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1.  Association of Non-alcoholic Fatty Liver Disease with Chronic Kidney Disease: A Systematic Review and Meta-analysis 
PLoS Medicine  2014;11(7):e1001680.
In a systematic review and meta-analysis, Giovanni Musso and colleagues examine the association between non-alcoholic fatty liver disease and chronic kidney disease.
Please see later in the article for the Editors' Summary
Background
Chronic kidney disease (CKD) is a frequent, under-recognized condition and a risk factor for renal failure and cardiovascular disease. Increasing evidence connects non-alcoholic fatty liver disease (NAFLD) to CKD. We conducted a meta-analysis to determine whether the presence and severity of NAFLD are associated with the presence and severity of CKD.
Methods and Findings
English and non-English articles from international online databases from 1980 through January 31, 2014 were searched. Observational studies assessing NAFLD by histology, imaging, or biochemistry and defining CKD as either estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 or proteinuria were included. Two reviewers extracted studies independently and in duplicate. Individual participant data (IPD) were solicited from all selected studies. Studies providing IPD were combined with studies providing only aggregate data with the two-stage method. Main outcomes were pooled using random-effects models. Sensitivity and subgroup analyses were used to explore sources of heterogeneity and the effect of potential confounders. The influences of age, whole-body/abdominal obesity, homeostasis model of insulin resistance (HOMA-IR), and duration of follow-up on effect estimates were assessed by meta-regression. Thirty-three studies (63,902 participants, 16 population-based and 17 hospital-based, 20 cross-sectional, and 13 longitudinal) were included. For 20 studies (61% of included studies, 11 cross-sectional and nine longitudinal, 29,282 participants), we obtained IPD. NAFLD was associated with an increased risk of prevalent (odds ratio [OR] 2.12, 95% CI 1.69–2.66) and incident (hazard ratio [HR] 1.79, 95% CI 1.65–1.95) CKD. Non-alcoholic steatohepatitis (NASH) was associated with a higher prevalence (OR 2.53, 95% CI 1.58–4.05) and incidence (HR 2.12, 95% CI 1.42–3.17) of CKD than simple steatosis. Advanced fibrosis was associated with a higher prevalence (OR 5.20, 95% CI 3.14–8.61) and incidence (HR 3.29, 95% CI 2.30–4.71) of CKD than non-advanced fibrosis. In all analyses, the magnitude and direction of effects remained unaffected by diabetes status, after adjustment for other risk factors, and in other subgroup and meta-regression analyses. In cross-sectional and longitudinal studies, the severity of NAFLD was positively associated with CKD stages. Limitations of analysis are the relatively small size of studies utilizing liver histology and the suboptimal sensitivity of ultrasound and biochemistry for NAFLD detection in population-based studies.
Conclusion
The presence and severity of NAFLD are associated with an increased risk and severity of CKD.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Chronic kidney disease (CKD)—the gradual loss of kidney function—is becoming increasingly common. In the US, for example, more than 10% of the adult population (about 26 million people) and more than 25% of individuals older than 65 years have CKD. Throughout life, the kidneys perform the essential task of filtering waste products (from the normal breakdown of tissues and from food) and excess water from the blood to make urine. CKD gradually destroys the kidneys' filtration units, the rate of blood filtration decreases, and dangerous amounts of waste products build up in the blood. Symptoms of CKD, which rarely occur until the disease is very advanced, include tiredness, swollen feet, and frequent urination, particularly at night. There is no cure for CKD, but progression of the disease can be slowed by controlling high blood pressure and diabetes (two risk factors for CKD), and by adopting a healthy lifestyle. The same interventions also reduce the chances of CKD developing in the first place.
Why Was This Study Done?
CKD is associated with an increased risk of end-stage renal (kidney) disease and of cardiovascular disease. These life-threatening complications are potentially preventable through early identification and treatment of CKD. Because early recognition of CKD has the potential to reduce its health-related burden, the search is on for new modifiable risk factors for CKD. One possible new risk factor is non-alcoholic fatty liver disease (NAFLD), which, like CKD is becoming increasingly common. Healthy livers contain little or no fat but, in the US, 30% of the general adult population and up to 70% of patients who are obese or have diabetes have some degree of NAFLD, which ranges in severity from simple fatty liver (steatosis), through non-alcoholic steatohepatitis (NASH), to NASH with fibrosis (scarring of the liver) and finally cirrhosis (extensive scarring). In this systematic review and meta-analysis, the researchers investigate whether NAFLD is a risk factor for CKD by looking for an association between the two conditions. A systematic review identifies all the research on a given topic using predefined criteria, meta-analysis uses statistical methods to combine the results of several studies.
What Did the Researchers Do and Find?
The researchers identified 33 studies that assessed NAFLD and CKD in nearly 64,000 participants, including 20 cross-sectional studies in which participants were assessed for NAFLD and CKD at a single time point and 13 longitudinal studies in which participants were assessed for NAFLD and then followed up to see whether they subsequently developed CKD. Meta-analysis of the data from the cross-sectional studies indicated that NAFLD was associated with a 2-fold increased risk of prevalent (pre-existing) CKD (an odds ratio [OR]of 2.12; an OR indicates the chance that an outcome will occur given a particular exposure, compared to the chance of the outcome occurring in the absence of that exposure). Meta-analysis of data from the longitudinal studies indicated that NAFLD was associated with a nearly 2-fold increased risk of incident (new) CKD (a hazard ratio [HR] of 1.79; an HR indicates often a particular event happens in one group compared to how often it happens in another group, over time). NASH was associated with a higher prevalence and incidence of CKD than simple steatosis. Similarly, advanced fibrosis was associated with a higher prevalence and incidence of CKD than non-advanced fibrosis.
What Do These Findings Mean?
These findings suggest that NAFLD is associated with an increased prevalence and incidence of CKD and that increased severity of liver disease is associated with an increased risk and severity of CKD. Because these associations persist after allowing for established risk factors for CKD, these findings identify NAFLD as an independent CKD risk factor. Certain aspects of the studies included in this meta-analysis (for example, only a few studies used biopsies to diagnose NAFLD; most used less sensitive tests that may have misclassified some individuals with NAFLD as normal) and the methods used in the meta-analysis may limit the accuracy of these findings. Nevertheless, these findings suggest that individuals with NAFLD should be screened for CKD even in the absence of other risk factors for the disease, and that better treatment of NAFLD may help to prevent CKD.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001680.
The US National Kidney and Urologic Diseases Information Clearinghouse provides information about all aspects of kidney disease; the US National Digestive Diseases Information Clearinghouse provides information about non-alcoholic liver disease
The US National Kidney Disease Education Program provides resources to help improve the understanding, detection, and management of kidney disease (in English and Spanish)
The UK National Health Service Choices website provides information for patients on chronic kidney disease, including some personal stories, and information on non-alcoholic fatty liver disease
The US National Kidney Foundation, a not-for-profit organization, provides information about chronic kidney disease (in English and Spanish)
The not-for-profit UK National Kidney Federation provides support and information for patients with kidney disease and for their carers
The British Liver Trust, a not-for-profit organization, provides information about non-alcoholic fatty liver disease, including a patient story
doi:10.1371/journal.pmed.1001680
PMCID: PMC4106719  PMID: 25050550
2.  Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without hypertension: a meta-analysis 
Lancet  2012;380(9854):1649-1661.
Background
Hypertension is the most prevalent comorbidity in individuals with chronic kidney disease (CKD). It is unknown, however, whether the association of the CKD measures, estimated glomerular filtration rate (eGFR) and albuminuria, with mortality or end-stage renal disease (ESRD) differs by hypertensive status.
Methods
We performed a meta-analysis of 45 cohorts (25 general population, 7 high-risk and 13 CKD cohorts), including 1,127,656 participants (364,344 with hypertension). Adjusted hazard ratios (HRs) for all-cause mortality (84,078 deaths from 40 cohorts) and ESRD (7,587 events from 21 cohorts) by hypertensive status were obtained for each study and pooled using random-effects models.
