Pitfalls in Valganciclovir Prophylaxis Dose Adjustment Based on Renal Function in Kidney Transplant Recipients.

Valganciclovir (VGC) is administered as prophylaxis to kidney transplant recipients (KTR) CMV donor (D)+/recipient (R)- and CMV R+ after thymoglobulin-induction (R+/TG). Although VGC dose adjustments based on renal function are recommended, there is paucity of real-life data on VGC dosing and associations with clinical outcomes. This is a retrospective Swiss Transplant Cohort Study-embedded observational study, including all adult D+/R- and R+/TG KTR between 2010 and 2020, who received prophylaxis with VGC. The primary objective was to describe the proportion of inappropriately (under- or over-) dosed VGC week-entries. Secondary objectives included breakthrough clinically significant CMV infection (csCMVi) and potential associations between breakthrough-csCMVi and cytopenias with VGC dosing. Among 178 KTR, 131 (73.6%) patients had ≥2 week-entries for the longitudinal data of interest and were included in the outcome analysis, with 1,032 VGC dose week-entries. Overall, 460/1,032 (44.6%) were appropriately dosed, while 234/1,032 (22.7%) and 338/1,032 (32.8%) were under- and over-dosed, respectively. Nineteen (14.5%) patients had a breakthrough-csCMVi, without any associations identified with VCG dosing (p = 0.44). Unlike other cytopenias, a significant association between VGC overdosing and lymphopenia (OR 5.27, 95% CI 1.71-16.22, p = 0.004) was shown. VGC prophylaxis in KTR is frequently inappropriately dosed, albeit without meaningful clinical associations, neither in terms of efficacy nor safety.

[IgA nephropathy : update]. / Nouveautés dans la néphropathie à IgA.

IgA nephropathy is the most common primary glomerulopathy worldwide. However, it remains underdiagnosed because of its clinical heterogeneity. Its diagnosis is currently based on kidney biopsy and there are no clinically validated serological tests. Its pathogenesis is based on an anomaly in the glycosylation of type A immunoglobulins and a progression punctuated by multiple triggering events (hits). The conservative approach of using corticosteroid therapy and/or more selective immunosuppression in certain clinical situations remains the state-of-the-art treatment. New therapeutic perspectives seem promising but must be validated.

La néphropathie à immunoglobulines A est la glomérulopathie primaire la plus fréquente dans le monde. Elle reste néanmoins sous-diagnostiquée de par son hétérogénéité clinique. Son diagnostic repose actuellement sur la biopsie rénale et il n'existe pas de tests sérologiques cliniquement validés. Sa pathogenèse repose sur une anomalie de la glycosylation des immunoglobulines de type A et une progression rythmée par des événements déclencheurs multiples. L'approche conservatrice reste la pierre angulaire du traitement avec recours à la corticothérapie et/ou une immunosuppression plus sélective dans certaines situations cliniques. De nouvelles perspectives thérapeutiques semblent prometteuses, mais doivent être validées.

Calcification Propensity (T50) Predicts a Rapid Decline of Renal Function in Kidney Transplant Recipients.

BACKGROUND: Serum creatinine level, proteinuria, and interstitial fibrosis are predictive of renal prognosis. Fractional excretion of phosphate (FEP)/FGF23 ratio, tubular reabsorption of phosphate (TRP), serum calcification propensity (T50), and Klotho's serum level are emerging as determinants of poor kidney outcomes in CKD patients. We aimed at analysing the use of FGF23, FEP/FGF23, TRP, T50, and Klotho in predicting the rapid decline of renal function in kidney allograft recipients. METHODS: We included 103 kidney allograft recipients in a retrospective study with a prospective follow-up of 4 years. We analysed the predictive values of FGF23, FEP/FGF23, TRP, T50, and Klotho for a rapid decline of renal function defined as a drop of eGFR > 30%. RESULTS: During a follow-up of 4 years, 23 patients displayed a rapid decline of renal function. Tertile of FGF23 (p value = 0.17), FEP/FGF23 (p value = 0.78), TRP (p value = 0.62) and Klotho (p value = 0.31) were not associated with an increased risk of rapid decline of renal function in kidney transplant recipients. The lower tertile of T50 was significantly associated with eGFR decline >30% with a hazard ratio of 3.86 (p = 0.048) and remained significant in multivariable analysis. CONCLUSION: T50 showed a strong association with a rapid decline of renal function in kidney allograft patients. This study underlines its role as an independent biomarker of loss of kidney function. We found no association between other phosphocalcic markers, such as FGF23, FEP/FGF23, TRP and Klotho, with a rapid decline of renal function in kidney allograft recipients.

Management of Acute Wilsonian Hepatitis with Severe Hemolysis: A Successful Combination of Chelation and MARS Dialysis.

Wilson's disease is a rare hereditary disorder of copper metabolism leading to progressive accumulation of copper in several organs including the brain and the liver. Acute liver failure is a relatively rare hepatic manifestation of WD which may require urgent liver transplantation if medical treatment fails. We report here the case of a young woman who presented with classic acute Wilsonian hepatitis complicated by liver and renal failure and a severe hemolysis related to massive nonceruloplasmin bound copper accumulation requiring repeated blood transfusions. The early initiation of a combined treatment including conventional chelation therapy and repeated MARS dialysis sessions allowed a rapid control of hemolysis, a progressive decrease of free copper overload, and clinical recompensation without liver transplantation.

Management and outcomes of patients on maintenance dialysis during the first and second wave of the COVID-19 pandemic in Geneva, Switzerland.

BACKGROUND: Patients on maintenance dialysis are at high risk for serious complications from COVID-19 infection, including death. We present an overview of local experience with dialysis unit management and reorganisation, local epidemiology and outcomes during the COVID-19 outbreak in Geneva, Switzerland, where SARS-CoV-2 incidence was one of the highest in Europe. METHODS: All SARS-CoV-2-positive outpatients on maintenance dialysis were transferred from their usual dialysis facility to the Geneva University Hospitals dialysis unit to avoid creation of new clusters of transmission. Within this unit, appropriate mitigation measures were enforced, as suggested by the institutional team for prevention and control of infectious diseases. RESULTS: From 25 February to 31 December 2020, 82 of 279 patients on maintenance dialysis tested positive for SARS-CoV-2 during two distinct waves, with an incidence rate of 73 cases per 100,000 person-days during the first wave and 342 cases per 100,000 during the second wave, approximately four- to six-fold higher than the general population. The majority of infections (55%) during both waves were traced to clusters. Most infections (62%) occurred in men. Sixteen patients (34%) died from COVID-19 related complications. Deceased patients were older and had a lower body mass index as compared with patients who survived the infection. CONCLUSION: SARS-CoV-2 is associated with high infection and fatality rates in the dialysis population. Strict mitigation measures seemed to be effective in controlling infection spread among patients on maintenance dialysis outside of clusters. Large scale epidemiological studies are needed to assess the efficacy of preventive measures in decreasing infection and mortality rates within the dialysis population.