Abstract
Diabetes mellitus is a strong risk factor for chronic kidney disease and end-stage renal disease. Whether sex differences in chronic kidney disease and end-stage renal disease incidence exist among diabetic patients remains unclear. This systematic review and meta-analysis was conducted to evaluate the relative effect of diabetes on chronic kidney disease and end-stage renal disease risk in women compared with men. We systematically searched Embase, PubMed, and the Cochrane Library for both cohort and case–control studies until October 2015. Studies were selected if they reported a sex-specific relationship between diabetes mellitus and chronic kidney disease or end-stage renal disease. We generated pooled estimates across studies using random-effects meta-analysis after log transformation with inverse variance weighting. Ten studies with data from more than 5 million participants were included. The pooled adjusted risk ratio of chronic kidney disease associated with diabetes mellitus was 3.34 (95 % CI 2.27, 4.93) in women and 2.84 (95 % CI 1.73, 4.68) in men. The data showed no difference in diabetes-related chronic kidney disease risk between the sexes (pooled adjusted women-to-men relative risk ratio was 1.14 [95 % CI 0.97, 1.34]) except for end-stage renal disease—the pooled adjusted women-to men relative risk ratio was 1.38 (95 % CI 1.22, 1.55; p = 0.114, I² = 38.1 %). The study found no evidence of a sex difference in the association between diabetes mellitus and chronic kidney disease. However, the excess risk for end-stage renal disease was higher in women with diabetes than in men with the same condition, from which we assume that the female gender could accelerate the disease progression. Further studies are needed to support this notion and elucidate the underlying mechanisms.
Similar content being viewed by others
References
L. Guariguata, D.R. Whiting, I. Hambleton, J. Beagley, U. Linnenkamp, J.E. Shaw, Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res. Clin. Pract. 103(2), 137–149 (2014). doi:10.1016/j.diabres.2013.11.002
V. Jha, G. Garcia-Garcia, K. Iseki, Z. Li, S. Naicker, B. Plattner, R. Saran, A.Y.-M. Wang, C.-W. Yang, Chronic kidney disease: global dimension and perspectives. Lancet 382(9888), 260–272 (2013). doi:10.1016/s0140-6736(13)60687-x
M. Kastarinen, A. Juutilainen, H. Kastarinen, V. Salomaa, P. Karhapaa, J. Tuomilehto, C. Gronhagen-Riska, P. Jousilahti, P. Finne, Risk factors for end-stage renal disease in a community-based population: 26-year follow-up of 25,821 men and women in eastern Finland. J. Intern. Med. 267(6), 612–620 (2010). doi:10.1111/j.1365-2796.2009.02197.x
Y.T. Chang, J.L. Wu, C.C. Hsu, J.D. Wang, J.M. Sung, Diabetes and end-stage renal disease synergistically contribute to increased incidence of cardiovascular events: a nationwide follow-up study during 1998-2009. Diabetes Care 37(1), 277–285 (2014). doi:10.2337/dc13-0781
S. Nag, R. Bilous, W. Kelly, S. Jones, N. Roper, V. Connolly, All-cause and cardiovascular mortality in diabetic subjects increases significantly with reduced estimated glomerular filtration rate (eGFR): 10 years’ data from the South Tees Diabetes Mortality study. Diabetic Med. 24(1), 10–17 (2007). doi:10.1111/j.1464-5491.2007.02023.x
J. Neugarten, A. Acharya, S.R. Silbiger, Effect of gender on the progression of nondiabetic renal disease: a meta-analysis. J. Am. Soc. Nephrol. 11(2), 319–329 (2000)
