Polyoma viral infection in renal transplantation: the role of immunosuppressive therapy

BACKGROUND: Polyoma virus infection in renal transplant recipients has been observed with increasing frequency in recent years. Renal allograft involvement in this condition may occur as a result of primary infection or secondary to reactivation of the latent virus. Interstitial nephritis, ureteric stenosis, rise in serum creatinine and allograft function loss have been attributed to this viral infection. METHODS: In this study we reviewed our experience with 8 patients who developed polyoma viral infection confirmed by allograft biopsy. All patients were receiving mycophenolate mofetil as part of the immunosuppression and 7 of the 8 patients were on tacrolimus. All patients have biopsy proven polyoma viral infection. The following therapeutic maneuvers were carried out following the diagnosis of polyoma viral infection: 1) stopping mycophenolate and 2) switching tacrolimus to cyclosporine or reducing the tacrolimus dose to adjust it at a lower therapeutic trough level. The clinical course and outcome of our patients were reviewed in relation to manipulation of immunosuppressive medications. RESULTS: The incidence of this infection in our transplant program in the last 3 yr was 5.3%. Seventy-five percent of the patients had at least one rejection episode and 63% had more than one rejection episode. The main risk factor for the development of polyoma viral infection was related to the intensity of immunosuppression. The use of antirejection therapy after histological diagnosis of polyoma virus infection was not associated with improvement of renal function despite the histological appearance of acute rejection. Thus, the interstitial nephritis associated with polyoma viral infection appears to be an inflammatory response to the virus rather than acute rejection. Six out of the 8 patients stabilized renal function with reduction in immunosuppression. CONCLUSIONS: Reduction in immunosuppression was associated with the stabilization of renal function when instituted early. However, these patients were left with a degree of allograft dysfunction and their outcome may be significantly compromised. The lack of effective antiviral therapy for polyoma virus may limit the use of newer and more potent immunosuppressive medications.     

BK virus nephropathy in a kidney transplant recipient: a case report and literature review

BK virus nephropathy (BKVN) has emerged as an important cause of allograft dysfunction and loss in kidney transplant recipients. We present a case in a 30-year-old female who underwent ABO-compatible living kidney transplant from her mother and was maintained with tacrolimus, mycophenolate mofetil and prednisolone. The serum creatinine level was stabilized about 0.9 mg/dl on postoperative day (POD) 35. On POD258, the serum creatinine increased to 1.8 mg/dl and the patient received methylpredonisolone pulse therapy under the diagnosis of acute rejection, which resulted in further increase in creatinine level from 1.8 to 2.6 mg/dl. Urine cytology showed decoy cells, but renal biopsy specimen showed no evidence of viral infection. Despite histopathological findings, positive urine and serum BKV-DNA suggested that allograft dysfunction was caused by BKVN. Therefore, the immunosuppession was reduced and gamma-globuline was given for 2 weeks. After the treatment, urine cytology became negative for decoy cells and serum creatinine level recovered to 2.0 mg/dl. On POD456, serum creatinine level was stabilized about 1.8 mg/dl and decoy cells remained negative.     

Polyoma virus infection after renal transplantation. Use of immunostaining as a guide to diagnosis

BACKGROUND: Polyoma virus infection is characterized by lymphocytic interstitial infiltrate in the kidney, and it mimics acute rejection. The purpose of this study is to estimate renal allograft outcome with this infection and characterize the lymphocytic infiltrates in polyoma virus-infected renal allografts. METHODS: Patients who had polyoma virus inclusions in renal allograft biopsies were identified. Other viral inclusions were excluded by immunohistochemistry. The lymphocytic infiltrates of six cases of polyoma virus infection were compared with six cases of definite acute rejection by immunostaining for T and B cells. RESULTS: There were 10 cases of polyoma virus infections in renal transplant recipients. Immunosuppressants consisted of mycophenolate mofetil with tacrolimus in eight cases and mycophenolate mofetil with cyclosporine in two. The median time of diagnosis of polyoma virus infection after transplantation was 9.5 months, and the time to graft failure after the diagnosis was 4 months. Reduced allograft survival was seen in patients who had polyoma virus infection. Immunostaining for T and B cells revealed marked increase in the B cells (CD20) in renal allografts with polyoma virus infection of 21% (range, 5-40%) compared with 6% (range, 0-10%) in those with acute rejection (P=0.039). Reduced cytotoxic T cells (TIA-1: median, 7%; range, 2-15%) were seen in polyoma virus-infected allografts compared with 24% (range, 15-30%) in those patients who had acute rejection (P=0.0159). CONCLUSION: Irreversible graft failure is more prevalent with polyoma virus infection. Enhanced immunosuppressants with mycophenolate mofetil with tacrolimus may play a role in the development of this infection. An increase in CD20 and a decrease in cytotoxic T cells in allografts is characteristic of polyoma virus infection.     

