Treatment of Chronic Renal Failure

Treatment of hypertension

• The target blood pressure level has become stricter for patients who are not undergoing dialysis or have not received a renal transplant. The aim of this is to reduce cardiovascular mortality and morbidity, not just nephroprotection. However, not all guidelines call for such strict target levels.
  • Systolic blood pressure < 120 mmHg
  • The diastolic blood pressure target has not been separately defined but an appropriate target of < 80 mmHg can probably be reached if systolic blood pressure is at the target level.
  • For organ transplant recipients, the target blood pressure level is < 130/80 mmHg.
  • If the strict target cannot be reached due to adverse effects, a higher level is considered acceptable http://pubmed.ncbi.nlm.nih.gov/33637192/, particularly in elderly patients and patients with multiple diseases as well as those with symptomatic postural hypotension.
• ACE inhibitors and angiotensin receptor blockers (ARBs) are the primary drugs. They reduce proteinuria Antiproteinuric and Renoprotective Effects of ACE Inhibitors and Angiotensin II Receptor Blockers and slow down progression of all proteinuric renal diseasesACE Inhibitors and Angiotensin Receptor Blockers for Progression of Non-Diabetic Renal Disease.
  • Prior to treatment and 1-3 weeks after the start of treatment, check plasma creatinine and potassium.
  • Start with a low dose, and increase the dose carefully if there is already more than mild renal failure. Medication can also be used for patients undergoing dialysis unless hyperkalaemia is a problem.
  • At the beginning of the therapy a slight increase in the creatinine concentration (< 20-30% of baseline) is sometimes detected. This does not prevent continuing therapy; however, follow-up is necessary. If a greater increase is seen, constriction of the renal arteries should be suspected. An acceptable increase in plasma potassium concentration is up to the level of 5.5 mmol/l but measures to lower the concentration should be started as soon as the reference range is exceeded (see section on hyperkalaemia).
  • If the patient has gastroenteritis or some other cause of fluid loss, he/she should be advised to temporarily discontinue taking drugs inhibiting the RAA system (risk of hyperkalaemia and aggravation of renal failure), but as soon as the acute situation becomes normalized, and after checking the plasma potassium and creatinine concentrations, the medication should be resumed.
• A combination of several antihypertensive drugs is often required: calcium channel blockers, diuretics and beta blockers are useful.
• Potassium-sparing diuretics should be used with caution (eGFR 30-59 ml/min.) as there is a risk of hyperkalaemia; they are not recommended for patients with severe renal failure. The risk is increased if potassium-sparing diuretics are used in combination with ACE inhibitors or ARBs Aldosterone Antagonists for Preventing the Progression of Chronic Kidney Disease. Thiazide diuretics may lose their effect if eGFR < 30 ml/min. Loop diuretics (furosemide) are then recommended.
• Similar lifestyle changes are recommended as for the general population, particularly restricting sodium intake to < 2 g/24 h and regular physical exercise.

Treatment of proteinuria Aldosterone Antagonists for Preventing the Progression of Chronic Kidney Disease

• The target of 24-hour urinary protein excretion level is < 1 g/24 h.
  • If the baseline urine protein level is high, a decrease of at least 50 to 60% should be sought.
• ACE inhibitors and ARBs decrease proteinuria independently Antiproteinuric and Renoprotective Effects of ACE Inhibitors and Angiotensin II Receptor Blockers.
• The combination of ACE inhibitors and ARBs is no longer recommended as this carries a risk of hyperkalaemia and significant aggravation of renal failure.

Other factors influencing the progress of chronic renal failureLow Protein Diets for Chronic Kidney Disease in Non-Diabetic Adults, , Interventions for Weight Loss in Overweight or Obese People with Chronic Kidney Disease, Protein Restriction for Diabetic Kidney Disease

