Polyomavirus nephropathy in renal allograft: prevalence and correlation of histology with graft failure

BACKGROUND: While polyomavirus nephropathy (PVN) is recognized as an emerging cause of graft loss in renal transplants, the prevalence rate of PVN in renal grafts is unclear in Taiwan. METHODS: Biopsies (n = 412) from 323 Taiwanese renal transplant patients were retrospectively analysed. PVN was diagnosed by the characteristic viropathic change in epithelial cells under light microscopic examination and a positive immunohistochemistry staining of anti-SV40 large T antigen. The viral cytopathic changes, interstitial inflammation, fibrosis and tubular atrophy were semiquantitatively assessed, based on the Banff 1997 classification and scoring for renal allograft. RESULTS: Seventeen cases were identified with evidence of PVN; the prevalence rate is 5.26%. Compared with non-PVN patients, they were more likely to have had previous rejection episodes, higher graft loss and shorter graft survival. CONCLUSION: This retrospective study showed that we have similar findings to other reports with at least 5% prevalence of PVN and that patients diagnosed early do better, while those diagnosed with severe inflammation or damage do worse or are likely to lose their grafts.     

The effect of acute rejection on long-term renal graft survival is mainly related to initial renal damage

Abstract It has been suggested that poor long-term prognosis of acute rejection is due to hyperfiltrationmediated injury secondary to the initial renal damage, rather than to ongoing immunological mechanisms. A total of 953 renal transplant recipients was reviewed to examine the effect of acute rejection episodes on graft function and survival; 40 % had no rejections, 45 % one, 12% two and 3% three. Rejection episodes adversely affected short- and long-term prognosis (5-year survival for no rejections, 62 %; one, 34 %; two, 26 %; three, 19 %, P <0.001) and creatinine clearance at one year (cl 1) (none, 56.7 ml/ min; one, 51.1; two, 52.9; three, 35.2, P < 0.01). This was mainly due to increased graft loss, but patient survival was also reduced (5-year survival for no rejections, 77 %; one, 76 %; two, 63 %; three, 53 %, P < 0.05). There was no overall effect of rejection number, independently of cl 1. However, subgroup analysis showed a detrimental effect of rejection number on grafts with high residual function, i.e. cl 1 > 60 ml/min (5-year graft survival none and one, 87 %; two and three, 71 %, P < 0.01). Late initial rejection episodes adversely affected prognosis (5-year survival 1–7 days, 34 %; 8–60, 31 %; 60–300, 21 %, P < 0.05) and residual graft function (cl 1 1–7 days, 56.2 ml/min; 8–60, 48.7; 60–300, 44.6, P < 0.01). In conclusion, the poor long-term prognostic effect of rejection episodes is mainly, but not entirely, related to initial graft destruction. Late (>2 months after transplantation) initial rejection is an important independent risk factor for graft loss.     

肾移植术后血脂的变化对移植肾功能的影响

目的:探讨肾移植患者血脂代谢情况及其对移植肾功能的影响。方法:检测89例肾移植患者肾移植前、后的血脂水平,并与移植后1年内发生急性排斥反应及移植后1年时发生慢性移植肾功能不全的患者进行血清肌酐水平相关性分析。结果:与正常对照组比较,肾移植前、后的血清总胆固醇、低密度脂蛋白胆固醇的水平显著升高(P<0.01),甘油三酯、高密度脂蛋白胆固醇、极低密度脂蛋白胆固醇水平无显著差异。血载脂蛋白A1水平显著低于正常对照组(P<0.01)。移植前、后上述血脂水平无显著差异。移植前高胆固醇血症与急性排斥反应的发生存在相关性,高胆固醇血症对慢性移植肾功能不全患者血清肌酐水平升高存在影响。结论:肾移植患者血脂代谢紊乱明显不同于正常人群,高脂血症对急性排斥反应及慢性移植肾功能不全的发生具有不良影响。     

