The Prevalence of Chronic Kidney Disease in a Primary Care Setting: A Swiss Cross-Sectional Study

Chronic kidney disease (CKD) often remains clinically silent and therefore undiagnosed until a progressed stage is reached. Our aim was to estimate the prevalence of CKD in a primary care setting in Switzerland. A multicenter, cross-sectional study with randomly selected general practitioners was performed. Adults visiting their general physician’s cabinet during defined periods were asked to participate. Baseline information was reported on a questionnaire, urine and blood samples were analyzed in a central laboratory. Renal status was assessed using the Kidney Disease: Improving Global Outcomes (KDIGO) classification. Extrapolation of results to national level was adjusted for age and gender. One thousand individuals (57% females) with a mean age of 57±17 years were included. Overall, 41% of the patients had normal estimated glomerular filtration rate (eGFR) and albumin creatinine ratio (ACR), whereas 36% of the subjects had slightly reduced excretory renal function with physiological albuminuria based on normal ACR. Almost one fourth of the subjects (23%) had either a substantially reduced eGFR or high levels of ACR. About 10% of the patients had a substantially reduced eGFR of <60 ml/min/1.73 m², and 17% showed relevant proteinuria (ACR >30 mg/g creatinine). Extrapolation to national level suggests that about 18% of primary care patients may suffer from CKD. CKD prevalence in a primary care population is therefore high, and preventive interventions may be advisable, in particular as CKD prevalence is likely to rise over the next decades.     

Comparison of Various Equations for Estimating GFR in Malawi: How to Determine Renal Function in Resource Limited Settings?

Background

Chronic kidney disease (CKD) is a probably underrated public health problem in Sub-Saharan-Africa, in particular in combination with HIV-infection. Knowledge about the CKD prevalence is scarce and in the available literature different methods to classify CKD are used impeding comparison and general prevalence estimates.

Methods

This study assessed different serum-creatinine based equations for glomerular filtration rates (eGFR) and compared them to a cystatin C based equation. The study was conducted in Lilongwe, Malawi enrolling a population of 363 adults of which 32% were HIV-positive.

Results

Comparison of formulae based on Bland-Altman-plots and accuracy revealed best performance for the CKD-EPI equation without the correction factor for black Americans. Analyzing the differences between HIV-positive and –negative individuals CKD-EPI systematically overestimated eGFR in comparison to cystatin C and therefore lead to underestimation of CKD in HIV-positives.

Conclusions

Our findings underline the importance for standardization of eGFR calculation in a Sub-Saharan African setting, to further investigate the differences with regard to HIV status and to develop potential correction factors as established for age and sex.     

Comparisons between the 2012 New CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) Equations and Other Four Approved Equations

Objective

The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) reported two equations in 2012: one based on cystatin C concentration (CKD-EPI_2012cys) and the other using both serum creatinine and cystatin C concentrations (CKD-EPI_2012Scr-cys). We compared the adaptability of new formulae with other four equations.

Methods

Participants (n = 788; median age, 54 [range, 19–94] years) were recruited from the First Affiliated Hospital of Nanjing Medical University. The reference glomerular filtration rate (rGFR) was measured by a ⁹⁹mTc-DTPA renal dynamic imaging method, and the estimated glomerular filtration rate (eGFR) was calculated separately by the Chinese adapted Modification of Diet in Renal Disease equation (C-MDRD), MacIsaac, Ma, serum creatinine-based CKD-EPI equation (CKD-EPI_2009Scr), CKD-EPI_2012cys and CKD-EPI_2012Scr-cys equations. We compared the performance of six equations with rGFR.

Results

Median rGFR was 76.35 (interquartile range, 59.03–92.50) mL/min/1.73 m². Compared with CKD-EPI_2009Scr, CKD-EPI_2012Scr-cys formula had better diagnostic value with larger area under the receiver operating characteristic curve (ROC^AUC, 0.879, p = 0.006), especially in young participants (ROC^AUC, 0.883, p = 0.005). CKD-EPI_2012cys equation did not perform better than other available equations. Accuracy (the proportion of eGFR within 30% of rGFR [P₃₀]) of the CKD-EPI_2012Scr-cys equation (77.03%) was inferior only to MacIsaac equation (80.2%) in the entire participants, but performed best in young participants with normal or mildly-injured GFR. Neither of the two new CKD-EPI equations achieved any ideal P₃₀ in the elderly participants with moderately-severely injured GFR. Linear regression analysis demonstrated a consistent result. In this study, CKD-EPI_2012Scr-cys had a relatively better diagnosis consistency of GFR stage between the eGFR and rGFR in the whole cohort.

