Biochemical Abnormalities in Chronic Kidney Disease–Mineral Bone Disease

Chronic kidney disease?Cmineral and bone disorders (CKD-MBD) is a term introduced by the Kidney Disease: Improving Global Outcomes (KDIGO) work group on mineral and bone disorder as a syndrome of interrelated biochemical, bone, and vascular abnormalities encountered in CKD. Biochemical abnormalities in CKD represent primary indicators for the diagnosis and management of CKD-MBD. This review discusses each abnormality separately, with references to both the Kidney Dialysis Outcomes Quality Initiative (KDOQI) Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease and KDIGO Guidelines for Mineral and Bone Disorder. Selected references to the association between biochemical abnormalities and adverse clinical outcomes in CKD population are provided.     

Bone Mineral Density in Chronic Kidney Disease Use and Misuse

Low bone mineral density (BMD) is a strong risk factor for low trauma fractures in the postmenopausal population without known chronic kidney disease (CKD). In stage 1?C3 CKD, low BMD can also be used to predict fracture risk with the gradient of risk similar to patients without CKD even though patients with stage 3 CKD have an approximate doubling of risk compared with age-matched patients without CKD. This greater risk of fracture in stage 3 CKD is not calculated in the current FRAX model. In stage 4?C5 CKD, BMD by dual-energy x-ray absorptiometry (DXA) is a poor predictor of fracture risk probably related to the severe derangements in bone metabolism in severe CKD, which alter bone quality and strength not measured by DXA. Serial BMD by DXA, however, may be useful in all stages of CKD to monitor for potential loss of BMD or effect of pharmacological agents to improve BMD. Newer radiological technologies, particularly high-resolution peripheral quantitative computerized tomography (HRpQcT) of the radius and tibia show promise to define the microstructural changes in bone that explain the greater risk of fracture observed in patients with CKD versus patients without CKD. BMD by DXA may still be of value across the spectrum of CKD, but physicians should realize its limitations and understand the greater risk of fracture in patients in all stages of CKD as compared to age-matched and BMD-matched patients without CKD.     

Critical Governance Issue of Parathyroid Hormone Assays and its Selection in the Management of Chronic Kidney Disease Mineral and Bone Disorders

Measurement of circulating parathyroid hormone (PTH) levels is essential for optimal management of mineral and bone disorders (MBD) in chronic kidney disease (CKD) patients. There are two major types of PTH assays currently in use: intact parathyroid hormone (i-PTH) and whole PTH (w-PTH) assays. The i-PTH assay is the current standard, and considerable information regarding the management of CKD-MBD has been obtained with this method. However, several limitations have been found with the i-PTH assay. One limitation is that i-PTH assay also measures fragments other than full-length PTH (1-84). Another limitation is the existence of multiple readout methods of the i-PTH assay. The w-PTH assay is theoretically ideal because it exclusively detects full-length PTH (1-84). However, clinical data proving the advantages of w-PTH measurement are not sufficient. For uremic patients, Kidney Disease Improving Global Outcomes suggest that PTH levels should be maintained within approximately two to nine times the upper normal limit of the i-PTH assays. The most critical issue in the evaluation of PTH levels is the lack of definitive PTH assay method. Evidence-based recommendations on clinical management goals of PTH are warranted.     

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.     

Mineral Metabolism and Inflammation in Chronic Kidney Disease Patients: A Cross-Sectional Study

