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?).

Validity of the Adrogué-Madias Formula for the Management of Acute Dysnatremias in Critically Ill Children: A Prospective Multicenter Analysis.

OBJECTIVE: Current conventional formulas do not predict the expected changes in serum sodium after administration of various fluids to correct serum sodium abnormalities. The Adrogué-Madias formula is currently the preferred and widely used fluid prescription for adult patients with dysnatremias, but its therapeutic efficacy has not been validated in pediatric patients. METHODS: In this prospective study, we used the Adrogué-Madias formula for calculating the appropriate rate of various fluids administration to correct serum sodium abnormalities in 7 critically ill children with acute dysnatremias. RESULTS: After administration of various intravenous fluids using the Adrogué-Madias formula, the anticipated as well as the achieved sodium concentrations were almost similar. CONCLUSIONS: This study demonstrates that the use of the Adrogué-Madias quantitative formula allows to calculate the appropriate rate of administration of various fluids. The calculated fluid administration resulted in the subsequent actual laboratory values and clinical changes.

Revisiting the Management of Pediatric Kidney Transplants, A Multicenter Analysis

The newest Kidney Disease Improving Global Outcomes (KDIGO) guideline recommendations were investigated mainly for the care of adult kidney transplant recipients, but no guideline exists for the management of pediatric transplant recipients. This review provides update recommendations in the management of pediatric kidney transplantation. Four electronic databases, PubMed, EMBASE, Google Scholar, and Web of Science were searched systematically for the last two decades, using Mesh terms in English language. The Grades of Recommendation Assessment, Development, and Evaluation (GRADE) approach was used for grading the quality of the overall evidence and the strength of recommendations for each outcome across the studies. The overall quality of evidence categorized as high (A), moderate (B), low (C), or poor (D). The strength of a recommendation was determined as level 1 (recommended) or level 2 (suggested). The ungraded statements were determined on the basis of common sense to provide general advice. Of the 317 citations which were screened for the evidence review, 62 were included in data extraction. The included studies were randomized controlled trials, prospective cohorts and cross-sectional, descriptive, and review studies. Of the 115 statements, 56 (48.6%) were graded 1 (we recommend), 34 (29.5%) were graded 2 (we suggest), and 25 (21.7%) were ungraded statements. Altogether, only 22 (19.1%) of recommendations reached the "A" or "B" levels of quality of evidence. The pediatric kidney transplant recipients are different from adult recipients regarding the primary kidney diseases, surgical techniques, drug metabolism, adherence to medications, growth and neurocognitive development and immunization needs prior to transplantation.  DOI: 10.52547/ijkd.7179.

Randomized controlled trial to compare safety and efficacy of mycophenolate vs. cyclosporine after rituximab in children with steroid-resistant nephrotic syndrome.

OBJECTIVE: The comparative safety and efficacy of maintenance mycophenolate mofetil (MMF) and cyclosporine (CYC) following rituximab (RTX) in children with steroid-resistance nephrotic syndrome are uncertain. STUDY DESIGN AND SETTING: Multicenter randomized controlled trial. PATIENTS: Sixty-six children between 2 and 6 years of age with SRNS. INTERVENTIONS: Patients were randomized to receive either MMF 1000 mg/m2 /day (n = 32) or CYC 5 mg/kg/day (n = 34) for 12 months following RTX induction therapy (375 mg/m2 ) given as needed for B-cell count. MAIN OUTCOMES: Complete remission and adverse events (AEs). RESULTS: Complete remission was observed in 26 patients (83.1%) in the MMF group compared with 21 patients (61.7%) in the CYC group (p = 0.02). The median time to remission was shorter in the MMF group than in the CYC group (2.64 vs. 3.4 months; hazard ratio [HR], 0.61; 95% CI, 0.74-0.90, p = 0.03). The median time to first relapse was longer in the MMF group compared with the CYC group (10.8 vs. 8.0 months; HR, 1.12; 95% CI, 1.31-1.54, p = 0.01), and this was significantly correlated with the median time to B-cell recovery in the two groups (8.6 vs. 5.2 months in MMF and CYC, respectively, p = 0.02). The overall incidence of adverse drug events was lower in the MMF group compared with the CYC group (59.3% vs. 76.4%, p = 0.03). CONCLUSIONS: MMF-RTX is superior to CYC-RTX in maintaining remission with fewer AEs in children with initial SRNS. Additional high-quality randomized control trials with long-term follow-up are needed to identify the long-term potential complications.

Electrocardiography is Unreliable to Detect Potential Lethal Hyperkalemia in Patients with Non-dialysis Chronic Kidney Disease.

