Body-mass index and the risk of albuminuria in hypertensive patients with a poor estimated glomerular filtration rate and the potential role of diabetes mellitus

BackgroundObesity-related to metabolic syndrome was associated with a greater risk for development of chronic kidney disease (CKD). We aimed to assess the association between obesity and micro/macroalbuminuria in hypertensive patients with a poor estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m².MethodsOne hundred old patients (median age 79 years ± inter-quartile range 68–84.7) with manifested hypertension (systolic blood pressure ≥ 130 mmHg and/or diastolic blood pressure ≥ 85 mmHg) and a permanently poor eGFR for a duration time more than 3 months were enclosed. Albuminuria was defined as urinary albumin-to-creatinine ratio (ACR) ≥ 30 mg/gr and it was classified according to KDIGO 2012. The obesity was defined by a high body mass index (BMI>30 kg/m²). The waist circumference, HDL-C, triglycerides and serum glucose were measured. Chi-square tests and an adjusted model were performed.ResultsChi-square tests showed significant association between classified albuminuria and both obesity and high serum triglycerides (x² = 7.2, p = 0.02 and x² = 8.3, p = 0.01 respectively). However, the adjusted model for the prediction of albuminuria showed that the presence of a high BMI was a non-significant risk factor, although diabetes mellitus and eGFR value were found to be significant risk factors (p = 0.03, OR = 4.3, 1.2–22.07 and p = 0.04, OR = 0.9, 0.9–1.007 respectively) adjusting to covariates including the high waist circumference.ConclusionObesity defined by a high BMI was not found to be a significant risk factor for micro/macroalbuminuria in hypertensive patients with a poor estimated glomerular filtration rate, when diabetes mellitus and the low eGFR value act as confounders.     

Relationship between plasma growth differentiation factor-15 level and estimated glomerular filtration rate in type 2 diabetes patients with and without albuminuria

AimTo assess the relationship between growth differentiation factor-15 (GDF-15) levels and estimated glomerular filtration rate (eGFR) in type 2 diabetes mellitus (DM) patients with and without albuminuria.MethodsWe examined 324 patients with type 2 DM in a cross-sectional study. eGFR was determined using equations from creatinine (eGFR_cr) and the combination of creatinine and cystatin C (eGFR_cr-cys). The patients were classified into two groups based on urinary albumin: creatinine ratio (ACR): the normoalbuminuria group (urinary ACR < 30 mg/g) and the albuminuria group (urinary ACR ≥ 30 mg/g).ResultsIn individuals both with and without albuminuria, higher GDF-15 levels were associated with lower eGFR_cr and eGFR_cr-cys. Plasma GDF-15 levels were inversely correlated with eGFR_cr in individuals both with and without albuminuria (γ = ?0.624, p < 0.001 and γ = ?0.509, p < 0.001, respectively). A multiple regression analysis showed that GDF-15 levels were significantly associated with eGFR_cr after adjusting for age, sex and other confounders, including urinary ACR as a continuous or categorical variable (β = ?0.309, p < 0.001 and β = ?0.318, p < 0.001, respectively). Similarly, these results were replicated when eGFR_cr-cys was considered instead of eGFR_cr in correlation and regression analyses.ConclusionGDF-15 levels were inversely associated with eGFR in patients with type 2 DM. This relationship was independent of albuminuria status.     

Cardiovascular events and all-cause mortality by albuminuria and decreased glomerular filtration rate in patients with vascular disease

