Living Donor Kidney Transplant in Recipients With Glomerulonephritis: Donor Recipient Biologic Relationship and Allograft Outcomes.

Using the Scientific Registry of Transplant Recipients, we examined the association between donor-recipient biologic relationship and long-term recipient and allograft survival among glomerulonephritis (GN) patients. Four GN types were studied: membranous nephropathy, IgA, lupus-associated nephritis, and focal segmental glomerulosclerosis (FSGS). We identified all adult primary living-donor recipients between 2000 and 2018 (n = 19,668): related (n = 10,437); unrelated (n = 9,231). Kaplan-Meier curves were generated for the recipient, death-censored graft survival and death with functioning graft through ten years post-transplant. Multivariable Cox proportional hazard models were used to examine the association between the donor-recipient relationship and outcomes of interest. There was an increased risk for acute rejection by 12 months post-transplant among the unrelated compared to the related group in IgA (10.1% vs. 6.5%, p<0.001), FSGS (12.1% vs. 10%, p-0.016), and lupus nephritis (11.8% vs. 9.2%; p-0.049). The biological donor-recipient relationship was not associated with a worse recipient or graft survival or death with functioning graft in the multivariable models. These findings are consistent with the known benefits of living-related-donor kidney transplants and counter the reports of the potential adverse impact of the donor-recipient biologic relationship on allograft outcomes.

A patient with end-stage renal disease who recovered from coronavirus disease 2019 then received a kidney transplant.

Since its emergence in December 2019 many end-stage renal disease (ESRD) patients have been infected with coronavirus disease 2019 (COVID-19). Herein, we describe the case of an ESRD patient who received a kidney transplant after recovering from COVID-19. We described the clinical course of COVID-19 and kidney transplant management, including the patient's symptoms, laboratory results, computed tomography, and antibody profiles. He recovered well, without complications. Chest computed tomography, PCR, and IgG results indicated no recurrence of COVID-19 during the subsequent two weeks. Therefore, kidney transplantation is feasible in an ESRD patient who has recovered from COVID-19, under a normal immunosuppressive regimen.

Síndrome de Sagliker / Sagliker Syndrome

No disponible

Newly Diagnosed Glomerulonephritis During COVID-19 Infection Undergoing Immunosuppression Therapy, a Case Report.

During the COVID-19 pandemic, we had a 25 years old male case without any underlying disease or history of autoimmune disease in COVID-19 Clinic, Isfahan, Iran. He presented with arthralgia and weakness so we started COVID-19 therapeutic regimen. In his hospitalization, creatinine increases and abnormalities in random urine sediment was seen. Methylprednisolone and cyclophosphamide were prescribed due to suspected glomerulonephritis. After renal biopsy the diagnose was confirmed as crescentic proliferative glomerulonephritis. The patient also, underwent plasmapheresis and intravenous immunoglobulin injection. He was discharged healthy without development of new pulmonary symptoms despite immunosuppressive treatment.

Recurrence of DNAJB9-Positive Fibrillary Glomerulonephritis After Kidney Transplantation: A Case Series.

RATIONALE & OBJECTIVE: Fibrillary glomerulonephritis (FGN) is a rare glomerular disease that often progresses to kidney failure requiring kidney replacement therapy. We have recently identified a novel biomarker of FGN, DnaJ homolog subfamily B member 9 (DNAJB9). In this study, we used sequential protocol allograft biopsies and DNAJB9 staining to help characterize a series of patients with native kidney FGN who underwent kidney transplantation. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: Between 1996 and 2016, kidney transplantation was performed on 19 patients with a reported diagnosis of FGN in their native/transplant kidneys. Using standard diagnostic criteria and DNAJB9 staining, we excluded 5 patients (4 atypical cases diagnosed as possible FGN and 1 donor-derived FGN). Protocol allograft biopsies had been performed at 4, 12, 24, 60, and 120 months posttransplantation. DNAJB9 immunohistochemistry was performed using an anti-DNAJB9 rabbit polyclonal antibody. Pre- and posttransplantation demographic and clinical characteristics were collected. Summary statistical analysis was performed, including nonparametric statistical tests. OBSERVATIONS: The 14 patients with FGN had a median posttransplantation follow-up of 5.7 (IQR, 2.9-13.8) years. 3 (21%) patients had recurrence of FGN, detected on the 5- (n=1) and 10-year (n=2) allograft biopsies. Median time to recurrence was 10.2 (IQR, 5-10.5) years. Median levels of proteinuria and iothalamate clearance at the time of recurrence were 243mg/d and 56mL/min. The remaining 11 patients had no evidence of histologic recurrence on the last posttransplantation biopsy, although the median time of follow-up was significantly less at 4.4 (IQR, 2.9-14.4) years. 3 (21%) patients had a monoclonal protein detectable in serum obtained pretransplantation; none of these patients had recurrent FGN. LIMITATIONS: Small study sample and shorter follow-up time in the nonrecurrent versus recurrent group. CONCLUSIONS: In this series, FGN had an indolent course in the kidney allograft in that detectable histologic recurrence did not appear for at least 5 years posttransplantation.

