Biomedical subjects

J D Pirsch

Publications and source records attributed to J D Pirsch.

At least 19 recordsLinked to original sources

PubMed2005

Predictors and outcomes of candiduria in renal transplant recipients.

BACKGROUND: The epidemiology of candiduria in renal transplantation is unknown. METHODS: We performed a nested case-control study to evaluate the epidemiology of candiduria in renal transplant recipients at the University of Wisconsin (Madison) over an 8-year period. RESULTS: Renal transplantations were performed on 1738 patients during this period, 192 of whom had 276 episodes of candiduria. Candida glabrata, which was recovered from 98 (51%) of 192 case patients, was the most common pathogen identified. Most case patients were asymptomatic. Independent predictors of candiduria were female sex (odds ratio [OR], 12.5; 95% confidence interval [CI], 6.7-23.0), intensive care unit admission (OR, 8.8; 95% CI, 2.3-35.0), antibiotic use during the month before candiduria (OR, 3.8; 95% CI, 1.7-8.3), presence of an indwelling bladder catheter (OR, 4.4; 95% CI, 2.1-9.4), diabetes (OR, 2.2; 95% CI, 1.3-3.9), neurogenic bladder (OR, 7.6; 95% CI, 2.1-27), and malnutrition (OR, 2.4; 95% CI, 1.3-4.4). Log-rank testing of Kaplan-Meier curves revealed that 60-day, 90-day, and cumulative survival rates were significantly different between case and control patients; there was no difference in the survival rate during the first 30 days after transplantation. A variety of regimens were used for treatment; 119 case patients (62%) underwent removal of the indwelling bladder catheter within 1 week after diagnosis of candiduria. Candiduria cleared in 148 case patients (77%). Treatment of candiduria was not associated with an improved survival rate. CONCLUSIONS: Candiduria occurs commonly in renal transplant recipients. Risk factors for candiduria in such persons are similar to those in hospitalized patients who have not received a transplant. Candiduria is associated with reduced survival rates among persons who have undergone renal transplantation; this is likely a marker for severity of illness. Treatment of asymptomatic candiduria in renal transplant recipients does not appear to result in improved outcome.

Adolescent↗

PubMed2004

Blood pressure control in kidney transplantation: therapeutic implications.

Post-transplant hypertension remains a significant risk factor for graft loss, but whether or not specific blood pressure (BP) medications affect graft outcome is still unknown. We assessed the interaction between BP control and antihypertensive drugs on graft outcome. We retrospectively examined clinic BP data for 1662 renal transplant (RTx) patients, transplanted between 1994 and 2000 at our centre. The analysis examined all patients who received central alpha-agonists and peripheral alpha-antagonists, beta-blockers, calcium channel blockers (CCBs), angiotensin-converting enzyme (ACE) inhibition (ACEI), angiotensin receptor blockers (ARBs). BP recordings during treatment were categorized for each agent. Thus, a particular BP could be categorized for multiple medications. A total of 1462 patients (pts) (88%) were Caucasian and 800 pts (46%) received cadaveric RTx. There were 10.6+/-6.8 BP measurements for each patient post-RTx. CCBs, alone among the classes of antihypertensive drugs evaluated, reduced the risk for graft loss (RR: 0.736; P=0.035) in the overall analysis. Interestingly, stratifying levels of BP control unmasked a beneficial effect on graft survival of ACEI/ARB therapy in individuals with higher levels of systolic (>152 mmHg) and diastolic blood pressure (>98 mmHg) treated with ACEI/ARBs compared to individuals treated with CCBs (P<0.01 for each). Thus, stabilizing BP is important post-RTx. CCBs are associated with improved rates of graft survival. Their role in a compromised RTx, however, deserves further study. ACEI/ARBs have clear benefits, improving graft survival in individuals with elevated systolic blood pressure and proteinuria. CCBs are not as efficacious in this setting.

Adult↗

PubMed2003

Sirolimus monotherapy following Campath-1H induction.

