Changes in graft function in long term renal transplant recipients – analysis by CKD stage and recipient characteristics U.P.Udayaraj, D.Ansell, R.Steenkamp, R.Ravanan, C.Dudley UK Renal Registry

Introduction (1) All renal transplant recipients (RTR) have CKD CKD staging in RTR is based on eGFR only CKD stage 1T>90 ml/min/1.73m 2 CKD stage 2T60-89 ml/min/1.73m 2 CKD stage 3T30-59 ml/min/1.73m 2 CKD stage 4T15-29 ml/min/1.73m 2 CKD stage 5T<15 ml/min/1.73m 2 KDIGO Guidelines - Levey et al. KI 2005;67:

Introduction (2) Prevalence of various CKD stages and related complications in RTR have been reported CKD in RTR is not necessarily progressive – GFR was stable or improved in 50 % of patients But factors that predict rate of decline in GFR in RTR have not been studied adequately Ansell et al. Am J Transplant 2007;7 : Gill et al. J Am Soc Nephrol 2003;14: Stage1-2TStage3TStage4TStage5T 14%57%16%3%

Objectives To study the association between Recipient characteristics and severity of CKD Recipient characteristics and rate of decline in eGFR The rate of decline in eGFR and graft function

Methods (1) Patient Selection All prevalent RTR in UKRR database on were considered ( n= 13369) Those with ethnicity and creatinine data in last 2 quarters of 2004 were included (n=9542) eGFR was calculated using 4v MDRD equation Cross- sectional analysis of 9542 patients to examine severity of CKD by recipient characteristics

Methods (2) eGFR decline in following year was examined in 5553 patients who Had a functioning transplant for >1 year Survived the following year Had a eGFR 60) eGFR of 9 ml/min/1.73m 2 was imputed for graft loss

Methods (3) Recipient factors (predicting eGFR decline) that were investigated Graft function ( as in Dec 2004) Age Gender Ethnicity Primary (native) renal disease causing ERF Social deprivation UKRR does not collect data on proteinuria, acute rejection. Data on BP, BMI, smoking are incomplete.

Methods (4) Measurement of social deprivation Townsend score calculated from 2001 census output area % unemployed % households overcrowded % households with no car % households not owner occupied Patients postcode matched to output area Postcodes divided into quintiles – quintile 5 being more deprived Statistical analysis Chi squared test Kruskal Wallis test

Prevalence of CKD stages by recipient characteristics

Graft loss in following year by CKD stage

Recipient factors and 1 year change in eGFR

Recipient factors and 1 year change in GFR

Discussion (1) Graft loss increases with increasing CKD stage ~ 50 % of stage 5T lost their graft in the following year – need planning on access and transition onto dialysis /re transplantation Rate of decline in eGFR in RTR is much lower than reported in clinical trials in native renal diseases ( 4 ml/min/1.73m 2 /year) MDRD study – KI 1997;51:

Discussion (2) Progression of transplant CKD is increased in Younger age Non-whites Diabetics but independent of Gender Graft function Social deprivation Progression of native CKD is increased in Older age Non-whites Diabetics Males Poor baseline renal function Socially deprived patients Smokers Obesity Poorly controlled BP proteinuria

Discussion (3) Limitations Serum creatinine assay not standardised across UK and not aligned to MDRD lab Proteinuria and BP – 2 important modifiable risk factors not studied Insufficient immunosuppression data Future work To study association of donor factors, HLA mismatch, cold ischemic time ( UKT link) and GFR decline UKRR dataset expanded to include proteinuria Improve returns on BP, co-morbidity, BMI, ethnicity

Conclusions The rate of decline in eGFR in Transplant CKD is lower than that reported in clinical trials of native renal diseases is independent of graft function is increased in non- whites, diabetics - similar to that seen in native renal diseases is independent of gender, social deprivation and increased in younger age – in contrast to that seen in native renal diseases