EPO affects FGF23 production and metabolism, which may have important implications for CKD patients.

Background and objectives The sodium glucose cotransporter 2 (SGLT-2) inhibitor dapagliflozin is a novel drug for the treatment of diabetes mellitus. Recent studies suggest that SGLT-2 inhibitors affect phosphate homeostasis, but their effects on phosphate-regulating hormones in patients with diabetic kidney disease are still unclear. Design, setting, participants, & measurements We performed a post-hoc analysis of a double-blind, randomized, crossover trial in patients with type 2 diabetes with early-stage diabetic kidney disease on stable reninangiotensin-aldosterone system blockade, with an albumin-to-creatinine ratio between 100 and 3500 mg/g, eGFR$45 ml/min per 1.73 m 2 , and glycosylated hemoglobin$7.2% and ,11.4%. Patients were randomized to dapagliflozin 10 mg/d or placebo during consecutive 6-week study periods, separated by a 6-week wash-out. We investigated effects on circulating phosphate, calcium, parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), 25-hydroxyvitamin D (25[OH]D), and 1,25-dihydroxyvitamin D (1,25[OH] 2 D) levels. Results Thirty-one patients (age 62 years; 23% female) were analyzed. Compared with placebo, dapagliflozin increased serum phosphate by 9% (95% confidence interval, 4% to 15%; P=0.002), PTH increased by 16% (3% to 30%; P=0.01), FGF23 increased by 19% (0.3% to 42%; P=0.05), and serum 1,25(OH) 2 D decreased by 212% (225% to 4%; P=0.12). Calcium and 25(OH)D were unaffected. We found no correlation between changes in markers of phosphate homeostasis and changes in eGFR or 24-hour albumin excretion during dapagliflozin treatment. Conclusions Dapagliflozin increases serum phosphate, plasma PTH, and FGF23. This effect was independent of concomitant changes in eGFR or 24-hour albumin excretion.

A rterial hypertension is prevalent in chronic kidney disease (CKD) and contributes to its adverse outcomes. 1 The major benefits of lowering blood pressure (BP) for survival and cardiovascular outcomes are well established, as are those of inhibiting the renin angiotensinaldosterone system (RAAS) to slow CKD progression. 2-8 BP control and RAAS inhibitor use are therefore major goals in the management of patients with CKD, 9 although no consensus exists about the ideal BP level. Current guidelines

Reduction of residual albuminuria during single-agent renin-angiotensin-aldosterone blockade is accompanied by improved cardiorenal outcomes in CKD. We studied the individual and combined effects of the vitamin D receptor activator paricalcitol (PARI) and dietary sodium restriction on residual albuminuria in CKD. In a multicenter, randomized, placebo (PLAC)-controlled, crossover trial, 45 patients with nondiabetic CKD stages 1-3 and albuminuria >300 mg/24 h despite ramipril at 10 mg/d and BP<140/90 mmHg were treated for four 8-week periods with PARI (2 g/d) or PLAC, each combined with a low-sodium (LS) or regular sodium (RS) diet. We analyzed the treatment effect by linear mixed effect models for repeated measurements. In the intention-to-treat analysis, albuminuria (geometric mean) was 1060 (95% confidence interval, 778 to 1443) mg/24 h during RS + PLAC and 990 (95% confidence interval, 755 to 1299) mg/24 h during RS + PARI (=0.20 versus RS + PLAC). LS + PLAC reduced albuminuria to 717 (95% confidence interval, 512 to 1005) mg/24 h (<0.001 versus RS + PLAC), and LS + PARI reduced albuminuria to 683 (95% confidence interval, 502 to 929) mg/24 h (<0.001 versus RS + PLAC). The reduction by PARI beyond the effect of LS was nonsignificant (=0.60). In the per-protocol analysis restricted to participants with ≥95% compliance with study medication, PARI did provide further albuminuria reduction (=0.04 LS + PARI versus LS + PLAC). Dietary adherence was good as reflected by urinary excretion of 174±64 mmol Na per day in the combined RS groups and 108±61 mmol Na per day in the LS groups (<0.001). In conclusion, moderate dietary sodium restriction substantially reduced residual albuminuria during fixed dose angiotensin-converting enzyme inhibition. The additional effect of PARI was small and nonsignificant.