Steroid-Resistant Nephrotic Syndrome due to NPHS2 Variants Is Not Associated With Posttransplant Recurrence.

Introduction: Unlike idiopathic nephrotic syndrome (NS), hereditary podocytopathies are not expected to recur after kidney transplantation. However, some reports of posttransplant recurrence of NS in patients carrying variants in the NPHS2 gene have been described, notably with the p.Arg138Gln variant, which is more prevalent in Europe. The objective of this study was to assess the risk of recurrence after kidney transplantation in a large cohort of patients with biallelic NPHS2 pathogenic variants. Methods: Since January 2010, 61 patients identified at Necker-Enfants Malades Hospital and 56 enrolled in the PodoNet Registry with biallelic variants in the NPHS2 gene were transplanted and were compared with 44 transplanted children with steroid-resistant NS (SRNS) without any identified pathogenic variant. Results: Of the 117 patients, 23 carried the p.Arg138Gln variant in the homozygous state and 16 in the compound heterozygous state. The other 78 patients carried different variants in the homozygous (n = 44) or compound heterozygous state. Only 1 patient with NPHS2-related SRNS experienced posttransplant recurrence (median follow-up of cohort 8.5 years [2.5-15]). Conversely, 7 of 44 patients (16%) without any identified pathogenic variant recurred within a maximum of 7 days after transplantation (median follow-up 8.9 years [0.6-13.9]). Conclusion: In this large cohort, the risk of patients with causative variants in the NPHS2 gene to develop NS recurrence after kidney transplantation was extremely low. This is coherent with the pathophysiology of intrinsic slit-diaphragm disease. These data are reassuring and should be considered when counselling patients, making living kidney donation, whether related or not, a safe choice.

Outcomes of steroid-resistant nephrotic syndrome in children not treated with intensified immunosuppression.

BACKGROUND: The aim of the current PodoNet registry analysis was to evaluate the outcome of steroid-resistant nephrotic syndrome (SRNS) in children who were not treated with intensified immunosuppression (IIS), focusing on the potential for spontaneous remission and the role of angiotensin blockade on proteinuria reduction. METHODS: Ninety-five pediatric patients who did not receive any IIS were identified in the PodoNet Registry. Competing risk analyses were performed on 67 patients with nephrotic-range proteinuria at disease onset to explore the cumulative rates of complete or partial remission or progression to kidney failure, stratified by underlying etiology (genetic vs. non-genetic SRNS). In addition, Cox proportional hazard analysis was performed to identify factors predicting proteinuria remission. RESULTS: Eighteen of 31 (58.1%) patients with non-genetic SRNS achieved complete remission without IIS, with a cumulative likelihood of 46.2% at 1 year and 57.7% at 2 years. Remission was sustained in 11 children, and only two progressed to kidney failure. In the genetic subgroup (n = 27), complete resolution of proteinuria occurred very rarely and was never sustained; 6 (21.7%) children progressed to kidney failure at 3 years. Almost all children (96.8%) received proteinuria-lowering renin-angiotensin-aldosterone system (RAAS) antagonist treatment. On antiproteinuric treatment, partial remission was achieved in 7 of 31 (22.6%) children with non-genetic SRNS and 9 of 27 children (33.3%) with genetic SRNS. CONCLUSION: Our results demonstrate that spontaneous complete remission can occur in a substantial fraction of children with non-genetic SRNS and milder clinical phenotype. RAAS blockade increases the likelihood of partial remission of proteinuria in all forms of SRNS. A higher resolution version of the Graphical abstract is available as Supplementary information.

Torque teno viral load reflects immunosuppression in paediatric kidney-transplanted patients-a pilot study.

