Notwithstanding the ongoing coronavirus disease-2019 (Covid-19) pandemic, information on its clinical presentation and prognosis in recipients of a kidney transplant remain scanty. The aim of this registry-based observational study was to explore characteristics and clinical outcomes of recipients of kidney transplants included in the French nationwide Registry of Solid Organ Transplant Recipients with Covid-19. Covid-19 was diagnosed in symptomatic patients who had a positive PCR assay for SARS-CoV-2 or having typical lung lesions on imaging. Clinical and laboratory characteristics, management of immunosuppression, treatment for Covid-19, and clinical outcomes (hospitalization, admission to intensive care unit, mechanical ventilation, or death) were recorded. Risk factors for severe disease or death were determined. Of the 279 patients, 243 were admitted to hospital and 36 were managed at home. The median age of hospitalized patients was 61.6 years; most had comorbidities (hypertension, 90.1%; overweight, 63.8%; diabetes, 41.3%; cardiovascular disease, 36.2%). Fever, cough, dyspnea, and diarrhea were the most common symptoms on admission. Laboratory findings revealed mild inflammation frequently accompanied by lymphopenia. Immunosuppressive drugs were generally withdrawn (calcineurin inhibitors: 28.7%; antimetabolites: 70.8%). Treatment was mainly based on hydroxychloroquine (24.7%), antiviral drugs (7.8%), and tocilizumab (5.3%). Severe Covid-19 occurred in 106 patients (46%). Forty-three hospitalized patients died (30-day

Sirolimus (SRL) allows to minimize the use of cyclosporine (CsA), but de novo administration after transplantation is associated with various complications. We report a prospective, open-label, multicenter randomized study to evaluate conversion from a CsAbased regimen to a SRL-based regimen 3 months after transplantation. One hundred ninety-two of a total of 237 patients were eligible at 3 months to be converted to SRL (n = 95) or to continue CsA (n = 97). All patients were also given mycophenolate mofetil (MMF) and oral steroids, planned to be discontinued at month 8. The primary endpoint, the clearance estimated according to Cockcroft and Gault at week 52, was significantly better in the SRL group (68.9 vs. 64.4 mL/min, p = 0.017). Patient and graft survival were not statistically different. The incidence of acute rejection episodes, mainly occurring after withdrawal of steroids, was numerically but not statistically higher in the SRL group (17% vs. 8%, p = 0.071). Sixteen patients discontinued SRL, mainly for adverse events (n = 11), and seven patients discontinued CsA for renal failure or acute rejection. Significantly, more patients in the SRL group reported aphthous, diarrhea, acne and high triglyceride levels. Conversion CsA to SRL 3 months after transplantation combined with MMF is associated with improvement in renal function.

There are no studies which have compared the risk of severe Covid‐19 and related mortality between transplant recipients and non‐transplant patients. We enrolled two groups of patients hospitalized for Covid‐19, i.e., kidney transplant recipients from the French Registry of Solid Organ Transplant (n=306) and a single‐center cohort of non‐transplant patients (n=795). An analysis was performed among subgroups matched for age and risk factors for severe Covid‐19 or mortality. Severe Covid‐19 was defined as admission (or transfer) to an intensive care unit, need for mechanical ventilation, or death.Transplant recipients were younger and had more comorbidities compared to non‐transplant patients. They presented with higher creatinine levels and developed more episodes of acute kidney injury. After matching, the 30‐day cumulative incidence of severe Covid‐19 did not differ between KTR and non‐transplant patients; however, 30‐day Covid‐19‐related mortality was significantly higher in KTR (17.9% versus 11.4%, respectively, p=0.038). Age >60 years, cardiovascular disease, dyspnea, fever, lymphopenia, and C‐reactive protein (CRP) were associated with severe Covid‐19 in univariate analysis, whereas transplant status and serum creatinine levels were not. Age >60 years, hypertension, cardiovascular disease, diabetes, CRP >60 mg/L, lymphopenia, kidney transplant status (HR=1.55), and creatinine level >115 µmol/L (HR=2.32) were associated with Covid‐19‐related mortality in univariate analysis. In multivariable analysis, cardiovascular disease, dyspnea, and fever were associated with severe disease, whereas age >60 years, cardiovascular disease, dyspnea, fever, and creatinine level>115 µmol/L retained their independent associations with mortality. Kidney transplant recipients had a higher Covid‐19‐related mortality compared to non‐transplant hospitalized patients.

The aim of this study was to estimate the incidence of COVID-19 disease in the French national population of dialysis patients, their course of illness and to identify the risk factors associated with mortality. Our study included all patients on dialysis recorded in the French REIN Registry in April 2020. Clinical characteristics at last follow-up and the evolution of COVID-19 illness severity over time were recorded for diagnosed cases (either suspicious clinical symptoms, characteristic signs on the chest scan or a positive reverse transcription polymerase chain reaction) for SARS-CoV-2. A total of 1,621 infected patients were reported on the REIN registry from March 16th, 2020 to May 4th, 2020. Of these, 344 died. The prevalence of COVID-19 patients varied from less than 1% to 10% between regions. The probability of being a case was higher in males, patients with diabetes, those in need of assistance for transfer or treated at a self-care unit. Dialysis at home was associated with a lower probability of being infected as was being a smoker, a former smoker, having an active malignancy, or peripheral vascular disease. Mortality in diagnosed cases (21%) was associated with the same causes as in the general population. Higher age, hypoalbuminemia and the presence of an ischemic heart disease were statistically independently associated with a higher risk of death. Being treated at a selfcare unit was associated with a lower risk. Thus, our study showed a relatively low frequency of COVID-19 among dialysis patients contrary to what might have been assumed.

