ROHHAD Syndrome an Inconspicuous Cause of Hypernatremia, A Case Report.

Rapid-onset obesity with hypoventilation, hypothalamic dysfunction, and autonomic dysregulation (ROHHAD) syndrome is a rare, life threatening disease with unknown etiology. Dysnatremia is a common finding in these patients. Here we present a 12-year-old boy with multiple admissions due to hypernatremia and was repeatedly misdiagnosed. An eventual diagnosis of ROHHAD syndrome was made by integration of the previous ignored findings of sleep apnea and obesity. The diagnosis of this rare but potentially fatal syndrome should be considered in patients with dysnatremia associated with obesity and sleep apnea disorders.

Outcome of Mini-Percutaneous Nephrolithotomy in Patients Under the Age of 18: An Experience With 112 Cases.

Purpose: Renal calculi are becoming more common among children. Although, extracorporeal shock wave lithotripsy (ESWL) is the first choice in this age group, minimal invasive surgeries, such as percutaneous nephrolithotomy (PCNL), are indicated for some patients. Recently, PCNL devices have become smaller in size with acceptable efficacy and lower complications. We evaluated the outcomes and complications of mini-PCNL (MPCNL) surgery in our referral training centers. Materials and Methods: Between September 2012 and January 2020, a total of 112 children under the age of 18, who had shown failure of ESWL, and/or their parents refused to do it, underwent MPCNL (15 Fr). The patients' profiles were reviewed for data collection including preoperative and stone data, operation information, and postoperative complications. Results: Of 112 patients, 69 were boys, and 43 were girls. Their mean age was 8.6 years (14 months to 18 years). Mean stone size was 20 mm (14-34 mm). Seventy-four cases had renal pelvic stone, 22 had pelvis and lower pole, and 16 had staghorn. The mean operation time was 65 min (35-100 min), and mean radiation time was 0.6 min (0.2-1.4 min). Low-grade fever was detected in 14 patients (12.5%). Four patients needed blood transfusion and two had increased creatinine, which improved with conservative management. One patient developed urosepsis that resolved with antibiotic therapy. None of the patients had kidney perforation or other organ injury or death. Early stone-free rate (SFR) after operation was 90.2% (101 patients). Six patients had residual fragment <5 mm, which passed spontaneously in 2 weeks after operation (total SFR 95.3%). Three patients underwent second-look nephroscopy, and ureteroscopy was done for two patients due to migrated stone fragments to the distal ureter. Conclusion: MPCNL is recommended as a safe alternative option for treatment of the nephrolithiasis in children with good outcome and acceptable complications.

Concomitant BK virus infection and visceral Leishmaniasis in a pediatric liver transplant recipient.

BACKGROUND: Solid organ transplant recipients are vulnerable to various unusual infections. Visceral Leishmaniasis (VL) is a protozoal opportunistic infection, which may affect the immune-suppressed hosts and solid organ transplant recipients. The BK virus infection is an evolving challenge in kidney transplant recipients. However, there are very few reports of BK virus (BKV) nephropathy involving the native kidney in liver transplant recipients. To the best of our knowledge, this is the first report of the simultaneous occurrence of these rare infections in a liver transplant recipient. CASE REPORT: The patient was a 9-year-old girl, a case of liver transplantation who presented with the incidental finding of proteinuria, azotemia, and cytopenia. Investigations revealed that she had concomitant BKV nephropathy and visceral leishmaniasis. Both infections were successfully treated. CONCLUSION: BK virus should be considered as a cause of nephropathy in liver transplant recipients. The presenting features of fever, cytopenia, and splenomegaly in a post-transplant patient should remind of unusual infections such as VL other than the common post-transplant conditions.

Acute necrotizing glomerulonephritis associated with COVID-19 infection: report of two pediatric cases.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is thought to cause kidney injury via a variety of mechanisms. The most common reported kidney injury following COVID-19 infection is acute tubular injury (ATI); however, the procoagulant state induced by the virus may also damage the kidneys. CASE-DIAGNOSIS/TREATMENT: Herein, we report two cases of acute necrotizing glomerulonephritis (GN) with fibrinoid necrosis in the context of COVID-19 infection. The one with more chronic features in the kidney biopsy progressed to permanent kidney failure but the second one had an excellent response to glucocorticoid pulse therapy with subsequent normal kidney function at 2-month follow-up. CONCLUSIONS: Both reported cases had an acute presentation of kidney injury with positive nasopharyngeal PCR test for COVID-19. Based on the data review by the researchers, this is the first report of acute necrotizing GN associated with COVID-19 infection.

