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A 3-year-old girl came to our attention for fever and upper respiratory tract infection associated with thrombocytopenia, non-immune hemolytic anemia, and acute kidney injury (AKI). Complete blood count and renal function slowly normalized, with no need for dialysis. She was always normotensive with valid diuresis; her neurological status also rapidly improved. Nasal swab turned out positive for influenza A H1N1; stool test was negative for Shiga toxin-producing Escherichia coli (STEC). The patient was treated with oseltamivir for 5 days with a favorable outcome. Association between hemolytic uremic syndrome (HUS) and H1N1 influenza is poorly reported in literature [1, 2, 3, 4]. The pathogenic role of the virus in causing HUS is still controversial and debated [1, 2, 3, 4]. In our patient, complement activity markers (serum C3 and C5b-9) alteration suggested a transient, virus-mediated complement activation.

Asymptomatic hyperuricemia is frequently observed in pediatric kidney transplant recipients; symptomatic hyperuricemia, however, is a rare complication. Only few data are available in this patient population. We, therefore, investigated the prevalence of hyperuricemia and its association with kidney transplant function and blood pressure in a multicenter cohort of pediatric kidney transplant recipients.This is a retrospective, observational multicenter registry study. All pediatric kidney transplant recipients in the CERTAIN database with at least one documented serum uric acid level and a follow-up of 5 years posttransplant were eligible. We identified 151 patients with 395 measurements of serum uric acid. We calculated the prevalence of hyperuricemia, analyzed potential risk factors and clinical consequences such as elevated blood pressure and reduced estimated glomerular filtration rate (eGFR). Statistical analysis was performed using IBM SPSS Statistics 26.One hundred and ten of 395 (27.8%) serum uric acid levels were above 416 µmol/L (7.0 mg/dL), defined as the upper limit of normal. Univariate analysis showed a significant (p = .026) inverse association of serum uric acid with eGFR overtime. There was no significant association of serum uric acid concentrations with body mass index (z-score), blood pressure (z-score), or sex. No episodes of gout were documented.This study shows that hyperuricemia is present in a considerable number of patients sometime after pediatric kidney transplantation and is associated with lower eGFR. Whether hyperuricemia contributes to faster decline of graft function or to the overall cardiovascular risk of these patients remains to be elucidated.

High volume haemodiafiltration (HDF) is associated with better survival than conventional haemodialysis (HD) in adults, but data concerning its use in children are lacking. The aim of this study was to assess the prevalence of paediatric HDF use and its associated factors in recent years in Italy. We retrospectively reviewed the files of patients from the Italian Pediatric Dialysis Registry’s database who were registered between January 1, 2004 and December 31, 2016 and treated with extracorporeal dialysis for at least 6 months, looking in particular at modality and its associated factors. One hundred forty-one out of 198 patients were treated exclusively with bicarbonate HD (71.2%), 57 with HDF (28.8%). Patients treated with HDF were younger (median 9.7 vs 13.2 years, p = 0.0008), were less often incident patients (52.6% vs 75.9%, p = 0.0031), had longer duration of the HD cycle (26.9 vs 20.8 months, p = 0.0036) and had a longer time to renal transplantation (32 vs 25 months, p = 0.0029) than those treated with bicarbonate HD only. The percentage of patients treated with HDF increased with dialysis vintage (16.9% at 6 months, 38.1% after more than 2 years of dialysis). The use of HDF was stable over time and was more common in the largest centres. Over the observation period, HDF use in Italy has been limited to roughly a quarter of patients on extracorporeal dialysis, in particular to those with high dialysis vintage, younger age or a long expected waiting time to renal transplantation.

Corticosteroid-related toxicity in children with steroid-sensitive nephrotic syndrome is primarily related to the cumulative dose of prednisone. To optimize treatment of relapses, we conducted the PROPINE study, a multicentric, open-label, randomized, superiority trial. Seventy-eight relapsing children aged 3-17 years who had not received steroid-sparing medications during the previous 12 months were randomized to receive, from day five after remission, either 18 doses of 40 mg/m2 of prednisone on alternate days (short arm), or the same cumulative dose tapered over double the time (long arm). Patients were monitored with an ad-hoc smartphone application, allowing daily reporting. The primary outcome was the six-month relapse rate at which time, 23/40 and 16/38 patients had relapsed in the long and short arms, respectively (no significant difference). Additionally, 40/78 patients were also enrolled in a secondary crossover study and were allocated to the opposite arm. Altogether, at six months, the relapse rate was 32/40 and 28/40 in the long and short arms, respectively (no significant difference). A post-hoc analysis excluding 30 patients treated with low-dose prednisone maintenance therapy failed to show significant differences between the two arms. No differences in adverse events, blood pressure and weight gain were observed. Thus, our data do not support the prescription of prolonged tapering schedules for relapses of steroid-sensitive nephrotic syndrome in children.

Dent disease (DD), an X-linked renal tubulopathy, is mainly caused by loss-of-function mutations in CLCN5 (DD1) and OCRL genes. CLCN5 encodes the ClC-5 antiporter that in proximal tubules (PT) participates in the receptor-mediated endocytosis of low molecular weight proteins. Few studies have analyzed the PT expression of ClC-5 and of megalin and cubilin receptors in DD1 kidney biopsies. About 25% of DD cases lack mutations in either CLCN5 or OCRL genes (DD3), and no other disease genes have been discovered so far. Sanger sequencing was used for CLCN5 gene analysis in 158 unrelated males clinically suspected of having DD. The tubular expression of ClC-5, megalin, and cubilin was assessed by immunolabeling in 10 DD1 kidney biopsies. Whole exome sequencing (WES) was performed in eight DD3 patients. Twenty-three novel CLCN5 mutations were identified. ClC-5, megalin, and cubilin were significantly lower in DD1 than in control biopsies. The tubular expression of ClC-5 when detected was irrespective of the type of mutation. In four DD3 patients, WES revealed 12 potentially pathogenic variants in three novel genes (SLC17A1, SLC9A3, and PDZK1), and in three genes known to be associated with monogenic forms of renal proximal tubulopathies (SLC3A, LRP2, and CUBN). The supposed third Dent disease-causing gene was not discovered.