Findings
Low eGFR and high albuminuria were associated with mortality in both non-hypertensive and hypertensive individuals in the general population and high-risk cohorts. Mortality risk was higher in hypertensives as compared to non-hypertensives at preserved eGFR but a steeper relative risk gradient among non-hypertensives than hypertensives at eGFR range 45-75 ml/min/1.73m2 led to similar mortality risk at lower eGFR. With a reference eGFR of 95 mL/min/1.73m2 in each group to explicitly assess interaction, adjusted HR for all-cause mortality at eGFR 45 mL/min/1.73m2 was 1.77 (95% CI, 1.57-1.99) in non-hypertensives versus 1.24 (1.11-1.39) in hypertensives (P for overall interaction =0.0003). Similarly, for albumin-creatinine ratio (ACR) of 300 mg/g (vs. 5 mg/g), HRs were 2.30 (1.98-2.68) in non-hypertensives versus 2.08 (1.84-2.35) in hypertensives (P for overall interaction=0.019). Similar results were observed for cardiovascular mortality. The associations of eGFR and albuminuria with ESRD, however, did not differ by hypertensive status. Results in CKD cohorts were comparable to results in general and high-risk population cohorts.
Interpretation
Low eGFR and elevated albuminuria were more strongly associated with mortality among individuals without hypertension than in those with hypertension, but the associations with ESRD were similar. CKD should be considered at least an equally relevant risk factor for mortality and ESRD in non-hypertensive as it is in hypertensive individuals.
Funding
The US National Kidney Foundation (sources include Abbott and Amgen).
doi:10.1016/S0140-6736(12)61272-0
PMCID: PMC3993095  PMID: 23013600
3.  Reduced Glomerular Filtration Rate and Its Association with Clinical Outcome in Older Patients at Risk of Vascular Events: Secondary Analysis 
PLoS Medicine  2009;6(1):e1000016.
Background
Reduced glomerular filtration rate (GFR) is associated with increased cardiovascular risk in young and middle aged individuals. Associations with cardiovascular disease and mortality in older people are less clearly established. We aimed to determine the predictive value of the GFR for mortality and morbidity using data from the 5,804 participants randomized in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER).
Methods and Findings
Glomerular filtration rate was estimated (eGFR) using the Modification of Diet in Renal Disease equation and was categorized in the ranges ([20–40], [40–50], [50–60]) ≥ 60 ml/min/1.73 m2. Baseline risk factors were analysed by category of eGFR, with and without adjustment for other risk factors. The associations between baseline eGFR and morbidity and mortality outcomes, accrued after an average of 3.2 y, were investigated using Cox proportional hazard models adjusting for traditional risk factors. We tested for evidence of an interaction between the benefit of statin treatment and baseline eGFR status. Age, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, C-reactive protein (CRP), body mass index, fasting glucose, female sex, histories of hypertension and vascular disease were associated with eGFR (p = 0.001 or less) after adjustment for other risk factors. Low eGFR was independently associated with risk of all cause mortality, vascular mortality, and other noncancer mortality and with fatal and nonfatal coronary and heart failure events (hazard ratios adjusted for CRP and other risk factors (95% confidence intervals [CIs]) for eGFR < 40 ml/min/1.73m2 relative to eGFR ≥ 60 ml/min/1.73m2 respectively 2.04 (1.48–2.80), 2.37 (1.53–3.67), 3.52 (1.78–6.96), 1.64 (1.18–2.27), 3.31 (2.03–5.41). There were no nominally statistically significant interactions (p < 0.05) between randomized treatment allocation and eGFR for clinical outcomes, with the exception of the outcome of coronary heart disease death or nonfatal myocardial infarction (p = 0.021), with the interaction suggesting increased benefit of statin treatment in subjects with impaired GFRs.
Conclusions
We have established that, in an elderly population over the age of 70 y, impaired GFR is associated with female sex, with presence of vascular disease, and with levels of other risk factors that would be associated with increased risk of vascular disease. Further, impaired GFR is independently associated with significant levels of increased risk of all cause mortality and fatal vascular events and with composite fatal and nonfatal coronary and heart failure outcomes. Our analyses of the benefits of statin treatment in relation to baseline GFR suggest that there is no reason to exclude elderly patients with impaired renal function from treatment with a statin.
Using data from the PROSPER trial, Ian Ford and colleagues investigate whether reduced glomerular filtration rate is associated with cardiovascular and mortality risk among elderly people.
Editors' Summary
Background.
Cardiovascular disease (CVD)—disease that affects the heart and/or the blood vessels—is a common cause of death in developed countries. In the USA, for example, the single leading cause of death is coronary heart disease, a CVD in which narrowing of the heart's blood vessels slows or stops the blood supply to the heart and eventually causes a heart attack. Other types of CVD include stroke (in which narrowing of the blood vessels interrupts the brain's blood supply) and heart failure (a condition in which the heart can no longer pump enough blood to the rest of the body). Many factors increase the risk of developing CVD, including high blood pressure (hypertension), high blood cholesterol, having diabetes, smoking, and being overweight. Tools such as the “Framingham risk calculator” assess an individual's overall CVD risk by taking these and other risk factors into account. CVD risk can be minimized by taking drugs to reduce blood pressure or cholesterol levels (for example, pravastatin) and by making lifestyle changes.
Why Was This Study Done?
Another potential risk factor for CVD is impaired kidney (renal) function. In healthy people, the kidneys filter waste products and excess fluid out of the blood. A reduced “estimated glomerular filtration rate” (eGFR), which indicates impaired renal function, is associated with increased CVD in young and middle-aged people and increased all-cause and cardiovascular death in people who have vascular disease. But is reduced eGFR also associated with CVD and death in older people? If it is, it would be worth encouraging elderly people with reduced eGFR to avoid other CVD risk factors. In this study, the researchers determine the predictive value of eGFR for all-cause and vascular mortality (deaths caused by CVD) and for incident vascular events (a first heart attack, stroke, or heart failure) using data from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER). This clinical trial examined pravastatin's effects on CVD development among 70–82 year olds with pre-existing vascular disease or an increased risk of CVD because of smoking, hypertension, or diabetes.
What Did the Researchers Do and Find?
The trial participants were divided into four groups based on their eGFR at the start of the study. The researchers then investigated the association between baseline CVD risk factors and baseline eGFR and between baseline eGFR and vascular events and deaths that occurred during the 3-year study. Several established CVD risk factors were associated with a reduced eGFR after allowing for other risk factors. In addition, people with a low eGFR (between 20 and 40 units) were twice as likely to die from any cause as people with an eGFR above 60 units (the normal eGFR for a young person is 100 units; eGFR decreases with age) and more than three times as likely to have nonfatal coronary heart disease or heart failure. A low eGFR also increased the risk of vascular mortality, other noncancer deaths, and fatal coronary heart disease and heart failure. Finally, pravastatin treatment reduced coronary heart disease deaths and nonfatal heart attacks most effectively among participants with the greatest degree of eGFR impairment.
What Do These Findings Mean?
These findings suggest that, in elderly people, impaired renal function is associated with levels of established CVD risk factors that increase the risk of vascular disease. They also suggest that impaired kidney function increases the risk of all-cause mortality, fatal vascular events, and fatal and nonfatal coronary heat disease and heart failure. Because the study participants were carefully chosen for inclusion in PROSPER, these findings may not be generalizable to all elderly people with vascular disease or vascular disease risk factors. Nevertheless, increased efforts should probably be made to encourage elderly people with reduced eGFR and other vascular risk factors to make lifestyle changes to reduce their overall CVD risk. Finally, although the effect of statins in elderly patients with renal dysfunction needs to be examined further, these findings suggest that this group of patients should benefit at least as much from statins as elderly patients with healthy kidneys.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000016.
The MedlinePlus Encyclopedia has pages on coronary heart disease, stroke, and heart failure (in English and Spanish)
MedlinePlus provides links to many other sources of information on heart disease, vascular disease, and stroke (in English and Spanish)
The US National Institute of Diabetes and Digestive and Kidney Diseases provides information on how the kidneys work and what can go wrong with them, including a list of links to further information about kidney disease
The American Heart Association provides information on all aspects of cardiovascular disease for patients, caregivers, and professionals (in several languages)
More information about PROSPER is available on the Web site of the Vascular Biochemistry Department of the University of Glasgow
doi:10.1371/journal.pmed.1000016
PMCID: PMC2628400  PMID: 19166266
4.  Multicenter Epidemiological Study to Assess the Population of CKD Patients in Greece: Results from the PRESTAR Study 
PLoS ONE  2014;9(11):e112767.