Prevalence of Renal Dysfunction Among Pediatric Liver Transplant Recipients.

INTRODUCTION: Renal dysfunction is among the common and considerable complications after liver transplantation and is principally attributable to immunosuppressive medications .The purpose of this study was to define the prevalence of hypertension and renal dysfunction among pediatric liver transplant recipients. METHODS: 46 pediatric liver transplant recipients were assessed for hypertension utilizing ambulatory blood pressure monitoring (ABPM), and glomerular, and tubular renal function at the transplant clinic of Shiraz University of Medical Sciences. Results were analyzed using SPSS 19 and P value < .05 was considered statistically significant. RESULTS: The mean age of the patients was 12.2 ± 3.3 years and 24 of them were female. Considering ABPM measurements 20 patients (43.5%) were hypertensive, 37% were systolic and 36.6% were diastolic non-dippers respectively. eGFR was calculated based on different formulations and Cystatin C-based equation estimated lower GFR than Cr-based equation. Micro-albuminuria was noticed in 26.1%. Additional parameters of tubular dysfunction included hyperuricosuria (4.3%), hypercalciuria (6.5%), abnormal fractional excretion of Mg (FeMg) (43.5%), abnormal tubular reabsorption of phosphate (TRP) (4.3%), and abnormal fractional excretion of uric acid (FEUA) in 13% of the patients. We noticed a statistically significant negative correlation between hypercalciuria, microalbuminuria, FeMg (P < .05) and GFR. CONCLUSION: Renal function impairment and hypertension are frequent complications amongst pediatric liver transplant recipients. Using Cyctatin C instead of Cr based formula for GFR estimation, and blood pressure monitoring by ABPM and regular screening of renal function are essential measures for recognition and treatment of renal dysfunction in these patients.

Schimke Immuno-osseous Dysplasia: A Case Report.

Schimke immuno-osseous dysplasia (SIOD) is a rare inherited disease characterized by steroid resistant nephrotic syndrome, spondyloepiphyseal dysplasia, and T-cell immunodeficiency. Focal segmental glomerulosclerosis (FSGS) is the most frequent renal pathological finding associated with proteinuria in SIOD. In this case report, we describe a 4.5-year-old boy who presented with nephrotic syndrome and ventricular septal defect followed by tremor in the limbs after-cerebral infarction. It is emphasized that SIOD should be considered in children with wide range of presentation, from growth retardation, steroid resistant nephrotic syndrome, and bone, cardiac, and neurological abnormalities in the late childhood or even adolescence.

Early Onset Cerebral Infarction in Schimke Immuno-Osseous Dysplasia.

Schimke Immuno-osseous Dysplasia (SIOD) is a rare autosomal recessive disease caused by a biallelic mutation in SMARCAL1 gene. Typical findings in SIOD include spondylo-epiphyseal dysplasia, steroid resistance nephrotic syndrome, progressive renal failure, T-cell immunodeficiency, bone marrow failure, and cerebral infarction. In this case report, we describe a 9-yr-old girl who presented with failure to thrive in infancy. Nephrotic syndrome was diagnosed at the age of four years. She had three episodes of admission with cerebral stroke due to moyamoya syndrome. In the last admission at Namazi Hospital, Shiraz, southern Iran, in October 2016, she had new cerebral ischemia, developed seizure, and finally died.

Mutation analysis of the CTNS gene in Iranian patients with infantile nephropathic cystinosis: identification of two novel mutations.

Nephropathic cystinosis is an inherited lysosomal transport disorder caused by mutations in the CTNS gene that encodes for a lysosomal membrane transporter, cystinosin. Dysfunction in this protein leads to cystine accumulation in the cells of different organs. The accumulation of cystine in the kidneys becomes apparent with renal tubular Fanconi syndrome between 6 and 12 months of age and leads to renal failure in the first decade of life. The aim of this study was to analyze the CTNS mutations in 20 Iranian patients, from 20 unrelated families, all of whom were afflicted with infantile nephropathic cystinosis. In these patients, seven different mutant alleles were found, including two new mutations, c.517T>C; p.Y173H and c.492_515del, that have not been previously reported. In addition, we observed that c.681G>A, the common Middle Eastern mutation, was the most common mutation in our patients. Moreover, a new minisatellite or variable number of tandem repeat marker (KX499495) was identified at the CTNS gene. Seven different alleles were found for this marker, and its allele frequency and heterozygosity degree were calculated in cystinosis patients and healthy individuals.