Sirolimus was used as a single agent for maintenance immunosuppression in a pilot trial of 29 primary kidney transplant patients using lymphocyte depletion with Campath-1H as an induction strategy. This allowed sirolimus to be analyzed (dose, blood level, and side effect profile) in the absence of steroid and calcineurin inhibitors. A sirolimus dose of 4 mg/day resulted in blood levels in the 8 to 9 ng/mL range. Of the 29 patients, 8 patients (28%) had rejection. The sirolimus levels were not significantly different in patients with or without rejection. The cardiovascular risk profile in terms of lipid profile and hypertension control was favorable. Increase in cholesterol and triglyceride levels at one month (not statistically significant) necessitated treatment in 60% of patients with decline in levels by 6 and 12 months. Management of hypertension was also favorable with the majority of patients (55%) being on one hypertensive medication. Sirolimus monotherapy was well tolerated on the whole. Wound healing, leukopenia, and anemia were not significant problems. In conclusion, monotherapy has been well tolerated with a favorable side effect profile. However, a rejection rate of 28% was noted.

Follow-Up Studies↗

PubMed2002

Simultaneous pancreas-kidney and pancreas transplantation.

The best available method currently for achieving steady normoglycemia in individuals with type 1 diabetes mellitus (DM) is replacing the pancreas, e.g. whole pancreas transplantation. Pancreatic transplantation, as either simultaneous pancreas-kidney (SPK) or solitary pancreas transplantation alone (PTA), has moved beyond simple metabolic or quality-of-life goals. It is now an effective treatment to reverse or minimize metabolic abnormalities and complications of type 1 DM as well as potentially extend the life span of those afflicted by type 1 DM and its many co-morbid complications. Candidates for SPK and PTA transplantation need to meet various criteria even to undergo the transplant procedure and receive a pancreatic allograft that is deemed suitable. SPK and PTA recipients, though free from insulin use, still may encounter common post-transplant medical complications, e.g. cardiovascular disease, high blood pressure, as well as complications unique to SPK and PTA transplantation. The advantages of PTA and SPK transplantation are frankly now more obvious as improvements in surgical technique and new immunosuppression have made an increasing number of PTA and SPK transplants viable and functional long-term. The idea of pancreas transplantation can be touted as a therapeutic advance for type 1 DM. It can improve survival and limit many diabetic-related complications, while improving quality of life, especially in those individuals also afflicted with diabetic-related kidney disease.

Drainage↗

PubMed2001

Utility of urinary cytology for diagnosing human polyoma virus infection in transplant recipients: a study of 37 cases with electron microscopic analysis.

Human polyoma virus (HPOV) infection is associated with hemorrhagic cystitis, tubulointerstitial nephritis, and renal transplant dysfunction/allograft loss. We evaluated the utility of cytologic examination to detect HPOV infection in 37 urinary cytology (UC) samples (3 bladder washings, and 34 voided samples) from 29 transplant patients, compared to electron microscopic studies (EMS). Evidence of viral infection was found in 11 specimens (30%). Five cases were diagnosed as HPOV by both UC and EMS. One was positive for HPOV by EMS only. Two cases diagnosed as HPOV by UC were demonstrated to be adenovirus (AV) with EMS. Two cases diagnosed as cytomegalovirus (CMV) by EMS had negative UC. One was called HPOV by UC; EMS in this case was negative. Compared to EMS, the sensitivity and specificity of UC for detecting HPOV were 83% and 90%, respectively, with a positive predictive value of 63% and a negative predictive value of 96%. We conclude that UC is a relatively sensitive and specific method for detecting active HPOV infection in transplant patients, and is important in light of the clinical significance of HPOV infection in transplant recipients. The sensitivity and accuracy of UC for diagnosing HPOV can be increased by adding EMS.

Adenoviridae↗

PubMed2001

Therapeutic drug monitoring of tacrolimus in pediatric liver transplant patients.

