Serum Phosphate and Mortality in Patients with Chronic Kidney Disease

Background and objectives: Higher phosphate is associated with mortality in dialysis patients but few prospective studies assess this in nondialysis patients managed in an outpatient nephrology clinic. This prospective longitudinal study examined whether phosphate level was associated with death in a referred population.Design, setting, participants & measurements: Patients (1203) of nondialysis chronic kidney disease (CKD) in the Chronic Renal Insufficiency Standards Implementation Study were assessed. Survival analyses were performed for quartiles of baseline phosphate relative to GFR, 12-month time-averaged phosphate, and baseline phosphate according to published phosphate targets.Results: Mean (SD) eGFR was 32 (15) ml/min per 1.73 m², age 64 (14) years, and phosphate 1.2 (0.30) mmol/L. Cox multivariate adjusted regression in CKD stages 3 to 4 patients showed an increased risk of all-cause and cardiovascular mortality in the highest quartile compared with that in the lowest quartile of phosphate. No association was found in CKD stage 5 patients. Patients who had values above recommended targets for phosphate control had increased risk of all-cause and cardiovascular death compared with patients below target. The highest quartile compared with the lowest quartile of 12-month time-averaged phosphate was associated with an increased risk of mortality.Conclusions: In CKD stages 3 to 4 patients, higher phosphate was associated with a stepwise increase in mortality. As phosphate levels below published targets (as opposed to within them) are associated with better survival, guidelines for phosphate in nondialysis CKD patients should be re-examined. Intervention trials are required to determine whether lowering phosphate will improve survival.Higher serum phosphate is associated with mortality in hemodialysis patients (1–3). There have been three studies in patients with chronic kidney disease (CKD), not on dialysis, evaluating the association of serum phosphate with mortality; two of these found a positive association (4–6). The relationship between serum phosphate and mortality in patients with CKD stages 3 to 5 (eGFR <60 ml/min per 1.73 m²) who are not on dialysis, and who are under regular nephrological review, has not previously been examined in a prospective systematic way. Survival data according to follow-up phosphate results are also lacking in CKD patients.The aims of this single-center study were to investigate whether an association of serum phosphate with all-cause and cardiovascular mortality could be shown prospectively in outpatients with advanced CKD (stage 5) not receiving dialysis and also in those with earlier (stages 3 and 4) CKD. The relationship of 12-month time-averaged phosphate and mortality and the influence upon survival of a serum phosphate within guideline targets was examined in this population.     

Elevated Serum Bone Morphogenetic Protein 4 in Patients with Chronic Kidney Disease and Coronary Artery Disease

Chronic kidney disease (CKD) is associated with increased coronary artery disease (CAD) and coronary artery calcification. We hypothesized that the osteogenic factor, bone morphogenetic protein-4 (sBMP-4), is elevated in subjects with both CKD and CAD. Serum was collected from 79 subjects undergoing diagnostic angiography and stratified according to CAD and CKD status. Subjects with both CAD and CKD had significantly elevated sBMP-4 compared to those with only one or no disease. sBMP-4 continued to be associated with the presence of both diseases after adjustment for other risk factors. To determine if sBMP-4 is associated with coronary artery calcification, we compared coronary artery calcium scores (CAC) to sBMP-4 in 22 subjects. A positive correlation between CAC and sBMP-4 was seen. In conclusion, sBMP-4 is elevated in patients with both CAD and CKD and positively correlates with CAC, suggesting a role for sBMP-4 in the increased CAD seen in CKD patients.     

