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Table of Contents
ORIGINAL ARTICLE
Year : 2021  |  Volume : 15  |  Issue : 4  |  Page : 307-312

Erectile dysfunction in renal transplant patient - A prospective observational study


Department of Urology and Renal Transplant, Mahatma Gandhi Medical College, Jaipur, Rajasthan, India

Date of Submission20-Dec-2020
Date of Decision21-Mar-2021
Date of Acceptance24-Mar-2021
Date of Web Publication30-Dec-2021

Correspondence Address:
Dr. Ketul Patel
Room No. 113, Type 4/B PG Hostel, Mahatma Gandhi Medical College, Sitapura, Jaipur, Rajasthan
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijot.ijot_157_20

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  Abstract 

Introduction: Erectile dysfunction (ED), defined as an inability to obtain or maintain an erection adequate for satisfactory sexual function, is present in up to 50–80% of patients with chronic kidney disease (CKD) (1). The rate of erectile dysfunction (ED) in patients with chronic kidney disease (CKD) was shown to be 75%, whereas it decreased to 59% in kidney transplantation recipients (KTRs). Materials and Methods: A 264 Renal Transplant Patient is included in this study. Both male and female patient included in this study. The International Index of Erectile Function questionnaire – 5 (IIEF-5) (SHIM) Scoring systems is used. Results: Total 264 patients are included in the study.34 patients not responded. According to SHIM score 4 patients have sever erectile dysfunction, 21 patient have moderate erectile dysfunction, 78 patients have mild to moderate erectile dysfunction, 104 patients have mild erectile dysfunction and 23 patients have no erectile dysfunction. After 1 year of renal transplant, according to SHIM score 3 patients have sever erectile dysfunction,14 patient have moderate erectile dysfunction, 47 patients have mild to moderate erectile dysfunction, 67 patients have mild erectile dysfunction and 99 patients have no erectile dysfunction. Conclusion: IIEF-5 is an effective means to establish and diagnose the erectile dysfunction. Advance age, prolonged dialysis, diabetes mellitus and smoking were important risk factors for erectile dysfunction. The incidence of ED in patients with ERSD and KTRs is quite high, and its management is particularly difficult due to many interfering factors.

Keywords: Erectile dysfunction, International Index of Erectile Function-5 score, renal transplantation, sexual dysfunction


How to cite this article:
Sadasukhi N, Patel K, Sadasukhi T C, Gupta M, Gupta H L, Sharma A, Malik S. Erectile dysfunction in renal transplant patient - A prospective observational study. Indian J Transplant 2021;15:307-12

How to cite this URL:
Sadasukhi N, Patel K, Sadasukhi T C, Gupta M, Gupta H L, Sharma A, Malik S. Erectile dysfunction in renal transplant patient - A prospective observational study. Indian J Transplant [serial online] 2021 [cited 2022 Jan 18];15:307-12. Available from: https://www.ijtonline.in/text.asp?2021/15/4/307/334426




  Introduction Top


Erectile dysfunction (ED), defined as an inability to obtain or maintain an erection adequate for satisfactory sexual function, is present in up to 50%–80% of patients with chronic kidney disease (CKD).[1] The rate of ED in patients with CKD was shown to be 75%, whereas it decreased to 59% in kidney transplantation recipients (KTRs).

Disturbances in sexual function are first noticed in the early phase of kidney failure and deteriorate further as renal function declines.[2],[3]

In male patients, 70% had ED. Other sexual problems reported by men are reduced libido, difficulty in achieving orgasm, and an ejaculation.[2],[4]

In female patients, sexual issues are twice as frequent compared to the general population; during dialysis, the prevalence of SD increases to 70%.[5],[6] Sexual issues reported by women are reduced libido and lubrication, difficulty in getting aroused, pain during intercourse, and difficulty in achieving orgasm.[2],[6]

The most cause of the CKD was diabetes mellitus in 35.59%, followed by glomerulonephritis in 20.34%, hypertension in 16.95% of patients, and other causes were abnormalities in the hypothalamic–pituitary–gonadal axis, autonomic nervous system disturbances, peripheral neuropathy, endothelial dysfunction, anemia, secondary hyperparathyroidism, medication effects, and psychological factors such as stress and depression contributing to various degrees.[4],[7]

Renal transplantation prolongs life and improves the quality of life in patients with CKD. Because of normalization of the hormonal disturbances, renal transplantation improves the sexual health (e.g., libido), energy, and fertility.[8],[9],[10]

However, after kidney transplantation, the prevalence of SD still remains 46% in both men and women. The persistence of SD after receiving a kidney transplant may have a negative impact on the patients' well-being.[11],[12],[13],[14]


  Materials and Methods Top


A total of 264 renal transplant patients were included in this study. Both male and female patients were included in this study. The International Index of Erectile Function questionnaire-5 (IIEF-5) (SHIM) scoring system is used.

