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Acute caloric restriction improves glomerular filtration rate in patients with morbid obesity and type 2 diabetes
Available online at
ScienceDirect www.sciencedirect.com Diabetes & Metabolism 40 (2014) 158–160
Short report
Acute caloric restriction improves glomerular filtration rate in patients with morbid obesity and type 2 diabetes I. Giordani a,b , I. Malandrucco a,b , S. Donno c,d , F. Picconi a,b , P. Di Giacinto a,b , A. Di Flaviani a,b , L. Chioma a,b , S. Frontoni a,b,∗ a Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy Unit of Endocrinology, Diabetes and Metabolism, S. Giovanni Calibita Fatebenefratelli Hospital, Lungotevere de’ Cenci 7, 00186 Rome, Italy c Service of Medical Statistics & Information Technology, Fatebenefratelli Association for Research (SeSMIT-AFaR), S. Giovanni Calibita Fatebenefratelli Hospital, Lungotevere de’ Cenci 5, 00186 Rome, Italy d AFaR, Unit of Internal Medicine, S. Giovanni Calibita Fatebenefratelli Hospital, Lungotevere de’ Cenci 5, 00186 Rome, Italy b
Received 3 November 2013; received in revised form 28 November 2013; accepted 10 December 2013
Abstract Aim. – The role of caloric restriction in the improvement of renal function following bariatric surgery is still unclear; with some evidence showing that calorie restriction can reduce proteinuria. However, data on the impact of caloric restriction on renal function are still lacking. Methods. – Renal function, as measured by glomerular filtration rate (GFR), was evaluated in 14 patients with type 2 diabetes mellitus, morbid obesity and stage 2 chronic kidney disease before and after a 7-day very low-calory diet (VLCD). Results. – After the VLCD, both GFR and overall glucose disposal (M value) significantly increased from 72.6 ± 3.8 mL/min/1.73 m−2 BSA to 86.9 ± 6.1 mL/min/1.73 m−2 BSA (P = 0.026) and from 979 ± 107 mol/min1 /m2 BSA to 1205 ± 94 mol/min1 /m2 BSA (P = 0.008), respectively. A significant correlation was observed between the increase in GFR and the rise in M value (r = 0.625, P = 0.017). Conclusion. – Our observation of improved renal function following acute caloric restriction before weight loss became relevant suggesting that calory restriction per se is able to affect renal function. © 2013 Elsevier Masson SAS. All rights reserved. Keywords: Caloric restriction; Glomerular filtration rate; Diabetes mellitus; Morbid obesity
1. Introduction Recent reports have associated weight loss following bariatric surgery with improvement in both glomerular hyperfiltration [1] and chronic renal disease [2] in severely obese patients with or without diabetes mellitus (DM). However, only a few clinical studies and case reports have shown dramatic reductions in proteinuria following weight loss by caloric restriction (CR) in obese subjects [3]. Although some preliminary clinical observations suggest a possible direct anti-proteinuric effect of CR itself, even before any significant weight loss [3], to the best of our knowledge, no clear data are currently available on the short-term impact of CR on glomerular filtration rate (GFR). ∗ Corresponding author. San Giovanni Calibita Fatebenefratelli Hospital, Endocrinology and Metabolism, Lungotevere de’ Cenci, 7, 00186 Rome, Italy. Tel.: +39 06 68 370 255; fax: +39 06 68 370 916. E-mail address: [email protected] (S. Frontoni).
