Neobook — clinical reference

Treatment and prevention strategies according to stage of disease

Consult with a specialist at the local referral centre

N18.1-5/N18.9

DESCRIPTION

Evidence of structural damage (e.g., proteinuria/haematuria) or loss of kidney function (eGFR <60 ml/min/1.73 m²), present for >3 months.
Markers of kidney damage include:

proteinuria; (UPCR = urine protein to creatine ratio; UACR = urine albumin to creatine ratio)
- Severely increased: UPCR >0.05 g/mmol (>0.500g/g); UACR > 30mg/mol (300mg/g)
- Moderately increased: UPCR 0.015-0.05 g/mmol (0.15-0.5 g/g); UACR 3-30 mg/mmol (30-300 mg/g)
- Normal or mildly increased: UPCR <0.015 g/mmol (<0.15 g/g); UACR <3 mg/mmol (<30 mg/g)

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urine dipstick positive for blood and/or protein (for females with haematuria: exclude current menstrual cycle)
increased serum creatinine or low eGFR <60 mL/min/1.73 m²
abnormal kidneys on ultrasound, e.g. polycystic, small in size, scarring
abnormalities on renal biopsy
electrolyte abnormalities due to tubular disorders
history of kidney transplant

eGFR calculator online access:
https://www.kidney.org/apps/professionals/egfr-calculator

Table 1: Common causes of CKD include:

Category	Example
Vascular	Hypertension, renal artery stenosis, vasculitis etc.
Glomerular diseases	Diabetes, autoimmune diseases (e.g. lupus nephritis), chronic systemic infections (e.g. HIV, HBV, syphilis), drugs, neoplasia
Tubulointerstitial diseases	UTI, drug-induced interstitial nephritis (e.g. rifampicin, allopurinol, fluoroquinolones, sulphonamides, betalactam antibiotics, proton pump inhibitors, non-steroidal anti-inflammatory drugs)
Structural	Polycystic kidneys, renal masses, obstruction (stones, strictures)
Others	Congenital

Chronic kidney disease can be entirely asymptomatic until over 75% of kidney function is lost.

TREATMENT AND PREVENTION STRATEGIES ACCORDING TO STAGE OF DISEASE

Adverse outcomes of CKD can often be prevented or delayed through early detection and treatment of risk factors for CKD. In patients with CKD, the stage of disease should be assigned based on the level of kidney function according to the classification below, irrespective of diagnosis.

Adults with early CKD i.e. stages 0–3 can be managed at primary care level once the cause and plan for care has been established. All stage 4 and 5 patients require referral/consultation with a specialist. If the patient is a candidate for long-term dialysis, referral to nephrology is advised.

Figure 1: Prognosis of CKD by GFR and albuminuria categories: KDIGO 2024

Click on image to enlarge.

^{ACR: albumin to creatinine ratio in urine specimen.

Green: low risk (if no other markers of kidney disease, no CKD); yellow: moderately increased risk; orange: high risk; red: very high risk; A1, A2, A3 = categories of albuminuria; G1, G2, G3a, G3b, G4, G5 = categories of eGFR}

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GENERAL MEASURES

Address cardiovascular disease risk factors. See Ischaemic heart disease and atherosclerosis, prevention .
Limit total daily salt intake (including salt in food). Consult with dietician as required.

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Avoid nephrotoxic drugs/agents like NSAIDs, aminoglycoside antibiotics and radiocontrast media.
Regular exercise and target BMI (BMI <25 kg/m²) according to South African reference ranges.
Screen for proteinuria.
- If urine dipstick 1+ or greater, repeat on a properly collected midstream urine specimen on another occasion.
- If proteinuria persists, quantify protein with a spot urine protein creatinine ratio. Significant proteinuria = spot urine PCR of >0.15 g/mmol.
- If urine dipstick < 1+, measure urine ACR.
Patients differ in their ability to excrete a salt and water load and therefore fluid balance should be individualised.
Refer patients to rehabilitation for multidisciplinary care and optimisation of function outcomes e.g., improved muscle strength and cardiovascular fitness, reduced blood pressure, weight management.