Objectives. Albuminuria and decreased estimated glomerular filtration rate (eGFR) are associated with increased cardiovascular risk, but do not necessarily coexist and have different pathophysiological mechanisms. This study aims to evaluate separate and combined effects of decreased eGFR and albuminuria on the occurrence of vascular diseases and mortality in patients with vascular disease. Design. Prospective cohort study. Setting. University Medical Center Utrecht, the Netherlands. Subjects and main outcome measures. 2600 patients with vascular disease were followed for vascular events, vascular and all‐cause mortality. Cox regression analysis was used to calculate hazard ratios (HRs) according to eGFR (MDRD) and albuminuria (albumin‐to‐creatinine ratio >3 mg mmol⁻¹). Results. In this population, 14.0% had albuminuria, 15.6% had eGFR <60 ml min⁻¹ 1.73 m⁻² and 5.2% had both. Nonalbuminuric decreased eGFR and albuminuria with normal eGFR generated moderately increased risks on all outcomes. eGFR <60 ml min⁻¹ 1.73 m⁻² without albuminuria mainly influenced the risk of vascular events (HR 1.50; 1.05–2.15) whilst albuminuria with eGFR ≥60 ml min⁻¹ 1.73 m⁻² principally affected all‐cause mortality (HR 1.53; 1.04–2.26). The combination of eGFR <60 ml min⁻¹ 1.73 m⁻² and albuminuria was associated with an increased risk for vascular events (HR 2.27; 1.54–3.34), vascular mortality (HR 2.22; 1.40–3.52) and all‐cause mortality (HR 1.84; 1.25–2.69). Comparable results were found in additional analyses amongst 759 diabetic patients. Conclusions. The combination of decreased eGFR with albuminuria is associated with the highest risks of vascular events, vascular and all‐cause mortality in patients with vascular diseases. To adequately estimate vascular risk associated with impaired renal function, both eGFR and urinary albumin should be considered.     

Association of standardized estimated glomerular filtration rate with the prevalence of hypertension among adults in the United States

National Kidney Disease Education Program has initiated a serum creatinine standardization program. Glomerular filtration rate (GFR) can be re-estimated from standardized serum creatinine measurements. How the standardized estimated GFR (eGFR) influences hypertension prevalence has not been evaluated. In this study, cross-sectional data from 21?205 participants aged 18 years in the National Health and Nutrition Examination Survey 1999-2006 were analyzed. The differences between standardized and non-standardized eGFRs in the prevalence of hypertension and low eGFR were evaluated. Multiple logistic regression models were conducted to determine the association of standardized eGFR with hypertension prevalence. The prevalence of low eGFR estimated from standardized eGFR was higher than that from non-standardized eGFR (all P<0.01), except for the 2005-2006 survey. The prevalence of hypertension under standardized eGFR was not significantly different from that under non-standardized eGFR in both groups of participants with eGFR>60 and eGFR60?ml?min(-1) per 1.73?m(2). Adjusted for age, education, gender, race/ethnicity, smoking, serum cholesterol and diabetes mellitus, the participants with standardized eGFR60?ml?min(-1) per 1.73?m(2) had 56.1% more chance to be hypertensive patients than those with normal eGFR (P<0.0001). The difference in the relationship to hypertension prevalence between standardized and non-standardized eGFR was not found significant.     

Tables estimating glomerular filtration rate from plasma creatinine

Chronic kidney disease (CKD) and its related complications have become an important health and social problem. Very expensive resources are required in end-stage renal disease, and both complications of CKD as well as the important associated cardiovascular risk demand for interventions long before renal substitution therapies are needed. Thus, early diagnosis of CKD is currently considered of paramount importance, and it is based essentially upon the estimation of the glomerular filtration rate by formulae such as the abbreviated equation of the MDRD study. Nevertheless, in spite of international published recommendations, an automatic calculation to estimate the glomerular filtration rate (GFR) from serum creatinine is not reported by most laboratories yet and the need for creatinine assay standardisation is far from being implemented. Thus, we have designed some tables to show the creatinine value corresponding to different GFR for ages between 20 and 90 y/o, at 5 years intervals and in both sexes with both the MDRD-4 and MDRD-IDMS equations (Modification of Diet in Renal Disease-Isotope Dilution Mass Spectrometry). Moreover, we have created a global table including an estimation of GFR from plasma creatinine, age and sex by the MDRD-IDMS formula, the recommended for those laboratories which measure serum creatinine with assays aligned to the reference method. These tables aim to increase the awareness of the different assays for serum creatinine and to facilitate the diagnosis of CKD converting serum creatinine into GFR. This action should allow not only the early detection but also the possibility to establish the appropriate medical actions recommended after CKD detection.     

