Sleep apnea common in both CKD and ESRD patients

November 11, 2005

Nov 11, 2005


Philadelphia, PA - Retrospective analysis of two large cohorts of patients, those with chronic kidney disease (CKD) but relatively preserved kidney function and those with end-stage renal disease (ESRD), shows a high prevalence of sleep apnea in both groups compared with those without kidney disease. Although these studies can't establish causality, their findings suggest that sleep apnea may be a modifiable risk factor for kidney disease, and future studies should look more closely at this connection.



Dr John J Sim



"We think there may be a causative factor here; that sleep apnea may be causing direct glomerular injury," Dr John J Sim (Kaiser Permanente, Los Angeles, CA) told renalwire . "We already know that sleep apnea causes hypertension and that hypertension causes kidney disease."

If some degree of causality can be shown, it's possible that treating sleep apnea may slow the progression of kidney disease, the authors speculate.

The reports were presented here during Renal Week 2005.


Sleep apnea in renal disease: Chicken or egg?

The association between sleep apnea and renal disease is becoming more evident, the researchers note, with some studies showing that upward of 70% of ESRD patients may be affected, compared with 2% to 3% of those in the general population. One theory is that the uremic milieu associated with the disease may cause chemical and structural changes, but the associations between these two conditions have not been well studied, particularly among those with earlier stages of disease.

In the first report, Sim and colleagues used the large Kaiser Permanente Southern California database to examine this question in subjects with chronic kidney disease vs control patients in the system without kidney disease [ 1 ]. CKD patients were those with proteinuria or a chronically depressed GFR <90 mL/min.

The analysis included 1.2 million patients, 528,590 of whom had CKD. The authors found that the rate of diagnosed sleep apnea was significantly higher among the CKD patients.

Prevalence of sleep apnea in patients with and without kidney disease


Population
Sleep apnea diagnosis, n (%)
Non-CKD patients
3436/693,115 (0.49)
CKD patients
15,516/528,590 (2.93)



To download table as a slide, click here



When they stratified the CKD patients by severity of disease using various GFR levels and the presence or absence of proteinuria, each class had a significantly greater prevalence of sleep apnea compared with non-CKD patients. Those with a GFR between 60 and 90 mL/min and proteinuria had the highest prevalence of sleep apnea, 5.39%, statistically significantly higher than any other CKD class.

The rate of sleep apnea was still twice that in non-CKD patients after controlling for hypertension, age, and gender, they note, raising the question of whether sleep apnea is a risk factor for CKD and its progression.

"The next step is probably going to be to...try to start treatment on these patients with sleep apnea and see whether there is improvement of proteinuria and renal dysfunction," Sim said. In their anecdotal experience at least, he said, "we've had patients come in with severe sleep apnea, proteinuria, and renal dysfunction, and they had improvement, almost resolution, of proteinuria and renal dysfunction with treatment with [continuous positive airway pressure] CPAP."


Sleep apnea in ESRD

The second study using the Kaiser Permanente database looked at the prevalence of sleep apnea in the population of end-stage renal disease patients [ 2 ]. Among almost 700,000 ESRD patients and controls, researchers found that the ESRD group had sleep apnea at a rate almost eight times that of controls.

Although it was not statistically significant, the point estimate related to sleep apnea for patients on peritoneal dialysis was about half that of those on hemodialysis, suggesting a role for the build-up of uremic toxins in the risk for sleep apnea.



Dr Tam T Pham



Dr Tam T Pham (Kaiser Permanente), Sim's colleague, who presented the ESRD paper, told renalwire that these findings should spur more prospective investigation into whether more intensive dialysis might have a positive impact on sleep apnea.

Sim speculated that there may actually be three mechanisms at work in patients with CKD and ESRD?obstructive sleep apnea may cause direct glomerular injury; hypertension that can be caused by sleep apnea causes kidney disease; and finally, the uremic component in ESRD patients with suboptimal clearance may then in turn drive sleep apnea.

In this study on ESRD patients, they excluded patients who had proceeded to transplant, assuming that this would normalize the uremia in these patients. However, the relationship may still be more complex, he pointed out. "There have been four or five case reports of patients who had sleep apnea while they were on dialysis who received transplants and their sleep apnea went away," Sim said.

They looked in their own database and found 44 patients who had a diagnosis of sleep apnea and a kidney transplant. "Our natural assumption initially was to think that maybe these patients had sleep apnea diagnosed while they were on dialysis and maybe it did improve after transplant?that the uremic component was actually responsible for it," Sim said. "But the surprise was that actually the sleep apnea was diagnosed after the renal transplant."

It's possible that yet another mechanism, perhaps a type of metabolic syndrome brought on by weight gain caused by immunosuppressive agents such as prednisone, may be causing further apnea in these patients. They plan to pursue these preliminary data further.



Sources

  1. Sim JJ et al. Sleep apnea: A novel risk factor for kidney disease? Renal Week 2005; November 8-13, 2005; Philadelphia, PA. Abstract TH-PO943.

  2. Sim JJ et al. Sleep apnea is more prevalent in the ESRD population. Renal Week 2005; November 8-13, 2005; Philadelphia, PA. Abstract TH-PO83.


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