Reproductive Endocrinology in Chronic Kidney Disease Patients: New Approaches to Old Challenges

Sexual dysfunction is a common yet underreported problem among chronic kidney disease (CKD) patients. This article will review sexual dysfunction in both genders, pregnancy outcomes, and best practices for successful full‐term pregnancy in patients with CKD, including those with dialysis dependence and kidney transplants.     

Therapy Insight: sexual dysfunction in patients with chronic kidney disease

Sexual dysfunction is common in people with chronic kidney disease (CKD). Sexual dysfunction in these patients should be thought of as a multifactorial problem that is affected by a variety of physiological and psychological factors, as well as by comorbid conditions. Assessment of sexual difficulties in patients with CKD, therefore, involves a careful investigation of a variety of domains. The development of treatment strategies presents challenges as it is often difficult to determine the primary factor(s) responsible for the sexual dysfunction. It is important to think of the treatment in the overall context of the management of various medical problems presented by patients with CKD. It must be remembered that the design of therapeutic approaches for each patient is dependent on the systematic evaluation of the functional and psychosocial problems presented, and assessment of the cause(s) of sexual dysfunction.     

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.     

Management of heart failure and coronary artery disease in patients with chronic kidney disease

Cardiovascular disease (CVD) is a major contributor to the mortality and morbidity of patients who suffer from chronic kidney disease (CKD). Heart failure and ischemic heart disease (IHD) are both highly prevalent in this population. The diagnosis of myocardial dysfunction is usually based on echocardiography. As in the general population, systolic dysfunction is treated with a combination of diuretics, renin-angiotensin system blockade, and beta-receptor antagonists. Diastolic dysfunction is best managed by eliminating the cause. Non-invasive tests for coronary artery disease (CAD) may be less reliable in patients with renal disease compared with nonuremic patients. Medical therapy of IHD in this population is generally similar to that for other patient groups, but surgical revascularization appears to carry a higher risk of complications with poorer clinical outcomes. The choice of revascularization procedure (coronary artery bypass grafting versus percutaneous transluminal angioplasty) should be based on the specific coronary anatomy of a given patient as well as a consideration of other comorbid factors.     

How to manage HIV-infected patients with chronic kidney disease in the HAART era

As human immunodeficiency virus (HIV)-infected patients now live longer while receiving highly active antiretroviral therapy (HAART), chronic kidney disease (CKD) has emerged as a significant cause of morbidity and mortality among urban HIV population. Risk factors associated with CKD in such HIV-infected population include aging, hypertension, diabetes mellitus, co-infection with hepatitis C virus, low CD4 cell count, and high HIV viral load. Clinical experience has shown that HIV-infected individuals often have one or more concurrent risk factors for CKD. The cumulative effect of multiple risk factors on the development of CKD should be noted in this population. Glomerular disease directly related to HIV infection, so-called HIV-associated nephropathy, remains an important cause of CKD among limited HIV population of African descent. The impact of exposure to nephrotoxic antiretroviral agents on the development of kidney disease is both an old and a new concern. In particular, the association of tenofovir with kidney disease has been an area of great interest. The findings regarding tenofovir's adverse effect on long-term kidney function vary among studies. Early identification and treatment of kidney disease is imperative for reducing the burden of patients requiring dialysis in HIV-infected populations. Periodic monitoring of urinary albumin excretion, tubular parameters such as low-molecular-weight proteinuria, and the estimated glomerular filtration rate may be useful for early diagnosis of patients at risk for incident CKD. This review focuses on recent developments in epidemiology, risk factors, identification, estimation, and management of CKD in HIV-infected population in the HAART era.     

