[Treatment of patients with COVID-19 on Hemodialysis: Efficacy of Remdesivir]. / Tratamiento de pacientes con COVID-19 en Hemodiálisis: Eficacia de Remdesivir.

BACKGROUND: There is no standard therapy for hemodialysis (HD) patients with COVID-19. Data on remdesivir in HD patients with COVID-19 are scarce. METHODS: We retrospectively analyzed 25 HD patients with COVID-19 treated with remdesivir. RESULTS: The median age of the patients was 78 years (range, 45-92 years) and was predominantly male (84%). A total of 44% of the patients had mild disease, 36% had moderate-1, and 20% had moderate-2. The most common symptoms were fever (76%) and coughing (44%). The most common comorbidity was renal failure (100%), followed by hypertension (60%) and cardiac disease (44%). The most frequent biomarker was elevated creatinine (100%), followed by C-reactive protein (80%), lymphopenia (76%), and D-dimer (68%). C-reactive protein levels decreased significantly before and after remdesivir administration (p < 0.001). Two patients showed deterioration, but none died. All patients recovered from COVID-19 and no adverse effects of treatment with remdesivir were observed. CONCLUSION: Our study suggests the safe use of remdesivir in HD patients with COVID-19.

Anti-pruritic effect of nemolizumab in hemodialysis patients with uremic pruritus: a phase II, randomized, double-blind, placebo-controlled clinical study.

BACKGROUND: The pathophysiology of uremic pruritus (UP), which is characterized by systemic and intractable itching, remains unclear. As interleukin (IL)-31 may be involved, we conducted a phase II, randomized, controlled study to evaluate nemolizumab (anti-IL-31 receptor A antibody) in Japanese hemodialysis patients with UP. METHODS: Patients were randomly assigned (1:1:1:1:1) to one of four double-blind groups (receiving a single subcutaneous injection of nemolizumab 0.125, 0.5, or 2.0 mg/kg, or placebo on Day 1) or an open-label reference group (receiving oral nalfurafine hydrochloride 2.5-5 µg once daily for 12 weeks). The primary endpoint was the difference in the absolute change in pruritus visual analog scale (VAS) at Week 4 between placebo and each nemolizumab group. RESULTS: The primary efficacy endpoint was not met. The mean change from baseline with all three nemolizumab doses at Week 1, and with 0.5 mg/kg at Week 4, was greater than with placebo. Least square mean differences (95% confidence intervals) in the absolute changes between the placebo arm and each nemolizumab arm were - 2.4 (- 19.7, 14.9) for 0.125 mg/kg, - 8.7 (- 26.6, 9.2) for 0.5 mg/kg, and 0.4 (- 17.0, 17.8) for 2.0 mg/kg. Secondary efficacy parameters including the Shiratori severity score and 5-D itch score failed to show between-group differences. Patients with higher serum IL-31 levels at screening tended to have greater pruritus VAS reductions following nemolizumab treatment. CONCLUSIONS: In this phase II study in patients with UP, the primary efficacy parameter was not met. Nemolizumab was generally well tolerated with no clinically significant safety concerns. CLINICAL TRIAL REGISTRATION: JAPIC: JapicCTI-152961, https://www.clinicaltrials.jp/cti-user/trial/ShowDirect.jsp?japicId=JapicCTI-152961 .

Zinc Burden Evokes Copper Deficiency in the Hypoalbuminemic Hemodialysis Patients.

