title: Modification of the relationship between blood pressure and renal albumin permeability by impaired excretory function and diabetes.
abstract: In animal models, reduced nephron mass impairs renal arteriolar autoregulation, increasing vulnerability of the remaining nephrons to elevated systemic blood pressure (BP). A feature of the resulting glomerular capillary hypertension is an increase in glomerular permeability. We sought evidence of a similar remnant nephron effect in human chronic kidney disease. In participants from the United States National Health and Nutrition Examination Surveys 1999 to 2010 (N=23 710), we examined the effect of reduced estimated glomerular filtration rate (eGFR) on the relationship between brachial artery BP and albumin permeability. Renal albumin permeability increased exponentially with systolic BP >110 mm Hg, and this association was modified by independent interactions with both excretory impairment and diabetes mellitus. Each 10 mm Hg increase in systolic BP was accompanied by an increase in fractional albumin excretion of 1.10-, 1.11-, 1.17-, 1.22-, and 1.38-fold for participants with eGFR≥90, 90>eGFR≥60, 60>eGFR≥45, 45>eGFR≥30, and eGFR<30 mL/min/1.73 m(2), respectively, adjusted for age, sex, race, antihypertensive use, eGFR category, diabetes mellitus, smoking, history of cardiovascular disease, body mass index, and C-reactive protein. A 10 mm Hg systolic BP increment was associated with increases in fractional albumin excretion of 1.10- and 1.21-fold in nondiabetic and diabetic participants, respectively. Using urine albumin creatinine ratio as an alternative measure of albumin leak in eGFR-adjusted analyses gave the same conclusions. Our findings are consistent with the presence of a remnant nephron effect in human kidney disease. Future trials should consider the nephroprotective benefits of systolic BP lowering in kidney disease populations stratified by eGFR.
authors.affiliation: From the Sheffield Kidney Institute, Northern General Hospital, Sheffield, UK (J.F., W.M., T.E.); Institute of Cardiovascular Sciences, University of Manchester, Manchester, UK (A.O.); and Department of Cardiovascular Science, University of Sheffield, Sheffield, UK (T.E.).
authors.forename: James
authors.initials: J
authors.lastname: Fotheringham
authors.affiliation: From the Sheffield Kidney Institute, Northern General Hospital, Sheffield, UK (J.F., W.M., T.E.); Institute of Cardiovascular Sciences, University of Manchester, Manchester, UK (A.O.); and Department of Cardiovascular Science, University of Sheffield, Sheffield, UK (T.E.).
authors.forename: Aghogho
authors.initials: A
authors.lastname: Odudu
authors.affiliation: From the Sheffield Kidney Institute, Northern General Hospital, Sheffield, UK (J.F., W.M., T.E.); Institute of Cardiovascular Sciences, University of Manchester, Manchester, UK (A.O.); and Department of Cardiovascular Science, University of Sheffield, Sheffield, UK (T.E.).
authors.forename: William
authors.initials: W
authors.lastname: McKane
authors.affiliation: From the Sheffield Kidney Institute, Northern General Hospital, Sheffield, UK (J.F., W.M., T.E.); Institute of Cardiovascular Sciences, University of Manchester, Manchester, UK (A.O.); and Department of Cardiovascular Science, University of Sheffield, Sheffield, UK (T.E.). T.Ellam@sheffield.ac.uk.
authors.forename: Timothy
authors.initials: T
authors.lastname: Ellam
mesh_terms: D000328:Adult; D000368:Aged; D000418:Albumins / Q000378:metabolism; D000419:Albuminuria / Q000503:physiopathology*; D001794:Blood Pressure / Q000502:physiology*; D002463:Cell Membrane Permeability / Q000502:physiology*; D003920:Diabetes Mellitus / Q000503:physiopathology*; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000503:physiopathology; D007674:Kidney Diseases / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009749:Nutrition Surveys / Q000706:statistics & numerical data; D012189:Retrospective Studies; D014481:United States
chemical_list: D000418:Albumins
keywords: albuminuria; autoregulation; blood pressure; diabetes mellitus; eGFR