Anemia in children with chronic kidney disease

Anemia is a common comorbidity in children with chronic kidney disease (CKD). This condition is associated with multiple adverse clinical consequences and its management is a core component of nephrology care. Increased morbidity and mortality, increased risk of cardiovascular disease and decreased quality of life have been associated with anemia of CKD in children. Although numerous complex factors interact in the development of this anemia, erythropoietin deficiency and iron dysregulation (including iron deficiency and iron-restricted erythropoiesis) are the primary causes. In addition to iron supplementation, erythropoietin-stimulating agents (ESAs) can effectively treat this anemia, but there are important differences in ESA dose requirements between children and adults. Also, hyporesponsiveness to ESA therapy is a common problem in children with CKD. Although escalating ESA doses to target increased hemoglobin values in adults has been associated with adverse outcomes, no studies have demonstrated this association in children. The question of appropriate target hemoglobin levels in children, and the approach by which to achieve these levels, remains under debate. Randomized, controlled studies are needed to evaluate whether normalization of hemoglobin concentrations is beneficial to children, and whether this practice is associated with increased risks.     

Hypertension management in patients with chronic kidney disease

Hypertension is one of the major risk factors for the development and progression of chronic kidney disease. The loss of renal function leads to impaired renal autoregulation and renders the kidney vulnerable to the damaging effects of uncontrolled hypertension. Mounting evidence indicates that angiotensin-converting enzyme inhibitors and angiotensin receptor blockers slow the progression of chronic kidney disease through effects beyond lowering blood pressure. Studies are needed to determine whether high doses of the single agent or combination therapy is most effective in providing renal protection. Urinary protein excretion is a useful tool for monitoring and titrating therapy to maximize renal protection. Changes in the serum creatinine concentration and hyperkalemia are complications of antihypertensive therapy in patients with chronic kidney disease that can be successfully managed to allow continued use of renin-angiotensin blockade.     

Anemia and chronic kidney disease are associated with poor outcomes in heart failure patients

Background

Chronic kidney disease (CKD) has been linked to higher heart failure (HF) risk. Anemia is a common consequence of CKD, and recent evidence suggests that anemia is a risk factor for HF. The purpose of this study was to examine among patients with HF, the association between CKD, anemia and inhospital mortality and early readmission.

Methods

We performed a retrospective cohort study in two Swiss university hospitals. Subjects were selected based the presence of ICD-10 HF codes in 1999. We recorded demographic characteristics and risk factors for HF. CKD was defined as a serum creatinine ≥ 124 956;mol/L for women and ≥ 133 μmol/L for men. The main outcome measures were inhospital mortality and thirty-day readmissions.

Results

Among 955 eligible patients hospitalized with heart failure, 23.0% had CKD. Twenty percent and 6.1% of individuals with and without CKD, respectively, died at the hospital (p < 0.0001). Overall, after adjustment for other patient factors, creatinine and hemoglobin were associated with an increased risk of death at the hospital, and hemoglobin was related to early readmission.

Conclusion

Both CKD and anemia are frequent among older patients with heart failure and are predictors of adverse outcomes, independent of other known risk factors for heart failure.     

Screening and management of patients with early chronic kidney disease

Diabetic nephropathy has become the most prevalent cause of end-stage renal disease (ESRD) in many countries. ESRD patients with diabetes have a particularly poor prognosis compared with patients without diabetes. The course of diabetic nephropathy can be modified with early management of the condition and it is important that diabetes patients are screened regularly for early signs of kidney damage. Blood pressure control and use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers have been shown to slow the progression of chronic kidney disease. Patients with diabetes are at considerable risk of cardiovascular complications, and modifiable cardiovascular risk factors, such as anaemia and dyslipidaemia, should be treated at an early stage. Correction of anaemia with recombinant human erythropoietin is associated with improvements in quality of life, functional status, and cardiovascular morbidity and mortality, and may slow the progression of renal disease. Abnormalities in calcium and phosphate metabolism and acidosis may also occur in patients with diabetes and nephropathy and these should be monitored regularly. It is important that patients with kidney disease are detected promptly to allow intervention to slow renal disease progression and to treat modifiable cardiovascular risk factors. Improved collaboration between diabetologists and nephrologists will also ensure that patients receive optimal care.     