BACKGROUND: Recent research has focused on the roles of trace minerals such as zinc and copper. In 2017, oral zinc acetate was approved to treat zinc deficiency, and the next year, the Japanese Society for Clinical Nutrition developed the guidelines for diagnosis and treatment for zinc deficiency. Accordingly, hemodialysis patients began receiving zinc acetate when zinc deficiency was diagnosed. However, studies regarding the values of zinc and copper in hemodialysis patients are extremely poor, thus it remains unclear if the guidelines for healthy subjects can be applied to hemodialysis patients. METHODS: We conducted a descriptive study, in which 132 patients were subjected to simply examine serum zinc concentration and its association with copper levels in hemodialysis patients (N = 65) versus healthy individuals attending a routine check-up (control group; N = 67) in our hospital. Analyses were performed with BellCurve for Excel (Social Survey Research Information Co., Ltd. Tokyo, Japan). RESULTS: The distribution of zinc level in the hemodialysis group was distinct from that in the control group (P < 0.001). The zinc level was correlated with serum albumin concentration. Zinc concentration was also negatively correlated with serum copper level in both groups. In the hemodialysis group, the upper limit of zinc to avoid copper deficiency was 109.7 µg/dL, and the safety upper limit was 78.3 µg/dL. CONCLUSIONS: Hemodialysis patients exhibited a lower level of zinc concentration compared to normal healthy subjects. Since albumin binds to zinc as a carrier, low zinc levels could be attributed to lower level of serum albumin. Importantly, zinc and copper levels were inversely correlated, thus administration of oral zinc acetate could increase a risk for copper deficiency. It might be better to check both zinc and copper values monthly after prescribing zinc acetate.

Annual Iron Loss Associated with Hemodialysis.

BACKGROUND: In order to keep up the optimal iron status in chronic hemodialysis patients, it is important to know how much iron is lost due to hemodialysis. Residual blood associated with the hemodialysis procedure together with blood sampling inevitably causes the loss of iron in chronic hemodialysis patients. Recent advances in hemodialysis techniques might have reduced this complication. In this cross-sectional study, we directly measured total iron loss by hemodialysis. METHODS: Two hundred thirty-nine patients who received chronic hemodialysis at Otowa Memorial Hospital were enrolled; 65.7% of patients were men, and mean age was 67 ± 6.4 years (mean ± SD) and 43.2% were diabetic. Residual blood in blood tubing set and dialyzer after rinse back with saline was collected and homogenized. The iron content including free, protein-bound and heme iron was measured using an atomic absorption spectrometry. RESULTS: The mean iron content in residual blood was 1,247.3 ± 796.2 µg (mean ± SD) and the median was 1,002 µg (95% CI 377.6-3,461.6 µg), indicating 160.8 mg (95% CI 58.9-540.0 mg) iron loss annually when hemodialysis was performed 156 times a year. Fifty milliliter whole blood for monthly blood test and another 2 ml of whole blood lost by paracentesis at every dialysis session contains 228.6 and 118.9 mg iron at 11 g/dl hemoglobin, respectively. Therefore, an annual total iron loss due to hemodialysis comes to 508.3 mg (95% CI 406.4-887.5 mg). CONCLUSIONS: Five hundred milligram of annual iron supplementation might be sufficient to maintain iron status in hemodialysis patients, which is less than the dose recommended as 1,000-2,000 mg a year. Further study will be required to verify this iron supplementation dosage with recent hemodialysis procedure.

Efficacy and tolerability of vildagliptin in type 2 diabetic patients on hemodialysis.

Anti-diabetic agent-related hypoglycemia is a serious complication in type 2 diabetic patients on hemodialysis. Therefore, we assessed the efficacy and tolerability of 24 weeks of monotherapy with vildagliptin, a dipeptidyl peptidase four inhibitor, which is a new class of antidiabetic agent. This open-label, single-arm clinical trial was performed on 26 patients on hemodialysis. The primary assessments were changes in postprandial glucose level and glycated albumin (GA). During the study, three patients dropped out, and data from 23 patients were analyzed. Significant reductions were seen in postprandial glucose (-2.60 ± 3.80 mmol/L, P < 0.001) and GA (-2.59 ± 2.33%, P < 0.001) levels. No serious drug-related adverse events were observed. Vildagliptin monotherapy can be recommended for glycemic control in type 2 diabetic patients on hemodialysis. This trial was registered with the University Hospital Medical Information Network (no. UMIN000003661). (J Diabetes Invest, doi: 10.1111/j.2040-1124.2011.00169.x, 2011).