NR supplementation holds a promising therapeutic potential for myocardial infarction-induced acute kidney injury

Evidence that has accumulated over the last three decades suggests that renal diseases start in utero...Low nephron number is one of the main contributors to chronic kidney disease (CKD) susceptibility in adulthood...Here, we show that a nephron number deficit and impaired renal architecture of mice born to mothers fed a low protein diet can be restored by NR supplementation during pregnancy through the induction of SIRT3 expression and activity...These findings have huge potential for clinical translation, given that inadequate nephrons at birth increase the risk in adulthood of hypertension and renal diseases. Chronic kidney disease affects over 10% of the adult population worldwide, with rising overall morbidity and mortality rates. In view of this, it is evident that prenatal kidney care is an important global health challenge.

...Overall, these data show that NR supplementation boosted NAD metabolism to augment mitochondrial function, reducing inflammation and thereby preventing progression of diabetic kidney disease.

...We now present an overview of research on therapy with vitamin B3 vitamers and derivate molecules {niacin, Nicotinamide [NAM; niacinamide], NAM riboside [Nicotinamide riboside (NR)], Reduced nicotinamide riboside [NRH] and NAM mononucleotide} in kidney injury, including an overview of ongoing clinical trials, and discuss the potential explanations for diverging reports on the impact of these therapeutic approaches on pre-clinical acute and chronic kidney disease.

Chronic kidney disease (CKD) is a global public health problem with high morbidity and mortality. Decreased nicotinamide adenine dinucleotide (NAD+) levels were found to be associated with aging, cancer, and neurodegenerative and metabolic disorders. However, the alteration of renal NAD+ levels and biosynthesis pathways in CKD is less known. In the present study, we aimed to evaluate renal NAD+ levels and tested the expression of key enzymes in three NAD+ biosynthesis pathways in two different types of CKD rat model...In conclusion, NAD+ biosynthesis was significantly impaired in CKD, which may attribute to downregulation of QPRT and NMNAT 1/3.

Diabetic nephropathy (DN) is a complex disease with microvascular complications, profound changes in metabolism, inflammation, and redox status, leading to structural and functional changes that can culminate in End Stage Kidney Disease (ESKD)...500NMN mice had lower mortality and significantly improved urinary albumin-creatinine ratios even at 20 weeks post-treatment compared with the db/db mice. ...Therapeutic protocols leading to legacy effects by epigenetic reprogramming of the salvage pathway to sustain or even increase kidney NAD+ show promise for slowing the development of DN.

Nicotinamide riboside and pterostilbene increases whole blood NAD+ levels among patients with mild AKI. However, there is considerable interindividual variability in the NAD+ response to NRPT and the increase occurs at 48 h, suggesting strategies with earlier administration should be considered in future studies. NRPT is safe and well tolerated at all doses in patients with AKI.

...In acute kidney injury (AKI), substantial decreases in the levels of NAD+ impair energy generation and, ultimately, the core kidney function of selective solute transport. Conversely, augmentation of NAD+ may protect the kidney tubule against diverse acute stressors. For example, NAD+ augmentation can ameliorate experimental AKI triggered by ischaemia–reperfusion, toxic injury and systemic inflammation. NAD+-dependent maintenance of renal tubular metabolic health may also attenuate long-term profibrotic responses that could lead to chronic kidney disease. Further understanding of the genetic, environmental and nutritional factors that influence NAD+ biosynthesis and renal resilience may lead to novel approaches for the prevention and treatment of kidney disease.

...NAM improved BP and kidney injury, prolonged pregnancy periods, and improved fetal growth in the pregnant MRL/lpr-LPS mice. The results suggest that SLE patients are prone to develop poor pregnancy outcome, and likely develop severe nephropathy and kidney inflammation. NAM may be a novel therapeutic option that improves kidney injury and pregnancy outcomes, thereby benefiting pregnant patients with SLE.