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Kidney transplant candidates with high anti-M-type phospholipase A2 receptor antibody activity may be at increased risk for early postkidney transplant recurrence and allograft loss. Pretransplant treatment to induce serological remission may be warranted to improve allograft survival. In this case report, a patient seeking their third kidney transplant, who lost 2 prior living donor transplants from early recurrent membranous nephropathy, underwent pretransplant treatment for membranous nephropathy with serological remission and no evidence of recurrent disease.

Immunoglobulin A nephropathy (IgAN) is the commonest glomerulonephritis worldwide, a category that represents the third most frequent cause of end-stage kidney disease (ESKD) in the United States. Kidney transplantation remains the optimal treatment of ESKD, and yet the prospects of IgAN recurrence post-transplant dampens the enthusiasm for living kidney donation in some instances, in addition to limiting the longevity of the kidney allograft. Moreover, the lack of a standardized method for detecting IgAN recurrence, since not all centers perform protocol allograft biopsies, has led to an underestimation of the extent of the issue. The pathogenesis of de novo IgAN remains conjectural, let alone the pathways for recurrent disease, but is increasingly recognized as a multi-hit injury mechanism. Identification of recurrent disease rests mainly on clinical symptoms and signs (e.g., hematuria, proteinuria) and could only be definitively proven with histologic evidence which is invasive and prone to sampling error. Treatment had relied mainly on nonspecific goals of proteinuria reduction, and in some cases, immunosuppression for active, crescentic disease. More recently, newer targets have the potential to widen the armamentarium for directed therapies, with more studies on the horizon. This review article provides an update on recurrent IgAN post-transplant.

Immunoglobulin A nephropathy (IgAN) is the commonest glomerulonephritis worldwide, a category that represents the third most frequent cause of end-stage kidney disease (ESKD) in the United States. Kidney transplantation remains the optimal treatment of ESKD, and yet the prospects of IgAN recurrence post-transplant dampens the enthusiasm for living kidney donation in some instances, in addition to limiting the longevity of the kidney allograft. Moreover, the lack of a standardized method for detecting IgAN recurrence, since not all centers perform protocol allograft biopsies, has led to an underestimation of the extent of the issue. The pathogenesis of de novo IgAN remains conjectural, let alone the pathways for recurrent disease, but is increasingly recognized as a multi-hit injury mechanism. Identification of recurrent disease rests mainly on clinical symptoms and signs (e.g., hematuria, proteinuria) and could only be definitively proven with histologic evidence which is invasive and prone to sampling error. Treatment had relied mainly on nonspecific goals of proteinuria reduction, and in some cases, immunosuppression for active, crescentic disease. More recently, newer targets have the potential to widen the armamentarium for directed therapies, with more studies on the horizon. This review article provides an update on recurrent IgAN post-transplant. [ABSTRACT FROM AUTHOR]

Introduction: We evaluated the long‐term outcomes of recurrent glomerulonephritis (RGN) using clinical, histopathological, and demographic predictors. Methods: A retrospective cohort study of kidney transplant recipients (KTR) in two renal centers between 2005 and 2020. Clinical and native kidney histological data were analyzed. The risk factors and outcomes of each primary glomerulonephritis subtype were assessed using Cox methods. Result: 336 recipients with primary glomerulonephritis were analyzed. RGN was diagnosed in 17%, 20%, 25%, and 13% of recipients with IgA nephropathy (IgAN), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN) and membranoproliferative glomerulonephritis (MPGN), respectively. Median time to recurrence was shortest in FSGS (.6 years IQR.2‐2.9) and longest in MN (6.3 years IQR 3.3‐8.0) whereas time to graft loss after diagnosis was shortest in MPGN (.3 years IQR.1‐1.7) and longest in IgAN (2.9 year IQR 1.3‐4.3). Recipients with recurrent IgAN were likely to be younger, have higher proteinuria at diagnosis, receive living donor allografts, receive cyclosporine treatment, have a history of acute rejection, and have segmental sclerosis in native glomeruli. Younger age of the donors, higher proteinuria at diagnosis, alemtuzumab, proteinuria within the first 12 months, acute rejection, low baseline eGFR, mesangial proliferation, and IgG and IgA deposits were associated with FSGS recurrence. MPGN recurrence was predicted by lower BMI at transplantation, and crescentic native disease. Death‐censored graft survival at 5‐, 10‐, and 15‐years was 83%, 51%, and 29% in the RGN group and 95%, 93%, and 84%, respectively in the non‐RGN group. Over 15 years, recipients with RGN are nine times more likely than those without RGN to lose their grafts, regardless of donor type, acute rejection, and baseline eGFR. Transplant recipients of related donor allograft were not more likely to have recurrent GN than non‐related donors. [ABSTRACT FROM AUTHOR]

Background: Long term outcomes in transplant recipients experiencing recurrent focal segmental glomerulosclerosis (FSGS) remains poor. Despite early treatment, more than half lose their graft. The aims of this study were to evaluate treatment patterns, outcomes and to evaluate for predictors of treatment failure in recurrent FSGS. Methods: This was a single center retrospective observational study. Between 1/2014 and 8/2019, 1860 kidney transplantations were performed at UCLA, 100 of which had end stage renal disease due to biopsy-proven FSGS. Comparative statistics were obtained and a multivariate analysis for graft outcomes in patients with recurrence was constructed. The primary outcomes were recurrent FSGS, allograft failure and pheresis dependence. Results: Twenty-six of the 100recipients experienced FSGS recurrence. Patients with recurrence were younger (34.3 vs. 44.9, p = 0.001) and more likely to have had native nephrectomy (27% vs. 3%, p = 0.001). Gender, race, comorbidities, donor type, previous transplants and rates of rejection were similar between the recurrence and non-recurrence groups. Most patients received plasmapheresis (n = 24) with or without rituximab (11 vs. 13) which allowed for recovery of graft function in 18 patients (75%). Those experiencing a complete recovery required a median of 9 pheresis sessions, while those with graft failure (n = 3) or who became plasmapheresis-dependent (n = 5) required a median of 59 and 158 sessions, respectively. A multivariate analysis was constructed and no additional predictors of graft failure were encountered. Conclusions: Patients with recurrent FSGS whoexperienced remissiondid so following a short course of plasmapheresis. The patients whose recurrence never resolved or who lost their graft underwent much longer courses of plasmapheresis. If this pattern of early durable response is validated in larger studies, there may be a future when transplant teams discuss the possibility of re-gifting based on treatment response to plasmapheresis following recurrence.