BACKGROUND: Chronic deterioration of kidney graft function is related to inadequate immunosuppression (IS). A novel tool to assess the individual net state of IS in transplanted patients might be the monitoring of Torque teno virus (TTV) viral load. TTV is a non-pathogen virus detectable in almost all individuals. TTV level in the peripheral blood has been linked to the immune-competence of its host and should thus reflect IS after solid organ transplantation. METHODS: TTV plasma load was quantified monthly by RT-PCR for a period of 1 year in 45 kidney-transplanted children. Post-transplant time was at least 3 months. The relation of the virus DNA levels to IS and transplant-specific clinical and laboratory parameters was analysed longitudinally. RESULTS: TTV DNA was detectable in 94.5% of the plasma samples. There was a significant association with the post-transplant follow-up time as well as with the type of IS regimen, with lower virus loads in patients after longer post-transplant time and mTOR inhibitor-based IS. Furthermore, a significant positive correlation with the dose of prednisolone and mycophenolate mofetil was found. CONCLUSIONS: TTV levels show an association/correlation with the strength of IS. Further studies are needed in order to evaluate TTV measurement as a tool for IS monitoring for hard clinical outcomes such as presence of donor-specific antibodies, rejections or infections-common consequences of insufficient or too intense IS.

Long-term outcome of pediatric renal transplantation in boys with posterior urethral valves.

PURPOSE: To determine whether there is a difference in the outcome of renal transplantation (RT) in patients with posterior urethral valves (PUV) and children with non-uropathy related end stage renal disease. METHODS: Data were acquired retrospectively. We analyzed possible factors that influence the function of renal allografts and graft survival. Between 1995 and 2016 there were 149 RT. Out of them, there were 27 boys with PUV, who received 29 kidneys. Thirty patients, who received a total of 31 renal grafts due to a non-uropathic (NU) diagnosis, served as control group. Mean follow-up was 7.4 to 10.2 years. RESULTS: There was no difference in estimated graft survival between patients with PUV and NU patients. Graft failure occurred in 23.1% of PUV patients and 34.5% patients of the NU group. There was no statistically significant disparity in graft function between the two groups. Age at transplantation and donor age were the only factors that had a significant impact on renal function. There was a higher incidence of UTI in the PUV group (96%) than in the NU group (67%). Vesicostomy was the favourable intervention in regards of graft function. CONCLUSIONS: RT in PUV patients is successful with the same outcome as in NU patients. Bladder dysfunction may not have a major impact on graft function and graft survival. It seems that the type of pre-transplant surgical procedures may influence outcome. Therefore, these interventions -if necessary- should be limited to a minimum. TYPE OF STUDY: Retrospective Comparative Study LEVEL OF EVIDENCE: Level III.

A Pediatric Patient with a CYP24A1 Mutation: Four Years of Clinical, Biochemical, and Imaging Follow-Up.

BACKGROUND: A female infant was admitted to hospital due to failure to thrive. She presented hypercalcemia (4.09 mmol/L, normal range: 2.2-2.65 mmol/L), high 25-hydroxyvitamin D (283 nmol/L, normal range: 75-250 nmol/L), 1,25-dihydroxyvitamin D in the upper normal range, and low parathyroid hormone. Vitamin D intoxication was suspected. The patient had received routine rickets prophylaxis. METHODS: Williams-Beuren syndrome was genetically excluded. Sequencing of CYP24A1 showed 2 mutations: c.443T>C and c.1186C>T. RESULTS: The patient's clinical status improved after intravenous rehydration, cessation of supplementation, and on a low-calcium diet. 25-Hydroxyvitamin D concentrations normalized within days, while 1,25-dihydroxyvitamin D remained in the upper normal range. We also investigated our patient's bone health. CONCLUSION: The patient was hospitalized initially on suspicion of vitamin D intoxication but proved to be a case of compound heterozygosity. Data on the long-term clinical and biochemical evolution of patients with idiopathic infantile hypercalcemia are sparse. Our follow-up showed seasonal variations of vitamin D and calcium parameters, with no influence on kidney function or bone health for the investigated period.

Addition of Alanyl-Glutamine to Dialysis Fluid Restores Peritoneal Cellular Stress Responses - A First-In-Man Trial.

