Clinically detectable diabetic nephropathy (DN) begins with the development of microalbuminuria (MA). However, early renal dysfunction may be overlooked despite using that method. On the other hand, the gold standard in DN detection-that is, renal biopsy-is highly invasive. The aim of this study was to evaluate the level of neutrophil-gelatinase-associated lipocalin (NGAL) and interleukin (IL)-18 and their relations to albumin excretion rate (AER) in children with normal-range albuminuria, e.g. in those considered as not presenting diabetic nephropathy. The study group consisted of 22 children (age 12.7 +/- 3.5 years) with type 1 diabetes mellitus (T1DM). Long-term glycemic control was assessed on hemoglobin A1c (HbA1c) levels (8.52 +/- 1.78%). All patients presented normal estimated glomerular filtration rate (eGFR) (141 +/- 23 ml/min/1.73 m(2)) and normal urinary albumin excretion (13.09 +/- 7.63 mg/24 h). Fourteen healthy children served as a control group. Children with T1DM showed increased NGAL values with respect to controls-interestingly, both in serum (sNGAL) (867.43 +/- 341.98 vs. 655.29 +/- 196.17 ng/ml; p = 0.04) and in urine (uNGAL) (420.04 +/- 374.16 vs. 156.53 +/- 185.18 ng/ml, p = 0.04). IL-18 levels were not different in both groups both in serum (58.52 +/- 20.11 vs. 69.79 +/- 58.76 ng/ml; NS) and in urine (14.53 +/- 12.74 vs. 14.60 +/- 10.92 ng/ml; NS). Despite the relatively small study group, the positive correlation between sNGAL and AER was found [AER (mg/24 h) = 3.1893 + 0.01141 x sNGAL (ng/ml); r = 0.51; p = 0.014] as well as between uNGAL and AER [AER (mg/24 h) = 8.7538 + 0.01032 x uNGAL (ng/ml); r = 0.51; p = 0.016]. No relationship between sNGAL and uNGAL, and GFR and HbA1c were found. Normal-range albuminuria does not exclude diabetic nephropathy defined as increased sNGAL and uNGAL concentration. NGAL measurement can be more sensitive than MA and may become a useful tool for evaluating renal involvement in diabetic children.

Neurogenic bladder (NB) is a nonspecific term that may describe conditions ranging from areflectic noncontractile bladder to detrusor overactivity. The most common cause of NB in children is the presence of dysraphic malformations. Urodynamic evaluations make it possible to describe bladder dysfunctions and to plan a therapeutic strategy for each patient. In a child with NB there are two major dangerous functional problems seen in urodynamic investigations: high intravesical pressure in the storage phase and high pressure during urination. The basic goals of urologic treatment for a child with NB are the protection of the urinary tract from complications and improvement of continence. Treatment for a child with NB is usually conservative, and focuses on achieving safe bladder pressures during storage with reliable emptying, via voiding or catheterization. The two most important forms of conservative treatment are clean intermittent catheterization and pharmacological treatment of functional disorders. Some drugs are used in the treatment of functional disorders in children with NB, but none of the drugs are officially approved for small children and babies.

This study evaluated whether one (or more) of three doses of onabo-tulinumtoxinA were safe and effective to treat neurogenic detrusor overactivity (NDO) in children. Methods: This was a 48-week prospective, multicenter, randomized, doubleblind study in children (aged 5-17 years) with NDO and urinary incontinence (UI) receiving one onabotulinumtoxinA treatment (50, 100, or 200 U; not to exceed 6 U/kg). Primary endpoint: change from baseline in daytime UI episodes. Secondary endpoints: change from baseline in urine volume at first morning catheterization, urodynamic measures, and positive response on the treatment benefit scale. Safety was also assessed. Results: There was a similar reduction in urinary incontinence from baseline to Week 6 for all doses (−1.3 episodes/day). Most patients reported positive responses on the treatment benefit scale (75.0%−80.5%). From baseline to Week 6, increases were observed in urine volume at first morning clean intermittent catheterization (50 U, 21.9 ml; 100 U, 34.9 ml; 200 U, 87.5 ml; p = 0.0055, 200 U vs. 50 U) and in maximum cystometric capacity (range 48.6−63.6 ml) and decreases in maximum detrusor pressure during the storage phase (50 U, −12.9; 100 U, −20.1; 200 U, −27.3 cmH 2 O; p = 0.0157, 200 U vs. 50 U). The proportion of patients experiencing involuntary detrusor contractions dropped from baseline (50 U, 94.4%; 100 U, 88.1%; 200 U, 92.6%) to Week 6 (50 U, 61.8%; 100 U, 44.7%; 200 U, 46.4%). Safety was similar across doses; urinary tract infection was most frequent. Conclusions: OnabotulinumtoxinA was well tolerated and effective for the treatment of NDO in children; 200 U showed greater efficacy in reducing bladder pressure and increasing bladder capacity.