The clinical utility of tacrolimus monitoring in adults has been well documented. The present study compared tacrolimus monitoring in a pediatric population of 34 liver transplant patients in four US centers with an adult population of 111 patients in six US centers. Subjects (adult and pediatric) were evaluated, at defined intervals over 12 weeks post-transplantation (Tx), for tacrolimus trough concentrations and 12 additional laboratory chemistries. Pediatric patient and graft survival for the 12 weeks were 91% and 88%, respectively, as compared to 97% and 93%, respectively, for the adult population. The mean oral dosage of tacrolimus for pediatric patients was 0.13 +/- 0.1 mg/kg/day at week 1, increased to 0.30 +/- 0.3 mg/kg/day by week 3 and remained constant for the remainder of the study. These dosages were two- to three-fold higher than the dosage used in the adult population. In contrast, the mean whole-blood trough concentration, as determined by PRO-Tractrade mark II enzyme-linked immunosorbent assay (ELISA), decreased from 11.3 +/- 5.1 ng/mL at week 1 to 6.3 +/- 3.7 ng/mL by week 12 and was not significantly different from the trough concentration in adults. The incidence and distribution of the clinical end-points for the pediatric subjects (rejection, nephrotoxicity, death, re-Tx) were different from those observed in adults. The total percentage of pediatric subjects reaching any end-point was 74%, as compared to 54% in the adult population. These data indicate several differences between the adult and pediatric populations in their response to tacrolimus.

Child↗

PubMed2001

Life satisfaction in renal transplant recipients: preliminary results from the transplant learning center.

The Transplant Learning Center (TLC) was designed to improve quality of life (QOL) and preserve graft function in solid-organ transplant recipients. To meet the specific goals of the program, the Life Satisfaction Index and Transplant Care Index were designed to serve as composite measures for measuring transplant-specific QOL and the ability to care for a transplant, respectively. In this study, we analyzed self-reported health information to examine relationships between comorbidities and individual posttransplantation side effects, life satisfaction, and transplant care, defined by renal transplant recipients. Patients entered the TLC through self-referral or referral by a health professional. Included in the analysis were 3,676 TLC enrollees with a mean time since transplantation of 4.8 years. Comorbidities and adverse effects were common, with high blood pressure reported by 89% of respondents and unusual hair growth reported by 70%. Sexual dysfunction and headache had a greater impact on QOL than more common adverse effects, such as changes in body and facial shape, hirsutism, and tremor. Regression modeling was used to identify the most significant associations between QOL indices and structural (nonmedical), medical, and psychosocial factors. Greater life satisfaction was most strongly associated with being in control of one's health and living a normally active life with satisfying emotional relationships. Management of such clinical problems as adverse effects of medication and nonadherence should be informed by the patient's perspective. Clinicians should actively solicit information about physical activity, appearance concerns, side effects of medications, nonadherence, and sexual and relationship issues when evaluating renal transplant recipients.

Adult↗

PubMed2001

Phase I chemoprevention study of difluoromethylornithine in subjects with organ transplants.

Individuals who receive life-saving organ transplants and the required immunosuppression often develop secondary cancers. One of the most common secondary cancers is nonmelanoma skin cancer in sun-exposed areas. Attempts to prevent these cancers have not been successful. Difluoromethylornithine (DFMO), a suicide inhibitor of ornithine decarboxylase (ODC), is a known experimental cancer prevention agent that is being evaluated in a number of human cancer prevention trials. This report describes a Phase I trial in 18 organ transplant recipients, randomized to 1.0 and 0.5 g of DFMO or a placebo, designed to look at short-term toxicities over 28 days as well as the impact of DFMO on two biological parameters, skin polyamines and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ODC activity. Blood levels of DFMO were also measured. The results indicate that DFMO was well tolerated over the 28-day period. The TPA-induced ODC activity in 3-mm skin biopsies was significantly lowered by 80 and 67% at the two dose levels. Polyamine levels were not affected significantly except for putrescine at the 0.5-g level. Blood levels of DFMO were about two times higher than expected, based on our prior pharmacokinetic studies. Our studies indicate that DFMO is a reasonable agent that should be tested further in larger Phase 2b trials in this population as a chemopreventive agent. TPA-induced ODC activity appears to be a relevant intermediate biological assay.

Adult↗

PubMed2001

Living-unrelated renal transplantation at the University of Wisconsin.

