Glomerular Filtration Rate and Proteinuria: Association with Mortality and Renal Progression in a Prospective Cohort of a Community-Based Elderly Population

Limited prospective data are available on the importance of estimated glomerular filtration rate (GFR) and proteinuria in the prediction of all-cause mortality (ACM) in community-based elderly populations. We examined the relationship between GFR or proteinuria and ACM in 949 randomly selected community-dwelling elderly subjects (aged ≥65 years) over a 5-year period. A spot urine sample was used to measure proteinuria by the dipstick test, and GFR was estimated using the chronic kidney disease-epidemiology collaboration (CKD-EPI) equation. Information about mortality and causes of death was collected by direct enquiry with the subjects and from the national mortality data. Compared to subjects without proteinuria, those with proteinuria of grade ≥1+ had a 1.725-fold (1.134–2.625) higher risk of ACM. Compared to subjects with GFR ≥90 ml/min/1.73 m², those with GFR<45 ml/min/1.73 m² had a 2.357 -fold (1.170–4.750) higher risk for ACM. Among the 403 subjects included in the analysis of renal progression, the annual rate of GFR change during follow-up period was −0.52±2.35 ml/min/1.73 m²/year. The renal progression rate was 7.315-fold (1.841–29.071) higher in subjects with GFR<60 ml/min/1.73 m² than in those with GFR ≥60 ml/min/1.73 m². Among a community-dwelling elderly Korean population, decreased GFR of <45 ml/min/1.73 m² and proteinuria were independent risk factors for ACM.     

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.     

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.     

Long-Term Follow-Up of Proteinuria and Estimated Glomerular Filtration Rate in HIV-Infected Patients with Tubular Proteinuria

Objective

The objective of this prospective observational study was to describe the evolution of tubular proteinuria detected in HIV-infected patients, and to evaluate the impact of tenofovir disoproxil fumarate (TDF) discontinuation.

Methods

Proteinuria and estimated glomerular filtration rate (eGFR) were followed during a median duration of 32 months, in 81 HIV-infected patients with tubular proteinuria and eGFR ≥ 60 ml/min/1.73 m² (determined using the Chronic Kidney Disease Epidemiology (CKD-EPI) Collaboration equation). Tubular proteinuria was defined by urine protein to creatinine ratio (uPCR) ≥200 mg/g and albumin to protein ratio (uAPR) <0.4.

Results

Twenty per cent of patients had persistence of tubular proteinuria: TDF continuation was the main factor associated with this persistence [OR 9.0; 95%CI: 1.9–41.4; p = 0.01]. Among the 23 patients who discontinued TDF, uPCR returned below the threshold of 200 mg/g in 11 patients. Overall, eGFR decreased with a mean rate of decline of 3.8 ml/min/1.73m²/year. The decline in eGFR was lesser after discontinuation of TDF (5.8 ml/min/1.73m²/year during TDF exposure versus 3 ml/min/1.73m²/year after TDF discontinuation; p = 0.01).

Conclusions

The continuation of TDF was the main factor associated with the persistence of proteinuria. Moreover, proteinuria was normalized in only half of the patients who discontinued TDF. The clinical significance of TDF-related low level of proteinuria as a factor associated with renal disease progression and bone loss remains poorly understood.     

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.     

Hospitalizations among adults with chronic kidney disease in the United States: A cohort study

