Urological fistulas after fetal cystoscopic laser ablation of posterior urethral valves: surgical technical aspects.

OBJECTIVE: To describe the surgical technical aspects associated with the development of urological fistulas after fetal antegrade cystoscopic laser fulguration of the posterior urethral valves (PUV). METHODS: The perioperative data for all fetal cystoscopies performed between January 2004 and August 2013 at three institutions in the USA, France and Brazil were reviewed, with particular emphasis on surgical technical aspects of the procedure and the complications encountered. RESULTS: A total of 40 fetal cystoscopies were performed at the three institutions. Laser fulguration of the PUV was performed in 23 of these cases, with a survival rate of 60.9% (14/23) and normal renal function in 85.7% (12/14) of these infants. Urological fistulas were diagnosed postnatally in four (10%) newborns. The presence of fistulas was associated with a higher gestational age at diagnosis of PUV (P < 0.01) and with the use of semi-curved rather than curved sheaths (P < 0.01), the use of a diode laser (P < 0.01) and the use of higher laser power and energy (P < 0.01 and P < 0.01, respectively), as well as with less operator experience (P < 0.01) and with absence of fetal anesthesia/immobilization (P = 0.02). CONCLUSION: Urological fistulas are a severe complication of fetal cystoscopic laser fulguration of PUV and are associated with type, energy and power settings of the laser and instrumentation. The use of appropriate technique and proper training of the operator are necessary to perform this fetal intervention safely.

Fetal intervention for severe lower urinary tract obstruction: a multicenter case-control study comparing fetal cystoscopy with vesicoamniotic shunting.

OBJECTIVE: To evaluate the efficacy of fetal intervention using fetal cystoscopy or vesicoamniotic shunting in the treatment of severe lower urinary obstruction (LUTO). METHODS: A cohort of 111 fetuses with severe LUTO attending two centers between January 1990 and August 2013 were included retrospectively. Fetuses were categorized into three groups based on the method of intervention: (1) fetal cystoscopy, (2) vesicoamniotic shunting or (3) no intervention. Multivariate analyses were performed to determine the probability of survival and normal renal function until 6 months of age by comparing fetal cystoscopy and vesicoamniotic shunting to no fetal intervention. RESULTS: Of the 111 fetuses with severe LUTO that were included in the analysis, fetal cystoscopy was performed in 34, vesicoamniotic shunting was performed in 16 and there was no fetal intervention in 61. Gestational age at diagnosis, method of fetal intervention and cause of bladder obstruction were associated with prognosis. In multivariate analysis and after adjustment for potential confounders (considering all causes of LUTO) the overall probability of survival was significantly higher with fetal cystoscopy and vesicoamniotic shunting when compared to no intervention (adjusted relative risk (ARR), 1.86 (95% CI, 1.01-3.42; P = 0.048) and ARR, 1.73 (95% CI, 1.01-3.08; P = 0.04) respectively). A clear trend for normal renal function was present in the fetal cystoscopy group (ARR, 1.73 (95% CI, 0.97-3.08; P = 0.06)) but was not observed in the vesicoamniotic shunt group (ARR, 1.16 (95% CI, 0.86-1.55; P = 0.33)). In cases in which there was a postnatal diagnosis of posterior urethral valves, fetal cystoscopy was effective in improving both the 6-month survival rate and renal function (ARR, 4.10 (95% CI, 1.75-9.62; P < 0.01) and 2.66 (95% CI, 1.25-5.70; P = 0.01) respectively) while vesicoamniotic shunting was associated only with an improvement in the 6-month survival rate (ARR, 3.76 (95% CI, 1.42-9.97; P < 0.01)) with no effect on renal function (ARR, 1.03 (95% CI, 0.49-2.17, P = 0.93)). CONCLUSION: Fetal cystoscopy and vesicoamniotic shunting improve the 6-month survival rate in cases of severe LUTO. However, only fetal cystoscopy may prevent impairment of renal function in fetuses with posterior urethral valves. Our data support the idea of performing a subsequent randomized controlled trial to compare the effectiveness of fetal cystoscopy vs vesicoamniotic shunting for severe fetal LUTO.

Peritoneal dialysis tailored to pediatric needs.

Consideration of specific pediatric aspects is essential to achieve adequate peritoneal dialysis (PD) treatment in children. These are first of all the rapid growth, in particular during infancy and puberty, which must be accompanied by a positive calcium balance, and the age dependent changes in body composition. The high total body water content and the high ultrafiltration rates required in anuric infants for adequate nutrition predispose to overshooting convective sodium losses and severe hypotension. Tissue fragility and rapid increases in intraabdominal fat mass predispose to hernia and dialysate leaks. Peritoneal equilibration tests should repeatedly been performed to optimize individual dwell time. Intraperitoneal pressure measurements give an objective measure of intraperitoneal filling, which allow for an optimized dwell volume, that is, increased dialysis efficiency without increasing the risk of hernias, leaks, and retrofiltration. We present the concept of adapted PD, that is, the combination of short dwells with low fill volume to promote ultrafiltration and long dwells with a high fill volume to improve purification within one PD session. The use of PD solutions with low glucose degradation product content is recommended in children, but unfortunately still not feasible in many countries.

Mutations in SDCCAG8/NPHP10 Cause Bardet-Biedl Syndrome and Are Associated with Penetrant Renal Disease and Absent Polydactyly.

The ciliopathies are an expanding group of disorders caused by mutations in genes implicated in the biogenesis and function of primary cilia. Bardet-Biedl syndrome (BBS) is a model ciliopathy characterized by progressive retinal degeneration, obesity, polydactyly, cognitive impairment, kidney anomalies and hypogonadism. Mutations in SDCCAG8(NPHP10) were described recently in patients with nephronophthisis and retinal degeneration (Senior-Loken syndrome; SLS). Given the phenotypic and genetic overlap between known ciliopathy genes, we hypothesized that mutations in SDCCAG8 might also contribute alleles to more severe, multisystemic ciliopathies. We performed genetic and phenotypic analyses of 2 independent BBS cohorts. Subsequent to mutation screening, we made a detailed phenotypic analysis of 5 families mutated for SDCCAG8 (3 homozygous and 2 compound heterozygous mutations) and conducted statistical analyses across both cohorts to examine possible phenotype-genotype correlations with mutations at this locus. All patients with mutations in SDCCAG8 fulfilled the diagnostic criteria for BBS (retinal degeneration, obesity, cognitive defects, renal failure, hypogonadism). Interestingly, none of the patients with primary SDCCAG8 mutations had polydactyly, a frequent but not obligatory BBS feature. In contrast, the same patients displayed early-onset renal failure, obesity, as well as recurrent pulmonary and ENT infections. Comparison of the phenotypes of these families with our entire BBS cohort indicated that renal impairment and absent polydactyly correlated significantly with causal SDCCAG8 mutations. Thus, SDCCAG8 mutations are sufficient to cause BBS in 1-2% of our combined cohorts, and define this gene as the sixteenth BBS locus (BBS16). The absence of polydactyly and the concomitant, apparently fully penetrant association with early kidney failure represents the first significant genotype-phenotype correlation in BBS that potentially represents an indicator for phenotype-driven priority screening and informs specific patient management.