1262-3636/$ – see front matter © 2013 Elsevier Masson SAS. All rights reserved. http://dx.doi.org/10.1016/j.diabet.2013.12.006
For this reason, the present preliminary proof-of-concept study has analyzed data from our previously published report [4] to investigate the possible impact of short-term CR on renal function in patients with type 2 DM, severe obesity and stage 2 chronic kidney disease (CKD). 2. Methods A total of 14 morbidly obese [body mass index (BMI) > 40 kg/m2 ] patients with type 2 DM (seven men and seven women), aged 60.3 ± 3.02 years and with diabetes duration of 4.8 ± 1.7 years and good metabolic control (HbA1c < 58 mmol/mol or < 7.5%), were recruited from the diabetes division of the Fatebenefratelli Hospital in Rome, Italy. Inclusion and exclusion criteria have been previously reported elsewhere [4]. Following a 7-day period to wash out all hypoglycaemic and anti-hypertensive medications, our patients were assessed
I. Giordani et al. / Diabetes & Metabolism 40 (2014) 158–160
at baseline and after 7 days of following a very low-calory diet (VLCD). During the VLCD, water and salt intakes were standardized to 1.5 L/day and < 6 g/day, respectively. Metabolic data have been reported elsewhere [4]. The VLCD consisted of a 400-kcal/day diet, the composition and adherence assessment of which has also been described previously, as have the analytical methods applied [4]. Patients’ 24-h blood pressure (BP) was recorded using an ambulatory BP monitoring system (TM2430, Intermed, Cape Town, South Africa) at baseline and after the VLCD. GFR was calculated using the Modification of Diet in Renal Disease (MDRD), Cockcroft–Gault (CG) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulas. 2.1. Statistical methods All data are presented as means ± SEMs. Within-subject comparisons before and after the VLCD were assessed by non-parametric tests (Mann–Whitney U test or Wilcoxon’s signed-rank test, as appropriate). Correlations were assessed by Spearman’s non-parametric correlation coefficient rho. P < 0.05 was considered statistically significant. All statistical analyses were performed using IBM SPSS Statistics 20.0 software (IBM SPSS Inc, Armonk, NY, USA). 2.2. Ethics In compliance with the Declaration of Helsinki, this study was approved by the Bioethics Committee of Fatebenefratelli Hospital, and all participants gave their written informed consent. 3. Results As previously reported, a 7-day VLCD resulted in significant decreases in weight (3.22 ± 0.56%; 3.58 ± 0.6 kg), BMI (from 44.8 ± 1.6 kg/m2 to 43.5 ± 1.6 kg/m2 ; P = 0.001), waist circumference (from 132.3 ± 3.4 cm to 129.93 ± 3.41 cm; P = 0.001), and significant changes in glucose disposal (M value) related to increased beta-cell function, particularly, first-phase insulin secretion [acute insulin response (AIR); P = 0.016]. After the VLCD, lean mass decreased from 63.8 ± 3.4 kg to 60.7 ± 3.2 kg (P = 0.001) and the M value (glucose disposal) significantly increased from 979 ± 107 mol/min1 /m2 BSA to 1205 ± 94 mol/min1 /m2 BSA (P = 0.008). As for renal function, GFR evaluated according to the MDRD formula significantly increased following CR from 72.6 ± 3.8 mL/min/1.73 m−2 BSA to 86.9 ± 6.1 mL/min/1.73 m−2 BSA (P = 0.026), while a significant correlation was observed between the increase in GFR and rise in M value (r = 0.625, P = 0.017). No correlation was found between changes in GFR and reductions in BMI and waist circumference, or with changes in BP either during the day or at night. Also, despite a significant reduction in muscle mass observed after VLCD, this change also did not correlate with the increase in GFR (correlation lean mass – GFR; P = 0.76). In addition, systolic (SBP) and
159
