Improved home BP profile with dapagliflozin is associated with amelioration of albuminuria in Japanese patients with diabetic nephropathy: the Yokohama add-on inhibitory efficacy of dapagliflozin on albuminuria in Japanese patients with type 2 diabetes study (Y-AIDA study).

BACKGROUND: The Y-AIDA study was designed to investigate the renal- and home blood pressure (BP)-modulating effects of add-on dapagliflozin treatment in Japanese individuals with type 2 diabetes mellitus (T2DM) and albuminuria. METHODS: We conducted a prospective, multicenter, single-arm study. Eighty-six patients with T2DM, HbA1c 7.0-10.0%, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min/1.73 m2, and urine albumin-to-creatinine ratio (UACR) ≥ 30 mg/g creatinine (gCr) were enrolled, and 85 of these patients were administered add-on dapagliflozin for 24 weeks. The primary and key secondary endpoints were change from baseline in the natural logarithm of UACR over 24 weeks and change in home BP profile at week 24. RESULTS: Baseline median UACR was 181.5 mg/gCr (interquartile range 47.85, 638.0). Baseline morning, evening, and nocturnal home systolic/diastolic BP was 137.6/82.7 mmHg, 136.1/79.3 mmHg, and 125.4/74.1 mmHg, respectively. After 24 weeks, the logarithm of UACR decreased by 0.37 ± 0.73 (P < 0.001). In addition, changes in morning, evening, and nocturnal home BP from baseline were as follows: morning systolic/diastolic BP - 8.32 ± 11.42/- 4.18 ± 5.91 mmHg (both P < 0.001), evening systolic/diastolic BP - 9.57 ± 12.08/- 4.48 ± 6.45 mmHg (both P < 0.001), and nocturnal systolic/diastolic BP - 2.38 ± 7.82/- 1.17 ± 5.39 mmHg (P = 0.0079 for systolic BP, P = 0.0415 for diastolic BP). Furthermore, the reduction in UACR after 24 weeks significantly correlated with an improvement in home BP profile, but not with changes in other variables, including office BP. Multivariate linear regression analysis also revealed that the change in morning home systolic BP was a significant contributor to the change in log-UACR. CONCLUSIONS: In Japanese patients with T2DM and diabetic nephropathy, dapagliflozin significantly improved albuminuria levels and the home BP profile. Improved morning home systolic BP was associated with albuminuria reduction. Trial registration The study is registered at the UMIN Clinical Trials Registry (UMIN000018930; http://www.umin.ac.jp/ctr/index-j.htm ). The study was conducted from July 1, 2015 to August 1, 2018.

Efficacy of cyclosporine combination therapy for new-onset minimal change nephrotic syndrome in adults.

BACKGROUND: Cyclosporine and prednisolone combination therapy has been used in the treatment of minimal change nephrotic syndrome (MCNS). However, few studies have evaluated the efficacy of cyclosporine combined with intravenous methylprednisolone pulse therapy (MPT) as a first-line treatment for new-onset MCNS. We conducted a retrospective clinical study to evaluate the efficacy and safety of cyclosporine combined with MPT and oral prednisolone for new-onset MCNS in adults. METHODS: Forty-six adult patients with biopsy-proven MCNS were analyzed retrospectively. This study included three groups. Group 1 (n = 17) was treated with intravenous MPT (0.5 or 1.0 g/day for 3 days) followed by oral cyclosporine (2-3 mg/kg/day) and prednisolone (30 mg/day). Group 2 (n = 15) was treated with intravenous MPT followed by oral prednisolone (0.4-0.8 mg/kg/day). Group 3 (n = 14) was treated with oral prednisolone (0.6-1.0 mg/kg/day) alone. RESULTS: The length of hospital stay was the shortest in Group 1 (P < 0.001). The mean duration to achieve <20 mg/day of prednisolone was also the shortest in Group 1 (P < 0.05). Complete remission rates were 100 % in Group 1, 85.7 % in Group 2, and 69.2 % in Group 3 during the 9-month follow-up (P = 0.073). The rate of adverse effects caused by prednisolone was less in Group 1 (P < 0.05). Multivariate analysis revealed that the independent determinants of durations of remission were the selectivity index (P = 0.004), eGFR (P = 0.001) and the use of cyclosporine (P = 0.045). CONCLUSIONS: Combination therapy with cyclosporine may be a beneficial treatment option for new-onset MCNS in adults because of its clinical efficacy and safety.

