First Pediatric Pyeloplasty Using the Senhance® Robotic System-A Case Report.

A pediatric robotic pyeloplasty has been performed with the Senhance® robotic system for the first time in January 2021 on a 1.5-year-old girl with symptomatic ureteropelvic junction stenosis. A Senhance® robotic system (Asensus Surgical® Inc., Durham, NC, USA) with three arms and 5 mm instruments was used, providing infrared eye tracking of the 5 mm camera and haptic feedback for the surgeon, facilitating suturing of the anastomosis and double-J stent insertion. The robotic surgery lasted 4.5 h, was uneventful and successful, without recurrence of the ureteropelvic junction obstruction after six months, and with normal development of the patient's growth and organ function. The use of the robotic system was shown to be safe and feasible; long term follow-up will be conducted subsequently in pediatric surgery.

Presentation of pediatric Henoch-Schönlein purpura nephritis changes with age and renal histology depends on biopsy timing.

BACKGROUND: This study correlates the clinical presentation of Henoch-Schönlein purpura nephritis (HSPN) with findings on initial renal biopsy. METHODS: Data from 202 pediatric patients enrolled in the HSPN registry of the German Society of Pediatric Nephrology reported by 26 centers between 2008 and 2014 were analyzed. All biopsy reports were re-evaluated for the presence of cellular crescents or chronic pathological lesions (fibrous crescents, glomerular sclerosis, tubular atrophy >5%, and interstitial fibrosis >5%). RESULTS: Patients with HSPN with cellular glomerular crescents were biopsied earlier after onset of nephritis (median 24 vs 36 days, p = 0.04) than those without, whereas patients with chronic lesions were biopsied later (57 vs 19 days, p < 0.001) and were older (10.3 vs 8.6 years, p = 0.01) than those without. Patients biopsied more than 30 days after the onset of HSPN had significantly more chronic lesions (52 vs 22%, p < 0.001), lower eGFR (88 vs 102 ml/min/1.73m2, p = 0.01), but lower proteinuria (2.3 vs 4.5 g/g, p < 0.0001) than patients biopsied earlier. Children above 10 years of age had lower proteinuria (1.98 vs 4.58 g/g, p < 0.001), lower eGFR (86 vs 101 ml/min/1.73m2, p = 0.002) and were biopsied significantly later after onset of nephritis (44 vs 22 days, p < 0.001) showing more chronic lesions (45 vs 30%, p = 0.03). Proteinuria and renal function at presentation decreased with age. CONCLUSIONS: In summary, we find an age-dependent presentation of HSPN with a more insidious onset of non-nephrotic proteinuria, impaired renal function, longer delay to biopsy, and more chronic histopathological lesions in children above the age of 10 years. Thus, HSPN presents more like Immunoglobulin A (IgA) nephritis in older than in younger children.

Exposure to furosemide as the strongest risk factor for nephrocalcinosis in preterm infants.

BACKGROUND: The objective of this study was to determine which of the many risk factors for nephrocalcinosis (NC) in preterm infants are most relevant. METHODS: In 55 neonates born before 32 completed weeks of gestation, parameters relevant to NC were analyzed. Median birthweight was 1010 g (range 500-2070 g). Fifteen (27%) asymptomatic children had ultrasonographic NC. RESULTS: In multivariate analysis the strongest independent risk factor was furosemide therapy above 10 mg per kg bodyweight cumulative dose, with a 48-fold increased risk of NC (odds ratio confidence interval 4.0-585, P < 0.01). The risk of NC was 1.65-fold higher per 100 g lower weight (1.07-2.56, P= 0.02) and 4.5-fold higher per mmol/l of urinary calcium concentration (1.14-17.7, P= 0.03). Many other risk factors were only significant in univariate analysis (gestational age, mechanical ventilation, infection, broncho-pulmonary dysplasia, blood transfusions, intraventricular hemorrhage, surfactant therapy, vasopressors, phenobarbital or caffeine, duration of hospital stay), indicating an indirect effect only. Other parameters of calcium and phosphate homeostasis were not significant, possibly due to standardized supplementation. CONCLUSION: We suggest that in preterm infants, furosemide should be prescribed with caution and close monitoring of calcium excretions is advisable. Some guidelines for infant respiratory distress syndrome now favor calcium-sparing thiazides if diuretics are considered.

