Journal of Nephrology

, Volume 31, Issue 5, pp 743–749 | Cite as

Prediabetes is associated with glomerular hyperfiltration in a European Mediterranean cohort study

  • Antonio Rodriguez-Poncelas
  • Gabriel Coll-de-Tuero
  • Jordi Blanch
  • Marc Comas-Cufí
  • Marc SaezEmail author
  • Maria Antònia Barceló
Original Article



Glomerular hyperfiltration is well recognized as an early renal alteration in subjects with diabetes mellitus. However, what is not well-known is whether hyperfiltration also occurs in the early stages of hyperglycaemia, for instance in prediabetes. Identifying subjects with glomerular hyperfiltration from among those with prediabetes might be helpful to implement preventive and therapeutic strategies. This study aimed to investigate the association of prediabetes with glomerular hyperfiltration and its associated variables.


A representative sample of 9238 people aged ≥ 30 years and whose entire clinical and laboratory data were available, were included in this study. Hyperfiltration was defined as an estimated glomerular filtration rate (eGFR) above the age- and gender-specific 95th percentile. The eGFR was assessed using the Chronic Kidney Disease Epidemiology Collaboration equation.


After adjustment for age, gender, body mass index, systolic blood pressure and diastolic blood pressure, cholesterol, log (triglycerides), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, serum uric acid, smoking status, hypertension, and use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, fasting plasma glucose (FPG) was found to be independently positively associated with eGFR. The hazard ratios (95% confidence interval) for hyperfiltration were 1.61 (1.28–2.03) and 2.30 (1.89–2.79) for prediabetes and diabetes, respectively, when compared with participants with normoglycemia.


Prediabetes was associated with glomerular hyperfiltration. Longitudinal studies are needed to investigate whether hyperfiltration in prediabetes is associated with a later decline in eGFR.


Prediabetes Impaired fasting glucose Glomerular hyperfiltration Chronic kidney disease Retrospective poblational cohort 



We appreciate the comments of the editor and of anonymous reviewers of a previous version of this work who, without doubt, helped us to improve our work.

Author contributions

ARP had the original idea of the paper. GCT and MS designed the study. The bibliographic search and the writing of the introduction were made by ARP and GCT. The choice of methods and statistical analysis was performed by JB and MC. JB, MC and ARP built the tables and figures. All authors (ARP, JB, MC, MS, MAB, GCT) wrote the results and the discussion. The writing and final editing was done by JB, ARP and MAB. All authors reviewed and approved the manuscript.


This work was partly funded by the research project PI15/00140 from FIS, ‘Instituto de Salud Carlos III’, ISCIII, Spanish Ministry of Economy and Competitiveness and by the projects ‘Grant to improve the scientific productivity of the research groups of the University of Girona 2016–2018’ (MPCUdG2016) and GDRCompetUdG2017. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Compliance with ethical standards

Conflict of interest

The authors have declared that no conflict of interest exists. All authors will disclose any actual or potential conflict of interest including any financial, personal or other relationships with other people or organizations that could inappropriately influence or be perceived to influence their work, within 3 years of beginning the submitted work.

Ethical approval

The data for this study came from an anonymised clinical administrative database and only the lead researcher, where necessary, had access to the identity of each individual. This study has also been revised and approved by the Ethics and Clinical Research Committee (CEIC) of the Institute of Health Care (IAS), Girona, Spain).