BackgroundAdults with chronic kidney disease (CKD) are hospitalized more frequently than those without CKD, but the magnitude of this excess morbidity and the factors associated with hospitalizations are not well known.Methods and findingsData from 3,939 participants enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study between 2003 and 2008 at 7 clinical centers in the United States were used to estimate primary causes of hospitalizations, hospitalization rates, and baseline participant factors associated with all-cause, cardiovascular, and non-cardiovascular hospitalizations during a median follow up of 9.6 years. Multivariable-adjusted Poisson regression was used to identify factors associated with hospitalization rates, including demographics, blood pressure, estimated glomerular filtration rate (eGFR), and proteinuria. Hospitalization rates in CRIC were compared with rates in the Nationwide Inpatient Sample (NIS) from 2012. Of the 3,939 CRIC participants, 45.1% were female, and 41.9% identified as non-Hispanic black, with a mean age of 57.7 years, and the mean eGFR is 44.9 ml/min/1.73m². CRIC participants had an unadjusted overall hospitalization rate of 35.0 per 100 person-years (PY) [95% CI: 34.3 to 35.6] and 11.1 per 100 PY [95% CI: 10.8 to 11.5] for cardiovascular-related causes. All-cause, non-cardiovascular, and cardiovascular hospitalizations were associated with older age (≥65 versus 45 to 64 years), more proteinuria (≥150 to <500 versus <150 mg/g), higher systolic blood pressure (≥140 versus 120 to <130 mmHg), diabetes (versus no diabetes), and lower eGFR (<60 versus ≥60 ml/min/1.73m²). Non-Hispanic black (versus non-Hispanic white) race/ethnicity was associated with higher risk for cardiovascular hospitalization [rate ratio (RR) 1.25, 95% CI: 1.16 to 1.35, p-value < 0.001], while risk among females was lower [RR 0.89, 95% CI: 0.83 to 0.96, p-value = 0.002]. Rates of cardiovascular hospitalizations were higher among those with ≥500 mg/g of proteinuria irrespective of eGFR. The most common causes of hospitalization were related to cardiovascular (31.8%), genitourinary (8.7%), digestive (8.3%), endocrine, nutritional or metabolic (8.3%), and respiratory (6.7%) causes. Hospitalization rates were higher in CRIC than the NIS, except for non-cardiovascular hospitalizations among individuals aged >65 years. Limitations of the study include possible misclassification by diagnostic codes, residual confounding, and potential bias from healthy volunteer effect due to its observational nature.ConclusionsIn this study, we observed that adults with CKD had a higher hospitalization rate than the general population that is hospitalized, and even moderate reductions in kidney function were associated with elevated rates of hospitalization. Causes of hospitalization were predominantly related to cardiovascular disease, but other causes contributed, particularly, genitourinary, digestive, and endocrine, nutritional, and metabolic illnesses. High levels of proteinuria were observed to have the largest association with hospitalizations across a wide range of kidney function levels.

Hsiang-Yu Chen and colleagues report the factors associated with hospitalization in patients with Chronic Kidney Disease.     

NT-proBNP Linking Low-Moderately Impaired Renal Function and Cardiovascular Mortality in Diabetic Patients: The Population-Based Casale Monferrato Study

Background

Few data are available to assess whether a low-moderate reduction in estimated glomerular filtration rates (eGFR) has a role per se on cardiovascular (CV) mortality or other biomarkers such as NT-proBNP allow to explain such association.

Methods and Findings

In a prospective study including 1,645 type 2 diabetic subjects of the population-based Casale Monferrato Study, who had no clinical evidence of heart failure and eGFR >45 ml/min/1.73 m², we examined 6 years CV mortality. Multivariate Cox proportional hazards modeling were used to estimate the effect of NT-proBNP on the association between eGFR and mortality, independently of baseline CV risk factors, albumin excretion rate (AER) and C-reactive protein (CRP). During follow-up, 327 people died (149 of CV diseases) out of 8334.5 person-years. Compared to eGFR≥90 ml/min/1.73 m², values of 60–89 and 45–59 ml/min/1.73 m² conferred a fully adjusted hazard ratios (HRs) of CV mortality of 1.74 (1.08–2.82) and 1.95 (1.03–3.68), respectively. After further adjustment for NT-proBNP, however, HRs were no longer significant (HRs 1.42, 0.83–2.42 and 1.22, 0.59–2.51). In this model, HR for logNT-proBNP was 1.84 (1.52–2.22). Adding NT-proBNP to the model improved the C-statistic of CV mortality from 0.79 (0.76–0.83) to 0.84 (0.81–0.87), yielded an IDI of 0.03 (p = 0.02), and a NRI of 0.44 (p = 0.016).

