Association of Estimated Glomerular Filtration Rate with Hemoglobin Level in Korean Adults: The 2010–2012 Korea National Health and Nutrition Examination Survey

PurposeLittle is known about anemia in patients with early renal dysfunction. We aimed to investigate the association of hemoglobin level and anemia prevalence with estimated glomerular filtration rate (eGFR) decline using a nation-wide representative sample of the adult Korean population.MethodsIn total, 17,373 participants (7,296 men; weighted n = 18,330,187; mean age, 44.2±0.3 years; 9,886 women, weighted n = 18,317,454; mean age, 46.9±0.3 years) were included. eGFR was divided into 5 groups: Group 1, ≥105; Group 2, 90–104; 75–89; Group 4, 60–74; and Group 5, <60 mL/min/1.73m².ResultsThe weighted anemia prevalence rates were 2.6% in men and 12.8% in women. In men, the weighted hemoglobin level increased with a decrease in eGFR; this value peaked at an eGFR of 60–89 mL/min/1.73m² and decreased thereafter at an eGFR of <60 mL/min/1.73m² (15.19±0.03, 15.35±0.03, 15.53±0.03, 15.52±0.06, and 14.90±0.12 g/dL from Groups 1 to 5) after adjustment for age, college graduation, cancer history, current smoking, waist circumference, serum cholesterol level, serum triglyceride level, and diastolic blood pressure. In women, the weighted hemoglobin level increased with a decrease in eGFR; this value peaked with an eGFR of 75–89 mL/min/1.73m² and decreased thereafter (12.90±0.03, 13.08±0.02, 13.20±0.04, 13.14±0.05, and 12.47±0.11 g/dL from Groups 1 to 5) after adjustment for menstruation, pregnancy, estrogen replacement, and the above-mentioned variables. In both sexes, the weighted prevalence of anemia with an eGFR of 60–104 mL/min/1.73m² was significantly lower than that with an eGFR of ≥105 mL/min/1.73m² (men, 3.2±0.4%, 1.9±0.3%, 1.8±0.3%, 2.0±0.9%, and 18.1±3.1%; women, 14.0±0.8%, 11.2±0.7%, 10.5±1.0%, 13.2±1.6%, and 32.3±3.2% from Groups 1 to 5).ConclusionsWe noted a compensatory increase in the hemoglobin level with a minor decline in kidney function (in the range of eGFR ≥60 mL/min/1.73m²) prior to a marked decrease in hemoglobin level with severe renal dysfunction.     

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.     

Associations between Renal Hyperfiltration and Serum Alkaline Phosphatase

Renal hyperfiltration, which is associated with renal injury, occurs in diabetic or obese individuals. Serum alkaline phosphatase (ALP) level is also elevated in patients with diabetes (DM) or metabolic syndrome (MS), and increased urinary excretion of ALP has been demonstrated in patients who have hyperfiltration and tubular damage. However, little was investigated about the association between hyperfiltration and serum ALP level. A retrospective observational study of the 21,308 adults in the Korea National Health and Nutrition Examination Survey IV-V databases (2008–2011) was performed. Renal hyperfiltration was defined as exceeding the age- and sex-specific 97.5^th percentile. We divided participants into 4 groups according to their estimated glomerular filtration rate (eGFR): >120, 90–119, 60–89, and <60 mL/min/1.73 m². The participants with eGFR >120 mL/min/1.73 m² showed the highest risk for MS, in the highest ALP quartiles (3.848, 95% CI, 1.876–7.892), compared to the lowest quartile. Similarly, the highest risk for DM, in the highest ALP quartiles, was observed in participants with eGFR >120 ml/min/1.73 m² (2.166, 95% CI, 1.084–4.329). ALP quartiles were significantly associated with albuminuria in participants with eGFR ≥ 60 ml/min/1.73m². The highest ALP quartile had a 1.631-fold risk elevation for albuminuria with adjustment of age and sex. (95% CI, 1.158-2.297, P = 0.005). After adjustment, the highest ALP quartile had a 1.624-fold risk elevation, for renal hyperfiltration (95% CI, 1.204–2.192, P = 0.002). In addition, hyperfiltration was significantly associated with hemoglobin, triglyceride, white blood cell count, DM, smoking, and alcohol consumption (P<0.05). The relationship between serum ALP and metabolic disorders is stronger in participants with an upper-normal range of eGFR. Higher ALP levels are significantly associated with renal hyperfiltration in Korean general population.     

