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

Dysmetabolic and Toxic Nephropathies
Alcohol and the Kidneys

The polarity of opinions regarding the Kidneys as a target organ for ethanol (M.D. Mazurenko et al., 1992; V.S. Paukov, 1994; B.I. Shulutko et al., 1994; M. Ishigami et al., 1997) does not preclude identifying specific forms of renal damage resulting from alcohol exposure in the body. This is justified by several factors.

First, the state's loss of its monopoly on the production and distribution of alcoholic beverages has led to a catastrophic surge in the manufacturing of homemade drinks with high concentrations of toxic surrogates (ethers, aldehydes, propyl and octyl alcohols, which interact competitively with ethanol). Consequently, there is an increase in acute alcohol-induced renal injury cases, alongside the spread of alcoholism as a social phenomenon among youth, the consequences of which for the future health of the nation are difficult to foresee.

Second, alcoholic Kidney damage quite frequently dictates the prognosis and quality of life, notwithstanding The Significance of hepatic, pancreatic, and cardiac involvement in alcoholism.

Acute alcoholic renal injuries occur comparatively less frequently than lesions of the Central Nervous system, Liver, or myocardium. They manifest as ACUTE RENAL FAILURE (ARF) culminating in acute tubular necrosis, acute renal tubular blockage, hepatorenal syndrome, primary necrotizing papillitis, acute Pyelonephritis, and acute Glomerulonephritis (A.Yu. Nikolaev, 1990). The primary target of acute alcoholic kidney injury is the proximal tubules (R.V. Babakhanyan et al., 1998) due to the highest concentration of unchanged ethanol and its metabolites accumulating there.

ARF typically develops following an intensive alcohol binge, although our clinical practice has included episodes arising after the consumption of relatively small doses of alcohol (100–200 ml). Both alcohol and its metabolites exert toxic effects on renal structures. Concurrently, we must acknowledge the contributing role of hypercatecholemia, hyperuricemia, hypertriglyceridemia, and hypophosphatemia—conditions that typically accompany such binge episodes—in the onset of ARF.

The most frequent cause of ARF in alcohol-induced kidney injury is acute tubular necrosis. Its underlying mechanism is the increased susceptibility of patients with acute Alcohol poisoning to comatose (colaptoid) states, followed by the rapid development of oliguria, anuria, and typical syndromes of hyperazotemia, hyperhydration, and acidosis. Hyposthenuria and hypernatriuria develop quite rapidly, while urinary sediment is predominated by casts (granular, hyaline) against a Background of moderate proteinuria and microhematuria.

Primary necrotizing papillitis develops As a result of predominant damage to the arterioles and capillaries of the renal medulla, leading to ischemic infarctions of the renal papillae. In this condition, anuria occurs abruptly, preceded by Renal Colic caused by the obstruction of the Urinary Tract lumen by necrotic renal papillae and macrohematuria.

Acute blockage of renal tubules by uric acid crystals develops after excessive (and frequently concurrent) consumption of alcohol and purine-rich foods. Renal lesions in this case resemble those described in the section “Renal Involvement in Gout.”

Hepatorenal syndrome is a form of prerenal (hemodynamic) ARF accompanying acute alcoholic hepatitis or liver cirrhosis. Hemodynamic disorders are associated with portal Hypertension, hypovolemia, activation of the renin-angiotensin-aldosterone system (RAAS), and the NEGATIVE IMPACT OF angiotensin II on renal Blood flow. Symptoms of tubular Structure damage predominate here. The clinical picture is characterized by progressive weakness, lethargy, thirst, ascites, and jaundice. Laboratory tests reveal a significant elevation in serum blood urea nitrogen (BUN) levels with moderately pronounced hypercreatininemia and hyponatremia. The concentration capacity of the kidneys remains relatively preserved, and urinary sediment shows minimal changes.

According to A.S. Mukhin et al. (1985), two prognostically distinct hemodynamic variants of hepatorenal syndrome are distinguished:

- with normal blood pressure, decreased cardiac index, hypovolemia, and an increase in Glomerular Filtration rate (GFR) in response to intravenous dextran infusion;

- with lowered blood pressure, normovolemia, preserved cardiac index, and no GFR response to intravenous dextran infusion.

The prognosis for hepatorenal syndrome, particularly its second hemodynamic variant, is extremely unfavorable. The most frequent causes of death are hepatic coma and profuse hemorrhages.

Acute pyelonephritis in acute alcoholic renal injury frequently arises against the background of mechanical (Nephrolithiasis, necrotizing papillitis) or functional (refluxes, atonia) urinary tract blockages, hyperuricemia, calcium-phosphorus METABOLISM disorders (Renal Tubular Acidosis, hypophosphatemia), and a decrease in general and local nonspecific immune reactivity. It is characterized by the hematogenous spread of infection within renal structures, intermittent hyperthermia, and lumbar pain.

