Differential scaling of glomerular filtration rate and ingested metabolic burden: implications for gender differences in chronic kidney disease outcomes

Background. Men commence dialysis with a higher estimated glomerular filtration rate (eGFR) than women and are more likely to transition from chronic kidney disease (CKD) to endstage renal disease. We hypothesized that for a given estimated body surface area (BSA) men have a greater metabolic burden, and that consequently, the practice of indexing GFR to BSA results in gender differences in the degree of biochemical uraemia. Methods. Metabolic burden was assessed as estimated dietary protein, calorie, phosphorus, sodium and potassium intakes and urinary urea nitrogen excretion in the Chronic Renal Insufficiency Cohort, Modification of Diet in Renal Disease study, and National Health and Nutrition Examinations Surveys (NHANES) 1999-2010. Uraemia was characterized by serum biochemistry. Results. Per m2 BSA, men had greater urea nitrogen excretion and intakes of all dietary parameters (P < 0.001 for all). For a given BSA-indexed iothalamate GFR or eGFR, male gender was associated with a 10-15% greater serum urea nitrogen (P < 0.001), giving men with a BSA-indexed GFR of 70-75 mL/min/1.73 m2 the same serum urea nitrogen concentration as women with a GFR of 60 mL/min/1.73 m2. However, indexing metabolic burden and GFR to alternative body size measures (estimated total body water, lean body mass or resting energy expenditure) abolished/reversed the gender associations. In NHANES, BSA-indexed eGFR distribution was very similar for men and women, so that adjusting for eGFR had little effect on the gender difference in serum urea. Conclusions. Indexing GFR to BSA across genders may approximate nature's indexing approach, but gives men a greater ingested burden of protein, calories, sodium, phosphorus and potassium per mL/min GFR. This has implications for gender differences in CKD outcomes.