• Optimal diabetes control will delay the emergence and progression of diabetic nephropathy .
  • The HbA_1c target level varies individually, being < 47-64 mmol/mol (< 6.5-8%) before the dialysis stage.
  • Of antidiabetic drugs, SGLT-2 inhibitors and GLP-1 analogues additionally decreasing proteinuria and/or slowing down eGFR reduction are particularly useful.
• Avoidance of nephrotoxic agents (e.g. NSAIDs, CT contrast media). Check, if available, electronic database(s) for the usability of drugs in different levels of renal function.
• Avoidance of smoking Smoking Cessation
• Dietary protein intake
  • The general intake target for patients with diabetes before the dialysis stage is similar to the WHO recommendations (0.8 g/kg ideal weight/24 h).
  • Keeping the dietary protein intake at a moderate level of 0.8-1.0 g/kg ideal weight/24 h is also recommended for other patients with renal failure Protein Restriction for Diabetic Kidney Disease; at the dialysis stage, the need for dietary protein will increase.
  • Phosphate restriction usually involves partial protein restriction. A daily protein intake exceeding 1.3 g/kg is not recommended if there is a risk of progressive renal failure.
  • Protein restriction probably has no benefit in patients with an eGFR ≥ 60 ml/min.
  • A varied diet rich in vegetables may prevent renal failure and slow down its progression.
• Avoidance of obesity
• Metabolic acidosis caused by renal failure may also be a risk factor for progression of renal failure, and its treatment is also useful from the viewpoint of nephroprotection.
• There is no unequivocal evidence that medication lowering serum urate levels slows down the progression of renal failure.
• SGLT-2 inhibitors
  • slow down the progression of chronic renal disease, decrease the risk of acute renal damage, decrease deaths from cardiovascular causes and hospital treatment of heart failure regardless of whether the patient has diabetes Sglt-2 Inhibitors and GLP-1 Agonists for Diabetes and Chronic Kidney Disease.
    • There is currently no evidence of benefits in all patient groups (organ transplant recipients, patients with polycystic kidney disease, vasculitis, lupus).
    • Medication is useful regardless of diabetes control or other antidiabetic medication.
    • Empagliflozin also prevents eGFR reduction in patients with hardly any proteinuria, regardless of whether they have diabetes.
      • Starting such medication is not currently recommended if eGFR is < 20 ml/min/1.73 m² , but medication already started can probably be continued until the beginning of the dialysis stage.
      • At least patients (according to trial inclusion criteria) with eGFR 20-45 (even without proteinuria) or eGFR 45-90 and urine albumin/creatinine ratio 22.6 mg/mmol or more at the start of medication will benefit of it.
    • Dabagliflozin slows down the progression of renal failure and reduces proteinuria in patients with and without diabetes.
      • Starting such medication is not currently recommended if eGFR is < 25 ml/min/1.73 m² , but medication already started can probably be continued until the beginning of the dialysis stage.
      • At least patients (according to trial inclusion criteria) with eGFR 25-75 and urine albumin/creatinine ratio 22.6-565 mg/mmol at the start of medication will benefit of it.
    • Dabagliflozin and empagliflozin are so far the only SLGT-2 inhibitors indicated for the treatment of chronic kidney disease.
  • Starting treatment with any SGLT-2 inhibitor is associated with an acutely reduced glomerular filtration rate (GFR). The amount of reduction is to some extent proportional to the long-term efficacy of the medication and should not lead to pausing the medication in the absence of other reasons.
    • About 1 month after starting the medication, check eGFR, particularly if the patient has a history of episodes of acute renal failure, if the glomerular filtration rate was significantly reduced at the beginning of medication or if there is reason to suspect problems related to dehydration.
• Mineralocorticoid receptor blockers
  • Steroidal mineralocorticoid receptor blockers (spironolactone, eplerenone) lower blood pressure and reduce proteinuria and may stabilize renal function regardless of the diabetes status, but they increase the risk of hyperkalaemia if combined with ACE inhibitors or ARBs.
  • Of non-steroidal mineralocorticoid receptor blockers, finerenone has been studied the most. Combined with ACE inhibitors or ARBs, it reduces proteinuria and slows down the progression of renal failure in people with diabetes. It is indicated in the treatment of chronic kidney disease (with albuminuria) associated with type 2 diabetes.

Treatment of complications of renal failure

Dyslipidaemia

• Treatment of dyslipidaemia will reduce mortality at least at the pre-dialysis stageStatins for People with Chronic Kidney Disease Not Requiring Dialysis, but probably has no effect on the progression of renal failure. The target LDL cholesterol level is the same as in a high-risk (< 1.8) or a very high-risk (< 1.4) patient.Statins for People with Chronic Kidney Disease Not Requiring Dialysis

