Post-transplant Glomerulonephritis Research Articles

Incidence, Risk Factors, and Effect on Allograft Survival of Glomerulonephritis Post-transplantation in a United Kingdom Population: Cohort Study.

Post-transplant glomerulonephritis (PTGN) has been associated with inferior long-term allograft survival, and its incidence varies widely in the literature. This is a cohort study of 7,623 patients transplanted between 2005 and 2016 at four major transplant UK centres. The diagnosis of glomerulonephritis (GN) in the allograft was extracted from histology reports aided by the use of text-mining software. The incidence of the four most common GN post-transplantation was calculated, and the risk factors for disease and allograft outcomes were analyzed. In total, 214 patients (2.8%) presented with PTGN. IgA nephropathy (IgAN), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), and membranoproliferative/mesangiocapillary GN (MPGN/MCGN) were the four most common forms of post-transplant GN. Living donation, HLA DR match, mixed race, and other ethnic minority groups were associated with an increased risk of developing a PTGN. Patients with PTGN showed a similar allograft survival to those without in the first 8 years of post-transplantation, but the results suggest that they do less well after that timepoint. IgAN was associated with the best allograft survival and FSGS with the worst allograft survival. PTGN has an important impact on long-term allograft survival. Significant challenges can be encountered when attempting to analyze large-scale data involving unstructured or complex data points, and the use of computational analysis can assist.

P1670GLOMERULAR C4D IN POST-TRANSPLANT IG-A GLOMERULONEPHRITIS IS ASSOCIATED WITH DECREASED ALLOGRAFT SURVIVAL

Abstract Background and Aims Post transplant (pTX) glomerulonephritis (GN) is an important factor contributing to early and late allograft failure. De novo or recurrent IgA GN are the most frequent pTX-GN forms, however little is known about the optimal risk and therapeutic assessment. Recently, immunopathological evidence of glomerular C4d staining has been suggested as a prognostic tool in native glomerular kidney disease, in particular IgA GN. While peritubular capillary C4d is an accepted diagnostic criterion for antibody mediated rejection (ABMR), the role of glomerular C4d in pTX-GN is unkown. The primary hypothesis was that the finding of immunohistochemical glomerular C4d may be associated renal graft survival in post TX IgA GN. Method This large retrospective cohort study included all indication biopsies performed for cause in 885 kidney allografts from 1999-2006. Cases were screened for biopsy verified de novo or recurrent pTX-GN. GN cases were re-assessed by a single nephropathologist (NK). Primary endpoint was death-sensored graft survival followed until 01.01.2017. Results The prevalence of pTX-GN was 9.6% (n=85/885). De novo or recurrent IgA-GN was the most common pTX GN form with 40%. Of the 34 cases with pTX IgA GN, 27 had adequate material for interpretation of immunohistochemical glomerular C4d in the biopsy specimen. Eighteen of the 27 cases (66%) with pTx-IgA GN showed positive immunohistochemical C4d staining along glomerular capillary walls. There was no difference in renal function at biopsy or after one year comparing glomerular C4d positive vs. C4d negative pTX IgA GN. In univariate KM analysis glomerular C4d positive pTX-IgA GN showed significantly worse renal allograft survival rates (28%) compared to glomerular C4d negative pTX IgA GN (50%) or cases without GN (66%), p<0.001, respectively. In a multivariate Cox-Regression analysis including baseline covariates as well C4d+ABMR, Borderline lesion and TCMR, C4d+pTX IgA-GN remained independently associated with death censored graft-loss (HR 2.92, 95% CI 1.51-5.64, p=0.001). Conclusion Glomerular C4d staining in post transplant IgA glomerulonephritis is an independent risk factor for worse allograft survival and may provide a valuable risk assessment tool for prognostic and therapeutic decisions in post transplant glomerulonephritis.