Effect of Proteinuria and Glomerular Filtration Rate on Renal Outcome in Patients with Biopsy-Proven Benign Nephrosclerosis

Background

Reduced estimated glomerular filtration rate (eGFR) and proteinuria are risk factors for end-stage renal disease (ESRD), of which benign nephrosclerosis is a common cause. However, few biopsy-based studies have assessed these associations.

Methods

We performed retrospective cohort study of 182 Japanese patients who underwent renal biopsy from June 1985 through March 2014 and who were diagnosed with benign nephrosclerosis. Competing risk regression analyses were used to investigate the effect of eGFR and proteinuria levels at the time of renal biopsy on the risk for renal events (ESRD or a 50% decline in eGFR from baseline).

Results

During a median 5.8-year follow-up, 63 (34.6%) patients experienced renal events. The incidence of renal events increased with lower baseline eGFR and greater baseline proteinuria levels. After adjustment for baseline covariates, lower eGFR levels (subhazard ratios [SHRs], 1.30; 95% confidence interval [CI], 1.01–1.67, per 10 mL/min/1.73 m²) and higher proteinuria levels (SHR, 1.52; 95% CI, 1.23–1.87, per 1.0 g/day) at the time of renal biopsy were associated independently with higher risk for renal events. Lower levels of serum albumin (SHR, 2.07; 95% CI, 1.20–3.55 per 1.0 g/dL) were also associated with renal events. Patients with both eGFR <30 mL/min/1.73 m² and proteinuria ≥0.5 g/day had a 26.7-fold higher risk (95% CI, 3.97–179.4) of renal events than patients with both eGFR ≥60 mL/min/1.73 m² and proteinuria <0.5 g/day.

Conclusions

Reduced eGFR and increased proteinuria as well as lower serum albumin at the time of renal biopsy are independent risk factors for renal events among patients with biopsy-proven benign nephrosclerosis.     

Waist Circumference,Not Body Mass Index,Is Associated with Renal Function Decline in Korean Population: Hallym Aging Study

Background

Prospective investigation of obesity and renal function decline in Asia is sparse. We examined the associations of body mass index (BMI) and waist circumference (WC) with renal function decline in a prospective study of Korean population.

Methods

A total of 454 participants who had baseline estimated glomerular filtration rate (eGFR) levels of more than 60 mL/min/1.73 m² in Hallym Aging Study (HAS) were included and followed for 6 years. Renal function decline was defined as follows: (1) an eGFR decline ≥3 mL/min/1.73 m²/year (n = 82 cases); (2) an eGFR decrease of 20% or greater (n = 87 cases) at follow-up; (3) an eGFR decrease of 20% greater at follow-up or eGFR decline ≥3 mL/min/1.73 m²/year (n = 91 cases); and (4) an eGFR <60 mL/min/1.73 m² at follow-up (n = 54 cases). eGFR was determined based on the Modification of Diet in Renal Disease (MDRD) Study equation. Multivariate logistic regression model was used to determine the association between obesity and renal function decline.

Results

We found that central obesity was associated with faster renal function decline. Comparing WC of >95 cm in men or >90 cm in women with ≤90 cm in men or ≤85 cm in women, ORs (95% CIs) ranged from 2.31 (1.14–4.69) to 2.78 (1.19–6.50) for the 4 definitions of renal function decline (all p-values for trend <0.05). Waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) also was associated with renal function decline. There was no significant association of BMI with renal function decline.

