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  1. Article ; Online: Tubule-Derived Follistatin Is Increased in the Urine of Rats with Renal Ischemia and Reflects the Severity of Acute Tubular Damage

    Izumi Nagayama / Kaori Takayanagi / Hajime Hasegawa / Akito Maeshima

    Cells, Vol 12, Iss 801, p

    2023  Volume 801

    Abstract: Activin A, a member of the TGF-beta superfamily, is a negative regulator of tubular regeneration after renal ischemia. Activin action is controlled by an endogenous antagonist, follistatin. However, the role of follistatin in the kidney is not fully ... ...

    Abstract Activin A, a member of the TGF-beta superfamily, is a negative regulator of tubular regeneration after renal ischemia. Activin action is controlled by an endogenous antagonist, follistatin. However, the role of follistatin in the kidney is not fully understood. In the present study, we examined the expression and localization of follistatin in normal and ischemic rat kidneys and measured urinary follistatin in rats with renal ischemia to assess whether urinary follistatin could serve as a biomarker for acute kidney injury. Using vascular clamps, renal ischemia was induced for 45 min in 8-week-old male Wistar rats. In normal kidneys, follistatin was localized in distal tubules of the cortex. In contrast, in ischemic kidneys, follistatin was localized in distal tubules of both the cortex and outer medulla. Follistatin mRNA was mainly present in the descending limb of Henle of the outer medulla in normal kidneys but was upregulated in the descending limb of Henle of both the outer and inner medulla after renal ischemia. Urinary follistatin, which was undetectable in normal rats, was significantly increased in ischemic rats and peaked 24 h after reperfusion. There was no correlation between urinary follistatin and serum follistatin. Urinary follistatin levels were increased according to ischemic duration and were significantly correlated with the follistatin-positive area as well as the acute tubular damage area. These results suggest that follistatin normally produced by renal tubules increases and becomes detectable in urine after renal ischemia. Urinary follistatin might be useful to assess the severity of acute tubular damage.
    Keywords follistatin ; acute kidney injury ; ischemia reperfusion ; Biology (General) ; QH301-705.5
    Subject code 630
    Language English
    Publishing date 2023-03-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Correlation between albuminuria and interstitial injury marker reductions associated with SGLT2 inhibitor treatment in diabetic patients with renal dysfunction

    Saeko Sato / Kaori Takayanagi / Taisuke Shimizu / Koichi Kanozawa / Takatsugu Iwashita / Hajime Hasegawa

    European Journal of Medical Research, Vol 27, Iss 1, Pp 1-

    2022  Volume 9

    Abstract: Abstract Background We investigated the effects of sodium–glucose cotransporter 2 inhibitor (SGLT2i) administration focusing on its involvement in tubulo-interstitial disorders in diabetic kidney. Methods Enrolled patients with diabetic kidney disease ... ...

    Abstract Abstract Background We investigated the effects of sodium–glucose cotransporter 2 inhibitor (SGLT2i) administration focusing on its involvement in tubulo-interstitial disorders in diabetic kidney. Methods Enrolled patients with diabetic kidney disease received a mean dose of 52.3 mg of an SGLT2i (ipragliflozin) daily. Blood and urine were sampled at 0, 1, and 12 months (M). Results Non-renal-dysfunction patients (NRD: baseline eGFR ≥ 60 mL/min/1.73 m2, n = 12) and renal-dysfunction patients (RD: baseline eGFR < 60 mL/min/1.73 m2, n = 9) were analyzed separately. The median urine albumin-to-Cr ratio (ACR) was significantly decreased at 1 M in both groups (NRD: 163.1 at 0 M vs 118.5 mg/g Cr at 1 M, RD: 325.2 at 0 M vs 136.0 mg/g Cr at 1 M). In the RD, but not the NRD group, reduction of urine monocyte chemotactic protein-1 (MCP-1) by SGLT2i showed a significant difference between high-responders (HR: − 25.7 ± 11.4%) and low-responders (LR: 59.2 ± 17.0%), defined by ACR reduction at 1 M. Univariate analysis showed a significant correlation between the reduction of ACR and MCP-1 (R = 0.683, p = 0.042) in RD. Conclusion SGLT2i exerted an anti-albuminuric effect regardless of the presence/absence of renal dysfunction. However, the anti-albuminuric effect of SGLT2i in patients with renal dysfunction appears more closely associated with amelioration of tubulo-interstitial disorders compared to patients without renal dysfunction.
    Keywords Diabetic tubulopathy ; Fibrosis ; MCP-1 ; Proteinuria ; Type 2 diabetes ; N-Acetyl-β-D-glucosaminidase ; Medicine ; R
    Subject code 616
    Language English
    Publishing date 2022-08-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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