Recurrent glomerulonephritis following renal transplantation and impact on graft survival

BackgroundRecurrence of primary glomerulonephritis in the post-transplant period has been described in the literature but the risk remains poorly quantified and its impact on allograft outcomes and implications for subsequent transplants remain under-examined. Here we describe the rates and timing of post-transplant glomerulonephritis recurrence for IgA nephropathy, focal segmental glomerulosclerosis, mesangiocapillary GN and membranous GN based on 28 years of ANZDATA registry transplant data.MethodsWe investigated the rates of GN recurrence and subsequent graft outcomes in 7236 patient from 28 years of ANZDATA transplant registry data. Data were analysed in R, using Kaplan Meier Survival analysis and adjusted analyses performed using Cox Proportional Hazards methods. A competing risk model was also analysed.ResultsGN recurrence occurred in 10.5% of transplants and was most common in mesangiocapillary GN. Median time to recurrence was shorter for FSGS compared to IGAN. GN recurrence was less common in patients over 50 years of age and after unrelated kidney donation. We identified a significantly higher risk of recurrence in secondary grafts following recurrence in a primary allograft for FSGS (RR 5.70, 95 CI: 2.41–13.5, p < 0.001) but not IGAN, MCGN or MN. At 10 years, recurrence occurs in 8.7, 10.8, 13.1, and 13.4% of allografts for FSGS, IGAN, MCGN and MN respectively. In all GN, recurrence significantly reduced death censored graft survival at 5 and 10 years.ConclusionsGN recurrence occurs in a minority of patients at a significantly different rate for each GN. After a recurrence, there is no evidence for an increased risk of further recurrence in a subsequent graft except in FSGS.

Hepatitis C virus infection in kidney transplantation-changing paradigms with novel agents.

Hepatitis C virus (HCV) is a common cause of increased morbidity and mortality in kidney transplant patients. It is associated with posttransplant glomerulonephritis, chronic allograft nephropathy, and New Onset Diabetes after Transplant (NODAT). In the past, HCV was difficult to treat due to the presence of interferon alpha-based therapies that were difficult to tolerate and were associated with adverse side-effects, such as the risk of rejection. With the advent of oral directly acting antiviral therapies, the landscape for HCV and transplantation has changed. These agents are highly effective and well tolerated with minimal side-effects. Sustained viral response rates in excess of 90% are achieved with most current treatment regimens active against all HCV genotypes. These new agents may show an improvement in graft and patient survival while essentially eliminating the risk of acute rejection from the use of prior interferon-based HCV therapies. These agents may also result in an improvement in organ allocation for HCV donor/HCV recipient transplantation. This review is meant to discuss the epidemiology of HCV, the new oral direct-acting antiviral agents (DAAs) and future opportunities for research in the field of HCV related transplantation.

Early Focal Segmental Glomerulosclerosis as a Cause of Delayed Graft Function With Combined Acute Antibody Rejection: A Case Report

Focal segmental glomerulosclerosis (FSGS) is the most common form of post-transplant glomerulonephritis. We describe a case where a biopsy proved that early recurrence of FSGS on postoperative day 1 was the cause of delayed graft function. A 39-year-old man, on hemodialysis for 15 years due to polycystic kidney disease, received a cadaveric renal transplantation. On postoperative day 1, his hourly urine output decreased from 700–800 mL to 50 mL. The graft biopsy showed a mild acute kidney injury confusing nephrotic syndrome. On postoperative day 45, his creatinine level increased to 3.02 mg/dL with severe proteinuria. A kidney biopsy showed focal segmental glomerulosclerosis. On postoperative day 120, his creatinine level elevated again, concomitant with proteinuria. A kidney biopsy showed FSGS with antibody-mediated rejection. After plasmapheresis, his creatinine level decreased to 1.3 mg/dL with mild proteinuria. Once active in the allograft, de novo FSGS is a potentially aggressive process. In this case, it could be managed because of an accurate diagnosis and appropriate treatment.