Abstract Background Recurrence of IgA nephropathy (IgAN) after kidney transplantation occurs in about 30% of patients. The relevance of recurrence for the long-term graft survival is expected to increase, since graft survival continues to improve. Methods In a nested study within the Swiss Transplant Cohort Study the incidence of IgAN recurrence, predictive factors, graft function and graft and patient survival were evaluated. Serum concentration of total IgA, total IgG, Gd-IgA1 and IgA-IgG immune complex were measured using ELISA-based immunologic assays. Results Between May 2008 and December 2016, 28 women and 133 men received their kidney allograft for end-stage kidney disease due to IgAN in Switzerland. Over a median follow-up time of 7 years after transplantation, 43 out of 161 patients (26.7%) developed an IgAN recurrence, of which six (13.9%) had an allograft failure afterwards and further four patients (9.3%) died. During the same follow-up period, 6 out of 118 patients (5%) each experienced allograft failure or died without prior IgAN recurrence. After 11 years the risk for IgAN recurrence was 27.7% (95%-CI: 20.6–35.3%). Renal function was similar in patients with and without recurrence up to 7 years after transplantation, but worsened thereafter in patients with recurrence (eGFR median (interquartile range) at 8 years: 49 ml/min/1.73m2 (29–68) vs. 60 ml/min/1.73m2 (38–78)). Serum concentration of total IgA, total IgG, Gd-IgA1 and IgA-IgG immune complex within the first year posttransplant showed no significant effect on the recurrence of IgAN. Younger recipients and women had a higher risk of recurrence, but the latter only in the short term. Conclusions Our study showed a recurrence risk of 28% at 11 years after transplantation, which is consistent with previous literature. However, the predictive value of known biomarkers, such as serum Gd-IgA1 and IgA-IgG IC, for IgAN recurrence could not be confirmed.

Hereditary forms of hemolytic uremic syndrome (HUS), formerly known as atypical HUS, typically involve mutations in genes encoding for components of the alternative pathway of complement, therefore they are often referred to as complement-mediated HUS (cHUS). This condition has a high risk of recurrence in the transplanted kidney, leading to accelerated graft loss. The availability of anti-complement component C5 antibody eculizumab has enabled successful transplantation with a notably reduced recurrence rate and improved prognosis. Open questions are related to the potential for complement inhibitor discontinuation, ideal timing of treatment withdrawal, and patient selection based on genetic abnormalities. Our review delves into the pathophysiology, classification, genetic predispositions, and management strategies for cHUS in the native and transplant kidneys. • Patients with complement-mediated HUS (cHUS) have a high risk of recurrence in the transplanted kidney and accelerated graft loss. • The availability of anti-complement component C5 antibody eculizumab has significantly reduced the rate of recurrence and improved prognosis, allowing for successful transplantation. • Currently, it is still unclear whether complement inhibitor therapy can be safely discontinued, what the ideal timing of treatment withdrawal is, and whether genetic abnormalities can identify patients in whom withdrawal is safer. [ABSTRACT FROM AUTHOR]

Background: Recurrence of IgA nephropathy (IgAN) after kidney transplantation occurs in about 30% of patients. The relevance of recurrence for the long-term graft survival is expected to increase, since graft survival continues to improve.Methods: In a nested study within the Swiss Transplant Cohort Study the incidence of IgAN recurrence, predictive factors, graft function and graft and patient survival were evaluated. Serum concentration of total IgA, total IgG, Gd-IgA1 and IgA-IgG immune complex were measured using ELISA-based immunologic assays.Results: Between May 2008 and December 2016, 28 women and 133 men received their kidney allograft for end-stage kidney disease due to IgAN in Switzerland. Over a median follow-up time of 7 years after transplantation, 43 out of 161 patients (26.7%) developed an IgAN recurrence, of which six (13.9%) had an allograft failure afterwards and further four patients (9.3%) died. During the same follow-up period, 6 out of 118 patients (5%) each experienced allograft failure or died without prior IgAN recurrence. After 11 years the risk for IgAN recurrence was 27.7% (95%-CI: 20.6-35.3%). Renal function was similar in patients with and without recurrence up to 7 years after transplantation, but worsened thereafter in patients with recurrence (eGFR median (interquartile range) at 8 years: 49 ml/min/1.73m2 (29-68) vs. 60 ml/min/1.73m2 (38-78)). Serum concentration of total IgA, total IgG, Gd-IgA1 and IgA-IgG immune complex within the first year posttransplant showed no significant effect on the recurrence of IgAN. Younger recipients and women had a higher risk of recurrence, but the latter only in the short term.Conclusions: Our study showed a recurrence risk of 28% at 11 years after transplantation, which is consistent with previous literature. However, the predictive value of known biomarkers, such as serum Gd-IgA1 and IgA-IgG IC, for IgAN recurrence could not be confirmed. [ABSTRACT FROM AUTHOR]

