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

Leading Semiotics of Renal Diseases
Chronic Kidney Disease

Chronic renal failure (CRF) is a complex of clinical and laboratory symptoms that develop in any Kidney disease As a result of a reduction in the number of functioning nephrons to 25–30%.

According to L.A. Pyrih et al. (2001), the clinical syndrome of CRF occurs when 50% of the excretory, metabolic, and incretory Functions of the Kidneys are lost.

In terminal renal failure, the number of functioning nephrons is less than 10% of the initial value. On average, CRF is detected in 100 individuals per 1 million population.

The most common causes of CRF are primary kidney diseases (subacute and Chronic Glomerulonephritis, Chronic Pyelonephritis), diffuse Connective Tissue diseases (systemic lupus erythematosus, periarteritis nodosa, hemorrhagic vasculitis), Metabolic Disorders (Diabetes Mellitus, Renal Amyloidosis, Gout), congenital renal pathologies (Polycystic Kidney Disease, Fanconi and Alport syndromes, Tubulopathies), renal vascular lesions (Essential Hypertension, renal artery stenosis), and obstructive nephropathies (urolithiasis, prostate adenoma and tumors, Ormond's disease).

Regardless of the etiological factor, renal changes during The Development of CRF are uniform and consist of the replacement of functioning nephrons with connective tissue (glomerulosclerosis), accompanied by compensatory hypertrophy and Hyperfunction of the remaining nephrons.

The most well-substantiated theory regarding the onset and progression of CRF is associated with W. Brenner et al., who in 1982 created an experimental model of this condition (the intact nephron hypothesis). These researchers proved that Hemodynamic changes in unaffected, functioning glomeruli are capable of driving the subsequent development of glomerulosclerosis in the same regions.

Vasodilation of the afferent arteriole as a compensatory mechanism to maintain Homeostasis is accompanied by an increase in intraglomerular pressure, GFR, and hypertrophy of active (uninjured) nephrons.

Somewhat later, El Nahas et al. (1989) confirmed that, in accordance with Laplace's law (the degree of vessel stretch = vessel pressure multiplied by its radius), elevated intraglomerular pressure is a leading factor in the progression of CRF.

Increased permeability of the stretched glomerular capillary walls to plasma macromolecules, followed by the deposition of the latter within the renal mesangial structures, triggers the infiltration of the mesangium and glomeruli by macrophages, along with enhanced platelet aggregation.

Infiltration of damaged glomeruli by monocytes is accompanied by The formation of foam Cells and mesangiocyte proliferation (M.O. Kolesnyk et al., 1998). The walls of glomerular capillaries are infiltrated by protein elements and Lipids, which reduces the capacity for adjustments in capillary lumen size (and consequently, intraglomerular pressure) necessary to maintain systemic homeostasis (W. Brenner et al., 1996).

It should also be noted that endothelial damage, regardless of the Etiology, leads to local Blood hypercoagulation and increased production of thromboxane A and serotonin. This results in the formation of microthrombi within the glomerular vessels.

From the above, it becomes evident that slowing The rate of CRF progression is primarily associated with targeting the main pathogenetic mechanisms of its development—intraglomerular pressure, blood hypercoagulation, and the proliferation of mesangiocepts and macrophages (A. Schena et al., 1997). Furthermore, the negative role of proteinuria and arterial hypertension in CRF progression is indisputable, as they exacerbate vacuolization of glomerular epithelial cells, their destruction and detachment from the glomerular basement membrane, as well as hyperlipidemia and impaired Lipid Peroxidation processes (Zh.D. Semydotska, 1999; N.D. Paolo et al., 1996).

Despite certain similarities in the clinical and morphological changes in CRF, the specific nosological entity, disease course, and patient age leave their imprint on the Clinical presentation. Evaluating these factors is crucial for determining Treatment strategies and prognosis.