Higher Incidence of Renal Allograft Glomerulonephritis in Living-Related Donor Kidney Transplantation

Glomerulonephritis recurrence has emerged as one of the leading causes of allograft loss. We aimed to investigate the effect of living-related and deceased donation on the incidence of renal allograft glomerulonephritis and its effect on renal allograft survival. MethodsAdult renal allograft recipients with primary glomerulonephritis were enrolled. Transplantation date was from Feb 2004 to Dec 2015. Exclusion criteria included combined organ transplantation, structural abnormality, diabetic nephropathy, hypertension nephropathy, obstructive nephropathy, and primary uric acid nephropathy. The incidence of biopsy-proven allograft glomerulonephritis was compared between the living-related donor group and the deceased donor group. Graft survival was assessed with Kaplan-Meier method, and Cox proportional hazard model was used to evaluate the effect of posttransplant glomerulonephritis on graft outcome. ResultsThere were 525 living-related donor kidney transplant recipients (LRKTx) and 456 deceased donor kidney transplant recipients (DDKTx) enrolled. The incidence of IgA nephropathy was 8.8% in the LRKTx group and 1.3% in the DDKTx group (P < .001); the incidence of focal segmental glomerulosclerosis (FSGS) was 3.8% in the LRKTx group and 1.5% in the DDKTx group (P = .03). FSGS increased the risk of graft failure compared with non-FSGS (hazard ratio [HR], 3.703 [1.459–9.397]; P = .006). IgA nephropathy increased the risk of graft failure by over 5 times 5 years after kidney transplantation compared with non-IgA nephropathy, but it did not affect early allograft survival (HR for ≥5 years, 6.139; 95% CI, 1.766–21.345; P = .004; HR for <5 years, 0.385 [0.053–2.814]; P = .35). ConclusionsHigher incidence of IgA nephropathy and FSGS in renal allograft was observed in living-related donor kidney transplantation compared with deceased donor kidney transplantation. De novo or recurrent IgA nephropathy and FSGS impaired long-term renal allograft survival.

Recurrent and de novo glomerulonephritis following renal transplantation: higher rates of rejection and lower graft survival.

In this retrospective study with case-control design, we aimed to determine the clinical and pathological characteristics of post-transplant glomerulonephritis (GN), and their effects on transplant recipients. One hundred and twenty renal transplant recipients with biopsy-proven recurrent or de novo primary GN were compared with two matched control groups including 120 transplant recipients with nonrecurrent primary GN (nonrecurrent GN group) and 120 transplant recipients with non-GN etiology (non-GN group). Primary outcome was allograft loss, and secondary outcomes were biopsy-confirmed cellular or antibody-mediated rejection. In recurrent/de novo GN, nonrecurrent GN and non-GN groups, 54.2% (n=65), 16.7% (n=20) and 8.3% (n=10) of patients reached primary outcome after a median follow-up of 96 (IQR: 56-149) months, respectively. Allograft loss was significantly higher in recurrent/de novo GN group compared to nonrecurrent GN and non-GN groups (p<0.001). At 10years, allograft loss rates in recurrent/de novo GN group were 54.2% for focal segmental glomerulosclerosis, 53.2% for membranoproliferative glomerulonephritis, and 33.4% for IgA nephropathy cases. Biopsy-confirmed rejection rate was significantly higher in the recurrent/de novo GN group (n=25, 20.8%) compared to non-GN (n=8, 6.7%) group (p=0.001). Recurrent/de novo GN is associated with higher risk of rejection and worse allograft survival.

Immunoglobulin A (IgA) Nephropathy in Protocol Graft Kidney Biopsy done at six months Post Transplantation in a Tertiary Care Center Hospital of Nepal

Background: Renal transplantation is the treatment of choice for end stage renal disease. The focus of interest has been to increase the life of the transplanted graft. Recurrence of native kidney disease or occurrence of denovo glomerulonephritis has adverse effects in graft survival. Protocol graft biopsy done at fixed time interval after transplantation aids in early identification of post-transplant glomerulonephritis before development of clinical signs and symptoms. This study describes the incidence of post-transplant IgA Nephropathy in protocol renal graft biopsies done at six months post- transplantation.Materials and Methods: This is a hospital based observational descriptive study, done in Tribhuvan University Teaching Hospital, Kathmandu, Nepal, a tertiary medical referral center in the capital. Protocol biopsy of the graft kidney was performed at six months post-transplantation in all recipients who underwent kidney transplantation in this hospital between 2071 Kartik and 2072 Ashwin.Results: Protocol biopsy was performed in total 47 recipients. Mean age of the recipients was 33.7 years ±10.83 years. The study population consisted of 33 (70.2%) male and 14 (29.8%) female recipients. IgA Nephropathy was present in 6 (12.8%) recipients.Conclusion: Our study demonstrates that IgA Nephropathy does occur in patients with stable GFR and without any clinical or laboratory abnormalities. Protocol biopsy is valuable in detection of early histologic abnormalities before onset of clinical manifestations, thus helping in prompt management with aim to prolong the graft survival.Journal of Nobel Medical CollegeVolume 6, Number 1, Issue 10 (January-June, 2017)

