VITAMIN D–HORMONE INTERPLAY AS A DRIVER OF MUSCLE RECOVERY IN END-STAGE KIDNEY DISEASE: INSIGHTS FROM A SIX-MONTH PROSPECTIVE STUDY

The hormonal basis of sarcopenia, especially the effects of long-term vitamin D therapy, remains understudied. This study evaluated hormonal correlations, risk factors, and the impact of six-month cholecalciferol supplementation on sarcopenia and quality of life.

CKD5 patients aged 18–60 years were screened for sarcopenia using handgrip strength and bioimpedance-based muscle mass. Sarcopenia was classified as probable, confirmed, and severe categories. Confirmed sarcopenic cases were supplemented with 60,000 IU weekly cholecalciferol for 12 weeks in vitamin D deficit and fortnightly for 6 weeks in sufficient patients. Comprehensive nine hormonal profile and risk factor assessment in all sarcopenic patients were done.  All were subjected for QoL by KDQOL-36 SF at baseline and 6 months. Changes in Sarcopenia, physical and mental domains of QoL (PCS and MCS) were studied at baseline and 6th month. 

In this prospective interventional study, 535 CKD stage 5 patients were screened, and 401 eligible participants were analyzed for sarcopenia. The prevalence of probable, confirmed, and severe sarcopenia was 82.3%, 33.4%, and 25.4%, respectively, with dialysis patients showing slightly higher rates. Sarcopenic individuals were older, predominantly male, and had lower BMI, muscle mass, and strength. Diabetes, hypertension, and CAD were more common among them, and vitamin D deficiency was significantly higher (mean 28.3 ± 1.6 ng/mL vs 32.4 ± 4.7 ng/mL, p = 0.002). Following cholecalciferol supplementation, functional and biochemical improvements were evident. At three months, 13.2% of confirmed sarcopenic patients fully recovered and 5.4% improved to probable sarcopenia, while by six months, 23.3% fully recovered and 13.3% moved to the probable category (p = 0.001). Severe cases showed remarkable gains in gait speed—from 51.3 to 79.6 cm/s (p < 0.001). ASMI increased from 5.09 ± 1.39 to 6.08 ± 1.53 kg/m², and handgrip strength from 15.8 ± 1.4 to 18.3 ± 1.2 kg (p < 0.001). Mean serum 25(OH)D rose from 21.76 ± 13.91 to 44.72 ± 13.35 ng/mL (p < 0.001), with deficiency rates dropping from 80.6% to 16.4%. Responders had higher baseline vitamin D, handgrip, and ASMI values, and fewer diabetics (34% vs 66%, p = 0.014). Non-responders exhibited elevated prolactin (66.9 ng/mL, p = 0.02), higher HOMA-IR (4.12, p = 0.004), and lower IGF-1 (30.6 ng/mL, p = 0.013) and T3 (p = 0.032). Among non-responders who remained vitamin D deficient, vitamin D levels showed a positive correlation with IGF-1 (r = 0.76) and testosterone (r = 0.64) and a negative correlation with insulin resistance (r = –0.61), suggesting persistent endocrine interplay despite supplementation. Baseline hormonal abnormalities among sarcopenic patients included IGF-1 deficiency (85.8%), hyperprolactinemia (68%), subclinical hypothyroidism (56.7%), and insulin resistance (47.5%). Diabetes (OR 9.25, p = 0.004) and vitamin D deficiency (OR 1.05, p = 0.038) were independent predictors of sarcopenia, while low handgrip, ASMI, and elevated prolactin or HOMA-IR predicted poor response. KDQOL-36 scores improved significantly—PCS from 2495.0 ± 590.6 to 2626.6 ± 972.4 (p < 0.001) and MCS from 3461.4 ± 511.6 to 3590.6 ± 934.0 (p < 0.001), reflecting overall enhancement in both physical and mental quality of life following vitamin D therapy.  

Diabetes and vitamin D deficiency are risk factor for sarcopenic CKD5 patients. Six months vitamin D supplementation improved sarcopenia and quality of life in them. Non responsive sarcopenic patients had hormonal imbalances which remain uncorrected or may have blunted therapeutic effects of vitamin D.