. 2023 Mar 18;15(6):1466. doi: 10.3390/nu15061466

Table 4.

Experimental studies investigating the effects of creatine supplementation on kidney function in clinical populations.

Study	Sample Characteristics	Experimental Design	Creatine Supplementation Protocol	Main Findings
Hayashi et al. (2014) [60]	Children with SLE (15 ± 2 years old)	Double-blind randomized placebo-controlled crossover trial (n = 15) (i) Creatine (ii) Placebo	Creatine monohydrate 0.1 g∙kg⁻¹∙day⁻¹ for 12 weeks	↔ mGFR ↔ Serum Crn ↔ Urinary Crn ↔ BUN ↔ Urinary urea ↔ Serum electrolytes ↔ Proteinuria ↔ Albuminuria
Alves et al. (2013) [5]	Middle-aged women with fibromyalgia (49 ± 9 years old) *	Double-blind randomized controlled trial (i) Creatine (n = 15) (ii) Placebo (n = 13)	Creatine monohydrate L: 20 g∙day⁻¹ for 5 days M: 5 g∙day⁻¹ for 15 weeks	↔ Serum Crn ↔ Urinary Crn ↔ BUN ↔ Urinary urea ↔ Serum electrolytes ↔ Urinary electrolytes ↔ Proteinuria ↔ Albuminuria
Earnest et al. (1996) [40]	Middle-aged adults with hypercholesterolemia (51 ± 12 years old)	Double-blind randomized controlled trial (i) Creatine (n = 20; 9 men/11 women) (ii) Placebo (n = 14; 9 men/5 women)	Creatine monohydrate L: 20 g∙day⁻¹ for 5 days M: 10 g∙day⁻¹ for 51 days	↔ Serum Crn ↔↑ BUN ^#
Gualano et al. (2011) [56]	Sedentary older adults with T2DM (57 ± 6 years old) *	Double-blind randomized controlled trial (i) Creatine + CT (n = 13) (ii) Placebo + CT (n = 12)	Creatine monohydrate 5 g∙day⁻¹ for 12 weeks	↔ mGFR ↔ Serum Crn ↔ Urinary Crn ↔ Crn clearance ↔ BUN ↔ Urinary urea ↔ Serum electrolytes ↔ Urinary electrolytes ↔ Proteinuria ↔ Albuminuria
Neves et al. (2011) [57]	Postmenopausal women with knee osteoarthritis (58 ± 3 years old)	Double-blind randomized controlled trial (i) Creatine (n = 13) (ii) Placebo (n = 11)	Creatine monohydrate L: 20 g∙day⁻¹ for 1 week M: 5 g∙day⁻¹ for 11 weeks	↔ mGFR ↔ Serum Crn ↔ Urinary Crn ↔ Crn clearance ↔ BUN ↔ Urinary urea ↔ Proteinuria ↔ Albuminuria
Lobo et al. (2015) [63]	Postmenopausal women with osteopenia (58 ± 5 years old) *	Double-blind randomized controlled trial (i) Creatine (n = 56) (ii) Placebo (n = 53)	Creatine monohydrate 1 g∙day⁻¹ for 12 months	↔ Serum Crn ↔ Urinary Crn ↔ Albuminuria
Sales et al. (2020) [67]	Postmenopausal women with osteopenia (58 ± 6 years old)	Double-blind randomized controlled trial (i) Creatine (n = 106) (ii) Placebo (n = 94)	Creatine monohydrate 3 g∙day⁻¹ for 24 months	↔ Serum Crn ↔ Urinary Crn ↔ Albuminuria
Groeneveld et al. (2005) [50]	Young to older adults with ALS (58 ± 11 years old)	Double-blind randomized controlled trial (i) Creatine (n = 88; 57 men/31 women) (ii) Placebo (n = 87; 63 men/24 women)	Creatine monohydrate 10 g∙day⁻¹ for 310 days	↔↑ Serum Crn ^† ↔ BUN ↔ Albuminuria
Bender et al. (2008) [53]	Middle-aged patients with Parkinson (60 ± 10 years old)^*	Double-blind randomized controlled trial (i) Creatine (n = 40; 28 men/12 women) (ii) Placebo (n = 20; 15 men/5 women)	Creatine monohydrate L: 20 g∙day⁻¹ for 6 days M: 2–4 g∙day⁻¹ for 6–24 months	↔↑ Serum Crn ^‡ ↔ Urinary Crn ↔ Serum CysC ↔ BUN ↔ Hematuria ↔ Albuminuria
Kieburtz et al. (2015) [62]	Middle-aged and older adults with Parkinson (62 ± 10 years old) *	Double-blind randomized controlled trial (i) Creatine (n = 477) (ii) Placebo (n = 478)	Creatine monohydrate 10 g∙day⁻¹ for 5–8 years	↔↑ Serum Crn ^¥
Domingues et al. (2020) [66]	Middle-aged and older adults with peripheral arterial disease (64 ± 9 years old) *	Double-blind randomized controlled trial (i) Creatine (n = 14) (ii) Placebo (n = 15)	Creatine monohydrate L: 20 g∙day⁻¹ for 1 week M: 5 g∙day⁻¹ for 7 weeks	↔ Serum Crn ↔ Urinary Crn ↔ Crn clearance
Roschel et al. (2021) [68]	Pre-frail and frail older adults (72 ± 6 years old)	Double-blind randomized controlled trial (i) Creatine (n = 22) (ii) Creatine + Whey (n = 22) (iii) Whey (n = 22) (iv) Placebo (n = 22)	Creatine monohydrate 6 g∙day⁻¹ for 16 weeks	↔ mGFR ↔ Serum Crn ↔ Urinary Crn ↔ BUN ↔ Urinary urea ↔ Proteinuria ↔ Albuminuria

ALS: amyotrophic lateral sclerosis; BUN: blood urea nitrogen; Crn: creatinine; CT: combined aerobic and strengthening exercise training; CysC: Cystatin C; eGFR: estimated glomerular filtration rate; L: loading phase; M: maintenance phase; mGFR: measured glomerular filtration rate; SLE: systemic lupus erythematosus; T2DM: type 2 diabetes mellitus. * whole sample estimated pooled mean ± SD from available data. ^# significantly increased at one of four time-points in women, but not in men. ^†increased only when assessed by enzymatic methods, but not with HPLC (High Performance Liquid Chromatography). ^‡ between-group significant difference detected at only one out of the seven time-points of sampling. ^¥ heat maps by treatment group showed an immediate increase in serum Crn levels at the first post-baseline visit followed by stabilization in the creatine group. Arrows indicate similar results (↔) between-groups or significant increased (↑)/decreased (↓) in creatine-supplemented groups versus placebo/control.