[HIF-ɑ: New Target For Treatment of Renal Anemia. Molecular Aspects and Activation of Pathway HREs].

Roxadustat, recently approved, is a hypoxia-inducible factor prolyl hydroxylase inhibitor that has demonstrated favorable safety and efficacy in the treatment of renal anemia. This article reviews main features and possible effects by activation of pathway sequences HREs.

[Case Report: MPO-ANCA Associated Vasculitis After Pfizer-BioNTech COVID-19 mRNA Vaccination].

We report a case of MPO-anti-neutrophil cytoplasmic antibody ANCA-associated vasculitis, with pulmonary-renal syndrome, after the mRNA booster third dose vaccine Pfizer BioNTech against COVID-19 in 71-year-old Caucasian man with no specific past medical history. A kidney biopsy diagnosed ANCA-associated pauci-immune crescentic glomerulonephritis. Renal function and constitutional symptoms have been partially improved with treatment with dialysis, intravenous rituximab and steroid pulse therapy. No disease following either infection or vaccination with fourth dose against COVID-19.

Parathyroidectomy and survival in a cohort of Italian dialysis patients: results of a multicenter, observational, prospective study.

BACKGROUND: Severe secondary hyperparathyroidism (SHPT) is associated with mortality in end stage kidney disease (ESKD). Parathyroidectomy (PTX) becomes necessary when medical therapy fails, thus highlighting the interest to compare biochemical and clinical outcomes of patients receiving either medical treatment or surgery. METHODS: We aimed to compare overall survival and biochemical control of hemodialysis patients with severe hyperparathyroidism, treated by surgery or medical therapy followed-up for 36 months. Inclusion criteria were age older than 18 years, renal failure requiring dialysis treatment (hemodialysis or peritoneal dialysis) and ability to sign the consent form. A control group of 418 patients treated in the same centers, who did not undergo parathyroidectomy was selected after matching for age, sex, and dialysis vintage. RESULTS: From 82 Dialysis units in Italy, we prospectively collected data of 257 prevalent patients who underwent parathyroidectomy (age 58.2 ± 12.8 years; M/F: 44%/56%, dialysis vintage: 15.5 ± 8.4 years) and of 418 control patients who did not undergo parathyroidectomy (age 60.3 ± 14.4 years; M/F 44%/56%; dialysis vintage 11.2 ± 7.6 y). The survival rate was higher in the group that underwent parathyroidectomy (Kaplan-Meier log rank test = 0.002). Univariable analysis (HR 0.556, CI: 0.387-0.800, p = 0.002) and multivariable analysis (HR 0.671, CI:0.465-0.970, p = 0.034), identified parathyroidectomy as a protective factor of overall survival. The prevalence of patients at KDOQI targets for PTH was lower in patients who underwent parathyroidectomy compared to controls (PTX vs non-PTX: PTH < 150 pg/ml: 59% vs 21%, p = 0.001; PTH at target: 18% vs 37% p = 0.001; PTH > 300 pg/ml 23% vs 42% p = 0.001). The control group received more intensive medical treatment with higher prevalence of vitamin D (65% vs 41%, p = 0.0001), calcimimetics (34% vs 14%, p = 0.0001) and phosphate binders (77% vs 66%, p = 0.002). CONCLUSIONS: Our data suggest that parathyroidectomy is associated with survival rate at 36 months, independently of biochemical control. Lower exposure to high PTH levels could represent an advantage in the long term.

Ionised and total serum magnesium in renal transplant patients.

BACKGROUND: Hypomagnesemia in renal transplant patients is almost always documented through total serum values (MgT), but it has recently become user-friendly to assay the biologically active, ionised fraction (Mg++). We verified the prevalence of true ionised magnesemia and the correspondence between total and ionised Mg assays in our transplanted patients, taking into account renal Mg excretion and the possible role of other reputed factors of hypomagnesemia (cyclosporine, secondary hyperparathyroidism and acid-base balance). METHODS: Thirty-eight transplanted patients (25M/13F, aged 41 +/- 11 years) and 38 age and sex matched controls were enrolled. Blood chemistries included: ionised Mg and Ca, total Mg and Ca, phosphate, creatinine, albumin, bicarbonate, alkaline phosphatase, parathyroid hormone and, in patients, cyclosporine (CyA). A 24-h urine collection (for Ca and Mg) and a fasting spot sample (for pH, Mg, Ca, phosphate, creatinine) were also obtained. RESULTS: Patients with mild renal failure (creatinine: Cr=1.75 +/- 0.83 mg/dL), mild persistent secondary hyperparathyroidism and almost normal tubular acidification capacity had MgT lower than controls (0.76 +/- 0.08 vs 0.82 +/- 0.08 mmol/L; p<0.002), with 10 cases (26%) of total hypomagnesemia. Mg++ was also significantly low (0.51 +/- 0.08 vs 0.53 +/- 0.05 mmol/L; p<0.03), but there were only four cases (10%) of true ionised hypomagnesemia. MgT and Mg++, although correlated (with a low r value: =0.49; p<0.001), showed poor correspondence in individual patients and MgT was not useful to identify cases of true ionised hypomagnesemia. Neither assay correlated with renal function. Daily urinary excretion of Mg was normal (3.5 +/- 1.3 vs 3.0 +/- 0.24 mmol/day; n.s.), with no case of definite hypomagnesuria. Fasting excretion fraction (EF) of Mg, calculated with both assays, was increased in approximately 60% of patients (EF(MgT) 4.9 +/- 2.6 vs 2.32 +/- 0.7%; p<0.0001; EF(Mg++) 7.74 +/- 4.9 vs 3.63 +/- 1.18%; p<0.0001) and positively correlated with serum Cr (r=0.62; p<0.0001 with EF(MgT); and r=0.467; p<0.005 with EF(Mg++) but not with CyA. Neither Mg assay correlated with serum CyA, calcium, phosphate, PTH or bicarbonate. CONCLUSIONS: In long term renal transplant patients not taking diuretics, the prevalence of true ionised hypomagnesemia is low. Renal insufficiency, typically associated with Mg retention, is the major cause of increased EF(Mg) and, as such, plays an antagonistic role to CyA and other factors of renal Mg wasting. Because MgT and Mg++ are not closely related, assay of the ionised fraction seems advisable in case of total hypomagnesemia. However, because diagnosis of depletion can hardly rely on serum assay alone, a fuller evaluation (urinary excretion and other clinical and biochemical signs of hypomagnesemia) is suggested before diagnosis is made.