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.

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.

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.

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.

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.

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.

Blood pressure screening in school-aged children in Tehran.

INTRODUCTION: Hypertension is one of the most common diseases in the world and a major risk factor for cardiovascular, renal, and neurologic diseases. It seems that hypertension and overweight in children are a growing epidemic. The aim of this study was to investigate the prevalence of hypertension in school-aged children in Tehran. MATERIALS AND METHODS: In a cross-sectional study, blood pressure and anthropometric measurements were performed on school-aged children in Tehran from 2008 to 2009. Children aged 7 to 11 years from 5 public schools in Tehran were included. Blood pressure, weight, and height measurement were performed at the school. At each screening, 3 seated blood pressure, weight, and height measurements were made and at least after 3 minutes of rest and choosing proper cuff, blood pressure was measured by a pediatric nephrologist and a pediatric assistant. RESULTS: A total of 425 school-aged children were included. Twenty-four percent of the primary school children had hypertension and 12% were shown to be overweight. Hypertension was more common in students of the north of Tehran in comparison to other geographic parts of Tehran. There was a significant difference in the prevalence of hypertension between girl students of north of Tehran and girls of the other parts of Tehran. CONCLUSIONS: We concluded that hypertension is a common problem in school-aged children. Our study re-emphasized the need for prevention and control of high blood pressure in children to manage the global diseases burden due to hypertension.

Technetium Tc 99m dimercaptosuccinic acid renal scintigraphy in children with acute pyelonephritis: correlation with other imaging tests.

INTRODUCTION. Urinary tract infection is the most common serious bacterial infection in children. The aim of this study was to compare the value of different laboratory and imaging techniques in detecting renal involvement in acute pyelonephritis. MATERIALS AND METHODS. In a cross-sectional study of patients 1 month to 14 years of age diagnosed with urinary tract infection were examined with systemic inflammatory markers, renal ultrasonography, voiding cystourethrography (VCUG), and technetium Tc 99m dimercaptosuccinic acid ((99m)Tc-DMSA) renal scintigraphy. A total of 1467 pediatric patients were eligible for treatment of pyelonephritis. Evaluations included a complete blood count, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), urinalysis, urine culture, and measurement of serum blood urea nitrogen and creatinine levels. RESULTS. The results of (99m)Tc-DMSA scans were normal in 20.2%, mild decreased cortical uptake in 45.0%, moderate decreased cortical uptake in 12.3%, severe decreased cortical uptake in 12.0%, and decreased cortical function plus irregularity or scar formation in 10.5%. Voiding cystourethrography showed vesicoureteral reflux in 25.9%. The sensitivity of (99m)Tc-DMSA for prediction of vesicoureteral reflux was 84.1% with a negative predictive value of 80.6%. Significant differences were found in the level of blood leukocyte count (P = .03), urine leukocyte count (P = .003), ESR (P = .008), and age (P = .04) between patients with normal and abnormal (99m)Tc-DMSA scan results. CONCLUSIONS. We found that in patient with clinical signs of pyelonephritis, (99m)Tc-DMSA renal scintigraphy can detect pyelonephritis more accurately than the other inflammatory and imaging tests.

Diagnostic potential of urinary tumor necrosis factor-alpha in children with acute pyelonephritis.

