Prophylactic or Early Use of Eculizumab and Graft Survival in Kidney Transplant Recipients With Atypical Hemolytic Uremic Syndrome in the United States: Research Letter.

INTRODUCTION: Among kidney transplant recipients (KTRs) with end-stage kidney disease (ESKD) due to atypical hemolytic uremic syndrome (aHUS), recurrence is associated with poor allograft outcomes. We compared graft and patient survival of aHUS KTRs with and without prophylactic/early use of eculizumab, a monoclonal antibody that binds complement protein C5, at the time of transplantation. METHODS: We conducted a retrospective cohort study using the United States Renal Data System. Out of 123 624 ESKD patients transplanted between January 1, 2008, and June 1, 2016, we identified 348 (0.28%) patients who had "hemolytic uremic syndrome" as the primary cause of ESKD. We then linked these patients to datasets containing the Healthcare Common Procedure Coding System (HCPCS) code for eculizumab infusion. Patients who received eculizumab prior to or within 30 days of transplant represented the exposure group. We calculated crude incidence rates and conducted exact logistic regression, adjusted for recipient age and sex, for the study outcomes of graft loss, death-censored graft loss, and mortality. We also estimated the average treatment effect (ATE) by propensity-score matching, to reduce the bias in the estimated treatment effect on graft loss. RESULTS: Our final study cohort included 335 aHUS KTRs (23 received eculizumab, 312 did not), with a mean duration of follow-up of 5.8 ± 2.7 years. There were no significant differences in baseline demographic and clinical characteristics between the eculizumab versus non-eculizumab group. Patients who received prophylactic/early eculizumab were less likely to experience graft loss compared with those who did not receive eculizumab (0% vs 20%, P = .02), with an adjusted odds ratio of 0.13 (P = .02). In the propensity-score-matched sample, the ATE (eculizumab vs non-eculizumab) was -0.20 (95% confidence interval [CI] = -0.25 to -0.15, P < .001); thus, treatment was associated with an average of 20% reduction in graft loss. There was no significant difference in the risk of death between the 2 groups. CONCLUSIONS: Although there was no significant difference in the risk of death, prophylactic/early use of eculizumab was significantly associated with improved graft survival among aHUS KTRs. Given the high cost of eculizumab, randomized controlled trials are much needed to guide prophylactic strategies to prevent graft loss.

INTRODUCTION: Chez les receveurs d'une greffe rénale (RGR) dont l'insuffisance rénale terminale (IRT) est due au syndrome hémolytique et urémique atypique (SHUa), la récidive est associée à de mauvais résultats d'allogreffe. Nous avons comparé la survie du greffon et des patients RGR-SHUa avec et sans administration prophylactique/précoce d'éculizumab, un anticorps monoclonal qui lie la protéine C5 du complément, au moment de la transplantation. MÉTHODOLOGIE: Nous avons mené une étude de cohorte rétrospective en utilisant le United States Renal Data System. Parmi les 123 624 patients atteints d'IRT transplantés entre le 1er janvier 2008 et le 1er juin 2016, nous avons répertorié 348 (0,28 %) patients présentant un « syndrome hémolytique urémique ¼ comme cause principale de l'IRT. Nous avons ensuite lié ces patients à des ensembles de données contenant le code du Healthcare Common Procedure Coding System (HCPCS) pour la perfusion d'éculizumab. Les patients ayant reçu de l'éculizumab avant l'intervention ou dans les 30 jours suivant la transplantation représentaient le groupe d'exposition. Nous avons calculé les taux bruts d'incidence et procédé à une régression logistique exacte, corrigée selon l'âge et le sexe du receveur, pour les résultats de l'étude concernant la perte du greffon, la perte du greffon censurée par le décès et la mortalité. Nous avons également estimé l'effet de traitement moyen (ETM) par appariement des scores de propension, afin de réduire le biais de l'effet estimé du traitement sur la perte du greffon. RÉSULTATS: Notre cohorte d'étude finale comprenait 335 patients RGR-SHUa (23 ayant reçu de l'éculizumab et 312 n'en ayant pas reçu) dont le suivi s'établissait à 5,8 ± 2,7 ans. Aucune différence significative n'a été observée entre les caractéristiques cliniques et démographiques initiales des deux groupes de sujets. Les patients ayant reçu de l'éculizumab prophylactique/précoce étaient moins susceptibles de subir une perte du greffon que ceux qui n'en avaient pas reçu (0 % vs 20 %; P = 0,02), avec un rapport de cotes corrigé de 0,13 (P = 0,02). Dans l'échantillon aux scores de propension appariés, l'ETM (éculizumab vs sans éculizumab) était de −0,20 (IC 95 %: −0,25 à −0,15; P < 0,001), le traitement a donc été associé à une réduction moyenne de 20 % de la perte du greffon. Aucune différence significative n'a été observée entre les deux groupes quant au risque de décès. CONCLUSION: Bien qu'aucune différence significative n'ait été observée pour le risque de mortalité, l'administration prophylactique/précoce d'éculizumab a été associée de façon significative à une amélioration de la survie du greffon chez les patients RGR-SHUa. Étant donné le coût élevé de l'éculizumab, des essais contrôlés randomisés sont nécessaires pour orienter les stratégies prophylactiques visant à prévenir la perte du greffon.