In this study, the average duration of CKD of these patients was 6 months to 24 months, calcineurin inhibitors (CNIs), i.e., cyclosporine, tacrolimus, and mycophenolate mofetil are use immunosuppressant in our patient in post transplant time, patient whoes baseline thyroid function were normal are include in our study , pretransplant and 1 year after transplant ED calculated in this study. Posttransplant graft dysfunction and infection were not included in this study.

The questionnaire consisted of five questions dealing with erectile function and overall satisfaction.[15] These questionnaires have been validated for the diagnostic purpose by the National Institute of Health (NIH). Each five questions have 5 grading from very low to very high according to severity.

The optimal cutoff score of 21 was defined by receiver operating curve analysis which has demonstrated to have excellent sensitivity and specificity (0.98 and 0.88, respectively) for discriminating between normal and ED.[16] The severity of sexual dysfunction was classified in five categories, i.e., severe (5–7), moderate (8–11), mild to moderate (12–16), mild (17–21), and no ED (21–25).[15]

The statistical calculations were done.

The descriptive purpose of our study is displayed in frequency and percentages for categorical data and mean and standard deviation for continuous variables.

Correlations were done using the two-tailed t-tests with 95% confidence interval, P < 0.05 was considered statistically significant.

There was a significant correlation with three of the elements of the IIFE-5, i.e., penile hardness prepenetration, maintaining erection during intercourse, and difficulty to maintain erection to complete the intercourse (P = 0.015, 0.011, and 0.023), respectively, and the overall improvement after transplantation which showed a P < 0.031, while there was no significant correlation with confidence with erection and satisfaction with intercourse before and after transplantation (P = 0.113 and 0.121), respectively.

Statistical analysis

The statistical calculations were done.

The descriptive purpose of our study is displayed in frequency and percentages for categorical data and mean and standard deviation for continuous variables.

Correlations were done using the two-tailed t-tests with 95% confidence interval, P < 0.05 was considered statistically significant.

There was a significant correlation with three of the elements of the IIFE-5, i.e., penile hardness prepenetration, maintaining erection during intercourse, and difficulty to maintain erection to complete the intercourse (P = 0.015, 0.011, and 0.023), respectively, and the overall improvement after transplantation which showed a P < 0.031, while there was no significant correlation with confidence with erection and satisfaction with intercourse before and after transplantation (P = 0.113 and 0.121), respectively.

Patient consent

All the patient in this study given informed and written consent.

Ethics statement

The ethical clearance was obtained from MGUMST, Jaipur Ethics Committee on May 31, 2021, with IRB number NO.MGMCH/IEC/JPR/2021/455. The privacy and confidentiality of each participant were ensured. The procedure was carried out in accordance with the Declaration of Helsinki and International Council for Harmonization-Good Clinical Practice (ICH-GCP).


  Results Top


A total of 264 patients are included in the study. About 34 patients not responded.

According to the SHIM score, 4 patients have severe ED, 21 patients have moderate ED, 78 patients have mild to moderate ED, 104 patients have mild ED, and 23 patients have no ED [Figure 1].
Figure 1: Distribution of ED in pretransplant patient

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After 1 year of renal transplant, according to the SHIM score, 3 patients have severe ED, 14 patients have moderate ED, 47 patients have mild to moderate ED, 67 patients have mild ED, and 99 patients have no ED [Figure 2].
Figure 2: Distribution of ED in renal transplant patient after 1 year

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Age was an important risk factor for ED, i.e., ED patients had higher age then normal patients. (42.45 ± 9.75 vs. 32 ± 8.34 years).

According to age, ED present in 73 patients in 21–30 years age, 103 patients in 31–40 years age, 41 patients in 41–50 years age, and 13 patients in 51–60 years age [Figure 3].
Figure 3: Age disrubution for ED in renal transplant patient

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Longer duration of pretransplant dialysis (6.06 ± 3.8 vs. 3.77 ± 2.4 months) and smoking status (25.5% vs. 5%) were associated with higher incidence and severity of sexual dysfunction. Diabetes mellitus also had higher risk for ED in comparison to nondiabetic patients (27% vs. 9%).

