The impact of nocturnal hemodialysis on sexual function

Sexual dysfunction is common in men and women with end stage renal disease (ESRD) [1‐5], contributed to by both the diseases that cause ESRD, as well as the consequences of kidney failure [4, 6]. Recently, Vecchio et al. published a systematic review examining the treatments available to ESRD patients with sexual dysfunction [7]. Their report highlights the limited treatment options available, noting that phosphodiesterase-5 inhibitors improve erectile dysfunction in men with ESRD, with little research available to guide therapy in women with ESRD.

Frequent nocturnal hemodialysis (NHD) has gained popularity recently as a form of renal replacement therapy, and among other reported benefits, some studies have reported improved sexual function. Published literature however shows conflicting results, although these are based mainly on small observational studies comparing pre-NHD to post-NHD quality of life scores, usually compared with patients on conventional hemodialysis (CvHD) [8‐12]. Ting et al. followed 42 patients and noted that sexual function improved after conversion to NHD [11] while Lockridge et al. observed an increase in sexual desire after NHD initiation in 40 patients [10]. However, other studies have not documented improvement, including a recent prospective observational study of 63 patients which demonstrated no improvement in sexual function scores after conversion to NHD [9].

Our group has previously reported a randomized controlled trial in which we examined the effects of NHD on both left ventricular mass as well as quality of life [13‐15]. One of the quality of life tools used was the kidney disease quality of life: short form (KDQOL-SF) questionnaire [16], containing specific questions assessing sexual arousal and sexual enjoyment. These questions have not been analyzed nor reported previously. Herein we report the results of a post hoc analysis to determine if frequent NHD was associated with an improvement in sexual activity and responses to sexual related questions listed in the Kidney Disease Quality of Life Short Form questionnaire compared to thrice weekly conventional hemodialysis.

The baseline characteristics between the two groups are listed in Table 2. Fifty-one patients answered the QOL questionnaire at randomization and 48 at study end. No significant differences in baseline characteristics were detected between the two groups. Approximately 1/3 of patients had diabetes and the cohort was relatively young with an average age of 55 in the NHD group and 53 in the CvHD group. The majority of patients who participated in the study were Caucasian and a greater proportion of participants were male than female. There was no difference in the number of patients in relationships in either group with 72% with a partner in the NHD group and 73% in the CvHD group.

The Cronbach’s alpha of the sexual arousal and enjoyment questions was 0.97 in patients who had engaged in sexual activity indicating excellent reliability of these questions. The Pearson R correlation coefficient of the burden of kidney disease on sex life question was 0.61 (p = 0.01) with both the sexual enjoyment and arousal questions indicating a strong correlation between these questions. The Cronbach’s alpha of all three questions analyzed together was 0.89 suggesting good reliability.

With respect to our primary outcome, there was no change in the proportion of patients who reported being sexually active at six months compared to randomization (Figure 1). Of the patients with recent sexual activity, there was also no significant difference between the two groups at 6 months when changes in the proportion of patients enjoying sex or becoming sexually aroused were considered.

For the burden of kidney disease on sex life question (a measure of sexual function), at six months, 39% patients in the NHD group had scores indicating that they were not at all bothered to moderately bothered by sexual dysfunction, compared with 60% in the CvHD group (p = 0.28). When comparing the burden of kidney disease scores, 45% and 32% of NHD and conventional hemodialysis patients, respectively, experienced an improvement by one category in their scores (p = 0.2) (Figure 2). In women and patients below the age of 60 years old, there was a statistically significant improvement in burden of kidney disease on sex life scores for patients allocated to nocturnal hemodialysis (χ ² = 7.90, p = 0.02 and χ ² = 5.12 p = 0.02) (Figure. 2).

In this post-hoc analysis of a randomized controlled trial we observed no improvement in sexual activity or or self-reported arousal, enjoyment or burden of kidney disease on sex life between patients on NHD versus CvHD overall. Consistent with prior reports of sexual activity on hemodialysis, only 43 percent of patients indicated that they were sexually active in the 4 weeks prior to either randomization or study completion [3]. Our findings are not consistent with prior research suggesting that NHD may improve sexual activity and sexually related concerns.