Red Cell Distribution Width Is Independently Related to Endothelial Dysfunction in Patients With Chronic Kidney Disease

BackgroundRed cell distribution width (RDW) is a measure of erythrocyte size variability and has been shown as an independent predictor of mortality. The aim of this article was to evaluate the association of RDW with endothelial dysfunction in patients with chronic kidney disease (CKD).MethodsPatients with 1 to 5 stages of CKD were included in the study. Endothelial function was assessed with flow-mediated dilatation (FMD). Estimated glomerular filtration rate (eGFR) and carotid intima media thickness (CIMT) were determined. Clinicode-mographic characteristics, biochemical values, complete blood counts, ferritin, C-reactive protein (CRP) and cholesterol levels were recorded. Spearman's correlation was used to determine correlates of RDW. Multivariate linear regression model was used to assess independent associates of FMD.ResultsOverall, 367 patients with CKD 1 to 5 were included in the study. RDW showed a significant increase from stage 1 to stage 5 CKD. Median RDW was 13.5. Patients with RDW values higher than median had significantly lower hemoglobin, eGFR and FMD values and higher CIMT and CRP values compared with patients who had RDW values below median. RDW showed a significant positive correlation with the presence of diabetes mellitus, CIMT and CRP, whereas a significant negative correlation with eGFR, ferritin and FMD. Multivariate analysis showed independent predictors of FMD as RDW, presence of diabetes, hemoglobin, eGFR, CRP, and serum albumin.ConclusionsMultivariate regression model revealed RDW as a significant predictor of FMD independent of major confounding factors, such as diabetes, inflammation, anemia and kidney function in CKD.     

Resistance Training Increases Muscle Mitochondrial Biogenesis in Patients with Chronic Kidney Disease

Background and objectives: Muscle wasting, a common complication in chronic kidney disease (CKD), contributes to poor outcomes. Mitochondrial biogenesis is critical for the maintenance of skeletal muscle function and structural integrity. The present study—a secondary analysis from a published randomized controlled trial—examined the effect of resistance exercise training on skeletal muscle mitochondrial (mt)DNA copy number and determined its association with skeletal muscle phenotype (muscle mass and strength).Design, setting, participants, & measurements: Twenty-three patients with moderate-to-severe CKD were randomized to resistance training (n = 13) or an attention-control (n = 10) group for 12 weeks. After a run-in period of a low-protein diet that continued during the intervention, mtDNA copy number in the vastus lateralis muscle was estimated by quantitative real-time PCR at baseline and 12 weeks.Results: Participants mean age was 64 ± 10 (SD) years and median (interquartile range, IQR) GFR 27.5 (37.0) ml/min. There were no differences between groups at baseline. Median (IQR) mtDNA copy number was 13,713 (10,618). There was a significant increase in muscle mtDNA with exercise compared with controls (1306 [13306] versus −3747 [15467], P = 0.01). The change in muscle mtDNA copy number was positively correlated with previously reported changes in types I and II muscle fiber cross-sectional area.Conclusions: In this pilot study, resistance training was highly effective in enhancing mitochondrial content in patients with moderate-to-severe CKD. This finding suggests that the mitochondrial dysfunction observed with chronic disease could potentially be restored with this exercise modality and should be investigated further.Protein-energy wasting in chronic kidney disease (CKD) is defined as the loss of body protein mass and fuel reserves. Loss of body protein mass includes a reduction in muscle mass caused by wasting and/or sarcopenia (1). The wasting syndrome of CKD represents a significant public health concern given that approximately 19 million adults in the U.S. have CKD not requiring kidney replacement therapy and that the prevalence of kidney failure has increased by 51% during the last decade (2). Data from the Third National Health and Nutrition Examination Survey (NHANES III) suggest that sarcopenia is common in community-dwelling adults with CKD (3).Mitochondrial biogenesis is critical in maintaining the functional and structural integrity of postmitotic tissues like skeletal muscle (4). Mitochondria are the main source of cellular energy. However, mitochondrial dysfunction caused by a reduction in the number of those functionally intact or DNA deletions is believed to play a role in the loss of skeletal muscle mass and alterations in contractile function (sarcopenia) seen with aging (5). Similar to the sarcopenia of aging, the muscle wasting of CKD may be associated with mitochondrial dysfunction (5).Kidney failure is associated with mitochondrial abnormalities. Lim et al. (6,7) showed a high prevalence of somatic mitochondrial (mt)DNA mutations in skeletal muscle, specifically the 4977-bp deletion. The study by Rao et al. (8) in a cohort of prevalent maintenance hemodialysis patients from the Hemodialysis (HEMO) study found that mtDNA copy number, a measure of mitochondrial content, was significantly lower among older dialysis patients compared with older healthy subjects and was predictive of poor outcome and survival. In this study mtDNA⁴⁹⁷⁷ deletions were present in 31% of the dialysis patients and seemed to predict survival (8). These observations raise important questions about the role of mitochondrial content and function in the development of uremic complications and clinical outcomes, which need to be investigated further.Older adults may benefit through the exercise-induced adaptations in mitochondrial biogenesis and cellular antioxidant defense (9). Resistance exercise training is an exercise modality shown to reverse sarcopenia (10) and enhance mitochondrial function in aging muscle (11). We and others have examined the beneficial effects of resistance exercise on muscle mass and contractile function in CKD (12,13) and dialysis (14–18) patients. However, the effect of resistance exercise on mitochondrial biogenesis in CKD patients is not known. We undertook the present study to examine the effect of resistance exercise training on mtDNA copy number and to determine its association with skeletal muscle phenotype (i.e., measures of muscle mass and strength). This study represents a secondary analysis from a published randomized controlled trial that reported the anabolic effects of a 12-week high-intensity resistance exercise training program in patients with CKD stages 3 and 4 who were prescribed a low-protein diet (approximately 0.6 g/kg body wt per day) (12).     

