Slide 1

Thank you. Today I’m going to speak about sleep apnea in renal transplantation.

Slide 2

Renal transplantation is the best renal replacement therapy. Although after renal transplantation the Framingham risk factors like hypertension, high cholesterol, diabetes or obesity become rampant. Also emerging risk factors like high homocysteine and high C-reactive protein are highly represented in renal transplant recipients.
Despite this renal transplanted patients after renal transplantation die less than the uremic patients on the waiting list. This dramatic fall in the death risk is not only remarkable under an epidemiological point of view but it’s also surprising under the perspective of the Framingham risk factors.

Slide 3

Let me show you again and again this slide about the annual mortality of patients on dialysis. This is the nightmare of nephrologists who care for uremic patients. As you can see, dialysis patients die much more than the coeval subjects in the general population. But after renal transplantation the survival curve improves. This marked improvement in the survival curve is due to many reasons but it is unclear which one is the most important. For instance, after renal transplantation the recovery of renal function in the face of increasing levels of classical risk factors could in some way abate non-traditional risk factors.
Today in the 15 minutes I’m going to present data testing the hypothesis that renal transplantation maybe improves the survival in uremic patients after renal transplantation because it abates one important risk factor in dialysis patients like sleep apnea.

Slide 4

What is sleep apnea? During sleep if respiratory control is altered, disease can be generated. Disturbed sleep is a risk generating situation if breathing is stopped completely, apnea and also when the depth of breathing is halved, hypopnea. 

Slide 5

Now, I’ll synthesise the mechanisms that lead to cardiovascular damage assessed by using polysomnographic recordings in which I included also the measurement of sympathetic nerve activity at the peroneal nerve. When respiratory air flow stops, oxygen saturation falls and this causes an increase in sympathetic bursts. This then increases arterial pressure. All these intermediate mechanisms lead to chronic hypertension, left ventricular hypertrophy and arrhythmias, particularly atrial fibrillation. At the end the result is an increase in cardiovascular morbidity and mortality.

Slide 6

Sleep apnea is a very frequent complication in ESRD patients. In fact, it is about 15% in unselected dialysis population but it climbs up to 75% in selected because of symptoms, it means in the snoring patients. There is no doubt that sleep apnea in ESRD is a cardiovascular risk factor as well as in the general population.

Slide 7

The question now to be addressed is whether sleep apnea is a modifiable risk factor and whether it can be reversed by renal transplantation.

Slide 8

To date about this issue there are only a few case reports and in these rhapsodic descriptions in case reports it is claimed that renal transplantation reverses sleep apnea. The few sizeable original articles with a sizeable number of patients are based on questionnaires, I mean sleep apnea is assessed by questionnaires and is not assessed by polysomnographic studies that is the golden standard.

Slide 9

The issue of whether renal transplantation reverses or attenuates sleep apnea can be approached in two ways. One is the case-control approach that is studying the prevalence of sleep apnea in a population of transplant patients and comparing it to a well-matched general population sample. The second approach is the longitudinal approach that is investigating the influence of treatment switching (transplantation to dialysis or the other way round) on sleep apnea syndrome.

Slide 10

As far as the case control study, we considered as a reference population an Italian general population and a North American general population. I’ll go into detail in a moment. The Italian general population is a population from the city of Abbiategrasso which is a city in the North of Italy. This database that has been very productive to date involves 365 males and almost 350 females. The age is between 40 and 69.
In this study the sleep apnea was assessed by pulse oximetry. From this database we extracted, selected 70 males and 35 females accurately matched to renal transplanted patients for age, sex and BMI.

Slide 11

The other population was the North American population coming from the Wisconsin study. The Wisconsin study is a cornerstone in sleep apnea research. In this database were studied 600 men and women the age was between 30 and 60 and sleep apnea was assessed by polysomnography or done with pulse oximetry.

Slide 12

Now, the sleep apnea data in renal transplantation. We studied 163 renal transplant patients. These patients had a GFR on average of 62 and the age was 47 on average. 113 men and 50 women. The sleep apnea in these patients was assessed by polysomnography and by pulse oximetry.

Slide 13

As is recommended in polysomnographic studies the indicators we took into consideration were number of apneic and hypopneic episodes per hour, oxygen desaturation episodes per hours. Average and minimal O2 saturation.

Slide 14

Now, the results. We looked first at the comparison between renal transplanted patients and the normal Italian population. As you know, sleep apnea is age and sex dependent. So we analysed the data dividing the subjects and the patients by gender and age. As you can see, the transplanted patients that are the yellow balls showed no difference in O2 desaturation episodes as compared to the normal population.

Slide 15

Now, let’s look at the minimal nocturnal O2 saturation. Minimal nocturnal O2 saturation was very similar in transplanted patients and in the reference population.

Slide 16

Importantly in this head to head age specific comparison BMI was not a confounder because the BMI in transplanted patients did not differ from that in the general population, as you can see clearly in this slide.

Slide 17

Data analysis according to the number of episodes of oxygen desaturation and minimal oxygen saturation revealed that there is no excess risk of hypoxemia in renal transplanted patients as compared to the general population. However, as you know, pulse oxymetry is a less sensitive method than polysomnography to detect sleep apnea syndrome. Then it is important to compare the frequency of sleep apnea in renal transplanted patients and the general population by using a polysomnographic-derived apnea-hypopnea index.

Slide 18

Now, we’ll look at what happened in the database of the Wisconsin researchers. Age and sex specific prevalence of sleep apnea was assessed in 600 subjects using two cut off points for the apnea-hypopnea score. Between 5 and 14 was mild apnea and more than 15 severe apnea.

Slide 19

As you can see, in the general population, the Wisconsin population 16% of men and 8% of women had a mild form of apnea-hypopnea. 12% of men and 5% of women had a severe kind of apnea. Sleep apnea then in the general population is not so rare and is more frequent in men than in women. Now, we look at the data in transplanted patients in yellow. As you can see, 22% of men and 6% of transplanted women had a mild apnea, while 6% of men and 2% of women had severe apnea. So the prevalence of sleep apnea in renal transplanted patients did not differ from that of the general population.

Slide 20

The second point is to assess the problem by the longitudinal approach that is investigating the influence of treatment switching (transplantation to dialysis or the other way round) on sleep apnea syndrome.

Slide 21

Here we considered three patients who returned to dialysis after kidney transplantation failure and we studied the three patients when they were successful renal transplanted recipients and then when they were back on dialysis. As you can see, all these parameters apnea-hypopnea, episodes of O2 desaturation went up, worsened when patients returned back to dialysis.

Slide 22

At this point I have to recall you that sleep apnea that some years ago we published a paper about the nocturnal hypoxemia in dialysis patients and in this paper non-hypoxemic patients on hemodialysis had a better survival than hypoxemic patients in this Cox model where data were adjusted for age and traditional risk factors.

Slide 23

So let me show again this slide and after renal transplantation you can see that the survival curve improves. The reversibility of sleep apnea after successful renal transplantation could be one of the factors which improves survival of renal transplant patients.

Slide 24

In conclusion, sleep apnea frequency in renal transplant patients seems to be as common as that in the general population matched for age, sex, and BMI. Sleep apnea which contributes to the high cardiovascular risk of the chronic kidney disease population might be reversed by renal transplantation. Thank you.