Normal sexual function involves a complex interplay between the hormonal, vascular, neurological and psychological systems. These can all be impacted by ESRD. Patients with ESRD have abnormalities in the hypothalamic-pituitary axis, in particular, hypogonadism and hyperprolactinemia which are thought to be secondary to the accumulation of uremic toxins [18]. The diseases that cause ESRD and the condition itself can cause vascular insufficiency as well as sensory and autonomic neuropathy [4]. Finally, the complex social and psychological factors that are embroiled with ESRD impact normal sexual function [19]. Given this, the mechanism by which NHD might improve sexual function in ESRD patients is not clear. Since NHD improves clearance of uremic toxins it might improve hormonal dysfunction, but it may not address other inhibitors of normal sexual function. NHD does not alleviate the comorbid conditions that cause ESRD which are well known to cause sexual dysfunction. Specifically, NHD is unlikely to reverse pre-existing vascular and neurological damage causing impairment. In addition, it may have variable effects on the social and psychological dynamics caused by ESRD. In particular, sexual activity might be either positively or negatively affected by undergoing dialysis in the home. Transplantation provides a good example of the potential multi-factorial nature of sexual dysfunction in that despite normalization of kidney function, many patients still experience sexual dysfunction [20].

While we did not note any improvement with NHD on sexual activity or self-reported arousal, enjoyment or burden of kidney disease on sex life overall, a subgroup analysis suggested that patients less than 60 years of age and women were less burdened by the effect of their kidney disease on their sex life after 6 months of NHD. It is plausible that younger patients might be more likely to experience benefit with NHD since it is conceivable that they might have fewer and less severe comorbid diseases, which themselves may impair sexual function. It is uncertain why women might benefit from NHD with respect to the burden of kidney disease of sex life. While both sexes suffer from decreased libido, there are differences in sexual dysfunction between men and women with ESRD with men generally suffering from impotence [4] and women suffering from anorgasmia, decreased lubrication and dyspareunia [21]. NHD may have no impact on impotence in men, while it is possible that women perceive NHD to be less intrusive on normal sexual function than CvHD. While this study did not specifically measure these outcomes, it is possible that changes in these domains could have impacted the burden of kidney disease on sex-life in these sub-groups. Alternatively, while the burden kidney disease on sex life diminished in these patients, there are other burdens aside from kidney disease that may be impacting proper sexual activity and function which may explain why we did not observe a concomitant increase in sexual activity.

Our study is the first randomized controlled trial documenting the association between NHD and sexual activity and self-reported sexual function. However, it has several limitations which should be considered. The original RCT was not specifically designed to examine the impact of NHD on sexual function. While the KDQOL-SF does include domains designed to measure sexual function and activity, it would have been preferable to use dedicated sexual function scales such as the International Index of Erectile Function [22] or the Female Sexual Function Index [23]. Despite this, we feel that our study provides much needed insight into a poorly studied area that is pervasive in dialysis patients. Other limitations include that the RCT was not powered to detect differences in quality of life, and that all analyses documented herein are posthoc and exploratory in nature. Given the limited number of patients and that few patients answered the sexual function questions, our subgroup findings should be interpreted with particular caution. However, our findings can be tested within secondary analyses of other recently reported randomized trials of frequent hemodialysis [24, 25]. It should also be noted that given the nature of the intervention it is highly unlikely that a randomized controlled trial focussed on this particular outcome will ever be undertaken.

In conclusion, our study is the first randomized controlled trial examining the effect of NHD on sexual activity or self-reported sexual arousal, enjoyment or burden of kidney disease on sex life. While NHD does not appear to improve sexual activity overall, women and patients younger than 60 years old might experience improvement - the validity of the subgroup findings should be assessed in future RCTs.