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American Journal of Kidney Diseases

Bariatric Surgery, Kidney Function, Insulin Resistance, and Adipokines in Patients With Decreased GFR: A Cohort Study

Published:November 17, 2014DOI:https://doi.org/10.1053/j.ajkd.2014.09.018
      To the Editor:
      Bariatric surgery induces long-term sustainable weight loss and improves type 2 diabetes and hypertension, thereby contributing to lower mortality.
      • Kashyap S.R.
      • Bhatt D.L.
      • Wolski K.
      • et al.
      Metabolic effects of bariatric surgery in patients with moderate obesity and type 2 diabetes: analysis of a randomized control trial comparing surgery with intensive medical treatment.
      • Schauer P.R.
      • Bhatt D.L.
      • Kirwan J.P.
      • et al.
      Bariatric surgery versus intensive medical therapy for diabetes—3-year outcomes.
      • Sjostrom L.
      • Narbro K.
      • Sjostrom C.D.
      • et al.
      Effects of bariatric surgery on mortality in Swedish obese subjects.
      The resulting weight loss also improves glomerular hyperfiltration and albuminuria.
      • Navaneethan S.D.
      • Yehnert H.
      • Moustarah F.
      • Schreiber M.J.
      • Schauer P.R.
      • Beddhu S.
      Weight loss interventions in chronic kidney disease: a systematic review and meta-analysis.
      • Afshinnia F.
      • Wilt T.J.
      • Duval S.
      • Esmaeili A.
      • Ibrahim H.N.
      Weight loss and proteinuria: systematic review of clinical trials and comparative cohorts.
      However, the conclusion that bariatric surgery improves kidney function has been based on using only estimated GFR or 24-hour creatinine clearance in those with CKD.
      • Navaneethan S.D.
      • Yehnert H.
      Bariatric surgery and progression of chronic kidney disease.
      • Getty J.L.
      • Hamdallah I.N.
      • Shamseddeen H.N.
      • et al.
      Changes in renal function following Roux-en-Y gastric bypass: a prospective study.
      In this prospective cohort study, we directly measured kidney function (by measured GFR) in obese individuals with reduced GFR after bariatric surgery and investigated metabolic mechanisms that might account for the effects of weight loss on changes in kidney function.
      Fifteen patients undergoing bariatric surgery who had serum creatinine > 1.3 mg/dL were included; 13 completed the last follow-up. Patients came to the Clinical Research Unit before and 3, 6, and 12 months after surgery to assess body composition, lipid, metabolic (oral glucose tolerance, adipokines, inflammatory markers), kidney function, and QoL parameters (Table 1; detailed methods in Item S1). Changes from baseline to 12 months postsurgery were evaluated using Wilcoxon signed rank test. Spearman correlations were used to determine associations between change in mGFR, other kidney function markers, and changes in metabolic markers.
      Table 1Changes in Obesity, Lipid, Metabolic, Kidney Function, and QoL Parameters Before and 12 Months After Bariatric Surgery
      VariableBaseline12 moChangeP
      Wilcoxon signed rank test.