Anemia in chronic kidney disease and congestive heart failure

Anemia is seen in chronic kidney insufficiency (CKI), dialysis patients, congestive heart failure (CHF), and renal transplantation. Anemia can lead to progressive cardiac damage as well as progressive renal damage. It is not generally appreciated that CHF itself may be a very common contributor to both the production of anemia as well as to the progression of the renal failure. Correction of the anemia with erythropoietin and, as necessary, intravenous iron, may prevent the deterioration of both the heart and the kidneys. We suggest that there is a triangular relationship, a vicious circle, between CHF, CKI and anemia where each of these three can both cause and be caused by the other. We call this syndrome the cardio-renal anemia (CRA) syndrome. All physicians, especially cardiologists and internists who treat CKI and CHF, should be made aware of the dangers of anemia in CKI and CHF and should work with nephrologists to correct it.     

Anemia treatment in chronic kidney disease: shifting uncertainty

Epidemiologic observations showing associations between higher levels of some biologic markers such as blood pressure and serum cholesterol with heightened risk of death and non-fatal cardiovascular events have provided important data to develop hypotheses regarding pharmacologic therapies to modify these markers to improve prognosis. Randomized controlled trials have shown that strategies to reduce blood pressure with a variety of antihypertensive agents and LDL cholesterol with statins do, indeed, result in important improvements in clinical outcomes. However, there are several instances where a hypothesis based on strong observational data has been rejected based on surprising counterintuitive evidence generated from randomized controlled clinical trials. Use of inotropic therapies for patients with reduced left ventricular ejection fraction heart failure, administration of class I antiarrhythmic agents to suppress ventricular arrhythmias in high-risk patients, and use of hormone replacement therapy for postmenopausal women have each shown that therapies presumed to be of benefit may actually be producing unfavorable clinical results. Use of erythropoietic stimulating agents (ESA) in chronic kidney disease patients with anemia is similarly based on strong observational data indicating that the degree of anemia is independently associated with higher risk for cardiovascular morbidity and mortality. In non-dialysis patients with mild to moderate anemia, current clinical outcome studies have only addressed arbitrary hemoglobin targets for ESA therapy and have shown that targeting the higher hemoglobin levels was not associated with the benefit and may even result in harm. This review will outline the importance of having a placebo-controlled trial in this patient population to better assess the risk benefit profile of this therapy.     

Hepatitis C in patients with chronic kidney disease: Course and management

The prevalence of chronic hepatitis C (CHC) is significantly higher in patients with end-stage renal disease undergoing hemodialysis than in the general population. CHC adversely affects survival in patients on hemodialysis and those who have undergone renal transplantation (RT); routine screening for hepatitis C virus infection is recommended for both groups. Treatment of CHC in post-RT patients and those undergoing hemodialysis remains challenging. Data on nonpegylated interferon alfa and pegylated interferon alfa monotherapies remain limited, and treatment-induced adverse effects are common. Ribavirin is contraindicated in these patients, but a combination of low-dose ribavirin with interferon is being assessed in clinical trials. Further studies are needed to clarify the pathogenesis and natural history of CHC in hemodialysis patients and post-RT patients and to develop effective treatment for hepatitis C virus infection in these patients.     

