Outcomes In Renal Transplant Recipients Research Articles

Hepatitis G virus infection in renal transplant recipients.

To determine the prevalence and clinical significance of hepatitis G virus (HGV)/GB virus C (GBV-C) infection in renal transplant recipients, prospectively collected serum samples from a cohort of cadaveric renal transplant patients were studied for the presence of HGV RNA using a sensitive reverse transcription 'nested'-polymerase chain reaction (RT-PCR) based on primers derived from the 5' untranslated region. All positive PCR amplicons were sequenced bidirectionally and aligned. The nucleotide substitution rate was estimated by the 6-parameter method, and a phylogenetic tree was constructed using the Neighbour-joining method. HGV RNA was detected in 11/93 (12%) patients pretransplant and in 15/90 (17%) patients 1-4 years post-transplant. All PCR amplicons were confirmed to be specific for HGV by sequencing. Phylogenetic tree construction revealed that 17 PCR amplicons had sequences related to HGV and one had a sequence related to GBV-C. Two HGV RNA-positive patients pretransplant became HGV RNA negative post-transplant, and seven HGV RNA-negative patients pretransplant became HGV RNA positive post-transplant. There was no relationship between hepatitis C virus (HCV) and HGV infection. There were also no differences in age, gender distribution, ethnic origin, the total number of blood units transfused and either graft or patient survival between patients who were positive or negative for HGV RNA. We conclude that HGV infection is common among renal transplant candidates and recipients. Most of the isolates had sequences related to the HGV prototype. HGV infection does not appear to adversely affect clinical outcome in renal transplant recipients during early follow-up.

Serum total homocysteine concentration does not predict outcome in renal transplant recipients

Established cardiovascular risk factors such as hypercholesterolemia have been claimed to adversely influence the outcome of renal transplants. The aim of the present study was to assess the effect of another risk factor, hyperhomocysteinemia, on graft outcome. This was relevant for two reasons; hyperhomocysteinemia is by now recognized as an independent risk factor for the development of atherosclerosis and it is highly prevalent in both dialysis patients and renal transplant recipients. The serum concentration of total homocysteine (tHcy) was analyzed in samples collected before transplantation in 81 patients and at 6 months after transplantation in 57 of these patients. Before transplantation, mean tHey was 33.2±19.2 μmol/L and the prevalence of hyperhomocysteinemia was 94%. Six months after transplantation. mean they was 27.7±14.6 μmol/L and the prevalence of hyperhomocysteinemia was 88%. The patients were followed up for 5 yr. Six months and 5 yr after transplantation, serum creatinine concentration and endogenous creatinine clearance were determined. After 6 months, allograft biopsy was evaluated. Neither prenor post‐transplant tHey was found to influence patient or graft survival, graft function or histopathology. Thus, tHey does not seem to predict either short‐term or long‐term outcome of renal transplantation.

THE COURSE AND MANAGEMENT OF HEPATITIS B AND C IN TWENTY-YEAR RENAL ALLOGRAFT RECIPIENTS (LEVEL 5A)

