Model systems demonstrate that progression to ESRD is driven by progressive podocyte depletion (the podocyte depletion hypothesis) and can be noninvasively monitored through measurement of urine pellet podocyte mRNAs. To test these concepts in humans, we analyzed urine pellet mRNAs from 358 adult and pediatric kidney clinic patients and 291 controls (n=1143 samples). Compared with controls, urine podocyte mRNAs increased 79-fold (P,0.001) in patients with biopsy-proven glomerular disease and a 50% decrease in kidney function or progression to ESRD. An independent cohort of patients with Alport syndrome had a 23-fold increase in urinary podocyte mRNAs (P,0.001 compared with controls). Urinary podocyte mRNAs increased during active disease but returned to baseline on disease remission. Furthermore, urine podocyte mRNAs increased in all categories of glomerular disease evaluated, but levels ranged from high to normal, consistent with individual patient variability in the risk for progression. In contrast, urine podocyte mRNAs did not increase in polycystic kidney disease. The association between proteinuria and podocyturia varied markedly by glomerular disease type: a high correlation in minimalchange disease and a low correlation in membranous nephropathy. These data support the podocyte depletion hypothesis as the mechanism driving progression in all human glomerular diseases, suggest that urine pellet podocyte mRNAs could be useful for monitoring risk for progression and response to treatment, and provide novel insights into glomerular disease pathophysiology.

Objective To evaluate inpatient health care utilization for children with systemic lupus erythematosus (SLE) with and without kidney disease. Methods The Healthcare Cost and Utilization Project Kids’ Inpatient Database for the years 2000, 2003, and 2006 was used for this analysis. SLE hospitalizations from the 2006 cohort were identified and classified as those with versus without kidney involvement by International Classification of Diseases, Ninth Revision, Clinical Modification codes. Analyses were performed to examine determinants of hospitalization charges and changes in charges over time. Results In the US, 7,390 SLE-related pediatric hospitalizations generated $267 million in total charges in 2006. Of these, 4,193 discharges had kidney involvement. The average hospitalization charge was greater for SLE patients with kidney involvement compared to those without kidney involvement ($43,100 versus $28,500; P < 0.0001). In multivariate analysis, kidney involvement remained a significant predictor of hospitalization charges, independent of demographic and hospital characteristics (P < 0.0001). SLE-associated acute kidney failure, transplant, and end-stage kidney disease resulted in greater hospitalization charges than SLE without kidney involvement by $74,900 (P < 0.0001), $32,700 (P = 0.0002), and $27,400 (P < 0.0001), respectively. Conclusion In the US, >7,000 hospitalizations occurred in 2006 among children with SLE, with nearly 57% demonstrating kidney involvement. Kidney involvement is a major determinant of hospitalization charges for these children. This study represents one of the first large-scale assessments of in-hospital health care utilization by children with SLE.

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