No abstract

Levamisole has been considered the least toxic and least expensive steroid-sparing drug for preventing relapses of steroid-sensitive idiopathic nephrotic syndrome (SSINS). However, evidence for this is limited as previous randomized clinical trials were found to have methodological limitations. Therefore, we conducted an international multicenter, placebo-controlled, double-blind, randomized clinical trial to reassess its usefulness in prevention of relapses in children with SSINS. The efficacy and safety of one year of levamisole treatment in children with SSINS and frequent relapses were evaluated. The primary analysis cohort consisted of 99 patients from 6 countries. Between 100 days and 12 months after the start of study medication, the time to relapse (primary endpoint) was significantly increased in the levamisole compared to the placebo group (hazard ratio 0.22 [95% confidence interval 0.11-0.43]). Significantly, after 12 months of treatment, six percent of placebo patients versus 26 percent of levamisole patients were still in remission. During this period, the most frequent serious adverse event (four of 50 patients) possibly related to levamisole was asymptomatic moderate neutropenia, which was reversible spontaneously or after treatment discontinuation. Thus, in children with SSINS and frequent relapses, levamisole prolonged the time to relapse and also prevented recurrence during one year of treatment compared to prednisone alone. However, regular blood controls are necessary for safety issues.

Several studies support the hypothesis that bacterial contamination of the dialysate stimulates the inflammatory response to hemodialysis (HD) and increases the long-term morbidity of HD patients; this phenomenon could also be modulated by the nature of the HD membrane. Therefore, this study was designed to compare the effects of non-sterile (NSBD, mean endotoxin content +/- SEM 97 +/- 22 EU/ml) and ultrapure bicarbonate dialysate (UPBD, sterile and pyrogen-free, obtained by ultrafiltration through polyamide) on several aspects of the inflammatory reaction during in vitro HD. The HD sessions (7 in each experimental group) were performed using miniaturized new cuprophane (CU) and polyacrylonitrile (PAN) hollow fiber dialyzers, and closed dialysate and blood circuits (the latter filled with heparinized blood from healthy donors). Plasma C3aDesarg levels were significantly increased after 15 minutes (t1) and increased further after three hours (t2) of CU HD, while during PAN dialysis they decreased from t0 to t1 and t2; however, no difference appeared between experiments with NSBD and UPBD. Granulocyte (PMN) and monocyte (MNC) expression of LFA-1, Mac-1, and CD45 at the start (t0), t1 and t2 was quantitated by flow cytometry analysis, after staining of the cells with specific fluorescinated monoclonal antibodies. In contrast with published data of in vivo HD, LFA-1 was overexpressed at t1 and peaked at t2, which suggests that the leukocytes expressing more LFA-1 leave the systemic circulation during in vivo HD. During CU HD, Mac-1 and CD45 on PMN and MNC were significantly increased at t1, and still more at t2. During PAN HD, Mac-1 and CD45 remained unchanged at t1, but increased significantly at t2 on PMN as on MNC. Again, no significant difference was found between NSBD and UPBD in LFA-1, Mac-1 and CD45 expression on PMN and MNC, during both CU and PAN HD. AFter three hours of dialysis, plasma levels of TNF-alpha, but not of IL-6, were significantly increased with CU and PAN. Again, no difference appeared when NSBD and UPBD were compared. Moreover, the lack of influence of bacterial contamination of the dialysate on TNF-alpha production was confirmed when MNC were cultured up to 24 hours after the end of the HD session. We conclude that complement activation products, either in plasma (CU) of those adsorbed on the HD membrane (CU and PAN) play the major role in the overexpression of beta 2-integrins and CD45 by PMN and MNC during HD. Also, bacterial products (at the levels that can be found in clinical conditions) do not influence either beta 2-integrin overexpression or TNF-alpha production induced by the dialysis membrane.

OBJECTIVE To determine the pharmacodynamic properties of a new oral lyophilisate formulation of desmopressin (in single doses of 30, 60, 120, 240, 360 or 480 µg) in children with known primary nocturnal enuresis (PNE) and thus identify those dosages that could provide a duration of action corresponding to a typical length of night‐time sleep in children with PNE; additional objectives were to determine the safety and tolerability of desmopressin in this population. PATIENTS AND METHODS Children with PNE (mean three or more wet nights/week), aged 6–12 years, were randomized into a double‐blind, placebo‐controlled study. An overhydration technique was used before dosing to suppress endogenous vasopressin production and thereby ensure that any antidiuresis could be attributed to treatment. Dosing with desmopressin or placebo occurred when urinary production was >0.13 mL/min/kg. Urinary volume, osmolality and duration of urinary‐concentrating action (above three threshold levels: 125, 200 and 400 mOsm/kg) were determined as endpoints. RESULTS All 72 participants receiving desmopressin had a pharmacodynamic response to the drug, while there was no change in urinary output in the 12 placebo‐treated patients. There was a clear relationship between desmopressin dose and duration of action and osmolality during action, although the three highest‐dose groups had similar results. The mean duration of action of desmopressin at the lowest osmolality threshold level was 3.6–10.6 h, according to dose; for the highest threshold, the values were 1.3–8.6 h. CONCLUSION Desmopressin, as the oral lyophilisate, causes a marked decrease in urinary output in hydrated children with PNE. A small dose range (120–240 µg) is likely to control diuresis for a period corresponding to a night's sleep (7–11 h) in most children with PNE. However, some patients might require a higher dose to obtain antidiuresis for the complete night.

Kidney transplantation (KT) is often delayed in small children because of fear of postoperative complications. We report early- and long-term outcomes in children transplanted at ≤15 kg in the two largest Belgian pediatric transplant centers. Outcomes before (period 1) and since the introduction of basiliximab and mycophenolate-mofetil in 2000 (period 2) were compared. Seventy-two KTs were realized between 1978 and 2016: 38 in period 1 and 34 in period 2. Organs came from deceased donors in 48 (67%) cases. Surgical complications occurred in 25 KTs (35%) with no significant difference between the two periods. At least one acute rejection (AR) occurred in 24 (33%) KTs with significantly less patients experiencing AR during period 2: 53% and 12% in period 1 and, period 2 respectively (P < 0.001). Graft survival free of AR improved significantly in period 2 compared with period 1: 97% vs. 50% at 1 year; 87% vs. 50% at 10 years post-KT (P = 0.003). Graft survival tended to increase over time (period 1: 74% and 63% at 1 and 5 years; period 2: 94% and 86% at 1 and 5 years; P = 0.07), as well as patient survival. Kidney transplantation in children ≤15 kg remains a challenging procedure with 35% of surgical complications. However, outcomes improved and are nowadays excellent in terms of prevention of AR, patient and graft survival.