Teaching points

• Incretin GI losses (nausea, vomiting, poor intake) plus a RAAS blocker ± NSAID recreate the classic “triple whammy” — a prerenal AKI in which volume depletion, not the drug’s renal handling, is the driver.
• FENa <1%, high urine osmolality, and a bland sediment distinguish prerenal from tubular injury.
• Manage with isotonic fluid, hold the RAAS blocker and NSAID, pause the incretin — and teach sick-day rules at every titration.

Teaching points

• On a RAAS-inhibitor + SGLT2-inhibitor foundation, meaningful residual risk remains; among glucose-lowering drugs, only SGLT2 inhibitors and GLP-1 receptor agonists carry proven kidney and cardiovascular benefit.
• In FLOW, weekly semaglutide reduced major kidney events by 24% (HR 0.76, 95% CI 0.66–0.88), with fewer cardiovascular events and lower mortality — additive to the SGLT2 inhibitor and largely independent of A1c.
• This additive approach is now reflected in KDIGO 2024 and the 2026 multisociety CKM guidance.

Teaching points

• Obesity-related glomerulopathy is a hyperfiltration lesion, not primary FSGS — so it does not respond to steroids.
• The treatment fork worth teaching explicitly: start a RAAS blocker + SGLT2 inhibitor (protective even without diabetes — DAPA-CKD, EMPA-KIDNEY).
• Then add weight loss (a GLP-1 RA or bariatric surgery) as root-cause therapy — treating the obesity to treat the kidney.

Teaching points

• Creatinine is a by-product of muscle, so in sarcopenic obesity the body makes less of it and creatinine-based eGFR reads falsely high — masking real CKD.
• Cystatin C is muscle-independent; here the combined creatinine–cystatin C eGFR (CKD-EPI 2021) falls from 82 to 45, reclassifying the patient as CKD G3a.
• KDIGO 2024 recommends confirming the GFR category with eGFRcr–cys whenever creatinine may mislead — which also prevents unsafe dosing of renally-cleared drugs.

Teaching points

• Semaglutide, dulaglutide, liraglutide, and tirzepatide need no renal dose adjustment and are used across CKD stages; only exenatide (renally cleared) is avoided at eGFR <30.
• The real hazard is not drug accumulation but GI-loss volume depletion and prerenal AKI on a RAAS inhibitor + diuretic + SGLT2 inhibitor — so titrate slowly, counsel hydration, and teach sick-day rules.
• Keep the RAASi + SGLT2i foundation; the GLP-1 adds weight, cardiovascular, and kidney benefit.

Teaching points

• On an SGLT2 inhibitor, glucose can stay near-normal while a full ketoacidosis develops — glycosuria hides the number and the drug promotes ketogenesis, here tipped over by incretin-driven poor intake.
• In any unwell patient on an SGLT2 inhibitor, a normal glucose does not reassure: check β-hydroxybutyrate and the anion gap.
• Stop the SGLT2 inhibitor, give isotonic fluid and insulin with co-infused dextrose.

Teaching points

• The fourth pillar is finerenone, a non-steroidal mineralocorticoid-receptor antagonist: residual albuminuria on a RAAS blocker plus an SGLT2 inhibitor reflects ongoing mineralocorticoid-receptor–driven inflammation and fibrosis.
• In the FIDELITY pooled analysis (13,026 patients with type 2 diabetes and CKD on optimized RAAS blockade), finerenone cut the composite kidney outcome by 23% (HR 0.77) with cardiovascular benefit — the right answer here, not dual RAAS blockade or high-dose spironolactone.
• Eligible if eGFR >25 and UACR ≥30 with potassium ≤4.8–5.0; start 10–20 mg and recheck K at ~4 weeks. Keeping the SGLT2 inhibitor on board lowers the hyperkalemia risk — the four pillars (RAASi + SGLT2i + GLP-1 RA + finerenone) target the residual risk that keeps DKD progressing.