Since 1984, we have performed 243 living-unrelated renal transplants at the University of Wisconsin. Rejection occurred in 47% of the patients. Graft loss occurred in 59 patients and 39 patients died. Graft survival in LURD transplants at 10 years is 54% and 43% at 15 years. Patient survival is 68% at 10 years and 54% at 15 years. These long-term results demonstrate that LURD is equivalent to haploidentical renal transplantation and superior to cadaveric transplantation. Husband-to-wife donation demonstrated improved graft survival when compared with wife-to-husband and nonspousal donation. Living-unrelated renal transplantation has been utilized successfully at the University of Wisconsin and may help to alleviate the donor shortage.

Academic Medical Centers↗

PubMed2000

Long-term results of liver transplantation in older patients 60 years of age and older.

BACKGROUND: Advances in perioperative care and immunosuppression have enabled clinicians to broaden the indications for organ transplantation. Advanced age is no longer considered a contraindication to transplantation at most centers. Although short-term studies of elderly liver transplant recipients have demonstrated that the incidence of complications and overall patient survival are similar to those of younger adults, transplant center-specific, long-term data are not available. METHODS: From August of 1984 to September of 1997, 91 patients 60 years of age or older received primary liver transplants at the University of Wisconsin, Madison. This group of patients was compared with a group of younger adults (n=387) ranging in age from 18 to 59 years who received primary liver transplants during the same period. The most common indications for transplantation in both groups were Laennec's cirrhosis, hepatitis C, primary biliary cirrhosis, primary sclerosing cholangitis, and cryptogenic cirrhosis. There was no difference in the preoperative severity of illness between the groups. Results. The length of hospitalization was the same for both groups, and there were no significant differences in the incidence of rejection, infection (surgical or opportunistic), repeat operation, readmission, or repeat transplantation between the groups. The only significant difference identified between the groups was long-term survival. Five-year patient survival was 52% in the older group and 75% in the younger group (P<0.05). Ten-year patient survival was 35% in the older group and 60% in the younger group (P<0.05). The most common cause of late mortality in elderly liver recipients was malignancy (35.0%), whereas most of the young adult deaths were the result of infectious complications (24.2%). CONCLUSION: Although older recipients at this center did as well as younger recipients in the early years after liver transplantation, long-term survival results were not as encouraging.

Aged↗

PubMed2000

Renin-angiotensin system gene expression in post-transplant hypertension predicts allograft function.

BACKGROUND: Registry analyses and single-center studies have demonstrated that hypertension significantly increases the risk for chronic graft loss. The graft itself may contribute to posttransplant hypertension, and intragraft vasoactive hormones therefore, may be dysregulated in posttransplant hypertension. METHODS: We used the reverse-transcription polymerase chain reaction to assess the intragraft regulation of renin-angiotensin system transcripts in biopsy samples from 42 stable renal transplant patients with posttransplant hypertension. We also examined mRNA expression of inducible nitric oxide synthase, transforming growth factor-beta (TGF-beta), select cytokines, and metalloproteinase transcripts in biopsy tissue. Polymerase chain reaction products were quantitated using high performance liquid chromatography and normalized to beta-actin mRNA expression. Serum creatinine, glomerular filtration rate or creatinine clearance and tubular atrophy on biopsy were concurrently assessed. RESULTS: Renin and select Thl cytokine mRNA expression correlated with blood pressure. Type 1 angiotensin II receptor mRNA expression significantly correlated with glomerular filtration rate or creatinine clearance (P = 0.034) and inversely correlated with Th1 cytokines, inducible nitric oxide synthase, and cyclooxygenase-1 mRNA expression (P< or =0.013 for each). Type 1 angiotensin II receptor mRNA also approached a significant inverse correlation with TGF-beta mRNA expression (P = 0.09). Conversely, angiotensin-converting enzyme mRNA expression directly correlated with Thl cytokine (P< or =0.008 for each) and TGF-beta mRNA expression (P = 0.006). Type 1 angiotensin II receptor mRNA expression also correlated with matrix metalloproteinase-1 promoter region, tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) and tissue inhibitor of matrix metalloproteinase-3 mRNA expression. Notably, matrix metalloproteinase-1 promoter region, tissue inhibitor of matrix metalloproteinase-2, and tissue inhibitor of matrix metalloproteinase-3 inversely correlated with TGF-beta mRNA expression (P< or =0.0027 for each). Type 1 angiotensin II receptor mRNA expression at biopsy directly correlated with glomerular filtration rate at 2 year's follow-up. However, angiotensin-converting enzyme mRNA expression at biopsy inversely correlated with glomerular filtration rate at 2 year's follow-up. CONCLUSIONS: These data suggest that allograft-level RAS gene expression may be predictive of future graft function in the setting of diastolic hypertension.

