NKF 2014 Spring Clinical Meetings Abstracts

CHARACTERISTICS OF ADPKD PATIENTS WITH RAPID PROGRESSION TO RENAL FAILURE: LESSONS FROM CRISP. Arlene B Chapman,1 Patrice Gibbs,2 Frederic Rahbari-Oskoui,1Ty Bae,2Harpreet Singh Bhutani,1 Jared Grantham,3Peter Harris,4 Michal Mrug,5 Vicente Torres,4 Alan Yu,3 Micheal Flessner,6 Doug Landsittel.2 1Emory University, Atlanta GA; 2University of Pittsburgh, Pittsburgh PA; 3Kansas University Medical Center; 4Mayo College of Medicine; 5 University of Alabama, Birmingham; 6 National Institutes of Health. ADPKD is characterized by cyst development and expansion leading to kidney enlargement, worsening kidney function and ESRD and is the fourth leading cause of renal failure in the USA. Although inherited, ESRD typically occurs in the 6th decade. The Consortium for Radiologic Imaging in ADPKD (CRISP) studies are evaluating ADPKD individuals between ages 15 and 45 with initial creatinine clearance > 70 mls/min over 15 years. We report those individuals who progressed to ESRD (n=27) during the first 8 years of study. Individuals underwent MR imaging (TKV), iothalamate clearance (GFR) and renal blood flow (RBF) determinations as well as standard clinical evaluations. Twenty seven of 215 (13%) with complete data began renal replacement therapy. Those progressing to renal failure, were significantly older (37.2 vs. 32.4 yrs), with increased TKV (2075 vs. 953 mls), reduced GFR (72.4 vs. 100.3 mls/min) and RBF (540 vs. 765 mls/min) and serum bicarbonate levels (24.8 vs. 26.2 mEq/L). No differences in race, gender, filtration fraction, PKD1 status (92.6 vs. 78.4%), dietary sodium or phosphorus intake or LDL cholesterol were seen. Average GFR decline was 6.2 ml/min/year vs. 1.8 ml/min/year in ESRD vs. non-ESRD patients. TKV, RBF and reduced serum bicarbonate are characteristics of ADPKD patients with rapid progression (> 6 mls/min/year) to renal failure. Steps to slow kidney growth are needed to reduce progression to renal failure.

PHARMACOLOGIC AGENTS AS RISK FACTORS FOR POST-OPERATIVE ACUTE KIDNEY INJURY

Yana Cavanagh,* Allison Thomas, * Emma Punni,* Vincent DeBari ^ Chandra B. Chandran * *St. Joseph’s Regional Medical Center, Paterson, NJ ^ Seton Hall University, S. Orange, NJ USA This study was to determine if the use of renin angiotensin aldosterone system (RAASi), beta adrenergic receptor blockers (βB) or calcium channel blockers (CCB) prior to surgery, contributed to the risk of post-op AKI. We conducted a case-control study nested within a cohort of patients undergoing surgery from 2007 to 2013. Our cohort (n = 562) was bifurcated into 103 patients with AKI, and a control group consisting of 456 patients without AKI. On a univariate basis, each exposure was tested for association with outcome (AKI/no AKI) with Fisher’s exact test; multivariable adjustment for potential confounders (group-wise difference: p ≤ 5α (p ≤0.25) was performed via logistic regression. Odds ratios (OR) and 95% confidence intervals (CI) were computed for all associations. For this study α was set at 0.05; p < 0.25 (two-sided) was required for rejection of Ho. Baseline characteristics considered as potential confounders were female gender, age > 60y, coronary artery disease (CAD), hypertension (HTN), elevated creatinine and/or BUN (> 1.0 mg/dl and 15 mg/dl, respectively) as well as decreased hematocrit (< 38%). Univariate analysis of RAASi as an exposure for AKI (n = 179) yielded OR (CI): 1.60 (1.03 to 2.49); p = 0.046. When adjusted for age CAD, HTN and BUN we did not detect a significant association. For CCB (n = 106), univariate OR (CI) was 2.06 (1.26 to 3.36), p = 0.005; CCB were however, sensitive to age and HTN. For βB (n = 177), OR (CI) were 2.33 (1.50 to 3.60), p < 0.001. Only HTN substantially altered this association, with OR (CI): 1.60 (0.99 to 2.57), p = 0.054. Although all agents examined were significantly associated with an increased risk for AKI on a univariate basis, none were identifiable as independent risk factors. However, βB, even when adjusted for a significant covariate, appear to represent risk for AKI post-operatively.