According to L.A. Pyrih (1999), in the 1970s the predominant causes of CRF were chronic glomerulonephritis (36.6–79.6% of cases) and chronic pyelonephritis (6.7–51.5%). By the early 1990s, arterial hypertension (11.4–24.2%) and diabetes mellitus (15.2–24.5%) began to rival chronic glomerulonephritis as the most frequent causes of CRF; in 14.8% of cases, the cause of CRF could not be determined. According to J.A. Shayman (1999), in the USA glomerulonephritis ranks only third (14.2%) among the causes of CRF, trailing behind diabetes mellitus (34.2%) and hypertensive nephrosclerosis (29.2%).

In Ukraine, hypertensive nephrosclerosis as a cause of CRF is diagnosed quite rarely, which, according to T.D. Nykula (2001), is due to "... incorrect clinical interpretation of arterial hypertension in kidney diseases by nephrologists."

In childhood, the most frequent causes of CRF are congenital renal pathologies and immuno-inflammatory kidney diseases (M.S. Ihnatova et al., 1989).

According to A. Wing et al. (1992), in individuals under 15 years of age, the most common causes of CRF are chronic pyelonephritis (24.7%), chronic glomerulonephritis (18.0%), and congenital nephropathies (17.8%); for ages 15–34 — chronic glomerulonephritis (40.5%), diabetes mellitus (8.2%); ages 35–54 — chronic glomerulonephritis (28.6%), diabetes mellitus (12.1%); ages 55–64 — chronic glomerulonephritis and chronic pyelonephritis (17.5% each), diabetes mellitus (14.0%); over 65 years — chronic pyelonephritis (20.5%), nephrosclerosis (13.4%), and diabetes mellitus (12.7%).

L.A. Pyrih (1999) cites the following average ages of patients with CRF: associated with chronic glomerulonephritis — 39.5 ± 5.4, chronic pyelonephritis — 54.5 ± 4.2, diabetes mellitus — 48.7 ± 6.8, systemic connective tissue diseases — 33.0 ± 2.8, and renal amyloidosis — 44.5 ± 3.2 years.

Let us also note certain features in the development of CRF depending on the underlying cause.

In immuno-inflammatory renal lesions, impairments in the Excretory Function of the kidneys and arterial hypertension with the development of a hypertensive Heart come to the forefront, with the terminal stage potentially developing just a few months after disease onset.

Interstitial nephritis presents with early disturbances in electrolyte balance, acid-base status, and anemia; primary vascular lesions present with persistent arterial hypertension and defects in tubular sodium reabsorption.

CRF caused by inflammatory kidney diseases is characterized by a cyclic course and a positive response to anti-inflammatory therapy, with anemia and arterial hypertension syndromes dominating the clinical picture.

Renal amyloidosis with signs of CRF is frequently accompanied by renal vessel thrombosis.

CRF resulting from hypertensive nephrosclerosis occurs less frequently than other complications of essential hypertension (coronary artery disease, stroke). However, the premise that CRF is relatively rare in essential hypertension may be due to the underutilization of renal needle biopsy as a criterion for the Differential Diagnosis between glomerulonephritis and essential hypertension. Thus, according to J.C. Genette et al. (1990), essential hypertension currently holds the primary place among the causes of CRF in the USA.

CRF caused by atherosclerotic nephrosclerosis generally features a more favorable clinical course.

The Clinical presentation of CRF is also largely determined by The impact of the underlying disease on homeostasis (blood disorders, tumors, metabolic and endocrine nephropathies, hereditary kidney diseases) as well as the patient's general condition (dehydration, blood loss, anemia, Heart Failure, AGE AND SEX, adverse drug reactions, etc.). The prognosis of CRF is significantly worsened by NS, the genesis of which should be investigated by first ruling out a paraneoplastic origin.