Hypertension in patients with chronic kidney disease

Hypertension is very common in patients with chronic kidney disease (CKD); it causes early loss of kidney function and accelerated cardiovascular morbidity and mortality. African American patients with hypertension and genetic disposition are at an even higher risk for renal disease and ultimately renal failure. Hypertensive patients with CKD should aim for stringent blood pressure (BP) control (target < 130/80 mm Hg) requiring more than one drug with renin-angiotensin-aldosterone system blockade as a component of therapy targeting both hyper tension and proteinuria. Management of hypertension in the dialysis population should focus on ambulatory measurements of BP and the use of longer-acting antihypertensive drugs, with their dosage and timing adjusted according to their dialytic clearances. Hypertension is also common among kidney transplant recipients and contributes to graft loss and premature death. The target BP in transplant recipients is the same as in the CKD population, with no preference for one drug group over another. Unless contraindicated, angiotensin-converting enzyme inhibitors remain the drugs of choice for hypertension in patients with autosomal-dominant polycystic kidney disease, in whom diastolic cardiac dysfunction is a prominent feature.     

Infections in patients with chronic kidney disease

There has been a notable lack of research activity regarding major infections in patients with advanced chronic kidney disease. To an outsider, this might seem unexpected, because uremia has long been considered a state of immune hyporesponsiveness and rates of major bacterial infection, like septicemia and pneumonia, are known to be orders of magnitude more likely in dialysis populations than in the general population. This article reviews recent literature on the topic, focusing predominantly on the clinical epidemiology of major bacterial infections in dialysis patients, the links between bacterial infections and cardiovascular disease, and randomized trials of interventions designed to prevent these infections.     

Motivational interviewing to engage patients in chronic kidney disease management

Patients with chronic kidney disease (CKD) must manage numerous medical treatments and lifestyle changes that strain their treatment adherence. An important strategy to improve adherence is to activate the patients' motivation to manage their CKD. This article describes an approach for enhancing patients' motivation for change, called motivational interviewing (MI), a treatment that is increasingly being used in health care settings to counsel patients with chronic diseases. Its basic principles, techniques, empirical support, published applications for improving CKD patients' self-management, and how to learn MI are presented. Research is needed to determine the efficacy and mechanisms of MI for CKD treatment as well as the development of innovative ways to deliver it to patients and train busy health care practitioners in the approach.     

Hypertension management: Special considerations in chronic kidney disease patients

It has been estimated that approximately 11% of the US adult population has chronic kidney disease (CKD), and it has been demonstrated that the prevalence of hypertension rises significantly as renal function declines. Even mild CKD significantly increases mortality risk, and cardiovascular disease remains the main cause of death among these patients. Although CKD patients have generally been excluded from trials testing the effect of lowering blood pressure on cardiovascular outcomes, guidelines suggest lowering blood pressure in hopes of reducing cardiovascular mortality and slowing the progression of renal disease. The preferred antihypertensive agents among these patients are drugs that block the renin-angiotensin system. In most hypertensive CKD patients, however, multiple agents are necessary to reach blood pressure targets. In general, diuretics and calcium channel blockers are added subsequently as adjunctive therapy. Hopefully, with increased recognition of the unique aspects of treating hypertension in this population, end-stage renal disease and cardiovascular morbidity and mortality will be delayed or avoided in the millions of patients with CKD.     

慢性肾脏病患者发生心血管事件危险因素的研究

目的 探讨慢性肾脏病(CKD)患者发生院内心血管事件的相关危险因素及对CKD患者院内死亡的影响.方法 选取2006年我院557例患有3期或3期以上CKD的住院患者,分析影响CKD患者发生心血管事件的相关危险因素以及心血管事件对CKD患者院内死亡的影响.结果 557例CKD患者中,男性332例,女性225例;住院期间心血管事件的发生率为29.3%(163/557).发生心血管事件的独立危险因素包括:年龄、既往冠心病史、空腹血糖水平和血红蛋白水平.发生心血管事件患者的住院死亡率显著高于未发生心血管事件患者的住院死亡率(9.82%比2.28%,X2=15.3,P＜0.001).结论 对于CKD患者,除年龄、既往冠心病史和空腹血糖这些传统的心血管事件危险因素外,贫血是其较为独特的独立危险因素.     

