Efficacy and safety of lisinopril for mild childhood IgA nephropathy: a pilot study

Even in children with mild immunoglobulin (Ig)A nephropathy (IgA-N) showing minimal/focal mesangial proliferation, persistent proteinuria seems to be a risk factor for progression of the disease, indicating the need for an effective and safe treatment even in such cases. Studies carried out to date have indicated that angiotensin-converting enzyme inhibitors (ACEIs) reduce urinary protein excretion and preserve renal function in adult IgA-N. However, no prospective study of ACEI only for childhood IgA-N has yet been carried out. In this prospective single-arm pilot trial, we administered lisinopril (0.4 mg/kg per day) as therapeutic treatment to 40 children with mild IgA-N with proteinuria [morning urinary protein/creatinine ratio (uP/Cr) ≥ 0.2 g/g]. Thirty-three patients reached the primary endpoint (uP/Cr < 0.2) during the 2-year treatment period. The cumulative disappearance rate of proteinuria determined by the Kaplan–Meier method was 80.9%. Mean uP excretion was reduced from 0.40 to 0.18 g/m²/day (p < 0.0001). Of the 40 patients treated, five (12.5%) showed dizziness, and four of these five needed the lisinopril dose reduced. However, lisinopril therapy was continued in all patients during the 2-year treatment period. No other side effect, such as cough, was observed. We conclude that the efficacy and safety of lisinopril is seemingly acceptable for the treatment of children with mild IgA-N. The participants in the Japanese Pediatric IgA Nephropathy Treatment Study Group are listed in the Appendix.     

Assessment of long-term renal complications in extremely low birth weight children

We assessed the long-term renal complications in a regional cohort of extremely low birth weight (ELBW) children born in 2002–2004. The study group, comprising 78 children born as ELBW infants (88% of the available cohort), was evaluated with measurement of serum cystatin C, urinary albumin excretion, renal ultrasound, and 24-h ambulatory blood pressure measurements. The control group included 38 children born full-term selected from one general practice in the district. Study patients were evaluated at a mean age of 6.7 years, and had a median birthweight of 890 g (25th–75th percentile: 760–950 g) and a median gestational age of 27 weeks (25th–75th percentile: 26–29 weeks). Mean serum cystatin C levels were significantly higher (0.64 vs. 0.59 mg/l; p = 0.01) in the ELBW group. Hypertension was diagnosed in 8/78 ELBW and 2/38 of the control children (p = 0.5). Microalbuminuria (>20 mg/g of creatinine) was detected only in five ELBW children (p = 0.17). The mean renal volume was significantly lower in the ELBW group (absolute kidney volume 81 ml vs. 113 ml; p < 0.001, relative kidney volume 85 vs. 97%; p < 0.001). Abnormally small kidneys (<2/3 of predicted size) were detected in 19 ELBW and four control children (p = 0.08). Multivariate logistic regression revealed that the only independent risk factor for renal complications was weight gained during neonatal hospitalization (odds ratio: 0.67; 95% confidence interval: 0.39–0.94). Serum cystatin C and kidney volume are significantly lower in school-age ELBW children. It is important to include systematic renal evaluation in the follow-up programs of ELBW infants.     

Long-term outcome of idiopathic steroid-resistant nephrotic syndrome: a multicenter study

