Application of TruGraf v1: A Novel Molecular Biomarker for Managing Kidney Transplant Recipients With Stable Renal Function.

TruGraf v1 is a laboratory-developed DNA microarray-based gene expression blood test to enable proactive noninvasive serial assessment of kidney transplant recipients with stable renal function. It has been previously validated in patients identified as Transplant eXcellence (TX: stable serum creatinine, normal biopsy results, indicative of immune quiescence), and not-TX (renal dysfunction and/or rejection on biopsy results). TruGraf v1 is intended for use in subjects with stable renal function to measure the immune status as an alternative to invasive, expensive, and risky surveillance biopsies. MATERIALS AND METHODS: In this study, simultaneous blood tests and clinical assessments were performed in 192 patients from 7 transplant centers to evaluate TruGraf v1. The molecular testing laboratory was blinded to renal function and biopsy results. RESULTS: Overall, TruGraf v1 accuracy (concordance between TruGraf v1 result and clinical and/or histologic assessment) was 74% (142/192), and a result of TX was accurate in 116 of 125 (93%). The negative predictive value for TruGraf v1 was 90%, with a sensitivity 74% and specificity of 73%. Results did not significantly differ in patients with a biopsy-confirmed diagnosis vs those without a biopsy. CONCLUSIONS: TruGraf v1 can potentially support a clinical decision enabling unnecessary surveillance biopsies with high confidence, making it an invaluable addition to the transplant physician's tool kit for managing patients. TruGraf v1 testing can potentially avoid painful and risky invasive biopsies, reduce health care costs, and enable frequent assessment of patients with stable renal function to confirm the presence of immune quiescence in the peripheral blood.

Investigator Assessment of the Utility of the TruGraf Molecular Diagnostic Test in Clinical Practice.

BACKGROUND: TruGraf v1 is a well-validated DNA microarray-based test that analyzes blood gene expression profiles as an indicator of immune status in kidney transplant recipients with stable renal function. METHODS: In this study, investigators assessed clinical utility of the TruGraf test in patient management. In a retrospective study, simultaneous blood tests and clinical assessments were performed in 192 patients at 7 transplant centers, and in a prospective observational study they were performed in 45 subjects at 5 transplant centers. RESULTS: When queried regarding whether or not the TruGraf test result impacted their decision regarding patient management, in 168 of 192 (87.5%) cases the investigator responded affirmatively. The prospective study indicated that TruGraf results supported physicians' decisions on patient management 87% (39/45) of the time, and in 93% of cases physicians indicated that they would use serial TruGraf testing in future patient management. A total of 21 of 39 (54%) reported results confirmed their decision that no intervention was needed, and 17 of 39 (44%) reported that results specifically informed them that a decision not to perform a surveillance biopsy was correct. CONCLUSIONS: TruGraf is the first and only noninvasive test to be evaluated for clinical utility in determining rejection status of patients with stable renal function and shows promise of providing support for clinical decisions to avoid unnecessary surveillance biopsies with a high degree of confidence. TruGraf is an invaluable addition to the transplant physician's tool kit for managing patient health by avoiding painful and invasive biopsies, reducing health care costs, and enabling frequent assessment of patients with stable renal function to confirm immune quiescence.

Outcomes of vitrectomy for advanced diabetic retinopathy at Groote Schuur Hospital, Cape Town, South Africa.

BACKGROUND: Present limitations in primary and secondary prevention of diabetic retinopathy mean that many patients with diabetes present with advanced retinal complications, often requiring surgery (vitrectomy). OBJECTIVES: To determine the outcomes of vitrectomy for advanced diabetic retinopathy and to examine context-specific risk factors that may influence outcomes and decisions affecting resource allocation. METHODS: This was a retrospective cohort study of 124 vitrectomies with up to 6 months' follow-up. RESULTS: Visual acuity was 6/60 or worse in the better eye in 23.4% of patients at presentation. The mean visual acuity of the listed eye was 2/60. The fellow eye was considered inoperable in 20.2% of cases. Visual function declined significantly in 26.2% of patients while awaiting surgery. The average waiting time until surgery was 2.9 months (range 1 day - 9 months). Epiretinal membranes were present in 93.6% of cases, and posterior iatrogenic breaks occurred in 49.2%. Silicone oil was used in 24.2%. Visual acuity improved in 54.9%, was unchanged in 30.1%, and worsened in 14.0% of cases at 6 months. Patients with poorer vision at surgery were more likely to improve (odds ratio 2.15; p=0.048). Factors associated with a worse visual outcome were increased age at surgery (p=0.042) and posterior iatrogenic retinal breaks (p=0.007). Renal dysfunction was not associated with worse visual outcomes. CONCLUSION: Vitrectomy improved or stabilised vision in 85.0% of cases, although outcomes were unpredictable. A long waiting time to surgery contributed to patient morbidity. The presence of renal dysfunction did not predict poorer visual outcomes.