656 BACKGROUND: Infection with hepatotropic viruses [hepatitis B virus (HBV) and hepatitis C virus (HCV)] is common in patients who had received hemodialysis and are undergoing renal transplantation. The long-term impact of this infection on patients' outcome is not known. AIM: To determine the long-term outcome of renal transplant recipients infected with HBV and HCV. METHOD: Clinical data were obtained from chart reviews of renal allograft recipients between 1963 and 1978. Laboratory data including liver profile, hepatitis serology [hepatitis B surface antigen, hepatitis C antibody (ELISA II)], hepatic ultrasound (US), and α fetoprotein (AFP) were gathered. Patients with serology positive for hepatitis B or C had further testing with hepatitis B DNA (by hybridization method) and hepatitis C RNA [by PCR method(amplicore)] performed. Clinical evidence of cirrhosis (splenomegaly, ascites, jaundice, or thrombocytopenia) and mortality data were obtained. RESULTS: 79 of 511 renal transplants performed at the Cleveland Clinic from January 1963 to January 1978 are known to have functioned over 20 years (Level 5A). Of these, 49 patients had hepatitis testing updated after 19 years of transplantation. Fifteen patients had evidence of ongoing viral infection. Persistent hepatitis B surface antigen was present in 3 (6%), hepatitis C antibody in 11 (22%), and both viruses in 1 (2%). Four patients have died of non-hepatic causes (meningitis: 1, sepsis: 1, coronary artery disease: 2). Of the surviving 11 patients, 8 were tested further for viral replication. Hepatitis C RNA was positive in 6/7 (86%) and HBV DNA was positive in one of two (50%). Elevated ALT (over 35 u/L)was present in 7/8. Cryoglobulins >50μg/ml were present in 3/6 (50%) and α fetoprotein >10.0 ng/ml in 2/8 (25%), all in patients with HCV. One patient who was co-infected with HBV and HCV had clinical evidence of cirrhosis. Hepatic US was negative in all 8 patients tested. There was no liver-related mortality in this cohort. One additional patient 3 years post transplant with evidence of HBV replication has been treated with lamivudine (100 mg/day) and cleared HBV DNA and HBeAg after 6 months of therapy. CONCLUSION: Renal allograft recipients infected with hepatotropic viruses (HBV and HCV) have a high rate of active viral replication. Although cirrhosis and possibly hepatocellular carcinoma can develop in these individuals, liver-related deaths are rare, and long-term outcome (>20 years) is good. In patients with active HBV replication, treatment with lamivudine seems promising. Although the role of screening for hepatocellular carcinoma remains controversial, given the paucity of data, a screening program with AFP ± US is recommended.

Lipoprotein pattern in end‐stage renal disease and following successful renal transplantation

Lipoprotein abnormalities are common in uremia and frequently persist after successful renal transplantation (RT). Based on the influence of immunosuppression on lipoprotein metabolism, this prospective study in 76 patients has been focused on lipoprotein pattern in end‐stage renal disease and after successful RT during a follow‐up period of 18 months. Additionally, the influence of different immunosuppressive regimes has been evaluated. Hyperlipidemia was present in 32% of the patients before and in 59% after grafting. Total cholesterol was 5.42±1.57 mmol/l (mean (SD) before RT and continuously and significantly increased during the entire observation period, being highest 18 months after RT (6.8±1.63 mmol/l; p<0.01). This was mainly due to an increase in LDL‐cholesterol (before RT: 3.68 (1.41 mmol/1; 18 months after RT: 4.69±1.88 mmol/l; p< 0.05) while HDL‐cholesterol values only slightly increased (before RT: 0.99±0.36 mmol/1; 18 months after RT: 1.13±0.3 mmol /1; p<0.05). Changes in total HDL‐cholesterol were mainly due to an increase in HDL 3, while HDL 2 moderately increasing remained at low concentrations. As corticosteroid dosage was substantially reduced during the entire observation period, other factors such as cyclosporin A have to be considered for hyperlipidemia in renal transplant recipients. The observation on LDL‐cholesterol being highest 18 months after transplantation suggests lipid lowering interventions to be indicated and might improve long‐term outcome in renal transplant recipients.

Angiotensin-converting enzyme genotype and renal allograft survival.

Increased activity of the renin-angiotensin system has been implicated in decreased, long-term survival of renal allografts. Recent studies suggest that a deletion variant of the angiotensin-converting enzyme, associated with increased humoral and tissue activity of this enzyme, is a risk factor for the development of diabetic nephropathy and the progression of IgA nephropathy. To determine whether the deletion variant of the angiotensin-converting enzyme gene influences the long-term outcome in renal transplant recipients, the relationship between donor and recipient angiotensin-converting enzyme genotype and clinical outcome were examined over a follow-up period up to 30 mo in a cohort of 269 Caucasian patients undergoing kidney transplantation between 1988 and 1993. In a subsequent case control study, the frequencies of the angiotensin-converting enzyme genotype were compared in a group of Caucasian patients with a graft survival of less than 3 yr (mean survival, 11 mo; n = 328) with the frequencies in patients with a graft survival of at least 3 yr (mean survival, 65 mo, n = 461). Neither in the cohort nor in the case control study was there a significant effect of recipient or donor angiotensin-converting enzyme genotype on transplant survival. Furthermore, the frequency of the angiotensin-converting enzyme deletion allele both in recipients and donors was similar to that reported in Caucasian controls. This study, therefore, does not support the hypothesis that the recipient or donor angiotensin-converting enzyme insertion/deletion polymorphism is an important determinant of transplant survival in Caucasian patients undergoing renal transplantation.