C. Maric, Sex, diabetes and the kidney. Am. J. Physiol. Renal Physiol. 296(4), F680–F688 (2009). doi:10.1152/ajprenal.90505.2008
A. Mollsten, M. Svensson, I. Waernbaum, Y. Berhan, S. Schon, L. Nystrom, H.J. Arnqvist, G. Dahlquist, Swedish Childhood Diabetes Study, G., Diabetes Incidence Study in, S., Swedish Renal, R. Cumulative risk, age at onset, and sex-specific differences for developing end-stage renal disease in young patients with type 1 diabetes: a nationwide population-based cohort study. Diabetes 59(7), 1803–1808 (2010). doi:10.2337/db09-1744
K. Raile, A. Galler, S. Hofer, A. Herbst, D. Dunstheimer, P. Busch, R.W. Holl, Diabetic nephropathy in 27,805 children, adolescents, and adults with type 1 diabetes: effect of diabetes duration, A1C, hypertension, dyslipidemia, diabetes onset, and sex. Diabetes Care 30(10), 2523–2528 (2007). doi:10.2337/dc07-0282
P. Hovind, L. Tarnow, P. Rossing, B.R. Jensen, M. Graae, I. Torp, C. Binder, H.H. Parving, Predictors for the development of microalbuminuria and macroalbuminuria in patients with type 1 diabetes: inception cohort study. Br. Med. J. 328(7448), 1105 (2004). doi:10.1136/bmj.38070.450891.FE
M.K. Yu, C.R. Lyles, L.A. Bent-Shaw, B.A. Young, A. Pathways, Risk factor, age and sex differences in chronic kidney disease prevalence in a diabetic cohort: the pathways study. Am. J. Nephrol. 36(3), 245–251 (2012). doi:10.1159/000342210
M.K. Yu, W. Katon, B.A. Young, Associations between sex and incident chronic kidney disease in a prospective diabetic cohort. Nephrology 20(7), 451–458 (2015). doi:10.1111/nep.12468
M.C. Monti, J.T. Lonsdale, C. Montomoli, R. Montross, E. Schlag, D.A. Greenberg, Familial risk factors for microvascular complications and differential male-female risk in a large cohort of American families with type 1 diabetes. J. Clin. Endocrinol. Metab. 92(12), 4650–4655 (2007). doi:10.1210/jc.2007-1185
P. Rossing, P. Hougaard, H.H. Parving, Risk factors for development of incipient and overt diabetic nephropathy in type 1 diabetic patients: a 10-year prospective observational study. Diabetes Care 25(5), 859–864 (2002)
J.A. Breyer, R.P. Bain, J.K. Evans, N.S. Nahman Jr., E.J. Lewis, M. Cooper, J. McGill, T. Berl, Predictors of the progression of renal insufficiency in patients with insulin-dependent diabetes and overt diabetic nephropathy. The Collaborative Study Group. Kidney Int. 50(5), 1651–1658 (1996)
K. Okada, M. Yanai, K. Takeuchi, K. Matsuyama, K. Nitta, K. Hayashi, S. Takahashi, Sex differences in the prevalence, progression, and improvement of chronic kidney disease. Kidney Blood Press. Res. 39(4), 279–288 (2014). doi:10.1159/000355805
A. Stang, Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur. J. Epidemiol. 25(9), 603–605 (2010). doi:10.1007/s10654-010-9491-z
P.E. Stevens, A. Levin, Kidney disease: improving global outcomes chronic kidney disease guideline development work group, M., Evaluation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline. Ann. Intern. Med. 158(11), 825–830 (2013). doi:10.7326/0003-4819-158-11-201306040-00007
A.S. Levey, J. Coresh, T. Greene, J. Marsh, L.A. Stevens, J.W. Kusek, F. Van Lente, Chronic Kidney Disease Epidemiology, C.: Expressing the modification of diet in renal disease study equation for estimating glomerular filtration rate with standardized serum creatinine values. Clin. Chem. 53(4), 766–772 (2007). doi:10.1373/clinchem.2006.077180
