Introduction. Causes of death-censored KTX loss are multiple and often non-alloimmune mediated. Examination of KTX biopsies after 5 years revealed an increasing number of cases of DMGS. Our aim was to assess the incidence of biopsy proven DMGS post-KTX, risk factors and impact on KTX survival.

Methods. Included are 2197 adult KTX recipients, transplanted 1998-2012, 58.3% males and 79.8% living donor recipients followed for 86+49 months. Immunosuppression: 87.8% tacrolimus, 6.2% sirolimus and 5.9% cyclosporine. DMGS was diagnosed in protocol or clinical biopsies. Additionally, 10 years protocol biopsies were reviewed (LC) for the presence of mesangial sclerosis (MS) the hallmark of DMGS in biopsies without other glomerulopathies.

Results. At one year, 1236 recipients (56%) had abnormal glucose metabolism, including 507 (23.2%) pre-KTX diabetes (DM), 159 (7.6%) new onset DM (NODM, FBS>126 mg/dl) and 570 (27.3%) fasting hyperglycemia (FBS 101-125). Furthermore, 765 recipients were either obese (23.3%) or morbidly obese (20.9%). Eighty two (3.7%) recipients developed DMGS. The cumulative incidence of DMGS rose rapidly after 5 years: at 5, 10 and 12 years the incidence was 0.9%, 5.4% and 10.4%, respectively. The risk of DMGS related to glycemia at one year (post- KTX hyperglycemia [HR=5.5 (1.15-26.6),p=0.033], NODM [33.1 (7.3-149),p<0.0001], DM [73.6 (17.9-301.6),p<0.0001])(Table), higher BMI [1.06 (1.01-1.13),p=0.030), increasing donor age [1.23 (1.18-1.30),p=0.014] and more recent KTX year [1.76 (1.53-2.02),p<0.0001). At diagnosis, DMGS had mild clinical manifestations, including creatinine 1.2+0.6 mg/dl, eGFR 46.9+19, proteinuria >1000 mg/24h in 23% and microalbuminuria >30 mg/24h in 68%. Still, DMGS was associated with marked increased risk of graft loss (HR=3.93 (2.26-6.82), p<0.0001) independent of recipient age, reduced graft function and acute rejection. The prevalence of MS in 119 10 year protocol biopsies was 35% and this lesion related to obesity and independently, with hyperglycemia.

Discussion. Obesity and hyperglycemia are very common after KTX. These two reversible risk factors relate to the development of MS/DMGS which is an independent predictor of poor KTX survival. The risk of DMGS increases exponentially beyond 5 years. The high prevalence of MS 10 years post-KTX portends poorly for KTX survival beyond that time.

CITATION INFORMATION: Cosio F, Cornell L, Stegall M. Development of Diabetic Glomerulosclerosis (DMGS) After Kidney Transplantation (KTX). Am J Transplant. 2016;16 (suppl 3).

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