Review article: Managing sleep apnoea in kidney diseases

A higher prevalence of sleep apnoea (SA) has been observed in the chronic kidney disease (CKD) population compared with estimates in the general population. Increased rates of SA have been described in patients with various renal‐related diagnoses including dialysis, renal transplant, early‐stage CKD and proteinuria. The mechanism or underlying aetiology for this association is different for each type of kidney disease. The extracellular fluid volume and metabolic derangements that characterize the uremic state likely contributes to SA in the dialysis population. SA causing direct renal insults from haemodynamic changes, ischaemic stress, or an intermediary condition such as hypertension, can lead to early CKD and proteinuria. While renal transplantation has cured SA in some patients, the post‐transplant state is itself a risk factor for SA. The high prevalence of SA in kidney disease and the associated clinical implications warrant vigilance in diagnosis and treatment of SA in the CKD patient. This review focuses on the prevalence of SA in patients with CKD including dialysis and transplant patients, and those with early‐stage CKD and proteinuria. SA may vary in form and aetiology depending on type or stage of CKD. Based on these associations, we discuss our rationale for recommendations on screening and management of SA specific to the CKD population.     

Elevated relative mortality risk with mild-to-moderate chronic kidney disease decreases with age.

BACKGROUND: Renal disease is common in the general population and whilst few people progress to end-stage renal failure, mortality is increased. The aim of this study was to examine all-cause mortality risk in relation to chronic kidney disease (CKD) stages defined by estimated glomerular filtration rate (eGFR). METHODS: Data were extracted from a computerized central laboratory system for a defined geographical area over a 3-year study period. The eGFR was calculated using the four-variable Modification of Diet in Renal Disease (MDRD) formula and aligned to the MDRD laboratory. Average annual mortality and relative risk (RR) of all-cause mortality was determined and compared for defined age and CKD bands. RESULTS: 106 366 participants (55.5% female; 85% White, 13% South Asian, 2% Black and others) were eligible and studied, representing 49% of the Coventry adult population. 12 540 (12%) of the sample had some evidence of decreased kidney function, with an eGFR <60 ml/min/1.73 m2. 7611 (7%) participants died and there were significantly elevated risks of mortality with increasing renal dysfunction; RR = 4.0, 8.3, 16.2 and 43.5 for eGFR 45-59, 30-44, 15-29 and <15 ml/min/1.73 m2, respectively. Within age bands, RRs were statistically significantly raised with CKD progression and within CKD stage, RR of death decreased as age increased. CONCLUSIONS: CKD prevalence increased with age and absolute and RR of mortality increased with progression of CKD. People aged over 75 years, with mild-to-moderate renal disease, representing 41% of this age group, have no increased RR of mortality. Further study of CKD and mortality, particularly progression over time and with respect to age is needed.     

Bariatric surgery for morbid obesity: risks and benefits in chronic kidney disease patients

Obesity is one of the most preventable causes of morbidity and mortality of the 21st century. Chronic kidney disease (CKD) has been a largely overlooked consequence of obesity; however, accumulating evidence elucidates the association. Obesity is at the core, promoting a cascade of secondary pathologies including diabetes, dyslipidemia, inflammation, hypertension, and the metabolic syndrome; these comorbidities constitute great risk for CKD. With the diagnosis of CKD, there is an increased threat of cardiovascular disease and the attendant increase in morbidity and mortality rates. Substantial weight loss in the obese population can be effectively achieved and maintained through bariatric surgery, which confers major health benefits by producing resolution or improvement of obesity-related comorbidities. This surgical procedure presents an early hazard of acute on chronic kidney failure, which is offset by a potential improvement in the risk of CKD progression with anticipated improvement in hypertension, diabetes, and CKD risk factors. Future research is needed to describe the clinical course and risks and benefits of bariatric surgery in the CKD population.     

Outcomes associated with hypogonadism in women with chronic kidney disease

The successful use of renal replacement therapy has resulted in longer survival and a population of older patients with chronic kidney disease (CKD) that includes patients with other significant preexisting illnesses. In this review, we analyze the short-term and long-term outcomes associated to persisting hypogonadism in CKD patients. The short-term manifestations, commonly observed in normal postmenopausal women, are either a rare complaint of women with CKD or are frequently attributed to the uremic state. These symptoms include hot flashes, sleep disturbances and depression, sexual dysfunction, vaginal dryness and atrophy, urinary incontinence, and skin aging and wrinkling. The long-term outcomes of hypogonadism have potentially devastating effects on bone, cardiovascular system, and cognitive function, which could significantly alter the quality of life and survival of women with stage 5 CKD (CKD-5). Postmenopausal osteoporosis has been recognized as an important entity associated with renal osteodystrophy, and efforts have begun to tackle the reduced bone-mineral density (BMD) and increased fracture rate seen in this population. Similarly, cardiovascular disease represents the major cause of death in the CKD-5 population, with a 10 to 20 times greater mortality than in the general population. The accumulating evidence for a possible link between osteoporosis and atherosclerosis is discussed, as well as new directions in the understanding of postmenopausal osteoporosis in the context of renal bone disease, under the guidance of the Global Bone and Mineral Initiative endorsed by the Kidney Disease: Improving Global Outcomes initiative. Nephrologists must face gynecological issues with their women patients and design interdisciplinary clinical studies that include strategies that utilize well-tested and newer drug regimens in the management of osteoporosis, cardiovascular disease, and other postmenopausal manifestations in CKD-5 patients.     

