Sexual dysfunction in men and women with chronic kidney disease and end-stage kidney disease

Sexual dysfunction is a common finding in both men and women with chronic kidney failure. Common disturbances include erectile dysfunction in men, menstrual abnormalities in women, and decreased libido and fertility in both sexes. These abnormalities are primarily organic in nature and are related to uremia as well as the other comorbid conditions that frequently occur in the chronic kidney failure patient. Fatigue and psychosocial factors related to the presence of a chronic disease are also contributory factors. Disturbances in the hypothalamic-pituitary-gonadal axis can be detected before the need for dialysis but continue to worsen once dialytic therapy is initiated. Impaired gonadal function is prominent in uremic men, whereas the disturbances in the hypothalamic-pituitary axis are more subtle. By contrast, central disturbances are more prominent in uremic women. Therapy is initially directed toward optimizing the delivery of dialysis, correcting anemia with recombinant erythropoietin, and controlling the degree of secondary hyperparathyroidism with vitamin D. For many practicing nephrologists, sildenafil has become the first line therapy in the treatment of impotence. In the hypogonadal man whose only complaint is decreased libido, testosterone may be of benefit. Regular gynecologic follow-up is required in uremic women to guard against potential complications of unopposed estrogen effect. Uremic women should be advised against pregnancy while on dialysis. Successful transplantation is the most effective means of restoring normal sexual function in both men and women with chronic kidney failure.     

Sexual function in chronic kidney disease

Endocrine abnormalities are common in patients with chronic kidney disease (CKD) and lead to sexual dysfunction, anemia, hyperparathyroidism, and altered mineral metabolism. Common clinical problems include disturbances in menstruation in women, erectile dysfunction in men, and decreased libido and infertility in both sexes. Organic factors tend to be prominent and are related to uremia and other comorbid illnesses. Psychological factors and depression may exacerbate the primary problem. Alterations in the hypothalamic-pituitary axis are seen early in CKD and tend to worsen after patients start dialysis. Hypogonadism plays a dominant role in male sexual function, whereas changes in hypothalamic-pituitary function predominate in female sexual dysfunction. In patients on dialysis, treatment strategies include optimizing dose of dialysis, correction of anemia with erythropoietin, and correction of hyperparathyroidism. Successful kidney transplantation may restore normal sexual function, especially in younger patients.     

Ultrastructural changes of corpora cavernosa in men with erectile dysfunction and chronic renal failure

Erectile dysfunction (ED) is a common and often distressing side effect of renal failure. Uremic men of different ages report a high variety of sexual problems, including sexual hormonal pattern alterations, reduced or loss of libido, infertility, and impotence, thereby influencing their well-being. The pathogenic mechanisms include physiologic, psychologic, and organic causes. To determine the contribution of morphologic factors to impotence we studied the ultrastructure of the corpora cavernosa in 20 patients with end-stage renal disease who were treated with chronic dialysis and compared the findings with 6 individuals with no clinical history of impotence. Our results indicated that in male uremic patients with sexual disturbances there were major changes in smooth muscle cells. This was characterized by reduction of dense bodies in the cytoplasm, thick basement membranes, and increased interstitial collagen fibers with resultant reduction of cell-to-cell contact. In addition, there was thickening and lamination of basement membranes of endothelial cells and increased accumulation of collagen between nerve fibers. These alterations were more evident in patients with longer time on dialysis and were independent of type of primary renal disease. We hypothesize that ED in dialysis patients is not related to the primary disease but to the uremic state.     

Gonadal dysfunction in men with chronic kidney disease: clinical features, prognostic implications and therapeutic options

