Kidney Week

Abstract: FR-PO168

Association Between Plasma Myostatin Levels and Loop Diuretic Use in Non-Dialysis-Dependent CKD Patients

Session Information

• CKD: Epidemiology, Risk Factors, Prevention - II
  October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 1901 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention

Authors

• Ishikawa, Seiko, Tokyo Kyosai Hospital, Tokyo, Japan

Seiko Ishikawa,

• Naito, Shotaro, Department of Nephrology, Tokyo Medical and Dental University, Tokyo, Japan

Shotaro Naito,

• Iimori, Soichiro, Department of Nephrology, Tokyo Medical and Dental University, Tokyo, Japan

Soichiro Iimori,

• Isobe, Kiyoshi, Department of Nephrology, Tokyo Medical and Dental University, Tokyo, Japan

Kiyoshi Isobe,

• Nomura, Naohiro, Department of Nephrology, Tokyo Medical and Dental University, Tokyo, Japan

Naohiro Nomura,

• Sohara, Eisei, Department of Nephrology, Tokyo Medical and Dental University, Tokyo, Japan

Eisei Sohara,

• Okado, Tomokazu, Department of Nephrology, Tokyo Medical and Dental University, Tokyo, Japan

Tomokazu Okado,

• Rai, Tatemitsu, Department of Nephrology, Tokyo Medical and Dental University, Tokyo, Japan

Tatemitsu Rai,

• Uchida, Shinichi, Department of Nephrology, Tokyo Medical and Dental University, Tokyo, Japan

Shinichi Uchida,

Background

Myostatin (MSTN) is mainly synthesized in skeletal muscles and acts as a negative regulator of skeletal muscle mass. It is up-regulated in patients with chronic kidney disease (CKD) and considered to be associated with the development of sarcopenia. Recently, we have reported that loop diuretics, commonly used in patients with advanced CKD, suppress skeletal muscle differentiation (Mandai S. Sci Rep. 2017). So far, the association between serum MSTN (sMSTN) levels and loop diuretic use is unknown.

Methods

We conducted a cross-sectional study comprised of 362 non-dialysis-dependent CKD patients over 20 years of age. The primary outcome was sMSTN levels. Multiple linear regression analyses were conducted to assess the associations between sMSTN levels (logarithmically transformed) and baseline characteristics including skeletal mass index (SMI). Interaction between loop diuretic use and SMI to sMSTN levels was estimated after stratifying patients by loop diuretic use. We calculated SMI as follows: Total body skeletal muscle mass measured by DEXA was divided by height squared.

Results

Median age was 71 years, 64.4% were male, mean SMI was 6.49 kg/m², mean eGFRcysC was 39.0 ml/min/1.73m², median sMSTN level was 1130 pg/ml, and 14.6% were treated with loop diuretics. Multivariate analysis showed that sMSTN levels were positively correlated with SMI (β=0.128, P<0.001), and negatively with eGFRcysC and loop diuretic use (β=-0.004, P=0.005 and β=-0.231, P<0.001, respectively). When stratified by loop diuretic use, adjusted coefficient β of SMI for sMSTN was higher in patients treated with loop diuretics than in patients not treated with loop diuretics (β=0.237, P=0.001 and β=0.118 P<0.001), respectively).

Conclusion

Loop diuretic use was independently associated with lower sMSTN levels. This result indicates that loop diuretics serve as negative regulator of skeletal muscle mass and therefore sMSTN levels may be attenuated by negative feedback. However, the increase of sMSTN level associated with SMI among the patients treated with loop diuretics was larger than those without loop diuretics. Other potential factors which elevate sMSTN levels in patients treated with loop diuretics are suggested to affect the relationship between sMSTN levels and SMI.