Frank Daniels

Incidence and Mortality of Acute Renal Failure in Medicare Beneficiaries, 1992 to 2001

This studys objective was to determine the incidence and mortality of acute renal failure (ARF) in Medicare beneficiaries. Data were from hospitalized Medicare beneficiaries (5,403,015 discharges) between 1992 and 2001 from the 5% sample of Medicare claims. For 1992 to 2001, the overall incidence rate of ARF was 23.8 cases per 1000 discharges, with rates increasing by approximately 11% per year. Older age, male gender, and black race were strongly associated (P < 0.0001) with ARF. The overall in-hospital death rate was 4.6% in discharges without ARF, 15.2% in discharges with ARF coded as the principal diagnosis, and 32.6% in discharges with ARF as a secondary diagnosis. In-hospital death rates were 32.9% in discharges with ARF that required renal dialysis and 27.5% in those with ARF that did not require dialysis. Death within 90 d after hospital admission was 13.1% in discharges without ARF, 34.5% in discharges with ARF coded as the principal diagnosis, and 48.6% in discharges with ARF as a secondary diagnosis. Discharges with ARF were more (P < 0.0001) likely to have intensive care and other acute organ dysfunction than those without ARF. For discharges both with and without ARF, rates for death within 90 d after hospital admission showed a declining trend. In conclusion, the incidence rate of ARF in Medicare beneficiaries has been increasing. Those of older age, male gender, and black race are more likely to have ARF. These data show ARF to be a major contributor to morbidity and mortality in hospitalized patients.

Identification of the CD4+ T cell as a major pathogenic factor in ischemic acute renal failure

Leukocytes have been implicated in the pathogenesis of ischemic acute renal failure (ARF), but the roles of the individual cell types involved are largely unknown. Recent indirect evidence suggests that T cells may play an important role in a murine model of ARF. In the current study, we found that mice deficient in T cells (nu/nu mice) are both functionally and structurally protected from postischemic renal injury. Reconstitution of nu/nu mice with wild-type T cells restored postischemic injury. We then analyzed the contribution of the individual T cell subsets to postischemic injury and found that mice deficient in CD4(+) T cells, but not mice deficient in CD8(+) T cells, were significantly protected from ARF. Direct evidence for a pathophysiologic role of the CD4(+) T cell was obtained when reconstitution of CD4-deficient mice with wild-type CD4(+) T cells restored postischemic injury. In addition, adoptive transfers of CD4(+) T cells lacking either the costimulatory molecule CD28 or the ability to produce IFN-gamma were inadequate to restore injury phenotype. These results demonstrate that the CD4(+) T cell is an important mediator of ischemic ARF, and targeting this cell may yield novel therapies.

Excerpts From the US Renal Data System 2009 Annual Data Report

This 21st US Renal Data System Annual Data Report covers data through 2007, and again includes a section on chronic kidney disease (CKD) in the United States. Using NHANES and employer group health plan data, we estimate the relationship between kidney disease markers and mortality risk and the likelihood of blood pressure and lipid control by CKD stage; illustrate use of the new ICD-9-CM CKD diagnosis codes; and report on morbidity, mortality, care and costs during the transition to ESRD. New chapters address CKD patient care, the transition to ESRD, and acute kidney injury. In 2007, 111,000 patients started end-stage renal disease (ESRD) therapy, and the prevalent population reached 527,283 (including 368,544 dialysis patients); 17,513 transplants were performed, and 158,739 patients had a functioning graft at year’s end. Program expenditures reached

United States Renal Data System 2008 Annual Data Report Abstract

35.3 billion, with

B Cell Deficiency Confers Protection from Renal Ischemia Reperfusion Injury

23.9 billion from Medicare (accounting for 5.8% of total Medicare expenditures). The incident rate fell 2.1%, to 354 per million. Fistula use in prevalent patients declined 2.6 percent; catheter use continues to be a concern. The percentage of patients with hemoglobin levels above 13 g/dl has fallen since 2006, but levels in the incident population frequently exceed 12. First-year mortality and morbidity among hemodialysis patients—particularly the increasing rate of hospitalizations due to infections—continue to be major concerns, and pediatric patient survival has not improved. The public health impact of kidney disease is larger than previously appreciated, and early detection, education, intervention, and risk factor control need to address the heavy burden of cardiovascular disease and adverse events in this vulnerable population.

Protective effect of T cell depletion in murine renal ischemia-reperfusion injury

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Protective Effect of HMG-CoA Reductase Inhibitor on Experimental Renal Ischemia-Reperfusion Injury

Recent data have demonstrated a role for CD4+ cells in the pathogenesis of renal ischemia reperfusion injury (IRI). Identifying engagement of adaptive immune cells in IRI suggests that the other major cell of the adaptive immune response, B cells, may also mediate renal IRI. An established model of renal IRI was used: 30 min of renal pedicle clamping was followed by reperfusion in B cell-deficient (μMT) and wild-type mice. Renal function was significantly improved in μMT mice compared with wild-type mice at 24, 48, and 72 h postischemia. μMT mice also had significantly reduced tubular injury. Both groups of mice had similar renal phagocyte infiltration postischemia assessed by myeloperoxidase levels and similar levels of CD4+ T cell infiltration postischemia. Peritubular complement C3d staining was also similar in both groups. To identify the contribution of cellular vs soluble mechanism of action, serum transfer into μMT mice partially restored ischemic phenotype, but B cell transfers did not. These data are the first demonstration of a pathogenic role for B cells in ischemic acute renal failure, with a serum factor as a potential underlying mechanism of action.

