The effect of statins on urinary albumin excretion and glomerular filtration rate: results from both a randomized clinical trial and an observational cohort study.

BACKGROUND: Statins improve cardiovascular outcome, but less is known on the renal outcome. We, therefore, studied the relationship between the use of statins and urinary albumin excretion (UAE) and glomerular filtration rate (GFR) in two settings: a randomized controlled trial (RCT) and an observational cohort study, in which patients were included to study the impact of an elevated UAE on renal and cardiovascular prognosis. METHODS: We used data from the Prevention of REnal and Vascular ENd-stage Disease Intervention trial (PREVEND-IT) and the PREVEND cohort study. The PREVEND-IT subjects (788 with a UAE 15-300 mg/day) received pravastatin 40 mg/day vs placebo and/or fosinopril 20 mg/day vs placebo in a 2x2 factorial-RCT design. Of the 3440 cohort subjects, 469 used statins during the 4-year follow-up period. Multivariate-regression adjusted for confounding factors and the propensity score was used to estimate the relation between statin use and UAE and GFR. RESULTS: In the RCT, pravastatin did not change UAE or GFR, neither in fosinopril yes/no subgroups. In the observational cohort, statin use was associated with a rise in UAE (+12.1%), compared with statin non-use (+3.6%, P<0.001). This rise was most pronounced in those on statins prior to the first screening [+24.8% (95% CI: 11.9-39.2)], those using statins>3 years [+18.5% (7.3-30.8)] and those with >1 or >2 defined daily doses (+15.7 and +17.3%, respectively). These differences remained significant after adjustment for relevant variables and propensity score. The rise in UAE could not be attributed to a higher dose or a specific statin. GFR fell in 4 years in both statin users and non-users (4.6+/-13.5 and 2.4+/-11.2, respectively). The fall in GFR between groups was not different after adjustment (P=0.11). CONCLUSIONS: We conclude from the RCT data that statins do not lower UAE in subjects selected because of an elevated UAE instead of hyperlipidaemia. In the observational cohort study, the use of statins similarly was not associated with a fall in UAE; UAE instead increased. Statin treatment was not associated with a significant change in GFR in these subjects with only modestly impaired GFR.     

Chronic kidney disease as a risk factor for cardiovascular disease and all-cause mortality: a pooled analysis of community-based studies

Chronic kidney disease (CKD) is a major public health problem. Conflicting evidence exists among community-based studies as to whether CKD is an independent risk factor for adverse cardiovascular outcomes. After subjects with a baseline history of cardiovascular disease were excluded, data from four publicly available, community-based longitudinal studies were pooled: Atherosclerosis Risk in Communities Study, Cardiovascular Health Study, Framingham Heart Study, and Framingham Offspring Study. Serum creatinine levels were indirectly calibrated across studies. CKD was defined by a GFR between 15 and 60 ml/min per 1.73 m(2). A composite of myocardial infarction, fatal coronary heart disease, stroke, and death was the primary study outcome. Cox proportional hazards models were used to adjust for study, demographic variables, educational status, and other cardiovascular risk factors. The total population included 22,634 subjects; 18.4% of the population was black, and 7.4% had CKD. There were 3262 events. In adjusted analyses, CKD was an independent risk factor for the composite study outcome (hazard ratio [HR], 1.19; 95% confidence interval [CI], 1.07-1.32), and there was a significant interaction between kidney function and race. Black individuals with CKD had an adjusted HR of 1.76 (95% CI, 1.35-2.31), whereas whites had an adjusted HR of 1.13 (95% CI, 1.02-1.26). CKD is a risk factor for the composite outcome of all-cause mortality and cardiovascular disease in the general population and a more pronounced risk factor in blacks than in whites. It is hypothesized that this effect may be due to more frequent or more severe subclinical vascular disease secondary to hypertension or diabetes in black individuals.     

