What are the indications for initiating hemodialysis (HD) in patients with end-stage renal disease?

Indications for Initiating Hemodialysis

Hemodialysis should be initiated based on clinical symptoms and complications of uremia—not on GFR or laboratory values alone—with absolute indications including uremic pericarditis, encephalopathy, refractory volume overload, severe hyperkalemia unresponsive to medical therapy, severe metabolic acidosis, and protein-energy malnutrition that persists despite nutritional intervention. 1, 2

Clinical (Symptom-Based) Indications

The decision to start dialysis must be driven by the presence of uremic complications rather than arbitrary laboratory thresholds:

Absolute Indications for Immediate Dialysis

• Uremic pericarditis (pericardial friction rub or effusion) warrants immediate hemodialysis regardless of GFR level 3, 2
• Uremic encephalopathy manifesting as confusion, asterixis, or seizures requires prompt initiation 3, 2
• Intractable nausea or vomiting that fails to respond to antiemetic therapy 3, 2
• Bleeding diathesis due to uremic platelet dysfunction 3, 2
• Refractory volume overload (persistent pulmonary edema or peripheral edema despite maximal diuretic therapy) 1, 3, 2
• Uncontrolled hypertension that cannot be managed with optimal medical therapy 3, 2
• Severe hyperkalemia (typically >6.5-7.0 mEq/L or any level with ECG changes) unresponsive to medical management including dietary restriction, diuretics, potassium binders, and insulin/dextrose 3, 2
• Severe metabolic acidosis (pH <7.20 or bicarbonate <10 mmol/L) refractory to oral alkali therapy 3, 2
• Protein-energy malnutrition that develops or persists despite vigorous nutritional optimization, with no other identifiable cause 1, 3, 2

GFR Thresholds and Timing

When to Continue Conservative Management

• Conservative management should continue until GFR falls below 15 mL/min/1.73 m² unless specific clinical indications (listed above) mandate earlier initiation 1, 3, 4
• Asymptomatic patients can safely defer dialysis until measured GFR reaches 5-7 mL/min/1.73 m² with careful clinical monitoring 4, 5

Target GFR for Initiation

• The theoretical target GFR for initiating dialysis is approximately 10 mL/min/1.73 m² 4
• In practice, mean GFR at dialysis initiation is 9.8 mL/min/1.73 m², with lower values (7-9 mL/min/1.73 m²) for young and middle-aged adults and higher values (10-10.5 mL/min/1.73 m²) for children and elderly patients 4

Critical Evidence Against Early Initiation

Early dialysis initiation (GFR >10 mL/min/1.73 m²) in asymptomatic patients provides no survival benefit and may cause harm:

• The IDEAL randomized controlled trial (highest quality evidence) demonstrated that starting dialysis at GFR 10-14 mL/min/1.73 m² versus symptom-driven initiation (actual start ≈7-8 mL/min/1.73 m²) showed no difference in all-cause mortality, cardiovascular events, infectious complications, or quality of life 4, 5
• Patients in the late-start arm experienced a median 5.6-month longer dialysis-free interval without adverse outcomes 4
• After correcting for lead-time bias, there is no clear survival advantage to starting dialysis at higher GFR levels 4

Important Limitations of eGFR

Do not rely solely on estimated GFR for dialysis initiation decisions:

• Serum creatinine-based eGFR is unreliable in advanced CKD because it is heavily influenced by muscle mass, leading to overestimation in sarcopenic, elderly, or malnourished patients 4, 5
• Obtain measured GFR using 24-hour urine collection for creatinine and urea clearance in patients with unusual creatinine generation or altered tubular secretion 3, 4
• Observational studies showing higher mortality with higher eGFR at dialysis start reflect patient selection bias—sicker, frailer patients tend to start earlier, and their poorer outcomes reflect underlying illness rather than timing of dialysis 4

Initial Dialysis Protocol

When dialysis is indicated, use a "low and slow" approach for the first treatment to minimize dialysis disequilibrium syndrome and hemodynamic instability:

• Initial session duration: 2-2.5 hours (not full 4 hours) 3, 2
• Blood flow rate: 200-250 mL/min 3, 2
• Minimal ultrafiltration during first session, focusing on clearance rather than fluid removal 3, 2
• Frequent vital sign monitoring every 15-30 minutes during the first session 3, 2
• Gradual dose escalation over subsequent sessions as tolerated 3, 2

Critical Pitfalls to Avoid

Do Not Initiate Based on GFR Alone

• Dialysis should never be started based solely on a low GFR in the absence of symptoms—this provides no benefit and exposes patients to unnecessary risks 1, 3, 4

Recognize the Harms of Dialysis Itself

• Hemodialysis-related hypotension may accelerate loss of residual kidney function, which is particularly important for volume control, phosphate clearance, and quality of life 3, 4
• Vascular access complications (infection, thrombosis) increase morbidity 3, 4
• Dialysis does not replace all kidney functions and imposes substantial physical, psychological, and economic burdens on patients, families, and healthcare systems 3, 4, 6

Avoid Aggressive First Dialysis Sessions

• Rapid removal of uremic toxins can cause dialysis disequilibrium syndrome (cerebral edema, seizures) and cardiovascular instability 3

Special Populations

• Patients with diabetes should generally initiate dialysis at higher levels of residual kidney function than non-diabetic patients, though specific thresholds remain based on clinical symptoms rather than GFR alone 2
• Older patients with multiple comorbidities and frailty may experience worse outcomes and quality of life with dialysis initiation; conservative care should be carefully considered in appropriate cases 5, 7

Preparation and Planning

Early preparation improves outcomes even when delaying dialysis initiation:

• Education should begin at CKD stage 4 (GFR <30 mL/min/1.73 m²) about kidney failure and treatment options including transplantation, peritoneal dialysis, home hemodialysis, in-center hemodialysis, and conservative management 1
• Vascular access planning should occur well in advance, with arteriovenous fistula creation 3-6 months before anticipated need to allow maturation 1
• Preserve peripheral veins in patients with stage III-V CKD by avoiding unnecessary venipuncture 7