Kidney international
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Kidney international · Jan 2018
Pooled analysis of Phase III trials indicate contrasting influences of renal function on blood pressure, body weight, and HbA1c reductions with empagliflozin.
Sodium glucose cotransporter 2 (SGLT2) inhibitors reduce HbA1c, blood pressure, and weight in patients with type 2 diabetes. To investigate the effect of renal function on reductions in these parameters with the SGLT2 inhibitor empagliflozin, we assessed subgroups by baseline estimated glomerular filtration rate (eGFR; Modification of Diet in Renal Disease) in pooled data from five 24-week trials of 2286 patients with type 2 diabetes randomized to empagliflozin or placebo. Reductions in HbA1c with empagliflozin versus placebo significantly diminished with decreasing baseline eGFR. ⋯ Weight loss with empagliflozin versus placebo tended to be attenuated in patients with a lower eGFR. Results were consistent in a 12-week ambulatory blood pressure monitoring trial in 823 patients with type 2 diabetes and hypertension. Thus, unlike HbA1c reductions, systolic blood pressure and weight reductions with empagliflozin are generally preserved in patients with chronic kidney disease.
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Kidney international · Dec 2017
ReviewThe promise of single-cell RNA sequencing for kidney disease investigation.
Recent techniques for single-cell RNA sequencing (scRNA-seq) at high throughput are leading to profound new discoveries in biology. The ability to generate vast amounts of transcriptomic data at cellular resolution represents a transformative advance, allowing the identification of novel cell types, states, and dynamics. ⋯ We discuss available software tools for analyzing scRNA-Seq data and summarize current computational challenges. Finally, we outline ways in which this powerful technology might be applied to discovery research in kidney development and disease.
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Kidney international · Dec 2017
The fragility of significant results underscores the need of larger randomized controlled trials in nephrology.
The Fragility Index is a tool for testing robustness of randomized controlled trial results for dichotomous outcomes. It describes the minimum number of individuals in whom changing an event status would render a statistically significant result nonsignificant. Here we identified all randomized controlled trials in five nephrology and five general journals from 2005-2014. ⋯ Compared to a reported p value of 0.05 to 0.01, those reporting 0.01 to 0.001 or less than 0.001 had a significant 57% and 472% increase in the median Fragility Index, respectively. Forty-one percent had a Fragility Index less than the total loss to follow-up, indicating a potential to change a trial result had all individuals been accounted for. Thus, our study highlights the need for larger randomized controlled trials with accurate accounting for loss to follow-up to adequately guide evidence-based practice.
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Kidney international · Nov 2017
Comparative StudyParicalcitol and cinacalcet have disparate actions on parathyroid oxyphil cell content in patients with chronic kidney disease.
The parathyroid oxyphil cell content increases in patients with chronic kidney disease (CKD), and even more in patients treated with the calcimimetic cinacalcet and/or calcitriol for hyperparathyroidism. Oxyphil cells have significantly more calcium-sensing receptors than chief cells, suggesting that the calcium-sensing receptor and calcimimetics are involved in the transdifferentiation of a chief cell to an oxyphil cell type. Here, we compared the effect of the vitamin D analog paricalcitol (a less calcemic analog of calcitriol) and/or cinacalcet on the oxyphil cell content in patients with CKD to further investigate the genesis of these cells. ⋯ Cinacalcet treatment leads to a significant increase in parathyroid oxyphil cell content but paricalcitol does not, reinforcing a role for the calcium-sensing receptor activation in the transdifferentiation of chief-to-oxyphil cell type. Thus, two conventional treatments for hyperparathyroidism have disparate effects on parathyroid composition, and perhaps function. This finding is provocative and may be useful when evaluating future drugs for hyperparathyroidism.