Rituximab in post-transplant pediatric recurrent focal segmental glomerulosclerosis.

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) recurs in 20-40 % of allografts. Plasmapheresis (TPE) has been one of the mainstays of treatment with variable results. Rituximab (RTX), a monoclonal antibody to the protein CD20, is being used for treatment of recurrent FSGS (recFSGS) but pediatric experience is limited. METHODS: We conducted a retrospective review of eight patients with recFSGS, treated with RTX (1-4 doses) after having minimal response to TPE. Complete response was defined as a decrease in urine protein creatinine ratio (Up/c) to less than 0.2 and partial response was a decrease in Up/c ratio by 50 % of baseline and in the sub-nephrotic range (U p/c <2). RESULTS: Complete response was seen in two of eight patients, and partial response was seen in four of eight patients. Two patients had no response. At last follow-up, all the partial responders had sub-nephrotic range proteinuria (Up/c ratios ranging from 0.29 to 1.6). Delayed response, up to 9 months post-RTX, was also seen in some of the patients. Significant complications such as rituximab-associated lung injury (RALI), acute tubular necrosis, and central nervous system(CNS) malignancy were also observed in our case series. CONCLUSIONS: Rituximab can be used with caution as a treatment for recFSGS. Efficacy is variable from none to complete response. Even partial reduction in proteinuria is of benefit in prolonging the life of the allograft. Long-term, multicenter studies are needed to prove its sustained efficacy in those who respond and to monitor for serious adverse effects.

Evaluating Kidney Function Decline in Children with Chronic Kidney Disease Using a Multi-Institutional Electronic Health Record Database.

BACKGROUND: The objectives of this study were to use electronic health record data from a US national multicenter pediatric network to identify a large cohort of children with CKD, evaluate CKD progression, and examine clinical risk factors for kidney function decline. METHODS: This retrospective cohort study identified children seen between January 1, 2009, to February 28, 2022. Data were from six pediatric health systems in PEDSnet. We identified children aged 18 months to 18 years who met criteria for CKD: two eGFR values <90 and ≥15 ml/min per 1.73 m2 separated by ≥90 days without an intervening value ≥90. CKD progression was defined as a composite outcome: eGFR <15 ml/min per 1.73 m2, ≥50% eGFR decline, long-term dialysis, or kidney transplant. Subcohorts were defined based on CKD etiology: glomerular, nonglomerular, or malignancy. We assessed the association of hypertension (≥2 visits with hypertension diagnosis code) and proteinuria (≥1 urinalysis with ≥1+ protein) within 2 years of cohort entrance on the composite outcome. RESULTS: Among 7,148,875 children, we identified 11,240 (15.7 per 10,000) with CKD (median age 11 years, 50% female). The median follow-up was 5.1 (interquartile range 2.8-8.3) years, the median initial eGFR was 75.3 (interquartile range 61-83) ml/min per 1.73 m2, 37% had proteinuria, and 35% had hypertension. The following were associated with CKD progression: lower eGFR category (adjusted hazard ratio [aHR] 1.44 [95% confidence interval (95% CI), 1.23 to 1.69], aHR 2.38 [95% CI, 2.02 to 2.79], aHR 5.75 [95% CI, 5.05 to 6.55] for eGFR 45-59 ml/min per 1.73 m2, 30-44 ml/min per 1.73 m2, 15-29 ml/min per 1.73 m2 at cohort entrance, respectively, when compared with eGFR 60-89 ml/min per 1.73 m2), glomerular disease (aHR 2.01 [95% CI, 1.78 to 2.28]), malignancy (aHR 1.79 [95% CI, 1.52 to 2.11]), proteinuria (aHR 2.23 [95% CI, 1.89 to 2.62]), hypertension (aHR 1.49 [95% CI, 1.22 to 1.82]), proteinuria and hypertension together (aHR 3.98 [95% CI, 3.40 to 4.68]), count of complex chronic comorbidities (aHR 1.07 [95% CI, 1.05 to 1.10] per additional comorbid body system), male sex (aHR 1.16 [95% CI, 1.05 to 1.28]), and younger age at cohort entrance (aHR 0.95 [95% CI, 0.94 to 0.96] per year older). CONCLUSIONS: In large-scale real-world data for children with CKD, disease etiology, albuminuria, hypertension, age, male sex, lower eGFR, and greater medical complexity at start of follow-up were associated with more rapid decline in kidney function.