Polyomavirus-associated nephropathy in simultaneous kidney-pancreas transplant recipients: a single-center experience

BACKGROUND: With the introduction of more potent immunosuppressive agents, rejection rates have decreased markedly in simultaneous pancreas-kidney transplant (SPK) recipients. However, with more intense immunosuppression, opportunistic infections such as polyoma virus have been more frequent. The purpose of this article is to outline the clinical course of SPK patients who developed documented polyoma infection in the transplanted kidney. METHODS: A retrospective review of 146 consecutive SPK recipients from 1996 to 2002 was performed. Induction and maintenance immunosuppression, surgical complications, rejection episodes, and opportunistic infections were reviewed. Patients who developed biopsy-proven polyoma virus infection in the renal allograft were identified. RESULTS: Nine patients (6%) were identified who developed polyoma. All had received induction therapy with either OKT3 (5 mg/d for 10.5 days) or thymoglobulin (5.7 mg/kg). Patients without polyoma had received similar induction. Maintenance immunosuppression included Prograf/MMF in six patients, CsA/MMF in two, and CsA/azathioprine in one. Time to diagnosis was an average of 359.3 days (range 136 to 836) after transplantation. Two patients had undergone treatment for kidney rejection prior to the diagnosis of polyoma. Immunosuppression was decreased in all patients when polyoma was identified, and more recently Cidofovir has been administered. Despite these interventions, five of the nine lost kidney function (creatinine > 5.0 or resumption of dialysis). However, none of the nine developed pancreatic abnormalities as demonstrated by normal blood glucose and amylase and no requirement for exogenous insulin. Two patients underwent LRRT more than 1 year after polyoma diagnosis; both have normal kidney function (Cr < 1.5 mg/dL) at 4 years of follow-up. Polyoma virus was the leading cause of renal loss in this cohort of patients. CONCLUSIONS: Polyoma is a serious concern for SPK transplant recipients. The pancreas, however, is spared from clinical evidence of infection, and no rejection was noted when immunosuppression was decreased. These graft losses appear to be a penalty of more potent immunosuppression, and a better treatment strategy is needed to prevent renal graft loss when polyoma is diagnosed. Retransplantation can be considered based on our limited experience.     

BK virus infection in kidney transplant recipients

INTRODUCTION: Nephropathy associated with the polyomavirus type BK virus (BKV) has emerged as a cause of allograft failure linked to immunosuppressive regimens containing tacrolimus or mycophenolate mofetil (MMF). The outcome in BKV nephropathy is generally unfavorable, namely 50% of patients lose graft function. We herein report nine cases of BKV nephropathy after kidney transplantation. METHODS: From October 1998 to May 2003, 138 of 169 consecutive kidney transplant patients received tacrolimus-based immunosuppression, and 31 received cyclosporine-based immunosuppression. Additionally, 88.2% of the patients received mycophenolate mofetil (MMF). The diagnosis of BK infection was made by the presence of decoy cells in the urine and by allograft biopsy. RESULTS: There were nine cases of BKV nephropathy in kidney transplant recipients, an incidence of 5.3%. All patients with BKV nephropathy received tacrolimus, MMF, and steroids. The median time to diagnosis of BKV infection was 7.8 months after transplantation. All patients experienced an elevated serum creatinine, which stabilized or decreased in seven patients with altered or decreased immunosuppression. After a mean follow-up of 11.1 months, 2 (22.2%) of nine patients lost the graft. CONCLUSION: Because BKV nephropathy is a rare but serious complication after kidney transplantation, it should be included in the clinical differential of transplant dysfunction. In the absence of documented antiviral treatment, early diagnosis and judicious use of immunosuppressive agents is indicated to minimize the occurrence of BKV infection.     

