Excellent Clinical Long-Term Outcomes of Kidney Transplantation From Small Pediatric Donors (Age ≤ 5 Years) Despite Early Hyperfiltration Injury.

Background: The use of small pediatric donors (age ≤ 5 years and body weight < 20kg) for adult transplant recipients is still regarded controversially in terms of early complications, long-term outcomes, and development of hyperfiltration injury due to body size mismatch. Objective: To investigate long-term outcomes of adult renal allograft recipients receiving a kidney from small pediatric donor (SPD) in terms of kidney function and early features of hyperfiltration injury such as histological changes and proteinuria. Design: Retrospective, single center study. Settings: Transplant center of the University Hospital of Basel, Switzerland. Patients: Adult renal allograft recipients receiving a kidney from a small pediatric donor at our center between 2005 and 2017. Methods: The outcome of 47 transplants from SPD were compared with 153 kidney transplants from deceased-standard criteria donors (SCD) occurring during the same time period. Incidence of clinical signs of hyperfiltration injury (eg, proteinuria) was investigated. According to our policy, surveillance biopsies were taken at 3 and 6 months post-transplant and were evaluated in terms of signs of hyperfiltration injury. Results: At a median follow-up of 2.3 years post-transplant, death-censored graft survival of SPD was comparable to transplants from SCD (94% vs 93%; P = .54). Furthermore, allograft function at last follow-up (estimated glomerular filtration rate-Modification of Diet in Renal Disease) was significantly higher in pediatric transplant (80 vs 55 ml/min/1.73 m2, P = .002). We found histological signs of early hyperfiltration injury in 55% of SPD. There was an equally low proteinuria in both groups during follow-up. Limitations: It is a single center and retrospective observational study with small sample size. The outcomes were investigated in a well-selected population of recipients with low body mass index, low immunological risk, and well-controlled hypertension and was not compared with equal selected group of recipients. Conclusions: Early histological and clinical signs of hyperfiltration injury in SPD is frequent. Despite the hyperfiltration injury, there is an equal allograft survival and even superior allograft function in SPD compared with SCD during follow-up. This observation supports the concept of high adaptive capacity of pediatric donor kidneys.

Contexte: Le recours à de très jeunes donneurs pédiatriques (âge: ≤ 5 ans; poids < 20 kg), pour des greffes chez des receveurs adultes, suscite encore des préoccupations quant aux complications précoces, aux résultats à long terme et au développement de lésions d'hyperfiltration liées à la disproportion de taille corporelle. Objectif: Examiner les résultats à long terme de patients adultes greffés rénaux ayant reçu l'organe d'un très jeune donneur pédiatrique (TJDP), soit la fonction rénale et les signes précoces de lésions d'hyperfiltration (p. ex. changements histologiques et protéinurie). Type d'étude: Étude rétrospective dans un seul établissement. Cadre: Le centre de transplantation de l'hôpital universitaire de Bâle (Suisse). Sujets: Les adultes ayant reçu une greffe rénale provenant d'un très jeune donneur pédiatrique dans notre centre entre 2005 et 2017. Méthodologie: Les résultats de 47 transplantations impliquant des TJDP ont été comparés à ceux de 153 transplantations rénales survenues au cours de la même période, mais impliquant des donneurs décédés répondant aux critères standard (DDCS). L'incidence des signes cliniques de lésions d'hyperfiltration (p. ex. protéinurie) a été étudiée. Selon notre politique, des biopsies de surveillance ont été réalisées à 3 et 6 mois post-transplantation et évaluées pour les signes d'hyperfiltration. Résultats: Lors d'un suivi médian de 2,3 ans post-transplantation, le pourcentage de survie du greffon (censurée pour les décès) provenant de TJDP était comparable à celui de DDCS (94 % c. 93 %; p = 0,54). De plus, la fonction du greffon lors du dernier suivi (DFGe basé sur l'équation MDRD) était significativement plus élevée dans les cas de transplantation pédiatrique (80 ml/min/1,73 m2 contre 55 ml/min/1,73 m2; p=0,002). Des signes histologiques de lésions précoces dues à une hyperfiltration ont été observés dans 55 % des cas impliquant un TJDP. La protéinurie était peu importante et équivalente dans les deux groupes au cours du suivi. Limites: Il s'agit d'une étude observationnelle et rétrospective menée dans un seul centre et sur un faible échantillon. Les résultats ont été obtenus dans une population bien précise de receveurs avec un IMC peu élevé, un risque immunologique faible et une hypertension bien contrôlée; ces résultats n'ont pas été comparés à un autre groupe de receveurs équivalents. Conclusion: Des signes histologiques et cliniques précoces de lésion d'hyperfiltration sont fréquents chez les TJDP. Malgré cela, pendant la période de suivi, la survie de greffon provenant d'un TJDP s'est avérée comparable à celles d'organes provenant de DDCS et la fonction supérieure. Cette observation appuie l'hypothèse d'une grande capacité d'adaptation des reins provenant de donneurs pédiatriques.