Eicosapentaenoic Acid Combined with Optimal Statin Therapy Improves Endothelial Dysfunction in Patients with Coronary Artery Disease

Purpose

Eicosapentaenoic acid (EPA) has been reported to augment endothelial function and improve clinical outcomes in patients with coronary artery disease (CAD). The purpose of this study was to determine whether EPA could improve residual endothelial dysfunction despite adequate lipid-lowering with statin in CAD patients.

Methods

Eighty patients with established CAD, who had been on statin treatment and had serum low-density lipoprotein cholesterol (LDL-C) levels <100 mg/dl, were randomly assigned to receive either 1,800 mg of EPA daily plus statin (EPA group, n?=?40) or statin alone (Control group, n?=?40). Lipid profiles and flow-mediated dilation (FMD) were assessed just before and after more than 3 months of treatment in both groups. Only patients who had impaired FMD (<6 %) before randomization were enrolled.

Results

After treatment for 5.2?±?1.7 months, the EPA group showed a significant increase in the serum concentration of EPA and EPA to arachidonic acid (AA) (EPA/AA) ratio (62.5?±?38.1 to 159.8?±?53.8 μg/ml, 0.45?±?0.34 to 1.20?±?0.55, p?<?0.01 for both). In the EPA group, serum triglycerides significantly decreased (150.7?±?92.9 to 119.3?±?60.7 mg/dl, p?=?0.02), whereas no significant change was seen in the Control group. FMD, the primary study endpoint, showed a significant improvement in the EPA group (2.6?±?1.6 % to 3.2?±?1.6 %, p?=?0.02), whereas no significant change was observed in the Control group (2.7?±?1.6 % to 2.4?±?1.7 %, p?=?0.29).

Conclusions

EPA improved endothelial function and impaired FMD in patients with established CAD who were on optimal statin therapy.     

Serum Endocan Levels are Associated With Paraoxonase 1 Concentration in Patients With Chronic Kidney Disease