A familial cluster, including a kidney transplant recipient, of Coronavirus Disease 2019 (COVID-19) in Wuhan, China.

In December 2019, an outbreak of COVID-19 occurred in Wuhan, China, and spread to the whole of China and to multiple countries worldwide. Unlike SARS and MERS, where secondary transmission mostly occurred in hospital settings, COVID-19 transmission occurs in large numbers within families. Herein we report three cases of a familial cluster with one family member being a kidney transplant recipient. The initial clinical symptoms of COVID-19 in these three patients were the same, but their progression was different. Based on the severity of clinical symptoms, chest computer tomography findings and SARS-Cov-2 RNA test results, we admitted the husband to the respiratory intensive care unit (RICU) and used a treatment consisting of immunosuppressant reduction/cessation and low dose methylprednisolone-based therapy, and his wife to the respiratory isolation ward. In contrast, the son received in-home isolation and home-based care. All three family members made a full recovery.

Successful recovery of COVID-19 pneumonia in a renal transplant recipient with long-term immunosuppression.

The current outbreak of Coronavirus Disease 2019 (COVID-19) has raised great concern worldwide, but its impact on transplant recipients is unknown. We report here the clinical features and therapeutic course of the first reported renal transplant recipient with confirmed COVID-19 pneumonia. This is a 52-year-old man who received kidney transplantation 12 years ago. His overall clinical characteristics (symptoms, laboratory examinations, and chest CT) were similar to those of non-transplanted COVID-19 patients. Following a treatment regimen consisting of reduced immunosuppressant use and low dose methylprednisolone-based therapy, the COVID-19 pneumonia in this long-term immunosuppressive patient was successfully recovered. This effectively treated case has reference value for the future treatment of other transplant patients with COVID-19 pneumonia.

Eculizumab in post-transplant C3 glomerulonephritis caused by a C3 mutation
.

C3 glomerulonephritis (C3GN) is a disorder of excess alternative complement activation leading to glomerular injury. Following kidney transplantation, C3GN has a high recurrence rate, and the overall prognosis is poor without treatment. However, treatment efficacy is highly variable. Eculizumab, a humanized monoclonal antibody that targets complement C5 to inhibit terminal complement activity, has emerged as a potential treatment option for C3G, although data regarding its clinical utility remains limited. In this report, we describe the successful use of eculizumab to treat a patient with recurrent post-transplant C3GN caused by a C3 gene gain-of-function mutation, and also review the published literature regarding the use of eculizumab for the treatment of recurrent C3 glomerulopathy.

A Case Report of Chyloretroperitoneum Post Living-Donor Transplantation.

Chyloretroperitoneum is a rare complication of urological surgery. Here we report a case of chyloretroperitoneum that occurred in a 28-year-old man post living-donor transplantation. Twenty-nine days post transplantation, perirenal fluid collection and hydronephrosis were detected and percutaneous drainage was performed. The fluid was chylous and revealed a very high triglyceride concentration (1,197 mg/dL). Total parenteral nutrition and administration of octreotide were performed, but the leakage did not improve. On the contrary, the drainage fluid gradually increased to 1,600 mL/day, and a laparoscopic fenestration was performed owing to a concern about the adverse effects of massive lymph loss. Ascites temporarily appeared but disappeared 3 months post fenestration. To our knowledge, this is the first case report of pelvic chyloretroperitoneum post living-donor transplantation. Furthermore, if chyloretroperitoneum treatment using diet control or octreotide is ineffective, laparoscopic fenestration can be considered as a treatment option.

Using Electronic Health Record Data to Rapidly Identify Children with Glomerular Disease for Clinical Research.

