Abstract
Purpose
The association of type 2 diabetes with proteinuria remission and renal function decline in patients with idiopathic membranous nephropathy (IMN) remains elusive. This study was designed to assess such association.
Methods
In this retrospective cohort study, we included 656 IMN patients treated with immunosuppressants or plus corticosteroids, of whom 72 were diagnosed as type 2 diabetes prior to or at diagnosis of IMN. Data on age, sex, body mass index, presence of hypertension and diabetes, laboratory tests, and therapeutic regimens were retrospectively retrieved from medical record. Cox regression was used to analyze risks of failure to achieve remission, relapse, and developing a ≥ 30% decline in estimated glomerular filtration rate (eGFR) or end-stage renal disease (ESRD) associated with baseline diabetes.
Results
The patients were followed for 36.6 (IQR 17.5–59.0) months, of whom 451 reached complete remission, 92 achieved partial remission, and 61 developed a ≥ 30% eGFR decline or ESRD. IMN relapse occurred in 30.6% of the 543 remitted patients. Baseline diabetes was associated with failure to achieve complete remission (HR 0.61, 95% CI 0.43–0.86, P = 0.005) in patients with IMN, independently of age, sex, hypertension, baseline serum albumin, urine protein levels, and eGFR, and therapeutic regimens. However, we failed to identify independent association between baseline diabetes and failure to achieve total remission (HR 0.85, 95% CI 0.63–1.1, P = 0.29), IMN relapse (OR 0.92, 95% CI 0.49–1.7, P = 0.80), or ≥ 30% decline in eGFR or ESRD (HR 1.4, 95% CI 0.78–2.7, P = 0.24) in patients with IMN.
Conclusions
Baseline diabetes may be independently associated with failure to achieve complete remission, but not with IMN relapse and renal function decline in IMN patients.
Similar content being viewed by others
References
Zhu P, Zhou FD, Wang SX, Zhao MH, Wang HY (2015) Increasing frequency of idiopathic membranous nephropathy in primary glomerular disease: a 10-year renal biopsy study from a single Chinese nephrology centre. Nephrology (Carlton) 20(8):560–566. https://doi.org/10.1111/nep.12542
Cattran DC, Alexopoulos E, Heering P, Hoyer PF, Johnston A, Meyrier A, Ponticelli C, Saito T, Choukroun G, Nachman P, Praga M, Yoshikawa N (2007) Cyclosporin in idiopathic glomerular disease associated with the nephrotic syndrome: workshop recommendations. Kidney Int 72(12):1429–1447. https://doi.org/10.1038/sj.ki.5002553
Troyanov S, Wall CA, Miller JA, Scholey JW, Cattran DC, Toronto Glomerulonephritis Registry G (2004) Idiopathic membranous nephropathy: definition and relevance of a partial remission. Kidney Int 66(3):1199–1205. https://doi.org/10.1111/j.1523-1755.2004.00873.x
Chapter 7: Idiopathic membranous nephropathy (2012). Kidney international supplements 2 (2):186–197. https://doi.org/10.1038/kisup.2012.20
Zhang L, Long J, Jiang W, Shi Y, He X, Zhou Z, Li Y, Yeung RO, Wang J, Matsushita K, Coresh J, Zhao MH, Wang H (2016) Trends in chronic kidney disease in China. N Engl J Med 375(9):905–906. https://doi.org/10.1056/NEJMc1602469
Hobeika L, Hunt KJ, Neely BA, Arthur JM (2015) Comparison of the rate of renal function decline in nonproteinuric patients with and without diabetes. The American Journal of the Medical Sciences 350(6):447–452. https://doi.org/10.1097/MAJ.0000000000000583
American Diabetes A (2011) Standards of medical care in diabetes—2011. Diabetes Care 34(Suppl 1):S11–S61. https://doi.org/10.2337/dc11-S011
Horvatic I, Tisljar M, Kacinari P, Matesic I, Bulimbasic S, Galesic Ljubanovic D, Katic T, Kristovic D, Galesic K (2014) Non-diabetic renal disease in Croatian patients with type 2 diabetes mellitus. Diabetes Res Clin Pract 104(3):443–450. https://doi.org/10.1016/j.diabres.2014.03.016
Cai J, Fan X, Mou L, Gao B, Liu X, Li J, Liu L, Wang H, Guo Z, Liu X, Li H, Li X, Li X (2012) Association of reduced renal function with hepatitis B virus infection and elevated alanine aminotransferase. Clin J Am Soc Nephrol 7(10):1561–1566. https://doi.org/10.2215/CJN.07410711
Stevens PE, Levin A, Kidney Disease: Improving Global Outcomes Chronic Kidney Disease Guideline Development Work Group M (2013) 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. https://doi.org/10.7326/0003-4819-158-11-201306040-00007
Shin DH, Lee MJ, Oh HJ, Koo HM, Doh FM, Kim HR, Han JH, Park JT, Han SH, Choi KH, Yoo TH, Kang SW (2013) Stepwise treatment using corticosteroids alone and in combination with cyclosporine in korean patients with idiopathic membranous nephropathy. Yonsei Med J 54(4):973–982. https://doi.org/10.3349/ymj.2013.54.4.973
Cattran DC, Kim ED, Reich H, Hladunewich M, Kim SJ, Toronto Glomerulonephritis Registry g (2017) Membranous nephropathy: quantifying remission duration on outcome. J Am Soc Nephrol 28(3):995–1003. https://doi.org/10.1681/ASN.2015111262
Coresh J, Turin TC, Matsushita K, Sang Y, Ballew SH, Appel LJ, Arima H, Chadban SJ, Cirillo M, Djurdjev O, Green JA, Heine GH, Inker LA, Irie F, Ishani A, Ix JH, Kovesdy CP, Marks A, Ohkubo T, Shalev V, Shankar A, Wen CP, de Jong PE, Iseki K, Stengel B, Gansevoort RT, Levey AS, Consortium CKDP (2014) Decline in estimated glomerular filtration rate and subsequent risk of end-stage renal disease and mortality. Jama 311(24):2518–2531. https://doi.org/10.1001/jama.2014.6634