A case report of BK virus nephropathy after an ABO-incompatible living kidney transplantation

We present a case of 29-year-old female who underwent an ABO-incompatible living kidney transplantation from her father. The serum creatinine (s-Cr) level of this patient was stabilized about 1.1-1.2 mg/dl during the first 3 months after the transplantation. Thereafter, the function of allograft was deteriorated gradually. A biopsy performed on post-transplant day (PTD) 520 to evaluate a rise in creatinine revealed an interstitial nephritis and chronic renal allograft nephropathy. The renal function worsened persistently, although we increased the dosage of immunosuppressant subsequently. The following biopsy performed on PTD 630 showed a suspicion of BK virus nephropathy, with a mass of tubular epithelial nuclear inclusions and an interstitial nephritis. The diagnosis of BK virus nephropathy was confirmed on the immunohistochemistry staining using anti-SV40 antibody and PCR analysis. Despite reducing the immunosuppressants, the function of the allograft worsened progressively and was lost on PTD 912.     

Renal allograft loss as the result of polyomavirus interstitial nephritis after simultaneous kidney-pancreas transplantation: results with kidney retransplantation

BACKGROUND: Polyomavirus (PV) infection in kidney transplant patients has been reported to cause interstitial nephritis and subsequent graft loss. The cornerstone of current therapy is a reduction in immunosuppression, which can subsequently lead to kidney allograft rejection. This dilemma becomes even more challenging in the setting of simultaneous kidney-pancreas transplantation, because a reduction in immunosuppression may result in rejection of the pancreas allograft. Antiviral therapy has not been shown to be clinically successful in decreasing the risk of graft loss secondary to PV infection. Furthermore, because of limited experience, the decision to perform retransplantation in patients who lost their primary kidney grafts to PV interstitial nephritis becomes a difficult one. METHODS: Retrospective review and case studies. RESULTS: We report two successful living donor kidney retransplants in simultaneous kidney-pancreas transplant patients who lost their first kidney grafts to PV infection. Both patients are receiving rimantadine therapy and performing well, with functioning kidney and pancreas grafts and no evidence of recurrent PV interstitial nephritis 22 and 37 months after retransplantation. CONCLUSIONS: Although follow-up is limited, our initial experience would indicate that graft loss secondary to PV interstitial nephritis is not an absolute contraindication for kidney retransplantation.     

A Mouse Model for Polyomavirus-Associated Nephropathy of Kidney Transplants

Polyomavirus-associated nephropathy is an important cause of dysfunction and failure of renal transplants. BK virus is an ubiquitous human polyoma virus that persistently infects the kidney. This otherwise silent infection can reactivate in immunosuppressed individuals, resulting in renal complications. Because polyoma viruses are highly species-specific, we developed a mouse polyoma virus-renal transplant model in order to investigate the pathogenesis of polyomavirus-associated nephropathy. Using this model, we found that polyoma virus preferentially replicates in the allogeneic kidney grafts, accelerating graft failure; thus, this animal model is able to mimic the polyomavirus-associated nephropathy seen in human renal transplant patients. Acute polyoma virus infection of mouse allograft recipients augmented the alloreactive CD8⁺ T-cell response, while maintaining the anti-viral CD8⁺ T-cell response. In addition to the known virus-induced cytopathology, these findings demonstrate a potential role for an enhanced anti-donor T-cell response in the pathogenesis of polyomavirus-associated nephropathy.     

Late calcineurin inhibitor withdrawal as a strategy to prevent graft loss in patients with suboptimal kidney transplant function

