such as cold, a virus, or another antigen) on neutrophil granulocytes and monocytes not only causes cytoplasmic degranulation and the generation of free oxygen radicals, but also stimulates these formed elements to produce interleukin-1 beta and tumor necrosis factor-alpha. The released cytokines then bind to receptors on T-helper lymphocytes, indirectly stimulating B-lymphocytes and resulting in The production of ANCA. Subsequent binding of ANCA with Complement and cytokines induces focal Necrosis of the endothelium surrounded by an area of active inflammation.

Systemic vasculitides are most commonly classified According to the caliber of the affected Blood Vessels (Figure 2).

Figure 2. Vascular involvement according to the clinical form of vasculitis (J.C. Jenette et al., 1994).

Vasculitides are also categorized based on the presence (temporal arteritis, non-specific aortoarteritis, Wegener's granulomatosis, Churg-Strauss syndrome) or absence (polyarteritis nodosa, Kawasaki disease, Henoch-Schönlein purpura, cryoglobulinemic vasculitis) of granulomas.

Among the Various Forms of systemic vasculitides, special attention should be given to those in which renal involvement is predominant and dictates the patient's quality and life expectancy: non-specific aortoarteritis, polyarteritis nodosa, Wegener's granulomatosis, Goodpasture's syndrome, Henoch-Schönlein purpura (HSP), and retroperitoneal fibrosis.

Non-specific aortoarteritis (NAA, pulseless disease, young female arteritis, Takayasu's arteritis) was first described in 1856 by W. Savory and A. Kussmaul. In 1908, M. Takayasu described central retinal artery abnormalities combined with an absent radial pulse in a 21-year-old woman. In 1948, K. Shimizu and K. Sano provided a detailed clinical description of NAA, which has been referred to as Takayasu's arteritis since 1954. Its incidence is approximately 2.6 cases per 100,000 population, which is comparable to that of Wegener's granulomatosis and polyarteritis nodosa. It predominantly affects young women.

The Etiology of NAA remains unknown, though a certain association with Crohn's disease, Ulcerative Colitis, and Still's disease has been established, suggesting an immune-complex pathogenesis for this condition.

Four types of NAA are distinguished. Type I involvement is restricted to the aortic arch and its branches (8% of cases). Type II is characterized by lesions of the descending aorta (11%), Type III involves both the aortic arch and its descending portion (65%), and Type IV exhibits the Features of the first three variants combined with arteritis of the pulmonary artery branches (45%). Morphological examination reveals granulomatous or sclerosing arteritis. The inflammatory process primarily affects the tunica media and tunica adventitia. The cellular infiltrate consists of lymphocytes, plasma cells, and macrophages; intra-organ Arteries are spared.

In individuals under the age of 20, the disease typically begins acutely, characterized by fever, asthenia, weight loss, myalgia, arthralgia, Skin lesions, and arrhythmias. In older patients, the onset is more often insidious and gradual (manifesting as ischemic syndrome).

Overall, 10 clinical syndromes are distinguished in NAA: inflammatory reactions, aortic arch branch involvement, coarctation syndrome, renovascular Hypertension, abdominal ischemia, aortic bifurcation involvement, coronary syndrome, aortic regurgitation, pulmonary artery involvement, and aortic aneurysm. Laboratory findings are non-specific and include an elevated ESR, anemia, dysproteinemia, and moderate proteinuria.

The MAIN CLINICAL MANIFESTATIONS of NAA include signs of ischemic syndrome, Asymmetry or absence of pulses, vascular bruits over major arteries, and arterial hypertension in young individuals, predominantly women.

The acute course of the disease is characterized by high fever, marked articular syndrome, anemia, and a significantly elevated ESR. Ischemic disorders develop within the first year and progress rapidly. Conservative therapy is generally ineffective.

In the subacute course, vascular symptoms develop more slowly (over years), with low-grade fever and moderate dysproteinemia.

A chronic course is observed in individuals over 30 years of age. The most frequent presentation is an ischemic syndrome of varying localization (vertebrobasilar insufficiency, visual disturbances, signs of coronary artery disease, renovascular arterial hypertension).

