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Original Article

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Metabolic and Hormonal Determinants of Glomerular Filtration Rate and Renal Hemodynamics in Severely Obese Individuals

Vitolo E.a · Santini E.a · Salvati A.a · Volterrani D.b · Duce V.b · Bruno R.M.a · Solini A.b

Author affiliations

aDepartment of Clinical and Experimental Medicine,University of Pisa, Pisa, Italy; bDepartment of Translational Research and Novel Technologies, University of Pisa, Pisa, Italy

Corresponding Author

Anna Solini, MD PhD

Department of Clinical and Experimental Medicine

University of Pisa

56126 Pisa, Italy

anna.solini@med.unipi.it

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Abstract

Objective: Renal function is often compromised in severe obesity. A true measurement of glomerular filtration rate (GFR) is unusual, and how estimation formulae (EstForm) perform in such individuals is unclear. We characterized renal function and hemodynamics in severely obese individuals, assessing the reliability of EstForm. Methods: We measured GFR (mGFR) by iohexol plasma clearance, renal plasma flow (RPF) by 123I-ortho-iodo-hippurate, basal and stimulated vascular renal indices, endothelium-dependent and -independent vasodilation using flow-mediated dilation (FMD) as well as metabolic and hormonal profile in morbid, otherwise healthy, obese subjects. Results: Compared with mGFR, the better performing EstForm was CKD-EPI (5.3 ml/min/1.73 m2 bias by Bland-Altman analysis). mGFR was directly related with RPF, total and incremental glucose AUC, and inversely with PTH and h8 cortisol. Patients with mGFR below the median shown significantly higher PTH and lower vitamin D3. Basal or dynamic renal resistive index, FMD, pulse wave velocity were not related with mGFR. In an adjusted regression model, renal diameter and plasma flow remained related with mGFR (R2 = 0.67), accounting for 15% and 21% of mGFR variance, respectively. Conclusions: CKD-EPI formula should be preferred in morbid obesity; glucose increments during oral glucose tolerance test correlate with hyperfiltration; RPF and diameter are independent determinants of mGFR; slightly high PTH values, frequent in obesity, might influence mGFR.

