Lawrence Y. Agodoa

Serum β-2 Microglobulin Levels Predict Mortality in Dialysis Patients: Results of the HEMO Study

In the randomized Hemodialysis (HEMO) Study, chronic high-flux dialysis, as defined by higher beta-2 microglobulin (beta(2)M) clearance, compared with low-flux dialysis did not significantly alter all-cause mortality in the entire cohort but was associated with lower mortality in long-term dialysis patients. This analysis examined the determinants of serum beta(2)M levels and the associations of serum beta(2)M levels or dialyzer beta(2)M clearance with mortality. In a multivariable regression model that examined 1704 patients, baseline residual kidney urea clearance and dialyzer beta(2)M clearance were strong predictors of predialysis serum beta(2)M levels at 1 mo of follow-up, with regression coefficients of -7.21 (+/-0.69 SE) mg/L per ml/min per 35 L urea volume (P < 0.0001) and -1.94 (+/-0.30) mg/L per ml/min (P < 0.0001),respectively. In addition, black race and baseline years on dialysis correlated positively whereas age, diabetes, serum albumin, and body mass index correlated negatively with serum beta(2)M levels (P < 0.05). In time-dependent Cox regression models, mean cumulative predialysis serum beta(2)M levels but not dialyzer beta(2)M clearance were associated with all-cause mortality (relative risk = 1.11 per 10-mg/L increase in beta(2)M level; 95% confidence interval 1.05 to 1.19; P = 0.001), after adjustment for residual kidney urea clearance and number of prestudy years on dialysis. This association is supportive of the potential value of beta(2)M as a marker to guide chronic hemodialysis therapy.

Posttransplant lymphoproliferative disorders after renal transplantation in the United States in era of modern immunosuppression.

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.

Liver cysts in patients with autosomal dominant polycystic kidney disease

Liver cysts were found in 46 (29 per cent) of 158 patients over 10 years of age with documented autosomal dominant-type polycystic kidney disease (PKD) from 62 unrelated families. Hepatic cysts were not found in any patient at risk for PKD in whom renal cysts were not detected. The prevalence of liver cysts increased with advancing age and with declining rate of glomerular filtration. Results of clinical and laboratory studies indicate that polycystic liver disease in patients with autosomal dominant-type PKD is a benign condition, rarely, if ever, causing impaired liver function or portal hypertension.

Progressive Multifocal Leukoencephalopathy and Use of Mycophenolate Mofetil After Kidney Transplantation

Mycophenolate mofetil (MMF) use may be associated with progressive multifocal leukoencephalopathy (PML). We conducted a retrospective cohort study of 32,757 renal transplant recipients using the United States Renal Data System kidney transplant files for the incidence, prognosis, and clinical features associated with PML occurring after kidney transplant. Subjects were transplanted from January 1, 2000 to July 31, 2004 and followed through December 31, 2004. The incidence density of PML in MMF users was 14.4 cases/100,000 person-years at risk versus 0 for non-MMF users (P=0.11) by log rank test. Factors significantly associated with PML were BK virus infection (22.2% vs. 1.1%), pretransplant transfusion (75% vs. 34%), panel reactive antibody more than 20% (56% vs. 14%), and use of antirejection medications in the first year (33% vs. 9.2%), all P less than 0.05. PML is rare in the renal transplant population. There was no significant association between PML and MMF, but MMF use in this cohort is too high to accurately assess an association.

The hemodialysis (HEMO) study: Rationale for selection of interventions

Garabed Eknoyan Andrew S. Levey, Gerald J. Beck, Lawrence Y. Agodoa, John T. Daugirdas John W. Kusek, Nathan W. Levin and Gerald Schulman for the HEMO Study Group Department of Medicine, Baylor College of Medicine, Houston, Texas; New England Medical Center, Boston, Massachusetts; Division of BiostatiStics, Cleveland Clinic Foundation, Cleveland, Ohio; NIDDK NiH, Bethesda, Maryland; Veterans Affairs Westside Medical Center, Chicago, ililnois; Beth israei Medical Center, New York, New York; and Dbision of Nephrology, Vanderbllt University Medical Center, Nashville, Tennessee

Design and baseline characteristics of participants in the African American Study of Kidney Disease and Hypertension (AASK) Pilot Study

Hypertension and end-stage renal disease (ESRD) are major causes of morbidity and mortality in the United States, especially among African Americans. The African American Study of Kidney Disease and Hypertension (AASK) Pilot Study evaluated the feasibility of conducting a long-term clinical trial to compare the effects of two levels of blood pressure control and three different antihypertensive drug regimens on the rate of decline in glomerular filtration rate (GFR) in African Americans with clinically diagnosed hypertensive renal disease. African American men and women aged 18-70 years with a GFR of 25-70 ml/min/ 1.73m2 and hypertension were randomized in a 3 x 2 factorial design to initial treatment with either an angiotensin-converting enzyme inhibitor (enalapril), a calcium channel blocker (amlodipine), or a beta blocker (atenolol) and to a mean arterial blood pressure (goal MAP) of either 102-107 mm Hg or < or = 92 mm Hg. Furosemide, doxazosin, clonidine, hydralazine, and minoxidil were added sequentially until goal MAP was achieved. To compare the pathologic diagnosis with the clinical diagnosis of renal disease, study participants without contraindication were also asked to undergo a renal biopsy. The goals of the AASK Pilot Study were to evaluate recruitment techniques, adherence to prescribed antihypertensive drug regimens, ability of the antihypertensive regimens to achieve blood pressure goals, rates of participation in scheduled clinic visits and procedures, and variability of GFR measurements. A further goal was to obtain renal biopsy data in at least 75% of the randomized study participants. Compared to the ESRD patient population whose renal disease is caused by hypertension, women were underrepresented in the AASK Pilot Study. AASK Pilot Study participants had higher unemployment rates and lower income levels than African Americans in the general U.S. population.

