The role of genetic testing in the diagnostic workflow of pediatric patients with kidney diseases: the experience of a single institution.

PURPOSE: Inherited kidney diseases are among the leading causes of kidney failure in children, resulting in increased mortality, high healthcare costs and need for organ transplantation. Next-generation sequencing technologies can help in the diagnosis of rare monogenic conditions, allowing for optimized medical management and therapeutic choices. METHODS: Clinical exome sequencing (CES) was performed on a cohort of 191 pediatric patients from a single institution, followed by Sanger sequencing to confirm identified variants and for family segregation studies. RESULTS: All patients had a clinical diagnosis of kidney disease: the main disease categories were glomerular diseases (32.5%), ciliopathies (20.4%), CAKUT (17.8%), nephrolithiasis (11.5%) and tubular disease (10.5%). 7.3% of patients presented with other conditions. A conclusive genetic test, based on CES and Sanger validation, was obtained in 37.1% of patients. The highest detection rate was obtained for ciliopathies (74.4%), followed by nephrolithiasis (45.5%), tubular diseases (45%), while most glomerular diseases and CAKUT remained undiagnosed. CONCLUSIONS: Results indicate that genetic testing consistently used in the diagnostic workflow of children with chronic kidney disease can (i) confirm clinical diagnosis, (ii) provide early diagnosis in the case of inherited conditions, (iii) find the genetic cause of previously unrecognized diseases and (iv) tailor transplantation programs.

Increase of continuous treatments and regional citrate anticoagulation during renal replacement therapy in the ICUs of the North-West of Italy from 2007 to 2015.

BACKGROUND: Few reports have addressed the change in renal replacement therapy (RRT) management in the Intensive care Units (ICUs) over the years in western countries. This study aims to assess the trend of dialytic practice in a 4.5-million population-based study of the northwest of Italy. METHODS: A nine-year survey covering all the RRT provided in the ICUs. Consultant nephrologists of the 26 Nephrology and Dialysis centers reported their activities in the years 2007, 2009, 2012, and 2015. RESULTS: From 2007 to 2015 the patients treated increased from 1042 to 1139, and the incidence of RRT from 254 to 263 cases/10^6 inhabitants. The workload for dialysis center was higher in the larger hub hospitals. RRT for acute kidney injury (AKI), continuation of treatment in chronically dialyzed patients, or extrarenal indications accounted for about the stable rate of 70, 25 and 5% of all RRT sessions, respectively. Continuous modality days increased from 2731 days (39.5%) in 2007 to 5076 (70.6%) in 2015, when the continuous+prolonged treatment days were 6880/7196 (95.6% of total days). As to RRT timing, in 2015 only the classical clinical criteria, and no K-DIGO stage were adopted by most Centers. As to RRT interruption, in 2015 urine volume was the first criterion. Implementation of citrate anticoagulation (RCA) for RRT patients significantly increased from 2.8% in 2007 to 30.9% in 2015, when it was applied in all 26 Centers. CONCLUSIONS: From 2007 to 2015, current practice has changed towards shared protocols, with increasing continuous modality and RCA implementation.

Splenic Vessels as a Rescue for Pediatric Kidney Retransplantation in Children With Iliac-caval Agenesis or Thrombosis.

BACKGROUND: Unavailability of the iliac-caval system due to thrombosis or aberrant anatomy may preclude kidney transplantation (KT) in small infants, exposing them to the complications of long-term dialysis. A tailored approach may enable KT also in these difficult patients. METHODS: We report the cases of 2 pediatric patients with a history of long-term hemodialysis, a previously failed KT, pending exhaustion of vascular accesses for dialysis, and unsuitability of the iliac-caval axis as a site for KT. Both patients were successfully managed by using splenic vessels as a source of arterial inflow or venous drainage during KT. Notably, one patient also had a previous liver transplant. RESULTS: Both kidney grafts showed primary function. Posttransplant courses were uneventful, and no rejection episode was observed. At 64- and 10-mo follow-ups, both children had optimal renal function and excellent quality of life. CONCLUSIONS: When the iliac-caval system is unavailable, kidney graft implantation on splenic vessels represents a safe and effective option for pediatric KT.