Background and objectives: Mineral metabolism abnormalities and inflammation are concerns in chronic kidney disease (CKD). Interrelationships among these parameters have not been analyzed.Design, setting, participants, & measurements: The study included 133 patients with CKD not on dialysis and not receiving calcium (Ca) supplements, phosphate binders, or vitamin D. Estimated GFR (eGFR) was 34.1 ± 6.8 ml/min/1.73 m²; 107 participants had stage 3 CKD, and 26 had stage 4.Results: Patients were classified by tertiles of Ca, phosphorus (P), Ca-P product (Ca x P), and parathyroid hormone (PTH). After adjustment for age, gender, and eGFR, the levels of C-reactive protein (CRP) and IL-6 (IL-6) of the third tertile of P, Ca x P, and PTH were significantly higher than those of the first and second tertiles. Serum P and Ca x P directly correlated with CRP and IL-6, whereas HDL-cholesterol and eGFR inversely correlated with the levels of the inflammatory parameters. After partial correlation analysis, the previous associations between CRP and eGFR, and serum P, as well as the relationship between IL-6 and eGFR, and serum P, remained significant. Multiple regression analysis demonstrated that eGFR and serum P were independently associated with CRP and IL-6. Finally, logistic regression analysis using the presence/absence of an inflammatory state as the dependent variable showed that eGFR was a protective factor, whereas serum P was an independent risk factor for the presence of an inflammatory state.Conclusions: Elevated serum P might play a role in the development of inflammation in CKD.Alteration of mineral metabolism is a prevalent condition in chronic kidney disease (CKD). Large epidemiologic studies have shown a strong relationship between elevated levels of calcium (Ca), phosphorus (P), Ca-P product (Ca x P), and parathyroid hormone (PTH) with cardiovascular morbidity and mortality (1–3). Among abnormalities of mineral metabolism, one of the most prominent and relevant is hyperphosphatemia. Elevated serum P has been related to cardiovascular morbidity and mortality in both hemodialysis and predialysis patients. Vascular and coronary artery calcification have been suggested as the link between abnormal mineral metabolism in general, and hyperphosphatemia in particular, and cardiovascular events in this population (4–6). Hyperphosphatemia has been pointed out as the primary culprit in the process of cardiovascular calcification (4,8–10), an event already present in the early phases of renal failure (7,8). More interesting, a significant association between the progression of coronary artery calcification and serum P concentration was observed in CKD patients, despite serum P being in the normal range. Faster progression was found in patients with a high-normal serum P, which was accompanied by more frequent cardiovascular events (11). However, despite these previous findings, the mechanisms by which serum P contributes to cardiovascular disease are not completely known.Vascular and coronary artery calcification are markers of atherosclerotic disease. In the last decades, intensive investigations have led to a paradigm shift in the interpretation of atherosclerosis, from a purely metabolic process (i.e., mainly driven by hypercholesterolemia) to a disease where inflammation is the dominant pathophysiological and biochemical alteration (12). Cardiovascular disease is up to 20-fold more frequent in ESRD patients and accounts for up to 50% of all deaths, with accelerated atherosclerosis being consistently implicated in this process (13). Traditional cardiovascular risk factors cannot completely explain the prevalence of atherosclerosis, the elevated cardiovascular risk, and the disproportional predisposition for adverse cardiovascular outcomes in this population. Therefore, novel emergent cardiovascular risk factors are suggested to contribute to atherogenesis and have been associated with cardiovascular risk. Among these, it is now known that inflammation is a highly prevalent condition in CKD patients, with diverse studies having documented increased concentrations of inflammatory mediators in dialysis patients as well as subjects with advanced renal failure (14,15). More importantly, it has been demonstrated that several inflammatory parameters, mainly C-reactive protein (CRP) and IL-6 (IL-6), are strong and independent predictors of all-cause and cardiovascular mortality (16–19).In spite of the important prevalence and relevance of alterations of mineral metabolism and inflammation in CKD patients, the interrelationships among these factors have been scarcely analyzed, especially in predialysis patients. Most previous studies have been performed in hemodialysis, with a limited number of subjects, and with the potentially confounding effect of concomitant treatment with Ca supplements, phosphate binders, or vitamin D derivates (20,21). The aim of this study was to examine the interrelationships among the main parameters of mineral metabolism (Ca, P, Ca x P, and PTH) and inflammation (CRP and IL-6) in patients with advanced CKD.     

Circulating Follistatin in Patients with Chronic Kidney Disease: Implications for Muscle Strength,Bone Mineral Density,Inflammation, and Survival

Summary

Background and objectives

Follistatin mediates muscle growth and bone mineralization. At present, it is unknown whether circulating follistatin levels are altered in chronic kidney disease (CKD) or links to CKD risk factors and outcomes.

