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 end-stage 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 m(2) 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 m(2) the same serum urea nitrogen concentration as women with a GFR of 60 mL/min/1.73 m(2). 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.
Sheffield Kidney Institute, Northern General Hospital, Sheffield, UK Department of Cardiovascular Science, University of Sheffield, Medical School, Royal Hallamshire Hospital, Sheffield, UK.
Timothy
T
Ellam
Sheffield Kidney Institute, Northern General Hospital, Sheffield, UK School of Health and Related Research, University of Sheffield, Sheffield, UK.
James
J
Fotheringham
Sheffield Kidney Institute, Northern General Hospital, Sheffield, UK.
Bisher
B
Kawar
D000328:Adult; D000368:Aged; D001806:Blood Urea Nitrogen; D001830:Body Surface Area; D015331:Cohort Studies; D017281:Cost of Illness; D002149:Energy Intake; D004734:Energy Metabolism / Q000502:physiology; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology*; D006801:Humans; D007677:Kidney Function Tests / Q000592:standards; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000453:epidemiology* / Q000378:metabolism / Q000503:physiopathology*; D012737:Sex Factors; D016896:Treatment Outcome; D014508:Urea / Q000378:metabolism; D014511:Uremia / Q000378:metabolism
D014508:Urea
CKD complications; GFR; body surface area; gender; uraemia