First clinical application of cord blood mesenchymal stromal cells in children with multi-drug resistant nephrotic syndrome.

BACKGROUND AND OBJECTIVES: Children with multi-drug resistant idiopathic nephrotic syndrome (MDR-INS) usually progress to end-stage kidney disease with a consistent risk of disease recurrence after transplantation. New therapeutic options are needed for these patients. Mesenchymal stromal cells (MSCs) are multipotential non-hematopoietic cells with several immunomodulatory properties and growing clinical applications. Cord blood-derived MSC have peculiar anti-inflammatory and immunosuppressive properties. We aimed at assessing safety and efficacy of cord-blood-derived MSCs (CB-MSCs) in children with MDR-INS. DESIGN, SETTING, PARTICIPANTS: Prospective, open-label, single arm phase I-II pilot study. Pediatric patients with MDR-INS, resistant to at least two lines of therapy, were enrolled. Allogenic CB-MSCs were administered intravenously on days 0, 14, and 21 at a dose of 1.5 × 106 cells/kg. Patients were followed for at least 12 months. The primary outcomes were safety and toxicity. The secondary outcome was remission at 12 months evaluated by urinary protein/urinary creatinine ratio (uPr/uCr). Circulating regulatory T cells (Tregs) were monitored. RESULTS: Eleven pediatric patients with MDR-INS (10 females, median age 13 years) resistant to a median of 3 previous lines of therapy were enrolled. All patients completed the CB-MSC infusion schedule. No patient experienced any infusion-related adverse event or toxicity. Nine patients were assessable for efficacy. At the 12 months follow-up after the treatment, the median uPr/uCr did not change significantly from baseline (8.13 vs. 9.07; p = 0.98), while 3 patients were in partial or complete remission. A lower baseline uPr/uCr was a predictor of remission (2.55 vs. 8.74; p = 0.0238). Tregs count was not associated with CB-MSCs therapy. CONCLUSIONS: CB-MSCs are safe and may have a role in the immunosuppressive therapy of pediatric patients with MDR-INS. This preliminary experience paves the way toward further phase II studies addressing MSC efficacy in immune-mediated kidney diseases.

Results of the PROPINE randomized controlled study suggest tapering of prednisone treatment for relapses of steroid sensitive nephrotic syndrome is not necessary in children.

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.

Colchicine: An Impressive Effect on Posttransplant Capillary Leak Syndrome and Renal Failure.

Capillary leak syndrome is a critical condition occasionally occurring posttransplant and is characterized by acute endothelial hyperpermeability leading to systemic protein-rich fluid extravasation and consequent hypovolemia, hypoperfusion, and acute kidney injury. Treatment is merely supportive and is based on osmotic drugs, diuretics, continuous renal replacement therapy, and surgical drainage. However, removal of the underlying inflammatory cause is mandatory to achieve stable resolution. Herein, we report the first successful treatment with colchicine in 2 life-threatening pediatric cases of capillary leak syndrome with renal failure occurring after transplant (heart and bone marrow) and unresponsive to any other line of therapy. Both cases were only palliated by supportive therapy and revealed an impressively rapid response to colchicine both in terms of diuresis and clinical condition recovery, allowing for the cessation of renal replacement therapy in a few hours. In both patients, colchicine was temporarily discontinued for transient leukopenia (attributed to an additive effect with mycophenolate mofetil), resulting in extravasation, and renal failure recurrence was restored only after colchicine reintroduction. Although the association of colchicine with an immunosuppressive drug was formerly contraindicated, no other adverse events were noted when using a minimized dose. Both patients are now maintaining a good renal function without recurrence of extravasation after 6 months of follow-up. In conclusion, this strikingly positive experience forces physicians to consider this old and cost-effective drug as a new, powerful rescue tool in such critical cases.

Haemodiafiltration use in children: data from the Italian Pediatric Dialysis Registry.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

A propensity-matched comparison of hard outcomes in children on chronic dialysis.

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.