Background
Chronic Kidney Disease (CKD) is a relatively common condition not only associated with increased morbidity and mortality but also fuelling End Stage Renal Disease (ESRD). Among developed nations, Greece has one of the highest ESRD incidence rates, yet there is limited understanding of the epidemiology of earlier stages of CKD.
Methods
Cross-sectional survey of pre-dialysis CKD outpatients in nephrology clinics in the National Health Care system between October 2009 and October 2010. Demographics, cause of CKD, blood pressure, level of renal function, duration of CKD and nephrology care, and specialty of referral physician were collected and analyzed. Different methods for estimating renal function (Cockroft-Gault [CG], CKD-Epi and MDRD) and staging CKD were assessed for agreement.
Results
A total of 1,501 patients in 9 centers were enrolled. Diabetic nephropathy was the most common nephrologist assigned cause of CKD (29.7%). In total, 36.5% of patients had self-referred to the nephrologist; patients with diabetes or serum creatinine above 220 µmol/l (eGFR<40 ml/min/1.73 m2) were more likely to have been referred by a physician. Agreement between MDRD and CKD-Epi, but not between CG, the other estimating equations, was excellent. There was substantial heterogeneity with respect to renal diagnoses, referral patterns and blood pressure among participating centers.
Conclusions
In this first epidemiologic assessment of CKD in Greece, we documented delayed referral and high rates of self-referral among patients with CKD. eGFR reporting, currently offered by a limited number of laboratories, may facilitate detection of CKD at an earlier, more treatable stage.
doi:10.1371/journal.pone.0112767
PMCID: PMC4236082  PMID: 25406080
5.  Age and the Association of Kidney Measures with Mortality and End-Stage Renal Disease 
Context
Chronic kidney disease (CKD) is prevalent in older individuals, but the risk implications of low estimated glomerular filtration rate (eGFR) and high albuminuria across the full age range are controversial.
Objective
To evaluate possible effect modification (interaction) of age on the association of estimated GFR and albuminuria with clinical risk examining both relative and absolute risk.
Design, Setting, Participants
We investigated 2,051,244 participants from 33 general population or high-risk (of vascular disease) cohorts and 13 CKD cohorts from Asia, Australesia, Europe, and North/South America conducted during 1972–2011 with mean follow-up time of 5.8 years (range 0–31 years).
Main Outcome Measures
Hazard ratios (HRs) of mortality and end-stage renal disease (ESRD) according to eGFR and albuminuria were meta-analyzed across age categories after adjusting for sex, race, cardiovascular disease, diabetes, systolic blood pressure, cholestserol, body mass index, and smoking. Absolute risks were estimated using HRs and average incidence rates.
Results
Mortality (112,325 deaths) and ESRD (8,411 events) risk were higher at lower eGFR and higher albuminuria in every age category. In general/high-risk cohorts, relative mortality risk for reduced eGFR decreased with increasing age: e.g., adjusted HRs (95% CI) at eGFR 45 vs. 80 ml/min/1.73m2 were 3.50 (2.55–4.81), 2.21 (2.02–2.41), 1.59 (1.42–1.77), and 1.35 (1.23–1.48) in age categories 18–54, 55–64, 65–74 and 75+ years, respectively (P-values for age interaction <0.05). Absolute risk differences for the same comparisons were higher at older age (9.0 [95% CI, 6.0–12.8], 12.2 [10.3–14.3], 13.3 [9.0–18.6], and 27.2 [13.5–45.5] excess deaths per 1,000 person-years, respectively). For increased albuminuria, reduction of relative risk with increasing age were less evident, while differences in absolute risk were higher in the older age categories (7.5 [95% CI, 4.3–11.9], 12.2 [7.9–17.6], 22.7 [15.3–31.6], and 34.3 [19.5–52.4] excess deaths per 1,000 person-years, respectively by age category, at ACR 300 mg/g compared to 10 mg/g). In CKD cohorts, adjusted relative hazards of mortality did not decrease with age. In all cohorts, ESRD relative risks and absolute risk differences at lower eGFR or higher albuminuria were comparable across age categories.
Conclusions
Both low eGFR and high albuminuria were independently associated with mortality and ESRD regardless of age across a wide range of populations. Mortality showed lower relative risk but higher absolute risks differences at older age.
doi:10.1001/jama.2012.16817
PMCID: PMC3936348  PMID: 23111824
6.  Estimated GFR and Incident Cardiovascular Disease Events in American Indians: The Strong Heart Study 
Background
In populations with high prevalence of diabetes and obesity, estimating glomerular filtration rate (GFR) by using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation may predict cardiovascular disease risk better than by using the Modification of Diet in Renal Disease (MDRD) Study equation.
Study design
Longitudinal cohort study comparing the association of GFR estimated using either the CKD-EPI or MDRD Study equations with incident cardiovascular disease outcomes.
Setting and participants
American Indians participating in the Strong Heart Study, a longitudinal population-based cohort with high prevalences of diabetes, cardiovascular disease, and CKD.
Predictor or factor
eGFR predicted using the CKD-EPI and MDRD Study equations.
Outcomes
Fatal and nonfatal cardiovascular events, consisting of coronary heart disease, stroke, and heart failure.
Measurements
The association between eGFR and outcomes was explored in Cox proportional hazards models, adjusted for traditional risk factors and albuminuria; the net reclassification index and integrated discrimination improvement were determined for the CKD-EPI versus MDRD Study equations.
Results
Among 4549 participants, diabetes was present in 45%, cardiovascular disease in 7%, and stage 3–5 CKD in 10%. Over a median of 15 years, there were 1280 cases of incident CVD, 929 of incident coronary heart disease, 305 of incident stroke, and 381 of incident heart failure. Reduced eGFR (<90 mL/min/1.73 m2) was associated with adverse events in most models. Compared with the MDRD Study equation, the CKD-EPI equation correctly reclassified 17.0% of 2,151 participants without incident CVD to a lower risk (higher eGFR) category and 1.3% (n=28) were incorrectly reclassified to a higher risk (lower eGFR) category.
Limitations
Single measurements of eGFR and albuminuria at study visits.
Conclusions
Although eGFR based on either equation had similar associations with incident cardiovascular disease, coronary heart disease, stroke, and heart failure events, among those not having events, reclassification of participants to eGFR categories was superior using the CKD-EPI equation compared with the MDRD Study equation.
doi:10.1053/j.ajkd.2012.06.015
PMCID: PMC3473098  PMID: 22841159
cardiovascular disease risk; chronic kidney disease; estimated glomerular filtration rate; Strong Heart Study
7.  Race differences in prevalence of chronic kidney disease among young adults using creatinine-based glomerular filtration rate-estimating equations 
Nephrology Dialysis Transplantation  2010;25(12):3934-3939.
Background. Despite a higher incidence of end-stage renal disease (stage 5), blacks have been shown to have the same or lower prevalence of chronic kidney disease (CKD stages 3 and 4). Current creatinine-based glomerular filtration rate (GFR)-estimating equations may misclassify young, healthy blacks.
Methods. Among 3501 young adults (mean age 45), we compared the prevalence of CKD in blacks and whites using the Modification of Diet in Renal Disease (MDRD) and the CKD Epidemiology Collaboration (CKD-EPI) equations. In addition, we used measured creatinine excretion rates to determine the actual excretion ratio for CARDIA (race coefficient 12%) and applied this to the CKD-EPI equation. We also studied the prevalence of CKD risk factors among black and white participants near the CKD threshold cut-off (eGFR CKD-EPI 60–80 mL/min/1.73 m2) to estimate the relative likelihood of misclassification in blacks and whites.
Results. Using the MDRD equation, prevalence of CKD stages 4 and 5 was higher for blacks compared with whites (0.6% vs. 0.1%, P-value 0.05). In contrast, prevalence of eGFR <60 mL/min/1.73 m2 was significantly higher for whites (3.6%) compared with blacks (1.9%), due to higher prevalence of stage 3 among whites. Prevalence of CKD was similar for blacks and whites using CKD-EPI equation (1.2%), but was higher among blacks when using the CARDIA-derived race coefficient (1.6% vs.1.2%, P-value = 0.03). Among persons with eGFR by CKD-EPI of 60–80 mL/min/1.73 m2, blacks had higher levels of albuminuria, uric acid, systolic blood pressure and higher diabetes prevalence.