Design, setting, participants, & measurements

Plasma follistatin levels were cross-sectionally analyzed in relation to protein-energy wasting (PEW), handgrip strength (HGS), bone mineral density (BMD), and inflammatory markers in 280 CKD stage 5 patients, 32 CKD stage 4 patients, 16 CKD stage 3 patients, and 32 control subjects. In CKD stage 5 patients survival was prospectively investigated during a follow-up period of up to 5 years.

Results

The plasma follistatin concentration was not higher in CKD stage 5 patients than in other CKD stages or controls. In CKD stage 5 patients, circulating follistatin positively correlated with age, high-sensitivity C-reactive protein (hsCRP), and IL-6; negatively correlated with HGS, serum creatinine, and BMD; and was increased in patients with PEW. In a multivariate logistic regression model, lower HGS, lower BMD, and higher hsCRP independently correlated with higher follistatin levels. In a Cox regression model, follistatin levels were not associated with all-cause mortality.

Conclusions

Circulating follistatin levels were neither elevated nor predicted outcome in patients with CKD. However, increased follistatin levels occurred together with increased inflammation, reduced muscle strength, and low BMD, suggesting an involvement of a mechanism including follistatin in the uremic wasting process.     

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.     

Pediatric Patients with Chronic Kidney Disease-Mineral Bone Disorder

Chronic kidney disease-mineral bone disorder (CKD-MBD) is a systemic disorder of mineral and bone metabolism that has deleterious consequences on skeletal and cardiovascular health. Nowhere is the morbidity of this disorder more telling than in children. During childhood and adolescence, CKD-MBD may result in poor growth and skeletal deformities, while the mineral dysregulation can manifest in cardiovascular disease in early adulthood, a development that places the patients at high risk for severe morbidity and early mortality. Unfortunately, management of CKD-MBD has been less than satisfactory in children despite recent advances and is limited by the lack of evidence-based treatment guidelines. More positive are ongoing research efforts, such as the Chronic Kidney Disease in Children and the Cardiovascular Comorbidity in Children with CKD (4C) studies that are currently providing important insights which should help better elucidate the pathogenesis and progression of mineral dysregulation and its clinical impact in children. Data from these studies and others will undoubtedly also help formulate clinical trials and the generation of evidence-based therapeutic options designed to provide more effective management of CKD-MBD in the pediatric population.     

Revascularization Options in Patients with Chronic Kidney Disease

Cardiovascular disease is the leading cause of death in patients who have chronic kidney disease or end-stage renal disease and are undergoing hemodialysis. Chronic kidney disease is a recognized risk factor for premature atherosclerosis. Unfortunately, most major randomized clinical trials that form the basis for evidence-based use of revascularization procedures exclude patients who have renal insufficiency. Retrospective, observational studies suggest that patients with end-stage renal disease and severe coronary occlusive disease have a lower risk of death if they undergo coronary revascularization rather than medical therapy alone. Due to a lack of prospective studies, however, the relative merits of percutaneous versus surgical revascularization are merely a matter of opinion. Several small, retrospective studies have shown that coronary artery bypass grafting is associated with higher procedural death but better long-term survival than is percutaneous coronary intervention. This difference appears to result from poor long-term results of percutaneous coronary intervention in patients who have chronic kidney disease or end-stage renal disease.Because randomized trials comparing percutaneous coronary intervention and coronary artery bypass grafting have included patients undergoing balloon angioplasty and placement of bare-metal stents, their conclusions are suspect in the era of drug-eluting stents. In this review, we discuss different revascularization options for patients with chronic kidney disease, the outcomes of revascularization procedures, and the risk factors for adverse outcomes.Key words: Angioplasty, transluminal, percutanous coronary; coronary artery bypass; coronary artery bypass, off-pump; creatinine/blood/metabolism; drug-eluting stents; extracorporeal circulation; glomerular filtration rate; kidney failure, chronic; renal dialysis; stents; treatment outcomeThe prevalence of end-stage renal disease (ESRD), defined as renal dysfunction requiring chronic renal replacement therapy, is increasing. In 2007, there were about 341,000 patients with ESRD on hemodialysis and 143,000 patients with transplanted kidneys in the United States.¹ An additional 8% of adults in the U.S. have chronic kidney disease stages 3 and 4 (characterized by a glomerular filtration rate [GFR] between 15 and 60 mL/min/1.73 m²).² The United States Renal Data System (USRDS) projects that, at the current growth rate, the number of patients with ESRD will increase to 534,000 by the year 2020.¹ Within 18 to 24 months of beginning renal replacement therapy, 12% of patients will have an acute myocardial infarction, more than 60% will receive a diagnosis of congestive heart failure, and, by 3 years, 38% will die suddenly, presumably of cardiovascular causes.¹ In chronic kidney disease patients who are not hemodialysis dependent, the risk of dying of cardiovascular disease is greater than the risk of developing ESRD.³ In addition to the traditional risk factors for atherosclerosis,⁴ an abnormal GFR contributes independently to the risk of atherosclerosis-related events in patients with kidney disease.⁵     