Chronic haemodialysis in small children: a retrospective study of the Italian Pediatric Dialysis Registry.

BACKGROUND: Chronic haemodialysis (HD) in small children has not been adequately investigated. METHODS: This was a retrospective investigation of the use of chronic HD in 21 children aged <2 years (n = 12 aged <1 year) who were registered in the Italian Pediatric Dialysis Registry. Data collected over a period of >10 years were analysed. RESULTS: The median age of the 21 children at start of HD was 11.4 [interquartile range (IQR) 6.2-14.6] months, and HD consisted mainly of haemodiafiltration for 3-4 h in ≥4 sessions/week. A total of 51 central venous catheters were placed, and the median survival of tunnelled and temporary lines was 349 and 31 days, respectively (p < 0.001). Eight children (38 %) showed evidence of central vein thrombosis. Although 19 % of patients received growth hormone and 63.6 % received enteral feeding, the weight and height of these patients remained suboptimal. During the HD period the haemoglobin level increased in all patients, but not to normal levels (from 8.5 to 9.6 g/dl) despite erythropoietin administration (503-600 U/kg/week). The hospitalisation rate was 1.94/patient-year. Seventeen patients underwent renal transplantation at a median age of 3.0 years. Four patients, all affected by severe comorbidities, died during follow-up (in 2 cases due to absence of a vascular access). The 5- and 10-year cumulative survival was 82.4 and 68.7 %, respectively. CONCLUSIONS: Extracorporeal dialysis is feasible in children aged <2 years, but comorbidities, vascular access, growth and anaemia remain major concerns.

[Bone protection in corticosteroid treated patients]. / Indagine sulla terapia di prevenzione del danno osseo nei pazienti trattati con corticosteroidi in Piemonte e valle d'Aosta.

The Piedmont Group of Clinical Nephrology compared the activity of 15 nephrology centers in Piedmont and Aosta Valley as regards bone protection in patients on corticosteroids therapy. Fracture prevalence shows great variability: in 4/15 centers (27%) no fractures were found, in 6/15 centers (40%) fractures were present in 1-4% of cases, in 1 center in 18% of patients. Clinical risk of fracture was based on sex, age and postmenopausal status in 11/14 of the centers (79%), history of fractures and bone disease in 4/14 centers (27%), smoking and alcohol consumption in 3 and 2 centers respectively, glucocorticoid dose and duration in 4, in children bone age and calcium phosphorus status. Dual energy X-ray absorptiometry was performed in 12 centers based on risk factors, in 8 (57%) DXA was performed during the follow-up, in 4 it was performed after 12 months and in 2 after 2-3 years. DXA is not prescribed in children. Only in one center, risk assessment is based on FRAX. Most of the patients are treated with vitamin D supplementation at a dose of steroids of 5 mg/d (80%). Calcium carbonate is used in 9 centers (60%), in two it is used only in the presence of low ionized calcium or bone mineral density. Bisphosphonates are used following AIFA prescription, in particular alendronate in all centers, risedronate in seven and denosumab in one. The analysis shows the great variability of the clinical and therapeutic approach regarding bone protection in patients on corticosteroids therapy, in Piedmont and Aosta Valley.

Mineral metabolism in European children living with a renal transplant: a European society for paediatric nephrology/european renal association-European dialysis and transplant association registry study.

BACKGROUND AND OBJECTIVES: Data on mineral metabolism in pediatric renal transplant recipients largely arise from small single-center studies. In adult patients, abnormal mineral levels are related to a higher risk of graft failure. This study used data from the European Society for Paediatric Nephrology/European Renal Association-European Dialysis and Transplant Association Registry to study the prevalence and potential determinants of mineral abnormalities, as well as the predictive value of a disturbed mineral level on graft survival in a large cohort of European pediatric renal transplant recipients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study included 1237 children (0-17 years) from 10 European countries, who had serum calcium, phosphorus, and parathyroid hormone measurements from 2000 onward. Abnormalities of mineral metabolism were defined according to European guidelines on prevention and treatment of renal osteodystrophy in children on chronic renal failure. RESULTS: Abnormal serum phosphorus levels were observed in 25% (14% hypophosphatemia and 11% hyperphosphatemia), altered serum calcium in 30% (19% hypocalcemia, 11% hypercalcemia), and hyperparathyroidism in 41% of the patients. A longer time since transplantation was associated with a lower risk of having mineral levels above target range. Serum phosphorus levels were inversely associated with eGFR, and levels above the recommended targets were associated with a higher risk of graft failure independently of eGFR. CONCLUSIONS: Abnormalities in mineral metabolism are common after pediatric renal transplantation in Europe and are associated with graft dysfunction.