Conclusion

CKD-EPI_2012Scr-cys appeared less biased and more accurate in overall participants. Neither of the new CKD-EPI equations achieved ideal accuracy in senior participants with moderately-severely injured GFR. A large-scale study with more subjects and cooperating centers to develop new formulae for the elderly is assumed to be necessary.     

Association between Kidney Function and Framingham Global Cardiovascular Disease Risk Score: A Chinese Longitudinal Study

Background

Chronic kidney disease (CKD) is generally considered an independent risk factor for cardiovascular disease (CVD) development, but rates in individuals with estimated glomerular filtration rate (eGFR) >60 ml/min/1.73 m² are uncertain. The Framingham global CVD risk score (FRS) equation is a widely accepted tool used to predict CVD risk in the general population. The purpose of the present study was to examine whether an association exists between eGFR and FRS in a Chinese population with no CKD or CVD.

Methods

A total of 333 participants were divided into three groups based on FRS. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and CKD-EPI equation for Asians (CKD-EPI-ASIA) were used to measure eGFR.

Results

A significant inverse association between eGFR and FRS was confirmed with Pearson correlation coefficients of –0.669, –0.698 (eGFR_CKD-EPI, P<0.01) and –0.658, –0.690 (eGFR_CKD-EPI-ASIA, P<0.01). This association gradually diminished with progression from the low- to high-risk groups (eGFR_CKD-EPI, r = –0.615, –0.282, –0.197, P<0.01, P<0.01, P>0.05; similar results according to the CKD-EPI-ASIA equation). In the low- or moderate-risk new-groups, this association became stronger with increased FRS (eGFR_CKD-EPI-ASIA, r = –0557, –0.622 or –0.326, –0.329, P<0.01). In contrast to the results from 2008, eGFR was independently associated with FRS following adjustment for traditional cardiovascular risk factors (P<0.05).

Conclusion

Renal function has multiple influences on predicting CVD risk in various populations. With increasing FRS and decreasing eGFR, it is also independently associated with CVD, even in individuals with eGFR >60 ml/min/1.73 m².     

Albuminuria as a Risk Factor for Anemia in Chronic Kidney Disease: Result from the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD)

Background

Anemia is a common complication among patients with chronic kidney disease (CKD), and it is associated with unfavorable clinical outcomes in patients with CKD independent of the estimated glomerular filtration rate (eGFR). We assessed the association of the urinary albumin-to-creatinine ratio (ACR) and eGFR with anemia in CKD patients.

Methods

We conducted a cross-sectional study using baseline data from the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD). Multiple regression analysis was performed to identify the independent association of albuminuria with anemia. Furthermore, odds ratios for anemia were calculated by cross-categorization of ACR and eGFR.

Results

Among 1,456 patients, the mean age was 53.5 ± 12.4 years, and the mean eGFR and ACR were 51.9 ± 30.5 mL/min per 1.73 m² and 853.2 ± 1,330.3 mg/g, respectively. Anemia was present in 644 patients (40.5%). Multivariate analysis showed that the odds ratio of anemia increased according to ACR levels, after adjusting for age, sex, eGFR, body mass index, pulse pressure, cause of CKD, use of erythropoiesis stimulating agents, serum calcium and ferritin (ACR < 30 mg/g as a reference group; 30–299 mg/g, adjusted odds ratio (OR) = 1.43, 95% confidence interval (CI) = 0.88–2.33; ≥300 mg/g, adjusted OR = 1.86, 95% CI = 1.12–3.10). In addition, graded associations were observed in cross-categorized groups of a higher ACR and eGFR compared to the reference group with an ACR <30 mg/g and eGFR ≥60 mL/min per 1.73 m².

Conclusion

The present study demonstrated that albuminuria was a significant risk factor for anemia in CKD patients independent of the eGFR.     

Low Ankle-Brachial Index Is Associated with Early-Stage Chronic Kidney Disease in Type 2 Diabetic Patients Independent of Albuminuria

Aims

The role of low ankle-brachial index (ABI) in early-stage chronic kidney disease (CKD) is not fully known. This study was designed to investigate the prevalence of low ABI in early-stage CKD defined as an estimated glomerular filtration rate (eGFR) between 60–89 ml/min/1.73 m² of type 2 diabetic patients without albuminuria and to determine the association between the low ABI and mildly decreased eGFR.