Recurrence of nephrotic syndrome following kidney transplantation in a child with congenital nephrotic syndrome.

Recurrence of original disease is a common threat in the field of transplantation. Recurrence of nephrotic syndrome is not common in children with congenital nephrotic syndrome (CNS). We report a case of a female child with CNS who presented with nephrotic state at first month of age and became dialysis dependent at 17 months of age. After seven months of continuous ambulatory peritoneal dialysis, she received a kidney from a deceased donor. Eight months after transplantation, she presented with a full-blown feature of nephrotic syndrome. She responded well to rituximab.

Renal function in children with cyanotic congenital heart disease: pre- and post-cardiac surgery evaluation.

OBJECTIVE: Cyanotic congenital heart diseases (CCHDs) are a series of cardiac anomalies that have long been recognized as a potential cause of nephropathy. There have been few reports on renal impairment in patients with CCHD before and after corrective cardiac surgery. The aim of this study was to evaluate the prevalence of renal dysfunction before and after cardiac surgery and the impact of some risk factors on final renal outcome. METHODS: Thirty children with CCHD who had done corrective cardiac surgery in the previous 6 months were enrolled in this study. All data prior to surgery were collected from the charts. Post-operation data including blood and spot urine samples were taken simultaneously for CBC, Cr, and uric acid and 24 hour urine was collected for microalbumin and Cr during the follow up visits. Pre- and post-operation parameters were compared to study the impact of cardiac surgery on renal function. Findings : Pre- and post-operative GFRs were not significantly different. Final GFR was significantly and inversely associated with pre- and post-operation age (P=0.008 r=-0.48, P=0.03 r=-0.38). Three (10%) patients had microalbuminuria. The prevalence of microalbuminuria in children older than 10 years was 30%. There was no link between microalbuminuria and age, GFR, and hematocrit (P=0.1, P=0.3, P=0.3, respectively). Patients with preoperation hematocrit >45 had a significantly lower final GFR compared to children with HCT <45 (83.7±6.5 vs 111.10.2, P=0.001). The mean uric acid fraction (FEua) excretion was 8.21±4.75. Pre-operative HCT was inversely associated to FEua (P=0.01, r=-0.44). There was no relationship between FEua and age, serum uric acid, and GFR (P=0.7, P=0.4, P=0.2). CONCLUSION: Children with CCHD are at increased risk of renal injury which is related more to the duration of cyanosis and higher degree of hematocrit level. To lower the risk, corrective cardiac surgery is recommended to be done as soon as possible to improve renal function and stop more renal impairment.

The evaluation of cisplatin effect on tubular function in children on chemotherapy.

The dose limiting side effect of cisplatin is nephrotoxicity. The aim of this study was to investigate tubular function in children who have received cisplatin and forced diuresis. We performed a cohort study on 20 children under 15 years of age with various type of malignancy on cisplatin-based chemotherapy. Twenty-four-hour urine was collected in three periods: before the first, third, and fifth doses of cisplatin administration to check urine for sodium (Na), magnesium (Mg), uric acid, creatinine (Cr), phosphorus (P), calcium (Ca), beta-2 microglobulin, and N-acetyl-beta-D-glucosaminidase (NAG) levels. At the same time, blood samples were taken to check serum Cr, Na, Mg, Ca, P, and uric acid levels. Then, we compared the mean of glomerular filtration rate (GFR); fraction excretions (FE,%) of Na, Mg, and uric acid; tubular phosphorous reabsorption (TPR,%), 24-hour urine Ca (mg); urine beta-2 microglobulin (mcg/mL); and NAG (IU/L) in three periods of cisplatin administration. The FE of Na, Mg, and urine beta-2 microglobulin increased after administration of cisplatin but TPR, FE, uric acid, and NAG decreased in the 2nd and 3rd period compared to 1st period. GFR revealed a little change that was not significant. Urine calcium was decreased significantly in the second and third periods of cisplatin administration. Since the patients were hydrated for forced diuresis and received magnesium sulfate to prevent nephrotoxicity, we did not see significant tubular dysfunction. But we saw that urine calcium excretion decreased after cisplatin injection without any change in serum calcium in spite of preventive measures.

Reduced elastogenesis: a clue to the arteriosclerosis and emphysematous changes in Schimke immuno-osseous dysplasia?