Hemodialysis patients with hypercalcemia are less likely to manifest the usual electrocardiographic changes associated with hyperkalemia than in those with normal renal function. This study was conducted to determine whether electrocardiography (ECG) is a reliable indicator to detect severe life-threatening hyperkalemia in non-dialysis CKD patients. The study was conducted at three referral university hospitals between July 2017 and June 2018. Severe hyperkalemia was defined as serum potassium concentration ≥ 8.0 mEq/L. Serum potassium, sodium, bicarbonate, calcium, and creatinine concentrations were measured and simultaneous 12-lead ECG was obtained. Patients with end-stage renal disease receiving renal replacement therapy were excluded. Also excluded were patients with the usual ECG abnormalities to hyperkalemia. Of the 438 patients screened, 10 (2.3%) aged 2-14 years with severe hyperkalemia and normal ECG findings were identified. Median serum potassium level was 8.6 mEq/L (range 8.2-9.0). All had regular sinus rhythm. P, QRS, ST segment, T morphology, PR and QT interval, and QRS duration were all normal. Hyperkalemia was associated with CKD, metabolic acidosis, and hypercalcemia in all cases. Therapy with intravenous 0.9% saline, sodium bicarbonate, glucose, insulin, calcium, and salbutamol corrected the hyperkalemia in 7 patients. The remaining three patients evinced arrhythmias requiring hemodialysis. Although rare, non-dialysis CKD patients with hypercalcemia may not manifest the usual electrographic abnormalities associated with hyperkalemia. Thus, a normal ECG finding in non-dialysis CKD patients should be interpreted with caution.

Long-term cardiometabolic consequences among adolescent offspring born to women with type1 diabetes.

AIM: The aim of this study was to compare cardiometabolic measures between adolescents born to women with and without type1diabetes. METHODS: In this cross-sectional study, 103 adolescents (51 males) aged 14-19 years, born to women with type1diabetes were enrolled in the study. Body mass index, blood pressure, urine microalbumin to creatinine ratio, hemoglobin A1c, serum urate, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, and estimated glomerular filtration rate (eGFR) were measured in all. The results were compared with 98 adolescents born to non-diabetic women. RESULTS: In multiple linear regression models, adolescent offspring of women with type 1 diabetes had significantly higher blood pressure (Odds ratio [OR] 2·45; 95% Confidence interval [CI] 2.1-2.8, hypertension (OR 2.52; 95% CI 1.99-3.01), body mass index (OR 2.22; 95% CI: 1.76-2.69), elevated total cholesterol (OR 1.5; 95% CI 0.2-2.9), low-density lipoprotein cholesterol (OR·33; 95% CI 1.06-1.64), triglyceride (OR 1.34; 95% CI: 1.05-1.70), eGFR (OR 0.96 ;95% CI 0.81-1.11) and microlabuminuria (OR 1.1; 95% CI: 0.87-1.12) compared to offspring of women without diabetes. CONCLUSION: The study demonstrates a strong correlation between maternal exposure to type1diabetes and higher risk of developing obesity, hypertension, dyslipidemia, eGFR, and microalbumiuria in the adolescent offspring.

Serum Interleukin-6 and Interleukin-8 are Sensitive Markers for Early Detection of Pyelonephritis and Its Prevention to Progression to Chronic Kidney Disease.

BACKGROUND: Pyelonephritis is the most common bacterial infection in children that can cause renal failure if not diagnosed or treated early. We used serum biomarker interleukins (IL-6 and IL-8) and then confirmed the results by the findings dimercaptosuccinic acid (DMSA) scan to distinguish upper-tract infection from lower-tract infection. METHODS: Serum IL-6 and IL-8 were measured in 57 children with newly diagnosed untreated urinary tract infection (UTI) documented by a positive urine culture. All children had a DMSA to determine whether serum IL6, IL-8 can be used as a marker to predict upper-tract from lower-tract infection. IL-6 and IL8 were determined by the enzyme link immunosorbent assay (ELISA) technique. RESULTS: Of the 57 patients, 24 (42%) had renal parenchymal lesions on the DMSA scan. Patients with abnormal DMSA had significantly higher serum IL-6 and IL-8 compared with those with normal DMSA scan (187.1 ± 113.1 ng/mL vs. 396.1 ± 246.0 ng/mL, P = 0.005; and 165 ± 76.1 ng/mLvs. 190.8 ± 60.8 ng/mL, P = 0.026, respectively). Pyelonephritis was more frequent in children younger than 20 months old (n = 36, 63%, P < 0.005) and more prevalent in girls (n = 36, 63%, P = 0.005). Serum IL-6 had a sensitivity of 67.3% and a specificity of 63.0% and serum IL8 had a sensitivity of 80.1% and a specificity of 73.5% in the differential diagnosis of pyelonephritis and cystitis (P = 0.03). CONCLUSIONS: Serum levels of IL-6 and IL-8 are both sensitive biomarkers of UTI and can discriminate the upper from lower tract urinary infections. Determination of these biomarkers may help to identify patients with acute pyelonephritis and need for DMSA study.