Chronic allograft nephropathy is a major cause of progressive renal failure in renal transplant recipients. Its etiology is multifactorial and may include both immunologic and nonimmunologic causes. In this observational cohort study we set out to see if calcineurin inhibitor withdrawal would reduce the likelihood of graft loss. METHODS: One hundred and five renal transplant recipients with impaired kidney function (mean serum creatinine 3.0 +/- 0.1 mg/dl) and biopsy-proven chronic allograft nephropathy had the dose of their calcineurin inhibitors, cyclosporine (CSA), or tacrolimus (FK), reduced or discontinued with either the addition of, or continuation of mycophenolate mofetil and low-dose corticosteroids. This intervention occurred at a mean of 29.0 +/- 2.7 months after transplantation. Follow-up after intervention was 54.3 +/- 4.1 months in the reduced CSA group (n = 64), 41.6 +/- 3.2 months in the reduced FK group (n = 28), and 75.5 +/- 6.7 months in the calcineurin inhibitor withdrawal group (n = 13). RESULTS: There were 24 graft failures in the reduced CSA group, 9 graft failures in the reduced FK group, and 1 graft lost in the calcineurin inhibitor withdrawal group. The unadjusted relative risk for graft failure in the CSA and FK groups combined (confidence interval 1.05-31.6), was 4.07 using the calcineurin inhibitor withdrawal group as the reference, p = 0.05. A Cox proportional hazards model adjusting for baseline covariates including age, gender, race, type of transplant, delayed graft function, baseline blood pressure and random serum glucose and cholesterol demonstrated that only calcineurin inhibitor dose reduction but not withdrawal, older age, delayed graft function, higher serum creatinine at the time of intervention, and higher diastolic blood pressure and serum glucose, correlated with graft loss. Only 6 of the 105 patients developed Banff grade acute rejection. All responded to steroid therapy. We conclude that although this observational cohort study may have a selection bias, late calcineurin inhibitor withdrawal in patients with chronic allograft nephropathy and impaired kidney function appears safe and durable as a treatment strategy to reduce the likelihood of graft failure.     

Polyomavirus nephropathy after renal transplantation: a single centre experience

BACKGROUND: Polyomavirus associated nephropathy (PVN) in renal transplant recipients has been observed with increasing frequency recently and has emerged as a cause of allograft failure linked to highly potent new immunosuppressive regimens containing tacrolimus or mycophenolate mofetil (MMF). METHODS: Polyomavirus associated nephropathy was identified in nine out of 182 patients who received renal transplantation between October 1998 and July 2003. PVN was confirmed by allograft biopsy. The clinical records of these nine patients were reviewed, as were all of the allograft biopsies. Electron microscopy was performed in all nine cases. After the diagnosis of PVN, maintenance immunosuppression was reduced. The clinical course and outcome of the PVN patients were reviewed in relation to manipulation of immunosuppressive agents. RESULTS: There were nine cases of PVN in renal transplant recipients and the incidence of PVN was 4.9%. All patients with PVN were under triple immunosuppression comprising tacrolimus and MMF. The mean time to a diagnosis of PVN was 7.8 months after transplantation. Three of the nine patients received antirejection therapy prior to PVN. Seven out of nine PVN patients presenting acute allograft dysfunction were initially treated with high-dose intravenous steroid pulse or OKT3 before reduction of the immunosuppression. After reduction of the immunosuppression, seven patients stabilized their renal function. Two (22%) lost their grafts due to persistent PVN and chronic rejection. Two (22%) patients later developed acute rejection after reduction of the immunosuppression. CONCLUSION: PVN can cause allograft dysfunction and graft loss. Renal allograft recipients who are at risk of PVN should be routinely screened with urine cytology and quantitative measurements of viral load in the blood, particularly patients who had graft dysfunction. Early diagnosis and judicious alteration of immunosuppressive agents might permit a superior prognosis and reduce the graft loss from PVN in renal transplant recipients.     

Renal transplant patient with polyoma virus bladder infection and subsequent polyoma virus nephropathy

Polyoma virus nephropathy (PVN) is a significant cause of renal allograft dysfunction in transplant patients. A 58-year-old male received a cadaveric renal transplant and 12 weeks later presented with fever, diarrhea, and dysuria. He was diagnosed with a polyoma virus infection of the bladder by a transurethral bladder biopsy. One year post-transplant, he presented with renal allograft dysfunction and was diagnosed by biopsy with PVN of the non-native kidney. The diagnosis of a polyoma virus infection was confirmed by immunoreactivity to the polyoma T-antigen. We suggest that polyoma virus infection of the bladder be included in the differential diagnosis of urinary dysfunction in post-transplant patients, as such infections might be an under-recognized comorbidity in individuals with PVN.     

