Search

The efficacy and safety of rituximab in childhood steroid-resistant nephrotic syndrome (SRNS) remains unclear. Therefore, we conducted a retrospective cohort study at 28 pediatric nephrology centers from 19 countries in Asia, Europe, North America and Oceania to evaluate this. Children with SRNS treated with rituximab were analyzed according to the duration of calcineurin inhibitors (CNIs) treatment before rituximab [6 months or more (CNI-resistant) and under 6 months]. Primary outcome was complete/partial remission (CR/PR) as defined by IPNA/KDIGO guidelines. Secondary outcomes included kidney failure and adverse events. Two-hundred-forty-six children (mean age, 6.9 years; 136 boys; 57% focal segmental glomerulosclerosis, FSGS) were followed a median of 32.4 months after rituximab. All patients were in non-remission before rituximab. (146 and 100 children received CNIs for 6 month or more or under 6 months before rituximab, respectively). In patients with CNI-resistant SRNS, the remission rates (CR/PR) at 3-, 6-, 12- and 24-months were 26% (95% confidence interval 19.3-34.1), 35.6% (28.0-44.0), 35.1% (27.2-43.8) and 39.1% (29.2-49.9), respectively. Twenty-five patients were in PR at 12-months, of which 22 had over 50% reduction in proteinuria from baseline. The remission rates among children treated with CNIs under 6 months before rituximab were 42% (32.3-52.3), 52% (41.8-62.0), 54% (44.3-64.5) and 60% (47.6-71.3) at 3-, 6-, 12-, and 24-months. Upon Kaplan-Meier analysis, non-remission and PR at 12-months after rituximab, compared to CR, were associated with significantly worse kidney survival. Adverse events occurred in 30.5% and most were mild. Thus, rituximab enhances remission in a subset of children with SRNS, is generally safe and CR following rituximab is associated with favorable kidney outcome., (Copyright © 2024 International Society of Nephrology. All rights reserved.)

Pediatric patients on kidney replacement therapy (KRT) are among the most vulnerable during large-scale disasters, either natural or man-made. Hemodialysis (HD) treatments may be impossible because of structural damage and/or shortage of medical supplies, clean water, electricity, and healthcare professionals. Lack of peritoneal dialysis (PD) solutions and increased risk of infectious/non-infectious complications may make PD therapy challenging. Non-availability of immunosuppressants and increased risk of infections may result in graft loss and deaths of kidney transplant recipients. Measures to mitigate these risks must be considered before, during, and after the disaster including training of staff and patients/caregivers to cope with medical and logistic problems. Soon after a disaster, if the possibility of performing HD or PD is uncertain, patients should be directed to other centers, or the duration and/or number of HD sessions or the PD prescription adapted. In kidney transplant recipients, switching among immunosuppressants should be considered in case of non-availability of the medications. Post-disaster interventions target treating neglected physical and mental problems and also improving social challenges. All problems experienced by pediatric KRT patients living in the affected area are applicable to displaced patients who may also face extra risks during their travel and also at their destination. The need for additional local, national, and international help and support of non-governmental organizations must be anticipated and sought in a timely manner., (© 2022. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Introduction: In observational studies, increased water intake improves kidney function but not in adults with CKD stage 3 and more. CKD WIT trial has shown a nonsignificant gradual decline in kidney function after 1 year of coaching to increase water intake (CIWI) [1]. We propose that CIWI may benefit in CKD stage 1-2 (G1 and G2) and depends on functional renal functional reserve (RFR) [2, 3]., Objective: Parallel-group randomized trial was aimed to determinate the effectiveness of CIWI dependence of estimated glomerular filtration rate (eGFR) stage and RFR in adults with CKD 1-2 stages., Methods: CKD WIT trial was taken as the basis for prospective multicenter randomized trial named "Early Coaching to Increase Water Intake in CKD (ECIWIC)." The primary outcome was the change in kidney function by eGFR from baseline to 12 months. Secondary outcomes included 1-year change in urine albumin/Cr ratio, and patient-reported overall quality of health (QH) ranged from 0 (worst possible) to 10 (best possible). CIWI aimed to have the diuresis being 1.7-2 L. There were 4 groups with nondiet sodium restriction which consisted of 31 patients each: 2 groups with CKD G1 and CKD G2, undergoing CIWI and 2 others with CKD G1 and CKD G2 without CIWI (Fig. 1a). Overall checks were made at 0, 6, and 12 months. RFR evaluation was performed using 0.45% sodium chloride oral solution., Results: Of our randomized 124 patients (mean age 53.2 years; men 83 [67%], 0 died), mean change in 24-h urine volume was 0.6 L per day in G1 with CIWI group and 0.5 L in G2. No statistically significant data on eGFR depending CIWI were obtained (Fig. 1b). However, the trend suggests that CIWI improves eGFR in CKD G1 (from 95 to 96 mL/min/1.73 m2) and preserves eGFR decline in CKD G2 (78-78). The QH values were also preserved (from 7 to 7 in G1 and G2 groups). Although coaching to maintain the same water intake did not preserve physiological and pathological eGFR decreasing in CKD G1-2 (G1 from 96 to 93, G2 from 76 to 73; t = 0.6, p = 0.29, and p ≤ 0.05 in all groups) and the QH was declined (from 7 to 6 in both groups). An individual analysis of the RFR has shown that patients with RFR more than 50% (G1 19 patients, 61%, and G2 13 patients, 42%) had reliable preservation of eGFR with its increase of 1.5 mL/min on CIWI, while patients with low functional renal reserve had a drop of eGFR at 1.1 mL/min/m2 within 12 months. Patients with low normal serum sodium levels have shown worse results on CIWI., Conclusions: With CKD G1, the CIWI leads to the preservation of the renal function with its increase of GFR per 1 mL/min/m2/per year in comparison with the same water intake. In CKD G2, the CIWI prevents physiological and pathological loss of renal function, and RFR above 50% aids restoration of eGFR both in CKD G1-2. ECIWIC trial demonstrates benefit of CIWI in patients with CKD 1-2 and preserved RFR., (© 2021 The Author(s). Published by S. Karger AG, Basel.)