Alemtuzumab Induction and Post-Transplant Glomerulonephritis in Kidney Transplantation.

Background: The incidence and nature of Post-Transplant Glomerulonephritis (PTGN) in patients receiving Alemtuzumab induction has been rarely reported. In this study we investigate the incidence of PTGN and its effect on outcomes in kidney transplant recipients receiving a steroid sparing immunosuppressive regime with Alemtuzumab induction. Methods: We retrospectively reviewed the medical records of 848 (544 male, mean age 48.4 +/- 13.3 years) kidney transplant recipients in our centre between November 2005 and June 2013 for the occurrence of PTGN. All the patients received a steroid sparing immunosuppressive regime with Alemtuzumab induction and tacrolimus monotherapy. Steroids and MMF were only introduced to treat rejection. Results: 66 out of 848 patients (7.8%) developed biopsy proven PTGN. A male predominance was found in the PTGN group (9.56% male vs 4.8% female, p=0.01), while PTGN was found not to be related to ethnicity (p=0.404), or donor type (p=0.167). Mean follow up of PTGN patients was 40.3 (+24.5) months and mean time from transplantation to diagnosis was 20.4 (+20.2) months. Out of 66 PTGN patients, 16(1.9%) were diagnosed with Focal Segmental Glomerulosclerosis (FSGS), 37(4.4%) IgA Nephropathy (IGAN), 2(0.2%) Lupus nephritis(LN), 3(0.4%) Membranous Nephropathy (MN) and 8(0.9%) with other PTGN's.Table: No Caption available.There was no difference in patient survival between the PTGN and the non-PTGN groups at 1 (98.4 vs 97.8%) and 3 years (96.7% vs 94.3%) post transplantation. (p=0.2) Censored allograft survival did not differ between the 2 groups (95.6% and 91.1% in the PTGN vs. 100% and 88.3% in the non-PTGN group at 1 and 3 years; p=0.11). When stratified according to diagnosis, censored allograft survival was found to be lower in the patients diagnosed with FSGS (100% and 67.3% at 1 and 5 years) when compared to the non-PTGN group (95.6% and 87.1%% at 1 and 5 years). (p=0.02) Conclusion: Although these are medium term data, the incidence of PTGN in patients receiving Alemtuzumab induction appears similar to other induction agents. Post-transplant FSGS is associated with a poor prognosis and we are developing new strategies to deal with this problem.

Post-Transplant Glomerulonephritis Has a Molecular Behavior of Antibody Mediated Rejection.

Post-transplant glomerulonephritis (GN) is a common cause of kidney transplant failure. We studied conventional and molecular features in 69 biopsies diagnosed as GN from 62 patients, identified in prospective studies of 703 unselected indication biopsies from 562 kidney transplants. We grouped these biopsies as 19 IgAN, seven FSGS, four MGN, seven MPGN, 10 proliferative GN, and 22 that were not considered classifiable by the pathologist. Using the microarray-based molecular microscope system, we studied transcript sets and molecular scores, particularly the Acute Kidney Injury (AKI) Score and the Antibody-Mediated Rejection (ABMR) Score. GN biopsies had molecular abnormalities, generally intermediate between ABMR and normal transplants, and were not related to the GN type. In biopsies with GN, the AKI and ABMR Scores in multivariable analysis were independent predictors of failure, and both correlated with histologic scarring and reduced GFR. High ABMR Scores in GN also correlated with cg and g lesions. Positive ABMR Scores in some biopsies with a histologic diagnosis of GN could reflect two diseases (ABMR plus GN), ABMR-like mechanisms in some GN, or mistaken diagnosis of GN in ABMR. GN biopsies with high ABMR score had a worse graft survival than the others.Figure: No Caption available.The strong association of molecular scores such as the AKI Score with outcomes in post transplant GN provides new prognostic insight, and suggests potential for application of molecular methods in primary GN. DISCLOSURE:Halloran, P.: Speaker’s Bureau, Astellas, Novartis, OneLamba.

