Duration of chronic kidney disease: As predisposition factor for erectile dysfunction in routine hemodialysis patients

Background: Chronic kidney disease (CKD) has a high global prevalence with an estimated prevalence of 10.6%. While the global prevalence of erectile dysfunction (ED) is 18.4% in men aged > 20 years and 33% aged> 50 years. ED is found in 70% of CKD patients. The aim of the study is to determine the relationship between duration of chronic kidney disease with ED in patients undergoing routine hemodialysis. Method: A cross-sectional study conducted from 1 October 2018 to 18 June 2019 of 60 CKD patients undergoing hemodialysis. History and examination were carried out using the International Erectile Function Index (IIEF-5) questionnaire. Result: Out of 60 samples, 42 patients (70%) had ED. The average duration of chronic kidney disease resulting in mild, moderatemoderate and moderate ED was 10.94 ± 10.79, 24.20 ± 17.84 and 38.40 ± 16.78 months, respectively. Univariate analysis using Spearman rank correlation showed a direct relationship between the duration of CKD and DE (P = 0.00, R squared 0.814). Conclusion: Duration of chronic kidney disease has strong relationship with ED in hemodialysis patients


INTRODUCTION
Chronic kidney disease (CKD) is a condition of kidney structure or function disorder that occurs for more than 3 months and has health implications. 1-3 The global incidence of CKD is 10.6% (95% CI 9.2% -12.2%). In Indonesia showed that the province with the highest prevalence of CKD was Central Sulawesi 0.5%, followed by Gorontalo, North Sulawesi, and Aceh each by 0.4%. 4, 5 Sexual dysfunction is one of complication of chronic kidney disease. Erectile dysfunction (ED) occurs in 70% of cases of chronic kidney disease. 6 In addition, it was reported that about 40% of men undergoing hemodialysis experience ED accompanied by a decrease in libido, 30% of patients with CKD do not engage in sexual activity and 44% of patients only engage in one sexual activity per week. 7 The process of ED in chronic multifactorial CKD includes decreased arterial blood flow, venous leakage due to shunts, changes in penile smooth muscle function, hormonal disorders, drug side effects, and neurogenic dysfunction. 8, 9 In addition, psychological and physical pressure also plays a role in this situation. The purpose of this study was to determine the relationship between the patient's duration of chronic kidney disease and the incidence of ED in the dr. Zainoel Abidin General Hospital of Banda Aceh.

ORIGINAL ARTICLE
of CKD patients including etiology, degree of ED and aspects of patient psychology ( Table 3). The relationship between the degree of ED and duration of chronic kidney disease is presented in table 4. In patients without ED, the mean duration of developing chronic kidney disease is 2.5 ± 2.12 months. The longer the patient suffered from chronic kidney disease, the higher the degree of DE patients (P = 0.00). The mean duration of patients suffering from chronic kidney disease resulting in mild, moderate, moderate or severe ED, respectively 10.94 ± 10.79, 24.20 ± 17.84 and 38.40 ± 16.78 months. In the statistical analysis, there was a significant difference between the duration of chronic kidney disease and the level of ED (p = 0.00).
The relationship between the duration of suffering from CKD on the incidence of ED is presented in table 5. The longer the patient suffering from CKD, the more likely the patient to experience ED. This can be seen in the onset of 0-6 months, only 7 (11.67%) patients with ED compared to 17 (28.33%) normal patients. Whereas at the time of onset of more than 12 months, all patients experienced ED (Figure 1).
There is a direct relationship between the duration of suffering from CKD and the degree of DE (P = 0.00, R square 0.814). At the onset of 0-6 months, 28.3% of patients did not have ED while 6.8% had mild dysfunction and 1.7% mild-moderate dysfunction. However, in the onset of 7-12 months,