Hypertension in Pediatric Long-term Hemodialysis Patients in the United States

Background. Ischemia-reperfusion injury (IRI) is the main cause of acute renal failure in both allograft and native kidney. Studies using T cell knockout mice have established an important role for T cells in renal IRI. T cell depletion strategies are effective in human allograft rejection. However, it is not known whether those are effective in renal IRI. Therefore, the effect of T cell depletion in a murine model of renal IRI using well-characterized antibodies (Abs) that have been effective in preventing experimental allograft rejection was studied. Methods. T cell depleting Abs to CD4 (GK1.5), CD8 (2.43) or pan-T cells (30.H12) were purified from hybridoma culture supernatant. Thymectomized C57BL/6 mice, treated with different combinations of T cell depleting Abs, underwent 30 min of bilateral renal IRI, followed by assessment of renal function, structure, and degree of T cell depletion in spleen, lymph nodes, and peripheral blood by flow cytometry. Results. Mice given both GK1.5 and 2.43 had considerable CD4 and CD8 cell depletion but no protection of renal function after ischemia-reperfusion (I/R) as measured by the rise in serum creatinine. However, when GK1.5 and 2.43 was administered combined with 30.H12, which more effectively depleted CD4 T cell numbers, a significant protection of renal function and structure was observed after I/R. Antibody combinations did not significantly alter other leukocyte populations. Conclusions. These data demonstrate that T cell depletion can improve the course of experimental renal IRI. However, more aggressive T cell depletion strategies were required compared with that needed to prevent experimental allograft rejection.

Utility and limitations of serum creatinine as a measure of renal function in experimental renal ischemia-reperfusion injury.

Background: Increasing evidence supports an important role for inflammation in the pathogenesis of renal ischemia-reperfusion injury (IRI). Recently, HMG-CoA reductase inhibitors, ‘statins’, have demonstrated anti-inflammatory effects independent of cholesterol-lowering. Hypothesis: We tested the hypothesis that a statin would improve outcome in a murine model of renal IRI. Upon finding a protective effect, we tested the hypothesis that the mechanisms by which statins protected in renal IRI was by reducing neutrophil and macrophage infiltration and upregulating the anti-inflammatory cytokine IL-6. Methods: Cerivastatin at various dosing regimens was administered to NIH Swiss mice to evaluate the effects on renal IRI. Analysis of renal structure, function, neutrophil and macrophage infiltration, cytokine production, as well as mortality was performed in cerivastatin- and saline-treated groups. Results:Primary: Cerivastatin pretreatment for 3 days led to a significant improvement in renal function, tubular injury as well as survival after IRI compared to saline-treated mice. Secondary: Neutrophil and macrophage infiltration into kidney tissue was similar in both groups. IL-6 was markedly upregulated early in the kidneys of statin-treated compared to saline-treated mice. Conclusion: These data demonstrate that a statin compound can improve the course of ischemic acute renal failure. Induction of protective molecules such as IL-6 may underlie this effect.

Diagnosis of cardiac disease in pediatric end-stage renal disease

BACKGROUND AND OBJECTIVES Data are limited regarding BP distribution and the prevalence of hypertension in pediatric long-term dialysis patients. This study aimed to examine BP distribution in U.S. pediatric long-term hemodialysis patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This cross-sectional study of all U.S. pediatric (aged 0-< 18 yr, n = 624) long-term hemodialysis patients was performed as part of the Centers for Medicare & Medicaid Services End-Stage Renal Disease (ESRD) Clinical Performance Measures Project. BP and clinical information were collected monthly in October, November, and December 2001. Hypertension was defined as the mean of pre- and postdialysis systolic or diastolic BP above the 95th percentile for age, height, and sex, or antihypertensive medication use. Results were calculated by age, sex, race, ethnicity, ESRD duration, body mass index percentile, primary cause of ESRD, and laboratory data. RESULTS Hypertension was present in 79% of patients; 62% used antihypertensive medication. Five percent of patients were prehypertensive (mean BP at 90th to 95th percentile). Hypertension was uncontrolled in 74% of treated patients. Characteristics associated with hypertension included acquired kidney disease, shorter duration of ESRD, and lower mean hemoglobin and calcium values. Characteristics associated with uncontrolled hypertension were younger age and shorter duration of ESRD. CONCLUSIONS Hypertension is common in U.S. pediatric long-term hemodialysis patients, uncontrolled in 74% of treated patients, and untreated in 21% of hypertensive patients. It is concluded that a more aggressive approach to treatment of hypertension is warranted in pediatric long-term hemodialysis patients.