Outcomes of kidney allograft in recipients with kidney disease of unknown etiology

The etiology of renal disease is important because the primary renal pathology may affect the outcomes of kidney allograft with respect to recurrence, rejection, and survival. However, for a significant number of patients who undergo kidney transplantation, the disease etiology is unknown. Here, allograft outcomes for patients with kidney disease of unknown etiology (UEK) at three affiliated Korean hospitals were identified. The incidence of biopsy-proven acute rejection (BPAR) for UEK was 22.9%, which was similar to the rates for diabetic nephropathy (DN, 24.4%) and IgA nephropathy (IgAN, 20.0%; p = 0.345). The cumulative incidence of post-transplant glomerulonephritis (PTGN) among patients with UEK was significantly lower than that among patients with IgAN (p < 0.001). Overall graft survival of the UEK group was superior to that of the DN group (hazards ratio 0.39, 95% confidence interval 0.17-0.92, p = 0.030). Preemptive transplantation for UEK significantly reduced the incidence of BPAR (preemptive vs. non-preemptive 9.6% vs. 30.3%, p = 0.001), but graft survival and recurrence were not affected by preemptive transplantation. The outcomes of kidney transplantation for patients with UEK were not inferior to those for patients with IgAN or DN. Preemptive kidney transplantation may be encouraged for UEK patients.

Incidence of post-transplant glomerulonephritis and its impact on graft outcome

BackgroundHerein, the significance of post-transplant glomerulonephritis (PTGN) has been revisited to investigate whether PTGN induces allograft failure. The aim of this study was to identify the incidence of PTGN and its association with allograft failure, as well as to analyze the risk factors for PTGN. MethodsAmong the 996 Korean patients who underwent kidney transplantation in a multicenter cohort from 1995 to 2010, 764 patients were enrolled in this study. ResultsThe incidence rate of PTGN was 9.7% and 17.0% at 5 and 10 years of follow-up, respectively. PTGN was diagnosed in 17.8% of the recipients with results of biopsy tests or clinical diagnosis identifying glomerular diseases as the underlying cause, compared with 0.0%, 4.4%, 4.9%, 5.5%, and 5.7% of the recipients with renal vascular diseases, renal interstitial diseases/pyelonephritis/uropathy, diabetic renal disease, hereditary renal diseases, and diseases with unknown etiologies, respectively. Allograft survival was significantly decreased in patients with PTGN. PTGN was associated with a fourfold increase in graft failure with a hazard ratio of 7.11 for both acute rejection and PTGN. Results of the risk factor analysis for PTGN revealed that the underlying glomerular renal diseases and treatment methods using drugs such as tacrolimus and basiliximab significantly increased PTGN development, after adjusting for other risk factors. ConclusionWe conclude that PTGN is strongly associated with poor kidney allograft survival. Therefore, optimal management of recurrent or de novo GN should be the critical focus of post-transplant care.

Post-Transplant Glomerulonephritis

Posttransplant glomerulonephritis (PTGN) is the third most common cause of late allograft loss. This could be classified into recurrent or de novo PTGN. The prevalence of PTGN is about 6–8%. There are several challenges with the diagnosis of PTGN. In addition, these diseases are not common, mostly described in case reports, case series and registry analysis. The reports vary in their definitions and approach to diagnosis. There is no high quality evidence for management of these conditions. This review focuses on summarizing the current evidence on the prevalence, clinical features, risk factors and management of PTGN.