BACKGROUND: Peritonitis and ultrafiltration failure remain serious complications of chronic peritoneal dialysis (PD). Dysfunctional cellular stress responses aggravate peritoneal injury associated with PD fluid exposure, potentially due to peritoneal glutamine depletion. In this randomized cross-over phase I/II trial we investigated cytoprotective effects of alanyl-glutamine (AlaGln) addition to glucose-based PDF. METHODS: In a prospective randomized cross-over design, 20 stable PD outpatients underwent paired peritoneal equilibration tests 4 weeks apart, using conventional acidic, single chamber 3.86% glucose PD fluid, with and without 8 mM supplemental AlaGln. Heat-shock protein 72 expression was assessed in peritoneal effluent cells as surrogate parameter of cellular stress responses, complemented by metabolomics and functional immunocompetence assays. RESULTS: AlaGln restored peritoneal glutamine levels and increased the primary outcome heat-shock protein expression (effect 1.51-fold, CI 1.07-2.14; p = 0.022), without changes in peritoneal ultrafiltration, small solute transport, or biomarkers reflecting cell mass and inflammation. Further effects were glutamine-like metabolomic changes and increased ex-vivo LPS-stimulated cytokine release from healthy donor peripheral blood monocytes. In patients with a history of peritonitis (5 of 20), AlaGln supplementation decreased dialysate interleukin-8 levels. Supplemented PD fluid also attenuated inflammation and enhanced stimulated cytokine release in a mouse model of PD-associated peritonitis. CONCLUSION: We conclude that AlaGln-supplemented, glucose-based PD fluid can restore peritoneal cellular stress responses with attenuation of sterile inflammation, and may improve peritoneal host-defense in the setting of PD.

Donor-specific HLA antibodies and graft function in kidney-transplanted children - the Vienna cohort.

In the pediatric population, little is known on de novo DSA development, its impact on graft function, and association with suboptimal IS. We assessed the prevalence of de novo DSA in the Vienna cohort of 40 renal transplanted children and adolescents and prospectively followed its association with clinical parameters, graft function, and proteinuria for one yr. At the cross-sectional analysis (median post-transplant time of five yr), 17% of the patients had developed de novo DSA. All HLA-Ab were anti-HLA class II antibodies and persisted in 85% of the cases until the follow-up screening performed within one yr. Basic clinical and laboratory parameters did not differ between DSA-negative and DSA-positive patients at the time of HLA-Ab screening. Suboptimal IS due to reduced medication or non-adherence could not be proven in DSA-positive patients. The changes in eGFR did not differ during the prospective study period, but there was a significantly higher proteinuria in the DSA-positive patients during the follow-up. Our data demonstrate an overall prevalence of 17% of de novo DSA in a pediatric renal transplant cohort. During 12 months of prospective follow-up time, we could demonstrate a significant impact of de novo DSA presence on proteinuria.

WDR73 Mutations Cause Infantile Neurodegeneration and Variable Glomerular Kidney Disease.

Infantile-onset cerebellar atrophy (CA) is a clinically and genetically heterogeneous trait. Galloway-Mowat syndrome (GMS) is a rare autosomal recessive disease, characterized by microcephaly with brain anomalies including CA in some cases, intellectual disability, and early-infantile-onset nephrotic syndrome. Very recently, WDR73 deficiency was identified as the cause of GMS in five individuals. To evaluate the role of WDR73 mutations as a cause of GMS and other forms of syndromic CA, we performed Sanger or exome sequencing in 51 unrelated patients with CA and variable brain anomalies and in 40 unrelated patients with a diagnosis of GMS. We identified 10 patients from three CA and from two GMS families with WDR73 mutations including the original family described with CA, mental retardation, optic atrophy, and skin abnormalities (CAMOS). There were five novel mutations, of which two were truncating and three were missense mutations affecting highly conserved residues. Individuals carrying homozygous WDR73 mutations mainly presented with a pattern of neurological and neuroimaging findings as well as intellectual disability, while kidney involvement was variable. We document postnatal onset of CA, a retinopathy, basal ganglia degeneration, and short stature as novel features of WDR73-related disease, and define WDR73-related disease as a new entity of infantile neurodegeneration.

A fetal sheep model for studying compensatory mechanisms in the healthy contralateral kidney after unilateral ureteral obstruction.