Relationship between plasma S-adenosylhomocysteine concentration and glomerular filtration rate in children

S-Adenosylhomocysteine (SAH) is the metabolic precursor of all the homocysteine (Hcy) produced in the body. It is formed by the enzyme SAH hydrolase in a reversible reaction. In a previous study we have shown that plasma SAH is a more sensitive indicator of the risk for cardiovascular disease, and in a second study involving patients with renal disease, we also showed that it is a more sensitive indicator of renal insufficiency than plasma Hcy. However, in the latter study, the patients with renal disease were older and had a variety of other diseases such as diabetes and primary hypertension, which are associated with vascular disease and which could reduce renal function by involvement of the kidneys. Our objective was to rule out these complicating factors as the cause of the elevated SAH in renal disease and determine whether renal insufficiency alone was the cause of the elevated SAH. We therefore measured SAH, Hcy, folate, and vitamin B12 in 23 patients between the ages of 1 and 18 years with a wide range of renal function, but who had none of these complicating factors. Glomerular filtration rate (GFR) was calculated using serum creatinine according to the Schwartz formula. None of the children were deficient in folate or vitamin B12. After adjusting for age, folate, and vitamin B12, there was a modest and insignificant decrease of 0.033 micromol/L of Hcy associated with an increase of 1 mL/min of GFR (95% confidence interval, -0.066 to 0.0002). However, there was a strong and statistically significant association between log(SAH) and log(GFR): P < .0005, R2 = 0.76. This result suggests that plasma SAH rather than Hcy is the metabolite primarily affected in renal disease. We suggest that plasma Hcy elevations that have been linked to vascular disease may be due to elevated SAH resulting from renal insufficiency.     

Reduced glomerular filtration rate and cardiovascular damage in diabetes: a key role for abnormal albuminuria

There is general agreement that a fall rate in glomerular filtration rate (GFR) is the principal endpoint in diabetics with renal disease, and that abnormal albuminuria (including microalbuminuria) is an important intermediate end-point. The relative roles of blood pressure (BP) elevation and abnormal albuminuria in the prediction and genesis of renal disease are a matter of debate, and are further analysed in this paper. New studies show that neither genetic predisposition to hypertension (parental BP) nor parental abnormal albuminuria can be used to predict renal disease in patients with type 1 (insulin-dependent) diabetes. However, parental predisposition to proteinuria seems to be important to certain types of patients with type 2 (non-insulin-dependent) diabetes. Cross-sectional as well as follow-up studies document that GFR is generally well preserved in microalbuminuria (in both type 1 and type 2 patients), while the transition to clinical proteinuria is associated with a decline in GFR. Thus, prevention of overt proteinuria is important in clinical trials in microalbuminuric patients. In type 1 diabetes clear ultrastructural changes have been documented with microalbuminuria and a good correlation between abnormal albuminuria and structural damage is seen. Structural damage in normo- and microalbuminuric patients correlates poorly with BP. New studies in type 1 diabetes document that microalbuminuria (but not elevated BP) predicts not only clinical diabetic nephropathy but also end-stage renal failure and mortality. In type 2 diabetes microalbuminuria is the strongest predictor of mortality, whereas BP elevation is not a predictor. Several studies now document that antihypertensive treatment, especially with inhibitors of angiotensin converting enzyme, is able to reverse or reduce abnormal albuminuria, even in non-hypertensive type 1 patients, and possibly preserve GFR. Therefore, microalbuminuria may be the main indicator for starting antihypertensive treatment in these patients. With respect to organ damage in the retina, abnormal albuminuria is an important indicator of the risk of severe diabetic retinopathy. BP elevation seems not to be an initiating factor, but rather aggravates established retinopathy. Left ventricular hypertrophy has a stronger correlation with BP elevation than normoalbuminuria, suggesting that left ventricular hypertrophy is at least partially a phenomenon secondary to elevated BP in diabetic patients with abnormal albuminuria. Generally, abnormal albuminuria is a strong indicator of cardiovascular renal damage in diabetic patients and in most organs is a stronger factor than elevated BP.     

Association of serum bilirubin levels with development and progression of albuminuria,and decline in estimated glomerular filtration rate in patients with type 2 diabetes mellitus

Aims/Introduction

Recent observational studies suggest elevated levels of bilirubin, an endogenous anti‐oxidant, might protect against kidney disease. We carried out an observational cohort study to assess whether higher baseline levels of bilirubin, within normal range, could predict the rate of development and progression of diabetic nephropathy in patients with type 2 diabetes.

Materials and Methods

Japanese type 2 diabetic patients with normo‐ or microalbuminuria and normal serum bilirubin (<1.2 mg/dL) were recruited from a single center, and categorized according to baseline serum bilirubin levels. Two independent end‐points were specified: development or progression of diabetic nephropathy, based on transition to a more advanced stage of albuminuria (albuminuria cohort), and the rate of change in estimated glomerular filtration rate (eGFR cohort).