© 2016 The Author(s) Published by S. Karger GmbH, Freiburg


References

  1. Kramer HJ, Saranathan A, Luke A, Durazo-Arvizu RA, Giuchan C, Hou S, Cooper R: Increasing body mass index and obesity in the incident ESRD population. J Am Soc Nephrol 2006;17:1453-1459.
  2. Hsu CY, McCulloch CE, Iribarren C, Darbinian J, Go AS: Body mass index and risk for end-stage renal disease. Ann Int Med 2006;144:21-28.
  3. Iseki K, Ikemiya Y, Kinjo K, Inoue T, Iseki C, Takishita S: Body mass index and the risk of development of end-stage renal disease in a screened cohort. Kidney Int 2004;65:1870-1876.
  4. de Vinuesa SG, Goicoechea M, Kanter J, Puerta M, Cachofeiro V, Lahera V, Gomez-Campdera F, Luño J: Insulin resistance, inflammatory biomarkers, and adipokines in patients with chronic kidney disease: effects of angiotensin II blockade. J Am Soc Nephrol 2006;17(12 suppl 3):S206-S212.
  5. Ritz E, Koleganova N, Piecha G: Is there an obesity-metabolic syndrome related glomerulopathy? Curr Opin Nephrol Hypert 2011;20:44-49
  6. Matsushita K, van der Velde M, Astor BC, Woodward M, Levey AS, de Jong PE, Coresh J, Gansevoort RT, Chronic Kidney Disease Prognosis Consortium: Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis. Lancet 2010;375:2073-2081.
  7. Van der Velde M, Matsushita K, Coresh J, Astor BC, Woodward M, Levey A, de Jong P, Gansevoort RT; Chronic Kidney Disease Prognosis Consortium: Lower estimated glomerular filtration rate and higher albuminuria are associated with all-cause and cardiovascular mortality. A collaborative meta-analysis of high-risk population cohorts. Kidney Int 2011;79:1341-1352.
  8. Bello AK, Peters J, Wight J, El Nahas M: The Kidney Evaluation and Awareness Program in Sheffield (KEAPS): a community-based screening for microalbuminuria in a British population. Nephron Clin Pract 2010;116:c95-c103.
  9. Tang J, Yan H, Zhuang S: Inflammation and oxidative stress in obesity-related glomerulopathy. Int J Nephrol 2012;608397.
  10. Henegar JR, Bigler SA, Henegar LK, Tyagi SC, Hall JE: Functional and structural changes in the kidney in the early stages of obesity. J Am Soc Nephrol 2001;12:1211-1217.
    External Resources
  11. Wuerzner G, Pruijm M, Maillard M, Bovet P, Renaud C, Burnier M, Bochud M: Marked association between obesity and glomerular hyperfiltration: a cross-sectional study in an African population. Am J Kidney Dis 2010;56:303-312.
  12. de Vries AP, Ruggenenti P, Ruan XZ, Praga M, Cruzado JM, Bajema IM, D'Agati VD, Lamb HJ, Pongrac Barlovic D, Hojs R, Abbate M, Rodriquez R, Mogensen CE, Porrini E; ERA-EDTA Working Group Diabesity: Fatty kidney: emerging role of ectopic lipid in obesity-related renal disease. Lancet Diabetes Endocrinol 2014;2:417-426.
  13. Jerums G, Premaratne E, Panagiotopoulos S, MacIsaac RJ: The clinical significance of hyperfiltration in diabetes. Diabetologia 2010;53:2093-2104.
  14. Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J; CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration): A new equation to estimate glomerular filtration rate. Ann Intern Med 2009;150:604-612.
  15. Murata K, Baumann NA, Saenger AK, Larson TS, Rule AD, Lieske JC: Relative performance of the MDRD and CKD-EPI equations for estimating glomerular filtration rate among patients with varied clinical presentations. Clin J Am Soc Nephrol 2011;6:1963-1972.
  16. Bouquegneau A, Vidal-Petiot E, Vrtovsnik F, Cavalier E, Rorive M, Krzesinski JM, Delanaye P, Flamant M: 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;28:122-130.
  17. Abouchacra S, Chaaban A, Gebran N, Hussein Q, Ahmed M, Bernieh B, Torab F, Kayyal Y, Al Omary H, Nagelkerke N: GFR estimation in the morbidly obese pre- and postbariatric surgery: one size does not fit all. Intern Urol Nephrol 2013;45:157-162.
  18. Redal-Baigorri B, Rasmussen K, Heaf JG: The use of absolute values improves performance of estimation formulae: a retrospective cross sectional study. BioMed Central Nephrol 2013;14:271.
  19. Tublin ME, Bude RO, Platt JF: The resistive index in renal Doppler sonography: where do we stand? Am J Roentgenology 2003;180:885-892.
