Vitamin D deficiency in patients with cystic fibrosis: a systematic review and meta-analysis.

AIM: Vitamin D is a prominent modulator of immunity and respiratory function. It plays a vital role in respiratory diseases such as cystic fibrosis (CF). S. However, there is a dearth of information on patients with CF. The purpose of the meta-analysis is to highlight the importance of following the existing guidelines regarding maintenance of Vitamin D serum levels in patients with CF. METHODS: The systematic search was conducted without utilizing any time or language limitations in original database from the beginning until March 2022. The meta-analysis was performed using a random-effects model. Heterogeneity was determined by I2 statistics and Cochrane Q test. RESULTS: Pooled analysis using the random-effects model of the 8 case-control studies with 13 effect sizes revealed that the serum 25-OH-vitamin D in participants with cystic fibrosis was significantly lower than controls in pediatrics and adolescences (WMD: - 3.41 ng/ml, 95% CI - 5.02, - 1.80, p = < 0.001) and adults (WMD: - 2.60 ng/ml, 95% CI - 4.32, - 0.89, p = 0.003). Based on data from 12 studies (21 effect sizes) with a total of 1622 participants, the prevalence of vitamin D levels of 20-30 ng/ml in CF patients was 36% among pediatrics/adolescents and 63% among adults. In addition, 27% of pediatric/adolescent CF patients and 35% of adult CF patients had vitamin D levels of below 20 ng/ml. CONCLUSIONS: As a result, according to the existing guidelines, our results proved the need to pay attention to the level of vitamin D in these patients.

Inborn errors of immunity with kidney and urinary tract disorders: a review.

Human inborn errors of immunity (IEIs), previously referred to as primary immunodeficiency disorders (PIDs), are a heterogeneous spectrum of inherited abnormalities of the immune system with different organ involvement. The number of identified IEIs is rapidly increasing, highlighting the non-negligible role of an interdisciplinary approach in clinical diagnosis. Kidney disorders are one of the important comorbidities in some of the affected patients and play a significant role in the diagnosis and course of disease. According to recent studies, 22 types of human IEI with renal manifestations have been identified so far, including immunodeficiency with congenital thrombocytopenia, thymic defects with additional congenital anomalies, complement deficiencies, type 1 interferonopathies, immunity related to non-hematopoietic tissues, congenital neutropenia's, common variable immunodeficiency disorder (CVID) phenotype and immuno-osseous dysplasia. Based on this classification, we herein review IEIs with renal features and explain the genetic defect, inheritance, and type of renal manifestations.

General Principles of Vaccination of Pediatric Candidates of Kidney Transplant in Iran.

Pediatric organ transplantation, specifically kidney transplant, has improved considerably in recent decades in Iran. Since infections are the most common cause of morbidity and mortality among transplanted children, pre-transplant vaccination is an effective preventive tool in this regard. In addition, administration of some vaccines is contraindicated in post- transplant period and the efficacy and immunogenicity of authorized vaccines may also be suboptimal in comparison to normal population. Therefore, pre-transplant period offers an outstanding chance to boost the immunization of this population. With regard to this population, it is imperative to establish a localized vaccination guideline, which can be used by nephrologists and other clinicians who are part of the transplant team, in Iran. Currently, such a local guideline for Iranian pediatric kidney transplant candidates is not available. The aim of this study is to provide a comprehensive overview of the existing vaccines recommended for these cases regarding the Expanded Program on Immunization (EPI) and available vaccines in Iran. In addition, general principles of vaccination, the use of specific vaccines as well as accelerated vaccination in this population are discussed in this article. This review could be a preliminary guide for preparing a comprehensive guideline for vaccination of this population in Iran.  DOI: 10.52547/ijkd.7660.

A Systematic Review and Meta-analysis of Rituximab-Associated Infections Among Children and Adolescents With Glomerular Disease: Focus on the Risk of Infections.