diastolic blood pressure (DBP) both non-significantly increased after 1 week of anti-hypertensive treatment washout (P = 0.10 and P = 0.20, respectively), and remained unchanged at the end of 1 week of calory restriction (SBP: from 135.1 ± 3.7 mmHg to 133.6 ± 1.9, mmHg, P = 0.5; DBP: from 74.2 ± 1.6 mmHg to 74.5 ± 1.6 mmHg, P = 0.9). 4. Conclusion In severely obese patients with type 2 DM and stage 2 CKD, our preliminary proof-of-concept study has demonstrated that short-term CR is associated with acute improvement in renal function. Bariatric surgery has been associated with improved renal function in both established chronic renal impairment [2] and reduced hyperfiltration [1,5,6]. However, to the best of our knowledge, all reported studies were performed within a period ranging from 1 to 48 months [5,7] after surgery, when weight loss had already occurred and may have influenced decrease in BP and markers of renal inflammation, whereas our preliminary observation of an increased GFR following acute CR at a time when changes in body weight and BP were negligible, suggesting a direct impact of VLCD on renal function. Surprisingly, despite numerous epidemiological studies linking obesity and the development of CKD, few clinical studies have investigated the effect of diet on renal function in obese subjects, but those that did have found some preliminary observations, suggesting an anti-proteinuric effect directly induced by CR itself and well before the presence of significant weight loss [3]. The present data show a significant increase in GFR in patients with type 2 DM and stage 2 CKD following CR that was unrelated to weight loss and BP changes, and only related to glucose disposal. GFR is highly dependent on the state of hydration. In the present study, water and salt intake were standardized and kept constant throughout the trial. The impact of changes in the state of hydration on the observed modification of GFR following the VLCD can therefore be excluded. A correlation between insulin sensitivity (IS) and albuminuria has previously been reported [8] in subjects without diabetes, while insulin resistance was found to be related to kidney function in patients with type 2 DM [9]. Our present study has confirmed the correlation between IS and GFR in diabetic patients and demonstrated for the first time that an improvement in glucose disposal following calorie restriction may be responsible for the increase in GFR. The loss of muscle mass could have influenced the modification of serum creatinine and, thus, the improvement in GFR. However, no correlation between GFR and muscle mass was found in our patients, thereby, precluding any possible impact of lean mass reduction on the observed GFR increase. In the present report, BP non-significantly increased after 1 week of anti-hypertensive treatment washout and, more important, remained unchanged at the end of 1 week of calorie restriction, whereas GFR appeared, on the contrary, to be significantly increased. Given the small size of our study population, only a high correlation (0.63) can be considered significant (a bilateral alpha
160
I. Giordani et al. / Diabetes & Metabolism 40 (2014) 158–160
of 0.05) with adequate power (0.80). This makes it impossible to definitively predict that increasing the number of subjects would allow the detection of a correlation between change in ambulatory BP and change in GFR. Another limitation of our study was the low precision of the methods used to estimate GFR (compared with isotopic or non-isotopic gold-standard methods, such as inulin clearance). Nevertheless, this was a retrospective subanalysis of a previously published study and, in an attempt to overcome this limitation, GFR in the present analysis was calculated using the MDRD, CG and CKD-EPI formulas, and the results were always consistent. Also, as a lower bias with the MDRD equation vs the CKD-EPI formula has previously been reported [10], the MDRD equation was chosen for our obese patient population. The correlation between improvement in GFR and increase in glucose disposal, but not with changes in body weight, muscle mass or BP, suggests the influence of IS and/or insulin secretion on GFR in patients with DM. Disclosure of interest The authors declare that they have no conflicts of interest concerning this article. Acknowledgements Conception and design of the study: Simona Frontoni; generation, collection, assembly, analysis and/or interpretation of data: Ilaria Giordani, Ilaria Malandrucco, Fabiana Picconi, Paola Di Giacinto, Alessandra Di Flaviani, Laura Chioma; and drafting or revision of the manuscript: Silvia Donno, Simona Frontoni; approval of the final version of the manuscript: Simona Frontoni. Sources of funding: AFAR (Fatebenefratelli Association for Research).
Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.diabet. 2013.12.006. References [1] Saliba J, Kasim NR, Tamboli RA, Isbell JM, Marks P, Feurer ID, et al. Rouxen-Y gastric bypass reverses renal glomerular but not tubular abnormalities in excessively obese diabetics. Surgery 2010;147:282–7. [2] Alexander JW, Goodman HR, Hawver LR, Cardi MA. Improvement and stabilization of chronic kidney disease after gastric bypass. Surg Obes Relat Dis 2009;5:237–413. [3] Praga M, Morales E. Obesity-related renal damage: changing diet to avoid progression. Kidney Int 2010;78:633–5. [4] Malandrucco I, Pasqualetti P, Giordani I, Manfellotto D, De Marco F, Alegiani F, et al. Very-low-calorie diet: a quick therapeutic tool to improve  cell function in morbidly obese patients with type 2 diabetes. Am J Clin Nutr 2012;95:609–13. [5] Navaneethan SD, Yehnert H, Moustarah F, Schreiber MJ, Schauer PR, Beddhu S. Weight loss interventions in chronic kidney disease: a systematic review and meta-analysis. Clin J Am Soc Nephrol 2009;4:1565–74. [6] Chagnac A, Weinstein T, Herman M, Hirsh J, Gafter U, Ori Y. The effects of weight loss on renal function in patients with severe obesity. J Am Soc Nephrol 2003;14:1480–6. [7] Jose B, Ford S, Super P, Thomas GN, Dasgupta I, Taheri S. The effect of biliopancreatic diversion surgery on renal function – a retrospective study. Obes Surg 2013;23:634–7. [8] Nistala R, Whaley-Connell A. Resistance to insulin and kidney disease in the cardiorenal metabolic syndrome; role for angiotensin II. Mol Cell Endocrinol 2013;378:53–8. [9] De Cosmo S, Trevisan R, Minenna A, Vedovato M, Viti R, Santini SA, et al. Insulin resistance and the cluster of abnormalities related to the metabolic syndrome are associated with reduced glomerular filtration rate in patients with type 2 diabetes. Diabetes Care 2006;29:432–4. [10] Bouquegneau A, Vidal-Petiot E, Vrtovsnik F, Cavalier E, Rorive M, Krzesinski JM, et al. Modification of diet in renal disease versus chronic kidney disease epidemiology collaboration equation to estimate glomerular filtration rate in obese patients. Nephrol Dial Transplant 2013;28(Suppl. 4):iv122–30.
ScienceDirect www.sciencedirect.com Diabetes & Metabolism 40 (2014) 158–160
Short report
Acute caloric restriction improves glomerular filtration rate in patients with morbid obesity and type 2 diabetes I. Giordani a,b , I. Malandrucco a,b , S. Donno c,d , F. Picconi a,b , P. Di Giacinto a,b , A. Di Flaviani a,b , L. Chioma a,b , S. Frontoni a,b,∗ a Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy Unit of Endocrinology, Diabetes and Metabolism, S. Giovanni Calibita Fatebenefratelli Hospital, Lungotevere de’ Cenci 7, 00186 Rome, Italy c Service of Medical Statistics & Information Technology, Fatebenefratelli Association for Research (SeSMIT-AFaR), S. Giovanni Calibita Fatebenefratelli Hospital, Lungotevere de’ Cenci 5, 00186 Rome, Italy d AFaR, Unit of Internal Medicine, S. Giovanni Calibita Fatebenefratelli Hospital, Lungotevere de’ Cenci 5, 00186 Rome, Italy b
Received 3 November 2013; received in revised form 28 November 2013; accepted 10 December 2013
Abstract Aim. – The role of caloric restriction in the improvement of renal function following bariatric surgery is still unclear; with some evidence showing that calorie restriction can reduce proteinuria. However, data on the impact of caloric restriction on renal function are still lacking. Methods. – Renal function, as measured by glomerular filtration rate (GFR), was evaluated in 14 patients with type 2 diabetes mellitus, morbid obesity and stage 2 chronic kidney disease before and after a 7-day very low-calory diet (VLCD). Results. – After the VLCD, both GFR and overall glucose disposal (M value) significantly increased from 72.6 ± 3.8 mL/min/1.73 m−2 BSA to 86.9 ± 6.1 mL/min/1.73 m−2 BSA (P = 0.026) and from 979 ± 107 mol/min1 /m2 BSA to 1205 ± 94 mol/min1 /m2 BSA (P = 0.008), respectively. A significant correlation was observed between the increase in GFR and the rise in M value (r = 0.625, P = 0.017). Conclusion. – Our observation of improved renal function following acute caloric restriction before weight loss became relevant suggesting that calory restriction per se is able to affect renal function. © 2013 Elsevier Masson SAS. All rights reserved. Keywords: Caloric restriction; Glomerular filtration rate; Diabetes mellitus; Morbid obesity