Oestradiol and SERM treatments influence oestrogen receptor coregulator gene expression in human skeletal muscle cells.

AIM: Oestrogen receptors (ER) are present in human skeletal muscle (hSkM) cells; however, the function of the receptor is currently unknown. We investigated the influence of oestradiol and selective ER modulators [tamoxifen (TAM), raloxifene (RAL)] on ER coregulator mRNA expression in hSkM. METHODS: Human skeletal muscle cells were treated with 10 nm oestradiol, 5 microm TAM and 10 microm RAL over a 24-h period. Following the treatment period, mRNA expression was quantified using real-time PCR to detect changes in ER-alpha, ER-beta, steroid receptor coactivator (SRC), silencing mediator for retinoid and thyroid hormone receptors (SMRT), MyoD, GLUT4 and c-fos. RESULTS: ER-alpha mRNA expression increased with all three drug treatments (P < 0.05) while there was no change in mRNA expression of ER-beta in hSkM cells. mRNA expression of SRC increased and SMRT decreased with oestradiol, TAM and RAL in hSkM cells (P < 0.05). Importantly, mRNA expression of MyoD increased with oestradiol and decreased with TAM and RAL in hSkM cells (P < 0.05). mRNA expression of GLUT4 increased with oestradiol and RAL and decreased with TAM in hSkM cells (P < 0.05). CONCLUSIONS: These findings are novel in that they provide the first evidence that oestradiol and selective ER modulators influence ER-alpha function in hSkM cells. This demonstrates the importance of the ER and alterations in its coregulators, to potentially prevent sarcopenia and promote muscle growth in postmenopausal women using these forms of hormone replacement therapy.

Histone H4 lysine 20 monomethylation promotes transcriptional repression by L3MBTL1.

Lethal 3 malignant brain tumor 1 (L3MBTL1), a homolog of the Drosophila polycomb tumor suppressor l(3)mbt, contains three tandem MBT repeats (3xMBT) that are critical for transcriptional repression. We recently reported that the 3xMBT repeats interact with mono- and dimethylated lysines in the amino termini of histones H4 and H1b to promote methylation-dependent chromatin compaction. Using a series of histone peptides, we now show that the recognition of mono- and dimethylated lysines in histones H3, H4 and H1.4 (but not their trimethylated or unmodified counterparts) by 3xMBT occurs in the context of a basic environment, requiring a conserved aspartic acid (D355) in the second MBT repeat. Despite the broad range of in vitro binding, the chromatin association of L3MBTL1 mirrors the progressive accumulation of H4K20 monomethylation during the cell cycle. Furthermore, transcriptional repression by L3MBTL1 is enhanced by the H4K20 monomethyltransferase PR-SET7 (to which it binds) but not SUV420H1 (an H4K20 trimethylase) or G9a (an H3K9 dimethylase) and knockdown of PR-SET7 decreases H4K20me1 levels and the chromatin association of L3MBTL1. Our studies identify the importance of H4K20 monomethylation and of PR-SET7 for L3MBTL1 function.

Pancreatic panniculitis associated with allograft pancreatitis and rejection in a simultaneous pancreas-kidney transplant recipient.

Pancreatic panniculitis is an uncommon condition that can occur in association with pancreatic disease. We present a case of pancreatic panniculitis in a female pancreas-kidney transplant recipient 5 months post-transplant. The patient was on standard immunosuppressive medications and had acute rejection of her renal allograft. The diagnosis of allograft pancreatitis and rejection presenting with pancreatic panniculitis was supported clinically, histopathologically and by laboratory and imaging data. This is the fourth case of pancreatic panniculitis occurring in a transplant recipient and the first in a simultaneous pancreas-kidney transplant recipient. It is also the first case associated with allograft rejection. Clinicians should be aware that pancreatic panniculitis may be a manifestation of underlying allograft pancreatic disease.

