Renal Klotho expression in patients with acute kidney injury is associated with the severity of the injury
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background/Aims: The potential physiologic roles of Klotho in acute kidney injury (AKI) have recently been demonstrated in animal models. However, to date, there have been no human studies investigating the expression of renal Klotho in AKI. Methods: We retrospectively collected biopsy specimens and clinical data of AKI patients between January 2001 and December 2012. Klotho expression was determined by immunohistochemical staining, and the clinical-pathological correlation was examined. Results: Among the 34 patients diagnosed with acute tubular necrosis or acute tubulointerstitial nephritis, 21 patients without chronic histological lesions were included. The mean age was 37.3 ± 18.5 years and the mean peak creatinine level was 8.2 ± 5.5 mg/dL. In total, 10 patients (47.6%) received temporary renal replacement therapy (RRT); however, 17 patients (81%) showed functional recovery with creatinine levels of < 1.3 mg/dL after 1 month. The intensity of Klotho expression was scored as a percentage of Klotho-positive area. The renal Klotho score showed a significant negative correlation with the initial or peak creatinine level. When the patients were divided into three groups according to the Klotho score (low, middle, high), the low group had a significantly higher peak creatinine level and a more frequent requirement for RRT. However, the Klotho score was not a significant predictor of renal recovery. Conclusions: The results demonstrated that renal Klotho expression in humans decreased significantly according to the severity of AKI, regardless of the etiology, and that low expression was associated with a poor short-term outcome.
Abstract
Background/Aims: The potential physiologic roles of Klotho in acute kidney injury (AKI) have recently been demonstrated in animal models. However, to date, there have been no human studies investigating the expression of renal Klotho in AKI. Methods: We retrospectively collected biopsy specimens and clinical data of AKI patients between January 2001 and December 2012. Klotho expression was determined by immunohistochemical staining, and the clinical-pathological correlation was examined. Results: Among the 34 patients diagnosed with acute tubular necrosis or acute tubulointerstitial nephritis, 21 patients without chronic histological lesions were included. The mean age was 37.3 ± 18.5 years and the mean peak creatinine level was 8.2 ± 5.5 mg/dL. In total, 10 patients (47.6%) received temporary renal replacement therapy (RRT); however, 17 patients (81%) showed functional recovery with creatinine levels of < 1.3 mg/dL after 1 month. The intensity of Klotho expression was scored as a percentage of Klotho-positive area. The renal Klotho score showed a significant negative correlation with the initial or peak creatinine level. When the patients were divided into three groups according to the Klotho score (low, middle, high), the low group had a significantly higher peak creatinine level and a more frequent requirement for RRT. However, the Klotho score was not a significant predictor of renal recovery. Conclusions: The results demonstrated that renal Klotho expression in humans decreased significantly according to the severity of AKI, regardless of the etiology, and that low expression was associated with a poor short-term outcome.
참고문헌 (14)
- Kuro-o M, "Mutation of the mouse klotho gene leads to a syndrome resembling ageing", Nature, 390, pp.45~51 (1997)
- Koizumi M, "Parathyroid function in chronic kidney disease: role of FGF23-Klotho axis", Contrib Nephrol, 180, pp.110~123 (2013)
- Komaba H, "The role of FGF23 in CKD: with or without Klotho", Nat Rev Nephrol, 8, pp.484~490 (2012)
- Chen CD, "Insulin stimulates the cleavage and release of the extracellular domain of Klotho by ADAM10 and ADAM17", Proc Natl Acad Sci U S A, 104, pp.19796~19801 (2007)
- Hu MC, "Secreted klotho and chronic kidney disease", Adv Exp Med Biol, 728, pp.126~157 (2012)
- Hu MC, "Klotho as a potential biomarker and therapy for acute kidney injury", Nat Rev Nephrol, 8, pp.423~429 (2012)
- Doi S, "Klotho inhibits transforming growth factor-beta1 (TGF-beta1) signaling and suppresses renal fibrosis and cancer metastasis in mice", J Biol Chem, 286, pp.8655~8665 (2011)
- Panesso MC, "Klotho has dual protective effects on cisplatin-induced acute kidney injury", Kidney Int, 85, pp.855~870 (2014)
- Sugiura H, "Klotho reduces apoptosis in experimental ischaemic acute kidney injury via HSP-70", Nephrol Dial Transplant, 25, pp.60~68 (2010)
- Sugiura H, "Klotho reduces apoptosis in experimental ischaemic acute renal failure", Nephrol Dial Transplant, 20, pp.2636~2645 (2005)
- Hu MC, "Klotho deficiency is an early biomarker of renal ischemia-reperfusion injury and its replacement is protective", Kidney Int, 78, pp.1240~1251 (2010)
- Moreno JA, "The inflammatory cytokines TWEAK and TNFalpha reduce renal klotho expression through NFkappaB", J Am Soc Nephrol, 22, pp.1315~1325 (2011)
- John GB, "Role of Klotho in aging, phosphate metabolism, and CKD", Am J Kidney Dis, 58, pp.127~134 (2011)
- Shimamura Y, "Serum levels of soluble secreted alpha-Klotho are decreased in the early stages of chronic kidney disease, making it a probable novel biomarker for early diagnosis", Clin Exp Nephrol, 16, pp.722~729 (2012)