Relationship Between Psychiatric Disorders and Quality of Life in Nondialysis Patients With Chronic Kidney Disease

BackgroundThe aim of this study was to investigate the relationship between psychiatric disorders (anxiety and depression) and quality of life (QOL) in nondialysis patients with chronic kidney disease (CKD).MethodsQOL was evaluated in a sample of 57 nondialysis patients with CKD using the 36-item Short Form Health Survey questionnaire comprising 8 scales, including the physical component summary and mental component summary measures. Depression and anxiety were estimated using the Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale, respectively.ResultsDepression and anxiety scores were negatively correlated with 7 of the 8 scales of the Short Form 36 questionnaire, and with the physical component summary and mental component summary scores, despite 38.6% patients with depression and 54.4% with anxiety, whereas QOL in the depression group, the anxiety group, and the anxiety and depression comorbid group was lower than that for those without the corresponding psychiatric disorders (P < 0.05).ConclusionsThis study demonstrates that depression and anxiety, commonly encountered in patients with CKD, could be a risk factor for QOL in these patients.     

Coronary Calcification in Patients with Chronic Kidney Disease and Coronary Artery Disease

Background and objectives: A close linkage between chronic kidney disease (CKD) and cardiovascular disease (CVD) has been demonstrated. Coronary artery calcification (CAC) is considered to be the causal link connecting them. The aim of the study is to determine the relationship between level of kidney function and the prevalence of CAC.Design, setting, participants, & measurements: Autopsy subjects known to have coronary artery disease and a wide range of kidney function were studied. Patients without CKD were classified into five groups depending on estimated GFR (eGFR) and proteinuria: eGFR ≥60 ml/min/1.73 m² without proteinuria; CKD1/2: eGFR ≥60 ml/min/1.73 m² with proteinuria; CKD3: 60 ml/min/1.73 m² >eGFR ≥30 ml/min/1.73 m²; CKD4/5: eGFR <30 ml/min/1.73 m²; and CKD5D: on hemodialysis. Intimal and medial calcification of the coronary arteries was evaluated. Risk factors for CVD and uremia were identified as relevant to CAC using logistic regression analysis.Results: Intimal calcification of plaques was present in all groups, but was most frequent and severe in the CKD5D group and less so in the CKD4/5 and CKD3 groups. Risk factors included luminal stenosis, age, smoking, diabetes, calcium-phosphorus product, inflammation, and kidney function. Medial calcification was seen in a small number of CKD4/5 and CKD5D groups. Risk factors were use of calcium-containing phosphate binders, hemodialysis treatment, and duration.Conclusions: It was concluded that CAC was present in the intimal plaque of both nonrenal and renal patients. Renal function and traditional risks were linked to initimal calcification. Medial calcification occurred only in CKD patients.Cardiovascular disease (CVD) is the main cause of morbidity and mortality in patients with end-stage renal disease (ESRD) (1,2) or chronic kidney disease (CKD) (3–7). The mechanisms underlying this increased cardiovascular risk are not clearly understood. In the general population, traditional risk factors for CVD have been well characterized (8), and these are also present in CKD (3–6,9). The mechanisms involved in the connection between CKD and CVD are probably numerous (3–6). Vascular calcification, such as coronary artery calcification (CAC) (10,11), is considered to be the causal link between them.Vascular calcification is common in physiologic and pathologic conditions such as aging, diabetes, dyslipidemia, genetic diseases, and diseases with disturbances of calcium metabolism (12–14). In CKD patients, vascular calcification is even more common, developing early and contributing to the markedly increased cardiovascular risk. Pathomorphologically, atherosclerosis (plaque-forming degenerative changes of the aorta and of large elastic arteries) and arteriosclerosis (concentric medial thickening and hyalinosis of muscular arteries) can be distinguished. Increased knowledge about the mechanisms of calcification together with improved imaging techniques have provided evidence that vascular calcification should be divided into two distinct entities according to the specific site of calcification within the vascular wall: plaque calcification, involving patchy calcification of the intima in the vicinity of lipid or cholesterol deposits, and calcification of the media in the absence of such lipid or cholesterol deposits, known as Mönckeberg-type atherosclerosis (12–14). These two types of calcification may vary in terms of the type of vessel affected, the location along the arterial tree (proximal versus distal), clinical presentation, and treatment and prognosis (12–14). In the general population and in patients with CKD, electron-beam computed tomography (EBCT) has proven CAC as a potent predictor of cardiac events (15–18). Both the prevalence and intensity of CAC are increased in patients with CKD (19–27). Several studies have been undertaken to investigate whether calcification occurs in the intima or media of the coronaries and whether the morphologic details of calcified plaques differ between renal and nonrenal patients (12–14,24). Causal elements for either type of CAC have not been definitively determined (12–14).Autopsy studies are limited in terms of patient selection, but have a major advantage in terms of being able to distinguish intimal from medial calcification. Therefore, our primary goal is to determine whether, among autopsy subjects known to have CAD, there exists a direct relationship between level of kidney function and the prevalence of intimal or medial calcification.     