Until recently, it was believed that the clinical picture of CRF was caused by the accumulation of End products of nitrogen METABOLISM in the Body, primarily creatinine and urea. However, recent studies have demonstrated that patients with identical GFR values and serum creatinine levels can exhibit vastly different manifestations and severity of CRF (T.D. Nykula et al., 1999, 2001). For instance, urea—elevated levels of which are associated with nausea, vomiting, headache, and occasionally intestinal bleeding—is actually the least toxic product of Protein metabolism. Similarly, there is relatively little evidence supporting the high toxicity of creatinine (I.Ye. Tareyeva et al., 1995), although certain metabolic precursors such as creatine are thought to provoke hemolysis and impair intestinal calcium absorption. At the same time, The Role of urea and creatinine in developing various uremic symptoms should not be entirely dismissed. Specifically, work by A.M. Yesayan et al. (1997) proved that urea makes a substantial contribution to the progression of glomerular hyalinosis by increasing plasma osmolarity and, consequently, elevating intraglomerular pressure. Most likely, the toxicity of creatinine and urea is linked to the accumulation of their disturbed metabolic products in the blood, such as citrulline, guanidinosuccinic acid, and monoamine oxidase. A certain role in uremic symptoms is also attributed to aromatic and aliphatic amines, phenols, indican, Polyamines, and dimethylarginine (T.D. Nykula, 1983; J.T. Kielstein et al., 2001).

Recently, researchers have been actively and reasonably exploring the role of so-called middle molecules (MMs) in the Pathogenesis of CRF—products of normal body metabolism, although their exact role in this pathological process remains incompletely defined (A.Sh. Rumyantsev, 1998). Blood levels of MMs increase significantly in various pathological states and degrees of renal impairment. It is believed that uremic toxins include substances with a higher relative molecular weight than urea and creatinine, ranging from 200 to 2000 Daltons, with a "peak" between 400 and 1000 Daltons. Back in 1976, F. Furst et al. proved that these substances show no correlation with serum urea and creatinine levels and are poorly cleared by hemodialysis.

MMs encompass about 30 substances with established biological activity, including vasopressin, oxytocin, neurotensin, angiotensin, adrenocorticotropic hormone, Glucagon, Calcitonin, vasoactive intestinal polypeptide, secretin, motilin, Sleep factor, endorphins, enkephalins, glucuronic acid compounds, serum protein degradation products, and intestinal bacterial metabolites (N.V. Beloborodova, 2002; P. Odou et al., 2001). Universal uremic toxins also include parathyroid hormone, atrial natriuretic peptide, THYROID Hormones, retinol-binding protein, gastrin, Growth Hormone, Ribonuclease, and interleukins.

Particular significance is attached to parathyroid hormone, whose toxic effect under conditions of reduced functioning nephrons is realized through changes in calcium distribution within cellular depots and the Cytoplasm, resulting from increased membrane permeability to ionized calcium (M.V. Ogluzdina et al., 1998). Classical target Organs for this hormone are also considered to be myocardial cells, visceral and vascular smooth Muscle cells, the Pancreas and Thymus, Liver vessels, and Brain Neurons (T.A. Barabanova, 1996; R.V. Babakhanyan et al., 1998; M. Smogorzewski, 1995).

Impairments in nonspecific immune reactivity, lipid and Carbohydrate Metabolism, hemopoiesis, as well as the development of polyneuropathy and encephalopathy, are associated with the action of individual MMs. As early as 1989, R.N. Akalayev et al. convincingly demonstrated that MMs themselves are capable of forming additional conductive channels on the bilayer lipid membranes of Nerve Cells, which clinically manifests as neurotoxicosis (seizure activity, polyneuropathy, encephalopathy, impaired motor coordination). Notably, traditional scheduled hemodialysis yields no positive clinical effect, regardless of the mode of urea and creatinine correction.

Equally important in the pathogenesis of CRF are Disorders of the endocrine balance, electrolyte metabolism, acid-base balance, lipid peroxidation processes and antioxidant defense activity, urinary loss of antioxidant defense factors, as well as disturbances in hemostasis, erythropoiesis, platelet functional activity, and blood rheological properties.

The most typical manifestations of endocrine imbalance include elevated blood levels of growth hormone, follicle-stimulating hormone, calcitonin, gastrin, glucagon, Insulin, luteinizing hormone, parathyroid hormone, prolactin, thyroxine, and triiodothyronine, alongside reduced levels of testosterone.