Early complications after living donor nephrectomy: analysis of the Swiss Organ Living Donor Health Registry.

BACKGROUND: We evaluated the prospectively collected data about the incidence of early peri- and postoperative complications, and potential risk factors for adverse outcomes after living kidney donation in Switzerland. METHODS: Peri- and postoperative events were prospectively recorded on a questionnaire by the local transplant teams of all Swiss transplant centres and evaluated by the Swiss Organ Living Donor Health Registry. Complications were classified according to the Clavien grading system. A total of 1649 consecutive donors between 1998 and 2015 were included in the analysis. RESULTS: There was no perioperative mortality observed. The overall complication rate was 13.5%. Major complications defined as Clavien ≥3 occurred in 2.1% of donors. Obesity was not associated with any complications. Donor age >70years was associated with major complications (odds ratio [OR] 3.99) and genitourinary complications (urinary tract infection OR 5.85; urinary retention OR 6.61). There were more major complications observed in donors with laparoscopic surgery versus open surgery (p = 0.048), but an equal overall complication rate (p = 0.094). CONCLUSION: We found a low rate of major and minor complications, independent of surgical technique, after living donor nephrectomy. There was no elevated complication rate in obese donors. In contrast, elderly donors >70 years had an elevated risk for perioperative complications.

Acute Rejection Phenotypes in the Current Era of Immunosuppression: A Single-Center Analysis.

BACKGROUND: Besides 'definitive rejection', the Banff classification includes categories for 'suspicious for rejection' phenotypes. The aim of this study was to determine the frequency and phenotypes of rejection episodes in 316 consecutive renal transplants from 2009 to 2014 grouped into patients without/with pretransplant HLA-DSA (ptDSAneg, n = 251; ptDSApos, n = 65). METHODS: All adequate indication (n = 125) and surveillance biopsies (n = 538) performed within the first year posttransplant were classified according to the current Banff criteria. RESULTS: 'Suspicious for rejection' phenotypes were 3 times more common than 'definitive rejection' phenotypes in biopsies from ptDSAneg patients (35% vs 11%) and equally common in biopsies from ptDSApos patients (25% vs 27%). In both groups, 'suspicious for rejection' phenotypes were more frequent in surveillance than in indication biopsies (28% vs 16% in ptDSAneg patients, and 37% vs 29% in ptDSApos patients). 'Borderline changes: 'Suspicious' for acute T-cell mediated rejection' (91%) were the dominant 'suspicious for rejection' phenotype in ptDSAneg patients, whereas 'borderline changes' (58%) and 'suspicious for acute/active antibody-mediated rejection' (42%) were equally frequent in biopsies from ptDSApos patients. Inclusion of 'suspicious for rejection' phenotypes increased the 1-year incidence of clinical (ptDSAneg patients: 18% vs 8%, P = 0.0005; ptDSApos patients: 24% vs 18%, P = 0.31) and (sub)clinical rejection (ptDSAneg patients: 59% vs 22%, P < 0.0001; ptDSApos patients: 68% vs 40%, P = 0.004). CONCLUSIONS: 'Suspicious for rejection' phenotypes are very common in the current era and outnumber the frequency of 'definitive rejection' within the first year posttransplant.

