About This Page
This is a clinician-written, evidence-based summary aligned to the 2026 MLA Content Map. It is intended for medical students and junior doctors preparing for the UKMLA. Always cross-reference with NICE guidance, local protocols, and clinical judgement.
The Bottom Line
- Leading cause of ESRD in the UK. Affects ~40% of diabetics to some degree
- Screening: annual urine ACR from diagnosis in T2DM, from age 12 or 5 years post-diagnosis in T1DM, plus annual eGFR
- Microalbuminuria (ACR 3–30 mg/mmol) = earliest detectable sign. Macroalbuminuria (ACR >30) = established nephropathy
- First-line renoprotective: ACE inhibitor or ARB — start if ACR ≥3 mg/mmol even if normotensive
- SGLT2 inhibitors (dapagliflozin, empagliflozin): proven renoprotective benefit in addition to ACEi/ARB — use if eGFR ≥20
- Finerenone (non-steroidal MRA): additional renoprotective + cardiovascular benefit in T2DM with CKD and albuminuria
- BP target: <130/80 mmHg in diabetic kidney disease
Overview
Diabetic nephropathy (diabetic kidney disease, DKD) is a progressive microvascular complication of diabetes characterised by glomerular hyperfiltration, progressive albuminuria, declining GFR, and ultimately end-stage renal disease. It is the leading cause of ESRD requiring dialysis or transplantation in the UK. The pathology involves glomerular basement membrane thickening, mesangial expansion, nodular glomerulosclerosis (Kimmelstiel-Wilson nodules), and tubulointerstitial fibrosis. The natural history progresses from hyperfiltration → microalbuminuria → macroalbuminuria → declining GFR → ESRD over 10–25 years, though not all patients follow this trajectory. ACE inhibitors/ARBs, SGLT2 inhibitors, and finerenone have all been shown to slow this progression. Coexistent hypertension and dyslipidaemia accelerate decline and increase cardiovascular mortality.
Epidemiology
Approximately 40% of people with diabetes develop some degree of nephropathy. It accounts for approximately 25–30% of all new dialysis patients in the UK. In T1DM, clinically evident nephropathy rarely develops within the first 10 years, peaking in incidence at 15–20 years. In T2DM, albuminuria may be present at diagnosis (reflecting pre-diagnostic disease). Risk factors include: poor glycaemic control, hypertension (both cause and consequence), genetic susceptibility, ethnicity (South Asian, Afro-Caribbean at higher risk), smoking, and dyslipidaemia. Diabetic nephropathy rarely occurs in isolation — most patients with nephropathy also have retinopathy (if absent, consider alternative renal diagnosis).
Clinical Features
Symptoms
Early disease (microalbuminuria) is ASYMPTOMATIC — detected only by screening
Peripheral oedema (nephrotic-range proteinuria or fluid retention from CKD)
Fatigue and lethargy (anaemia of CKD, uraemia)
Nausea, reduced appetite (advanced CKD/uraemia)
Frothy urine (heavy proteinuria)
Signs
Hypertension (very common — both cause and consequence of nephropathy)
Peripheral oedema
Coexistent diabetic retinopathy (present in ~90% with established nephropathy — if ABSENT, consider alternative renal diagnosis)
Signs of advanced CKD: pallor (anaemia), skin excoriations (pruritus), uraemic frost (very late)
Investigations
First-line
Urine albumin:creatinine ratio (ACR)First morning sample preferred. Normal <3 mg/mmol. Microalbuminuria (moderately increased) 3–30 mg/mmol. Macroalbuminuria (severely increased) >30 mg/mmol. Confirm on 2 of 3 samples over 3–6 months
eGFR (serum creatinine-based)Baseline and annual. Stage CKD: G1 ≥90, G2 60–89, G3a 45–59, G3b 30–44, G4 15–29, G5 <15
Second-line
U&Es (full profile)Monitor potassium (ACEi/ARB/finerenone can cause hyperkalaemia), sodium, urea
HbA1cAssess glycaemic control. NB: less reliable in advanced CKD (altered RBC turnover)
Lipid profileDyslipidaemia accelerates nephropathy progression and cardiovascular risk
FBCAnaemia of CKD (EPO deficiency) — normocytic, normochromic