A reduction in functioning nephron mass and, consequently, a drop in GFR are accompanied by a decrease in the filtered sodium load. To maintain sodium balance, the reduction in sodium filtration must be counteracted by a decrease in its reabsorption. However, There is a certain limit to this compensation in CRF: further suppression of filtration leads to sodium retention in the body, resulting in hypernatremia, hypervolemia, and edema. This state can be partially mitigated by dietary sodium restriction. Conversely, another scenario is possible: if dietary sodium restriction is maintained while excretion continues at the same rate against a Background of polyuria, it will inevitably lead to persistent hyponatremia, dehydration, acidosis, and, in some cases, a catastrophic drop in GFR.

The Initial Stages of CRF are characterized by the development of hypokalemia (marked muscle weakness, hypoventilation, cramps, cardiac rhythm disturbances, ECG changes such as T-wave flattening, QT-segment prolongation, ST-segment depression below the isoelectric line, and the appearance of a U wave). In contrast, advanced and terminal stages feature hyperkalemia (increased muscle excitability, hyperactive deep tendon Reflexes progressing to flaccid paralysis, bradycardia up to cardiac arrest, atrioventricular conduction disturbances, arrhythmias, tall peaked T waves, PQ interval prolongation, QRS complex widening), hypocalcemia (bone pain, cramps, localized muscle twitching, Osteoporosis), and hypermagnesemia (depression, stupor, loss of tendon reflexes, bradycardia).

There are numerous causes of hyperkalemia, including decreased potassium excretion in response to reduced sodium reabsorption, the predominance of catabolic processes with enhanced intracellular potassium release, and acidosis, since elevated plasma hydrogen ion concentrations promote their entry into cells in exchange for potassium.

Calcium metabolism disorders are of no less importance in CRF. Overall (S.I. Ryabov et al., 2000), four variants of calcium-phosphorus metabolism disorders are distinguished in this condition:

1) high-turnover bone disease, characterized by an increased number of osteoblasts, osteoclasts, osteoid surface area, and resorption lacunae, along with fibrosis of the peritrabecular space and Bone Marrow;

2) low-turnover bone disease, featuring a significant decrease in bone metabolism, a reduction in repair sites and Bone tissue cellularity, and an expanded osteoid area due to impaired mineralization;

3) mixed form, combining signs of high-turnover bone disease with a simultaneous decrease in bone repair intensity and/or defective mineralization;

4) adynamic bone disease, characterized by impairments not only in mineralization but also in Cell-mediated bone matrix synthesis—a near-normal ratio of mineralized to unmineralized bone tissue coupled with a practical halt in mineralization and osteoid synthesis.

The development of acidosis significantly potentiates the Clinical symptoms of CRF (apathy, drowsiness) and affects the efficacy of prescribed medications, most of which are designed to work in a weakly alkaline environment (pH 7.36–7.42).

Various metabolic disorders in CRF, one of the causes of which is Structural and functional alterations in Introduction/36.html">Biological Membranes, manifest as uremic dyslipoproteinemia and the pathological activation of lipid peroxidation processes (I.A. Rudko et al., 1995; I.Ye. Tareyeva, 1996; A.V. Smirnov, 1998; H.H. Nikulina et al., 1999; T.S. Ospanova et al., 2000; H. Oda, 1998). According to many authors, uremic dyslipoproteinemia begins to manifest once GFR drops to 30–40 mL/min, and hemodialysis does not correct these abnormalities (P.O. Attman, 1993; G.A. Kauser, 1994). Their progression accelerates the development of atherosclerosis and fatal cardiovascular complications (A.V. Smirnov, 1998; P.O. Attman, 1993).

The triggering mechanism for activating lipid peroxidation is the Excessive production of reactive oxygen species by neutrophils, macrophages, and renal mesangial cells. In addition to excessive oxidation of biomembrane lipids, reactive oxygen species inhibit antioxidant defense Enzymes and reduce blood levels of non-enzymatic antioxidants, thereby exacerbating impairments in vital biomembrane properties such as permeability, ion transport, and enzymatic activity (Yu.I. Grinshtein et al., 1991.

Hemostatic system disorders in CRF most commonly present as hemorrhagic diathesis, although some patients also exhibit thrombotic manifestations.

