Exstrophy-epispadias complex: are the kidneys and kidney function spared?

BACKGROUND: Exstrophy-epispadias complex (EEC) is a complex malformation of the lower abdominal wall, bladder, and pelvic floor, which necessitates multiple successive reconstruction procedures. Surgical and infectious complications are frequent. Our aim was to evaluate kidney function in these patients. METHODS: This cross-sectional study included patients with EEC, followed since birth in a pediatric urology clinic, who underwent nephrological evaluation (blood pressure (BP) measurement and blood and urine chemistries) and imaging studies (urinary tract ultrasound and DMSA kidney scan) during 2017-2020. RESULTS: Forty-three patients (29 males), median age 9 years (interquartile range 6-19), were included. Eleven (26%) used clean intermittent catheterization (CIC) for bladder drainage. At least one sign of kidney injury was identified in 32 (74%) patients; elevated BP, decreased kidney function (estimated glomerular filtration rate (eGFR) < 90 ml/min/1.73 m2), and proteinuria/albuminuria were detected in 29%, 12%, and 36% of patients, respectively. Urinary tract dilatation (UTD) was found in 13 (37%) ultrasound examinations. Parenchymal kidney defects were suspected in 46% and 61% of ultrasound and DMSA scintigraphy, respectively. UTD was significantly associated with DMSA-proven kidney defects (p = 0.043) and with elevated BP, 39% vs. 20% in those without UTD. Decreased eGFR and elevated BP were less frequent among patients on CIC than among patients who voided spontaneously: 10% vs. 14% and 18% vs. 36%, respectively. Recurrent UTIs/bacteriuria and nephro/cystolithiasis were reported by 44% and 29% patients, respectively. CONCLUSION: The high rate of signs of kidney injury in pediatric patients with EEC dictates early-onset long-term kidney function monitoring by joint pediatric urological and nephrological teams. A higher resolution version of the Graphical abstract is available as Supplementary information.

Linear growth of children with X-linked hypophosphatemia treated with burosumab: a real-life observational study.

To assess the long-term efficacy of burosumab for pediatric patients with X-linked hypophosphatemia, focusing on linear growth. This multi-center retrospective study included 35 pediatric patients who began treatment with burosumab between January 2018 and January 2021. We collected clinical data, anthropometric measurements, laboratory results, and Rickets Severity Score (RSS), from 2 years prior to treatment initiation and up to 4 years after. Burosumab was initiated at a mean age of 7.5 ± 4.4 years (range 0.6-15.9), with a mean initial dose of 0.8 ± 0.3 mg/kg, which was subsequently increased to 1.1 ± 0.4 mg/kg. The patients were followed for 2.9 ± 1.4 years (range 1-4) after initiating burosumab. Serum phosphorus levels increased from 2.7 ± 0.8 mg/dl at burosumab initiation to 3.4 ± 0.6 mg/dl after 3 months and remained stable (p < 0.001). Total reabsorption of phosphorus increased from 82.0 ± 6.8 to 90.1 ± 5.3% after 12 months of treatment (p = 0.041). The RSS improved from 1.7 ± 1.0 at burosumab initiation to 0.5 ± 0.6 and 0.3 ± 0.6 after 12 and 24 months, respectively (p < 0.001). Both height z-score and weight z-score improved from burosumab initiation to the end of the study: from - 2.07 ± 1.05 to - 1.72 ± 1.04 (p < 0.001) and from - 0.51 ± 1.12 to - 0.11 ± 1.29 (p < 0.001), respectively. Eight children received growth hormone combined with burosumab treatment. Height z-score improved among those who received growth hormone (from - 2.33 ± 1.12 to - 1.94 ± 1.24, p = 0.042) and among those who did not (from - 2.01 ± 1.01 to - 1.66 ± 1.01, p = 0.001). CONCLUSION:  Burosumab treatment in a real-life setting improved phosphate homeostasis and rickets severity and enhanced linear growth. WHAT IS KNOWN: • Compared to conventional therapy, burosumab treatment has been shown to increase serum phosphate levels and reduce the severity of rickets. • The effect of burosumab on growth is still being study. WHAT IS NEW: • Height z-score improved between the start of burosumab treatment and the end of the study (-2.07 ± 1.05 vs. -1.72 ± 1.04, p < 0.001). • Eight children received burosumab combined with growth hormone treatment without side effects during the concomitant treatments.

