Iman O. Hypolite

Hospitalizations for Bacterial Septicemia after Renal Transplantation in the United States

Background: It is common belief in the transplant community that rates of septicemia in transplant recipients have declined, but this has not been studied in a national population. Methods: Therefore, 33,479 renal transplant recipients in the United States Renal Data System from July 1, 1994 to June 30, 1997 were analyzed in a retrospective registry study of the incidence, associated factors, and mortality of hospitalizations with a primary discharge diagnosis of septicemia (ICD9 Code 038.x). Results: Renal transplant recipients had an adjusted incidence ratio of hospitalizations for septicemia of 41.52 (95% CI 35.45–48.96) compared to the general population. Hospitalizations for septicemia were most commonly associated with urinary tract infection as a secondary diagnosis (30.6%). In multivariate analysis, diabetes and urologic disease, female gender, delayed graft function, rejection, and pre-transplant dialysis, but not induction antibody therapy, were associated with hospitalizations for septicemia. Recipients hospitalized for septicemia had a mean patient survival of 9.03 years (95% CI 7.42–10.63) compared to 15.73 years (95% CI 14.77–16.69) for all other recipients. Conclusions: Even in the modern era, renal transplant recipients remain at high risk for hospitalizations for septicemia, which are associated with substantially decreased patient survival. Newly identified risks in this population were female recipients and pre-transplant dialysis.

Hospitalizations for fungal infections after renal transplantation in the United States

Abstract: Fungal infections in renal transplant recipients have not been studied in a national population. Therefore, 33,420 renal transplant recipients in the United States Renal Data System from 1 July 1994 to 30 June 1997 were analyzed in a retrospective registry study of hospitalized fungal infections (FI). FI were most commonly associated with secondary diagnoses of esophagitis (68, 23.9%), pneumonia (57, 19.8%), meningitis (23, 7.6%), and urinary tract infection (29, 10.3%). Opportunistic organisms accounted for 95.4% of infections, led by candidiasis, aspergillosis, cryptococcosis, and zygomycosis. Most fungal infections (66%) had occurred by six months post‐transplant, but only 22% by two months. In logistic regression analysis, end‐stage renal disease due to diabetes, duration of pre‐transplant dialysis, maintenance tacrolimus and allograft rejection were associated with FI. In Cox regression analysis, recipients with FI had a relative risk of mortality of 2.88 (95% CI=2.22–3.74) compared to all other recipients. Among FI, zygomycosis and aspergillosis were independently associated with both increased patient mortality and length of hospital stay. Most fungal infections in renal transplant recipients were opportunistic, occurred later than previously reported, and were associated with greatly decreased patient survival. Recipients with diabetes, prolonged pre‐transplant dialysis, rejection, and tacrolimus immunosuppression should be considered high risk for FI.

Hospitalizations for fractures after renal transplantation in the United States.

PURPOSE To investigate the incidence, risk factors, and associated mortality of fractures in renal transplant recipients. METHODS Retrospective registry study of 33,479 patients in the United States Renal Data System (USRDS) who received kidney transplants between 1 July 1994 and 30 June 1997. Associations with hospitalizations for a primary discharge diagnosis of fractures (all causes) were assessed. RESULTS Renal transplant recipients had an adjusted incidence ratio for fractures of 4.59 (95% confidence interval 3.29 to 6.31). In multivariate analysis, recipients with prevalent fractures, as well as recipients who were Caucasian, women, in the lower quartiles of recipient weight (<95.9 kg), had end stage renal disease caused by diabetes, and had prolonged pretransplant dialysis were at increased risk for hospitalization because of fractures after transplantation. Recipients hospitalized for hip fractures had decreased all-cause survival (hazard ratio for mortality 1.60, 95% CI 1.13 to 2.26) in Cox Regression analysis. CONCLUSIONS In the early post-transplant course (<3 years), renal transplant recipients had a greater incidence of fractures than the general population, which were associated with decreased patient survival. Preventive efforts should focus on recipients with the risk factors identified in this analysis, most of which can be easily obtained through history and physical examination.

