Factors and outcome in BK virus nephropathy in a Hispanic kidney transplant population.

UNLABELLED: BK virus nephropathy (BKVN) is an increasingly recognized cause of kidney allograft loss and is thought to be related to the newer, more potent immunosuppressive agents. Conflicting information has been reported on risk factors for BK infection. PURPOSE: To determine incidence, associated factors, and outcome of BKVN in our kidney transplant population in order to improve identification and management. METHODS: Kidney transplants from January 2000 to December 2005 were retrospectively reviewed. Data were collected for patients with biopsy-proven BKVN including age, sex, body mass index (BMI), etiology of renal failure, other medical diseases, donor type, surgical complications, rejection and infection, time to diagnosis, induction, immunosuppressive and antiviral therapy, and clinical outcome. A control group of patients matched for sex, age, type of graft, etiology of kidney disease, and BMI, was established for comparison. STUDY GROUP: During this period, 20 (4%) of 497 transplanted patients were diagnosed with BKVN. Thirteen (65%) were males, 8 (40%) were young adults (ages 21-40), and 18 (90%) received grafts from cadaveric donors (P=0.05). Twelve (60%) had hypertensive renal disease, 2 (10%) also had diabetes, and 16 (80%) had a BMI >25 (P=0.01). Lymphoceles occurred in 5 patients (25%). Mean creatinine level at diagnosis was 2.7 mg/dL and mean time to diagnosis was 23 months. Ten patients (50%) had leukopenia at or within a year before biopsy (P=0.001). Viruses other than BK occurred in 9 patients: varicella zoster virus in 3, cytomegalovirus in 2, herpes simplex virus in 1, molluscum contagiosum in 1, Epstein-Barr virus in 1, and human papillomavirus in 1. Eighteen patients (90%) had related rejection (P= 0.001) and 4 (20%) suffered allograft loss (P= 0.001). Basiliximab (living donors) and anti-thymocyte globulin (cadaver donors) were given for induction. All patients were on triple therapy; 15 on prednisone and sirolimus, with either tacrolimus in 8, cyclosporine in 4, mycophenolate in 1, or mycophenolate and tacrolimus in 2. The other 5 received prednisone with tacrolimus and mycophenolate. Graft loss occurred in 2 patients on tacrolimus and mycophenolate, 1 patient on tacrolimus and sirolimus, and 1 patient on cyclosporine and sirolimus. Immunosuppression was decreased in all patients. Two were given cidofovir for 6 months and had stable creatinine levels at the end of the study. Records were reviewed until April 2007. There were no deaths in this cohort. CONTROL GROUP: The number of rejections experienced by patients with BKV was much higher (P<0.0001), but the rate of graft loss was similar between the 2 groups (P=0.19). Viral co-infection was more frequent in patients with BKV (P=0.04). No episodes of leukopenia were reported for any of the patients in the control group (P=0.001). Immunosuppression with tacrolimus and sirolimus was more frequent in the BKV group, but this was not statistically significant (P=0.18, 0.28, respectively). The number of lymphoceles was larger in patients with BKV, but the difference was not statistically significant (P=0.35). CONCLUSION: BKVN is present in our transplant population and results in a high rate of allograft rejection with varying rates of graft loss. Associated factors were deceased donor and immunosuppression with potent agents, particularly tacrolimus and sirolimus. We also found a higher frequency of obesity, viral co-infection, and leukopenia. Routine screening and timely biopsy could prove cost-effective and significantly reduce morbidity.

The fate of organs refused locally and transplanted elsewhere.

