Table 1.

Clinical trials of N-acetylcysteine (NAC) administration in chronic kidney disease (CKD), hemodialysis (HD) and peritoneal dialysis (PD) patients

Study ref	Year	Design	Population	Intervention	Outcome	Result
CKD
Moist et al. [82]	2010	Double-blind, placebo-controlled RCT	60 CKD3 patients	4 doses of NAC (1200 mg) po at 12 h intervals	Plasma creatinine, eGFR, proteinuria, Cystatin C	No effect
Hasemi et al. [85]	2012	RCT	70 patients with diabetic nephropathy	600 mg × 2 NAC po + losartan 25 mg for 8 weeks	Proteinuria	No effect
Mainra et al. [83]	2007	Prospective	30 CKD3 patients	600 mg NAC po	Plasma creatinine, Cystatin C	No effect
Rehman et al.[84]	2008	Prospective	29 CKD3-5 patients	1200 mg × 2 NAC po for 2 days	Plasma creatinine, Cystatin C	No effect
Renke et al. [53]	2008	RCT, open-label, two-period cross-over	20 non-diabetic patients with proteinuria	1200 mg NAC po added to RAAS blockers for 8 weeks	Proteinuria	No effect
Agarwal et al. [86]	2004	Randomized, open-label, parallel	20 CKD3-4 patients receiving iron IV	600 mg × 2 NAC po for a week	Plasma MDA, ferritin, GSH, GSSG, SOD, GPX	Improvement in OS
HD
Trimarchi et al. [91]	2003	Placebo-controlled RCT	24 HD patients	600 mg × 2 NAC po for 8 weeks	MDA levels	Improvement in OS
Thaha et al. [94]	2008	Double-blind RCT	40 HD patients	NAC 5 g IV during HD session	ADMA levels	Improvement in OS
Swarnalatha et al. [5]	2010	Double-blind, cross-over RCT	24 HD patients receiving iv iron infusion	600 mg × 2 NAC po for 10 days	MDA, TAC, hs-CRP,	Improvement in OS
Garcia-Fernandez et al. [92]	2010	Placebo-controlled, cross-over RCT	40 HD patients	2 g NAC IV 15 min before iron infusion	MDA, TAC	Improvement in OS
Tepel et al. [101]	2003	RCT	134 HD patients	600 mg × 2 NAC po	Major CV events	Improvement
Hsu et al. [55]	2010	Non-randomized, nested case–control	323 HD patients	200mgx3 NAC po for 3 months	Anemia	Improvement
Giannikouris [93]	2015	Prospective	48 HD patients	600mgx2 NAC po for 6 months	Hb, ADMA, MDA, MPO	Improvement of OS, inflammation and anemia
Saddadi et al. [95]	2014	Prospective	24 HD patients	600 mg × 2 po for 12 weeks	IL-6, hs-CRP	Improvement of inflammation
Feldman et al. [105]	2012	Prospective open-label, self-controlled	20 HD patients with RRF urine volume > 100 mL/d	1200mgx2 NAC po for 2 weeks	RRF, NO, ADMA	Improvement of RRF
Ahmadi et al. [10]	2017	Randomized, parallel-group, open-label	54 HD patients with RRF urine volume > 100 mL/d	1200mgx2 NAC po for 4 weeks	GFR, 24 h urine volume, Kt/V	Improvement of kidney function
Shahbazian et al. [2]	2019	Double-blind RCT	40 HD patients	600 mg × 2 NAC po for 6 weeks	TAC	Improvement of OS
Tsai et al. [108]	2010	RCT	43 high-flux HD patients with or without RRF	Addition of 5 g NAC IV to normal saline during HD session	Serum TNF-α, IL-10, hs-CRP, total Hcy	Decrease in total Hcy
Thaha et al. [106]	2006	Placebo-controlled RCT	60 HD patients	4 h NAC IV during HD session	Plasma Hcy, heart rate, pulse pressure	Decreased Hcy, improvement in pulse pressure
Scholze et al. [68]	2004	Placebo-controlled, cross-over RCT	20 HD patients	4 h NAC IV during HD session	Plasma Hcy, pulse waves during HD	Decreased Hcy, improvement in pulse pressure and endothelial function
Friedman [109]	2003	Placebo-controlled RCT	38 HD patients	1200mgx2 NAC po for 4 weeks	Hcy plasma levels	No effect
Perna et al. [66]	2012	Open, parallel	145 HD patients	MTHF +—5 g NAC IV during HD for 10 sessions	Hcy plasma levels	Decrease in Hcy
Bashardoust et al. [49]	2017	Placebo-controlled RCT	51 HD patients	1200 mg NAC po for 4 weeks	Hb, ferritin, hs-CRP	Improvement in anemia and inflammation
Bostom et al. [107]	1996	Prospective	11 HD patients	1 dose of 1200 mg po NAC	Hcy plasma levels	No effect
Modarresi et al. [9]	2017	Double-blind, placebo-controlled RCT	57 kidney transplant recipients	NAC po: 600 mg before- followed by twice daily up to the fifth day after transplantation	GPX activity, serum MDA levels, first week eGFR, graft function	No effect on GPX/MDA 28% better graft function, 14 ml/min higher eGFR
PD
Nascimento et al. [117]	2010	Placebo-controlled clinical	30 PD patients	600 mg × 2 NAC po for 8 weeks	hs-CRP, IL-6, TNF-a, AOPPs, GSH, Hcy, ADMA, free sulfhydryls	Improvement of inflammation No effect on OS
Purwanto et al. [6]	2012	Placebo-controlled clinical	32 PD patients	600 mg × 2 NAC po for 8 weeks	PCT, IL-6, IL-1, C3, SICAM, hs-CRP, TNF-a	Improvement of inflammation
Feldman et al. [119]	2011	Prospective open-label, self-controlled	10 PD patients	1200 mg × 2 NAC po for 4 weeks	RRF, Urine volume Residual Renal Kt/V	Improvement
Najafi et al. [118]	2021	Quasi-experimental self-controlled	50 PD patients	600 mg × 2 NAC po for 8 weeks	hs-CRP	Improvement

A summary of clinical trials investigating the use of NAC in CKD, HD and PD assessing its antioxidant and anti-inflammatory properties

ADMA asymmetric dimethylarginine, AOPPs advanced oxidative protein products, C3 complement C3, CD11b/CD18 cluster of differentiation 11b/cluster of differentiation 18, CKD chronic kidney disease, CV cardiovascular, GPX glutathione peroxidase, GSH reduced glutathione, GSSG oxidized glutathione, Hb hemoglobin, Hcy homocysteine, HD hemodialysis, hs-CRP high-sensitivity C reacting protein, IL-1 interleukin 1, IL-10 interleukin 10, IL-6 interleukin 6, IL-8 interleukin 8, IV intravenous, MDA malondialdehyde, MPO myeloperoxidase, MTHF 5-methyltetrahydrofolate, NO nitrogen oxide, OS oxidative stress, PCT procalcitonin, po per os, RAAS renin–angiotensin–aldosterone system, RCT randomized controlled trial, RRF residual renal function, sICAM-1 soluble intercellular adhesion molecule-1, SOD erythrocyte superoxide dismutase, TAC total antioxidant capacity, TNF-α tumor necrosis factor-a, vWF Von Willebrand factor