## Most Common Cause of Decreased GFR **Key Point:** Diabetes mellitus is the leading cause of chronic kidney disease (CKD) and progressive GFR decline globally, accounting for approximately 30–40% of all CKD cases in developed nations and an even higher proportion in India. ### Pathophysiology of Diabetic GFR Decline 1. **Hyperglycemia-induced glomerular injury** - Increased intraglomerular pressure via afferent arteriolar vasodilation - Advanced glycation end products (AGEs) accumulate in the glomerular basement membrane - Mesangial expansion and nodular glomerulosclerosis (Kimmelstiel-Wilson lesion) 2. **Progressive proteinuria → nephrotic syndrome → CKD** - Albuminuria appears within 5–10 years of diabetes onset - Without intervention, GFR declines ~10 mL/min/year **High-Yield:** Diabetes is the *single most common* cause of end-stage renal disease (ESRD) requiring dialysis or transplantation in both the USA and India. ### Why Other Options Are Less Common | Cause | Frequency | Clinical Context | |-------|-----------|------------------| | **Acute tubular necrosis (ATN)** | Common in ICU/acute settings | Reversible; accounts for ~45% of acute kidney injury, not chronic GFR decline | | **RPGN** | Rare (~1–5% of renal biopsies) | Presents acutely; causes rapid GFR loss but uncommon overall | | **Renal artery stenosis** | ~5–10% of hypertension | Significant but less frequent than diabetic nephropathy | **Clinical Pearl:** In an Indian patient presenting with CKD, always screen for diabetes (fasting glucose, HbA1c, urine albumin-to-creatinine ratio) before attributing GFR decline to other causes. **Mnemonic — Top 3 Causes of CKD Globally:** **DDH** - **D**iabetes mellitus (most common) - **D**iastolic hypertension (second most common) - **H**yperglomerulonephritis / Hereditary (third) [cite:Harrison 21e Ch 280]
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