J.L. Teruel, J. Sabater, C. Galeano, M. Rivera, J.L. Merino, M. Fernandez Lucas, R. Marcen, J. Ortuno, [The Cockcroft-Gault equation is better than MDRD equation to estimate the glomerular filtration rate in patients with advanced chronic renal failure]. Nefrologia 27(3), 313–319 (2007)
A.A. Sanusi, A. Akinsola, A.A. Ajayi, Creatinine clearance estimation from serum creatinine values: evaluation and comparison of five prediction formulae in Nigerian patients. Afr. J. Med. Med. Sci. 29(1), 7–11 (2000)
A.S. Levey, L.A. Stevens, C.H. Schmid, Y.L. Zhang, A.F. Castro 3rd, H.I. Feldman, J.W. Kusek, P. Eggers, F. Van Lente, T. Greene, J. Coresh, E.P.I. Ckd, A new equation to estimate glomerular filtration rate. Ann. Intern. Med. 150(9), 604–612 (2009)
L. Hoste, L. Dubourg, L. Selistre, V.C. De Souza, B. Ranchin, A. Hadj-Aissa, P. Cochat, F. Martens, H. Pottel, A new equation to estimate the glomerular filtration rate in children, adolescents and young adults. Nephrol. Dial. Transpl. 29(5), 1082–1091 (2014). doi:10.1093/ndt/gft277
S.A.E. Peters, R.R. Huxley, M. Woodward, Diabetes as a risk factor for stroke in women compared with men: a systematic review and meta-analysis of 64 cohorts, including 775 385 individuals and 12 539 strokes. Lancet 383(9933), 1973–1980 (2014). doi:10.1016/S0140-6736(14)60040-4
J.P. Higgins, S.G. Thompson, Quantifying heterogeneity in a meta-analysis. Stat. Med. 21(11), 1539–1558 (2002). doi:10.1002/sim.1186
M. Egger, G. Davey Smith, M. Schneider, C. Minder, Bias in meta-analysis detected by a simple, graphical test. Br. Med. J. 315(7109), 629–634 (1997)
S. Duval, E. Weinhandl, Correcting for Publication Bias in the Presence of Covariates. Methods Research Report (Prepared by the Minnesota Evidence-based Practice Center under Contract No. 290-02-0009.) AHRQ Publication No. 11-EHC041-EF. Rockville, MD: Agency for Healthcare Research and Quality. September 2011. Available at: www.effectivehealthcare.ahrq.gov/reports/final.cfm
F. Hoffmann, B. Haastert, M. Koch, G. Giani, G. Glaeske, A. Icks, The effect of diabetes on incidence and mortality in end-stage renal disease in Germany. Nephrol. Dial. Transpl. 26(5), 1634–1640 (2011). doi:10.1093/ndt/gfq609
J.C. van Blijderveen, S.M. Straus, R. Zietse, B.H. Stricker, M.C. Sturkenboom, K.M. Verhamme, A population-based study on the prevalence and incidence of chronic kidney disease in the Netherlands. Int. Urol. Nephrol. 46(3), 583–592 (2014). doi:10.1007/s11255-013-0563-3
J.L. Xue, P.W. Eggers, L.Y. Agodoa, R.N. Foley, A.J. Collins, Longitudinal study of racial and ethnic differences in developing end-stage renal disease among aged medicare beneficiaries. J. Am. Soc. Nephrol. 18(4), 1299–1306 (2007). doi:10.1681/ASN.2006050524
J. Hippisley-Cox, C. Coupland, Predicting the risk of chronic kidney disease in men and women in England and Wales: prospective derivation and external validation of the QKidney Scores. BMC Fam. Pract. 11, 49 (2010). doi:10.1186/1471-2296-11-49
K. Nagai, C. Saito, F. Watanabe, R. Ohkubo, C. Sato, T. Kawamura, K. Uchida, A. Hiwatashi, H. Kai, K. Ishida, T. Sairenchi, K. Yamagata, Annual incidence of persistent proteinuria in the general population from Ibaraki annual urinalysis study. Clin. Exp. Nephrol. 17(2), 255–260 (2013). doi:10.1007/s10157-012-0692-5
M. Tohidi, M. Hasheminia, R. Mohebi, D. Khalili, F. Hosseinpanah, B. Yazdani, A.A. Nasiri, F. Azizi, F. Hadaegh, Incidence of chronic kidney disease and its risk factors, results of over 10 year follow up in an Iranian cohort. PloS One 7(9), e45304 (2012). doi:10.1371/journal.pone.0045304