Methods

The cross-sectional study enrolled 448 type 2 diabetic patients with normoalbuminuria. The patients were stratified into two groups according to the CKD-EPI eGFR level: the normal group with eGFR level ≥90 mL/min/1.73 m² and the lower group with eGFR of 60–89. ABI was categorized as normal (1.0–1.39), low-normal (0.9–0.99), and low (<0.9). Both stepwise forward multiple linear regression and binary logistic regression analyses were performed to examine the association between ABI categories and eGFR levels and to assess the relation of low ABI and early-stage CKD.

Results

The prevalence of low ABI in early-stage CKD of type 2 diabetic patients without albuminuria was 39.5%. Low ABI was associated with an approximate 3-fold greater risk of early-stage CKD in bivariate logistic regression analysis, and remained significantly associated with a 2.2 fold risk (95% confidence interval: 1.188–4.077; P = 0.012) after adjusting traditional chronic kidney disease risk factors.

Conclusions

There was a high prevalence of low ABI in early-stage CKD patients of type 2 diabetes with normoalbuminuria and a close relation between low ABI and early-stage CKD, suggesting that we should pay much more attention to the patients who have only mildly decreased eGFR and normoalbuminuria but have already had a low ABI in clinic work and consider the preventive therapy in early stage.     

Comparison of Estimated Glomerular Filtration Rate by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Equations with and without Cystatin C for Predicting Clinical Outcomes in Elderly Women

Background

Reduced estimated glomerular filtration rate (eGFR) using the cystatin-C derived equations might be a better predictor of cardiovascular disease (CVD) mortality compared with the creatinine-derived equations, but this association remains unclear in elderly individuals.

Aim

The aims of this study were to compare the predictive values of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)-creatinine, CKD-EPI-cystatin C and CKD-EPI-creatinine-cystatin C eGFR equations for all-cause mortality and CVD events (hospitalizations±mortality).

Methods

Prospective cohort study of 1165 elderly women aged>70 years. Associations between eGFR and outcomes were examined using Cox regression analysis. Test accuracy of eGFR equations for predicting outcomes was examined using Receiver Operating Characteristic (ROC) analysis and net reclassification improvement (NRI).

Results

Risk of all-cause mortality for every incremental reduction in eGFR determined using CKD-EPI-creatinine, CKD-EPI-cystatin C and the CKD-EPI-creatinine-cystatic C equations was similar. Areas under the ROC curves of CKD-EPI-creatinine, CKD-EPI-cystatin C and CKD-EPI-creatinine-cystatin C equations for all-cause mortality were 0.604 (95%CI 0.561–0.647), 0.606 (95%CI 0.563–0.649; p = 0.963) and 0.606 (95%CI 0.563–0.649; p = 0.894) respectively. For all-cause mortality, there was no improvement in the reclassification of eGFR categories using the CKD-EPI-cystatin C (NRI -4.1%; p = 0.401) and CKD-EPI-creatinine-cystatin C (NRI -1.2%; p = 0.748) compared with CKD-EPI-creatinine equation. Similar findings were observed for CVD events.

Conclusion

eGFR derived from CKD-EPI cystatin C and CKD-EPI creatinine-cystatin C equations did not improve the accuracy or predictive ability for clinical events compared to CKD-EPI-creatinine equation in this cohort of elderly women.     

Renal Function and Coronary Microvascular Dysfunction in Women with Symptoms/Signs of Ischemia