Effect of Donor Factors on Early Graft Survival in Adult Cadaveric Renal Transplantation

Previous studies of the effect of donor factors on renal transplant outcomes have not tested the role of recipient body mass index, donor/recipient weight ratios and age matching, and other factors. We analyzed 20 309 adult (age 16 or older) recipients having solitary cadaveric renal transplants from adult donors from 1 July 1994 to 30 June 1998 in an historical cohort study (the 2000 United States Renal Data System) of death censored graft loss by the Cox proportional hazards models, which corrected for characteristics thought to affect outcomes. The only independently significant findings in Cox Regression analysis were a high donor/recipient age ratio (≥ 1.10, e.g. a 55‐year‐old donor given to a recipient age 50 years or younger, adjusted hazard ratio (AHR) 3.22, 95% confidence interval (CI) 2.36–4.39) and African American donor kidneys (AHR 1.64, 95% CI, 1.24–2.17). African American recipients and older donors were not at independently increased risk of graft failure in this model. Among donor factors, older donor kidneys given to younger recipients and donor African American kidneys were independently associated with graft loss in recipients of cadaver kidneys. The task for the transplant community should be to find the best means for managing all donor organs without discouraging organ donation.

Factors associated with improved short term survival in obese end stage renal disease patients

PURPOSE In contrast to its role in the general population, obesity, defined as body mass index (BMI) > or = 30 kg/m(2), has been associated with improved survival in patients with end stage renal disease (ESRD). This apparent benefit has not been explained. METHODS Using the United States Renal Data System (USRDS), we performed an historical cohort study on 151,027 patients initiated on ESRD therapy between January 1, 1995 and June 30, 1997, who never received renal transplants, and who had information sufficient to calculate BMI. We explored the association of various comorbidities present at the time of dialysis initiation (from HCFA Form 2728) with the presence of obesity by logistic regression, and the association of obesity with patient survival, including specific causes of death, by Cox regression adjusting for factors known to be associated with survival in this population. RESULTS Obese patients had an unadjusted two-year survival of 68% compared with 58% for non obese patients. Obesity was independently associated with a reduced risk of mortality among chronic dialysis patients (adjusted hazard ratio (AHR) 0.75, 95% confidence interval, 0.72-0.78), after controlling for all comorbidities and risk factors. However, there were significantly adverse interactions among whites (AHR 1.22, 1.14-1.30, across all causes of death) and females (AHR 1.12, 1.04-1.20, entirely due to an increased risk of infectious death). CONCLUSIONS Obesity in patients presenting with ESRD is associated independently with reduced all cause mortality; however, the relationship is complex and is stronger in African Americans. In addition, subgroup analysis suggests that obesity is associated with increased risk of infectious death in females.

Hospitalizations for Cytomegalovirus Disease after Renal Transplantation in the United States

PURPOSE Risk factors, sites, and mortality of hospitalized cytomegalovirus (CMV) disease in renal transplant recipients have not been studied in a national population. METHODS Therefore, 33,479 renal transplant recipients in the United States Renal Data System from 1 July 1, 1994 to June 30, 1997 were analyzed in an historical cohort study of patients with a primary discharge diagnosis of CMV disease (ICD9 Code 078.5x). RESULTS Renal transplant recipients had an incidence density of hospitalized CMV disease of 1.26/100 person years, and 79% of hospitalizations for CMV disease occurred in the first six months post transplant. The leading manifestation of hospitalized infection was pneumonia (17%). In logistic regression analysis controlling for transplant era, pre-transplant dialysis > or = 6 months, maintenance mycophenolate mofetil (MMF) therapy, and allograft rejection, but not induction antibody therapy, were significantly associated with hospitalized CMV disease. Compared with recipients with negative CMV serology (R-) who had donor kidneys with negative CMV serology (D-), D+/R- had the highest risk of hospitalization for CMV disease [adjusted odds ratio (AOR) 5.19, 95% confidence interval (CI) 3.89-6.93] followed by D+/R+ recipients, whereas D-/R+ were not at significantly increased risk. In Cox Regression analysis the relative risk of death associated with hospitalized CMV disease was 1.32 (95% CI 1.02-1.71). CONCLUSIONS Even in modern era, renal transplant recipients were at high risk for hospitalizations for CMV disease, which were associated with decreased patient survival. Current prophylactic measures have apparently not reduced the high risk of D+/R- recipients. Prolonged pre-transplant dialysis and maintenance MMF should also be considered risk factors for hospitalized CMV infection, and prospective trials of prophylactic antiviral therapy should be performed in these subgroups.