We report the first worldwide experience with continuous veno-venous hemodialysis (CVVHD) in children using the last generation Cardio-Renal Pediatric Dialysis Emergency Machine (CARPEDIEM)TM device. Thirteen children received 1,008 h of CVVHD during 95 sessions, using a 0.15 (n = 7) or a 0.25 m2 (n = 6) hemofilter. The median weight was 3 kg (interquartile range [IQR] 2.5–6.2). In 10 patients, CVVHD was conducted using a 5 Fr double-lumen central vascular access, whereas in 3 children, bigger sizes were used (6.5 and 8 Ch). The median prescribed Qb was 17 mL/min (IQR 10–29.5), with a median Qd of 10 mL/min. Circuits were primed with 5% albumin in 12 out of 13 patients, using anticoagulation with heparin in all 13 cases. The median delivered/prescribed time ratio yielded a 100% result (95–100%). The most common cause for “downtime” was clotting that however occurred in only 3% of all treatments. Survivals at continuous renal replacement therapy discontinuation and ICU discharge were 100 and 69% respectively. The CARPEDIEMTM machine allowed successful delivery of diffusive blood purification modality to very small patients, using small catheters, no blood primes, and excellent concordance between delivered and prescribed treatment duration.

Background Symptoms and signs of acute tubulointerstitial nephritis (ATIN) are nonspecific; therefore, renal biopsy is often necessary to clarify the diagnosis. The aim of this study was to evaluate the use of 99mTc-dimercaptosuccinic acid (DMSA) scintigraphy in the diagnosis and follow-up of ATIN. Methods We retrospectively reviewed the charts of five patients (nine renal units) with a median age of 14 years who underwent DMSA scan after a clinical and/or biopsy-proven diagnosis of ATIN. The exam was performed within 1 month after disease onset and repeated at a median time of 12 months after the acute phase. Results DMSA renal scans performed during the acute phase allowed the discovery of suggestive findings, including diffuse reduction of the renal uptake of radionuclide and presence of multiple ‘cold’ focal lesions in a corticomedullary distribution. The follow-up scintigraphy resulted normal in two patients who were treated with steroids and in one patient who presented a mild renal dysfunction in the acute phase. By contrast, the control scan showed persistent renal damage in one patient who was further readmitted because of hypertension and in one renal transplanted patient who presented a Stage 3 acute kidney injury in the acute phase. Conclusions DMSA renal scan might be a reliable tool for an early non-invasive diagnosis of ATIN in children and might be particularly useful in those patients who are not candidates for a kidney biopsy. Moreover, DMSA scan gives accurate follow-up evaluation, as it allows monitoring of the evolution of acute renal parenchymal inflammation with potential risk of renal scar formation. Due to the small sample size, our findings warrant further validation in a larger study.

WOS: 000412042200025, PubMed ID: 28566477, We investigated the value of genetic, histopathologic, and early treatment response information in prognosing long-term renal outcome in children with primary steroid-resistant nephrotic syndrome. From the PodoNet Registry, we obtained longitudinal clinical information for 1354 patients (disease onset at >3 months and, E-Rare (German Ministry of Education and Research); Polish Ministry of Science and Education grant [N402631840]; German Research FoundationGerman Research Foundation (DFG) [Scha 477/11-1]; Scientific and Technological Research Council of TurkeyTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [108S417]; European Union (EU) Seventh Framework Programme (EURenOmics) grant [2012-305608], The PodoNet project has been made possible by support received from E-Rare (German Ministry of Education and Research), European Union (EU) Seventh Framework Programme (EURenOmics) grant 2012-305608, Polish Ministry of Science and Education grant N402631840, German Research Foundation grant Scha 477/11-1, and Scientific and Technological Research Council of Turkey grant 108S417.

Background Steroid resistant nephrotic syndrome (SRNS) is a frequent cause of end stage renal disease in children and post-transplant disease recurrence is a major cause of graft loss. Methods We identified all children with SRNS who underwent renal transplantation in Italy, between 2005 and 2017. Data were retrospectively collected for the presence of a causative gene mutation, sex, histology, duration of pre-transplant dialysis, age at onset and transplant, HLA matching, recurrence, therapy for recurrence, and graft survival. Results 101 patients underwent a first and 22 a second renal transplant. After a median follow-up of 58.5 months, the disease recurred on the first renal transplant in 53.3% of patients with a non-genetic and none with a genetic SRNS. Age at transplant > 9 years and the presence of at least one HLA-AB match were independent risk factors for recurrence. Duration of dialysis was longer in children with relapse, but did not reach statistical significance. Overall, 24% of patients lost the first graft, with recurrence representing the commonest cause. Among 22 patients who underwent a second transplant, 5 suffered of SRNS recurrence. SRNS relapsed in 5/9 (55%) patients with disease recurrence in their first transplant and 2 of them lost the second graft. Conclusions Absence of a causative mutation represents the major risk factor for post-transplant recurrence in children with SRNS, while transplant can be curative in genetic SRNS. A prolonged time spent on dialysis before transplantation has no protective effect on the risk of relapse and should not be encouraged. Retransplantation represents a second chance after graft loss for recurrence.

Ozcakar, Zeynep/0000-0002-6376-9189; Memaran, Nima/0000-0002-9510-3154; DUZOVA, ALI/0000-0002-4365-2995; Sugianto, Rizky Indrameikha/0000-0002-7929-507X WOS: 000511956000006 PubMed: 31811541 Background High prevalence of arterial hypertension is known in pediatric renal transplant patients, but how blood pressure (BP) distribution and control differ between age groups and whether sex and age interact and potentially impact BP after transplantation have not been investigated. Methods This retrospective analysis included 336 pediatric renal transplant recipients (62% males) from the Cooperative European Pediatric Renal Transplant Initiative Registry (CERTAIN) with complete BP measurement at discharge and 1, 2 and 3 years post-transplant. Results At discharge and 3 years post-transplant, arterial hypertension was highly prevalent (84% and 77%); antihypertensive drugs were used in 73% and 68% of the patients. 27% suffered from uncontrolled and 9% from untreated hypertension at 3 years post-transplant. Children transplanted at age < 5 years showed sustained high systolic BP z-score and received consistently less antihypertensive treatment over time. Younger age, shorter time since transplantation, male sex, higher body mass index (BMI), high cyclosporine A (CSA) trough levels, and a primary renal disease other than congenital anomalies of the kidney and urinary tract (CAKUT) were significantly associated with higher systolic BP z-score. Sex-stratified analysis revealed a significant association between high CSA and higher systolic BP in older girls that likely had started puberty already. An association between BP and estimated glomerular filtration rate was not detected. Conclusions BP control during the first 3 years was poor in this large European cohort. The description of age- and sex-specific risk profiles identified certain recipient groups that may benefit from more frequent BP monitoring (i.e. young children) or different choices of immunosuppression (i.e. older girls).