Diagnosis of NAA is based on evaluating the patient's sex and age, medical history, typical symptoms, and instrumental imaging results. Among the latter, excretory urography, scintigraphy, vascular Doppler ultrasound, and angiography are preferred. Isolated renovascular hypertension in NAA is rare; in most cases, it is combined with symptoms of aortic arch branch involvement and stenosis of the thoracic or abdominal aortic bifurcation. A definitive diagnosis of renal artery involvement (bilateral in two-thirds of cases) is established based on characteristic deformation of the aorta, ostium, and the first segment of the renal artery on aortography. The distal lumen of the renal artery usually remains normal even in the presence of complete proximal occlusion.

Management of NAA includes both conservative therapy (glucocorticoids, immunosuppressants, anticoagulants, antiplatelet agents, antioxidants, angiotensin II receptor antagonists, and ACE inhibitors—the latter used with extreme caution!) and Surgical Treatment (resection of the affected aortic segment with graft replacement). The prognosis for NAA is somewhat more favorable than for other vasculitides: 5-year survival is 90–95% for uncomplicated cases and 50–65% for complicated cases. Surgical mortality ranges from 18 to 35%.

Polyarteritis nodosa is a systemic necrotizing vasculitis of medium- and small-sized arteries with an immune-complex-mediated mechanism. The disease was first described in 1866 by Kussmaul and Maier (in their work "On a peculiar, previously undescribed disease of the arteries – periarteriitis nodosa, accompanied by Bright's disease of the Kidneys and rapidly progressive muscular paralysis").

It is believed that the underlying immune dysfunction involves polyantigenic hypersensitization, leading to The formation of immune complexes of varying complexity. These complexes exert a damaging effect on the vascular wall. The role of the hepatitis B virus in the development of polyarteritis nodosa was demonstrated as early as the 1970s; today, the frequency of this association is estimated to be around 50% (B. Mulian, 2000).

In this disease, the kidneys justly rank first in terms of frequency of involvement (70–80%) and severity of prognosis. The primary pathological changes occur at the level of the renal arteries (extending to interlobular arteries) and glomerular arterioles. Immune-mediated vascular wall injury, followed by mucoid Swelling, fibrinoid necrosis, and sclerosis, leads to microaneurysmal dilations, ischemic glomerular damage, and Collagen deposition. These are compounded by recurrent acute changes—circumferentially or eccentrically distributed infiltrates composed of neutrophils, lymphocytes, monocytes, and occasionally eosinophils (S. Rosen et al., 1991). Arterial thrombosis with areas of cortical infarction may also develop. Scars form at the sites of previous necrosis, and the arterial lumen narrows. Similar vasculitides develop in multiple vascular beds simultaneously or sequentially; however, cases occur where the onset of polyarteritis nodosa manifests for a prolonged period as involvement of a single vascular zone (pulmonary, coronary) or peripheral nerves. The end-stage of renal pathology is characterized by nephroangiosclerosis and progressive renal failure.

Clinical symptoms of renal involvement typically develop 4 to 6 months after the onset of the disease, although this timeframe is not absolute. Malignant arterial hypertension predominates and sometimes precedes urinary abnormalities. Hypertension rapidly leads to hypertensive Heart disease, left ventricular failure, arrhythmias, and ischemic or thrombotic complications. The malignant nature of hypertension in polyarteritis nodosa, as in systemic sclerosis, is driven by the hyperproduction of angiotensin II due to the activation of systemic and local renin-angiotensin-aldosterone systems (RAAS), other pressor factors (endothelial), and the rapid exhaustion of renal depressor mechanisms. Concomitant tubular dysfunction is accompanied by glucosuria, Aminoaciduria, and hypernatriuria. Urinary abnormalities are observed in 4–5% of patients, presenting as moderate proteinuria (up to 1 g/day) and microhematuria. Massive proteinuria (up to 6–8 g/day) typically accompanies malignant hypertension. Renal functional capacity declines quite rapidly, manifested by a decrease in Glomerular Filtration rate (GFR) and impaired renal concentrating ability.

