The use of Magnesium and Fast Mimicking Diet in kidney diseases

Dietary interventions, such as magnesium supplementation and fasting mimicking diet (FMD), significantly affect human physiology and the course of multiple chronic diseases, and can regulate the immune system. Systemic Lupus Erythematosus (SLE) has a strong genetic susceptibility, but little is known about the impact of diet on disease severity. The Western diet is typically deficient in magnesium (Mg), and given the immunomodulatory effects of Mg, we hypothesized that increasing Mg intake would reduce severity of murine lupus. Hence, we placed 12-week old MRL/lpr female lupus mice on a normal (Mg500) or a high (Mg2800) Mg diet for 9 weeks. Urine and blood samples were collected during the study for quantification of urinary albumin, BUN, anti-dsDNA antibodies, and immune phenotyping. Lupus mice on high Mg2800 diet had significantly fewer skin lesions and less severe skin histology score, and reduced levels of pathogenic anti-dsDNA antibodies, compared with the Mg500 group (47.4±36.2 vs. 143.8±75.0  × 106U/ml; P < 0.05). The high Mg2800 group had a nearly two-fold increase in the percentage of CD4+FOXP3+ Treg cells compared to controls (19.9±5.4% vs. 11.4±5.5%; P < 0.05), and Treg percentages inversely correlated with the concentration of anti-dsDNA. None of the mice developed arthritis during the observation period and there were no significant differences in weight, proteinuria, BUN or kidney histology. In conclusion, oral supplementation of Mg has a protective effect in a murine lupus model and may represent an inexpensive and safe adjuvant in the treatment. The impact of fasting on acute kidney injury (AKI) and progression to chronic kidney disease (CKD) is unclear. We compared periodic fast mimicking diet (FMD) cycles with ad libitum (ad lib) diet in mouse models of AKI and CKD induced by aristolochic acid (AA) and folic acid. Mechanisms were studied using flow cytometry, immunofluorescence, and a C-C chemokine receptor type 2 (CCR2) inhibitor. FMD significantly reduced serum creatinine levels, histological kidney injury, and expression of maladaptive repair markers in AA-injected mice and accelerated kidney recovery compared to ad lib diet. These benefits were consistent across different models. FMD also lowered the renal expression of cytokines and profibrotic markers, reduced CCL2 chemokine levels, decreased monocyte recruitment into the kidney, and promoted protective monocyte phenotypes during late repair. When started at the peak of AKI, FMD improved kidney repair and reduced monocyte recruitment. In the presence of a CCR2 inhibitor, FMD had no additional nephroprotective effects, suggesting that FMD prevents kidney injury through a CCL2/CCR2-mediated mechanism. In conclusion, FMD mitigates AKI and CKD severity by reducing CCL2- mediated monocyte recruitment. This supports future studies testing the safety/efficacy profile of diet-based therapies for kidney disease in humans.