Anemia as a risk factor for cardiovascular disease and all-cause mortality in diabetes: the impact of chronic kidney disease

Anemia is a potential nontraditional risk factor for cardiovascular disease (CVD). This study evaluated whether anemia is a risk factor for adverse outcomes in people with diabetes and whether the risk is modified by the presence of chronic kidney disease (CKD). Persons with diabetes from four community-based studies were pooled: Atherosclerosis Risk in Communities, Cardiovascular Health Study, Framingham Heart Study, and Framingham Offspring Study. Anemia was defined as a hematocrit <36% in women and <39% in men. CKD was defined as an estimated GFR of 15 to 60 ml/min per 1.73 m(2). Study outcomes included a composite of myocardial infarction (MI)/fatal coronary heart disease (CHD)/stroke/death and each outcome separately. Cox regression analysis was used to study the effect of anemia on the risk for outcomes after adjustment for potential confounders. The study population included 3015 individuals: 30.4% were black, 51.6% were women, 8.1% had anemia, and 13.8% had CKD. Median follow-up was 8.6 yr. There were 1215 composite events, 600 MI/fatal CHD outcomes, 300 strokes, and 857 deaths. In a model with a CKD-anemia interaction term, anemia was associated with the following hazard ratios (95% confidence intervals) in patients with CKD: 1.70 (1.24 to 2.34) for the composite outcome, 1.64 (1.03 to 2.61) for MI/fatal CHD, 1.81 (0.99 to 3.29) for stroke, and 1.88 (1.33 to 2.66) for all-cause mortality. Anemia was not a risk factor for any outcome in those without CKD (P > 0.2 for all outcomes). In persons with diabetes, anemia is primarily a risk factor for adverse outcomes in those who also have CKD.     

Evidence-based statin prescription for cardiovascular protection in renal impairment

Dyslipidemia is a well-known risk factor for cardiovascular disease in the general population, and the cardioprotective role of statins is well established. However, although cardiovascular disease is the major cause of morbidity and mortality in chronic kidney disease (CKD), the role of statin therapy is still under investigation. In CKD the atherosclerotic burden is high and pathophysiology of dyslipidemia is complex; however, the majority of large-scale statin trials excluded patients with CKD. Statins could have different effects in the different stages of CKD. Two large trials involving haemodialysis patients showed unfavourable results, whereas in renal transplant subjects as well as in early CKD subjects, statins reduced cardiovascular risk. The studies involving early CKD patients are post-hoc analyses of large trials and they showed that statins are more effective in secondary than in primary prevention. The aim of this study was to evaluate the effectiveness of statins for prevention of cardiovascular events by calculating the number of patients needed to be treated in different interventional trials. We conclude that dyslipidemia is a modifiable cardiovascular risk and statins appear to be an effective treatment especially in the early stages of CKD. Patients on renal replacement therapy could obtain an advantage from this treatment; however, the patient’s clinical prognosis should be taken into account when evaluating treatment.     

International comparison of the relationship of chronic kidney disease prevalence and ESRD risk

ESRD incidence is much lower in Europe compared with the United States. This study investigated whether this reflects a difference in the prevalence of earlier stages of chronic kidney disease (CKD) or other mechanisms. CKD prevalence in Norway was estimated from the population-based Health Survey of Nord-Trondelag County (HUNT II), which included 65,181 adults in 1995 through 1997 (participation rate 70.4%). Data were analyzed using the same methods as two US National Health and Nutrition Examination Surveys in 1988 through 1994 (n = 15,488) and 1999 through 2000 (n = 4101). The primary analysis used gender-specific cutoffs in estimating persistent albuminuria for CKD stages 1 and 2. ESRD rates and other relevant data were extracted from national registries. Total CKD prevalence in Norway was 10.2% (SE 0.5): CKD stage 1 (GFR >90 ml/min per 1.73 m2 and albuminuria), 2.7% (SE 0.3); stage 2 (GFR 60 to 89 ml/min per 1.73 m2 and albuminuria), 3.2% (SE 0.4); stage 3 (GFR 30 to 59 ml/min per 1.73 m2), 4.2% (SE 0.1); and stage 4 (GFR 15 to 29 ml/min per 1.73 m2), 0.2% (SE 0.01). This closely approximates reported US CKD prevalence (11.0% in 1988 through 1994 and 11.7% in 1999 through 2000). The relative risk for progression from CKD stages 3 or 4 to ESRD in US white patients compared with Norwegian patients was 2.5. This was only modestly modified by adjustment for age, gender, and diabetes. Age and GFR at start of dialysis were similar, hypertension and cardiovascular mortality in the populations were comparable, but US white patients were referred later to a nephrologist and had higher prevalence of obesity and diabetes. In conclusion, CKD prevalence in Norway was similar to that in the United States, suggesting that lower progression to ESRD rather than a smaller pool of individuals at risk accounts for the lower incidence of ESRD in Norway.     

