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.

Urine anion gap can differentiate respiratory alkalosis from metabolic acidosis in the absence of blood gas results.

INTRODUCTION: Low plasma bicarbonate concentration due to chronic respiratory alkalosis may be misdiagnosed as metabolic acidosis and mistreated with administration of alkali therapy, particularly when arterial blood gas is not available. METHODS: We measured urine anion gap [urine (Na+ + K+ ) - (Cl- )], as a surrogate of renal ammonium excretion in 15 patients presenting with hyperventilation and low serum bicarbonate concentration to distinguish chronic respiratory alkalosis (CRA) from metabolic acidosis (MA) when blood gas was unavailable. RESULTS: Hyperventilation and low serum bicarbonate concentrations were associated with urine pH above 5.5 and positive urine anion gap in all, suggesting CRA. The diagnosis was later confirmed by obtaining capillary blood gas, which showed a decrease in PCO2 and high normal pH values. CONCLUSION: The use of urine anion gap can help to differentiate between chronic respiratory alkalosis and metabolic acidosis, especially when arterial blood gas is not obtained.

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.

Colistin induced acute kidney injury in critically ill children: a prospective study utilizing RIFLE criteria.

BACKGROUND: Colistin is one of the last resort antibiotic options for resistant gram-negative pathogens. Renal injury is the most common side effect of colistin. Characteristics of nephrotoxicity are well described in adults. However, this data is sparse in children. OBJECTIVES: In this study we evaluated the incidence, severity, time course and risk factors of colistin nephrotoxicity in a pediatric population. METHODS: In a prospective study over a 9-month period, children who received intravenous colistin for at least 48 h were evaluated for renal side effect by utilizing Risk-Injury-Failure-Loss-End Stage Kidney Disease (RIFLE) criteria. Children receiving renal replacement therapy (RRT) or received a repeated course of colistin were excluded. RESULTS: Thirty-seven children were included. Median age of participants was 4.5 months. Overall, 48.6% of the cases developed AKI and consisted 56% in the Risk, 33% in the Injury and 11% in the Failure categories of RIFLE criteria. AKI was reversible while colistin continued and no one required RRT. Mean ± SD time to AKI development was 10.94 ± 7.51 days. Multivariate logistic regression analysis demonstrated that total cumulative dose of colistin was an independent predictor of nephrotoxicity (standardized ß = 1.024, P = 0.034). CONCLUSION: AKI is a common side effect of colistin therapy in critically ill children developing in nearly half of recipients. However, with the dosage range utilized in this study, in the majority of children, renal injury seemed to be mild to moderate in nature. Given the limited treatment options available in critically ill children with resistant gram-negative pathogens, colistin remains a marvelous therapeutic option. Further studies are required to fully elucidate the risk factors and clinical pictures of colistin-induced nephrotoxicity.

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.

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.

Validity of anthropometric indices in predicting high blood pressure risk factors in Iranian children and adolescents: CASPIAN-V study.

Anthropometric indices have been used as indicators for predicting hypertension (HTN) in children and adolescents but it is not clear which anthropometric measures are a better index for identifying elevated blood pressure (EBP) risk factors in pediatric population. Body mass index (BMI), waist circumference (WC), weight-height ratio (WHR), a body shape index (ABSI) and blood pressure were measured in 14 008 children and adolescents aged 7-18 years in a national school-aged survey CASPIN V. Hypertension (HTN) was defined according to the 2017 American Academy of Pediatrics guidelines, using the 95th percentile. The predictive power of anthropometric indices for HTN risk factors was examined using receiver operating characteristic (ROC) analyses. Multivariate logistic regression analysis was used to compare areas under ROC curves (AUCs) among the four anthropometric indices. BMI, WC, WHR, and ABSI were significantly higher in adolescents than in children. EBP was more prevalent in boys (7.2%) than girls (5.5%), whereas the prevalence of HTN was higher in girls (11.3%) than boys 10.4%. Prevalence odds ratio was around 2 for BMI, WC, and WHR with AUCs scores of nearly 0.6 to predict EBP in both children and adolescents of both sexes. Thus, the ability of BMI z-score, WC, WHR or ASBI to identify Iranian children and adolescents at higher risk of EBP was week. WC, WHR or ASBI in combination with BMI did not improve predictive power to identify subjects at higher risk of EBP.

