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Purpose of Review: Acute phosphate nephropathy (APN) has been identified in renal biopsy specimens of patients exposed to oral sodium phosphate (OSP) bowel purgatives. Biopsy confirmed cases presented with bland urinary sediment, low-grade proteinuria, and varying degrees of creatinine elevation. Prospective identification of APN is difficult in that definitive diagnosis requires renal biopsy, and biopsy is rarely performed for patients with this clinical presentation., Recent Findings: Observational studies evaluating acute kidney injury after OSP exposure using interval changes in creatinine as a surrogate for APN have reported conflicting results. Although these studies have produced estimates of disease occurrence, they have been unable to definitively quantify the overall risk of APN with OSP as compared with alternative bowel-cleansing agents., Summary: On the basis of association of APN and OSP, the US Food and Drug Administration issued a boxed warning and manufacturers have ceased production and distribution of some OSP products. As this is a temporary solution, more studies are needed to delineate the pathophysiology of this disease and to better identify the subset of the population at risk for APN.

Background: Published analyses of clinical outcomes for patients requiring large-volume blood transfusion conflict with respect to the impact upon plasma potassium levels. We analyzed a cohort of trauma patients to ascertain the impact of component product transfusion upon plasma potassium values., Methods: We performed an observational analysis of previously, prospectively collected clinical data on 131 noncrush trauma patients undergoing resuscitation during the initial 12 hours after admission to a combat support hospital. Comparisons were made between those who received packed red blood cell (PRBC) transfusion and those who did not. Primary outcome was hyperkalemia (plasma potassium level >5.5 mmol/L)., Results: Ninety-six of one hundred thirty-one patients (73.3%) received PRBCs (mean number of PRBC units 11.2, range, 0-55.0). For transfusion versus nontransfusion patients, baseline plasma potassium value (3.7 +/- 0.57 mmol/L vs. 3.6 +/- 0.36 mmol/L, p = 0.22) rose significantly after transfusion (5.3 +/- 1.2 mmol/L, vs. 4.0 +/- 0.78 mmol/L, p < 0.001). During the study period, 38.5% of transfusion patients developed hyperkalemia, versus 2.9% of those who did not (p = 0.003). In multivariate logistic regression analysis, transfusion of greater than 7 units of PRBCs was independently associated with the development of hyperkalemia (RR 4.72, 95% CI 1.01-21.97, p = 0.048). Transfusion of other cell-based products, baseline base deficits, and plasma bicarbonate levels were not. Spearman's rank correlation coefficient for the relationship of number of transfused PRBC units to the highest recorded potassium value was 0.554 (p < 0.001). The predictive accuracy of the logistic regression model for hyperkalemia was 0.824 (95% CI 0.747-0.901, p < 0.001)., Conclusions: Hyperkalemia is common after PRBC transfusion, and often severe. PRBC transfusion is independently associated with the development of hyperkalemia. The findings suggest the need for interventional studies examining the impact of alternative resuscitative approaches after severe trauma.

Background: Hodgkin disease and myeloma were recently included in the classification of posttransplant lymphoproliferative disorder (PTLD). However, because their incidence is low, not much is known about their particular features., Methods: The incidence, characteristics, risk, and prognostic factors of myeloma, Hodgkin disease, and lymphoid leukemia using the United States Renal Data System from 1991 to 2000 among 66,159 Medicare patients were analyzed., Results: In all, 1,169 recipients developed a lymphoid disease: 823 (1.2%) non-Hodgkin's lymphomas (NHL), 160 (0.24%) myelomas, 60 (0.1%) Hodgkin lymphomas, and 126 (0.2%) lymphoid leukemias. Older age was associated with an increased risk of myeloma and leukemia. The incidence of hepatitis C virus infection was higher in recipients with myeloma (6.9 vs. 3.9%, P=0.05). Induction therapy was associated with a greater risk of myeloma and leukemia, but not Hodgkin disease. Azathioprine was associated with a lower risk of myeloma, and tacrolimus with a lower risk of Hodgkin disease. According to the type of malignancy, ten-year survival rates were significantly different: 42, 26, 55 and 39% respectively for NHL, myeloma, Hodgkin disease, and leukemia., Conclusion: These results support specific features and risk factors related to the occurrence of each type of lymphoid-proliferation and suggest for the first time a possible association between hepatitis C virus and myeloma in kidney transplant recipients.