Royston P, White IR (2011) Multiple imputation by chained equations (MICE): implementation in Stata. J Stat Softw 45(4):1–20
Rucker G, Messerer D (1988) Remission duration: an example of interval-censored observations. Stat Med 7(11):1139–1145. https://doi.org/10.1002/sim.4780071106
Cattran DC, Pei Y, Greenwood CM, Ponticelli C, Passerini P, Honkanen E (1997) Validation of a predictive model of idiopathic membranous nephropathy: its clinical and research implications. Kidney Int 51(3):901–907
Cattran DC, Delmore T, Roscoe J, Cole E, Cardella C, Charron R, Ritchie S (1989) A randomized controlled trial of prednisone in patients with idiopathic membranous nephropathy. N Engl J Med 320(4):210–215
Thompson A, Cattran DC, Blank M, Nachman PH (2015) Complete and partial remission as surrogate end points in membranous nephropathy. J Am Soc Nephrol 26(12):2930–2937. https://doi.org/10.1681/ASN.2015010091
Yang W, Lu J, Weng J, Jia W, Ji L, Xiao J, Shan Z, Liu J, Tian H, Ji Q, Zhu D, Ge J, Lin L, Chen L, Guo X, Zhao Z, Li Q, Zhou Z, Shan G, He J, China National D, Metabolic Disorders Study G (2010) Prevalence of diabetes among men and women in China. N Engl J Med 362(12):1090–1101. https://doi.org/10.1056/NEJMoa0908292
Soleymanian T, Hamid G, Arefi M, Najafi I, Ganji MR, Amini M, Hakemi M, Tehrani MR, Larijani B (2015) Non-diabetic renal disease with or without diabetic nephropathy in type 2 diabetes: clinical predictors and outcome. Ren Fail 37(4):572–575. https://doi.org/10.3109/0886022X.2015.1007804
Qian Y, Zuo K, Li S, Zeng C, Liu Z, Wu Y (2017) Membranous nephropathy occurring with type 2 diabetes mellitus. Clin Nephrol 87(3):140–146. https://doi.org/10.5414/CN108951
Bhadauria D, Chellappan A, Kaul A, Etta P, Badri V, Kumar Sharma R, Prasad N, Gupta A, Jain M (2018) Idiopathic membranous nephropathy in patients with diabetes mellitus: a diagnostic and therapeutic quandary! Clin Kidney J 11(1):46–50. https://doi.org/10.1093/ckj/sfx055
Qiu TT, Zhang C, Zhao HW, Zhou JW (2017) Calcineurin inhibitors versus cyclophosphamide for idiopathic membranous nephropathy: a systematic review and meta-analysis of 21 clinical trials. Autoimmun Rev 16(2):136–145. https://doi.org/10.1016/j.autrev.2016.12.005
Caro J, Gutiérrez-Solís E, Rojas-Rivera J, Agraz I, Ramos N, Rabasco C, Espinosa M, Valera A, Martín M, Frutos MÁ, Perea L, Juárez GF, Ocaña J, Arroyo D, Goicoechea M, Fernández L, Oliet A, Hernández Y, Romera A, Segarra A, Praga M (2015) Predictors of response and relapse in patients with idiopathic membranous nephropathy treated with tacrolimus. Nephrol Dial Transplant 30(3):467–474. https://doi.org/10.1093/ndt/gfu306
Kanigicherla DA, Short CD, Roberts SA, Hamilton P, Nikam M, Harris S, Brenchley PE, Venning MC (2016) Long-term outcomes of persistent disease and relapse in primary membranous nephropathy. Nephrol Dial Transplant 31(12):2108–2114. https://doi.org/10.1093/ndt/gfv435
Shen Y, Cai R, Sun J, Dong X, Huang R, Tian S, Wang S (2017) 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(1):66–76. https://doi.org/10.1007/s12020-016-1014-6
Krolewski AS, Skupien J, Rossing P, Warram JH (2017) Fast renal decline to end-stage renal disease: an unrecognized feature of nephropathy in diabetes. Kidney Int 91(6):1300–1311. https://doi.org/10.1016/j.kint.2016.10.046
Acknowledgements
The study was supported by the Education Foundation for Youth Teachers of the Peking Union Medical College Hospital (Grant number 2015zlgc0707) and Teaching Reform Project for Postgraduate Courses of Peking Union Medical College (Grant number 10023201800101).
Funding
The study was funded by the Education Foundation for Youth Teachers of the Peking Union Medical College Hospital (Grant number 2015zlgc0707) and Teaching Reform Project for Postgraduate Courses of Peking Union Medical College (Grant number 10023201800101). None of the sponsors participated in the design of study or in the collection, analysis, or interpretation of the data.
Author information
Authors and Affiliations
Contributions
JC, HL, and HX had full access to all of the data and take responsibility for the data, data analyses and interpretation. JC and HL had the right to publish any or all data. All authors participated in the conduct of the research, and contributed to the manuscript for important intellectual content.
Corresponding authors
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Ethics approval
This study was approved by the Institutional Review Board of the Peking Union Medical College Hospital.
Informed consent
Informed consent was obtained from all individual participants included in the study.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Xie, H., Li, C., Wen, Y. et al. Association of diabetes with failure to achieve complete remission of idiopathic membranous nephropathy. Int Urol Nephrol 52, 337–342 (2020). https://doi.org/10.1007/s11255-019-02348-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11255-019-02348-2