INTRODUCTION: Tumor necrosis factor-alpha (TNF-alpha) is an important mediator of the inflammatory response in serious bacterial infections. The aim of this study was to evaluate the potential of urinary TNF-alpha for diagnosis of acute pyelonephritis in children. MATERIALS AND METHODS: This study was conducted from March 2006 to December 2007 on children with confirmed diagnosis of acute pyelonephritis. They all had positive renal scintigraphy scans for pyelonephritis and leukocyturia. The ratios of urinary TNF-alpha to urine creatinine level were determined and compared in patients before and after antibiotic therapy. RESULTS: Eighty-two children (13 boys and 69 girls) with acute pyelonephritis were evaluated. The mean pretreatment ratio of urinary TNF-alpha to urinary creatinine level was higher than that 3 days after starting on empirical treatment (P = .03). The sensitivity of this parameter was 91% for diagnosis of acute pyelonephritis when compared with demercaptosuccinic acid renal scintigraphy as gold standard. CONCLUSIONS: Based on our findings in children, the level of urinary TNF-alpha-creatinine ratio is acute increased in pyelonephritis and it decreases after appropriate therapy with a high sensitivity for early diagnosis of the disease. Further research is warranted for shedding light on the potential diagnostic role of urinary TNF-alpha in pyelonephritis 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.

Urinary interleukin-8 in acute pyelonephritis of children: a before-after study.

INTRODUCTION: The aim of this study was to assess urinary interleukin-8 (IL-8) levels in pyelonephritis and its relation with the clinical course of the infection and of inflammatory changes detected by renal scintigraphy. MATERIALS AND METHODS: In this quasi-experimental before-after study, we evaluated 91 children aged 1 to 144 months (mean 34.4 +/- 35.2 months) with pyelonephritis. Inflammatory markers including erythrocyte sedimentation rate, C-reactive protein, leukocyte count, and urinary IL-8, together with the results of ultrasonography, voiding cystourethrography, and dimercaptosuccinic acid renal scintigraphy were evaluated in these children. The ratios of urinary IL-8 to creatinine (IL-8/C) before and after the treatment were compared with each other. RESULTS: Urinary IL-8/C levels were significantly higher after the empirical treatment in comparison with those before the treatment (0.19 +/- 0.21 versus 0.51 +/- 0.53, P < .001). No correlation was found between the urinary IL-8 levels and leukocyturia, urine culture results, other inflammatory markers, or findings of imaging examinations. CONCLUSIONS: We found high urinary IL-8 levels in children with pyelonephritis. We also documented its increasing after the treatment. We conclude that evaluation of urinary IL-8 can be a noninvasive test for diagnosis of upper urinary tract infection and its response to treatment.

Ceftriaxone associated nephrolithiasis: a prospective study in 284 children.

Urinary tract calculi have been reported to account for between 1 in 1,000 and 1 in 7,600 hospital admissions in children in the USA. The annual incidence of urolithiasis in patients older than 10 years is 109 per 100,000 of the population in men and 36 per 100,000 of the population in women in Minnesota. The use of various medications is considered to be one of the etiologic factors of nephrolithiasis. Ceftriaxone is a widely used third-generation cephalosporin that is generally considered very safe, but complications such as biliary pseudolithiasis, and rarely, nephrolithiasis have been reported in children. There is limited information about urolithiasis as a side effect of ceftriaxone. The aim of this study was evaluation of the incidence of nephrolithiasis following ceftriaxone therapy in children. This quasi-experimental before and after study was conducted in Mofid Children's Hospital between 2003 and 2005. All patients were treated with 75 mg/kg intravenous ceftriaxone. Diagnosis of pyelonephritis was based on standard criteria. The first renal ultrasonography was performed on the first or second day of admission and was repeated on the last day of treatment. We also evaluated complicated patients for the third time with renal ultrasonography 3 months after treatment. Stone-forming patients underwent metabolic kidney stone risk factor evaluation. We evaluated 284 patients with pyelonephritis, 185 girls and 99 boys. The first ultrasonography was normal in all of our patients. On the second ultrasonography renal stones were reported in 4 out of 284 cases (1.4% and CI=0.96-1.83%). Underlying metabolic risk factors could not be identified in stone-forming patients. Follow-up ultrasonography 3 months later was normal. The results of our study suggest that ceftriaxone-treated patients may be at an increased risk of kidney stone formation. Stones passed spontaneously in all affected patients so the use of this effective drug can be safely continued. Close monitoring of ceftriaxone-treated patients with regard to kidney stone formation is recommended.