Results

Albuminuria and eGFR cohorts were constructed consisting of 1,915 patients and 1,898 patients, respectively, with 1,738 patients overlapping. Mean follow up was 4.4 and 5.4 years for the two cohorts, respectively. Within the albuminuria cohort, 132 (9%) of 1,418 patients with normoalbuminuria developed microalbuminuria, and 56 (11%) of 497 patients with microalbuminuria developed macroalbuminuria. Higher baseline bilirubin levels were associated with significantly lower risk of progression from microalbuminuria to macroalbuminuria in both the univariate and multivariate analyses. In normoalbuminuric patients, an inverse association was found when restricted to a subgroup with elevated hemoglobin A1c levels. There was no relationship between bilirubin levels and the rate of change in eGFR.

Conclusions

Higher serum bilirubin levels, within normal range, might be predictive of a lower risk of progression of nephropathy in type 2 diabetic patients.     

Endothelin-specific antibodies decrease blood pressure and increase glomerular filtration rate and renal plasma flow in spontaneously hypertensive rats.

OBJECTIVE: Studies were undertaken to clarify the pathophysiologic significance of endogenous endothelin in the control of blood pressure and renal hemodynamics in spontaneously hypertensive rats (SHR). DESIGN: The technique of passive immunization was used to neutralize endogenous endothelin in order to estimate the contribution of endothelin to the in vivo control of blood pressure and renal hemodynamics. METHODS: Endothelin-specific antibodies were administered intravenously into anesthetized SHR and Wistar-Kyoto (WKY) rats, and the effects upon blood pressure and renal function (renal plasma flow and glomerular filtration rate) assessed. Using the same antibodies, baseline plasma levels of endothelin in both strains of rats were determined by radioimmunoassay. RESULTS: Infusion of endothelin-specific antibodies into SHR decreased mean arterial pressure by approximately 10% and renal vascular resistance and renal vascular resistance by approximately 35%. Glomerular filtration rate and renal plasma flow both increased by approximately 50% over control. In contrast, infusion of normal rabbit serum into SHR or of endothelin-specific antibodies into WKY rats did not result in any significant change in renal hemodynamics or arterial blood pressure. Baseline plasma levels of immunoreactive endothelin in SHR were significantly lower than those in WKY rats. CONCLUSION: These results suggest that endothelin plays an important role in the modulation of systemic blood pressure and renal function in SHR.     

Gauging adequacy of cardiovascular disease treatment: importance of estimating glomerular filtration rate and time-varying albuminuria

Objective measures of cardiovascular disease (CVD) are often lacking until patients develop clinical symptomatology associated with either coronary, cerebral, or peripheral vascular disease. Estimating risk for CVD is often based on classic Framingham Heart Study criteria such as age, gender, blood pressure (BP), cholesterol, glucose levels, and family history. Moreover, there is a well-described continuous relationship between BP,cholesterol, and glucose and risk for cardiovascular events. Estimating glomerular filtration rate equations using simple formulae and screening quantitatively for albuminuria may provide an important opportunity for identifying patients at increased risk for cardiovascular events. These safe, simple, and cost-effective measures of estimating CVD risk can be used to gauge the adequacy of response to cardiovascular risk-reducing therapies.     

Estimated glomerular filtration rate,albuminuria and mortality in type 2 diabetes: the Casale Monferrato study

Aims/hypothesis Estimated glomerular filtration rate (eGFR) predicts mortality in non-diabetic populations, but its role in people with type 2 diabetes is unknown. We assessed to what extent a reduction in eGFR in people with type 2 diabetes predicts 11-year all-cause and cardiovascular mortality, independently of AER and other cardiovascular risk factors. Materials and methods The study population was the population-based cohort (n = 1,538; median age 68.9 years) of the Casale Monferrato Study. GFR was estimated by the abbreviated Modification of Diet in Renal Disease Study equation. Results At baseline, the prevalence of chronic kidney disease (eGFR <60 ml min⁻¹ 1.73 m⁻²) was 34.3% (95% CI 33.0–36.8). There were 670 deaths in 10,708 person-years of observation. Hazard ratios of 1.23 (95% CI 1.03–1.47) for all-cause mortality and 1.18 (95% CI 0.92–1.52) for cardiovascular mortality were observed after adjusting for cardiovascular risk factors and AER. When five levels of eGFR were analysed we found that most risk was conferred by eGFR 15–29 ml min⁻¹ 1.73 m⁻², whereas no increased risk was evident in people with eGFR values between 30 and 59 ml min⁻¹ 1.73 m⁻². In an analysis stratified by AER categories, a significant increasing trend in risk with decreasing eGFR was evident only in people with macroalbuminuria. Conclusions/interpretation Our study suggests that in type 2 diabetes macroalbuminuria is the main predictor of mortality, independently of both eGFR and cardiovascular risk factors, whereas eGFR provides no further information in normoalbuminuric people.     