BACKGROUND: The rarity of pediatric glomerular disease makes it difficult to identify sufficient numbers of participants for clinical trials. This leaves limited data to guide improvements in care for these patients. METHODS: The authors developed and tested an electronic health record (EHR) algorithm to identify children with glomerular disease. We used EHR data from 231 patients with glomerular disorders at a single center to develop a computerized algorithm comprising diagnosis, kidney biopsy, and transplant procedure codes. The algorithm was tested using PEDSnet, a national network of eight children's hospitals with data on >6.5 million children. Patients with three or more nephrologist encounters (n=55,560) not meeting the computable phenotype definition of glomerular disease were defined as nonglomerular cases. A reviewer blinded to case status used a standardized form to review random samples of cases (n=800) and nonglomerular cases (n=798). RESULTS: The final algorithm consisted of two or more diagnosis codes from a qualifying list or one diagnosis code and a pretransplant biopsy. Performance characteristics among the population with three or more nephrology encounters were sensitivity, 96% (95% CI, 94% to 97%); specificity, 93% (95% CI, 91% to 94%); positive predictive value (PPV), 89% (95% CI, 86% to 91%); negative predictive value, 97% (95% CI, 96% to 98%); and area under the receiver operating characteristics curve, 94% (95% CI, 93% to 95%). Requiring that the sum of nephrotic syndrome diagnosis codes exceed that of glomerulonephritis codes identified children with nephrotic syndrome or biopsy-based minimal change nephropathy, FSGS, or membranous nephropathy, with 94% sensitivity and 92% PPV. The algorithm identified 6657 children with glomerular disease across PEDSnet, ≥50% of whom were seen within 18 months. CONCLUSIONS: The authors developed an EHR-based algorithm and demonstrated that it had excellent classification accuracy across PEDSnet. This tool may enable faster identification of cohorts of pediatric patients with glomerular disease for observational or prospective studies.

Successful re-transplantation in patient with recurrent parvovirus B19 pure red cell aplasia.

Impaired cell-mediated, as well as antibody-mediated immunity predisposes a renal transplant recipient to a wide variety of atypical infection. With an increasing number of re-transplant, the balance between immunosuppression and the risk of recurrent disease poses a clinical and therapeutic challenge. Here, we report a successful re-transplantation in a case of parvovirus B19 infection leading to anaemia and collapsing glomerulopathy in the allograft managed with intravenous immunoglobulin (IVIG) and reduction of immunosuppression. This case emphasizes re-consideration to renal transplant after clearance of the virus in a previous renal allograft lost to PVB19 infection.

Podocytes and Proteinuria in ANCA-Associated Glomerulonephritis: A Case-Control Study.

Proteinuria has been identified as prognosticator of renal outcome in patients with ANCA-associated glomerulonephritis, but whether proteinuria is related to podocyte abnormalities in these patients is largely unknown. We here investigate podocyte foot process width and number of podocytes positive for the podocyte marker WT-1 in diagnostic renal biopsies of 25 Caucasian patients with ANCA-associated glomerulonephritis in relation to proteinuria. Control tissue was used from pre-transplantation donor kidney biopsies. Proteinuria at 10 weeks follow-up correlated significantly with foot process width (P = 0.04). Biopsies with foot process width ≥600 nm belonged more often to the crescentic or mixed class, whereas biopsies with a foot process width <600 nm were most often categorized as focal class (P = 0.03). The mean number of podocytes based upon expression of WT-1 was significantly lower in patients compared to controls (15 vs. 34 podocytes per glomerulus; P < 0.0001). The significant decrease in expression of the podocyte WT-1 marker in ANCA-associated glomerulonephritis is considered indicative of actual podocyte loss or at least, of a loss of functionality. Furthermore, our study indicates that podocyte foot process width at baseline could be indicative for proteinuria at short term follow up. For prognostic purposes, we therefore suggest to include a description of the foot process width in the diagnostic report of a biopsy with ANCA-associated glomerulonephritis.

Association of sirolimus with pericardial effusion in renal transplant patient and discussion of potential mechanism.

Sirolimus is an important immunosuppressive drug in renal transplantation but contains numerous side effects. In this study, we describe a case of renal transplant recipient treated with sirolimus who developed pericardial effusion associated with interstitial pneumonia. An extensive search for alternative causes were all negative, and all symptoms disappeared after sirolimus interruption. Therefore, this case demonstrates that sirolimus can cause pericardial effusion possibly through a proinflammatory mechanism.