Mutational landscape of B-cell post-transplant lymphoproliferative disorders.

It is currently unclear whether post-transplant diffuse large B-cell lymphomas (PT-DLBCL) display a similar genomic landscape as DLBCL in immunocompetent patients (IC-DLBCL). We investigated 50 post-transplant lymphoproliferative disorders (PTLDs) including 37 PT-DLBCL samples for somatic mutations frequently observed in IC-DLBCL. Targeted Next Generation Sequencing (NGS) using the Ion Torrent platform and a customized panel of 68 genes was performed on genomic DNA. Non-tumoural tissue was sequenced to exclude germline variants in cases where available. A control cohort of 76 IC-DLBCL was available for comparative analyses. In comparison to IC-DLBCLs, PT-DLBCL showed more frequent mutations of TP53 (P = 0·004), and absence of ATM and B2M mutations (P = 0·004 and P = 0·016, respectively). In comparison to IC-DLBCLs, Epstein-Barr virus (EBV)+ PT-DLBCL had fewer mutated genes (P = 0·007) and particularly fewer mutations in nuclear factor-κB pathway-related genes (P = 0·044). TP53 mutations were more frequent in EBV- PT-DLBCL as compared to IC-DLBCL (P = 0·001). Germinal centre B cell (GCB) subtype of PT-DLBCL had fewer mutations and mutated genes than GCB-IC-DLBCLs (P = 0·048 and 0·04 respectively). Polymorphic PTLD displayed fewer mutations as compared to PT-DLBCL (P = 0·001). PT-DLBCL differs from IC-DLBCL with respect to mutations in genes related to DNA damage control and immune-surveillance, and EBV association is likely to have a bearing on the mutational pattern.

Comprehensive phenotypic characterization of PTLD reveals potential reliance on EBV or NF-κB signalling instead of B-cell receptor signalling.

Post-transplant lymphoproliferative disorders (PTLD) are a major problem in transplant medicine. So far, the insights into pathogenesis and potentially druggable pathways in PTLD remain scarce. We investigated a cohort of PTLD patients, consisting of both polymorphic (n = 3) and monomorphic (n = 19) B-cell lymphoproliferations. Several signalling pathways, cell of origin of PTLD and their relation to viruses were analysed by immunohistochemistry and in situ hybridization. Most PTLD were of activated B-cell origin. Two-thirds of cases showed an Epstein-Barr virus (EBV) infection of the neoplastic cells. NF-κB signalling components were present in the majority of cases, except for EBV-infected cases with latency type III lacking CD19 and upstream B-cell signalling constituents. Proteins involved in B-cell receptor signalling like Bruton tyrosine kinase were only present in a minority of cases. Phosphoinositide 3-kinase (PI3K) was expressed in 94% of cases and the druggable PI3K class 1 catalytic subunit p110 in 76%, while proteins of other signalling transduction pathways were expressed only in single cases. Unsupervised cluster analysis revealed three distinct subgroups: (i) related to EBV infection, mainly latency type III and mostly lacking CD19, upstream B-cell signalling and NF-κB constituents; (ii) mostly related to EBV infection with expression of the alternative NF-κB pathway compound RelB, CD10, and FOXP1 or MUM1; and finally, (iii) mostly unrelated to virus infection with expression of the classic NF-κB pathway compound p65. EBV and NF-κB are important drivers in PTLD in contrast to B-cell receptor signalling. The main signal transduction pathway is related to PI3K. This links PTLD to other subgroups of EBV-related lymphomas, highlighting also new potential treatment approaches. Copyright © 2016 John Wiley & Sons, Ltd.

Influence of IFNL3/4 polymorphisms on the incidence of cytomegalovirus infection after solid-organ transplantation.