Long-term outcome of idiopathic steroid-resistant nephrotic syndrome was retrospectively studied in 78 children in eight centers for the past 20 years. Median age at onset was 4.4 years (1.1–15.0 years) and the gender ratio was 1.4. Median follow-up period was 7.7 years (1.0–19.7 years). The disease in 45 patients (58%) was initially not steroid-responsive and in 33 (42%) it was later non-responsive. The main therapeutic strategies included administration of ciclosporine (CsA) alone (n = 29; 37%) and CsA + mycophenolate mofetil (n = 18; 23%). Actuarial patient survival rate after 15 years was 97%. Renal survival rate after 5 years, 10 years and 15 years was 75%, 58% and 53%, respectively. An age at onset of nephrotic syndrome (NS) > 10 years was the only independent predictor of end-stage renal disease (ESRD) in a multivariate analysis using a Cox regression model (P < 0.001). Twenty patients (26%) received transplants; ten showed recurrence of the NS: seven within 2 days, one within 2 weeks, and two within 3–5 months. Seven patients lost their grafts, four from recurrence. Owing to better management, kidney survival in idiopathic steroid-resistant nephrotic syndrome (SRNS) has improved during the past 20 years. Further prospective controlled trials will delineate the potential benefit of new immunosuppressive treatment.     

Predictors and consequences of higher estimated glomerular filtration rate at dialysis initiation

There have been no studies in pediatric dialysis patients to evaluate the impact of higher estimated glomerular filtration rate (eGFR) at dialysis initiation on clinical outcomes. Baseline clinical and demographic information was collected for children aged 1–18 years undergoing incident dialysis from 1995–2002 within the United States Renal Data System. Baseline eGFRs calculated by the Schwartz formula were categorized as high (>15 ml/min/1.73 m²) or low (≤15 ml/min/1.73 m²). We determined predictors of eGFR at baseline, and associations between baseline eGFR and subsequent hospitalization for hypertension (HTN) or pulmonary edema (PE) in a longitudinal nonconcurrent pediatric end-stage renal disease (ESRD) cohort. Twenty percent of children had a high eGFR at initiation. Black children were less likely to initiate dialysis with a high eGFR [adjusted odds ratio (adjOR) 0.71, p < 0.001]. Girls were less likely to have a high eGFR at baseline (adjOR 0.71, p < 0.001). Children who received predialysis erythropoietin therapy were more likely to start dialysis with a high eGFR (adjOR 6.67, p < 0.001). Children with higher baseline eGFR were found to have a 21% decreased risk of hospitalization [adjusted hazard ratio (HR) 0.79, 95% confidence interval (CI) 0.65–0.96, p = 0.02]. It is not known whether this clinical benefit will result in decreased mortality and complication rates from cardiovascular disease.     

Combination therapy with mizoribine for severe childhood IgA nephropathy: a pilot study

In two previous randomized controlled trials we showed that treatment of severe childhood immunoglobulin A nephropathy (IgA-N) using prednisolone, azathioprine, heparin–warfarin, and dipyridamole prevented any increase of sclerosed glomeruli and that prednisolone alone did not prevent a further increase of sclerosed glomeruli. Accordingly, the immunosuppressant is considered to be important. Often, however, we were unable to complete azathioprine regimen due to toxicity. Therefore, a different but effective immunosuppressant may be worth trying. Mizoribine, like azathioprine, is an antimetabolite that exerts its immunosuppressant effect by inhibiting lymphocyte proliferation. In this pilot study, we administered mizoribine instead of azathioprine as part of the combination therapy for treating 23 children with severe IgA-N and evaluated the efficacy and safety. Eighteen patients reached the primary endpoint (urine protein/creatinine ratio <0.2) during the 2-year treatment period. The cumulative disappearance rate of proteinuria determined by Kaplan–Meier was 80.4%. Median protein excretion was reduced from 1.19 g/m²/day to 0.05 g/m²/day (p < 0.0001). After treatment, the median percentage of glomeruli showing sclerosis was unchanged in comparison with that before treatment. No patients required a change of treatment. In conclusion, the efficacy and safety of the mizoribine combination seems to be acceptable for treating children with severe IgA-N. *Participants listed at end of paper.     

