What are the determinants for initiating dialysis in patients with end-stage renal disease (ESRD) or acute kidney injury (AKI), particularly those with impaired renal function, such as a glomerular filtration rate (GFR) less than 15 mL/min/1.73m^2, and a history of diabetes, hypertension, or other kidney diseases?

Determinants of Dialysis Initiation

Dialysis should be initiated based on clinical symptoms and signs of uremia—not on GFR alone—with most patients starting when GFR falls below 10 mL/min/1.73 m², unless specific absolute indications mandate earlier intervention. 1, 2

GFR Thresholds: When to Consider Dialysis

The target GFR for dialysis initiation is approximately 10 mL/min/1.73 m², with conservative management continuing until GFR decreases below 15 mL/min/1.73 m² unless specific clinical indications exist. 1, 2 The National Kidney Foundation defines kidney failure as GFR <15 mL/min/1.73 m², which is accompanied in most cases by signs and symptoms of uremia, or a need to start kidney replacement therapy. 1

• Approximately 98% of patients with kidney failure in the United States begin dialysis when their GFR is less than 15 mL/min/1.73 m². 1
• The 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. 2

Critical Caveat: GFR Estimation Limitations

In patients with unusual creatinine generation (low muscle mass, malnutrition, elderly) or altered tubular secretion, measured GFR using 24-hour urine collection for creatinine and urea clearance is more accurate than estimated GFR. 3, 2 Serum creatinine-based eGFR may be misleading in individuals with advanced CKD, particularly the elderly or those with multiple comorbid conditions, due to dependence on creatinine generation from muscle mass. 1

Absolute Indications for Dialysis (Override GFR)

Dialysis must be initiated when any of the following are present, regardless of GFR level:

Uremic Symptoms

• Pericarditis (uremic pericarditis is an absolute indication) 3, 2
• Encephalopathy (altered mental status, asterixis, seizures attributable to uremia) 3, 2
• Intractable nausea/vomiting (refractory to antiemetic therapy) 3, 2
• Bleeding diathesis (uremic platelet dysfunction causing clinically significant bleeding) 3, 2

Volume and Hemodynamic Derangements

• Volume overload refractory to diuretic therapy (pulmonary edema, severe peripheral edema unresponsive to maximal diuretic doses) 3, 2
• Uncontrolled hypertension despite maximal medical management (three or more antihypertensive agents at optimal doses) 3, 2

Metabolic Derangements

• Hyperkalemia unresponsive to medical therapy (potassium >6.5 mEq/L despite dietary restriction, diuretics, and potassium binders) 3, 2
• Severe metabolic acidosis (pH <7.2 or bicarbonate <10 mEq/L refractory to oral alkali therapy) 3, 2

Nutritional Deterioration

• Protein-energy malnutrition that develops or persists despite vigorous nutritional intervention (declining edema-free body weight, falling serum albumin <4.0 g/dL, lean body mass <63%) 3, 2, 4
• Progressive deterioration in nutritional status with no apparent cause other than low nutrient intake 2

When Dialysis Can Be Safely Deferred

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

• Stable or increased edema-free body weight 2
• Adequate nutritional parameters (serum albumin ≥4.0 g/dL, stable lean body mass) 2, 4
• Complete absence of clinical signs or symptoms attributable to uremia 2

Additional Predictors of Earlier Dialysis Need

Certain predialysis characteristics predict patients who will require dialysis at higher GFR levels (≥7.8 mL/min/1.73 m²):

• Heart failure (adjusted odds ratio 3.68) 4
• Serum albumin <4.0 g/dL (adjusted odds ratio 2.22) 4
• BUN/creatinine ratio >15 mg/mg (adjusted odds ratio 1.92) 4
• Hyperuricemia (adjusted odds ratio 1.84) 4

For patients with these characteristics, clinicians should provide predialysis counseling in advance and consider early creation of vascular access to avoid unplanned urgent dialysis initiation. 4

Evidence Against Early Dialysis Initiation

There is no compelling evidence that initiation of dialysis based solely on measurement of kidney function leads to improvement in clinical outcomes, including overall mortality. 1 Multiple observational studies show that patients starting dialysis at higher GFR levels (>10 mL/min/1.73 m²) have higher mortality rates, though this reflects patient selection bias (sicker patients start earlier) rather than harm from early initiation per se. 1, 2

When corrected for lead-time bias, early dialysis initiation (eGFR >7.9 mL/min/1.73 m²) shows no survival benefit and may be associated with survival disadvantage. 5 The IDEAL trial found no signal of harm with initiation at higher GFR levels, but also no benefit, and most participants were healthier than typical dialysis patients. 1

Initial Dialysis Prescription: "Low and Slow" Approach

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

• Initial session duration: 2-2.5 hours (not full 4 hours) 3, 2
• Reduced blood flow rates: 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, with close observation for neurological symptoms 3
• Gradual dose escalation over subsequent sessions as tolerated 3, 2

Critical Pitfalls to Avoid

Starting dialysis based on GFR alone in asymptomatic patients provides no survival benefit and may cause harm. 3, 2 Dialysis does not replace all kidney functions (tubular secretion, reabsorption, endocrine function) and provides only 10-20% of physiological clearance. 1

Hemodialysis-related hypotension may accelerate loss of residual kidney function, which is particularly problematic in patients who may recover renal function (such as those with AKI or chemotherapy-induced kidney injury). 3, 2 Residual kidney function is a major contributor to total urea and creatinine clearance and is a positive factor for patient outcomes. 6

Aggressive first dialysis sessions can cause cerebral edema, seizures, and cardiovascular instability due to rapid removal of uremic toxins. 3 Dialysis imposes significant burden on patients and families, with risks including vascular access complications and dialysate-related complications. 2

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 This requires clinical judgment based on individual patient factors including age, comorbidities, vascular access status, transplant candidacy, and home dialysis eligibility. 2

In otherwise asymptomatic individuals, there is no reason to begin maintenance dialysis solely based on serum creatinine or eGFR value. 1 Rather, in patients with advanced CKD without clear uremic symptoms, efforts should be directed at preparing patients for a seamless and safe transition to kidney replacement therapy. 1