Ulceroglandular tularemia in a toddler in Germany after a mosquito bite.

INTRODUCTION: Although tularemia is a long-known disease, its significance had diminished over the last decades in Middle Europe. However, over the past years, there is new evidence suggesting that tularemia has re-emerged in Germany. In 2007, the highest number of human cases for almost 50 years has been notified. Beside typical vectors, new ways of transmission seem to gain significance. So far, mosquito bite-transmitted tularemia has only been known from Scandinavia but not from Middle Europe. CASE REPORT: We report the first case of a 1-year-old toddler from Southwestern Germany with mosquito bite-associated ulceroglandular tularaemia. The new and interesting features of this case are the young age of the patient and the unusual transmission route. The available data suggesting changes in the epidemiology for tularemia in Germany are reviewed. This is an interesting case of infantile tularemia with a very unusual transmission route, highlighting ongoing changes in the epidemiology of tularemia in Germany.

SOS1 is the second most common Noonan gene but plays no major role in cardio-facio-cutaneous syndrome.

BACKGROUND: Heterozygous gain-of-function mutations in various genes encoding proteins of the Ras-MAPK signalling cascade have been identified as the genetic basis of Noonan syndrome (NS) and cardio-facio-cutaneous syndrome (CFCS). Mutations of SOS1, the gene encoding a guanine nucleotide exchange factor for Ras, have been the most recent discoveries in patients with NS, but this gene has not been studied in patients with CFCS. METHODS AND RESULTS: We investigated SOS1 in a large cohort of patients with disorders of the NS-CFCS spectrum, who had previously tested negative for mutations in PTPN11, KRAS, BRAF, MEK1 and MEK2. Missense mutations of SOS1 were discovered in 28% of patients with NS. In contrast, none of the patients classified as having CFCS was found to carry a pathogenic sequence change in this gene. CONCLUSION: We have confirmed SOS1 as the second major gene for NS. Patients carrying mutations in this gene have a distinctive phenotype with frequent ectodermal anomalies such as keratosis pilaris and curly hair. However, the clinical picture associated with SOS1 mutations is different from that of CFCS. These findings corroborate that, despite being caused by gain-of-function mutations in molecules belonging to the same pathway, NS and CFCS scarcely overlap genotypically.

Nephrocystin and ciliary defects not only in the kidney?

Cystoproteins have been recognized to play a major role in the development of cystic kidney diseases (CKDs) via interaction with the cilia/centrosome complex. We highlight our present knowledge on nephrocystin as the defective protein in nephronophthisis type I. Nephrocystin has been localized to the ciliary transition zone not only of renal tubule cells but also of respiratory and retinal cilia. Thus, multi-system involvement as in Senior-Løken-syndrome (retinal degeneration plus nephronophthisis) can be explained by a functional ciliary defect in various tissues. In addition, we illustrate that ciliated respiratory cells have a high potential for diagnostics in CKDs and will further aid understanding of the underlying molecular mechanisms.

Nephrocystin specifically localizes to the transition zone of renal and respiratory cilia and photoreceptor connecting cilia.

Nephronophthisis (NPHP) is a hereditary cystic kidney disorder that causes renal failure in children and young adults and can be associated with various extrarenal disorders, including retinitis pigmentosa. Six NPHP genes, whose functions are disrupted by autosomal recessive mutations in patients with NPHP, have been identified. The majority of patients with NPHP carry homozygous deletions of NPHP1 encoding nephrocystin. Previous data indicate that nephrocystin forms a complex at cell junctions and focal adhesions. Here, it is shown that nephrocystin specifically localizes at the ciliary base to the transition zone of renal and respiratory cilia and to photoreceptor connecting cilia. During in vitro ciliogenesis of primary human respiratory epithelial cells, nephrocystin can be detected first with a diffuse cytoplasmic localization as soon as cell polarization starts, and translocates to the transition zone when cilia are formed. In columnar respiratory cells, nephrocystin is attached tightly to the axonemal structure of the transition zone at a region that contains the calcium-sensitive cilia autotomy site. In patients with homozygous NPHP1 deletions, nephrocystin is absent from the entire respiratory cell, including the transition zone, which might be of interest for future diagnostic approaches. Cilia formation is not altered in primary nephrocystin-deficient respiratory cells, which is consistent with previous findings obtained for the Caenorhabditis elegans ortholog. In addition, it is shown that the localization pattern of intraflagellar transport proteins and nephrocystin differs, suggesting distinct functional roles. In conclusion, nephrocystin deficiency or dysfunction at the transition zone of renal monocilia and the photoreceptor connecting cilium might explain renal failure and retinal degeneration that are observed in patients with NPHP1.