Differentiating syndrome of inappropriate ADH, reset osmostat, cerebral/renal salt wasting using fractional urate excretion.

OBJECTIVES: Clinical and laboratory data of reset osmostat (RO) and cerebral/renal salt wasting (C/RSW) mimic syndrome of inappropriate antidiuretic hormone (SIADH) and can pose diagnostic challenges because of significant overlapping between clinical and laboratory findings. Failure to correctly diagnose hyponatremia may result in increased mortality risk, longer hospital stay, and is cost-effective. We aim to illustrate clinical and laboratory similarities and difference among patients with hyponatremic disorders and discuss the diagnostic value of factional uprate excretion (FEurate) to differentiate SIADH from RO and C/RSW. CASE PRESENTATIONS: We report the use of FEurate in the evaluation of three patients with hyponatremia and elevated urine osmolality in the absence of edema or clinical evidence of dehydration to differentiate SIADH from RO and C/RSW. CONCLUSIONS: Measurement of FEurate may offset in part the diagnostic confusion imparted by the diagnoses of SIADH, RO, and C/RSW.

Adjunctive acetazolamide therapy for the treatment of Bartter syndrome.

PURPOSE: Bartter syndrome is a rare hereditary salt-losing tubulopathy caused by mutations of several genes in the thick ascending limb of Henle's loop, characterized by polyuria, hypokalemic metabolic alkalosis, growth retardation and normal blood pressure. Cyclooxygenase inhibitors, potassium-sparing diuretics and angiotensin-converting enzyme inhibitors are currently used to treat electrolyte derangements, but with poor response. Whether treatment with acetazolamide, a carbonic-anhydrase inhibitor, would result in better clinical outcomes is unknown. METHODS: We randomly assigned children with Bartter syndrome in a 1:1 ratio to either receive indomethacin, enalapril, and spironolactone or indomethacin, enalapril, and spironolactone plus acetazolamide once daily in the morning for 4 weeks. After 2 days of washout, participants crossed over to receive the alternative intervention for 4 weeks. The present study examines the serum bicarbonate lowering effect of acetazolamide as an adjunctive therapy in children with Batter syndrome. RESULTS: Of the 43 patients screened for eligibility, 22 (51%), between the ages 6 and 42 months, were randomized to intervention. Baseline characteristics were similar between the two groups. Addition of acetazolamide for a period of 4 weeks significantly reduced serum bicarbonate and increased serum potassium levels, parallel with a reduction in serum aldosterone and plasma renin concentration. The 24-h urine volume, sodium, potassium, and chloride decreased significantly. CONCLUSION: Our data define a new physiologic and therapeutic role of acetazolamide for the management of children with Bartter syndrome.

Urinary polyomavirus: novel biomarker of congenital ureteropelvic junction obstruction.

BACKGROUND: Pregnancy is associated with reactivation and transmission of latent polyomavirus to fetus. Polyomavirus is also known to cause ureteral stenosis and hydronephrosis. OBJECTIVE: The aim of this study was to investigate whether the urinary polyomavirus could be used as a potential biomarker in newborns with ureteropelvic junction obstruction (UPJO). STUDY DESIGN: Urinary polyomavirus virus was measured by PCR in 42 newborn infants with fetal hydronephrosis history. Random urine samples were obtained from newborns immediately after birth and from their mothers at the time of delivery. Results were compared with 25 healthy infants matched for gestational and postnatal ages. The diagnosis of UPJO was established by diuretic renal scintigraphy. UPJO was graded according to the Society for Fetal Urology (SFU) classification. RESULTS: The urine samples of healthy infants showed no detectable polyomavirus. No statistically significant difference was found in the median urinary polyomavirus level between grade 1 (1000 copies/mL) and grade 2 (1500 copies/mL) UPJO infants. When the median urinary BKV values were compared for each grade of UPJO, patients with grade 3 and 4 had significantly higher urinary polyomavirus levels than those with grades 1 or 2 (P < 0.001). There was a strong correlation between the median polyomavirus in the urine of pregnant women and the urine of newborns with UPJO (P < 0.001). DISCUSSION: Data suggest that routine screening of urinary polyomavirus may help to identify infants with severe obstruction in whom early surgical intervention could reduce the risk of developing progressive kidney disease. To the best of our knowledge this is the first prospective study to present the role of urinary polyomavirus in newborn infants with UPJO to distinguish between patients who would benefit from early surgical intervention. CONCLUSION: Urinary polyomavirus is a potential biomarker of UPJO in newborns with fetal hydronephrosis.

