Diabetic Kidney Disease

Diabetic kidney disease is chronic kidney damage from diabetes, shown by persistent albuminuria, reduced eGFR, or both, in the presence of retinopathy or other evidence of microvascular disease.

• It occurs in 30 to 40 percent of people with type 1 or type 2 diabetes and is the leading cause of end stage kidney disease worldwide.
• Pathology: glomerular basement membrane thickening, mesangial expansion, nodular glomerulosclerosis, podocyte loss, arteriolar hyalinosis, tubulointerstitial fibrosis.
• Risk factors: poor glycaemic control, hypertension, longer duration, obesity, smoking, dyslipidaemia, genetic susceptibility, African ancestry, and early age at diagnosis.

Silent in early disease; foamy urine, oedema, hypertension, fatigue and anaemia later.

• Natural history: hyperfiltration, microalbuminuria (3 to 30 mg/mmol or 30 to 300 mg/g) after 5 to 10 years, macroalbuminuria, nephrotic syndrome, then falling eGFR.
• Reduced insulin requirements and hypoglycaemia as eGFR falls; frequent coexisting retinopathy and neuropathy.
• Differential diagnosis: hypertensive nephrosclerosis, glomerulonephritis (haematuria, rapid decline, no retinopathy, short duration of diabetes), obstructive uropathy, renovascular disease, amyloidosis, HIV nephropathy, drug nephrotoxicity, renal tuberculosis.
• Complications: chronic kidney disease progression, cardiovascular disease (leading cause of death), hyperkalaemia, type 4 renal tubular acidosis, anaemia, mineral bone disease, acute kidney injury, infections, diabetic foot disease and end stage kidney disease.

Urine albumin-to-creatinine ratio (first morning spot) at least 3 mg/mmol (30 mg/g) on two of three samples over 3 to 6 months, after excluding infection, exercise, fever and menstruation; eGFR from creatinine below 60 mL/min/1.73 m2 for over 3 months.

• Staging by eGFR and albuminuria categories; HbA1c, lipids, blood pressure, retinal examination, potassium, bicarbonate, haemoglobin, calcium, phosphate, parathyroid hormone.
• Renal ultrasound (normal or large kidneys in early disease).
• Consider other causes if haematuria with red cell casts, rapid eGFR fall (above 5 mL/min/year), sudden onset nephrotic syndrome, absent retinopathy in type 1 disease, or onset within 5 years of type 1 diabetes; renal biopsy then.

Supportive: lifestyle (weight loss, exercise, stop smoking), sodium below 2 g daily, protein 0.8 g/kg/day, avoid NSAIDs, nephrotoxins and contrast without precautions.

Pharmacological

• Glycaemic control: an individualised HbA1c target of about 53 mmol/mol (7 percent), set higher in frail patients; reduce insulin and sulfonylurea doses as eGFR falls.
• Blood pressure below 130/80 mmHg: ACE inhibitor (lisinopril 10 to 40 mg daily, enalapril 10 to 20 mg twice daily) or angiotensin receptor blocker (losartan 50 to 100 mg daily) titrated to the maximum tolerated dose in anyone with albuminuria; check creatinine and potassium 1 to 2 weeks after starting or changing the dose (accept up to 30 percent creatinine rise); avoid dual blockade.
• Sodium-glucose cotransporter 2 inhibitor: empagliflozin 10 mg or dapagliflozin 10 mg once daily (start with eGFR 20 mL/min/1.73 m2 or above; continue until dialysis); hold during acute illness (sick day rules), and monitor for genital infection and ketoacidosis.
• Mineralocorticoid receptor antagonist finerenone 10 mg daily (eGFR 25 to 59) or 20 mg daily (eGFR 60 or above) if potassium is 5.0 mmol/L or below and albuminuria persists.
• Semaglutide 1 mg weekly or dulaglutide 1.5 mg weekly for glycaemic and cardiovascular and renal benefit.
• Statin: atorvastatin 20 to 40 mg at night; aspirin 75 mg daily for established cardiovascular disease.
• Metformin: reduce to a maximum of 1 g daily when eGFR is 30 to 44, stop below 30 mL/min/1.73 m2; avoid sulfonylureas with long action; linagliptin 5 mg needs no adjustment.
• Hyperkalaemia: dietary advice, loop or thiazide diuretic, sodium zirconium cyclosilicate 10 g daily; anaemia: ferrous sulfate or intravenous iron, then erythropoietin (epoetin alfa 50 to 100 units/kg three times weekly) when haemoglobin is below 10 g/dL; phosphate binders and vitamin D analogues as needed.

Procedures: retinal laser or injections; dialysis (haemodialysis or peritoneal) when eGFR is below 10 to 15 mL/min or complications arise; kidney (or kidney and pancreas) transplantation.

Special groups: pregnancy (stop ACE inhibitors and angiotensin receptor blockers before conception; use labetalol or nifedipine), elderly (individualise targets), African ancestry (higher risk).

Red flags: eGFR fall above 5 mL/min/year, nephrotic syndrome, potassium above 6.0 mmol/L, eGFR below 30, hypoglycaemia, active haematuria.

Follow-up: urine albumin-to-creatinine ratio and eGFR yearly (3 to 4 times yearly if albuminuria or eGFR below 60); refer to nephrology for eGFR below 30, albumin-to-creatinine ratio above 30 mg/mmol (300 mg/g), rapid decline, or unexplained findings.