Endocan is a soluble proteoglycan released by the vascular endothelium. The increase of its serum levels is associated with inflammation, endothelial dysfunction and cardiovascular events in patients with chronic kidney disease (CKD). We studied the association of serum endocan with the lipid profile of 105 CKD patients with dyslipidemia, divided in two groups, non‐dialyzed (CKD, N = 57) and hemodialysis (HD, N = 48) in comparison with 30 normal controls (NC). We also analyzed endocan in relation with the concentration of two serum HDL‐linked members of the paraoxonase (PON) family, PON1 and PON3, which have been previously found to have antiatherogenic properties. The results showed that endocan levels were significantly higher in HD patients than in CKD patients (P < 0.001) and NC (P < 0.001). PON1 was significantly decreased only in HD patients compared to NC (P < 0.001), whereas PON3 was significantly increased in both patient groups (P < 0.001). Endocan levels were significantly and positively correlated with total cholesterol and LDL‐C in CKD and additionally were negatively correlated with HDL‐C in HD group. PON1 levels were significantly correlated with endocan in both groups, while no correlation was observed for PON3 in either group. Multiple regression analysis between endocan and the above lipid parameters in the total of patients revealed that endocan was independently associated only with PON1 (β = ?0.513, P = 0.002). It is concluded that the increase of serum endocan levels in patients with CKD may be associated with the decrease of PON1 concentration, irrespective of lipid alterations produced by atherosclerosis development.     

Hypertension Treatment for Patients with Advanced Chronic Kidney Disease

Chronic kidney disease is common and frequently complicated with hypertension. As a major modifiable risk factor for cardiovascular disease in this high risk population, treatment of hypertension in chronic kidney disease is of paramount importance. We review the epidemiology and pathogenesis of hypertension in chronic kidney disease and then update the latest study results for treatment including salt restriction, invasive endovascular procedures, and pharmacologic therapy. Recent trials draw into question the efficacy of renal artery stenting or renal denervation for hypertension in chronic kidney disease, as well as renin-angiotensin-aldosterone system blockade as first line therapy of hypertension in end stage renal disease. Positive trial results reemphasize salt restriction and challenge the prevailing prejudice against the use of thiazide-like diuretics in advanced chronic kidney disease. Last, clinical practice guidelines are trending away from recommending tight blood pressure control in chronic kidney disease.     

Optimal Treatment Strategies in Patients with Chronic Kidney Disease and Coronary Artery Disease

Background

Chronic kidney disease is an independent risk factor for coronary artery disease and is associated with an increase in adverse outcomes. However, the optimal treatment strategies for patients with chronic kidney disease and coronary artery disease are yet to be defined.

Methods

MEDLINE, EMBASE, and CENTRAL were searched for studies including at least 100 patients with chronic kidney disease (defined as estimated glomerular filtration rate ≤60 mL/min/1.73 m² or on dialysis) and coronary artery disease treated with medical therapy, percutaneous coronary intervention, or coronary artery bypass surgery and followed for at least 1 month and reporting outcomes. The outcome evaluated was all-cause mortality. Meta-analysis was performed to evaluate the outcomes with revascularization (percutaneous coronary intervention or coronary artery bypass surgery) when compared with medical therapy alone. In addition, outcomes with percutaneous coronary intervention vs coronary artery bypass surgery were evaluated.

Results

The search yielded 38 nonrandomized studies that enrolled 85,731 patients. Revascularization (percutaneous coronary intervention or coronary artery bypass surgery) was associated with lower long-term mortality (mean 4.0 years) when compared with medical therapy alone (relative risk [RR] 0.73; 95% confidence interval [CI], 0.62-0.87), driven by lower mortality with percutaneous coronary intervention vs medical therapy and coronary artery bypass surgery vs medical therapy. Coronary artery bypass surgery was associated with a higher upfront risk of death (RR 1.81; 95% CI, 1.47-2.24) but a lower long-term risk of death (RR 0.94; 95% CI, 0.89-0.98) when compared with percutaneous coronary intervention.

Conclusions

In chronic kidney disease patients with coronary artery disease, the current data from nonrandomized studies indicate lower mortality with revascularization, via either coronary artery bypass surgery or percutaneous coronary intervention, when compared with medical therapy. These associations should be tested in future randomized trials.     