The aetiology and pathogenesis of chronic allograft nephropathy

Renal transplantation is the ultimate form of renal replacement therapy, and is the treatment of choice for many patients with end-stage renal failure. The advent of calcineurin inhibitor based immunosuppression resulted in the 1-year renal allograft failure rate dropping from around 50% twenty years ago to less than 10% in more recent times. Despite a massive improvement in renal allograft survival in the first year following transplantation 10-year graft survival can be as low as 50%. Chronic allograft nephropathy (CAN) is recognised as the main cause of renal allograft failure following the first year after transplantation. The diagnosis of CAN can only be made histologically. Typically biopsy specimens in grafts with CAN demonstrate an overall fibrotic appearance effecting the vascular endothelium, renal tubules, interstitium, and glomerulus. The risk factors for CAN are divided into alloimmune and alloimmune independent. Alloimmune dependent factors include acute cellular rejection, severity of rejection, subclinical rejection and HLA mismatch. Alloimmune independent factors such as delayed graft function, donor age, Cytomegalovirus infection, donor/recipient co-morbidity and of course calcineurin inhibitor toxicity are important in the development of CAN. The pathogenesis of CAN is complex, multifactorial, and unfortunately incompletely understood. There are a number of pivotal steps in the initiation and propagation of the fibrosis seen in biopsy specimens from kidneys with CAN. Endothelial activation in response to one or more of the aforementioned risk factors stimulates leukocyte activation and recruitment. Recruited leukocytes subsequently infiltrate through the endothelium and induce key effector cells to secrete excessive and abnormal extracellular matrix (ECM). Enhanced deposition of ECM is a histological hallmark of CAN. This paper aims to present a concise yet accurate and up-to-date review of the literature concerning the aetiological factors and pathological processes which are present in the generation of CAN.     

Chronic renal allograft nephropathy

Chronic rejection/chronic allograft nephropathy is the most prevalent cause of renal graft loss after the first year post-transplant. Chronic rejection/chronic allograft nephropathy is characterized by a slow progressive deterioration of graft function, often in combination with proteinuria and hypertension. Both immunologic and non-immunologic factors play key roles in the pathogenesis of chronic allograft nephropathy. Acute rejection episodes are the most prevalent risk factor for chronic rejection. Many risk factors for chronic allograft nephropathy have been identified, such as delayed graft function, nephron-dosing mismatch, repeated acute rejection episodes, and pathologically severe rejection. However, the precise pathogenesis of chronic allograft nephropathy remains elusive. The differential diagnosis of immunologically mediated chronic rejection and chronic rejection caused by non-immunologic factors is usually not possible using clinical parameters. The histopathologic findings of chronic allograft nephropathy are progressive interstitial fibrosis and remodelling of the vascular wall, and these findings are nonspecific. However, typical chronic transplant glomerulopathy, which affects glomerular tufts, as well as the multilayering of the peritubular capillary basement membrane, are characteristic of immunologic chronic rejection. Furthermore, in long-surviving patient with an allograft treated with a potent immunosuppressive agent, a calcineurin inhibitor, two or more concomitant independent lesions often develop. Therefore, the term "chronic allograft nephropathy" may be clinically preferable to "chronic rejection" to describe the gradual decline in graft function months or years after transplantation, in the absence of a well defined mechanism of graft dysfunction. The most effective way to prevent chronic allograft nephropathy is to avoid any kind of graft damage via either immunologic or non-immunologic mechanisms. Received: April 1, 2000 / Accepted: May 2, 2000     

Improvement in long-term graft survival in cadaveric renal transplant recipients treated with mycophenolate mofetil

Though mycophenolate mofetil has markedly reduced the incidence of acute rejection in renal transplantation, a significant improvement in graft survival has been more difficult to demonstrate. This retrospective study compares an historical control group of 210 consecutive renal transplant patients, who had received ATG induction associated with cyclosporin, prednisolone and azathioprine, with 187 patients receiving mycophenolate instead of azathioprine. The incidence of acute rejection was decreased with mycophenolate. In rejection-free patients, the 3-year graft survival rates were equivalent. In contrast, graft survival at 3 years improved significantly for patients who experienced a rejection crisis and remained under the initial triple drug regimen with mycophenolate compared to the patients of the historical group who were kept on azathioprine after a rejection episode. In conclusion, mycophenolate mofetil is not only able to reduce the incidence of acute rejection but could also improve the prognostic significance of acute rejection crises.     