[Hypertension with chronic kidney disease: anti-hypertensive therapy recommended for the management of hypertension with CKD in JSN-CKD GL 2013 and JSH2014].

For clinical practice guidelines for the management of hypertension with CKD, the Japanese Society of Nephrology (JSN) and the Japanese Society of Hypertension (JSH) evaluated recently published evidence in corporation with each other. After considerable and careful discussion, both JSN and JSH revised their respective guidelines [the Evidence-based Clinical Practice Guideline for CKD 2013 (JSN-CKD GL 2013) and JSH2014]. This section will mainly introduce anti-hypertensive therapy recommended for the management of hypertension with CKD in both guidelines. Recommendation statements for the Management of Hypertension with CKD are as follows: 1) Anti-hypertensive therapy in CKD is strongly recommended to inhibit or prevent the progression of renal dysfunction and to prevent the occurrence or recurrence of CVD by reducing blood pressure (BP) (Grade A). 2) In all diabetic CKD, the target level of clinic BP is recommended as < 130/80 mmHg, irrespective of the presence or absence of albuminuria/proteinuria (Grade B). 3) In all non-diabetic CKD, the target level of clinic BP is strongly recommended as consistently < 140/90 mmHg, irrespective of the presence or absence of albuminuria/proteinuria (Grade A). 4) In non-diabetic CKD with A2 and A3 categories, the target level of clinic BP can be set as < 130/80 mmHg (Grade C1). 5) In diabetic CKD with A1 category, ARBs and ACE inhibitors are suggested as first-line anti-hypertensive drugs(Grade C1). 6) In diabetic CKD with A2 and A3 categories, ARBs and ACE inhibitors are recommended as first-line anti-hypertensive drugs (Grade A). 7) In non-diabetic CKD with A1 category, ARBs, ACE inhibitors, calcium channel blockers (CCBs) and diuretics are recommended as first-line anti-hypertensive drugs (Grade B). 8) In non-diabetic CKD with A2 and A3 categories, ARBs and ACE inhibitors are recommended as first-line anti-hypertensive drugs (Grade B).

Relationship between basal sodium intake and the effects of dapagliflozin in albuminuric diabetic kidney disease.

We investigated the impact of basal dietary sodium intake on the dapagliflozin-induced changes in albuminuria and blood pressure (BP) measured at home in patients with diabetic kidney disease (DKD).This was a secondary analysis of the Y-AIDA Study, in which DKD patients with estimated glomerular filtration rate (eGFR) ≥ 45 ml/min/1.73 m2 and urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g creatinine were administered dapagliflozin for 24 weeks, and dapagliflozin significantly improved albuminuria levels and home BP profiles. The effects on UACR, home-measured BP, and eGFR were compared between high- and low-sodium intake groups (HS and LS groups), which were created using baseline urinary sodium-to-creatinine ratio of 84 participants with available basal sodium-to-creatinine ratios. At baseline, clinic-/home-measured BPs, UACR, and eGFR, were comparable in the two groups. After 24 weeks, the reductions from baseline in ln-UACR were comparable in the two groups. In contrast, the reductions in evening home systolic BP and eGFR from baseline were larger in HS than in LS (BP: - 13 ± 2.08 vs. - 6 ± 1.88, P = 0.020; eGFR: - 3.33 ± 1.32 vs. 0.37 ± 1.29, P = 0.049). The home BP-lowering effects of dapagliflozin are larger in HS than LS, concomitant with a larger reduction in eGFR, suggesting a dapagliflozin-induced improvement in glomerular relative hyperfiltration in HS.