Volume expansion mitigates Shiga toxin-producing E. coli-hemolytic uremic syndrome in children.

BACKGROUND: Shiga toxin-producing E. coli-hemolytic uremic syndrome (STEC-HUS) is associated with high morbidity and relevant mortality. Previous small studies showed that volume expansion could improve the course and outcome of STEC-HUS. The aim of this single-center study was to evaluate the effect of volume expansion on the clinical course and outcome in STEC-HUS. METHODS: Data of pediatric patients with STEC-HUS were analyzed retrospectively. Course and outcome of patients treated with volume expansion (VE) from 2019 to 2022 (n = 38) were compared to historical controls (HC) from 2009 to 2018 (n = 111). RESULTS: Patients in the VE group had a significant relative median weight gain compared to HC (7.8% (3.4-11.3) vs. 1.2% (- 0.7-3.9), p < 0.0001) 48 h after admission. The need for dialysis was not reduced by VE (VE 21/38 (55.3%) vs. HC 64/111 (57.7%), p = 0.8). However, central nervous system involvement (impairment of consciousness, seizures, focal neurological deficits, and/or visual disturbances) was significantly reduced (VE 6/38 (15.8%) vs. HC 38/111 (34.2%), p = 0.039). None of the patients in the VE group died or developed chronic kidney disease (CKD) stage 5, whereas in the HC group, three patients died and three patients had CKD stage 5 at discharge. CONCLUSIONS: This study suggests that volume expansion may be associated with the mitigation of the acute course of STEC-HUS, especially severe neurological involvement and the development of CKD. Prospective trials should lead to standardized protocols for volume expansion in children with STEC-HUS.

Postnatal Repair of Open Neural Tube Defects: A Single Center with 90-Month Interdisciplinary Follow-Up.

After publication of the Management of Myelomeningocele Study (MOMS) there is confusion regarding which treatment of open neural tube defects (NTD) is best. We report our results of postnatally repaired open NTDs born between 2007-2018 (n = 36) in critical reflection of the MOMS study. Neurosurgical, orthopedic, and urologic data were assessed. We also introduce a new entity: "status post prenatal repair". FU ranged from 29 to 161 months (mean: 89.1 m) in 7 cases of myeloschisis and 24 myelomeningoceles in the final collective n = 31. The shunt rate was 41.9%, and the endoscopic third ventriculostomy rate was 16.1%. Hydrocephalus requiring treatment was not associated with the anatomical level, but with premature birth (p = 0.048). Myeloschisis was associated with shunt placement (p = 0.008). ROC analysis revealed birth <38.5th week predicts the necessity for hydrocephalus treatment (sensitivity: 89%; specificity: 77%; AUC= 0.71; p = 0.055). Eight (25.8%), patients are wheelchair-bound, 2 (6.5%) ambulate with a posterior walker, 10 (32.3%) with orthosis and 11 (35.5%) independently. One (3.2%) patient underwent detethering at 5.5 years. A total of three patients underwent five Chiari decompressions (9.6%). Further, nineteen orthopedic procedures were performed in nine patients (29.0%). A total of 17 (54.8%) patients self-catheterize, which was associated with an anatomical lesion at L3 or below (p = 0.032) and 23 (74.2%) take anticholinergic medication. In conclusion, shunt dependency is associated with myeloschisis, not with the anatomical defect level. Hydrocephalus treatment is associated with premature birth. In this postnatal cohort with significantly longer follow-up data than the MOMs study, the ambulation rate is better, the shunt rate lower and the secondary tethered cord rate better compared to the MOMS study.

Propiverine vs oxybutynin for treating neurogenic detrusor overactivity in children and adolescents: results of a multicentre observational cohort study.

OBJECTIVE: To compare, in a retrospective observational cohort study, the efficacy, tolerability, safety and clinical effectiveness of propiverine and oxybutynin in children and adolescents with neurogenic detrusor overactivity (NDO). PATIENTS AND METHODS: In all, 255 children and adolescents (aged 1-18 years) with NDO (199 myelomeningocele, 46 spinal cord injury, 10 other diagnoses) were enrolled at 14 study centres. To evaluate the efficacy of propiverine and oxybutynin, urodynamic and clinical variables were assessed before and after at least 12 month of the antimuscarinic agents administered at variable doses. RESULTS: In all, 127 patients given propiverine and 128 given oxybutynin were enrolled. The primary efficacy outcome, i.e. reductions in urodynamically assessed individual maximum detrusor pressure (P(detmax)), was assumed to indicate success in 74.2% of those on propiverine vs 49.6% on oxybutynin. The mean P(detmax) was significantly reduced during treatment, from 59.8 to 36.7 cmH(2)O in the propiverine and from 65.2 to 54.9 cmH(2)O in the oxybutynin groups. The mean maximum cystometric bladder capacity increased from 146 to 242 mL in the propiverine and from 222 to 310 mL in the oxybutynin group. Propiverine was better tolerated than oxybutynin, having fewer adverse drug reactions (9.4% vs 17.2%, odds ratio 2.04), and for its severity grades and premature treatment termination (none vs 11 cases). CONCLUSION: In this non-interventional study, reflecting 'real-life' clinical practice, comparing the efficacy, tolerability and safety of propiverine and oxybutynin in children and adolescents with NDO, propiverine was at least as effective as oxybutynin, but better tolerated, resulting in superior clinical effectiveness than for oxybutynin.