Long-term biocompatibility of a corrodible peripheral iron stent in the porcine descending aorta.

Currently there are no biodegradable stents available for treatment of vascular obstructions in patients with congenital heart defects. This study was performed to evaluate the safety of a corrodible stent produced from pure iron in a peripheral stent design (6-12mm diameter) in a slotted tube design similar to a commercially available 316-L stent which served as control. Both stents were implanted into the descending aorta of 29 minipigs with an overstretch injury without technical problems. Two animals died after the implantation not related to the iron stent. The remaining 27 minipigs were followed for 1-360 days. Histomorphometry and quantitative angiography showed no difference with regard to the amount of neointimal proliferation between 316-L and iron stents. Histopathological examination of heart, lung, spleen, liver, kidney and para-aortic lymphatic nodes demonstrated no signs of iron overload or iron-related organ toxicity. Adjacent to the iron stent struts, there was no evidence for local toxicity due to corrosion products. We conclude that iron is a suitable metal for the production of a large-size degradable stent with no local or systemic toxicity. A faster degradation rate, however, is desirable and further studies have to focus on the modification of the composition and design of the stent to expedite the degradation process.

Percutaneous endoscopic gastrostomy in children on peritoneal dialysis.

OBJECTIVE: Insertion of percutaneous endoscopic gastrostomies (PEG) in patients on chronic peritoneal dialysis (PD) has been reported to be contraindicated due to an increased risk of morbidity and mortality. However, no systematic survey on this topic has yet been published. DESIGN: Retrospective multicenter study. SETTING: 23 pediatric dialysis units associated with the working group Arbeitsgemeinschaft für Pädiatrische Nephrologie (APN). DATA SOURCE: A structured questionnaire on clinical details of PD patients who had undergone PEG insertion or open gastrostomy (OG) since 1994 was distributed to all pediatric dialysis units of the APN. RESULTS: 27 PD patients (20 males) from 12 centers in whom PEG insertion was performed after Tenckhoff catheter introduction were evaluated. Age at intervention ranged from 0.25 to 10.9 years (median 1.3 years). Most patients were malnourished, with standard deviation score (SDS) for body weight between -4.2 and -0.6 (median -2.2). Major complications were early peritonitis < 7 days after PEG in 10/27 (37%) patients, episodes of fungal peritonitis in 7/27 (26%) patients, 4 cessations of PD and change to hemodialysis, and 2 associated deaths. However, in 14 patients, no such problems were encountered and, in 4 patients, early peritonitis effectively treated with intraperitoneal antibiotics was the only major complication. Thus, in 18/27 (67%) patients, PD was successfully reinitiated shortly after PEG insertion. Among all participating centers, only two OG procedures were reported during the study period, illustrating a clear preference for the PEG over the OG procedure among members of the APN. CONCLUSION: PEG insertion following PD initiation carries a high risk for fungal peritonitis and potential PD failure; however, complication rates in this largest reported series were lower than previously described. Antibiotic and antifungal prophylaxis, withholding PD for 2 - 3 days, and gastrostomy placement by an experienced endoscopy team are suggested precautions for lowering the risk of associated complications. When gastrostomy placement does not occur prior to or at the time of initiating PD, the risks and benefits of percutaneous versus open placement must be carefully weighed.

Primary hyperoxaluria--the German experience.