INTRODUCTION: Fetal unilateral ureteral obstruction (UUO) triggers complex pathophysiology involving not only the affected organ but also the contralateral kidney, which undergoes evident compensatory changes. OBJECTIVE: We hypothesized that it would be possible to characterize a transcriptomic fingerprint and selected molecular mechanisms for compensatory growth of contralateral kidneys in UUO, specifically focusing on mediators, carriers, membrane transport, and organ crosstalk in an ovine fetal UUO model. STUDY DESIGN: A fetal ovine model of complete UUO was created on the 60th day of gestation. For transcriptomics profiling, total RNA was extracted from vital renal biopsies of contralateral (non-obstructed) kidneys harvested on the 80th day of gestation, and kidneys of untreated fetuses served as controls. Statistical analysis provided the set of differentially regulated genes further forwarded to bioinformatics analysis for identification of eventual compensatory molecular mechanisms. Histological analysis was performed with hematoxylin and eosin and periodic acid-Schiff stains. RESULTS: Contralateral kidneys showed compensatory hypertrophic renal growth, represented on the molecular side by 324 protein coding genes differentially regulated compared with the control kidney samples. Bioinformatics analysis identified an interactome (Figure) consisting of 102 genes with 108 interactions mainly involving transporters (protein transport and protein localization as well as in protein degradation), signaling molecules, DNA/nucleotide/RNA processing, and components of catabolism and cell cycle regulation. Within the interactome, nine receptors were identified as differentially regulated on the contralateral kidney, involving potential renoprotective ligands of the prostaglandin and the bradykinin receptor, arginine vasopressin receptor 1B, and integrin beta 4. Interestingly, a broad range of molecules found differentially expressed, has been previously described in stress response, renoprotection and repair (e.g., MAPK3, MCP1, DICER1, and others). DISCUSSION: The compensatory renal growth interactome provides a network of transcripts significantly altered in the contralateral kidney, potentially allowing novel insights into mechanisms, interactions, and signaling pathways associated with compensatory growth, and renal protection and repair. Interestingly, the finding of an embedded gene signature reflecting signaling and communication suggests a key role of these processes in CRG either by crosstalk, soluble substances, carriers, or membrane signaling. CONCLUSIONS: Using a transcriptomics approach, it was possible to identify a gene expression fingerprint of contralateral renal growth in a fetal UUO model. Further studies are warranted to validate those processes and to allow incorporation of this knowledge in new fetal diagnostic or even therapeutic strategies.

Overexpression of Hsp70 confers cytoprotection during gliadin exposure in Caco-2 cells.

BACKGROUND: In Celiac disease (CD), cytoskeletal integrity of intestinal cells is disrupted by gliadin exposure. This study investigates the role of heat shock protein (Hsp)70 during cytoskeletal recovery in CD by assessing its induction and effects on junctional proteins. METHODS: Using an in-vitro model of CD, cytoskeletal injury and recovery was assessed in gliadin-exposed Caco-2 cells by measuring cellular distribution of ezrin, E-cadherin, and Hsp70 by differential centrifugation. Effects of Hsp70 were tested by an in-vitro repair assay, based on the incubation of injured or recovered cytoskeletal cellular fractions in noncytoskeletal supernatants containing low or high levels of Hsp70, or by transient transfection of Caco-2 cells with Hsp70. RESULTS: Cytoskeletal disruption of ezrin and E-cadherin was demonstrated in gliadin-exposed Caco-2 cells by their significant shift from the cytoskeletal pellet into the noncytoskeletal supernatant fraction. Recovery from gliadin exposure was associated with induction and cytoskeletal redistribution of Hsp70. The in-vitro repair assay delineated direct evidence for HSP-mediated repair by stabilization of junctional proteins by Hsp70. Overexpression of Hsp70 resulted in significantly increased cytoskeletal integrity. CONCLUSION: Our results establish an essential role of HSP-mediated cytoskeletal repair in Caco-2 cells during recovery from in-vitro gliadin exposure.

A combined transcriptome and bioinformatics approach to unilateral ureteral obstructive uropathy in the fetal sheep model.