Calcium, phosphate, PTH, vitamin DCKD-mineral bone disorder in advanced stages
Specialist
Renal USSIf atypical features (haematuria, absence of retinopathy, rapid GFR decline, asymmetric kidneys) — consider non-diabetic renal disease
Renal biopsyIf diagnostic uncertainty (e.g. nephritic features, active sediment, T1DM without retinopathy) — to exclude glomerulonephritis or other pathology
1
Glycaemic control
- Optimise HbA1c (target individualised — generally ≤48–53 mmol/mol)
- SGLT2 inhibitors: dapagliflozin or empagliflozin — proven renoprotective benefit independent of glucose lowering. Use if eGFR ≥20 mL/min
- Metformin: can continue with caution down to eGFR 30. Stop if <30 or acute illness (lactic acidosis risk)
- GLP-1 RAs: cardiovascular and potential renal benefit. Use alongside SGLT2i where indicated
- Insulin: adjust doses for declining GFR (reduced insulin clearance → hypoglycaemia risk)
2
Renin-angiotensin system blockade
- ACE inhibitor (ramipril) or ARB (losartan, candesartan): START if ACR ≥3 mg/mmol — even if normotensive
- Titrate to maximum tolerated dose
- Check U&Es 1–2 weeks after starting or dose change — tolerate up to 25% creatinine rise and K⁺ up to 5.5
- Do NOT combine ACEi + ARB (increased AKI and hyperkalaemia risk — no additional benefit)
3
Blood pressure management
- Target: <130/80 mmHg in diabetic kidney disease (NICE)
- ACEi/ARB first-line (dual renoprotective and antihypertensive effect)
- Add: CCB (amlodipine) or thiazide-like diuretic (indapamide) if additional agents needed
4
Additional renoprotective therapies
- Finerenone (non-steroidal MRA): additional renoprotective + CV benefit in T2DM with CKD + albuminuria. Add to ACEi/ARB + SGLT2i if ACR ≥3 and eGFR ≥25
- Statin: atorvastatin 20 mg — cardiovascular risk reduction (very high CVD risk in DKD)
- Smoking cessation: smoking accelerates nephropathy progression
- Dietary sodium restriction: <6 g/day salt
5
Advanced CKD management
- Refer to nephrology if eGFR <30, or ACR >70, or rapid decline (>25% in 12 months or >15 mL/min/year)
- Manage CKD complications: anaemia (EPO), bone mineral disorder (phosphate binders, vitamin D), acidosis (bicarbonate)
- Renal replacement therapy planning: dialysis access preparation if eGFR <15–20, transplant assessment
Complications
- ESRD: Requiring dialysis or transplantation — leading cause of ESRD in UK
- Cardiovascular disease: CKD + diabetes = very high CVD risk. Cardiovascular mortality is the leading cause of death (not ESRD)
- Hyperkalaemia: From CKD + ACEi/ARB + SGLT2i + finerenone. Monitor potassium closely
- Anaemia: EPO deficiency — normocytic normochromic. Treat with ESAs (epoetin, darbepoetin)
- CKD-mineral bone disorder: Hyperphosphataemia, secondary hyperparathyroidism, vitamin D deficiency → renal osteodystrophy
- Hypoglycaemia risk: Reduced insulin clearance in CKD → drug accumulation → hypoglycaemia (reduce insulin/SU doses)
UKMLA Exam Tips
- 1ACR screening: annual from diagnosis (T2DM) or from 5 years/age 12 (T1DM). ACR ≥3 = start ACEi/ARB
- 2ACEi/ARB for ALL patients with ACR ≥3 — even if normotensive. This is RENOPROTECTIVE, not just antihypertensive
- 3SGLT2 inhibitors (dapagliflozin, empagliflozin): proven renoprotective + CV benefit. Now standard alongside ACEi/ARB in DKD
- 4No retinopathy + nephropathy = consider NON-DIABETIC renal disease. Most diabetic nephropathy patients also have retinopathy
- 5eGFR decline >25% after starting ACEi/ARB: tolerate up to 25% creatinine rise. >30% rise = stop and investigate
- 6Hypoglycaemia risk increases as GFR falls — insulin clearance reduced. Reduce insulin/SU doses proactively
- 7Finerenone: newest addition to DKD armamentarium — non-steroidal MRA with proven renoprotective + CV benefit
practicetest your knowledge on diabetic nephropathyApply what you've learnt with UKMLA-style questions from the iatroX Q-Bank — endocrine and beyond.
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