Overall, the Cytology/cytology/16.html">Early stages of CRF feature typical consumption coagulopathy with hypofibrinogenemia, a decreased prothrombin index, reduced plasminogen concentration, and high plasma levels of soluble fibrin monomer complexes and fibrinogen/fibrin degradation products (M.M. Kozachok et al., 1999). Platelet dysfunction involves Changes in the viscosity and fluidity of their membrane lipid layer, increased aggregability, and enhanced secretion of histamine and serotonin (T.V. Horbach et al., 1999).

As CRF progresses, uremic thrombocytopathy comes to the forefront, characterized by diminished platelet adhesion and aggregation properties, alongside an increased tendency toward destruction and the release of a specific growth factor (TGF-beta). Enhanced production of the latter is believed to play a crucial role in the onset and progression of various conditions accompanied by excessive CONNECTIVE TISSUE CELL proliferation (glomerulonephritis, atherosclerosis, Cancer, myelofibrosis, scleroderma) (V.A. Almazov et al., 1984; I. Dudar et al., 1999).

Anemia, as one of the symptoms of CRF, is detected in all patients when creatinine levels exceed 0.45 mmol/L. The causes of this condition cannot be attributed solely to Erythropoietin deficiency. It is underpinned by profound metabolic disorders at the nucleic acid level, accompanied by disruptions in globin and porphyrin synthesis systems, as well as iron metabolism pathology that impairs heme synthesis.

Thus, as CRF develops, all organs and Tissues without exception are drawn into the pathological process, even though every patient arrives at this condition, so to speak, "by their own path."

The clinical presentation of CRF depends on its stage. Staging is determined by taking into account the severity of a range of clinical signs and deviations in homeostatic parameters.

It should be emphasized that there is no consensus on this issue due to varying views regarding the principles, number of grading stages of CHRONIC KIDNEY DISEASE (CKD), Selection of criteria, and their interpretation.

In European countries and the USA, the Classification of CKD proposed by J. Knöchel et al. (1981) has become widespread, which identifies 4 stages of CKD: diminished renal reserve, renal impairment, renal failure, and uremia. The division into stages in this classification is based on the percentage reduction in renal function.

Below is the classification of CKD stages that is widely used in Ukraine (Table 2).

Class="center">Classification of CKD Stages (A.P. Peleshchuk, 1980; L.A. Pyrih, 1995)

However, the absence of clinical signs of CKD, indicators of Glomerular Filtration and urinary concentration functions among the criteria, along with the applicability of this classification exclusively to chronic kidney diseases, significantly limits its value. Furthermore, according to T.D. Nykula (2000), hypocalcemia and hypermagnesemia rank only 27th and 28th (out of 100 parameters) in the informativeness table for assessing the severity of CKD (noting that the top 5 positions are occupied by blood creatinine levels, GFR, blood urea, residual nitrogen, and blood hemoglobin levels).

The initial stages of CKD are characterized by an endogenous Intoxication syndrome combined with a moderate decrease in renal filtration and concentration functions. Regarding the latter point—the characterization of the functional state of the kidneys at various degrees of CKD—there has been no consensus until recently. Most researchers (A.P. Peleshchuk, 1973; M.Ya. Ratner, 1973; H.P. Shultsev, 1975; L.A. Pyrih, 1977; T.D. Nykula, 1983; O.V. Siniachenko et al., 1999; I.P. Tarchenko et al., 2000) believe that the GFR value indeed most accurately reflects the onset of CKD; however, literature data regarding its specific thresholds vary from 50 to 90 mL/min (N.A. Lopatkin et al., 1973; O.V. Siniachenko et al., 1999; M.M. Shekhtman, 2000).

Resolving this issue is associated with the studies of T.D. Nykula (2000, 2001), who applied polynomial regression analysis to prove that changes in serum creatinine levels first become statistically significant at a GFR value of 70 mL/min/1.73 m². Concurrently, the shapes of the regression curves for maximum relative urine density, hemoglobin, erythrocytes, and blood calcium change sharply as well. Thus, in diagnosing the early stage of CKD, primary importance should be given to a decrease in GFR to 70 mL/min (normalized to a standard body surface area of 1.73 m²) coupled with a drop in maximum relative urine density to 1.018 and below. Conversely, in all subsequent stages of CKD, serum creatinine surpasses all other criteria in diagnostic informativeness, including the GFR value.