In cases of predominantly unilateral involvement with a blocked kidney, urinalysis changes may be absent, and renal failure develops slowly (by the second to third week). Acute pyelonephritis is frequently complicated by The Development of apostematous nephritis, bacterial Shock, and metastatic purulent lesions of the Lungs, Brain, and liver.

In our practice, we have encountered isolated cases of myorenal syndrome resulting from prolonged ischemia of major Muscle groups (arm, leg) due to the compression of arterial vessels during severe alcohol intoxication. In such cases, renal tubular blockage is caused by massive myoglobinuria.

The clinical picture is characterized by tenderness in the damaged muscle groups, laboratory signs of myonecrosis—a significant increase in blood levels of aspartate aminotransferase, Alanine aminotransferase, Lactate dehydrogenase, Myoglobin, creatine phosphokinase, and uric acid—alongside hypocalcemia, pronounced hyperkalemia, oliguria, and altered urine color (brown).

In recent years, cases of alcoholic toxic nephropathies caused by the consumption of alcohol surrogates have become more frequent. Their clinical course features specific characteristics: they occur in patients who did not previously abuse alcohol, and clinically manifest with minimal signs of toxic liver damage. The disease typically develops acutely, 2–3 days after surrogate consumption, presenting with decreased diuresis, rapidly progressive edema, arterial hypertension, vomiting, diarrhea, and transient fever. According to S.I. Ryabov (2000), edema is massive, most commonly intracavitary (ascites, hydrothorax in 60% and 49% of patients, respectively). Clinical and laboratory evaluations reveal urinary or nephrotic syndromes, impaired renal concentrating function, and anemia and hypercreatininemia in the blood. A favorable response to glucocorticoids suggests that the Pathogenesis of this form of acute alcoholic kidney injury is primarily driven by toxic vascular damage with increased permeability. These manifestations completely resolve within 1–2 months, yet impairments in partial renal Functions persist for a considerable time.

Chronic alcoholic kidney diseases develop within the framework of alcoholic disease, the pathogenesis of which is quite well understood. These include alcoholic glomerulonephritis, renal tubular acidosis, and hepatic glomerulopathy.

The development of alcoholic glomerulonephritis (60–65% of cases) is primarily attributed to the formation in various Tissues and Organs of a specific protein—alcoholic hyaline—which possesses antigenic properties and induces The production of highly specific Antibodies (Class A IMMUNOGLOBULINS). These antibodies are incorporated into circulating immune complexes (CICs), with Complement activation proceeding via The alternative pathway. Thus, alcoholic glomerulonephritis closely resembles primary IgA glomerulonephropathy (Berger's disease). CICs containing class A immunoglobulins and the C₃ complement component can be deposited in the glomerular capillary basement membrane, tubules, mesangium, and the endothelium of other organs, leading to the development of generalized microangiopathy (M. Orellana et al., 1998).

Clinical manifestations of alcoholic glomerulonephritis in the form of Nephrotic Syndrome and arterial hypertension are infrequent; a persistent and slowly progressive course predominates. Exacerbations of clinical and laboratory symptoms of alcoholic glomerulonephritis are generally linked to alcohol consumption. Rarely (1–3%), a rapidly progressive course is observed, leading to end-stage renal failure within 1–2 years. The 5-, 10-, and 15-year survival rates for alcoholic glomerulonephritis are 79%, 74%, and 51%, respectively. Unfavorable prognostic signs include proteinuria exceeding 1 g/day, nephrotic syndrome, patient age under 40, presence of glomerular immune complexes, and fibroplastic transformation of mesangioproliferative glomerulonephritis (A.Yu. Nikolaev et al., 1986).

Diagnostic criteria for alcoholic glomerulonephritis include an isolated decrease in the renal concentrating function with a less pronounced decline in filtration capacity, and elevated blood levels of class A immunoglobulins. The urinary syndrome is characterized by painless microhematuria (60–70% of cases) and moderate proteinuria. In 50–54% of patients, histological examination reveals a tubulointerstitial component—pronounced epithelial dystrophy of the tubules, lymphohistiocytic infiltration, and stromal sclerosis—alongside clinically reduced relative urine density.

Diagnosis of alcoholic glomerulonephritis takes into account signs of damage to other organs (liver, Pancreas, Heart) and a positive response to abstinence. Concurrently, it is necessary to exclude A number of urological disorders characterized by Hematuria, as well as gouty nephropathy, generalized amyloidosis, Berger's disease, acute glomerulonephritis with isolated urinary syndrome in systemic vasculitis, and bacterial endocarditis.

Renal tubular acidosis is characterized by preferential damage to the distal segments of the renal tubules. This condition presents with increased urinary loss of potassium and calcium, and a sharp reduction in sodium excretion due to the suppression of renal synthesis of a group of renal natriuretic Peptides. As a result, the kidneys' ability to compensate for metabolic acidosis via adequate urinary excretion of H⁺ ions is impaired, leading to an alkaline urine reaction, nephrolithiasis, and nephrocalcinosis.

