Primary hyperoxaluria as an indication of liver and kidney transplantation: Case report and literature review

Primary Hyperoxaluria (PH) is a metabolic liver disease that results in oxalate overproduction that cannot be metabolized by the liver [1]. PH is caused by mutations in one of three genes that encode enzymes involved in glyoxylate metabolism. As oxalate is primarily excreted in the urine, the kidney is the prime target for oxalate deposition, which leads to end-stage kidney disease [2]. A patient named MN with Nephrocalcinosis (NC) was referred to the Children`s Memorial Health Institute of Warsaw in early childhood. The patient was diagnosed with PH type 1. PH type 1 is caused by mutations in a gene called AGXT that encodes alanine-glyoxylate aminotransferase. This enzyme is found in hepatic peroxisomes. It converts a compound called glyoxylate to the amino acid glycine [3]. In 02.12.1996, at the age of 13 the patient received a first kidney transplant from family member. In 16/09/1998 graftectomy was performed due to rapidly progressive kidney failure, nephrocalcinosis and infections. The patient had to return to hemodialysis after renal allograft loss. Also the patient was diagnosed with chronic HCV genotype 4 infection in 1998. In 08.11.2002, at the age of 19, the patient was qualified for a simultaneous liver and second kidney transplantation due to primary hyperoxaluria. The patient was treated with combination of: Daclizumab, steroid, tacrolimus, mycophenolate mofetil. Since October, 2015 the patient had been treating with combination of ombitasvir, paritaprevir, ribavirin and ritonavir. Hepatitis C Virus (HCV) was successfully eliminated. Patients with kidney failure from primary hyperoxaluria type 1 should not undergo kidney transplantation alone due to the very high risk of recurrence. Combined liver and kidney transplantation is the treatment of choice [4]. Keywords: Primary hyperoxaluria; kidney insufficiency; kidney transplantation; combined liver; kidney transplantation.

The FCGR3A 158 V/V-genotype is associated with decreased survival of renal allografts with chronic active antibody-mediated rejection

Natural killer (NK) cells express the Fc-gamma receptor CD16 (FCGR3A) and could therefore mediate renal endothelial cell damage in cases of chronic-active antibody mediated rejection (c-aABMR). The V/V-genotype of the FCGR3A 158 F/V polymorphism is associated with increased CD16 expression and cytotoxicity by NK cells. This study evaluated whether this genotype is associated with the diagnosis of c-aABMR and renal allograft loss. The distribution of the FGCR3A 158 F/V-genotypes was not different for c-aABMR cases (N = 133) compared to control kidney transplant recipients (N = 116, P = 0.65). The V-allele was associated with increased median fluorescence intensity (MFI) of CD16 by NK cells (MFI 3.5 × 104 versus 1.3 × 104 for V/V and F/F-genotype, P < 0.001). Increased expression of CD16 correlated with CD16-dependent degranulation of NK cells (R = 0.4; P = 0.02). Moreover, the V/V-genotype was significantly associated with a higher glomerulitis score and an independent risk factor (HR 1.98; P = 0.04) for decreased allograft survival. Death-censored graft survival in c-aABMR cases at 3 years follow-up was 33% for the FCGR3A 158 V/V-genotype versus 62% for the F/F-genotype. In conclusion, the FCGR3A V/V-genotype increases CD16-mediated NK cell cytotoxicity and is associated with a higher glomerulitis score and decreased graft survival in cases with c-aABMR.