Background and objectives Nephrotic syndrome is a typical presentation of genetic podocytopathies but occasionally other genetic nephropathies can present as clinically indistinguishable phenocopies. We hypothesized that extended genetic testing followed by reverse phenotyping would increase the diagnostic rate for these patients. Design, setting, participants, & measurements All patients diagnosed with nephrotic syndrome and referred to our center between 2000 and 2018 were assessed in this retrospective study. When indicated, whole-exome sequencing and in silico filtering of 298 genes related to CKD were combined with subsequent reverse phenotyping in patients and families. Pathogenic variants were defined according to current guidelines of the American College of Medical Genetics. Results A total of 111 patients (64 steroid-resistant and 47 steroid-sensitive) were included in the study. Not a single pathogenic variant was detected in the steroid-sensitive group. Overall, 30% (19 out of 64) of steroid-resistant patients had pathogenic variants in podocytopathy genes, whereas a substantial number of variants were identified in other genes, not commonly associated with isolated nephrotic syndrome. Reverse phenotyping, on the basis of a personalized diagnostic workflow, permitted to identify previously unrecognized clinical signs of an unexpected underlying genetic nephropathy in a further 28% (18 out of 64) of patients. These patients showed similar multidrug resistance, but different long-term outcome, when compared with genetic podocytopathies. Conclusions Reverse phenotyping increased the diagnostic accuracy in patients referred with the diagnosis of steroid-resistant nephrotic syndrome.

Introduction: Children admitted to paediatric intensive care unit (PICU) are at risk of acute kidney injury (AKI). However, few paediatric studies have focused on the identification of factors potentially associated with the development of this condition. The aim of our study was to assess the incidence rate of AKI, identify risk factors, and evaluate clinical outcome in a large sample of critically ill children. Methods: This retrospective observational study was conducted including patients admitted to our PICU from January 2014 to December 2016. AKI was defined according to Kidney Disease: Improving Global Outcome criteria. Results: A total of 222 PICU patients out of 811 (27%) had AKI (stage I 39%, stage II 24%, stage III 37%). The most common PICU admission diagnoses in AKI cases were heart disease (38.6%), respiratory failure (16.8%) and postsurgical non-cardiac patients (11%). Hypoxic-ischaemic was the most frequent cause of AKI. Significant risk factors for AKI following multivariate analysis were age >2 months (OR 2.43; 95% CI 1.03–7.87; p = 0.05), serum creatinine at admission >44 µmol/L (OR 2.23; 95% CI 1.26–3.94; p = 0.006), presence of comorbidities (OR 1.84; 95% CI 1.03–3.30; p = 0.04), use of inotropes (OR 2.56; 95% CI 1.23–5.35; p= 0.012) and diuretics (OR 2.78; 95% CI 1.49–5.19; p = 0.001), exposure to nephrotoxic drugs (OR 1.66; 95% CI 1.01–2.91; p= 0.04), multiple organ dysfunction syndrome (OR 2.68; 95% CI 1.43–5.01; p = 0.002), and coagulopathy (OR 1.89; 95% CI 1.05–3.38, p = 0.03). AKI was associated with a significant longer PICU stay (median LOS of 8 days, interquartile range [IQR] 3–16, versus 4 days, IQR 2–8, in non-AKI patients; p < 0.001). The mortality rate resulted tenfold higher in AKI than non-AKI patients (12.6 vs. 1.2%; p < 0.001). Conclusions: The incidence of AKI in critically ill children is high, with an associated increased length of stay and risk of mortality. In the PICU setting, risk factors of AKI are multiple and mainly associated with illness severity.

Renal replacement therapy in infants and small children is the treatment of choice for severe oligoanuric renal dysfunction, with an increasing consensus that early initiation might contribute to preventing acute kidney injury complications. Safer renal replacement therapy devices specifically designed for neonates may contribute to ameliorating outcomes and increasing chances of survival. One of the crucial factors to achieve an effective renal replacement therapy in small infants is adequate vascular access. The interaction of small size central vascular catheters with renal replacement therapy devices has never been investigated. The aim of this study was to characterize both the operating conditions and performance of three different central vascular catheters sizes (4F, 5F, and 7F) connected to two different extracorporeal blood circulation models (adult and pediatric). The rheologic performance of each vascular access size in combination with the adult and pediatric renal replacement therapy models was described.Series of experimental extracorporeal circulation circuit tests were conducted with different setups. A two-roller pump was used to simulate a standard adult dialysis machine, whereas a small three-roller pump served as pediatric renal replacement therapy device.A pressure-flow setup aimed to collect pressure and flow values under different test conditions. A second experiment focused on hemolysis estimation induced by the extracorporeal system. Hemolysis exclusively induced by the 4F catheter was also evaluated. Finally, our data were applied to estimate the optimal catheter size theoretically capable of delivering adequate doses basing on anthropometric data (patient weight and cannulation site) in absence of direct ultrasound vessel measurement.In vitro tests conducted on simulated extracorporeal circuit models of continuous pediatric and neonatal renal replacement therapy.None.When 4F and 5F catheters are used, maximal blood flows within safe circuit pressures can be set at the values of 13 and 29 mL/min, respectively, when a small pump is used. Differently, when using adult roller pumps, only maximal flows of 10 and 20 mL/min are reached. However, hemolysis is higher when using a three-roller pump compared with the two-roller. The clinical impact of this increased hemolytic burden is likely not relevant.Small size central vascular catheters display optimal rheologic performances in terms of pressures and flows particularly when the renal replacement therapy device is equipped with pumps proportional to central vascular catheters sizes, and even when relatively high blood flows are set. This is achieved at the risk of a higher hemolysis rate.