Diagnosis and management of kidney involvement in Fabry disease

Interest in the diagnosis and treatment of Fabry disease has been greatly stimulated by the availability of Food and Drug Administration-approved, effective enzyme replacement therapy. This review will update the progress in this area since enzyme replacement therapy has become available. Fabry disease is often associated with proteinuric chronic kidney disease (CKD), and it appears that the treatment paradigms that have proven to be so effective in diabetes mellitus and other forms of proteinuric kidney disease are also effective in conjunction with enzyme replacement therapy for treating the kidney manifestations of Fabry disease. As such, Fabry disease represents an interesting example of progressive proteinuric kidney disease in which the usual blood pressure is lower than in other forms of CKD. This makes the use of effective antiproteinuric therapy challenging, especially considering the autonomic dysfunction that appears to be part of the disease. Comprehensive therapy for Fabry disease includes enzyme replacement therapy and all of the adjunctive therapies that are currently used to treat all forms of proteinuric CKD. It is anticipated that this approach will preserve kidney function and also benefit the cardiac and cerebrovascular systems in patients with Fabry disease.     

Cardiovascular disease in children with chronic kidney disease

In children with end-stage renal disease (ESRD), cardiovascular disease (CVD) mortality has not changed for the past 3 decades. Cardiac disease remains the second most common cause of death. Recent data demonstrate a high incidence and prevalence of traditional and chronic kidney disease (CKD)-related CVD risk factors in children. Early markers of cardiomyopathy, such as left ventricular hypertrophy (LVH) and left ventricular dysfunction (LV dysfunction), and early markers of atherosclerosis, such as increased carotid artery intima-media thickness (IMT) and carotid arterial wall stiffness, are frequently found in this patient population. Early identification of modifiable risk factors and treatment of asymptomatic CVD might lead to decrease of cardiovascular morbidity and mortality in young adults who developed CKD during childhood.     

Under-recognition of chronic kidney disease in elderly outpatients

The elderly are the fastest growing segment of the United States population. Age is a key predictor of chronic kidney disease (CKD). A major obstacle in the recognition of CKD in the elderly is the reliance on serum creatinine measurements as an estimation of glomerular filtration rate (GFR). We hypothesized that early stages of CKD would not be recognized by primary care clinicians providing care to elderly men in a highly structured setting. This study was a retrospective study of outpatients 70 years and older seen in VISN 9 at Veterans Administration Medical Centers from 1/1/2001 thru 12/31/2003. GFR was estimated using the MDRD formula. We abstracted demographic and medical data from the electronic medical record. The population consisted primarily of elderly white male (7,289 men; 91% Caucasian). In CKD Stage 2, 3, and 4, men had a diagnosis code reflecting kidney disease in 1.2%, 20%, and 74.6% of the charts. Despite declining kidney function, nephrology consults were requested in fewer than 5%. In summary, we have shown in a large outpatient population of elderly men that CKD is frequently under-recognized, but most pronounced in CKD Stages 2 and 3. Stages 2 and 3 may be the stages in which the most beneficial effects of interventions can be obtained.     

