Alkali therapy protects renal function, suppresses inflammation, and modulates cellular metabolism in kidney disease

Purpose: Characterize the renal transcriptome of a chronic kidney disease model in the presence and absence of alkali therapy (bicarbonate supplementation in water) Methods: Crystal nephropathy mice were fed a calcium-free, 0.67% oxalate diet for 10 days. Control mice were fed a calcium-free diet for the same period. Afterwards, mice were fed a standard diet containing calcium for 28 days (recovery). Therapeutically treated mice ("late") received 0.2M NaHCO3 in water during the whole recovery period. An untreated group drank tap water instead. Total RNA was extracted from whole kidney samples and used for RNAseq. Results: Using a PolyA, Truseq strategy with p-value <0.05 and log2(fold change) = 0.5 or = - 0.5, we identified that crystallopathy altered the expression levels of 4923 transcripts. Alkali therapy normalized or attenuated the dysregulation of 795 of those genes. Alkali therapy also altered the expression of 179 transcripts in control kidneys. Conclusions: Pathway analysis identified that alkali therapy mostly restored pathways associated to inflammation and cell metabolism. Overall design: Alkali therapy via bicarbonate supplementation in crystal nephropathy mice.