Monitoring oral propranolol for infantile hemangiomata.

Treating infantile hemangiomas with oral propranolol may be initiated in accordance with various protocols some require hospitalization. However, different adverse events have been reported during treatment, thus it is of special importance to find a protocol which is both safe and feasible. We performed a retrospective cohort study of all cases of infantile hemangiomas treated with oral propranolol at our institute between January 2010 and February 2020. Pretreatment evaluation consisted of pediatric cardiologist evaluation including electrocardiography and echocardiography. The propranolol starting dosage was 0.5 mg/kg bid; 2 weeks later the dosage was escalated to 1 mg/kg bid. During the initiation and escalation visits, heart rate and blood pressure were measured before and every hour for a total of 3 h, and blood glucose level was measured within the first hour of treatment. A total of 131 children were treated during the study period. Scalp, facial and genital region infantile hemangiomas were more prevalent in regard to their relative body surface area. No symptomatic bradycardia, hypotension, hypoglycemia, or any other adverse events were documented; few patients had asymptomatic bradycardia and hypotension, which were more common in infants below 6-months of age. Only one patient had asymptomatic hypoglycemia, not requiring any intervention. Initiation and escalation of propranolol treatment for infantile hemangiomas proved to be safe, and without symptomatic adverse effects. However, considering the young age of the patients and the possible asymptomatic adverse reactions, we recommend the following simple protocol as presented, for pretreatment evaluation and short monitoring during treatment initiation and dose escalation.

Asymptomatic bacteriuria and antibiotic resistance profile in children with neurogenic bladder who require clean intermittent catheterization.

STUDY DESIGN: A retrospective cohort study. OBJECTIVES: To document the prevalence of asymptomatic bacteriuria and to characterize the resistance patterns to antibiotics among children with neurogenic bladder who require clean intermittent catheterization, with an emphasis on multidrug resistance. SETTING: A national referral pediatric and adolescent rehabilitation facility in Jerusalem, Israel. METHODS: Routine urine cultures were collected before urodynamic studies in suitable individuals during 2010-2018. None of them had symptoms of urinary tract infection at the time of specimen collection. Cultures were defined as being positive if a single bacterial species was isolated together with a growth of over 105 colony-forming units/ml. Resistance patterns were defined as extended-spectrum beta-lactamase (ESBL) and resistant to 3 antimicrobial groups (multi-drug resistant, MDR). RESULTS: In total, 281 urine cultures were available for 186 participants (median age 7 years, range 0.5-18). Etiologies for CIC included myelomeningocele (n = 137, 74%), spinal cord injury (n = 16, 9%) and caudal regression syndrome (n = 9, 5%). Vesicoureteral reflux was diagnosed in 36 participants (19%), 14 of whom were treated with prophylactic antibiotics. Asymptomatic bacteriuria was present in 217 specimens (77%, 95%CI [0.72-0.82]). The bacteria species were E. coli (71%), Klebsiella (13%), and Proteus (10%). ESBL was found in 11% of the positive cultures and MDR in 9%, yielding a total of 34 (16% of positive cultures) positive for ESBL and/or MDR bacteria. CONCLUSIONS: Asymptomatic bacteriuria and resistance to antimicrobials are common in pediatric individuals who require CIC.

Long-term outcomes during 37 years of pediatric kidney transplantation: a cohort study comparing ethnic groups.