BACKGROUND: Polymorphisms in IFNL3 and IFNL4, the genes encoding interferon λ3 and interferon λ4, respectively, have been associated with reduced hepatitis C virus clearance. We explored the role of such polymorphisms on the incidence of cytomegalovirus (CMV) infection in solid-organ transplant recipients. METHODS: White patients participating in the Swiss Transplant Cohort Study in 2008-2011 were included. A novel functional TT/-G polymorphism (rs368234815) in the CpG region upstream of IFNL3 was investigated. RESULTS: A total of 840 solid-organ transplant recipients at risk for CMV infection were included, among whom 373 (44%) received antiviral prophylaxis. The 12-month cumulative incidence of CMV replication and disease were 0.44 and 0.08 cases, respectively. Patient homozygous for the minor rs368234815 allele (-G/-G) tended to have a higher cumulative incidence of CMV replication (subdistribution hazard ratio [SHR], 1.30 [95% confidence interval {CI}, .97-1.74]; P = .07), compared with other patients (TT/TT or TT/-G). The association was significant among patients followed by a preemptive approach (SHR, 1.46 [95% CI, 1.01-2.12]; P = .047), especially in patients receiving an organ from a seropositive donor (SHR, 1.92 [95% CI, 1.30-2.85]; P = .001), but not among those who received antiviral prophylaxis (SHR, 1.13 [95% CI, .70-1.83]; P = .6). These associations remained significant in multivariate competing risk regression models. CONCLUSIONS: Polymorphisms in the IFNL3/4 region influence susceptibility to CMV replication in solid-organ transplant recipients, particularly in patients not receiving antiviral prophylaxis.

Guías Europeas sobre manejo y evaluación de receptores y donantes renales / European Renal Best Practice Guideline on the Management and Evaluation of the Kidney Donor and Recipient

El objetivo de esta Guía de Práctica Clínica es ofrecer orientación para la evaluación tanto del donante como del receptor del trasplante de riñón y para el manejo del receptor durante el periodo perioperatorio. Ha sido diseñada para informar y asistir en la toma de decisiones. En ningún caso pretende definir una norma asistencial ni su carácter debe concebirse como tal ni interpretarse como prescriptivo de un manejo exclusivo. La versión original de esta guía fue publicada en larevista Nephrology, Dialysis and Transplantation. Esta versión reducida pretende colaborar en la divulgación de esta guía en los países y comunidades trasplantadoras hispanohablantes (AU)

The purpose of this Clinical Practice Guideline is to provide guidance on evaluation of the kidney donor and transplant recipient as well as on the management of the recipient in the perioperative period. It is designed to provide information and aid decision-making. It is not intended to define a standard of care, and should neither be construed as one nor should it be interpreted as prescribing an exclusive course of management. The original version of this guideline was published in Nephrology, Dialysis and Transplantation and this current version is a reduced article aiming to disseminate the guideline into Spanish-speaking countries and transplant communities (AU)

European renal best practice guideline on the management and evaluation of the kidney donor and recipient.

The purpose of this Clinical Practice Guideline is to provide guidance on evaluation of the kidney donor and transplant recipient as well as on the management of the recipient in the perioperative period. It is designed to provide information and aid decision-making. It is not intended to define a standard of care, and should neither be construed as one nor should it be interpreted as prescribing an exclusive course of management. The original version of this guideline was published in Nephrology, Dialysis and Transplantation and this current version is a reduced article aiming to disseminate the guideline into Spanish-speaking countries and transplant communities.

A road map for patients with imminent end-stage renal disease.

Chronic kidney disease (CKD) represents a relevant medical and financial burden. More than 5% of the population suffers from CKD. There should be an accurately timed evaluation of best renal replacement therapy in all patients with CKD. Kidney transplantation is the treatment of choice for patients with end-stage renal disease. Living donated kidney transplantation offers the best results and should be evaluated in every patient suitable for transplantation. Haemodialysis and peritoneal dialysis are equally effective treatment options in patients not suitable for transplantation and should be individually evaluated. Conservative treatment, avoiding a dialysis treatment, can also be an option. Close cooperation of the general practitioner with a nephrologist improves patient management and helps to lower costs.

