Nephrology
Chronic Kidney Disease
Five stages of nephron loss — and the five drugs that slow them
CKD is sustained eGFR <60 or kidney damage markers for ≥3 months. Diabetes drives ~40% of ESRD; hypertension drives ~25%. About 15% of US adults have CKD, most of them undiagnosed. Stage 5 (eGFR <15) means dialysis or transplant.
- CKD prevalence~15% of US adults
- Diagnostic thresholdeGFR <60 for ≥3 months
- Diabetes share#1 cause, ~40% of ESRD
- HTN share#2 cause, ~25%
- SGLT2i benefit~30% progression risk reduction
- 5-yr survival~40% dialysis / ~80% transplant
Interactive visualization
Watch a kidney walk through the five CKD stages — shrinking, scarring, with eGFR collapsing toward dialysis.
Watch the 60-second explainer
A condensed visual walkthrough — narrated, captioned, under a minute.
The KDIGO staging system
CKD is staged on two axes: estimated GFR and albuminuria. The eGFR axis runs G1 (≥90) through G5 (<15); the albuminuria axis runs A1 (<30 mg/g) through A3 (>300 mg/g). A patient with eGFR 75 and UACR 800 — G2A3 — has a worse prognosis than a patient with eGFR 35 and UACR 12 (G3bA1), even though the second looks worse on eGFR alone. The KDIGO heatmap that combines them is the right way to think about risk: red zones (G4–5 anything, or A3 from G3a down) carry cardiovascular and renal event rates many times higher than the green zone.
Worked clinical example — the diabetic patient
A 62-year-old woman with type 2 diabetes for 18 years comes for routine follow-up. Creatinine 1.4 mg/dL (CKD-EPI eGFR 42 mL/min/1.73 m²), UACR 480 mg/g, BP 142/88, HbA1c 8.1%, LDL 118. By KDIGO she is G3bA3 — high risk for both progression and cardiovascular events. The plan: empagliflozin 10 mg daily (proven in EMPA-KIDNEY to slow progression at this eGFR), losartan 50 mg titrating to 100 mg (RAAS blockade for albuminuria), continue metformin (safe down to eGFR 30, hold below), atorvastatin 40 mg, BP target <130/80 (add a thiazide-like — chlorthalidone), referral to nephrology, follow-up creatinine and K in 1–2 weeks (RAAS plus SGLT2i may bump creatinine 10–25% acutely — accept this as a hemodynamic effect that signals long-term protection, not injury).
CKD stages at a glance
| Stage | eGFR (mL/min/1.73 m²) | What's happening | Clinical actions |
|---|---|---|---|
| G1 | ≥90 with damage | Normal GFR, microalbuminuria or imaging finding | Treat cause, BP <130/80, RAAS if albuminuria, lifestyle |
| G2 | 60–89 with damage | Mild GFR loss | Same as G1; SGLT2i if UACR ≥200 |
| G3a | 45–59 | Mild–moderate; CV risk rises | Statin, refer if rapid decline or A3 |
| G3b | 30–44 | Anemia, hyperPTH start; nephrologist now | SGLT2i, finerenone (DM), bone mineral panel |
| G4 | 15–29 | Symptoms emerge; plan RRT | AV fistula creation, transplant listing, vaccinations |
| G5 | <15 (ESRD) | Uremia, dialysis or transplant | Hemodialysis, PD, or pre-emptive transplant |
The five drugs that slow CKD
- RAAS blockade (ACEi or ARB). Decades-old foundation. Reduces glomerular hyperfiltration via efferent dilation; slows albuminuria-driven progression. Tolerate up to 30% creatinine rise. Hold transiently in volume depletion.
- SGLT2 inhibitors. Dapagliflozin (DAPA-CKD), empagliflozin (EMPA-KIDNEY). Approved for CKD with or without diabetes down to eGFR ~20. ~30% reduction in composite kidney/CV outcomes. Watch for genitourinary infections, euglycemic DKA in T1DM (avoid).
- Non-steroidal MRA — finerenone. FIDELIO-DKD: 18% reduction in kidney composite, 14% in CV composite in diabetic CKD. Less hyperkalemia than spironolactone.
- GLP-1 receptor agonists. FLOW (semaglutide, 2024): 24% reduction in major kidney events in T2DM + CKD. Also helps weight, A1c, CV outcomes.
- Statin. Reduces CV death — the leading killer in CKD — by ~20%. SHARP trial confirmed benefit; CV risk equivalent of established CAD by Stage 3b.
Complications you treat alongside the GFR
- Anemia of CKD. EPO falls as peritubular fibroblasts die. ESAs (epoetin, darbepoetin) titrated to Hb 10–11.5 g/dL — higher targets increased CV events in TREAT. IV iron first; HIF-prolyl hydroxylase inhibitors (roxadustat, daprodustat) are emerging oral alternatives.
