Key result
Riociguat attenuates hypertension and improves kidney function in rats with chronic kidney disease.
Why the study?
cGMP regulates kidney function, but the possible protective effects of the soluble guanylate cyclase activator riociguat on the kidneys in chronic kidney disease remained to be investigated.
Does riociguat improve kidney function and reduce injury in a rat model of adenine-induced chronic kidney disease?
Does riociguat improve kidney function and reduce injury in a rat model of adenine-induced chronic kidney disease?
Riociguat demonstrates renoprotective effects in a rat model of adenine-induced chronic kidney disease, likely through anti-inflammatory and antioxidant mechanisms.
Riociguat may protect kidneys in rat CKD; leaves open translation to human disease.
Riociguat is a soluble guanylate cyclase (sGC) activator that increases the levels of cyclic guanosine monophosphate (cGMP). cGMP is known to play a key role in regulating kidney function. This research sought to investigate the possible protective effects of riociguat on the kidneys in the context of chronic kidney disease (CKD). CKD was induced in male Wistar rats through adenine administration. A total of 24 rats were allocated into four groups and administered treatments over a period of 35 days. Group 1 received a normal diet and a vehicle (carboxymethylcellulose (0.5%)), serving as the control. Group 2 received adenine (0.25% w/w) in the feed and a vehicle. Groups 3 and 4 received adenine in the feed (0.25% w/w) plus riociguat (3 mg/kg/day) and riociguat (10 mg/kg/day), respectively. Adenine administration significantly elevated systolic blood pressure, plasma creatinine, urea, and neutrophil gelatinase-associated lipocalin (NGAL). Furthermore, adenine reduced creatinine clearance and increased the urinary albumin-to-creatinine ratio and urinary N-Acetyl-β-D-Glucosaminidase (NAG). Histopathologically, adenine caused renal tubular necrosis and fibrosis. Furthermore, adenine elevated the plasma concentration of interleukins (IL-1β and IL-6) and tumor necrosis factor-alpha (TNF-α). Adenine significantly increased renal malondialdehyde (MDA) and reduced glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT), and total antioxidant capacity (TAC). Treatment with riociguat attenuated adenine-induced hypertension, improved kidney function, and ameliorated histopathological changes. Riociguat also reduced kidney injury markers, inflammation, and renal oxidative stress. The renoprotective effect of riociguat is probably due to anti-inflammatory and antioxidant actions. This indicates that riociguat may have the potential to slow the progression of kidney damage in chronic kidney disease (CKD).
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Abdelrahman et al. (2025) studied Adenine-Induced Chronic Kidney Disease (n=24). Riociguat vs. Adenine + vehicle was evaluated on Kidney function, histopathological changes, inflammation, and oxidative stress. Riociguat attenuated adenine-induced hypertension, improved kidney function, and reduced kidney injury markers, inflammation, and oxidative stress in rats with chronic kidney disease.
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