1. Introduction Recent reports have associated weight loss following bariatric surgery with improvement in both glomerular hyperfiltration [1] and chronic renal disease [2] in severely obese patients with or without diabetes mellitus (DM). However, only a few clinical studies and case reports have shown dramatic reductions in proteinuria following weight loss by caloric restriction (CR) in obese subjects [3]. Although some preliminary clinical observations suggest a possible direct anti-proteinuric effect of CR itself, even before any significant weight loss [3], to the best of our knowledge, no clear data are currently available on the short-term impact of CR on glomerular filtration rate (GFR). ∗ Corresponding author. San Giovanni Calibita Fatebenefratelli Hospital, Endocrinology and Metabolism, Lungotevere de’ Cenci, 7, 00186 Rome, Italy. Tel.: +39 06 68 370 255; fax: +39 06 68 370 916. E-mail address: [email protected] (S. Frontoni).
1262-3636/$ – see front matter © 2013 Elsevier Masson SAS. All rights reserved. http://dx.doi.org/10.1016/j.diabet.2013.12.006
For this reason, the present preliminary proof-of-concept study has analyzed data from our previously published report [4] to investigate the possible impact of short-term CR on renal function in patients with type 2 DM, severe obesity and stage 2 chronic kidney disease (CKD). 2. Methods A total of 14 morbidly obese [body mass index (BMI) > 40 kg/m2 ] patients with type 2 DM (seven men and seven women), aged 60.3 ± 3.02 years and with diabetes duration of 4.8 ± 1.7 years and good metabolic control (HbA1c < 58 mmol/mol or < 7.5%), were recruited from the diabetes division of the Fatebenefratelli Hospital in Rome, Italy. Inclusion and exclusion criteria have been previously reported elsewhere [4]. Following a 7-day period to wash out all hypoglycaemic and anti-hypertensive medications, our patients were assessed
I. Giordani et al. / Diabetes & Metabolism 40 (2014) 158–160
at baseline and after 7 days of following a very low-calory diet (VLCD). During the VLCD, water and salt intakes were standardized to 1.5 L/day and < 6 g/day, respectively. Metabolic data have been reported elsewhere [4]. The VLCD consisted of a 400-kcal/day diet, the composition and adherence assessment of which has also been described previously, as have the analytical methods applied [4]. Patients’ 24-h blood pressure (BP) was recorded using an ambulatory BP monitoring system (TM2430, Intermed, Cape Town, South Africa) at baseline and after the VLCD. GFR was calculated using the Modification of Diet in Renal Disease (MDRD), Cockcroft–Gault (CG) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulas. 2.1. Statistical methods All data are presented as means ± SEMs. Within-subject comparisons before and after the VLCD were assessed by non-parametric tests (Mann–Whitney U test or Wilcoxon’s signed-rank test, as appropriate). Correlations were assessed by Spearman’s non-parametric correlation coefficient rho. P < 0.05 was considered statistically significant. All statistical analyses were performed using IBM SPSS Statistics 20.0 software (IBM SPSS Inc, Armonk, NY, USA). 2.2. Ethics In compliance with the Declaration of Helsinki, this study was approved by the Bioethics Committee of Fatebenefratelli Hospital, and all participants gave their written informed consent. 