- CKD-MBD (mineral and bone disorder). Phosphate retention + low calcitriol → secondary hyperparathyroidism. Treat with phosphate binders (sevelamer, lanthanum, ferric citrate), active vitamin D (calcitriol, paricalcitol), calcimimetics (cinacalcet, etelcalcetide) when PTH stays high.
- Metabolic acidosis. Impaired ammoniagenesis. Oral sodium bicarbonate to keep serum HCO₃ >22; lowers progression risk and preserves muscle.
- Hyperkalemia. Common on RAAS + SGLT2 + finerenone. Patiromer or sodium zirconium allow staying on guideline-directed therapy instead of stopping it.
- Cardiovascular disease. Half of CKD deaths. Aspirin in established disease, statin, LVH screening, BP control.
Common misconceptions
- "My creatinine is normal so my kidneys are fine." Creatinine reflects muscle mass — an elderly cachectic patient with Cr 0.9 may have eGFR 40. Check eGFR and UACR.
- "ACEi raised my creatinine — stop it." A 10–25% rise within weeks of starting RAAS or SGLT2i is hemodynamic and predicts long-term renal protection. Only stop if rise >30%, hyperkalemia, or hypotension.
- "Drink lots of water for CKD." Hydration matters in stones and dehydration — but excess water in advanced CKD with low UOP causes hyponatremia. Match input to output.
- "Avoid bananas because of K." Diet matters only at later stages. Plant-based diets are protective overall; selective restriction guided by labs, not folk rules.
- "Dialysis is a death sentence." Five-year dialysis survival ~40% — sobering, but for many patients it is years of meaningful life and a bridge to transplant.
Frequently asked questions
What are the 5 stages of CKD?
KDIGO 2012 staging by eGFR in mL/min/1.73 m². G1: ≥90 with markers of damage. G2: 60–89 with damage. G3a: 45–59. G3b: 30–44. G4: 15–29. G5: <15, end-stage renal disease — RRT generally required. Albuminuria layers on top: A1 <30 mg/g, A2 30–300, A3 >300. The KDIGO heatmap (eGFR × albuminuria) drives prognosis better than eGFR alone.
What causes CKD?
Globally and in the US: diabetes #1 (~40% of new ESRD), hypertension/nephrosclerosis #2 (~25%), glomerulonephritis #3 (~10%), polycystic kidney disease (~3%). Other drivers: chronic urinary obstruction, recurrent stones or pyelonephritis, lithium, lupus and other systemic vasculitides, HIV-associated nephropathy, congenital anomalies (CAKUT).
How do you slow CKD progression?
Five evidence-backed pillars: (1) Blood pressure <130/80 with RAAS blockade. (2) SGLT2 inhibitors — dapagliflozin (DAPA-CKD) and empagliflozin (EMPA-KIDNEY) cut CKD progression and CV death by 25–30% even without diabetes. (3) Finerenone for diabetic CKD. (4) GLP-1 RAs for diabetes + CKD. (5) Avoid NSAIDs, treat hyperlipidemia, stop smoking, restrict dietary protein to 0.6–0.8 g/kg/day in late CKD.
What complications come with advanced CKD?
Anemia (EPO deficiency — ESAs targeting Hb 10–11.5 and IV iron). Renal osteodystrophy / CKD-MBD (phosphate binders, calcimimetics, vitamin D analogs). Metabolic acidosis (sodium bicarbonate to keep HCO₃ >22). Hyperkalemia (patiromer, sodium zirconium). Cardiovascular — the leading cause of death; CV risk equivalent to coronary artery disease by Stage 3b.
When does CKD need dialysis?
eGFR <15 (Stage 5) is the threshold to plan and prepare. Actual initiation is symptom-driven, not number-driven: uremic symptoms, fluid overload not controlled with diuretics, refractory hyperkalemia or acidosis. The IDEAL trial showed early start (eGFR 10–14) was no better than late (5–7). Modality choice: hemodialysis, peritoneal dialysis, or transplant.
How is eGFR calculated?
CKD-EPI 2021 creatinine equation — race-free, replacing the 2009 version. Inputs: serum creatinine, age, sex. Estimates GFR in mL/min/1.73 m². Limitations: creatinine reflects muscle mass — overestimates GFR in cachexia and elderly. Cystatin C-based eGFR is the recommended confirmatory test when creatinine eGFR is borderline. Pair with urine albumin-creatinine ratio (UACR) on a spot sample.
Is kidney transplant always better than dialysis?
For most candidates, yes. Five-year patient survival on dialysis is ~40%, on deceased-donor transplant ~80%, on living-donor transplant ~90%. Pre-emptive transplant (before any dialysis) carries the best outcomes. Wait times for deceased-donor kidney 3–7 years in the US. Immunosuppression — typically tacrolimus + mycophenolate + low-dose prednisone — carries infection and malignancy risk for life.