There are no specific laboratory criteria for diagnosing polyarteritis nodosa. Findings may include anemia, leukocytosis, a significantly elevated ESR, moderate hyperproteinemia, hyper-alpha₂- and hypergammaglobulinemia, hyperfibrinogenemia, and the presence of C-reactive protein. Immunological tests often show elevated circulating immune complexes (CICs), the presence of rheumatoid factor, and increased titers of antineutrophil cytoplasmic antibodies (ANCA) specific to myeloperoxidase and proteinase-3.

The prognosis is serious, with a 5-year survival rate from the onset of the disease of approximately 50%.

Infrequent forms of Kidney involvement include total renal cortical necrosis, perirenal hematoma, and acute renal vessel thrombosis complicated by renal infarction (Yarygin et al., 1980; Semenkova, 1980).

The drugs of choice for treatment are prednisolone and cytostatics (most commonly in combination), along with concomitant plasmapheresis or hemoperfusion; in the event of Chronic Kidney Disease (CKD), hemodialysis is preferred. Hypertension is generally resistant to antihypertensive agents; simultaneous use of drugs from several classes (Diuretics, beta-blockers, calcium channel blockers, angiotensin II receptor antagonists) is preferred.

Allergic (eosinophilic) granulomatous angiitis is considered a variant of polyarteritis nodosa. The underlying mechanism involves a disruption of allergic reactivity, which is confirmed by marked eosinophilia and elevated serum levels of immunoglobulin E (IgE). It occurs more frequently in males (4:1) aged 40–50 years. Eosinophilic infiltrates are found in the walls of medium- and small-sized vessels, whereas the kidneys exhibit focal segmental Glomerulonephritis with crescents.

Frequent allergic rhinitis is observed during the prodromal period. Disease progression is characterized by persistent eosinophilia, the appearance of pulmonary eosinophilic infiltrates, and Bronchial Asthma attacks. Subsequently, the characteristic presentation of vasculitis emerges, featuring typical skin rashes. In some cases, abdominal syndrome, myocardial involvement (endocardial fibrosis), and renal disease (glomerulonephritis) are diagnosed.

Key diagnostic findings include eosinophilia, leukocytosis, an elevated ERYTHROCYTE SEDIMENTATION RATE (ESR), increased serum immunoglobulin E levels, and elevated titers of antineutrophil cytoplasmic antibodies.

Wegener's granulomatosis (granulomatous-necrotizing vasculitis, necrotizing granulomatosis) predominantly affects small- and medium-sized Arteries of the Upper Respiratory Tract, Lungs, and kidneys. The disease is diagnosed more frequently in males (2:1) over the age of 40. Its incidence ranges from 2 to 8.5 cases per 1 million population (Watts et al., 1995).

The etiology of the disease remains insufficiently understood. Viral (particularly cytomegalovirus) and microbial infections play a certain role, exerting their effects against the Background of genetically determined features of the immune reactivity system. The primary mechanism involves the formation of circulating immune complexes (CICs) and their deposition in the vessel walls of the aforementioned regions. Similar to Other forms of vasculitis, hyperactivation of hemocoagulation mechanisms is also ascribed a certain pathogenetic significance in Wegener's granulomatosis.

Specific Indicators of immune alterations in this pathology include elevated blood levels of immunoglobulin E and the presence of IgG antibodies directed against non-nuclear components of polymorphonuclear granulocytes.

Morphological changes involve the development of destructive-proliferative and proliferative vasculitis, as well as Multinucleated giant cell-containing polymorphonuclear granulomas located primarily within the bronchial walls and peribronchial tissue. Signs of renal involvement develop immediately following ulceronecrotic lesions of the upper respiratory tract. This is accompanied by the presentation of “pauci-immune” glomerulonephritis—meaning without significant deposition of IMMUNOGLOBULINS and complement components—characterized by necrotic processes in small and medium-sized renal arterioles with the rapid development of fibrinoid necrosis, destruction of glomerular capillaries, massive infiltrates, subendothelial deposits of IgA, IgG, and complement components along the glomerular capillary basement membrane and in the mesangium, as well as cellular or fibrous crescents (Min et al., 1994). Occasionally, granulomas with multinucleated giant cells and arterial aneurysms are observed, whereas thrombi and infarctions are rare.