ObjectivesChronic kidney disease (CKD) is more prevalent among women and is associated with adverse cardiovascular events. Among women with symptoms and signs of ischemia enrolled in the Women’s Ischemia Syndrome Evaluation (WISE), a relatively high mortality rate was observed in those with no obstructive coronary artery disease. Coronary microvascular dysfunction or reduced coronary flow reserve (CFR) was a strong and independent predictor of adverse outcomes. The objective of this analysis was to determine if renal function was associated with coronary microvascular dysfunction in women with signs and symptoms of ischemia.MethodsThe WISE was a multicenter, prospective, cohort study of women undergoing coronary angiography for suspected ischemia. Among 198 women with additional measurements of CFR, we determined the estimated glomerular filtration rate (eGFR) with the CKD-EPI equation. We tested the association between eGFR and CFR with regression analysis.ResultsThe median eGFR was 89 ml/min. The eGFR correlated with CFR (r = 0.22; P = 0.002). This association persisted even after covariate adjustment. Each 10-unit decrease in eGFR was associated with a 0.04-unit decrease in CFR (P = 0.04).There was a strong interaction between eGFR and age (P = 0.006): in those ≥60 years old, GFR was strongly correlated with CFR (r = 0.55; P<0.0001). No significant correlation was noted in those <60 years old.ConclusionsReduced renal function was significantly associated with lower CFR in women with symptoms and signs of ischemia. Coronary microvascular dysfunction warrants additional study as a mechanism contributing to increased risk of cardiovascular events in CKD.     

An Age-Calibrated Definition of Chronic Kidney Disease: Rationale and Benefits

Defining chronic kidney disease (CKD) is the subject of intense debate in the current nephrology literature. The debate concerns the threshold value of estimated glomerular filtration rate (eGFR) used to make the diagnosis of CKD. Current recommendations argue that a universal threshold of 60 mL/min/1.73m² should be used. This threshold has been defended by epidemiological studies showing that the risk of mortality or end-stage renal disease increases with an eGFR below 60 mL/min/1.73m². However, a universal threshold does not take into account the physiologic decline in GFR with ageing nor does it account for the risk of mortality and end-stage renal disease being trivial with isolated eGFR levels just below 60 mL/min/1.73m² in older subjects and significantly increased with eGFR levels just above 60 mL/min/1.73m² among younger patients. Overestimation of the CKD prevalence in the elderly (medicalisation of senescence) and underestimation of CKD (potentially from treatable primary nephrologic diseases) in younger patients is of primary concern. An age-calibrated definition of CKD has been proposed to distinguish age-related from disease-related changes in eGFR. For patients younger than 40 years, CKD is defined by eGFR below 75 mL/min/1.73m². For patients with ages between 40 and 65 years, CKD is defined by 60 mL/min/1.73m². For subjects older than 65 years without albuminuria or proteinuria, CKD is defined by eGFR below 45 mL/min/1.73m².     

A metabolomics-based approach for predicting stages of chronic kidney disease

Chronic kidney disease (CKD) is a major epidemiologic problem and a risk factor for cardiovascular events and cerebrovascular accidents. Because CKD shows irreversible progression, early diagnosis is desirable. Renal function can be evaluated by measuring creatinine-based estimated glomerular filtration rate (eGFR). This method, however, has low sensitivity during early phases of CKD. Cystatin C (CysC) may be a more sensitive predictor. Using a metabolomic method, we previously identified metabolites in CKD and hemodialysis patients. To develop a new index of renal hypofunction, plasma samples were collected from volunteers with and without CKD and metabolite concentrations were assayed by quantitative liquid chromatography/mass spectrometry. These results were used to construct a multivariate regression equation for an inverse of CysC-based eGFR, with eGFR and CKD stage calculated from concentrations of blood metabolites. This equation was able to predict CKD stages with 81.3% accuracy (range, 73.9–87.0% during 20 repeats). This procedure may become a novel method of identifying patients with early-stage CKD.     

Combined Biomarker Analysis for Risk of Acute Kidney Injury in Patients with ST-Segment Elevation Myocardial Infarction

Background

Acute kidney injury (AKI) complicating ST-segment elevation myocardial infarction (STEMI) increases subsequent morbidity and mortality. We combined the biomarkers of heart failure (HF; B-type natriuretic peptide [BNP] and soluble ST2 [sST2]) and renal injury (NGAL [neutrophil gelatinase-associated lipocalin] and cystatin C) in predicting the development of AKI in patients with STEMI undergoing primary percutaneous coronary intervention (PCI).

