Cysteine catabolism plays a role in diet-induced renal stress-resistance – Healio

Cysteine catabolism plays a role in diet-induced renal stress-resistance – Healio

Source/Disclosures

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Source:

Koehler F, et al. FR-OR10. Presented at: ASN Kidney Week; Nov. 4-7, 2021 (virtual meeting).

Disclosures:
Koehler reports funding from Else Kröner-Fresenius-Stiftung, German Research Foundation under Germany’s Excellence Strategy, Köln Fortune program from the University of Cologne, Germany and Fresenius Kabi.

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Diets with a common metabolic pattern regarding cysteine catabolism can protect from ischemia-reperfusion injury-induced AKI, according to a speaker at ASN Kidney Week.

“Caloric restriction (CR) is efficient in protecting from acute kidney injury in rodent models. However, the transfer of caloric restriction into this clinical setting has not been successful yet,” Felix C. Koehler, MD, from the department II of internal medicine at the University Hospital Cologne in Germany, said. “We went on to characterize the efficacy of dietary interventions beyond calorie restriction in a rodent model of renal ischemia reperfusion injury. In addition to this, we went on to identify mechanisms of cellular stress resistance and to identify mechanisms that are indeed conserved in humans.”

In a murine model of renal ischemia-reperfusion injury (IRI), researchers observed six targeted dietary preconditioning protocols to quantify diet-induced kidney protection. The protocols included fasting mimicking diet (FMD), ketogenic diet (KD), dietary restriction of branched chain amino acids (BCAA) and two dietary regimens restricting sulfur containing amino acids (SAA) by 80% (SR80) or entirely (SR100), known as SR80/100, and CR.

Targeted metabolite and proteome profiling were used to determine shared mechanisms of dietary-achieved renal resilience. Additionally, a human cohort of cardiac surgery patients following a low-SAA diet confirmed the results.

Of the six protocols, FMD, SR80/100 and CR protected rodents from IRI-induced AKI quantified by kidney function, tissue damage and survival rates. Rodents preconditioned with KD showed moderate benefits after IRI, while BCAA did not protect from renal ischemic damage.

According to the abstract, “targeted metabolite and proteome profiling revealed overlapping changes in oxidative and hydrogen sulfide (H2S)-dependent cysteine catabolism as a pivotal mechanism of kidney protection in response to FMD, SR80/100 and CR identifying sulfite as its central component.”

Overall, FMD, SR80/100 and CR are efficient protectors of IRI-induced AKI and share common metabolic patterns in regard to cysteine catabolism. The study suggests these metabolic changes can be repeated in patients experiencing a low-SAA diet indicating a conserved metabolic response.

Koehler wrote, “Since FMD and low-SAA diets are feasible in humans our findings provide an important outlook towards novel protective strategies in the patient setting.”



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Source: https://www.healio.com/news/nephrology/20211215/cysteine-catabolism-plays-a-role-in-dietinduced-renal-stressresistance

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