Conclusions

Central obesity, but not BMI, is associated with faster renal function decline in Korean population. Our results provide important evidence that simple measurement of central fat deposition rather than BMI could predict decline in renal function in Korean 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.     

Effect of Non-Alcoholic Fatty Liver Disease on Estimated Glomerular Filtration Rate Could Be Dependent on Age

There is a gap between the association of non-alcoholic fatty liver disease (NAFLD) and renal function in an apparently healthy population. This study aims to assess whether NAFLD is associated with estimated glomerular filtration rate (eGFR) levels and to understand early changes of eGFR in NAFLD. A cross-sectional study was performed among apparently healthy persons who underwent general health screening including laboratory assessments and hepatic ultrasonography from January 2013 to December 2013 at the First Affiliated Hospital of Zhejiang University, College of Medicine, China. This study included 1,193 subjects with a mean age of 48 years. Prevalence of NAFLD was 31.3%. Mean eGFR was significantly lower in NAFLD than in controls (107 ± 19 mL/min/1.73 m² vs. 113 ± 23 mL/min/1.73 m², P<0.001). Correlation analysis between eGFR and NAFLD related risk factors revealed an inverse correlation between eGFR levels and some NAFLD risk factors (all P<0.01). All subjects were classified into five phases according to age. Average eGFR levels of NAFLD were lower than controls in three phases for subjects with ≤ 50 years of age (all P<0.05), while there were no significant differences on average eGFR levels between NAFLD and controls in two phases for subjects with >50 years of age (Both P>0.05). The eGFR level is significantly associated with NAFLD and its risk factors in an apparently healthy population. Effects of NAFLD on eGFR could be dependent on age.     

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.     

Renal Function in Chinese HIV-Positive Individuals following Initiation of Antiretroviral Therapy

Aim

To identify the prevalence and predictors of abnormal renal function among HIV-positive Chinese patients prior to antiretroviral therapy (ART) initiation and to evaluate subsequent changes in renal function after ART exposure.

Methods

We conducted a nationwide cohort study of subjects who enrolled in the national Chinese ART program from January 1, 2012 to December 31, 2012. We estimated the glomerular filtration rate (eGFR) of subjects prior to and after initiating ART. Risk factors for abnormal renal function, as defined by eGFR <60 ml/min/1.73m², at baseline and follow-up were assessed by logistic regression and Cox proportional hazards regression models, respectively.

Results

Among 41,862 subjects, at ART baseline, 3.3% had a baseline eGFR <60 ml/min/1.73m² and 24.2% had eGFR = 60–90 ml/min/1.73m². Adjusted baseline risk factors for baseline eGFR <60 ml/min/1.73m² were older age (Adjusted odds ratio [AOR] = 5.19, 95% confidence interval [CI]: 4.52–5.67), female (AOR = 1.68, 95% CI: 1.47–1.93), hemoglobin <120g/L (AOR = 1.68, 95% CI: 1.47–1.93), blood glucose >6.1 mmol/L (AOR = 1.46, 95% CI: 1.25–1.72), and hepatitis C co-infection (AOR = 1.36, 95% CI: 1.06–1.73). Among subjects with baseline eGFR >90 ml/min/1.73m², the incidence of the eGFR falling to <60 ml/min/1.73m² was 0.92/100 person-years after a median of 15.0 months of ART. Being on a tenofovir with lopinavir/ritonavir regimen (Adjusted hazard ratio [AHR] = 3.02, 95% CI: 1.96–4.66) and having an unsuppressed viral load (AHR = 2.70, 95% CI: 1.80–4.03) were independent predictors for eGFR <60 ml/min/1.73m² after ART initiation as well as older age, female, and hemoglobin <120 g/L.

Conclusion

A high proportion of HIV-positive subjects in China presented with abnormal renal function prior to ART initiation. But the incidence of the eGFR decrease after ART was low. Patient renal function should be regularly monitored by eGFR before initiating and during ART.     