OBJECTIVE: This systematic review and meta-analysis aimed to explore rituximab (RTX) associated infectious complications in children with glomerular disease. METHODS: We performed an electronic search of PubMed, International Scientific Information (ISI), Scopus, and EMBASE between January 2010 and July 2021. Infection rates and total drug-related adverse events were the outcomes. Statistical heterogeneity was evaluated by using the I2 statistic. When there was statistical evidence of heterogeneity (I2 > 50%, p > 0.1), a random-effect model was adopted. Data analysis was performed with Stata17.0 software. RESULTS: A total of 7 studies with 668 patients (136 with lupus nephritis [LN] and 532 with nephrotic syndrome were included in the meta-analysis. The pooled risk ratio showed that the administration of RTX was significantly associated with lower risk of infectious complications in patients with LN and nephrotic syndrome (0.72 [95% CI 0.58, 0.85]) when compared with population data of patients without glomerular disease (p = 0.2). There was no significant difference between the LN and nephrotic syndrome groups in terms of total serious adverse events or the occurrence of infections. There was significant heterogeneity among the reported studies (Q = 42.39, p < 0.001, I2 = 81%). CONCLUSION: Administration of RTX in children with glomerular disease is associated with a lower rate of infections when compared with population data of patients without LN or nephrotic syndrome. Additional high-quality randomized controlled trials with long-term follow-up are needed to identify the long-term potential complications. Trial registration PROPERO ID: CRD42021274869 (https://www.crd.york.ac/prospero/display_record.php?).

Food allergy masquerading as persistent proteinuria in post-infectious glomerulonephritis: a case report.

BACKGROUND: Post-infectious glomerulonephritis (PIGN) is one of the most common causes of pediatric acute glomerulonephritis. Immune system dysregulation manifesting as food allergy may predispose PIGN patients to nephrotic-range proteinuria. CASE PRESENTATION: The patient was a 3-year-old male that presented with edema, gross hematuria and reduced urine output following a mild fever, rhinorrhea and lethargy. Due to the persistence of proteinuria and hematuria, he underwent a kidney biopsy. The patient was diagnosed with atypical PIGN and was placed on oral prednisolone. During treatment, a relationship between the consumption of dairy products and the degree of proteinuria was noted. The clinical manifestations and urinalysis indices improved upon steroid discontinuation and initiation of a hypoallergic diet. CONCLUSION: The association between the degree of proteinuria and consumption of dairy products in this PIGN patient led to the identification of food allergy as an underlying factor for nephrotic-range proteinuria.

Intestinal hypomagnesemia in an Iranian patient with a novel TRPM6 variant: a case report and review of the literature.

TRPM6 is predominantly expressed in the kidney and colon and encodes a protein containing an ion channel domain and a protein kinase domain. It is crucial for magnesium homeostasis and plays important roles in epithelial magnesium transport and the active magnesium absorption. In this study, we present a 70-day-old Iranian female patient from consanguineous parents with hypomagnesemia and secondary hypocalcemia. She presented with seizures 19 days after birth and refractory watery non-bloody diarrhea. She consequently had failure to thrive. Other features included hypotonia, wide anterior fontanel, ventriculomegaly, and pseudotumor cerebri following administration of nalidixic acid. She had severe hypomagnesemia and hypocalcemia which were treated with magnesium and calcium supplementation. Despite initial unstable response to supplemental magnesium, she eventually improved and the diarrhea discontinued. The patient was discharged by magnesium and calcium therapy. At the last follow-up at age 2.5 years, the patient remained well without any recurrence or complication. Genetic testing by whole-exome sequencing revealed a novel homozygous frameshift insertion-deletion (indel) variant in exon 26 of the TRPM6 gene, c.3693-3699del GCAAGAG ins CTGCTGTTGACATCTGCT, p.L1231Ffs*36. Segregation analysis revealed the TRPM6 heterozygous variant in both parents. Patients with biallelic TRPM6 pathogenic variants typically exhibit hypomagnesemia with secondary hypocalcemia and present with neurologic manifestations including seizures. In some patients, this is also complicated by chronic diarrhea and failure to thrive. Long-term complications are rare and most of the patients show a good prognosis with supplemental magnesium therapy.