Decreased incidence of acute rejection in adolescent kidney transplant recipients using antithymocyte induction and triple immunosuppression

BACKGROUND: Acute rejection is a frequent event in pediatric renal transplantation; it can diminish allograft function and affect long-term outcome. Recent data from the North American Pediatric Renal Transplant Cooperative Study indicates that the rate of acute rejection remains high despite current immunosuppressive regimens. METHODS: In this retrospective series, we examined 37 pediatric renal transplant recipients who received induction doses of antithymocyte globulin combined with maintenance immunotherapy using tacrolimus, mycophenolate mofetil, and prednisone. The postoperative course was reviewed for initial and total hospital stay, number of rehospitalizations, evidence of posttransplant complications, graft fibrosis, and overall patient and graft survival. RESULTS: Three episodes of acute rejection (8.1%) were recorded in the first year posttransplant. The median initial hospital stay for patients receiving a kidney transplant was 8 days. Patient and graft survival were 100% and 91.9% at 1 year, respectively. The incidence of viral infection (cytomegalovirus, BK virus, and Epstein-Barr virus) and posttransplant lymphoproliferative disease remained low. Urinary tract infection and fluid and electrolyte complications were the main causes of posttransplant hospitalization. CONCLUSIONS: We conclude that induction with antithymocyte globulin and maintenance immunosuppression with tacrolimus, mycophenolate, and prednisone should be considered a valuable tool in the management of children undergoing renal transplantation.     

Functional and morphologic evaluation of kidney proximal tubuli and correlation with renal allograft prognosis

Renal transplant patients with stable graft function and proximal tubular dysfunction (PTD) have an increased risk for chronic allograft nephropathy (CAN). In this study, we investigated the histologic pattern associated with PTD and its correlation with graft outcome. Forty‐nine transplant patients with stable graft function were submitted to a biopsy. Simultaneously, urinary retinol‐binding protein (uRBP) was measured and creatinine clearance was also determined. Banff’s score and semi‐quantitative histologic analyses were performed to assess tubulointerstitial alterations. Patients were followed for 24.0 ± 7.8 months. At biopsy time, mean serum creatinine was 1.43 ± 0.33 mg/dl. Twelve patients (24.5%) had uRBP ≥1 mg/l, indicating PTD and 67% of biopsies had some degree of tubulointerstitial injury. At the end of the study period, 18 (36.7%) patients had lost renal function. uRBP levels were not associated with morphologic findings of interstitial fibrosis and tubular atrophy (IF/TA), interstitial fibrosis measured by Sirius red or tubulointerstitial damage. However, in multivariate analysis, the only variable associated with the loss of renal function was uRBP level ≥1 mg/l, determining a risk of 5.290 of loss of renal function (P = 0.003). Renal transplant patients who present PTD have functional alteration, which is not associated with morphologic alteration. This functional alteration is associated to progressive decrease in renal function.     

Stable kidney function in the second decade after kidney transplantation while on cyclosporine-based immunosuppression

BACKGROUND: Calcineurin inhibitors (CNIs) have been the mainstay of immunosuppressive protocols in kidney transplantation over the past 20 years. However, in some recipients, the adverse effects of CNIs contribute to chronic allograft nephropathy and death with function--the two leading causes of late graft loss. Other recipients maintain stable graft function. METHODS: We studied the impact of continuing CNI-based immunosuppression in the second decade after kidney transplantation. From 1984 through 1996, a total of 1,263 patients underwent a primary kidney transplant at the University of Minnesota and received cyclosporine-based immunosuppression. Antibody induction was used only in deceased donor recipients. RESULTS: The actuarial 20-year patient survival rate was 38%; graft survival, 30%; and death-censored graft survival, 60%. The annual mean serum creatinine level for recipients whose grafts survived > or =1 year remained stable, although recipients with a history of > or =1 acute rejection episode had a higher serum creatinine level vs. recipients who were rejection-free. The annual mean calculated creatinine clearance was also stable over time. In addition, for recipients who were acute rejection-free, chronic allograft nephropathy/chronic rejection was only responsible for 9% of graft losses. CONCLUSIONS: Our study suggests that some kidney transplant recipients tolerate long-term CNI-based immunosuppression with stable creatinine levels. Identifying certain recipients' predisposition to CNI toxicity and individualizing immunosuppressive therapy may be important in order to improve long-term kidney function, while simultaneously preserving low short-term acute rejection rates.     