  1. 1.
    Jones SL, Wiseman MJ, Viberti GC (1991) Glomerular hyperfiltration as a risk factor for diabetic nephropathy: five-year report of a prospective study. Diabetologia 34:59–60CrossRefPubMedGoogle Scholar
  2. 2.
    Magee GM, Bilous RW, Cardwell CR, Hunter SJ, Kee F, Fogarty DG (2009) Is hyperfiltration associated with the future risk of developing diabetic nephropathy? A meta-analysis. Diabetologia 52:691–697CrossRefPubMedGoogle Scholar
  3. 3.
    Okada R, Yasuda Y, Tsushita K, Wakai K, Hamajima N, Matsuo S (2012) Glomerular hyperfiltration in prediabetes and prehypertension. Nephrol Dial Transplant 27:1821–1825CrossRefPubMedGoogle Scholar
  4. 4.
    Tomaszewski M, Charchar FJ, Maric C, McClure J, Crawford L, Grzeszczak W, Sattar N, Zukowska-Szczechowska E, Dominiczak AF (2007) Glomerular hyperfiltration: a new marker of metabolic risk. Kidney Int 71:816–821CrossRefGoogle Scholar
  5. 5.
    Li Z, Woollard JR, Wang S, Korsmo MJ, Ebrahimi B, Grande JP, Textor SC, Lerman A, Lerman LO (2011) Increased glomerular filtration rate in early metabolic syndrome is associated with renal adiposity and microvascular proliferation. Am J Physiol Renal Physiol 301:F1078–F1087CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Barbieri SS, Zacchi E, Amadio P, Gianellini S, Mussoni L, Weksler BB, Tremoli E (2011) Cytokines present in smokers’ serum interact with smoke components to enhance endothelial dysfunction. Cardiovasc Res 90:475–483CrossRefPubMedGoogle Scholar
  7. 7.
    Stefansson VT, Schei J, Jenssen TG, Melsom T, Eriksen BO (2016) Central obesity associates with renal hyperfiltration in the non-diabetic general population: a cross-sectional study. BMC Nephrol 17:172CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Kovesdy CP, Furth SL, Zoccali C, World Kidney Day Steering Committee (2017) Obesity and kidney disease: hidden consequences of the epidemic. J Nephrol 30(1):1–10CrossRefPubMedGoogle Scholar
  9. 9.
    American Diabetes Association (2013) Standards of medical care in diabetes—2013. Diabetes Care 36(Suppl 1):S11–S66CrossRefGoogle Scholar
  10. 10.
    Stevens PE, Levin A, Kidney Disease: Improving Global Outcomes Chronic Kidney Disease Guideline Development Work Group Members (2013) Evaluation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline. Ann Intern Med 158:825–830CrossRefPubMedGoogle Scholar
  11. 11.
    Sunder-Plassmann G, Hörl WH (2004) A critical appraisal for definition of hyperfiltration. Am J Kidney Dis 43:396CrossRefPubMedGoogle Scholar
  12. 12.
    Premaratne E, Macisaac RJ, Tsalamandris C, Panagiotopoulos S, Smith T, Jerums G (2005) Renal hyperfiltration in type 2 diabetes: effect of age-related decline in glomerular filtration rate. Diabetologia 48:2486–2493CrossRefPubMedGoogle Scholar
  13. 13.
    Melsom T, Fuskevåg OM, Mathisen UD, Strand H, Schei J, Jenssen T, Solbu M, Eriksen BO (2015) Estimated GFR is biased by non-traditional cardiovascular risk factors. Am J Nephrol 41:7–15CrossRefPubMedGoogle Scholar
  14. 14.
    Cachat F, Combescure C, Cauderay M, Girardin E, Chehade H (2015) A systematic review of glomerular hyperfiltration assessment and definition in the medical literature. Clin J Am Soc Nephrol 10:382–389CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Melsom T, Mathisen UD, Ingebretsen OC, Jenssen TG, Njølstad I, Solbu MD, Toft I, Eriksen BO (2011) Impaired fasting glucose is associated with renal hyperfiltration in the general population. Diabetes Care 34:1546–1551CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J (2009) CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration). A new equation to estimate glomerular filtration rate. Ann Intern Med 150:604–612CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    American Diabetes Association (2012) Standards of medical care in diabetes–2012. Diabetes Care 35 (Suppl 1):S11–S63Google Scholar
  18. 18.