Preceding T-Cell-Mediated Rejection Is Associated with the Development of Chronic Active Antibody-Mediated Rejection by de Novo Donor-Specific Antibody

<b><i>Aim:</i></b> Chronic active antibody-mediated rejection (CAABMR) is an important cause of late-stage renal allograft loss. Early inflammatory events such as acute rejection and infection after transplantation are considered to be the risk factors of de novo donor-specific antibody (dnDSA) production. In this study, we investigated the relationship between pre­disposing T-cell-mediated rejection and dnDSA-positive CAABMR. <b><i>Methods:</i></b> We recruited 365 patients who underwent ABO-compatible renal transplantation at our hospital. Among them, 16 patients diagnosed as having dnDSA-positive CAABMR were designated as a CAABMR group, and 38 randomly selected patients were designated as a control group. All biopsies from 1 month after transplantation were included in the study. The presence or absence of borderline changes (BLCs), acute T-cell-mediated rejection (ATMR), microvascular inflammation (MVI), and C4d positive on peritubular capillaries (C4d-P) was examined. <b><i>Results:</i></b> In the CAABMR group, BLC/ATMR was found in 12 cases (75%), and the mean duration until appearance of BLC/ATMR was 282.7 ± 328.7 days. C4d-P was found in 11 cases (68.8%), and the mean duration until its appearance was 1,432 ± 1,307 days. MVI was found in all cases, and the mean duration until its appearance was 1,333 ± 1,126 days. The mean duration until diagnosis of CAABMR was 2,268 ± 1,191 days. In the control group, BLC/ATMR was found in 13 cases (34.2%), and the mean duration until the appearance of BLC/ATMR was 173.1 ± 170.4 days. C4d-P was found in 2 cases (5.3%), and the durations until its appearance were 748 and 1,881 days. No cases of MVI were found in the control group. The frequency of BLC/ATMR was significantly higher in the CAABMR group (<i>p</i> &#x3c; 0.01). <b><i>Conclusion:</i></b> Preceding BLC/ATMR is associated with the development of CAABMR with dnDSA.

Acute antibody mediated rejection associated with acute herpetic gingiva-stomatitis in kidney transplant patient: A case report

Introduction: Antibody-mediated rejection (AMR) is the most serious cause of renal allograft loss. Most of the acute AMR attacks occur within the first week post-transplant. Subject: In this case report, we present a case of AMR that occurred five months post-transplant in association with acute oral viral infection. This patient had history of bone marrow hypoplasia two months following onset of hemodialysis and was maintained on cyclosporine and prednisolone beside switch to hirudin as anticoagulant. During that period, she also received 6 units of whole blood till she underwent kidney transplant after 2 years on dialysis. The post-transplant course was uneventful till the patient developed severe acute herpetic gingivastomatitis 5 months post-transplant that was associated with abrupt rise of renal chemistry. Biopsy proven AMR showed resistance to treatment with plasma exchange [PE] and Intravenous immunoglobulins. The patient was readmitted to regular hemodialysis unit for 2 months together with minimization of immunosuppressive treatment. Outcome: During routine follow-up investigations, kidney function tests became near to the pre-rejection levels. We discontinued dialysis and re-administered the initial immunosuppressive regimen. Conclusion: This is the first reported case of AMR in association with acute Herpes simplex infection that shows delayed spontaneous recovery.

Postinfectious Acute Glomerulonephritis in Renal Transplantation: An Emergent Aetiology of Renal Allograft Loss

Despite the high incidence of posttransplant infections, postinfectious acute glomerulonephritis (PIAGN) in renal allograft is a rare entity, without effective treatment and a bad prognosis. We describe two cases of PIAGN: the first one was developed 2 years after kidney transplantation, secondary to Staphylococcus aureus bacteremia with presence of extracapillary proliferation in biopsy. The patient was treated with methylprednisolone and plasma exchanges without response, remaining dialysis dependent. The second case was reported 5 years after kidney transplantation, secondary to influenza A infection. Kidney biopsy showed an IgA-dominant PIAGN and methylprednisolone boluses were initiated without clinical response, suffering a progressive worsening and loss of kidney graft. Due to the aggressive clinical course of this entity, PIAGN should be considered in the differential diagnosis of acute kidney graft failure in the context of an infection. Elderly patients have a higher risk of more severe acute renal dysfunction, requiring dialysis in a great proportion of cases.