Pediatric cadaver kidney transplants into adults

During a 5-year period 77 adults received single kidney cadaver transplants from donors 16 months to 16 years old. Cyclosporin immunosuppression was not used. Three recipients had ischemic ureteral complications, 1 of which resulted in allograft loss. Of the kidney grafts 34 were from donors 8 years old or younger, and comparison of renal function was made with the 43 adult recipients of cadaver kidneys from older children. The mean 1-month serum creatinine nadir was significantly higher in the recipients of kidneys from the younger children (2.6 plus or minus 1.6 versus 1.9 plus or minus 0.8 mg./per dl.). There were no statistically significant differences in 1-week dialysis requirement, 1-month kidney graft function or actuarial kidney graft survivals and serum creatinine levels at 3, 6, 12 and 24 months after grafting. Cadaver kidneys from young donors can be transplanted successfully into adults.     

The high incidence of BK polyoma virus infection among renal transplant recipients in India

BK polyoma virus causes allograft dysfunction as a result of tubulo-interstitial nephritis in 2% to 5% of renal transplant recipients. The incidence of BK virus infection among renal transplant recipients in India is unknown. We used routine histologic examination, immunohistochemistry, and electron microscopy to retrospectively screen for BK polyoma virus in 414 renal allograft biopsy specimens from 321 transplant recipients presenting with allograft dysfunction. All patients had received a combination of cyclosporine, azathioprine, and prednisolone. A total of 30 biopsy specimens (9.3%) were positive for BK polyoma virus, suggesting a high incidence of this infection in Indian transplant recipients. BK virus infection coexisted with acute rejection in a majority of patients. This is the first report of this infection among Indian renal transplant recipients.     

Successful third kidney transplantation with intensive immunosuppression in a highly sensitized recipient

HLA sensitization associated with previous kidney transplantation is a major drawback to retransplantation. Recently we successfully performed a third graft using intensive immunosuppression for a highly sensitized recipient. The patient was a 31-year-old man who had previously undergone a living donor graft from his father at our institute in 1999. His kidney graft function had deteriorated due to chronic allograft nephropathy, returning to hemodialysis therapy in 2005. He received a second graft from a deceased donor in another country on August 14, 2006. It rejected on postoperative day 3 possibly due to acute accelerated rejection. He was offered a third kidney from his brother. Panel-reactive antibody (PRA) tested before the third procedure revealed positive class I (88%) and class II (96%) PRAs. Mycophenolate mofetil (MMF) was started 3 weeks before the third transplantation, and preoperative plasmapheresis performed thrice. He underwent the living donor graft on March 9, 2007. Immunosuppression consisted of tacrolimus, MMF, methylprednisolone, and basiliximab. Immediately afterward there was a sudden decrease in allograft blood flow and urine output, implying hyperacute rejection. Following treatment with plasmapheresis and a single dose of rituximab (200 mg), the kidney allograft function recovered, although the PRA at 3 weeks was still positive. Six months posttransplantation, he is well with a creatinine of 0.9 mg/dL. Our protocol may reduce the risk for graft loss in a highly sensitized transplant recipient.     

Kidney retransplantation in the cyclosporine era

The results of kidney retransplantation in the cyclosporine era remain to be determined. Over a 42-month period, 76 nonprimary renal transplants (66 second, 7 third, 3 fourth allografts) were performed in 73 recipients under cyclosporine immunosuppression. The patient population was predominantly white (90.4%) with a mean age of 32.3 years. Twenty-one recipients (28.8%) were diabetic, and 36 (49.3%) were highly sensitized (panel-reactive antibody [PRA] greater than 50%). Sixty-two patients received cadaver donor grafts while the remaining donations were living-related (12) or living-unrelated (2). A sequential antilymphocyte globulin/cyclosporine protocol was employed, with cyclosporine therapy delayed until adequate renal function occurred. Overall patient and graft survival is 92.1% and 60.5%, respectively, after a mean follow-up of 20.0 months. The mean serum creatinine is 1.64 mg/dl in the 46 functioning allografts. Graft survival is 63.6% for secondary grafts, 28.6% for tertiary grafts, and 66.7% for fourth kidney transplants. In second transplants, recipients of cadaver donor kidneys have a graft survival of 58.5%, while living-related donor graft survival is 84.6% (P = 0.07). In the cadaver retransplant population, duration of previous transplant function greater than one year and HLA-DR matching were associated with increased graft survival, while age over 39 and presence of diabetes mellitus with reduced graft survival. However, these trends were not significant. Peak PRA above 50% did demonstrate a significant negative impact on graft survival both in the univariate and multivariate analyses of risk factors. Acute rejection occurred in 50 patients (65.8%), and was successfully reversed 50% of the time. Of the 30 grafts lost, 25 (83.3%) occurred within four months of retransplantation. Transplant nephrectomy was performed in 20 patients. Cyclosporine was not administered in 21 (70%) of these early graft failures, negating any potential beneficial effect. Retransplantation can be performed safely, with living-donor graft survival superior to cadaver retransplant rates. Rejection and early graft loss are common, especially in the highly sensitized patient. The impact of cyclosporine immunosuppression in renal retransplantation is much less dramatic than in primary transplantation in a protocol that delays cyclosporine therapy until allograft function is demonstrated.     