Relative adrenal insufficiency in post-transplant lymphoproliferative disorder.

Post-transplant lymphoproliferative disorder is treated with rapid decrement of immunosuppressive therapy. This cannot be achieved with ease in patients on long-term glucocorticoid therapy, as chronically suppressed adrenal glands may not be capable of mounting adequate response to stress. A 52-year-old Caucasian male presented with fever, orthostatic hypotension, lymphadenopathy and hyponatraemia. Serum cortisol levels were within normal levels with a sub optimal response to stimulation by ACTH. Hyponatraemia and orthostasis responded poorly to fluid restriction, saline and salt repletion but corrected after increasing the steroid dose. The normal baseline cortisol levels represented a stimulated adrenal gland, however, the ACTH stimulation had inadequate response. This sub optimal stimulation and a good response to increased steroids suggest the presence of relative or occult adrenal insufficiency. Relative adrenal insufficiency must be considered in patients who have received prolonged glucocorticoid therapy and have symptoms such as hypotension and/or hyponatraemia.

Efficacy of incisional vs punch biopsy in the histological diagnosis of periocular skin tumours.

AIMS: The aim of this study was to compare the accuracy of incisional and punch biopsy techniques in obtaining correct histological diagnosis of periorbital eyelid tumours. The technique of punch biopsy is presented and described in detail. METHODS: A retrospective analysis was made of 20 consecutive incisional biopsies and 20 consecutive punch biopsies. In each case, the histology obtained at biopsy was compared with that identified at the time of tumour excision. RESULTS: A total of 40 consecutive biopsies on 38 patients were analysed. The first 20 were incisional; the second 20 were punch biopsies. Of the 20 incisional biopsy specimens, 19 were confirmed accurate at the time of excision of the lesion. Of the 20 punch biopsies, 17 were confirmed accurate at the time of excision. These correspond to accuracy rates of 95 and 85%, respectively. CONCLUSIONS: Both incisional and punch biopsy techniques have relatively high accuracy rates and there is a high concordance between tissue diagnoses made by each of these techniques. Incisional techniques should preferably be performed on any atypical lesion. Punch biopsy is a quick and simple procedure. It is easy to perform in an outpatient environment and requires a minimum of surgical equipment and no specific surgical skills. If the site of biopsy is carefully chosen, this simple technique provides tissue specimens of adequate size and quality for accurate histology and is a most useful adjunct in the management of periocular tumours.

Histone methylation versus histone acetylation: new insights into epigenetic regulation.

Post-translational addition of methyl groups to the amino-terminal tails of histone proteins was discovered more than three decades ago. Only now, however, is the biological significance of lysine and arginine methylation of histone tails being elucidated. Recent findings indicate that methylation of certain core histones is catalyzed by a family of conserved proteins known as the histone methyltransferases (HMTs). New evidence suggests that site-specific methylation, catalyzed by HMTs, is associated with various biological processes ranging from transcriptional regulation to epigenetic silencing via heterochromatin assembly. Taken together, these new findings suggest that histone methylation may provide a stable genomic imprint that may serve to regulate gene expression as well as other epigenetic phenomena.

Methylation of the BRCA1 promoter is associated with decreased BRCA1 mRNA levels in clinical breast cancer specimens.

Functional inactivation of BRCA1 is an important mechanism involved in breast cancer pathogenesis. Mutation is often responsible for BRCA1 inactivation in familial breast cancer, but is not responsible for the decreased levels of BRCA1 seen in a subset of sporadic breast cancer patients. To determine if aberrant cytosine methylation of the BRCA1 promoter is associated with decreased BRCA1 gene expression in human breast cancer, high resolution bisulfite sequence analysis was used to analyze the cytosine methylation status of the BRCA1 promoter in 21 axillary node negative breast cancer patients with known levels of BRCA1 expression. Aberrant cytosine methylation of the BRCA1 promoter was detected in three of 21 patient specimens. These three specimens also expressed the lowest levels of BRCA1. Results from this analysis show that aberrant cytosine methylation of the BRCA1 promoter is directly correlated with decreased levels of BRCA1 expression in human breast cancer, and suggest that epigenetic silencing may be one mechanism of transcriptional inactivation of BRCA1 in sporadic mammary carcinogenesis.

Transcriptional repression of BRCA1 by aberrant cytosine methylation, histone hypoacetylation and chromatin condensation of the BRCA1 promoter.

