Publications

Clear cell renal cell carcinoma (ccRCC) represents the most common type of kidney cancer with high mortality in its advanced stages. Our study aim was to explore the correlation between tumor epithelial-to-mesenchymal transition (EMT) and patient survival. Renal biopsies of tumorous and adjacent nontumorous tissue were taken with a 16 g needle from our patients ( = 26) undergoing partial or radical nephrectomy due to ccRCC RNA sequencing libraries were generated using Illumina TruSeq Access library preparation protocol and TruSeq Small RNA library preparation kit. Next generation sequencing (NGS) was performed on Illumina HiSeq2500. Comparative analysis of matched sample pairs was done using the Bioconductor Limma/voom R-package. Liquid chromatography-tandem mass spectrometry and immunohistochemistry were applied to measure and visualize protein abundance. We detected an increased generic EMT transcript score in ccRCC Gene expression analysis showed augmented abundance of and , as well as down-regulated expression of (klotho). Moreover, microRNA analyses demonstrated a positive expression correlation of miR-34a and its targets and Survival analysis based on a subset of genes from our list EMT-related genes in a publicly available dataset showed that the EMT genes correlated with ccRCC patient survival. Several of these genes also play a known role in fibrosis. Accordingly, recently published classifiers of solid organ fibrosis correctly identified EMT-affected tumor samples and were correlated with patient survival. EMT in ccRCC linked to fibrosis is associated with worse survival and may represent a target for novel therapeutic interventions.

OBJECTIVE

Among African Americans, the apolipoprotein L1 () risk variants have been associated with various types of kidney disease and chronic kidney disease progression. We aimed to determine whether these same risk variants also confer an increased risk for cardiovascular disease.

APPROACH AND RESULTS

In a cohort of African Americans with hypertension-attributed chronic kidney disease followed for up to 12 years, we used Cox proportional hazards models to estimate the relative hazard of a composite cardiovascular disease outcome (cardiovascular death or hospitalization for myocardial infarction, cardiac revascularization procedure, heart failure, or stroke) for the high- (2 risk variants) versus low-risk (0-1 risk variant) genotypes. We adjusted for age, sex, ancestry, smoking, heart disease history, body mass index, cholesterol, randomized treatment groups, and baseline and longitudinal estimated glomerular filtration rate, systolic blood pressure, and proteinuria. Among 693 participants with genotyping available (23% high risk), the high-risk group had lower mean estimated glomerular filtration rate (44.7 versus 50.1 mL/min per 1.73 m) and greater proteinuria (median 0.19 versus 0.06) compared with the low-risk group at baseline. There was no significant association between genotypes and the composite cardiovascular disease outcome in both unadjusted (hazard ratio=1.23; 95% confidence interval: 0.83-1.81) and fully adjusted (hazard ratio=1.16; 95% confidence interval: 0.77-1.76) models; however, in using an additive model, high-risk variants were associated with increased cardiovascular mortality.

CONCLUSIONS

Among African Americans with hypertension-attributed chronic kidney disease, risk variants were not associated with an overall risk for cardiovascular disease although some signals for cardiovascular mortality were noted.