[59] The effect of Alda-1, aldehyde dehydrogenase-2 agonist, on the renal functions following ischaemia–reperfusion injury

Objective To investigate the effect Alda-1, aldehyde dehydrogenase-2 (ALDH2) agonist, on renal functions following ischaemia–reperfusion (IRI) injury. IRI induces the production of aldehydes, which are detoxified by aldehyde dehydrogenases (ALDHs). Alda-1 is a selective ALDH2 agonist and its protective effect has been demonstrated in several conditions; however, the effect of Alda-1 on the kidney or on renal IRI has not been investigated. Methods We investigated the effect of Alda-1 on renal dysfunction following IRI. Wistar rats underwent left IRI for 40 min. Group-Alda ( n  = 11) received Alda-1 starting 24 h before IRI and continued for 7 days and then renal functions were measured. Group-Vx ( n  = 11) underwent the same protocol but received only the dissolvent. Results Alda-1 did not affect renal blood flow or glomerular filtration rate in the left ischaemic kidney in Group-Alda compared to the Group-Vx [mean (SD) 3.05 (0.50) vs 3.53 (0.70) mL/min, and 0.40 (0.06) vs 0.51 (0.08) mL/min/1.73 m 2 , respectively; both P  > 0.05]. However, left renal fractional sodium excretion was significantly worse in Group-Alda [mean (SD) 2.80 (0.43) vs 1.37 (0.36)%; P  = 0.02). Alda-1 also adversely affected the gene expressions of kidney injury molecule-1 ( KIM-1 ) and neutrophil gelatinase-associated lipocalin ( NGAL ) [mean (SD) 217 (38) vs 99 (13) and 49 (13) vs 20 (5), respectively; both P P  ⩽ 0.05]. This was associated with intratubular crystal deposition suggestive of crystalline nephropathy. Conclusion Alda-1 exacerbated the IRI-induced renal tubular dysfunction and alterations in pro-inflammatory and pro-fibrotic cytokines, which appears be due to crystalline nephropathy. Extreme caution should be taken when administering ALda-1 or other potentially crystal-forming medications to subjects with underlying kidney disease.