Johnny Sayegh

A case of sulphasalazine-induced DRESS syndrome with delayed acute interstitial nephritis

Drug rash with eosinophilia and systemic symptoms (DRESS syndrome) is a rare and severe drug-induced hypersensitivity syndrome characterized by haematological abnormalities (hypereosinophilia and/or mononucleosis) and multiorgan involvement. Renal failure has been rarely described. We report the case of a 77-year-old female with sulphasalazine-induced DRESS syndrome who improved rapidly on corticosteroid treatment. After prednisone withdrawal, the patient developed renal failure that necessitated a session of haemodialysis. A kidney biopsy showed acute tubulointerstitial nephritis with an intense lymphocytic infiltrate and tubular necrosis. Kidney function normalized after a further 2 weeks of corticosteroid treatment. This is the first histologically proven case of acute tubulointerstitial nephritis in the setting of sulphasalazine-induced DRESS syndrome.

Reduction of Extended‐Release Tacrolimus Dose in Low‐Immunological‐Risk Kidney Transplant Recipients Increases Risk of Rejection and Appearance of Donor‐Specific Antibodies: A Randomized Study

The aim of this study (ClinicalTrials.gov, NCT01744470) was to determine the efficacy and safety of two different doses of extended‐release tacrolimus (TacER) in kidney transplant recipients (KTRs) between 4 and 12 mo after transplantation. Stable steroid‐free KTRs were randomized (1:1) after 4 mo: Group A had a 50% reduction in TacER dose with a targeted TacER trough level (C0) >3 μg/L; group B had no change in TacER dose (TacER C0 7–12 μg/L). The primary outcome was estimated GFR at 1 year. Of 300 patients, the intent‐to‐treat analysis included 186 patients (group A, n = 87; group B, n = 99). TacER C0 was lower in group A than in group B at 6 mo (4.1 ± 2.7 vs. 6.7 ± 3.9 μg/L, p < 0.0001) and 12 mo (5.6 ± 2.0 vs. 7.4 ± 2.1 μg/L, p < 0.0001). Estimated GFR was similar in both groups at 12 mo (group A, 56.0 ± 17.5 mL/min per 1.73 m²; group B, 56.0 ± 22.1 mL/min per 1.73 m²). More rejection episodes occurred in group A than group B (11 vs. 3; p = 0.016). At 1 year, subclinical inflammation occurred more frequently in group A than group B (inflammation score [i] >0: 21.4% vs. 8.8%, p = 0.047; tubulitis score [t] >0: 19.6% vs. 8.7%, p = 0.076; i + t: 1.14 ± 1.21 vs. 0.72 ± 1.01, p = 0.038). Anti‐HLA donor‐specific antibodies appeared only in group A (6 vs. 0 patients, p = 0.008). TacER C0 should be maintained >7 μg/L during the first year after transplantation in low‐immunological‐risk, steroid‐free KTRs receiving a moderate dose of mycophenolic acid.

Thrombotic microangiopathy due to acquired ADAMTS13 deficiency in a patient receiving interferon-beta treatment for multiple sclerosis

Thrombotic microangiopathies (TMAs) can be due to inherited or acquired ADAMTS13 deficiency. Acquired deficiency is mainly associated with autoantibodies directed to ADAMTS13, including drug-induced forms. A few cases of TMA have been reported in association with interferon-alpha treatment and more rarely with interferon-beta. We report the case of a 52-year-old male with TMA-associated severe renal failure secondary to severe ADAMTS13 deficiency due to an anti-ADAMTS13 IgG antibody which developed after interferon-beta treatment for multiple sclerosis. Treatment included interferon-beta discontinuation, immediate plasma exchange therapy, corticosteroids, and hemodialysis. After an initial hematologic improvement, early hemolysis relapse led us to introduce rituximab allowing durable hematologic recovery. This is the first reported case of interferon-beta-induced TMA due to acquired ADAMTS13 deficiency that was treated by rituximab.

Relation between pretransplant magnesemia and the risk of new onset diabetes after transplantation within the first year of kidney transplantation.

Background New-onset diabetes after transplantation (NODAT) is a frequent condition associated with a poor outcome. In kidney transplantation, hypomagnesemia is a frequent posttransplant complication and has been associated with calcineurin inhibitors use. Previous studies have analyzed the relationship between posttransplant hypomagnesemia and the risk of NODAT and provided conflicting conclusions. We conducted an observational study to analyze the relationship between pretransplant magnesemia (Mg) and the risk of NODAT within the first year of kidney transplantation. Methods A cohort study was conducted to determine the risk conferred by pretransplant magnesium level on development of NODAT within 1 year posttransplant. First time kidney transplant recipients between January 2005 and December 2010 with more than 6 months of follow-up were included. Mg was measured within the 24 hours preceding kidney transplantation. NODAT was defined according to the American Diabetes Association criteria. Results Among the 154 patients analyzed, 28 (18.2%) developed NODAT at year 1. NODAT patients had lower levels of pretransplant Mg as compared with non-NODAT patients (P<0.02). When patients were divided into tertiles of Mg level, NODAT developed more frequently in patients in the lower tertile (Mg <2 mg/dL) as compared with patients in the higher tertile (Mg >2.3 mg/dL) (log rank, P<0.05). A multivariate analysis after adjustment to several variables demonstrated pretransplant Mg to be an independent risk factor of NODAT. Conclusion This study supports that a low pretransplant Mg level is an independent risk factor of NODAT in kidney transplant recipients.

