Chronic renal failure: treatment

Conservative treatment of chronic renal failure is divided into symptomatic and pathogenetic. His tasks include:

• inhibition of the progression of chronic renal failure (nephroprotective effect);
• slowing down the formation of left ventricular hypertrophy (cardioprotective effect);
• elimination of uremic intoxication, hormonal and metabolic disorders;
• elimination of infectious complications of chronic renal failure.

Optimal for monotherapy of chronic renal failure is a drug with a nephroprotective and cardioprotective effect, metabolically neutral, without any side effects.

The main directions of conservative treatment of chronic renal failure are correction of nitrogenous and water-electrolyte homeostasis, treatment of arterial hypertension and anemia.

[1], [2], [3], [4], [5], [6]

Correction of violations of homeostasis and metabolic disorders

The low protein diet (MVD) eliminates symptoms of uremic intoxication, reduces azotemia, gout symptoms, hyperkalemia, acidosis, hyperphosphatemia, hyperparathyroidism, stabilizes residual kidney function, inhibits the development of terminal uremia, improves well-being and lipid profile. The effect of a low protein diet is more pronounced when applied in the initial stage of chronic renal failure and with initially slow progression of chronic renal failure. The low protein diet, which limits the intake of animal proteins, phosphorus, sodium, maintains serum albumin level, preserves nutritional status, enhances the nephroprotective and cardioprotective effect of pharmacotherapy (ACE inhibitors). On the other hand, treatment with epoetin preparations, providing an anabolic effect, contributes to a long-term adherence to a low-protein diet.

The choice of a low protein diet as one of the priority methods for treating chronic renal failure depends on the etiology of nephropathy and the stage of chronic renal failure.

• In the early stage of chronic renal failure (creatinine less than 0.25 mmol / l), a diet with a moderate protein restriction (1.0 g / kg body weight), a calorie content of not less than 35-40 kcal / kg is allowed. In this case, vegetable soy proteins (up to 85%), enriched with phytoestrogens, antioxidants and containing less phosphorus than meat, fish, and milk protein - casein are preferable. In this case, products from genetically modified soybeans should be avoided.
• In chronic renal failure with a creatinine level of 0.25-0.5 mmol / l, a greater protein restriction (0.6-0.7 g / kg), potassium (up to 2.7 g / day), phosphorus (up to 700 mg / day) at the same caloric value (35-40 kcal / kg). For the safe use of a low protein diet, prevention of nutritional status disorders, it is recommended to use keto analogues of essential amino acids [ketosteril "in a dose of 0.1-0.2 g / (kg x 10)].
• With pronounced chronic renal failure (creatinine more than 0.5 mmol / l,) retain protein and energy quotas at the level of 0.6 g protein per 1 kg body weight of the patient, 35-40 kcal / kg, but limited to potassium to 1.6 g / day and phosphorus up to 400-500 mg / day. In addition, a complete complex of essential keto / amino acids is added [ketosteryl 0.1-0.2 g / (kg x 10)). Ketosteril "not only reduces hyperfiltration and PTH production, eliminates negative nitrogen balance, but also reduces insulin resistance.
• In chronic renal failure in patients with gouty nephropathy and type 2 diabetes (NIDDM) recommend a low-protein diet with lipid-lowering properties, modified by dietary supplements with a cardioprotective effect. Enrich the diet PUFA: seafood (omega-3), vegetable oil (omega-6), soyproducts, add dietary cholesterol sorbents (bran, cereals, vegetables, fruits), folic acid (5-10 mg / day). An important way to overcome uremic insulin resistance is the use of a complex of physical exercises normalizing excess body weight. At the same time, an increase in exercise tolerance is provided by epoetin therapy (see below).
• To reduce the intake of phosphorus, in addition to animal proteins, limit the consumption of legumes, mushrooms, white bread, red cabbage, milk, nuts, rice, cocoa. At the tendency to hyperkalemia, dry fruits (dried apricots, dates), crunchy, fried and baked potatoes, chocolate, coffee, dried mushrooms, restrict juices, bananas, oranges, tomatoes, cauliflower, beans, nuts, apricots, plums, grapes, black bread , boiled potatoes, rice.
• A sharp restriction in the diet of phosphate-containing foods (including dairy products) leads the patient with chronic renal failure to a disturbed diet. Therefore, along with a low-protein diet, moderately sequestering phosphate intake, drugs that bind phosphate in the digestive tract (calcium carbonate or calcium acetate) are used. An additional source of calcium are the essential keto / amino acids in the form of calcium salts. In the event that the level of blood phosphates achieved in this way does not completely suppress the hyperproduction of PTH, it is necessary to attach the active metabolites of vitamin D ₃ - calcitriol to the treatment , as well as to correct the metabolic acidosis. If the full correction of acidosis with a low protein diet is impossible, give citrates or sodium bicarbonate inside to maintain the SB level within 20-22 meq / l.

