title: Time-varying maximal proteinuria correlates with adverse cardiovascular events and graft failure in kidney transplant recipients.
abstract: OBJECTIVE
  In the general population, proteinuria is associated with progression to kidney failure, cardiovascular disease, and mortality. Here, we analyzed the effects of proteinuria on outcomes in kidney transplant recipients.
  
  
  METHODS
  We performed a retrospective, multi-centre cohort study involving 2047 recipients to evaluate the effects of post-transplant proteinuria on adverse cardiovascular events, graft failure, and mortality. Patients were classified into two groups according to their levels of proteinuria: patients without proteinuria (<150 mg/day, n = 1113) and proteinuric patients (≥ 150 mg/day, n = 934). Multivariate Cox hazard model was conducted with using the maximal proteinuria as time-varying covariate.
  
  
  RESULTS
  During a median 55.3-month (range, 0.6-167.1) follow-up, there were 50 cases of major adverse cardiac events (cardiac death, nonfatal myocardial infarction, or coronary revascularization), 115 cases of graft failure, and 52 patient deaths. In multivariate Cox regression with time-varying covariate, proteinuric recipients were significantly associated with major adverse cardiac events (hazard ratio [HR] 8.689, 95% confidence interval [CI] 2.929-25.774, P < 0.001) compared to those without proteinuria. Recipients with proteinuria showed significantly higher incidences of acute rejection (23.1% vs. 9.4%, P < 0.001) and graft failure rate (HR 6.910, 95% CI 3.270-14.601, P < 0.001). In addition, mortality rate was also significantly higher in patients with proteinuria (HR 6.815, 95% CI 2.164-21.467, P = 0.001).
  
  
  CONCLUSIONS
  Post-transplant proteinuria correlates with adverse cardiovascular events, graft failure, and mortality. Therefore, proteinuria should be evaluated and managed to improve the outcomes of renal recipients.
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.|Department of Internal Medicine, Kangdong Sacred Heart Hospital, Seoul, Korea.
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: Jeon
authors.affiliation: Graduate School of Public Health, Seoul National University, Seoul, Korea.
authors.forename: Clara Tammy
authors.initials: CT
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea.
authors.forename: Jung Nam
authors.initials: JN
authors.lastname: An
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Hajeong
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Asan Medical Center and University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Hyosang
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Asan Medical Center and University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Su-Kil
authors.initials: SK
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Kwon Wook
authors.initials: KW
authors.lastname: Joo
authors.affiliation: Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea.
authors.forename: Chun Soo
authors.initials: CS
authors.lastname: Lim
authors.affiliation: Department of Surgery, Seoul National University Boramae Medical Center, Seoul, Korea.
authors.forename: In Mok
authors.initials: IM
authors.lastname: Jung
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Curie
authors.initials: C
authors.lastname: Ahn
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Yon Su
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Department of Surgery, Asan Medical Center and University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Young Hoon
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea.
authors.forename: Jung Pyo
authors.initials: JP
authors.lastname: Lee
mesh_terms: D000328:Adult; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000453:epidemiology* / Q000401:mortality; D016009:Chi-Square Distribution; D005260:Female; D006084:Graft Rejection / Q000175:diagnosis / Q000453:epidemiology* / Q000401:mortality; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D011507:Proteinuria / Q000175:diagnosis / Q000453:epidemiology* / Q000401:mortality; D056910:Republic of Korea / Q000453:epidemiology; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
keywords: cardiovascular diseases; kidney transplantation; proteinuria