Table 2.

The double-edged effects of HA in kidney diseases. This table outlines the beneficial and detrimental effects of HMW- and LMW-HA in the various kidney diseases discussed in this review. Here, one can appreciate that HMW-HA lends itself to protective effects, whereas LMW-HA promotes the deleterious characteristics of each disease

Disease	Positive effects of HA	Negative effects of HA
Acute kidney injury (AKI)	IL-10-induced HMW-HA reduces fibrosis in I/R model [22]	LMW-HA [46]-CD44 interaction increases the presence of fibrotic molecules (collagen, α-SMA) and causes tubular damage [47]
Chronic kidney diseases (CKD)	Can potentially serve as a biomarker to distinguish between CKD and AKI in certain clinical cases	Increases pro-fibrotic cells and molecules (macrophage presence, CD44 and LYVE-1 expression, α-SMA levels) [46]
Diabetic nephropathy	Maintains structure of glomerular endothelium [48]; HMW-HA associated with less CD44-dependent inflammation [49]	Elevated levels associated with disease development [50]
IgA nephropathy		HA-CD44 interaction plays a role in disease development [51] and fibrotic complications (crescentic glomerulonephritis) [52]
Obstructive uropathy	IL-10-induced HMW-HA reduces fibrosis [22]	Acts as nidus for calcium stone formation to cause obstructive disease [53–55]
Transplant	Can serve as a predictive biomarker for unsuccessful transplant [56]	Associated with organ rejection [57]
Vesicoureteral reflux	Reduces occurrence of UTIs caused by VUR [58]