Encapsulating peritoneal sclerosis in paediatric peritoneal dialysis patients: the experience of the Italian Registry of Pediatric Chronic Dialysis.

BACKGROUND: Paediatric literature about encapsulating peritoneal sclerosis (EPS) is limited and comes primarily from anecdotic experiences. In this study, we described the incidence and characteristics of EPS in a large paediatric chronic peritoneal dialysis (CPD) patient population. METHODS: We reviewed files of patients starting CPD at <16 years of age, recorded from January 1986 to December 2011 by the Italian Registry of Pediatric Chronic Dialysis (n = 712). Moreover, in December 2011, a survey was performed involving all the Italian Pediatric Nephrology Units to report such EPS cases that occurred after CPD withdrawal. RESULTS: Fourteen EPS cases were reported, resulting in a prevalence of 1.9%. The median age of EPS cases was 4.8 years (range 0.6-14.4) at the start of CPD and 14.3 years (6.5-26.8) at EPS diagnosis. Eleven EPS cases received CPD for longer than 5 years. At diagnosis, nine patients were still on CPD, two were on haemodialysis and three were transplanted. In eight patients, the primary renal disease was represented by glomerulopathy, mainly focal segmental glomerulosclerosis (n = 5). In the last 6 months prior to CPD discontinuation, 10 patients were treated with solutions containing more than 2.27% glucose. Peritonitis incidence was 1:26.8 CPD-months, similar to that calculated in children >12 months of age from the same registry (1:28.3 CPD-months). The mortality rate was 43%. A more aggressive course and an association with calcineurin inhibitors were observed in transplanted patients. CONCLUSIONS: Surveillance for EPS should be maintained in high-risk children who received long-term PD even after years from CPD withdrawal.

[Children on peritoneal dialysis and enteral feeding: indications and outcomes]. / Bambini in dialisi peritoneale e nutrizione enterale: indicazioni ed outcome

Despite improvements in overall prognosis, in the quality of life and in growth targets, children on peritoneal dialysis are subject to a high risk of growth retardation, especially if the disease begins in the early stages of life. In these patients, spontaneous feeding often does not provide an adequate intake of nutrients and early start of enteral nutrition needs to be considered. An intensive nutritional approach should always be established early and can be technically achieved using either a naso-gastric tube or a gastrostomy. In Italy, the first approach often involves the use of a naso-gastric tube despite epidemiological data suggesting the superiority of gastrostomy when the required outcome is improvement in growth parameters. Particular attention should be paid to the technique of gastrostomy. Despite this intensive approach, not all patients achieve the desired outcome of adequate growth probably because not all the possible mechanisms involved have yet been discovered.

Saquinavir in steroid-dependent and -resistant nephrotic syndrome: a pilot study.