Repeat true surveillance biopsies in kidney transplantation.

BACKGROUND: Protocol biopsies are assigned to fixed points in time after transplantation irrespective of renal function. Usually, it is not known whether there is graft dysfunction at the time of biopsy. This study analyzes repeat protocol biopsies in the absence of any clinical signs of graft dysfunction at the time of biopsy (i.e., "true surveillance biopsy"). METHODS: Observational single center study. Kidney transplant recipients with protocol biopsies after 3 and 6 months were analyzed. RESULTS: Three hundred seventy patients had protocol biopsies after 3 and 6 months. One hundred forty-eight patients (40%; 296 biopsies) with a median follow-up of 3.4 years (range, 0.95-7.7 years), fulfilled the criteria of repeat true surveillance biopsies. Graft survival censored for death was 100% at 1 year, 96% at the end of follow-up. One hundred eighty-four biopsies (62%) revealed pathological findings, mainly subclinical rejection (3/6 months: 41% vs. 45%; P = 0.2) and chronic lesions (3/6 months: 22% vs. 44%; P<0.001). Grafts with repeat pathological findings at 3 and 6 months had a significant decline in graft function at end of follow-up compared with grafts with no or only singular pathology (median delta estimated glomerular filtration rate: -10.24 vs. -0.19; P = 0.005). Ninety-three of 148 patients (63%) had a therapeutic intervention as a consequence of the biopsy. CONCLUSIONS: Less than 50% of protocol biopsies were performed in the absence of any clinical signs of graft dysfunction. A high proportion of these biopsies revealed pathological findings that were associated with a significant decrease in long-term graft function.

Morbidity and mortality on chronic haemodialysis: a 10-year Swiss single centre analysis.

BACKGROUND: Patient survival on chronic haemodialysis varies considerably among different countries and healthcare systems. To date, the survival of Swiss dialysis patients has not been analysed separately. METHODS: We consecutively enrolled 266 patients entering the chronic haemodialysis program of the University Hospital Basel between 01.01.1995 and 30.06.2006 into a cohort study. Patient survival on chronic haemodialysis was the primary endpoint. Pre-specified sub-group analyses were performed for female and diabetic patients. RESULTS: Patient age ranged from 15 to 90 years. Seventy-two percent suffered either from coronary artery, peripheral artery or cerebrovascular disease and 34% from diabetes. Sixty-nine (26%) patients underwent kidney transplantation. Transplanted patients were significantly younger (p <0.01) and less likely to suffer from diabetes (p <0.01) and atherosclerotic diseases (coronary, peripheral, cerebrovascular p for all ≤0.01). Median survival was 4.25 years (95%CI 3.66-5.50), with one, three and five year survival rates reaching 88%, 68% and 46%. Survival rates were equal in men and women (p = 0.34), among diabetic and non-diabetic patients (p = 0.41) and among men and women stratified for the presence of diabetes (p = 0.13). Overall, 34% (91/266) patients died during the observational period. Thirty three percent of all deaths were caused by cardiac events, followed by malignant diseases (8%) and infections (7%). In 9% (23/266) dialysis was withdrawn and withdrawal of dialysis contributed to death in 25% (23/91). CONCLUSION: Survival on chronic haemodialysis treatment in Switzerland compares favourably to international reference values. Dialysis withdrawal and the frequency of kidney transplantation impact long term patient outcome and should be adjusted for when comparing mortality analysis.

Silent recovery of native kidney function after transplantation in a patient with membranous nephropathy.

Recurrence of membranous nephropathy (MN) is frequently seen after transplantation. However, there are no published data about the course of MN in the native kidneys after transplantation. Disease progression in almost all cases is assumed to be the 'natural' course after transplantation. We report on a patient suffering from end-stage renal disease due to MN. Eight years after transplantation, nephrectomy was performed due to chronic rejection and unexpectedly, partial recovery of native kidney function was noted. As far as we know, there is no other similar case reported in the literature. The potential impact of the immunosuppression, especially of calcineurin inhibitors, is discussed.