The diagnosis of renal tubular acidosis in alcoholic kidney injury is based on detecting a persistently alkaline urine reaction combined with hypokalemia, nephrolithiasis, and increased calciuria.

Hepatic glomerulopathy is characterized by focal lesions of the glomerular capillary basement membrane, its thickening, and mesangial expansion with the deposition of specific structures known as black lobules and laminated bodies. In some cases, proliferation of glomerular Cells and the presence of circulating immune complexes (CICs) are observed, similar to alcoholic glomerulonephritis. The leading pathogenetic factor in hepatic glomerulopathy is Metabolic Disorders involving protein, carbohydrate, and Lipid Metabolism. Its clinical course is typically benign, with urinary syndrome being the dominant clinical manifestation.

Management of alcohol-related kidney disease. The Treatment of acute renal failure (ARF) in acute alcohol-induced kidney injury depends on its underlying cause.

In acute tubular necrosis, intravenous administration of mannitol, dextrans, and dopamine-furosemide is used (see the section «Treatment of Acute Renal Failure»).

In uric acid nephropathy (uric acid blockade of the kidneys), urine alkalinization combined with diuresis intensification is required.

Treatment of hepatorenal syndrome involves increasing diuresis, reducing ascites and portal hypertension (veroshpiron up to 300–400 mg/day), and correcting hypokalemia and hypoalbuminemia (glucose-Insulin-potassium infusion, reinfusion of ascitic fluid, and portosystemic shunting).

For alcohol-induced toxic nephropathy, glucocorticoids are prescribed in medium therapeutic doses (30–60 mg/day).

Apostematous Pyelonephritis requires Surgical treatment exclusively.

The primary objectives in managing bacteremic shock are eliminating circulatory collapse (dextrans, plasma, pressor amines, prednisolone up to 1000 mg/day, heparin) and restoring urinary tract patency. Once blood pressure stabilizes and urine flow is re-established, Antibiotics are prescribed taking into account their nephrotoxic and hepatotoxic profiles. Notably, Tetracyclines, lincomycin, biseptol, and nitrofuran derivatives exhibit hepatotoxic effects.

The preferred approach involves the administration of second- and third-generation Cephalosporins and imipenem. Imipenem is a broad-spectrum antibiotic and the first representative of a new class of beta-lactam antibiotics, the thienamycins. Combined with sodium cilastatin (an enzymatic inhibitor that blocks renal metabolism of imipenem and significantly increases the concentration of unchanged imipenem in the urinary tract), it is available as the pharmaceutical preparation Tienam. The antibacterial spectrum of Tienam is exceptionally broad, covering virtually all known pathogenic bacterial strains. In life-threatening conditions such as bacteremic shock, Tienam is administered intravenously, with dosages adjusted According to the degree of renal impairment. Specifically, for a creatinine clearance (CC) of 31–70 mL/min, the daily dose of Tienam is 1.5–2 g; for 21–30 mL/min, it is 1–2 g; and up to 20 mL/min, it is 0.5–1.0 g. The administration of Rulid, a macrolide antibiotic, is also considered appropriate (150–300 mg/day, or 75–150 mg/day in hepatic impairment).

In myorenal syndrome, medical management depends on urine output. If diuresis is preserved, prolonged continuous intravenous infusion of alkaline solutions is recommended, with a target urine output of 200–300 mL/h serving as the criterion of adequacy. To manage hyperkalemia, a glucose-insulin solution with added calcium gluconate is used. Furosemide is administered to stimulate diuresis, while hemodialysis is employed if hyperkalemia worsens.

The Management of chronic alcoholic kidney disease is based on the absolute cessation of alcohol consumption, which alone can lead to complete clinical and laboratory remission.

If treatment for alcoholic glomerulonephritis fails, aminoquinoline derivatives (delagil, plaquenil), allopurinol, alkaline solutions (in case of hyperuricemia), antiplatelet agents (persantine, agapurin, ticlid), antioxidants (vitamin E, nicotinic acid, ascorbic acid), sorbents (fibrabet, enterosgel), and antihypertensive drugs (selective beta-blockers, calcium channel blockers, ACE inhibitors) are employed. In cases of massive proteinuria (PU) with preserved liver function, NSAIDs are used (preferably COX-2 inhibitors).

Treatment of renal tubular acidosis comes down to prescribing potassium supplements (panangin, asparkam) and Diuretics (veroshpiron). To acidify the urine, ascorbic acid, Methionine, ammonium chloride, and decoctions of madder ROOT or wild carrot leaves are used.

Management of hepatic glomerulopathy involves the aforementioned antiplatelet agents, antioxidants, and sorbents.