UNLABELLED: The number of kidney allografts procured from deceased donors has been fairly constant in the past few years, while organs from living donors steadily increase. In our program, existing protocols refused some kidneys which were subsequently accepted and transplanted at other hospitals. Thus, a review of our criteria to accept kidneys became necessary. METHODS: We studied the outcome of all kidneys refused by us but transplanted in other programs between 2002 and 2004. The data analyzed included ID no. donor, transplant center, procurement date, donor age, ischemic times, recipient alive or dead, creatinine level (when it was offered), initial function, hypertension, diabetes mellitus, biopsy, reason why the kidney was not accepted in our program, kidney functioning or lost, and cause of graft failure. The chi-square, Fisher, and t tests were used to analyze our data; P values of <.05 were regarded as significant. RESULTS: Originally 137, we excluded kidneys exported due to mandatory sharing (26 of 137 = 18.97%) and multiorgan placement (10 of 137 = 7.3%). Thus, 101 kidneys were not accepted by us because they did not meet the existing criteria of our program, but were accepted elsewhere. Reasons for nonacceptance were divided into donor quality, donor social history, donor age, donor size/weight, positive serological test, as well as organ preservation time, organ anatomical damage, elevated creatinine, abnormal urinalysis, abnormal biopsy, and decreased urine output. Donor issues were 66 of 101 (65.3%) with a graft loss of 13.6%, and organ issues were 35 of 101 (34.7%) with a graft loss of 66.6%. Donor quality totaled 24 of 66 (36.4%) and donor social history totaled 20 of 66 (30.3%); these were the most common causes for kidney nonacceptance related to donor issues. Reasons related to organ quality included elevated creatinine (15 of 35 = 42.9%; graft loss, 46.6%), and abnormal biopsy (9 of 35 = 25.7%; graft loss, 11.1%) and organ anatomical damage (4 of 35 = 11.4%; graft loss, 75%) (P = .42). Graft loss was more frequent with creatinine levels above 2.4 mg/dL (P < .001, RR gf = 1.5). Long-term fate of these 101 kidneys transplanted elsewhere: 82 (81.2%) were still working while 19 (18.8%) were lost. The causes of graft loss were renal artery thrombosis (42.1%), renal venous thrombosis (26.3%), death for other reasons (15.8%), graft never worked (10.5%), and ESRD (5.7%). The results suggest that the criteria for refusal related to donor issues, including hypertension, diabetes mellitus, donor age and donor size, should be revised owing to the low percentage of graft loss. Other donor issues such as positive serological test and donor social history (drug use, alcoholism) represent a serious potential risk for the health of recipients; for this reason, considering these persons as possible donors is very difficult irrespective of the graft outcome. Kidney refusals related to organ issues (especially elevated creatinine and anatomical damage) due to the very high percentage of graft loss should be considered high risk and probably be excluded. The increase in the demand of kidneys to be transplanted is a very important reason for a continuous and systematic review of donor exclusion criteria in every transplant program. The results presented here have helped us to improve both our outcomes and utilizations based on scientific evidence.

Study of factors that affect complications after renal transplantation.

There are no multifactorial studies of complications after renal transplant in the Hispanic population. The objective of this study was to identify which factors are associated with the development of complications after renal transplantation. This retrospective study was performed on all patients transplanted in the Puerto Rico Transplant Program during 2002. Independent variables included preoperative albumin, white blood cell (WBC) count, hemoglobin, creatinine, weight, height, body mass index (BMI), type of dialysis, time on dialysis, and urine production after transplant. Dependent parameters included posttransplant diuresis, wound infection, wound dehiscence, lymphoceles, acute tubular necrosis, length of stay, postoperative weight, graft survival, and patient survival. Data were analyzed with parametric and nonparametric techniques using STAT 200 software. Sixty-four patients were included in the study: 37 male, 27 female. No significant differences in complication rate or length of stay were found with age, preoperative albumin, WBC count, hemoglobin, creatinine, weight, height, dialysis modality, and donor type. Significant factors included type of dialysis, time on dialysis, and BMI. Preoperative albumin if > 3 was not a prognostic indicator for the development of surgical complications following renal transplantation. Only preoperative weight, BMI, and dialysis duration were significant factors in the development of postoperative complications and prolonged hospital stay in this sample Hispanic transplant population. These data are important in formulating selection, education, and transplant management policy.

HLA is not predictive of posttransplant diabetes mellitus.

