# Long-Term Functional and Structural Renoprotection After Experimental Acute Kidney Injury in Subclinical Chronic Kidney Disease In Vivo

## TL;DR

The study shows that a dual treatment protects kidney function and structure in rats with subclinical kidney disease after acute injury.

## Contribution

A novel dual treatment combining nicotinamide riboside and SkQR1 provides long-term renoprotection in subclinical chronic kidney disease.

## Key findings

- Dual treatment preserved kidney functional reserve and reduced structural damage after injury.
- Treatment upregulated Sirt1, Nrf2, and antioxidant genes, indicating mitochondrial and redox protection.
- Treatment improved vascular integrity and blood volume in injured kidneys.

## Abstract

Subclinical chronic kidney disease (sCKD) predisposes one to acute kidney injury (AKI) and chronic kidney disease (CKD). Reduced kidney functional reserve (KFR) detects sCKD in preclinical studies and predicts AKI after cardiac surgery. We evaluated renal protection in a rat model of kidney injury where ischaemia–reperfusion injury (IRI) was induced after sCKD. Dual treatment boosting nicotinamide adenine dinucleotide (NAD) by nicotinamide riboside (NR) combined with the mitochondria-targeted antioxidant SkQR1 protected the KFR and reduced structural kidney damage, including markers of vascular integrity and the relative blood volume (rBV). The dual treatment upregulated Sirt1 and Nrf2, increased the nuclear localisation of the mitochondrial biogenesis regulator PGC-1α and the mitochondrial protein marker COX4, and upregulated the antioxidant gene NOQ1. These observations suggest mitochondrial protection and modulation of the cellular redox state provided long-term structural and functional protection against kidney injury superimposed on background sCKD.