Use of anti‐CD20 antibody in the treatment of post‐transplant glomerulonephritis

Post-transplant glomerulonephritis (PTGN) accounts for 4-10% of late graft loss. Six consecutive patients who developed PTGN 3-72 months post-transplant presented to our center with deteriorating kidney function and proteinuria. Three had focal segmental glomerulosclerosis; one had membranoproliferative glomerulonephritis Type 1; one recurrent membranous nephropathy; and one recurrent immunoglobin A nephropathy. All six were treated with an aggressive immunosuppression regimen including rituximab, pulse steroids and/or maximization of mycophenolic acid and calcineurin inhibitor therapy. Four of the six patients received plasma exchange. The patients were followed for a minimum of nine months after treatment. Proteinuria decreased from 7.2 ± 4.4 to 1.4 ± 1.5g (p = 0.04), while mean estimated glomerular filtration rate was 31.2 ± 13.1 and 42.5 ± 21.7 mL/min (p = 0.07) at nine months. No adverse events were noted. These observations suggest that immune modulating therapy may be of benefit in the treatment of PTGN.

The Changes of Graft Survival and Causes of Graft Failure after Kidney Transplantation

Methods: We reviewed patients who underwent kidney transplantation between 1982 and 2007. We compared the causes of graft loss for three decades: 1982∼1990 (period I), 1991∼2000 (period II), and 2001∼2007 (period III), with the clinical characteristics of patients with functioning grafts and patients who lost their allografts. Results: There were 785 recipients with a mean age of 36.1 years, and 65.2% were male. Graft loss occurred in 329 patients (41.9%), and the most common cause of graft loss was chronic allograft nephropathy (CAN, 52.0%), followed by patient death (17.6%), post-transplant glomerulonephritis (12.8%), and non compliance (7.9%). During the three time periods, 129, 172, and 28 patients lost their grafts, respectively. Five-year graft survival was 61.5%, 78.4%, and 90.8%, respectively, and increased significantly (P<0.000). CAN, as a cause of graft loss, fell from 65.1% (period I) to 32.1% (period III, P<0.000), but patient death increased from 12.4% to 32.1% (P=0.034). A multivariate analysis revealed that significant risk factors for graft loss included an older donor, transplantation at period I, and dual immunosuppression. Use of tacrolimus and mycophenolate mofetil was associated with a significantly reduced risk of graft loss. Conclusions: Graft survival has increased over the last three decades whereas the proportion of CAN, the most common cause of graft loss, has decreased. Attention to the main causes of graft loss, CAN, and patient death will offer potential improvement in graft survival.

Introduction

This supplement contains the proceedings of the 13th Japanese Clinico-Pathological Conference on Renal Allograft Pathology, which was held on July 18, 2009, in Tokyo, Japan. The importance of kidney transplant pathology to evaluate graft condition and select optimal therapy has been widely acknowledged. The conference on renal allograft pathology has been held every year since 1997, and clinical nephrologists, transplant surgeons, urologists, and renal and general pathologists in Japan discuss renal transplant cases and topics related to renal transplantation. Every year’s conference has included unique topics concerning renal transplantation and provided an opportunity for debate from residents and fellows to specialists in pathology, internal medicine, and surgical fields. This year’s conference consisted of four special mini-lectures and 22 scientific studies and case presentations. Before the session, attendees could view all of the renal allograft case samples via a virtual microscope system at the front of the conference room. In addition, the histopathological features of two cases were discussed using virtual slides and a high-definition television system. The theme of the special mini-lectures in this meeting was “New therapeutic strategy for renal transplantation: Induction of tolerance in clinical and preclinical kidney transplantation.” In particular, the lecture “Induction of tolerance in clinical kidney transplantation” presented by Dr. Kawai from Massachusetts General Hospital/Harvard Medical School, Boston, USA, was quite educational for us in terms of the next practical and ideal strategy for kidney transplantation. Drs. Bashuda (Juntendo University, Tokyo, Japan) and Yamashita (Hokkaido University School of Medicine, Hokkaido, Japan) presented new strategies using adoptive transfer of regulatory T-cell-like cells (anergic cells) or anti-CD40 monoclonal antibody in preclinical studies, using non-human primates. For scientific studies and case presentations, we prepared five topics for detailed discussion: ABO-incompatible transplantation, acute antibody-mediated rejection, acute T-cell-mediated rejection, post-transplant glomerulonephritis, and pathology of surgical complications and others. Within each heading, four to five cases or studies were presented and discussed clinico-pathologically. Under the topic “ABO-incompatible transplantation,” pathology within 90 d of transplantation was characterized, and the very rare cases that show hyperacute rejection and acute antibody-mediated rejection in Epstein syndrome with thrombocytopenia were reported. Other topics included acute antibody or cell-mediated rejection. The clinico-pathological characterization of acute vascular rejection was discussed, and cases showing BK virus infection and plasma cell-rich acute rejection were reported. Under the topic “post-transplant glomerulonephritis,” the pathology and treatment of recurrence or de novo focal glomerulosclerosis (FSGS) and essential cryoglobulinemia were discussed. “Pathology of surgical complications and others” covered cases of pregnancy-induced thrombotic thrombocytopenic purpura and anemia-associated progressive interstitial fibrosis after transplantation, and the usefulness of baseline renal biopsy in the evaluation of the condition of living donor kidneys was reported. From the discussion of the scientific studies and transplant cases, we reconfirm that the examination of renal morphology in allograft patients is essential to evaluation of graft condition and achieving appropriate therapy. We believe that the reports appearing in this supplement address the above-mentioned issues that are important to the field of renal transplantation. The guest editors thank all authors and participants for their contributions. We also gratefully acknowledge the outstanding effort and support of Novartis Pharma K.K. (Japan) in holding this meeting. In addition, the sponsorship of the many cooperating firms listed on the title page made it possible to hold the meeting and publish this supplement. Finally, I express my sincere appreciation to Dr. Morozumi and Dr. Yamaguchi for their dedication to this meeting.