A portion of products in 1 g, containing 5 g of protein

Products |	Serving weight, g
Bread	60
Rice	75
Cereals (buckwheat, oatmeal)	55-75
Egg of chicken (one)	50
Meat	25
A fish	25
Cottage cheese	Thirty
Cheese	15-25
Salo (shpig)	300
Milk	150
Sour cream, cream	200
Butter	500
Potatoes	300
Beans	25
Fresh peas	75
Fresh mushrooms	150
Chocolate	75
Ice Cream	150

Enterosorbents (povidone, hydrolytic lignin, activated carbon, oxidized starch, oxycellulose) or intestinal dialysis are used in the early stage of chronic renal failure or when it is impossible (unwillingness) to observe a low-protein diet. Intestinal dialysis is carried out by intestinal perfusion with a special solution (sodium chloride, calcium, potassium together with sodium bicarbonate and mannitol). Taking povidone for 1 month reduces the level of nitrogenous slags and phosphates by 10-15%. When ingested for 3-4 hours, 6-7 liters of solution for intestinal dialysis is removed to 5 g of non-protein nitrogen. As a result, blood urea levels decrease for the procedure by 15-20%, a decrease in acidosis.

[7], [8], [9], [10]

Treatment of arterial hypertension

Treatment of chronic renal failure consists in correcting arterial hypertension. The optimal level of arterial pressure, which maintains sufficient renal blood flow in chronic renal failure and does not induce hyperfiltration, varies between 130 / 80-85 mm Hg. In the event that there is no severe coronary or cerebral atherosclerosis. At an even lower level - 125/75 mm Hg. It is necessary to maintain blood pressure in patients with chronic renal failure with proteinuria exceeding 1 g / day. In any stage of chronic renal failure, ganglion blockers are contraindicated; guanetidine, it is inappropriate to systematically use sodium nitroprusside, diazoxide. The tasks of antihypertensive therapy of the conservative stage of chronic renal failure are most responsive to saluretics, ACE inhibitors, angiotensin II receptor blockers, beta-blockers, and central action drugs.

Preparations of the central action

Drugs of central action reduce blood pressure by stimulating adrenoreceptors and imidazoline receptors in the central nervous system, which leads to blockade of peripheral sympathetic innervation. Clonidine and methyldopa are poorly tolerated by many patients with chronic renal insufficiency due to worsening of depression, induction of orthostatic and intradialytic hypotension. In addition, the involvement of the kidneys in the metabolism of these drugs dictates the need for dosage adjustment in chronic renal failure. Clonidine is used to stop the hypertensive crisis in chronic renal failure, block diarrhea in autonomic uremic neuropathy of the gastrointestinal tract. Moxonidine, unlike clonidine, has a cardioprotective and antiproteinuric effect, a smaller central (depressive) effect and intensifies the hypotensive effect of drugs of other groups, without violating the stability of central hemodynamics. Dosage of moxonidine should be reduced as chronic renal failure progresses, as 90% of the drug is excreted by the kidneys.