Increased prevalence of oxidant stress and inflammation in patients with moderate to severe chronic kidney disease

BACKGROUND: The prevalence of increased oxidative stress and acute-phase inflammation in patients with chronic kidney disease (CKD) has not been thoroughly investigated. METHODS: Biomarkers of oxidative stress and acute-phase inflammation were measured in a cohort of 60 patients with stage 3-5 CKD compared to a healthy subject cohort. Levels of oxidative stress and inflammation were also compared to estimated glomerular filtration rate (GFR) using the Modification of Diet in Renal Disease (MDRD) formula. RESULTS: All biomarkers of oxidative stress (plasma protein carbonyl group content, plasma free F2-isoprostane content, plasma protein reduced thiol content) and all markers of inflammation [C-reactive protein (CRP), interleukin-6 (IL-6)] differed significantly between CKD patients and healthy subjects. There was no significant relationship between estimated GFR and any oxidative stress or inflammation biomarker. CRP levels were higher in patients with known coronary vascular disease (CVD) and in patients not taking angiotensin II inhibitors. Plasma IL-6 levels were significantly higher in patients with known coronary vascular disease and lower in patients taking statins. Biomarkers of oxidative stress were significantly higher in patients with diabetes and hypercholesterolemia. CONCLUSION: There is evidence of increased oxidative stress and acute-phase inflammation in patients with stage 3-5 chronic kidney disease compared to healthy subjects that does not closely correlate with estimates of GFR. Among CKD patients, inflammatory biomarkers correlate with known CVD and inversely correlate with the use of angiotensin II inhibitors and statins. A further increase in oxidative stress was noted in diabetic and hypercholesterolemic patients. Inflammation and oxidative stress may contribute to cardiovascular risk in CKD patients.     

Contrasting Cholesterol Management Guidelines for Adults with CKD

The Kidney Disease Improving Global Outcomes Lipid Work Group recommends statins for adults ≥50 years old with CKD. The American College of Cardiology/American Heart Association endorses statins for adults with atherosclerotic cardiovascular disease, adults with LDL cholesterol≥190 mg/dl, and adults 40–79 years old with LDL cholesterol=70–189 mg/dl and diabetes or a 10-year predicted risk for atherosclerotic cardiovascular disease ≥7.5% estimated using the Pooled Cohort risk equations. Using data from the Reasons for Geographic and Racial Differences in Stroke Study, we calculated the agreement for statin treatment between these two guidelines for adults 50–79 years old with CKD (eGFR<60 ml/min per 1.73 m² or albuminuria≥30 mg/g) not on dialysis. We assessed the validity of the Pooled Cohort risk equations in individuals with CKD. Study participants were enrolled between 2003 and 2007, and we report incident cardiovascular disease events (stroke and coronary heart disease) through December of 2010. Among 4726 participants with CKD, 2366 (50%) were taking statins, and 1984 (42%) were recommended statins by the American College of Cardiology/American Heart Association guideline but not taking them. Overall, 376 (8%) participants did not meet the American College of Cardiology/American Heart Association criteria for initiating statin treatment. Cardiovascular disease incidence was low (3.0/1000 person-years; 95% confidence interval, 0.1 to 5.9) among these participants. The Pooled Cohort risk equations were well calibrated (Hosmer–Lemeshow chi-squared=2.7, P=0.45) with moderately good discrimination (C index, 0.71; 95% confidence interval, 0.65 to 0.77). In conclusion, these guidelines show high concordance for statin treatment for adults with CKD.     

Effects of anemia and left ventricular hypertrophy on cardiovascular disease in patients with chronic kidney disease

