The Effects of Weight Loss on Renal Function in Patients with Severe Obesity

Abstract

Abstract. Severe obesity is associated with increased renal plasma flow (RPF) and glomerular filtration rate (GFR). The aim of the present study was to examine whether weight loss may reverse glomerular dysfunction in obese subjects without overt renal disease. Renal glomerular function was studied in eight subjects with severe obesity (body mass index [BMI] 48.0 Ϯ 2.4) before and after weight loss. Nine healthy subjects served as controls. GFR and RPF were determined by measuring inulin and PAH clearance. In the obese group, GFR (145 Ϯ 14 ml/min) and RPF (803 Ϯ 39 ml/min) exceeded the control value by 61% (90 Ϯ 5 ml/min, P ϭ 0.001) and 32% (610 Ϯ 41 ml/min, P Ͻ 0.005), respectively. Consequently, filtration fraction was increased.Mean arterial pressure, although normal, was higher than in the control group (101 Ϯ 4 versus 86 Ϯ 2 mmHg, P Ͻ 0.01). After weight loss, BMI decreased by 32 Ϯ 4%, to 32.1 Ϯ 1.5 (P ϭ 0.001). GFR and RPF decreased to 110 Ϯ 7 ml/min (P ϭ 0.01) and 698 Ϯ 42 ml/min (P Ͻ 0.02), respectively. Albumin excretion rate decreased from 16 g/min (range, 4 to 152 g/min) to 5 g/min (range, 3 to 37 g/min) (P Ͻ 0.01). Fractional clearance of albumin decreased from 3.2 ϫ 10 Ϫ6 (range, 1.1 to 23 ϫ 10Ϫ6 (range, 0.5 to 6.8 ϫ 10 Ϫ6) (P Ͻ 0.02). This study shows that obesity-related glomerular hyperfiltration ameliorates after weight loss. The improvement in hyperfiltration may prevent the development of overt obesity-related glomerulopathy.Severe obesity is associated in with increased systemic arterial pressure (1), high renal plasma flow (2-4), increased GFR (2,5), and enhanced albumin excretion rate (6,7). We have previously studied glomerular hemodynamics in patients with severe obesity by measuring the fractional clearances of dextrans of broad size distribution (8). Analysis of the dextran sieving data, using a theoretical model of macromolecule transport through a heteroporous membrane, showed that the glomerular capillary bed was subjected to an elevated transcapillary hydraustatic pressure gradient resulting in hyperfiltration. In addition to these physiologic abnormalities, many reports have associated obesity with the occurrence of nephrotic syndrome and renal failure (9 -19). Obesity-related glomerulopathy was recently defined morphologically as glomerulomegaly with or without focal segmental glomerulosclerosis (20). Obesity may also accelerate the course of idiopathic glomerular disease, such as IgA glomerulopathy (21). The prevalence of obesity-related glomerulopathy, which may lead to end-stage renal disease, has increased tenfold over the last 15 yr as a consequence of "the spread of the obesity epidemic" (22). Although a cause-and-effect relationship between the obesityassociated glomerular hyperfunction and the development of nephrotic syndrome and renal failure has not been demonstrated, experimental and clinical data suggest that hyperfiltration and glomerulomegaly may lead to glomerular damage. Therefore, reducing glomerular hyperfiltration may provide a way to prevent or delay the deve...

Effects of weight loss on renal function in overweight Japanese men

“…48 The decrease in GFR and arterial pressure after WL is comparable with this hypothesis. Chagnac et al, 15 however, reported that obesity-related glomerular hyperfiltration was improved after WL in morbidly obese subjects as assessed using insulin and p-aminohippuric acid clearance. In the present study, we also observed that several subjects did not improve CCr as calculated using the Cockcroft-Gault equation, even though their creatinine levels decreased with WL.…”

“…1,2,5,6 Furthermore, several large cohort studies have demonstrated close associations between obesity, especially abdominal obesity and the onset of chronic kidney disease (CKD) [7][8][9][10][11] and faster CKD progression. 10 Intentional weight loss (WL) reduced the risk of the onset and development of hypertension, 12,13 diabetes 14 and renal injury 15 in overweight or obese individuals.…”

“…Many epidemiological and clinical studies have shown the presence of microalbuminuria 32,33 or proteinuria 15 as a marker of cardiovascular risks, however, Farbom et al 34 reported that microalbuminuria and renal function (creatinine, blood urea nitrogen and creatinine clearance (CCr)) are independently associated with future cardiovascular events. The decrease in CCr (glomerular filtration rate, GFR) was a precursor for the future cardiovascular events.…”

The clinical significance of hyperfiltration in diabetes

“…In another study by the same group, GFR determined by inulin clearance in eight participants with severe obesity decreased from 145±14 to 110±7 ml/min 12 months after gastroplasty, with a concomitant 32% decrease in BMI [36]. However, in both of the above studies, GFR was not corrected for body surface area.…”

Obesity-Related Glomerulopathy

“…Weight loss, either after bariatric surgery or after lifestyle modification, normalizes blood glucose (4) and decreases BP and plasma lipids (5,6) in obese patients. Similarly, a significant reduction in urinary albumin excretion and glomerular hyperfiltration has been reported in morbidly obese patients with a dramatic decrease of body mass index (BMI) (7,8). Moreover, even a small decrease in BMI is related to the reduction of proteinuria in patients with diabetic nephropathy and other chronic kidney diseases (9 -11).…”