Impact of Therapeutic Changes on Renal Graft Survival With Posttransplant Glomerulonephritis

Introduction Posttransplant glomerulonephritis (GN) is the third cause of graft loss after 1 year of transplant follow-up; few approaches have been efficient in reversing this outcome. The aim of this study was to evaluate whether the modification of the immunosuppressive therapy for treating posttransplant GN had an impact on allograft survival. Patients and Methods Forty-nine patients who underwent renal transplantation and developed posttransplant GN were divided into two groups: group 1, 22 patients with modified immunosuppressive treatment (72.3%, pulse of methylprednisolone; 13.6%, high-dose oral corticosteroid), and group 2, where it was maintained. Additionally, the impact of the concomitant use of drugs that promote the renin–angiotensin–aldosterone system blockade (RAASB) was analyzed in terms of graft survival. Results We established the diagnosis of GN at 17.9 months (range, 0.57 to 153.4) after transplantation, when serum creatinine (Cr) was 2.2 mg/dL (range, 0.8 to 12.5) and proteinuria 3.2 g/L (range, 0.2 to 24.2). Graft survivals at 1 and 3 years after diagnosis were 69.2% and 52.9%, respectively. The patients of group 1 showed a lower prevalence of graft loss (27.2% versus 48.1%, P = .40) and better survival at the end of 1 year (73.2% versus 60.4%) and 3 years (62.5% versus 38.0%, P = .26), but the differences were not significant. RAASB showed a positive impact on survival at the end of 3 years in both groups: for group 1, 83.8% with RAASB, 41.4% without RAASB; and for group 2, 75% with RAASB and 14.8% without RAASB ( P < .001). Conclusion Although treatment of posttransplant GN with modification of immunosuppression seemed to improve graft survival in the first 3 years after diagnosis, RAASB improved this effect.