  20. Kawai T, Kamide K, Onishi M, Yamamoto-Hanasaki H, BabaY, Hongyo K, Shimaoka I, Tatara Y, Takeya Y, Ohishi M, Rakugi H: Usefulness of the resistive index in renal Doppler ultrasonography as an indicator of vascular damage in patients with risks of atherosclerosis. Nephrol Dial Transplant 2011;26:3256-3262.
  21. Blaufox MD, Aurell M, Bubeck B, Fommei E, Piepsz A, Russell C, Taylor A,Thomsen HS, Volterrani D: Report of the Radionuclides in Nephrourology Committee on renal clearance. J Nucl Med 1996;37:1883-1890.
    External Resources
  22. Ghiadoni L, Faita F, Salvetti M, Cordiano C, Biggi A, Puato M, Di Monaco A, De Siati L, Volpe M, Ambrosio G, Gemignani V, Muiesan ML, Taddei S, Lanza GA, Cosentino F: Assessment of flow-mediated dilation reproducibility: a nationwide multicenter study. J Hypertens 2012;30:1399-1405.
  23. Van Bortel LM, Laurent S, Boutouyrie P, Chowienczyk P, Cruickshank JK, De Backer T, Filipovsky J, Huybrechts S, Mattace-Raso FU, Protogerou AD, Schillaci G, Segers P, Vermeersch S, Weber T; Artery Society; European Society of Hypertension Working Group on Vascular Structure and Function; European Network for Noninvasive Investigation of Large Arteries: Expert consensus document on the measurement of aortic stiffness in daily practice using carotid-femoral pulse wave velocity. J Hypertens 2012;30:445-448.
  24. Bland JM, Altman DG: Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986;1:307-310.
  25. Nair S, Mishra V, Hayden K, Lisboa PJ, Pandya B, Vinjamuri S, Hardy KJ, Wilding JP: The four-variable modification of diet in renal disease formula underestimates glomerular filtration rate in obese type 2 diabetic individuals with chronic kidney disease. Diabetologia 2011;54:1304-1307.
  26. Friedman AN, Moe S, Fadel WF, Inman M, Mattar SG, Shihabi Z, Quinney SK: Predicting the glomerular filtration rate in bariatric surgery patients. Am J Nephrol 2014;39:8-15.
  27. Belhatem N, Mohammedi K, Rouzet F, Matallah N, Al Baloshi A, Travert F, Velho G, Roussel R, Le Guludec D, Marre M, Hansel B: Impact of morbid obesity on the kidney function of patients with type 2 diabetes. Diabetes Res Clin Pract 2015;108:143-149.
  28. Michels WM, Grootendorst DC, Verduijn M, Elliott EG, Dekker FW, Krediet RT; NECOSAD Study Group: Performance of the Cockcroft-Gault, MDRD, and new CKD-EPI formulas in relation to GFR, age, and body size. Clin J Am Soc Nephrol 2010;5:1003-1009.
  29. Lemoine S, Guebre-Egziabher F, Sens F, Nguyen-Tu MS, Juillard L, Dubourg L, Hadj-Aissa A: Accuracy of GFR estimation in obese patients. Clin J Am Soc Nephrol 2014;9:720-727.
  30. Okada R, Yasuda Y, Tsushita K, Wakai K, Hamajima N, Matsuo S: Glomerular hyperfiltration in prediabetes and prehypertension. Nephrol Dial Transplant 2012;27:1821-1825.
  31. Melsom T, Mathisen UD, Ingebretsen OC, Jenssen TG, Njølstad I, Solbu MD, Toft I, Eriksen BO: Impaired fasting glucose is associated with renal hyperfiltration in the general population. Diabetes Care 2011;34:1546-1551.
  32. Upadhyay A, Hwang SJ, Mitchell GF, Vasan RS, Vita JA, Stantchev PI, Meigs JB, Larson MG, Levy D, Benjamin EJ, Fox CS: Arterial stiffness in mild-to-moderate CKD. J Am Soc Nephrol 2009;20:2044-2053.
  33. Bruno RM, Penno G, Daniele G, Pucci L, Lucchesi D, Stea F, Landini L, Cartoni G, Taddei S, Ghiadoni L, Del Prato S: Type 2 diabetes mellitus worsens arterial stiffness in hypertensive patients through endothelial dysfunction. Diabetologia 2012;55:1847-1855.
  34. Vlachopoulos C, Aznaouridis K, O'Rourke MF, Safar ME, Baou K, Stefanadis C: Prediction of cardiovascular events and all-cause mortality with central haemodynamics: a systematic review and meta-analysis. Eur Heart J 2010;31:1865-1871.
  35. Maccario M, Tassone F, Grottoli S, Rossetto R, Gauna C Ghigo E: Neuroendocrine and metabolic determinants of the adaptation of GH/IGF-I axis to obesity. Ann Endocrinol (Paris) 2002;63:140-144.
    External Resources
  36. Grunenwald S, Tack I, Chauveau D, Bennet A, Caron P: Impact of growth hormone hypersecretion on the adult human kidney. Ann Endocrinol (Paris) 2011;72:485-495.