      Obesity measures
       Weight (kg)160.3 [123.5 to 172.0]109.0 [96.1 to 125.3]−30.7 [−38.9 to −24.0]<0.001
       Height (cm)176.5 [172.0 to 181.9]
       BMI (kg/m2)51.0 [36.8 to 57.8]34.4 [30.8 to 46.7]−9.3 [−14.0 to −8.1]<0.001
       Waist circumference (cm)138.5 [122.0 to 157.5]118.5 [106.0 to 130.0]−21.8 [−25.3 to −15.0]<0.001
       Fat %47.2 [40.1 to 53.2]34.2 [30.2 to 44.6]−10.2 [−15.7 to −5.3]<0.001
       Fat mass (kg)68.3 [46.0 to 89.2]37.4 [28.6 to 59.8]−24.8 [−31.5 to −20.4]<0.001
       Fat-free mass (kg)72.1 [68.5 to 87.7]68.4 [64.1 to 77.6]−7.6 [−10.1 to −3.2]0.002
      Lipid parameters
       Total cholesterol (mg/dL)134.0 [122.0 to 146.0]133.0 [107.0 to 138.0]−13.0 [−26.0 to 15.0]0.3
       HDL cholesterol (mg/dL)34.0 [31.0 to 38.0]44.0 [38.0 to 61.0]11.0 [8.0 to 14.0]0.001
       Serum triglycerides (mg/dL)156.0 [106.0 to 183.0]99.0 [75.0 to 119.0]−54.0 [−90.0 to 2.0]0.05
       LDL cholesterol (mg/dL)60.2 [47.6 to 71.8]57.4 [46.8 to 69.2]−0.80 [−23.0 to 6.6]0.5
      Metabolic parameters
       Log(hs-CRP)0.98 [0.90 to 1.00]0.30 [−0.18 to 0.76]−0.56 [−1.1 to −0.24]<0.001
       HOMA-IR18.6 [5.2 to 34.1]4.8 [3.0 to 6.0]−13.8 [−29.2 to −1.5]0.008
       Matsuda index0.91 [0.42 to 1.9]2.4 [1.9 to 2.7]1.5 [0.51 to 2.2]0.04
       HMW adiponectin2,244 [1,654 to 3,438]6,617 [2,696 to 7,771]1,939 [869 to 5,559]<0.001
       Total adiponectin4,815 [4,339 to 7,858]14,491 [5,837 to 17,756]8,329 [1,021 to 12,180]<0.001
       Leptin37.8 [22.8 to 60.8]10.6 [6.0 to 16.1]−15.7 [−26.2 to −7.2]0.001
      Kidney function
       Serum creatinine (mg/dL)1.6 [1.5 to 1.8]1.4 [1.2 to 1.6]−0.27 [−0.34 to −0.08]0.006
       Cystatin C (mg/dL)1.8 [1.7 to 1.9]1.6 [1.5 to 2.0]0.02 [−0.17 to 0.10]0.5
       B2M (mg/dL)3.5 [3.3 to 3.8]3.5 [2.9 to 3.8]0.00 [−0.40 to 0.40]0.9
       eGFRcr (mL/min)47.7 [37.4 to 52.4]52.3 [45.1 to 63.8]7.9 [0.77 to 16.2]0.01
       eGFRcr (mL/min/1.73 m2)30.5 [26.8 to 34.5]36.5 [35.9 to 44.8]11.0 [3.9 to 14.3]<0.001
       eGFRcys (mL/min)34.6 [33.4 to 37.7]41.7 [31.0 to 46.2]−0.73 [−2.5 to 10.9]0.3
       eGFRcys (mL/min/1.73 m2)23.7 [22.4 to 29.0]28.9 [24.6 to 34.9]2.2 [0.57 to 10.7]0.003
       eGFRcr-cys (mL/min)41.6 [32.3 to 47.2]45.8 [34.6 to 56.3]4.8 [0.82 to 9.2]0.02
       eGFRcr-cys (mL/min/1.73 m2)26.0 [25.2 to 31.5]34.3 [26.8 to 41.9]6.3 [3.4 to 10.4]<0.001
       mGFR (mL/min)82.0 [60.9 to 89.7]80.5 [63.0 to 111.5]1.2 [−1.6 to 10.9]0.3
       mGFR (mL/min/1.73 m2)50.0 [44.0 to 58.0]64.0 [48.0 to 87.0]8.0 [5.0 to 12.0]0.02
       24-h proteinuria (g)0.60 [0.16 to 1.60]0.43 [0.16 to 0.85]−0.02 [−0.28 to 0.28]0.8
      QoL composite score
       SF-12 physical health39.8 [25.3 to 47.8]49.1 [42.1 to 51.6]4.9 [0.77 to 19.3]0.007
       SF-12 mental health49.9 [40.1 to 57.8]56.4 [48.9 to 58.2]2.8 [−1.6 to 11.6]0.2
      Note: N = 13. Values are given as median [interquartile range].