ABO blood group-incompatible living donor kidney transplantation: a prospective, single-centre analysis including serial protocol biopsies.

BACKGROUND: ABO incompatible kidney transplantation using antigen-specific immunoadsorption is increasingly performed but data on outcome, complications and protocol biopsies are still scarce. The present prospective single-centre study was aimed at these issues. METHODS: This was a prospective single-centre cohort study of 10 successive ABO incompatible living donor kidney transplantations at the University Hospital Basel from September 2005 to October 2007. The following parameters were closely monitored during the whole follow-up: graft function, albuminuria, blood group antibody titres, CD19+ cell count, total IgG and IgG subclasses, CMV antigenaemia, decoy cells in the urine, EBV and polyoma BK virus PCR in the blood. Protocol biopsies were performed on Days 0 and 7 after 3, 6, 12 and 18 months. RESULTS: Patient and graft survival is 100% after a median follow-up of 489 days (range 183-916 days). Median serum creatinine is 137 micromol/l (range 70-215 micromol/l), and median urine albumin-creatinine ratio (UACR) is 3.1 mg/ mmol (range 0.6-7.8 mg/mmol) at the time of the last follow-up. All patients had sustained diminished CD19+ cell count and/or total IgG concentrations. Neither CMV antigenaemia nor EBV replication in the blood was observed. Seven patients had positive polyoma BK virus replication in the blood but none developed polyoma virus-associated nephropathy (PVAN). Protocol biopsies revealed rejection Banff IIa in three patients on Day 7, and in one patient after 3 and 6 months. Banff Ia rejection was found in five patients. All rejection episodes resolved. Mild signs of chronic antibody-mediated rejection were observed in five patients. CONCLUSIONS: ABO-incompatible kidney transplantation seems to be successful and safe. Modifications of the current protocol may be possible and may further reduce potential side effects and costs.

Comparison of CT angiography with MR angiography in the preoperative assessment of living kidney donors.

BACKGROUND: The aim of the study was to prospectively compare the diagnostic performance of CT angiography (CTA) with MR angiography (MRA) in the preoperative assessment of living renal donors. METHODS: Forty-eight potential living renal donors (mean 51 years, 29-67 years) underwent multislice CTA and gadolinium-enhanced MRA. Six potential donors were excluded. Forty-two donors underwent minimal invasive retroperitoneoscopic nephrectomy (left 36, right 6) and their datasets available for analysis independently performed by two blinded radiologists. The surgical status served as gold standard. RESULTS: In 42 donors (84 kidneys), CTA identified 63 kidneys with 1 artery (MRI 61), 19 with 2 arteries (MRI 20), one with three arteries (MRI 2), and one with four arteries (MRI 1). Considering only the side with the surgical status available for verification, both CT and MRI correctly characterized 35 of 36 donors with a single renal artery and five of six with one supernumerary artery. Two false positives were two arteries suggested as supernumerary both in CT and MRI not confirmed during surgery. CTA and MRA both correctly identified three accessory renal veins in two donors. CONCLUSION: CTA and MRA had the same accuracy for characterization of renal vasculature in the preoperative assessment of living renal donors.