Comparative clinical outcomes between pediatric and young adult dialysis patients

Published data on the comparative achievement of The Kidney Disease Dialysis Outcome Quality Initative (KDOQI) recommended clinical performance targets between children and young adults on dialysis are scarce. To characterize the achievement of KDOQI targets among children (<18 years) and young adults (18–24 years) with prevalent end stage renal disease (ESRD), we performed a cross-sectional analysis of data collected by the Mid-Atlantic Renal Coalition, in conjunction with the 2007 and 2008 ESRD Clinical Performance Measures Projects. Data on all enrolled pediatric dialysis patients, categorized into three age groups (0–8, 9–12, 13–17 years), and on a random sample of 5% of patients ≥18 years in ESRD Network 5 were examined for two study periods: hemodialysis (HD) data were collected from October to December 2006 and from October to December 2007 and peritoneal dialysis (PD) data were collected from October 2006 to March 2007 and from October 2007 to March 2008. In total, 114 unique patients were enrolled the study, of whom 41.2% (47/114) were on HD and 58.8% (67/114) on PD. Compared to the pediatric patients, young adults were less likely to achieve the KDOQI recommended serum phosphorus levels and serum calcium × phosphorus product values, with less than one-quarter demonstrating values at or below each goal. Multivariate analysis revealed that both young adults and 13- to 17-year-olds were less likely to achieve target values for phosphorus [young adults: odds ratio (OR) 0.04, 95% confidence interval (95% CI) 0.01–0.19, p < 0.001; 13- to 17-year-olds: OR 0.17, 95% CI 0.04–0.77, p = 0.02] and calcium × phosphorus product (young adults: OR 0.01, 95% CI 0.002–0.09, p <  0.001; 13- to 17-year-olds: OR 0.09, 95% CI 0.02–0.56, p = 0.01) than younger children. In summary, there are significant differences in clinical indices between pediatric and young adult ESRD patients.     

Genotype–phenotype correlation in children with autosomal dominant polycystic kidney disease

Adults with autosomal dominant polycystic kidney disease (ADPKD) and PKD1 mutations have a more severe disease than do patients with PKD2 mutations. The aim of this study was to compare phenotypes between children with mutations in the PKD1/PKD2 genes. Fifty PKD1 children and ten PKD2 children were investigated. Their mean age was similar (8.6 ± 5.4 years and 8.9 ± 5.6 years). Renal ultrasound was performed, and office blood pressure (BP), ambulatory BP, creatinine clearance and proteinuria were measured. The PKD1 children had, in comparison with those with PKD2, significantly greater total of renal cysts (13.3 ± 12.5 vs 3.0 ± 2.1, P = 0.004), larger kidneys [right/left kidney length 0.89 ± 1.22 standard deviation score (SDS) vs 0.17 ± 1.03 SDS, P = 0.045, and 1.19 ± 1.42 SDS vs 0.12 ± 1.09 SDS, P = 0.014, successively] and higher ambulatory day-time and night-time systolic BP (day-time/night-time BP index 0.93 ± 0.10 vs 0.86 ± 0.05, P = 0.021 and 0.94 ± 0.07 vs 0.89 ± 0.04, P = 0.037, successively). There were no significant differences in office BP, creatinine clearance or proteinuria. Prenatal renal cysts (14%), hypertension defined by ambulatory BP (27%) and enlarged kidneys (32%) were observed only in the PKD1 children. This is the first study on genotype–phenotype correlation in children with ADPKD. PKD1 children have more and larger renal cysts, larger kidneys and higher ambulatory BP than do PKD2 children. Renal cysts and enlarged kidneys detected prenatally are highly specific for children with PKD1.     

