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Eight weeks of dietary overfeeding increases renal filtration rates in humans: implications for the pathogenesis of diabetic hyperfiltration.

ABSTRACT: Diabetic nephropathy is characterized at its onset by glomerular hyperfiltration. Prospective studies in humans measuring filtration rates with weight gain are lacking. We investigated renal filtration following weight gain induced by overfeeding.Eight weeks of overfeeding (40% above energy requirements, 44% fat, 15% protein and 41% carbohydrate) as well as a 6-month follow-up after the overfeeding intervention.Thirty-five participants (age: 26.7 ±5.3 years; body mass index: 25.5 ± 2.2 kg m(-2) ; 29 m/6f).Creatinine clearance rate (Ccr) from 24-h urine collection, estimated glomerular filtration rate (eGFR) from the modification of diet in renal disease (MDRD), insulin sensitivity/glucose disposal rate (GDR) by a euglycemic-hyperinsulinemic clamp, components from basic metabolic panels and serum lipid panels.Both eGFR and Ccr increased with overfeeding (P = 0.04) and serum lipids (all P < 0.05), along with a decrease in insulin sensitivity (P = 0.003). Fasting glucose concentration was not affected (P = 0.98), but the per cent change in Ccr correlated positively with the change in GDR with overfeeding (r = 0.39, P = 0.02). Six months following overfeeding, serum glucose was maintained, and no evidence of urinary glucose was observed at any time-point.These data suggest that renal hyperfiltration may act as a mechanism to preserve insulin sensitivity through maintenance of systemic glucose homoeostasis with caloric excess.

SUBMITTER: Covington JD

PROVIDER: S-EPMC4560986 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Eight weeks of dietary overfeeding increases renal filtration rates in humans: implications for the pathogenesis of diabetic hyperfiltration.

Covington J D JD Bray G A GA Redman L M LM Johannsen D L DL Ravussin E E

Journal of internal medicine 20150615 4

<h4>Objective</h4>Diabetic nephropathy is characterized at its onset by glomerular hyperfiltration. Prospective studies in humans measuring filtration rates with weight gain are lacking. We investigated renal filtration following weight gain induced by overfeeding.<h4>Design</h4>Eight weeks of overfeeding (40% above energy requirements, 44% fat, 15% protein and 41% carbohydrate) as well as a 6-month follow-up after the overfeeding intervention.<h4>Subjects</h4>Thirty-five participants (age: 26.7 ...[more]

PMID: 25903638

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Project description:BACKGROUND:High glomerular filtration rate (GFR) is often used as a surrogate for single-nephron hyperfiltration. Our objective was to determine the definition for high GFR that best reflects clinical and structural characteristics of hyperfiltration. METHODS:We studied living kidney donors at the Mayo Clinic and Cleveland Clinic. Potential donors underwent evaluations that included measured GFR (mGFR) by iothalamate clearance and estimated GFR (eGFR) by the serum creatinine-based Chronic Kidney Disease-Epidemiology collaboration (CKD-EPI) equation. High GFR was defined by the 95th percentile for each method (mGFR or eGFR) using either overall or age-specific thresholds. High mGFR was defined as both corrected and uncorrected for body surface area. The association of high GFR by each definition with clinical characteristics and radiologic findings (kidney volume) was assessed. In the subset that donated, the association of high GFR with kidney biopsy findings (nephron number and glomerular volume) and single-nephron GFR was assessed. RESULTS:We studied 3317 potential donors, including 2125 actual donors. The overall 95th percentile for corrected mGFR was 134?mL/min/1.73 m2 and for eGFR was 118?mL/min/1.73 m2. The age-based threshold for uncorrected mGFR was 198?mL/min - 0.943×Age, for corrected mGFR it was 164?mL/min/1.73 m2 - 0.730×Age and for eGFR it was 146?mL/min/1.73 m2 - 0.813×Age. High age-based uncorrected mGFR had the strongest associations with higher single-nephron GFR, larger glomerular volume, larger kidney volume, male gender, higher body mass index and higher 24-h urine albumin, but also had the strongest association with high nephron number. A high age-height-gender-based uncorrected mGFR definition performed almost as well but had a weaker association with nephron number and did not associate with male gender. CONCLUSIONS:High age-based uncorrected mGFR showed the most consistent associations reflective of hyperfiltration. However, high age-based uncorrected mGFR has limited clinical utility because it does not distinguish between hyperfiltration and high nephron number.

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Eight weeks of dietary overfeeding increases renal filtration rates in humans: implications for the pathogenesis of diabetic hyperfiltration.

Publications

Eight weeks of dietary overfeeding increases renal filtration rates in humans: implications for the pathogenesis of diabetic hyperfiltration.

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