Conclusions. CKD classification among young blacks is very sensitive to the race coefficients. Despite whites having higher rates of CKD stage 3, blacks with eGFRs just above the CKD threshold had higher rates of CKD risk factors. Current equations used to define CKD may systematically miss a high-risk group of blacks at a time in the disease course when interventions are crucial.
doi:10.1093/ndt/gfq299
PMCID: PMC3108366  PMID: 20519233
chronic kidney disease; glomerular filtration rate; race
8.  Low documentation of chronic kidney disease among high-risk patients in a managed care population: a retrospective cohort study 
BMC Nephrology  2009;10:25.
Background
Early detection of chronic kidney disease (CKD) is sub-optimal among the general population and among high risk patients. The prevalence and impact of major CKD risk factors, diabetes (DM) and hypertension (HTN), on CKD documentation among managed care populations have not been previously reported. We examined this issue in a Kaiser Permanente Georgia (KPG) CKD cohort.
Methods
KPG enrollees were included in the CKD cohort if they had eGFRs between 60 and 365 days apart that were <90 ml/min during 1999-2006. The current analysis is restricted to participants with eGFR 10-59 ml/min/1.73 m2. CKD documentation was defined as a presenting diagnosis of CKD by a primary care physician or nephrologist using ICD-9 event codes. The association between CKD documentation and DM and HTN were assessed with multivariate logistic regression models.
Results
Of the 50,438 subjects within the overall KPG CKD cohort, 20% (N = 10,266) were eligible for inclusion in the current analysis. Overall, CKD diagnosis documentation was low; only 14.4% of subjects had an event-based CKD diagnosis at baseline. Gender and types 2 diabetes interacted on CKD documentation. The prevalence of CKD documentation increased with the presence of hypertension and/or type 2 diabetes, but type 2 diabetes had a lower effect on CKD documentation. In multivariate analysis, significant predictors of CKD documentation were eGFR, hypertension, type 2 diabetes, congestive heart failure, peripheral artery disease, statin use, age and gender. CKD documentation was lower among women than similarly affected men.
Conclusion
Among patients with an eGFR 10-59, documentation of CKD diagnosis by primary and subspecialty providers is low within a managed care patient cohort. Gender disparities in CKD documentation observed in the general population were also present among KPG CKD enrollees.
doi:10.1186/1471-2369-10-25
PMCID: PMC2753574  PMID: 19758452
9.  High Prevalence of Stage 3 Chronic Kidney Disease in Older Adults Despite Normal Serum Creatinine 
BACKGROUND
Serum creatinine is commonly used to diagnose chronic kidney disease (CKD), but may underestimate CKD in older adults when compared with using glomerular filtration rates (eGFR). The magnitude of this underestimation is not clearly defined.
OBJECTIVE
Using the Modification of Diet in Renal Disease (MDRD) equation, to describe both the prevalence and the magnitude of underestimation of stage 3 CKD (GFR 30–59 ml/min/1.73 m2), as well as ideal serum creatinine cutoff values to diagnose stage 3 CKD among Americans ≥65 years of age.
DESIGN
Cross-sectional.
PARTICIPANTS
A total of 3,406 participants ≥65 years of age from the 1999–2004 National Health and Nutrition Examination Surveys (NHANES).
MEASUREMENTS
Serum creatinine levels were used to determine eGFR from the MDRD equation. Information on clinical conditions was self-reported.
RESULTS
Overall, 36.1% of older adults in the US have stage 3 or greater CKD as defined by eGFR values. Among older adults with stage 3 CKD, 80.6% had creatinine values ≤1.5 mg/dl, and 38.6% had creatinine values ≤1.2 mg/dl. Optimal cutoff values for serum creatinine in the diagnosis of stage 3 CKD in older adults were ≥1.3 mg/dl for men and ≥1.0 mg/dl for women, regardless of the presence or absence of hypertension, diabetes, or congestive heart failure.
CONCLUSION
Use of serum creatinine underestimates the presence of advanced (stage 3 or greater) CKD among older adults in the US. Automated eGFR reporting may improve the accuracy of risk stratification for older adults with CKD.
doi:10.1007/s11606-008-0850-3
PMCID: PMC2607515  PMID: 18987917
chronic kidney disease; serum creatinine; older adults; glomerular filtration rate
10.  Risk Factors for Chronic Kidney Disease among American Indians and Alaska Natives – Findings from the Kidney Early Evaluation Program 
American Journal of Nephrology  2008;29(5):440-446.
Background
American Indians and Alaska Natives (AIAN) have a high incidence of end-stage renal disease. Less is known about chronic kidney disease (CKD) among AIAN and whether risk factors differ for low estimated glomerular filtration rate (eGFR) versus albuminuria with a normal eGFR.
Methods
Cross-sectional study examining the associations of age, sex, smoking, obesity, diabetes, hypertension, family history, and geographic region with CKD among a screened population of AIAN participants in the Kidney Early Evaluation Program from 2000 to 2006. CKD was defined by the presence of either a low eGFR, <60 ml/min/1.73 m2, or albuminuria, a urine albumin/creatinine ratio ≥30 mg/g.
Results
The prevalence of any CKD was 29%, of low eGFR was 17%, and of albuminuria with a normal eGFR was 12%. Older age was the strongest predictor of low eGFR (61+ years OR 8.42, 95% CI 5.92–11.98), followed by hypertension (OR 2.38, 95% CI 1.74–3.26). In contrast, diabetes (OR 2.04, 95% CI 1.57–2.64) and hypertension (OR 2.63, 95% CI 1.93–3.59) were the only predictors of albuminuria among persons with a normal eGFR.
Conclusion
The burden of CKD was high among this screened population of AIAN, and different risk factor patterns were associated with low eGFR and albuminuria. Innovative programs and longitudinal research are needed to address CKD among AIAN.
doi:10.1159/000174857
PMCID: PMC2821946  PMID: 19011277
Chronic kidney disease; Risk factors; American Indians; Alaska Natives
11.  Prevalence and Risk Factors of CKD in Chinese Patients with Periodontal Disease 
PLoS ONE  2013;8(8):e70767.
Background
Periodontal disease is common among adults and is associated with an increasing risk of chronic kidney disease (CKD). We aimed to investigate the prevalence and risk factors of CKD in patients with periodontal disease in China.
Methods
In the current cross-sectional study, patients with periodontal disease were included from Guangdong Provincial Stomatological Hospital between March 2011 and August 2011. CKD was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, the presence of albuminuria, or hematuria. All patients with periodontal disease underwent a periodontal examination, including periodontal probing pocket depth, gingival recession, and clinical attachment level by Florida Probe. They completed a questionnaire and had blood and urine samples taken. The adjusted prevalence of indicators of kidney damage was calculated and risk factors associated with CKD were analyzed.
Results
A total of 1392 patients with periodontal disease were invited to participate this study and 1268 completed the survey and examination. After adjusting for age and sex, the prevalence of reduced eGFR, albuminuria, and hematuria was 2.7% (95% CI 1.7–3.7), 6.7% (95% CI 5.5–8.1) and 10.9% (95% CI 9.2–12.5), respectively. The adjusted prevalence of CKD was 18.2% (95% CI 16.2–20.3). Age, male, diabetes, hypertension, history of CKD, hyperuricemia, and interleukin-6 levels (≥7.54 ng/L) were independent risk factors for reduced eGFR. Female, diabetes, hypertension, history of CKD, hyperuricemia, high level of cholesterol, and high sensitivity C-reactive protein (hsCRP) (≥1.03 mg/L) and TNF-α levels (≥1.12 ng/L) were independently associated with an increased risk of albuminuria. Female, lower education (
Conclusions
18.2% of Chinese patients with periodontal disease have proteinuria, hematuria, or reduced eGFR, indicating the presence of kidney damage. Whether prevention or treatment of periodontal disease can reduce the high prevalence of CKD, however, remains to be further investigated.
doi:10.1371/journal.pone.0070767
PMCID: PMC3737364  PMID: 23951003
PLoS Medicine  2007;4(9):e270.
Background
End-stage chronic kidney disease is associated with striking excesses of cardiovascular mortality, but it is uncertain to what extent renal function is related to risk of subsequent coronary heart disease (CHD) in apparently healthy adults. This study aims to quantify the association of markers of renal function with CHD risk in essentially general populations.