Gonadal dysfunction is a frequent finding in men with chronic kidney disease and with end-stage renal disease. Testosterone deficiency, usually accompanied by elevation of serum gonadotropin concentrations, is present in 26-66% of men with different degrees of renal failure. Uremia-associated hypogonadism is multifactorial in its origin, and rarely improves with initiation of dialysis, although it usually normalizes after renal transplantation. Experimental and clinical evidence suggests that testosterone may have important clinical implications with regards to kidney disease progression, derangements in sexual drive, libido and erectile dysfunction, development of anemia, impairment of muscle mass and strength, and also progression of atherosclerosis and cardiovascular disease. Additionally, low testosterone levels in hemodialysis patients have been associated with increased mortality risk in some studies. Currently, we count with available therapeutic options in the management of uremic hypogonadism, from optimal delivery of dialysis and adequate nutritional intake, to hormone replacement therapy with different testosterone preparations. Other potential options for treatment include the use of antiestrogens, dopamine agonists, erythropoiesis-stimulating factors, vitamins, essential trace elements, chorionic gonadotropin and renal transplantation. Potential adverse effects of androgen replacement therapy in patients with kidney disease comprise, however, erythrocytosis, prostate and breast cancer growth, reduced fertility, gynecomastia, obstructive sleep apnea and fluid retention. Androgen preparations should be used with caution with stringent monitoring in uremic men. Although there are encouraging data suggesting plausible benefits from testosterone replacement therapy, further studies are needed with regards to safety and effectiveness of this therapy.     

Potential strategies to normalize the levels of homocysteine in chronic renal failure patients

Recently published evidence suggests that, either than folate therapy, the enhancement of homocysteine remethylation in tissues by correcting the multiple abnormalities of the remethylation pathway in chronic renal failure that extend beyond folate-related disturbances, or else the improved removal of uremic toxins and/or Hcy through intensified dialysis procedures may represent two strategies to normalize total homocysteine in uremic patients.     

男性慢性肾功能不全病人的性功能障碍研究

目的 :研究四川省男性慢性肾功能不全病人性功能障碍的发病情况、表现形式和相关因素。　方法 :多中心合作、临床横断面调查 ,利用性功能电脑测评与诊断系统 (SCASF) ,对四川省 12 4例慢性肾功能不全病人和 12 5例慢性肾脏病肾功能正常病人 (对照组 )的性功能状态进行综合评价 ,同时测定其血常规、肾功能、性激素、性激素结合球蛋白等指标。　结果 :①慢性肾功能不全病人性功能障碍主要表现为性欲减退、勃起功能障碍 (ED)、早泄。②慢性肾功能不全病人性欲减退、ED、早泄、性操作焦虑、性合作缺乏的发生率明显高于对照组 (P <0 .0 5 )。③血液透析和腹膜透析病人各种形式的性功能障碍的发生率和障碍的严重程度没有差异 ;透析组 (血液透析和腹膜透析 )、未替代治疗组、肾移植组比较 ,未替代治疗组性欲减退和性操作焦虑的发生率高于透析组与肾移植组 ;未替代治疗组和透析组ED的发生率高于肾移植组。④多因素分析表明 ,性功能障碍的发生与病人的病程、肌酐清除率、甲状旁腺激素、血浆白蛋白无关。贫血、抑郁和应用 β受体阻滞剂是性欲减退的危险因素。年龄增加是ED的危险因素。应用血管紧张素转换酶抑制剂或血管紧张素受体拮抗剂和应用人基因重组促红细胞生成素 (r HuEpo)可减少ED的发生。　结论 :男性慢性     

Outcomes associated with hypogonadism in men with chronic kidney disease

Chronic kidney disease is commonly accompanied by disturbances in the hypothalamic-pituitary-gonadal axis. Such disturbances in men give rise to hypogonadism and low circulating testosterone levels. The deficiency in testosterone can contribute to clinical outcomes such as sexual dysfunction, decreased bone mineralization, malnutrition and decreased muscle mass, and anemia. The administration of androgens to nonuremic hypogonadal men is usually effective in treating such outcomes. By contrast, the response to therapy in uremic men tends to be much less predictable. This variability in response is not surprising, because these same clinical outcomes can be the result of other aspects of the uremic state or the comorbid conditions that are frequently present in men with chronic kidney disease. Although further studies are needed, testosterone therapy may prove most useful as an adjunct to other more general therapies designed to address the uremic state.     

Diamine oxidase activity in plasma and urine in uremia.