PURPOSE: Fetal obstructive uropathy is a leading cause of loss of renal function. Characterizing the molecular fingerprint of cellular responses to obstruction in a fetal model of complete unilateral ureteral obstruction may help elucidate the activated mechanisms and suggest new therapeutic interventions. MATERIAL AND METHODS: Unilateral ureteral obstruction was created in 3 sheep fetuses at day 60 of gestation. For transcriptome analysis total RNA was extracted from vital renal biopsies 2 weeks after intervention from obstructed kidneys and from control kidneys of untreated twins. cDNA preparation, hybridization to the GeneChip® Bovine Genome Array and array scanning were done according to manufacturer protocols. Bioinformatics analysis was used to derive functional biological processes linked to obstructive uropathy. Quantitative reverse-transcriptase-polymerase chain reaction and immunohistochemistry were used to validate microarray results. RESULTS: Seven biological processes were identified as significantly affected by differentially regulated features that characterize unilateral ureteral obstruction, namely protein metabolism and modification, other metabolism, neuronal activity, ligand mediated signaling, amino acid metabolism, coenzyme/prosthetic group metabolism and rRNA metabolism. Literature mining identified 17 candidate genes previously reported as key in the context of unilateral ureteral obstruction, related pathological mechanisms or other kidney diseases. CONCLUSIONS: Combined transcriptome and bioinformatics analysis allowed the identification of enriched processes in the fetal sheep model of unilateral ureteral obstruction that are likely associated with renal damage but to our knowledge have not been previously identified. Future clarification of these molecular fingerprints may eventually provide therapeutic targets and early predictive markers involved in the pathogenesis of fetal uropathy.

Renal failure, comorbidity and mortality in preterm infants.

OBJECTIVE: To evaluate patient characteristics and risk factors for mortality in critically ill preterm infants with renal failure, with a special focus on infants with extremely low birth weight. DESIGN: Retrospective cohort study with five year follow-up of all premature infants who were treated in the neonatal intensive care unit in 2002 and developed postnatal serum creatinine > or =1.5 mg/dl and/or urine output <1 ml/kg per h. SETTING: Tertiary Care University Hospital of the Medical University of Vienna PATIENTS: Sixteen of 359 premature infants (9 boys, 7 girls) fulfilled the inclusion criteria for renal failure. Their median gestational age was 30 weeks (range 24-36) with a median birth weight of 811.5 g (range 588-2662). MEASUREMENTS AND MAIN RESULTS: The most common causes of renal failure were sepsis and ischemic events. All infants were managed conservatively with corrections of fluids, electrolytes and acidosis, including medication with diuretics and dopamine. Eleven infants with renal failure (69%) died in multiorgan failure. Infants with low urine output, higher scores for failed organs or low birth weight were significantly more likely to die. Infants with very low birth weights had higher scores for failed organs (all P < 0.05). CONCLUSION: Oliguria/anuria, multiorgan failure and immaturity were significant risk factors for mortality in preterm infants with renal failure. Further studies and/or more registry data are needed to determine whether these infants died with or from renal failure, and whether dialysis would improve outcome in this special population.

Evidence for HSP-mediated cytoskeletal stabilization in mesothelial cells during acute experimental peritoneal dialysis.

Low biocompatibility of peritoneal dialysis fluid (PDF) injures mesothelial cells and activates their stress response. In this study, we investigated the role of heat shock proteins (HSP), the main cytoprotective effectors of the stress response, in cytoskeletal stabilization of mesothelial cells in experimental peritoneal dialysis. In cultured human mesothelial cells, cytoskeletal integrity was assessed by detergent extractability of marker proteins following in vitro PDF exposure. Effects of HSP on stabilization of ezrin were evaluated by a conditioning protocol (PDF pretreatment) and repair assay, based on coincubation of cytoskeletal protein fractions with recombinant HSP-72 or HSP-72 antibodies. In the rat model, detachment of mesothelial cells from their peritoneal monolayer during in vivo PDF exposure was assessed with and without overexpression of HSP-72 (by heat conditioning). In vitro, cytoskeletal disruption on sublethal PDF exposure was demonstrated by significantly altered detergent extractability of ezrin and ZO-1. Restoration was associated with significant induction and cytoskeletal redistribution of HSP during recovery. Both the conditioning protocol and in vitro repair assay provided evidence for HSP-72-mediated cytoskeletal stabilization. In the rat model, overexpression of HSP-72 following heat conditioning resulted in significantly reduced detachment of mesothelial cells on in vivo exposure to PDF. Our results establish an essential role of HSP in repair and cytoprotection of cytoskeletal integrity in mesothelial cells following acute in vitro and in vivo exposure to PDF. Repeated exposure to PDF, as is the rule in the clinical setting, may not only cause repeat injury to mesothelial cells but rather represents a kind of inadvertent conditioning treatment.