BRCA1 expression is repressed by aberrant cytosine methylation in sporadic breast cancer. We hypothesized that aberrant cytosine methylation of the BRCA1 promoter was associated with the transcriptionally repressive effects of histone hypoacetylation and chromatin condensation. To address this question, we developed an in vitro model of study using normal cells and sporadic breast cancer cells with known levels of BRCA1 transcript to produce a 1.4 kb 5-methylcytosine map of the BRCA1 5' CpG island. While all cell types were densely methylated upstream of -728 relative to BRCA1 transcription start, all normal and BRCA1 expressing cells were non-methylated downstream of -728 suggesting that this region contains the functional BRCA1 5' regulatory region. In contrast, the non-BRCA1 expressing UACC3199 cells were completely methylated at all 75 CpGs. Chromatin immunoprecipitations showed that the UACC3199 cells were hypoacetylated at both histones H3 and H4 in the BRCA1 promoter compared to non-methylated BRCA1 expressing cells. The chromatin of the methylated UACC3199 BRCA1 promoter was inaccessible to DNA-protein interactions. These data indicate that the epigenetic effects of aberrant cytosine methylation, histone hypoacetylation and chromatin condensation act together in a discrete region of the BRCA1 5' CpG island to repress BRCA1 transcription in sporadic breast cancer.

Epigenetic silencing of maspin gene expression in human breast cancers.

Maspin is a tumor suppressor whose expression is lost in many advanced breast cancers. Maspin has been shown to inhibit cell motility, invasion and metastasis; however, its precise role in normal mammary epithelium remains to be elucidated. Although expression of maspin mRNA is low or absent in most human breast cancer cells, the maspin gene is rarely re-arranged or deleted. We hypothesized that aberrant cytosine methylation and chromatin condensation of the maspin promoter participates in the silencing of maspin expression during neoplastic progression. To test this hypothesis, we compared cultured normal human mammary epithelial cells (HMECs) to 9 cultured human breast cancer cell lines. HMECs expressed maspin mRNA and displayed a completely non-methylated maspin gene promoter with an open chromatin structure. In contrast, 7 of 9 breast cancer cell lines had no detectable maspin expression and 6 of these 7 maspin-negative breast cancer cell lines also displayed an aberrant pattern of cytosine methylation of the maspin promoter. Interestingly, the maspin promoter was completely methylated in maspin-negative normal peripheral blood lymphocytes. This indicates that the maspin promoter is not a functional CpG island and that cytosine methylation of this region may contribute to normal tissue-restricted gene expression. Chromatin accessibility studies with MCF-7 cells, which lack maspin expression and have a methylated maspin promoter, showed a closed chromatin structure compared with HMECs. Moreover, maspin gene expression could be re-activated in MCF-7 cells by treatment with 5-aza-2;-deoxycytidine, a DNA demethylating agent. Thus, aberrant cytosine methylation and heterochromatinization of the maspin promoter may silence maspin gene expression, thereby contributing to the progression of human mammary cancer.

Expression of the polymeric immunoglobulin receptor and excretion of secretory IgA in the postischemic kidney.

The humoral mucosal immune response of the kidney involves the transport of secretory IgA (S-IgA) through renal epithelial cells by the polymeric immunoglobulin receptor (pIgR). The pIgR is cleaved and released as free secretory component (FSC) or attached to IgA (S-IgA). We examined the effects of an ischemic model of acute renal failure (ARF) on the expression of pIgR and the secretion of FSC and S-IgA in the urine. Kidney pIgR mRNA levels decreased in ischemic animals by 55% at 4 h and by 85% at 72 h compared with controls. pIgR protein expression in the medullary thick ascending limb (TAL) decreased within 24 h and was nearly undetectable by 72 h. Urinary S-IgA and FSC concentrations decreased by 60% between days 3 and 6. pIgR mRNA and pIgR protein in the kidney returned to approximately 90% of control levels and urinary FSC and S-IgA concentrations returned to approximately 55% of control levels by day 7. We demonstrate that ischemic ARF decreases renal mucosal S-IgA transport in vivo and may contribute to the increased incidence of urinary tract infections.

Antipolymer antibody reactivity in a subset of patients with fibromyalgia correlates with severity.