BACKGROUND: This study aimed to evaluate short- and long-term outcomes of kidney transplantation over 37 years in a national referral center and compare outcomes between Israeli Jewish and Arab children. METHODS: Data on 599 pediatric transplantations performed in 545 children during 1981-2017, including demographic parameters, kidney failure disease profile, and pre-transplant dialysis duration, were retrieved from our computerized database and patient files. Patient and graft survival were estimated using the Kaplan-Meier method. RESULTS: Twenty-year patient survival was 91.4% for live donor (LD) and 80.2% for deceased donor (DD) kidney recipients. Respective 10-year and 20-year graft survival rates for first kidney-only transplants were 75.2% and 47.0% for LD and 60.7% and 38.4% for DD grafts. Long-term graft survival improved significantly (p < 0.001) over the study period for recipients of both LD and DD allografts and reached 7-year graft survival of 92.0% and 71.3%, respectively. The proportion of DD transplantations was higher in the Arab subpopulation: 73.8% vs. 48.4% (p < 0.001). Graft survival was not associated with age at transplantation and did not differ between the Arab (N = 202) and Jewish children (N = 343). Median (IQR) waiting time on dialysis did not differ significantly between the Arab and Jewish children: 18 (10-30) and 15 (9-30) months, respectively (p Mann-Whitney = 0.312). CONCLUSIONS: Good and progressively improving long-term results were obtained in pediatric kidney transplantation at our national referral center, apparently due to expertise gained over time and advances in immunosuppression. Equal access to DD kidney transplant and similar graft survival were found between ethnic groups.

[DISTENDED FETAL BLADDER].

INTRODUCTION: Distended fetal bladder, also known as fetal megacystis, usually points to lower urinary tract obstruction (LUTO) which is most commonly caused by posterior urethral valves (PUV) in the male fetus. We present a short case-series of fetal megacystis without oligohydramnion where primary vesicoureteral reflux (VUR) was the leading aetiology. These cases also displayed a high rate of kidney dysplasia with early-onset renal dysfunction. By contrast, late-onset diagnosis of isolated megacystis, i.e without significant renal parenchymal or upper urinary tract abnormalities, had a surprisingly benign postnatal course with spontaneous resolution after birth. Our case series also display the associated risk for extra-renal malformations and specifically neuro-cognitive developmental abnormalities which should be sought on genetic and imaging evaluation.

[SOLITARY KIDNEY - IS IT TOO LITTLE?]

INTRODUCTION: Solitary functioning kidney (SFK) occurs with unilateral renal agenesis (URA) in 1/2000 live births - or after uninephrectomy for tumor, trauma, uncontrolled infections or hypertension and post-kidney donation. URA-associated states include urological, cardiac, gastrointestinal and skeletal anomalies or it might be a component of a genetic syndrome. In 10% of cases of URA another family member is affected. In any case of SFK a compensatory process is triggered consisting of glomerular hypertension with hyperfiltration which achieves 75% of two kidneys' function. In the long-run this process might be detrimental causing further loss of functioning nephrons, inability to sustain functional compensation and progressive kidney function deterioration. The risk for this chain of events is determined in the first place by the number of nephrons in the SFK, which cannot be assessed in vivo. Hints for reduced nephron number in the single kidney include prematurity or SGA-small for date birth weight, urological anomalies with or without accompanying infections, lack of increased single kidney size - compensatory hypertrophy. Age of onset of the compensatory process and acquired factors including nephrotoxin exposure, overweight/obesity, excessive salt and/or protein intake contribute to the risk of progressive renal damage. Life-long follow-up of all subjects with SFK is recommended from early age for lifestyle education: recommended diet and tailored physical activity, nephrotoxin avoidance along with early detection of renal injury signs: albuminuria, hypertension or depressed kidney function - GFR (glomerular filtration rate) targeting timely intervention for preservation of functioning renal mass.

Focal segmental glomerulosclerosis in pediatric kidney transplantation: 30 years' experience.

From 1982 to 2011, 53 kidney transplantations (KT) for pediatric focal segmental glomerulosclerosis (FSGS) were recorded in the National Israeli Kidney Transplant Registry (NIKTR): 22-primary (1◦) FSGS, 25-proved/suspected genetic-secondary (2◦) FSGS, six lost/incomplete files/other. Half (56%) of 23 patients with 2◦ FSGS were Israeli-Arabs vs 29% of 1◦ FSGS KT recipients. 1◦ FSGS recurrence occurred in 64% (14/22) of 22 KT in 17 patients aged (median) 14 years vs 1/25 of 2◦ FSGS (P<.001). Early graft days/nonfunction occurred in 9/14 (64%), 2/8 (25%) and 2/25 (4%) of recurrent 1◦ FSGS (rFSGS), nonr1◦ FSGS and 2◦ FSGS, respectively. Twelve biopsies performed in nine of these grafts at (median) 8 days (range 5-60 days) post-KT showed: ATN-5, suspected rejection-4, rFSGS-2, normal kidney-1; rFSGS was diagnosed eventually in 8/9. Dialysis need during the first month post-KT was significantly associated with FSGS recurrence: 6/14 (43%) for rFSGS vs 2/8 (25%) for non-rFSGS. Plasmapheresis (PP) achieved complete and partial rFSGS remission in 5/9 and 2/9 grafts, respectively. Three grafts were excised during the first 60 days post-KT for: nonfunction (1) and bleeding (2). Remaining grafts' GFR was: 78, 42, and 91 mL/min (median) at 5.3, 4.75, and 8 years follow-up for non-rFSGS, rFSGS, and 2◦ FSGS grafts, respectively. CONCLUSIONS: Early PP implementation should be considered after KT for 1◦ FSGS patients with early graft dysfunction despite delayed proteinuria and nonspecific biopsy.