Risk factors analysis for acute kidney injury in the newborn infants: predictive strategies.

INTRODUCTION: Acute kidney injury (AKI) in the newborn infants is associated with increased mortality and morbidity. The purpose of this study was to investigate the prevalence, risk factors and outcome of AKI in the premature neonates. METHODS: Between January 2014 and January 2015, 206 premature neonates between 27 and 36 weeks gestations were studied in the newborn intensive care unit of Amir-AL Momenin Hospital, in Semnan, Iran. All neonates were followed-up for seven days after birth. The diagnosis of AKI was based on urine output (UOP) < 1.5 mL/kg/h for 24 hours and serum creatinine SCr > 0.3 mg/dL or increased by 150% to 200% from baseline value. Data collected included gestational age, gender, birth weight, first, and fifthminutes Apgar scores, use of mechanical ventilation, continuous positive airway pressure (CPAP), sepsis, congenital heart disease, and respiratory distress syndrome (RDS). RESULTS: Gestational age (OR = 12.09, 95% CI = 3.51-41.63; P < .001), the use of mechanical ventilation (OR = 6.72, 95% CI = 1.44-31.41; P < .05), and the first and fifth minutes Apgar scores (OR = 0.65, 95% CI = 0.44-0.95; P < .05) were significantly related with AKI occurrence. Presence of congenital heart disease, sepsis, birth weight and RDS also had a significant relationship with AKI development (P < .05). CONCLUSION: The most important risk factors associated with AKI development were prematurity and low-birth weight, low 1 and 5 minutes Apgar scores, and the need for mechanical ventilation, as well as the coexistent of sepsis.

Simplified Algorithm for Evaluation of Proteinuria in Clinical Practice: How should A Clinician Approach?

BACKGROUND: Proteinuria is a common laboratory finding among children and adolescents. It can be identified as either a transient or a persistent finding and can represent a benign condition or a serious disease. METHODS: Pertinent medical literature for asymptomatic proteinuria in children and adolescents published in English was searched between January 1980 and May 2017 using PubMed, MEDLINE, EMBASE, and Google Scholar research databases. Of the 64 reviewed articles, 24 studies were eligible for inclusion. RESULTS: Random spot urine protein-to-creatinine (PCR) ratio is widely used to reliably detect proteinuria. The normal value for the spot PCR in children aged 2 years or older is less than 0.3. In children aged below 2 years, the PCR can be as high as 0.5. Orthostatic proteinuria is defined as urine PCR greater than 0.3 detected in a urine specimen during the daytime activity but less than 0.3 on the first morning void specimen. PCR above 3.0 signifies heavy proteinuria as seen in nephrotic syndrome. Orthostatic proteinuria is a frequent cause of proteinuria in asymptomatic children and adolescents, which require no specific therapy except for health maintenance follow-up. Pediatric nephrologist referral is indicated when the proteinuria is constant and persists over 6 months or is associated with hematuria, hypertension, or renal dysfunction. CONCLUSIONS: We provide a simplified diagnostic algorithm for evaluation of proteinuria in primary care adolescents who appear well and in whom proteinuria is incidentally discovered during a routine examination.

Renal tubular dysfunction measured by N-acetyl-beta glucosaminidase/Creatinine activity index in children receiving antiepileptic drugs: a randomized controlled trial.

To evaluate renal side-effects of anti-epileptic medication by valproate (VPA) and carbamazepine (CBZ), we performed a prospective study to assess renal tubular function by measuring N-acetyl-ß glucosaminidase (NAG)/Cr activity index in epileptic children. The study was conducted on 112 children who were diagnosed with epilepsy (28 patients were observed before treatment with anti-epileptics, 28 children were administered VPA, 28 children were treated with CBZ, and 28 healthy children were selected age &sex matched for). An especial NAG assay kit was used for quantitative measuring of NAG in patient urine samples. The patients receiving VPA exhibited higher rate of NAG activity compared with the two groups which not receiving anti-epileptic drugs. Measurement of urinary NAG/Cr index in the children who received CBZ also, was significantly higher than those who were not administered anti-epileptic drugs. The measurement of NAG/Cr index in the VPA group was significantly higher than that in the CBZ group (NAG index: 2.75 versus 1.71). Children on anti-epileptic treatment with VPA or CBZ might demonstrate signs of renal tubular dysfunction, reflected by NAG/Cr activity index. This side effect can be potentially more occurred following VPA administration.