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.     

Short and Long-Term Effects of Telaprevir on Kidney Function in Patients with Hepatitis C Virus Infection: A Retrospective Cohort Study

Background

Recent reports suggest that telaprevir, a protease inhibitor used to treat hepatitis C infection, is associated with decline in kidney function during therapy, particularly in patients with baseline renal impairment.

Methods

Patients treated with telaprevir in a single healthcare network were retrospectively reviewed. Kidney function was determined at baseline, during therapy, and twelve weeks and twelve months after telaprevir discontinuation. Significant creatinine rise during therapy was defined as an increase in serum creatinine ≥ 0.3mg/dL from baseline during treatment with telaprevir.

Results

Between July 2011 to January 2013,seventy-eight patients began treatment. The majority completed the prescribed twelve weeks of telaprevir therapy; 32% discontinued due to side effects. The average rise in serum creatinine during therapy was 0.22mg/dL (standard deviation 0.22mg/dL). Thirty-one percent experienced a significant creatinine rise during therapy. Decline in estimated glomerular filtration rate (eGFR) was lower in those with baseline eGFR < 90 mL/min/1.73m² compared to the group with baseline eGFR ≥ 90 mL/min/1.73m² (12 vs. 18 mL/min/1.73m², P = 0.047). Serum creatinine fully normalized by twelve weeks after cessation of telaprevir in 83% of patients, however experiencing a significant creatinine rise during telaprevir use was associated with a 6.6mL/min/1.73m² decrease in estimated glomerular filtration rate at twelve months in an adjusted model.

Conclusions

Decline in kidney function during therapy with telaprevir is common and is not associated with baseline eGFR < 90mL/min/1.73m² as previously reported.     

Mortality Rates Across 25-Hydroxyvitamin D (25[OH]D) Levels among Adults with and without Estimated Glomerular Filtration Rate <60 ml/min/1.73 m2: The Third National Health and Nutrition Examination Survey

Background

Previous studies exploring the association between 25[OH]D levels and mortality in adults with and without kidney disease utilized 25[OH]D thresholds that have recently been scrutinized by the Institute of Medicine Committee to Review Dietary References Intakes for Vitamin D and Calcium.

Objective

We explored all-cause mortality rates across the spectrum of 25[OH]D levels over an eighteen-year follow-up among adults with and without an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m².

Design

The study included 1,097 U.S. adults with eGFR <60 ml/min/1.73 m² and 14, 002 adults with eGFR ≥60 ml/min/1.73 m². Mortality rates and rate ratios (RR) across 25[OH]D groups were calculated with Poisson regression and restricted cubic splines while adjusting for covariates.

Results

Prevalence of 25[OH]D levels <30 and <20 ng/ml among adults with eGFR <60 ml/min/1.73 m² was 76.5% (population estimate 6.2 million) and 35.4% (population estimate 2.9 million), respectively. Among adults with eGFR ≥60 ml/min/1.73 m², 70.5% had 25[OH]D levels <30 ng/ml (population estimate 132.2 million) while 30.3% had 25[OH]D levels <20 ng/ml (population estimate 56.8 million). Significantly higher mortality rates were noted among individuals with 25[OH]D levels <12 ng/ml compared to referent group (24 to <30 ng/ml): RR1.41 (95% CI 1.17, 1.71) among individuals with eGFR <60 ml/min/1.73 m² and RR 1.32 (95% CI 1.13, 1.56) among individuals with eGFR ≥60 ml/min/1.73 m² after adjustment for covariates including co-morbid conditions. Mortality rates were fairly similar across all 25[OH]D groups with levels >20 ng/ml after adjustment for all covariates.

Conclusions

Regardless of presence of eGFR <60 ml/min/1.73 m², mortality rates across groups with 25[OH]D levels 20–40 ng/ml are similar.     