The clinical picture is characterized by a classic triad: involvement of the upper respiratory tract, lungs, and kidneys. Renal involvement (occurring in 65–90% of cases) manifests as proteinuria (up to 1–3 g/day) and persistent (!) microhematuria; Nephrotic Syndrome and hypertension arise relatively infrequently. Concentration and nitrogen-excreting renal Functions remain unimpaired during the Initial Stages of the disease, and the onset of renal failure typically occurs within 1.5–3 years. In 5–10% of cases, rapidly progressive glomerulonephritis accompanied by ACUTE RENAL FAILURE is observed. Rarely, renal involvement serves as the initial manifestation of the disease, while upper respiratory tract changes remain mild. Some authors (Lugmani, 1994) distinguish between “renal” and “non-renal” forms of Wegener's granulomatosis, although renal failure itself remains the most frequent cause of death in this condition.

If histological examination identifies renal injury as “pauci-immune” crescentic glomerulonephritis, the next step in Differential diagnosis involves serological testing: Wegener's granulomatosis is characterized by the presence of antibodies to proteinase-3, whereas microscopic polyangiitis (Churg–Strauss syndrome), which also belongs to the group of primary small-vessel vasculitides, is characterized by antibodies to myeloperoxidase (Geffriaud-Ricouard et al., 1993).

Pathogenetic treatment includes Steroids and immunosuppressants (cyclophosphamide, cytoxan; Hoffman et al., 1992; Aasarod et al., 2000), antithymocyte globulin, and intranasal mupirocin combined with sessions of plasmapheresis. Cyclophosphamide is preferred at a dosage of 1–2 mg/kg of body weight/day, administered initially intravenously and subsequently orally. Long-term administration (spanning years) forms the cornerstone of therapy. Various treatment regimens exist for patients with the renal form of Wegener's granulomatosis—namely MEPEX, NORAM, CYCLOPS, REMAIN, SOLUTION, and MUPIBAC—which incorporate the aforementioned agents in various combinations (Kolesnyk et al., 2001).

Goodpasture syndrome. Goodpasture syndrome represents a form of glomerulonephritis that fully satisfies Witebsky's criteria for classification as an autoimmune disease.

Currently, the term “Goodpasture disease” is applied when pulmonary-renal syndrome is caused by the presence of circulating anti-basement membrane (anti-BM) antibodies. Only under these conditions, due to the cross-reactivity of anti-BM antibodies with alveolar basement membrane antigens, does combined injury to the kidneys (crescentic glomerulonephritis) and lungs (Pulmonary Hemorrhage) occur. When glomerulonephritis accompanied by pulmonary hemorrhage occurs in the absence of detectable anti-BM antibodies, the condition is referred to as “Goodpasture syndrome.” The antigen, known as the Goodpasture antigen, is a peptide located on the α3 chain of the type IV collagen molecule; the antibodies typically belong to the IgG isotype and, more rarely, IgA.

A definite role, particularly in the onset of massive hemorrhages, is also played by disturbances within the hemocoagulation system, notably those associated with massive iron deposition (ferritin, hemosiderin) in alveolar macrophages and hepatic Kupffer cells, as well as the inhibitory effect of ferritin on fibrin polymerization and vascular wall tone (Prokopchuk et al., 1984).

Thus, taking into account this specific pathogenetic mechanism, true Goodpasture syndrome accounts for approximately 50% of patients presenting with glomerulonephritis and pulmonary hemorrhage, while the remaining 50% are attributed to hemorrhagic vasculitis, systemic lupus erythematosus, or cryoglobulinemia.