In the stage of pronounced CKD, alongside the deterioration of the patient's general condition, polyuria, nocturia, hypo- and isosthenuria, and hypercreatininemia are observed.

Terminal stages of CKD (III–IV) are accompanied by metabolic disorders across all pathways and impaired functions of all organs and systems against the background of acidosis. Examination of such patients reveals weight loss, Skin pallor and dryness, hemorrhagic rashes, and scratch marks. Involvement of the Respiratory system (uremic pneumonitis according to S.I. Ryabov, 2000, in 62–100% of cases) manifests as alterations in voice timbre, persistent dry cough, bronchospasm, tracheobronchitis, Pneumonia, hydrothorax, and non-cardiogenic pulmonary edema. Due to blood pressure stabilization at high levels—with the crucial role of the renin-angiotensin-aldosterone system (RAAS) unquestioned here (N.L. Lifshits et al., 1999)—hypertensive heart disease develops (Left Ventricular Hypertrophy, arrhythmias, myocardial dystrophy, subacute left ventricular failure) along with uremic cardiopathy (a term introduced by G. Bailey et al., 1967). It should be noted that uremic cardiopathy arises in the early stages of CKD due to impaired Energy balance in cardiomyocytes. Dry pericarditis is quite common, and hydropericardium may also develop. Anorexia, morning nausea, frequent vomiting, and diarrhea are characteristic of uremic gastroenterocolitis (uremic gastropathy according to E.S. Ryss et al., 1997), which further exacerbates electrolyte imbalances and catabolic processes. Progressive anemia, musculoskeletal disorders (muscle twitching, osteofibrosis, osteoporosis), Nervous system disorders (apathy, irritability, nocturnal insomnia and daytime somnolence, euphoria, manic states, delirium, polyneuropathies, paresthesias), and visual impairment (amaurosis) complete the clinical symptomatology of terminal CKD.

Below are summarizing data on the clinical manifestations of CKD (L.A. Pyrih, 1995; A.E. Bahriy, 1998; A.I. Dyadyk et al., 1998; T.D. Nykula, 2001; J.N. Greenberger et al., 1990; J. Himmelfarb, 1998).

1. Cardiovascular manifestations:

- left ventricular hypertrophy;

- coronary artery disease;

- left ventricular systolic and diastolic dysfunction;

- arterial hypertension, hypertensive heart disease;

- cardiomegaly and myocardial dystrophic changes;

- pericarditis (dry, exudative, constrictive);

- arrhythmias;

- valvular abnormalities;

- chronic heart failure;

- rapidly progressive atherosclerosis;

- left ventricular failure (acute, subacute).

2. Respiratory system manifestations:

- non-cardiogenic pulmonary edema (syn.: uremic lung);

- Pleurisy;

- uremic Bronchitis.

3. Gastrointestinal manifestations:

- mucosal lesions (cheilitis, glossitis, stomatitis, esophagitis, gastropathy, enteritis, colitis, ulcers);

- functional disorders (anorexia, dysgeusia, ageusia, nausea, vomiting, hiccups, constipation, diarrhea, flatulence, intestinal obstruction);

- cholecystopathies, hepatopathies;

- organic glandular lesions (parotitis, pancreatitis).

4. Hematopoietic system manifestations:

- anemia;

- lymphopenia;

- leukopenia;

- hemorrhagic diathesis;

- thrombocytopathy.

5. Skin changes:

- hyperpigmentation, yellowish pallor, dryness, excoriation marks;

- various types of hemorrhagic rashes;

- uremic frost.

6. Endocrine manifestations:

- hyperparathyroidism, elevated blood levels of glucagon, insulin, enkephalin, calcitonin, prolactin, growth hormone, hyper- and hypoglycemia, decreased libido, impotence, gynecomastia, oligo- and Amenorrhea, Infertility.

7. Metabolic manifestations:

- hypothermia, Skeletal Muscle pain and weakness, cramps, proximal myopathy, bone pain (ostalgia), fractures, aseptic bone necrosis, Renal osteodystrophy, gout, pseudogout, skin and subcutaneous calcifications, ammoniacal breath odor, hypertriglyceridemia.