Acute Kidney Injury in Pediatric Patients with COVID-19; Clinical Features and Outcome.

INTRODUCTION: Renal disorders have been reported as the underlying cause as well as complications of critical COVID-19 in pediatric patients. The purpose of this study was to investigate the pattern of kidney involvement, particularly acute kidney injury (AKI), among pediatric patients with COVID-19. METHODS: In this prospective study, hospitalized pediatric patients with a clinical diagnosis of COVID-19 were enrolled. Demographic, clinical, and laboratory findings were collected and analyzed using a mixed method of qualitative and quantitative approaches and descriptive statistics. RESULTS: One hundred and eighty-seven patients, including 120 (64.2%) males and 67 (35.8%) females with COVID-19 with a median age (interquartile range) of 60 (24 to 114) months were enrolled in this study. Most patients (n = 108, 58.1%) had one or two underlying comorbidities, mainly malnutrition (77.4%), neurologic/learning disorders (21.4%), and malignancy (10.2%). According to the Kidney Disease Improving Global Outcomes (KDIGO) classification, AKI was detected in 38.5% of patients (stage 1: 55.6%, stage 2: 36.1%, and stage 3: 8.3%) at presentation or during hospitalization. Nine patients (4.8%) required hemodialysis and 16 (8.6%) eventually died. There was no significant association between AKI and admission to the pediatric intensive care unit (PICU) (P > .05), a multisystem inflammatory syndrome in children (MIS-C) (P > .05), comorbidities (P > .05), and mortality rate (P > .05). CONCLUSION: Kidneys are among the major organs affected by COVID-19. Although kidney abnormalities resolve in the majority of pediatric COVID-19 infections, particular attention should be paid to serum creatinine and electrolyte levels in patients affected by COVID-19, particularly children with a history of malnutrition and kidney disorders.  DOI: 10.52547/ijkd.7151.

Clinical Outcomes of 141 Cases of Isolated Antenatal Hydronephrosis; An Observational Study.

INTRODUCTION: Hydronephrosis, a condition that is mostly congenital, is considered as the most common type of pediatric urinary tract disorder. The aim of this study was the evaluation of the prognosis and outcomes of hydronephrosis in cases of congenital hydronephrosis. METHODS: In a cross-sectional study, run in a tertiary clinic of pediatric nephrology, from 2015 to 2020, patients with fetal hydronephrosis were selected. Ultrasonography, urinalysis and kidney function tests were ordered for all patients and in the presence of hydronephrosis, repeated ultrasonography, voiding cystourethrography and dimercaptosuccinic acid scan were performed. In cases with evidence of obstruction, a diethylenetriamine pentaacetic acid scan and relative surgical procedures were performed. RESULTS: Among 141 cases, mean age was 8 ± 1.4 years and 80.9% were male. Partial or complete obstruction in the right and left kidney was found in 16.3 and 24.8% of patients, respectively. The degree of hydronephrosis was mild in 46.1%, moderate in 39%, and severe in 9.2% of the patients. At the last follow-up period, hydronephrosis recovered in 46% of the patients, while 54% experienced persistence or exacerbation of the disease. Meanwhile, 7.1% of patients showed neurogenic bladder, 19.1% urinary tract infection and 22.7% urinary stones. CONCLUSION: Our study revealed that fetal hydronephrosis ends in complete recovery following birth in 46% of the cases. However, in cases experiencing persistent or exacerbating hydronephrosis, optimized treatment and/or surgical intervention are required.  DOI: 10.52547/ijkd.6516.

Clinical Efficacy of Persian Medicine Diet Combined with Western Medicine-Based Diet on Proteinuria in Pediatric Nephrotic Syndrome: A Randomized Controlled Clinical Trial.