To elucidate the pathophysiology of dietary calcium independent hypercalciuria, 42 calcium stone formers (Ca SF) were selected because they had on free diet a calciuria greater than 0.1 mmol/kg/day. For four days they were put on a diet restricted in calcium (Ca RD) by exclusion of the dairy products. They collected 24 hour urines on free diet and on day 4 of Ca RD as well as the two-hour fasting urines on the morning of the day 5 and the four-hour urines passed after an oral calcium load of 1 g, for measurement of creatinine, Ca, PO4, urea and total hydroxyprolinuria (THP). On day 5 fasting plasma concentrations of Ca, PO4, intact PTH, Gla protein, calcidiol and calcitriol were measured. The patients were firstly classified into dietary hypercalciuria (DH, 18 patients) and dietary calcium-independent hypercalciuria (IH, 24 patients) on the basis of the disappearance or not of hypercalciuria on Ca RD. Then the patients with IH were subclassified into absorptive hypercalciuria (AH) because of normal fasting calciuria (8 patients) and into fasting hypercalciuria (16 patients). Fasting hypercalciuric patients were subsequently divided according to the PTH levels into renal hypercalciuria (RH, 1 patient) with elevated fasting PTH becoming normal after the Ca load and undetermined hypercalciuria (UH, 15 patients) with normal PTH levels. Furthermore, their vertebral mineral density (VMD) was measured by quantitative computerized tomography which was normal in DH (91 +/- 6% of the normal mean for age and sex) but was decreased in IH to 69 +/- 4%. No difference in VMD was observed between AH and UH. Urinary excretions of urea, phosphate and THP was higher in IH than in DH and comparable in AH and UH. Sodium excretion Ca RD was the same in all groups and subgroups as well as the plasma parameters. Plasma calcitriol was increased in IH and DH comparatively to normal in spite of normal plasma calcidiol. Calciuria increase after oral calcium load, an index of Ca absorption, was higher in IH than in controls and comparable in IH and DH as well as in the three subgroups of IH. From these data and correlation studies in IH it is concluded: (1.) VMD is decreased in Ca stone formers with IH but not in those with DH, making the distinction of these two groups of hypercalciuria patients clinically relevant.(ABSTRACT TRUNCATED AT 400 WORDS)

This nationwide study highlights the prognostic factors for PTLD and enables the development of a new prognostic score. After validation in an independent cohort, the use of this score should allow treatment strategies to be better tailored to individual patients in the future.

Lactic acidosis in diabetics on metformin therapy is rare but still associated with poor prognosis. The authors report here five cases. Three patients were initially with a cardiovascular collapse and all had an acute renal failure. Sodium bicarbonate haemodialysis therapy led to a dramatic improvement. Consciousness and hemodynamic status recovered rapidly. Severe metabolic and blood gases derangements were also rapidly corrected. Plasma metformin removal, appreciated by repeated blood samplings in 3 cases, was satisfactory. All patients survived. However, blood metformin levels remained abnormally high at the end of the dialytic therapy. In conclusion, (1) bicarbonate dialysis is an adequate treatment of lactic acidosis observed in diabetic patients treated with metformin since it rapidly corrects the acid-base disorders and partially removes metformin; (2) the sole accumulation of metformin is not sufficient to explain lactic acidosis since this latter might be corrected in spite of persisting high levels of blood metformin.

Background Although anti-HLA antibodies (Abs) cause most antibody-mediated rejections of renal allografts, non-anti-HLA Abs have also been postulated to contribute. A better understanding of such Abs in rejection is needed. MethodsWe conducted a nationwide study to identify kidney transplant recipients without anti-HLA donor-specific Abs who experienced acute graft dysfunction within 3 months after transplantation and showed evidence of microvascular injury, called acute microvascular rejection (AMVR). We developed a crossmatch assay to assess serum reactivity to human microvascular endothelial cells, and used a combination of transcriptomic and proteomic approaches to identify non-HLA Abs. ResultsWe identified a highly selected cohort of 38 patients with early acute AMVR. Biopsy specimens revealed intense microvascular inflammation and the presence of vasculitis (in 60.5%), interstitial hemorrhages (31.6%), or thrombotic microangiopathy (15.8%). Serum samples collected at the time of transplant showed that previously proposed anti-endothelial cell Abs-angiotensin type 1 receptor (AT1R), endothelin-1 type A and natural polyreactive Abs-did not increase significantly among patients with AMVR compared with a control group of stable kidney transplant recipients. However, 26% of the tested AMVR samples were positive for AT1R Abs when a threshold of 10 IU/ml was used. The crossmatch assay identified a common IgG response that was specifically directed against constitutively expressed antigens of microvascular glomerular cells in patients with AMVR. Transcriptomic and proteomic analyses identified new targets of non-HLA Abs, with little redundancy among individuals. ConclusionsOur findings indicate that preformed IgG Abs targeting non-HLA antigens expressed on glomerular endothelial cells are associated with early AMVR, and that in vitro cell-based assays are needed to improve risk assessments before transplant.