The Factors That May Predict Response to Rituximab Therapy in Recurrent Focal Segmental Glomerulosclerosis: A Systematic Review

Recurrence of FSGS occurs in 30–40% of allografts. Therapies for recurrence are not well established. We retrieved all published reports depicting kidney transplant recipients with focal segmental glomerulosclerosis (FSGS) recurrence, treated with rituximab, to determine factors associated with treatment response. We found 18 reports of 39 transplant recipients who received rituximab. By univariate analysis for two outcomes (no response versus any response), fewer rituximab infusions and normal serum albumin at recurrence were associated with treatment response. For 3 outcomes (no response, partial and complete remission), male gender, fewer rituximab infusions, shorter time to rituximab treatment, and normal serum albumin were associated with remission. Multivariate analysis for both models revealed that normal serum albumin at FSGS recurrence and lower age at transplant were associated with response. Rituximab for recurrence of FSGS may be beneficial for only some patients. A younger age at transplant and normal serum albumin level at recurrence diagnosis may predict response

The Preserving Kidney Function in Children with CKD (PRESERVE) Study: Rationale, design, and methods

RATIONALE & OBJECTIVE: PRESERVE seeks to provide new knowledge to inform shared decision-making regarding blood pressure (BP) management for pediatric chronic kidney disease (CKD). PRESERVE will compare the effectiveness of alternative strategies for monitoring and treating hypertension on preserving kidney function; expand the National Patient-Centered Clinical Research Network (PCORnet) common data model by adding pediatric- and kidney-specific variables and linking electronic health record data to other kidney disease databases; and assess the lived experiences of patients related to BP management. STUDY DESIGN: Multicenter retrospective cohort study (clinical outcomes) and cross-sectional study (patient-reported outcomes [PROs]). SETTING & PARTICIPANTS: PRESERVE will include approximately 20,000 children between January 2009-December 2022 with mild-moderate CKD from 15 health care institutions that participate in 6 PCORnet Clinical Research Networks (PEDSnet, STAR, GPC, PaTH, CAPRiCORN, and OneFlorida+). The inclusion criteria were ≥1 nephrologist visit and ≥2 estimated glomerular filtration rate (eGFR) values in the range of 30 to \u3c90 mL/min/1.73 m EXPOSURES: BP measurements (clinic-based and 24-hour ambulatory BP); urine protein; and antihypertensive treatment by therapeutic class. OUTCOMES: The primary outcome is a composite event of a 50% reduction in eGFR, eGFR of \u3c15 mL/min/1.73 m ANALYTICAL APPROACH: Longitudinal models for dichotomous (proportional hazards or accelerated failure time) and continuous (generalized linear mixed models) clinical outcomes; multivariable linear regression for PROs. We will evaluate heterogeneity of treatment effect by CKD etiology and degree of proteinuria and will examine variation in hypertension management and outcomes based on socio-demographics. LIMITATIONS: Causal inference limited by observational analyses. CONCLUSIONS: PRESERVE will leverage the PCORnet infrastructure to conduct large-scale observational studies that address BP management knowledge gaps for pediatric CKD, focusing on outcomes that are meaningful to patients. PLAIN-LANGUAGE SUMMARY: Hypertension is a major modifiable contributor to loss of kidney function in chronic kidney disease (CKD). The purpose of PRESERVE is to provide evidence to inform shared decision-making regarding blood pressure management for children with CKD. PRESERVE is a consortium of 16 health care institutions in PCORnet, the National Patient-Centered Clinical Research Network, and includes electronic health record data for \u3e19,000 children with CKD. PRESERVE will (1) expand the PCORnet infrastructure for research in pediatric CKD by adding kidney-specific variables and linking electronic health record data to other kidney disease databases; (2) compare the effectiveness of alternative strategies for monitoring and treating hypertension on preserving kidney function; and (3) assess the lived experiences of patients and caregivers related to blood pressure management

Kidney transplantation in children

Transplantation in children with kidney failure once presented many technical, immunologic, and logistic problems that led to worse patient and allograft survival, as compared with adults. Advances in all these areas and the development of pediatric-trial groups have resulted in dramatic improvements, such that young children now have the best long-term graft survival among all age groups, including adults