PubMedID: 30949986 The number of children with acute kidney injury (AKI) requiring dialysis is increasing. To date, systematic analysis has been largely limited to critically ill children treated with continuous renal replacement therapy (CRRT). We conducted a survey among 35 European Pediatric Nephrology Centers to investigate dialysis practices in European children with AKI. Altogether, the centers perform dialysis in more than 900 pediatric patients with AKI per year. PD and CRRT are the most frequently used dialysis modalities, accounting for 39.4% and 38.2% of treatments, followed by intermittent HD (22.4%). In units treating more than 25 cases per year and in those with cardiothoracic surgery programs, PD is the most commonly chosen dialysis modality. Also, nearly one quarter of centers, in countries with a gross domestic product below $35,000/year, do not utilize CRRT at all. Dialysis nurses are exclusively in charge of CRRT management in 45% of the cases and pediatric intensive care nurses in 25%, while shared management is practiced in 30%. In conclusion, this survey indicates that the choice of treatment modalities for dialysis in children with AKI in Europe is affected by the underlying ethiology of the disease, organization/set-up of centers and socioeconomic conditions. PD is utilized as often as CRRT, and also intermittent HD is a commonly applied treatment option. A prospective European AKI registry is planned to provide further insights on the epidemiology, management and outcomes of dialysis in pediatric AKI. © 2019, Italian Society of Nephrology.

BK polyomavirus-associated nephropathy (BKPyVAN) constitutes a serious cause of kidney allograft failure, but large-scale data in pediatric renal transplant recipients and a comprehensive analysis of specific risk factors are lacking.We analyzed the data of 313 patients in the Cooperative European Pediatric Renal Transplant Initiative Registry, with an observation period of 3.3 years (range, 1-5). The net state of immunosuppressive therapy was assessed by the modified Vasudev score.Presumptive BKPyVAN (defined as sustained [3 wk] high-level BK viremia10 copies/mL) within 5 years posttransplant occurred in 49 (15.8%) of 311 patients, and biopsy-proven BKPyVAN in 14 (4.5%) of 313. BKPyV viremia was observed in 115 (36.7%) of 311 patients, of whom 11 (9.6%) of 115 developed viremia late, that is, after the second year posttransplant. In 6 (12.5%) of 48 patients with high-level viremia and in 3 (21.4%) of 14 with BKPyVAN, this respective event occurred late. According to multivariable analysis, BKPyV viremia and/or BKPyVAN were associated not only with a higher net state of immunosuppression (odds ratio [OR], 1.3; P0.01) and with tacrolimus-based versus ciclosporin-based immunosuppression (OR, 3.6; P0.01) but also with younger recipient age (OR, 1.1 per y younger; P0.001) and obstructive uropathy (OR, 12.4; P0.01) as primary renal disease.Uncontrolled BKPyV replication affects a significant proportion of pediatric renal transplant recipients and is associated with unique features of epidemiology and risk factors, such as young recipient age, obstructive uropathy, and overall intensity of immunosuppressive therapy. BKPyV surveillance should be considered beyond 2 years posttransplant in pediatric patients at higher risk.

Nail Patella syndrome (NPS) is a rare autosomal dominant disease characterized by varying degrees of patella, nail, and elbows dysplasia and also ocular and renal congenital abnormalities. The renal involvement, ranging from hematuria and proteinuria to end-stage renal disease, is present in 22-60% of NPS cases. Heterozygous variants in LMX1B are known to be responsible of NPS and it has been hypothesized that the variable expressivity is due to the interaction of LMX1B with other developmental genes. We reported a case of co-presence of LMX1B and PAX2 variants in a child with extrarenal manifestation of NPS and end-stage renal disease but congenital bilateral renal hypodysplasia and vesicoureteral reflux. The LMX1B variant was de novo, whereas the PAX2 variant was inherited from the mother that had bilateral renal hypoplasia although in presence of only a mild chronic kidney disease. The molecular interaction between LMX1B and PAX2 has been already reported in vitro and this finding suggest that the worst renal NPS phenotype of our patient could be due to the defective expression of these two genes during nephrogenesis. In conclusion, our finding suggests that PAX2 may act as modifier gene in Nail Patella phenotype.

Infants with a body weight of less than 10 kg are often not considered to be suitable candidates for renal transplantation (RTx). The objective of this study was to evaluate this arbitrary weight threshold for pediatric RTx. We conducted a multicenter, retrospective, match-controlled cohort study on infants weighing less than 10 kg at time of engrafting (low-weight group [LWG], n = 38) compared to a matched control group (n = 76) with a body weight of 10–15 kg, using data from the first 2 years post-transplant derived from the CERTAIN Registry. Patient survival was 97 and 100% in the LWG and control groups, respectively (P = 0.33), and death-censored graft survival was 100 and 95% in the LWG and control groups, respectively (P = 0.30). Estimated glomerular filtration rate at 2 years post-transplant was excellent and comparable between the groups (LWG 77.6 ± 34.9 mL/min/1.73 m2; control 74.8 ± 29.1 mL/min/1.73 m2; P = 0.68). The overall incidences of surgery-related complications (LWG 11%, control 23%; P = 0.12) and medical outcome measures (LWG 23%, control 36%, P = 0.17) were not significantly different between the groups. The medical outcome measures included transplant-related viral diseases (LWG 10%, control 21%; P = 0.20), acute rejection episodes (LWG 14%, control 29%; P = 0.092), malignancies (LWG 3%, control 0%; P = 0.33) and arterial hypertension (LWG 73%, control 67%; P = 0.57). These data suggest that RTx in low-weight children is a feasible option, at least in selected centers with appropriate surgical and medical expertise.

Rationale & Objective Although primary atypical hemolytic uremic syndrome (aHUS) is associated with abnormalities in complement genes and antibodies to complement factor H, the role of complement in secondary aHUS remains debatable. We evaluated the usefulness of an ex vivo test to: (1) detect complement activation within the endothelium in primary and secondary aHUS, (2) differentiate active disease from remission, (3) monitor the effectiveness of eculizumab therapy, and (4) identify relapses during eculizumab dosage tapering and after discontinuation of treatment. Study Design Case series. Setting & Participants 121 patients with primary aHUS and 28 with secondary aHUS. Serum samples were collected during acute episodes, following remission, and during eculizumab treatment and were assessed using a serum-induced ex vivo C5b-9 endothelial deposition test. Results Serum-induced C5b-9 deposition on cultured microvascular endothelium was quantified by calculating the endothelial area covered by C5b-9 staining; values were expressed as percentage of C5b-9 deposits induced by a serum pool from healthy controls. Testing with adenosine diphosphate–activated endothelium demonstrated elevated C5b-9 deposits for all untreated patients with aHUS independent of disease activity, while testing with unstimulated endothelium demonstrated deposits only in active disease. Similar findings were observed in secondary aHUS. Serum-induced C5b-9 deposits on activated and unstimulated endothelium normalized during eculizumab treatment. 96% (22/23) of patients receiving eculizumab at extended 3- or 4-week dosing intervals demonstrated normal C5b-9 deposits on activated endothelium, despite most patients having CH50Eq (serum complement activity) > 20 UEq/mL, indicating that adequate complement control was achieved even with incomplete blockade of circulating C5. During eculizumab dosage tapering or after treatment discontinuation, all patients experiencing relapses versus only 6% (1/17) of those in stable remission had elevated C5b-9 deposits on unstimulated endothelium. Limitations The C5b-9 endothelial deposition test can be performed in only specialized laboratories. Findings on eculizumab dosage tapering need to be confirmed with longitudinal monitoring of C5b-9 deposition. Conclusions The C5b-9 endothelial deposition assay may represent an advance in our ability to monitor aHUS activity and individualize therapy.