Methods and Findings
Estimated glomerular filtration rate (eGFR) was calculated using standard prediction equations based on serum creatinine measurements made in 2,007 patients diagnosed with nonfatal myocardial infarction or coronary death during follow-up and in 3,869 people without CHD in the Reykjavik population-based cohort of 18,569 individuals. There were small and nonsignificant odds ratios (ORs) for CHD risk over most of the range in eGFR, except in the lowest category of the lowest fifth (corresponding to values of <60 ml/min/1.73m2), in which the OR was 1.33 (95% confidence interval 1.01–1.75) after adjustment for several established cardiovascular risk factors. Findings from the Reykjavik study were reinforced by a meta-analysis of six previous reports (identified in electronic and other databases) involving a total of 4,720 incident CHD cases (including Reykjavik), which yielded a combined risk ratio of 1.41 (95% confidence interval 1.19–1.68) in individuals with baseline eGFR less than 60 ml/min/1.73m2 compared with those with higher values.
Conclusions
Although there are no strong associations between lower-than-average eGFR and CHD risk in apparently healthy adults over most of the range in renal function, there may be a moderate increase in CHD risk associated with very low eGFR (i.e., renal dysfunction) in the general population. These findings could have implications for the further understanding of CHD and targeting cardioprotective interventions.
John Danesh and colleagues conclude there may be a moderate increase in risk of coronary heart disease associated with very low estimated glomerular filtration rate.
Editors' Summary
Background.
Coronary heart disease (CHD), the leading cause of death in most Western countries, is a “cardiovascular” disease—literally a disorder affecting the heart and/or blood vessels. In CHD, the blood vessels that supply the heart become increasingly narrow. Eventually, the flow of blood to the heart slows or stops, causing chest pains (angina), breathlessness, and heart attacks. Many factors increase the risk of developing CHD and other cardiovascular diseases, including high blood pressure, high blood levels of cholesterol (a type of fat), or being overweight. Individuals can reduce their chances of developing cardiovascular disease by taking drugs to reduce their blood pressure or cholesterol levels or by making lifestyle changes (so-called cardioprotective interventions). Another important risk factor for cardiovascular disease is end-stage chronic kidney disease (CKD), a condition in which the kidneys stop working. (In healthy people, the kidneys remove waste products and excess fluid from the body.) People with end-stage CKD (which is treated by dialysis) have about a five times higher risk of dying from cardiovascular disease compared with healthy people.
Why Was This Study Done?
End-stage CKD is preceded by a gradual loss of kidney function. There is a clear association between non-dialysis–dependent CKD and the incidence of cardiovascular events (such as heart attacks) in people who already have signs of cardiovascular disease. But are people with slightly dysfunctional kidneys (often because of increasing age) but without any obvious cardiovascular disease at greater risk of developing cardiovascular diseases than people with fully functional kidneys? If the answer is yes, it might be possible to reduce CHD deaths by minimizing the exposure of people with CKD to other risk factors for cardiovascular disease. In this study, the researchers have taken two approaches to answer this question. In a population-based study, they have examined whether there is any association in healthy adults between kidney function measured at the start of the study and incident CHD (the first occurrence of CHD) over subsequent years. In addition, they have systematically searched the published literature for similar studies and combined the results of these studies using statistical methods, a so-called “meta-analysis.”
What Did the Researchers Do and Find?
Between 1967 and 1991, nearly 19,000 middle-aged men and women without a history of heart attacks living in Reykjavik, Iceland, enrolled in a prospective study of cardiovascular disease. Baseline blood samples were taken at enrollment and the participants' health monitored for 20 years on average. The researchers identified 2,007 participants who suffered a nonfatal heart attack or died of CHD during follow-up and 3,869 who remained disease free. They then calculated the estimated glomerular filtration rate (eGFR; a measure of kidney function) for each participant from baseline creatinine measurements (creatinine is a muscle waste product). There was no association between lower-than-average eGFRs and the risk of developing CHD over most of the range of eGFR values. However, people whose eGFR was below approximately 60 units had about a 40% higher risk of developing CHD after allowing for established cardiovascular risk factors than individuals with higher eGFRs. This finding was confirmed by the meta-analysis of six previous studies, which included a further 2,700 incident CHD cases.
What Do These Findings Mean?
These findings indicate that people with an eGFR below about 60 units (the cut-off used to define CKD) may have an increased risk of developing CHD. They also indicate a nonliner association between kidney function and CHD risk. That is, any association with CHD became evident only when the eGFR dropped below about 60 units. These findings need confirming in different ethnic groups and by using more accurate methods to measure eGFRs. Nevertheless, they suggest that improving kidney function across the board is unlikely to have much effect on the overall incidence of CHD. Instead, they suggest that targeting cardioprotective interventions at the one in ten adults in Western countries whose eGFR is below 60 units might be a good way to reduce the burden of CHD.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040270.
MedlinePlus encyclopedia pages on coronary heart disease, chronic kidney failure, and end-stage kidney disease (in English and Spanish).
Information for patients and carers from the American Heart Association on all aspects of heart disease, including prevention of CHD
Information from the British Heart Foundation on heart disease and on keeping the heart healthy
Information on chronic kidney disease from the US National Kidney Foundation, and the US National Kidney and Urologic Diseases Information Clearing House (in English and Spanish)
Information on chronic kidney disease from the UK National Kidney Foundation
doi:10.1371/journal.pmed.0040270
PMCID: PMC1961630  PMID: 17803353
BMC Nephrology  2013;14:132.
Background
For chronic kidney disease (CKD) patients, national treatment guidelines recommend a low-density lipoprotein cholesterol (LDL-C) goal <100 mg/dL and blood pressure (BP) target <130/80 mmHg. This analysis assessed the current status of cardiovascular (CV) risk factor treatment and control in US adults with CKD.
Methods
Weighted prevalence estimates of CV-related comorbidities, utilization of lipid- and BP-lowering agents, and LDL-C and BP goal attainment in US adults with CKD were assessed among 9,915 men and nonpregnant women aged ≥20 years identified from the fasting subsample of the 2001–2010 National Health and Nutritional Examination Survey (NHANES). Analyses were performed using SAS survey procedures that consider the complex, multistage, probability sampling design of NHANES. All estimates were standardized to the 2008 US adult population (≥20 years). Data were stratified by CKD stage based on presence of albuminuria and estimated glomerular filtration rate (eGFR), calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Stage 3 CKD was subdivided into 3a (eGFR 45–59 mL/min/1.73 m2) and 3b (eGFR 30–44 mL/min/1.73 m2); Stage 5 CKD and dialysis recipients were excluded.
Results
Of the 9,915 NHANES participants identified for analysis, 1,428 had CKD (Stage 1–4), corresponding to a prevalence estimate for US adults aged ≥20 years of 10.2%. Prevalence of CV-related comorbidities increased markedly with CKD stage, with a ~6–12-fold increase in cardiovascular disease, coronary heart disease (CHD), stroke and congestive heart failure between CKD Stage 1 and 4; prevalence of diabetes, hyperlipidemia and hypertension increased by ~1.2–1.6-fold. Use of lipid-lowering agents increased with CKD stage, from 18.1% (Stage 1) to 44.8% (Stage 4). LDL-C goal attainment increased from 35.8% (Stage 1) to 52.8% (Stage 3b), but decreased in Stage 4 (50.7%). BP goal attainment decreased between Stage 1 and 4 (from 49.5% to 30.2%), despite increased use of antihypertensives (from 30.2% to 78.9%).
Conclusions
Individuals with CKD have a high prevalence of CV-related comorbidities. However, attainment of LDL-C or BP goals was low regardless of disease stage. These findings highlight the potential for intensive risk factor modification to maximize CV event reduction in CKD patients at high risk for CHD.
doi:10.1186/1471-2369-14-132
PMCID: PMC3701605  PMID: 23802885
Chronic Kidney Disease; Low-density Lipoprotein Cholesterol; Blood Pressure; Cardiovascular Risk Factors; Goal Attainment
Background
The National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative (NKF’s KDOQI) staging system for chronic kidney disease (CKD) is based primarily on estimated GFR (eGFR). This study aimed at assessing whether reclassification of subjects with type 2 diabetes using two recent classifications based on both eGFR and albuminuria, the Alberta Kidney Disease Network (AKDN) and the Kidney Disease: Improving Global Outcomes (KDIGO), provides a better definition of burden from cardiovascular disease (CVD) and diabetic retinopathy (DR) than the NKF’s KDOQI classification.
