Prolonged immunosuppression preserves nonsensitization status after kidney transplant failure.

BACKGROUND: When kidney transplants fail, transplant medications are discontinued to reduce immunosuppression-related risks. However, retransplant candidates are at risk for allosensitization which prolonging immunosuppression may minimize. We hypothesized that for these patients, a prolonged immunosuppression withdrawal after graft failure preserves nonsensitization status (PRA 0%) better than early immunosuppression withdrawal. METHODS: We retrospectively examined subjects transplanted at a single center between July 1, 1999 and December 1, 2009 with a non-death-related graft loss. Subjects were stratified by timing of immunosuppression withdrawal after graft loss: early (≤3 months) or prolonged (>3 months). Retransplant candidates were eligible for the main study where the primary outcome was nonsensitization at retransplant evaluation. Non-retransplant candidates were included in the safety analysis only. RESULTS: We found 102 subjects with non-death-related graft loss of which 49 were eligible for the main study. Nonsensitization rates at retransplant evaluation were 30% and 66% for the early and prolonged immunosuppression withdrawal groups, respectively (P=0.01). After adjusting for cofactors such as blood transfusion and allograft nephrectomy, prolonged immunosuppression withdrawal remained significantly associated with nonsensitization (adjusted odds ratio=5.78, 95% CI [1.37-24.44]). No adverse safety signals were seen in the prolonged immunosuppression withdrawal group compared to the early immunosuppression withdrawal group. CONCLUSIONS: These results suggest that prolonged immunosuppression may be a safe strategy to minimize sensitization in retransplant candidates and provide the basis for larger or prospective studies for further verification.

Methotrexate nephrotoxicity: Novel treatment, new approach.

This is the report of a case of methotrexate nephrotoxicity for which glucarpidase was used. We use the case to review a number of teaching points related to this new treatment option.

Update on clinical trials for the prevention of acute kidney injury in patients undergoing cardiac surgery.

BACKGROUND: Effective therapeutic agents for the prevention and treatment of acute kidney injury (AKI) after cardiac surgery remain elusive despite the tremendous advances in surgical techniques, technology, and understanding of disease processes. Recent developments and their effect on the incidence of AKI after cardiac surgery are discussed. DATA SOURCES: Published clinical trials in PubMed, strength of evidence assessed by the guidelines of the American Family Physicians. CONCLUSIONS: The definition of AKI has changed, and the focus of interventions has shifted from treatment to prevention to recovery from AKI. Antioxidants and biological agents have been added to classic armaments of hydration and diuretics in addition to tighter metabolic control to prevent AKI. Although the treatment options remain unsatisfactory, a lot of progress nevertheless continues to be made in the prevention and treatment of AKI.

Synthetic marijuana and acute kidney injury: an unforeseen association.

Synthetic cannabinoids (SCs) have emerged as drugs of abuse with increasing popularity among young adults. The potential renal complication related to the abuse of SC was not recognized until recently. Here, we present a case of severe acute kidney injury (AKI) that developed after inhalation of SC in an otherwise healthy young patient. A kidney biopsy revealed severe acute tubular necrosis, and supportive management resulted in the recovery of the kidney function. Herein, we briefly summarize the only two previous reports (a total of 21 cases) on the association between SC abuse and renal dysfunction and identify the common aspects in all observations.

Nonobstructive hydronephrosis due to social polydipsia: a case report.

INTRODUCTION: Excessive fluid intake can lead to water intoxication, electrolyte abnormalities, exacerbation of heart failure and anatomical changes in the urinary tract that may present diagnostic and therapeutic challenges for patients and physicians. Although the development of nonobstructive hydronephrosis is recognized in patients with central and nephrogenic diabetes insipidus, pregnancy or psychiatric polydipsia, it is rarely a diagnostic consideration in healthy individuals with excessive fluid ingestion. We now present what we believe to be the first report of nonobstructive hydronephrosis associated with social polydipsia. CASE PRESENTATION: A 53-year-old African-American woman with moderate back pain was found to have bilateral moderate hydronephrosis and hydroureter by abdominal computed tomography. She underwent ureteral stent placement followed by exploratory laparoscopy with lysis of adhesions and a right oophorectomy, without resolution of the nonobstructive hydronephrosis. A careful assessment revealed a social habit of consuming approximately 5.5L of fluid daily in an effort to remain hydrated in accordance with public health service announcements. It was recommended that the patient reduce her fluid intake. A repeat ultrasound after six weeks revealed complete resolution of the bilateral hydronephrosis and hydroureter. CONCLUSION: Recognition of the nonobstructive nature of hydronephrosis caused by polydipsia in healthy individuals is important to prevent unnecessary interventions.