      Abbreviations: B2M, β2-microglobulin; BMI, body mass index; cr, creatinine; cys, cystatin C; HDL, high-density lipoprotein; HOMA-IR, homeostatic model assessment of insulin resistance; hs-CRP, high-sensitivity C-reactive protein; HMW, high-molecular-weight; LDL, low-density lipoprotein; m/eGFR: measured/estimated glomerular filtration rate; SF-12, 12-Item Short Form Health Survey.
      a Wilcoxon signed rank test.
      Patients underwent Roux-en-Y gastric bypass (n = 7), laparoscopic adjustable gastric banding (n = 3), or laparoscopic sleeve gastrectomy (n = 3). Median age was 56 (IQR, 49-63) years, with 92% men and 77% white. All included patients had hypertension and hyperlipidemia and most had type 2 diabetes. At baseline, median unadjusted and BSA-adjusted mGFRs were 82 (IQR, 60.9-89.7) mL/min and 50 (IQR, 44.0-58.0) mL/min/1.73 m2, respectively.
      Twelve months after surgery, BMI, waist circumference, fat mass, and fat-free mass decreased significantly, along with some improvement in lipid profile and SF-12 physical composite scores. Matsuda index and total/HMW adiponectin also increased, while HOMA-IR, plasma leptin, and hs-CRP levels decreased (Table 1). These anthropometric and metabolic changes corresponded with improvements in most kidney disease measures. Although unadjusted mGFR did not change significantly, there was significant improvement in BSA-adjusted mGFRs at 3-, 6- and 12-months’ follow-up (Item S1). Serum cystatin C and B2M levels did not change at last follow-up (Table 1). Item S1 reports a sensitivity analysis focusing on the Roux-en-Y gastric bypass patients. Change in kidney function (both adjusted and unadjusted mGFR) correlated with leptin and B2M level changes (Table 2), while change in BMI and fat mass did not correlate with kidney function and metabolic parameters.
      Table 2Spearman Correlations Between Changes in Kidney Function, Obesity, Adipokine, and Insulin Resistance Measures
      VariableCorrelation With Change inρ (95% CI)P
      Change in mGFR (mL/min)Matsuda index0.33 (−0.30 to 0.96)0.3
      Leptin−0.60 (−1.00 to −0.07)0.03
      Total adiponectin0.08 (−0.58 to 0.74)0.8
      β2 microglobulin−0.65 (−1.00 to −0.14)0.02
      Cystatin C−0.26 (−0.90 to 0.38)0.4
      Log(hs-CRP)−0.50 (−1.00 to 0.07)0.08
      Change in mGFR (mL/min/1.73 m2)Matsuda index0.54 (−0.02 to 1.00)0.06
      Leptin−0.74 (−1.00 to −0.29)0.004
      Total adiponectin0.21 (−0.44 to 0.86)0.5
      β2 microglobulin−0.76 (−1.00 to −0.33)0.003
      Cystatin C−0.36 (−0.98 to 0.26)0.2
      Log(hs-CRP)−0.61 (−1.00 to −0.09)0.03
      Change in Matsuda indexLeptin−0.73 (−1.00 to −0.28)0.005
      Total adiponectin0.24 (−0.41 to 0.88)0.4
      β2 microglobulin−0.47 (−1.00 to 0.11)0.1
      Cystatin C−0.23 (−0.88 to 0.41)0.5
      Log(hs-CRP)−0.35 (−0.97 to 0.28)0.3
      Change in HOMA-IRLeptin0.63 (0.11 to 1.00)0.02
      Total adiponectin−0.02 (−0.68 to 0.65)0.9
      β2 microglobulin0.76 (0.33 to 1.00)0.002
      Cystatin C0.64 (0.13 to 1.00)0.02
      Log(hs-CRP)0.12 (−0.54 to 0.78)0.7
      Our results suggest potential benefits of bariatric surgery and the variations among the different measures of kidney function in those with reduced GFRs. The metabolic effects of gastric bypass are well known; as expected, we noted improvements in metabolic parameters with bariatric surgery. We speculate that the absence of decline in kidney function over the course of our study may be a potential benefit in those with reduced GFRs, but the lack of a control group precludes definitive conclusions.