Impact of banff borderline acute rejection among renal allograft recipients

OBJECTIVE: This study was performed to determine the incidence, treatment, and outcomes of Banff borderline acute rejection (AR) among renal transplant recipients. PATIENTS AND METHODS: We reviewed the courses of adult kidney transplant recipients with borderline AR on clinically indicated biopsies performed at our center from January 2003 to July 2006. Patients with complete transplant records and serum creatinine values at 6 and 12 months were included in this study. The primary outcome measures were serum creatinine values at 1 to 2 weeks after treatment, and at 6 and 12 months after graft biopsy. RESULTS: Among 428 renal graft biopsies, borderline AR was observed in 100 cases (23%). Patients were maintained on the same immunosuppression. The 86 who had complete data were included in the study. Seventy-eight percent of the patients received treatment with 3 days of methylprednisolone, while 22% were untreated. Mean serum creatinine values in the treated group were 2.9 +/- 1.0, 2.6 +/- 2.5, and 3.0 +/- 2.9 mg/dL at the time of biopsy, and at 6 and 12 months thereafter, respectively. In the untreated group, mean serum creatinine values were 2.2 +/- 1.0, 1.9 +/- 0.8, and 2.3 +/- 1.2 mg/dL during biopsy, and at 6 and 12 months thereafter, respectively. There was no significant difference in the serum creatinine at any of the measured time points between the 2 groups. Twelve patients had repeat renal graft biopsies which showed AR (6%), chronic allograft nephropathy (2.4%), and borderline changes (3.8%). Nine of the patients in the treated group eventually developed graft loss. CONCLUSIONS: Patients with borderline AR showed a progressive increase in serum creatinine over time. They should be followed closely; immunosuppression may need to be intensified.     

Rapid kidney allograft failure in patients with polyoma virus nephritis with prior treatment with antilymphocyte agents

Interstitial nephritis owing to polyoma virus infection (PVi) mimics acute allograft rejection. The risk factors for graft failure associated with PVi are unknown. This prompted us to analyse the relationship between the use of antilymphocyte agents (ALA) and graft dysfunction in renal transplant recipients with PVi. Renal transplant recipients who were diagnosed to have PVi nephritis at the Medical College of Wisconsin were included in this study. PVi nephritis was confirmed by urine cytology and characteristic renal histological findings in a total of 14 cases. Other viruses were excluded by immunohistochemistry studies. Patients were divided into two groups: Group A (n = 7) received ALA (OKT3/ATGAM) as treatment for presumptive acute rejection and Group B (n = 7) did not receive ALA therapy. The progression of renal function (GFR) was estimated by a 100/ plasma creatinine and an actuarial kidney survival was estimated by the Kaplan-Meier method. The demographics (age, gender, race, retransplant and kidney versus. kidney/pancreas), prior treatment with steroids for presumptive acute rejection, and renal function at the time of PVi diagnosis were similar betwoen groups. The fall in GFR/month was 6 mL/min/month with prior ALA therapy compared with 1 mL/min/month in those who did not receive ALA, p = 0.002. All seven grafts were lost in the ALA group compared with only two of seven grafts in the other group, p = 0.005. The use of ALA was associated with a rapid fall in GFR and graft failure in patients with PVi nephritis. Careful diagnosis of PVi is warranted in renal allograft recipients prior to initiating ALA therapy.