Peritubular capillary C4d deposition and renal outcome in post‐transplant IgA nephropathy

Immunological staining of the transplanted kidney for C4d in peritubular capillaries (C4d(PTC)) has emerged as a useful method to detect antibody-mediated rejection in situ. In this retrospective study, we evaluated the prevalence of C4d(PTC) deposition in allograft renal biopsies diagnosed of IgA nephropathy (IgAN) and analysed its clinical significance. Sixty-six biopsy specimens of post-transplant IgAN, which were obtained to evaluate azotemia and/or heavy proteinuria, were examined by immunohistochemical staining of the paraffin sections with polyclonal antibody for C4d. C4d was stained positively in peritubular capillaries in 16 (24%) of the 66 cases. The C4d(PTC)-negative (n=50) and C4d(PTC)-positive groups (n=16) were not different in recipient gender, age, donor age, type of donor (living vs. cadaveric), interval from transplantation to graft biopsy (41.6+/- 21.8 vs. 48.3+/-26.1 months) and post-biopsy follow-up period (60.3+/-23.3 vs. 56.9+/-25.4 months). During the follow-up period, 12 of 50 (24%) although the incidence of graft failure was not different by the C4d deposition in peritubular capillaries, intervals from renal biopsy to graft failure tended to be shorter in C4d(PTC)-positive cases than C4d(PTC)-negative cases. In Kaplan-Meier analysis, the renal allograft function of the C4d(PTC)-positive group deteriorated more rapidly than that of the C4d(PTC)-negative group (p<0.05). Histologically, the C4d(PTC)-positive group had findings suggestive of acute cellular rejection more commonly than the C4d(PTC)-negative group (p<0.01). Evidence of humoral rejection, as demonstrated by C4d(PTC) deposition, was concurrently present in significant portions of post-transplant IgAN biopsy specimens and was associated with more rapid deterioration of renal function. These results suggest that C4d(PTC) positivity needs to be determined at the time of biopsy even in cases of post-transplant glomerulonephritis and immunosuppression may need to be modified accordingly.

Initial Response to Immunosuppressive and Renoprotective Treatment in Posttransplant Glomerulonephritis

The current studies on posttransplant glomerulonephritis (PTxGN) do not establish when, how, or how long we must treat these patients. This study sought to compare the initial response to immunosuppressive treatment and renoprotection in PTxGN. Patients and methods This prospective study was performed in 23 patients with a histological diagnosis of PTxGN. Results Mean follow-up was 12 months (3–18); 91% received immunosuppressants, and 56.5% just renoprotective drugs. The best results (reduction of serum creatinine [SCr] and proteinuria) with immunosuppression were observed in patients with recurrent membranous PTxGN using the scheme of Ponticelli (IV + PO corticosteroid [CS] + PO cyclophosphamide [CPP]). A similar response was also seen in subjects with recurrent or de novo focal glomerulosclerosis treated with PO CS or CPP, except when the initial SCr > 2.5 mg/dL. In de novo IgA nephropathy, reduction of proteinuria occurred with use of PO CS, with or without CPP, but without improvement in SCr. Patients with recurrent or de novo crescentic PTxGN used renoprotective drugs and always immunosuppressants. In this group, good results were seen with IV + PO CS, with or without CPP, when there was less than 50% of glomeruli with crescents, or more than 50% with crescents but an initial SCr < 2.5 mg/dL. Conclusion Immunosuppression seemed to give a better initial response than renoprotection in cases of membranous, IgA, and focal segmental glomulerulosclerosis PTxGN. Patients with an initial SCr ≥ 2.5 mg/dL displayed worse outcomes.

Renal transplantation and secondary hyperparathyroidism.

Secondary hyperparathyroidism (2'HPT) improves after renal transplantation (RTx) along with recovered function of the renal allograft. However, normal renal function does not last long due to rejection, drug-induced nephrotoxic nepthropathy, or recurrence of post-transplant glomerulonephritis. Therefore, improved calcium and phosphate metabolism, and parathyroid function after RTx fluctuate in accordance with the function of the renal allograft. In cases with severe 2'HPT, parathyroidectomy should be performed before RTx because hypercalcemia due to secondary or tertiary hyperparathyroidism aggravates the renal allograft function. In the follow-up of mild 2'HPT after RTx, hypercalcemia and vascular calcification should be monitored carefully by serum parathyroid hormone, calcium and phosphate concentrations, alkaline phosphatase activity, and bone X-ray film. If serum calcium level exceeds 12 mg/dl, parathyroidectomy (PTx) should be performed to prevent the acceleration of vascular calcification. Total PTx with forearm allograft is a preferred surgical procedure for 2'HPT even after RTx.