Methods
This is a cross-sectional analysis of patients with type 2 diabetes (n = 15,773) from the Renal Insufficiency And Cardiovascular Events Italian Multicenter Study, consecutively visiting 19 Diabetes Clinics throughout Italy in years 2007-2008. Exclusion criteria were dialysis or renal transplantation. CKD was defined based on eGFR, as calculated from serum creatinine by the simplified Modification of Diet in Renal Disease Study equation, and albuminuria, as measured by immunonephelometry or immunoturbidimetry. DR was assessed by dilated fundoscopy. Prevalent CVD, total and by vascular bed, was assessed from medical history by recording previous documented major acute events.
Results
Though prevalence of complications increased with increasing CKD severity with all three classifications, it differed significantly between NKF’s KDOQI stages and AKDN or KDIGO risk categories. The AKDN and KDIGO systems resulted in appropriate reclassification of uncomplicated patients in the lowest risk categories and a more graded independent association with CVD and DR than the NKF’s KDOQI classification. However, CVD, but not DR prevalence was higher in the lowest risk categories of the new classifications than in the lowest stages of the NKF’s KDOQI, due to the inclusion of subjects with reduced eGFR without albuminuria. CVD prevalence differed also among eGFR and albuminuria categories grouped into AKDN and KDIGO risk category 1 and moderate, respectively, and to a lesser extent into higher risk categories.
Conclusions
Though the new systems perform better than the NKF’s KDOQI in grading complications and identifying diabetic subjects without complications, they might underestimate CVD burden in patients assigned to lower risk categories and should be tested in large prospective studies.
Trial registration
ClinicalTrials.gov; NCT00715481
doi:10.1186/1475-2840-13-59
PMCID: PMC4008155  PMID: 24624891
Chronic kidney disease; Classification; eGFR; Albuminuria; Cardiovascular disease; Diabetic retinopathy
Background
The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) recently published an equation for estimated glomerular filtration rate (eGFR) using the same variables (serum creatinine, age, gender and race) as the Modification of Diet in Renal Disease Study (MDRD) equation. Although the CKD-EPI equation estimates GFR more precisely as compared with the MDRD equation, whether this equation improves risk prediction is unknown.
Study Design
Prospective cohort study, the Atherosclerosis Risk in Communities (ARIC) Study.
Setting & Participants
13,905 middle-aged participants without a history of cardiovascular disease with median follow-up of 16.9 years.
Predictor
eGFR
Outcomes & Measurements
We compared the association of eGFR in categories (≥120, 90–119, 60–89, 30–59, <30 ml/min/1.73m2) by the CKD-EPI and MDRD equations with risk of incident end-stage renal disease (ESRD), all-cause mortality, coronary heart disease (CHD), and stroke.
Results
Median of eGFRCKD-EPI was higher than that of eGFRMDRD (97.6 vs. 88.8 ml/min/1.73m2, P<0.001). The CKD-EPI equation reclassified 44.9% (n=3,079) and 43.5% (n=151) of participants with eGFRMDRD 60–89 and 30–59, respectively, upward to a higher eGFR category but no one with eGFRMDRD 90–119 or <30, lowering the prevalence of CKD stage 3–5 from 2.7% to 1.6%. Participants with eGFRMDRD 30–59 who were reclassified upward had lower risk as compared to those who were not reclassified (ESRD incidence rate ratio, 0.10 [95% CI, 0.03–0.33], all-cause mortality, 0.30 [0.19–0.48], CHD, 0.36 [0.21–0.61], stroke, 0.50 [0.24–1.01]). Similar results were observed for participants with eGFRMDRD 60–89. More frequent reclassification of younger, female, and white participants explained some of these trends. Net reclassification improvement among participants with eGFR <120 was positive for all outcomes (P<0.001).
Limitations
Limited number of cases with eGFR <60 and no measurement of albuminuria.
Conclusions
The CKD-EPI equation more appropriately categorized individuals with respect to long-term clinical risk as compared to the MDRD equation, suggesting improved clinical usefulness in this middle-aged population.
doi:10.1053/j.ajkd.2009.12.016
PMCID: PMC2858455  PMID: 20189275
American Journal of Kidney Diseases  2011;57(3 Suppl 2):S9-16.
Background
The National Kidney Foundation has recommended that the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation replace the Modification of Diet in Renal Disease (MDRD) Study equation. Before implementing this change in the Kidney Early Evaluation Program (KEEP), we compared characteristics of reclassified individuals and mortality risk predictions using the new equation.
Methods
Of 123,704 eligible KEEP participants, 116,321 with data available for this analysis were included. Glomerular filtration rate (GFR) was estimated using the MDRD Study (eGFRMDRD) and CKD-EPI (eGFRCKD-EPI) equations with creatinine level calibrated to standardized methods. Participants were characterized by eGFR category: >120, 90-119, 60-89, 45-59, 30-44, and <30 mL/min/1.73 m2. Clinical characteristics ascertained included age, race, sex, diabetes, hypertension, coronary artery disease, congestive heart failure, cerebrovascular disease, peripheral vascular disease, and anemia. Mortality was determined over a median of 3.7 years of follow-up.
Results
The prevalence of eGFRCKD-EPI <60 mL/min/1.73 m2 was 14.3% compared with 16.8% using eGFRMDRD. Using eGFRCKD-EPI, 20,355 participants (17.5%) were reclassified to higher eGFR categories, and 3,107 (2.7%), to lower categories. Participants reclassified upward were younger and less likely to have chronic conditions, with a lower risk of mortality. A total of 3,601 deaths (3.1%) were reported. Compared with participants classified to eGFR of 45-59 mL/min/1.73 m2 using both equations, those with eGFRCKD-EPI of 60-89 mL/min/1.73 m2 had a lower mortality incidence rate (6.4 [95% CI, 5.1-7.7] vs 18.5 [95% CI, 17.1-19.9]). Results were similar for all eGFR categories. Net reclassification improvement was 0.159 (P < 0.001).
Conclusions
The CKD-EPI equation reclassifies people at lower risk of CKD and death into higher eGFR categories, suggesting more accurate categorization. The CKD-EPI equation will be used to report eGFR in KEEP.
doi:10.1053/j.ajkd.2010.11.007
PMCID: PMC3298760  PMID: 21338849
Chronic kidney disease; glomerular filtration rate estimation; mortality; risk factors
BMC Nephrology  2013;14:183.
Background
The number of adults with diabetes mellitus is increasing worldwide, particularly in Asia and Africa. In sub-Saharan Africa, renal complications of diabetes may go unrecognized due to limited diagnostic resources. The prevalence of chronic kidney disease (CKD) among adult diabetics in sub-Saharan Africa has not been well described.
Methods
This study was conducted at the diabetes mellitus clinic of Bugando Medical Centre in Mwanza, Tanzania. A total 369 consecutive adult diabetic patients were enrolled and interviewed. Each patient provided a urine sample for microalbuminuria and proteinuria and a blood sample for serum creatinine level. Estimated glomerular filtration rate (eGFR) was calculated using the Cockroft-Gault equation. CKD was staged according to the Kidney Disease Improving Global Outcomes system.
Results
A total of 309 (83.7%) study participants had CKD; 295 (80.0%) had significant albuminuria and 91 (24.7%) had eGFR < 60 ml/min. None of these patients were aware of their renal disease, and only 5 (1.3%) had a diagnosis of diabetic nephropathy recorded in their file. Older age was significantly associated with CKD in this population [OR 1.03, p = 0.03, 95%CI (1.00-1.05)].
Conclusions
Chronic kidney disease is highly prevalent among adult diabetic outpatients attending our clinic in Tanzania, but is usually undiagnosed. Nearly ¼ of patients had an eGFR low enough to require dose adjustment of diabetic medications. More diagnostic resources are needed for CKD screening among adults in Tanzania in order to slow progression and prevent complications.
doi:10.1186/1471-2369-14-183
PMCID: PMC3765892  PMID: 24228774
Diabetes mellitus; Microalbuminuria; Proteinuria; CKD; Chronic kidney disease; Sub-Saharan Africa
Nephrology Dialysis Transplantation  2012;27(7):2839-2847.
lipoprotein risk factors for atherosclerosis, i.e., increased LDL cholesterol, increased triglycerides and decreased HDL cholesterol, also are associated with progression of loss of kidney function...Goek and coworkers describe the association of the apoliproteins A1 and B and eGFR in two large cohorts derived from the general polulation [the NHANES III (N=7,023) and the ARIC study (n=10,292)]. The results were similar in both cohorts...