Prevalence of chronic kidney disease (CKD) in the Japanese general population predicted by the MDRD equation modified by a Japanese coefficient

Background The number of patients with end-stage renal disease (ESRD) in Japan has continuously increased in the past three decades. In 2005, 36 063 patients whose average age was 66 years entered a new dialysis program. This large number of ESRD patients could be just the tip of the iceberg of an increasing number of patients with chronic kidney disease (CKD). However, to date, a nationwide epidemiological study has not been conducted yet to survey the CKD population. Methods Data for 527 594 (male, 211 034; female, 316 560) participants were obtained from the general adult population aged over 20 years who received annual health check programs in 2000–2004, from seven different prefectures in Japan: Hokkaido, Fukushima, Ibaraki, Tokyo, Osaka, Fukuoka, and Okinawa prefectures. The glomerular filtration rate (GFR) for each participant was estimated from the serum creatinine values, using the abbreviated Modification of Diet in Renal Disease (MDRD) study equation modified by the Japanese coefficient. Results The prevalences of CKD stage 3 in the study population, stratified by age groups of 20–29, 30–39, 40–49, 50–59, 60–69, 70–79, and 80–89 years, were 1.4%, 3.6%, 10.8%, 15.9%, 31.8%, 44.0%, and 59.1%, respectively, predicting 19.1 million patients with stage 3 CKD in the Japanese general adult population of 103.2 million in 2004. CKD stage 4 + 5 was predicted in 200 000 patients in the Japanese general adult population. Comorbidity of hypertension, diabetes, and proteinuria increased as the estimated GFR (eGFR) decreased. The prevalence of concurrent CKD was significantly higher in hypertensive and diabetic populations than in the study population overall when CKD was defined as being present with an eGFR of less than 40 ml/min per 1.73 m² instead of less than 60 ml/min per 1.73 m². Conclusions About 20% of the Japanese adult population (i.e., approximately 19 million people) are predicted to have stage 3 to 5 CKD, as defined by a GFR of less than 60 ml/min per 1.73 m². This work was presented in part at the 48^th annual meeting of the Japanese Society of Nephrology at Yokohama in 2005.     

Henoch-Schönlein purpura nephritis with nephrotic state in children: predictors of poor outcomes

Nephritis develops in 18–81% of Henoch-Sch?nlein purpura patients, and the long-term outcomes of this nephritis show great variation. A nephrotic state at disease onset has been proposed as a predictor of poor renal outcomes. We studied 42 children with Henoch-Sch?nlein purpura nephritis (HSPN) who presented with a nephrotic state during the early phase of the disease. The median age of the patients at the time of diagnosis was 7.4 years. The median follow-up period was 6.2 years. Twenty-five children (60%) made a complete recovery; nine (21%) progressed to end-stage renal disease. Multivariate logistic regression analyses revealed that the nephrotic state lasting for more than 3 months had a significant effect on renal outcomes (odds ratio 11.6; 95% confidential interval, 1.16–348.4; p = 0.03), whereas initial renal insufficiency, renal pathological findings, age at onset, and types of treatment did not. These findings indicate that clinical presentation, particularly duration of the nephrotic state, is related to long-term outcomes in HSPN patients with nephrosis. Our results also indicate that the therapeutic options for HSPN patients with a nephrotic state should be based on the clinical presentation rather than on the initial pathological findings alone.     

Does Microvascular Invasion Affect Outcomes After Liver Transplantation for HCC? A Histopathological Analysis of 155 Consecutive Explants

Macroscopic vascular invasion (macroVI) is associated with poor outcomes after liver transplantation (LT) for hepatocellular carcinoma (HCC). Whether microvascular invasion (microVI) is associated with the same adverse prognosis is unclear. One hundred and fifty-five consecutive patients with confirmed HCC after LT from March 1991 to 2004 at our institution were reviewed. Patients had to satisfy Milan criteria to be accepted for LT. They were followed with surveillance images every 3 months while on the waiting list. Disease-free survival (DFS) and overall survival (OS) were evaluated by Kaplan–Meier analysis. Demographic, tumor, and histopathologic characteristics were tested for their prognostic significance. Median follow-up after LT was 30 months. Overall graft survival rates were 87, 74, and 65% at 1, 3, and 5 years, respectively. All recurrences (22/155, 14%) developed within 4 years after LT with an overall 5-year DFS of 79%. Vascular invasion, either microVI or macroVI, was more likely in patients with multicentric HCC (n ≥ 3, p < 0.001) and larger tumor size >4 cm (p = 0.04). Tumor size >5 cm (p = 0.04), advanced pathological TMN stage (p = 0.007), microVI (p = 0.001), and macroVI (p < 0.001) predicted poor tumor-free survival on univariate analysis, but only macroVI was significant in multivariate analysis (hazard ratio 54.2, 95% confidence interval 11, 266). Furthermore, only macroVI was a significant predictor of mortality after LT (p = 0.01). Macrovascular invasion is strongly associated with high rates of recurrence and diminished survival after LT whereas microVI is not an independent risk factor. Presented at the 2005 American Transplant Congress, Seattle, WA, May 20–23, 2005.     