8. Central Nervous System involvement:

- asthenic symptoms (malaise, increased fatigue, impaired concentration and memory, irritability, sleep disturbances), depressive symptoms (depressed mood, decreased mental activity, suicidal ideation), phobias (thanatophobia), paranoid state, emotional coldness, apathy, eccentric behavior, impaired consciousness (stupor, sopor, coma), vascular complications (strokes, transient ischemic attacks).

9. Peripheral Nervous System involvement:

- uremic polyneuropathy, paralysis, paresis.

10. Immune alterations:

- Splenomegaly and hypersplenism;

- susceptibility to infections;

- hypocomplementemia;

- decreased antitumor Immunity.

The classification of CKD stages, which incorporates both clinical and laboratory criteria, was proposed by T.D. Nikula (2000, 2001). According to this classification, the following stages are distinguished: absence of CKD, early-stage CKD, manifest CKD, and terminal-stage CKD (end-stage renal disease).

In the absence of CKD, impairments of basic renal functions are not detected, GFR exceeds 70 mL/min/1.73 m², and the relative urine density (specific gravity) exceeds 1.018.

The early stage of CKD is characterized by a multiple and persistent decrease in baseline renal functions while maintaining the normal functioning of the kidney-Organism system through the engagement of renal and extrarenal compensatory mechanisms; GFR is less than 70 mL/min/1.73 m², relative urine density does not exceed 1.018; erythrocyte count is up to 4.7 ∙ 10¹²/L, urea is up to 21 mmol/L, and creatinine is up to 0.350 mmol/L.

In the manifest stage of CKD, a gradual deterioration of all renal functions is observed, along with varying clinical severity of disorders in the kidney-organism system, yet without severe, life-threatening functional impairments thanks to the preservation of extrarenal compensatory mechanisms; GFR does not exceed 35 mL/min/1.73 m², relative urine density is 1.015; erythrocyte count is 4.1 ∙ 10¹²/L, blood urea level is 33 mmol/L, and creatinine is 0.650 mmol/L.

The terminal stage of CKD is the stage of complications. Renal compensatory mechanisms are virtually exhausted, profound disorders in the functioning of the kidney-organism system are observed, and extrarenal compensatory mechanisms are depleted, resulting in severe extrarenal complications that are life-threatening to the patient; GFR does not exceed 15 mL/min/1.73 m², relative urine density is 1.012, erythrocyte count is 3.2 ∙ 10¹²/L; blood urea level exceeds 33 mmol/L, and creatinine exceeds 0.650 mmol/L.

While positively evaluating this classification of CKD stages, we must point out that the erythrocyte values cited by the author are somewhat overestimated, since even in healthy individuals, an erythrocyte count around 4.7 ∙ 10¹²/L is more of an exception than a rule.

The diagnosis of CKD should take into account the fact that impaired Nitrogen metabolism, as the leading clinical and laboratory syndrome of CKD, can also occur in other pathological conditions. For instance, acid-base balance disorders, oliguria, and elevated levels of nitrogenous compounds in the blood are observed in frequent vomiting and diarrhea, severe liver or pancreatic damage, accelerated breakdown of protein structures (Sepsis, blood disorders, tumors), and The Use of Diuretics.

This diagnosis does not pose a major challenge when an anamnestic history of chronic kidney disease is available. In such cases, it is simply necessary to determine the degree of impaired renal functional status, i.e., to establish the CKD stage while identifying the etiological cause.

Difficulties arise in the absence of any anamnestic or clinical data regarding chronic bilateral kidney damage. Quite frequently, the cause of CKD in such cases is latent chronic glomerulonephritis, polycystic kidney disease, or secondary renal amyloidosis.

In our clinical practice, we have encountered cases where even physicians (!) sought assistance for chronic glomerulonephritis only at the CKD stage; secondary renal amyloidosis accompanied by symptoms of CKD, confirmed post-mortem, developed 30 (!) years after an episode of humeral Osteomyelitis, and polycystic kidney disease as the cause of CKD was diagnosed following abdominal Palpation, although the patient had previously sought medical attention multiple times for general malaise.