The article deals with the analysis of the results of radionuclide studies in 624 children with the nephrotic form of glomerulonephritis according to the effect of pathogenetic therapy in the immediate and late-term periods. The authors determined the values characterizing the renal hemodynamics and the functional and metabolic condition of the kidneys and allowing the probable outcome of the disease to be appraised. The severity of the functional disorders in the period of marked clinical manifestations of glomerulo-nephritis and the changes of the values during treatment allows the tactics of the therapeutic measures to be determined. The persistence of renal hemodynamic disorders in the follow-up of patients with a complete clinico-laboratory remission is shown, which dictates the necessity for increasing the time of medical rehabilitation in the nephrotic form of glomerulonephritis in children.

Development, course and treatment of glomerulonephritis in comparison with other nephropathies was studied in 295 Hb-carriers with the nephrotic syndrome. Results of quantitative content of Hb-antigens in the blood serum and urine and nephrobiopsy materials were evaluated to show the etiopathogenetic role of Hb-viral infection in the development of glomerulonephritis. Four groups of Hb-carriers of the nephrotic syndrome were studied depending on hepatitis B markers in the blood serum. Treatment results are described in this category of patients.

Morphofunctional properties of the lymphocyte suspension of patients susceptible and resistant to glucocorticoids in nephrotic form of glomerulonephritis were studied. Ultrastructural study of lymphocytes was performed as well as immune tests (the determination of lymphocyte glucocorticoid receptors number, proliferative activity of mononuclears, HIA genotypes) in 216 children. Morphofunctional insufficiency of the patient lymphocytes as compared to that in donors was established. A higher morphologic variety, functional sufficiency of lymphocytes, a higher number of glucocorticoid receptors and a preferable HIA genotype were found in the hormone-susceptible patients. Lymphocytes of hormone-resistant patients were characterized by a high activity of RNA-synthesizing apparatus, the presence of damaged organelles, low number of glucocorticoid receptors and by the failure of proliferative response to the dexamethasone test. These differences allow the differential approach to glucocorticoid therapy.

A mathematical model is proposed for prediction of the efficacy of glucocorticoid therapy developed on the basis of the Bayes theorem and successive Wald's analysis. The model uses the retrospective values of the results of radioligand determination of the number of glucocorticoid receptor of lymphocytes and static renal scintigraphy. By means of the blind method the informative value of the mathematical model to predict the inefficacy of glucocorticoid therapy in nephrotic glomerulonephritis was 96%. A nomogram was developed.

A modified method for the determination of glucocorticoid receptors in human lymphocytes is suggested. The principal distinction of the method is standardization by the lymphocyte count in a sample (1 mln) and the labeled hormone concentration. The modification saves time and money, limits the range of the data variations, and makes use of a lesser volume of blood. Examinations of 70 children aged 4 to 15 suffering from the nephrotic form of glomerulonephritis have made it possible to distinguish two groups of patients: with relatively high values of specific binding X = 6820.1 +/- 530.0 (n = 30, p = 0.95, t = 2.04), this corresponding to a clinical form of hormone-sensitive glomerulonephritis, and with relatively low values of specific binding X = 1815.2 +/- 302.8 (n = 40, p = 0.95, t = 1.96), that corresponds to hormone-resistant glomerulonephritis. Dynamic studies have not shown any statistically significant changes in the specific binding values. These results permit regarding the specific binding value as a prognostic criterion in the assessment of corticosteroid therapy; this allows a wide employment of the described method in practical nephrology.

Children with nephrotic glomerulonephritis were examined for incorporation of 99mTc-pyrophosphate and 99mTc-phosphone. The relationship was discovered between the accumulation of the radiopharmaceutical drug and the sensitivity to glucocorticoids used in the pathogenetic treatment. Accumulation of the drug in the course of the treatment documents the presence of complete, partial remission or the disease activity. It is recommended that static gammascintigraphy should be carried out for early assessment of the efficacy of the treatment and its correction.