Adult↗

PubMed2000

Safety and efficacy of tacrolimus in combination with mycophenolate mofetil (MMF) in cadaveric renal transplant recipients. FK506/MMF Dose-Ranging Kidney Transplant Study Group.

BACKGROUND: Tacrolimus (FK506) is a safe and effective treatment for the prevention of rejection of renal allografts. Mycophenolate mofetil (MMF) has been used as adjunct immunosuppressive therapy with cyclosporine and corticosteroids for the same purpose. The objective of this study was to investigate the safety and efficacy of FK506 and MMF in renal transplant recipients. METHODS: After cadaveric renal transplant, patients were randomized to receive tacrolimus in combination with either azathioprine (AZA, n=59), MMF 1 g/day (n=59), or MMF 2 g/day group (n=58). Patients were followed for 1 yr posttransplant for the incidence of biopsy-confirmed acute rejection, patient and graft survival, and adverse events. RESULTS: Tacrolimus doses and trough concentrations were similar between treatment groups at all time points; 80% of patients were maintained within a range of 5.0-13.9 ng/ml at 12 months posttransplant. The mean dose of MMF decreased in the 2 g/day group to 1.5 g/day by 6 months posttransplant, primarily due to gastrointestinal GI-related disorders. The incidence of biopsy-confirmed acute rejection at 1 year was 32.2%, 32.2%, and 8.6% in the AZA, MMF 1 g/day, and MMF 2 g/day groups, respectively (P<0.01). The use of antilymphocyte antibodies for the treatment of rejection was comparable across treatment groups. The incidence of most adverse events was similar across treatment groups and comparable with previous reports. The overall incidence of posttransplant diabetes mellitus was 11.9%, with the lowest rate observed in the MMF 2 g/day group (4.7%), and was reversible in 40% of patients. The incidence of malignancies and opportunistic infections was low and not different across treatment groups. CONCLUSION: Tacrolimus in combination with an initial dose of MMF 2 g/day is a very effective and safe regimen in cadaveric kidney transplant recipients.

Acute Disease↗

PubMed2000

Using renal transplantation to evaluate a simple approach for predicting the impact of end-stage renal disease therapies on patient survival: observed/expected life span.

The effectiveness of therapy for a chronic disease can be assessed by evaluating the length of time that a patient survives after receiving treatment. We used a novel means for measuring the effectiveness of renal replacement therapy for patients with end-stage renal disease (ESRD): the ratio of observed life span divided by expected life span. This ratio incorporated observed life span for patients from the time of ESRD and expected life span based on state-specific life-table analyses. A total of 3,782 individuals with ESRD were analyzed (average follow-up, 14.2 +/- 4.9 years); 3, 192 patients in that group received a kidney transplant at some point during their course of ESRD. For each patient, we determined a curve of observed/expected life span. Separate patient groups were analyzed to determine the median population observed/expected life span or the percentage of patients who reached 0.5 observed/expected life span. Younger transplant recipients (<21 years) had a median observed/expected life span of 67%, significantly greater than the median observed/expected life span for those aged 21 to 40 years (49%; P = 0.01) and 41 to 60 years (47%; P = 0.01). Surprisingly, 57% of the patients aged older than 60 years reached their median observed/expected life span (P = 0.02 versus <21 years; P = not significant against all others). A Cox proportional hazards model identified era of immunosuppression (hazards ratio, 0.32) and atherosclerotic vascular disease-related ESRD (hazards ratio, 2.07) as significant variables influencing patient survival and observed/expected life span. This simple ratio is easy to use and may be a helpful tool for assessing the survival benefits of risk-factor modifications and therapeutic advances in transplantation and ESRD care.

Adult↗

PubMed2000

Simultaneous pancreas-kidney transplantation reduces excess mortality in type 1 diabetic patients with end-stage renal disease.

