Thierry Schurmans

Early prognostic factors of infants with chronic renal failure caused by renal dysplasia

Abstract Renal dysplasia (RD) is a common cause of chronic renal failure (CRF) in children. The evolution towards end-stage renal failure is unpredictable due to the paucity of early prognostic factors. In order to identify early prognostic clinical criteria, we have retrospectively analyzed renal function and growth in 11 infants with RD and CRF from birth up to 4 years of age. Children with obstructive RD were not included. Glomerular filtration rate (GFR) was estimated from Schwartz formula. In infants with a GFR below 15 ml/min per 1.73 m2 at 6 months of age (group A, n=5), kidney function did not further improve; 4 reached end-stage renal failure between 8 months and 6 years of age. In contrast, infants with a GFR above 15 ml/min per 1.73 m2 at 6 months of age (group B, n=6) experienced a significant improvement in renal function during follow-up, and none required renal replacement therapy. During the first 3 months of life all infants with RD and CRF developed severe growth retardation. Between 6 months and 4 years of age, children from group B grew significantly better than those from group A. In conclusion, our experience suggests that GFR, estimated from Schwartz formula at 6 months of age, is a useful prognostic factor in infants with RD and CRF. Infants with a GFR below 15 ml/min per 1.73 m2 are at risk of severe growth delay and the need for early renal replacement therapy, whereas those with a GFR above 15 ml/min per 1.73 m2 have a relatively favorable long-term prognosis.

Cuprophane haemodialysis induces upregulation of LPS receptor (CD14) on monocytes: role of complement activation

BACKGROUND The CD14 molecule is a high-affinity receptor for the complex formed by lipopolysaccharide (LPS) and LPS-binding protein. METHODS We examined by flow cytometry the effect of in vitro and in vivo haemodialysis on cuprophane membrane and recombinant C5a on the expression of CD14 molecules at the surface on monocytes. Monocyte CD14 expression was also studied during in vitro and in vivo haemodialysis on polyacrylonitrile AN69 membrane. RESULTS In vitro haemodialysis of whole blood from healthy volunteers on cuprophane membrane resulted within 30 min in upregulation of monocyte CD14 expression. The reuse of the cuprophane membrane abolished both complement activation and CD14 upregulation. Moreover, incubation of whole blood with recombinant C5a led to an increased monocyte CD14 expression supporting a role for complement activation in the rapid cuprophane-induced CD14 upregulation. During AN69 dialysis which is not associated with complement activation in the blood phase, monocyte CD14 expression did not change during the first 60 min but was significantly increased after 3 h of in vitro haemodialysis. This late increase might be related to the presence of complement activation products adsorbed on the membrane. In vivo dialysis on cuprophane membrane also resulted in early monocyte CD14 upregulation as indicated by higher CD14 expression found after 60 min on monocytes obtained from the efferent as compared to the afferent line of the dialyser, a phenomenon that was not observed during haemodialysis on AN69 membrane. CONCLUSION Haemodialysis on the complement-activating cuprophane membrane induces the rapid upregulation of the CD14 LPS-receptor on monocytes.

A randomized clinical trial indicates that levamisole increases the time to relapse in children with steroid-sensitive idiopathic nephrotic syndrome

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.

Outcomes of kidney transplantations in children weighing 15 kilograms or less: a retrospective cohort study

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.

Impact of growth hormone treatment on a Belgianpopulation of short children with renal allografts

We retrospectively analyzed the effects of recombinant human growth hormone (rhGH) in a Belgian population of 36 short children with renal allografts. Seven children were dropped from the growth study: 1 had skeletal dysplasia and in 6 cases rhGH was given for less than 1 yr (1 died, 1 developed genu valgum, 2 were non-compliant and 2 grafts deteriorated). Final height was reached in 17 patients, and 12 children were still growing at the end of the study. Median height standard deviation score (SDS) in the 29 patients was -2.3 at the time of transplantation, and -2.7 when rhGH therapy was initiated. During rhGH therapy (median duration 3.2 yr, range 0.6-7.7 yr), height SDS increased by a mean of 0.4 per year, and bone maturation was not accelerated. Final height reached was 162.7 (149.0-169.5) cm (median SDS -1.8) in males and 151.0 (130.5-169.5) cm (median SDS -1.9) in females. Final height is significantly greater in males than females compared with a historical control group of untreated patients. Final height is within the parental target height range in 6 out of the 17 patients. The increase in height SDS in patients who were at an advanced stage of puberty (Tanner stages 4-5) when rhGH therapy was initiated exceeded our expectations (mean height gain 14.2 cm in boys and 10 cm in girls). In the cohort of 36 children, 4 patients developed an acute allograft rejection, all of whom had an underlying chronic rejection. This resulted in 3 graft losses within 5 yr. Our results indicate that rhGH treatment has a positive effect in short children with renal allografts, even if it is started in late puberty. In the presence of underlying chronic rejection, rhGH treatment needs careful monitoring to minimize the risk of graft loss.