Outcome of lupus nephritis in Iranian children: prognostic significance of certain features

The objective of this study was to determine the clinical and histopathological features and outcome of children with lupus nephritis (LN). Of 84 children with systemic lupus erythematosus (SLE), we retrospectively studied 58 children (69%) under 15 years of age with biopsy-proven LN who had been followed between October 1989 and January 2005. The mean age at diagnosis or initial referral was 10.6 ± 2.25 years, and the mean follow-up was 5.3 ± 4.1 years. Class IV LN was observed in 34 (58.6%) patients. The 5-year patient and renal survival rates were 82.5 and 78.5%, respectively, in the total group, and 75 and 85.8%, respectively, in patients with Class IV LN. No independent predictor of unfavorable outcome, including renal histology, was detected by multivariate analysis. The mid-term patient and the renal survival rates of Iranian children with biopsy-proven LN are high. Within 5 years of follow-up, renal histology was not a predictor for survival.     

Anastomotic Leakage is Associated with Poor Long-Term Outcome in Patients After Curative Colorectal Resection for Malignancy

The impact of anastomotic leakage on long-term outcomes after curative surgery for colorectal cancer has not been well documented. This study aimed to investigate the effect of anastomotic leakage on survival and tumor recurrence in patients who underwent curative resection for colorectal cancer. Prospectively collected data of the 1,580 patients (904 men) of a median age of 70 years (range: 24–94), who underwent potentially curative resection for colorectal cancer between 1996 and 2004, were reviewed. Cancer-specific survival and disease recurrence were analyzed using Kaplan Meier method, and variables were compared with log rank test. Cox regression model was used in multivariate analysis. The cancer was situated in the colon and the rectum in 933 and 647 patients, respectively. Anastomotic leakage occurred in 60 patients (clinical leakage: n = 48; radiological leak: n = 12). The leakage rate was significantly higher in patients with surgery for rectal cancer (6.3 vs 2.0%, p < 0.001). The 5-year cancer-specific survivals were 56.9% in those with leakage and 75.9% in those without leakage (p = 0.012). The 5-year systemic recurrence rates were 48.4 and 22.6% in patients with and without anastomotic leak, respectively (p = 0.001), whereas the 5-year local recurrence rates were 12.9 and 5.7%, respectively (p = 0.009). Anastomotic leakage remained an independent factor associated with a worse cancer-specific survival (p = 0.043, hazard ratio: 1.63, 95% CI: 1.02–2.60) and a higher systemic recurrence rate (hazard ratio: 1.94, 95% CI: 1.23–3.06, p = 0.004) on multivariate analysis. In rectal cancer, anastomotic leakage was an independent factor for a higher local recurrence rate (hazard ratio: 2.55, 95% CI: 1.07–6.06, p = 0.034). In conclusion, anastomotic leakage is associated with a poor survival and a higher tumor recurrence rate after curative resection of colorectal cancer. Efforts should be undertaken to avoid this complication to improve the long-term outcome. This work was presented in the plenary session of the 47th Annual Meeting of the Society for Surgery of the Alimentary Tract at the Digestive Disease Week in Los Angeles on 22 May 2006.     