BACKGROUND: Diabetic renal disease continues to be the most significant cause of end-stage renal disease (ESRD) in the United States. Renal transplantation improves diabetic ESRD patient survival; however, the diabetic state remains associated with poor patient survival. Simultaneous pancreas-kidney (SPK) transplantation can restore normoglycemia and thus may improve outcomes. METHODS: We assessed the impact of SPK on age-range-matched type 1 diabetic patients who underwent renal transplantation at a single center. The observed/expected life span and annual mortality rates (AMRs) were used as measures of survival. A Cox proportional hazards analysis was used to analyze the impact of potential variables on mortality in SPK recipients. RESULTS: SPK transplantation (N = 335) increased the observed/expected life span compared with diabetic cadaveric (DM-Cad, N = 147) and live-donor (DM-Live, N = 160) transplant recipients (P = 0.004) and significantly reduced the AMRs (SPK, 1. 5%; DM-Cad, 6.27%; DM-Live, 3.65%, P = 0.008, SPK vs. other DM). Moreover, the SPK observed/expected life span and AMR were not significantly different from that of age-range-matched nondiabetic transplant recipients (N = 492). The only variable that was significantly associated with patient survival was discharge serum creatinine (relative risk 1.16, P < or = 0.0154). CONCLUSION: These data demonstrate that SPK improves the ability for type 1 diabetic patients to live more of their expected life span. This suggests that glycemic control, even as a late intervention in a diabetic patient's lifetime, may beneficially affect survival.

Adult↗

PubMed2000

Liver transplantation from controlled non-heart-beating donors.

BACKGROUND: The use of organs from non-heart-beating donors (NHBDs) has been proposed as one way to increase the donor pool. However, few centers have transplanted livers from NHBDs. We report here the results of 19 liver transplants from controlled NHBDs. METHODS: From January 1993 through August 1999, 364 liver transplantations were performed from heart-beating donors (HBDs) and 19 liver transplantations were performed from NHBDs. Donor and recipient characteristics, posttransplant complications, and patient and allograft survival were compared. RESULTS: No differences in hepatic artery, portal vein, or biliary complications were noted between the groups. However, the rate of primary nonfunction was higher in recipients of livers from NHBDs (10.5% vs. 1.3%; P = .04). No difference in patient survival was seen between recipients of NHBDs or HBDs (72.6% vs. 84.8%; P =.36); however, allograft survival was lower in recipients who received livers from NHBDs (53.8% vs. 80.9%; P =.007). CONCLUSIONS: Liver transplantation from controlled NHBDs results in similar patient survival and post-transplant complications. However, primary nonfunction was higher and allograft survival was less in recipients of livers from NHBDs. The results of liver transplantation from controlled NHBDs are encouraging and should continue to be cautiously pursued as one way to help alleviate the current shortage of donor livers.

Adult↗

PubMed2000

Simultaneous pancreas-kidney transplantation and living related donor renal transplantation in patients with diabetes: is there a difference in survival?

OBJECTIVE: To compare the outcome of simultaneous pancreas-kidney transplantation (SPK) and living related donor renal transplantation (LRD) in patients with diabetes. SUMMARY BACKGROUND DATA: It remains unanswered whether diabetic patients with end-stage renal failure are better served by LRD or SPK. METHODS: Using a longitudinal database, data from all diabetic patients receiving LRD or cadaveric renal transplants or SPKs from January 1986 through January 1996 were analyzed. Patient and graft survival, early graft function, and the cause of patient and graft loss were compared for 43 HLA-identical LRDs, 87 haplotype-identical LRDs, 379 SPKs, and 296 cadaveric renal transplants. RESULTS: The demographic composition of the SPK and LRD groups were similar, but because of less strict selection criteria in the cadaveric transplant group, patients were 10 years older, more patients received dialysis, and patients had been receiving dialysis longer before transplantation. Patient survival was similar for the SPK and LRD groups but was significantly lower for the cadaveric renal transplant group. Similarly, there was no difference in graft survival between SPK and LRD recipients, but it was significantly lower for recipients in the cadaveric renal transplant group. Delayed graft function was significantly more common in the cadaveric renal transplant group. Discharge creatinine, the strongest predictor of patient and graft survival, was highest in the SPK group and lowest in the HLA-identical LRD group. The rate of rejection within the first year was greatest in SPK patients (77%), intermediate in the haplotype-identical LRD and cadaveric transplant groups (57% and 48%, respectively), and lowest (16%) in the HLA-identical LRD group. Cardiovascular disease was the primary cause of death for all groups. Acute rejection, chronic rejection, and death with a functioning graft were the predominant causes of graft loss. CONCLUSIONS: This study demonstrates that there was no difference in patient or graft survival in diabetic patients receiving LRD or SPK transplants. However, graft and patient survival rates in diabetic recipients of cadaveric renal transplants were significantly lower than in the other groups.

