End-Stage Renal Disease and Dialysis
Stage 5 CKD (eGFR <15) requiring renal replacement therapy or kidney transplant.
Also known as: ESRD, ESKD, kidney failure, dialysis, hemodialysis, peritoneal dialysis
Overview
Permanent loss of kidney function requiring renal replacement therapy (RRT) — hemodialysis (HD), peritoneal dialysis (PD), or kidney transplantation — to sustain life. Generally corresponds to eGFR <15 mL/min/1.73 m² (CKD stage G5) with uremic symptoms or complications.
Epidemiology
Over 800,000 Americans live with ESRD. Diabetes (~45%) and hypertension (~30%) are the dominant causes. Black patients have nearly 4× the incidence of white patients.
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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 reversible
- Advanced CKD without indication for RRT — eGFR <15 but asymptomatic, normal electrolytes/volume; continue conservative management
- Hepatorenal syndrome — Advanced cirrhosis with progressive AKI unresponsive to volume; bridge to transplant
- Cardiorenal syndrome — Heart failure with renal hypoperfusion; ultrafiltration may be needed but underlying cardiac issue drives course
Diagnostic 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 |
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 Disease
- USRDS 2023 — United States Renal Data System Annual Data Report 2023
- KDOQI 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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