Effect of Acute Kidney Injury on Chronic Kidney Disease Progression and Proteinuria: Initial Results from a Pilot Study Horne K1, Scott R1, Packington R1 , McIntyre CW1,2, Kolhe NV1, Fluck RJ1, Monaghan J3, Reilly T4, Selby NM1,2 1Department of Renal Medicine, Derby Hospitals NHS Foundation Trust, Derby, UK, 2Faculty of Medicine and Health Sciences, University of Nottingham, UK, 3Department of Clinical Biochemistry, Derby Hospitals NHS Foundation Trust, Derby, UK, 4Department of Informatics, Derby Hospitals NHS Foundation Trust, Derby, UK Introduction There is increasing recognition that episodes of AKI may have negative longer term sequelae on renal function and patient outcome. However, many of the studies in this area are retrospective or focus on specific patient groups. There is therefore a need to examine the long term effects of AKI in prospective studies that include general hospitalised patients from across the entire spectrum of AKI severity, and include appropriate control groups. Prior to commencing a large scale, observational case-control study, we performed a pilot study to test a novel method of patient recruitment. We also sought to determine if an effect of AKI on longer term outcomes exists in a general hospitalised population containing a significant proportion of patients with AKI stage 1. We report the one year results from this pilot study. Methods Cases (patients with AKI) and controls (hospitalised patients who did not sustain AKI) were identified from a hospital-wide electronic reporting system for AKI based on the AKIN criteria (Selby et al, CJASN 2012 Apr;7(4):533). A novel system of postal recruitment and consent was developed so patients would only be approached after recovery from their acute illness. Full approval was given by Derby Research Ethics Committee. Potential participants were invited to the study using a carefully designed patient information leaflet. Interested patients telephoned a dedicated number in the research office. Identity was verified and after confirmation that the patients were in possession of the information required to provide valid consent, consent forms were posted, signed and returned in a pre-paid envelope. Controls and AKI patients were matched (1:1) for baseline CKD stage and age ± 5yrs. Renal function and proteinuria were measured 3 months and 1 year after AKI (or index hospital admission for controls). They will be measured again at 3 years. Baseline demographics, AKI data, co-morbidity and hospital stay data were extracted from the electronic patient record. The Medical Research Information Service (MRIS) will be used to track survival data of participants to five years. More patients in the AKI group had proteinuria at 3 months and 1 year. The prevalence of proteinuria in each group and time point are shown in fig 4. Median uPCR at three months was higher in AKI group as compared with controls (15 mg/mmol vs. 11mg/mmol, p=0.007). Fig 5 shows the correlation between ACR and PCR; a large proportion of patients had non-albumin proteinuria, suggesting a non-glomerular/tubular origin. The main factor associated with CKD progression was the presence of AKI; there was also a trend towards an association with proteinuria at 3 months. At one year, there were 7 deaths in the AKI group (4.7%) and 4 in the control group (2.7%). Conclusions Episodes of AKI are associated with a decline in renal function that persists to at least one year, even in a group containing a large proportion of patients with AKI stage 1. The pattern of decline in renal function is one of incomplete recovery after AKI rather than ongoing CKD progression between 3 months and year 1; this pattern may alter with longer follow up. A higher prevalence of proteinuria in the AKI group may reflect parenchymal injury at the time of AKI; alternatively higher levels of pre-existing proteinuria may have predisposed to AKI. This successful pilot study has allowed the commencement of a larger study with similar methodology. As well as examining the effects of AKI on long term renal function and mortality, this study will examine novel and traditional biomarkers with the aim of developing strategies to identify patients at higher risk of adverse outcomes. Results Recruitment rate was 20%. A patient survey was 100% positive regarding postal consent and study methods. 298 patients were matched successfully. Baseline CKD stage was identical between cases and controls (fig. 1). There were no differences between groups at baseline in age (71yrs vs. 72yrs, p=0.487), eGFR (68ml/min vs. 65ml/min, p=0.132) or serum creatinine (93mol/l vs. 97mol/l, p=0.13). Gender, ethnicity and co-morbidity were similar between groups, except for a trend towards an excess of diabetes mellitus in the AKI group (13.1% vs. 22.1%, p=0.061). 72% of cases had AKI stage 1 with 14% in each of stages 2 and 3. This proportion of AKI stage 1 is representative of a generalised hospital AKI population. During hospital admission and at each point in follow up, serum creatinine was significantly higher in the AKI group (Fig 2). eGFR declined in the AKI group at both 3 months and 1 year; this was in contrast to a slight increase in eGFR in the controls (Fig 3). A greater proportion of patients in the AKI group progressed by at least one CKD stage at both three months (31.4% vs 6.4%, p<0.001) and at one year (29.5% vs 8.6%, p<0.001). There was no difference between the AKI and control groups in the proportion of patients that had progression of CKD stage between three months and one year (10% vs 10.1%, p=0.98). Figure 1. Distribution of patients’ baseline CKD stage, demonstrating successful matching between AKI and control groups. Figure 4. Proportion of patients with proteinuria (defined as uPCR>15mg/mmol) at 3 months and 1 year. * p=0.02 Figure 5. Correlation of PCR and ACR at 3 months. The regression line for the whole group lies below the expected regression line if albumin is the predominant urinary protein. Figure 2. Comparison of serum creatinine over time between AKI and controls. Error bars: 95% CI, *p<0.001 Figure 3. Change in eGFR from baseline at 3 months and 1 year in AKI and control groups. For comparison between AKI and control groups at each time point *p<0.001, **p=0.004 nicholas.selby@nottingham.ac.uk