Saluretics

Saluretics normalize blood pressure by correcting hypervolemia and eliminating excess sodium. Spironolactone, used in the initial stage of chronic renal failure, has a nephroprotective and cardioprotective effect due to the counteraction of uremic hyperaldosteronism. With CF less than 50 ml / min, loop and thiazide-like diuretics are more effective and safe. They increase the excretion of potassium, metabolized by the liver, so for chronic renal failure their dosages are not changed. Of thiazide-like diuretics in chronic renal failure, indapamide is the most promising. Indapamide controls hypertension both at the expense of diuretic action, and by vasodilation - reducing OPSS. In severe chronic renal failure (CF less than 30 ml / min), the combination of indapamide with furosemide is effective. Thiazide-like diuretics prolong the natriuretic effect of loop diuretics. In addition, indapamide due to inhibition caused by loop diuretics hypercalciuria corrects hypocalcemia and thereby slows the formation of uremic hyperparathyroidism. However, for the monotherapy of hypertension in chronic renal failure, saluretics are not used, as with prolonged use they aggravate hyperuricemia, insulin resistance, hyperlipidemia. On the other hand, saluretics enhance the antihypertensive effect of central antihypertensive agents, beta-blockers, ACE inhibitors and ensure the safety of spironolactone in the initial stage of chronic renal failure - by excretion of potassium. Therefore, it is more advantageous to periodically (1-2 times a week) prescribe saluretics against the background of a constant intake of these groups of antihypertensive drugs. Because of the high risk of hyperkalemia, spironolactone is contraindicated in patients with diabetic nephropathy in the initial stage of chronic renal failure, and in patients with nondiabetic nephropathies - with CF less than 50 ml / min. Patients with diabetic nephropathy are recommended loop diuretics, indapamide, xypamide. In the political stage of chronic renal failure, the use of loop diuretics without adequate control of the water-electrolyte balance often leads to dehydration with acute chronic renal failure, hyponatremia, hypokalemia, hypocalcemia, heart rhythm disturbances and tetany. Loop diuretics also cause severe vestibular disturbances. Ototoxicity sharply increases with a combination of saluretics with aminoglycoside antibiotics or cephalosporins. With hypertension in the framework of cyclosporine nephropathy loop diuretics can aggravate, and spironolactone - reduce the nephrotoxicity of cyclosporine.

ACE inhibitors and angiotensin II receptor blockers

ACE inhibitors and angiotensin II receptor blockers have the most pronounced nephro- and cardioprotective effect. Angiotensin II receptor blockers, saluretics, calcium channel blockers and statins increase, and acetylsalicylic acid and NSAIDs weaken the hypotensive effect of ACE inhibitors. With poor tolerability of ACE inhibitors (painful cough, diarrhea, angioedema) they are replaced with angiotensin II receptor blockers (losartan, valsartan, eprosartan). Losartan has a uricosuric effect, correcting hyperuricemia. Eprosartan has the properties of a peripheral vasodilator. Preferred prolonged drugs metabolized in the liver and therefore prescribed to patients with chronic renal failure in low-dose: fosinopril, benazepril, spirapril, losartan, valsartan, eprosartan. Doses of enalapril, lisinopril, perindopril, cilazapril should be reduced in accordance with the degree of decrease in CF; they are contraindicated in ischemic kidney disease, severe nephroangiosclerosis, hyperkalemia, terminal chronic renal failure (creatinine of blood more than 6 mg / dl), and also after transplantation - with hypertension caused by cyclosporin nephrotoxicity. The appointment of ACE inhibitors in conditions of severe dehydration (against long-term use of large doses of saluretics) leads to prerenal acute renal failure. In addition, ACE inhibitors sometimes reduce the anti-anemic effect of epoetin preparations.