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.     

他汀在慢性肾功能不全患者中的应用

慢性肾功能不全患者的总体死亡风险和心血管疾病死亡风险较之普通人群都有显著提高,该类患者血脂的质和量都存在异常。他汀具有降低胆固醇、抗炎、抗氧化以及稳定现有斑块等作用。现就他汀在慢性肾功能不全患者中的疗效观察进行综述,并且介绍他汀在临床应用方面的最新进展。     

Bone Mineral Affection in Asymptomatic Adult Patients with Celiac Disease

Objectives: Osteopenia is a well-known complication of overt celiac disease, but whether such defective bone mineralization is present among asymptomatic or silent patients is not known. Our objectives were: 1 ) to examine bone mineralization of a group of asymptomatic celiac patients; 2 ) to compare these results with those of symptomatic patients. Methods: Bone mineral density of the spine and total skeleton by dual energy x-ray ab-sorptiometry and serum parameters of mineral metabolism of eight recently diagnosed asymptomatic patients with celiac disease were studied. Results were compared with those obtained in 20 untreated symptomatic celiacs, 14 patients treated with gluten-free diet for a mean time of 15 yr, and 153 healthy adult subjects, matched by sex and age. Results: Four and five out of eight asymptomatic patients presented with reduced mineralization of the spine and the total skeleton, respectively (>1 SD below normal values for sex and age). Two patients presented with severe osteopenia of the spine, and the other three presented with severe osteopenia of the whole skeleton (>2 SD below mean normal values). Osteopenia at plane bone level (total skeleton) was significantly lower when compared to healthy controls ( P < 0.02). Symptomatic untreated patients had significantly more severe deterioration of bone mineralization than did asymptomatics ( P < 0.05) and treated patients ( P < 0.05). No difference in bone mineral density was observed between treated patients and asymptomatic celiacs. Serum levels of calcium, alkaline phosphatase, 25-OH vitamin D, and parathormone did not show conclusive abnormalities. Conclusions: Our findings provide direct evidence that reduced bone mineralization occurs in asymptomatic celiac patients before any other symptom becomes evident. Only early diagnosis and treatment of celiac disease can avoid the deterioration of the bone structure observed in all clinical status of celiac 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.     