BACKGROUND: Arteriosclerosis and emphysema develop in individuals with Schimke immuno-osseous dysplasia (SIOD), a multisystem disorder caused by biallelic mutations in SMARCAL1 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1). However, the mechanism by which the vascular and pulmonary disease arises in SIOD remains unknown. METHODS: We reviewed the records of 65 patients with SMARCAL1 mutations. Molecular and immunohistochemical analyses were conducted on autopsy tissue from 4 SIOD patients. RESULTS: Thirty-two of 63 patients had signs of arteriosclerosis and 3 of 51 had signs of emphysema. The arteriosclerosis was characterized by intimal and medial hyperplasia, smooth muscle cell hyperplasia and fragmented and disorganized elastin fibers, and the pulmonary disease was characterized by panlobular enlargement of air spaces. Consistent with a cell autonomous disorder, SMARCAL1 was expressed in arterial and lung tissue, and both the aorta and lung of SIOD patients had reduced expression of elastin and alterations in the expression of regulators of elastin gene expression. CONCLUSIONS: This first comprehensive study of the vascular and pulmonary complications of SIOD shows that these commonly cause morbidity and mortality and might arise from impaired elastogenesis. Additionally, the effect of SMARCAL1 deficiency on elastin expression provides a model for understanding other features of SIOD.

SMARCAL1 deficiency predisposes to non-Hodgkin lymphoma and hypersensitivity to genotoxic agents in vivo.

Schimke immuno-osseous dysplasia (SIOD) is a multisystemic disorder with prominent skeletal, renal, immunological, and ectodermal abnormalities. It is caused by mutations of SMARCAL1 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1), which encodes a DNA stress response protein. To determine the relationship of this function to the SIOD phenotype, we profiled the cancer prevalence in SIOD and assessed if defects of nucleotide excision repair (NER) and nonhomologous end joining (NHEJ), respectively, explained the ectodermal and immunological features of SIOD. Finally, we determined if Smarcal1(del/del) mice had hypersensitivity to irinotecan (CPT-11), etoposide, and hydroxyurea (HU) and whether exposure to these agents induced features of SIOD. Among 71 SIOD patients, three had non-Hodgkin lymphoma (NHL) and one had osteosarcoma. We did not find evidence of defective NER or NHEJ; however, Smarcal1-deficient mice were hypersensitive to several genotoxic agents. Also, CPT-11, etoposide, and HU caused decreased growth and loss of growth plate chondrocytes. These data, which identify an increased prevalence of NHL in SIOD and confirm hypersensitivity to DNA damaging agents in vivo, provide guidance for the management of SIOD patients.

Non-hodgkin lymphoma in a child with schimke immuno-osseous dysplasia.

Schimke immuno-osseous dysplasia is a rare autosomal recessive multisystem disorder characterized by steroid-resistant nephrotic syndrome, immunodeficiency, and spondyloepiphyseal dysplasia. Mutations in SWI/SNF2 related, matrix associated, actin dependent regulator of chromatin, subfamily a-like 1 (SMARCAL1) gene are responsible for the disease. The present report describes, for the first time, a Schimke immuno-osseous dysplasia child with SMARCAL1 missense mutation (R561H) and manifestations of intussusception secondary to Epstein-Barr virus-negative non-Hodgkin lymphoma, who expired due to septicemia following chemotherapy. The report emphasizes the necessity of more limited immunosuppressive protocols in Schimke immuno-osseous dysplasia patients with lymphoproliferative disorders.

Glomerular malondialdehyde levels in patients with focal and segmental glomerulosclerosis and minimal change disease.

Minimal change disease (MCD) and focal and segmental glomerulosclerosis (FSGS) are often studied together, because both present with heavy proteinuria and the nephrotic syndrome. The precise distinction between MCD and FSGS is sometimes difficult because of inadequate number of glomeruli for definite diagnosis. Some evidence suggests that markers of lipid peroxidation, such as malondialdehyde (MDA) is an index of free radical mediated injury and may be involved in the pathogenesis of FSGS. In this study, we assessed the immunoreactivity of MDA, the end product of lipid peroxidation in glomeruli of patients with idiopathic FSGS, MCD as well as normal controls (NC). Our results showed that the immunostaining level of MDA was significantly higher in patients with FSGS (mean = 1.5) than in either patients with MCD (mean = 0.16) or normal controls (mean = 0.11) with P value < 0.001. Glomerular MDA level correlated well with the degree of glomerulosclerosis in patients with idiopathic FSGS. Our data demonstrates that the glomerular level of MDA is higher in idiopathic FSGS than MCD. We suggest that MDA immunostaining can be helpful in differentiating between FSGS and MCD in problematic cases and when we do not have enough glomeruli for definite and correct diagnosis.

Risk of nephropathy after consumption of nonionic contrast media by children undergoing cardiac angiography: a prospective study.

