Diabetes and obesity are already recognized as potential risk factors for nephrolithiasis, especially for uric acid stones. Insulin resistance and hyperinsulinemia actively contribute to impaired ...ability to excrete an acid load and altered ammonium production, leading to a lower urinary pH compared to non-diabetic controls. All these electrolytic disorders play an important role in stone formation and aggregation, especially in uric acid stones. There are still missing points in scientific evidence if the increased risk in stone formation is already existing even in the prediabetic statuses (isolated impaired glucose tolerance, isolated impaired fasting glucose, and associated impaired glucose tolerance/impaired fasting glucose) as well as it is worth to consider the same level of risk. Urolithiasis is the most frequent urological cause of hospitalization in diabetic patients and its cost is usually higher compared to non-diabetic patients, but less is known in others altered glycaemic diseases. The aim of this review article is to focus on the association between stone formation and altered glycaemic statuses, beyond the already known link between nephrolithiasis and diabetes mellitus.
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.
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Pediatric steroid-sensitive nephrotic syndrome (pSSNS) is the most common childhood glomerular disease. Previous genome-wide association studies (GWAS) identified a risk locus in the HLA Class II ...region and three additional independent risk loci. But the genetic architecture of pSSNS, and its genetically driven pathobiology, is largely unknown. Here, we conduct a multi-population GWAS meta-analysis in 38,463 participants (2440 cases). We then conduct conditional analyses and population specific GWAS. We discover twelve significant associations-eight from the multi-population meta-analysis (four novel), two from the multi-population conditional analysis (one novel), and two additional novel loci from the European meta-analysis. Fine-mapping implicates specific amino acid haplotypes in HLA-DQA1 and HLA-DQB1 driving the HLA Class II risk locus. Non-HLA loci colocalize with eQTLs of monocytes and numerous T-cell subsets in independent datasets. Colocalization with kidney eQTLs is lacking but overlap with kidney cell open chromatin suggests an uncharacterized disease mechanism in kidney cells. A polygenic risk score (PRS) associates with earlier disease onset. Altogether, these discoveries expand our knowledge of pSSNS genetic architecture across populations and provide cell-specific insights into its molecular drivers. Evaluating these associations in additional cohorts will refine our understanding of population specificity, heterogeneity, and clinical and molecular associations.
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.
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.
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%).
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.
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.
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.
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.
Surveillance for EPS should be maintained in high-risk children who received long-term PD even after years from CPD withdrawal.
Loss-of-function mutations in the CYP24A1 gene, which encodes the vitamin D-24 hydroxylase, have been recognized as a cause of elevated 1,25-dihydroxyvitamin D concentrations, hypercalcemia, ...hypercalciuria, nephrocalcinosis and nephrolithiasis in infants and adults. As only a case report describing 2 adult patients has been reported in Italian population, we report here the mutation analysis of CYP24A1 gene in an Italian cohort of 12 pediatric and adult patients with idiopathic infantile hypercalcemia (IIH).
We performed mutational screening of CYP24A1 gene in a cohort of 12 Italian patients: 8 children with nephrocalcinosis, hypercalcemia and PTH levels <10 pg/ml and 4 adult patients with nephrolithiasis, mild hypercalcemia and PTH levels <10 pg/ml from 11 unrelated Italian families. Clinical and biochemical data were collected. Genomic DNA was extracted from peripheral blood leucocytes using standard methods, and whole coding sequence of CYP24A1 gene was analysed in all patients and family members by polymerase chain reaction and direct sequencing. The potential pathogenicity of the newly identified missense mutations was evaluated by 3 different in silico approaches (Sorting Intolerant from Tolerant, Polyphen and Mutation Taster) and by comparative analysis in 14 different species using ClustalW software.
CYP24A1 bi-allelic mutations were found in 8 individuals from 7 Italian families (7/11; 64%). Overall, 6 different CYP24A1 mutations, including one small deletion (p.Glu143del), 4 missense mutations (p.Leu148Pro; p.Arg396Trp; p.Pro503Leu; p.Glu383Gln) and one nonsense mutation (p.Tyr220*) were identified. Two out of 6 mutations (p.Tyr220* and p.Pro503Leu) were not previously described. Moreover, a new CYP24A1 variant was identified by genetic screening of asymptomatic controls.
To the best of our knowledge, this is the first report of a CYP24A1 molecular analysis performed in an Italian cohort of adult and pediatric Italian patients. This study (1) confirms that CYP24A1 plays a causal role in some but not all cases of IIH (64%); (2) expands the spectrum of known CYP24A1 pathogenic mutations; (3) describes 2 hotspots detected in 50% of all Italian cases; and (4) emphasizes the importance of recognition and genetic diagnosis of CYP24A1 defects in infantile as well as adult hypercalcemia.
Background
The optimal therapeutic regimen for managing childhood idiopathic nephrotic syndrome (INS) is still under debate. We have evaluated the choice of steroid regimen and of symptomatic ...treatment adopted by pediatricians and pediatric nephrologists in a large number of centers as the first step towards establishing a shared protocol
Methods
This was a multicenter, retrospective study. A total of 231 children (132 admitted to pediatric units) aged 6 months to <15 years who presented with onset of nephrotic syndrome to 54 pediatric units and six pediatric nephrology units in Italy between 2007 and 2009 were eligible for entry into the study.
Results
Median steroid dosing was 55 (range 27–75) mg/m
2
/day. The overall median cumulative dose regimen for the first episode was 3,440 (1,904–6,035) mg/m
2
, and the median duration of the therapeutic regimen was 21 (9–48) weeks. The total duration and cumulative steroid dose were significantly higher in patients treated by pediatricians than in those treated by pediatric nephrologists (
p
= 0.001 and
p
= 0.008). Among the patient cohort, 55, 64 and 22 % received albumin infusions, diuretics and acetyl salicylic acid treatment, respectively, but the laboratory and clinical data did not differ between children treated or not treated with symptomatic drugs. Albumin and diuretic use did not vary between patients in pediatric units and those in pediatric nephrology units.
