How Well Do ICD‐9‐CM Codes Predict True Congenital Heart Defects? A Centers for Disease Control and Prevention‐Based Multisite Validation Project

Background The Centers for Disease Control and Prevention's Surveillance of Congenital Heart Defects Across the Lifespan project uses large clinical and administrative databases at sites throughout the United States to understand population‐based congenital heart defect (CHD) epidemiology and outcomes. These individual databases are also relied upon for accurate coding of CHD to estimate population prevalence. Methods and Results This validation project assessed a sample of 774 cases from 4 surveillance sites to determine the positive predictive value (PPV) for identifying a true CHD case and classifying CHD anatomic group accurately based on 57 International Classification of Diseases, Ninth Revision, Clinical Modification (ICD‐9‐CM) codes. Chi‐square tests assessed differences in PPV by CHD severity and age. Overall, PPV was 76.36% (591/774 [95% CI, 73.20–79.31]) for all sites and all CHD‐related ICD‐9‐CM codes. Of patients with a code for complex CHD, 89.85% (177/197 [95% CI, 84.76–93.69]) had CHD; corresponding PPV estimates were 86.73% (170/196 [95% CI, 81.17–91.15]) for shunt, 82.99% (161/194 [95% CI, 76.95–87.99]) for valve, and 44.39% (83/187 [95% CI, 84.76–93.69]) for “Other” CHD anatomic group (X2=142.16, P64 years of age, (X2=4.23, P<0.0001). Conclusions While CHD ICD‐9‐CM codes had acceptable PPV (86.54%) (508/587 [95% CI, 83.51–89.20]) for identifying whether a patient has CHD when excluding patients with ICD‐9‐CM codes for “Other” CHD and code 745.5, further evaluation and algorithm development may help inform and improve accurate identification of CHD in data sets across the CHD ICD‐9‐CM code groups

Blockade of TSP1-Dependent TGF-β Activity Reduces Renal Injury and Proteinuria in a Murine Model of Diabetic Nephropathy

Transforming growth factor-β (TGF-β) is key in the pathogenesis of diabetic nephropathy. Thrombospondin 1 (TSP1) expression is increased in diabetes, and TSP1 regulates latent TGF-β activation in vitro and in diabetic animal models. Herein, we investigate the effect of blockade of TSP1-dependent TGF-β activation on progression of renal disease in a mouse model of type 1 diabetes (C57BL/6J-Ins2Akita) as a targeted treatment for diabetic nephropathy. Akita and control C57BL/6 mice who underwent uninephrectomy received 15 weeks of thrice-weekly i.p. treatment with 3 or 30 mg/kg LSKL peptide, control SLLK peptide, or saline. The effects of systemic LSKL peptide on dermal wound healing was assessed in type 2 diabetic mice (db/db). Proteinuria (urinary albumin level and albumin/creatinine ratio) was significantly improved in Akita mice treated with 30 mg/kg LSKL peptide. LSKL treatment reduced urinary TGF-β activity and renal phospho-Smad2/3 levels and improved markers of tubulointerstitial injury (fibronectin) and podocytes (nephrin). However, LSKL did not alter glomerulosclerosis or glomerular structure. LSKL did not increase tumor incidence or inflammation or impair diabetic wound healing. These data suggest that selective targeting of excessive TGF-β activity through blockade of TSP1-dependent TGF-β activation represents a therapeutic strategy for treating diabetic nephropathy that preserves the homeostatic functions of TGF-β