Transplantation of kidneys from uncontrolled donation after circulatory determination of death: comparison with brain death donors with or without extended criteria and impact of normothermic regional perfusion.

The aim of this study was to compare the outcomes of kidney transplants from uncontrolled DCD (uDCD) with kidney transplants from extended (ECD) and standard criteria donors (SCD). In this multicenter study, we included recipients from uDCD (n = 50), and from ECD (n = 57) and SCD (n = 102) who could be eligible for a uDCD program. We compared patient and graft survival, and kidney function between groups. To address the impact of preservation procedures in uDCD, we compared in situ cold perfusion (ICP) with normothermic regional perfusion (NRP). Patient and graft survival rates were similar between the uDCD and ECD groups, but were lower than the SCD group (P < 0.01). Although delayed graft function (DGF) was more frequent in the uDCD group (66%) than in the ECD (40%) and SCD (27%) groups (P = 0.08 and P < 0.001), graft function was comparable between the uDCD and ECD groups at 3 months onwards post‐transplantation. The use of NRP in the uDCD group (n = 19) was associated with a lower risk of DGF, and with a better graft function at 2 years post‐transplantation, compared to ICP‐uDCD (n = 31) and ECD. In conclusion, the use of uDCD kidneys was associated with post‐transplantation results comparable to those of ECD kidneys. NRP preservation may improve the results of uDCD transplantation.

Low Serum Complement C3 Levels at Diagnosis of Renal ANCA-Associated Vasculitis Is Associated with Poor Prognosis

Background Recent studies have demonstrated the key role of the complement alternative pathway (cAP) in the pathophysiology of experimental ANCA-associated vasculitis (AAV). However, in human AAV the role of cAP has not been extensively explored. In the present work, we analysed circulating serum C3 levels measured at AAV onset and their relation to outcomes. Methods We conducted a retrospective observational cohort study including 45 consecutive patients with AAV diagnosed between 2000 and 2014 with serum C3 measurement at diagnosis, before immunosuppressive treatment initiation. Two groups were defined according to the median serum C3 level value: the low C3 group (C3<120 mg/dL) and the high C3 level group (C3≥120 mg/dL). Patient and renal survivals, association between C3 level and renal pathology were analysed. Results Serum complement C3 concentration remained in the normal range [78–184 mg/dL]. Compared with the high C3 level, the patients in the low C3 level group had lower complement C4 concentrations (P = 0.008) and lower eGFR (P = 0.002) at diagnosis. The low C3 level group had poorer patient and death-censored renal survivals, compared with the high C3 level group (P = 0.047 and P = 0.001, respectively). We observed a significant negative correlation between C3 levels and the percentage of glomeruli affected by cellular crescent (P = 0.017, r = -0.407). According to the Berden et al renal histologic classification, patients in the crescentic/mixed category had low C3 levels more frequently (P<0.01). Interestingly, we observed that when patients with the crescentic/mixed histologic form were analysed according to C3 level, long term renal survival was significantly greater in the high C3 level group than in the low C3 level group (100% vs 40.7% at 6 years, p = 0.046). No relationship between serum C4 and renal outcome was observed. Conclusion A Low C3 serum level in AAV patients at diagnosis is associated with worse long-term patient and renal survival.

An unexpected cause of progressive renal failure in a 66-year-old male after liver transplantation: secondary hyperoxaluria

BackgroundHyperoxaluria is a rare metabolic disorder characterized by calcium oxalate deposition in different tissues. It is caused either by an inherited disease of oxalate metabolism [primary hyperoxalurias (PH)] or by an acquired disturbance (secondary hyperoxaluria).CaseWe report here an atypical presentation of enteric hyperoxaluria-induced renal failure that occurred after liver transplantation. Despite adapted treatment and intensive haemodialysis, the patient did not recover. This case allows the reviewing of the multiple pathophysiological mechanisms involved in this disease.ConclusionOxalate nephropathy should be considered in the differential diagnosis of acute renal failure, especially when previous renal impairment and fat malabsorption are present. We suggest performing renal biopsy early to allow a prompt diagnosis and therapeutic intervention.

Successful long-term outcome of kidney transplantation in a patient with X-linked thrombocytopenia: 9-year follow-up.