Introduction: Graft dysfunction (GD) is the major complication of renal transplantation, and may result in graft loss. The major causes of GD are immunological rejection and non-rejection injury (NRI), which have different prognostic and therapeutic connotations. Meticulous renal allograft biopsy (RAB) evaluation and its correlation with clinico-laboratory features are crucial for timely identification of the varied NRI. Objectives: To evaluate the clinico-laboratory characteristics and histopathologic features of NRI in "clinically indicated" RABs in our institution. Patients and Methods: This was a prospective study conducted over a period of five years on renal transplant recipients who underwent "clinically indicated" RAB for GD. Results: A total of 192 biopsies were evaluated which showed NRI, rejection and NRI with concurrent rejection in 57.3%, 26.6% and 3.6% cases respectively. The NRI category, with or without concurrent rejection, comprised of acute tubular injury (ATI) (44%), calcineurin inhibitor induced (CNI) toxicity (19.7%), infections (12.8%), recurrent glomerulonephritis (GN) (7.7%), de novo GN (1.7%), chronic interstitial nephritis (9.4%), thrombotic microangiopathy (2.6%) and renal vein thrombosis (1.7%). Mean patient age was 34.9 years with male: female ratio of 8:1. Conclusion: Timely differentiation between rejection and NRI is indispensable for improved allograft survival. Acute tubular injury is the major NRI causing delayed graft function (DGF), and is commonly associated with deceased donor renal transplantation. The blood concentration of CNI does not correlate with the extent of renal damage. Acute tubular injury and CNI toxicity are the major NRI, in the first six months post-transplantation and after six months post-transplantation, respectively.

Introduction: Graft dysfunction (GD) is the major complication of renal transplantation, and may result in graft loss. The major causes of GD are immunological rejection and non-rejection injury (NRI), which have different prognostic and therapeutic connotations. Meticulous renal allograft biopsy (RAB) evaluation and its correlation with clinico-laboratory features are crucial for timely identification of the varied NRI. Objectives: To evaluate the clinico-laboratory characteristics and histopathologic features of NRI in "clinically indicated" RABs in our institution. Patients and Methods: This was a prospective study conducted over a period of five years on renal transplant recipients who underwent "clinically indicated" RAB for GD. Results: A total of 192 biopsies were evaluated which showed NRI, rejection and NRI with concurrent rejection in 57.3%, 26.6% and 3.6% cases respectively. The NRI category, with or without concurrent rejection, comprised of acute tubular injury (ATI) (44%), calcineurin inhibitor induced (CNI) toxicity (19.7%), infections (12.8%), recurrent glomerulonephritis (GN) (7.7%), de novo GN (1.7%), chronic interstitial nephritis (9.4%), thrombotic microangiopathy (2.6%) and renal vein thrombosis (1.7%). Mean patient age was 34.9 years with male: female ratio of 8:1. Conclusion: Timely differentiation between rejection and NRI is indispensable for improved allograft survival. Acute tubular injury is the major NRI causing delayed graft function (DGF), and is commonly associated with deceased donor renal transplantation. The blood concentration of CNI does not correlate with the extent of renal damage. Acute tubular injury and CNI toxicity are the major NRI, in the first six months post-transplantation and after six months post-transplantation, respectively. [ABSTRACT FROM AUTHOR]

The complement system is part of innate immunity and is pivotal in protecting the body against pathogens and maintaining host homeostasis. Activation of the complement system is triggered through multiple pathways, including antibody deposition, a mannan-binding lectin, or activated complement deposition. C3 glomerulopathy (C3G) is a rare glomerular disease driven by complement dysregulation with high post-transplantation recurrence rates. Its treatment is mainly based on immunosuppressive therapies, specifically mycophenolate mofetil and glucocorticoids. Recent years have seen significant progress in understanding complement biology and its role in C3G pathophysiology. New complement-tergeting treatments have been developed and initial trials have shown promising results. However, challenges persist in C3G, with recurrent post-transplantation cases leading to suboptimal outcomes. This review discusses the pathophysiology and management of C3G, with a focus on its recurrence after kidney transplantation. • C3 glomerulopathy (C3G) is a rare glomerular disease driven by complement dysregulation with high post-transplantation recurrence rates. • Treatment of native cases is primarily based onmycophenolate mofetil and glucocorticoids, but these immunosuppressice drugs are often ineffective in recurrent cases. • The growing availability of complement-targeting therapies is expected to improve the outcomes of affected individuals. [ABSTRACT FROM AUTHOR]

Background: Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) is a glomerular disease defined by non-organized glomerular deposits of heavy and light chain–restricted immunoglobulin and is rarely reported in children. Methods: We characterized a series of nine pediatric patients from two academic centers with biopsy-proven PGNMID and additionally describe two patients with monotypic IgG in the setting of IgM deposition. Results: Each patient presented with hematuria and/or proteinuria; however, only five had elevated serum creatinine. Prodromal or concurrent infection was identified in six patients, low C3 in five, and alternate complement pathway gene variants in two. No monoclonal serum proteins were identified in five tested patients. Seven patients had monotypic deposits composed of IgG3-λ, two showed IgG3-κ, and one each IgG1 and IgG3 with lambda dominance in the setting of IgM deposition. The glomerular pattern was predominantly mesangial proliferative or membranoproliferative glomerulonephritis (MPGN). Treatment and outcomes were variable; four patients have recent PGNMID diagnoses and therefore minimal follow up, one had relatively stable kidney function for over a decade, and six experienced kidney failure, with four receiving transplants. Recurrent deposits of the same isotype were identified in five of six transplanted kidneys, corresponding to three of four transplanted patients. One of these patients developed PGNMID recurrences in three separate kidney allografts over a 20-year disease course. Conclusions: Our study emphasizes the need for upfront IgG subclass investigation in pediatric mesangial or MPGN with IgG deposition and monotypic or biased light-chain staining. Furthermore, this pediatric experience suggests expanded pathogenic considerations in PGNMID. [ABSTRACT FROM AUTHOR]

A spectrum of kidney diseases besides classic human immunodeficiency virus (HIV)-associated nephropathy (HIVAN) exists in HIV-infected patients. Immune complex-mediated glomerulonephritis has emerged as a significant contributor to the burden of kidney disease in this population, particularly in patients of non-African descent. Lupus-like nephritis, a form of immune complex glomerulonephritis with histologic features identical to lupus nephritis in the absence of clinical or serologic markers of lupus, is well recognized as a cause of end-stage renal disease in HIV-infected patients. None of the HIV-associated kidney lesions, whether classic HIVAN or non-HIVAN, has been reported to recur in kidney transplants. We report here for the first time clinical and histologic recurrence of HIV-associated lupus-like nephritis after successful kidney transplantation, causing proteinuria, hematuria, and impaired kidney transplant function.