Persistent parvovirus B19 infections with different clinical outcomes in renal transplant recipients: diagnostic relevance of polymerase chain reaction (PCR) and of quantification of B19 DNA in sera

OBJECTIVE: To study parvovirus B19 infection in immunocompromised subjects such as renal transplantation recipients. METHODS: Two cases of B19 infection in renal transplant recipients have been included in the study. The outcome of the infection has been studied by both serologic and virologic methods. A monitoring of the DNAemia was done by a nested PCR in endpoint titration assays. RESULTS: In one patient with severe anemia an acute B19 infection was diagnosed by PCR 26 days after the transplant; a high level of DNAemia persisted until an intravenous immunoglobulin treatment. Then a sharp decrease of the DNAemia was shown, without full clearance of B19 virus. In a lymphocyte suspension from the organ donor, B19 DNA was detected. In the other patient, who recovered spontaneously from anemia, a persistent B19 infection was demonstrated at day 106 after transplantation and was still demonstrable after 470 days. CONCLUSIONS: A high level of B19 DNAemia was associated with symptomatic infection, with severe anemia, whereas low-level DNAemia was long-lasting in asymptomatic subjects with impaired immunologic responses. The endpoint titration assay by nested PCR was very useful for the monitoring of B19 infection, particularly following the therapeutic intravenous immunoglobulin administration.

Relationship between Pretransplant Noncompliance and Posttransplant Outcomes in Renal Transplant Recipients

Approximately 5% to 18% of kidney transplant recipients do not comply with their posttransplant medical treatment. This study examined the relationship between pretransplant noncompliance and posttransplant outcomes. Using a longitudinal retrospective chart audit, pretransplant and posttransplant data were collected for 126 kidney transplant recipients over a 3-year period. Sixty-one percent of those identified as noncompliant before transplant lost their graft or died after transplant. Significant relationships between pretransplant noncompliance and graft loss and between pre- and posttransplant noncompliance were found. Clinicians must identify those with pretransplant noncompliance, as they are at risk for poor outcomes and might benefit from an intensive posttransplant follow-up regimen.

Relationship between pretransplant noncompliance and posttransplant outcomes in renal transplant recipients.

Approximately 5% to 18% of kidney transplant recipients do not comply with their posttransplant medical treatment. This study examined the relationship between pretransplant noncompliance and posttransplant outcomes. Using a longitudinal retrospective chart audit, pretransplant and posttransplant data were collected for 126 kidney transplant recipients over a 3-year period. Sixty-one percent of those identified as noncompliant before transplant lost their graft or died after transplant. Significant relationships between pretransplant noncompliance and graft loss and between pre- and posttransplant noncompliance were found. Clinicians must identify those with pretransplant noncompliance, as they are at risk for poor outcomes and might benefit from an intensive posttransplant follow-up regimen.