BackgroundThe entity called renal dysplasia is considered to be a frequent cause of chronic kidney disease in children. Formally, the entity is defined by histological parameters. In current nephrology practice, however, the appearance of kidneys on ultrasound scanning is often used as a basis for the diagnosis.MethodsThe European Society for Paediatric Nephrology Working Group on Congenital Anomalies of the Kidney and Urinary Tract hypothesised that the current diagnostic approach with regard to renal dysplasia was not homogeneous. Accordingly, we here report the results of a survey targeting pediatric nephrologists with 12 questions regarding their perceptions of the ultrasonographic characteristics of renal dysplasia and further tests that they might undertake.ResultsOf almost 1200 physicians who successfully received the invitation, 248 from 54 countries completed the survey. There was a notable lack of homogeneity regarding the ultrasonographic diagnosis of renal dysplasia and also of follow up tests, including genetic testing and further radiology.ConclusionsBased on the responses to this large survey, a picture emerges of nephrologist’s current clinical practise with a focus on renal dysplasia. The Working Group consider that these results serve as an important sounding board that can inform more definitive recommendations regarding the challenges to clinical diagnosis and diagnostic follow-up of the this important entity.

Data concerning outcomes of children on hemodialysis (HD) and peritoneal dialysis (PD) are scarce and frequently derived from single-center experiences. We sought to compare survival and transplantation rates in a large cohort of PD and HD patients. We extracted all patients initiating dialysis under 16 years of age between 2004 and 2013 from the Italian Registry of Pediatric Chronic Dialysis. Patients on PD were propensity-matched to those on HD based on gender, age, primary cause of ESRD, and the number of co-morbidities. Stratified Cox proportional hazard models were used to compare outcomes by dialysis modality. Three hundred ten patients were matched from 452 incident patients. In the unmatched cohort, PD patients were younger, more likely to be diagnosed with CAKUT, and had a higher urine output than HD patients. In the propensity-matched cohort, covariates were balanced between the two groups. At 2 years, the cumulative hazard ratio for death was similar (CHR 0.95, 95% CI 0.17–5.20) for HD relative to PD patients; and at 5 years, the CHR was lower for HD patients (0.22 95% CI 0.16–0.29). The cumulative incidence of transplantation at 3 years after dialysis initiation was 60.9% in HD patients and 59.7% in PD patients, with a CHR of 1.03 (95% CI 0.73–1.45). Conclusions: Pediatric PD and HD patients have distinct characteristics. After controlling for treatment-selection biases, children selected to start on PD or HD exhibit a similar mortality risk during the first 2 years on treatment, after which this risk increases in PD children.What is Known:• Few studies have compared hard outcomes in children on maintenance dialysis.• Children started on different dialysis modalities have distinct characteristics that impact on survival.What is New:• After controlling for treatment-selection biases, children selected to start dialysis on PD or HD exhibit a similar mortality risk during the first 2 years on treatment, after which this risk appears to be increased in PD children.• An “integrative care” approach should be used in children on PD, switching them to HD when PD-related morbidity tends to increase.

Steroid-dependent nephrotic syndrome (SDNS) carries a high risk of toxicity from steroids or steroid-sparing agents. This open-label, noninferiority, randomized controlled trial at four sites in Italy tested whether rituximab is noninferior to steroids in maintaining remission in juvenile SDNS. We enrolled children age 1-16 years who had developed SDNS in the previous 6-12 months and were maintained in remission with high prednisone doses (≥0.7 mg/kg per day). We randomly assigned participants to continue prednisone alone for 1 month (control) or to add a single intravenous infusion of rituximab (375 mg/m(2); intervention). Prednisone was tapered in both groups after 1 month. For noninferiority, rituximab had to permit steroid withdrawal and maintain 3-month proteinuria (mg/m(2) per day) within a prespecified noninferiority margin of three times the levels among controls (primary outcome). We followed participants for ≥1 year to compare risk of relapse (secondary outcome). Fifteen children per group (21 boys; mean age, 7 years [range, 2.6-13.5 years]) were enrolled and followed for ≤60 months (median, 22 months). Three-month proteinuria was 42% lower in the rituximab group (geometric mean ratio, 0.58; 95% confidence interval, 0.18 to 1.95 [i.e., within the noninferiority margin of three times the levels in controls]). All but one child in the control group relapsed within 6 months; median time to relapse in the rituximab group was 18 months (95% confidence interval, 9 to 32 months). In the rituximab group, nausea and skin rash during infusion were common; transient acute arthritis occurred in one child. In conclusion, rituximab was noninferior to steroids for the treatment of juvenile SDNS.

Background and objectives Genetic and acquired abnormalities causing dysregulation of the complement alternative pathway contribute to atypical hemolytic uremic syndrome (aHUS), a rare disorder characterized by thrombocytopenia, nonimmune microangiopathic hemolytic anemia, and acute kidney failure. However, in a substantial proportion of patients the disease-associated alterations are still unknown. Design, setting, participants, & measurements Whole-exome and whole-genome sequencing were performed in two unrelated families with infantile recessive aHUS. Sequencing of cDNA from affected individuals was used to test for the presence of aberrant mRNA species. Expression of mutant diacylglycerol kinase epsilon (DGKE) protein was evaluated with western blotting. Results Whole-exome sequencing analysis with conventional variant filtering parameters did not reveal any obvious candidate mutation in the first family. The report of aHUS-associated mutations in DGKE , encoding DGKE, led to re-examination of the noncoding DGKE variants obtained from next-generation sequencing, allowing identification of a novel intronic DGKE mutation (c.888+40A>G) that segregated with disease. Sequencing of cDNA from affected individuals revealed aberrant forms of DGKE mRNA predicted to cause profound abnormalities in the protein catalytic site. By whole-genome sequencing, the same mutation was found in compound heterozygosity with a second nonsense DGKE mutation in all affected siblings of another unrelated family. Homozygous and compound heterozygous patients presented similar clinical features, including aHUS presentation in the first year of life, multiple relapsing episodes, and proteinuria, which are prototypical of DGKE -associated aHUS. Conclusions This is the first report of a mutation located beyond the exon-intron boundaries in aHUS. Intronic mutations such as these are underreported because conventional filtering parameters used to process next-generation sequencing data routinely exclude these regions from downstream analyses in both research and clinical settings. The results suggest that analysis of noncoding regions of aHUS-associated genes coupled with mRNA sequencing might provide a tool to explain genetically unsolved aHUS cases.