The epidemics of cardiovascular disease in elderly patients with chronic kidney disease – Two facets of the same problem

There is increasing evidence that even mild renal dysfunction is a novel potent cardiovascular risk factor in the general elderly population. With more severe renal impairment, cardiovascular risk increases proportionately. This issue deserves attention, as chronic kidney disease (CKD) is predominantly a disease of the elderly, and the mean age of end-stage renal disease patients entering dialysis is growing constantly. In the dialysis population, when clinically significant cardiovascular disease (CVD) (particularly congestive heart failure) is present, survival is worse. Thus, every effort should be made to identify and treat cardiovascular risk factor in the early stages of CKD. However, elderly renal patients receive less proper cardiovascular therapy compared to non-renal subjects of the same age. This review deals briefly with the most significant data published in the last decade on CVD in elderly with CKD.     

Vitamin D supplements in chronic kidney disease

Abstract

Chronic kidney disease (CKD) is a significant public health problem and Vitamin D deficiency is prevalent in CKD and might be associated with calcium and phosphate metabolism, cardiovascular disease, infections as well as the progress of kidney dysfunction. Emerging evidence implies that Vitamin D supplements may be of benefit to CKD. Based on existing laboratory and clinical evidence, this review intends to discuss the effectiveness of Vitamin D supplements and controversy in clinical practice. The effect of Vitamin D in CKD patients is summarized in detail from CKD–mineral bone disease, the progression of renal function, cardiovascular events and immune system. Considerable disputes exist for the Vitamin D supplements in CKD, and a growing amount of experimental evidence and some clinical evidence are now gathering from in vitro, animal and epidemiological studies.     

代谢综合征及其代谢因子与慢性肾损害相关性的临床研究

目的 探讨代谢综合征及其各组成因子与包括轻度肾损害在内的慢性肾损害的相关性&#65377; 方法 收集我院2003年1月至2003年12月心内科&#65380; 肾内科和内分泌科符合入选标准的住院患者966例进行回顾性分析&#65377;按有&#65380; 无慢性肾脏病(CKD)或轻度肾损害分组, 比较代谢综合征各因素与慢性肾脏损害的关系&#65377; 统计学处理包括单变量t检验&#65380;卡方检验和Logistic多因素回归分析&#65377;结果 (1)CKD组的年龄&#65380; 身体质量指数(BMI)&#65380; 总胆固醇(TC)&#65380; 甘油三酯(TG)&#65380; 高血糖&#65380; 高血压和尿酸水平, 冠心病&#65380; 脑卒中的患病率均高于无CKD组, 而高密度脂蛋白(HDL)水平明显低于无CKD组患者; (2)随着代谢综合征因子数量的增多, CKD发病率上升; (3)代谢综合征中各因子并存较各因子单独存在的CKD的危险性增加, 与高血糖并存的频率最高; (4)BMI增加也是CKD的重要危险因素; (5)高血糖患者发生轻度肾损害的风险最大(优势比OR=7.698)&#65377;结论 代谢综合征及其各组成因子是包括轻度肾损害在内的CKD的重要危险因素&#65377;随着代谢综合征因子的增多, CKD的危险也随之增加&#65377; 除了高血糖和高血压, BMI增加也是其中重要的影响因子&#65377;     

Cardiovascular risk in stage 4 and 5 nephropathy

Severity of heart disease of almost all types, as well as mortality risk associated with heart disease, increases in step with severity of kidney disease, although not necessarily in a linear fashion. Heart failure is more common and just as lethal as ischemic heart disease in patients with severe chronic kidney disease (CKD). The incidence of nonfatal heart disease in dialysis and transplant populations has now been described in detail. Although standard risk factors for heart disease that are more common among patients with CKD than in the general population do not adequately explain the greatly increased risk of heart disease in patients with severe CKD, neither do as yet identified "nontraditional" risk factors. However, in addition to the factors not common in the general population, such as anemia, hyperphosphatemia, and markers of systemic inflammation, patients with CKD in the modern era may also exhibit excessive thrombotic tendencies. Screening for heart disease in this population relies mainly on dobutamine stress echocardiography or nuclear scintigraphy. The role of electron beam CT (EBCT) scanning is currently controversial. The indications for coronary angiography are the same for patients with CKD as for the general population, but patients with CKD are at greatly increased risk for contrast-associated nephropathy, the least controversial preventive therapy, which consists of isotonic saline and N-acetylcysteine. Finally, patients with CKD do not currently receive adequate medical therapy for prevention and treatment of heart disease.     