健康老年人群血浆可溶性血栓调节蛋白和肾小球滤过率的关系

目的：探讨老年人群血浆可溶性血栓调节蛋白（sTM）与估算的肾小球滤过率（eGFR）的相关性。方法采用整群随机抽样的方法对北京市9个社区283名≥65岁健康老年人进行研究,酶联免疫吸附法测定血浆可溶性血栓调节蛋白水平,应用CKD-EPI公式评估eGFR,同时行人体学测量及血清生化指标测定,并做相关和回归分析。结果北京社区健康老年人群eGFR水平与sTM、年龄、尿素氮、肌酐、C反应蛋白（CRP）及收缩压呈负相关,与白蛋白、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）水平呈正相关;在校正了年龄、血压、血糖（GLU）、CRP、血脂、尿酸（UA）等指标后,健康老年人血浆sTM仍然和eGFR呈负相关（B＝-3.340,P＝0.000）。在进一步的研究中,将入组的北京社区健康老年人分为老年（65～80岁）和高龄老年（＞80岁）两组;两组之间eGFR和sTM水平差异均无统计学意义（P＞0.05）,老年组和高龄老年组eGFR均与sTM水平呈负相关（r＝-0.229,P＝0.000;r＝-0.3613,P＝0.02）,校正了年龄、血压、GLU、CRP、血脂、UA等指标后差异仍有统计学意义（B＝-3.26,P＝0.000;B＝-4.45,P＝0.013）。结论 sTM可作为判断老年人群肾功能下降的指标。     

Metabolic syndrome and albuminuria show an additive effect in modulating glomerular filtration rate in patients with Type 2 Diabetes Mellitus

BackgroundAlthough metabolic syndrome (MetSyn) or albuminuria (MA) most often occurs in concomitance in Type 2 Diabetes Mellitus patients (T2DM), their mode of interaction in increasing the risk of low glomerular filtration rate (GFR) has been poorly investigated.ObjectiveWe evaluated in a cohort of 1659 T2DM patients the relationship between MetSyn and MA in modulating the risk for low GFR. The risk of developing low GFR by graded number of MetSyn traits was also evaluated.MethodsThis was a cross-sectional study where 1659 T2DM patients were studied. Low GFR was defined as estimated-GFR (e-GFR) <60 ml min^?1 × 1.73 m^?2 (modification of diet in renal disease, MDRD, formula).Resultse-GFR progressively decreased from 91 ± 25 of patients MetSyn?MA?, to 82 ± 27 of patients MetSyn?MA+, 81 ± 24 of patients MetSyn+MA? and 76 ± 30 ml min^?1 × 1.73 m^?2 of patients MetSyn+MA+ (adjusted p < 0.0001). A progressive gradient of the frequency of patients with low e–GFR with concomitance of MetSyn and MA was also observed [MetSyn?MA? (6.1%), MetSyn?MA+ (15.3%), MetSyn+MA?(16.6%), MetSyn+MA+ (26.8%); p < 0.0001]. As compared to patients with MetSyn?MA?, the risk progressively increased to 2.80 (95% C.I. 1.46–5.37; p = 0.002) in MetSyn+MA?, to 2.83 (95% C.I. 1.12–7.10; p = 0.027) in MetSyn?MA+ and to 5.73 (95% C.I. 2.99–10.9; p < 0.0001) in MetSyn+MA+ patients. Estimated-GFR progressively decreased by number of MetSyn traits in the whole population (adjusted p < 0.0001).ConclusionsMetSyn or MA has an additive effect in increasing the risk of having low GFR in patients with T2DM. Furthermore, e-GFR is negatively affected by graded number of MetSyn traits independently of albuminuria.