Therapeutic plasma exchange (TPE) in neonates and small infants is a treatment method at the forefront that may become a potentially life-saving procedure in a wide array of severe conditions. Indications for TPE in the pediatric population have been mainly derived from adult literature, with neonatal hyperbilirubinemia being the most notable exception. The only alternative to TPE in small pediatric patients is manual blood exchange transfusion, which, however, bears an unacceptably high risk of severe complications. Still, technical issues due to extracorporeal circulation in neonates have burdened TPE so far, since machines developed for adults require a relatively large blood volume to operate. We in this study, describe our preliminary experience of TPE for treating 2 potentially life-threatening conditions in neonatal age. To overcome the aforementioned limitations, plasmapheresis was performed in both cases using a machine specifically designed for patients weighing less than 10 kg.

Mutations in human SIX1 gene cause branchiootorenal or branchiootic syndrome. Six1 deficient mice exhibit uni- or bilateral renal hypoplasia or kidney agenesis. Furthermore a lack of Six1 gene in the ureter leads to hydroureter and hydronephrosis. These murine malformations resemble human kidney and urinary tract congenital anomalies (CAKUT), a group of diseases with a diverse anatomical spectrum which includes duplex collecting system as much as urethra kidney and ureteropelvic anomalies. Our study focuses on whether mutations or deletion of this gene may be associated with nonsyndromic CAKUT. Fifty unrelated patients (13–21 years) with nonsyndromic CAKUT were retrospectively recruited for SIX1 sequence variations analysis, and compared to three subjects without malformative nephrouropathies (controls). SIX1 coding sequence was screened by high resolution melt analysis (HRMA) and by Sanger direct sequencing. A quantitative comparative real-time polymerase chain reaction (PCR) was later performed in order to detect the presence of SIX1 gene deletion. We did not find significant differences in the HRMA melting curves for each of the SIX1 coding exons between patients and controls, as also confirmed by Sanger direct sequencing. Moreover quantitative comparative real-time PCR for SIX1 and data normalization excluded total SIX1 gene deletion in our patients. We did not find sequence variations in SIX1 coding regions or complete gene deletion in our CAKUT population. These results suggest that alterations in these sequences are unlikely to be a major cause of nonsyndromic CAKUT. Nevertheless, further studies are necessary to understand if altered SIX1 expression may play a role in human development of kidney and urinary tract congenital anomalies.

This consensus document is aimed at providing an updated, multidisciplinary overview on the diagnosis and treatment of pediatric nephrotic syndrome (NS) at first presentation. It is the first consensus document of its kind to be produced by all the pediatric nephrology centres in Italy, in line with what is already present in other countries such as France, Germany and the USA. It is based on the current knowledge surrounding the symptomatic and steroid treatment of NS, with a view to providing the basis for a separate consensus document on the treatment of relapses. NS is one of the most common pediatric glomerular diseases, with an incidence of around 2–7 cases per 100000 children per year. Corticosteroids are the mainstay of treatment, but the optimal therapeutic regimen for managing childhood idiopathic NS is still under debate. In Italy, shared treatment guidelines were lacking and, consequently, the choice of steroid regimen was based on the clinical expertise of each individual unit. On the basis of the 2015 Cochrane systematic review, KDIGO Guidelines and more recent data from the literature, this working group, with the contribution of all the pediatric nephrology centres in Italy and on the behalf of the Italian Society of Pediatric Nephrology, has produced a shared steroid protocol that will be useful for National Health System hospitals and pediatricians. Investigations at initial presentation and the principal causes of NS to be screened are suggested. In the early phase of the disease, symptomatic treatment is also important as many severe complications can occur which are either directly related to the pathophysiology of the underlying NS or to the steroid treatment itself. To date, very few studies have been published on the prophylaxis and treatment of these early complications, while recommendations are either lacking or conflicting. This consensus provides indications for the prevention, early recognition and treatment of these complications (management of edema and hypovolemia, therapy and prophylaxis of infections and thromboembolic events). Finally, recommendations about the clinical definition of steroid resistance and its initial diagnostic management, as well as indications for renal biopsy are provided.

Primary distal renal tubular acidosis is a rare genetic disease. Mutations in SLC4A1 , ATP6V0A4, and ATP6V1B1 genes have been described as the cause of the disease, transmitted as either an autosomal dominant or recessive trait. Particular clinical features, such as sensorineural hearing loss, have been mainly described in association with mutations in one gene instead of the others. Nevertheless, the diagnosis of distal renal tubular acidosis is essentially based on clinical and laboratory findings, and the series of patients described so far are usually represented by small cohorts. Therefore, a strict genotype-phenotype correlation is still lacking, and questions about whether clinical and laboratory data should direct the genetic analysis remain open. Here, we applied next-generation sequencing in 89 patients with a clinical diagnosis of distal renal tubular acidosis, analyzing the prevalence of genetic defects in SLC4A1 , ATP6V0A4, and ATP6V1B1 genes and the clinical phenotype. A genetic cause was determined in 71.9% of cases. In our group of sporadic cases, clinical features, including sensorineural hearing loss, are not specific indicators of the causal underlying gene. Mutations in the ATP6V0A4 gene are quite as frequent as mutations in ATP6V1B1 in patients with recessive disease. Chronic kidney disease was frequent in patients with a long history of the disease. Thus, our results suggest that when distal renal tubular acidosis is suspected, complete genetic testing could be considered, irrespective of the clinical phenotype of the patient.