Conclusions

In diabetic people a modest reduction in renal function increased 6-year CV mortality independently of albuminuria. This association, however, was mainly explained by the effect of NT-proBNP, that remained the strongest prognostic marker for a worse CV outcome, even after adjustment for other CV risk factors and pre-existing CVD.     

Association of Socioeconomic Status with Overall and Cause Specific Mortality in the Republic of Seychelles: Results from a Cohort Study in the African Region

Background

Low socioeconomic status (SES) is consistently associated with higher mortality in high income countries. Only few studies have assessed this association in low and middle income countries, mainly because of sparse reliable mortality data. This study explores SES differences in overall and cause-specific mortality in the Seychelles, a rapidly developing small island state in the African region.

Methods

All deaths have been medically certified over more than two decades. SES and other lifestyle-related risk factors were assessed in a total of 3246 participants from three independent population-based surveys conducted in 1989, 1994 and 2004. Vital status was ascertained using linkage with vital statistics. Occupational position was the indicator of SES used in this study and was assessed with the same questions in the three surveys.

Results

During a mean follow-up of 15.0 years (range 0–23 years), 523 participants died (overall mortality rate 10.8 per 1000 person-years). The main causes of death were cardiovascular disease (CVD) (219 deaths) and cancer (142 deaths). Participants in the low SES group had a higher mortality risk for overall (HR = 1.80; 95% CI: 1.24–2.62), CVD (HR = 1.95; 1.04–3.65) and non-cancer/non-CVD (HR = 2.14; 1.10–4.16) mortality compared to participants in the high SES group. Cancer mortality also tended to be patterned by SES (HR = 1.44; 0.76–2.75). Major lifestyle-related risk factors (smoking, heavy drinking, obesity, diabetes, hypertension, hypercholesterolemia) explained a small proportion of the associations between low SES and all-cause, CVD, and non-cancer/non-CVD mortality.

Conclusions

In this population-based study assessing social inequalities in mortality in a country of the African region, low SES (as measured by occupational position) was strongly associated with overall, CVD and non-cancer/non-CVD mortality. Our findings support the view that the burden of non-communicable diseases may disproportionally affect people with low SES in low and middle income countries.     

Reduced Glomerular Filtration Rate and Its Association with Clinical Outcome in Older Patients at Risk of Vascular Events: Secondary Analysis

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.     

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.     

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.     

Seasonal Variation of Overall and Cardiovascular Mortality: A Study in 19 Countries from Different Geographic Locations

Background

Cardiovascular diseases (CVD) mortality has been shown to follow a seasonal pattern. Several studies suggested several possible determinants of this pattern, including misclassification of causes of deaths. We aimed at assessing seasonality in overall, CVD, cancer and non-CVD/non-cancer mortality using data from 19 countries from different latitudes.

Methods and Findings

Monthly mortality data were compiled from 19 countries, amounting to over 54 million deaths. We calculated ratios of the observed to the expected numbers of deaths in the absence of a seasonal pattern. Seasonal variation (peak to nadir difference) for overall and cause-specific (CVD, cancer or non-CVD/non-cancer) mortality was analyzed using the cosinor function model. Mortality from overall, CVD and non-CVD/non-cancer showed a consistent seasonal pattern. In both hemispheres, the number of deaths was higher than expected in winter. In countries close to the Equator the seasonal pattern was considerably lower for mortality from any cause. For CVD mortality, the peak to nadir differences ranged from 0.185 to 0.466 in the Northern Hemisphere, from 0.087 to 0.108 near the Equator, and from 0.219 to 0.409 in the Southern Hemisphere. For cancer mortality, the seasonal variation was nonexistent in most countries.

Conclusions

In countries with seasonal variation, mortality from overall, CVD and non-CVD/non-cancer show a seasonal pattern with mortality being higher in winter than in summer. Conversely, cancer mortality shows no substantial seasonality.     