Outcome of Renal Transplant Recipients in the ICU

To determine the outcome of renal transplant recipients in an intensive care unit (ICU). Prospective, cohort study. Surgical ICU in a tertiary care hospital. Consecutive adult renal transplant recipients admitted to an ICU. Demographic data, underlying diseases, indications for admission to the ICU, number of prior kidney transplantations, duration of immunosuppression, duration of mechanical ventilation, length of stay in ICU and hospital, and ICU and hospital mortality were recorded. Seventy-one patients were included in the study. Twenty-seven patients were admitted to the surgical ICU immediately after renal transplantation surgery for postoperative monitoring (group 1). One patient died in this group. The remaining 44 patients were renal transplant recipients admitted to the surgical ICU with various complications (group 2). The mean posttransplant time in group 2 was 23 +/- 30 months. Seven patients died in group 2. The overall ICU mortality in this study was 11% and hospital mortality was 14%. The hospital mortality for postoperative patients (3.7% in group 1) was below the rate predicted based on the acute physiology and chronic health evaluation (APACHE II) score (15%). APACHE II score, duration of mechanical ventilation, and ICU length of stay were significantly higher among nonsurvivors. The ICU mortality among renal transplant recipients was higher than that of other patients (6%) admitted to the surgical ICU during the study period. The ICU mortality of renal transplant recipients was twice that of general surgical ICU patients. The hospital mortality rate for recipients admitted immediately postoperatively to the ICU (group 1) was less than predicted by APACHE II.

Prognostic value of serum erythropoietin levels in late acute rejection of renal transplants

Since renal allograft rejection is frequently associated with a blunted erythropoiesis, we investigated erythropoietin (EPO) serum concentrations in 17 patients with acute rejection, eight patients with chronic rejection, and 18 transplant recipients with stable graft function. All rejection episodes were proven by biopsy. Erythropoietin serum levels were significantly reduced in patients with chronic rejection (6.2 ± 3.4 mU/mL; P < 0.01) compared with individuals with acute rejection (35.6 ± 33.9 mU/mL) or stable graft function (24.0 ± 19.7 mU/mL). Suppressed EPO levels were associated with marked anemia in chronic rejection patients. In a subgroup of patients with acute rejection and bad responses to an intensified immunosuppressive regimen or with transplant failure, we found significantly suppressed EPO levels (11.6 ± 6.1 mU/mL) compared with a subgroup of patients with a beneficial acute rejection outcome (57.0 ± 34.2 mU/mL; P < 0.01). A correlation between histologic parameters of acute rejection and hormone levels showed that signs of moderate glomerulitis were associated with elevated EPO levels, whereas lesions of moderate tubulitis were associated with low values. We conclude that serum EPO may have prognostic value for rejection outcome in renal transplant recipients.

INCIDENCE, DETERMINANTS, AND CONSEQUENCES OF SUBCLINICAL NONCOMPLIANCE WITH IMMUNOSUPPRESSIVE THERAPY IN RENAL TRANSPLANT RECIPIENTS

In this descriptive cross-sectional study, we investigated the incidence, determinants, and consequences of subclinical noncompliance with immunosuppressive therapy in 150 adult renal transplant recipients with more than one year posttransplant status. Symptom frequency and symptom distress, and self-care agency were measured by the Transplant Symptom Frequency and Symptom Distress Scale, and the Appraisal for Self-Care Agency Scale, respectively. The Long-Term Medication Behavior Self-Efficacy Scale and a renal transplant knowledge questionnaire were developed as part of this study to measure perceived self-efficacy and knowledge of the therapeutic regimen. Demographic variables were also measured. The incidence of subclinical noncompliance with immunosuppressive therapy as assessed by interview was 22.3%. Compliers and noncompliers differed significantly on the variables of marital status (P = 0.03), situational-operational knowledge (P = 0.02), self-care agency (P = 0.03), and perceived self-efficacy related to long-term medication intake (P = 0.048). A logistic regression model using gender, marital status, perceived self-efficacy, self-care agency, knowledge about medication administration and signs of infection, and situational operational knowledge as predictor variables, revealed a 78.6% correct classification of compliers versus noncompliers and a sensitivity ratio of 95.9%. There were significantly more acute late rejection episodes (P = 0.003) in the noncompliant group. Graft survival at 5 years in this group was also significantly lower (P = 0.03) than the compliant patients. No significant difference was found in terms of the occurrence of chronic rejection episodes or in terms of patient survival at 5 years. Because noncompliance is a risk factor for negative clinical outcome in renal transplant recipients, it is of utmost importance to develop intervention strategies to enhance compliance in this population by using determinants identified in exploratory studies.