BACKGROUND: Some difficult cases of idiopathic nephrotic syndrome (NS) have been treated with a HIV protease inhibitor provided with proteasome-inhibiting activity. The objective of this study was to limit nuclear factor κB (NF-κB) activation which is up-regulated in these patients, aiming at decreasing proteinuria and prednisone need. METHODS: Ten cases with long-lasting (up to 15 years) history of NS with steroid dependence (six cases, of which three with secondary steroid resistance) or resistance to steroids (four cases) unsuccessfully treated with multiple immunosuppressive drugs, accepted a treatment with the protease inhibitor saquinavir. p50/p65 NF-κB nuclear localization and immunoproteasome/proteasome messenger RNA (mRNA) were monitored in peripheral blood mononuclear cells (PBMCs). The effects of saquinavir on NF-κB nuclear localization in cultured PBMCs and in immortalized human podocytes were assessed. RESULTS: After a median follow-up of 14.7 months (6-68.7), 1/4 primary steroid-resistant NS (SRNS) and 5/6 steroid-dependent NS or secondary SRNS became infrequent (5) or frequent (1) relapsers, with 63% prednisone reduction (from 25.3 to 8.4 mg/kg/month, P = 0.015). Saquinavir was effective in association with low doses of calcineurin inhibitors (cyclosporine 2 mg/kg/day or tacrolimus 0.01-0.06 mg/kg/day). No side effects were observed apart from transitory mild diarrhoea. In PBMCs, NF-κB was down-regulated, while MECL-1 immunoproteasome/beta2 proteasome mRNA ratio was reversed to normal values. In culture, saquinavir blunted NF-κB activation in human podocytes and in PBMCs. CONCLUSIONS: In this pilot study, a HIV antiprotease drug reduced proteinuria and had a steroid-sparing effect in some multidrug-resistant/-dependent NS. This observation warrants further investigation.

Peritoneal dialysis in infants: the experience of the Italian Registry of Paediatric Chronic Dialysis.

BACKGROUND: Although chronic peritoneal dialysis (CPD) is considered the replacement therapy of choice for infants with end-stage renal failure, many questions persist about treatment risks and outcomes. METHODS: We present data on 84 infants who started CPD at <1 year of age; these patients represent 12% of the total population of the Italian Registry of Paediatric Chronic Dialysis. We analysed patient records from all children consecutively treated with CPD between 1995 and 2007 in Italy. Growth data analysis was performed only in infants with complete auxological parameters at 0, 6 and 12 months of follow-up. RESULTS: Median age at the start of CPD was 6.9 months, weight was 6.1 kg and length 63.6 cm. In one-half of the study population diagnosis leading to renal failure was congenital nephrouropathy. Twenty-eight per cent of the children had at least one pre-existing comorbidity. The mean height standard deviation score was -1.65 at the start of CPD, -1.82 after 12 months and -1.53 after 24 months. Catch-up growth was documented in 50% of patients during dialysis. A positive correlation was observed between longitudinal growth and both exchange volume (R(2) = 0.36) and dialysis session length (R(2) = 0.35), while a negative association was found with the number of peritonitis cases (P = 0.003). Peritonitis incidence was 1:20.7 episode:CPD-months (1:28.3 in the older children from the same registry) and was significantly higher in children with oligoanuria (1:15.5 episode:CPD-months) compared to infants with residual renal function (1:37.4 episode:CPD-months). Catheter survival rate was 70% at 12 months and 51% at 24 months. Catheter-related complications were similar in infants and older children (1:20.5 versus 1:19.8 episode:CPD-months), while clinical complications were more frequent in children under 1 year of age (1:18.3 versus 1:25.2 episode:CPD-months; P < 0.05). During the follow-up period, 33 patients were transplanted (39.3%), 18 were shifted to haemodialysis (21.4%) and 8 died (9.5%). The mortality rate was 4-fold greater than in older children (2.3%). CONCLUSIONS: Our data confirm that infants on CPD represent a high-risk group; however, our experience demonstrated that growth was acceptable and a large portion was successfully transplanted. Increased efforts should be aimed at optimizing dialysis efficiency and preventing peritonitis. The higher mortality rate in infants was largely caused by comorbidities.

Bone alterations in children and young adults with renal transplant assessed by phalangeal quantitative ultrasound.

