Inhaled nitric oxide therapy and risk of renal dysfunction: a systematic review and meta-analysis of randomized trials

Table 5 Animal and human studies investigating the effects of inhaled nitric oxide (iNO) on the kidneys

Study (year)	Species	Protocols of iNO	Main findings
Valvini (1995) [38]	Human	40 ppm for 3 days followed by 90 ppm for 2 days	1. Inhaling 40 ppm nitric oxide would result in a daily nitrogen oxide load of about 25 mmol.
Valvini (1995) [38]	Human	40 ppm for 3 days followed by 90 ppm for 2 days	2. Impairment of renal function would cause an increase in serum nitrogen oxides.
Troncy (1997) [9]	Swine	40 ppm iNO	Inhaled nitric oxide increased renal blood flow, glomerular filtration rate and urinary flow.
Preiser (1998) [37]	Human	1 to 20 ppm	1. Renal excretion of NO₂ ⁻ and NO₃ ⁻ was unaltered by nitric oxide inhalation.
Preiser (1998) [37]	Human	1 to 20 ppm	2. Long-term nitric oxide inhalation was associated with a consistent increase in the NO₃ ⁻ plasma concentration.
Wraight (2001) [36]	Human	40 ppm for 2 h	Inhaled nitric oxide may alter tubular salt and water resorbtion.
Kielbasa (2001) [35]	Rat	49 or 107 ppm iNO for 4 h	High dose of iNO increased nitric oxide synthase III protein expression, and nitrotyrosine and phosphotyrosine immunoreactivity.
Da (2007) [34]	Swine	30 ppm iNO for 3.5 h	Decreased swelling and necrosis of glomeruli.
Gozdzik (2009) [33]	Swine	40 ppm iNO for 30 h	1. Transient natriuretic effect.
Gozdzik (2009) [33]	Swine	40 ppm iNO for 30 h	2. Renal tubular apoptosis promotion after 30 h of iNO treatment.
Göranson (2014) [44]	Swine	30 ppm iNO for 30 h	Combined therapy with iNO and intravenous steroid is associated with partial protection of kidney function.

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