A Panel of Novel Biomarkers Representing Different Disease Pathways Improves Prediction of Renal Function Decline in Type 2 Diabetes

ObjectiveWe aimed to identify a novel panel of biomarkers predicting renal function decline in type 2 diabetes, using biomarkers representing different disease pathways speculated to contribute to the progression of diabetic nephropathy.ResultsPatients’ average age was 63.5 years and baseline eGFR was 77.9 mL/min/1.73m². The average rate of eGFR decline was -2.0 ± 4.7 mL/min/1.73m²/year. When modeled on top of established risk markers, the biomarker panel including matrix metallopeptidases, tyrosine kinase, podocin, CTGF, TNF-receptor-1, sclerostin, CCL2, YKL-40, and NT-proCNP improved the explained variability of eGFR decline (R² increase from 37.7% to 54.6%; p=0.018) and improved prediction of accelerated eGFR decline (C-index increase from 0.835 to 0.896; p=0.008).ConclusionsA novel panel of biomarkers representing different pathways of renal disease progression including inflammation, fibrosis, angiogenesis, and endothelial function improved prediction of eGFR decline on top of established risk markers in type 2 diabetes. These results need to be confirmed in a large prospective cohort.     

Longitudinal Study of the Decline in Renal Function in Healthy Subjects

Background

Chronic kidney disease is an important concern in preventive medicine, but the rate of decline in renal function in healthy population is not well defined. The purpose of this study was to determine reference values for the estimated glomerular filtration rate (eGFR) and rate of decline of eGFR in healthy subjects and to evaluate factors associated with this decline using a large cohort in Japan.

Methods

Retrospective cross-sectional and longitudinal studies were performed with healthy subjects aged ≥18 years old who received a medical checkup. Reference values for eGFR were obtained using a nonparametric method and those for decline of eGFR were calculated by mixed model analysis. Relationships of eGFR decline rate with baseline variables were examined using a linear least-squares method.

Results

In the cross-sectional study, reference values for eGFR were obtained by gender and age in 72,521 healthy subjects. The mean (±SD) eGFR was 83.7±14.7ml/min/1.73m². In the longitudinal study, reference values for eGFR decline rate were obtained by gender, age, and renal stage in 45,586 healthy subjects. In the same renal stage, there was little difference in the rate of decline regardless of age. The decline in eGFR depended on the renal stage and was strongly related to baseline eGFR, with a faster decline with a higher baseline eGFR and a slower decline with a lower baseline eGFR. The mean (±SD) eGFR decline rate was ‒1.07±0.42ml/min/1.73m²/year (‒1.29±0.41%/year) in subjects with a mean eGFR of 81.5±11.6ml/min/1.73m².

Conclusions

The present study clarified for the first time the reference values for the rate of eGFR decline stratified by gender, age, and renal stage in healthy subjects. The rate of eGFR decline depended mainly on baseline eGFR, but not on age, with a slower decline with a lower baseline eGFR.     

