Stage 5 CKD (eGFR <15) requiring renal replacement therapy or kidney transplant.
Also known as: ESRD, ESKD, kidney failure, dialysis, hemodialysis, peritoneal dialysis
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Risk factors Diabetic and hypertensive nephropathy (combined >70%) Glomerulonephritis, PKD, recurrent AKI, obstructive uropathy Non-adherence with ACEi/ARB or BP control Late nephrology referral (eGFR <30 without prior care) Cardiovascular disease, age >65 Pathophysiology Loss of >90% of nephrons impairs solute clearance, fluid balance, acid-base regulation, and endocrine functions (EPO, calcitriol). Retained uremic toxins (urea, creatinine, beta-2 microglobulin, indoxyl sulfate, p-cresyl sulfate) drive multisystem dysfunction including pericarditis, encephalopathy, platelet defects, and immune impairment.
Clinical presentation Symptoms Fatigue, weakness, anorexia, nausea, vomiting Pruritus, restless legs, muscle cramps, sleep disturbance Dyspnea from volume overload or anemia Cognitive slowing, confusion, seizures (uremic encephalopathy) Easy bruising or bleeding (uremic platelet dysfunction) Signs / physical exam Volume overload: edema, elevated JVP, crackles, hypertension Sallow uremic complexion, uremic frost (rare in modern era) Pericardial friction rub (uremic pericarditis — RRT indication) Asterixis, myoclonus in advanced uremia AV fistula thrill/bruit on physical exam in established HD patients Classic findings Uremic fetor (urine-like breath odor), uremic frost on skin, and pericardial rub are late findings demanding urgent dialysis initiation.
Differential diagnosis Acute on chronic kidney disease — Superimposed acute insult — volume depletion, nephrotoxin, obstruction; potentially reversibleAdvanced CKD without indication for RRT — eGFR <15 but asymptomatic, normal electrolytes/volume; continue conservative managementHepatorenal syndrome — Advanced cirrhosis with progressive AKI unresponsive to volume; bridge to transplantCardiorenal syndrome — Heart failure with renal hypoperfusion; ultrafiltration may be needed but underlying cardiac issue drives courseDiagnostic workup Diagnostic criteria RRT indications (AEIOU): refractory Acidosis, Electrolyte disturbance (especially hyperkalemia), Ingestion of dialyzable toxin, Overload (refractory pulmonary edema), Uremia (pericarditis, encephalopathy, bleeding). Asymptomatic eGFR <6 is also commonly an indication.
Labs Serum creatinine, BUN, electrolytes (especially K, HCO3, Ca, phosphate) CBC (normocytic anemia of CKD), iron studies Intact PTH, 25-OH vitamin D Albumin (nutritional marker), lipid panel Hepatitis B surface antibody status (vaccinate if non-immune) Imaging Renal ultrasound — small echogenic kidneys (or large in PKD, diabetes, amyloid) Echocardiogram pre-RRT and annually — high CVD burden Vascular mapping ultrasound for AV access planning Diagnostic algorithm Modality Schedule Access Pros Cons In-center HD 3-4 h, 3×/wk AV fistula/graft Supervised, no home equipment Travel, hemodynamic shifts, schedule Home HD Daily/nocturnal AV fistula/graft Better BP and outcomes, flexibility Training burden, partner required CAPD (PD) 4 exchanges/day PD catheter Independence, residual function Peritonitis risk, manual exchanges APD (PD) Overnight cycler PD catheter Daytime free Equipment dependent Transplant N/A N/A Best survival, quality of life Surgical risk, immunosuppression, rejection
Renal replacement therapy modality comparison. Choice individualized to patient lifestyle, comorbidities, and access. Treatment First-line Multidisciplinary CKD clinic and modality education starting at eGFR <30 Vascular access: AV fistula preferred (created 6+ months before HD start); AV graft if poor vessels; tunneled catheter only for urgent start Hemodialysis — typically 3-4 h sessions × 3/week in-center; nocturnal or home HD options available Peritoneal dialysis — continuous ambulatory (CAPD) or automated (APD) using PD catheter; preserves residual renal function Kidney transplantation — best long-term survival; living donor preferred; preemptive transplant ideal Second-line / adjunct ESA — epoetin alfa, darbepoetin alfa — target Hb 10-11.5 Iron — IV ferric gluconate, iron sucrose, ferric carboxymaltose — most HD patients require IV iron Phosphate binders — sevelamer, lanthanum, calcium acetate, ferric citrate, sucroferric oxyhydroxide — with meals Active vitamin D — calcitriol, paricalcitol, doxercalciferol Calcimimetics — cinacalcet (oral), etelcalcetide (IV) — for secondary hyperparathyroidism Conservative (non-dialytic) management — for frail or terminal patients prioritizing quality of life over longevity Complications Cardiovascular disease (leading cause of death, ~50%) Access complications: thrombosis, infection, steal syndrome, aneurysm Peritonitis (PD), exit-site infection, catheter malfunction CKD-MBD: vascular calcification, calciphylaxis, fractures Dialysis-related amyloidosis (β2-microglobulin) — carpal tunnel, arthropathy Hypotension during HD, disequilibrium syndrome at initiation Depression, cognitive impairment, sexual dysfunction PANCE pearls Avoid placing PIVs, blood draws, or BP cuffs on the AV fistula arm — preserve access. Hyperkalemia in ESRD: emergent dialysis if EKG changes or K >6.5 not responsive to medical management. Calciphylaxis: painful violaceous skin lesions, often on adipose areas; sodium thiosulfate, lower phosphate, normalize calcium-phosphate product. PD peritonitis: cloudy effluent with WBC >100 (>50% PMN); empiric intraperitoneal cefazolin + ceftazidime (or vancomycin if MRSA risk). Kidney transplant doubles life expectancy vs HD and is more cost-effective; refer early — even before dialysis (preemptive). References KDIGO 2024 — KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney DiseaseUSRDS 2023 — United States Renal Data System Annual Data Report 2023KDOQI 2020 — KDOQI Clinical Practice Guideline for Vascular Access: 2019 Update (AJKD 2020)ISPD 2022 — ISPD Peritonitis Recommendations: 2022 Update on Prevention and Treatment
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