[11], [12]

Calcium channel blockers

The benefits of calcium channel blockers include cardioprotective effect with inhibition of calcification of the coronary arteries, normalizing the effect on the daily rhythm of atrial pressure in chronic renal failure, absence of delay of Na and uric acid. At the same time, in connection with the negative inotropic effect, it is not recommended to use calcium channel blockers in chronic heart failure. In hypertension and cyclosporin nephrotoxicity, their ability to influence afferent vasoconstriction and inhibit glomerular hypertrophy is useful. Most drugs (with the exception of isradipine, verapamil, nifedipine) are used for chronic renal failure in usual doses due to the predominantly hepatic type of metabolism. Calcium channel blockers dihydropyridine series (nifedipine, amlodipine, isradipine, felodipine) reduce the production of endothelin-1, but in comparison with ACE inhibitors less affect glomerular autoregulation, proteinuria and other mechanisms of progression of chronic renal failure. Therefore, in the conservative stage of chronic renal failure, dihydropyridine calcium channel blockers should be used in combination with ACE inhibitors or angiotensin II receptor blockers. For monotherapy, verapamil or diltiazem is more suitable, with a distinct nephroprotective and antianginal effect. These drugs, as well as felodipine, are most effective and safe in the treatment of hypertension in acute and chronic nephrotoxicity of cyclosporin and tacrolimus. They also have immunomodulatory, normalizing phagocytosis effect.

Hypotensive therapy of renal hypertension depending on the etiology and clinical features of chronic renal failure

Etiology and features of chronic renal failure	Contraindicated	Showing
CHD	Ganglia-blockers, peripheral vasodilators	Beta-adrenoblockers, calcium channel blockers, nitroglycerin
Ischemic kidney disease	ACE inhibitors, angiotensin II receptor blockers	Beta-adrenoblockers, calcium channel blockers, peripheral vasodilators
Chronic heart failure	Non-selective beta-blockers, calcium channel blockers	Loop diuretics, spironolactone, ACE inhibitors, beta-adrenoblockers, carvedilol
Diabetic Nephropathy	Thiazide diuretics, spironolactone, nonselective beta-blockers, ganglion blockers, methyldopa	Loops, thiazide-like diuretics, ACE inhibitors, angiotensin II receptor blockers, calcium channel blockers, moxonidine, nebivolol, carvedilol
Gouty Nephropathy	Thiazide diuretics	ACE inhibitors, angiotensin II receptor blockers, beta adrenoblockers, loop diuretics, calcium channel blockers
Benign prostatic hyperplasia	Gangliablockers	A1-Adrenoblockers
Cyclosporine nephropathy	Loops, thiazide diuretics, ACE inhibitors	Calcium channel blockers, spironolactone, beta-blockers
Hyperparathyroidism with uncontrolled hypercalcemia	Thiazide diuretics, beta-blockers	Loop diuretics, calcium channel blockers

[13], [14], [15], [16], [17], [18], [19], [20], [21],

Beta-adrenoblockers, peripheral vasodilators

Beta-adrenoblockers, peripheral vasodilators are used in severe renin-dependent renal hypertension with contraindications to the use of ACE inhibitors and angiotensin II receptor blockers. Most beta-blockers, as well as carvedilol, prazosin, doxazosin, terazolin are prescribed for chronic renal failure in usual dosages, and propranolol for the relief of hypertensive crisis is used even at dosages significantly higher than the mediotherapy. Dosages of atenolol, acebutolol, nadolol, betaxolol, hydralazine should be reduced, as their pharmacokinetics are impaired in chronic renal failure. Beta-adrenoblockers have a pronounced antianginal and antiarrhythmic effect, therefore they are used to treat hypertension in patients with chronic renal failure complicated by coronary artery disease, supraventricular arrhythmias. For systematic use in chronic renal failure, beta-selective drugs (atenolol, betaxolol, metoprolol, bisoprolol) are shown. With diabetic nephropathy, nebivolol and carvedilol are preferred, with little effect on carbohydrate metabolism, normalizing the diurnal rhythm of arterial pressure, and the synthesis of NO in the endothelium. Metoprolol, bisoprolol and carvedilol effectively protect the myocardium from the effects of increased tone of sympathetic innervation and catecholamines. With severe uremic cardiomyopathy (ejection fraction less than 30%), they reduce cardiac mortality by 30%. When appointing alpha1-adrenoblockers (doxazosin, alfuzosin, terazosin), it should be taken into account that along with the hypotensive effect they delay the development of benign prostatic hyperplasia.

