APOL1 polymorphisms and development of CKD in an identical twin donor and recipient pair.: Kidney donation in twins with APOL1 variant

International audienceWe report an occurrence of progressive loss of transplant function and ultimately transplant failure after living related kidney transplantation involving monozygotic twin brothers of Afro-Caribbean origin who were both heterozygous for the G1 and G2 kidney disease risk alleles in the APOL1 gene, which encodes apolipoprotein L-I. A 21-year-old man with end-stage kidney disease of unknown cause received a kidney from his brother, who was confirmed as a monozygotic twin by microsatellite analysis. Thirty months after transplantation, the patient presented with proteinuria and decreased estimated glomerular filtration rate; a biopsy of the transplant showed typical focal segmental glomerulosclerosis lesions. He received steroid therapy, but progressed to kidney failure 5 years later. The twin brother had normal kidney function without proteinuria at the time of transplantation; however, 7 years later, he was found to have decreased estimated glomerular filtration rate (40mL/min/1.73m(2)) and proteinuria (protein excretion of 2.5g/d). APOL1 genotyping revealed that both donor and recipient were heterozygous for the G1 and G2 alleles. This case is in stark contrast to the expected course of kidney transplantation in identical twins and suggests a role for APOL1 polymorphisms in both the donor and recipient

Intravenous immunoglobulin therapy in kidney transplant recipients with de novo DSA: Results of an observational study.

Approximately 25% of kidney transplant recipients develop de novo anti-HLA donor-specific antibodies (dnDSA) leading to acute antibody-mediated rejection (ABMR) in 30% of patients. Preemptive therapeutic strategies are not available.We conducted a prospective observational study including 11 kidney transplant recipients. Inclusion criteria were dnDSA occurring within the first year after transplant and normal allograft biopsy. All patients were treated with high-dose IVIG (2 g/kg 0, 1 and 2 months post-dnDSA). The primary efficacy outcome was incidence of clinical and subclinical acute ABMR within 12 months after dnDSA detection as compared to a historical control group (IVIG-).Acute ABMR occurred in 2 or 11 patients in the IVIG+ group and in 1 of 9 patients in the IVIG- group. IVIG treatment did not affect either class I or class II DSA, as observed at the end of the follow-up. IVIG treatment significantly decreased FcγRIIA mRNA expression in circulating leukocytes, but did not affect the expression of any other markers of B cell activation.In this first pilot study including kidney allograft recipients with early dnDSA, preemptive treatment with high-dose IVIG alone did not prevent acute ABMR and had minimal effects on DSA outcome and B cell phenotype

Clinical characteristics of treatment groups.

<p>Clinical characteristics of treatment groups.</p

At the time of <i>de novo</i> DSA (biopsy #1).

<p>At the time of <i>de novo</i> DSA (biopsy #1).</p

Blood leukocyte phenotypes and gene expression before and after IVIG treatment.

<p>Blood leukocyte phenotypes and gene expression before and after IVIG treatment.</p

Evolution of the DSA characteristics and lesion histology from the time of <i>dn</i>DSA detection (biopsy #1) to the time of the second biopsy (biopsy #2).

<p>1.A: Evolution of class I and class II DSA characteristics (number, MFI max and MFI sum). The evolution of all DSA characteristics was similar in the IVIG+ and the IVIG- group. DSA characteristics were also similar in the IVIG+ <i>vs</i>, IVIG- group, at both time points tested. 1.B: Evolution of chronic histologic lesions (ci, ct, cv and ah) as defined in Banff’13 updated classification. No histological differences were found between biopsy #1 and #2, in either the IVIG+ or IVIG- groups. The IVIG+ and control groups were also similar at both time points.</p

Intravenous immunoglobulin therapy in kidney transplant recipients with <i>de novo</i> DSA: Results of an observational study

<div><p>Background</p><p>Approximately 25% of kidney transplant recipients develop <i>de novo</i> anti-HLA donor-specific antibodies (<i>dn</i>DSA) leading to acute antibody-mediated rejection (ABMR) in 30% of patients. Preemptive therapeutic strategies are not available.</p><p>Methods</p><p>We conducted a prospective observational study including 11 kidney transplant recipients. Inclusion criteria were <i>dn</i>DSA occurring within the first year after transplant and normal allograft biopsy. All patients were treated with high-dose IVIG (2 g/kg 0, 1 and 2 months post-<i>dn</i>DSA). The primary efficacy outcome was incidence of clinical and subclinical acute ABMR within 12 months after <i>dn</i>DSA detection as compared to a historical control group (IVIG-).</p><p>Results</p><p>Acute ABMR occurred in 2 or 11 patients in the IVIG+ group and in 1 of 9 patients in the IVIG- group. IVIG treatment did not affect either class I or class II DSA, as observed at the end of the follow-up. IVIG treatment significantly decreased FcγRIIA mRNA expression in circulating leukocytes, but did not affect the expression of any other markers of B cell activation.</p><p>Conclusions</p><p>In this first pilot study including kidney allograft recipients with early <i>dn</i>DSA, preemptive treatment with high-dose IVIG alone did not prevent acute ABMR and had minimal effects on DSA outcome and B cell phenotype.</p></div

Membranous Nephropathy Associated With Immunological Disorder-Related Liver Disease

International audienceThe association between membranous nephropathy (MN) and immunological disorder-related liver disease has not been extensively investigated, and the specific features of this uncommon association, if any, remain to be determined.We retrospectively identified 10 patients with this association. We aimed to describe the clinical, biological, and pathological characteristics of these patients and their therapeutic management. The possible involvement of the phospholipase A2 receptor (PLA2R) in these apparent secondary forms of MN was assessed by immunohistochemistry with renal and liver biopsy specimens.The mean delay between MN and liver disease diagnoses was 3.9 years and the interval between the diagnosis of the glomerular and liver diseases was <1.5 years in 5 patients. MN was associated with a broad spectrum of liver diseases including primary biliary cirrhosis (PBC), autoimmune hepatitis (AIH), and primary sclerosing cholangitis (PSC). AIH whether isolated (n = 3) or associated with PBC (n = 2) or PSC (n = 2) was the most frequent autoimmune liver disease. Circulating PLA2R antibodies were detected in 4 out of 9 patients but the test was performed under specific immunosuppressive treatment in 3 out of 9 patients. Seven of the 9 patients with available renal tissue specimens displayed enhanced expression of PLA2R in glomeruli whereas PLA2R was not expressed in liver parenchyma from these patients or in normal liver tissue. The study of immunoglobulin (Ig) subclasses of deposits in glomeruli revealed that the most frequent pattern was the coexistence of IgG1 and IgG4 immune deposits with IgG4 predominating.Detection of PLA2R antibodies in glomeruli but not in liver parenchyma is a common finding in patients with MN associated with autoimmune liver disease, suggesting that these autoantibodies are not exclusively detected in idiopathic MN