Methods and Results

From March 2010 to September 2013, 189 STEMI patients were sequentially enrolled and serum samples were collected at presentation for BNP, sST2, NGAL and cystatin C analysis. 37 patients (19.6%) developed AKI of varying severity within 48 hours of presentation. Univariate analysis showed age, Killip class ≥2, hypertension, white blood cell counts, hemoglobin, estimated glomerular filtration rate, blood urea nitrogen, creatinine, and all the four biomarkers were predictive of AKI. Serum levels of the biomarkers were correlated with risk of AKI and the Acute Kidney Injury Network (AKIN) stage and all significantly discriminated AKI (area under the receiver operating characteristic [ROC] curve: BNP: 0.86, sST2: 0.74, NGAL: 0.75, cystatin C: 0.73; all P < 0.05). Elevation of ≥2 of the biomarkers higher than the cutoff values derived from the ROC analysis improved AKI risk stratification, regardless of the creatine level (creatinine < 1.24 mg/dL: odds ratio [OR] 11.25, 95% confidence interval [CI] 1.63-77.92, P = 0.014; creatinine ≥ 1.24: OR 15.0, 95% CI 1.23-183.6, P = 0.034).

Conclusions

In this study of STEMI patients undergoing primary PCI, the biomarkers of heart failure (BNP and sST2) and renal injury (NGAL and cystatin C) at presentation were predictive of AKI. High serum levels of the biomarkers were associated with an elevated risk and more advanced stage of AKI. Regardless of the creatinine level, elevation of ≥2 of the biomarkers higher than the cutoff values indicated a further rise in AKI risk. Combined biomarker approach may assist in risk stratification of AKI in patients with STEMI.     

Chronic Kidney Disease and Diabetic Retinopathy in Patients with Type 2 Diabetes

Purpose

To explore the relationship between chronic kidney disease (CKD) and diabetic retinopathy (DR) in a representative population of type 2 diabetes mellitus (DM2) patients in Catalonia (Spain).

Methods

This was a population-based, cross-sectional study. A total of 28,344 patients diagnosed with DM2 who had recorded ophthalmologic and renal functional examinations were evaluated. Data were obtained from a primary healthcare electronic database of medical records. CKD was defined as an estimated glomerular filtration ratio (eGFR) of <60 ml/min/1.73m² and/or urine albumin to creatinine ratio (UACR) ≥30 mg/g. DR was categorized as non-vision threatening diabetic retinopathy and vision threatening diabetic retinopathy.

Results

CKD was associated with a higher rate of DR [OR], 95% confidence interval [CI], 1.5 (1.4–1.7). When we analyzed the association between different levels of UACR and DR prevalence observed that DR prevalence rose with the increase of UACR levels, and this association was significant from UACR values ≥10 mg/g, and increased considerably with UACR values ≥300mg/g (Odds ratio [OR], 95% confidence interval [CI], 2.0 (1.6–2.5). This association was lower in patients with eGFR levels 44 to 30 mL/min/1.73m² [OR], 95% confidence interval [CI], 1.3 (1.1–1.6).

Conclusions

These results show that CKD, high UACR and/or low eGFR, appear to be associated with DR in this DM2 population.     

Multicenter Study of Creatinine- and/or Cystatin C-Based Equations for Estimation of Glomerular Filtration Rates in Chinese Patients with Chronic Kidney Disease

Objective

To establish equations for the estimation of glomerular filtration rates (eGFRs) based on serum creatinine (SCr) and/or serum cystatin C (SCysC) in Chinese patients with chronic kidney disease (CKD), and to compare the new equations with both the reference GFR (rGFR) and the literature equations to evaluate their applicability.

Methods

The 788 Chinese CKD patients were randomly divided into two groups, the training group and the testing group, to establish new eGFR-formulas based on serum CysC and to validate the established formulas, respectively. ^99mTc-DTPA clearance (as the rGFR), serum Cr, and serum CysC were determined for all patients, and GFR was calculated using the Cockcroft-Gault equation (eGFR1), the MDRD formula (eGFR2), the CKD-EPI formulas (eGFR3, eGFR4), and the Chinese eGFR Investigation Collaboration formulas (eGFR5, eGFR6). The accuracy of each eGFR was compared with the rGFR.

Results

The training and testing groups'' mean GFRs were 50.84±31.36 mL/min/1.73 m² and 54.16±29.45 mL/min/1.73 m², respectively. The two newly developed eGFR formulas were fitted using iterative computation: and . Significant correlation was observed between each eGFR and the rGFR. However, proportional errors and constant errors were observed between rGFR and eGFR1, eGFR2, eGFR4, eGFR5 or eGFR6, and constant errors were observed between eGFR3 and rGFR, as revealed by the Passing & Bablok plot analysis. The Bland-Altman analysis illustrated that the 95% limits of agreement of all equations exceeded the previously accepted limits of <60 mL/min •1.73 m², except the equations of eGFR7 and eGFR8.