Contraindications to the use of beta-blockers, in addition to the well-known (expressed bradycardia, violation of atrioventricular conduction, unstable diabetes mellitus), chronic renal failure include hyperkalemia, decompensated metabolic acidosis, and severe uremic hyperparathyroidism, when the risk of calcification of the conduction system of the heart is high.

[22], [23], [24], [25], [26]

Immunosuppressive therapy

Applied in patients with primary and secondary nephritis.

In chronic renal failure, extrarenal systemic signs of secondary glomerulonephritis are often absent or do not reflect the activity of the renal process. Therefore, with a rapid increase in renal failure in patients with primary or secondary glomerulonephritis with normal kidney size, one should think about exacerbation of nephritis in the background of chronic renal failure. The detection of signs of severe exacerbation of glomerulonephritis with kidney biopsy requires active immunosuppressive therapy. Dosages of cyclophosphamide should be corrected in chronic renal failure. Glucorticosteroids and cyclosporin, metabolized primarily by the liver, should also be prescribed in chronic renal failure in reduced doses due to the risk of aggravation of hypertension and violations of intrarenal hemodynamics.

Treatment of anemia

Since neither a low protein diet nor antihypertensive drugs corrected renal anemia (ACE inhibitors sometimes increase it), prescribing epoetin preparations in the conservative stage of chronic kidney failure is often necessary. Indications for epoetin. In the conservative stage of chronic renal failure epoetin is administered subcutaneously in a dose of 20-100 ED / kg once a week. It is necessary to strive for complete early correction of anemia (Ht more than 40%, Hb 125-130 g / l). Deficiency of iron, developed against epoetin therapy in the conservative stage of chronic renal failure, is usually corrected by ingestion of fumarate or iron sulfate together with ascorbic acid. Eliminating anemia, epoetin has a pronounced cardioprotective effect, slowing hypertrophy of the left ventricle and decreasing myocardial ischemia in IHD. Epoetin normalizes appetite, enhances the synthesis of albumin in the liver. This increases the binding of drugs with albumin, which normalizes their effect in chronic renal failure. But with eating disorders, hypoalbuminemia, resistance to anti-anemia and other drugs may develop, therefore, rapid correction of these disorders with irreplaceable keto / amino acids is recommended. Under the condition of complete control of hypertension, epoetin has a nephroprotective effect due to a decrease in renal ischemia and normalization of cardiac output. With insufficient control of blood pressure, epoetin-induced hypertension accelerates the rate of progression of chronic renal failure. With the development of the relative resistance to epoetin caused by ACE inhibitors or blockers of angiotensin II receptors, therapeutic tactics should be selected individually. If ACE inhibitors are used to correct arterial hypertension, it is advisable to replace them with calcium channel blockers or beta-blockers. In the event that ACE inhibitors (or angiotensin II receptor blockers) are used to treat diabetic nephropathy or uremic cardiomyopathy, treatment is continued against the background of an increase in the dose of epoetin.

Treatment of infectious complications

In acute pneumonia and urinary tract infections, semisynthetic penicillins or cephalosporins of the II-III generation are preferred, providing a bactericidal concentration in the blood and urine that are characterized by moderate toxicity. It is possible to use macrolides (erythromycin, azithromycin, clarithromycin), rifampicin and synthetic tetracyclines (doxycycline), metabolized by the liver and not requiring significant dose adjustment. In polycystic disease with the infection of cysts only lipophilic drugs (chloramphenicol, macrolides, doxycycline, fluoroquinolones, clindamycin, co-trimoxazole) administered parenterally are used. In generalized infections caused by a conditionally pathogenic (more often - gram-negative) flora, drugs from the group of fluoroquinolones or aminoglycoside antibiotics (gentamycin, tobramycin) are used, characterized by high total and nephrotoxicity. Doses of these drugs, metabolized by the kidneys, must be reduced in accordance with the severity of chronic renal failure, and the time of their application - to limit 7-10 days. Correction of dosage is necessary for many antiviral (acyclovir, ganciclovir, ribavirin) and antifungal (amphotericin B, fluconazole) drugs.

Treatment of chronic renal failure is a very complex process and requires the involvement of physicians of many specialties.