High-density lipoprotein in uremic patients: metabolism,impairment, and therapy

Several studies have shown that HDL has altered antioxidant and anti-inflammatory effects in chronic uremia, either by the reduction in its antioxidant enzymes or by the impairment of their activity. Systemic oxidative stress, which is highly prevalent in chronic kidney disease (CKD) patients, has been shown to decrease antioxidant and anti-inflammatory effects of HDL and even transform it into a pro-oxidant and pro-inflammatory agent. For this reason, we believe that the propensity for accelerated cardiovascular disease in CKD is facilitated by a few key features of this disease, namely, oxidative stress, inflammation, hypertension, and disorders of lipid metabolism. In a nutshell, oxidative stress and inflammation enhance atherosclerosis leading to increased cardiovascular mortality and morbidity in this population. In this detailed review, we highlight the current knowledge on HDL dysfunction and impairment in chronic kidney disease as well as the available therapy.     

Clinical assessment and management of dyslipidemia in patients with chronic kidney disease

Chronic kidney disease (CKD) is a common cause of cardiovascular disease (CVD). Several factors contribute to the onset and progression of atherosclerosis and CVD in CKD patients. Most of the cases of coronary heart disease in the general population can be explained by traditional risk factors, whereas non-traditional risk factors, including oxidative stress, anemia, inflammation, malnutrition, vascular calcification, and endothelial dysfunction, have been proposed to play a central role in the pathogenesis of CVD in CKD patients. However, the precise mechanism of CVD initiation in CKD patients remains unclear. Lipid-lowering therapies may decrease proteinuria, and increase or maintain renal function. Because the serum levels of triglyceride-rich lipoproteins are increased in CKD patients, particularly in advanced stages, the serum non-HDL cholesterol level may be a better biomarker of dyslipidemia than the serum LDL cholesterol level in this population. A meta-analysis showed that statin therapy was associated with decreased albuminuria in comparison with a placebo. Moreover, lipid-lowering therapy with statins is effective in reducing the risk of CVD in the early stages of CKD, whereas the benefit of statins in patients with end-stage renal disease may be limited.     

New insights on inflammation in chronic kidney disease-genetic and non-genetic factors

Cardiovascular disease (CVD) remains the major cause of morbidity and mortality in chronic kidney disease (CKD). As traditional risk factors cannot alone explain the unacceptable high prevalence and incidence of CVD in this population, inflammation (which is interrelated to insulin resistance, oxidative stress, wasting and endothelial dysfunction) has been suggested to be a significant contributor. Indeed, several different inflammatory biomarkers, such as high sensitivity C-reactive protein (CRP) has been shown to independently predict mortality in CKD patients. The causes of the highly prevalent state of inflammation in CKD are multiple and include factors such as volume overload, co-morbidity, intercurrent clinical events, the dialysis procedure per se as well as genetic factors. Indeed, multiple cytokine DNA polymorphisms may affect the inflammatory state, the clinical phenotype as well as outcome in this patient population.     

The interest of statins in nephrology

STATINS IN THE CASE OF CHRONIC RENAL DISEASE: Data of several large clinical trials in the general population demonstrated that hydroxymethyl glutaryl coenzyme A reductase inhibitors (statins) are effective in cardiovascular disease prevention with a relatively safe profile. Patients with chronic kidney disease (CKD) are at high risk for developing premature cardiovascular disease, so the benefits of statin therapy might be expected to be substantial in this population. Adjusted dose of statins to calcinurine inhibitors and renal function seem to exhibit a favorable risk/benefit ratio in CKD patients. STUDY RESULTS: Statin use is CKD patients has been associated with a certain efficacy of cardiovascular disease prevention in several uncontrolled trials, and one randomized trial in renal transplant recipients. Several other large-scale randomized trials in CKD patients [4D (atorvastatin), AURORA (rosuvastatin) and SHARP (simvastatin/ezetimib) are currently underway. The results of these trials will permit evidence-based medicinal arguments justifying life-long clinical use of statins for cardiovascular prevention in CKD patients with progressive renal dysfunction, but data are inconclusive. OTHER POSSIBLE EFFECTS: Clinically relevant plethoric effects associated with statin therapy in CKD patients might be restricted to the decrease of inflammation and oxidative stress.