C4d in pediatric renal allograft biopsies: a marker for negative outcome in steroid-resistant rejection.

Recently, deposition of C4d, reflecting complement activation via the classical pathway, has been established as marker of antibody-mediated rejection. As C4d can be detected in paraffin sections, it allows for retrospective analysis in populations with low case loads, such as in pediatric transplantation. In this study we re-evaluated consecutive renal transplant biopsies obtained since 1990 in 36 children (18 boys, 18 girls) who had received their allograft (nine living, 27 cadaveric) at an age of 10.12+/-4.4 yr. Clinical indications for biopsy were 16 acute steroid resistant rejections (ASRs), 11 chronic rejections and nine other diagnoses. Overall, C4d deposition was found in nine cases (25%), eight of them with diagnosed ASR. Six out of these eight allografts were lost during 36 months of clinical follow-up, a significantly higher rate than in C4d-negative biopsies (p<0.05). C4d status therefore turned out to be an excellent predictor for inferior graft survival following ASR. None of the other histopathologic markers were sensitive for humoral rejections. In conclusion, the high prevalence of C4d-positive staining in ASR demonstrates the importance of the humoral part of the immune system in pediatric transplantation. The worse outcome of C4d-positive rejections despite massive immunosuppressive therapy clearly indicates the need for innovative therapies in this high-risk population.

Risk factors for peritonitis in pediatric peritoneal dialysis: a single-center study.

Recent US registry data and a European multicenter study described increased risk of peritonitis in young children on peritoneal dialysis (PD). No underlying age-specific risk factors could be defined in these reports. Therefore, we analyzed risk factors for peritonitis in children treated by PD as primary renal replacement therapy at the Kinderdialyse, Vienna, and particularly searched for age-specific aspects. Thirty children (15 boys, mean age 4.6 years) received PD [21 automated peritoneal dialysis (APD), nine continuous ambulatory peritoneal dialysis (CAPD)] for 13 months (3-49 months). During the total observation period of 395 dialysis months, 27 peritonitis episodes were diagnosed (1:14.6 months or 0.82/patient per year). Of our population, 43% remained peritonitis free; seven patients suffered from more than one peritonitis episode. Ten potential risk factors [age, gender, PD modality, duration of PD, exit-site status, urine volume, residual glomerular filtration rate (GFR), Kt/V, normalized protein catabolic rate (nPCR), albumin] and four indices of peritonitis outcome (peritonitis incidence, peritonitis burden, risk of suffering more than one episode of peritonitis and chance of staying free from peritonitis) were analyzed. Our study identified six risk factors in univariate analysis, namely age, APD treatment, exit-site infections, low urinary volume, low residual GFR and low nPCR, which were significantly correlated with two or more of the outcome indices. Multivariate analysis identified exit-site infection and residual urine volume as strong independent predictors. In summary, our study identified several age-dependent and age-independent risk factors for peritonitis in pediatric PD. These data demonstrate that the risk for peritonitis in small children is not pre-determined but might be open to therapeutic interventions, such as optimizing exit-site care, dialysis prescription and nutrition management.

Changes of blood pressure and left ventricular mass in pediatric renal transplantation.