Hospitalizations for Fungal Infections after Initiation of Chronic Dialysis in the United States

Aims: Hospitalized fungal infections are reported frequently in renal transplant recipients and peritoneal dialysis patients, but the frequency of hospitalized fungal infections in dialysis patients has not been studied in a national population. Methods: 327,993 dialysis patients in the United States Renal Data System initiated from January 1, 1992 to June 30, 1997 were analyzed in a retrospective registry study of fungal infections (based on ICD9 Coding). Results: Dialysis patients had an age-adjusted incidence ratio for fungal infections of 9.80 (95% confidence interval (CI) 6.34–15.25)) compared to the general population in 1996 (the National Hospital Discharge Survey). Candidiasis accounted for 79% of all fungal infections, followed by cryptococcosis (6.0%) and coccidioidomycosis (4.1%). In multivariate analysis, fungal infections were associated with earlier year of dialysis, diabetes, female gender, decreased weight and serum creatinine at initiation of dialysis, chronic obstructive lung disease and AIDS. In Cox regression analysis the hazard ratio for mortality of fungal infections was 1.35 (95% CI 1.28–1.42). Conclusions: Dialysis patients were at increased risk for fungal infections compared to the general population, which substantially decreased patient survival. Female and diabetic patients were at increased risk for fungal infections. Although candidiasis was the dominant etiology of fungal infections, the frequency of cryptococcosis and coccidioidomycosis were higher than previously reported.

Acute coronary syndromes after renal transplantation in patients with end-stage renal disease resulting from diabetes.

Coronary heart disease is the leading cause of death in both diabetes mellitus and end‐stage renal disease. Although renal transplantation is known to reduce mortality in end‐stage renal disease, its effect on the incidence of acute coronary syndromes is unknown. Using data from the United States Renal Data System, we studied 11 369 patients with end‐stage renal disease due to diabetes enrolled on the renal and renal‐pancreas transplant waiting list from 1 July 1994 to 30 June 1997. Cox nonproportional hazards regression models were used to calculate the adjusted, time‐dependent relative risk for the most recent hospitalization for acute coronary syndromes (including acute myocardial infarction, unstable angina, or other acute coronary syndromes, ICD9 Code 410.x or 411.x) for a given patient in the study period. Demographics and comorbidities were controlled by using data from the medical evidence form (HCFA 2728). After renal transplantation, patients had an incidence of acute coronary syndromes of 0.79% per patient year, compared to 1.67% per patient year prior to transplantation. In comparison to maintenance dialysis, renal transplantation was independently associated with a lower risk for acute coronary syndromes (hazard ratio 0.38, 95% confidence interval, 0.30–0.49). Patients with end‐stage renal disease due to diabetes on the renal transplant waiting list were much less likely to be hospitalized for acute coronary syndromes after renal transplantation. The reasons for this decreased risk should be the subject of further study.

Hospitalized Congestive Heart Failure after Renal Transplantation in the United States

PURPOSE African Americans have increased risk for congestive heart failure (CHF) compared to Caucasians in the general population, but the risk of CHF in African American renal transplant recipients has not been studied in a national renal transplant population. METHODS Therefore, 33,479 renal transplant recipients in the United States Renal Data System (USRDS) from 1 July, 1994 to 30 June, 1997 were analyzed in an historical cohort study of the incidence, associated factors, and mortality of hospitalizations with a primary discharge diagnosis of CHF [International Classification of Diseases-9 (ICD9) Code 428.x]. RESULTS African American renal transplant recipients had increased age-adjusted risk of hospitalizations for congestive heart failure compared to African Americans in the general population [rate ratio 4.60, 95% confidence interval (CI) 4.59-4.62]. In logistic regression analysis, African American recipients had increased risk of congestive heart failure after renal transplantation, independent of other factors. Among other significant factors associated with congestive heart failure, the strongest were graft loss and allograft rejection. No maintenance immunosuppressive medications were associated with CHF. In Cox regression analysis patients hospitalized for CHF had increased all-cause mortality compared with all other recipients (hazard ratio 3.69, 95% CI, 2.23-6.10), but African American recipients with CHF were not at significantly increased risk of mortality compared to Caucasian recipients with CHF. CONCLUSIONS African Americans recipients were at high risk for CHF after transplant independent of other factors. The reasons for this increased risk should be the subject of further study. All potential transplant recipients should receive particular attention for the diagnosis and prevention of CHF in the transplant evaluation process, which includes preservation of allograft function.