Diamine oxidase activity was measured in plasma or urine in 12 normal men, 4 men with chronic liver or heart disease, 13 men with chronic renal failure, and 12 men undergoing maintenance hemodialysis. Also in five studies in 4 patients, plasma diamine oxidase activity and total amine levels were measured at hourly intervals during a hemodialysis treatment. Plasma diamine oxidase activity was normal in patients with liver or heart disease and was at least three times normal in chronically uremic patients and in patients undergoing maintenance hemodialysis. Plasma diamine oxidase activities before and after a hemodialysis therapy were similar and did not change during dialysis until the 4th hour when they fell transiently; plasma total amine levels, which were elevated initially, tended to rise during the 4th hour of dialysis. Urinary diamine oxidase activity was reduced in the chronically uremic patients as compared to normal subjects. These observations are consistent with three alterations in diamine oxidase in patients with renal failure: activity (a) is increased in plasma of chronically uremic patients and those undergoing maintenance hemodialysis, (b) does not increase normally in response to heparin administration during dialysis therapy, and (c) is reduced in urine of chronically uremic patients.     

Sexualität nach Nierentransplantation

The quality of life of patients after kidney transplantation is of increasing interest. In this connection, issues of sexuality are meaningful too. Many patients with end-stage kidney disease suffer from sexual disorders. More than 50% of the male patients on dialysis and even more females are affected by disturbances such as erectile dysfunction and loss of libido or abnormal menstrual cycles. After successful kidney transplantation most symptoms in women are improved, whereas in men disturbances in erectile function often persist or even deteriorate. In these patients treatment with inhibitors of phosphodiesterase type 5 is a valid option with an effective response. In women with stable graft function pregnancy can be achieved successfully. Nevertheless, pregnant kidney allograft recipients should be considered as high-risk patients needing special care under the supervision of a team of obstetricians and nephrologists.     

Prevalence and Pathogenesis of Impotence in One Hundred Uremic Men

In a study of dialysis patients 79% of men complained of sexual dysfunction and 61% erectile impotence following uremia and the onset of regular dialysis therapy. Plasma testosterone levels were significantly higher in patients treated by continuous ambulatory peritoneal dialysis (p = 0.001) but the incidence of sexual dysfunction was not different from patients treated by hemodialysis. Although follicle-stimulating hormone levels were higher (p = 0.001) and penile blood pressure index levels lower (p < 0.05) in patients with impotence, sexual function was not improved by exogenous testosterone, and vasculogenic impotence was identified in only 6% of patients. These findings suggest that a major component of uremic impotence is unrelated to primary testicular failure or penile vascular insufficiency.     

The prevalence and clinical relevance of sexual dysfunction in women and men with chronic heart failure

Sexual dysfunction is a common problem of increasing incidence that is associated with multiple co-morbid conditions and chronic diseases. In heart failure, however, exact numbers are unknown, in part secondary to under-reporting and under-interrogating by health care providers. A gender-specific questionnaire was modified from established sexual dysfunction questionnaires to correspond to a non-randomized outpatient heart failure population, to assess the prevalence and demographic distribution of sexual dysfunction and potential treatments expectations. One-hundred patients in a stable hemodynamic condition in New York Heart Association classes I-III participated. Eighty-seven percent of women were diagnosed with female sexual dysfunction compared to 84% of men with erectile dysfunction. Eighty percent of women reported reduced lubrication, which resulted in frequent unsuccessful intercourse in 76%. Thirty-six percent of patients thought that sexual activity could harm their current cardiac condition; 75% of females and 60% of men stated that no physicians ever asked about potential sexual problems. Fifty-two percent of men considered sexual activity in their current condition as an essential aspect of quality of life and 61% were interested in treatment to improve sexual function. Sexual dysfunction appears to be high in prevalence in both men and women with chronic compensated heart failure and represents a reduction in quality of life for most. Despite the fact that most patients are interested in receiving therapy to improve sexual dysfunction, treatment options are rarely discussed or initiated.     

Vascular erectile dysfunction in chronic renal failure

The prevalence of erectile dysfunction (ED) has increased dramatically worldwide in parallel with the aging of the population. In 1995, ED was estimated to be present in more than 150 million men. Considering population aging in Western countries, estimates predict that more than 300 million men will be affected by ED by the year 2025. ED is a common and often distressing side effect of renal failure. It is present in 30% of patients with chronic renal failure and in 50% of patients undergoing dialysis treatment. Uremic men of different ages report a high variety of sexual problems including sexual hormonal pattern alterations, reduced or loss of libido, infertility, and impotence, thereby influencing their well-being. The pathogenetic mechanisms include physiologic, psychologic, and organic causes. Since the release of sildenafil citrate, the relationship between ED and the presence of cardiovascular disease (CVD) has been evaluated in several studies. Many of the risk factors for ED are the same as those for cardiac disease. CVD and ED are closely interrelated disease processes. Indeed, ED can be considered a symptom of vascular endothelial damage. Therefore, it can be expected that impotence will appear along with CVD, and the presence of ED suggests the existence of CVD. An accurate evaluation of the sexual histories of all men who present to internists, cardiologists, and also nephrologists for early detection of ED may allow for early diagnosis and management of CVD.     