Background
Circulating lipoproteins and their protein constituents, apolipoproteins, are risk factors for chronic kidney disease (CKD). The associations between apolipoprotein A1, apolipoprotein B and their ratio with glomerular filtration rate estimated from the new CKD Epidemiology Collaboration (CKD-EPI) equation (eGFR) are not well studied in the general population.
Methods
Associations between apolipoprotein A1, B and their ratio with the outcomes of eGFR, CKD (eGFR <60 mL/min/1.73m2) and albuminuria were examined in the Atherosclerosis Risk in Communities study (ARIC, n = 10 292, 1996–98) and the Third National Health and Nutrition Examination Survey (NHANES III, n = 7023, 1988–91). Cross-sectional multivariable-adjusted analyses were performed using linear and logistic regression. Prospective analyses related baseline apolipoprotein levels to subsequent CKD incidence over 10 years using the ARIC Carotid MRI follow-up cohort (n = 1659).
Results
Higher apolipoprotein A1 quartiles were associated with a lower prevalence of CKD [Q4 versus Q1: odds ratio (OR) 0.73, P-trend = 0.02 in ARIC; Q4 versus Q1: OR 0.53, P-trend <0.01 in NHANES III] as well as with higher eGFR (P-trend <0.01 in ARIC and NHANES III). No consistent significant associations were found for apolipoprotein B in either study. The apolipoprotein B/A1 ratio was significantly associated with eGFR across quartiles in both studies (P-trend <0.01) and with CKD in ARIC (Q4 versus Q1: OR 1.23, P-trend = 0.01). Prospectively, there were trends for the association of apolipoproteins with incident CKD [Q4 versus Q1: incidence rate ratio (IRR) = 0.68 for apolipoprotein A1, P-trend = 0.1; Q4 versus Q1: IRR = 1.35 for apolipoprotein B, P-trend = 0.2]. Associations were not systematically stronger when comparing traditional lipids (total cholesterol, low-density lipoprotein or high-density lipoprotein) to apolipoproteins.
Conclusions
Higher serum apolipoprotein A1 was associated with lower prevalence of CKD and higher eGFR estimated by the CKD-EPI equation in two large multiethnic population-based samples. While apolipoprotein B showed no consistent associations, a higher apolipoprotein B/A1 ratio was significantly associated with lower eGFR in both studies. The direction and magnitude of the longitudinal associations between apolipoproteins and CKD incidence were overall similar to those observed cross-sectionally. No consistent differences became apparent between traditional lipids and apolipoproteins.
doi:10.1093/ndt/gfr795
PMCID: PMC3471548  PMID: 22287661
apolipoprotein; ARIC; chronic kidney disease; epidemiology; NHANES
Context:
Pigment epithelium-derived factor (PEDF), a circulating glycoprotein with antiangiogenic, antioxidative, and anti-inflammatory properties, protects against diabetic nephropathy (DN) in animal models.
Objective:
We investigated whether circulating PEDF predicted the progression of DN in a 4-year prospective study.
Design, Setting, and Participants:
Baseline plasma PEDF levels were measured in type 2 diabetic subjects recruited from the Hong Kong West Diabetes Registry. The role of PEDF in predicting chronic kidney disease (CKD) and albuminuria progression was analyzed using Cox regression analysis.
Main Outcome Measure:
We evaluated CKD progression, defined as deterioration in CKD staging and a 25% or greater drop in estimated glomerular filtration rate (eGFR) according to International Society of Nephrology statements.
Results:
At baseline, plasma PEDF levels increased progressively with CKD staging (P for trend <.001; n = 1136). Among 1071 subjects with baseline CKD stage ≤3, plasma PEDF levels were significantly higher in those with CKD progression (n = 171) during follow-up than those without (P < .001). Baseline PEDF was independently associated with CKD progression (hazard ratio = 2.76; 95% confidence interval = 1.39–5.47; P = .004), adjusted for age, sex, waist circumference, diabetes duration, hemoglobin A1c, systolic blood pressure, use of antihypertensive drugs, C-reactive protein, and eGFR. Elevated baseline PEDF was also associated with the development of microalbuminuria/albuminuria in a subgroup with normoalbuminuria and eGFR >60 mL/min/1.73 m2 (n = 462) at baseline (hazard ratio = 2.75; 95% confidence interval = 1.01–7.49; P < .05), even after adjustment for potential confounders.
Conclusions:
Elevated PEDF levels may represent a compensatory change in type 2 diabetic patients with renal disease and appear to be a useful marker for evaluating the progression of DN.
doi:10.1210/jc.2014-2235
PMCID: PMC4223434  PMID: 25166721
Diabetes Care  2012;35(11):2317-2323.
OBJECTIVE
To evaluate the rate and determinants of concordance between advanced diabetic retinopathy (DR) and chronic kidney disease (CKD), as assessed by both albuminuria and estimated glomerular filtration rate (eGFR), in the large cohort of the Renal Insufficiency And Cardiovascular Events (RIACE) Italian multicenter study.
RESEARCH DESIGN AND METHODS
Patients with type 2 diabetes (n = 15,773) visiting consecutively 19 hospital–based diabetes clinics in years 2007 and 2008 were examined. DR was assessed by dilated fundoscopy. CKD was defined based on albuminuria and eGFR.
RESULTS
CKD was present in 58.64% of subjects with advanced DR, whereas advanced DR was detectable only in 15.28% of individuals with any CKD and correlated with the albuminuric CKD phenotypes more than with the nonalbuminuric phenotype. Age, male sex, diabetes duration, hemoglobin A1c, hypertension, triglycerides, previous cardiovascular disease, and, inversely, HDL-cholesterol correlated independently with the presence of any CKD in individuals with advanced DR; correlates differed according to the presence of albuminuria, reduced eGFR, or both. Conversely, factors associated with the presence of advanced DR in subjects with any CKD were diabetes treatment, previous cardiovascular disease, albuminuria, and, inversely, smoking, eGFR, and age at diagnosis.
CONCLUSIONS
Concordance of CKD with advanced DR is low in subjects with type 2 diabetes, and CKD without advanced DR is more frequent than isolated advanced DR, at variance with type 1 diabetes. Factors independently associated with the presence of any CKD in individuals with advanced DR differ, at least in part, from those correlating with the presence of advanced DR in subjects with any CKD and by CKD phenotype.
doi:10.2337/dc12-0628
PMCID: PMC3476898  PMID: 23093684
Introduction
Chronic kidney disease (CKD) is an emerging worldwide epidemic but few data are available in African populations. We aimed to assess prevalence of CKD in adult populations of Saint-Louis (northern Senegal).
Methods
In a population-based survey between January and May 2012, we included 1,037 adults aged =18 years living in Saint-Louis. Socio-demographical, clinical and biological data were collected during household visits. Serum creatinine was measured by Jaffé method. We estimated glomerular filtration rate (eGFR) using the 4-variables MDRD equation and CKD was defined by eGFR < 60 mL/min/1.73m2 and/or albuminuria > 1g/L. A multivariate logistic regression was performed to identify factors associated with CKD.
Results
Mean participants’ age was 47.9 ±16.9 years (18-87) and sex-ratio was 0.52. Majority of participants lived in urban areas (55.3% rural) and had school education (65.6%). Overall prevalences of hypertension, diabetes and obesity were 39.1%, 12.7% and 23.4% respectively. Prevalence of CKD was 4.9% (95% CI= 3.5 – 6.2) and 0.9% had GFR < 30 mL/min/1.73m2. Albuminuria >1g/l was found in 3.5% of people. CKD was significantly more frequent among hypertensive patients compared to normotensive participants. Only 23% of patients were aware of their disease before the survey. After multivariate logistic analysis, presence of CKD was significantly associated with hypertension (OR=1.12, p= 0.02) and age (OR=1.03, p= 0.02).
Conclusion
CKD is frequent in adult population living Northern Senegal. Main associated factors are hypertension and age. Prevention strategy is urgently needed to raise awareness and promote CKD detection and early treatment in both urban and rural areas.
doi:10.11604/pamj.2014.18.307.3636
PMCID: PMC4247887  PMID: 25469200
Chronic kidney disease; epidemiology; population; Senegal
BMC Nephrology  2014;15(1):198.