Dementia as a Predictor of Mortality in Dialysis Patients

The life expectancy of patients who have dementia and are initiated on dialysis in the United States has not been described in the medical literature. A retrospective cohort study was conducted of 272,024 Medicare/Medicaid primary patients in the US Renal Data System who were started on ESRD therapy between April 1, 1995, and December 31, 1999, and followed through December 31, 2001. Cox regression was used to calculate adjusted hazard ratios for risk for death after initiation of dialysis for patients whose dementia was diagnosed before the initiation of dialysis as shown by Medicare claims. The average time to death for patients with dementia was 1.09 versus 2.7 yr (P < 0.001) with an adjusted hazard ratio of 1.87 (95% confidence interval 1.77 to 1.98). The 2-yr survival for patients with dementia was 24 versus 66% for patients without dementia (P < 0.001 via log rank test). Dementia that is diagnosed before initiation on dialysis is an independent risk factor for subsequent death. Such patients should be considered for time-limited trials of dialysis and careful discussion in choosing whether to pursue initiation of dialysis or palliative care.

Myeloma, hodgkin disease, and lymphoid leukemia after renal transplantation : Characteristics, risk factors and prognosis

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-Hodgkins 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.

Analysis of USRDS: Incidence and Risk Factors for Pneumocystis jiroveci Pneumonia

Background. To investigate the effect of modern immunosuppression on the incidence, risk factors, morbidity, and mortality of Pneumocystis pneumonia (PCP) in recipients of kidney transplants. Methods. We conducted a retrospective cohort study of 32,757 Medicare primary transplant recipients in the United States Renal Data System from January 1, 2000 through July 31, 2004. PCP infection was defined by Medicare claims using International Classification of Disease, 9th Revision codes. The incidence of PCP infections, graft loss, and death were measured. Results. There were a total of 142 cases (cumulative incidence 0.4%) of PCP after kidney transplantation during the study period. By using multivariate analysis with Cox regression, expanded criteria donor, donation after cardiac death, and earlier year of transplant were associated with development of PCP disease. Induction immunosuppression and acute rejections were not associated with risk for PCP infections. However, based on adjusted hazard ratio (AHR), maintenance immunosuppression regimens containing the combination of tacrolimus and sirolimus (AHR 3.60, confidence interval [CI] 2.03–6.39), Neoral and mycophenolate mofetil (AHR 2.09, CI 1.31–3.31), and sirolimus and mycophenolate mofetil (AHR 2.77, CI 1.40–5.47), were associated with development of PCP. As a time dependent variable, PCP was associated with an increased risk of both graft loss and death. Conclusion. PCP infections are rare in the modern era of prophylaxis; however, these infections are a serious risk factor for graft loss and patient death, in particular, in patients who are on sirolimus as part of the immunosuppressive regimen. The median time to development of PCP after transplant was 0.80±0.95 years, suggesting a longer period of PCP prophylaxis.

Impact of Diabetes and Hepatitis after Kidney Transplantation on Patients Who Are Affected by Hepatitis C Virus

Complications associated with use of donor hepatitis C-positive kidneys (DHCV+) have been attributed primarily to posttransplantation liver disease (as a result of hepatitis C disease). The role of posttransplantation diabetes has not been explored in this setting. With the use of the United States Renal Data System database, 28,942 Medicare KT recipients were studied from January 1, 1996, through July 31, 2000. Cox proportional hazards regression models were used to calculate adjusted hazard ratios (AHR) for the association of sero-pairs for HCV (D+/R-, D+/R+, D-/R+ and D-/R-) with Medicare claims for de novo posttransplantation HCV and posttransplantation diabetes. The peak risk for posttransplantation HCV was in the first 6 mo after transplantation. The incidence of posttransplantation HCV after transplantation was 9.1% in D+/R-, 6.3% in D+/R+, 2.4% in D-/R+, and 0.2% in D-/R-. The incidence of posttransplantation diabetes after transplantation also peaked early and was 43.8% in D+/R-, 46.6% in D+/R+, 32.3% in D-/R+, and 25.4% in D-/R-. Associations for both complications were significant in adjusted analysis (Cox regression). Both posttransplantation HCV (AHR, 3.36; 95% confidence interval, 2.44 to 4.61) and posttransplantation diabetes (AHR, 1.81; 95% confidence interval, 1.54 to 2.11) were independently associated with an increased risk of death, but posttransplantation diabetes accounted for more years of life lost, particularly among recipients of DHCV+ kidneys. Posttransplantation diabetes may contribute substantially to the increased risk of death associated with use of DHCV+ kidneys and accounts for more years of life lost than posttransplantation HCV. Because HCV infection acquired after transplantation is so difficult to treat, methods that have been shown to reduce viral transmission warrant renewed attention.