Capillary rarefaction, hypoxia, VEGF and angiogenesis in chronic renal disease

Abstract

Tubulointerstitial hypoxia and peritubular capillary rarefaction are typical features of chronic progressive renal disease. In response to low oxygen supply, hypoxia-inducible factors (HIFs) are activated but until now, it is unclear if this increased expression leads to a stabilization of the disease process and thus is nephroprotective or contributes to interstitial fibrosis and/or tubular atrophy. This duality has also been described as far as vascular endothelial growth factor (VEGF), one of the major target genes of HIFs, is concerned. On the one hand, neoangiogenesis driven by VEGF, if intact, ameliorates hypoxia, on the other, VEGF is a potent pro-inflammatory mediator and neoangiogenesis, if defective because interference by other pathologies exaggerates injury. In summary, experimental data support the idea that dependent on timing and predominant pathology, hypoxia counter-regulatory factors exert beneficial or undesirable effects. Thus, before their therapeutic potential can be fully explored, a better way to characterize the clinical and pathophysiological situation in an individual patient is mandatory.

Urinary cytokine levels in apparently healthy cats and cats with chronic kidney disease

“…Whether this is a protective mechanism or whether VEGF also functions as a pro-inflammatory cytokine in CKD is unclear. 22 VEGF does, however, appear to have significant value as a prognostic indicator and a marker for response to therapy in humans with CKD. 12,22 The availability of such a tool in feline patients would be very valuable.…”

“…In previous studies in humans urinary VEGF excretion is reduced in more severe kidney disease. 21,22 The purpose of this study was to evaluate levels of relevant cytokines and chemokines in feline urine as a means of indirectly assessing renal inflammation, fibrosis and vascular health in cats. We hypothesized that levels of pro-inflammatory and pro-fibrotic cytokines would be increased in the urine of cats with CKD when compared with healthy cats.…”

Hypoxia: The Force that Drives Chronic Kidney Disease

“…251,252 As a consequence, the vascular architecture of the kidney fails to be maintained with reductions in capillary number as well as individual capillary caliber and area. [252][253][254][255] Thus, the initial hypoxia insult caused by an episode of AKI is consolidated by subsequent capillary rarefaction that reduces oxygen delivery. This chronic hypoxia then induces a slew of pathological processes in tubular epithelial cells including apoptosis, the prevention of redifferentiation after regeneration and conversion to myofibrolasts.…”

Identification of urinary exosomal noncoding RNAs as novel biomarkers in chronic kidney disease

“…Histological hallmarks are an increased degree of tubulo-interstitial atrophy and fibrosis. These pathological changes are preceded and promoted by events such as infiltration by inflammatory cells, fibroblast activation and proliferation, excessive production and deposition of extracellular matrix components, and rarefaction of peritubular capillaries (Liu 2011;Mayer 2011). At the molecular level, these processes are regulated by integrated actions of various damaging as well as protective/regenerative biological pathways (Keller et al 2012).…”