Patients after a cardiac surgery in cardiopulmonary bypass often present an acute kidney failure. Continuous renal replacement therapy (CRRT) is often required. The aim of this study was to present effectiveness and safety of CRRT with regional citrate anticoagulation (RCA-CRRT) in small children after cardiac surgery. A retrospective analysis was conducted on 15 patients after cardiac surgery and who had RCA-CRRT performed in 2014. The established protocol was followed. Mean time on the RCA-CRRT was 192 h 40 min with the circuit mean lifetime of 43 h 33 min. Clotting was found to be a cause of shutdown in 29% of circuits. No severe electrolyte and metabolic disorders were observed. The RCA-CRRT is a safe procedure for critically ill children with contraindications to the CRRT with heparin anticoagulation. To avoid adverse effects related to metabolic disorders a proper procedure protocol has to be followed.

The aim of this study was to assess the usefulness of selective α1-blockers in children with neurogenic urinary tract dysfunctions and increased leak point pressure (LPP). 14 children from age 6 to 16 years with neurogenic urinary tract dysfunctions (neurogenic bladder) and LPP > 40 cm H2O were enrolled in the study. All patients received a selective α1-blocker (doxazosin) for 6–8 weeks with an initial dosage of 0.03 mg/kg. During the observation period the continuation of oral anticholinergics, Clean Intermittent Catheterization (CIC), observation of “urinary dryness” and urinary incontinence periods were recommended. Patients were scheduled for a follow-up visit and urodynamic investigation after 6–8 weeks after the doxazosin therapy was started. In 4 patients, urine leakage occurred at lower pressures; in 9 patients, no significant changes in urine leak point pressures were detected; in 3 patients, there was a significant increase in the bladder capacity; in one patient, deterioration in continence was noted. The differences both in LPP and LPV before and after the treatment were not statistically significant. Our observations are consistent with the conclusions from other studies and showed no evident efficacy of doxazosin in children with neurogenic bladder.

Lower urinary tract obstruction (LUTO) is, in most cases, caused by anatomical blockage of the bladder outlet. The most common form are posterior urethral valves (PUVs), a male-limited phenotype. Here, we surveyed the genome of 155 LUTO patients to identify disease-causing CNVs. Raw intensity data were collected for CNVs detected in LUTO patients and 4.392 healthy controls using CNVPartition, QuantiSNP and PennCNV. Overlapping CNVs between patients and controls were discarded. Additional filtering implicated CNV frequency in the database of genomic variants, gene content and final visual inspection detecting 37 ultra-rare CNVs. After, prioritization qPCR analysis confirmed 3 microduplications, all detected in PUV patients. One microduplication (5q23.2) occurred de novo in the two remaining microduplications found on chromosome 1p36.21 and 10q23.31. Parental DNA was not available for segregation analysis. All three duplications comprised 11 coding genes: four human specific lncRNA and one microRNA. Three coding genes (FBLIM1, SLC16A12, SNCAIP) and the microRNA MIR107 have previously been shown to be expressed in the developing urinary tract of mouse embryos. We propose that duplications, rare or de novo, contribute to PUV formation, a male-limited phenotype.

Background. Clean intermittent catheterization (CIC) is a standard treatment for patients who are unable to empty the bladder. In the absence of the urethra or if catheterization through the urethra is problematic, a continent vesicostomy is used as a catheterizable conduit. The Malone procedure is an established treatment option for children with neurogenic constipation and fecal incontinence.

Purpose of Review The neurogenic bladder is a medical term that describes a variety of bladder and sphincter dysfunctions. There are two major dangerous functional problems in a child with neurogenic bladder: high intravesical pressure in the storage phase and high pressure during urination. Two basic goals for urologic treatment in those children are protection of urinary tract from complications and improvement of continence in older children. This review focuses on the current role of botulinum toxin treatment in children with neurogenic bladder. Recent Findings At the beginning, treatment in this group of children is conservative. Oral anticholinergic therapy is aimed at decreasing bladder pressures during the storage phase. Clean intermittent catheterization enables bladder emptying if voiding is insufficient. Nevertheless, in a number of children such an approach fails, in some patients, troublesome side effects occur. In cases when standard therapy provides no improvement or if complications develop on the proper conservative treatment, surgical procedures are suggested. Operations are aimed at the surgical enlargement of bladder capacity. There are some reports on the efficacy of cystoscopic detrusor botulinum toxin injections in the treatment of neurogenic bladder in children. Summary Cystoscopic administration of botulinum toxin represents an alternative method of treatment to surgery for children with neurogenic bladder and could be considered an alternative to oral anticholinergic therapy.