Renoprotective Effect of Telmisartan in Patients with Chronic Kidney Disease

Although the activation of the renin-angiotensin system has a major role in the development of chronic renal failure, little is known about the effect of angiotensin receptor blockers on tubulointerstitial injury. To evaluate the renoprotective effect of telmisartan, we measured urinary protein excretion, urinary liver-type fatty acid binding protein (L-FABP) excretion, and urinary collagen IV in 30 hypertensive patients with chronic kidney disease (CKD). These patients were randomly assigned to receive 40 mg/day (n = 15) or 80 mg/day (n = 15) of telmisartan before the initiation of treatment and 6 and 12 months after treatment. Both doses of telmisartan reduced systolic and diastolic blood pressure after 6 (p < 0.001) and 12 (p < 0.001) months compared with baseline levels. Blood pressure reduction rate were similar between both doses. Urinary protein, urinary L-FABP excretion, and urinary collagen IV levels declined significantly 6 (p < 0.001) and 12 (p < 0.001) months after telmisartan treatment in both doses. The reduction rate in parameters was more pronounced in patients receiving 80 mg/day compared with those taking 40 mg/day telmisartan at 12 months (p < 0.001). Telmisartan reduces proteinuria, urinary L-FABP excretion, and urinary collagen IV levels in hypertensive CKD patients.     

Prevalence of Subclinical Hypothyroidism in Patients with Chronic Kidney Disease

Background and objectives: Subclinical primary hypothyroidism is highly prevalent in the general population, especially in the elderly. However, the prevalence of subclinical primary hypothyroidism in persons with chronic kidney disease (CKD) not requiring chronic dialysis is not well defined.Design, setting, participants, and measurements: Cross-sectional data from 3089 adult outpatients, who were consecutively referred by general practitioners for routine blood testing over the last two years, were analyzed. Glomerular filtration rate (GFR) was estimated by the abbreviated Modification of Diet in Renal Disease equation. Multivariable logistic regression was used to evaluate the independent association between prevalent subclinical primary hypothyroidism and estimated GFR.Results: Among 3089 adult participants, 293 (9.5%) had subclinical primary hypothyroidism and 277 (9%) had an estimated GFR <60 ml/min per 1.73 m². The prevalence of subclinical primary hypothyroidism increased from 7% at an estimated GFR ≥90 ml/min per 1.73 m² to 17.9% at an estimated GFR <60 ml/min per 1.73 m² (P < 0.0001 for trend). Compared with participants with an estimated GFR ≥60 ml/min per 1.73 m², those with estimated GFR <60 ml/min per 1.73 m² had an increased odds of subclinical primary hypothyroidism after adjusting for age, gender, fasting plasma glucose, total cholesterol, and triglyceride concentrations.Conclusions: These findings suggest that subclinical primary hypothyroidism is a relatively common condition (∼18%) among persons with CKD not requiring chronic dialysis, and it is independently associated with progressively lower estimated GFR in a large cohort of unselected outpatient adults.The concept of subclinical primary hypothyroidism has emerged over the past several decades, as our ability to detect subtle changes in thyroid function tests is progressively improved (1,2). Although it is recognized that patients with subclinical primary hypothyroidism may have subtle symptoms of thyroid dysfunction, the definition is purely a biochemical one, defined as elevated serum thyrotropin (TSH) levels but normal free thyroxine (FT₄) levels (3).Subclinical primary hypothyroidism has been recognized in several studies to be associated with markers of cardiovascular risk and cardiac impairment (4–7). Even minor deviations from serum TSH normal range might accelerate the development of atherosclerosis and have adverse effects on cardiovascular performance in the general population (4–7). Moreover, subclinical primary hypothyroidism has been identified as a strong predictor of all-cause mortality in chronic dialysis patients and as a risk factor for nephropathy and cardiovascular events in type 2 diabetic patients (8,9). There is, however, limited quantitative evidence regarding the prevalence of subclinical primary hypothyroidism in large samples of individuals, including large non-U.S. cohorts at different levels of estimated glomerular filtration rate (GFR) (10).To explore this question, we have performed a cross-sectional analysis using a large database from a Clinical Chemistry Laboratory, with the purpose of estimating the prevalence of subclinical primary hypothyroidism at different levels of kidney function.