ABSTRACT
Capillary rarefaction is broadly defined as a reduction in vascular density. Capillary rarefaction in the kidneys is thought to promote hypoxia, impair hemodynamic responses and predispose to chronic kidney disease (CKD) progression and hypertension development. Various mechanisms have been suggested to play a role in the development of capillary rarefaction, including inflammation, an altered endothelial-tubular epithelial cell crosstalk, a relative deficiency in angiogenic growth factors, loss of pericytes, increased activity of Transforming growth factor -ß1 and thrombospondin-1, vitamin D deficiency, a link to lymphatic neoangiogenesis and INK4a/ARF (Cylin-dependent kinase inhibitor 2a; CDKN2A). In this review, we summarize the tools available to monitor capillary rarefaction noninvasively in the clinic, the contribution of capillary rarefaction to CKD and hypertension, the known mechanisms of capillary rarefaction, and potential future strategies to attenuate capillary rarefaction and reduce its negative impact. Therapeutic strategies to be explored in more detail include optimization of antihypertensive therapy, vitamin D receptor activators, sirtuin 1 activators, Hypoxia inducible factor prolyl hydroxylase inhibitors and stem cell therapy.
ABSTRACT
BACKGROUND: Procalcitonin (PCT) and C-reactive protein (CRP) are used most widely in the diagnosis/treatment of bacterial infections. These are not infection-specific and may also show increases in other inflammation-causing cases. AIM: To establish a new cut-off value for PCT and CRP to eliminate confusion in the diagnosis and treatment of bacterial infections in haemodialysis (HD) patients. METHODS: A total of 1110 patients, 802 with undocumented infection and 308 with documented infection, was included in the study. RESULTS: A total of 802 patients with undocumented infection had a mean CRP value of 12.2 ± 9.6 mg/dL and a mean PCT value of 0.51 ± 0.96 ng/mL and the 308 patients with documented infection had a mean CRP value of 125.9 ± 83.3 mg/dL and a mean PCT value of 13.9 ± 26.9 ng/mL at the time of admittance. In HD patients, the cut-off values for CRP was determined as 19.15 mg/dL and for PCT as 0.685 ng/mL in the presence of infection. The use of these two parameters in combination (CRP ≥19.15 mg/dL and PCT ≥ 0.685 ng/mL) was found to have 95% positive predictive value (PPV) and 93% negative predictive value (NPV) for the diagnosis of infectious diseases in HD patients. When CRP ≥100 mg/dL and PCT ≥5 ng/mL, this was found to have 100% PPV and 94% NPV for the diagnosis of sepsis in HD patients. CONCLUSION: We specified PCT and CRP cut-off values with high PPV and NPV for revealing the presence of bacterial infection and sepsis in HD patients.