Nonprogressive Kidney Dysfunction and Outcomes in Older Adults with Chronic Kidney Disease

OBJECTIVES: To determine whether a subgroup of patients with severe but nonprogressive renal dysfunction exist and to characterize this subgroup. DESIGN: Retrospective longitudinal monocentric cohort study. SETTING: Nephrology clinic for chronic kidney disease (CKD). PARTICIPANTS: Between January 1998 and December 2004, 177 consecutive patients aged 80 and older were referred for the first time to nephrology for CKD. MEASUREMENTS: The characteristics of patients with nonprogressive or progressive CKD (estimated glomerular filtration rate (eGFR) decline of < and ≥1 mL/min per 1.73 m² per year, respectively) were observed and analyzed, and their risk of dying or requiring dialysis was determined. After exclusion of subjects requiring immediate dialysis or followed up for less than 6 months, 138 patients remained eligible for analysis. RESULTS: In the study cohort (initial mean eGFR 31.8 mL/min per 1.73 m², median follow‐up 47 months), patients were more likely to require dialysis than to die; 36% of patients had nonprogressive CKD. This characteristic, predicted by low proteinuria, lack of hypertension, and low cardiovascular comorbidity, was the strongest predictor of global survival. In progressors, two independent covariates (eGFR <30 mL/min per 1.73 m² and hemoglobin ≤11 g/dL at inclusion) predicted the risk of requiring dialysis. CONCLUSION: More than one‐third of subjects aged 80 and older referred to a nephrology center had severe but nonprogressive kidney dysfunction. This subgroup had a lower mortality rate than those with progressive kidney dysfunction. Simple covariates (low proteinuria, lack of hypertension, low cardiovascular comorbidity) predicted nonprogression of CKD. Distant nephrology follow‐up of such patients may be sufficient.     

Serum Indoxyl Sulfate Is Associated with Vascular Disease and Mortality in Chronic Kidney Disease Patients

Background and objectives: As a major component of uremic syndrome, cardiovascular disease is largely responsible for the high mortality observed in chronic kidney disease (CKD). Preclinical studies have evidenced an association between serum levels of indoxyl sulfate (IS, a protein-bound uremic toxin) and vascular alterations. The aim of this study is to investigate the association between serum IS, vascular calcification, vascular stiffness, and mortality in a cohort of CKD patients.Design, setting, participants, & measurements: One-hundred and thirty-nine patients (mean ± SD age: 67 ± 12; 60% male) at different stages of CKD (8% at stage 2, 26.5% at stage 3, 26.5% at stage 4, 7% at stage 5, and 32% at stage 5D) were enrolled.Results: Baseline IS levels presented an inverse relationship with renal function and a direct relationship with aortic calcification and pulse wave velocity. During the follow-up period (605 ± 217 d), 25 patients died, mostly because of cardiovascular events (n = 18). In crude survival analyses, the highest IS tertile was a powerful predictor of overall and cardiovascular mortality (P = 0.001 and 0.012, respectively). The predictive power of IS for death was maintained after adjustment for age, gender, diabetes, albumin, hemoglobin, phosphate, and aortic calcification.Conclusions: The study presented here indicates that IS may have a significant role in the vascular disease and higher mortality observed in CKD patients.Cardiovascular disease (CVD) mortality is significantly higher in patients with chronic kidney disease (CKD) than in the general population (1,2). Vascular calcification and arterial stiffness are considered to be major contributors to this elevated mortality (3). The pathophysiology of CVD in a CKD setting is not completely understood; in addition to the traditional CVD risk factors, uremia-related elements play an important role. Although these elements may differ from one individual to another, the accumulation of toxic compounds is a common scenario in CKD. These compounds are classified according to their molecular weight and protein binding ability and several have been shown to exert adverse biologic effects and thus enhance the potential for cardiovascular damage (4). Interestingly, we recently observed that cardiac and aortic abnormalities were independently associated with the extent of endothelial dysfunction and renal failure in a mouse model of CKD (5), corroborating the hypothesis whereby the accumulation of uremic toxins is involved in the development of CKD-related cardiovascular abnormalities.Indoxyl sulfate (IS) is a protein-bound uremic toxin that results from the metabolism of dietary tryptophan. Briefly, tryptophan is metabolized into indole by intestinal bacteria and after intestinal absorption is further converted to IS in the liver. The kidneys excrete the toxin via proximal tubular secretion. Consequently, IS accumulates in the blood of patients with impaired renal function. Moreover, IS cannot be efficiently removed by conventional hemodialysis because of its high binding affinity for albumin (6). The role of IS as a uremic toxin was first revealed by its accelerating effects on the progression of CKD (7). Recently, it has been reported that IS may also act as a vascular toxin. In endothelial cells, IS has been shown to (1) induce oxidative stress by modifying the balance between pro- and antioxidant mechanisms (8), (2) stimulate the release of endothelial microparticles (9), and (3) blunt endothelial healing ability (10). Furthermore, IS directly stimulates rat vascular smooth muscular cell proliferation in a concentration-dependent manner (11). Accordingly, increased aortic wall thickness and severe aortic calcification with colocalization of osteoblast-specific proteins (e.g., Cbfa-1, osteopontin, and alkaline phosphatase) were observed in Dahl salt-sensitive, hypertensive rats to which IS was administered (12). These findings suggest that IS may play a role in vascular dysfunction in CKD patients.To investigate this hypothesis, we assessed serum IS levels, aortic calcification, and vascular stiffness (as measured by pulse wave velocity, PWV) in a cohort of CKD patients. We further examined whether IS levels might predict mortality in this population.     

