Erectile Dysfunction in Renal Failure and Transplant Patients

Julia V. Fiuk; Nicholas N. Tadros

Disclosures

Transl Androl Urol. 2019;8(2):155-163. 

In This Article

Treatment of ED in CKD Patients

PDE5 Inhibitors

For erections to occur in human males, sexual arousal must stimulate neural pathways to release NO from nerves and endothelial cells within the penis. NO then penetrates through the membranes of smooth muscle cells, binds to guanylyl cyclase and results in formation of 3'-5'-cyclic guanosine monophosphate (cGMP). Cyclic GMP then binds with and activates cGMP dependent protein kinase, which phosphorylates several proteins and acts as the intracellular trigger for erection. These phosphorylated proteins lead to an influx of calcium, relaxation of arterial and trabecular smooth muscle, influx of blood into the penis and consequent venous compression, ultimately leading to tumescence.[69]

PDE5 is an enzyme that degrades cGMP back to its inactive form; thus PDE5 inhibitors prolong the duration of active cGMP and improve erections. Multiple studies have demonstrated the efficacy of PDE5 inhibitors in the CKD and dialysis population with success rates comparable to non-CKD patients.[70–74] The side effect profile is similar to the non-CKD patient population, with headache, flushing, and GI upset reported as the most common adverse effects.[75] As PDE5 inhibitors may have a protective effect against renal injury, renal protective dose adjustment is not usually required in the CKD population.[76–78] However, some authors have noted an increase in transient hypotension after administering 50 mg of sildenafil, particularly on those days that patients receive hemodialysis and may already be hypotensive compared to baseline. It has been suggested that PDE5 inhibitors should only be used on non-dialysis days and that a smaller starting dose (25 mg of sildenafil) be used.[79] Data on the use of more selective drugs, such as vardenafil and tadalafil (both more selective for PDE5 compared to other PDEs), is still lacking in the CKD population.

Testosterone Replacement Therapy

Testosterone simultaneously upregulates the activity of neuronal nitric oxide synthase (nNOS) and PDE5, thus increasing NO levels and increasing the degradation of cGMP.[80,81] These two antagonistic effects may effectively cancel each other out, explaining why administration of testosterone to CKD patients usually fails to restore libido and erections, despite an increase in serum testosterone.[82,83] While combination therapy with testosterone and PDE5 inhibitors has been shown to be effective in hypogonadal men who do not respond to PDE5 inhibitors alone, the data is mixed in the CKD population.[84–88] In particular, a recent randomized, double blind, placebo-controlled trial failed to show significant improvement of erectile function with the addition of testosterone to sildenafil in the CKD population.[89] Thus the role of testosterone supplementation for the purpose of improving erections in the CKD population remains controversial at best.

Other ED Treatments

Further ED treatments include vacuum erectile devices, intracavernosal injections, urethral suppositories, and prosthesis implantation. A single study evaluated effectiveness of vacuum therapy in dialysis patients, with 73.1% of patients achieving erection with the vacuum device. Of note, all hypogonadal men in this cohort first received testosterone therapy via implantation of depo-testosterone.[82] Intracavernosal injections may be performed with a variety of medications in combination or alone, including prostaglandin E1, papaverine, and phentolamine. While the success rate in the general population is 80–85%, they must be used with caution in the CKD population, particularly with ESRD, due to a greater degree of coagulopathy leading to potential bleeding complications at the needle injection site.[90] Alprostadil suppositories have not been studied in the CKD population. Penile prostheses, often used after failure of first and second line therapies, can safely be performed in CKD patients without an increased risk of infection.[91] Given that erectile function improves for many men post renal transplantation, it is recommended that penile prosthesis placement wait until after transplantation. One potentially challenging step during penile prosthesis placement post-transplant is selecting a location for the reservoir. The authors favor placing the reservoir on the contralateral side of the transplant as a first choice. If the patient has had a hernia repair with mesh or another kidney transplant on that side, the authors propose a small, open midline fascial incision or an ectopic submuscular reservoir placement. We have begun favoring ectopic placement in this situation due to several studies showing good outcomes with this technique.[92,93]

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