Urodynamic effects of propiverine hydrochloride in children with neurogenic detrusor overactivity: a prospective analysis.

OBJECTIVES: To evaluate prospectively the efficacy and tolerability of propiverine for treating neurogenic detrusor overactivity (NDO) in children. PATIENTS AND METHODS: Twenty children (mean age 8.9 years; median 5.6) with NDO due to an upper motor neurone lesion were enrolled (17 had myelomeningocele). In the urodynamic examination, reflex volume (RV), maximum detrusor pressure (MDP), maximum cystometric bladder capacity (MCBC) and bladder compliance (BC) before and after a twice-daily propiverine hydrochloride regimen were determined. The urodynamic follow-up was after 3-6 months. Incontinence was assessed by an incontinence score. RESULTS: The mean (sem) RV increased from 103.8 (21.3) to 174.5 (33.7) mL (P < 0.005), MDP decreased from 52.5 (7.9) to 40.1 (6.2) cmH(2)O (P < 0.05), MCBC increased from 166 (28.8) to 231.9 (34.8) mL (P < 0.005), and BC improved from 11.2 (2.8) to 30.6 (9.7) mL/cmH(2)O (P < 0.01), with propiverine treatment. The incontinence score (scale 0-3) improved from 2.4 (0.2) to 1.6 (0.3) (P < 0.05). Propiverine was well tolerated, although some children were given higher doses than recommended. CONCLUSIONS: Propiverine hydrochloride is effective and well tolerated in the treatment of children with NDO. Because of its dual mode of action, it is well tolerated even in children who need higher doses. Propiverine hydrochloride is a preferable alternative to oxybutynin, the anticholinergic most frequently used in children with NDO to date.

Mycophenolate mofetil-induced reversal of glomerular filtration loss in children with chronic allograft nephropathy.

BACKGROUND: Mycophenolate mofetil (MMF) has been used for the treatment of chronic allograft nephropathy (CAN) in adults with inconsistent results, but data in children are rare. To evaluate its impact on advanced CAN, we studied changes in glomerular filtration rate (GFR) and the correlation of GFR changes to histology. METHODS: Thirty-six children (13.1+/-3.6 years) with a progressive decline in GFR of 16.9+/-12.4 mL/min per 1.73 m2/year and biopsy confirmed CAN 4.3+/-2.9 years after transplantation were studied. MMF was added to conventional immunosuppression (IS) consisting of cyclosporine (CsA) and prednisolone (n=26) or tacrolimus (n=1) or replaced azathioprine in triple IS (n=9). Alterations of GFR were correlated to histologic guidelines according to the Banff chronic score (BCS). RESULTS: One year after conversion, 22 (61%) children showed a rise in GFR (7.5+/-6 mL/min per 1.73 m2), 8 (22%) remained stable, and 6 (17%) showed a further decline of GFR (7.4+/-2 mL/min per 1.73 m2). Mean CsA trough levels were 114 ng/mL before and 98 ng/mL 1 year after conversion. MMF side effects required dose reduction in 14 children. Children responding to MMF with increasing GFR showed a trend toward less fibrosis, less incidence of vasculopathy, and transplant glomerulopathy in the initial biopsy but had a similar incidence of borderline tubulitis compared with the other groups. CONCLUSIONS: Cotreatment with MMF reversed the progressive loss of GFR in approximately two thirds of children with CAN for at least 1 year. Less chronicity signs in histology seem to indicate a more favorable response to treatment.

Computer-assisted quantification of fibrosis in chronic allograft nephropaty by picosirius red-staining: a new tool for predicting long-term graft function.

