Diabetic nephropathy and its staging

Definition. Diabetic nephropathy is persistent albuminuria with progressive decline in GFR in a person with diabetes, usually accompanied by retinopathy and hypertension, in the absence of another renal disease. It is one of the frequent secondary glomerulopathies in the elderly.

Mogensen staging (classical, five stages). Stage I — hyperfiltration and renal hypertrophy. Stage II — silent stage, GBM thickening and mesangial expansion with normoalbuminuria. Stage III — incipient nephropathy, microalbuminuria 30–300 mg/day. Stage IV — overt nephropathy, macroalbuminuria >300 mg/day, hypertension, falling GFR. Stage V — end-stage renal disease.

Current KDIGO "CGA" staging is now used in practice: Cause + G1–G5 by eGFR (≥90, 60–89, 45–59, 30–44, 15–29, <15) + A1–A3 by albuminuria (UACR <30, 30–300, >300 mg/g). Risk of progression is graded green–yellow–orange– red on this grid.

Histopathology. GBM thickening, mesangial expansion, Kimmelstiel–Wilson nodular glomerulosclerosis, hyaline arteriolosclerosis of both afferent and efferent arterioles. RPS classification: Class I–IV with separate interstitial and vascular scores.

Risk factors. Duration of diabetes, poor glycaemic control, hypertension, smoking, dyslipidaemia, obesity, genetic susceptibility, and pre-existing age-related nephrosclerosis.

Geriatric-specific caveats. A normoalbuminuric CKD phenotype is common; sarcopenia lowers serum creatinine so eGFR overestimates true renal function; ageing itself brings glomerulosclerosis and aglomerular circulation, so a fall in eGFR is often multifactorial.

Screening. Annual UACR plus eGFR from the time of diagnosis in type 2 diabetes. Confirm an abnormal UACR on 2 of 3 samples over 3–6 months; exclude fever, infection, exercise, heart failure and menstruation as transient causes.

When to suspect non-diabetic renal disease and biopsy: absence of retinopathy, active urinary sediment (RBC casts), short duration of diabetes, abrupt onset of heavy proteinuria, rapid unexplained fall in GFR, or features of a systemic disease such as myeloma or vasculitis.

Management pillars. Individualised glycaemic control (see targets below), blood pressure control, RAS blockade with a single agent — ACE inhibitor or ARB, never both — statin therapy, smoking cessation, protein moderation and avoidance of nephrotoxins (NSAIDs, aminoglycosides, contrast). Accept a creatinine rise of up to 30% after starting a RAS blocker; monitor potassium.

Complications and prognosis. Progression to ESRD, very high cardiovascular mortality, hyperkalaemia, anaemia of CKD, CKD–mineral and bone disorder, and increased drug toxicity. In the very old, the competing risk of death exceeds the risk of reaching dialysis — this must shape how aggressively you treat. Patient group HbA1c target Blood pressure Lipids Functionally independent / non-frail 7.0–7.5% <140/90 mmHg Statin unless contraindicated; intensity Functionally dependent 7.0–8.0% <140/90 mmHg by CVD risk Frail / highly comorbid / poor health <8.0–8.5% <150/90 mmHg Consolidated from EDWPOP, IDF and ADA targets as tabulated in Pathy's. Avoid HbA1c <6% — a J/U-shaped relationship exists, with optimal HbA1c around 7.5–8%.

FLOW trial (NEJM 2024) — the fourth pillar. In 3,533 adults with type 2 diabetes and CKD (mean age 66.6 years), semaglutide 1 mg weekly reduced major kidney disease events by 24%, MACE by 18% and all-cause death by 20%, and slowed eGFR decline by 1.16 mL/min/1.73 m²/year. Benefit was consistent across all strata of CKD severity. Current therapy of diabetic kidney disease is therefore four-pillar: RAS blocker + SGLT2 inhibitor + finerenone + GLP-1 receptor agonist.

ADA Standards of Care 2026 (Section 13, endorsed by the American Geriatrics Society). A tighter blood pressure goal for those at high cardiovascular or kidney risk and a more relaxed goal for most other older adults. Also: in kidney failure, recent blood loss or erythropoietin therapy, HbA1c is unreliable — use blood glucose monitoring and/or CGM for goal setting instead; CGM is now recommended for older adults with type 2 diabetes on insulin.