Introduction: Nephrotic syndrome (NS) is a common chronic kidney disorder during childhood. The most important characteristic of this disease is proteinuria. The Persian medicine (PM) has important dietary recommendations for strengthening the kidney function and treatment of this disease. The aim of this study was to investigate the effect of a diet including PM recommendations and general principles of Western medicine. Materials and Methods: Twenty children with nephrotic syndrome were randomly divided into intervention and control groups and monitored for one month. The control group received a diet based on the general principles of Western medicine. In the intervention group, in addition to the Western medicine diet, dietary recommendations of PM were also prescribed including the pomegranate (Cydonia oblonga mill.), quince (Cydonia oblonga mill.), and whole grains (wheat and barley). A 24-hour dietary questionnaire was applied and anthropometric and biochemical indices including spot urine protein (proteinuria), albumin (Alb), urea, creatinine (Cr), total cholesterol (TC), and triglyceride (TG) were measured before and after the study. Results: The amount of protein intake reduced significantly in the diet of both groups but the differences between the two groups were not significant. Proteinuria reduced significantly in both the Western and PM groups; however, proteinuria was significantly lower in the Persian medicine group compared to the control group. TC and Cr levels reduced significantly in the intervention group, although the changes were not significant compared to the control group. Conclusion: The results of this study showed that adding dietary recommendations of the Persian medicine to the general rules of the Western medicine diet reduced proteinuria and improved the combat against nephrotic syndrome.

Exacerbation of Congenital Hydronephrosis as the First Presentation of COVID-19 Infection in Children.

Background: Congenital hydronephrosis is one of the most common abnormalities of the upper urinary tract, which can be exacerbated by a variety of intrinsic or extrinsic triggers. The urinary tract system is one of the major organs complicated by COVID-19 infection. Case Presentations. Here, we report five patients with an established diagnosis of congenital hydronephrosis, who presented with acute abdominal pain and fever and an abrupt increase in the anteroposterior pelvic diameter (APD). Patients had a previous stable course and were under regular follow-up with serial ultrasonographic studies. They underwent surgery or supportive treatment due to the later exacerbation of hydronephrosis. Based on the clinical and imaging findings, no plausible etiologies for these exacerbation episodes, including infection, nephrolithiasis, or abdominal masses, could be postulated. The common aspect in all these patients was the evidence of a COVID-19 infection. Conclusions: Infection with COVID-19 in children with antenatal hydronephrosis may exacerbate the degree of hydronephrosis and renal APD in ultrasonography, which itself may be mediated by the increase in inflammatory mediators.

Prevalence of reflux nephropathy in Iranian children with solitary kidney: results of a multi-center study.

BACKGROUND: Given the importance of the function of the remnant kidney in children with unilateral renal agenesis and the significance of timely diagnosis and treatment of reflux nephropathy to prevent further damage to the remaining kidney, we aimed to determine the prevalence of reflux nephropathy in this subgroup of pediatric patients. METHODS: In general, 274 children referred to pediatric nephrologists in different parts of Iran were evaluated, of whom 199 had solitary kidney and were included in this cross-sectional study. The reasons for referral included urinary tract infection (UTI), abnormal renal ultrasonography, being symptomatic, and incidental screening. Demographic characteristics, including age and gender were recorded. History of UTI and presence of vesicoureteral reflux (VUR) were evaluated. RESULTS: Of the 274 children evaluated in this study with the mean age (SD) of 4.71 (4.24) years, 199 (72.6%) had solitary kidney. Among these, 118 (59.3%) were male and 81 (60.7%) were female, 21.1% had a history of UTI, and VUR was present in 23.1%. The most common cause of referral was abnormal renal ultrasonography (40.2%), followed by incidental screening (21.1%), being symptomatic (14.1%), and UTI (5.5%). In 116 children (58.3%), the right kidneys and in 83 (41.7%) the left kidneys were absent. Besides, 14.6% of the participants had consanguineous parents and 3% had a family history of solitary kidney. Upon DMSA scan, the single kidney was scarred in 13.1%, of which only 7.5% were associated with VUR. In addition, proteinuria and hematuria were observed in 6.5% and 1.5% of children, respectively. CONCLUSIONS: The prevalence of reflux nephropathy was 7.5% in children with solitary kidney with a male predominance. Given the relatively high prevalence of reflux nephropathy in these children, screening for VUR in the remnant kidney appears to be essential in this population.