3. Results As previously reported, a 7-day VLCD resulted in significant decreases in weight (3.22 ± 0.56%; 3.58 ± 0.6 kg), BMI (from 44.8 ± 1.6 kg/m2 to 43.5 ± 1.6 kg/m2 ; P = 0.001), waist circumference (from 132.3 ± 3.4 cm to 129.93 ± 3.41 cm; P = 0.001), and significant changes in glucose disposal (M value) related to increased beta-cell function, particularly, first-phase insulin secretion [acute insulin response (AIR); P = 0.016]. After the VLCD, lean mass decreased from 63.8 ± 3.4 kg to 60.7 ± 3.2 kg (P = 0.001) and the M value (glucose disposal) significantly increased from 979 ± 107 mol/min1 /m2 BSA to 1205 ± 94 mol/min1 /m2 BSA (P = 0.008). As for renal function, GFR evaluated according to the MDRD formula significantly increased following CR from 72.6 ± 3.8 mL/min/1.73 m−2 BSA to 86.9 ± 6.1 mL/min/1.73 m−2 BSA (P = 0.026), while a significant correlation was observed between the increase in GFR and rise in M value (r = 0.625, P = 0.017). No correlation was found between changes in GFR and reductions in BMI and waist circumference, or with changes in BP either during the day or at night. Also, despite a significant reduction in muscle mass observed after VLCD, this change also did not correlate with the increase in GFR (correlation lean mass – GFR; P = 0.76). In addition, systolic (SBP) and
159
diastolic blood pressure (DBP) both non-significantly increased after 1 week of anti-hypertensive treatment washout (P = 0.10 and P = 0.20, respectively), and remained unchanged at the end of 1 week of calory restriction (SBP: from 135.1 ± 3.7 mmHg to 133.6 ± 1.9, mmHg, P = 0.5; DBP: from 74.2 ± 1.6 mmHg to 74.5 ± 1.6 mmHg, P = 0.9). 4. Conclusion In severely obese patients with type 2 DM and stage 2 CKD, our preliminary proof-of-concept study has demonstrated that short-term CR is associated with acute improvement in renal function. Bariatric surgery has been associated with improved renal function in both established chronic renal impairment [2] and reduced hyperfiltration [1,5,6]. However, to the best of our knowledge, all reported studies were performed within a period ranging from 1 to 48 months [5,7] after surgery, when weight loss had already occurred and may have influenced decrease in BP and markers of renal inflammation, whereas our preliminary observation of an increased GFR following acute CR at a time when changes in body weight and BP were negligible, suggesting a direct impact of VLCD on renal function. Surprisingly, despite numerous epidemiological studies linking obesity and the development of CKD, few clinical studies have investigated the effect of diet on renal function in obese subjects, but those that did have found some preliminary observations, suggesting an anti-proteinuric effect directly induced by CR itself and well before the presence of significant weight loss [3]. The present data show a significant increase in GFR in patients with type 2 DM and stage 2 CKD following CR that was unrelated to weight loss and BP changes, and only related to glucose disposal. GFR is highly dependent on the state of hydration. In the present study, water and salt intake were standardized and kept constant throughout the trial. The impact of changes in the state of hydration on the observed modification of GFR following the VLCD can therefore be excluded. A correlation between insulin sensitivity (IS) and albuminuria has previously been reported [8] in subjects without diabetes, while insulin resistance was found to be related to kidney function in patients with type 2 DM [9]. Our present study has confirmed the correlation between IS and GFR in diabetic patients and demonstrated for the first time that an improvement in glucose disposal following calorie restriction may be responsible for the increase in GFR. The loss of muscle mass could have influenced the modification of serum creatinine and, thus, the improvement in GFR. However, no correlation between GFR and muscle mass was found in our patients, thereby, precluding any possible impact of lean mass reduction on the observed GFR increase. In the present report, BP non-significantly increased after 1 week of anti-hypertensive treatment washout and, more important, remained unchanged at the end of 1 week of calorie restriction, whereas GFR appeared, on the contrary, to be significantly increased. Given the small size of our study population, only a high correlation (0.63) can be considered significant (a bilateral alpha