Cardiovascular events are among the most frequent causes for long-term morbidity and mortality in children after renal transplantation. The aim of this study was to analyze the effects of post-transplant changes in arterial hypertension, as assessed by 24-h ambulatory blood pressure measurement (ABPM), on myocardial architecture, as assessed by echocardiography. In a retrospective chart review analysis, 39 children were identified in whom 24-h ABPM and echocardiography had been assessed within a 3-month interval after a mean of 4 years post transplantation; 20 repeated pairs of measurements after a mean of 2 years of follow-up were available to analyze the longitudinal effects of post-transplant changes of blood pressure control on left ventricular mass index (LVMI). Arterial hypertension (59%) and left ventricular hypertrophy (50%) were highly prevalent in children after renal transplantation. Renal allograft function and number of antihypertensive medications, but not ABPM variables, were correlated with LVMI at the initial observation. However, at repeat assessment, a significant correlation between ABPM and LVMI was found. In the longitudinal assessment, left ventricular remodeling was dependent on change of dosage of cyclosporine and interval changes of blood pressure levels. Hence, control of blood pressure correlates with changes of LVMI in children with renal allografts. These results clearly underline the importance of blood pressure control for the maintenance of the myocardial architecture.

Upper urinary tract: when is obstruction obstruction?

PURPOSE OF REVIEW: Obstruction can either be defined as a condition that hampers optimal renal development, or, more conservatively, as a restriction to urinary outflow that, when left untreated, will cause progressive renal deterioration. Currently, management is mostly based on the latter definition, but still remains controversial. Relevant work published before 2002 is considered because of a lack of recent literature. RECENT FINDINGS: Almost all reports comparing the primary conservative treatment of suspected obstruction versus early surgical intervention show comparable results, but there are different interpretations. The approach of 'watch and wait' for a unilateral hydronephrotic kidney with normal function is usually quite safe, with a very low risk of the permanent loss of renal function when accompanied by close monitoring, but it is certainly not without risk. At this time, the main underlying problems are that all currently applied diagnostic methods only detect effects secondary to obstruction, and the currently used definition of obstruction is based on a longitudinal observation period. The most relevant publication in the observation period was an in-depth report on a workshop in which the need for valid prospective markers for renal maldevelopment and 'significant' obstruction was expressed. SUMMARY: The optimal management of infants with congenital hydronephrosis and suspected obstruction will remain controversial until new diagnostic methods are able to discriminate between 'harmful' and 'harmless' obstruction. Most experts currently advocate primary conservative management, with close follow-up and surgical intervention only if there are signs of reduced function of the obstructed kidney.

Management of congenital hydronephrosis with ureteropelvic junction obstruction: the Vienna-AKH experience 1986-2001.

One of the most common causes of congenital hydronephrosis is obstruction of the ureteropelvic junction. The obstruction can be detected with prenatal ultrasonography screening and treated before renal function is reduced; the obstruction may also resolve spontaneously. Currently, there is no test for predicting the outcome of this obstruction. Management guidelines for neonates with asymptomatic obstruction of the ureteropelvic junction are based on expert opinions, but not on evidence-based data. In our retrospective study, we evaluated management and outcome of 26 renal units in 23 infants (15 boys, 8 girls) with congenital obstruction of the ureteropelvic junction treated in our institution between 1986 and 2001. These infants had isolated hydronephrosis on prenatal and postnatal sonography, showed an obstructive curve pattern in the postnatal diuretic nephrogram and had at least one follow-up nephrogram during a follow-up period of at least 1.5 years. Of these renal units, 16 demonstrated normal function (Group I), five moderate function (Group II) and five severely reduced function (Group III). In group I, 6 of 12 primarily conservatively managed kidneys resolved spontaneously and remained normal in function. In group II, all infants were operated and 83% improved their kidney function. In group III, all infants were operated but none demonstrated relevant improvement. These data support the current expert opinion of the Arbeitsgemeinschaft Pädiatrische Nephrologie (APN), that ureteropelvic junction obstruction in neonates with normal renal function can be managed primarily conservatively with close monitoring. In neonates with moderately--but not with severely--reduced renal function, early surgery is effective in the prevention of deterioration.