Serum and urine fibronectin levels in children with vesicoureteral reflux

The study objective was to assess serum and urine fibronectin (FN) levels in children with vesicoureteral reflux (VUR) depending on reflux grade and urine osmolality. The study group (1) consisted of 54 VUR children, median age 4.28 (range 0.6–15) years: subgroup A, 19 children with grade II; subgroup B, 19 with grade III; and subgroup C, 16 with grade IV or V VUR. The control group (2) included 27 healthy children. The immunoenzymatic method enzyme immunoassay (EIA) was used to determine serum soluble and urine FN levels, with an osmometer to measure urinary osmolality. The median urine FN in VUR children was 224.1 (15.4–3537) ng/mg creatinine (Cr), compared with the control group: 137.9 (20.3–670.6) ng/mg Cr (p < 0.05), whereas median serum FN was 395.0 (13.0–779.9) ng/ml and 121.9 (25–345.1) ng/ml (p < 0.05), respectively. A detailed analysis showed that only in subgroup C was the level of urinary FN significantly higher than in the control group (p < 0.01). However, serum concentration was elevated in all VUR children (A–C) compared with controls (p < 0.01). Reduced osmolality, below 800 mOsm/kg H₂O, was observed in subgroup C. Negative correlation between urinary osmolality and urinary FN was found (r = −0.426, p < 0.01). In children with VUR, serum FN increased with reflux grade, whereas its urinary level was elevated only in grade IV and V reflux with impaired urine concentration.     

Self-reported quality of life in children and young people with chronic kidney disease

Chronic kidney disease (CKD) would be expected to impact upon the quality of life (QoL) of children and young people; therefore, it is important that they are given the means to express their opinions about how they perceive their own QoL. We used the Generic Children’s Quality of Life Measure (GCQ) in 225 paediatric renal patients (118 male, mean age 13.6 years, range 6.2–18.9 years) from seven UK centres. Of these, 47 were on dialysis (23 on haemodialysis), 128 were post-transplant (47 pre-emptive) and 49 had advanced CKD. A comparison between the 124 renal patients (65 male, mean age 11.2 years) in the same age range as the general population (6–14 years) showed a higher GCQ QoL score for the renal patients (p = 0.02). Analysis of the whole group of renal patients (n = 225) revealed no significant difference between the mean GCQ scores of participants in various treatment modalities (p = 0.26) and no significant differences between gender (p = 0.90) and age group (p = 0.44). The results indicate that young people can perceive their QoL as good despite living with what others may perceive as severe limitations. This may seem counter-intuitive, but QoL is a subjective measure and thus may be difficult to predict from observable limitations (health status). The GCQ is an ideal measure for use in annual departmental audits of generic paediatric QoL and may help to individualise the work of psychosocial teams with each patient.     

Comparison of chronic peritoneal dialysis outcomes in children with and without spina bifida

This study was designed to compare chronic peritoneal dialysis (CPD) long-term outcomes (patient and technique survival, incidence of peritonitis, and overall average death outcomes) between seven patients with lumbar spina bifida (SB) and 20 controls without SB. Both groups were matched for potentially outcome-confounding factors: gender, and socioeconomic status (SES). SES was established using modified Graffar’s method. No significant differences were found in CPD outcomes. The incidence of peritonitis was one episode per 17.6 and 10.3 months in SB patients and controls, respectively (p = 0.5). Overall patient survival at 5 years was 86% and 73% in SB patients and controls, respectively (p = 0.55). Overall average death rate between SB and control patients was 47.6/1,000 and 79.4/1,000 patient years, respectively (p = 0.63). Overall technique survival at 5 years was 83% and 73% in SB patients and controls, respectively (p = 0.84). There were no cases of retrograde brain ventricular infection secondary to PD-related peritonitis. We conclude that SB is not a risk factor for CPD, and therefore, it is an effective renal replacement alternative in children with SB.     