Serum Resistin and Glomerular Filtration Rate in Patients with Type 2 Diabetes

BackgroundHigh serum levels of the pro-inflammatory adipokine resistin have been associated with decreased renal function in the general population. The goal of this study was to investigate whether such association is also present among diabetic subjects, who are at increased risk of renal function loss.MethodsThe cross-sectional association between serum resistin levels and estimated glomerular filtration rate (eGFR) was investigated in 1,560 type 2 diabetic (T2D) patients of European ancestry comprised in two different cohorts: 762 patients from San Giovanni Rotondo (SGR; Italy) and 798 patients from Boston (US).ResultsSerum resistin was inversely associated with eGFR in SGR [β (SE) for one SD of resistin increment = -1.01 (0.70) ml/min/1.73m², p = 0.019] and in Boston [β (SE) = -5.31 (0.74) ml/min/1.73m², p < 0.001] samples, as well as in the two studies combined [β (SE) = -3.42 (0.52) ml/min/1.73m², p < 0.001]. The association was unaffected by adjustment for smoking habits, BMI, waist circumference, diabetes duration, HbA1c, insulin treatment, hypertension and lipid-lowering therapy: β (SE) for one SD of resistin increment = -1.07 (0.70), p = 0.02; -5.50 (0.88), p < 0.001; and -2.81 (0.55) ml/min/1.73m², p < .001, in SGR, Boston and the two studies combined, respectively. The association was significantly stronger in men than in women (p for resistin-by-gender interaction = 0.003). For each resistin SD increment, the odds of having eGFR < 0 ml/min/1.73m² increased by 22% (OR = 1.22; 95% CI 1.02–1.44; p = 0.025) in SGR sample, 69% (OR = 1.69; 95% CI 1.38–2.07; p < 0.001) in Boston sample, and 47% (OR = 1.47; 95% CI 1.29–1.68; p < 0.001) in the two studies considered together. Similar associations were observed in the adjusted model: OR 95% CI for each SD resistin increment being 1.23 (1.03–1.46), p = 0.021; 1.52 (1.20–1.92), p < 0.001; 1.33 (1.16–1.53), p < 0.001, in SGR, Boston and the two studies combined, respectively.ConclusionsThis is the first report of an association between high serum resistin and low eGFR in patients with T2D of European ancestry.     

Mortality Prediction in the Oldest Old with Five Different Equations to Estimate Glomerular Filtration Rate: The Health and Anemia Population-based Study

Background

Kidney function declines considerably with age, but little is known about its clinical significance in the oldest-old.

Objectives

To study the association between reduced glomerular filtration rate (GFR) estimated according to five equations with mortality in the oldest-old.

Design

Prospective population-based study.

Setting

Municipality of Biella, Piedmont, Italy.

Participants

700 subjects aged 85 and older participating in the “Health and Anemia” Study in 2007–2008.

Measurements

GFR was estimated using five creatinine-based equations: the Cockcroft-Gault (C-G), Modification of Diet in Renal Disease (MDRD), MAYO Clinic, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Berlin Initiative Study-1 (BIS-1). Survival analysis was used to study mortality in subjects with reduced eGFR (<60 mL/min/1.73m²) compared to subjects with eGFR ≥60 mL/min/1.73m².

Results

Prevalence of reduced GFR was 90.7% with the C-G, 48.1% with MDRD, 23.3% with MAYO, 53.6% with CKD-EPI and 84.4% with BIS-1. After adjustment for confounders, two-year mortality was significantly increased in subjects with reduced eGFR using BIS-1 and C-G equations (adjusted HRs: 2.88 and 3.30, respectively). Five-year mortality was significantly increased in subjects with eGFR <60 mL/min/1.73m² using MAYO, CKD-EPI and, in a graduated fashion in reduced eGFR categories, MDRD. After 5 years, oldest old with an eGFR <30 mL/min/1.73m² showed a significantly higher risk of death whichever equation was used (adjusted HRs between 2.04 and 2.70).

Conclusion

In the oldest old, prevalence of reduced eGFR varies noticeably depending on the equation used. In this population, risk of mortality was significantly higher for reduced GFR estimated with the BIS-1 and C-G equations over the short term. Though after five years the MDRD appeared on the whole a more consistent predictor, differences in mortality prediction among equations over the long term were less apparent. Noteworthy, subjects with a severely reduced GFR were consistently at higher risk of death regardless of the equation used to estimate GFR.     

Progression of Kidney Disease in Non-Diabetic Patients with Coronary Artery Disease: Predictive Role of Circulating Matrix Metalloproteinase-2, -3, and -9

Background

Circulating matrix metalloproteinase (MMP)-2, -3 and -9 are well recognized in predicting cardiovascular outcome in coronary artery disease (CAD), but their risks for chronic kidney disease (CKD) are lacking. Therefore, the present study aimed to investigate whether circulating MMP levels could independently predict future kidney disease progression in non-diabetic CAD patients.