M.K. Haroun, Risk factors for chronic kidney disease: a prospective study of 23,534 men and women in Washington County, Maryland. J. Am. Soc. Nephrol. 14(11), 2934–2941 (2003). doi:10.1097/01.asn.0000095249.99803.85
R.F. Dyck, L. Tan, Rates and outcomes of diabetic end-stage renal disease among registered native people in Saskatchewan. Can. Med. Assoc. J. 150(2), 203–208 (1994)
K. Yamagata, K. Ishida, T. Sairenchi, H. Takahashi, S. Ohba, T. Shiigai, M. Narita, A. Koyama, Risk factors for chronic kidney disease in a community-based population: a 10-year follow-up study. Kidney Int. 71(2), 159–166 (2007). doi:10.1038/sj.ki.5002017
E.S. Johnson, D.H. Smith, M.L. Thorp, X. Yang, J. Juhaeri, Predicting the risk of end-stage renal disease in the population-based setting: a retrospective case-control study. BMC Nephrol. 12, 17 (2011). doi:10.1186/1471-2369-12-17
R. Retnakaran, C.A. Cull, K.I. Thorne, A.I. Adler, R.R. Holman, U.S. Group, Risk factors for renal dysfunction in type 2 diabetes: U.K. prospective diabetes study 74. Diabetes 55(6), 1832–1839 (2006). doi:10.2337/db05-1620
V.L. Roger, A.S. Go, D.M. Lloyd-Jones, E.J. Benjamin, J.D. Berry, W.B. Borden, D.M. Bravata, S. Dai, E.S. Ford, C.S. Fox, H.J. Fullerton, C. Gillespie, S.M. Hailpern, J.A. Heit, V.J. Howard, B.M. Kissela, S.J. Kittner, D.T. Lackland, J.H. Lichtman, L.D. Lisabeth, D.M. Makuc, G.M. Marcus, A. Marelli, D.B. Matchar, C.S. Moy, D. Mozaffarian, M.E. Mussolino, G. Nichol, N.P. Paynter, E.Z. Soliman, P.D. Sorlie, N. Sotoodehnia, T.N. Turan, S.S. Virani, N.D. Wong, D. Woo, M.B. Turner; American Heart Association Statistics, C., Stroke Statistics, S.: Heart disease and stroke statistics—2012 update: a report from the American Heart Association. Circulation 125(1), e2–e220 (2012). doi:10.1161/CIR.0b013e31823ac046
A.O. Luk, W.Y. So, R.C. Ma, A.P. Kong, R. Ozaki, V.S. Ng, L.W. Yu, W.W. Lau, X. Yang, F.C. Chow, J.C. Chan, P. C. Tong, Hong Kong Diabetes, R.: Metabolic syndrome predicts new onset of chronic kidney disease in 5,829 patients with type 2 diabetes: a 5-year prospective analysis of the Hong Kong Diabetes Registry. Diabetes Care 31(12), 2357–2361 (2008). doi:10.2337/dc08-0971
I. Gouni-Berthold, H.K. Berthold, C.S. Mantzoros, M. Bohm, W. Krone, Sex disparities in the treatment and control of cardiovascular risk factors in type 2 diabetes. Diabetes Care 31(7), 1389–1391 (2008). doi:10.2337/dc08-0194
G. Penno, A. Solini, E. Bonora, C. Fondelli, E. Orsi, G. Zerbini, R. Trevisan, M. Vedovato, G. Gruden, L. Laviola, A. Nicolucci, G. Pugliese, I. Renal; Cardiovascular Events Study, G.: Gender differences in cardiovascular disease risk factors, treatments and complications in patients with type 2 diabetes: the RIACE Italian multicentre study. J. Int. Med. 274(2), 176–191 (2013). doi:10.1111/joim.12073
D.J. Wexler, R.W. Grant, J.B. Meigs, D.M. Nathan, E. Cagliero, Sex disparities in treatment of cardiac risk factors in patients with type 2 diabetes. Diabetes Care 28(3), 514–520 (2005)
A. Ferrara, C.M. Mangione, C. Kim, D.G. Marrero, D. Curb, M. Stevens, J.V. Selby, Translating Research Into Action for Diabetes Study, G.: Sex disparities in control and treatment of modifiable cardiovascular disease risk factors among patients with diabetes: translating research into action for diabetes (TRIAD) study. Diabetes Care 31(1), 69–74 (2008). doi:10.2337/dc07-1244