Teaching points

• Reported eGFR is indexed to a body surface area of 1.73 m²; in someone much larger than 1.73 m² that number no longer equals the clearance you dose against. De-index it: absolute GFR = eGFR × (BSA ÷ 1.73) — here ≈ 70 mL/min, so a reflexive dose reduction would underdose.
• The opposite trap: Cockcroft-Gault with actual body weight overestimates creatinine clearance by 10–40% in obesity (adipose tissue barely makes creatinine) — that direction overdoses. The pragmatic fix is adjusted body weight: IBW + 0.4 × (actual − IBW).
• Confirm with cystatin C or a measured GFR; this matters most for narrow-margin drugs (DOACs, LMWH, vancomycin, aminoglycosides, carboplatin). KDIGO 2024 recommends de-indexing eGFR for drug dosing at the extremes of body size.

Teaching points

• A real tension: KDOQI suggests 0.6–0.8 g/kg/day for non-dialysis diabetic CKD to protect the kidney (opinion-level), but ~30% of the weight lost on a GLP-1 is lean mass and older women are at highest risk of sarcopenic obesity — over-restricting during active weight loss accelerates muscle loss.
• The hidden variable is which body weight you calculate against: actual (98 kg × 0.8 ≈ 78 g) overestimates, ideal (57 kg ≈ 46 g) underestimates, adjusted (67 kg ≈ 54 g) is the pragmatic middle. Adjusted body weight = ideal BW + 0.25 × (actual − ideal).
• Plan: aim ~0.8 g/kg adjusted BW (~54 g/day), do not restrict aggressively while actively losing weight; distribute protein (20–30 g leucine-rich per meal), fuel adequately (25–35 kcal/kg/day), add resistance training and monitor muscle (handgrip and function). The goal is fat loss, not muscle loss.

Teaching points

• Yes — obesity injures the kidney directly: excess weight drives glomerular hyperfiltration and glomerulomegaly (the physiology behind obesity-related glomerulopathy), a modifiable renal risk factor.
• In a matched cohort, bariatric surgery was associated with a 58% lower risk of significant kidney-function decline (≥30% eGFR drop; HR 0.42), persisting after adjustment; meta-analyses show albuminuria regresses and eGFR/hyperfiltration improve.
• Caveats: the evidence is observational (a shared, individualized decision); watch perioperative AKI and, after gastric bypass, enteric hyperoxaluria (oxalate nephropathy, stones); re-check renally-cleared drug doses as weight falls. RAAS blockade and an SGLT2 inhibitor remain the foundation.

Teaching points

• Yes, and the reason is mechanistic: SGLT2-inhibitor renoprotection is largely glucose-independent — blocking proximal sodium/glucose reabsorption restores tubuloglomerular feedback and lowers intraglomerular pressure, with or without diabetes.
• In DAPA-CKD, dapagliflozin cut the kidney/CV composite by 39% (HR 0.61), with an at-least-as-large effect in the non-diabetic subgroup (HR 0.50); EMPA-KIDNEY (~54% non-diabetic) reduced kidney progression or CV death by ~29% (HR 0.71). KDIGO 2024: offer an SGLT2 inhibitor for CKD with eGFR ≥20 and UACR ≥200 on a RAAS blocker, regardless of diabetes.
• Start well: keep the ARB; expect a small reversible eGFR “dip” of ~3–5 mL/min in the first weeks (hemodynamic, not injury); counsel genital mycotic infection and sick-day / peri-procedure holds. Bonus: SGLT2 inhibitors modestly lower serum potassium.

Teaching points

• Usually not: discontinuing RAAS blockade or an MRA for mild hyperkalemia is associated with higher mortality and more cardiovascular events — you trade a manageable lab value for the loss of proven organ protection. And 5.4 is below finerenone’s hold threshold (>5.5): optimize and recheck.
• Work the potassium in layers: confirm it is real (rule out pseudohyperkalemia); dietary counseling (beware potassium-chloride “salt substitutes”); keep the SGLT2 inhibitor (it lowers potassium); correct metabolic acidosis; add or up-titrate a loop/thiazide diuretic if volume allows; if persistent, a potassium binder (patiromer or sodium zirconium cyclosilicate) — in DIAMOND, patiromer enabled patients to stay on target-dose RAAS therapy.
• For finerenone: hold if potassium >5.5, restart when <5.0. The SGLT2 inhibitor and MRA are complementary — one offsets the other’s hyperkalemia risk. Potassium is manageable; the pillars are not easily replaced.