Wiskott-Aldrich syndrome (WAS) is a rare X-linked syndrome including microthrombocytopenia, eczema, and cellular and humoral immunodeficiency with a high susceptibility to infections, autoimmune diseases, and Epstein-Barr virusYdriven lymphoproliferative disease (1, 2). Renal disease is found in 3% of patients with WAS, in particular immunoglobulin A nephropathy (IGAN) (3). Three cases of renal transplantation in WAS patients have been previously reported in the literature (4Y6). We report herein a case of successful 9-year followup of renal transplantation in a patient with X-linked thrombocytopenia, an attenuated form of WAS with minimal or no immunodeficiency A 29-year-old male with a family history of WAS is regularly followed-up in our center for a first kidney transplantation. During early childhood, he developed thrombocytopenia (30 10/mm) and eczema without any history of opportunist infections or autoimmune manifestations. At the age of 8 years, he developed proteinuria and macroscopic hematuria. Renal biopsy showed typical IGAN. Thereafter, he developed progressively an end-stage chronic kidney disease and began dialysis in January 2004 until successful renal transplantation in 2005. He received a deceased donor graft in May 2005; there were three human leukocyte antigen A-B-DR mismatches and no pretransplant human leukocyte antigen antibodies. Cytomegalovirus serology was donor positiveYrecipient negative, whereas Epstein-Barr virus serology was positive in both. The immunosuppressive regimen included initially basiliximab, prednisone, tacrolimus, and mycophenolate mofetil (MMF). He received anti-cytomegalovirus prophylaxis by valaciclovir and antipneumo cystis prophylaxis by sulfamethoxazoletrimethorprim for 3 months in accordance with usual protocol in our center. He did not develop any perioperative bleeding thanks to appropriate anesthesia management and platelet transfusion. Kidney function was defined by Modification of the Diet In Renal Disease-Glomerular Filtration Rate (MDRD-GFR) 56 ml/min at month 1 (M1) post transplantation and maintenance immunosuppressive therapy included tacrolimus and MMF (1000 mg/day) since M5. Four years after transplantation, he developed proteinuria (0.8 g/L) of glomerular profile. Renal biopsy showed IGAN relapse that we treated by three pulses of 500 mg of methylprednisolone then prednisone orally at 1 mg/kg per day with gradual tapering and the introduction of perindopril. After 9 years of follow-up, the patient has stable graft function (MDRD-GFR 52 mL/min) with proteinuria around 0.4 g/L. Fortunately, he did not develop any rejection, serious infection, or malignancy. In 2013, we performed genetic analysis that showed a known WAS mutation ‘‘c.223G9A p.Val75Met’’ which corresponds most to an X-linked thrombocytopenia phenotype. We thought that it is worth to report the successful long-term outcome of renal transplantation in this patient given the fact that in 2004, while we decided to transplant him, the outcome of renal transplantation in WAS patients was very doubtful regarding the fatal outcome in the cases reported in the literature at that time. In the case reported by Webb et al., the patient died 35 months after transplantation from a cause probably unrelated to the WAS. The postmortem examination did not find any evidence of lymphoproliferative disease (4). In the case reported by Fischer et al., the patient received a livingrelated kidney graft and was treated by antithymocyte globulin for 7 days. He developed many infectious complications and a malignant high-grade B-cell non-Hodgkin lymphoma. He died 98 days after transplantation; autopsy was refused by family and postmortem liver biopsy showed persistent lymphoma (6). Table 1 summarizes the main characteristics and the outcome of the previously reported kidney transplanted patients with WAS. To minimize the risk of infection and malignancy, we have chosen to avoid antithymocyte globulin in our patient. At year 7 after transplantation, the dose of MMF was reduced to 500 mg per day. Wiskott-Aldrich syndrome has a large spectrum of clinical manifestations: the classic full-blown WAS, the mild X-linked thrombocytopenia (XLT), and X-linked neutropenia (1, 2). X-linked thrombocytopenia is considered as an attenuated form of WAS because it is characterized by minimal or no immunodeficiency. X-linked thrombocytopenia is associated with a high overall survival rate but also a risk of lifethreatening complications because of thrombocytopenia (2). Surgical risk is still present but can be lowered by appropriate preoperative care. Given the growing knowledge of genetic mutations and their corresponding phenotypes in WAS, we decided to perform the genetic analysis in our patient after 8 years of successful renal transplantation without significant complications. That analysis showed a genetic mutation corresponding mostly to an XLT phenotype in accordance with his evolution so far. In conclusion, WAS patients, who need renal transplantation must be evaluated carefully and genetic mutation, should be identified if possible. Kidney transplantation in XLT patients can be successful with appropriate perioperative care to minimize the risk of bleeding and well-chosen immunosuppressive regimen to minimize the risk of developing life-threatening infections or malignancies. LETTERS TO THE EDITOR

Hypogammaglobulinemia and risk of severe infection in kidney transplant recipients.

Recent data have outlined a link between hypogammaglobulinemia (HGG) and infection risk and suggested that HGG correction may decrease post‐transplant infections.

Renal transplant malakoplakia: case report and review of the literature

Malakoplakia is a rare inflammatory disorder that affects predominantly the urinary tract and kidneys. Isolated renal parenchymal involvement occurs in 16% of all cases [1]. Urinary tract and digestive malakoplakia have been reported in transplant recipients but involvement in transplant tissue is rare. We report a case of renal allograft parenchymal malakoplakia and present a brief review of kidney transplant malakoplakia cases from the literature.