Vasa recta hyalinosis reflects severe arteriolopathy in renal allografts

Hyaluronan Inhibition as a Therapeutic Target for Diabetic Kidney Disease: What Is Next?

“…39 Future Directions for HAI in DKD AH and increased HA deposit in kidneys, seen among patients with DM and DKD, have been shown to be associated with increased ESKD incidence, worse proteinuria, increased cardiovascular events, worse renal graft survival, and worse glomerular disease outcomes. 42,46 Our study has shown the benefits of 4-MU, a HA synthesis inhibitor, in slowing DKD progression in animal experimental models with potential important benefit in glucose control. 3 Phase 1 study on 4-MU among healthy human adults has been completed and published, highlighting its safety and tolerabiltiy.…”

“…48 In summary, afferent and efferent AH are associated with increased ESKD incidence, proteinuria, increased cardiovascular events, worse renal graft survival, and worse glomerular disease outcomes. 42,46 In fact, one of the key ways AH leads to a worse outcome in DKD is through impairment of renal autoregulation resulting in glomerular sclerosis by subjecting the renal glomerulus to the effects of low or high systemic BP. 47 HA Synthesis Inhibitors 4-methylumbelliferone (4-MU) (Figure 2) is a derivative of coumarin, with the molecular formula C 10 H 8 O 3 , a molecular weight of 176.2 kDa, a chemical abstract service number of 90-33-5, a pKa of 7.79, and a melting point of 194-195°C.…”

“… 42 Another study by Oguchi et al evaluating 248 kidney transplants with 381 biopsy specimens showed that vasa recta hyalinosis (VRH) in the medulla of renal allografts is associated with worse graft survival rate. 46 One potential pathophysiologic outcome of AH is the reduction of the interstitial capillary bed and the glomerular blood flow, both leading to glomerular sclerosis. Another study of 109 patients with CKD who underwent renal biopsy shows that AH may potentiate susceptibility to BP-related glomerular damage because of dysregulated afferent and efferent arteriolar resistance.…”

“…In summary, afferent and efferent AH are associated with increased ESKD incidence, proteinuria, increased cardiovascular events, worse renal graft survival, and worse glomerular disease outcomes. 42 , 46 In fact, one of the key ways AH leads to a worse outcome in DKD is through impairment of renal autoregulation resulting in glomerular sclerosis by subjecting the renal glomerulus to the effects of low or high systemic BP. 47 …”