title: Doubling of serum creatinine as an outcome after renal transplant - pathological evidence of graft biopsy.
abstract: Background Doubling of serum creatinine (DSC) in transplantation has been seen as the end-point of renal function without pathological evidence. We conducted this study to elucidate the relationship between DSC and pathological findings. Material and Methods We conducted a retrospective cohort study to illustrate pathologic changes in patients receiving a kidney biopsy in the previous 5 years with clinicopathological correlations to DSC and proteinuria. Results Of a total of 99 kidney recipients (146 biopsies), results of graft biopsy were as follows: calcineurin inhibitor toxicity (CNI) (38.7%) and rejection (36.9%). Compared to males, females had higher proportions of class I (p=0.003) and class II PRA (p<0.001), and a higher rejection rate (p=0.042), but had the same clinical outcomes as males, like eGFR at follow-up (p=0.882), DSC (p=0.703), and proteinuria (p=0.745).                         Pathological diagnoses and findings were related to proteinuria: glomerulopathy (HR=4.9, p=0.01), AMR (HR=2.5, p=0.025), especially acute AMR (HR=2.9, p=0.008), chronic glomerular change (HR=10.2, p=0.002), arteriolar hyaline (HR=2.3, p=0.026), and mesangial matrix change (HR=6.3, p=0.002).                         BK nephropathy and rejection were the only 2 risk factors. Pathological findings favoring AMR (PTC infiltration and glomerulitis) showed a greater risk of DSC compared with those favoring CMR (interstitial inflammation, intimal arteritis, and tubulitis). DSC was correlated with clinical manifestation (rejection) and provided strong pathological evidence. Conclusions There was more acute rejection and chronic pathological change in women, but outcomes were the same due to less activity of renin-angiotensin-aldosterone and hyperfiltration in females. DSC as an end-point of graft function can be used to identify recipients, especially AMR or mixed AMR and CMR. 1. All forms of support received by each author: None of the authors received support. 2. Any potential conflict of interest for each author: No conflict of interest for any of the authors.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Shang-Feng
authors.initials: SF
authors.lastname: Tsai
authors.forename: Kuo-Hsiung
authors.initials: KH
authors.lastname: Shu
authors.forename: Hao-Chung
authors.initials: HC
authors.lastname: Ho
authors.forename: Cheng-Hsu
authors.initials: CH
authors.lastname: Chen
authors.forename: Ming-Ju
authors.initials: MJ
authors.lastname: Wu
authors.forename: Mei-Chin
authors.initials: MC
authors.lastname: Wen
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D003404:Creatinine / Q000097:blood*; D005260:Female; D006084:Graft Rejection / Q000097:blood / Q000175:diagnosis* / Q000473:pathology; D006801:Humans; D007668:Kidney / Q000473:pathology*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000473:pathology / Q000601:surgery*; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000097:blood / Q000209:etiology* / Q000473:pathology; D012189:Retrospective Studies; D012737:Sex Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D003404:Creatinine