      • Haynes R.
      • Staplin N.
      • Emberson J.
      • et al.
      Evaluating the contribution of the cause of kidney disease to prognosis in CKD: results from the Study of Heart and Renal Protection (SHARP).
      With rapid weight loss during the first few months after surgery, associated hemodynamic changes could lead to an acute decrease in GFR.
      • Weingarten T.N.
      • Gurrieri C.
      • McCaffrey J.M.
      • et al.
      Acute kidney injury following bariatric surgery.
      Our data suggest that mGFR did not change at 3 or 6 months postsurgery, suggesting an attenuation of the expected acute deterioration in kidney function (Item S1). Also, the observed correlations between leptin and mGFR suggest that leptin might act renoprotectively after surgery; further studies to understand this relationship and examine other potential mechanistic pathways are warranted.
      Because measuring GFR is expensive and time consuming, it is of interest whether novel filtration biomarkers can predict changes in mGFR in this setting. Given the loss of fat-free mass, serum creatinine and eGFR were expected to improve and did not correlate with mGFR. B2M is freely filtered, metabolized in the renal tubule, and reported to correlate with mGFR in other populations. Our results suggest its potential utility in bariatric surgery patients, but its role as a biomarker of change in kidney function should be studied in other cohorts. In a recent study with mean mGFR of 117 ± 40 mL/min, cystatin C was associated with mGFR in those undergoing bariatric surgery.
      • Friedman A.N.
      • Moe S.
      • Fadel W.F.
      • et al.
      Predicting the glomerular filtration rate in bariatric surgery patients.
      However, we did not observe changes in cystatin C and such correlation. This may be attributed to the differences in baseline kidney function or to our study’s small sample size.
      In summary, bariatric surgery is associated with improvement in insulin resistance, adipokines, and QoL, with no changes in kidney function at 12 months’ follow-up. B2M correlates with mGFR in this setting. Cumulatively, this hypothesis-generating study argues for larger long-term studies in this area.

      Acknowledgements

      We thank the research volunteers for outstanding dedication and effort and the nursing staff and technicians of the CCF Clinical Research Unit who helped with implementation of the study and data collection.
      The results of this study were presented as an abstract at the American Society of Nephrology meeting held November 9, 2013, in Atlanta, GA.
      Support: SDN was supported by a career development award from the National Center for Research Resources (NCRR) and the National Center for Advancing Translational Sciences (grant TR000440 ). SKM was supported by National Institutes of Health (NIH) grant T32 DK007319 . This work was supported in part by the NCRR Clinical and Translational Science Award 1UL1RR024989 . The article’s content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH, which did not have any role in study design; collection, analysis, and interpretation of data; writing the report; and the decision to submit the report for publication.
      Financial Disclosure: PRS is principal investigator of the STAMPEDE trial, funded by Ethicon, and consults for Ethicon. The remaining authors declare that they have no other relevant financial interests.
      Author Contributions: Research area and study design: SDN, JPK, PRS; data acquisition: SDN, SKM, JPK, PRS; data analysis and interpretation: SDN, SKM, SA, SRK, JPK, PRS. Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved. SDN takes responsibility that this study has been reported honestly, accurately, and transparently; that no important aspects of the study have been omitted, and that any discrepancies from the study as planned have been explained.

      Supplementary Material

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