Conclusion

The newly developed formulas, eGFR7 and eGFR8, provide precise and accurate GFR estimation using serum CysC detection alone or in combination with serum Cr detection. Differences in detection methods should be carefully considered when choosing literature eGFR equations to avoid misdiagnosis and mistreatment.     

Kidney Function,Endothelial Activation and Atherosclerosis in Black and White Africans with Rheumatoid Arthritis

Objective

To determine whether kidney function independently relates to endothelial activation and ultrasound determined carotid atherosclerosis in black and white Africans with rheumatoid arthritis (RA).

Methods

We calculated the Jelliffe, 5 Cockcroft-Gault equations, Salazar-Corcoran, Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) estimated glomerular filtration rate (EGFR) equations in 233 (112 black) RA patients.

Results

The CKD-EPI eGFR was <90 ml/min/1.73m² in 49.1% and 30.6% of black and white patients, respectively (odds ratio (95% confidence interval) = 2.19 (1.28–3.75), p = 0.004). EGFRs were overall consistently associated with monocyte chemoattractant protein-1 and angiopoietin 2 concentrations in white patients, and with carotid intima-media thickness and plaque in black participants. Amongst black patients, plaque prevalence was 36.7% and the area under the curve (AUC) of the receiver operating characteristic (ROC) curve was not associated with plaque presence for the MDRD equation (p = 0.3), whereas the respective relationship was significant or borderline significant (p = 0.003 to 0.08) and of similar extent (p>0.1 for comparisons of AUC (SE)) for the other 8 equations. Based on optimal eGFR cutoff values with sensitivities and specificities ranging from 42 to 60% and 70 to 91% respectively, as determined in ROC curve analysis, a low eGFR increased the odds ratio for plaque 2.2 to 4.0 fold.

Conclusion

Reduced kidney function is independently associated with atherosclerosis and endothelial activation in black and white Africans with RA, respectively. CKD is highly prevalent in black Africans with RA. Apart from the MDRD, eGFR equations are useful in predicting carotid plaque presence, a coronary heart disease equivalent, amongst black African RA patients.     

Physical Activity Is not Associated with Estimated Glomerular Filtration Rate among Young and Middle-Aged Adults: Results from the Population-Based Longitudinal Doetinchem Study

There is debate as to whether physical inactivity is associated with reduced kidney function. We studied the prospective association of (changes in) physical activity with estimated glomerular filtration rate (eGFR) in adult men and women. We included 3,935 participants aged 26 to 65 years from the Doetinchem Cohort study, examined every 5 years for 15 years. Physical activity was assessed at each round using the Cambridge Physical Activity Index. Using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation, GFR was estimated from routinely measured cystatin C concentrations, examining all available samples per participant in one assay run. We determined the association between 1) physical activity and eGFR and 2) 5-year changes in physical activity (becoming inactive, staying inactive, staying active, becoming active) and eGFR, using time-lagged generalized estimating equation analyses. At baseline, 3.6% of the participants were inactive, 18.5% moderately inactive, 26.0% moderately active, and 51.9% active. The mean (± SD) eGFR was 107.9 (± 14.5) mL/min per 1.73 m². Neither physical activity nor 5-year changes in physical activity were associated with eGFR at the subsequent round. The multivariate adjusted βeGFR was 0.57 mL/min per 1.73 m² (95% Confidence Interval (CI) -1.70, 0.56) for inactive compared to active participants. Studying changes in physical activity between rounds, the adjusted βeGFR was -1.10 mL/min per 1.73 m² (95% CI -4.50, 2.30) for those who stayed inactive compared with participants who became active. Physical activity was not associated with eGFR in this population-based study of adults.     

Association of Angiopoietin-2 with Renal Outcome in Chronic Kidney Disease

Background

The pathophysiological mechanisms of renal function progression in chronic kidney disease (CKD) have still not been completely explored. In addition to well-known traditional risk factors, non-traditional risk factors, such as endothelial dysfunction, have gradually attracted physicians'' attention. Angiopoietin-2 (Ang-2) impairs endothelial function through preventing angiopoietin-1 from binding to Tie2 receptor. Whether Ang-2 is associated with renal function progression in CKD is unknown.