A Report of Two Patients with Food Protein-induced Enterocolitis Mimicking Bartter Syndrome.

Food protein-induced enterocolitis syndrome (FPIES), is a non-IgE mediated food allergy presenting in infants younger than 12 months. Diagnostic delay may occur due to overlapping clinical symptoms with several conditions. Here, we present two cases of FPIES, mistakenly diagnosed and treated as Bartter syndrome. This study aims to emphasize the several features of this syndrome that may mimic other diagnoses and sometimes leading to near-death events due to delay in the diagnosis and improper treatment. The first patient was a 30-month-old boy with multiple episodes of profuse vomiting and diarrhea within 1 hour after breastfeeding, beginning from the first month of life progressing to hypokalemia and metabolic alkalosis at the age of 5 months leading to the diagnosis of Bartter syndrome. The second patient had a history of unremitting diarrhea which had been started soon after his first breastfeeding followed by biliary vomiting on the 7th day of life. He was treated in another hospital for neonatal sepsis, however, without an appropriate response to treatment. To conclude, despite the current belief on the rarity of FPIES, it is a more prevalent disease than expected with various non-specific manifestations imitating other conditions which may result in diagnostic delay and sometimes fatalities. To shed light on the importance of the physicians' awareness of this syndrome, these two cases are presented here as examples of FPIES imitating other disorders.

Leukocytoclastic vasculitis in patients with IL12B or IL12RB1 deficiency: case report and review of the literature.

BACKGROUND: Mendelian susceptibility to mycobacterial disease (MSMD) is an inborn error of immunity, resulting in susceptibility to weakly virulent mycobacteria and other intramacrophagic pathogens. Rheumatologic manifestations and vasculitis are considered rare manifestations in MSMD patients. CASE PRESENTATION: In this study, we reported a 20-year-old female who was presented with recurrent lymphadenitis following bacillus Calmette-Guérin (BCG) vaccination and a history of recurrent disseminated rash diagnosed as leukocytoclastic vasculitis (LCV). A slight reduction in lymphocyte subsets including CD4+, CD19+, and CD 16 + 56 T-cell count, as well as an elevation in immunoglobulins level (IgG, IgA, IgM, IgE), were observed in the patient. Whole exome sequencing revealed a homozygous Indel-frameshift mutation, c.527_528delCT (p. S176Cfs*12), at the exon 5 of the IL12B gene. She experienced symptom resolution after treatment with anti-mycobacterial agents and subcutaneous IFN-γ. We conducted a manual literature search for MSMD patients reported with vasculitis in PubMed, Web of Science, and Scopus databases. A total of 18 MSMD patients were found to be affected by a variety of vasculitis phenotypes mainly including LCV and Henoch-Schönlein purpura (HSP) with often skin involvement. Patients were all involved with vasculitis at the median age of 6.8 (2.6-7.7) years, nearly 6.1 years after the initial presentations. Sixteen patients (88.9%) had IL12RB1 defects and concurrent Salmonella infection was reported in 15 (88.2%) patients. CONCLUSION: The lack of IL-12 and IL-23 signaling/activity/function and salmonella infection may be triggering factors for the development of leukocytoclastic vasculitis. IL12B or IL12RB1 deficiency and salmonellosis should be considered in MSMD patients with vasculitis.

Novel Urinary Biomarkers for Diagnosis of Acute Pyelonephritis in Children.