A case of an accelerated uremic neuropathy

We present a 62-year-old man, with a prior history of diabetes mellitus, atherosclerotic heart disease, and chronic renal failure requiring peritoneal dialysis, who developed accelerated uremic sensorimotor polyneuropathy. Our patient significantly improved after effective hemodialysis. Although renal transplantation is a curable therapy for uremic neuropathy, effective dialysis is still an important treatment for the group of patients who cannot undergo renal transplantation.     

Hyperprolactinemia and sexual disturbances among uremic women on hemodialysis

The investigation of a sample of 99 women on maintenance hemodialysis has shown the presence of sexual disturbances to a great extent: the rate of sexual intercourse and the ability to reach orgasm were significantly lower than in age-matched control women. 80% declared a reduction in their sexual desire and the frequency of intercourse was also lower as compared to the period prior to dialysis. Ageing decreased the sexual activity in both the ill and healthy population, but in uremic patients the sexual activity ended at an earlier age. The patients with hyperprolactinemia reported lower frequencies of intercourse and lower percentages of orgasm than normoprolactinemic ones. The incidence of sexual dysfunction and the role of hyperprolactinemia in this respect were similar to those which are found among male patients on hemodialysis.     

Platelet dysfunction and end-stage renal disease

Patients with end-stage renal disease (ESRD) develop hemostatic disorders mainly in the form of bleeding diatheses. Hemorrhage can occur at cutaneous, mucosal, or serosal sites. Retroperitoneal or intracranial hemorrhages also occur. Platelet dysfunction is the main factor responsible for hemorrhagic tendencies in advanced kidney disease. Anemia, dialysis, the accumulation of medications due to poor clearance, and anticoagulation used during dialysis have some role in causing impaired hemostasis in ESRD patients. Platelet dysfunction occurs both as a result of intrinsic platelet abnormalities and impaired platelet-vessel wall interaction. The normal platelet response to vessel wall injury with platelet activation, recruitment, adhesion, and aggregation is defective in advanced renal failure. Dialysis may partially correct these defects, but cannot totally eliminate them. The hemodialysis process itself may in fact contribute to bleeding. Hemodialysis is also associated with thrombosis as a result of chronic platelet activation due to contact with artificial surfaces during dialysis. Desmopressin acetate and conjugated estrogen are treatment modalities that can be used for uremic bleeding. Achieving a hematocrit of 30% improves bleeding time in ESRD patients.     

Sleep disorders: a systematic review of an emerging major clinical issue in renal patients

The prevalence of sleep disorders is significantly higher (up to 80%) in patients with chronic uremia compared to the general population. Sleep disorders appear even in the early stages of chronic kidney disease. These disturbances are complex, including difficulties in falling asleep and awakening, interrupted sleep, nightmares, restless legs syndrome, sleep apnea syndrome, etc. There are still disagreements on the major etiological factors of sleep disorders in the uremic patient. Older age, long dialysis vintage, alcohol and tobacco abuse and, particularly, the presence of significant comorbidities are major determinants of sleep disorders in dialysis patients. Proper assessment of sleep disorders in the renal population is still under investigation; recent studies have mostly addressed patients’ perception based on questionnaires. More precise polysomnographic assessments are less studied in renal patients. Sleep disorders significantly affect quality of life in dialysis patients. An accurate and early identification of such disturbances would lead to a significant improvement in quality of life, and probably also in outcome, in uremic patients. Sleep apnea syndrome is extremely frequent in dialysis patients, with obvious consequences for cardiovascular morbidity and mortality. Proper diagnosis and therapy of sleep apnea syndrome could significantly reduce cardiovascular risk. Although sleep quality improves after renal transplantation, allograft recipients still have significantly more sleep disorders than healthy individuals. Here, we review recent data on sleep disturbances in renal patients, focusing on the end-stage renal disease patient treated by dialysis.     