Background: Recurrence of IgA nephropathy (IgAN) in the transplanted kidney is associated with graft survival, but no specific treatment is available. Tonsillectomy (TE) reportedly arrests the progression of IgAN in the native kidney. Thus, we conducted a single-center retrospective cohort study to evaluate the effect of TE prior to IgAN recurrence.Methods: Of the 36 patients with biopsy-proven IgAN who underwent kidney transplantation, 27 were included in this study. Nine patients underwent TE at 1 year after kidney transplantation (group 1), and the remaining 18 did not undergo TE (group 2).Results: The rate of histological IgAN recurrence was significantly lower in group 1 than in group 2 (11.1 vs. 55.6%, log-rank p = 0.046). In addition, half of the recurrent patients in group 2 exhibited active lesions, compared to none in group 1. Serum Gd-IgA1 levels decreased after TE in group 1, whereas they remained stable or increased slightly in group 2. In the recurrent cases, IgA and Gd-IgA1 were found in the germinal center in addition to the mantle zone of tonsils. Finally, mesangial IgA and Gd-IgA1 immunoreactivity was reduced after TE in some cases.Conclusion: Our data suggest that TE at 1 year after kidney transplantation might be associated with the reduced rate of histological IgAN recurrence. TE arrested or reduced serum Gd-IgA1 and mesangial Gd-IgA1 immunoreactivity. Therefore, we generated a hypothesis that serum Gd-IgA1 derived from the tonsils may play a pivotal role in the pathogenesis of IgAN. Based on these findings, we need to conduct verification in a prospective randomized controlled trial.

Grafted kidney abnormalities include a wide spectrum of diseases that differ in their nature, mechanisms of development, and rates of progression. In the early period after renal transplantation, the most important cause of graft dysfunction remains to be acute rejection that results from a recipient's immunological response to a donor's transplantation antigens and develops with the activation of both cellular and humural immune responses. In the late periods, one of the main causes of late graft losses is chronic graft dysfunction, the morphological substrate of which is progressive nephrosclerosis. The development of graft nephrosclerosis is generally associated with the combined effects of a large variety of both immune and nonspecific factors; however, the morphological features make it possible to identify the preponderance of this or that mechanism in its origin and, in this connection, individual nosological entities. The latter include chronic rejection, calcineurin inhibitorinduced nephrotoxicity, and nephrosclerosis caused by rejection-unassociated conditions, such as ischemic-reperfusion lesion, obstructive nephropathy, viral graft damage, etc. Moreover, as more time elapses after renal allotransplantation (RAT), there is a higher incidence of recurrent and de novo diseases, the most common types of which are IgA-nephropathy, focal segmental glomerulosclerosis, membranous nephropathy, diabetic nephropathy, etc. Puncture biopsy using immunofluorescence and electron microscopy is the gold standard of the diagnosis of graft kidney abnormalities since only the morphological verification of the diagnosis permits adequate immunosuppressive therapy, by improving the long-term results of RAT. The paper presents diagnostic criteria and morphological features of different types of renal graft diseases.

Glomerulonephritis (GN) is the underlying cause of end-stage renal failure in 30–50% of kidney transplant recipients. It represents the primary cause of end-stage renal disease for 25% of the dialysis population and 45% of the transplant population. For patients with GN requiring renal replacement therapy, kidney transplantation is associated with superior outcomes compared with dialysis. Recurrent GN was previously considered to be a minor contributor to graft loss, but with the prolongation of graft survival, the effect of recurrent disease on graft outcome assumes increasing importance. Thus the extent of recurrence of original kidney disease after kidney transplantation has been underestimated for several reasons. This review aims to provide updated knowledge on one particular recurrent renal disease after kidney transplantation, immunoglobulin A nephropathy (IgAN). IgAN is one of the most common GNs worldwide. The pathogenesis of IgAN is complex and remains incompletely understood. Evidence to date is most supportive of a several hit hypothesis. Biopsy is mandatory not only to diagnose the disease in the native kidney, but also to identify and characterize graft recurrence of IgAN in the kidney graft. The optimal therapy for IgAN recurrence in the renal graft is unknown. Supportive therapy aiming to reduce proteinuria and control hypertension is the mainstream, with corticosteroids and immunosuppressive treatment tailored for certain subgroups of patients experiencing a rapidly progressive course of the disease with active lesions on renal biopsy and considering safety issues related to infectious complications. [ABSTRACT FROM AUTHOR]

Background: Recurrence of IgA nephropathy (IgAN) in the transplanted kidney is associated with graft survival, but no specific treatment is available. Tonsillectomy (TE) reportedly arrests the progression of IgAN in the native kidney. Thus, we conducted a single-center retrospective cohort study to evaluate the effect of TE prior to IgAN recurrence. Methods: Of the 36 patients with biopsy-proven IgAN who underwent kidney transplantation, 27 were included in this study. Nine patients underwent TE at 1 year after kidney transplantation (group 1), and the remaining 18 did not undergo TE (group 2). Results: The rate of histological IgAN recurrence was significantly lower in group 1 than in group 2 (11.1 vs. 55.6%, log-rank p = 0.046). In addition, half of the recurrent patients in group 2 exhibited active lesions, compared to none in group 1. Serum Gd-IgA1 levels decreased after TE in group 1, whereas they remained stable or increased slightly in group 2. In the recurrent cases, IgA and Gd-IgA1 were found in the germinal center in addition to the mantle zone of tonsils. Finally, mesangial IgA and Gd-IgA1 immunoreactivity was reduced after TE in some cases. Conclusion: Our data suggest that TE at 1 year after kidney transplantation might be associated with the reduced rate of histological IgAN recurrence. TE arrested or reduced serum Gd-IgA1 and mesangial Gd-IgA1 immunoreactivity. Therefore, we generated a hypothesis that serum Gd-IgA1 derived from the tonsils may play a pivotal role in the pathogenesis of IgAN. Based on these findings, we need to conduct verification in a prospective randomized controlled trial. [ABSTRACT FROM AUTHOR]