Methods

The prospective study enrolled 251 non-diabetic subjects referred for coronary angiography, containing normal coronary artery (n = 30) and CAD with insignificant (n = 95) and significant (n = 126) stenosis. Estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI formula. eGFR decline rate was calculated and the primary endpoint was a decline in eGFR over 25% from baseline.

Results

The eGFR decline rate (ml/min/1.73 m² per year) in patients with CAD (1.22 [−1.27, 1.05]) was greater than that in those with normal coronary artery (0.21 [−2.63, 0.47], P<0.01). The circulating MMP-2, -3 and -9 were independently associated with faster eGFR decline among CAD patients. The mean follow-up period was 8.5±2.4 years, and 39 patients reached the primary endpoint. In multivariate Cox regression model, the adjusted hazard ratios of MMP-2 ≥861 ng/mL, MMP-3 ≥227 ng/mL and MMP-9 ≥49 ng/mL for predicting CKD progression were 2.47 (95% CI, 1.21 to 5.07), 2.15 (1.12 to 4.18), and 4.71 (2.14 to 10.4), respectively. While added to a model of conventional risk factors and baseline eGFR, MMP-2, -3 and -9 further significantly improved the model predictability for CKD progression (c statistic, 0.817). In the sensitivity analyses, the results were similar no matter if we changed the endpoints of a decline of >20% in eGFR from baseline or final eGFR < 60 mL/min/1.73 m².

Conclusion

Circulating MMP-2, -3 and -9 are independently associated with kidney disease progression in non-diabetic CAD patients and add incremental predictive power to conventional risk factors.     

Incident Chronic Kidney Disease and Newly Developed Complications Related to Renal Dysfunction in an Elderly Population during 5 Years: A Community-Based Elderly Population Cohort Study

Background

Few studies have evaluated the association between incident chronic kidney disease (CKD) and related complications, especially in elderly population. We attempted to verify the association between GFR and concurrent CKD complications and elucidate the temporal relationship between incident CKD and new CKD complications in a community-based prospective elderly cohort.

Method

We analyzed the available data from 984 participants in the Korean Longitudinal Study on Health and Aging. Participants were categorized into 6 groups according to eGFR at baseline examination (≥90, 75–89, 60–74, 45–59, 30–44, and <30 ml/min/1.73 m²).

Result

The mean age of study population was 76 ± 9.1 years and mean eGFR was 72.3 ± 17.0 ml/min/1.73 m². Compared to eGFR group 1, the odds ratio (OR) for hypertension was 2.363 (95% CI, 1.299-4.298) in group 4, 5.191 (2.074-12.995) in group 5, and 13.675 (1.611-115.806) in group 6; for anemia, 7.842 (2.265-27.153) in group 5 and 13.019 (2.920-58.047) in group 6; for acidosis, 69.580 (6.770-715.147) in group 6; and for hyperkalemia, 19.177 (1.798-204.474) in group 6. Over a 5-year observational period, CKD developed in 34 (9.6%) among 354 participants with GFR ≥ 60 ml/min/1.73 m² at basal examination. The estimated mean number of new complications according to analysis of co-variance was 0.52 (95% CI, 0.35–0.68) in subjects with incident CKD and 0.24 (0.19–0.29) in subjects without CKD (p = 0.002). Subjects with incident CKD had a 2.792-fold higher risk of developing new CKD complications. A GFR level of 52.4 ml/min/1.73 m² (p = 0.032) predicted the development of a new CKD complication with a 90% sensitivity.

Conclusion

In an elderly prospective cohort, CKD diagnosed by current criteria is related to an increase in the number of concurrent CKD complications and the development of new CKD complications.     

