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Treatment of Chronic Renal Failure
Essentials
- The aim of treatment is to slow down the deterioration of renal function and prevent organ complications.
- Patients belonging to risk groups for kidney disease (patients with diabetes or cardiovascular disease, hypertension, obesity or family history of kidney disease) should be screened (plasma creatinine and chemical urinalysis and/or urine albumin/creatinine ratio).
- The metabolic sequelae of renal failure and the risk factors for atherosclerosis should be identified and treated. The risk of cardiovascular disease increases as soon as there is proteinuria even if renal function is still normal.
- The number of patients with renal failure is increasing, particularly because type 2 diabetes is becoming more common and the population is ageing.
- It is important to start treatment as soon as possible.
- In an elderly person, eGFR may be decreased merely because of advanced age even though the plasma creatinine concentration is still completely normal. As a solitary finding, this is not a sign of renal disease.
Workup
- Renal function is assessed by measuring plasma creatinine levels and eGFR Increased Blood Creatinine Concentration, Egfr and Renal Function TestsGfr Calculator. Determining plasma cystatine C may also be of help when assessing the significance of a marginally elevated creatinine concentration or a marginally decreased eGFR.
- Renal ultrasonography is indicated if a problem in urine flow is suspected or if renal failure has suddenly progressed without a clear reason.
- If renal ultrasonography has never been done or not been done for several years, it should be done anyway.
- As part of the diagnostic workup, the level of proteinuria Proteinuria should be examined by determining the urine albumin/creatinine ratio (or 24-hour urinary protein excretion) and any haematuria should be identified (chemical urinalysis) and its extent determined by particle counting.
- The magnitude of proteinuria should be monitored. A high level of proteinuria is an independent risk factor for aggravation of renal failure.
- Haematuria is usually not an independent risk factor for aggravation of renal failure, but, if it is increasing, it is usually a sign of activation of renal disease (e.g. in vasculitis)
- As renal failure remains asymptomatic for a long time, monitoring of plasma creatinine and chemical screening of urine and/or measurement of urine albumin/creatinine ratio should be performed particularly in risk groups.
- Disease-specific calculators to predict the progression of renal failure are available (e.g. for type 2 diabetes, IgA glomerulonephritis), although the use of all of these in clinical practice is not yet established.
- Chronic renal disease is defined as renal damage (any abnormal renal finding; most commonly either an abnormal finding in a urine test and/or impaired renal filtration < 60 ml/min/1.73m2 ) that has lasted for at least 3 months.
- In an elderly person, eGFR may be decreased merely because of advanced age even though the plasma creatinine concentration is still completely normal. As a solitary finding, this is not a sign of renal disease.
- If urine analysis is normal and the plasma creatinine concentration is still increased on repeat testing, determining plasma cystatine C concentration may provide additional information on whether the patient has renal failure or not Increased Blood Creatinine Concentration, Egfr and Renal Function Tests.
Therapeutic interventions to slow the progression of renal disease
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.
- Optimal diabetes control will delay the emergence and progression of diabetic nephropathy .
- The HbA1c 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 HASH(0x2fcfe80) 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
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:
- 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.
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.
Follow-up and levels of care
- Primary health care
- Screening for renal failure in high-risk patients (patients with diabetes, hypertension or cardiovascular disease or family history of kidney disease) and its detection
- Detection, treatment and follow-up of factors affecting renal failure (blood pressure, diabetes, proteinuria, other factors, see here).
- Diet therapy (clinical dietitian): phosphate restriction, restriction of salt intake and, as necessary, restriction of potassium and protein intake
- Follow-up and management of mild and moderate renal failure
- Check-ups every 6-12 months for patients with an eGFR of 60-89 ml/min.
- Check-ups every 4-6 months for patients with an eGFR of 30-59 ml/min.
- Basic blood count with platelet count, creatinine, eGFR, potassium, sodium, urea, ionized calcium, inorganic phophate, parathyroid hormone (if possible), albumin, urinary albumin/creatinine ratio or 24-hour urinary protein excretion, chemical screening of urine, blood gas analysis (if possible), HbA1c (in patients with diabetes) and lipids (once a year plasma cholesterol, fasting plasma triglycerides, fasting plasma HDL cholesterol, plasma LDL cholesterol).
- Renal ultrasonography if a problem with urinary flow is suspected or if renal function has suddenly reduced without a clear reason.
- Specialized care
- More specific diagnosis of the renal disease, especially when renal biopsy is needed
- Difficulties in the management of blood pressure or oedema
- Initiation of erythropoietin therapy, HIF-PH inhibitor (roxadustat) or intravenous iron therapy
- Treatment of secondary hyperparathyroidism: initiation of treatment with calcium-free phosphate binders or alfacalcidol/paricalcitol/calcimimetic and consideration of operative treatment
- Significant increase in proteinuria despite optimal treatment of blood pressure and proteinuria (urinary protein excretion > 3 g/24 h)
- Rapid deterioration of renal function with no obvious reason
- Assessment for active intervention when eGFR is less than about 20 ml/min (some other level, such as < 30 ml/min., may have been agreed locally): will the patient benefit from possible initiation of dialysis treatment or organ transplant as the renal disease progresses?
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