移植肾间质中浸润细胞免疫标记蛋白的变化与急性细胞性排异的关系

观察移植肾发生急性细胞性排异（ＡＣＲ）和无ＡＣＲ时，肾间质浸润细胞中一组标记蛋白的变化，及其与间质浸润ＣＤ４或ＣＤ８细胞的关系。方法选择１７例肾移植患者，定期行移植肾活检，采用ＰＡＰ四层法对一组标记蛋白进行观察。结果无ＡＣＲ的肾组织中，增殖细胞核抗原（ＰＣＮＡ）和ＤＲ蛋白仅轻度增加，原癌蛋白２（Ｂｃｌ２）、ＩＬ２Ｒ和细胞间粘附分子１（ＩＣＡＭ１）的增加不明显。当移植肾出现ＡＣＲ时，上述标记蛋白均明显增加，尤以ＰＣＮＡ和ＩＬ２Ｒ增加最为显著，并与间质浸润的ＣＤ８密切相关。结论移植肾的免疫组化检查对移植肾急性细胞性排异反应有一定的意义；ＩＬ２Ｒ对于ＡＣＲ的诊断及鉴别诊断具有一定的临床应用价值。     

小剂量FK778对大鼠移植肾慢性排斥反应的预防作用

目的探讨小剂量FK778对大鼠移植肾慢性排斥反应的预防作用。方法应用显微外科技术制作移植肾慢性排斥反应大鼠模型，将肾移植大鼠分为两组。肾移植后第16周开始治疗组大鼠接受FK778每日5mg／kg体重灌胃，对照组接受赋形剂。移植后每4周行24h尿蛋白含量测定，第24周处死大鼠，对移植肾组织行组织学、免疫组织化学及实时定量RT—PCR检测。结果治疗组大鼠蛋白尿、肾组织病理损害程度，淋巴细胞和单核／巨噬细胞浸润程度和对照组比较显著减轻，肾组织生长因子TGF-β基因的表达也减少。结论小剂量FK778能预防大鼠移植肾慢性排斥反应。移植肾组织T淋巴细胞和单核／巨噬细胞浸润减轻，TGF-β生长因子基因表达的减少，可能是其预防同种移植肾慢性排斥反应机制中的重要环节。     

慢性移植肾肾病患者使用他克莫司联合麦考酚吗乙酯替代环孢素为基础的免疫抑制剂方案的疗效分析

目的探讨应用以环孢素(cyclosporine,CsA)为基础免疫抑制剂的慢性移植肾肾病(chronic allograft nephropathy,CAN)患者转换为他克莫司(tacrolimus,FK506)联合麦考酚吗乙酯(mycophenolate mofetil,MMF)治疗的疗效及安全性。方法使用CsA为基础免疫抑制方案的CAN患者76例,转换为FK506+MMF,随访6个月,根据移植肾穿刺病理结果将患者分为伴有慢性排斥反应组(CR组,41例)和不伴有慢性排斥反应组(non-CR组,35例)。观察两组的疗效及不良反应。结果 CR组好转27例(66%),稳定9例(22%),无效5例(12%);non-CR组好转11例(31%),稳定15例(43%),无效9例(26%),CR组疗效优于non-CR组(P0.05)。CR组和non-CR组转换后,24h尿蛋白定量均有所降低,高血压和高脂血症的病例数有所减少,而且未出现继发性高血糖、严重感染等不良反应。结论 CAN患者使用FK506+MMF替代CsA为基础的免疫抑制剂方案是安全有效的。     

Chronic renal allograft rejection: the significance of non-MHC alloantigens

We studied the role of polymorphic endothelial antigens other than MHC in antibody-mediated chronic renal allograft rejection in two models. In the first model, donor Lewis rat kidneys were transplanted into BN recipients that had been made tolerant for donor class I antigens at the B cell (antibody) level. In this setting Lewis kidney grafts were chronically rejected with stable renal function but increasing proteinuria (> 100 mg/24 h). Rejected graft tissue showed mononuclear cell infiltration and the presence of glomerular vasculonecrotic lesions with fibrinoid material, associated with IgG and IgM deposition, but with absent or weak C3 binding. Graft endothelium showed no expression of MHC class II antigens. Serum antibodies were not reactive with donor class I antigens, but did react with endothelial non-MHC alloantigens. In the second model, more direct information on the role of endothelial non-MHC alloantigens in renal allograft rejection was obtained by transplanting Lewis 1 N kidneys into unmodified BN recipients (MHC-matched transplants). Here, similar to the first model, the animals developed severe proteinuria with stable renal function. Histopathological examination showed mononuclear cell infiltration and deposition of IgM and IgG along the glomerular vasculature, but this time in the presence of strong C3 reactivity. However, glomerular vasculonecrotic lesions with intense fibrin deposition were not observed. The data showed that although clinically the two kidney transplantation models used gave similar chronic rejection phenomena, histopathologically some striking differences were observed in the glomeruli. The precise mechanisms effecting chronic rejection of the grafts is still a puzzle. However, immune reactivity against graft (endothelial) non-MHC antigens may play a significant role.     