Methods

This study enrolled 621 patients with stages 3–5 CKD to assess the association of circulating Ang-2 with commencing dialysis, doubling creatinine and rapid decline in renal function (the slope of estimated glomerular filtration rate (eGFR) greater than 5 ml/min per 1.73 m²/y) over follow-up of more than 3 years.

Results

Of all patients, 224 patients (36.1%) progressed to commencing dialysis and 165 (26.6%) reached doubling creatinine. 85 subjects (13.9%) had rapid decline in renal function. Ang-2 quartile was divided at 1494.1, 1948.8, and 2593.1 pg/ml. The adjusted HR of composite outcomes, either commencing dialysis or doubling creatinine was 1.53 (95% CI: 1.06–2.23) for subjects of quartile 4 compared with those of quartile 1. The adjusted OR for rapid decline in renal function was 2.96 (95% CI: 1.13–7.76) for subjects of quartile 4 compared with those of quartile 1. The linear mixed-effects model shows a more rapid decrease in eGFR over time in patients with quartile 3 or more of Ang-2 than those with the lowest quartile of Ang-2.

Conclusions

Ang-2 is an independent predictor of adverse renal outcome in CKD. Further study is needed to identify the pathogenic role of Ang-2 in CKD progression.     

Estimated Glomerular Filtration Rate,All-Cause Mortality and Cardiovascular Diseases Incidence in a Low Risk Population: The MATISS Study

Background

Chronic kidney disease (CKD) independently increases the risk of death and cardiovascular disease (CVD) in the general population. However, the relationship between estimated glomerular filtration rate (eGFR) and CVD/death risk in a general population at low risk of CVD has not been explored so far.

Design

Baseline and longitudinal data of 1465 men and 1459 women aged 35-74 years participating to the MATISS study, an Italian general population cohort, were used to evaluate the role of eGFR in the prediction of all-cause mortality and incident CVD.

Methods

Bio-bank stored sera were used to evaluate eGFR at baseline. Serum creatinine was measured on thawed samples by means of an IDMS-calibrated enzymatic method. eGFR was calculated by the CKD-EPI formula.

Results

At baseline, less than 2% of enrolled persons had eGFR < 60 mL/min/1.73m² and more than 70% had a 10-year cardiovascular risk score < 10%. In people 60 or more years old, the first and the last eGFR quintiles (<90 and ≥109 mL/min/1.73m², respectively) were associated to an increased risk for both all-cause mortality (hazard ratio 1.6, 95% confidence interval 1.2-2.1 and 4.3, 1.6-11.7, respectively) and incident CVD (1.6, 1.0-2.4 and 7.0, 2.2-22.9, respectively), even if adjusted for classical risk factors.

Conclusions

These findings strongly suggest that in an elderly, general population at low risk of CVD and low prevalence of reduced renal filtration, even a modest eGFR reduction is related to all-cause mortality and CVD incidence, underlying the potential benefit to this population of considering eGFR for their risk prediction.     

Impact of Thyroid Function on Serum Cystatin C and Estimated Glomerular Filtration Rate: A Cross-Sectional Study

ObjectiveTo determine the relationship between thyroid-stimulating hormone (TSH) and cystatin C (CysC) and estimated glomerular filtration rate calculated by Cys^C (e^GFRCysC).MethodsWe conducted a cross-sectional study including 8,126 male participants. Serum creatinine (Cr), CysC, eGFR calculated by Cr (eGFR_Cr), and eGFR_CysC were determined and compared in euthyroid and subclinical thyroid dysfunction patients. Relationships between TSH and Cr, cystatin C, eGFR_Cr, and eGFR_CysC were assessed by linear and quadratic trend analyses. Odds ratios (ORs) of chronic kidney disease (CKD; eGFR<60 mL/min/1.73m²) were calculated according to categories of thyroid function using TSH values of 2.01-3.00 mIU/L as a reference.ResultsSerum CysC level was significantly elevated, and eGFR_CysC was significantly reduced in both sub-clinical hypothyroidism and subclinical hyperthyroidism. TSH was negatively and linearly associated with Cr and eGFR_Cr (P<.001). Quadratic trends were found between TSH and cystatin C or eGFR_CysC (P<.001). Compared with individuals with TSH of 2.01-3.00 mIU/L, the prevalence of CKD_CysC was significantly higher in subjects with TSH<0.40 mIU/L, 3.01-4.00 mIU/L, and 4.01-7.00 mIU/L, while the prevalence of CKD_Cr was only significantly higher in subjects with TSH>7.0 mIU/L.ConclusionDespite only studying male subjects and using eGFR rather than standard GFR, we conclude that thyroid function differentially affects serum CysC and Cr concentrations. Subclinical hypothyroidism and subclinical hyperthyroidism are both associated with elevated CysC, reduced eGFR_CysC, and higher prevalence of CKD_CysC. Assessment of renal function with CysC should be avoided in patients with thyroid dysfunction. (Endocr Pract. 2013;19:397-403)     