    Schöttker B, Brenner H, Koenig W, Müller H, Rothenbacher D (2013) Prognostic association of HbA1c and fasting plasma glucose with reduced kidney function in subjects with and without diabetes mellitus. Results from a population-based cohort study from Germany. Prev Med 57:596–600CrossRefPubMedGoogle Scholar
  19. 19.
    Melsom T, Schei J, Stefansson VT, Solbu MD, Jenssen TG, Mathisen UD, Wilsgaard T, Eriksen BO (2016) Prediabetes and risk of glomerular hyperfiltration and albuminuria in the general nondiabetic population: a prospective cohort study. Am J Kidney Dis 67:841–850CrossRefPubMedGoogle Scholar
  20. 20.
    Hu W, Hao H, Yu W, Wu X, Zhou H (2015) Association of elevated glycosylated hemoglobin A1c with hyperfiltration in a middle-aged and elderly Chinese population with prediabetes or newly diagnosed diabetes: a cross-sectional study. BMC Endocr Disord 15:47CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Hou X, Wang C, Wang S, Yang W, Ma Z, Wang Y, Li C, Li M, Zhang X, Zhao X, Sun Y, Song J, Lin P, Liang K, Gong L, Wang M, Liu F, Li W, Yan F, Yang J, Wang L, Tian M, Liu J, Zhao R, Chen S, Chen L (2014) Fluctuation between fasting and 2-H postload glucose state is associated with glomerular hyperfiltration in newly diagnosed diabetes patients with HbA1c < 7%. PLoS One 9:e111173CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Moriya T, Tsuchiya A, Okizaki S, Hayashi A, Tanaka K, Shichiri M (2012) Glomerular hyperfiltration and increased glomerular filtration surface are associated with renal function decline in normo- and microalbuminuric type 2 diabetes. Kidney Int 81:486–493CrossRefPubMedGoogle Scholar
  23. 23.
    Bjornstad P, Cherney DZ, Snell-Bergeon JK, Pyle L, Rewers M, Johnson RJ, Maahs DM (2015) Rapid GFR decline is associated with renal hyperfiltration and impaired GFR in adults with type 1 diabetes. Nephrol Dial Transplant 30:1706–1711CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Ruggenenti P, Porrini EL, Gaspari F, Motterlini N, Cannata A, Carrara F, Cella C, Ferrari S, Stucchi N, Parvanova A, Iliev I, Dodesini AR, Trevisan R, Bossi A, Zaletel J, Remuzzi G (2012) GFR Study Investigators. Glomerular hyperfiltration and renal disease progression in type 2 diabetes. Diabetes Care 35:2061–2068CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Brenner BM, Lawler EV, Mackenzie HS (1996) The hyperfiltration theory: a paradigm shift in nephrology. Kidney Int 49:1774–1777CrossRefPubMedGoogle Scholar
  26. 26.
    Rodríguez-Arias JJ, Coll-de-Tuero G (2015) Could uric acid be considered a cardiovascular risk factor? J Clin Hypertens. CrossRefGoogle Scholar
  27. 27.
    De Nicola L, Gabbai FB, Liberti ME, Sagliocca A, Conte G, Minutolo R (2014) Sodium/glucose cotransporter 2 inhibitors and prevention of diabetic nephropathy: targeting the renal tubule in diabetes. Am J Kidney Dis 64:16–24CrossRefPubMedGoogle Scholar
  28. 28.
    Zeni L, Norden AGW, Cancarini G, Unwin RJ (2017) A more tubulocentric view of diabetic kidney disease. J Nephrol 30(6):701–717CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Ligthart S, van Herpt TT, Leening MJ, Kavousi M, Hofman A, Stricker BH, van Hoek M, Sijbrands EJ, Franco OH, Dehghan A (2016) Lifetime risk of developing impaired glucose metabolism and eventual progression from prediabetes to type 2 diabetes: a prospective cohort study. Lancet Diabetes Endocrinol 4:44–51CrossRefPubMedGoogle Scholar
  30. 30.
    Tancredi M, Rosengren A, Svensson AM, Kosiborod M, Pivodic A, Gudbjörnsdottir S, Wedel H, Clements M, Dahlqvist S, Lind M (2015) Excess mortality among persons with type 2 diabetes. N Engl J Med 373:1720–1732CrossRefPubMedGoogle Scholar

Copyright information

© Italian Society of Nephrology 2018

Authors and Affiliations

  1. 1.METHARISC GroupUSR Girona, IdIAP Gol i GorinaGironaSpain
  2. 2.Department of Medical SciencesUniversity of GironaGironaSpain
  3. 3.CIBER of Epidemiology and Public Health (CIBERESP)MadridSpain
  4. 4.Research Group on Statistics, Econometrics and Health (GRECS)University of GironaGironaSpain

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