The prevalence, pathogenesis, predictors, and natural course of patients with recurrent glomerulonephritis (GN) occurring after kidney transplantation remains incompletely understood, including whether there are differences in the outcomes and advances in the treatment options of specific GN subtypes, including those with de novo GN. Consequently, the treatment options and approaches to recurrent disease are largely extrapolated from the general population, with responses to these treatments in those with recurrent or de novo GN post-transplantation poorly described. Given a greater understanding of the pathogenesis of GN and the development of novel treatment options, it is conceivable that these advances will result in an improved structure in the future management of patients with recurrent or de novo GN. This review focuses on the incidence, genetics, characteristics, clinical course, and risk of allograft failure of patients with recurrent or de novo GN after kidney transplantation, ascertaining potential disparities between “high risk” disease subtypes of IgA nephropathy, idiopathic membranous glomerulonephritis, focal segmental glomerulosclerosis, and membranoproliferative glomerulonephritis. We will examine in detail the management of patients with high risk GN, including the pre-transplant assessment, post-transplant monitoring, and the available treatment options for disease recurrence. Given the relative paucity of data of patients with recurrent and de novo GN after kidney transplantation, a global effort in collecting comprehensive in-depth data of patients with recurrent and de novo GN as well as novel trial design to test the efficacy of specific treatment strategy in large scale multicenter randomized controlled trials are essential to address the knowledge deficiency in this disease.

The prevalence, pathogenesis, predictors, and natural course of patients with recurrent glomerulonephritis (GN) occurring after kidney transplantation remains incompletely understood, including whether there are differences in the outcomes and advances in the treatment options of specific GN subtypes, including those with de novo GN. Consequently, the treatment options and approaches to recurrent disease are largely extrapolated from the general population, with responses to these treatments in those with recurrent or de novo GN post-transplantation poorly described. Given a greater understanding of the pathogenesis of GN and the development of novel treatment options, it is conceivable that these advances will result in an improved structure in the future management of patients with recurrent or de novo GN. This review focuses on the incidence, genetics, characteristics, clinical course, and risk of allograft failure of patients with recurrent or de novo GN after kidney transplantation, ascertaining potential disparities between "high risk" disease subtypes of IgA nephropathy, idiopathic membranous glomerulonephritis, focal segmental glomerulosclerosis, and membranoproliferative glomerulonephritis. We will examine in detail the management of patients with high risk GN, including the pre-transplant assessment, post-transplant monitoring, and the available treatment options for disease recurrence. Given the relative paucity of data of patients with recurrent and de novo GN after kidney transplantation, a global effort in collecting comprehensive in-depth data of patients with recurrent and de novo GN as well as novel trial design to test the efficacy of specific treatment strategy in large scale multicenter randomized controlled trials are essential to address the knowledge deficiency in this disease. [ABSTRACT FROM AUTHOR]

ABSTRACT: Accurate interpretation of renal allograft biopsy is necessary to guide therapy, especially when an episode biopsy is taken to rescue the graft. Contrarily, a protocol biopsy is carried out routinely to identify baseline conditions (biopsy at 0 or 1 h), subclinical rejection, histological change under current immunosuppression regimen, drug nephrotoxicity, viral infection, and recurrence of glomerulonephritis. Semiquantitative scoring for active lesions including tubulitis, glomerulitis, capillaritis, arteritis, arteriopathy, and others such as polyomavirus infection are key factors in transplant pathology. Recently, the Banff classification has proposed several novel concepts focused on antibody‐mediated rejection (ABMR). This review presents the interpretation of transplant pathology from rejection to infection, recurrence of glomerulonephritis, and drug nephrotoxicity, with a description of ABMR according to the 2013 and 2017 Banff classification. [ABSTRACT FROM AUTHOR]

ABSTRACT: The extent of recurrence of original kidney disease after kidney transplantation has been underestimated for several reasons. First, the duration of observation varies among studies. Second, the criteria used to schedule protocol and episode biopsies differ among institutions. And third, diagnostic modalities used for early detection of recurrent original kidney disease also vary. Thus, rates of graft loss attributable to a recurrence of original kidney disease vary among institutions and are often underestimated. However, the recurrence of original disease is often thought to be less important than chronic rejection followed by loss of a functioning allograft. It is important to note that recent data have shown that in patients with certain limited primary kidney diseases (e.g., membranous proliferative glomerulonephritis [MPGN], IgA nephritis [IgAN], focal segmental glomerulonephritis [FSGS], and membranous nephropathy [MN]), the predominant (60%) cause of graft loss is the recurrence of original kidney disease. In addition, the rate of 5‐year graft survival in patients with recurrent original kidney disease averages 45%. Thus, research must address the recurrence of original kidney disease. Here we focus on this recurrence and discuss diagnoses, preventive strategies, treatments, and future research directions. [ABSTRACT FROM AUTHOR]

ABSTRACT: Proliferative glomerulonephritis with monoclonal immunoglobulin (Ig)G deposits (PGNMID) is a rare disease with a treatment that is not well established. Several cases of recurrent PGNMID after kidney transplantation have been documented, but almost all cases reported symptoms such as elevated serum creatinine and/or urinary protein levels; subsequently, episode biopsies were performed and a diagnosis was made. This is the case of a 27‐year‐old man who underwent living‐donor kidney transplantation. The aetiology of renal failure was membranoproliferative glomerulonephritis type III, which had been diagnosed at the age of 9 years. Protocol biopsy performed on postoperative day 62 revealed isolated granular C3 deposits in the glomerular capillaries and mesangium. We reviewed the native kidney biopsy and confirmed IgG3 deposition alone, with strong glomerular staining for lambda light chains and negative staining for kappa light chains. Accordingly, we re‐diagnosed the aetiology of his renal failure as PGNMID and suspected recurrent PGNMID in the early stage; therefore, we administered plasma exchange therapy. Thereafter, protocol biopsies were performed twice, which revealed persistent isolated C3 deposition; therefore, we made a diagnosis of recurrent PGNMID or C3 glomerulonephritis. Currently, the patient has normal renal function, with negative urine findings for >1 year. Here, we present the histological findings of consecutive allograft biopsies performed in this patient. [ABSTRACT FROM AUTHOR]

