Pediatric Longitudinal Glomerular Disease: a PNRC Multi-Institutional Cohort Study (PLUGGED IN)

Subjects diagnosed with IgA Nephropathy less than 18 years of age

Subjects diagnosed with IgA Vasculitis less than 18 years of age

Subjects diagnosed with Idiopathic Immune Complex Glomerulonephritis less than 18 years of age

Subjects diagnosed with C3 Glomerulopathy less than 18 years of age

Subjects diagnosed with Membranous Nephropathy less than 18 years of age

Subjects diagnosed with Focal and Segmental Glomerulosclerosis less than 18 years of age

Subjects diagnosed with Minimal Change Disease less than 18 years of age

Subjects diagnosed with Anti-Neutrophilic Cytoplasmic antibody-GN (ANCA) less than 18 years of age

Subjects diagnosed with Lupus Nephritis less than 18 years of age

Subjects diagnosed with Alport Syndrome less than 18 years of age

Subjects diagnosed with Infection-related or post-infectious Glomerulonephritis (with or without biopsy) less than 18 years of age

Subjects diagnosed with Idiopathic Nephrotic Syndrome (with or without biopsy) less than 18 years of age

To characterize the longitudinal trajectory and progression of proteinuria, measured by urine protein-creatinine ratio (UPCR), following diagnosis and to identify baseline demographic and clinical factors associated with changes in proteinuria over time.

To characterize longitudinal changes in kidney function as measured by estimated glomerular filtration rate (eGFR) and to identify baseline demographic and clinical factors associated with changes in kidney function over time.

Measures how much a patient's kidney filtering capacity has increased or decreased over time compared to their initial starting measurement

Describe longitudinal growth patterns (e.g., height, weight, BMI z -scores) and identify disease-related factors associated with impaired growth trajectories. Growth trajectory will be defined as change in height and weight over time. We will calculate height-for-weight Z score, weight-for-height Z score and BMI Z-score over time.

Characterizing developmental progression, measured over time and identify clinical factors associated with delays or deviations from expected developmental milestones. Time to attainment of key developmental milestones (derived from QOL survey of caregiver) will be summarized using mean and standard deviation or median and interquartile range. The proportion of patients with delayed development at baseline (first assessment after diagnosis) and follow up will also be reported.

Evaluation of educational outcomes over follow-up and examine associations between disease severity and academic achievement. Time to attainment of key educational milestones will be summarized using mean and standard deviation or median and interquartile range. The proportion of patients with delayed educational attainment at baseline (first assessment after diagnosis) and follow up will also be reported.

To quantify school absenteeism and examine its relationship with disease burden and clinical progression. Missed school days will be summarized using descriptive statistics (mean and standard deviation or median and interquartile range as appropriate)

To estimate the frequency and timing of unplanned hospitalizations and identify factors associated with unplanned hospitalizations. Unplanned Hospitalization will be summarized using descriptive statistics. The association between clinical factors and number of unplanned hospitalizations will be examined with a multivariable negative binomial regression model

To characterize the incidence and types of infections during follow -up and evaluate clinical factors associated with increased infection risk. The incidence and type of infection will be reported with the corresponding 95% CI at each follow up time point. The association between clinical factors and infection will be evaluated using multivariable mixed models with random effects for patient and site

To describe longitudinal changes in histopathological findings and evaluate associations between pathological features and disease progression. Histopathological Response will each be summarized in the analytic population during the exposure period using descriptive statistics. Distributions will be compared across age groups where appropriate, using Chi -Square or Fisher's exact test, for categorical variables, and Kruskal-Wallis for continuous variables

To determine the incidence and timing of progression to renal failure (including dialysis-dependence) and to identify prognostic factors associated with risk of progression. The incidence of renal failure will be summarized with the corresponding 95% confidence interval for each disease group.

The association between clinical characteristics and time to renal failure will be evaluated using Fine and Gray subdistribution hazard model with prespecified covariates (see above); accounting for mortality (not related to renal failure) and renal transplantation as competing risks.

To characterize the incidence and timing of renal transplantation and describe clinical characteristics associated with progression to transplant. The incidence of renal transplantation will be summarized with the corresponding 95% confidence interval for each disease group. Association between clinical characteristics and time to renal transplantation will be evaluated with Fine and Gray sub distribution hazard model with prespecified covariates; accounting for mortality (not related to renal transplantation) and renal failure as competing risks. Time to renal transplantation will be defined as time from diagnosis of GD to the first occurrence of renal transplantation and survivors who do not receive renal transplantation will be censored at the last day of follow up or end of study, whichever occurs first.

To estimate overall survival and identify baseline demographic and clinical factors associated with risk of death during follow-up. Association between clinical characteristics and mortality will be evaluated using a multivariable Cox proportional hazards regression with prespecified baseline and time-varying covariates (see below). Survival time will be defined as time from diagnosis of GD to death and survivors will be censored at the last day of follow up or end of study, whichever occurs first.