Association of Kidney Disease Measures with Cause-Specific Mortality: The Korean Heart Study

BackgroundThe link of low estimated glomerular filtration rate (eGFR) and high proteinuria to cardiovascular disease (CVD) mortality is well known. However, its link to mortality due to other causes is less clear.MethodsWe studied 367,932 adults (20–93 years old) in the Korean Heart Study (baseline between 1996–2004 and follow-up until 2011) and assessed the associations of creatinine-based eGFR and dipstick proteinuria with mortality due to CVD (1,608 cases), cancer (4,035 cases), and other (non-CVD/non-cancer) causes (3,152 cases) after adjusting for potential confounders.ResultsAlthough cancer was overall the most common cause of mortality, in participants with chronic kidney disease (CKD), non-CVD/non-cancer mortality accounted for approximately half of cause of death (47.0%for eGFR <60 ml/min/1.73m² and 54.3% for proteinuria ≥1+). Lower eGFR (<60 vs. ≥60 ml/min/1.73m²) was significantly associated with mortality due to CVD (adjusted hazard ratio 1.49 [95% CI, 1.24–1.78]) and non-CVD/non-cancer causes (1.78 [1.54–2.05]). The risk of cancer mortality only reached significance at eGFR <45 ml/min/1.73m² when eGFR 45–59 ml/min/1.73m² was set as a reference (1.62 [1.10–2.39]). High proteinuria (dipstick ≥1+ vs. negative/trace) was consistently associated with mortality due to CVD (1.93 [1.66–2.25]), cancer (1.49 [1.32–1.68]), and other causes (2.19 [1.96–2.45]). Examining finer mortality causes, low eGFR and high proteinuria were commonly associated with mortality due to coronary heart disease, any infectious disease, diabetes, and renal failure. In addition, proteinuria was also related to death from stroke, cancers of stomach, liver, pancreas, and lung, myeloma, pneumonia, and viral hepatitis.ConclusionLow eGFR was associated with CVD and non-CVD/non-cancer mortality, whereas higher proteinuria was consistently related to mortality due to CVD, cancer, and other causes. These findings suggest the need for multidisciplinary prevention and management strategies in individuals with CKD, particularly when proteinuria is present.     

An Estimation of the Prevalence and Progression of Chronic Kidney Disease in a Rural Diabetic Cambodian Population

Background

To date, there are no known estimates of the prevalence of chronic kidney disease within Cambodia, the vast majority of whose citizens live in rural areas with limited access to renal replacement therapy.

Methods

Observational analysis of patients from the Takeo province in Cambodia who presented to MoPoTsyo, a non-governmental organization, for screening and management of diabetes mellitus between 2010 and 2012 (n = 402; 75% females). Estimated glomerular filtration rate (eGFR) was calculated using the CKD-Epi equation.

Results

On average, women were younger, with a higher percentage of hypercholesterolemia but also high-density lipoprotein level. Men had a higher serum creatinine level (1.31 mg/dl) than that of women (1.13 mg/dl) at 95% CI. More than half of all screened patients had a reduced eGFR; 60% (95% CI 55%, 65%) had an eGFR<60 ml/min/1.73 m²; 54% (49%, 59%) had an eGFR 30–60 ml/min/1.73 m², and 5.7% (3.4%, 8.0%) with eGFR 15–30 ml/min/1.73 m². Women had a greater prevalence of stage 3 CKD (57% women vs. 47% men) and stage 4 CKD (7.0% vs. 2.0%). The adjusted odds ratio for females compared to males having an eGFR <60 ml/min/1.73 m² was 3.19 (95% CI 1.78, 5.43; p value<0.001). Thirty-two percent of patients lost ≥5 ml/min/1.73 m2 eGFR during median follow-up time of 433 days (IQR 462 days) days.

Conclusions

Over one-half of Cambodians with diabetes mellitus had reduced eGFR, implying a point-prevalence of chronic kidney disease of 1.2% in among adult Cambodians within the country. This high burden of kidney disease in a society that lacks universal access to renal replacement therapy underscores the importance of early diagnosis – a largely unmet need in Cambodia.