Background Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients. Methods A multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival. Results In the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6–24.0, P = 0.52) and 22.4% (97.5% CI: 17.2–28.3, P < 0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline. Conclusions Tocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline. Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092).

Background The known risks and benefits of native kidney biopsies are mainly based on the findings of retrospective studies. The aim of this multicentre prospective study was to evaluate the safety of percutaneous renal biopsies and quantify biopsy-related complication rates in Italy. Methods The study examined the results of native kidney biopsies performed in 54 Italian nephrology centres between 2012 and 2020. The primary outcome was the rate of major complications one day after the procedure, or for longer if it was necessary to evaluate the evolution of a complication. Centre and patient risk predictors were analysed using multivariate logistic regression. Results Analysis of 5304 biopsies of patients with a median age of 53.2 years revealed 400 major complication events in 273 patients (5.1%): the most frequent was a ≥ 2 g/dL decrease in hemoglobin levels (2.2%), followed by macrohematuria (1.2%), blood transfusion (1.1%), gross hematoma (0.9%), artero-venous fistula (0.7%), invasive intervention (0.5%), pain (0.5%), symptomatic hypotension (0.3%), a rapid increase in serum creatinine levels (0.1%), and death (0.02%). The risk factors for major complications were higher plasma creatinine levels (OR 1.12 for each mg/dL increase, 95% CI 1.08–1.17), liver disease (OR 2.27, CI 1.21–4.25), and a higher number of needle passes (OR for each pass 1.22, CI 1.07–1.39), whereas higher proteinuria levels (OR for each g/day increase 0.95, CI 0.92–0.99) were protective. Conclusions This is the first multicentre prospective study showing that percutaneous native kidney biopsies are associated with a 5% risk of a major post-biopsy complication. Predictors of increased risk include higher plasma creatinine levels, liver disease, and a higher number of needle passes.

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Background and Aims Currently the therapeutic strategies most frequently used in the treatment of secondary hyperparathyroidism (SHPT) are represented by vitamin D receptors activators (VDRAs) and cinacalcet. However, both drugs have side effects that limit their use. Recently, in the treatment of SHPT has been introduced the etelcalcetide, a second generation calcimimetic given intravenously (i.v.). This new route of administration could improve adherence to therapy and reduce gastrointestinal side effects. The aim of the study was to evaluate the efficacy and safety of the etelcalcetide in hemodialysis (HD) patients with SHPT inadequately controlled with traditional therapy (cinacalcet and/or VDRAs), or who had side effects with cinacalcet, or that were not adherent to cinacalcet therapy. Method For this purpose we have selected 28 HD patients with inadequate control of SHPT (PTH &gt; 500 pg / ml; range 502-2148 pg/ml). Serum albumin-corrected calcium (sCa), phosphate (P), calcium–phosphate product (Ca x P), and PTH were assessed monthly. Baseline 19 patients were taking stable doses of active vitamin D analogs and all patients were taking phosphate binders. Etelcalcetide was administered three times a week after each hemodialysis session. The starting dose was 2.5 or 5.0 mg and then adjusted between 2.5 and 10.0 mg according to sCa and PTH levels. Treatment was temporarily withheld for sCa &lt;7.5 mg/dl, or symptomatic hypocalcemia and was subsequently resumed at a lower dose. The primary endpoint was a PTH reduction &gt; 30% compared to baseline levels. Results At present 12 months have passed since the beginning of etelcalcetide therapy. In most patients PTH levels were reduced immediately after the start of therapy. After 12 months we observed a reduction &gt; 30% in 82% of patients, meanly -54% with a range between – 22% and – 81%. On average PTH levels decreased from 1167±444 to 558±310 pg/ml (P&lt;.001). Serum calcium significantly reduced already after one month of therapy settling on stable levels from the third month onward, sCa decreased from 9.7±0.4 to 9.2±0.5 mg/dl (P&lt;.01). However, the percentage of patients treated with calcium salts rose from 21% at baseline to 44% at F-U, mean dose at F-U 1.8 ± 0.9 g/d, while the percent of patients treated with VDRAs increased from 68% to 91%. Serum phosphate decreased from 6.4±1.4 to 4.6±1.3 mg/dl (P&lt;.001), Ca x P decreased from 60±13 to 42±12 mg2/dl2 (P&lt;.001). The median average dose of etelcalcetide at F-U was 6.2 ± 1.7 mg/HD, with a range of 2.5-10.0 mg/HD. Throughout the study, the only side effect was asymptomatic hypocalcemia that required the use of calcium salts. There were no gastrointestinal adverse effects. Conclusion Our results confirm that in hemodialysis etelcalcetide therapy is effective and safe in the control of SHPT refractory to conventional therapy over a 1-year treatment period.