Left ventricular hypertrophy (LVH) and anemia are highly prevalent in moderate chronic kidney disease (CKD). Because anemia may potentiate the adverse effects of LVH on cardiovascular outcomes, the effect of both anemia and LVH on outcomes in CKD was examined. Data from four community-based longitudinal studies were pooled: Atherosclerosis Risk in Communities Study, Cardiovascular Health Study, Framingham Heart Study, and Framingham Offspring Study. Serum creatinine levels were calibrated indirectly across studies, and GFR was estimated using the Modification of Diet in Renal Disease equation. CKD was defined as GFR between 15 and 60 ml/min per 1.73 m(2). LVH was based on electrocardiogram criteria. Anemia was defined as hematocrit <36% in women and 39% in men. The primary outcome was a composite of myocardial infarction, stroke, and death; a secondary cardiac outcome included only myocardial infarction and fatal coronary heart disease. Among 2423 patients with CKD, 96% had electrocardiogram and anemia data. Median follow-up was 102 mo. In adjusted analysis, LVH was associated with increased risk for composite and cardiac outcomes (hazard ratio [HR], 1.67 [95% confidence interval (CI), 1.34 to 2.07] and 1.62 [95% CI, 1.18 to 2.24], respectively), whereas anemia was associated with increased risk for the only composite outcome (HR, 1.51 [95% CI, 1.27 to 1.81]). The combination of anemia and LVH was associated with an increased risk for both study outcomes compared with individuals with neither risk factor (HR, 4.15 [95% CI, 2.62 to 6.56] and 3.92 [95% CI, 2.05 to 7.48]; P = 0.02 and 0.01 for interaction term, respectively). The combination of anemia and LVH in CKD identifies a high-risk population.     

Prevention of chronic kidney and vascular disease: toward global health equity--the Bellagio 2004 Declaration

Chronic kidney disease (CKD) not only reflects target organ injury in systemic vascular disease in the general population and in association with diabetes, hypertension, and smoking, but it is recognized as one of the major risk factors in the pathogenesis and outcome of cardiovascular disease. Recent surveys have revealed that the prevalence of CKD, particularly the hidden mild form (mildly elevated levels of serum creatinine or urinary albumin excretion), is surprisingly high in the general population. In recent years, the global epidemic of type 2 diabetes has led to an alarming increase in the number of patients with CKD. Most patients with CKD (over 50 million individuals worldwide) succumb to cardiovascular events, while each year over 1 million develop end-stage renal failure, which requires costly treatment and in many countries of the world, unaffordable renal replacement therapy by chronic dialysis or renal transplantation. Alarmed by the immense challenge to human morbidity and the economic burden of CKD and ensuing systemic cardiovascular disease, the International Society of Nephrology convened a multidisciplinary group of expert physicians and public health leaders from around the world to develop strategies to delay and avert this bleak future by effective prevention of CKD based on awareness, early detection, and effective treatment.     

Effects of Dapagliflozin in Stage 4 Chronic Kidney Disease

BackgroundIn the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) randomized, placebo-controlled trial, the sodium-glucose cotransporter 2 inhibitor dapagliflozin significantly reduced risk of kidney failure and prolonged survival in patients with CKD with or without type 2 diabetes.MethodsAdults with eGFR of 25–75 ml/min per 1.73 m² and urinary albumin-to-creatinine ratio of 200–5000 mg/g had been randomized to receive dapagliflozin 10 mg/d or placebo. Here, we conducted a prespecified analysis of dapagliflozin’s effects in patients with stage 4 CKD (eGFR,30 ml/min per 1.73 m²) at baseline. The primary end point was a composite of time to ≥50% sustained decline in eGFR, ESKD, or kidney or cardiovascular death. Secondary end points were a kidney composite (same as the primary end point but without cardiovascular death), a composite of cardiovascular death or heart failure hospitalization, and all-cause death.ResultsA total of 293 participants with stage 4 CKD received dapagliflozin and 331 received placebo. Patients with stage 4 CKD randomized to dapagliflozin experienced a 27% (95% confidence interval [95% CI]: −2 to 47%) reduction in the primary composite endpoint, and 29% (−2 to 51%), 17% (−53 to 55%), and 32% (−21 to 61%) reductions in the kidney, cardiovascular and mortality endpoints, respectively, relative to placebo. Interaction P-values were 0.22, 0.13, 0.63, and 0.95, respectively, comparing CKD stages 4 versus 2/3. The eGFR slope declined by 2.15 and 3.38 ml/min per 1.73 m² per year in the dapagliflozin and placebo groups, respectively (P=0.005). Patients treated with dapagliflozin or placebo had similar rates of serious adverse events and adverse events of interest.ConclusionsAmong patients with stage 4 CKD and albuminuria, the effects of dapagliflozin were consistent with those observed in the DAPA-CKD trial overall, with no evidence of increased risks.     