Cytomegalovirus-specific T-cell responses and viral replication in kidney transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) seronegative recipients (R-) of kidney transplants (KT) from seropositive donors (D+) are at higher risk for CMV replication and ganciclovir(GCV)-resistance than CMV R(+). We hypothesized that low CMV-specific T-cell responses are associated with increased risk of CMV replication in R(+)-patients with D(+) or D(-) donors. METHODS: We prospectively evaluated 73 consecutive KT-patients [48 R(+), 25 D(+)R(-)] undergoing routine testing for CMV replication as part of a preemptive strategy. We compared CMV-specific interferon-gamma (IFN-gamma) responses of CD4+CD3+ lymphocytes in peripheral blood mononuclear cells (PBMC) using three different antigen preparation (CMV-lysate, pp72- and pp65-overlapping peptide pools) using intracellular cytokine staining and flow cytometry. RESULTS: Median CD4+ and CD8+T-cell responses to CMV-lysate, pp72- and pp65-overlapping peptide pools were lower in D(+)R(-) than in R(+)patients or in non-immunosuppressed donors. Comparing subpopulations we found that CMV-lysate favored CD4+- over CD8+-responses, whereas the reverse was observed for pp72, while pp65-CD4+- and -CD8+-responses were similar. Concurrent CMV replication in R(+)-patients was associated with significantly lower T-cell responses (pp65 median CD4+ 0.00% vs. 0.03%, p = 0.001; CD8+ 0.01% vs. 0.03%; p = 0.033). Receiver operated curve analysis associated CMV-pp65 CD4+ responses of > 0.03% in R(+)-patients with absence of concurrent (p = 0.003) and future CMV replication in the following 8 weeks (p = 0.036). GCV-resistant CMV replication occurred in 3 R(+)-patients (6.3%) with pp65- CD4+ frequencies < 0.03% (p = 0.041). CONCLUSION: The data suggest that pp65-specific CD4+ T-cells might be useful to identify R(+)-patients at increased risk of CMV replication. Provided further corroborating evidence, CMV-pp65 CD4+ responses above 0.03% in PBMCs of KT patients under stable immunosuppression are associated with lower risk of concurrent and future CMV replication during the following 8 weeks.

Contribution of early failure to outcome on peritoneal dialysis.

BACKGROUND: The technique failure rate on peritoneal dialysis (PD) remains high despite technical progress. There are no data concerning the contribution of early failure to outcome on PD. AIM: To analyze the importance of early treatment failure in PD and to compare early with late failures with respect to reasons and predictors of risk for failure. METHODS: We performed a retrospective study of all patients admitted for PD from October 1983 to June 2005. The end point was PD failure-free survival. Differences between reasons for failure with respect to early (within 6 months) and late failure were analyzed. Multivariate associations of baseline covariates with early and late failure were investigated. RESULTS: We included 279 patients. 153 (55%) patients experienced PD failure: 97 (63%) of them had technique failure; 56 (37%) patients died due to non-PD-related causes. 29% (n = 44) of all PD failures and 40% (n = 39) of all technique failures occurred within 6 months. Catheter and psychosocial problems contributed more often to early than to late failure, whereas infections, leakages, and hernias contributed equally to early and late failure. Death was the predominant reason for late failure. Female sex was a risk factor for early failure and older age a risk factor for late failure. Higher cholesterol levels were associated with a decreased risk for both early and late failure. CONCLUSION: The contribution of early failure to outcome on PD is important, as one third of all PD failures and 40% of all technique failures may occur within the first 6 months, as shown in our study. Due to the retrospective nature and the single-center character, the results cannot be generalized. However, it is important to enhance recognition of patients at high risk for early PD failure prior to initiation of PD, in order to avoid unnecessary surgical interventions and medical complications, and for rational resource allocation.

Pulmonary infections diagnosed by BAL: a 12-year experience in 1066 immunocompromised patients.

Bronchoalveolar lavage (BAL) is a useful tool in the diagnosis of pulmonary infections in immunocompromised patients. We aimed to compare the spectrum of infectious pulmonary complications diagnosed using BAL in a large consecutive cohort of immunocompromised patients. The diagnostic yield of 1066 BAL specimens was analyzed in 4 different groups of immunocompromised patients (HIV; solid organ transplants; high-dose chemotherapy and/or stem cell transplants; other immunosuppressive therapy) suffering from fever, respiratory symptoms and/or infiltrates on chest X-ray. Specimens were analyzed for bacteria, mycobacteria, fungi, Pneumocystis jiroveci, cytomegalovirus (CMV) and other viruses. Two time periods were compared (1992-1996; 1997-2003). The overall diagnostic yield of BAL was 34% for bacteria, 22% for CMV, 15% for P. jiroveci, 6% for other viruses, 6% for mycobacteria and 2% for aspergillus. There were significant changes in the pattern of opportunistic infections between the 2 time periods. Mycobacterial infections decreased considerably in the HIV group (17.9 vs. 8.5%, P=0.02), while the incidence of P. jiroveci decreased mainly in the transplant group (32.6 vs. 7.9%, P<0.00001). This study demonstrates a changed pattern of pulmonary infections in immunocompromised patients diagnosed by BAL. The overall diagnostic yield of BAL remains high in immunocompromised patients with respiratory symptoms.

