Diabetic Nephropathy

Diabetic kidney disease (DKD) is CKD attributable to diabetes, defined by albuminuria and/or reduced eGFR, and is the leading cause of ESKD in many countries.

• Develops in 30 to 40% of patients with type 1 and type 2 diabetes, typically after 10 to 15 years in type 1; may be present at diagnosis in type 2.
• Pathophysiology: hyperglycaemia, glomerular hyperfiltration, advanced glycation end products, RAAS activation, inflammation, podocyte loss, mesangial expansion, nodular glomerulosclerosis (Kimmelstiel-Wilson), arteriolar hyalinosis.
• Stages by albuminuria (A1 under 30 mg/g, A2 30 to 300, A3 over 300) and eGFR (G1 to G5).
• Risk factors: poor glycaemic and blood pressure control, smoking, obesity, genetic predisposition, dyslipidaemia.
• Strongly linked to retinopathy in type 1; absence of retinopathy in type 1 suggests another cause.
• Cardiovascular events outnumber ESKD.

• Silent initially; microalbuminuria then proteinuria, hypertension, oedema, nephrotic syndrome.
• Falling insulin requirements with declining GFR (reduced clearance), hypoglycaemia.
• Other microvascular complications (retinopathy, neuropathy).
• Normocytic anaemia, hyperkalaemia, type 4 renal tubular acidosis.
• Atypical features suggesting non-diabetic disease: rapid GFR decline, haematuria, absent retinopathy, short diabetes duration, active sediment.

• Annual screening from diagnosis (type 2) or 5 years after diagnosis (type 1): urine albumin/creatinine ratio (spot morning sample) and eGFR.
• Confirm abnormal results in 2 of 3 samples over 3 to 6 months.
• Renal biopsy if atypical features: active sediment, rapidly rising creatinine, nephrotic syndrome with short duration.
• Renal ultrasound, retinal examination, HbA1c, lipids, potassium, haemoglobin, PTH, phosphate, vitamin D.
• Cardiovascular risk assessment.

• Glycaemic control: target HbA1c about 7% (individualised); prefer agents with kidney benefit.
• SGLT2 inhibitors for eGFR 20 mL/min or higher: empagliflozin 10 mg or dapagliflozin 10 mg daily (reduce progression, cardiovascular events, hospitalisation).
• GLP-1 receptor agonist (semaglutide up to 1 mg weekly) for glycaemic and cardiorenal benefit.
• RAAS blockade: ACE inhibitor or ARB (ramipril 10 mg, losartan 100 mg) titrated to maximum tolerated for albuminuria and hypertension; monitor potassium and creatinine at 1 to 2 weeks (accept rise up to 30%).
• Finerenone 10 to 20 mg daily (non-steroidal MRA) in type 2 diabetes with albuminuria and potassium under 4.8 mmol/L, on top of RAAS inhibitor.
• Blood pressure below 130/80 mmHg, with calcium channel blocker or diuretic added; statin (atorvastatin 20 to 40 mg); aspirin for secondary prevention; smoking cessation, weight loss, sodium under 2 g/day, protein 0.8 g/kg/day.
• Metformin dose reduction at eGFR 30 to 45, stop below 30; avoid NSAIDs; sick day rules.
• CKD complications: erythropoiesis stimulating agents (haemoglobin under 10 g/dL), phosphate binders, vitamin D, potassium binders (patiromer 8.4 g, sodium zirconium cyclosilicate 10 g).
• Refer to nephrology at eGFR under 30, rapid decline, or A3 albuminuria; plan dialysis or pre-emptive transplantation (including simultaneous pancreas-kidney in type 1).
• Monitor every 3 to 6 months.