Treatment Options for Sexual Dysfunction in Patients with Chronic Kidney Disease: A Systematic Review of Randomized Controlled Trials

Background and objectives: Sexual dysfunction is very common in patients with chronic kidney disease (CKD), but treatment options are limited. The benefits and harms of existing interventions for treatment of sexual dysfunction were assessed in patients with CKD.Design, setting, participants, & measurements: MEDLINE (1966 to December 2008), EMBASE (1980 to December 2008), and the Cochrane Trial Registry (Issue 4 2008) were searched for parallel and crossover randomized and quasi-randomized trials. Treatment effects were summarized as mean differences (MD) or standardized mean difference (SMD) with 95% confidence intervals (CI) using a random effects model.Results: Fourteen trials (328 patients) were included. Phosphodiesterase-5 inhibitors (PDE5i) compared with placebo significantly increased the overall International Index of Erectile Function-5 (IIEF-5) score (three trials, 101 patients, MD 1.81, 95% CI 1.51 to 2.10), all of its individual domains, and the complete 15-item IIEF-5 (two trials, 80 patients, MD 10.64, 95% CI 5.32 to 15.96). End-of-treatment testosterone levels were not significantly increased by addition of zinc to dialysate (two trials, 22 patients, SMD 0.19 ng/dl, 95% CI −2.12 to 2.50), but oral zinc improved end-of-treatment testosterone levels. There was no difference in plasma luteinizing and follicle-stimulating hormone level at the end of the study period with zinc therapy.Conclusions: PDE5i and zinc are promising interventions for treating sexual dysfunction in CKD. Evidence supporting their routine use in CKD patients is limited. There is an unmet need for studying interventions for male and female sexual dysfunction in CKD considering the significant disease burden.Sexual dysfunction is a set of disorders characterized by physical and psychologic changes that result in the inability to perform satisfactory sexual activities. The condition has been found to be significantly more common in men and women with chronic kidney disease (CKD) than in the general population (1). Men with CKD frequently suffer from reduced libido, erectile dysfunction, and difficulty reaching orgasm (2). Approximately 50% of male predialysis CKD patients and 80% of male dialysis patients have erectile dysfunction (3–6). Moreover, the prevalence of erectile dysfunction in male dialysis patients has been found to increase with age (63% <50 years versus 90% ≥50 years) (3). Similar results have been reported in women with CKD, with 55% of female dialysis patients reporting difficulty with sexual arousal (2). Dysmenorrhea, delayed sexual development, impaired vaginal lubrication, dyspareunia, and difficulties in reaching orgasm are also frequently observed (7,8).Multiple factors contribute to the frequent occurrence of sexual dysfunction in CKD patients, including hormonal disturbances (such as hyperprolactinemia, hypogonadism in males, and changes in hypothalamic-pituitary function in women) (9), anemia (10), CKD mineral and bone disorder (4), psychosocial factors (such as depression, anxiety, poor self-esteem, social withdrawal, marital discord, body image issues, fear of disability and death, loss of employment, and financial difficulties) (2,11,12), autonomic neuropathy (13), medications (including antihypertensives, antidepressant, and histamine receptor blockers) (2), and comorbid illness (such as diabetes mellitus, cardiovascular disease, and malnutrition) (2,14). Sexual dysfunction is inversely associated with GFR (7) and is improved after renal transplantation (15,16), suggesting that CKD per se may contribute to sexual dysfunction in these patients (15).Studies have also identified significant associations between sexual dysfunction in CKD patients and depression (8,17), impaired quality of life (8,17,18), and adverse cardiovascular outcomes (19). Effective treatment of sexual dysfunction in CKD patients may therefore potentially lead to improvement in these patient-level outcomes, although a causal link has not been definitively established (18).Therapies that have been used to treat sexual dysfunction include phosphodiesterase-5 inhibitors (PDE5i), intracavernosal injections, intraurethral suppositories, hormonal therapy, mechanical devices, and psychotherapy. Although many clinical trials and reviews have explored the role of these interventions for sexual dysfunction in nonuremic patients (20–24), the effectiveness and safety of these interventions in patients with CKD have not yet been studied thoroughly. Therefore, we aimed to evaluate the benefits and harms associated with various interventions for sexual dysfunction in patients with CKD.     

