RESUMO
Chronic kidney disease (CKD) stands as a prominent non-communicable ailment, significantly impacting life expectancy. Physiopathology stands mainly upon the triangle represented by parathormone-Vitamin D-Fibroblast Growth Factor-23. Parathormone (PTH), the key hormone in mineral homeostasis, is one of the less easily modifiable parameters in CKD; however, it stands as a significant marker for assessing the risk of complications. The updated "trade-off hypothesis" reveals that levels of PTH spike out of the normal range as early as stage G2 CKD, advancing it as a possible determinant of systemic damage. The present review aims to review the effects exhibited by PTH on several organs while linking the molecular mechanisms to the observed actions in the context of CKD. From a diagnostic perspective, PTH is the most reliable and accessible biochemical marker in CKD, but its trend bears a higher significance on a patient's prognosis rather than the absolute value. Classically, PTH acts in a dichotomous manner on bone tissue, maintaining a balance between formation and resorption. Under the uremic conditions of advanced CKD, the altered intestinal microbiota majorly tips the balance towards bone lysis. Probiotic treatment has proven reliable in animal models, but in humans, data are limited. Regarding bone status, persistently high levels of PTH determine a reduction in mineral density and a concurrent increase in fracture risk. Pharmacological manipulation of serum PTH requires appropriate patient selection and monitoring since dangerously low levels of PTH may completely inhibit bone turnover. Moreover, the altered mineral balance extends to the cardiovascular system, promoting vascular calcifications. Lastly, the involvement of PTH in the Renin-Angiotensin-Aldosterone axis highlights the importance of opting for the appropriate pharmacological agent should hypertension develop.
RESUMO
The COVID-19 pandemic has put a tremendous stress on the medical community over the last two years. Managing the infection proved a lot more difficult after several research communities started to recognize the long-term effects of this disease. The cellular receptor for the virus was identified as angiotensin-converting enzyme-2 (ACE2), a molecule responsible for a wide array of processes, broadly variable amongst different organs. Angiotensin (Ang) 1-7 is the product of Ang II, a decaying reaction catalysed by ACE2. The effects observed after altering the level of ACE2 are essentially related to the variation of Ang 1-7. The renin-angiotensin-aldosterone system (RAAS) is comprised of two main branches, with ACE2 representing a crucial component of the protective part of the complex. The ACE2/Ang (1-7) axis is well represented in the testis, heart, brain, kidney, and intestine. Infection with the novel SARS-CoV-2 virus determines downregulation of ACE2 and interrupts the equilibrium between ACE and ACE2 in these organs. In this review, we highlight the link between the local effects of RAAS and the consequences of COVID-19 infection as they arise from observational studies.