Medication adherence and growth in children with CKD.

BACKGROUND AND OBJECTIVES: Poor growth is a consequence of CKD, but can often be partially or fully prevented or corrected with the use of a number of medications. The extent of nonadherence with medications used to treat or mitigate growth failure in CKD has not been examined prospectively in children with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The prevalence of both prescription of and nonadherence to recombinant human growth hormone (rhGH), phosphate binders, alkali, active vitamin D, nutritional vitamin D, iron, and erythrocyte-stimulating agents was summarized over the first seven visits of the Chronic Kidney Disease in Children cohort study. The association between self-reported nonadherence to each medication group and the mean annual change in age- and sex-specific height z score was quantified using seven separate linear regression models with generalized estimating equations. RESULTS: Of 834 participants, 597 reported use of at least one of these medication groups and had adherence data available. Nonadherence ranged from 4% over all visits for erythrocyte-stimulating agents to 22% over all visits for nutritional vitamin D. Of the study participants, 451 contributed data to at least one of the analyses of adherence and changes in height z score. Children nonadherent to rhGH had no change in height z score, whereas those adherent to rhGH had a significant improvement of 0.16 SDs (95% confidence interval, 0.05 to 0.27); the effect size was slightly larger and remained significant after adjustment. Among participants with height≤3rd percentile and after adjustment, adherence to rhGH was associated with a 0.33 SD (95% confidence interval, 0.10 to 0.56) greater change in height z score. Nonadherence with other medication groups was not significantly associated with a change in height z score. CONCLUSIONS: Self-reported nonadherence to rhGH was associated with poorer growth velocity in children with CKD, suggesting an opportunity for intervention and improved patient outcome.

Association of glucocorticoid use and low 25-hydroxyvitamin D levels: results from the National Health and Nutrition Examination Survey (NHANES): 2001-2006.

CONTEXT: In many disorders requiring steroid therapy, there is substantial decrease in bone mineral density. The association between steroid use and 25-hydroxyvitamin D [25(OH)D] deficiency has not been confirmed in large population-based studies, and currently there are no specific vitamin D recommendations for steroid users. OBJECTIVE: The aim of the study was to evaluate the association of serum 25(OH)D deficiency [defined as 25(OH)D <10 ng/ml] with oral steroid use. DESIGN: Cross-sectional analysis was performed using NHANES 2001-2006. SETTING: We analyzed a nationally representative sample of U.S. children and adults. PARTICIPANTS: The study sample consisted of children, adolescents, and adults from NHANES 2001-2006 (n = 22,650), representative of 286 million U.S. residents, with serum 25(OH)D levels and data on other potential confounders. MAIN OUTCOME MEASURE: We measured serum 25(OH)D levels below 10 ng/ml. RESULTS: A total of 181 individuals (0.9% of the population) used steroids within the past 30 d. Overall, 5% of the population had 25(OH)D levels below 10 ng/ml. Among steroid users, 11% had 25(OH)D levels below 10 ng/ml, compared to 5% among steroid nonusers (P = 0.009). The odds of having 25(OH)D deficiency were 2-fold higher in those who reported steroid use compared to those without steroid use [odds ratio (OR), 2.36; 95% confidence interval (CI), 1.25, 4.45]. This association remained after multivariable adjustment (OR, 2.21; 95% CI, 1.01, 4.85) and in a multivariable model using NHANES III data (OR, 1.88; 95% CI, 1.01, 3.48). CONCLUSION: Steroid use is independently associated with 25(OH)D deficiency in this nationally representative cohort limited by cross-sectional data. It suggests the need for screening and repletion in patients on chronic steroids.