Despite increasing reports on nonionic contrast media-induced nephropathy (CIN) in hospitalized adult patients during cardiac procedures, the studies in pediatrics are limited, with even less focus on possible predisposing factors and preventive measures for patients undergoing cardiac angiography. This prospective study determined the incidence of CIN for two nonionic contrast media (CM), iopromide and iohexol, among 80 patients younger than 18 years and compared the rates for this complication in relation to the type and dosage of CM and the presence of cyanosis. The 80 patients in the study consecutively received either iopromide (group A, n = 40) or iohexol (group B, n = 40). Serum sodium (Na), potassium (K), and creatinine (Cr) were measured 24 h before angiography as baseline values, then measured again at 12-, 24-, and 48-h intervals after CM use. Urine samples for Na and Cr also were checked at the same intervals. Risk of renal failure, Injury to the kidney, Failure of kidney function, Loss of kidney function, and End-stage renal damage (RIFLE criteria) were used to define CIN and its incidence in the study population. Accordingly, among the 15 CIN patients (18.75%), 7.5% of the patients in group A had increased risk and 3.75% had renal injury, whereas 5% of group B had increased risk and 2.5% had renal injury. Whereas 33.3% of the patients with CIN were among those who received the proper dosage of CM, the percentage increased to 66.6% among those who received larger doses, with a significant difference in the incidence of CIN related to the different dosages of CM (p = 0.014). Among the 15 patients with CIN, 6 had cyanotic congenital heart diseases, but the incidence did not differ significantly from that for the noncyanotic patients (p = 0.243). Although clinically silent, CIN is not rare in pediatrics. The incidence depends on dosage but not on the type of consumed nonionic CM, nor on the presence of cyanosis, and although CIN usually is reversible, more concern is needed for the prevention of such a complication in children.

The outcome of Iranian children on continuous ambulatory peritoneal dialysis: the first report of Iranian National Registry.

BACKGROUND: Continuous ambulatory peritoneal dialysis is not a very common modality to treat Iranian children with end-stage renal disease; however, there is sometimes no choice but to offer this therapy to salvage the patient. Obviously, promotion in each program needs re-evaluation to find the pitfalls. Therefore, a nation-wide survey on pediatric continuous ambulatory peritoneal dialysis was conducted to find the cause of death or termination of dialysis. METHODS: All children, younger than 14 years old, treated by continuous ambulatory peritoneal dialysis in nine main pediatric nephrology wards in Iran between 1993 and 2006 were included in this historical cohort study. Patient and technique survival rates were determined. Kaplan-Mayer and Cox-regression analysis were used to compare the survival. 2 x 2 table was used to calculate the risk ratio. A P<0.05 was considered significant. RESULTS: One hundred twenty children with a mean age of 47.6 months were on continuous ambulatory peritoneal dialysis. The most frequent cause of renal failure was hereditary-metabolic-cystic disease. One hundred eighty-two peritoneal dialysis catheters were inserted surgically. The median first catheter exchange was 0.74 year (95%CI: 0.5 - 0.98). The most frequent cause of catheter replacement was catheter outflow failure due to displacement, adhesion, and infection (persistent peritonitis or tunnel infection). The mean patient survival was 1.22 years (95%CI: 0.91 - 1.53). The mortality rate was 55% before 1997, and 60% between 1998 and 2001, which declined to 23% after 2002 (P<0.05). Young age (<24 months) was the only independent factor that predicted mortality (P<0.05). The outcome of children was as follows: recovery of renal function (6.7%), renal transplantation (8.3%), switch to hemodialysis (16.7%), still on continuous ambulatory peritoneal dialysis (23.3%), death (43.3%), and lost to follow-up (1.7%). CONCLUSION: The mortality is still high among Iranian children on peritoneal dialysis. Young age is the most important factor influencing on survival and mortality.

Schimke immuno-osseous dysplasia.

Schimke immuno-osseous dysplasia SIOD is a rare autosomal recessive disorder characterized by steroid resistant nephrotic syndrome, immune deficiency, and osseous dysplasia. SW/SNF2 related, matrix associated, actin dependent regulator of chromatin, subfamily a-like 1 SMARCAL 1 is the gene responsible for SIOD but the underlying pathophysiologic mechanism is unclear, therefore, there is limited therapeutic options. To our best knowledge, less then 50 cases of SIOD have been published and we report 2 more cases with typical clinical and laboratory features from South of Iran. It is emphasized that this disorder should be considered in children with steroid resistant nephrotic syndrome and bone dysplasia.