ABSTRACT: Post‐transplant immunoglobulin A (IgA) nephropathy (IgAN) in the allograft is the major cause of allograft loss. Using a protocol biopsy, latent mesangial IgA deposition (IgAD) can be detected in the allograft. Latent IgAD is distinguished from IgAN by the absence of urinary abnormalities, although IgA is observed in the mesangium. However, the pathophysiology and most appropriate treatment strategy for latent mesangial IgAD in the allograft remain to be fully determined. Importantly, it is unknown whether all cases of post‐transplant asymptomatic IgAD progress to symptomatic IgAN; indeed, IgA deposits disappear in some cases. The differences in allograft prognosis between asymptomatic IgAD and IgAN have also not been determined. Non‐invasive methods of diagnosis of IgAD in the allograft using serological and pathological biomarkers are being developed. Possible serum biomarkers include serum galactose‐deficient IgA1 (Gd‐IgA1), Gd‐IgA1‐specific IgG and Gd‐IgA1‐specific IgA, and its immune complexes. Immunofluorescence analysis using Gd‐IgA1 monoclonal antibody may provide a pathological biomarker. These serological and pathological biomarkers may be suitable for the characterization of the stage of IgAD. However, there is insufficient information regarding whether serological and pathological biomarkers can predict the progression of asymptomatic IgAD to symptomatic IgAN. We propose that the pathogenesis of IgAN can be defined through the clinical study of IgAD in the allograft using protocol biopsies conducted by nephrologists involved in clinical kidney transplantation. [ABSTRACT FROM AUTHOR]

ABSTRACT: Aim: Recent studies have suggested that patients with post‐transplant immunoglobulin A nephropathy have poor graft survival. There is limited research on the therapeutic effectiveness for post‐transplant immunoglobulin A nephropathy, especially steroid pulse therapy. The present study evaluated the efficacy of steroid pulse therapy on post‐transplant immunoglobulin A nephropathy. Methods: We retrospectively analyzed patients diagnosed with de novo or recurrent immunoglobulin A nephropathy at Kyushu University Hospital between January 2013 and August 2015. Patients with moderate proteinuria (≥0.5 g/g creatinine) and/or cellular or fibrocellular crescents on a graft biopsy were treated with steroid pulse therapy. Steroid pulse therapy was 500 mg/day for 3 days in weeks 1 and 2, followed by 20 mg of oral prednisolone that was tapered after 6 months. Patients were followed for 2 years, and the estimated glomerular filtration rate, urinary findings, and adverse events were recorded. Results: Seven patients received steroid pulse therapy. The mean duration after kidney transplantation was 6.6 ± 4.7 years. After 2 years of treatment, 85.7% of patients reached complete remission of proteinuria, urinary protein excretion declined (0.82 ± 0.51 to 0.26 ± 0.22 g/g creatinine, P = 0.007), and the estimated glomerular filtration rate was maintained (48.7 ± 12.8 to 47.4 ± 14.0 mL/min per 1.73 m2, P = 0.98). Adverse events were observed in one patient who developed herpes zoster infection. Conclusion: Steroid pulse therapy for post‐transplant immunoglobulin A nephropathy effectively reduces proteinuria over 2 years. However, comparison of steroid pulse therapy and other regimens with a high‐quality design is required. [ABSTRACT FROM AUTHOR]

Abstract: Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis; the reported recurrence rate of IgAN after renal transplantation is as high as 13%‐50%. The impact of immunosuppressive therapy and steroid withdrawal on the risk of recurrence of IgAN is still under debate. We performed a retrospective single‐center study, selecting 123 kidney transplants (rtx) in 120 patients, between January 1995 and December 2012, with IgAN on the native kidney. In 51 of 123 transplants, at least one post‐transplantation biopsy for clinical indication was performed; in 28 of 51 transplants, IgAN recurrence (IgANr) was demonstrated. This group (G1; N = 28) was compared with a group without IgANr (G2; N = 23). In our study, clinically evident IgANr rate was 54.9% (28/51) on biopsied patients. At discharge, the use of the immunosuppressant drugs (tacrolimus, cyclosporine A, mycophenolate mofetil, azathioprine, mTor inhibitors) was not associated with an increased risk of IgANr (P = NS). At discharge, all patients were steroid treated. Neither the use of tacrolimus, mycophenolate mofetil, nor mTor inhibitors (mTori) at biopsy time were associated with IgANr. However, IgANr was significantly higher in patients who experienced steroid withdrawal at any post‐transplantation time (OR 7.7 P = .03). The median time to recurrence after steroid withdrawal was 59 months (min 4.18, max 113.2). [ABSTRACT FROM AUTHOR]

Proteinuria is common after renal transplantation and affects between 35%-45% of patients during the same year as their transplant. We report a case of dual pathology in the renal allograft as a cause of severe proteinuria. A 38-year-old male presented with end-stage renal disease. He underwent live related renal allograft transplant. His immediate post-transplant period was unremarkable. He developed rise in serum creatinine (2.1 mg/dl) 6 months after transplant and was biopsied. He was diagnosed as a case of acute cellular rejection type Ib with suspicion for antibody mediated rejection. He was treated with methylprednisolone to which he showed a good response with return of serum creatinine to 1.6 mg/dl. Subsequently, he developed a nephrotic range proteinuria 6 months after this episode of rejection. Repeat biopsy was performed. He was diagnosed as a case of immune complex mediated glomerulonephritis (GN) (morphologically consistent with pattern of membranoproliferative glomerulonephritis) with chronic humoral rejection in the form of transplant glomerulopathy (TG). IHC for C4d and immunofluorescence studies were instrumental making the diagnosis. He was treated with steroids and rituximab to which he showed a good response with remission of proteinuria. This case highlights the importance of picking up dual pathology in an allograft biopsy to ensure appropriate therapy. The role of C4d and its correct interpretation is further highlighted, especially with regard to pattern (granular versus linear) and location (glomerular capillaries versus peritubular capillaries).