S.G. Wannamethee, O. Papacosta, D.A. Lawlor, P.H. Whincup, G.D. Lowe, S. Ebrahim, N. Sattar, Do women exhibit greater differences in established and novel risk factors between diabetes and non-diabetes than men? The British Regional Heart Study and British Women’s Heart Health Study. Diabetologia 55(1), 80–87 (2012). doi:10.1007/s00125-011-2284-4
S. Xiao, D.G. Gillespie, C. Baylis, E.K. Jackson, R.K. Dubey, Effects of estradiol and its metabolites on glomerular endothelial nitric oxide synthesis and mesangial cell growth. Hypertension 37(2 Pt 2), 645–650 (2001)
L.L. Yanes, J.C. Sartori-Valinotti, J.F. Reckelhoff, Sex steroids and renal disease: lessons from animal studies. Hypertension 51(4), 976–981 (2008). doi:10.1161/HYPERTENSIONAHA.107.105767
S. Doublier, E. Lupia, P. Catanuto, S.J. Elliot, Estrogens and progression of diabetic kidney damage. Curr. Diabetes. Rev. 7(1), 28–34 (2011)
J.F. Reckelhoff, L.L. Yanes, R. Iliescu, L.A. Fortepiani, J.P. Granger, Testosterone supplementation in aging men and women: possible impact on cardiovascular-renal disease. Am. J. Physiol. Renal. Physiol. 289(5), F941–948 (2005). doi:10.1152/ajprenal.00034.2005
L.A. Fortepiani, L. Yanes, H. Zhang, L.C. Racusen, J.F. Reckelhoff, Role of androgens in mediating renal injury in aging SHR. Hypertension 42(5), 952–955 (2003). doi:10.1161/01.HYP.0000099241.53121.7F
A. Dixon, C. Maric, 17beta-Estradiol attenuates diabetic kidney disease by regulating extracellular matrix and transforming growth factor-beta protein expression and signaling. Am. J. Physiol. Renal Physiol. 293(5), F1678–F1690 (2007). doi:10.1152/ajprenal.00079.2007
P. Catanuto, S. Doublier, E. Lupia, A. Fornoni, M. Berho, M. Karl, G.E. Striker, X. Xia, S. Elliot, 17 beta-estradiol and tamoxifen upregulate estrogen receptor beta expression and control podocyte signaling pathways in a model of type 2 diabetes. Kidney Int. 75(11), 1194–1201 (2009). doi:10.1038/ki.2009.69
R.W. Mankhey, C.C. Wells, F. Bhatti, C. Maric, 17beta-Estradiol supplementation reduces tubulointerstitial fibrosis by increasing MMP activity in the diabetic kidney. Am. J. Physiol. Regul. Integr. Comp. Physiol. 292(2), R769–R777 (2007). doi:10.1152/ajpregu.00375.2006
R.W. Mankhey, F. Bhatti, C. Maric, 17beta-Estradiol replacement improves renal function and pathology associated with diabetic nephropathy. Am. J. Physiol. Renal Physiol. 288(2), F399–F405 (2005). doi:10.1152/ajprenal.00195.2004
Q. Xu, C.C. Wells, J.H. Garman, L. Asico, C.S. Escano, C. Maric, Imbalance in sex hormone levels exacerbates diabetic renal disease. Hypertension 51(4), 1218–1224 (2008). doi:10.1161/HYPERTENSIONAHA.107.100594
D.Z. Cherney, E.B. Sochett, J.A. Miller, Gender differences in renal responses to hyperglycemia and angiotensin-converting enzyme inhibition in diabetes. Kidney Int. 68(4), 1722–1728 (2005). doi:10.1111/j.1523-1755.2005.00588.x
C.A. Jones, A.S. Krolewski, J. Rogus, J.L. Xue, A. Collins, J.H. Warram, Epidemic of end-stage renal disease in people with diabetes in the United States population: do we know the cause?. Kidney Int. 67(5), 1684–1691 (2005). doi:10.1111/j.1523-1755.2005.00265.x
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Electronic Supplementary material
Rights and permissions
About this article
Cite this article
Shen, Y., Cai, R., Sun, J. et al. Diabetes mellitus as a risk factor for incident chronic kidney disease and end-stage renal disease in women compared with men: a systematic review and meta-analysis. Endocrine 55, 66–76 (2017). https://doi.org/10.1007/s12020-016-1014-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12020-016-1014-6