Background. High levels of preformed anti-HLA antibodies dramatically diminish renal transplant outcomes.Most desensitization programmes guarantee good intermediate outcomes but quite disappointing long-term prognosis. The search for a fully compatible kidney increases time on the waiting list. Methods. In February 2011, a nationwide hyperimmune programme (NHP) was begun in Italy: all available kidneys are primarily proposed to highly sensitized patients with a panel reactive antibody above 80%. In this manuscript, we evaluate the outcome of paediatric patients transplanted with this approach. Results. Twenty-one patients were transplanted. Complete data are available for 20 patients. Mean age at transplantation was 14.5 years [standard deviation (SD) 6 5.5)]. Mean time on the waiting list was 29.3 months (SD 6 27.5). Median follow-up was 29.2 months (range: 11.2-59.3). The average number of HLA mismatches in these patients was 2.3 versus 3.7 in 48 standard patients transplanted in the same period (P < 0.001). Only one graft was lost. Two cases of humoral rejection occurred and were successfully treated. No cellular rejection was reported. Median creatinine clearance was 84, 88, 77 and 77 mL/min/1.73 m2 respectively 1, 6, 12 and 24 months after transplant. Conclusions. Transplantation of sensitized patients avoiding prohibited antigens is feasible, at least in a selected cohort of patients. In order to be able to further improve this approach, which in our opinion is very successful, it would be necessary to expand the donor pool, possibly increasing the number of countries participating in the programme. In this series, time on the waiting list did not increase significantly. This allocation policy should ideally lead to an outcome comparable to that expected in standard patients, which is particularly desirable in young patients who have the longest life expectancy. Since long-term results of desensitization programmes are not (yet) convincing, we suggest that these programmes should be reserved for selected cases where compatible organs cannot be found within a reasonable time span.

Post-transplant lymphoproliferative disorder (PTLD) is a severe complication of solid organ transplantation that can be classified into two major subtypes, namely, early lesions and non-early lesions, based on histopathological findings. In the vast majority of cases, proliferating cells are B lymphocytes and, most frequently, proliferation is induced by Epstein–Barr virus (EBV) infection. The aim of our study was to evaluate the natural history of EBV infection and its possible evolution toward PTLD in a pediatric cohort of patients who received a renal transplant between January 2000 and December 2013. A total of 304 patients were evaluated for this study, of whom 103 tested seronegative for EBV at transplantation. Following transplantation, 50 of the 103 seronegative patients (48.5%) developed a first EBV infection, based on the results of PCR assays for EBV DNA, with 19 of these patients ultimately reverting to the negative state (

Comamonas testosteroni (C. testosteroni) has been rarely observed as an infectious agent in clinical practice. Few reports described its potential pathogenicity in bloodstream and abdominal infections. Here, we report our experience in the treatment of a C. testosteroni-associated peritonitis in a four-year-old girl receiving chronic peritoneal dialysis (PD). The organism was shown to be highly susceptible to appropriate antibiotic therapy. Infection responded promptly and the patient was managed conservatively without withdrawal from PD.

Background Patients with full-house nephropathy (FHN) present renal lesions that are indistinguishable from those of lupus nephritis (LN) but lack the systemic features necessary to meet diagnostic criteria for systemic lupus erithematosus (SLE). Some have been reported to develop a delayed SLE with time. The clinical outcome of children having FHN without SLE has never been reported. Methods Children with biopsy-proven FHN were selected after excluding SLE cases by the absence of America College of Rheumatology criteria. The proportion of patients with complete (proteinuria

Primitive nephrotic syndrome is one of the most common glomerular diseases in childhood and represents the clinical manifestation of various pathologic changes in the kidney. In children, nephrotic syndrome is classified based on the initial response to empiric corticosteroid treatment, which is considered as the best predictor of patients’ final outcome. The advent of next-generation sequencing technology showed that genetic alterations in structural genes of the podocyte can be recognized in a significant proportion of not only familial or syndromic patients with steroid-resistant nephrotic syndrome (SRNS), but also of sporadic cases, raising the question of whether it is time to update current protocols of patient care. In this review, we discuss the implications derived from several studies describing a high prevalence in children with SRNS of pathogenic mutations in a group of genes and their unresponsiveness to immunosuppressive therapy. We propose a diagnostic and therapeutic algorithm to reduce the exposure to immunosuppressants in individuals with unresponsive forms of the disease, sparing patients the untoward side effects of prolonged ineffective treatments, and at the same time guaranteeing the optimal immunosuppressive or other new therapy in potentially responsive patients.

The CARdiorenal PEDIatric EMergency (CARPEDIEM) machine was originally designed to perform only continuous venovenous hemofiltration (CVVH) in neonatal and pediatric patients. In some cases, adequate convective clearance may not be reached because of a limited blood flow. In such conditions, the application of diffusive clearance [continuous venovenous hemodialysis (CVVHD)] would help optimize blood purification. In this study, the CARPEDIEM™ machine was modified to enable the circulation of dialysis through the filter allowing testing of the performance of CARPEDIEM™ machine in CVVHD.Three different polyethersulfone hemodialyzers (surface area = 0.1 m(2), 0.2 m(2), and 0.35 m(2), respectively) were tested in vitro with a scheduled combination of plasma flow rates (Qp = 10-20-30 ml/min) and dialysis fluid flow rate (Qd = 5-10-15 ml/min). Three sessions were performed in co-current and one in counter-current configuration (as control) for each filter size. Clearance was measured from the blood and dialysate sides and results with mass balance error greater than 5 % were discarded.Urea and creatinine clearances for each plasma/dialysate combination are reported: clearance increase progressively for every filter proportionally to plasma flow rates. Similarly, clearances increase progressively with dialysate flow rates at a given plasma flow. The clearance curve tends to present a steep increase for small increases in plasma flow in the range below 10 ml/min, while the curve tends to plateau for values averaging 30 ml/min. As expected, the plateau is reached earlier with the smaller filter showing the effect of membrane surface-area limitation. At every plasma flow, the effect of dialysate flow increase is evident and well defined, showing that saturation of effluent was not achieved completely in any of the experimental conditions explored. No differences (p 0.05 for all values) were obtained in experiments using whole blood instead of plasma or using co-current versus counter-current dialysate flow configuration.Although plasma flow and filter surface give an important contribution to the level of clearance urea and creatinine, it appears evident that dialysate flow plays an essential role in the blood purification process, justifying the use of CVVHD versus CVVH in case of high dialysis dose requirement and/or limited blood flow rate.