Evaluation of advanced glycation end products accumulation, using skin autofluorescence, in CKD and dialysis patients

Purpose

Advanced glycation end products (AGE), biomarkers of metabolic stress, are frequently encountered in chronic kidney disease (CKD) patients with cardiovascular disease. Our aim was to evaluate tissue accumulation of AGEs in CKD patients and possible correlations with traditional and non-traditional cardiovascular risk factors.

Methods

Skin AF was measured using AGE Reader in 310 patients: 157 haemodialysis patients (HD) (mean age 60?years, dialysis vintage 29 months, 19.1% diabetic), 102 peritoneal dialysis patients (PD) (mean age 56.3?years, dialysis vintage 16 months, 17.6% diabetic), 32 CKD patients (mean age 68?years, CKD duration 30 months, 34.4% diabetic) and 19 type 2 diabetic patients, without renal failure (mean age 59?years and median duration of diabetes 36 months).

Results

HD patients have higher AGE levels compared to PD ones. Dialysis patients have the highest skin AF values compared to CKD patients (P?P?P?P?P?Conclusions CKD patients have higher AGE values depending on duration (disease, RRT) and GFR (dialysis adequacy and RRF). Other important determinants were diabetes and age.     

Prevalence of Chronic Kidney Disease Is Extremely High in Heart Transplant Recipients

Patients with cardiovascular disease often have renal dysfunction from concomitant diabetes mellitus, hypertension, or congestive heart failure. Glomerular filtration rate (GFR) less than 60 mL/min is predictive of premature death due to cardiovascular disease. The objective of the present study was to assess the prevalence of kidney dysfunction in 162 heart transplant recipients using estimated GFR according to the Cockcroft-Gault and the simplified Modification of Diet in Renal Disease (MDRD) formulas or creatinine clearance (24-hour urine collection). Normal serum creatinine concentrations were noted in 46% of patients. Mean (SD) GFR was 62.92 (31.04) mL/min using the Cockcroft-Gault formula, 55.38 (26.74) mL/min using the MDRD formula, and 62.62 (35.61) mL/min according to creatinine clearance. Using the Cockcroft-Gault formula, a diagnosis of stage 2 chronic kidney disease (CKD) (GFR 60–89 mL/min) was made in 92 patients (56.8%), stage 3 (GFR 30–59 mL/min) in 62 patients (38.3%), and stage 4 (GFR 15–29 mL/min) in 14 patients (8.6%). Using the MDRD formula, stage 2 CKD was present in 52 patients (28.5%), stage 3 in 77 (51.1%), and stage 4 in 28 (17.3%). According to creatinine clearance, stage 2 CKD was noted in 10 patients (6.2%), stage 3 in 114 (73.3%), and stage 4 in 21 (13.0%). We conclude that the prevalence of CKD is extremely high in heart transplant recipients. Evaluation of renal function is important to select the appropriate technique to reduce cardiovascular risk. A multidisciplinary approach in heart transplant recipients should include a nephrologist.     

Cost‐effectiveness of statins for primary prevention of atherosclerotic cardiovascular disease among people living with HIV in the United States

BackgroundExpanding statin use may help to alleviate the excess burden of atherosclerotic cardiovascular disease in people living with HIV (PLHIV). Pravastatin and pitavastatin are preferred agents due to their lack of substantial interaction with antiretroviral therapy. We aimed to evaluate the cost‐effectiveness of pravastatin and pitavastatin for the primary prevention of atherosclerotic cardiovascular disease among PLHIV in the United States.MethodsWe developed a microsimulation model that randomly selected (with replacement) individuals from the Data‐collection on Adverse Effects of Anti‐HIV Drugs study with follow‐up between 2013 and 2016. Our study population was PLHIV aged 40 to 75 years, stable on antiretroviral therapy, and not currently using lipid‐lowering therapy. Direct medical costs and quality‐adjusted life‐years (QALYs) were assigned in annual cycles and discounted at 3% per year. We assumed a willingness‐to‐pay threshold of $100,000/QALY gained. The interventions assessed were as follows: (1) treating no one with statins; (2) treating everyone with generic pravastatin 40 mg/day (drug cost $236/year) and (3) treating everyone with branded pitavastatin 4 mg/day (drug cost $2,828/year). The model simulated each individual’s probability of experiencing atherosclerotic cardiovascular disease over 20 years.ResultsPersons receiving pravastatin accrued 0.024 additional QALYs compared with those not receiving a statin, at an incremental cost of $1338, giving an incremental cost‐effectiveness ratio of $56,000/QALY gained. Individuals receiving pitavastatin accumulated 0.013 additional QALYs compared with those using pravastatin, at an additional cost of $18,251, giving an incremental cost‐effectiveness ratio of $1,444,000/QALY gained. These findings were most sensitive to the pill burden associated with daily statin administration, statin costs, statin efficacy and baseline atherosclerotic cardiovascular disease risk. In probabilistic sensitivity analysis, no statin was optimal in 5.2% of simulations, pravastatin was optimal in 94.8% of simulations and pitavastatin was never optimal.ConclusionsPravastatin was projected to be cost‐effective compared with no statin. With substantial price reduction, pitavastatin may be cost‐effective compared with pravastatin. These findings bode well for the expanded use of statins among PLHIV in the United States. To gain greater confidence in our conclusions it is important to generate strong, HIV‐specific estimates on the efficacy of statins and the quality‐of‐life burden associated with taking an additional daily pill.     