Serum RANKL, osteoprotegerin (OPG), and RANKL/OPG ratio in nephrotic children

Receptor activator of NF-kB ligand (RANKL) and osteoprotegerin (OPG) play key roles in the pathogenesis of glucocorticoid-induced osteoporosis (GIO). The aim of our study was to determine whether the cumulative glucocorticoid dose (CGCS) in children with idiopathic nephrotic syndrome (INS) has any effect on the concentration of serum RANKL and OPG and the RANKL/OPG ratio. The study population consisted of 90 children with INS, aged 3–20 years, who were treated with GCS. These children were divided into two groups according to the CGCS: low (L) <1 g/kg body weight (BW) and high (H) ≥1 g/kg BW, respectively. The control group (C) consisted of 70 healthy children. RANKL concentration was observed to be significantly higher and OPG significantly lower in INS children than in the reference group: 0.21 (range 0.01–1.36) versus 0.15 (0–1.42) pmol/l (p < 0.05), respectively, and 3.76 (1.01–7.25) versus 3.92 (2.39–10.23) pmol/l (p < 0.05), respectively. The RANKL/OPG ratio was significantly higher in INS children (p < 0.01). The concentration of RANKL, similar to the RANKL/OPG ratio, was significantly higher in Group H children than in Group L children: 0.46 (0.02–1.36 ) versus 0.19 (0.01–1.25) (p < 0.01) and 0.14 (0.01–0.71) versus 0.05 (0.002–0.37) (p < 0.01), respectively. The concentration of OPG was similar in both groups. There was a positive correlation between CGCS and the concentration of sRANKL as well as the RANKL/OPG ratio (in both cases r = 0.33, p < 0.05). Based on these results, we suggest that long-term exposure to GCS results in a dose-dependent increase in serum RANKL concentration and the RANKL/OPG ratio, but not in the level of serum OPG.     

Cardiorespiratory fitness is a marker of cardiovascular health in renal transplanted children

Children with renal transplants (TX) are at increased risk of cardiovascular (CV) disease. Study objectives were to assess the level of cardiorespiratory fitness (CR fitness) and daily physical activity (PA) in renal TX children and adolescents in relation to traditional cardiovascular risk factors. Laboratory testing included assessment of CR fitness by treadmill exercise testing (VO_2peak), 24-h ambulatory blood-pressure (ABPM) measurement, oral glucose tolerance test (OGTT), anthropometrics and measurement of lipid levels. PA was self-reported by questionnaire. Twenty-two TX patients with a median (range) age 14.5 (9–18) years were tested. Median V0_2peak was 66% (36–97) of the expected values compared with controls. Nineteen (86%) children reported <60 min of daily moderate to vigorous physical activity (MVPA). Sixteen (73%) were hypertensive and 8 (34%) were overweight or obese. Four children fulfilled the criteria for a metabolic syndrome. Children with at least 2 of the 3 metabolic risk factors (hypertension, overweight, and glucose intolerance, n = 7) achieved significantly lower VO_2peak compared with those with one or none of these factors (median V0_2peak 45% and 73% of the expected values respectively, p = 0.003). Renal TX children and adolescents have severely impaired CR fitness and PA. Reduced CR fitness was associated with the clustering of CV risk factors. Routine counseling for increased PA is strongly recommended.     