OBJECTIVE: To determine the prevalence of antipolymer antibodies (APA) in patients with fibromyalgia (FM) and autoimmune disease control groups and to determine if the presence of these antibodies correlates with severity in patients with FM. METHODS: Sera from patients with FM (n = 47), osteoarthritis (OA) (n = 16), and rheumatoid arthritis (RA) (n = 13) were analyzed. Patients with implants of any kind and patients with concurrent autoimmune conditions were excluded from study. Banked sera from autoimmune disease controls including poly/dermatomyosis (n = 15), RA (n = 30), systemic lupus erythmatosus (SLE) (n = 30), and systemic sclerosis (SSc) (n = 30) were also analyzed. To determine if seroreactivity correlates with severity, banked sera from patients with FM assessed as severe (n = 28) or mild (n = 37) and from controls (n = 21) were assayed. RESULTS: Following analysis, the prevalence of seroreactivity was found to be higher in patients with FM (22/47, 47%) compared to patients with OA (3/16, 19%; p<0.1) or RA (1/13, 8%; p<0.05) and the autoimmune disease control sera from poly/dermatomyosis (2/15, 13%; p<0.05), and patients with RA (3/30, 10%; p<0.01), SLE (1/30, 3%; p<0.01), and SSc (1/30, 3%; p<0.01). The prevalence of APA seroreactivity was also significantly higher in patients with severe FM (17/28, 61%) compared to patients with mild FM (11/37, 30%; p<0.05) and controls (4/21, 19%; p<0.01). In addition, both mean threshold and mean tolerance dolorimetry scores were significantly lower in the seropositive patients with mild FM (1.33+/-0.21, 1.95+/-0.25, respectively) compared to the seronegative patients (1.83+/-0.08, 2.53+/-0.11; p<0.05 for both comparisons, respectively). CONCLUSION: These results reveal that an immunological response, production of anti-polymer antibodies, is associated with a subset of patients with FM. The results also suggest that the APA assay may be an objective marker in the diagnosis and assessment of FM and may provide additional avenues of investigation into the pathophysiological processes involved in FM.

An analysis of program and family costs of case managed care for technology-dependent infants with bronchopulmonary dysplasia.

Caring for technology-dependent infants with bronchopulmonary dysplasia requires a wide range and intense level of services. Case management programs can offer comprehensive services to patients with complex needs. The Neonatal Pulmonary Program at Tulane University Medical Center is a case management program for infants with chronic pulmonary problems. The purpose of this study was to describe the costs of providing care for technology-dependent infants with bronchopulmonary dysplasia and to include the direct and indirect costs to families as well as the Program costs. The study population included 89 infants enrolled in the program from September 1987 through February 1992. Outpatient, inpatient, and professional staff costs were derived from hospital and clinic billing information; all other costs were determined through family interviews. Total costs for outpatient services were $59,627 (89), professional team members time $185,539 (89); inpatient services $1,144,930 (89), professional costs for inpatient services $88,946; direct health costs $32,543 (37) for home health care, equipment, medications, special diets; direct non-health costs $30,670 (37) for transportation, meals, child care, lodging during clinic visits and rehospitalizations and household expenses to accommodate equipment needs; and indirect costs $26,173 (37) for missed work days and employment changes.

Aberrant methylation of the BRCA1 CpG island promoter is associated with decreased BRCA1 mRNA in sporadic breast cancer cells.

BRCA1 mRNA is reduced in sporadic breast cancer cells despite the lack of mutations. Because a CpG island is found at the 5' end of the BRCA1 gene, we hypothesized that the decreased BRCA1 mRNA in sporadic breast cancer was associated with aberrant cytosine methylation of the CpG island. We examined BRCA1 mRNA expression in normal human mammary epithelial cells (HMECs), peripheral blood lymphocytes (PBLs) and six sporadic breast cancer cell lines using RT-PCR. The normal breast cells expressed high levels of BRCA1 mRNA. The sporadic breast cancer cell lines and PBLs expressed lower levels of BRCA1 mRNA ranging from a 3-16-fold decrease compared to the normal breast cells. We identified a 600 bp region of the BRCA1 CpG island that possessed strong promoter activity (approximately 40-fold above control), and determined the cytosine methylation patterns of the 30 CpG sites within this region by sodium bisulfite genomic sequencing. The HMECs, PBLs and five of the sporadic breast cancer cell lines were largely unmethylated. However, one sporadic breast cancer cell line, UACC3199, was > or = 60% methylated at all 30 CpG sites (18 sites were 100% methylated) and was associated with an eightfold decrease in BRCA1 mRNA compared to normal breast cells. These findings suggest that aberrant cytosine methylation of the BRCA1 CpG island promoter may be one mechanism of BRCA1 repression in sporadic breast cancer.