Efficacy and safety of Abelmoschus manihot for IgA nephropathy: A multicenter randomized clinical trial

Rationale and ObjectiveIgA nephropathy (IgAN) is an important cause for end-stage renal disease worldwide. The treatment for IgAN remains challenging, and few randomized and controlled clinical trials have been conducted to evaluate new therapies. The present study assesses the efficacy and safety of Abelmoschus manihot (AM) in IgAN patients.Study DesignRandomized, non-inferiority, double-blind, double-dummy multicenter trial.Setting and ParticipantsThis trial was designed to recruit 1,600 biopsy-proven IgAN patients (proteinuria between 0.5-3.0 g/d and estimated glomerular filtration rate [eGFR] of ≥ 45 ml/min/1.73 m²) across China.InterventionsThe participants were randomized at 1:1 to AM (2.5 g for three times per day) or losartan potassium (100 mg per day) for 48 weeks.OutcomesThe primary outcome was the change in 24-hour proteinuria from baseline to week 48. The secondary outcomes were the change in eGFR from baseline to week 48, and the incidents of endpoint events (proteinuria ≥ 3.5 g/24 h, doubling of serum creatinine, or receiving renal replacement treatment).ResultsAmong 1,470 randomized patients (mean age, 37.4 [SD, 10.6] years old; 777 [52.9%] were female; mean eGFR, 95.0 [SD, 24.3] mL/min/1.73 m²; mean 24-hour proteinuria, 1.2 [SD, 0.7] g/d), the mean decline in 24-h proteinuria at week 48 was 230 mg and 253 mg in the AM and losartan potassium groups, respectively (P = 0.676). The mean difference in the change in 24-h proteinuria between these two groups was -23.32 mg (95% confident interval: -123.2 to 76.6, p = 0.647). The mean decline in eGFR was 0.41 ml/min/1.73 m² and 0.76 ml/min/1.73 m² in the AM and losartan potassium groups, respectively (p = 0.661). The mean difference in the change in eGFR between these two groups was -0.43 ml/min/1.73 m² (95% confident interval: -1.99 to 1.13, p = 0.589). The incidence of endpoint events was 8.6% in the AM group and 8.2% in the losartan group (p = 0.851).LimitationsThe results of the trial may not be generalized to IgAN patients with a proteinuria of > 3.0 g/d and an eGFR of < 45 ml/min/1.73 m². The long-term benefits of AM in reducing the risk of progressive renal dysfunction remains unclear, based on this 48-week observation.ConclusionAM can be recommended as a promising treatment for IgAN patients.     

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.     

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.     

Epidemiology of CKD Regression in Patients under Nephrology Care

Chronic Kidney Disease (CKD) regression is considered as an infrequent renal outcome, limited to early stages, and associated with higher mortality. However, prevalence, prognosis and the clinical correlates of CKD regression remain undefined in the setting of nephrology care. This is a multicenter prospective study in 1418 patients with established CKD (eGFR: 60–15 ml/min/1.73m²) under nephrology care in 47 outpatient clinics in Italy from a least one year. We defined CKD regressors as a ΔGFR ≥0 ml/min/1.73 m²/year. ΔGFR was estimated as the absolute difference between eGFR measured at baseline and at follow up visit after 18–24 months, respectively. Outcomes were End Stage Renal Disease (ESRD) and overall-causes Mortality.391 patients (27.6%) were identified as regressors as they showed an eGFR increase between the baseline visit in the renal clinic and the follow up visit. In multivariate regression analyses the regressor status was not associated with CKD stage. Low proteinuria was the main factor associated with CKD regression, accounting per se for 48% of the likelihood of this outcome. Lower systolic blood pressure, higher BMI and absence of autosomal polycystic disease (PKD) were additional predictors of CKD regression. In regressors, ESRD risk was 72% lower (HR: 0.28; 95% CI 0.14–0.57; p<0.0001) while mortality risk did not differ from that in non-regressors (HR: 1.16; 95% CI 0.73–1.83; p = 0.540). Spline models showed that the reduction of ESRD risk associated with positive ΔGFR was attenuated in advanced CKD stage. CKD regression occurs in about one-fourth patients receiving renal care in nephrology units and correlates with low proteinuria, BP and the absence of PKD. This condition portends better renal prognosis, mostly in earlier CKD stages, with no excess risk for mortality.     

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.     

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.     

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.     

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.