BACKGROUND: Primary hyperoxaluria (PH) is a heterogeneous disease with variable age of onset and inconsistent progression into renal failure (ESRF). AIMS: In 1994 we initiated a survey within our Pediatric Nephrology working group to ascertain epidemiologic data and current practices. Updates were performed in 2000 and 2004. RESULTS: Diagnosis of PH was made in 65 patients (42 with PH type I, 3 with PH type II, 12 unclassified and 8 reported dead), which suggests a minimum prevalence of 0.7 per 1 million of the population. First symptoms were urolithiasis, nephrocalcinosis, urinary tract infection or hematuria. Diagnosis was often delayed and was made only in ESRF in 11% of patients. Measurement of urine metabolites or plasma oxalate in ESRF was performed in 76 and 57%, respectively. Determination of enzyme activity in liver biopsy (55% overall) and mutation analysis have increasingly been performed since 2000 (84.2 and 51%). Treatment included high fluid intake, pyridoxine, citrate and magnesium preparations. Pyridoxine response was reported in 21% of patients. No genotype/phenotype correlation was seen. Most patients (39) do not require renal replacement therapy, 5 patients receive chronic hemodialysis. Preemptive liver (n = 5) and combined liver-kidney transplantation (n = 9) were the preferred transplantation procedures. CONCLUSION: Despite increasing knowledge and awareness, diagnosis of PH is still too often delayed and diagnosis only made in ESRF. Most German patients, however, do currently not require renal replacement therapy. Genotype/phenotype correlations were not found. Combined liver kidney transplantation is the preferred procedure, but has its specific risks. Additional treatment options are clearly needed.

Complete remission of post-transplant FSGS recurrence by long-term plasmapheresis.

Focal segmental glomerulosclerosis (FSGS) is known to recur in approximately 30% of renal allografts with graft loss in about half of these cases. The exact etiology remains unclear, though a putative circulating permeability factor or loss of inhibitory substances is being discussed. Different therapeutic approaches have been used. We report on a 10-year-old Arabian boy with a recurrence of FSGS immediately after transplantation. In addition to intensifying immunosuppressive therapy with high-dose cyclosporin A and cyclophosphamide, plasmapheresis was initiated and remission was achieved after 8 months. Three weeks after cessation of plasmapheresis a relapse occurred. Plasmapheresis was resumed and remission was achieved again after four additional sessions. The interval between plasmapheresis treatments was then gradually increased and fourteen months after transplantation plasmapheresis was stopped again. Since then (1.5 years after cessation of treatment) the patient has been in complete remission without any further episode of proteinuria. In conclusion, complete and sustained remission with stable renal function was achieved in our patient by long-term plasmapheresis in combination with intensified immunosuppression. Therefore, continuation of plasmapheresis treatment should be considered even in the situation of initial non-response.

Assessment of subacute inflammatory and proliferative response to coronary stenting in a porcine model by local gene expression studies and histomorphometry.

The aim of the study was to analyse inflammatory and proliferative response early after coronary stenting by angiography, histomorphometry and local gene expression analysis using quantitative rt-PCR. Therefore, eight German domestic pigs underwent stenting of the left coronary artery. Selective coronary angiography was performed after 14 days. Explanted coronary arteries were examined histomorphometrically after methacrylate-embedding. Snap-frozen samples were examined for local gene expression of TGF-beta, TNF-alpha, GM-CSF, VEGF, PDGF and Fas Ligand (FasL) by real-time quantitative rt-PCR normalized to the housekeeping gene GAPDH and compared to unstented coronary arteries. All stented coronaries were patent with only little neointima formation. The median vessel diameter was 2.55 mm (range 2.43-2.68 mm). Histopathology revealed little inflammatory response limited to the tissue surrounding the stent struts; luminal area ranged from 84% to 91%. Compared to unstented control arteries, no significant differences in local gene expression were detected for VEGF, PDGF, TGF-beta, TNF-alpha and GM-CSF. Expression of FasL was upregulated as little as 1.7-fold (p=0.01). We conclude that, in native coronary arteries, no significant upregulation of investigated genes regulating vascular remodelling, inflammation or fibrogenesis was demonstrated 14 days after stenting. Whether upregulation of FasL as a marker gene of apoptosis is transient and biological significant requires further investigation.

Histopathological follow-up after bailout stenting for early postoperative stenosis of a central aorto-pulmonary shunt.

We treated a neonate with pulmonary atresia and a ventricular septal defect complicated by straddling of the atrioventricular valves by constructing a central aorto-pulmonary shunt. The postoperative course was complicated by obstruction of the shunt, which was treated by implantation of a coronary stent. Six months after the stenting, a Glenn anastomosis was created and the stented shunt removed. Analysis showed that the shunt was completely covered by a vascularized neointima. The stent had not produced injury to the shunt, with struts of the stent covered nicely by neoendothelium, with sparse inflammation surrounding the artificial implants.