Adult↗

PubMed1999

Clinically stable human renal allografts contain histological and RNA-based findings that correlate with deteriorating graft function.

BACKGROUND: Chronic rejection (CR) remains idiopathic, difficult to prospectively identify, and once detected, unresponsive to increased immunosuppression. We hypothesized that clinically stable human renal allografts have ongoing evidence of injury and immune activity, and that this correlates with the worsening of allograft function characteristic of CR. METHODS: The allografts of 40 stable renal allograft recipients were biopsied 2-3 years after transplantation. Biopsies were processed for histology and RNA extraction. RNA was evaluated by semi-quantitative RT-polymerase chain reaction for CD3y mRNA (a marker of T cell receptor turnover), and mRNA from cytokine genes previously shown to be transcribed during acute rejection: tumor necrosis factor-alpha, interferon-gamma, interleukin- (IL) 1beta, IL-2, IL-4, IL-6, and IL-8. Clinical parameters including urine protein and glomerular filtration rate were measured the day of biopsy. Findings were then compared with clinical outcome to establish associations between subclinical inflammation and graft dysfunction. Allograft function was measured again 2 years after biopsy and correlated with findings at the time of biopsy. RESULTS: Cytokine transcripts and histological evidence of injury were detected in more than two-thirds of stable grafts. The degree of the lymphocytic infiltrate correlated with the degree of proteinuria (P=0.034) and histological fibrosis (P=0.005). Similarly, the degree of intragraft CD3y transcription correlated with increasing proteinuria (P=0.043). IL-6 and IL-8 transcripts were also correlated with evidence of graft injury. After 2 years, those biopsies originally found to have evidence of fibrosis, tubular atrophy, or CD3gamma transcription had worsening graft function as determined by creatinine and glomerular filtration rate. CONCLUSIONS: These data demonstrate that significant injury and immune activity can be detected in patients who are stable on clinical grounds. Undetected subclinical graft injury may be a cause of chronic allograft rejection.

Biomarkers↗

PubMed1999

Cytomegalovirus infection and posttransplant lymphoproliferative disease in renal transplant recipients: results of the U.S. multicenter FK506 Kidney Transplant Study Group.

BACKGROUND: The recent U.S. multicenter randomized trial of FK506 versus cyclosporine (CsA) demonstrated equivalent patient and graft survival in patients treated with FK506 and statistically fewer rejection episodes in the first year posttransplant. METHODS: To determine if more effective posttransplant immunosuppression was associated with an increased risk of cytomegalovirus (CMV) or posttransplant lymphoproliferative disease (PTLD), we examined the incidence of these two opportunistic infections during 3 years of follow-up. RESULTS: CMV infection occurred in 40 (19.5%) FK506 and 40 (19.3%) CsA-treated patients. The incidence of CMV disease was 9.3% in FK506 and 6.8% in CsA-treated recipients; the most common site of CMV disease was the gastrointestinal tract. A multivariate analysis of several risk factors demonstrated that a CMV- recipient of a CMV+ donor was at greatest risk for CMV infection. The incidence of posttransplant lymphoproliferative disease was equal in the two treatment arms: six CsA- and five FK506-treated recipients. CONCLUSIONS: The results of this study suggest that the superior efficacy of FK506 in the prevention of acute rejection was not associated with an increased risk of CMV or posttransplant lymphoproliferative disease compared with CsA.

Cyclosporine↗