Post-operative serum uric acid and acute kidney injury.

BACKGROUND: We hypothesized that post-operative serum uric acid (SUA) may be associated with acute kidney injury (AKI). METHODS: In this prospective, observational study, the relationships between SUA, urine neutrophil gelatinase-associated lipocalin (uNGAL) and interleukin-18 (uIL-18), serum monocyte chemoattractant protein-1 (sMCP-1) and tumor necrosis factor-alpha (sTNF-alpha), and incidence of AKI were determined. SUA were divided into tertiles and their association with AKI investigated. RESULTS: A total of 100 cardiac surgery patients were included for analyses. The 1st, 2nd, and 3rd SUA tertiles were associated with 15.1%, 11.7%, and 54.5% incidence of AKI, respectively. The 3rd SUA tertile, compared to the referent 1st tertile, was associated with an eightfold (OR 8.38, CI95% 2.13-33.05, p=0.002) increased risk for AKI. Patients with AKI on post-operative day 1 (n=11) were then excluded for the purpose of determining the predictive value of SUA to diagnose AKI on postoperative day 2 and during hospital stay. In comparison to the referent 1st tertile, the 3rd tertile SUA was associated with an eightfold increased risk for AKI on post-operative day 2 (adjusted OR 7.94, CI95% 1.50-42.08, P=.015) and a five-fold increased risk for AKI during hospital stay (OR 4.83, CI95% 1.21-19.20, P=.025), respectively. SUA (Area Under Curve, AUC 0.77 (CI95% 0.66-0.88, P<.001), serum creatinine (0.73, CI95% 0.62-0.84, P<.001) and sTNF-alpha (0.76, CI95% 0.65-0.87, P<.001) had the best diagnostic performance measured by the Receiver Operating Characteristics curves. CONCLUSIONS: We conclude that post-operative SUA is associated with an increased risk for AKI and compares well to conventional markers of AKI.

The independent association between serum uric acid and graft outcomes after kidney transplantation.

BACKGROUND: Improving long-term outcomes of kidney transplantation depends on identifying novel risk factors that lead to poor outcomes. We sought to evaluate the predictive value of mean uric acid (UA) level during the first 6 months posttransplant for graft survival and function. METHODS: Two hundred twelve recipients of living donor kidneys transplanted during January 2000 to December 2001 were included. The study outcome included graft and patient survival and graft function at 1 year posttransplant. Regression models were used to adjust for the confounding variables including graft function during first 6 months. RESULTS: During 68.3 + or - 27.2 months follow-up, UA level (mg/dL) and hyperuricemia (n=45) were associated with graft loss (hazard ratio [HR]=1.26, P=0.026, 95% confidence interval [CI]=1.03-1.53, and HR=1.92, P=0.029, 95% CI=1.1-3.4, respectively) independent of graft function and other confounders. UA also seemed to be associated with risk of death with borderline significance (HR=1.2, P=0.096, 95% CI=0.97-1.46). Examining the predictive value for graft function, UA level and hyperuricemia were independent predictors of 1-year serum creatinine (beta=0.10, P=0.013, 95% CI=0.02-0.18, and beta=0.25, P<0.04, 95% CI=0.01-0.49, respectively). Similarly, both were associated with 1-year estimated glomerular filtration rate (beta=-3.9, P<0.001, 95% CI=-5.7 to -1.5 for UA, and beta=-7.6, P<0.02, 95% CI=-13.6 to -1.5 for hyperuricemia). Notably, these associations were all independent of renal function during first 6 months. CONCLUSION: The results of this study suggest that mean UA level during the first 6 months posttransplant is an independent predictor of long-term graft survival and short-term graft function. Further investigations are needed to evaluate its causal association with chronic allograft injury and cardiovascular disease.