Completely reversed acute rejection is not a significant risk factor for the development of chronic rejection in renal allograft recipients

Although acute rejection (AR) has been shown to correlate with decreased long-term renal allograft survival, we have noted AR in recipients who subsequently had stable function for more than 5 years. We reviewed 109 renal graft recipients with a minimum of 1 year graft survival and follow-up of 5–8 years. Post-transplant sodium iothalamate clearances (IoCl) measured at 3 months and yearly thereafter were used to separate recipients into 2 groups. In 61 patients (stable group), there was no significant decrease ( > 20 % reduction in IoCl over 2 consecutive years) in IoCl. Forty-eight patients had significant declines in IoCl (decline group). Groups were compared for incidence, severity, timing, and completeness of reversal of AR. Rejection was considered completely reversed if the post-AR serum creatinine (Scr) returned to or below the pre-AR nadir Scr after antirejection therapy. The incidence of AR was not significantly different between groups (47 % vs 52 %). A trend toward a lower mean number of AR episodes per patient was noted in the stable group (0.69 vs 1.04, P = 0.096), but the timing of AR was not different. Steroid-resistant AR occurred in approximately 25 % of both groups. A striking difference was seen in complete reversal of AR, with the stable group having 100 % (42/42 episodes of AR in 29 patients) complete reversal whereas only 32 % (8/25) of the patients in the decline group had complete reversal (P < < 0.001). Of 8 declining patients with complete reversal, graft loss was due to chronic rejection (CR) in only 3. Seventeen declining patients had incomplete reversal of AR, and 82 % (14/17) lost their grafts to CR. Overall, only 8 % (3/37) of the recipients with complete reversal of AR developed CR. No patients with incompletely reversed AR had stable long-term function as measured by IoCl. AR is not invariably deleterious to long-term renal graft function if each episode of AR can be completely reversed. Received: 9 March 1999/Revised: 28 December 2000/Accepted: 11 April 2000     

The increasing importance of chronic rejection as a cause of renal allograft failure

Abstract. A consequence of reducing early graft failure due to acute rejection has been that more patients are at risk of chronic rejection, something which has become an increasingly important cause of graft loss. We examine the graft survival rates and reasons for failure in our unit from 1981 to 1986. Patients were divided into two series according to treatment of acute rejection episodes. From 1983 onwards, by treating acute vascular (poor prognosis) episodes with antilymphocyte globulin (ALG), we have significantly improved the 6-month actuarial graft survival rate. However, the percentage of total graft failure due to chronic rejection in this second series has significantly increased. The need for greater understanding of the aetiology of chronic rejection, together with its present unsatisfactory treatment, is discussed.     

The increasing importance of chronic rejection as a cause of renal allograft failure

A consequence of reducing early graft failure due to acute rejection has been that more patients are at risk of chronic rejection, something which has become an increasingly important cause of graft loss. We examine the graft survival rates and reasons for failure in our unit from 1981 to 1986. Patients were divided into two series according to treatment of acute rejection episodes. From 1983 onwards, by treating acute vascular (poor prognosis) episodes with antilymphocyte globulin (ALG), we have significantly improved the 6-month actuarial graft survival rate. However, the percentage of total graft failure due to chronic rejection in this second series has significantly increased. The need for greater understanding of the aetiology of chronic rejection, together with its present unsatisfactory treatment, is discussed.     