Risk factors for chronic kidney disease in a community-based population: a 10-year follow-up study

The purpose of this study was to explore risk factors affecting the incidence of chronic kidney disease (CKD) in general population. We conducted a 10-year follow-up study with 123 764 (male: 41 012, female: 82 752) adults aged 40 years and over who received community-based annual examinations. The primary outcome for the analysis was the development of CKD during the follow-up period. Predictors for the development of CKD were obtained by the significant hazard ratios (HR) in Cox regression model by sex. During the follow-up period, 4307 subjects (male: 2048, female: 2259) developed CKD stage I or II, and 19 411 subjects (male: 4257, female: 15 154) developed CKD stage III or higher. The baseline-adjusted predictor of developing CKD included age, glomerular filtration rate, hematuria, hypertension, diabetes, serum lipids, obesity, smoking status, and consumption of alcohol. Treated diabetes in male subjects, and treated hypertension, systolic blood pressure >160 mm Hg and/or diastolic blood pressure >100 mm Hg, diabetes, and treated diabetes in female subjects were associated with more than a doubling of the HR. For the development of CKD stage III or higher, proteinuria of >or= + +, and proteinuria and hematuria were associated with more than a doubling of the HR in male subjects. The prevalence of newly developed CKD over 10 years was 23 718 subjects (19.2%) in adults. This study suggested that not only hypertension and diabetes but also several metabolic abnormalities were independent risk factors for developing CKD.     

Association between atherosclerotic cardiovascular diseases risk and renal outcome in patients with type 2 diabetes mellitus

AimsChronic kidney disease (CKD) and diabetes mellitus increase atherosclerotic cardiovascular diseases (ASCVD) risk. However, the association between renal outcome of diabetic kidney disease (DKD) and ASCVD risk is unclear.MethodsThis retrospective study enrolled 218 type 2 diabetic patients with biopsy-proven DKD, and without known cardiovascular diseases. Baseline characteristics were obtained and the 10-year ASCVD risk score was calculated using the Pooled Cohort Equation (PCE). Renal outcome was defined as progression to end-stage renal disease (ESRD). The association between ASCVD risk and renal function and outcome was analyzed with logistic regression and Cox analysis.ResultsAmong all patients, the median 10-year ASCVD risk score was 14.1%. The median of ASCVD risk score in CKD stage 1, 2, 3, and 4 was 10.9%, 12.3%, 16.5%, and 14.8%, respectively (p = 0.268). Compared with patients with lower ASCVD risk (＜14.1%), those with higher ASCVD risk had lower eGFR, higher systolic blood pressure, and more severe renal interstitial inflammation. High ASCVD risk (>14.1%) was an independent indicator of renal dysfunction in multivariable-adjusted logistic analysis (OR, 3.997; 95%CI, 1.385–11.530; p = 0.010), though failed to be an independent risk factor for ESRD in patients with DKD in univariate and multivariate Cox analysis.ConclusionsDKD patients even in CKD stage 1 had comparable ASCVD risk score to patients in CKD stage 2, 3, and 4. Higher ASCVD risk indicated severe renal insufficiency, while no prognostic value of ASVCD risk for renal outcome was observed, which implied macroangiopathy and microangiopathy in patients with DKD were related, but relatively independent.     