Disturbances in electrolyte and fluid balance

• The intake of sodium chloride usually has to be restricted (< 5 g/24 h or Na < 2 g/24 h) Altered Dietary Salt Intake in Chronic Kidney Disease.
  • This helps to achieve better blood pressure control and to alleviate oedema.
• In hyperkalaemia:
  • Dietary potassium intake should be restricted (guided by a therapeutic dietitian, as necessary).
  • Loop diuretics increase the loss of potassium in urine.
  • Drugs lowering potassium levels (sodium polystyrene sulphonate, patiromer, sodium zirconium cyclosilicate) Potassium Binders for Chronic Hyperkalaemia in People with Chronic Kidney Disease may be used, as necessary.
  • ACE inhibitors, ARBs and mineralocorticoid receptor blockers must be reduced if hyperkalaemia cannot otherwise be controlled.
  • An acceptable increase in plasma potassium concentration is up to the level of 5.5 mmol/l but measures to lower the concentration should be started as soon as the reference range is exceeded.
• Oedema can be managed by restricting sodium intake, by suppressing proteinuria and by loop diuretics. Fluid restriction may be needed in difficult cases.

Metabolic acidosis

• The acid excretion ability of the kidneys starts to decrease clearly when eGFR falls to 30-45 ml/min.
• Medication should be started when the bicarbonate level in the serum acid-base balance falls to below 22 mmol/. The usual target is the normal range.
• Metabolic acidosis can be corrected by calcium carbonate tablets otherwise used for phosphate restriction and, additionally, by sodium bicarbonate tablets, as necessary. The dosage is individual.

Anaemia Erythropoietin for Chronic Renal Failure Anaemia, Darbepoetin and Biosimilars for the Anaemia of Chronic Kidney Disease, Parenteral Versus Oral Iron Therapy for Adults and Children with Chronic Kidney Disease

• Renal erythropoietin production decreases in patients with renal failure.
• Normochromic and normocytic anaemia can be considered renal if other causes of anaemia have been excluded and eGFR has decreased to a level where renal anaemia commonly occurs. . Measurement of blood erythropoietin levels is not useful.
  • Anaemia develops gradually, and commonly occurs at eGFR levels of about 30 ml/min. In people with diabetes, particularly, it may occur at eGFR levels of 40-45 ml/min., already.
• Erythropoietin is given by injection (s.c. or i.v.) Erythropoietin for Chronic Renal Failure Anaemia in individual doses and at individual dosing intervals.
• An HIF-PH inhibitor (roxadustat) is the newest drug for the treatment of renal anaemia. It is taken orally 3 times a week.
• The most common target haemoglobin level is 100-120 g/l.
• Sufficient iron intake can be ensured by giving either oral products or intravenous products at regular intervals Parenteral Versus Oral Iron Therapy for Adults and Children with Chronic Kidney Disease.

Secondary hyperparathyroidism

• Reduced urinary phosphate excretion causes secondary hyperparathyroidism, which can be observed at an eGFR < 60 ml/min., already.
• Serum parathyroid hormone (PTH) concentration increases early, blood calcium and phosphate concentrations only later (calcium decreasing, phosphate increasing).
• Reduction of dietary phosphate intake and phosphate binding medication should only be started when the blood phosphate level exceeds the reference range. The main focus should be on the trends of repeated measurements and on their combined assessment.
  • Restriction of dietary phosphate intake (dairy products and wholemeal products) is of primary importance; a clinical dietitian can provide instructions.
  • Use of phosphate binders Phosphate Binders in Chronic Kidney Disease: start with calcium carbonate tablets or with combined calcium acetate/magnesium carbonate tablets, and add calcium-free phosphate binders (sevelamer, lanthanum carbonate) to the regimen, as necessary.
  • The number of calcium tablets should be kept reasonable; usually calcium doses exceeding 1.5 g/day are not recommended without a special reason (correction of hypocalcaemia, for example).
• Vitamin D2 or D3 should be given to all patients, unless the dietary intake appears to be certainly sufficient. Measure 25-OH vitamin D levels, as necessary.
• Active vitamin D (alfacalcidol or paricalcitol) is often used as the initial drug, if the problem is merely elevated PTH without hyperphosphatemia.
• The aim is to keep blood calcium and phosphate levels within the reference ranges and PTH approximately at a level close to but not exceeding the upper limit of the reference range, although the optimal PTH level prior to dialysis stage is unclear. At the dialysis stage, target phosphate and PTH levels are higher. Hypercalcaemia should be avoided at every stage.
• In severe secondary hyperparathyroidism, either initiation of calcimimetic Calcimimetics for Secondary Hyperparathyroidism in Chronic Kidney Disease Patients treatment or partial parathyroidectomy will be considered in specialized care.