Blood pressure load,proteinuria and renal function in pre-hypertensive children

It is as yet unclear whether blood pressure load (BPL) can affect renal function in pre-hypertensive children. We have studied 250 children, with a mean age of 9.12 ± 3.28 years, with the aim of assessing if pre-hypertension in children can indeed affect renal function. The study cohort consisted of 146 children with pre-hypertension (group P) and a control group of 104 children with normal blood pressure (group C). All children were tested for orthostatic proteinuria, an exclusion criterion, glomerular filtration rate (GFR), and proteinuria, and ambulatory blood pressure monitoring was performed. Based on the BPL, group P was further subdivided into group P1 (BPL ≤ 40%, low BPL) and group P2 (BPL > 40%, high BPL). We found that GFR was reduced in pre-hypertensive children (90.74 ± 48.69 vs. 110.32 ± 20.30 ml/min per 1.73 m², p < 0.0001) and that proteinuria was increased (145.36 ± 110.91 vs. 66.84 ± 42.94 mg/m² per 24 h; p < 0.0001). However, mean values were still within normal limits. A comparison of the group with high BPL and that with low BPL revealed that the former had relatively reduced GFR (79.15 ± 42.04 vs. 96.78 ± 51.20 ml/min per 1.73 m²; p < 0.006) and increased proteinuria (198.29 ± 142.17 vs. 118.31 ± 80.07 mg/m² per 24 h; p < 0.036). In comparison to the reference values of the normal population, the GFR was reduced and proteinuria was increased in the group with high BPL. Based on our results, pre-hypertension in children with high BPL seems to be associated with reduced GFR and increased proteinuria. A reasonable doubt remains that the patients with higher proteinuria and larger reduction of GFR may harbor an as yet unknown subclinical renal condition responsible for the onset of pre-hypertension. Therefore, children with even mildly elevated BP are at risk of developing renal damage and should change their lifestyle to prevent further increases in BP.     

Doppler ultrasonographic indices in diagnosing nutcracker syndrome in children

To elucidate the Doppler ultrasonographic cut-off value of nutcracker syndrome causing hematuria in children, we analyzed Doppler spectral findings between 15 children with nutcracker syndrome and 15 age- and sex-matched normal control subjects. A follow-up Doppler ultrasound (US) was also performed in children with nutcracker syndrome when hematuria subsided completely after a median period of 1.7 years (range: 1.0–3.5 years) (relieved nutcracker syndrome). The peak velocity (PV) ratios of the left renal vein (LRV) were significantly higher in children with nutcracker syndrome than in those with relieved nutcracker syndrome (P < 0.0001) and normal children (P < 0.0001). The PV ratios of the LRV at the follow-up US were significantly higher than those in the control subjects (P = 0.019). None of the 15 normal children showed PV ratios of the LRV > 3.7, but five of the 15 children with relieved nutcracker syndrome without hematuria had PV ratios of 3.91–5.02. When we set the cut-off values for nutcracker syndrome at the mean ± 2 SD (mean: 2.95 ± 0.92, range: 1.60–5.02) of 30 controls (normal children and relieved nutcracker without hematuria), the calculated cut-off value was 4.8, and the sensitivity and specificity were 100% and 93%, respectively. Given its high sensitivity, renal Doppler US can be used as a useful initial non-invasive test in the diagnosis of nutcracker syndrome in children with hematuria.     

Long-term outcome of nephropathic cystinosis: a 20-year single-center experience

Nephropathic cystinosis (NC) is a severe disease that is complicated by early-onset chronic renal failure (CRF) and other complications related to cystine deposition in tissue. Since the 1980s, the prognosis of NC has dramatically improved after the introduction of cysteamine treatment. Limited data are available documenting improvement in prognosis. We reviewed our long-term data (follow-up 6.3–27.8 years) on 23 patients followed in the past 26 years. Overall, stage III CRF was reached at 10 years of age in >90% of patients, whereas >80% reached end-stage renal disease before the age of 14 years. Three patients died during the follow-up. Our analysis shows a clear improvement in renal outcome (p = 0.001) and linear growth (p = 0.04) in patients treated more recently. Improvement in the evolution of renal function was significantly associated with early initiation of cysteamine (p = 0.006), with the dose of cysteamine (p = 0.04), and with the use of angiotensin-converting enzyme inhibitors (p = 0.01). Nonrenal long-term complications are similar to previously reported data. Of note, 3/23 patients developed rare forms of primary tumors that were successfully treated. In conclusion, our experience shows a significant improvement in the renal and nonrenal complications of cystinosis over the past decades and highlights the importance of early diagnosis in order to initiate cysteamine as soon as possible.