The Triad of Sleep Apnea, Hypertension, and Chronic Kidney Disease: A Spectrum of Common Pathology

Abstract

Obstructive sleep apnea (OSA), hypertension, and chronic kidney disease (CKD) are different entities and are generally managed individually most of the time. However, CKD, OSA, and hypertension share many common risk factors and it is not uncommon to see this complex triad together. In fact, they share similar pathophysiology and have been interlinked with each other. The common pathophysiology includes chronic volume overload, hyperaldosteronism, increased sympathetic activity, endothelial dysfunction, and increased inflammatory markers. The combination of this triad has significant negative impact on the cardiovascular health, and increases the mortality and morbidity in this complicated group of patients. On one hand, progression of CKD can lead to the worsening of OSA and hypertension; similarly, worsening sleep apnea can make the hypertension difficult to treat and enhance the progression of CKD. This review article highlights the bidirectional interlink among these apparently different disease processes which share common pathophysiological mechanisms and emphasizes the importance of treating them collectively to improve outcomes.

Approach and Management of Hypertension After Kidney Transplantation

“…There is a relationship between HTN, CKD, and OSA, and they have common risk factors and pathophysiology, including increased sympathetic activity, endothelial dysfunction, increased inflammatory markers, hyperaldosteronism, and chronic volume overload. In addition, these three conditions are associated with CV risks, morbidity, and mortality (117). If any of these three diseases is uncontrolled or progress the other two conditions tend to worsen or become more difficult to manage.…”

Insulin Resistance in Kidney Disease: Is There a Distinct Role Separate from That of Diabetes or Obesity

“…Beyond promoting glucose uptake and utilization, insulin-dependent PI3K/Akt activation also phosphorylates/activates endothelial nitric oxide (NO) synthase which in turn increases bioavailable NO in the vascular endothelium [22,23,24]. Thus, under conditions of tissue resistance to insulin, the alterations in insulin-dependent responses of the PI3K/Akt pathway lead to reductions in bioavailable NO, impaired NO-dependent vascular relaxation, and increased tissue inflammation and fibrosis.…”

Role of the Nox4/AMPK/mTOR signaling axe in adipose inflammation-induced kidney injury

“…Oxidative stress can also alter the intracellular signaling of adipocyte leading to dysfunctional adipose tissue and eventually insulin resistance [138]. Insulin-dependent stimulation of PI3K is impaired due to oxidative stress, and this, in turn, decreases the NO bioavailability and increases tissue inflammation and fibrosis [139][140][141]. Furthermore, oxidative stress in adipose tissue alters the adipokine profile causing disruption in the lipid metabolism in obese patients [142].…”