Polyomavirus-associated nephropathy in renal transplantation: critical issues of screening and management.

Polyomavirus-associated nephropathy (PVAN) is an emerging disease in renal transplant patients with variable prevalence of 1-10% and graft loss up to 80%. BK virus (BKV) is the primary etiologic agent, but JC virus (JCV) and possibly simian virus SV40 may account for some cases. Intense immunosuppression is viewed as the most important risk factor. However, the preferential manifestation in renal transplants as compared to other allografts or to autologous kidneys of other organ transplants suggests that organ determinants and immunologic factors synergize: Renal tubular epithelial cells and their compensatory proliferation to restore tubular integrity after immunologic, ischemic or toxic injury may provide the critical cellular milieu supporting polyomavirus replication while immune control is impaired due to maintenance immunosuppression, anti-rejection treatment and HLA-mismatches. Patient determinants (older age, male gender, seronegative recipient), and viral factors (genotype, serotype) may have a contributory role. The definitive diagnosis of PVAN requires allograft biopsy which is, however, challenged by (i) limited sensitivity due to (multi-)focal involvement (sampling errors); (ii) varying presentations with cytopathic-inflammatory and/or fibrotic/scarring patterns; (iii) coexisting acute rejection which is difficult to differentiate, but impacts on intervention strategies. Screening for polyomavirus replication in the urine and in the plasma complements allograft biopsy by high sensitivity and allows for noninvasive monitoring. Thus, we suggest a terminology similar to invasive fungal diseases where viruria ("decoy cells") defines patients at risk ("possible PVAN") who should be evaluated for plasma viral load. Increasing BK viremia (>10,000 copies/mL) or urine VP-1 mRNA (>6.5x10(5) copies/ng total RNA) load defines "presumptive PVAN" for which an intervention of reducing immunosuppression should be considered even if the diagnosis could not be confirmed by allograft biopsy ("definitive PVAN"). The response to intervention should be monitored using plasma DNA or urine mRNA load.

Polyomavirus-associated nephropathy in renal transplantation: interdisciplinary analyses and recommendations.

Polyomavirus-associated nephropathy (PVAN) is an emerging cause of kidney transplant failure affecting 1-10% of patients. As uncertainty exists regarding risk factors, diagnosis, and intervention, an independent panel of experts reviewed the currently available evidence and prepared this report. Most cases of PVAN are elicited by BK virus (BKV) in the context of intense immunosuppression. No specific immunosuppressive drug is exclusively associated with PVAN, but most cases reported to date arise while the patient is on triple immunosuppressive combinations, often comprising tacrolimus and/or mycophenolate mofetil plus corticosteroids. Immunologic control of polyomavirus replication can be achieved by reducing, switching, and/or discontinuing components of the immunosuppressive regimen, but the individual's risk of rejection should be considered. The success rate of this intervention is increased with earlier diagnosis. Therefore, it is recommended that all renal transplant recipients should be screened for BKV replication in the urine: 1) every three months during the first two years posttransplant; 2) when allograft dysfunction is noted; and 3) when allograft biopsy is performed. A positive screening result should be confirmed in <4 weeks and assessed by quantitative assays (e.g. BKV DNA or RNA load in plasma or urine). Definitive diagnosis of PVAN requires allograft biopsy. If PVAN and concurrent acute rejection is diagnosed, antirejection treatment should be considered, coupled with subsequently reducing immunosuppression. The antiviral cidofovir is not approved for PVAN, but investigational use at low doses (0.25-0.33 mg/kg intravenously biweekly) without probenicid should be considered for refractory cases. Retransplantation after renal allograft loss to PVAN remains a treatment option for patients clearing polyomavirus replication.