In our study, the external iliac artery was used for arterial anastomosis, i.e., the renal artery is anastomose to the external iliac artery in end to side in all renal transplant patients.

Ejaculatory dysfunction was present in 25% of patients. ED was present in 75% of patients. The most common ejaculatory dysfunction was premature ejaculation (91%) [Figure 4].
Figure 4: Distribution of erectile dysfunction and ejeculatory dysfunction in renal transplant patient

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  Discussion Top


ED is defined by the NIH consensus development conference as the inability to achieve or maintain an erection sufficient for satisfactory sexual performance.[16] Renal failure is a major risk for ED and half of patients with chronic renal failure may be impotent. The genesis is multifactorial and is primarily organic. In addition to the uremic milieu, peripheral neuropathy, autonomic insufficiency, peripheral vascular disease and pharmacotherapy, all play an important role in the genesis of ED.[17]

Although laboratory-based diagnostic procedures are available, it has been proposed that sexual function is best assessed in a naturalistic setting with patient self-reporting technique.[16] The IIEF is the most widely accepted self-administered questionnaire and is statistically validated in many languages. Initial IIEF was a 15-item questionnaire which addresses and quantifies five domains: erectile function, sexual desire, orgasmic function, intercourse satisfaction, and overall satisfaction. These questionnaires are cumbersome and to make it more useful, 5-item questionnaire of the IIEF-5 (SHIM) has been developed which mainly deals with erectile function and overall satisfaction. We had also included question pertaining to the ejaculatory problem because of high prevalence of ejaculatory dysfunction.

Major risk factors associated with high incidence of ED in our study were diabetes mellitus, older age, smoking, and longer duration of dialysis.

Diabetes mellitus causes ED through its vascular, neurologic, endothelial, and psychogenic complications. The molecular mechanism responsible for ED were pathologic changes in cavernous arteries,[18] ultrastructural changes in the cavernous smooth muscle cell, and impaired endothelium-dependent relaxation of the corporeal smooth muscle cell.[19] All these changes are aggravated by uremia and basically do not revert back after renal transplantation, therefore responsible for high incidence of ED.

Longer duration of hemodialysis was also a risk factor for ED. This has been attributed to permanent damage of cavernous micro- and macrovessels and smooth muscle, sustained during the long course of renal failure.[20] Early transplantation is recommended because it is more effective and less costly than hemodialysis.[21] Maintaining erectile function should be another reason for early transplant.

Another risk factor for ED is increasing age. All the endocrinal and microvascular changes with aging are aggravated by renal failure.

Gittes and Walter reported that a higher incidence of ED in patients who underwent bilateral renal transplantation using both internal iliac artery, explanation given for that was bilateral ligation of the internal iliac artery leads to penile revascularization.[22] Penile arteries are branches of the internal iliac artery, when the internal iliac artery used for end-to-end anastomosis with renal artery, this leads to a decrease in penile blood flow and may affect subsequent erection.[23]

Treatment option for ED like psychological counseling, oral drug therapy, and invasive therapy like intracavernosal injection therapy are used.

At present, sildenafil citrate has provided a significant improvement in the treatment with ED because it is effective, safe, easy to handle, and causes no serious side effects.[24] Its efficacy has been proven in renal transplant patients without significant interaction with cyclosporine/FK50615.In this respect, a self-administered questionnaire like IIEF-5 provides an easy and rapid way for accumulating data and could be used routinely for diagnosis and treatment evaluation.