Hepatocellular carcinoma in patients with chronic kidney disease

AIM: To investigate outcomes of hepatocellular carcinomas (HCCs) in patients with chronic kidney disease (CKD). METHODS: Four hundred and forty patients referred between 2000 and 2002 for management of HCCs were categorized according to their CKD stage, i.e. , estimated glomerular filtration rate (eGFR) > 90 (stage 1), 60-90 (stage 2), 30-60 (stage 3), 15-30 (stage 4), and < 15 (stage 5) mL/min per 1.73 m 2 , respectively. Demographic, clinical and laboratory data were collected and mortality rates and cause of mortality were analyzed. The mortality data were examined with Kaplan-meier method and the significance was tested using a log-rank test. An initial univariate Cox regression analysis was performed to compare the frequency of possible risk factors associated with mortality. To control for possible confounding factors, a multivariate Cox regression analysis (stepwise backward approach) was performed to analyze those factors that were significant in univariate models (P < 0.05) and met the assumptions of a proportional hazard model. RESULTS: Most HCC patients with CKD were elderly, with mean age of diagnosis of 60.6 ± 11.9 years, and mostly male (74.8%). Hepatitis B, C and B and C coinfection virus were positive in 61.6%, 45.7% and 14.1% of the patients, respectively. It was found that patients with stages 4 and 5 CKD were not only older (P = 0.001), but also had higher hepatitis C virus carrier rate (P = 0.001), lower serum albumin level (P = 0.001), lower platelet count (P = 0.037), longer prothrombin time (P = 0.001) as well as higher proportions of advanced cirrhosis (P = 0.002) and HCCs (P = 0.001) than patients with stages 1 and 2 CKD. At the end of analysis, 162 (36.9%) patients had died. Kaplan-Meier analysis revealed that patients with stages 4 and 5 CKD suffered lower cumulative survival than stages 1 and 2 CKD (log-rank test, χ 2 = 11.764, P = 0.003). In a multivariate Cox-regression model, it was confirmed that CKD stage [odds ratio (OR) = 1.988, 95%CI: 1.012-3.906, P = 0.046)], liver     

Vascular calcification in patients with chronic kidney disease

Vascular calcification is very prevalent in patients with chronic kidney disease (CKD). In addition to having more traditional cardiovascular (CV) risk factors, CKD patients also have a number of non-traditional CV risk factors that may play a prominent role in the pathogenesis of vascular calcification. The transformation of vascular smooth muscle cells into osteoblast-like cells seems to be a key element in the pathogenesis of vascular calcification in the presence of calcium (Ca) and phosphorus (P) deposition due to abnormal bone metabolism and impaired renal excretion. Vascular calcification causes increased arterial stiffness, left ventricular hypertrophy, decreased coronary artery perfusion, myocardial ischemia, and increased cardiovascular morbidity and mortality. Although current treatment strategies focus on correcting abnormal Ca, P, parathyroid hormone, or vitamin D levels in CKD, a better understanding of the mechanisms of abnormal tissue calcification may lead to the development of new therapeutic agents that are capable of reducing vascular calcification and improving the CV outcome of CKD patients. This review article summarizes the following: (i) the pathophysiological mechanism responsible for vascular calcification; (ii) the methods of detecting vascular calcification in CKD patients; and (iii) the treatment of vascular calcification in CKD patients.     

Metformin therapy in patients with chronic kidney disease

Metformin therapy is limited in patients with chronic kidney disease (CKD) due to the potential risk of lactic acidosis. This open‐label observational study investigated metformin and lactate concentrations in patients with CKD (n = 22; creatinine clearances 15–40 ml/min) and in two dialysed patients. Patients were prescribed a range of metformin doses (250–2000 mg daily) and metformin concentrations were compared with data from healthy subjects (scaled to 1500 mg twice daily). A subset of patients (n = 7) was controlled on low doses of metformin (250 or 500 mg daily). No correlation between metformin and lactate concentrations was observed. Three patients had high lactate concentrations (>2.7 mmol/l) and two had high metformin concentrations (3–5 mg/l), but none had any symptoms of lactic acidosis. Reducing metformin dosage and monitoring metformin concentrations will allow the safe use of metformin in CKD, provided that renal function is stable.