Chronic kidney disease and risk of postoperative cardiovascular events in elderly patients receiving hip fracture surgery

IntroductionThe long-term risk of cardiovascular events caused by chronic kidney disease (CKD) is well described in the general population. Less is known concerning the risk of postoperative cardiovascular events in geriatric hip fracture patients with CKD.MethodsThis study involved patients at least 65 years of age who received surgery for acute hip fracture between January 2000 and April 2016. We identified CKD patients with a baseline diagnosis of CKD or an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m² at admission. Each CKD patient was matched, for age, gender, fracture type, and year of admission, with 4 control non-CKD patients. The primary endpoint was a compositepostoperative cardiovascular events, including pulmonary embolism, angina pectoris, myocardial infarction, heart failure, arrhythmia, stroke, and death. Conditional logistic regression was used to evaluate the association between CKD and the outcome after adjusting for potential confounders including age, gender, fracture type, body mass index, preexisting comorbidities, history of cardiovascular events, and the Charlson Comorbidity Index (CCI).ResultsThree hundred and seventy-five CKD patients were matched with 1,438 non-CKD patients. The mean age of the CKD patients was 81.9 ± 7.0 (mean ± SD), 69.9% were females, and 59.2% had an intertrochanteric fracture. Compared to non-CKD patients, CKD patients had a higher proportion of preexisting comorbidities, including hypertension, coronary heart disease, heart failure, and type 2 diabetes (all p < 0.05). The risk of postoperative cardiovascular events was 125.3 per 1000 persons (95%CI, 91.8–158.8) in CKD patients and 64.7 per 1000 persons (95%CI, 52.0–77.4) in non-CKD patients. A 1.96-fold risk of cardiovascular events after hip fracture surgery was found in CKD patients than those without CKD (adjusted OR, 1.96; 95%CI, 1.23–3.12).ConclusionPatients with CKD were more likely to have cardiovascular events after hip fracture surgery than those without CKD. Appropriate preoperative cardiovascular risk assessment and corresponding preventive and therapeutic measures should be given to this vulnerable population to mitigate such complications.     

The lipid story in chronic kidney disease: a long story with a happy end?

Cardiovascular (CV) morbidity and mortality increase with the severity of kidney disease, reaching 30 times higher mortality rates in dialysis patients compared with the general population. Although dyslipidemia is a well-established CV risk factor in the general population, the relationship between lipid disorders and CV risk in patients with chronic kidney disease (CKD) is less clear. Despite the clear evidence that statins reduce the risk of atherosclerotic events and death from cardiac causes in individuals without CKD, the use of statins in patients with kidney disease is significantly less frequent. For a long time, one of the explanations was the lack of a prospective, randomized, controlled study designed specifically to CKD patients. After recent publication of the data from Study of Heart and Renal Protection trial, given the safety and potential efficacy of statins, this lipid-lowering treatment should be administered more frequently to individuals with CKD stage 1–4, as well as those undergoing dialysis.     

Statin therapy in kidney disease populations: potential benefits beyond lipid lowering and the need for clinical trials

PURPOSE OF REVIEW: This review outlines the limited information currently available on the effects of statins among patients with chronic kidney disease, and summarizes the ongoing randomized trials designed to address this question. RECENT FINDINGS: The effects of fluvastatin on major coronary events among renal transplant patients, and the effects of pravastatin and simvastatin in small subgroups of coronary patients with minor degrees of renal impairment, appear broadly compatible with those observed in trials conducted in non-renal populations. In addition, recent evidence from trials among patients with vascular disease or diabetes suggests that statin therapy may delay progressive loss of renal function. However, there remains substantial uncertainty regarding the effects of statin therapy among patients with established chronic kidney disease (pre-dialysis or dialysis patients). In particular, there does not appear to be a strongly positive relationship between blood cholesterol and cardiovascular events in such patients. This may be because uraemic cardiomyopathy and arteriosclerosis, which cause the majority of these events in chronic kidney disease patients, do not depend strongly on blood cholesterol. SUMMARY: Statins appear effective for the prevention of vascular events in people with established vascular disease and mild renal impairment, and may delay renal disease progression in such individuals. However, the effects of statins in patients with established chronic kidney disease are unknown, and we await the results of ongoing large-scale randomized trials of statin therapy among such patients.