Definition of the urinary protein composition would represent a potential tool for diagnosis in many clinical conditions. The use of new proteomic technologies allows detection of genetic and post-trasductional variants that increase sensitivity of the approach but complicates comparison within a heterogeneous patient population. Overall, this limits research of urinary biomarkers. Studying monogenic diseases are useful models to address this issue since genetic variability is reduced among first- and second-degree relatives of the same family. We applied this concept to Dent's disease, a monogenic condition characterised by low-molecular-weight proteinuria that is inherited following an X-linked trait. Results are presented here on a combined proteomic approach (LC-mass spectrometry, Western blot and zymograms for proteases and inhibitors) to characterise urine proteins in a large family (18 members, 6 hemizygous patients, 6 carrier females, and 6 normals) with Dent's diseases due to the 1070G > T mutation of the CLCN5. Gene ontology analysis on more than 1000 proteins showed that several clusters of proteins characterised urine of affected patients compared to carrier females and normal subjects: proteins involved in extracellular matrix remodelling were the major group. Specific analysis on metalloproteases and their inhibitors underscored unexpected mechanisms potentially involved in renal fibrosis. Biological significance Studying with new-generation techniques for proteomic analysis of the members of a large family with Dent's disease sharing the same molecular defect allowed highly repetitive results that justify conclusions. Identification in urine of proteins actively involved in interstitial matrix remodelling poses the question of active anti-fibrotic drugs in Dent's patients.

Renal coloboma syndrome, also known as papillorenal syndrome is an autosomal-dominant disorder characterized by ocular and renal malformations. Mutations in the paired-box gene, PAX2, have been identified in approximately half of individuals with classic findings of renal hypoplasia/dysplasia and abnormalities of the optic nerve. Prior to 2011, there was no actively maintained locus-specific database (LSDB) cataloguing the extent of genetic variation in the PAX2 gene and phenotypic variation in individuals with renal coloboma syndrome. Review of published cases and the collective diagnostic experience of three laboratories in the United States, France, and New Zealand identified 55 unique mutations in 173 individuals from 86 families. The three clinical laboratories participating in this collaboration contributed 28 novel variations in 68 individuals in 33 families, which represent a 50% increase in the number of variations, patients, and families published in the medical literature. An LSDB was created using the Leiden Open Variation Database platform: www.lovd.nl/PAX2. The most common findings reported in this series were abnormal renal structure or function (92% of individuals), ophthalmological abnormalities (77% of individuals), and hearing loss (7% of individuals). Additional clinical findings and genetic counseling implications are discussed.

PURPOSE: Upper pole histology has been poorly investigated in duplex system ectopic ureters and ureteroceles. We aimed to determine the differences in histology between the conditions, and to identify clinical markers of renal damage. METHODS: Twenty-two patients undergoing partial nephrectomy between 2001 and 2007 for poorly functioning upper poles associated with ectopic ureters (n = 11) or ureteroceles (n = 11) were considered. Histology was classified into three groups: normal, chronic interstitial nephritis (CIN), and dysplasia. Clinical and radiological variables were compared between the two conditions and between cases with normal and abnormal histology. RESULTS: Of the 22 upper pole specimens, 9 had normal histology, 8 dysplasia, and 5 CIN. Statistical analysis failed to show any significant difference in preoperative variables or histology between ectopic ureters and ureteroceles, and in preoperative variables between cases with normal and abnormal histology. CONCLUSIONS: We did not find significant differences in the histology of upper poles associated with ectopic ureters and ureteroceles. Histology was normal in more than one-third of patients, although the poles were poorly functioning. We hypothesize that these poles were hypoplasic rather than dysplasic. We failed to identify predictors of histological damage. Hence, the latter cannot be considered a factor guiding our decision-making.

Summary Background and objectives Prednisone and calcineurin inhibitors are the mainstay therapy of idiopathic nephrotic syndrome (INS) in children. However, drug dependence and toxicity associated with protracted use are common. Case series suggest that the anti-CD20 monoclonal antibody rituximab (RTX) may maintain disease remission. Design, setting, participants, & measurements This open-label randomized controlled trial was powered to show that a strategy based on RTX and lower doses of prednisone and calcineurin inhibitors was noninferior to standard doses of these agents in maintaining 3-month proteinuria as low as baseline or up to 1 g/d greater (noninferiority margin). Participants were stratified by the presence of toxicity to prednisone/calcineurin inhibitors and centrally assigned to add RTX (Mabthera, 375 mg/m 2 intravenously) to lower doses of standard agents or to continue with current therapy alone. The risk of relapse was a secondary outcome. Results Fifty-four children (mean age 11 4 years) with INS dependent on prednisone and calcineurin inhibitors for 12 months were randomized. Three-month proteinuria was 70% lower in the RTX arm (95% confidence interval 35% to 86%) as compared with standard therapy arm (intention-to-treat); relapse rates were 18.5% (intervention) and 48.1% (standard arm) (P 0.029). Probabilities of being drug-free at 3 months were 62.9% and 3.7%, respectively (P 0.001); 50% of RTX cases were in stable remission without drugs after 9 months. Conclusions Rituximab and lower doses of prednisone and calcineurin inhibitors are noninferior to standard therapy in maintaining short-term remission in children with INS dependent on both drugs and allow their temporary withdrawal. Clin J Am Soc Nephrol 6: 1308–1315, 2011. doi: 10.2215/CJN.09421010

We assessed LUTS at least 12 months after RTx in patients without evidence of lower urinary tract dysfunction (non-urologic) that had been anuric for at least six months before RTx. No bladder recycling was performed before RTx. LUTS were evaluated using a questionnaire. Clinical records were also reviewed. LUTS in anuric patients were compared with those in non-anuric patients. Fourteen anuric patients fulfilled the inclusion criteria. Median age at RTx was 11 (5-21) yr, median duration of anuria before RTx 24 (7-46) months, and median post-RTx follow-up 2.7 (1.9-10.2) yr. Daytime symptoms were exceptional. Nocturia was the most common symptom (10 patients). Only one patient reported symptoms to affect her quality of life. One patient experienced a febrile UTI and none graft failure. LUTS (nocturia) proved unrelated to duration of anuria, length of follow-up, and presence of (nocturnal) polyuria. LUTS were not statistically different in patients anuric and non-anuric before RTx. Non-urologic patients suffer from long-term storage symptoms, particularly nocturia. LUTS, however, do not seem to increase the risks of urinary infections or graft failure and appear to occur irrespective of the presence of anuria before RTx. Bladder recycling before RTx seems unnecessary.