Bi-organ paired exchange-Sentinel case of a liver-kidney swap.

Organ transplantation is the optimal treatment for patients with end stage liver disease and end stage renal disease. However, due to the imbalance in the demand and supply of deceased organs, most transplant centers worldwide have consciously pursued a strategy for living donation. Paired exchanges were introduced as a means to bypass various biologic incompatibilities (blood- and tissue-typing), while expanding the living donor pool. This shift in paradigm has introduced new ethical concerns that have hitherto been unaddressed, especially with nondirected, altruistic living donors. So far, transplant communities have focused efforts on separate liver- and kidney-paired exchanges, whereas the concept of a transorgan paired exchange has been theorized and could potentially facilitate a greater number of transplants. We describe the performance of the first successful liver-kidney swap.

Clinical course and outcome after kidney transplantation in patients with C3 glomerulonephritis due to CFHR5 nephropathy.

BACKGROUND: Complement factor H-related protein 5 (CFHR5) nephropathy is an inherited renal disease characterized by microscopic and synpharyngitic macroscopic haematuria, C3 glomerulonephritis and renal failure. It is caused by an internal duplication of exons 2-3 within the CFHR5 gene resulting in dysregulation of the alternative complement pathway. The clinical characteristics and outcomes of transplanted patients with this rare familial nephropathy remain unknown. METHODS: This is a retrospective case series study of 17 kidney transplant patients with the established founder mutation, followed-up over a span of 30 years. RESULTS: The mean (±SD) age of patients at the time of the study and at transplantation was 58.6 ± 9.9 and 46.7 ± 8.8 years, respectively. The 10- and 15-year patient survival rates were 100 and 77.8%, respectively. Proteinuria was present in 33.3% and microscopic haematuria in 58.3% of patients with a functional graft. Serum complement levels were normal in all. 'Confirmed' and 'likely' recurrence of CFHR5 nephropathy were 16.6 and 52.9%, respectively; however, 76.5% of patients had a functional graft after a median of 120 months post-transplantation. Total recurrence was not associated with graft loss (P = 0.171), but was associated with the presence of microscopic haematuria (P = 0.001) and proteinuria (P = 0.018). Graft loss was associated with the presence of proteinuria (P = 0.025). CONCLUSIONS: We describe for the first time the clinical characteristics and outcome of patients with CFHR5 nephropathy post-transplantation. Despite the recurrence of CFHR5 nephropathy, we provide evidence for a long-term favourable outcome and support the continued provision of kidney transplantation as a renal replacement option in patients with CFHR5 nephropathy.

Recurrent Proliferative Glomerulonephritis With Monoclonal Immunoglobulin Deposits in Kidney Allografts Treated With Anti-CD20 Antibodies.

BACKGROUND: Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is a distinct form of glomerulonephritis that often recurs after kidney transplantation causing severe graft injury and often failure. METHODS: We describe post transplant outcomes and response to therapy in 20 recipients with PGNMID. Evidence of PGNMID recurrence or lack thereof was determined by protocol and clinical biopsies. RESULTS: Histologic recurrence (deposition of monoclonal immunoglobulin) occurred in 18 of 20 recipients (90%), a median of 7 (1 to 65) months post transplant. At diagnosis, recurrence was generally associated with mild or no clinical manifestations and often with mild glomerular morphologic changes by light microcopy. Four of the 18 patients with recurrence did not progress and were not treated. Another 4 patients with recurrences were treated with cyclophosphamide with or without plasmapheresis, and 2 of these grafts were lost from glomerulonephritis. Nine patients with recurrences were treated with anti-CD20 antibodies (rituximab) alone, resulting in improvements in estimated glomerular filtration rate (31.5 ± 16 versus 38.8 ± 13.3 mL/min/1.73 m, P = 0.011) and proteinuria (1280 [117 to 3752] versus 168 [83 to 1613] mg/24 h, P = 0.012) although complete clinical remission was rare. One graft in this later group was lost from recurrence 141 months post transplant. Posttreatment biopsies demonstrated stable or improved glomerular histology in most cases. However, PGNMID did not resolve in any case. Four patients received rituximab 4 months pretransplant to prevent recurrence. However, 3 had mild recurrences. CONCLUSIONS: Rituximab treatment of early PGNMID recurrence is effective, resulting in reasonable, long-term graft survival. Whether pretransplant rituximab modifies the course of recurrence requires additional studies.