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MEDICINE TREATMENT

The following interventions may delay progression of kidney disease.

Proteinuria reduction

Ideal targets: UPCR <0.03 g/mmol or UACR <3 mg/mmol.
Most benefit is achieved by reducing UPCR to <0.1 g/mmol or UACR <100 mg/mmol.

Start treatment with a low dose of ACE-inhibitor and titrate up to the maximum tolerated dose, e.g.
Enalapril, oral.
- Start with 5 mg 12 hourly and titrate to 20 mg 12 hourly, if tolerated.
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- Monitor creatinine and potassium after 2 weeks if eGFR <60 mL/min/1.73 m² and after 4 weeks if GFR >60 mL/min/1.73 m².
If creatinine increases by >20% from the baseline, stop ACE-inhibitor and consult a specialist.

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ACE-inhibitor not tolerated due to intractable cough:

Consider an angiotensin II receptor blocker (ARB), e.g.: (specialist initiated)

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Losartan, oral,
- Start with 50 mg daily and titrate to 100 mg daily, if tolerated.
- Replacing ACE-inhibitor with ARB does not preclude the risk of angioedema.

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CAUTION

ACE-inhibitors and ARBs can cause or exacerbate hyperkalaemia in CKD. Check the serum potassium before starting these medicines, and monitor serum potassium on therapy.

Hypertension

Optimise BP control with additional antihypertensive agents. BP control results in a lowering of proteinuria and slower decline in eGFR.
Target BP for patients with hypertension: <140/90 mmHg.
Target BP for patients with hypertension and confirmed CKD and/or diabetes: <130/80 mmHg.
See Hypertension.

Hyperlipidaemia
If hyperlipidaemia is a co-existent cardiovascular risk factor, manage according to Ischaemic heart disease and atherosclerosis, prevention.

Diabetes mellitus

In diabetics, optimise control according to Diabetes mellitus.
In diabetics with kidney disease there is an increased risk of hypoglycaemia.
Insulin is the safer option to control blood glucose in patients with eGFR < 60 mL/minutes.

Note:

- Insulin requirements will decrease as renal disease progresses.
- Stop glibenclamide when eGFR <60 mL/min/1.73 m² because of an increased risk of hypoglycaemia.
- Reduce metformin dose when eGFR <60 mL/min/1.73 m² (maximum dose 500 mg 12 hourly).
- Discontinue metformin when eGFR <60 mL/min/1.73 m² because of the risk of lactic acidosis.

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Fluid overload and oedema

Furosemide, oral or IV, 20 to 80mg daily, as a single or divided doses, initiating at the lowest effective dose and titrating upwards. Dose may be increased to 160 mg daily (IV or oral) in divided doses.
- First establish an effective dose and ascertain if urination occurs within 1-2 hours of intake. If urination does not occur within 1-2 hours, the dose should be increased further until urination ensues.
- Diuretic action starts within 60 minutes of dose, hence divided doses should be given in the morning and afternoon, e.g. 8 AM and 2 PM.

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When fluid overloaded and eGFR <60 mL/min/1.73 m², start:

Furosemide, oral or IV, 40 mg in divided doses (e.g., 8 AM and 2 PM).
- Titrate to a maximum of 500 mg in divided doses (e.g., 8 AM and 2 PM).
- Furosemide is ineffective when patients are on dialysis and anuric.

Hypocalcaemia and hyperphosphataemia

The aim is to lower phosphate levels and maintain normal calcium levels to ensure calcium-phosphate product (i.e. Ca x PO₄) <4.4 mmol²/L² , to prevent calcium deposition in vessels and tissue which aggravates vascular disease.

Restrict dietary phosphate intake. (Dietitian consultation) https://unckidneycenter.org/kidneyhealthlibrary/nutrition-and-kidney-disease/

Patients with CKD stage 3–5, not on dialysis:

Hyperphosphataemia and/or hypocalcaemia:

Calcium (elemental), oral (calcium carbonate), 500 mg 8 hourly with meals if calcium-phosphate product <4.4 mmol²/L².
- Increase to approximately 1g 8 hourly with meals if hyperphosphatemia persists.