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Am J Kidney Dis. 2014;63(5):A1-A121

INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF) THERAPY MAY INDUCE RENAL ALLOGRAFT POROTEINURIA AND ANTIBODY MEDIATED INJURY Fouad Chebib, Wisit Cheungpasitporn, Lynn Cornell, Michelle Brodin, Hatem Amer, Mayo Clinic, Rochester, MN, USA. Systemic adverse effects of intravenous anti-VEGF therapy include: Hypertension, proteinuria, renal failure and thrombotic microangiopathy. Intravitreal therapy with these agents is believed to have little systemic effects. We report a case of a renal transplant recipient who developed significant allograft dysfunction that appeared temporally related to intravitreal anti-VEGF therapy. A 52-year-old male with tuberous sclerosis was a recipient of a living related kidney with diminished but stable allograft function 16 years from transplant with minimal proteinuria. Worsening renal function, increasing proteinuria and blood pressure control triggered increased surveillance and allograft biopsy. The exponential increase in proteinuria was noted a few months following the initiation of bilateral intraocular anti-VEGF therapy for AMD. He received a total of 10 monthly injections of ranibizumab and aflibercept. A biopsy performed due to increasing proteinuria showed evidence of acute on chronic antibody mediated injury, with intra glomerular thrombi and complement activation (C4d+ in the peritubular capillaries). Renal allografts when injured will increase tissue marker expression, both HLA and non-HLA. Thus anti VEGF inhibitors, by disrupting the normal survival signals mediated by VEGF, may result in a greater propensity for the development of alloreactive antibodies and greater pathogenicity of already present antibodies. The role of VEGF and its inhibition in transplant biology is complex and will require ongoing study. This case points to the need for careful follow up of renal transplant recipients receiving these beneficial agents with monthly creatinines and urine protein estimation.

SHOULD WE CHECK SERUM OXALATE LEVELS IN RENAL TRANSPLANT FOR PRIMARY HYPEROXALURIA?: Muhammad Chaudhry, Gaurav Agarwal, R. Allan Jhagroo. University of Wisconsin, Madison, WI. Primary Hyperoxalurias (PHs) are inborn errors of glyoxylate metabolism. The kidney is the prime target for oxalate deposition, which leads to end-stage renal disease. The maximal oxalate elimination via conventional hemodialysis (HD) and peritoneal dialysis (PD) is 950 to1440 micromol/day, which is significantly lower than the daily oxalate production of 3500 to 7500 micromol in patients with PH type 1. The serum supersaturation threshold of 30 micromol/L is then exceeded. When the glomerular filtration rate falls below 30 to 40 mL/min per 1.73 m2, the combination of oxalate overproduction and reduced urinary oxalate excretion results in systemic Oxalosis with multi-organ deposition of oxalate. We present a case of 27 year old male with a history of type I hyperoxaluria, who had a combined kidney and liver transplant in November 2006. He was on dialysis for 3 years prior to transplantation. The transplanted kidney failed due to chronic rejection and recurrent Oxalosis. He underwent a second kidney transplant on April, 2013. Post-transplant biopsy after his second kidney transplant was remarkable for recurrence of crystal deposit consistent with calcium oxalate. Our patient achieved no better than a GFR of 30-40 ml/min after first transplant. With his second transplant kidney in April 2013, he achieved a GFR of near 60 ml/min. We suggest following hypothesis, our patient never achieved an adequate GFR to get rid of deposited oxalate from his body but once he received a second kidney in 2013 his GFR improved remarkably and in turn oxalate mobility from tissues also improved, ultimately causing kidney deposition and injury to the transplant allograft. We suggest that the kidney injury for the second transplant may have been foreseen by checking serum oxalate levels since they correlate with tissue stores. Although not proven daily dialysis prior to transplant to lower oxalate stores may be considered, to improve outcomes.

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