Risk factors for chronic rejection in pediatric renal allograft recipients

To determine the risk factors predictive of graft loss from chronic rejection in pediatric renal allograft recipients, we reviewed the collaborative study database of the Société de Néphrologie Pédiatrique which registered 314 grafts from January 1987 to December 1991. Of the 289 grafts analyzed, 71 failed during follow-up, chronic rejection being the most common cause of graft loss (35%). The clinical features of the chronic rejection group (n = 25) were compared with those of the group without failure (n = 218). The variables tested by monovariate analysis were cyclosporine dose at 1 year, donor type, donor and recipient age, and acute rejection episodes. The incidence of graft loss due to chronic rejection was 4% (4/109) in patients who had no acute rejection and 16% (21/134) in those with at least one acute rejection episode (P = 0.002). Donor age (≤5 years) was a risk factor for chronic rejection (P = 0.024). Recipient age and donor type were not significantly different between the chronic rejection group and the control group. Using time-dependent covariates, the risk factors were an acute rejection episode (P = 0.003) and low cyclosporine doses at 1 year (P = 0.02). We conclude that acute rejection and low cyclosporine doses in these pediatric patients were risk factors for graft loss due to chronic rejection. Received 3 April 1995; received in revised form 28 December 1995; accepted 22 March 1996     

Effect of cyclosporin pharmacokinetics on renal allograft outcome in African-Americans

African-Americans (A-As) experience inferior outcome after transplantation compared with other ethnic groups. Bioavailability of cyclosporin (CsA) has been implicated as a possible contributing factor. This paper describes the outcome of 32 A-A recipients of de novo renal allograft who received CsA-based triple immunotherapy according to individual pharmacokinetic profiles. Patients received CsA-microemulsion q 12 h, dosed initially at 3.5 mg/kg (8 am) and 3.0 mg/kg (8 pm). The am and pm doses were independently adjusted to achieve a 12-h area under the concentration-time curve (AUC0-12) of 6600-7200 nghr/mL and morning trough level (C0) of 250-325 ng/mL, respectively. Mean age was 43 +/- 12 yr, 37% (12) female. Mean AUC0-12 in 1 wk, 1, 3, 6, and 12 months were 7810 +/- 1880 nghr/mL, 9057 +/- 2097 nghr/mL, 7674 +/- 1912 nghr/mL, 7132 +/- 2040 nghr/mL, and 6503 +/- 1410 ngl/h with corresponding C0 of 301 +/- 79 ng/mL, 316 +/- 66 ng/mL, 275 +/- 59 ng/mL, 273 +/- 66 ng/mL, and 224 +/- 49 ng/mL, respectively. Acute rejection occurred in two patients (6%) 1 yr after transplantation. Prospective use of CsA pharmocokinetic profiles improves renal allograft outcome in A-As.     

Risk factors for delayed graft function after renal transplantation and their significance for long-term clinical outcome

Abstract.Delayed graft function (DGF) remains a grieving complication after renal transplantation. In this study, we examined various factors related to organ donation, transport, and transplantation for their influence on the incidence of DGF and on long-term prognosis. The incidence of DGF, renal function after 5 years, and allograft survival were analyzed in 200 kidneys transplanted in Düsseldorf as well as in 193 partner kidneys transplanted at 43 other centers. The main risk factors for DGF were donor age, cold ischemia time (CIT) and organ shipment. DGF itself, as well as donor age, influenced the long term prognosis. A significant relationship between the partner organs regarding clinical outcome was demonstrated. Non-immunological factors strongly influence the clinical results after renal transplantation. Organs of older donors have a limited long-term prognosis. To minimize additional risks, prevention of DGF, especially by reducing CIT, should be regarded as of paramount importance.     

Risk factors for chronic rejection in pediatric renal transplant recipients – a single-center experience

Chronic rejection (CR) is the most common cause of graft loss beyond the 1st posttransplant year. The aim of this analysis was to identify the risk factors for the development of CR in pediatric renal transplant recipients. Between June 1984 and March 1994, 217 renal transplants were performed in children at our center. Immunosuppression included prednisone, azathioprine, cyclosporine (CsA), and prophylactic antibody. Using multivariate analysis, we studied the impact of the following variables on the development of biopsy-proven CR: age at transplant (≤5 years, >5 years), gender, race, transplant number (primary, retransplant), donor source (cadaver, living donor), donor age (<20 years, 20 – 49 years, >49 years), number of ABDR mismatches (0, 1 – 2, 3 – 4, 5 – 6), number of DR mismatches (0, 1, 2), percentage peak panel reactive antibody (PRA) (≤50%, >50%), percentage PRA at transplantation (≤50%, >50%), dialysis pretransplant, preservation time >24 h, acute tubular necrosis requiring dialysis, initial CsA dosage (≤5 mg/kg per day, >5 mg/kg per day), CsA dosage at 1 year posttransplant (≤5 mg/kg per day, >5 mg/kg per day), acute rejection (AR), number of AR episodes (ARE) (1, >1), timing of AR (≤6 months, >6 months), reversibility of AR (complete, partial), and infection [cytomegalovirus (CMV), non-CMV viral, bacterial]. Risk factors for the development of CR in pediatric renal transplant recipients were: AR (P <0.0001, odds ratio 19.4), multiple ARE (>1 vs. 1) (P <0.0001, odds ratio 30.1), and high percentage peak PRA (>50%) (P <0.03, odds ratio 3.6). Received December 21, 1995; received in revised form and accepted January 21, 1997     