High prevalence of elevated blood pressure among children with neurofibromatosis type 1.

BACKGROUND: Neurofibromatosis type 1 (NF1) is a common neurocutaneous disease characterized by café-au-lait spots, axillary and inguinal freckling, neurofibromas, and optic gliomas. Increased rates of hypertension (HTN) were reported among NF1 patients, however, the prevalence of HTN and pre-HTN in pediatric NF1 patients has not been clarified. METHODS: Blood pressure (BP) measurements, weight, and renal ultrasound were assessed in 224 NF1 pediatric patients followed in a specialized NF1 clinic. RESULTS: The cohort's mean age was 9.1 ± 4.1 years. Overweight and obesity were found in 12.9 and 10.3 % of them, respectively. BP was measured averagely 2.9 times per patient on different occasions. Blood pressure was in the pre-HTN and HTN ranges in 14.9 and 16.9 % of measurements, respectively. BP >95th was detected in 20.5 % at the first measurement. Of 114 children with at least three BP measurements, 18.4 % had two values in the HTN range and 6.14 % had at least three. Overweight was not associated with HTN among children with NF1. Urinary tract ultrasonographic abnormalities were detected in 6.8 % (11/161) of cases. CONCLUSIONS: The prevalence of increased BP in pediatric NF1 is much higher than in the general pediatric population. BP has to be regularly assessed and managed in this high-risk population.

Post-Infectious Glomerulonephritis in Pediatric Patients over Two Decades: Severity-Associated Features.

BACKGROUND: The incidence of post-infectious glomerulonephritis (PIGN) has decreased over the last decades. As a result, recent epidemiological data from industrialized countries are scarce. OBJECTIVES: To evaluate patterns of PIGN in children and detect possible predictors of disease severity. METHODS: We collected clinical and laboratory data of patients with PIGN admitted to Schneider Children's Medical Center during 1994-2011. Diagnostic criteria included presence of hematuria with/without other features of nephritic syndrome along with hypocomplementemia and/or microbiological/serological evidence of streptococcal infection. Patients with other diseases (systemic lupus erythematosus, vasculitis, etc.) were excluded from the study. RESULTS: A total of 125 patients with a mean age of 5.8 ± 3.3 years (range 1.5-17.6), of whom 16% were < 3 years, matched the study criteria. Presenting features included hypertension in 103 (82.4%) patients, azotemia in 87 (70.2%), fever in 49 (40/6), and elevated C-reactive protein in 75 (81.5%). Isolated macrohematuria was found in 21 (16%). Full-blown nephritic syndrome was diagnosed in 51 patients (41.1%) and 28 (22.9%) had nephritic syndrome with nephrotic-range proteinuria. Depressed C3 complement levels were associated with the presence of nephritic syndrome (OR 0.73, 95% CI 0.60-0.88, P = 0.001) as well as older age (OR 1.24, Cl 1.08-1.43, P = 0.001). At last follow-up (mean 42 months) all examined patients (100 of 125) had normal renal function, 6 had hypertension, and 1 had proteinuria. CONCLUSIONS: PIGN remains an important cause of glomerular disease in children and may affect very young patients. Nephrotic-range proteinuria with hypoalbuminemia seems to be more frequent than previously reported. Hypocomplementemia is associated with a more severe disease course, namely, azotemia and nephritic syndrome.

