Arnaud Lionet

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Although hepatic production of FGF23 has been suggested in chronic settings, there is no data indicating hypophosphatemia resulting from acute hepatic FGF23 production. Based on two clinical observations of profound hypophosphatemia in the setting of acute hepatitis, our study investigates the hypothesis of acute FGF23 liver expression. Retrospective analyses were conducted to estimate FGF23 liver expression both qualitatively (in situ hybridization) and quantitatively (relative FGF23 gene expression and protein production) on histological specimens of human and murine acute hepatitis livers, compared to controls of hepatic fibrosis or healthy liver. The index clinical case involves acute alcoholic hepatitis complicated by profound hypophosphatemia due to phosphate diabetes, revealing a major production of both FGF23 C-terminal fraction (cFGF23) and bio-intact form (iFGF23, 39 751 RU/mL, N: 21–91 and 228.6 pg/mL, N:22.7–93.1 respectively). A second case of acute hepatitis related to erythrocytic protoporphyria also exhibited comparable abnormalities. In both cases, no other cause of renal phosphate wasting was identified, and the hydroelectrolytic disorders disappeared in parallel with normalization of the liver balance and FGF23 levels. Histological data of acute hepatitis compared to cirrhosis and healthy liver confirmed our hypothesis of hepatic FGF23 overproduction. Furthermore, mouse models showed a significant increase in FGF23 RNA relative liver expression in acute hepatitis and a moderate increase in cirrhosis, compared to healthy liver (respectively 60.55 ± 16.75 and 3.70 ± 0.87 versus 1.00 ± 0.65, both P < 0.05). These findings were also confirmed at the protein level. This translational study raises the hypothesis of renal phosphate wasting induced by excessive hepatic production of FGF23 in case of acute hepatitis.

Background.: The benefit of extracorporeal photopheresis on the course of kidney transplant rejection is unknown. The aim of our study was to investigate the variations in transcriptomics on graft biopsies when extracorporeal photopheresis was used to treat chronic humoral rejection after kidney transplantation. Methods.: We retrospectively analyzed the mRNA expression of 770 genes of interest in graft biopsies performed before and after treatment. Eight patients received an average of 23 extracorporeal photopheresis sessions over 4 mo between the 2 biopsies. Results.: Transcriptomic analysis of the graft biopsies identified a significant (adjusted P < 0.05) increase in CAV1 mRNA in all patients and a significant decrease in CD19, IL21, PAX5, and SFTPA2 mRNAs in 7 of 8 patients. Conclusions.: In patients treated with extracorporeal photopheresis for chronic humoral rejection after renal transplantation, omic analysis of repeated biopsies shows a reduction in fibrotic and inflammatory transcriptomic biologicals markers.

For 30 years, photopheresis is used to treat graft versus host disease and heart or lung allograft rejection. In this review, we discuss the place of photopheresis in kidney transplantation both in prevention or treatment of rejection. Mechanisms of action in kidney transplantation are mainly based on results observed in graft versus host disease and in heart or lung transplantation. Photopheresis may induce innate and adaptive immunity changes with restauration of a favourable Th1/Th2 immune balance, an expansion of LT /LB reg subsets, and a local enrichment in IL-10. French national clinical and mechanistic studies are underway to define the place of photopheresis therapy in immunomodulation strategies in kidney transplantation.

MicroRNAs (miRNAs) are small, non-coding RNA species that control gene expression and confer robustness to biological processes. Over the last two decades, their important roles during kidney development, homeostasis and the treatment of diseases have been established, in particular during the onset and progression of various forms of acute and chronic renal disorders. In recent years, miR-21, one of the best-characterized miRNAs to date, has received much attention in renal physiology in particular given its high degree of conservation and expression in kidneys, as well as its potent pathogenic role in various debilitating renal diseases. This review summarizes the current knowledge on miR-21’s involvement in both renal homeostasis and diseases, in particular its double-edged-sword role in acute versus chronic kidney injuries. Finally, we also discuss the potential of miR-21 as a biomarker and therapeutic target in renal diseases.

Chronic urinary tract infections by urease-producing bacteria may increase urine pH and promote thereby the formation of recurrent kidney stones made of highly carbonated calcium phosphate apatite and struvite, a magnesium ammonium phosphate. To date, there is no safe and effective treatment decreasing urine pH on a long term. We hypothesized that fludrocortisone, a mineralocorticoid, would decrease urine pH by increasing proton secretion in the kidney collecting tubule. We report three cases of patients with kidney stone suffering from chronic urinary infection by urease-producing germs, treated by fludrocortisone on a long term. Urine pH decreased sustainably over several months and tolerance was good.

Uremic calciphylaxis is a rare disease that affects patients with chronic end-stage renal disease. It is a pathology of the microvessels of the dermis and hypodermis which are calcified and whose thrombosis leads to skin necrosis. Calciphylaxis lesions can be distal and axial. They lead to pain, infection and are associated with denutrition and in high mortality rate (40-80% at 1 year). This general review describes the clinical and para-clinical presentations of calciphylaxis. It summarizes the current knowledge on its pathogenesis and the therapeutical options that can be proposed to improve the management and attempt to reduce the mortality of patients with uremic calciphylaxis.

(2020). New visceral manifestations of fibrinogen alpha-chain amyloidosis. Amyloid. Ahead of Print.

Aim: Uremic calciphylaxis, also called calcific uraemic arteriolopathy (CUA), is a rare disease with a poor prognosis (mortality between 45% and 80%). Treatment is currently not standardized, and is based mainly on risk factor control, often with administration of sodium thiosulfate. We report the use of rheopheresis, a double filtration apheresis technique, specifically designed to improve blood rheology and tissue perfusion, as adjunctive therapy in eight patients with severe CUA.Methods: We retrospectively analysed eight cases of severe CUA treated by rheopheresis after failure of conventional measures, including administration of sodium thiosulfate and discontinuation of vitamin K antagonists.Results: Of the patients, there were 5 (63%) women, the median age was 69 (63.9‐73) years. Four (50%) patients had biopsy‐proven CUA. At diagnosis, the median dialysis vintage was 35 (3.9‐42) months; five (63%) patients were anuric. Weekly median dialysis duration and dose were 12 (12‐12.75) hours and 1.19 (1.13‐1.48) Kt/V per dialysis session, respectively. Median time from CUA onset to first rheopheresis therapy was 26 (3.2‐68) days. Patients started with 2‐3 weekly sessions, coupled with haemodialysis. Complete remission was obtained in five patients (66%) after 25 (19‐39) sessions over a duration of 119 (114‐196) days. Three patients died, two of which resulted from an infectious complication related to CUA.Conclusion: Rheopheresis is a promising approach, with a good safety profile, for the treatment of CUA. A prospective study with a larger population, would clarify its place in the therapeutic armamentarium.