Article / Publication Details

First-Page Preview
Abstract of Original Article

Received: January 04, 2016
Accepted: May 16, 2016
Published online: October 05, 2016
Issue release date: November 2016

Number of Print Pages: 11
Number of Figures: 1
Number of Tables: 5

ISSN: 1662-4025 (Print)
eISSN: 1662-4033 (Online)

For additional information: https://www.karger.com/OFA

References

  1. Kramer HJ, Saranathan A, Luke A, Durazo-Arvizu RA, Giuchan C, Hou S, Cooper R: Increasing body mass index and obesity in the incident ESRD population. J Am Soc Nephrol 2006;17:1453-1459.
  2. Hsu CY, McCulloch CE, Iribarren C, Darbinian J, Go AS: Body mass index and risk for end-stage renal disease. Ann Int Med 2006;144:21-28.
  3. Iseki K, Ikemiya Y, Kinjo K, Inoue T, Iseki C, Takishita S: Body mass index and the risk of development of end-stage renal disease in a screened cohort. Kidney Int 2004;65:1870-1876.
  4. de Vinuesa SG, Goicoechea M, Kanter J, Puerta M, Cachofeiro V, Lahera V, Gomez-Campdera F, Luño J: Insulin resistance, inflammatory biomarkers, and adipokines in patients with chronic kidney disease: effects of angiotensin II blockade. J Am Soc Nephrol 2006;17(12 suppl 3):S206-S212.
  5. Ritz E, Koleganova N, Piecha G: Is there an obesity-metabolic syndrome related glomerulopathy? Curr Opin Nephrol Hypert 2011;20:44-49
  6. Matsushita K, van der Velde M, Astor BC, Woodward M, Levey AS, de Jong PE, Coresh J, Gansevoort RT, Chronic Kidney Disease Prognosis Consortium: Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis. Lancet 2010;375:2073-2081.
  7. Van der Velde M, Matsushita K, Coresh J, Astor BC, Woodward M, Levey A, de Jong P, Gansevoort RT; Chronic Kidney Disease Prognosis Consortium: Lower estimated glomerular filtration rate and higher albuminuria are associated with all-cause and cardiovascular mortality. A collaborative meta-analysis of high-risk population cohorts. Kidney Int 2011;79:1341-1352.
  8. Bello AK, Peters J, Wight J, El Nahas M: The Kidney Evaluation and Awareness Program in Sheffield (KEAPS): a community-based screening for microalbuminuria in a British population. Nephron Clin Pract 2010;116:c95-c103.
  9. Tang J, Yan H, Zhuang S: Inflammation and oxidative stress in obesity-related glomerulopathy. Int J Nephrol 2012;608397.
  10. Henegar JR, Bigler SA, Henegar LK, Tyagi SC, Hall JE: Functional and structural changes in the kidney in the early stages of obesity. J Am Soc Nephrol 2001;12:1211-1217.
    External Resources
  11. Wuerzner G, Pruijm M, Maillard M, Bovet P, Renaud C, Burnier M, Bochud M: Marked association between obesity and glomerular hyperfiltration: a cross-sectional study in an African population. Am J Kidney Dis 2010;56:303-312.
  12. de Vries AP, Ruggenenti P, Ruan XZ, Praga M, Cruzado JM, Bajema IM, D'Agati VD, Lamb HJ, Pongrac Barlovic D, Hojs R, Abbate M, Rodriquez R, Mogensen CE, Porrini E; ERA-EDTA Working Group Diabesity: Fatty kidney: emerging role of ectopic lipid in obesity-related renal disease. Lancet Diabetes Endocrinol 2014;2:417-426.
  13. Jerums G, Premaratne E, Panagiotopoulos S, MacIsaac RJ: The clinical significance of hyperfiltration in diabetes. Diabetologia 2010;53:2093-2104.
  14. Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J; CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration): A new equation to estimate glomerular filtration rate. Ann Intern Med 2009;150:604-612.
  15. Murata K, Baumann NA, Saenger AK, Larson TS, Rule AD, Lieske JC: Relative performance of the MDRD and CKD-EPI equations for estimating glomerular filtration rate among patients with varied clinical presentations. Clin J Am Soc Nephrol 2011;6:1963-1972.
  16. Bouquegneau A, Vidal-Petiot E, Vrtovsnik F, Cavalier E, Rorive M, Krzesinski JM, Delanaye P, Flamant M: 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;28:122-130.
  17. Abouchacra S, Chaaban A, Gebran N, Hussein Q, Ahmed M, Bernieh B, Torab F, Kayyal Y, Al Omary H, Nagelkerke N: GFR estimation in the morbidly obese pre- and postbariatric surgery: one size does not fit all. Intern Urol Nephrol 2013;45:157-162.
  18. Redal-Baigorri B, Rasmussen K, Heaf JG: The use of absolute values improves performance of estimation formulae: a retrospective cross sectional study. BioMed Central Nephrol 2013;14:271.