Positional cloning uncovers mutations in PLCE1 responsible for a nephrotic syndrome variant that may be reversible.

Nephrotic syndrome, a malfunction of the kidney glomerular filter, leads to proteinuria, edema and, in steroid-resistant nephrotic syndrome, end-stage kidney disease. Using positional cloning, we identified mutations in the phospholipase C epsilon gene (PLCE1) as causing early-onset nephrotic syndrome with end-stage kidney disease. Kidney histology of affected individuals showed diffuse mesangial sclerosis (DMS). Using immunofluorescence, we found PLCepsilon1 expression in developing and mature glomerular podocytes and showed that DMS represents an arrest of normal glomerular development. We identified IQ motif-containing GTPase-activating protein 1 as a new interaction partner of PLCepsilon1. Two siblings with a missense mutation in an exon encoding the PLCepsilon1 catalytic domain showed histology characteristic of focal segmental glomerulosclerosis. Notably, two other affected individuals responded to therapy, making this the first report of a molecular cause of nephrotic syndrome that may resolve after therapy. These findings, together with the zebrafish model of human nephrotic syndrome generated by plce1 knockdown, open new inroads into pathophysiology and treatment mechanisms of nephrotic syndrome.

Cardiovascular risk factors in children after kidney transplantation--from short-term to long-term follow-up.

Cardiovascular-related mortality is 100-fold higher in pediatric renal transplant recipients than in the age-matched general population. Seventy-seven post-renal transplant children's charts were reviewed for cardiovascular risk factors at two and six months after transplantation (short term) and at two yr after transplantation and the last follow-up visit (mean 7.14 ± 3.5 yr) (long term). Significant reduction was seen in cardiovascular risk factors prevalence from two months after transplantation to last follow-up respectively: Hypertension from 52.1% to 14%, hypercholesterolemia from 48.7% to 33%, hypertriglyceridemia from 50% to 12.5%, anemia from 29.6% to 18.3%, hyperparathyroidism from 32% to 18.3% and hyperglycemia from 11.7% to 10%, and left ventricular hypertrophy from 25.8% at short term to 15%. There was an increase in the prevalence of obesity from 1.5% to 3.9% and of CKD 3-5 from 4.75% to 24%. The need for antihypertensive treatment decreased from 54% to 42%, and the percentage of patients controlled by one medication rose from 26% to 34%, whereas the percentage controlled by 2, 3, and 4 medications decreased from 21.9%, 5.5%, and 1.4% to 6%, 2%, and 0. Children after renal transplantation appear to have high rates of cardiovascular risk factors, mainly on short-term follow-up.

Renal hypodysplasia associates with a WNT4 variant that causes aberrant canonical WNT signaling.

Abnormal differentiation of the renal stem/progenitor pool into kidney tissue can lead to renal hypodysplasia (RHD), but the underlying causes of RHD are not well understood. In this multicenter study, we identified 20 Israeli pedigrees with isolated familial, nonsyndromic RHD and screened for mutations in candidate genes involved in kidney development, including PAX2, HNF1B, EYA1, SIX1, SIX2, SALL1, GDNF, WNT4, and WT1. In addition to previously reported RHD-causing genes, we found that two affected brothers were heterozygous for a missense variant in the WNT4 gene. Functional analysis of this variant revealed both antagonistic and agonistic canonical WNT stimuli, dependent on cell type. In HEK293 cells, WNT4 inhibited WNT3A induced canonical activation, and the WNT4 variant significantly enhanced this inhibition of the canonical WNT pathway. In contrast, in primary cultures of human fetal kidney cells, which maintain WNT activation and more closely represent WNT signaling in renal progenitors during nephrogenesis, this mutation caused significant loss of function, resulting in diminished canonical WNT/ß-catenin signaling. In conclusion, heterozygous WNT4 variants are likely to play a causative role in renal hypodysplasia.

Cardiovascular health in pediatric patients with X-linked hypophosphatemia under two years of burosumab therapy.