AIMS: New-onset posttransplant diabetes mellitus (PTDM) is a frequent complication of kidney transplantation. The goal of this study was to identify if the tendency to develop PTDM was associated to the HLA, as is seen in the general population. METHODS: A retrospective study was made of 525 patients who underwent renal transplantation between 1997 and 2004. They were divided into three categories depending on the diabetic status before and after kidney transplantation. The HLA profile of each patient was identified for class 1 and class 2 antigens including HLA-A, HLA-B, and DR-R. Antigen frequencies were calculated and gene frequencies derived. These were compared among the three groups and with the published data for the Puerto Rico population. Other variables studied included weight, age, gender, and family history. RESULTS: Seventy-two of 526 (13.7%) were diabetic before transplantation; 92/453 (20.3%) developed PTDM after kidney transplantation. Pretransplant diabetics showed a higher incidence of A3 (0.1102 vs 0.0869 vs 0.0361), DR4 (0.3334 vs 0.1932 vs 0.2124), and DR-13 (0.1835 vs 0.1115 vs 0.1175) than nondiabetics and the normal Puerto Rican population. Posttransplant diabetics showed a higher A3 (0.1154) and a higher DR3 (0.0675 vs 0.0295 vs 0.0022) than nondiabetics and normal population. CONCLUSION: PTDM was not associated statistically with the HLA in this group of transplant recipients, although A3 and DR3 were higher. Patients with the phenotype that is related to diabetes in the normal population did not have a higher incidence of diabetes in this series.

Assessing the risk of infection and rejection in Hispanic renal transplant recipients by means of an adenosine triphosphate release assay.

INTRODUCTION: Because of the necessary immunosuppression, transplant recipients have a high risk of infection. Conversely, underimmunosuppression carries with it the risk of rejection. It would be quite useful to have a test that could differentiate between infection and rejection in renal transplant patients and better still, to predict which patients are at risk of complications. A new assay, which measures adenosine triphosphate (ATP) synthesis by CD4+ T cells in response to stimulation by phytohemagglutinine (Immuknow assay, Cylex, Inc) is undergoing clinical evaluations. Preliminary investigations suggest that this test could be useful to assess and predict the immune status of patients with other conditions. METHODS: We examined the records of all patients who received a kidney transplant in our program between August 2004 and January 2005. Of 64 patients, 58 had pretransplant and posttransplant ATP level determinations. We searched for associations between ATP levels and immunosuppression type, doses, and levels; creatinine levels; white blood cell count; tissue typing; preformed antibodies; as well as ATP levels on infection and rejection, and changes in ATP levels with time. Chi-square, Fisher, t test, analysis of variance (ANOVA), and relative risks were used for analysis of data. RESULTS: There was no relation between ATP levels and immunosuppression type, doses, or levels; creatinine levels; white blood cell counts; HLA; and panel-reactive antibody (P > 0.05). However, patients with moderate or high pretransplant ATP levels had more rejection episodes (8/10) while patients with ATP levels in the low immune response had more infections (6/11) (P < .001; relative risk [RR] for rejection = 1.2; RR for infection = 4.4). The mean ATP levels for rejection was 423.3 ng/mL versus 268.45 ng/mL for infection and 277.15 ng/mL for no events (ANOVA, P = .0145). Although acute rejections occurred mostly above 300, this was not significant (P = .059; RR = 0.9). Infections were more frequent with ATP under 300 (RR = 7.3) and severe infection (endocarditis, meningitis, peritoneal abscesses, pneumonia, etc) were more frequent under 200 (P < .001). Comparing pretransplant with posttransplant values at the second week an increase correlated with rejection (P < .001, RR = 15.3), while a decrease did not correlate with the infection (P = .845, RR = 1.4). Patients who received antirejection treatment had a decrease in their ATP levels at 5 days (P = .002). CONCLUSION: This ATP release assays helpful in determining the risk of developing infection or rejection, as well as follow-up in the response to therapy.

A marked increase in organ donation in Puerto Rico.

During its first years of existence, the Puerto Rico Transplant Program barely reached 18 to 20 renal transplants per year. A brain death amendment to the law improved the numbers but only to a stable thirty/year. Polls and studies showed that, although people knew about transplantation and expressed willingness to donate, the powerful emotional grief reaction, as well as a peculiar decision-making process, all militated against effective donation. In 1995, LifeLink of Puerto Rico was created as part of the very successful LifeLink Foundation of Tampa, staffed by local professionals. Cadaveric donation increased exponentially by 1227% and in 2004, 22.4 donors per million population were recovered, up from 1.5, one of the steepest growth curves in the United States. As a result, kidney transplantation increased, a cardiac transplant program was inaugurated, a pancreas transplant program has started, and liver will follow. The success is the result of well-trained, culturally sensitive coordinators and requestors; continuous education to the public, hospitals, administrators, neurospecialists, and critical care units; hospital development; implementation of federal law; and a sensitive approach the deceased donor family, and not only to the waiting list patients. The results demonstrate that organizational and educational factors can override cultural obstacles.