Kidney Function Decline and Apparent Treatment-Resistant Hypertension in the Elderly

Background

Cross-sectional studies show a strong association between chronic kidney disease and apparent treatment-resistant hypertension, but the longitudinal association of the rate of kidney function decline with the risk of resistant hypertension is unknown.

Methods

The population-based Three-City included 8,695 participants older than 65 years, 4265 of them treated for hypertension. We estimated the odds ratios (OR) of new-onset apparent treatment-resistant hypertension, defined as blood pressure ≥ 140/90 mmHg despite use of 3 antihypertensive drug classes or ≥ 4 classes regardless of blood pressure, associated with the mean estimated glomerular filtration rate (eGFR) level and its rate of decline over 4 years, compared with both controlled hypertension and uncontrolled nonresistant hypertension with ≤ 2 drugs. GFR was estimated with three different equations.

Results

Baseline prevalence of apparent treatment-resistant hypertension and of controlled and uncontrolled nonresistant hypertension, were 6.5%, 62.3% and 31.2%, respectively. During follow-up, 162 participants developed apparent treatment-resistant hypertension. Mean eGFR decline with the MDRD equation was 1.5±2.9 mL/min/1.73 m² per year: 27.7% of the participants had an eGFR ≥3 and 10.1% ≥ 5 mL/min/1.73 m² per year. After adjusting for age, sex, obesity, diabetes, and cardiovascular history, the ORs for new-onset apparent treatment-resistant hypertension associated with a mean eGFR level, per 15 mL/min/1.73m² drop, were 1.23 [95% confidence interval 0.91–1.64] compared to controlled hypertension and 1.10 [0.83–1.45] compared to uncontrolled nonresistant hypertension; ORs associated with a decline rate ≥ 3 mL/min/1.73m² per year were 1.89 [1.09–3.29] and 1.99 [1.19–3.35], respectively. Similar results were obtained when we estimated GFR with the CKDEPI and the BIS1 equations. ORs tended to be higher for an eGFR decline rate ≥ 5 mL/min/1.73m² per year.

Conclusion

The speed of kidney function decline is associated more strongly than kidney function itself with the risk of apparent treatment-resistant hypertension in the elderly.     

Ten-Year Follow-up of Patients with Epidemic Post Infectious Glomerulonephritis

BackgroundScarce information on outcomes of epidemic post infectious glomerulonephritis is available. This is a 10-year follow-up of the patients that developed acute glomerulonephritis in an epidemic outbreak caused by group C Streptococcus zooepidemicus in Brazil in 1998, that were also previously evaluated 2 and 5 years after the acute episode.MethodsIn this prospective study 60 cases (out of 134 in 1998) were reevaluated after 10 years, as well as community controls matched by gender and age. They underwent clinical and renal function evaluation, including serum creatinine and cystatin C, estimated glomerular filtration rate (eGFR), albuminuria and hematuria.ResultsComparisons of clinical and renal function aspects of 60 patients and 48 community controls have not shown significant differences (eGFR <60 ml/min/1.73m² and/or albuminuria >30mg/g creatinine: 13.8% vs. 12.2%, respectively, p = 0.817) except for a higher frequency of hypertension in the cases (45.0% vs. 20.8%, p = 0.009). Comparing the same patients affected in the acute episode, 2, 5 and 10 years later, it was observed an improvement of median eGFR levels at 2 years and a trend toward subsequent stabilization in these levels, associated with decrease in albuminuria and increased hypertension rates in the last survey. At 10 years it was not observed additional reduction of renal function using serum creatinine, eGFR and cystatin C.ConclusionsDuring the acute episode of epidemic GN a considerable proportion of patients presented hypertension and reduced renal function; after 2 years and particularly at this 10-year follow-up survey there was no worsening of renal function parameters, except for persistent higher frequency of hypertension. Nevertheless, a longer follow up is necessary to confirm that progressive loss of renal function will not occur.