Metabonomics research of acute renal graft rejection patients based on UPLC- qTOF-MS system

Objective Plasma phospholipid metabolism analysis was employed to investigate plasma metabolic profile of acute renal graft rejection in order to find potential disease biomarkers and reveal its pathophysiological changes. Methods Selected 33 patients which did renal transplant in our hospital during 2009 to 2010, named preoperative group. 14 patients were diagnosed as acute graft rejection, and 19 patients were non-acute graft rejection. Then use ultra performance liquid chromatography (UPLC) coupled with quadrupole time of flight mass spectrometry (qTOF-MS) to establish the metabolic fingerprint in those patients. The date was preprocessed with software Markerlynx, and analyzed with partial least squares discriminant analysis (PLS-DA), and data from conventional laboratory techniques were used for assessing renal function. Results In the plasma of renal transplant patients, seventeen biomarkers were discovered: creatinine, four sphingomyelins (SM), nine phosphatidylcholines (PC), three lysophosphatidylcholine (LPC). While the creatinine was increased, the others were reduced obviously. Conclutions UPLC-qTOF-MS based metabonomics can analyze the plasma phospholipid metabolism in patients with renal transplantation, reveal the law of phospholipids metabolic changes in the process of acute rejection. The levels of plasma phosphatidylcholine's esterlysis and fatty acids' β-oxidation are increased. The immunosuppressive therapy can reduce the activity of phospholipase, inhibit the level of plasma phosphatidylcholine's esterlysis and fatty acids' β-oxidation, which restraines the development of acute rejection after renal transplantation. Therefore it may be a promising new technology in diagnosing acute renal graft rejection after renal transplantation.     

Kimura disease in a patient with renal allograft failure secondary to chronic rejection

Recent studies suggest that CD4⁺ T helper 2 (Th2) cell proliferation and overexpression of Th2 cytokines may play an important role in the development of Kimura disease. Chronic rejection of a renal allograft by the indirect allorecognition pathway is also induced by Th2 cytokines. We report a 12-year-old boy who had presented with nephrotic syndrome 10 years previously. He was found to have focal segmental glomerulosclerosis, which was attributed to vesicoureteral reflux, and he underwent renal transplantation at the age of 5 years. Allograft dysfunction secondary to chronic rejection was noted by 2 years post transplant, after which continuous ambulatory peritoneal dialysis was instituted. After discontinuation of immunosuppressive therapy, he progressively developed peripheral eosinophilia and eczema, followed by cervical lymphadenopathy and then epitrochlear lymphadenopathy. Kimura disease was diagnosed on lymph node biopsy. Our patient demonstrated that Kimura disease can occur after renal allograft failure secondary to chronic rejection. Both disorders involve the Th2-dominant immune response, according to previous observations.     

Low serial serum neopterin does not predict low risk for chronic renal graft rejection

Research has provided new and potent immunosuppressants which can potentially stop ongoing rejection. Subclinical rejection is a particular problem in the pediatric age group and early identification of children at risk is of the utmost importance. Neopterin has been previously shown to be a non-specific but sensitive marker for immunologic activity. In this study we hypothesized that low serum neopterin in the 1st year after transplantation predicts a low risk of chronic rejection. We retrospectively analyzed serial neopterin data obtained beyond the early postoperative period in 21 children and correlated the peak and average with glomerular filtration rate (GFR) loss during the subsequent years (P=0.63, NS, r=0.10). Our results show that serum neopterin did not differ between the majority of children who developed chronic transplant dysfunction and children with stable transplant function beyond the early post-transplant period. Thus serum neopterin failed to delineate a low-risk population who might be spared more invasive diagnostic procedures such as protocol biopsy. Received: 22 November 1999 / Revised: 3 August 2000 / Accepted: 11 August 2000