Background: Immunoglobulin A nephropathy (IgAN) is a main cause of end stage renal disease (ESRD). Many IgAN patients with ESRD accept kidney allograft for renal replacement. However, disease recurrence occurs after transplantation. Galactose-deficient immunoglobulin A1(Gd-IgA1) has been proved to be a crucial biomarker in the primary IgAN population., Methods: This meta-analysis aimed to explore the association between serum Gd-IgA1 and IgAN recurrence after renal transplantation and was registered on PROSPERO: CRD42022356952; A literature search was performed and relevant studies were retrieved from the PubMed, Embase and Cochrane library databases from inception to April 27, 2023. The inclusion criteria were: 1) full-text studies; 2) patients with histological diagnosis of IgAN of their native kidneys who underwent kidney transplantation; 3) studies exploring the relationship between serum Gd-IgA1 and IgAN recurrence after kidney transplantation. The exclusion criteria were: 1) reviews, case reports, or non-clinical studies. 2) studies with insufficient original data or incomplete data. 3) studies with duplicated data. Study quality was assessed using Newcastle Ottawa Scale (NOS). Data were pooled using a random-effects model., Results: 8 full-text studies including 515 patients were identified. The Newcastle-Ottawa Scale (NOS) score ranged from 6 to 8. The standard mean difference (SMD) of the level of Gd-IgA1 was significantly higher in recurrence group than in non-recurrence group (SMD = 0.50，95%CI = 0.15-0.85, p = 0.005). Furthermore, Gd-IgA1 levels were higher in recurrence patients than in non-recurrence in both Europe subgroup (SMD 0.45, 95%CI: 0.08-0.82, p = 0.02) and Asia subgroup (SMD 0.90, 95%CI: 0.10-1.70, p = 0.03). However, pretransplant Gd-IgA1 levels showed no significant difference between recurrence and non-recurrence group (SMD 0.46, 95%CI: 0.06-0.99, p = 0.08) in anther subgroup analysis while posttransplant Gd-IgA1 levels were significantly higher in recurrence population than in non-recurrence (SMD 0.57, 95%CI 0.21 to 0.92, p = 0.002)., Conclusions: This meta-analysis showed that posttransplant serum Gd-IgA1 levels are associated with IgAN recurrence after kidney transplantation; however, pretransplant serum Gd-IgA1 levels are not., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Invasive aspergillosis is a serious complication in renal transplant recipients. Hepatic involvement, although seen in liver transplant recipients, has not been reported following renal transplantation. We describe here an interesting occurrence of hepatic Aspergillus infection in a renal transplant recipient. The infection responded to anti-fungal therapy, but there was re-activation following a second renal transplant. In addition, the patient had recurrence of the underlying membrano-proliferative glomerulonephritis following both transplants. The relevant existing literature relating to these problems has been reviewed.

Recurrence of native kidney disease following kidney transplantation affects between 10% and 20% of patients, and accounts for up to 8% of graft failures. In a considerable number of recipients with transplant glomerulopathy, it is impossible to distinguish between recurrent and de novo types. An accurate estimate of the incidence of recurrence is difficult due to limitations in the diagnosis of recurrent glomerulonephritis. De novo glomerular lesions may be misclassified if histological confirmation of the patient's native kidney disease is lacking. Asymptomatic histological recurrence in renal allografts may be missed if protocol biopsies are not available. Studies based on protocol biopsy are pivotal to accurately estimate the incidence of recurrence. Many factors are known to influence recurrence of kidney disease after transplantation, including the type and severity of the original disease, age at onset, interval from onset to end-stage renal disease, and clinical course of the previous transplantation. Early recognition of recurrence is possible in several glomerular diseases. Factors such as the existence of circulating permeability factors, circulating urokinase receptor and anti-phospholipase A2 receptor antibody, as well as disorders of complement regulatory proteins like factor I mutation and factor H mutation factors are expected to be useful predictors of recurrence. Peculiar clinical course of atypical haemolytic uremic syndrome after kidney transplantation is an informative sign of recurrent glomerular disease. These factors play pivotal roles in the development of recurrence of certain types of glomerulopathies. Understanding the pathogenesis of recurrent glomerulonephritis is critical to optimize prevention as well as treat individual cases of recurrent glomerulonephritis. Subclinical recurrence of IgA nephropathy after kidney transplantation is well recognized. Only protocol biopsies of clinically silent recipient can provide the accurate prevalence of recurrent IgA nephropathy. The study of recurrent glomerulonephritis will contribute not only to improving long-term graft survival, but also to clarifying the pathogenesis of glomerulonephritis. Protocol biopsy is one the most effective methods for elucidating the pathogenesis of recurrent glomerulonephritis. [ABSTRACT FROM AUTHOR]

IgA nephropathy ( IgAN) is recurrent after transplantation; however, its time of recurrence is unpredictable. To date, factors influencing IgAN recurrence have not been elucidated. We present a case of a 23-year-old man with end-stage renal disease ( ESRD) who underwent living-related ABO-identical pre-emptive kidney transplantation ( PEKT) using his 57-year-old mother as a donor. IgAN started when the patient was 19 years old, and renal biopsy revealed the usual pathological findings of IgAN. In spite of steroid therapy including steroid pulse and tonsillectomy, the patient developed nephrotic syndrome and progressed to ESRD in 4 years. Protocol biopsy on day 19 following PEKT revealed active recurrent IgAN. Nephrotic-range proteinuria and mild deterioration of kidney function developed regardless of strong immunosuppressive therapy such as steroid pulse, double filtration plasmapheresis and rituximab. We report a case of refractory IgAN that recurred 19 days after transplantation. This case is considered of value to elucidate factors leading to active IgAN recurrence. [ABSTRACT FROM AUTHOR]