Proposed triggers for the development of Goodpasture syndrome include viral infections (Influenza), exposure to toxins (inhalation of gasoline fumes or lacquers), and The Use of medications (D-penicillamine), although the intensity of the ensuing immune response is considered genetically determined.

Histologically, signs of renal injury manifest as intracapillary proliferative-membranous and/or proliferative glomerulitis. These are characterized by endothelial proliferation, thickening and rupture of the glomerular capillary basement membranes, accumulation of polymorphonuclear leukocytes within the capillary lumina, mesangial cell proliferation, as well as stasis, thrombosis, and fibrinoid necrosis in isolated capillary segments. The interstitium exhibits edema and infiltration by mononuclear leukocytes. Acute exudative-infiltrative and proliferative processes culminate in glomerular fibrosis and sclerosis.

Although Goodpasture syndrome is traditionally considered a disease affecting both men and women over the age of 60, it may manifest at any age. Clinical signs of renal involvement typically follow hemoptysis or pulmonary hemorrhage, presenting with persistent proteinuria and continuous micro- or macrohematuria. Renal failure develops quite rapidly (within 1–3 weeks); edema, nephrotic syndrome, and hypertension occur rarely. The incidence of new cases exhibits two peaks: in the third and sixth decades of life. Sideropenia and the presence of siderophages in sputum or alveolar infiltration of lung tissue may serve as auxiliary diagnostic criteria.

Therapy is aimed at suppressing antibody production using immunosuppressants (cyclophosphamide up to 3 mg/kg body weight/day, prednisolone pulse therapy up to 1000 mg/day intravenously for 3 days, followed by oral administration at 100 mg/day with a gradual dose taper) and removing circulating antibodies via plasmapheresis. Such an “aggressive” treatment approach is employed in the absence of severe renal failure (Cohen et al., 1994).

Henoch–Schönlein purpura (hemorrhagic vasculitis, HV) is a disorder belonging to the group of vasculitides characterized by predominant involvement of the capillaries and arterioles of the skin, large joints, gastrointestinal tract, and kidneys.

The initial reports concerning Renal Involvement in hemorrhagic vasculitis were published by Russian researchers P.S. Koritin and A.T. Bogayevsky. The disease predominantly affects children under 14 years of age, with an incidence of 14 cases per 100,000 individuals in this age bracket; however, renal involvement is detected more frequently (56%) when the disease manifests in adults.

The triggering mechanism for the development of productive (less frequently necrotizing) vasculitis is the deposition within the microvasculature of the aforementioned regions of specialized immune complexes containing immunoglobulin A class antibodies that possess cryoglobulinemic properties (acting as a cold-exposure factor). The antigen directed against IgA may originate from the mucous membranes of the gastrointestinal tract, Respiratory system, or Bone Marrow.

The hyperproduction of polymeric IgA immunoglobulins characteristic of hemorrhagic vasculitis, along with their accumulation in the blood and circulating immune complexes, accounts for the generation of substantial quantities of autoantibodies directed against this immunoglobulin. Such immune complexes are detected within the vascular loops and mesangium of renal glomeruli in 96% of patients. The vascular wall is injured As a result of Proteolytic Enzymes released by leukocytes during the phagocytosis of immune complexes, alongside the deposition of fibrin beneath the microvascular endothelium and within the perivascular space (productive microvasculitis).

These microvasculitides are accompanied by the development of multiple mural microthrombi and an acute increase in vascular wall permeability, leading to the leakage of Plasma Proteins and formed elements from the bloodstream. Microvasculitides are coupled with “mesangial injury”—varying degrees of diffuse proliferation of mesangial cells, correspondingly designated as mesangial, focal segmental, diffuse proliferative (endocapillary), and endocapillary glomerulonephritis with extracapsular features (Dyadyk et al., 1991).

There are studies demonstrating that this is accompanied by an elevated blood level of other immunoglobulin classes, with the elevation of a specific class determining the clinical course and form of HS. Specifically, elevated levels of class G immunoglobulins indicate a relapsing course and the skin-articular form, whereas class M indicates a mixed form with renal involvement (E.V. Prokhorov, 1992).