BACKGROUND: Bone alterations in young renal transplant recipients were investigated in several studies with conflicting results. Quantitative ultrasound of the phalanges is a recently developed noninvasive procedure to assess skeletal status. STUDY DESIGN: Cross-sectional study at a single transplant center with values compared with previously studied healthy controls. SETTINGS & PARTICIPANTS: 40 children and young adult recipients of renal grafts (15 females, 25 males; age, 20.0 +/- 8.4 years) studied 7.1 +/- 3.8 years after kidney transplantation. PREDICTOR: Clinical, biochemical, and therapeutic features, including calcium, phosphate, and intact parathormone levels; and cumulative dosages of glucocorticoids and cyclosporine administered since transplantation. OUTCOME & MEASUREMENT: Phalangeal quantitative ultrasound, including amplitude-dependent speed of sound (AD-SoS) and bone transmission time (BTT), mainly dependent on mineral density and cortical thickness, respectively. Age- and sex-matched healthy controls were used to provide age-related z scores; sex- and height-matched healthy subjects, to provide z scores related to statural age. RESULTS: Mean z scores of AD-SoS and BTT were -0.05 +/- 1.59 and -0.54 +/- 1.17, respectively (P > 0.05 and P < 0.001, respectively). Multivariate analysis showed that AD-SoS z score was associated significantly with body mass index, intact parathormone level, cumulative glucocorticoids administered in the first posttransplantation year, and cyclosporine administered since transplantation (model r(2) = 0.79; P < 0.001); BTT z score was associated significantly with glucocorticoid dosage in the first posttransplantation year and age (model r(2) = 0.55; P < 0.001). LIMITATIONS: Absence of other measures of bone structure and longitudinal measures and comparison to a noncurrent control group. CONCLUSIONS: Children and young adults may have decreased cortical thickness with maintained overall mineral density after renal transplantation. The findings of phalangeal quantitative ultrasound parallel observations using other imaging techniques. Phalangeal quantitative ultrasound may be a useful method to assess bone alternations after renal transplantation.

Predictors of outcome in Henoch-Schönlein nephritis in children and adults.

BACKGROUND: Factors predictive of renal outcome were investigated in 219 cases of biopsy-proven Henoch-Schönlein purpura nephritis (HSPN); 83 children and 136 adults enrolled in a national study were followed up for up to 27 years (median, 4.5 years). METHODS: The criterion for defining disease progression was time elapsed until doubling of baseline creatinine level and until dialysis therapy. Age, sex, data at onset (renal function, proteinuria, hematuria, hypertension, and crescents), and data during follow-up (proteinuria and therapy) were tested as covariates. RESULTS: Multivariate Cox regression analysis indicated the following parameters as independent prognostic predictors: age (adults versus children, relative risk, 3.57; 95% confidence interval, 1.18 to 10.79; P = 0.024 for creatinine level doubling; relative risk, 14.89; 95% confidence interval, 1.72 to 129.07; P = 0.014 for dialysis therapy), sex (females versus males, relative risk, 5.71; 95% confidence interval, 1.67 to 19.55; P = 0.006 for creatinine level doubling; relative risk, 26.03; 95% confidence interval, 2.64 to 256.73; P = 0.005 for dialysis therapy), and mean proteinuria during follow-up (for each 1 g/d of protein increase, relative risk, 1.77; 95% confidence interval, 1.35 to 2.32; P < 0.001 for creatinine level doubling; relative risk, 1.73; 95% confidence interval, 1.18 to 2.52; P = 0.005 for dialysis therapy). Information for mean proteinuria levels during follow-up increased the sensitivity at logistic regression to 62.5%, with dialysis therapy as the end point. No data detected at diagnosis, including renal function impairment, proteinuria, hypertension, and crescentic nephritis (involving > 50% of glomeruli in only 2.6%), were significantly related to functional decline at multivariate Cox. CONCLUSION: This analysis indicates that, even more than when decreased renal function, severe proteinuria, hypertension, or crescents are present at onset, the risk for progression of HSPN (greater in adults and females) was associated with increasing mean proteinuria levels during follow-up.

Chronic peritoneal dialysis catheters in children: a fifteen-year experience of the Italian Registry of Pediatric Chronic Peritoneal Dialysis.