Treatment of erectile dysfunction in kidney transplant recipients

A wide variety of treatments to restore erectile function are safe and effective in KTRs. phosphodiesterase-5 inhibitors (PDE5is) have been studied in these patients, and among them, sildenafil[25],[26],[27],[28] and vardenafil[29] have been used with success, showing no significant interactions with immunosuppressive drugs.[30],[31] Additionally, psychosexual therapy, drug therapy, surgical treatment, transurethral or intracavernosal therapy, vacuum constriction devices, and low-intensity shockwave therapy (LiSWT) may be pursued. The detection of PDE5 expression in the cortex and inner medulla of human kidneys prompted the hypothesis of a possible natriuretic effect other than those exerted on penile vasculature itself. However, sildenafil administration in decompensated cirrhotic patients caused rapid activation of the renin–angiotensin–aldosterone system and sodium retention, which are associated with a decrease in arterial blood pressure.[32] Increased cyclic GMP levels have also been implicated in the control of renin secretion, and the administration of sildenafil exerted a stimulatory effect on renin secretion. This effect may help to explain why sildenafil has a minor effect on blood pressure, despite the widespread distribution of PDE5 in vascular tissues, and it is very safe on KTRs.[33] Sildenafil, the first available oral drug that has proven to be effective and safe for ED treatment in KTRs, as well as in patients undergoing hemodialysis, improves the penetration ability, maintenance frequency, and sexual domain scores (erectile function, sexual desire, intercourse, and overall satisfaction) without influencing the serum concentrations of cyclosporine.[34] Vardenafil is effective and well-tolerated in KTRs and shows similar efficacy and a similar safety profile as sildenafil.[35] The recommended starting dose of sildenafil in patients with severe kidney dysfunction (i.e., CLcr <30 mL/min) should be 25 mg. Vardenafil 5 mg may be administered in patients with mild, moderate, or severe renal insufficiency.[36] The recommended starting dose of tadalafil, a PDE5i with a long half-life, is 5 mg in patients with moderate kidney insufficiency (CLcr 31-50 mL/min), and the maximum total dose of 10 mg should not be exceeded in 48 h. For severely impaired patients (CLcr <30 mL/min) and patients with ESRD undergoing dialysis, a 5-mg total dose in 72 h is recommended. Once-daily treatment is not recommended in patients with CLcr <30 mL/min[36] because of poor safety evidence related to KTRs and in patients undergoing dialysis.

Second-line treatments are penile injections and urethral suppositories. Intracavernous injections of alprostadil have been successfully used in immunosuppressed KTRs without any reports of kidney impairment or changes in CNI levels attributable to this treatment for ED.[37] Alprostadil can be usefully delivered by a urethral suppository, and the dosage required is about 25 times higher than that used for intracavernous injection.

Third-line therapy includes penile implants, which should be carefully considered in these patients, taking into account the following aspects: (i) stable graft function for at least 6 months; (ii) low doses of immunosuppressant's; (iii) low probability of device malfunction; (iv) no intra-abdominal components to avoid confusion of the reservoir with the bladder in the event of subsequent kidney transplantation; (v) minimum tissue dissection; (vi) no skin or urinary tract infections; (vii) use of prophylactic antibacterial (parenteral, intraurethral, and topical); and (viii) treatment with postoperative broad-spectrum oral antibacterial for 1–2 weeks.[38]

LiSWT has recently emerged as a potential treatment for ED, and this has created considerable excitement due to its potential reparative mechanisms promoting the formation of new blood vessels and improving endothelial function in the corpora cavernosa. Yamaçake et al. have published promising results of the effects of six treatment sessions, with 7 out of 10 patients in the treatment group experiencing an improvement of at least 5 points in the IIEF-5 score versus only 1 out of 10 in the sham group.[39] At first glance, this seems to confirm a possible effect of Li-SWT and suggests that the treatment could be offered specifically to KTRs. However, these results must be interpreted cautiously because of the very small number of patients treated.

Limitations

The study is limited by small sample size.


  Conclusions Top


The prevalence of ED after renal transplant is quiet high and most of these problems are never discussed with the patients during routine evaluation. IIEF-5 is an effective means to establish and diagnose the ED. Advance age, prolonged dialysis, diabetes mellitus, and smoking were important risk factors for ED. The incidence of ED in patients with end stage renal disease and KTRs is quite high, and its management is particularly difficult due to many interfering factors. The first approach should refer to changing the pharmacological interference scenario, especially for those drugs upsetting sexuality at the central (i.e., gonadotropins and neurosteroids) and peripheral levels by shifting some adverse treatments to favorable ones whenever possible. The second approach may be to prescribe a PDE5i at a low dosage, considering that if testosterone-circulating levels are compatible with the diagnosis of hypogonadism, its efficacy may only be partial.[40] The possibility of using a combination of testosterone plus PDE5i should be considered, due to the beneficial effects on both systemic and local (penis and kidney) targets. Careful monitoring of KTRs is required both in terms of efficacy and safety because of the possible occurrence of treatment-emergent adverse events requiring drug withdrawal. Finally, topical or intracavernous injections of alprostadil in patients failing first- and second-line treatments are advised in the absence of contraindications. Penile implants should be regarded as third-line options arising from specific patient needs and compliance with the clinical conditions.[41]

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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