Biocompatibility of corroding tungsten coils: in vitro assessment of degradation kinetics and cytotoxicity on human cells.

This study was performed to determine the in vitro degradation rate of tungsten coils and to evaluate the potential local toxicity of tungsten on human pulmonary arterial endothelial (EC) and smooth muscle cells (SMC) and human dermal fibroblasts (FB). Therefore, tungsten coils were immersed in Ringer's solution and loss of mass and increase in tungsten concentration in the electrolyte were assessed in relation to immersion time (maximum: 140 days). Primary cultures of EC, SMC and FB were grown on multiplates for 1-10 days with ascending concentrations (0.1-5000 microg/ml) of tungsten in the growth medium. Metabolic activity was assessed by the use of the WST-1 Test (Roche). The in vitro degradation rate of the tungsten coil was 29 microg/day. EC were most susceptible to tungsten with a LD50 of 50 microg/ml. In contrast, the LD50 for SMC was 100 and 1000 microg/ml for FB after 10 days of incubation. We conclude that, in vitro, degradation rate of tungsten coils is slow (29 microg/day). Very high (>50 microg/ml [normal serum value 0.0002 microg/ml]) tungsten concentrations are needed to result in local cytopathologic effects on human EC, SMC and FB. These results correspond to clinical observations demonstrating the absence of toxicity of degrading tungsten coils in adult and pediatric patients despite elevated serum tungsten levels.

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.

Composition and in vitro biocompatibility of corroding tungsten coils.

The purpose of the article is to evaluate composition and biocompatibility of corroding mechanically detachable spirals (MDS, Balt Extrusion, Montmorency, France). Analysis of the material composition of corroding MDS coils was assessed by inductively coupled plasma atomic emission spectroscopy, inductively coupled plasma mass spectroscopy, and wavelength-dispersive x-ray spectrometry. Toxicity assays were performed with human venous endothelial cells, venous smooth muscle cells and fibroblasts. The analyses of the MDS coils demonstrated a tungsten content of the dissolving MDS spirals of > 99.9 mas%. In vitro, human endothelial, vascular smooth muscle cells and fibroblasts were not adversely affected by markedly elevated tungsten concentrations (60,500 microg/l) after 12 days in the culture medium. The examined cells showed an extensive vital growth on the coil surface. Corrosion of tungsten coils leads to markedly elevated tungsten levels in the culture medium. However, growth and vitality of endothelial cells, fibroblasts, and vascular smooth muscle cells are not adversely affected by elevated tungsten concentrations.

Acute pulmonary edema caused by epoprostenol infusion in a child with scimitar syndrome and pulmonary hypertension.

INTRODUCTION: Intravenous epoprostenol is frequently administered in adults and children for treatment of pulmonary hypertension. Although generally safe, pulmonary edema has been described in a few case reports of adult patients with pulmonary veno-occlusive disease. CASE REPORT: We present an infant who had an operation for scimitar syndrome and abnormal drainage of the right pulmonary veins into the inferior vena cava who developed pulmonary edema while receiving a prostacyclin infusion. The typical partial anomalous pulmonary venous drainage was operatively corrected at 6 days of age, and an accompanying coarctation was resected. At 7 months of age, diagnostic cardiac catheterization was performed to evaluate suspected pulmonary hypertension. Pulmonary pressure was elevated to supra-systemic values, and obstructed venous drainage of the right hypoplastic lung was demonstrated. To decrease pulmonary hypertension during weaning and extubation, epoprostenol infusion was initiated. Sixty minutes after extubation, massive acute pulmonary edema lead to reintubation. Mean airway pressure of 16 mm Hg (21 mbar) with pure oxygen ventilation was initially required, with an oxygenation index of 14, a ventilation index of 36, and an alveolar-arterial oxygen tension difference of 541 mm Hg. After discontinuation of epoprostenol, weaning and extubation was successful. CONCLUSION: Pulmonary edema caused by prostacyclin infusion in patients with impaired postcapillary pulmonary drainage may also be encountered in children and has to be anticipated.