OBJECTIVE: To analyze data on 503 chronic peritoneal dialysis (CPD) catheters implanted between 1986 and 2000 in pediatric patients enrolled in the Italian Registry of Pediatric Chronic Peritoneal Dialysis (the Registry), comparing three different time periods: 1986-1990, 1991-1995, and 1996-2000. DESIGN: Retrospective study. SETTING: 23 dialysis centers participating in the Registry. METHODS: Data were collected from questionnaires filled in every year. The information for each peritoneal catheter included type, site and technique of insertion, exit-site orientation, exit-site care, complications, survival, and reason for removal. PATIENTS: 503 catheters were implanted in 363 pediatric patients aged younger than 15 years at the start of CPD: 97 catheters in patients under 2 years of age, 67 in patients aged 2-5 years, and 339 in patients over 5 years of age. Mean patient age at onset of CPD was 8.0 +/- 5.1 years. All catheters were surgically implanted and omentectomy was performed in 82.4% of cases. The catheters used were Tenckhoff [468 (93.0%): 443 double cuff, 25 single cuff] and double-cuffed Valli [35 (7.0%)]. The entry site was in the midline in 153 cases (30.4%) and paramedian in 350 (69.6%). RESULTS: During 9048 dialysis-months we observed 451 catheter-related complications, yielding an incidence of 1 episode/20.1 CPD-months: 330 catheter infections (exit-site and/or tunnel infections), 26 leakages, 26 dislocations, 24 obstructions, 22 cuff extrusions, 6 hemoperitoneums, 17 others. 171 catheters were removed due to catheter-related causes; exit-site and/or tunnel infections were the main cause for removal (75.4%), followed by obstruction, dislocation, outer-cuff extrusion, and leakage. Younger children (< 2 years) had a higher risk of infectious causes of catheter removal compared to children aged 2-5 years (p = 0.004) and over 5 years of age (p = 0.002). During the 15-year observation period, a significant reduction in the incidence of leakage was observed and risk of leakage was lower in catheters with paramedian entry site compared to catheters with midline entry site. Removal and replacement of peritoneal catheters during the same surgical operation was performed in 76.3% of catheter removals. Catheter survival rate was 78.1% at 12 months, 58.5% at 24 months, 43.8% at 36 months, and 34.6% at 48 months. No difference in catheter survival was observed in younger children (< 2 years) compared with the two other age groups: < 2 years versus 2-5 years hazard ratio 0.7, 95% confidence interval (95%CI) 0.4-1.2; < 2 years versus > 5 years hazard ratio 0.8, 95%CI 0.5-1.1. CONCLUSIONS: In this survey, we observed better catheter survival in comparison with data reported by the Registry in 1998. Catheter survival improved especially in younger children (< 2 years), a group that previously had a decreased catheter survival rate compared to older age groups. In addition to the progressive increase in experience acquired by dialysis centers, this upward trend may also be related to greater use of double-cuffed catheters, with paramedian exit site, and a higher frequency of omentectomy.

A multicenter experience on patient and technique survival in children on chronic dialysis.

In this study we compared patient and technique survival of 163 new hemodialysis (HD) patients (age 11.4+/-3.1 years) and 295 peritoneal dialysis patients (7.7+/-4.8 years. P< 0.001), treated in 23 dialysis centers participating in the Italian Registry of Pediatric Chronic Peritoneal Dialysis (CPD) during the years 1989-2000. Three HD (1.8%) and 17 CPD (5.8%) patients died; the overall average death rate was 9.8/1,000 patient-years in HD and 29.8/1,000 patient-years in CPD patients. No statistically significant difference in patient survival between CPD and HD was found, while the survival of 102 CPD children younger than 5 years at the start of dialysis was lower ( P=0.0001) than that of 193 CPD and 160 HD patients aged 5-15 years. We registered 12 modality failures among HD (7.4%) patients and 44 among CPD (14.9%) patients. The main causes were vascular access failure and patient choice in HD, and infection in CPD patients. Technique survival was lower ( P=0.007) in CPD than in HD patients; a statistically significant difference ( P=0.01) was also observed between both the 0- to 5- and the 5- to 15-year-old CPD patients and the HD patients aged 5-15 years. Logistic regression analysis confirmed age at initiation of dialysis to be a predictor of patient death ( P=0.0001) in the whole patient population, and of technique failure in HD ( P=0.006) but not in CPD patients ( P=0.16).