Background: Although cyclosporine use has been associated with an increased risk of new-onset gout after renal transplantation, the incidence and risk factors for new-onset gout have not been reported in the era of modern immunosuppression., Methods: We conducted a retrospective cohort study of Medicare primary renal transplant patients reported in the United States Renal Data System (USRDS), using Medicare claims data to determine the incidence of new-onset gout. Cox regression analysis was used to calculate adjusted hazard ratios (AHR) for cyclosporine (including separate analysis of Neoral) compared directly with tacrolimus, for the risk of new-onset gout, adjusted for baseline demographic factors and posttransplant renal function., Results: The cumulative incidence of new-onset gout was 7.6% at 3 years posttransplant. The following factors were independently associated with an increased risk of new-onset gout: use of Neoral (vs. tacrolimus, AHR 1.25, 95% CI 1.07-1.47) at discharge, recipient male sex (AHR 1.44, 95% CI 1.25-1.67), older age, higher body mass index, and more recent year of transplant. No other immunosuppressive medications were associated with new-onset gout. Diabetes was associated with a significantly lower risk of new-onset gout. The development of new-onset gout was independently associated with decreased patient survival (AHR 1.26, 95% CI 1.08-1.47) as well as death-censored graft survival., Conclusions: Cyclosporine is an independent risk factor for new-onset gout after transplantation. The incidence of new-onset gout appears to be increasing even while the use of cyclosporine is decreasing, and the development of new-onset gout was an independent predictor for death and graft loss in this population.

Background: Posttransplant lymphoproliferative disorders (PTLD) still represent a major preoccupation after renal transplantation, even in the most recent years., Methods: We analyzed the incidence, risk, and prognostic factors of PTLD in a cohort of kidney recipients using the United States Renal Data System., Results: Among 25,127 Medicare patients transplanted between 1996 and 2000, 344 developed a PTLD defined as a non-Hodgkin lymphoma (1.4%). History of pretransplant malignancy (adjusted hazard ratio [AHR]=3.54, CI 2.31-5.43), younger age (AHR=1.91, CI 1.18-3.1), fewer HLA matches (AHR=1.32, CI 1.1-1.59) and treatment by ATG (AHR=1.55, CI 1.2-1.99) and OKT3 (AHR=1.37, CI 1-1.76), especially if given for rejection therapy were associated with an increased risk of PTLD. Mycophenolate and azathioprine were associated with a lower risk of PTLD (AHR=0.6, CI 0.47-0.78 and AHR=0.66, CI 0.46-0.95, respectively). IL2-receptor inhibitors and sirolimus did not modify the risk of PTLD. Patients without induction therapy treated with tacrolimus were at greater risk of lymphoma than those treated with new formulations of cyclosporine and those treated with antimetabolites (mycophenolate and azathioprine) have a lower risk of PTLD than those without. Patients with PTLD had poor survival (64% vs. 80% at 5 years). Older age, pretransplant malignancy and OKT3 were risk factors for death whereas treatment with mycophenolate was associated with a better survival (AHR=0.49, CI=0.28-0.82)., Conclusions: Our study highlights the contribution of patient history and immunosuppression in the risk of PTLD in the era of modern immunosuppression.

Background: Avascular necrosis (AVN) after renal transplantation has been largely attributed to the use of corticosteroids. However, other risk factors such as microvascular thrombosis and hyperlipidemia have been well described and may be of increased importance in the era of early steroid cessation and avoidance. We hypothesized that maintenance immunosuppressive medications known to be associated with these risk factors for AVN would also be associated with a higher risk of AVN., Methods: By using the U.S. Renal Data System database, we studied 27,772 primary patients on Medicare who received a solitary kidney transplant between January 1, 1996, and July 31, 2000. Cox proportional hazards regression models were used to calculate adjusted hazard ratios (AHRs) for patient- and transplant-related factors (including allograft rejection) with Medicare claims for AVN. The intensity and duration of corticosteroid use could not be assessed., Results: Among patients who were prescribed sirolimus at discharge, 3.5% of patients who received the combination of sirolimus-cyclosporine A (CsA) demonstrated AVN, compared with 1.4% of patients who received the combination of sirolimus-tacrolimus (P=0.06 by chi). In Cox regression, CsA use (vs. tacrolimus) (AHR 1.36, 95% confidence interval, 1.09-1.71) was independently associated with an increased risk of AVN. Sirolimus use showed a trend toward significance (AHR 1.59, 95% confidence interval, 0.99-2.56), with no significant interaction with CsA., Conclusions: Compared with other maintenance immunosuppression, AVN was significantly more common after use of CsA prescribed at the time of discharge for renal transplantation. Whether this increased risk of AVN was directly attributable to hyperlipidemia, microvascular thrombosis, or differences in corticosteroid dosing could not be determined.