The Significance of The Complement System and the activation of the kallikrein-kinin system in the pathogenesis of this disease should also be noted.

The complement system, with its nine main components (C1-C9), plays a leading role in the Antigen-Antibody Reaction in HS, although opinions regarding The pathway of its activation vary: The alternative pathway prevails (S. Petersen et al., 1991), the classical pathway is implicated (A.V. Mazurin et al., 1994), or both pathways are observed (N.S. Kislyak et al., 1991).

Activation of the kallikrein-kinin system, mediated by the C₁ and C₂ complement components, results from the deposition of immune complexes within the vascular wall (L.S. Zakharchuk, 1996).

Other studies investigating changes in T-lymphocyte and macrophage function, as well as the role of the HLA system in hemorrhagic vasculitis, remain inconclusive and contradictory.

According to the generally accepted pathomorphological classification (J.A. Mills et al., 1990), HS nephritis is divided into 6 classes:

- minimal changes (2.7 %);

- mesangioproliferative GN (33.3 %);

- intra- or extracoproliferative GN with crescents in 30-50 % of glomeruli (33.3 %);

- predominantly extracoproliferative GN with crescents in 50-75 % of glomeruli (28.3 %);

- predominantly extracoproliferative GN with crescents in 75-85 % of glomeruli (0.5 %);

- pseudomembranous GN (1.9 %).

The onset of the disease is invariably acute. Associations have been observed between this pathology and drug allergy, administration of sera or Vaccines, food idiosyncrasy, insect bites, cold allergy, trauma, and preceding streptococcal or viral infections.

Renal involvement develops more frequently in the abdominal form (30-40 %), and this percentage increases with age, although V. Parsons et al. (1995) claim that renal involvement occurs in 100 % of HS cases. Involvement of other Organs, including the intestine, is not a criterion of poor prognosis in adults (R. Coppo et al., 1997).

The severity of renal injury does not depend on the degree of extrarenal manifestations; conversely, as the Clinical presentation of HS nephritis progresses, these manifestations diminish or disappear entirely.

HS nephritis typically develops within the first 4-6 weeks of the disease (in 20 % of patients, after 6-12 months). In the latter cases, renal involvement takes on a severe course with an unfavorable prognosis.

In the typical clinical course of HS nephritis, the leading syndrome is microhematuria combined with moderate (up to 1 g/day) non-selective proteinuria. Recurrent macrohematuria is identified in 30-40 % of cases.

Atypical clinical variants of HS nephritis (nephrotic, mixed) are observed in 20-30 % of cases, and rapidly progressive GN in 5-10 % of cases. Arterial hypertension develops more frequently in adults, accounting for 10-15 %.

The prognosis of HS nephritis is consistently guarded: in 80-90 % of patients, it assumes a chronic course (persistent, relapsing, or progressive), leading to chronic renal failure in 20-30 % of cases. The prognosis is more favorable with a typical clinical variant, and unfavorable in HS with prior Liver involvement (a history of acute hepatitis or the presence of HBs antigenemia).

Criteria for an unfavorable prognosis also include patient age (over 20 years), male gender, high proteinuria (over 1 g/day), nephrotic syndrome, relapsing Acute Nephritic Syndrome, the combination of nephrotic syndrome with arterial hypertension, persistent macrohematuria, and morphological classes III-IV of structural changes (M.O. Kolesnyk, I.I. Latynska, 1999). Blood levels of IgA immunoglobulins and circulating immune complexes do not significantly affect the prognosis of HS nephritis (R. Coppo et al., 1997).

There is no treatment whose high efficacy in HS nephritis has been confirmed by randomized clinical trials, although patients with severe disease manifestations are treated with steroids and immunosuppressants (H.A. Austin et al., 1992), antiplatelet agents (dipyridamole, pentoxifylline, agapurin), anticoagulants (heparin combined with donor cryoplasma), nicotinic acid and its derivatives, alpha-blockers (nicergoline, pyroxan), and plasmapheresis (K.M. Sergeyeva et al., 2000).

