At what glomerular filtration rate (GFR) or clinical indication is it recommended to initiate hemodialysis (HD) in patients with End-Stage Renal Disease (ESRD)?

Hemodialysis Initiation in ESRD

Initiate hemodialysis when GFR falls below 10 mL/min/1.73 m² AND clinical indications are present, rather than based on GFR alone, as early initiation provides no survival benefit and may accelerate loss of residual kidney function. 1

GFR Thresholds for Dialysis Consideration

Conservative management should continue until GFR decreases to <15 mL/min/1.73 m² unless specific clinical indications mandate earlier initiation. 2, 1

• Target GFR for initiation is approximately 10 mL/min/1.73 m² based on theoretical considerations and clinical practice data. 2, 1

• The mean GFR at dialysis initiation in clinical practice is 9.8 mL/min/1.73 m², with variations by age: 7-9 mL/min/1.73 m² for young and middle-aged adults, and 10-10.5 mL/min/1.73 m² for children and elderly patients. 2, 1

• When corrected for lead-time bias, there is no survival advantage to starting dialysis at higher GFR levels (>10 mL/min/1.73 m²). 2, 1

Absolute Clinical Indications That Override GFR

Initiate hemodialysis immediately when ANY of the following are present, regardless of GFR level: 1

Uremic Symptoms

• Pericarditis (uremic pericardial friction rub or effusion) 1
• Uremic encephalopathy (altered mental status, asterixis, seizures) 1
• Intractable nausea and vomiting unresponsive to antiemetics 1
• Uremic bleeding diathesis 1

Volume and Hemodynamic Complications

• Volume overload refractory to maximal diuretic therapy (loop diuretics at high doses) 1
• Uncontrolled hypertension despite maximal medical management with multiple antihypertensive agents 1

Metabolic Derangements

• Severe metabolic acidosis (typically pH <7.20 or bicarbonate <12 mEq/L) unresponsive to oral alkali therapy 1
• Hyperkalemia unresponsive to medical therapy (potassium binders, insulin/glucose, beta-agonists) 1

Nutritional Deterioration

• Protein-energy malnutrition that develops or persists despite vigorous attempts to optimize protein-energy intake, with no apparent cause other than low nutrient intake. 2, 1
• Progressive decline in edema-free body weight 1
• Falling serum albumin levels 1

Critical Evidence Against Early Dialysis Initiation

Early dialysis initiation (GFR >10 mL/min/1.73 m²) in asymptomatic patients provides no survival benefit and causes harm. 1, 3

• Observational data show patients with more comorbidities start dialysis at higher GFR levels, but these frailer patients do not live longer than healthier patients who start later—this reflects patient selection bias, not benefit from early initiation. 2, 1

• Earlier dialysis initiation is associated with faster decline in residual kidney function, which independently predicts higher mortality. 4

• Hemodialysis-related hypotension accelerates loss of residual kidney function, which is particularly detrimental. 2, 1

• Research demonstrates that hemodialysis patients starting at lower GFR (<6 mL/min/1.73 m²) have slower decline in residual kidney function compared to those starting at higher GFR (≥10 mL/min/1.73 m²). 4

When Dialysis Can Be Safely Delayed

Dialysis may be safely deferred even when GFR <10 mL/min/1.73 m² if ALL of the following criteria are met: 1

• Stable or increasing edema-free body weight 1
• Adequate nutritional parameters (stable albumin, no signs of protein-energy wasting) 1
• Complete absence of clinical signs or symptoms attributable to uremia 1
• Close clinical follow-up with adequate patient education 3

In asymptomatic patients with stage 5 CKD, dialysis may be safely delayed until eGFR is as low as 5-7 mL/min/1.73 m² with careful monitoring. 3

Important Caveats About GFR Measurement

Creatinine-based eGFR equations are inaccurate in ESRD patients and should not be the sole basis for dialysis initiation. 3

• In patients with unusual creatinine generation (extremes of muscle mass, malnutrition, amputation) or altered tubular secretion, measured GFR using 24-hour urine collection for creatinine and urea clearance is more accurate. 2, 1

• Different eGFR equations yield significantly different values at dialysis initiation: corrected Cockcroft-Gault (7.8 mL/min), MDRD (6.2 mL/min/1.73 m²), CKD-EPI (5.6 mL/min/1.73 m²). 5

• The corrected Cockcroft-Gault equation shows the lowest coefficient of variation and best correlation with CKD-specific complications. 5

Initial Hemodialysis Prescription

When dialysis is initiated, the first treatment MUST use a "low and slow" approach to prevent dialysis disequilibrium syndrome: 1

• Initial session duration: 2-2.5 hours (not the standard 4 hours) 1
• Reduced blood flow rates: 200-250 mL/min 1
• Minimal ultrafiltration during first session—focus on solute clearance rather than fluid removal 1
• Gradual dose escalation over subsequent sessions as tolerated 1

Risks of Dialysis Therapy

Dialysis is not innocuous and does not replace all kidney functions: 2, 1

• Hemodialysis-related hypotension accelerates loss of residual kidney function 2, 1
• Vascular access complications (infection, thrombosis, steal syndrome) 2, 1
• Dialysate-related complications 2, 1
• Significant burden on patient, family, and healthcare system 2, 1

Special Considerations for Peritoneal Dialysis

Research from Indian ESRD patients shows that initiation of peritoneal dialysis at lower baseline measured GFR (≤5 mL/min/1.73 m²) is associated with poorer patient and technique survival compared to initiation at higher GFR (>10 mL/min/1.73 m²). 6

• Each 1 mL/min/1.73 m² increment in baseline GFR was associated with 10% reduced risk of death in peritoneal dialysis patients. 6
• This contrasts with hemodialysis data and suggests peritoneal dialysis may be initiated slightly earlier than hemodialysis. 6

Clinical Decision Framework

The decision to initiate dialysis represents a compromise designed to maximize quality of life by extending the dialysis-free period while avoiding uremic complications. 2, 1

Individual factors that influence timing include: 2, 1

• Dialysis accessibility and modality options (home dialysis, peritoneal dialysis eligibility) 2, 1
• Vascular access status (functioning arteriovenous fistula vs. catheter requirement) 2, 1
• Transplantation candidacy (preemptive transplant may be optimal before reaching stage 5 CKD) 2, 1
• Age and comorbidity burden 2, 1
• Compliance with conservative management (diet, medications, fluid restriction) 2, 1