Performance of modified blood pressure-to-height ratio for diagnosis of hypertension in children: The CASPIAN-V study.

This study aimed to evaluate the accuracy and performance of modified blood pressure-to-height ratio (MBPHR) for identifying high blood pressure (HBP) in a large population of children. This multicentric cross-sectional study was conducted on a nationally representative sample of 7349 Iranian students aged 7-12 years living in 30 provinces in Iran. High systolic blood pressure and diastolic blood pressure were defined according to the 2017 American Academy of Pediatrics (AAP) guidelines. The BP-to height ratio (BPHR) was calculated as BP (mmHg)/height (cm), MBPHR3 as BP (mmHg)/(height (cm) + 3 (13-age)), and MBPHR7 as BP (mmHg)/(height (cm) + 7 (13-age). The receiver-operating characteristic curve analysis was used to evaluate the performance of these three ratios for identification of HBP in children compared to the 2017 AAP guidelines as the gold standard. Mean age of participants was 12.29 ± 3.15 years and 3736 (50.8%) were girls. The prevalence of HBP was 11.9% (11.5% in boys, 12.3% in girls). The area under the curve (AUC) was higher for MSBPHR3/MDBPHR3 (0.97/0.98) than MSBPHR7/MDBPHR7 (0.96/0.97) and SBPHR/DBPHR (0.96/0.95) for identifying high Systolic and diastolic BP. The optimal cut-off points for MSBPHR3/MDBPH, MSBPHR7/MDBPHR7, and SBPHR/DBPHR were 0.76/0.50, 0.69/0.46, and 0.81/0.52 respectively. Negative predictive value was nearly perfect for three ratios (≥98%). Positive predictive value was higher for MBPHR3 (52.7%) than MBPHR7 (51.0%) and BPHR (39.8%). Overall, MBPHR3 had better performance than MBPHR7 and BPHR for identification of HBP in Iranian children and it may improve early hypertension recognition and control in primary screening.

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.

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.

The Growing Epidemic of Chronic Kidney Disease: Preventive Strategies to Delay the Risk for Progression to ESRD.

Hypertension, obesity and metabolic syndromes are leading risk factors for the development of chronic kidney disease (CKD). Considering the high prevalence of hypertension and obesity in children and adolescents and it's risk of progression to cardiovascular disease, CKD should be considered a serious long-term health issue in children with metabolic syndrome. Prevention of CKD requires a professional teamwork consisting of primary care physicians, nephrologists, nutritionist, pharmacist, and social work to identify and manage children at risk of developing CKD in order to provide a highly valuable management strategies. This review focuses on the principles underlying the importance of a team approach for CKD prevention.

Impact of dyslipidemia on estimated glomerular filtration rate in apparently healthy children and adolescents: the CASPIAN-V study.

BACKGROUND: Chronic kidney disease (CKD) is a leading risk factor for development of cardiovascular disease (CVD). Dyslipidemia is also known as risk factor for CVD development. However, the association of dyslipidemia with glomerular injury among healthy children and adolescents remains controversial. We aimed to investigate the relationship between estimated glomerular filtration rate (eGFR) and lipid profile risk factors among healthy children and adolescents. METHODS: In this nationwide survey, 3808 participants (1992 males, 1816 females), aged 7-18 years, were selected by cluster random sampling method from 30 provinces in Iran. Body mass index (BMI) and systolic and diastolic blood pressures were measured. Blood samples were obtained for serum creatinine, fasting blood glucose, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) determinations. GFR was estimated using Schwartz equation. RESULTS: Girls had higher eGFR than boys (P = 0.04). In a multiple regression analysis, eGFR demonstrated a positive correlation with systolic blood pressure, BMI, fasting glucose, TC, HDL-C, and TG. By the analysis of covariance, TC, HDL-C, and TG showed a negative correlation with eGFR after adjustments for BMI, systolic and diastolic blood pressures, and fasting glucose (OR = 0.56, 95% CI = 0.29-0.89). CONCLUSION: The study showed that dyslipidemia is associated with reduced eGFR among the healthy children and adolescents.