BACKGROUND: Chronic allograft nephropathy (CAN) has become the predominant limiting factor for long-term transplant survival. A cardinal histomorphologic correlate for CAN is interstitial fibrosis. Currently, no method has been established in routine use that reliably quantifies the extent of interstitial fibrosis in renal grafts. We have used staining with picrosirius red followed by computerized image analysis to study the correlation between graft fibrosis and future development of glomerular filtration rate (GFR) in a group of children with advanced CAN. METHODS: Renal biopsies were performed in 56 children (mean age, 13.7+/-3.6 years) after a mean period of 4.6+/-3.1 years after transplantation because of significant increases in serum creatinine. All biopsy specimens were stained with picrosirius red. The magnitude of fibrotic tissue was calculated by computerized image analysis. Linear regression analysis was performed correlating the intensity of graft fibrosis and the changes in the GFR at the time points of renal biopsy and 2 years later. RESULTS: There was a significant positive correlation (r=0.62, P<0.001) between the picrosirius red-stained cortical fractional interstitial fibrosis volume (V(intFib)) and the decrease of GFR within 2 years postrenal biopsy. When V(intFib) was below 5%, 82% of the patients had an increase in GFR within 2 years. Ninety-three percent of the patients with greater than 10% of fibrosis experienced a worsening renal function after 2 years. When comparing patients with stable GFR with patients having a decrease in GFR, a highly significant difference in V(intFib) was found (P=0.008). CONCLUSIONS: The quantitative measurement of fibrosis by picrosirius red staining appears to be a useful prognostic indicator for estimating long-term graft function in CAN and may provide an easy, fast, and inexpensive tool helpful for treatment decisions in patients developing CAN.

Cytokine single nucleotide polymorphisms and intrarenal gene expression in chronic allograft nephropathy in children.

BACKGROUND: Single nucleotide polymorphisms (SNPs) have been reported to influence cytokine production. Certain cytokine high producer genotypes have been associated with an increased risk for acute rejection and chronic allograft dysfunction (CAD) after transplantation. Our study evaluates SNP distribution for transforming growth factor-beta1 (TGF-beta1), interleukin-10 (IL-10), and tumor necrosis factor-alpha (TNF-alpha) in pediatric renal transplant recipients and control individuals and correlates them to corresponding intrarenal gene expression. METHODS: SNPs for TGF-beta1 (codon 10 and 25), IL-10 (positions -1082, -819, -592) and TNF-alpha (position -308) were determined in 30 patients with stable graft function, in 75 patients with CAD, and in 173 control individuals by allele-specific polymerase chain reaction (PCR). Intrarenal cytokine gene expression was studied in 25 biopsies with chronic allograft nephropathy (CAN) and 27 normal kidney specimens by real-time reverse transcription (RT)-PCR. RESULTS: No difference in allele and genotype frequency was detected in any of the investigated groups. No correlation between genotype and intragraft cytokine gene expression was recognized in CAN patients. However, in normal kidney specimens, the low producer TGF-beta1 genotype at codon 10 was associated with significant lower TGF-beta1 mRNA expression. This association was not found for IL-10 or TNF-alpha. CONCLUSION: Our results do not support the proposition that certain specific cytokine genotypes for TGF-beta1, IL-10, and TNF-alpha are associated with CAD. Intrarenal cytokine gene expression only correlated to one TGF-beta1 SNP in normal kidney specimens. Since overall TGF-beta1 expression was higher in transplanted patients compared to controls, this suggests that SNPs may not play a significant role once the immune system is activated.

Single centre experience with basiliximab in paediatric renal transplantation.

BACKGROUND: Introduction of IL-2-receptor antagonists has led to significantly decreasing numbers of acute rejection episodes in renal transplantation in adults. No data are available in paediatric recipients. METHODS: Between 1997 and 2000, 78 renal transplantations were performed in 77 children aged 0.5-16 years. Basiliximab, cyclosporin A (CsA) and prednisolone were administered in 48 children (age 7.8 +/- 5.3 years) and compared with 29 children (age 7.3 +/- 5.2 years) receiving CsA and prednisolone only. The number of acute rejections, survival, glomerular filtration rate (GFR) and side effects were determined for 3 years after transplantation. RESULTS: All 77 patients survived the observation period. One year graft survival in the basiliximab group was 95%, which is similar to the comparison group (93%). Children receiving basiliximab showed a lower incidence of acute rejection than the comparison group (14% vs 34%). The calculated GFR was lower in the basiliximab group when discharging from hospital, with 51 compared with 66 ml/min/1.73 m(2) in the non-basiliximab group. This was associated with higher CsA trough levels (214 vs 174 ng/ml) in the basiliximab patients. After 1 year the GFR was comparable in both groups (58 vs 52 ml/min/1.73 m(2)). CONCLUSIONS: Basiliximab offers excellent allograft survival, a lower incidence of acute rejections and almost no side effects. Therefore it can be recommended for routine immunosuppressive therapy in paediatric renal transplantation.