Urinary tract infection (UTI) is common among pediatric population. Pyelonephritis, especially in young infants, is associated with a significant morbidity. Usually, clinical manifestations, laboratory findings, and imaging are used to differentiate between lower and upper UTI. Lack of specific clinical findings and commonly used nonspecific blood indices are important hamper differentiation between lower and upper UTI in early stages. Imaging techniques are neither cost benefit nor safe for detection of UTI. Recent efforts have focused on characterization of novel serum and urinary biomarkers for early detection of acute pyelonephritis in children. It seems that urinary NGAL, NAG, TNF-α and IL-8 may be used as novel markers for early diagnosis of acute pyelonephritis in children.

Serum and Urine Leptin Concentrations in Children Before and After Treatment of Urinary Tract Infection.

INTRODUCTION: Urinary tract infection (UTI) among children is sometimes associated with anorexia and sometimes failure to thrive. Appetite-regulating hormones may be a causative factor. Leptin regulates appetite, food intake, and body weight via hypothalamic melanocortin-4 receptor. Leptin is also a potential cytokine for inflammation. The aim of this study was to evaluate serum and urine leptin before and after treatment of children with UTI. MATERIALS AND METHODS: In this before-after study, serum and urine leptin were measured in 40 patients with UTI at admission and 5 days after treatment. Pyelonephritis was suggested by signs and symptoms and confirmed with positive urine culture and dimercaptosuccinic acid renal scintigraphy. Other measurements included urinalysis, urine culture, urine creatinine level, complete blood count, erythrocyte sedimentation rate, C-reactive protein level and serum levels of urea, creatinine, glucose, cholesterol, and triglyceride. RESULTS: The mean serum leptin level was 6.85 ± 18.90 ng/mL before the treatment and 8.29 ± 18.30 ng/mL after the treatment, the difference of which was not significant (P = .64). There were significant correlations between serum leptin and age, weight, and C-reactive protein. Urine leptin levels were reduced significantly from 0.75 ± 0.82 ng/mL to 0.46 ± 0.27 ng/mL after the treatment (P = .03). A significant correlation was observed between urine leptin level with age and weight. CONCLUSIONS: Serum leptin level did not change significantly after treatment of UTI, but urine leptin significantly decreased. Serum leptin level was higher in patients with anorexia in comparison with children with normal appetite; however, the difference was not significant.

Tuberous sclerosis presenting with acute kidney failure, pyelonephritis, and polycystic kidney disease.

Tuberous sclerosis complex (TSC) is a multisystemic inherited autosomal dominant disease characterized by the development of hamartomas in the brain and kidneys. In about 2% of patients, polycystic kidney disease is present, which may result in different stages of renal insufficiency. Acute kidney failure has not been reported in infants with TSC. We report a female infant with TSC who was admitted to hospital with pyelonephritis, acute kidney injury, and polycystic kidney disease.

Diagnostic accuracy of renal pelvic dilatation in determining outcome of congenital hydronephrosis.

INTRODUCTIONS: The widespread use of prenatal ultrasonography results in increased recognition of congenital hydronephrosis, a therapeutic and diagnostic challenge. This study was conducted to investigate the natural course of prenatal hydronephrosis and the accuracy of postnatal APD in determining the outcome. MATERIALS AND METHODS: All newborns with prenatal hydronephrosis were followed up by ultrasonography after birth. Voiding cystoureterography, diethylene triaamine pentaacetic acid renal scintigraphy, and dimercaptosuccinic acid renal scintigraphy were done if indicated. The receiver operating characteristic curve was plotted to determine the best cutoff for the anterior-posterior pelvic diameter (APD) to distinguish surgical from spontaneously resolving group. RESULTS: Of 178 neonates, 42 (23%) required surgery. The area under the curve for APD to predict the need for surgery was 0.925 with an APD cutoff of 15 mm. The diagnostic value of APD for determining the need for surgery was determined by sensitivity and specificity of 95.2% and 73.5%, respectively. CONCLUSIONS: Postnatal APD on ultrasonography has a valuable diagnostic accuracy for requiring surgery and provides a useful guide for parental counseling.