During metabolic acidosis (MA), urinary phosphate excretion is increased and contributes to acid removal. Transcriptome analysis of kidneys from acidotic mice revealed a strong downregulation of the type IIc Na+/Pi cotransporter NaPi-IIc and a small reduction in IIa abundance. To further investigate the contribution of transporter regulation to phopshaturia, we induced MA for 2 and 7 days in normal and NaPi-IIa KO mice and confirmed the decrease of NaPi-IIc mRNA in WT and KO mice during MA. In contrast, Western blotting, revealed an increase of NaPi-IIa and IIc abundance in WT mice. However, in IIa KO mice, we observed a reduction of NaPi-IIc protein after 7 days treatment. BBM Na/Pi cotransport activity was progressively and significantly decreased in both acidotic KO mouse groups, whereas in WT animals a small increase after 2 days treatment was observed. These discrepancies between mRNA and protein expression levels and transport activity suggests that downregulation of NaPi-IIa/c abundance during MA is not the main mechanism responsible for the phosphaturia occuring during metabolic acidosis. Phosphaturia may be rather due to either decreased cotransporter function or the increased delivery of phosphate to the kidney.