Clinical course and management of children with IgA vasculitis with nephritis

BACKGROUND: IgA vasculitis is the most common vasculitis in children and is often complicated by acute nephritis (IgAVN). Risk of chronic kidney disease (CKD) among children with IgAVN remains unknown. This study aimed to describe the clinical management and kidney outcomes in a large cohort of children with IgAVN. METHODS: This observational cohort study used the PEDSnet database to identify children diagnosed with IgAV between January 1, 2009, and February 29, 2020. Demographic and clinical characteristics were compared among children with and without kidney involvement. For children followed by nephrology, clinical course, and management patterns were described. Patients were divided into four categories based on treatment: observation, renin-angiotensin-aldosterone system (RAAS) blockade, corticosteroids, and other immunosuppression, and outcomes were compared among these groups. RESULTS: A total of 6802 children had a diagnosis of IgAV, of whom 1139 (16.7%) were followed by nephrology for at least 2 visits over a median follow-up period of 1.7 years [0.4,4.2]. Conservative management was the most predominant practice pattern, consisting of observation in 57% and RAAS blockade in 6%. Steroid monotherapy was used in 29% and other immunosuppression regimens in 8%. Children receiving immunosuppression had higher rates of proteinuria and hypertension compared to those managed with observation (p \u3c 0.001). At the end of follow-up, 2.6 and 0.5% developed CKD and kidney failure, respectively. CONCLUSIONS: Kidney outcomes over a limited follow-up period were favorable in a large cohort of children with IgAV. Immunosuppressive medications were used in those with more severe presentations and may have contributed to improved outcomes. A higher resolution version of the Graphical abstract is available as Supplementary information

Clinical phenotypes and biologic treatment use in juvenile dermatomyositis-associated calcinosis

Abstract Background Few risk factors have been identified for the development of calcinosis among patients with Juvenile Dermatomyositis, and currently no clinical phenotype has been associated with its development. We analyzed a large database of patients to further elucidate any relationships among patients with and without calcinosis. Method The CARRA legacy registry recruited pediatric rheumatology patients from 55 centers across North America from 2010 through 2014, including over 650 subjects with Juvenile Dermatomyositis. We compared the demographic characteristics, clinical disease features and treatment histories of those with and without calcinosis using univariate and multivariate logistic regression. Results Of the 631 patients included in the analysis, 84 (13%) had a current or prior history of calcinosis. These patients were statistically more likely to have longer durations of disease prior to diagnosis and treatment, have lipodystrophy and joint contractures, and to have received intravenous immune globulin or rituximab as treatments. Conclusions Calcinosis is found more often in patients with prolonged active disease, severe disease, and certain clinical features such as lipodystrophy and joint contractures. When these factors are combined with other known associations and predictors, groups of at-risk patients can be more effectively identified, treated and studied to improve overall outcomes

Ureteral stent placement increases the risk for developing BK viremia after kidney transplantation.

The placement of ureteral stent (UrSt) at kidney transplantation reduces major urological complications but increases the risk for developing nephropathy from the BK virus. It is unclear whether UrSt placement increases nephropathy risk by increasing risk of precursor viral replication or by other mechanisms. We retrospectively investigated whether UrSt placement increased the risk for developing BK Viremia (BKVM) in adult and pediatric kidney transplants performed at the University of Florida between July 1, 2007, and December 31, 2010. In this period all recipients underwent prospective BKV PCR monitoring and were maintained on similar immunosuppression. Stent placement or not was based on surgeon preference. In 621 transplants, UrSt were placed in 295 (47.5%). BKVM was seen in 22% versus 16% without UrSt (P=0.05). In multivariate analyses, adjusting for multiple transplant covariates, only UrSt placement remained significantly associated with BKVM (P=0.04). UrSt placement significantly increased the risk for BKVM. Routine UrSt placement needs to be revaluated, since benefits may be negated by the need for more BK PCR testing and potential for graft survival-affecting nephritis

Cell-free DNA for the detection of kidney allograft rejection

Donor-derived cell-free DNA (dd-cfDNA) is an emerging noninvasive biomarker that has the potential to detect allograft injury. The capacity of dd-cfDNA to detect kidney allograft rejection and its added clinical value beyond standard of care patient monitoring is unclear. We enrolled 2,882 kidney allograft recipients from 14 transplantation centers in Europe and the United States in an observational population-based study. The primary analysis included 1,134 patients. Donor-derived cell-free DNA levels strongly correlated with allograft rejection, including antibody-mediated rejection (P \u3c 0.0001), T cell-mediated rejection (P \u3c 0.0001) and mixed rejection (P \u3c 0.0001). In multivariable analysis, circulating dd-cfDNA was significantly associated with allograft rejection (odds ratio 2.275; 95% confidence interval (CI) 1.902-2.739; P \u3c 0.0001) independently of standard of care patient monitoring parameters. The inclusion of dd-cfDNA to a standard of care prediction model showed improved discrimination (area under the curve 0.777 (95% CI 0.741-0.811) to 0.821 (95% CI 0.784-0.852); P = 0.0011) and calibration. These results were confirmed in the external validation cohorts (n = 1,748) including a cohort of African American patients (n = 439). Finally, dd-cfDNA showed high predictive value to detect subclinical rejection in stable patients. Our study provides insights on the potential value of assessing dd-cfDNA, in addition to standard of care monitoring, to improve the detection of allograft rejection. ClinicalTrials.gov registration: NCT05995379