  19. Tublin ME, Bude RO, Platt JF: The resistive index in renal Doppler sonography: where do we stand? Am J Roentgenology 2003;180:885-892.
  20. Kawai T, Kamide K, Onishi M, Yamamoto-Hanasaki H, BabaY, Hongyo K, Shimaoka I, Tatara Y, Takeya Y, Ohishi M, Rakugi H: Usefulness of the resistive index in renal Doppler ultrasonography as an indicator of vascular damage in patients with risks of atherosclerosis. Nephrol Dial Transplant 2011;26:3256-3262.
  21. Blaufox MD, Aurell M, Bubeck B, Fommei E, Piepsz A, Russell C, Taylor A,Thomsen HS, Volterrani D: Report of the Radionuclides in Nephrourology Committee on renal clearance. J Nucl Med 1996;37:1883-1890.
    External Resources
  22. Ghiadoni L, Faita F, Salvetti M, Cordiano C, Biggi A, Puato M, Di Monaco A, De Siati L, Volpe M, Ambrosio G, Gemignani V, Muiesan ML, Taddei S, Lanza GA, Cosentino F: Assessment of flow-mediated dilation reproducibility: a nationwide multicenter study. J Hypertens 2012;30:1399-1405.
  23. Van Bortel LM, Laurent S, Boutouyrie P, Chowienczyk P, Cruickshank JK, De Backer T, Filipovsky J, Huybrechts S, Mattace-Raso FU, Protogerou AD, Schillaci G, Segers P, Vermeersch S, Weber T; Artery Society; European Society of Hypertension Working Group on Vascular Structure and Function; European Network for Noninvasive Investigation of Large Arteries: Expert consensus document on the measurement of aortic stiffness in daily practice using carotid-femoral pulse wave velocity. J Hypertens 2012;30:445-448.
  24. Bland JM, Altman DG: Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986;1:307-310.
  25. Nair S, Mishra V, Hayden K, Lisboa PJ, Pandya B, Vinjamuri S, Hardy KJ, Wilding JP: The four-variable modification of diet in renal disease formula underestimates glomerular filtration rate in obese type 2 diabetic individuals with chronic kidney disease. Diabetologia 2011;54:1304-1307.
  26. Friedman AN, Moe S, Fadel WF, Inman M, Mattar SG, Shihabi Z, Quinney SK: Predicting the glomerular filtration rate in bariatric surgery patients. Am J Nephrol 2014;39:8-15.
  27. Belhatem N, Mohammedi K, Rouzet F, Matallah N, Al Baloshi A, Travert F, Velho G, Roussel R, Le Guludec D, Marre M, Hansel B: Impact of morbid obesity on the kidney function of patients with type 2 diabetes. Diabetes Res Clin Pract 2015;108:143-149.
  28. Michels WM, Grootendorst DC, Verduijn M, Elliott EG, Dekker FW, Krediet RT; NECOSAD Study Group: Performance of the Cockcroft-Gault, MDRD, and new CKD-EPI formulas in relation to GFR, age, and body size. Clin J Am Soc Nephrol 2010;5:1003-1009.
  29. Lemoine S, Guebre-Egziabher F, Sens F, Nguyen-Tu MS, Juillard L, Dubourg L, Hadj-Aissa A: Accuracy of GFR estimation in obese patients. Clin J Am Soc Nephrol 2014;9:720-727.
  30. Okada R, Yasuda Y, Tsushita K, Wakai K, Hamajima N, Matsuo S: Glomerular hyperfiltration in prediabetes and prehypertension. Nephrol Dial Transplant 2012;27:1821-1825.
  31. Melsom T, Mathisen UD, Ingebretsen OC, Jenssen TG, Njølstad I, Solbu MD, Toft I, Eriksen BO: Impaired fasting glucose is associated with renal hyperfiltration in the general population. Diabetes Care 2011;34:1546-1551.
  32. Upadhyay A, Hwang SJ, Mitchell GF, Vasan RS, Vita JA, Stantchev PI, Meigs JB, Larson MG, Levy D, Benjamin EJ, Fox CS: Arterial stiffness in mild-to-moderate CKD. J Am Soc Nephrol 2009;20:2044-2053.
  33. Bruno RM, Penno G, Daniele G, Pucci L, Lucchesi D, Stea F, Landini L, Cartoni G, Taddei S, Ghiadoni L, Del Prato S: Type 2 diabetes mellitus worsens arterial stiffness in hypertensive patients through endothelial dysfunction. Diabetologia 2012;55:1847-1855.
  34. Vlachopoulos C, Aznaouridis K, O'Rourke MF, Safar ME, Baou K, Stefanadis C: Prediction of cardiovascular events and all-cause mortality with central haemodynamics: a systematic review and meta-analysis. Eur Heart J 2010;31:1865-1871.
  35. Maccario M, Tassone F, Grottoli S, Rossetto R, Gauna C Ghigo E: Neuroendocrine and metabolic determinants of the adaptation of GH/IGF-I axis to obesity. Ann Endocrinol (Paris) 2002;63:140-144.
    External Resources
  36. Grunenwald S, Tack I, Chauveau D, Bennet A, Caron P: Impact of growth hormone hypersecretion on the adult human kidney. Ann Endocrinol (Paris) 2011;72:485-495.
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