Chronic Kidney Disease Awareness Among Individuals with Clinical Markers of Kidney Dysfunction

Summary

Background and objectives

Awareness of chronic kidney disease (CKD) among providers and patients is low. Whether clinical cues prompt recognition of CKD is unknown. We examined whether markers of kidney disease that should trigger CKD recognition among providers are associated with higher individual CKD awareness.

Design, setting, participants, & measurements

CKD awareness was assessed in 1852 adults with an estimated GFR <60 ml/min per 1.73 m² using 1999 to 2008 National Health and Nutrition Examination Survey data. CKD awareness was a “yes” answer to “Have you ever been told you have weak or failing kidneys?” Participants were grouped by distribution of the following abnormal markers of CKD: hyperkalemia, acidosis, hyperphosphatemia, elevated blood urea nitrogen, anemia, albuminuria, and uncontrolled hypertension. Odds of CKD awareness associated with each abnormal marker and groupings of markers were estimated by multivariable logistic regression.

Results

Among individuals with kidney disease, only those with albuminuria had greater odds of CKD awareness (adjusted odds ratio, 4.0, P < 0.01) than those without. Odds of CKD awareness increased with each additional manifested clinical marker of CKD (adjusted odds ratio, 1.3, P = 0.05). Nonetheless, 90% of individuals with two to four markers of CKD and 84% of individuals with ≥5 markers of CKD were unaware of their disease.

Conclusions

Although individuals who manifest many markers of kidney dysfunction are more likely to be aware of their CKD, their CKD awareness remains low. A better understanding of mechanisms of awareness is required to facilitate earlier detection of CKD and implement therapy to minimize associated complications.     

Hypertension Management in Patients with Chronic Kidney Disease

Hypertension and chronic kidney disease are closely linked. Patients with chronic kidney disease have hypertension almost universally and uncontrolled hypertension accelerates the decline in kidney function. The pathophysiology of hypertension in chronic kidney disease is complex, but is largely related to reduced nephron mass, sympathetic nervous system overactivation, involvement of the renin-angiotensin-aldosterone system, and generalized endothelial dysfunction. Consensus guidelines for blood pressure targets have adopted a blood pressure <120/80 mm Hg in native chronic kidney disease and <130/80 mm Hg in kidney transplant recipients. Guidelines also strongly advocate for renin-angiotensin-aldosterone system blockade as the first-line therapy.