Conclusions
This study shows major differences in steroid and symptomatic treatment of nephrotic syndrome by pediatricians and pediatric nephrologists. As these differences can influence the efficacy of the treatments and the appearance of side-effects, shared guidelines and their implementation through widespread educational activities are necessary.
Introduction
Chronic renal failure (CRF) compromises nutrition, growth, puberty, glycometabolic homeostasis, and adipokine secretion (i.e. adiponectin, resistin, and leptin). Adipokines play a role ...in the clinical outcome, but data in paediatric patients is scant.
Aim
To evaluate the link between kidney function, adiponectin, resistin, leptin, hormonal status, nutritional state and late outcome of CRF children.
Materials and methods
We studied leptin, adiponectin and resistin levels in 31 CRF patients (19 males, 12 females, aged 12.1 ± 4.47 years) managed conservatively, and 30 healthy age- and gender-matched controls. Clinical, auxological, biochemical, hormonal data, glucose and insulin levels were correlated with adipokine levels.
Results
Six percent of patients had glycaemia T0′ > 126 mg/dl, 23 % glycaemia T60′ > 126, and 23 % glycaemia T120′ ≥ 140. Glycated haemoglobin (HbA1c) measured during follow-up was in the normal range in all patients (4–5.6 %). Insulinaemia was significantly higher in CRF patients than controls. Homeostatic model of assessment-insulin resistance (HOMA-IR) levels were more elevated in patients (32 % had HOMA-IR > 2.5) than controls. Leptin levels were significantly higher in CRF patients than controls and differed significantly between males and females. Leptin correlated significantly with creatinine, body mass index (BMI), BA, pubertal stage, insulin-like growth factor 1, and HOMA-IR in females. Adiponectin levels were significantly higher in patients than controls, higher in patients with BMI < 85th centile and significantly inversely correlated to BMI, BA, haemoglobin, ferritin, proteins, albumin, and creatininuria. Resistin levels showed a direct correlation with C-reactive protein and an inverse correlation with haemoglobin.
Conclusion
Normal resistin levels are an expression of both adequate nutritional state and controlled inflammatory state. Adiponectin could protect against chronic inflammation, atherosclerosis, and cardiovascular diseases. Preventing obesity and ensuring a correct nutritional state are primary goals for physicians following children with CRF. Adipokines could be a useful marker in the follow-up.
Early detection of acute kidney injury (AKI) is crucial for timely intervention and improved patient outcomes after cardiac surgery. This study aimed to evaluate the potential of urinary collectrin ...as a novel biomarker for AKI in this patient population.
In this prospective, observational cohort study, 63 patients undergoing elective cardiac surgery with cardiopulmonary bypass (CPB) were studied at the Medical University of Vienna between 2016 and 2018. We collected urine samples prospectively at four perioperative time points, and urinary collectrin was measured using an enzyme-linked immunosorbent assay. Patients were divided into two groups, AKI and non-AKI, defined by Kidney Disease: Improving Global Outcomes Guidelines, and differences between groups were analyzed.
Postoperative AKI was found in 19 (30%) patients. Urine sample analysis revealed an inverse correlation between urinary collectrin and creatinine and AKI stages, as well as significant changes in collectrin levels during the perioperative course. Baseline collectrin levels were 5050 ± 3294 pg/mL, decreased after the start of CPB, reached their nadir at the end of surgery, and began to recover slightly on postoperative day (POD) 1. The most effective timepoint for distinguishing between AKI and non-AKI patients based on collectrin levels was POD 1, with collectrin levels of 2190 ± 3728 pg/mL in AKI patients and 3768 ± 3435 pg/mL in non-AKI patients (
= 0.01).
Urinary collectrin shows promise as a novel biomarker for the early detection of AKI in patients undergoing cardiac surgery on CPB. Its dynamic changes throughout the perioperative period, especially on POD 1, provide valuable insights for timely diagnosis and intervention. Further research and validation studies are needed to confirm its clinical usefulness and potential impact on patient outcomes.
The aim of this retrospective exploratory study was to investigate the prevalence of unfavorable findings during video-urodynamic studies (VUDS) in patients with minimally conscious state ...(MCS)/unresponsive wakefulness syndrome (UWS) and whether management of the lower urinary tract (LUT) was adjusted accordingly. A retrospective chart review was conducted to screen for patients diagnosed with MCS/UWS at our rehabilitation center between 2011 and 2020. Patients 18 years or older were included and underwent baseline VUDS after being diagnosed with MCS/UWS. We analyzed urodynamic parameters and subsequent changes in LUT management in this cohort. In total, 32 patients (7 females, 25 males, median age 37 years) with MCS/UWS were included for analysis. While at least one unfavorable VUDS finding (i.e., neurogenic detrusor overactivity NDO, detrusor sphincter dyssynergia {DSD, high maximum detrusor pressure during storage phase >40 cmH2O, low-compliance bladder <20 mL/cmH2O, and vesico–uretero–renal reflux VUR) was found in each patient, NDO (78.1%, 25/32) and DSD (68.8%, 22/32) were the two most frequent unfavorable VUDS findings. Following baseline VUDS, new LUT treatment options were established in 56.3% (18/32) of all patients. In addition, bladder-emptying methods were changed in 46.9% (15/32) of all patients, resulting in fewer patients relying on indwelling catheters. Our retrospective exploratory study revealed a high prevalence of NDO and DSD in patients with MCS/UWS, illustrating the importance of VUDS to adapt LUT management in this cohort accordingly.
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