Chronic kidney disease

Definition and staging

CKD is GFR <60 mL/min or kidney damage (albuminuria ≥30 mg/day) persisting ≥3 months (). An acute Cr rise is AKI until it lasts 3 months.

eGFR is extrapolated from creatinine or cystatin C and lies when filtration is changing in AKI (). Race in older eGFR equations undertreated Black patients and worsened transplant inequity; CKD-EPI 2021 does not include race ().
Cystatin C is made by all nucleated cells and is less affected by sex, age, size, and nutrition than creatinine (ExpRev 2020;25:10). Use combined eGFRCr-Cys when creatinine eGFR is untrustworthy (muscle-mass extremes, interfering drugs).
Etiology (USRDS 2018): DM 47%, HTN 28%, GN 7%, cystic kidney 3%, other (including tubulointerstitial) 15%.
Epidemiology: 15% of US adults. ESRD prevalence is 4-fold higher in Black than White patients (USRDS 2021). 13% of Black individuals in the US carry a high-risk APOL1 genotype, which confers ↑CKD risk.
Physiologic mean eGFR decline is ~1 mL/min/1.73 m² per year from a peak of ~120 in the third decade (J Nephrol 2014;27:635).

Risk is a heat map of GFR category (G1–G5) × albuminuria (A1–A3). Albuminuria multiplies risk at any GFR.

Band	What you do
G1–G3a	Risk-factor reduction
G3a–G3b	Evaluate and treat complications
G4 (or A3)	Nephrology referral; prepare for RRT / transplant
G5	RRT if indicated; transplant evaluation

Slowing progression

BP: goal <120/80 (). Mortality benefit with intensive SBP <120 mmHg ((20); (10449)). If proteinuria: ACE inhibitor / ARB. If edema and eGFR <30: loop; if eGFR >30: thiazide (chlorthalidone is an option in selected advanced CKD — ). Resistant HTN or HF: spironolactone.
Proteinuria independently predicts death and CKD progression. Goal <300 mg/day. Start RAAS blockade and uptitrate as tolerated (). If CKD with eGFR >20 plus T2DM, or UACR ≥200 mg/g, add an SGLT2 inhibitor to ↓ progression (). If T2DM, GFR ≥25, ACE/ARB maximized, SGLT2i started, K ≤4.8, and albuminuria still ≥30 mg/day: consider finerenone (non-steroidal MRA; ↓CV risk via fewer HF exacerbations — (23)).
Diabetes: HbA1c <7%. SGLT2i (if eGFR >20–30) and GLP-1 agonists (eGFR >30) both ↓ CKD progression (; ). Metformin is safe at eGFR >30–45. Insulin is safe at any eGFR — dose-adjust as clearance falls.
CVD risk is 2–4× the general population. Statin if age >50, eGFR <60, and not on dialysis / transplant (). SGLT2 inhibitors ↓ CKD progression, mortality, and CVD outcomes (). No benefit to an initial invasive vs conservative strategy in stable CAD plus advanced CKD with moderate/severe ischemia (ISCHEMIA-CKD, ).
Nephrotoxins: avoid NSAIDs, chronic PPIs, unnecessary contrast; dose antibiotics, tacrolimus, statins, and opioids to GFR.
Nutrition: nephrocaps (B-complex / C) in HD patients; Na <2 g/day; more fruit/vegetables than red meat in G3b–G5; protein 0.8 g/kg/day in G3–G5 (), not to exceed 1.3 g/kg/day (does not apply on dialysis); restrict K / phos as needed.
Monitoring: Cr and electrolytes, PTH, CBC, iron studies every 4–12 months. Annual UAlb/Cr and UProt/Cr, 25-OH vitamin D. Renal US at diagnosis.
Referral: GFR 30–45, sudden drop in GFR, severe proteinuria (Alb:Cr >300), UA with blood and protein plus ↓GFR, resistant HTN.
Prognosis: Tangri kidney-failure risk equation (), especially G3–G5, for RRT planning.

Complications

Type	Ca	PO4	PTH	Vit D	Pathophysiology
1° hyperPTH	↑	↓	↑	nl	Excess PTH from the parathyroid gland
2° hyperPTH (↓ vit D)	↓	↓	↑	↓	Decreased Ca absorption stimulates PTH
2° hyperPTH (CKD)	nl/↓	↑	↑	nl/↓	↓ PO4 excretion increases PTH secretion
3° hyperPTH	↑	↑	↑↑	nl/↓	Longstanding 2° hyperPTH → gland hyperplasia

Mineral and bone disorder: check Ca, PO4, ALP, 25-OH vitamin D (1,25-OH fluctuates) (). If PTH is rising or persistently above goal (2–9× ULN by CKD stage): restrict dietary phos, non-calcium binders (sevelamer preferred, with meals and snacks — ); add calcitriol if PTH remains high and calcium is low/normal. Severe / refractory PTH >1,000: calcimimetic vs parathyroidectomy if medical therapy fails.
Anemia: Hb <13 (men), <12 (women). Screen annually if eGFR >45, every 6 months if <45, every 3–6 months if already anemic. Goal Hb 10–11.5 (Kidney Int 2012). Iron: consider 1 g IV empirically if TSAT <20% and/or ferritin <100 ng/mL. If TSAT 20–30% and ferritin <500, challenge with iron or start an ESA. Recheck q3 months on ESA (). If iron-replete and Hb <10, consider an ESA (fewer transfusions, less iron overload and antibody formation). ESA is contraindicated in cancer, SBP >160, HF, stroke. Hb >13 on ESA raises stroke risk ().
Metabolic acidosis: NaHCO3 starting 650 mg 2–3×/day, titrate to 1,300 mg TID, goal HCO3 in the normal range (>18 mEq/L, ); avoid >29 mEq/L (↑ mortality). Slows CKD progression and improves bone health ().
Uremic bleeding: treat in context or pre-procedure. DDAVP 0.3–0.4 mcg/kg × 1, max 40 mcg.
HD access: no venipuncture in the non-dominant arm; no BP on an AVF arm; avoid subclavian / PICC lines (central stenosis precludes future AVF) → prefer IR small-bore tunneled IJ. Prefer left IJ CVC in case HD is needed.