Chronic renal failure and sexual functioning: clinical status versus objectively assessed sexual response

Background: Sexual dysfunctions are common among patients with chronic renal failure. The prevalence was assessed in a population of 281 patients (20-60 years), and it was attempted to determine whether their mode of treatment (haemodialysis, peritoneal dialysis, or kidney transplantation), or biochemical and endocrine variables and neuropathy affect sexual functioning. Patients with rheumatoid arthritis served as a comparison group. Methods: Assessment included clinical history, physical and laboratory examinations, questionnaires measuring erotosexual dysfunctions, and a psycho-physiological test procedure. The latter is a laboratory method which measures, in a waking state, subjective and physiological sexual arousal. Results: Men on haemodialysis or peritoneal dialysis suffered significantly more often from 'Hypoactive Sexual Desire Disorder', 'Sexual Aversion Disorder' and 'Inhibited Male Orgasm' than men with kidney transplantation or rheumatoid arthritis. Interestingly, the prevalence of 'Male Erectile Disorder' did not differ significantly between the four groups and ranged between 17 and 43%. Of the women, transplanted patients suffered significantly less from 'Hypoactive Sexual Desire Disorder' than the other three groups; the prevalence of other sexual dysfunctions did not differ between the groups. Although 'Male Erectile Disorder' and Female Sexual Arousal Disorder' had a relatively high prevalence there were no differences in the four groups of patients in genital responses during psychophysiological testing. Genital responses during psychophysiological assessment had no relationship to the duration of renal replacement treatment, biochemical/endocrine variables, or the presence/absence of neuropathy. Conclusion: The prevalence of sexual dysfunction was high. Sexual dysfunction in men on haemodialysis or peritoneal dialysis was not so much due to erectile failure but largely to loss of sexual interest, subjectively ascribed to fatigue. The latter was also found in women on haemodialysis or peritoneal dialysis.     

Appetite disorders in uremia.

Patients with chronic kidney disease frequently experience loss of appetite (anorexia), which increases in severity during the progression of the disease and may lead to protein-energy wasting, morbidity, and mortality. Anorexia represents a multiple, complex, and multifactorial disorder that may have its origin in renal failure (contemplating not only retention of uremic toxins but also peptides and cytokines) but that later on also involves metabolic abnormalities not yet corrected by dialysis therapy. This paper reviews current knowledge about the clinical signs of uremic anorexia as well as mechanisms involved. Based on megestrol acetate interventions and the recent observation that sex may modulate uremic appetite behavior, the potential role of sex hormones in treating chronic kidney disease anorexia needs to be further explored.     

Effect of aluminum on porphyrin metabolism in hemodialyzed patients

In patients with renal failure and on chronic hemodialysis, serum aluminum, serum delta-aminolevulinic acid, serum porphobilinogen and erythrocyte zinc protoporphyrin (ZPP) are significantly elevated, whereas erythrocyte delta-aminolevulinic acid dehydratase activity (ALAD, values in percent) is significantly reduced. The last two parameters (ZPP and ALAD) are statistically related to serum aluminum concentration (Al-S), but only the correlation between Al-S and ALAD remains statistically significant after standardization for the degree of renal insufficiency (expressed in terms of urea level). This study does not support the hypothesis that the retention of aluminum is responsible for the increase of ZPP in uremic patients on dialysis. The disturbances of porphyrin metabolism found in patients with renal failure and on chronic dialysis are not similar to those observed in porphyria cutanea tarda.     

Successful pregnancy in a patient with polycystic kidney disease and advanced renal failure without prophylactic dialysis

Pregnancies in women suffering from advanced chronic renal failure are frequently associated with deterioration of maternal renal function, premature births and low birth weights. Prophylactic dialysis is sometimes instituted since this intervention ameliorates the uremic milieu and improves maternal status and fetal uterine environment. This report describes a successful pregnancy and delivery in a hypertensive woman with advanced chronic renal failure due to polycystic kidney disease without accelerating the natural deterioration of renal function and without instituting prophylactic dialysis. The infant was delivered at full term with a normal birth weight. Thirty months after delivery, growth and development of the child were normal and the rate of deterioration of maternal renal function, assessed by 1/creatinine, was unaffected by pregnancy. Conservative management and effective control of blood pressure may be sufficient to achieve successful pregnancy outcome when women with advanced chronic renal failure become pregnant.