# The effects of elevated phosphate on the kidney - damaging the gatekeeper

## TL;DR

This paper explores how high phosphate levels can damage the kidneys, contributing to chronic kidney disease and kidney stones.

## Contribution

The paper introduces the idea that elevated renal tubular phosphate, not just serum phosphate, drives kidney injury.

## Key findings

- Tubular phosphate can form microcrystals that damage kidney cells and cause calcification.
- Hyperphosphaturia may contribute to kidney damage in both CKD and genetic diseases.
- High dietary phosphate intake could induce kidney damage even without CKD.

## Abstract

The kidney is a major regulator of phosphate metabolism. The body can lower systemic phosphate levels by increasing renal phosphate excretion, and kidney injury results in elevated serum phosphate concentrations (hyperphosphatemia). Chronic kidney disease (CKD) is associated with various organ injuries, including vascular calcification and cardiovascular disease, where hyperphosphatemia acts as a pathologic driver. Here we discuss hyperphosphatemia not as a consequence of kidney disease but as a potential contributor to kidney damage. We describe how increases in renal tubular phosphate levels (hyperphosphaturia), rather than hyperphosphatemia contribute to kidney injury in CKD. Tubular phosphate can form microcrystals with calcium which damages renal epithelial cells, induces fibrosis and inflammation, and causes parenchymal calcification. Calcium phosphate microcrystals can grow and form larger deposits in the renal collecting system, and potentially contribute to the formation of kidney stones. Therefore, hyperphosphaturia might not only contribute to kidney damage in CKD, but could also cause kidney injury in genetic diseases with reduced renal phosphate uptake. Finally, since high dietary phosphate intake increases renal phosphate excretion, we discuss if prolonged phosphate loading in the absence of CKD can induce kidney damage. We propose that a better understanding of the pathologic actions of phosphate on the kidney will help to identify novel therapeutic strategies to prevent renal injury and disease progression in patients with CKD and in other renal conditions, such as kidney stone formation. Lowering dietary phosphate intake might not only have reno-protective effects in patients with pre-existing kidney damage but also in healthy individuals.