Introduction: X-linked hypophosphatemia (XLH) is caused by an inactivating mutation in the phosphate-regulating endopeptidase X-linked (PHEX) gene whose defective product fails to control phosphatonin fibroblast growth factor 23 (FGF23) serum levels. Although elevated FGF23 levels have been linked with detrimental cardiac effects, the cardiologic outcomes in XLH patients have been subject to debate. Our study aimed to evaluate the prevalence and severity of cardiovascular morbidity in pediatric XLH patients before, during, and after a 2-year treatment period with burosumab, a recombinant anti-FGF23 antibody. Methods: This prospective observational study was conducted in a tertiary medical center, and included 13 individuals with XLH (age range 0.6-16.2 years) who received burosumab every 2 weeks. Clinical assessment at treatment initiation and after .5, 1, and 2 years of uninterrupted treatment included anthropometric measurements and cardiologic evaluations (blood pressure [BP], electrocardiogram, conventional echocardiography, and myocardial strain imaging). Results: The linear growth of all patients improved significantly (mean height z-score: from -1.70 ± 0.80 to -0.96 ± 1.08, P=0.03). Other favorable effects were decline in overweight/obesity rates (from 46.2% to 23.1%) and decreased rates of elevated BP (systolic BP from 38.5% to 15.4%; diastolic BP from 38.5% to 23.1%). Electrocardiograms revealed no significant abnormality throughout the study period. Cardiac dimensions and myocardial strain parameters were within the normative range for age at baseline and remained unchanged during the study period. Conclusion: Cardiologic evaluations provided reassurance that 2 years of burosumab therapy did not cause cardiac morbidity. The beneficial effect of this treatment was a reduction in cardiovascular risk factors, as evidenced by the lower prevalence of both overweight/obesity and elevated BP.

Hypothyroidism in children with steroid-resistant nephrotic syndrome.

BACKGROUND: Non-autoimmune hypothyroidism has been reported in children with congenital nephrotic syndrome. The hypothyroid state was attributed to massive prolonged thyroid hormone loss. However, this endocrine abnormality has not been reported in steroid-resistant nephrotic syndrome (SRNS) despite similar long-standing proteinuria. METHOD: We describe all the patients with SRNS in our clinic's follow-up who developed non-autoimmune hypothyroidism. RESULTS: Five children aged 3-11 years at diagnosis of SRNS and followed for 5-42 months developed hypothyroidism (depressed free thyroxin and elevated thyrotropin levels) without evidence of autoimmune thyroiditis. The diagnosis of hypothyroidism was not temporarily related to disease duration or renal function. The disease was resistant to all therapies, renal function deteriorated in all the patients within 1.5-14.5 years from diagnosis. Despite thyroxine treatment and a decline in renal function, thyroid hormone level normalized only after reaching end stage renal disease (ESRD) and hemodialysis start. Nephrotic syndrome recurrence after kidney transplantation (in three patients with focal segmental glomerulosclerosis) was not accompanied by recurrent hypothyroidism. CONCLUSION: It is our impression that non-autoimmune hypothyroidism is a potential significant complication of SRNS, and should be actively sought for especially in cases with renal function deterioration. Hypothyroidism usually resolved when these patients reach ESRD. The incidence and pathogenesis of this condition require further study.

Post-transplantation lymphoproliferative disorder in pediatric kidney-transplant recipients - a national study.

PTLD is the most common malignancy in pediatric kidney-transplant recipients. We examined the prevalence, clinical features, and outcome of PTLD in Israel. Twelve (4.4%) of 272 pediatric (<19 yr) kidney-transplant recipients retrieved from a search of the NIKTR for 1991-2008 had acquired PTLD at a median of 3.2 yr post-transplantation. PTLD-affected patients were younger at transplantation (4.2 vs. 12.5 yr, p = 0.02), had a higher rate of OKT3 therapy for acute rejection (25% vs. 4%, p = 0.015), and 5/12 were EBV-seropositive at transplantation. Graft dysfunction was the presenting sign in six (50%). PTLD was predominantly abdominal (83%) and B-cell type (67%); T-cell PTLD occurred exclusively in EBV-seropositive patients. Treatment consisted of immunosuppression cessation (6/12, 50%), antiviral agents (7/12, 58%), anti-CD20 monoclonal antibodies (4/12, 33%), and chemotherapy (6/12, 50%). Survival was 100% in the EBV-naïve patients and 40% in the EBV-seropositive patients. Graft loss occurred in three of eight survivors (37.5%). PTLD-associated mortality risk was older age: 11.2 vs. 3.4 yr, longer dialysis: 15 vs. 6.5 months, T-cell type disease (75%), later PTLD onset: 6.35 vs. 1.9 yr post-transplantation and era of transplantation (43% mortality before vs. 20% after 2001). Pretransplantation EBV-seronegative status might confer a survival benefit with early detected PTLD. EBV-seropositive patients are at risk for aggressive late-onset lethal PTLD.

