Does an elevation in hematocrit (Hct) affect Glomerular Filtration Rate (GFR)?

The Relationship Between Hematocrit and Glomerular Filtration Rate

Elevated hematocrit is associated with decreased glomerular filtration rate (GFR), with higher hematocrit values leading to increased filtration fraction and reduced GFR. 1

Physiological Relationship Between Hematocrit and GFR

• As hematocrit increases, there is a corresponding increase in blood viscosity which affects renal hemodynamics, leading to increased filtration fraction and decreased GFR 1
• Studies in rats have demonstrated that when hematocrit is experimentally elevated (to 62 ml/100 ml from a control of 51 ml/100 ml), there is a marked increase in filtration fraction due to changes in glomerular transcapillary hydraulic pressure and arteriolar resistance 1
• The increase in filtration fraction with elevated hematocrit occurs due to a relatively greater rise in efferent arteriolar resistance (RE) than in afferent arteriolar resistance (RA) 1

Clinical Evidence in Humans

• Cross-sectional analysis of 12,055 ambulatory adult patients showed that hematocrit levels are inversely related to renal function when GFR falls below certain thresholds 2
• In men, hematocrit decreases progressively when estimated creatinine clearance falls below 60 mL/min, while in women this occurs below 40 mL/min 2
• When renal function is indexed to body surface area using the MDRD equation, men with GFR 50-40 mL/min/1.73 m² had mean hematocrits that were lower by 2.0%, while those with GFR ≤20 mL/min/1.73 m² had hematocrits lower by 9.4% compared to those with GFR >80 mL/min/1.73 m² 2

Relationship in Chronic Kidney Disease

• The relationship between hematocrit and GFR is bidirectional - as GFR decreases in chronic kidney disease, anemia typically develops, particularly when GFR falls below 60 mL/min/1.73 m² in males and 45 mL/min/1.73 m² in females 3
• Studies consistently show that higher GFR is associated with higher hemoglobin and hematocrit levels, with a statistically significant correlation 3
• The prevalence of anemia increases at later stages of CKD (stages 4 and 5), with significant variability in hemoglobin levels at any given level of kidney function 3

Clinical Implications

• In patients with elevated hematocrit, monitoring renal function is important as the increased blood viscosity may contribute to reduced GFR 1
• The effect of hematocrit on GFR appears to be more pronounced in men than women at equivalent levels of renal function 2
• When body surface area is accounted for in GFR calculations, the gender differences in the hematocrit-GFR relationship diminish, suggesting that body size plays a role in this relationship 2

Monitoring Considerations

• In patients with elevated hematocrit, regular assessment of renal function is warranted to detect potential adverse effects on GFR 3
• Conversely, in patients with chronic kidney disease, hemoglobin testing should be carried out regardless of CKD stage or cause, with diagnosis of anemia warranted at Hb <13.5 g/dL in adult males and <12.0 g/dL in adult females 3

Pathophysiological Mechanism

• The mechanism by which elevated hematocrit affects GFR involves changes in renal hemodynamics, with increased blood viscosity leading to altered glomerular perfusion pressure and filtration dynamics 1
• The relationship between hematocrit and GFR appears to operate through a feedback mechanism that maintains tissue oxygenation, with evidence suggesting this mechanism operates at a lower set point in patients with chronic renal failure 4