Aluminium hydroxide 300mg/5ml, oral, 10 mL 8 hourly with meals if calcium-phosphate product >4.4 mmol²/L² , for two weeks only, then switch to calcium carbonate.

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Hypocalcaemia and low or normal serum phosphate:

Calcium (elemental), oral (Calcium carbonate), 500 mg 8 hourly two hours after meals, increase to approximately 1 g 8 hourly between meals.

In patients with CKD stage 5 who are not candidates for kidney replacement therapy, the benefits of phosphate binding are unclear, and regular PTH (parathyroid hormone) monitoring is not necessary.

Patients considered suitable candidates for renal replacement therapy:

Monitor Ca⁺⁺, PO₄ and PTH levels, as per figure 1.

For hyperphosphataemia uncontrolled on calcium carbonate:

Aluminium hydroxide BP (300 mg/5 mL), oral, 10 mL 8 hourly. Specialist initiated.
- To prevent dementia-associated aluminium toxicity, do not use for longer than 3 months.

For hyperparathyroidism, initiate when PTH levels > 2 times upper limit of normal range: (Specialist initiated)
(N25.8)

Calciferol, oral, 50 000 IU once weekly.

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Calcitriol, oral, 0.25–4 mcg daily.

Anaemia associated with CKD in patients on dialysis programmes
N18.1-5^† /N18.9^† + (D63.8*/Z49.1-2)

Patients on chronic haemodialysis or peritoneal dialysis are often anaemic due to iron deficiency and deficiency of erythropoietin (EPO).
Simultaneous administration of iron and EPO is recommended, as EPO should be administered in a patient with normal iron stores. Adequate iron stores are required to assist with red blood cell production immediately after EPO administration (see Anaemia, iron deficiency).

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Iron, elemental, oral. See Anaemia, iron deficiency, if no response, consider parenteral iron.

AND

Erythropoietin Stimulating Agents (ESAs), e.g.:

Erythropoietin alpha or beta, 40–50 IU/kg/dose, IV/SC 2–3 times weekly and assessed at 4 weekly intervals.
- Administer IV dose over 1–5 minutes.
- If necessary, dose may be increased by 25 IU/kg.

Note:

There is an increased risk of cardiovascular events with haemoglobin levels >12 g/dL.

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Definitive treatment, e.g. transplantation, usually improves anaemia. It is important to identify factors likely to aggravate anaemia, e.g. iron deficiency, infection, and vitamin B12 and folate deficiency.

Acidosis and hyperkalaemia
Specialist consultation for possible renal replacement therapy.

Check all medicines for possible dose adjustments. https://globalrph.com/renal/

CONSULT WITH A SPECIALIST AT THE LOCAL REFERRAL CENTRE

Unknown cause of kidney failure.
Rapid deterioration in renal function.
Resistant hypertension despite appropriate medication and adherence.
All patients with persistent proteinuria: on urine dipstick ≥ 1+ or proteinuria >1 g/24 hours (UPCR >0.1 g/mmol).
Patients with nephrotic-range proteinuria (UPCR >0.35 g/mmol) or nephrotic syndrome should be referred for possible kidney biopsy.

REFERRAL

All ESRD patients who may qualify for long term dialysis programs. See Renal replacement therapy.
CKD stage 3 and above (see figure 1: Prognosis of CKD by GFR and albuminuria categories).

Click here to access the pdf.

Standard Treatment Guidelines and Essential Medicines List for South Africa, Adult Hospital Level, 2020-2024_Version 1.0_17 October 2024

Chapter 7 Nephrology/Urological Disorders_7.1 Nephrology Disorders_7.1.1 Chronic Kidney Disease (CKD)

Chronic Kidney Disease (CKD)

Drugs mentioned

ICD-10 codes