DISCUSSION
Impaired sexual function is often found in patients with chronic kidney disease. In this study we evaluated the relationship between the duration of suffering from CKD on the occurrence of ED, so we can know the duration and progression of CKD until triggering ED, this can be a consideration in starting therapy. CKD patients in this study had an average age of 36.43 ± 3.24 years with CKD onset for 16.30 ± 17.78 months. Globally the incidence of chronic kidney disease increases with age. Meanwhile, when reviewed based on ED levels, the average age of patients when experiencing mild-moderate ED was 36.80 ± 2.67 years and increased to 37.60 ± 4.08 years in moderate dysfunction. These results are in accordance with the National Health and Nutrition Examination Survey (NHANES) report for 2007-2012 which explains that 5.7% of patients with chronic kidney disease are in the age range of 20-39 years, 8.9% at age 40-59 years and 33.2% above 60 years. In addition, Al Khallaf et al. reported that patients with ED in the population undergoing hemodialysis had an average age of 38.2 ± 6.6 years. 10, 11 But in another study by Nishida et al. in 2016 reported that ED was not affected by the length of undergoing hemodialysis. This might be influenced by the study sample which is dominated by the elderly (59.2 ± 10.7 years). In another study reported that old age was the main predictive factor of ED in CKD patients. 12 In laboratory evaluation it is known that patients with kidney failure have an average hemoglobin of 8.52 ± 0.65, leukocytes 8113.33 ± 2136.72, urea 155.15 ± 22.66 and creatinine 11.14 ± 5.67. This illustrates that anemia and uremia in kidney failure are common conditions. Anemia occurs due to kidney failure in producing erythropoietin (EPO) so that the stimulation of erythrocyte production is inhibited. The condition of uremia in patients with CKD will also slow the survival of erythrocytes. The prevalence of anemia increases based on the decrease in the patient's GFR. Patients with anemia, accompanied by other accompanying risk factors, will increase the risk of ED. Anemia and uremia can also cause ED due to decreased oxygen delivery to the corpora cavernosa, decreased nitriloside, failure of sympathetic stimulus for erection and increase in endothelium-derived factors that can inhibit erectile capacity. 13- 15 The most common causes of CKD in this study were hypertension (65%) followed by idiopathic (20%), and nephrolithiasis (15%). Globally it is explained that renal glomerular damage is most often caused by diabetes mellitus (33%), autoimmune, systemic infections and neoplasms. Meanwhile, in vascular damage, hypertension is the main cause of chronic renal failure (21%). Kidney obstruction such as nephrolithiasis and urinary tract stones has also been reported to be one cause of CKD. [16][17] Besides being caused by the etiologies mentioned above, ED can also be caused by the psychological aspects of the patient. In this study, 44 patients (73.3%) did not have depression. Psychological status of patients who need supervision as many as 14 patients (23.3%) and patients with moderate depression as many as 2 patients (3.3%). There are no patients with severe or very severe depression. This shows that there is a predominance of normal patients without depression in this study population. The mechanism of the relationship between depression and ED is still unclear. However, there is a role for behavioral models as well as biological changes that increase the risk of ED in depressed patients. Behavioral models explain that patients with depression tend to have negative thoughts and lack of confidence resulting in anxiety which reduces erectile function. Biologically, patients with depression will affect the hypothalamic-pituitary-adrenocortical (HPA) axis which causes excessive catecholamine production so that the relaxation function of the cavernous muscle deteriorates and ED occurs. 18 ED assessment in CKD patients using the index of erectile function (IIEF-5) score in this study had an average value of 17.22 ± 5.21. Patients with CKD had the most severe ED 28.3%, mild-moderate 25% and moderate 16.7%. In addition, we also found  In this study, we also divided the onset of the duration of illness experienced by patients, when 7-12 months were generally in the condition of mild dysfunction (15%), but at the time of> 12 months, the ED level experienced increased more to mild ED -is 15% and moderate dysfunction is 15%. The Kruskal Wallis test shows a direct relationship with a significantly strong correlation between the duration of suffering from CKD (p = 0.00, R-square 0.814). The longer the patient has CKD, the heavier the ED level. Mesquita et al. reported that 86.4% of CKD patients will experience ED in less than 60 months. Another report by Yuan et al. also in the follow-up of patients with CRF 2-4 years found the incidence of ED increased 9.10/ 1,000 patients each year and increased to reach 16.92/1,000 people annually after 4 years. 19-20

CONCLUSION
The duration of CKD has a correlation with the occurrence of ED in hemodialysis patients at Dr. Zainoel Abidin General Hospital in Banda Aceh. With a P-value of 0.00 and R-square 0.814, it shows that there is a very strong relationship between variables.