Hyponatremic hypertensive syndrome in pediatric patients: is it really so rare?

BACKGROUND: Hyponatremic hypertensive syndrome (HHS) is characterized by unilateral renal artery stenosis with secondary hypertension and glomerular and tubular dysfunction due to hyperfiltration and activation of the renin-angiotensin system (RAS). CASE-DIAGNOSIS/TREATMENT: We describe four children with HHS. All presented with polyuria and polydipsia, electrolyte disturbances, metabolic alkalosis, variable tubular dysfunction, and nephrotic range proteinuria along with hypertension. Interestingly, in one patient, glomerular and tubular abnormalities preceded the development of hypertension. All symptoms resolved after the underlying renal ischemia was corrected by percutaneous angioplasty. CONCLUSION: Hyponatremic hypertensive syndrome may be more common in children than previously thought. Clinicians should be alert of the signs and symptoms because cure is possible with timely diagnosis and treatment.

Mechanisms of compensatory renal growth.

Congenitally reduced renal mass- as with agenesis of one kidney, unilateral multicystic dysplastic kidney or with premature birth with early arrest of nephrogenesis- as well as acquired loss of a significant part of kidney tissue- as with kidney donation, after surgery for tumor etc- set in motion compensatory processes with main target to meet metabolic body needs. The sensors for reduced renal mass have not yet been identified. The effectors of the compensatory process include a wide range of growth factors- IGF1, TGF-b1, HGF- and signaling molecules-mTOR- which has intricate reciprocal interactions. As nephrogenesis stops at 34-36 weeks of gestation and can't be restarted thereafter, the main result of this compensatory process is increase in glomerular size (glomerulomegaly) and tubular hypertrophy. Renal volume evaluation by ultrasound is a practical noninvasive tool for assessment of compensatory kidney growth. The increased nephron and kidney size induced by the compensatory process have potential detrimental long-term effect through stretch-induced glomerular cell activation of profibrogenic and vasoconstrictor pathways as well as tubular cell nephrotoxicity caused by abnormal activation of reabsorptive mechanisms including GLUT1 and megalin. Deep understanding of these potentially damage process might help in timely implementation of protective strategies.

Impact of dialysis type on outcome of acute renal failure in children: a single-center experience.

BACKGROUND: Acute renal failure (ARF) is a common complication in critically ill children. It is known as an important predictor of morbidity and mortality in this population. Data on the factors affecting the choice of renal replacement therapy (RRT) modality and its impact on mortality of children with ARF are limited. OBJECTIVES: We retrospectively studied 115 children with ARF necessitating RRT during the period 1995-2005 to evaluate the effect of several prognostic factors as well as RRT type on their immediate outcome. METHODS: The data collected from charts included demographics, primary disease, accompanying medical conditions, use of vasopressor support, indications for dialysis, RRT modality, and complications of dialysis. Categorical variables were analyzed using chi-square or Fisher's exact tests. Variables associated with mortality (P < 0.1) at the univariable level were studied by a multivariable logistic regression model. RESULTS: The most common cause of ARF was congenital heart disease (n=75). RRT modalities included peritoneal dialysis (PD) (n=81), hemodialfiltration (HDF) (n=31) and intermittent hemodialysis (IHD) (n=18). Median RRT duration was 4 days (range 1-63 days). Overall mortality was 52.2%. IHD was associated with the best survival rate (P < 0.01 vs. PD and HDF), while children treated with HDF had the worse outcome. Hemodynamic instability and systemic infections were associated with greater mortality, but the rate of these complications did not differ between the study groups. CONCLUSIONS: Our results suggest that IHD when applied to the right patient in an appropriate setting may be a safe and efficient RRT modality in children with ARF. Randomized prospective trials are needed to further evaluate the impact of different RRT modalities on outcome in children with ARF.