Background
Diabetic patients with chronic kidney disease (CKD), as defined by a reduced glomerular filtration rate (GFR), are at greater risk for cardiovascular and renal events and mortality. The aim of this study was to determine the prevalence of CKD among diabetic patients attending a hospital in southern Ethiopia, and to assess underdiagnosis of renal insufficiency among those with normal serum creatinine.
Methods
A total of 214 randomly selected diabetics attending the follow-up clinic at Butajira hospital of southern Ethiopia participated in this study during the period from September 1 to October 31, 2013. All patients completed an interviewer-administered questionnaire and underwent clinical assessment. The simplified Modification of Diet in Renal Disease (MDRD) and Cockroft-Gault (C-G) equations were used to estimate GFR (eGFR) from serum creatinine.
Results
CKD, defined as eGFR < 60 ml/min/1.73 m2, was present in 18.2% and 23.8% of the study participants according to the MDRD and Cockcroft-Gault (C-G) equations, respectively. Only 9.8% of the total participants, and 48.7% (for the MDRD) and 37.3% (for C-G) of those with eGFR <60 ml/min/1.73 m2 had abnormal serum creatinine values, i.e. > 1.5 mg/dl. Normal serum creatinine was observed in 90.2% of participants attending the hospital. A large proportion of participants ranging from 38.9-56.5% have shown to have mild to moderate renal insufficiency (stage 2–3 CKD) despite normal creatinine levels. CKD, eGFR < 60 ml/min/1.73 m2, was found in 10.4 and 16.9% of participants with normal serum creatinine using the MDRD and C-G equations, respectively.
Conclusion
CKD is present in no less than 18% of diabetics attending the hospital, but it is usually undiagnosed. A significant number of diabetics have renal insufficiency corresponding to stages 2–3 CKD despite normal creatinine levels. Therefore, GFR should be considered as an estimate of renal insufficiency, regardless of serum creatinine levels being in normal range.
doi:10.1186/1471-2369-15-198
PMCID: PMC4277829  PMID: 25511372
Chronic kidney disease; Diabetes; Estimated glomerular filtration rate; Serum creatinine; Renal insufficiency
Background
Atrial fibrillation (AF) is common among patients with end-stage renal disease, but few data are available on its prevalence among adults with chronic kidney disease (CKD) of lesser severity.
Methods and Results
We evaluated the association of CKD with electrocardiogram-detected AF among 26,917 participants in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, a population-based cohort of African-American and white US adults ≥45 years of age. Estimated glomerular filtration rate (eGFR) was calculated using the abbreviated Modification of Diet in Renal Disease study equation and albuminuria was defined as a urinary albumin to creatinine ratio ≥30 mg/g. Participants were categorized by renal function: no CKD (eGFR ≥60 ml/min/1.73m2 without albuminuria, n=21,081), stage 1–2 CKD (eGFR ≥60 ml/min/1.73m2 with albuminuria n=2,938), stage 3 CKD (eGFR 30 to 59 ml/min/1.73m2, n=2,683) and stage 4–5 CKD (eGFR <30 ml/min/1.73m2, n=215). The prevalence of AF among participants without CKD, and with stage 1–2, stage 3, and stage 4–5 CKD was 1.0%, 2.8%, 2.7% and 4.2%, respectively. Compared to participants without CKD, the age, race, sex adjusted odds ratios for prevalent AF were 2.67 (95% CI 2.04 – 3.48), 1.68 (95% CI 1.26 – 2.24) and 3.52 (95% CI 1.73–7.15) among those with stage 1–2, stage 3 and stage 4–5 CKD. The association between CKD and prevalent AF remained statistically significant after further multivariable adjustment and was consistent across numerous subgroups.
Conclusions
- Regardless of severity, CKD is associated with an increased prevalence of AF among US adults.
doi:10.1161/CIRCEP.110.957100
PMCID: PMC3049935  PMID: 21076159
chronic kidney disease; atrial fibrillation; electrocardiography
BMC Nephrology  2014;15(1):150.
Background
The presence of chronic kidney disease (CKD) in type 2 diabetes mellitus (T2DM) increases the risk of cardiovascular disease (CVD) regardless of the presence of traditional cardiovascular risk factors. There is controversy about the impact of each of the manifestations of CKD on the prevalence of CVD, whether it is greater with decreased estimated glomerular filtration rate (eGFR) or increased urine albumin creatinine ratio (UACR).
Methods
This study is a national cross-sectional study performed in primary care consults. We selected participants of both sexes who were aged 40 years or older, had been diagnosed with T2DM and had complete information on the study variables recorded in their medical records. The participants were classified according to eGFR : ≥ 60; 45–59; 30–44; <30 mL/min/1.73 m2 and UACR : < 30; 30–299; ≥300 mg/gr. The results were adjusted to compare the prevalence of CVD across all categories.
Results
A total of 1141 participants were included. Compared to participants with eGFR > 60 mL/min/1.73 m2 those with eGFR between 30–44 mL/min/m2, (OR = 2.3; 95% CI, 1.4-3.9); and eGFR < 30 mL/min/1.73 m2 (OR = 4.1 95% CI 1.6-10.2) showed increased likelihood of having CVD. Participants with UACR ≥ 30 mg/g compared to participants with UACR < 30 mg/g increased significantly the likelihood of having CVD, especially with UACR above 300 mg/g, (OR = 1.6; 95% CI 1.1-2.4 for UACR = 30–299 mg/g; OR = 3.9; CI 1.6-9.5 for UACR ≥ 300 mg/g).
Conclusion
The decrease in eGFR and increase in UACR are independent risk factors that increase the prevalence of CVD in participants with T2DM and these factors are independent of each other and of other known cardiovascular risk factors. In our study the impact of mild decreased eGFR in T2DM on CVD was lower than the impact of increased UACR. It is necessary to determine not only UACR but also eGFR for all patients with T2DM, both at the time of diagnosis and during follow-up, to identify those patients at high risk of cardiovascular complications.
doi:10.1186/1471-2369-15-150
PMCID: PMC4181296  PMID: 25227555
Type 2 diabetes; Chronic kidney disease; Cardiovascular disease
Background
Lifetime risk estimates of chronic kidney disease (CKD) can motivate preventative behaviors at the individual level and forecast disease burden and health care utilization at the population level.
Study Design
Markov Monte Carlo model simulation study.
Setting & Population
Current U.S. black and white population.
Model, Perspective, & Timeframe
Markov models simulating kidney disease development, using an individual perspective and lifetime horizon.
Outcomes
Age-, sex- and race-specific residual lifetime risks of CKD stages 3a+ (eGFR<60 ml/min/1.73m2), 3b+ (eGFR<45 ml/min/1.73 m2), and 4+ (eGFR<30 ml/min/1.73m2), and end stage renal disease (ESRD).
Measurements
State transition probabilities of developing CKD and of dying prior to its development were modeled using: 1) mortality rates from National Vital Statistics Report, 2) mortality risk estimates from a 2-million person meta-analysis, and 3) CKD prevalence from National Health and Nutrition Examination Surveys. Incidence, prevalence, and mortality related to ESRD were supplied by the US Renal Disease System.
Results
At birth, the overall lifetime risks of CKD stages 3a+, 3b+, 4+, and ESRD were 59.1%, 33.6%, 11.5%, and 3.6%, respectively. Women experienced greater CKD risk yet lower ESRD risk than men; blacks of both sexes had markedly higher CKD stage 4+ and ESRD risk (lifetime risks for white men, white women, black men, and black women, respectively: 53.6%, 64.9%, 51.8%, and 63.6% [CKD stage 3a+]; 29.0%, 36.7%, 33.7%, and 40.2% [CKD stage 3b+]; 9.3%, 11.4%, 15.8%, and 18.5% [CKD stage 4+]; and 3.3%, 2.2%, 8.5%, and 7.8% [ESRD]). Risk of CKD increased with age, with approximately one-half of CKD stage 3a+ cases developing after 70 years of age.
Limitations
CKD incidence estimates were modeled from prevalence in the U.S. population.
Conclusions
In the U.S., the lifetime risk of developing CKD stage 3a+ is high, underscoring the importance of primary prevention and effective therapy to reduce CKD-related morbidity and mortality.
doi:10.1053/j.ajkd.2013.03.009
PMCID: PMC3723711  PMID: 23566637

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