S.I. Ryabov (2000) proposes the following treatment regimen for HS in cases of renal involvement:

- 3-5 sessions of plasmapheresis with removal of up to 500 ml of blood;

- prednisolone or methylprednisolone, intravenously at 300-500 mg for the first 3 days, followed by oral prednisolone at a daily dose of 60-80 mg for 1 month;

- in the following month, the dose of prednisolone is halved;

- a daily dose of 30-40 mg of prednisolone is administered for 4-6 months, after which it is halved and maintained for 12 months;

- after 1 year, in cases of a favorable clinical course, the question of extending prednisolone therapy for another year or switching to "mild" agents (plaquenil, delagil, NSAIDs) is considered.

Some clinicians also classify immune-mediated systemic vasculitis as retroperitoneal fibrosis (Ormond's disease, periureteral liposclerosis, chronic periureteritis, chronic idiopathic retroperitonitis). The disease was first described in 1948 by J.K. Ormond.

It is characterized by the proliferation of fibrous tissue in the retroperitoneal space, which envelops and compresses the aorta, renal arteries, Veins (INFERIOR VENA CAVA, major iliac veins), and frequently the Ureters, leading to typical clinical manifestations: symptoms of impaired urine outflow, and, upon compression of the renal vascular pedicle, renovascular arterial hypertension.

The etiology of the disease remains unknown. Proposed factors include Developmental anomalies of the Lymphatic vessels draining the Urogenital System, the use of sulfonamides and analgesics, chronic Urinary Tract infections, inflammatory processes in other abdominal organs, renal trauma, and peripelvic urinary granulomas. Histological examination of the retroperitoneal space reveals lympho-histio-plasmacytic infiltrates combined with sclerotic Changes in the glomeruli and interstitium, as well as tubular atrophy.

According to A.P. Peleshchuk (1983), this condition occurs with equal frequency in men and women of all ages, whereas G. Mazhdrakov et al. (1980) report different data, indicating that retroperitoneal fibrosis is more prevalent in men (13:2) aged over 50.

Three groups of symptoms of retroperitoneal fibrosis are distinguished:

- systemic (fever, anemia, asthenia of varying severity);

- local (pain in the lumbar spine, pelvis, and abdomen, paresthesia);

- symptoms caused by vascular or urinary tract obstruction.

Symptoms indicative of inferior vena cava, iliac vein, or arterial obstruction include unilateral or bilateral Varicocele, paresthesia, lower extremity edema, and intermittent claudication. Leriche Syndrome develops upon compression of major vessels or the aorta, hypertension results from renal artery involvement, dysuria, Renal Colic, and anuria stem from ureteral obstruction, constipation is caused by rectal narrowing, and nausea and vomiting result from duodenal compression. Occasionally, the disease manifests initially with symptoms of arterial hypertension or progressive renal failure.

Urinary syndrome is characterized by proteinuria (>1 g/day), moderate leukocyturia, and Hematuria. Blood tests reveal hyper-alpha₂- and hypergammaglobulinemia, anemia, leukocytosis, elevated ESR, a positive Coombs test, and occasionally eosinophilia.

Diagnosis relies primarily on instrumental Methods: ultrasound (uneven renal contours, impaired arterial inflow and venous outflow, venous dystonia on duplex Doppler sonography), excretory urography (delayed contrast excretion, pelvicalyceal stasis, ureteral displacement (Fig. 83)), lymphography (symmetric lymphatic obstruction at the lumbar level), intravenous pyelography (signs of obstruction), and cavography (contrast medium stasis).

Fig. 83. Retroperitoneal fibrosis, excretory urogram: a - normal excretory urogram; b - 2 years after the onset of lumbar pain and impaired urine passage: medial Displacement of the right Ureter with initial dilatation of the right renal pelvis and pronounced dilatation of the left renal pelvis (left ureter not visualized) (adapted from R. Christian, 1985).

The prognosis is unfavorable without surgical correction of impaired urine flow and relief of vascular compression.