Biotin supplement interference with immunoassays for parathyroid hormone and 25-hydroxyvitamin D in a patient with metabolic bone disease on maintenance hemodialysis.

Biotin (vitamin B7) is a dietary supplement that can lead to falsely abnormal endocrine function tests. The impact of biotin on both 25-hydroxyvitamin D [25(OH)D] and intact parathyroid hormone (iPTH) have not been previously described in end-stage renal disease (ESRD). A woman with ESRD on hemodialysis taking biotin 10 mg daily had a 25(OH)D spike from 25 to >100 ng/mL and an iPTH decrease from 966 to 63 pg/mL. After discontinuation of biotin, her 25(OH)D and iPTH returned to baseline. Biotin can cause erroneous 25(OH)D and iPTH results in ESRD that could adversely affect patient care.

Aliskiren as an adjunct therapy for atypical hemolytic uremic syndrome.

Direct renin inhibitors (DRIs) block the activation of the alternative complement pathway in vitro and could be a treatment option for refractory hypertension in atypical hemolytic uremic syndrome (aHUS). A 20-year-old male presented with primary aHUS complicated by end-stage renal disease and refractory malignant hypertension despite being on five antihypertensive medications at maximum dose. Only a partial response was achieved with aliskiren and eculizumab, but after increasing aliskiren to a supratherapeutic dose, antihypertensive medication was reduced, platelets increased, C3 increased and epoetin alfa requirement decreased. DRI may be an adjunct treatment for malignant hypertension associated with aHUS.

An unusual cause of acute kidney injury due to oxalate nephropathy in systemic scleroderma.

Oxalate nephropathy is an uncommon cause of acute kidney injury. Far rarer is its association with scleroderma, with only one other published case report in the literature. We report a case of a 75-year-old African-American female with a history of systemic scleroderma manifested by chronic pseudo-obstruction and small intestinal bacterial overgrowth (SIBO) treated with rifaximin, who presented with acute kidney injury with normal blood pressure. A renal biopsy demonstrated extensive acute tubular injury with numerous intratubular birefringent crystals, consistent with oxalate nephropathy. We hypothesize that her recent treatment with rifaximin for SIBO and decreased intestinal transit time in pseudo-obstruction may have significantly increased intestinal oxalate absorption, leading to acute kidney injury. Oxalate nephropathy should be considered in the differential diagnosis of acute kidney injury in scleroderma with normotension, and subsequent evaluation should be focused on bowel function to include alterations in gut flora due to antibiotic administration.