Twenty-yr patient and death-censored graft survival of 348 kidney transplant recipients with primary glomerulonephritis ( GN) and of 696 matched controls were 82.2% in GN patients and 75% in controls (p = 0.037) and 49.5% and 54%, respectively (p = 0.013). GN patients had a higher incidence of graft failure than controls even considering death as a competing risk (p = 0.004). In the GN group, graft survival of deceased and of living donor recipients was similar. At multivariate analysis, GN as primary disease ( RR: 1.47), delayed graft function recovery ( RR: 2.34), acute rejection ( RR: 2.36), and any PRA positivity ( RR: 1.01) were predictive of graft loss. GN recurred in 85 of 348 grafts (24.4%), and 43 were lost for recurrence. In non-recurrent patients, graft survival at 20 yr was significantly better than in recurrent patients (59.4% vs. 24.4%, p = 0.000), but not different from that of controls (59.4 vs. 54%, p = 0.9). At multivariate analysis, young age at transplantation ( RR: 0.97), shorter duration of dialysis ( RR: 1.05 per each dialysis year), and graft from living donors ( RR: 1.668) were independent predictors of recurrence. Patients with primary GN have reduced graft survival in comparison with controls, and this is mainly due to recurrence of original disease. However, the most frequent recurrence in living recipients does not compromise graft survival. [ABSTRACT FROM AUTHOR]

Background Few data are available on allograft survival at 15 years, the impact and the predictors of recurrence of the original disease in renal transplanted patients with IgA nephropathy (IgAN). Methods In this retrospective study, we compared the long-term outcome of renal transplant in 190 patients with IgAN with that of 380 non-diabetic controls and evaluated the impact of recurrence of IgAN on the graft outcome. Results At 15 years, the patient survival was 88.3% in IgAN patients and 82.6% in controls (P = 0.12), while the death-censored graft survival was 62.6 and 72.4%, respectively (P = 0.038). IgAN had a higher cumulative incidence of graft failures in comparison with controls even considering death as a competing risk (P = 0.025). At multivariate analysis, IgAN [relative risk (RR) = 1.468, P = 0.026], delayed graft function recovery (RR = 2.394, P = 0.000) and acute rejection (RR = 2.51, P = 0.000) were predictive of graft loss. IgAN recurred in 42 grafts (22.1%), of them, 12 were lost for recurrence and in another 6 recurrence was considered a concomitant cause of graft loss. The 15-year death censored graft survival was 68.3% in non-recurrent and 51.2% in recurrent patients (P = 0.069). Pure graft survival of non-recurrent IgAN patients was similar to that of controls (P = 0.406). At Cox analysis, the recurrence of IgAN significantly reduced from 1981 to 2010 (P = 0.0065, RR = 0.936). Conclusions IgAN emerged as an independent predictor of worse graft outcome in the long-term. Recurrence of IgAN seems to progressively reduce in transplants performed from 1981 to 2010. [ABSTRACT FROM PUBLISHER]

Background: Post-transplant glomerulonephritis (PTGN) has been associated with inferior long-term allograft survival, and its incidence varies widely in the literature., Methods: 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., Results: 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., Conclusions: 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., Competing Interests: MH-F is currently an employee of UCB Celltech, a pharmaceutical company. Her involvement in the conduct of this research was solely in her capacity as academic at King’s College London. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Aguiar, Bourmpaki, Bunce, Coker, Delaney, de Jongh, Oliveira, Weir, Higgins, Spiridou, Hasan, Smith, Mulla, Glampson, Mercuri, Montero, Hernandez-Fuentes, Roufosse, Simmonds, Clatworthy, McLean, Ploeg, Davies, Várnai, Woods, Lord, Pruthi, Breen and Chowdhury.)

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. [ABSTRACT FROM AUTHOR]

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Background. Little information is available about the long-term outcome of renal transplanted patients with idiopathic membranous nephropathy (MN).Methods. The outcomes of 35 first renal transplants performed between 1975 and 2008 in patients with MN were compared with those of 70 controls transplanted in the same period and matched for sex, age and source of donors.Results. The mean post-transplant follow-up was 117 ± 86 months for MN patients and 123 ± 83 months for controls. At 15 years, patient survival was 96% in patients with MN and 88% in the controls (P = ns), while graft survival rates were respectively 40% and 69% (P = 0.06). MN recurred in 12 patients (34%), namely in 4/8 (50%) patients who received the kidney from related living donors and in 8/27 (29.6%) who received the kidney from a deceased donor. Recurrence led to graft failure in six patients, all deceased donor kidney recipients, within 54 ± 33 months. The other six grafts are functioning 134 ± 73 months after transplantation. Patients with recurrence were more frequently females (42% vs 4.3%, P = 0.02). The recurrence occurred earlier (4.8 ± 3.0 vs 45.6 ± 46.9 months, P = 0.05), and there was a trend to develop a higher proteinuria (7.1 ± 5.5 vs 3.67 ± 2.6 g/24 h, P = 0.1) in grafts eventually lost because of recurrence.Conclusions. The long-term patient survival was similar in renal transplant recipients with MN and in controls. The graft survival was lower in MN patients than in controls, although the difference was at borderline significance. Recurrence occurred in one-third of the patients and caused graft loss in half of them. [ABSTRACT FROM AUTHOR]

Background. IgA nephropathy (IgAN) is a frequent cause of end-stage renal disease (ESRD) and recurrent disease causes deterioration and graft loss in transplant recipients. No definitive management is known to reduce the risk or severity of recurrent IgAN, and the evidence to support the use of renin–angiotensin system blockade in such patients is limited. [ABSTRACT FROM PUBLISHER]

Copyright of EMC-Nephrologie is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)