Saudi Journal of Kidney Diseases and Transplantation

LETTER TO THE EDITOR
Year
: 2016  |  Volume : 27  |  Issue : 5  |  Page : 1068--1070

Pathophysiology of central sleep apnea in chronic kidney disease


Gaurav Nigam, Muhammad Riaz 
 Sleep Disorders Center, University of Michigan, Michigan, USA

Correspondence Address:
Dr. Gaurav Nigam
Sleep Disorders Center, University of Michigan, Michigan
USA




How to cite this article:
Nigam G, Riaz M. Pathophysiology of central sleep apnea in chronic kidney disease.Saudi J Kidney Dis Transpl 2016;27:1068-1070


How to cite this URL:
Nigam G, Riaz M. Pathophysiology of central sleep apnea in chronic kidney disease. Saudi J Kidney Dis Transpl [serial online] 2016 [cited 2021 Oct 21 ];27:1068-1070
Available from: https://www.sjkdt.org/text.asp?2016/27/5/1068/190907


Full Text

To the Editor,

The Kidney Disease: Improving Global Outcomes Work Group defines chronic kidney disease (CKD) as the presence of a marker of kidney injury or a reduction in glomerular filtration rate to a value lower than 60 mL/min per 1.73 m 2 for three or more months. [1] CKD has been known to be associated with the development of sleep-disordered breathing.

Apnea in adults is scored on a diagnostic sleep study when there is a drop in the peak signal excursion by ≥90% of pre-event baseline using an oronasal thermal sensor. Sleep apnea can be broadly divided into two categories based on the respiratory effort: obstructive sleep apnea and central sleep apnea (CSA). Apnea is said to be central when there is no detectable effort in the abdominal or thoracic effort channels. When at least some effort is observed in the abdominal or thoracic effort channels, the apnea is said to be obstructive in character. Development of obstructive sleep apnea in patients with CKD has been relatively well studied. To a lesser extent, CSA has been associated with CKD, irrespective of the pre-sence of comorbidities.

Although limited, few studies have described the association of CSA with CKD. In one study, Fleischmann et al [2] while assessing the prevalence of sleep-disordered breathing in patients with CKD demonstrated the specific association of CSA with CKD even after statistical adjustment for the contribution from heart failure. CSA has been shown to be present in patients who are predialysis, [2] as well as those undergoing continuous ambulatory peritoneal dialysis [3] and hemodialysis. [4] The goal of this report is to understand the distinct pathophysiological mechanisms that could play a role in the development of CSA in patients with CKD.

Multiple mechanisms could lead to the development of CSA in patients with CKD [Figure 1]. All these mechanisms eventually contribute to "exaggerated chemoreflex sensitivity" leading to unstable ventilatory control of breathing during sleep.{Figure 1}

One well-known mechanism for the development of CSA involves the activation of pulmonary mechanoreceptors. In patients with CHF, interstitial pulmonary edema leads to central apneas and periodic breathing. [5] Patients with end-stage renal disease (ESRD) on hemodialysis are known to have excess extracellular fluid due to volume overload. There is a trend toward this extracellular fluid volume expansion to be more pronounced if they have coexisting CHF. [6] Fluid overload in these patients with ESRD often manifests as interstitial pulmonary edema [6] leading to central apnea, similar to what is seen in patients with pure CHF.

Metabolic acidosis or dilutional acidosis is commonly seen in patients with ESRD. Metabolic acidosis shifts the rebreathing hypercapnic ventilatory response curve to the left [7] leading to the central apnea and periodic breathing when PaCO [2] falls below apneic threshold. [8]

This could be one of the mechanisms for heightened chemoreflex sensitivity in patients with CKD.

Decreased clearance of uremic toxins over time can lead to uremic autonomic neuropathy, which is manifested by overactivation of the sympathetic nervous system. [9] This can be an additional pathway for heightened chemoreflex sensitivity. Better clearance of uremic toxins with certain forms of nocturnal dialysis leads to amelioration of CSA, which provides retrospective evidence for this hypothesis. [10] Compromised clearance of middle molecules such as beta-2 microglobulin [11] and endogenous opiates [12] that incrementally accumulate in patients with ESRD needs to be investigated in the pathogenesis of CSA in this patient population.

Periodic breathing during sleep onset is thought to be a transient phenomenon occurring in normal subjects. [13] In patients with CKD prolonged episodes of periodic breathing can occur, closely linked with hypoxia. It has been demonstrated that hypoxia induces hyperventilation and hypocapnic alkalosis, which can promote periodic breathing and central apneas during nonrapid eye movement sleep. [14]

Patients with ESRD are at increased risk of anemia and consequent hypoxia due to decreased erythropoietin synthesis. This hypoxia in the setting of hypocapnia induced by chronic metabolic acidosis triggers central apnea, hyperventilation, and periodic breathing. Providing supplemental oxygen or even preventing development of hypocapnia may abolish periodic breathing. [14]

In conclusion, distinct pathophysiological mechanisms exist that are associated with the development of CSA in patients with CKD. The putative mechanisms include the presence of interstitial pulmonary edema, chronic metabolic acidosis, anemia, and compromised clearance of uremic toxins. More than one mechanism is at work at any given time, and these could be operating even in the absence of other well-recognized risk factors such as CHF. More extensive studies will be needed in future to corroborate findings stated in the studies discussed in this review and to discover novel pathways that could be associated with the development of CSA in patients with CKD.

Conflict of interest: None declared.

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