160
I. Giordani et al. / Diabetes & Metabolism 40 (2014) 158–160
of 0.05) with adequate power (0.80). This makes it impossible to definitively predict that increasing the number of subjects would allow the detection of a correlation between change in ambulatory BP and change in GFR. Another limitation of our study was the low precision of the methods used to estimate GFR (compared with isotopic or non-isotopic gold-standard methods, such as inulin clearance). Nevertheless, this was a retrospective subanalysis of a previously published study and, in an attempt to overcome this limitation, GFR in the present analysis was calculated using the MDRD, CG and CKD-EPI formulas, and the results were always consistent. Also, as a lower bias with the MDRD equation vs the CKD-EPI formula has previously been reported [10], the MDRD equation was chosen for our obese patient population. The correlation between improvement in GFR and increase in glucose disposal, but not with changes in body weight, muscle mass or BP, suggests the influence of IS and/or insulin secretion on GFR in patients with DM. Disclosure of interest The authors declare that they have no conflicts of interest concerning this article. Acknowledgements Conception and design of the study: Simona Frontoni; generation, collection, assembly, analysis and/or interpretation of data: Ilaria Giordani, Ilaria Malandrucco, Fabiana Picconi, Paola Di Giacinto, Alessandra Di Flaviani, Laura Chioma; and drafting or revision of the manuscript: Silvia Donno, Simona Frontoni; approval of the final version of the manuscript: Simona Frontoni. Sources of funding: AFAR (Fatebenefratelli Association for Research).
Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.diabet. 2013.12.006. References [1] Saliba J, Kasim NR, Tamboli RA, Isbell JM, Marks P, Feurer ID, et al. Rouxen-Y gastric bypass reverses renal glomerular but not tubular abnormalities in excessively obese diabetics. Surgery 2010;147:282–7. [2] Alexander JW, Goodman HR, Hawver LR, Cardi MA. Improvement and stabilization of chronic kidney disease after gastric bypass. Surg Obes Relat Dis 2009;5:237–413. [3] Praga M, Morales E. Obesity-related renal damage: changing diet to avoid progression. Kidney Int 2010;78:633–5. [4] Malandrucco I, Pasqualetti P, Giordani I, Manfellotto D, De Marco F, Alegiani F, et al. Very-low-calorie diet: a quick therapeutic tool to improve  cell function in morbidly obese patients with type 2 diabetes. Am J Clin Nutr 2012;95:609–13. [5] Navaneethan SD, Yehnert H, Moustarah F, Schreiber MJ, Schauer PR, Beddhu S. Weight loss interventions in chronic kidney disease: a systematic review and meta-analysis. Clin J Am Soc Nephrol 2009;4:1565–74. [6] Chagnac A, Weinstein T, Herman M, Hirsh J, Gafter U, Ori Y. The effects of weight loss on renal function in patients with severe obesity. J Am Soc Nephrol 2003;14:1480–6. [7] Jose B, Ford S, Super P, Thomas GN, Dasgupta I, Taheri S. The effect of biliopancreatic diversion surgery on renal function – a retrospective study. Obes Surg 2013;23:634–7. [8] Nistala R, Whaley-Connell A. Resistance to insulin and kidney disease in the cardiorenal metabolic syndrome; role for angiotensin II. Mol Cell Endocrinol 2013;378:53–8. [9] De Cosmo S, Trevisan R, Minenna A, Vedovato M, Viti R, Santini SA, et al. Insulin resistance and the cluster of abnormalities related to the metabolic syndrome are associated with reduced glomerular filtration rate in patients with type 2 diabetes. Diabetes Care 2006;29:432–4. [10] Bouquegneau A, Vidal-Petiot E, Vrtovsnik F, Cavalier E, Rorive M, Krzesinski JM, et al. Modification of diet in renal disease versus chronic kidney disease epidemiology collaboration equation to estimate glomerular filtration rate in obese patients. Nephrol Dial Transplant 2013;28(Suppl. 4):iv122–30.