Nested case-control study of tumors of the hemopoietic and lymphatic systems among workers in the meat industry.

Workers in the meat industry are exposed to viruses that cause leukemia and lymphoma in cattle and chickens, and also to carcinogenic chemical agents. This case-control study, nested in a cohort of members of a meatcutters' union in Baltimore, Maryland, investigated whether occupational exposures are associated with death from tumors of the hemopoietic and lymphatic systems. Cases of these tumors represent all deaths which occurred in the cohort between 1949 and 1980. Excess risks of tumors of the hemopoietic and lymphatic systems were observed throughout the meat industry, except in meatpacking plants. Slaughtering activities involving heavy exposure to oncogenic viruses were strongly associated with these tumors, especially with lymphomas. Thus, elevated risks were observed for butchers who killed animals (odds ratio (OR) = 5.3, 95% confidence interval (CI) 1.0-27.0); workers in chicken-slaughtering plants (OR = 3.3, 95% CI 0.8-13.1); and workers in cattle/sheep/pig abattoirs (OR = 2.8, 95% CI 0.8-9.5). Among supermarket workers, wrapping meat (mainly a female activity) was associated with increased risk of tumors of the hemopoietic and lymphatic systems (OR = 3.8, 95% CI 1.0-14.3), with the odds of both lymphomas and tumors of the myeloid stem cell being elevated. On the other hand, meatcutting in supermarkets (almost exclusively a male activity) was associated with multiple myeloma; the odds ratio for men was 18.0 (95% CI 1.6-207.5), with no myeloma cases being recorded in women. These associations persisted after limited control for exposures outside the industry that have also been observed to be associated with excess risk, such as exposure to pesticides, working/living on pig farms, and exposure to X-rays. The findings provide evidence that workers in the meat industry may be at elevated risk of tumors of the hemopoietic and lymphatic systems. Further studies with larger sample sizes are needed to identify more conclusively which exposures play an etiologic role in the occurrence of the different histologic types of these tumors.

Nasal septal squamous cell carcinoma: a chart review and meta-analysis.

Squamous cell carcinoma of the nasal septum occurs infrequently and is often misdiagnosed because its symptoms are similar to everyday rhinologic complaints. The published series have been too small to determine the best form of treatment for this cancer. The authors of this study retrospectively reviewed nasal septal squamous cell carcinomas treated at three university-affiliated hospitals over a 30-year period. Sixteen primary tumors were identified and reviewed for presentation, staging, treatment, recurrence patterns, and risk factors. The authors then combined their findings with those of suitable literature series and performed a meta-analysis to evaluate predictors of survival. There were too few patients in each stage and treatment group to significantly determine the optimal treatment for nasal septal squamous cell carcinoma. However, based on the present study and the literature series, the authors suggest that small lesions may be confidently treated with either radiation or surgery and that combined therapy may be reserved for more advanced tumors.

Renal retransplants: effect of primary allograft nephrectomy on early function, acute rejection and outcome.

Although risk factors for failure of renal retransplants have been well studied, the impact of allograft nephrectomy on subsequent renal transplantation in the cyclosporin era is not well defined. The purpose of this study is to define the effect of nephrectomy of the primary allograft on subsequent allograft survival, early allograft function, incidence of acute rejection and patient sensitization. The records of 127 renal retransplant recipients were reviewed. Of these 127 patients who underwent retransplantation, 40 (31%) underwent nephrectomy of the primary allograft prior to retransplantation whereas 40 (31%) did not. Nephrectomy of cadaveric primary allografts was performed more commonly (48% vs 30%, p = 0.003) and earlier (78% vs 54% < 1 month post-transplant, p = 0.0006) in the pre-CSA period compared to the CSA period. Biopsy-proven acute rejection episodes occurred more frequently in the nephrectomy group (73% vs 42%, p = 0.03). Although primary allograft nephrectomy was associated with higher preformed antibody levels, it had no effect on early graft function, frequency of acute rejection or allograft outcome after retransplantation, in the CSA group. In conclusion, in the cyclosporin era, nephrectomy of the primary allograft has no significant influence on retransplantation.