Factors at de novo donor-specific antibody initial detection associated with allograft loss: a multicenter study.

We aimed to evaluate patient factors including nonadherence and viral infection and de novo donor-specific antibody (dnDSA) characteristics [total immunoglobulin G (IgG), C1q, IgG3, and IgG4] as predictors of renal allograft failure in a multicenter cohort with dnDSA. We performed a retrospective observational study of 113 kidney transplant recipients with dnDSA and stored sera for analysis. Predictors of death-censored allograft loss were assessed by Cox proportional modeling. Death-censored allograft survival was 77.0% (87/113) during a median follow-up of 2.2 (IQR 1.2-3.7) years after dnDSA detection. Predictors of allograft failure included medication nonadherence [HR 6.5 (95% CI 2.6-15.9)], prior viral infection requiring immunosuppression reduction [HR 5.3 (95% CI 2.1-13.5)], IgG3 positivity [HR 3.8 (95% CI 1.5, 9.3)], and time post-transplant (years) until donor-specific antibody (DSA) detection [HR 1.2 (95% CI 1.0, 1.3)]. In the 67 patients who were biopsied at dnDSA detection, chronic antibody-mediated rejection [HR 11.4 (95% CI 2.3, 56.0)] and mixed rejection [HR 7.4 (95% CI 2.2, 24.8)] were associated with allograft failure. We conclude that patient factors, including a history of viral infection requiring immunosuppression reduction or medication nonadherence, combined with DSA and histologic parameters must be considered to understand the risk of allograft failure in patients with dnDSA.

Kidney Transplantation in C3 Glomerulopathy: A Case Series.

RATIONALE & OBJECTIVE: C3 glomerulopathy (C3G), a form of glomerulonephritis associated with dysregulation of the alternative complement pathway, occurs either as dense deposit disease (DDD) or C3 glomerulonephritis (C3GN). Few studies have reported outcomes of patients with C3G after transplantation since its formal classification and the advent of complement-targeting therapies such as eculizumab. STUDY DESIGN: Case series of C3G. SETTING & PARTICIPANTS: We reviewed laboratory testing, native and allograft biopsy reports, and clinical charts of the 19 patients (12, C3GN; and 7, DDD) from our C3G registry who underwent transplantation between 1999 and 2016. RESULTS: During a median follow-up of 76 months, 16 patients had recurrent disease (10 of 12, C3GN; and 6 of 7, DDD), with median time to recurrence of 14 months in C3GN versus 15 months in DDD. Graft failure was more frequent in patients with DDD (6 of 7) than in patients with C3GN (3 of 12), occurred at a median time of 42 months posttransplantation, and was attributed to recurrent disease in half the failures. A rare genetic variant or autoantibody associated with alternative complement pathway abnormalities was detected in 9 of 10 screened patients. Treatment of 7 patients (8 allografts) with eculizumab was associated with variable clinical outcomes. LIMITATIONS: Incomplete testing for complement pathway abnormalities and genetic defects, incomplete records of HLA antigen matching, lack of centralized biopsy review, and limited sample size. CONCLUSIONS: In a case series of C3G transplant recipients, the proportion of disease recurrence was high in both C3GN and DDD, although graft loss appeared to occur more frequently in DDD. In a small subset of study patients, eculizumab therapy was not consistently followed by salutary outcomes.

Kidney transplantation in systemic lupus erythematosus: Outcomes and prognosis. / Resultados y pronóstico del trasplante renal en pacientes con lupus eritematoso sistémico.

INTRODUCTION: The outcome and prognosis of systemic lupus erythematosus (SLE) in long-term kidney transplantation (KT) is variable. The objective of this study was to analyse the survival of the graft and the patient, comparing rates with a control group (primary glomerulonephritis [PGN]). MATERIALS AND METHODS: Forty-three patients receiving a KT with diagnosis of lupus nephritis (LN) and 367 patients with PGN were compared between January 1980 and December 2014. The survival causes of loss and death of the graft and the patient were analysed. RESULTS: There were no significant differences between the variables analysed. The graft survival at five years (80% SLE vs. 70% PGN) and 10 years (63% SLE vs. 55% PGN) and the patient at 5 years (90% SLE vs. 90% PGN) and 10 years (76% LES vs. 79% PGN) were similar. Not recurrence of LN was observed in any patient. CONCLUSIONS: Patients with SLE are similar candidates to KT than that with other immunological kidney diseases. There was no recurrence of the disease in any patient.