Background and objectives: A low total nephron number, which is associated with low birth weight (LBW), may indicate increased susceptibility to early-onset renal diseases in children. However, few studies have assessed renal biopsy findings in LBW children. We examined the relationship between LBW and glomerular density (GD) and/or glomerular volume (GV) in renal biopsy samples as a surrogate for total nephron number. Design, setting, participants, & measurements: Renal biopsy findings of children of LBW were compared with those of age-matched control subjects of normal birth weight (NBW) who were histopathologically diagnosed with FSGS or minimal change nephrotic syndrome (MCNS) from 1995 to 2011. The GD and GV were estimated on the basis of measurements obtained by computerized image analysis. Results: A total of 31 subjects (mean age 11 years; eight with low birth weight–FSGS [LBW-FSGS], 10 with normal birth weight–FSGS [NBW-FSGS], and 13 with normal birth weight–minimal change nephrotic syndrome [NBW-MCNS]) were analyzed. The mean birth weight of each group was 777 g (629–1000), 3110 g (2888–3358), and 3120 g (2748–3398), respectively (median [25th–75th percentile]). Age, body mass index, BP, and degrees of globally sclerotic glomeruli at biopsy were comparable between the groups. The GD was lower (LBW-FSGS, 1.4±0.6/mm²; NBW-FSGS, 3.3±1.2/mm²; and NBW-MCNS, 3.6±1.1/mm²; P<0.05) and the GV was greater (LBW-FSGS, 4.1 [3.1–5.1]×10⁶ µm³; NBW-FSGS, 1.6 [1.5–2.1]×10⁶ µm³; and NBW-MCNS, 1.3 [1.1–1.8]×10⁶ µm³ [median, (25th–75th percentile)]; P<0.05) in patients with LBW-FSGS than in the other patient groups. The GD showed close positive correlations with birth weight (r=0.48) and gestational age (r=0.54), independent of renal function and degree of global glomerular sclerosis. Conclusions: A low GD together with marked glomerular enlargement characterizes renal biopsy samples of children born with a LBW at an early stage of gestation.

Background: The kidney is easily affected by aging‐associated changes, including glomerulosclerosis, tubular atrophy, and interstitial fibrosis. Particularly, renal tubulointerstitial fibrosis is a final common pathway in most forms of progressive renal disease. Angiotensin II type 1 receptor ( AT 1R)‐associated protein ( ATRAP ), which was originally identified as a molecule that binds to AT 1R, is highly expressed in the kidney. Previously, we have shown that ATRAP suppresses hyperactivation of AT 1R signaling, but does not affect physiological AT 1R signaling. Methods and Results: We hypothesized that ATRAP has a novel functional role in the physiological age‐degenerative process, independent of modulation of AT 1R signaling. ATRAP ‐knockout mice were used to study the functional involvement of ATRAP in the aging. ATRAP ‐knockout mice exhibit a normal age‐associated appearance without any evident alterations in physiological parameters, including blood pressure and cardiovascular and metabolic phenotypes. However, in ATRAP ‐knockout mice compared with wild‐type mice, the following takes place: (1) age‐associated renal function decline and tubulointerstitial fibrosis are more enhanced; (2) renal tubular mitochondrial abnormalities and subsequent increases in the production of reactive oxygen species are more advanced; and (3) life span is 18.4% shorter (median life span, 100.4 versus 123.1 weeks). As a key mechanism, age‐related pathological changes in the kidney of ATRAP ‐knockout mice correlated with decreased expression of the prosurvival gene, Sirtuin1 . On the other hand, chronic angiotensin II infusion did not affect renal sirtuin1 expression in wild‐type mice. Conclusions: These results indicate that ATRAP plays an important role in inhibiting kidney aging, possibly through sirtuin1‐mediated mechanism independent of blocking AT 1R signaling, and further protecting normal life span.

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 (bothP < 0.001), evening systolic/diastolic BP − 9.57 ± 12.08/− 4.48 ± 6.45 mmHg (bothP < 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 registrationThe 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.