Urinary Albumin Excretion and Glomerular Filtration Rate across the Spectrum of Glucose Abnormalities in Essential Hypertension

Josep Redon,* Francisco Morales-Olivas,† Alberto Galgo,‡ Miguel A´ ngel Brito,§ ʈ Javier Mediavilla, Rafael Marı´n,¶ Pilar Rodrı´guez,** Salvador Tranche,†† Jose´Vicente Lozano,‡‡ Claudia Filozof;§§ and the MAGAL Group *Internal Medicine Service, Hospital Clı´nico, and †Department of Pharmacology, University of Valencia, Valencia, ʈ ‡Centro de Salud Espronceda and §Endocrinology, Hospital Puerta de Hierro, Madrid, Centro de Salud Pampliega, Burgos, ¶Nephrology Service, Hospital Universitario Central de Asturias, Oviedo, **Fingoi Health CareCentre, Lugo, ††El Cristo Health Centre, Oviedo, ‡‡Centro de Salud Serrerı´a 2, Valencia, and §§Scientific Department, Cardiovascular Section, Bristol-Myers-Squibb, Madrid, Spain

The objective of this study was to assess the relationship between urinary albumin excretion (UAE) and GF across the spectrum of the glucose metabolism abnormalities in a large population of patients with hypertension. The Microaluminuria en Pacientes con Glucemia Basal Alterada (MAGAL) is a multicenter, cross-sectional study that was carried out by 1723 primary care physicians. A total of 6227 patients with essential hypertension (in three groups: [1] normal fasting glucose <100 mg/dl, [2] impaired fasting glucose >100 to 126 mg/dl, and [3] type 2 diabetes) were analyzed in this substudy. GFR was estimated by using the Modification of Diet in Renal Disease (MDRD) abbreviated equation. A single first-morning urine albumin/creatinine ratio was measured using Bayer reagent strip Microalbustix, a semiquantitative method. Abnormal UAE was defined as an albumin/creatinine ratio >3.4 mg/mmol (equivalent to >30 mg/g). The prevalence of abnormal UAE, >3.4 mg/mmol, increased across the spectrum of glucose abnormalities: 39.7, 46.2, 48.6, and 65.6% for normoglycemic, low-range, and (0.003 ؍ and high-range impaired fasting glucose and diabetes, respectively. UAE was positively related to SBP (P inversely to GFR (P < 0.001). Renal insufficiency (GFR <60 ml/min per 1.73 m2) was present in 21.8% of the patients, more frequently older patients, women, and those with diabetes. The factors that were related to renal insufficiency were UAE >3.4 mg/mmol (odds ratio 1.86; 95% confidence interval 1.60 to 2.17) and diabetes (odds ratio 1.62; 95% confidence interval 1.29 to 2.04). There is a close relationship between abnormal UAE and renal insufficiency in essential hypertension. This is more marked in patients with diabetes and moderate in patients with high-range impaired fasting glucose. J Am Soc Nephrol 17: S236–S245, 2006. doi: 10.1681/ASN.2006080920

n increase in urinary albumin excretion (UAE) even influence of renal function in cardiovascular risk to be assessed. to a small extent, microalbuminuria, has become a Therefore, alterations in renal function have emerged as a pre- A marker for cardiovascular and renal disease. Initially dictive marker for cardiovascular disease, and it has been re- tested in diabetes, its prognostic value in hypertensive patients flected as such in the guidelines for clinical management without diabetes and in subgroups of the general population (13,14). Several studies have shown calculated GFR to be a risk has been well established during the past few years (1–11). indicator for general mortality and cardiovascular death after In both patients with diabetes and without diabetes, elevated myocardial infarction (15–20) and also for mortality associated SBP and glucose levels are the main factors related to develop- with heart failure (21). Likewise, a large health registry has ment of increased UAE. One of the largest epidemiologic stud- revealed a gradual relationship between estimated GFR and the ies, the Australian Diabetes Obesity and Lifestyle Study (Aus- risk for death, cardiovascular events, and hospitalization, inde- Diab) (12), clearly showed the interaction of both factors in the pendent of other risk factors (22). prevalence of microalbuminuria. The relationship between Microalbuminuria and renal insufficiency frequently run in UAE and estimated GFR, however, has received less attention parallel (23). Both of them are influenced by BP and glucose even though GFR, like UAE, is a predictor of cardiovascular levels. Whereas BP is the major determinant of microalbumin- risk. uria, glucose level is the major determinant of renal insuffi- Widespread use of formulas to calculate GFR has enabled the ciency (23). Despite the frequent cluster of microalbuminuria and low GFR, the potential interaction between UAE and GFR is not well understood even though it can provide useful clin- Address correspondence to: Dr. Josep Redon, Hypertension Clinic, Internal Med- icine, Hospital Clinico, University of Valencia, 46010 Valencia, Spain. Phone: ical information. Therefore, the objective of the present study ϩ34-963862647; Fax: ϩ34-963862647; E-mail: [email protected] was to analyze the relationship between UAE and GFR across

Copyright © 2006 by the American Society of Nephrology ISSN: 1046-6673/1712-0236 J Am Soc Nephrol 17: S236–S245, 2006 Relationship between GFR and UAE S237 the spectrum of the glucose metabolism abnormalities in a large using the ␹2 or Fisher exact test, depending on the application condi- population of patients with hypertension. Combining both glu- tions. All hypothesis contrasts rejected the null hypothesis with an ␣ Ͻ cose abnormalities and hypertension, we included a population error 0.05. that was prone to developing microalbuminuria and renal in- The relationship between GFR and UAE was assessed by Pearson correlation coefficients and multiple regression analysis. Factors that sufficiency, which enabled us to assess their potential interac- were related to abnormal GFR were assessed by using a multiple tions logistic regression model. The odds ratio (OR) of these variables, to- gether with their CI and level of significance, were reported. The Materials and Methods analysis was carried out using SAS for Windows (version 9.1; SAS This study was a post hoc analysis from the Microaluminuria en Institute, Cary, NC). Pacientes con Glucemia Basal Alterada (MAGAL) study, the design of which is described elsewhere in this journal. In brief, it is a multicenter, Results cross-sectional, observational study that was carried out by 1723 pri- General Characteristics of the Study Population mary care physicians all over Spain. Each physician consecutively This post hoc analysis was performed in 6227 patients: 1138 enrolled six patients with essential hypertension and age Ͼ18 and Յ80 (18%) in the NFG group, 2491 (40%) in the IFG group (591 [9%] yr divided into three categories according to carbohydrate metabolism: (1) Normal fasting glucose (NFG): fasting plasma glucose Ͻ100 mg/dl; in the low-range IFG, 1900 [31%] in the high-range IFG), and (2) impaired fasting glucose (IFG): fasting plasma glucose Ն100 and 2598 (41%) in the diabetes group. The characteristics of the Ͻ126 mg/dl; and (3) type 2 diabetes. Hypertension was defined as a patients as grouped by the glucose categories are shown in previous diagnosis of hypertension and/or receiving antihypertensive Table 1. Age increased progressively from NFG to diabetes and medication. Exclusion criteria were type 1 diabetes, pregnancy or gender was equally distributed among the four groups. SBP breast-feeding, urinary tract infection, pyuria, hematuria, fever, and increased significantly from the normal carbohydrate metabo- having done strenuous physical exercise during the 24 h before UAE lism group to the diabetes group. A BP Ͻ140/90 mmHg was determination. The study was approved by the Ethics and Clinical observed in 41.4% of the patients with NFG and in 36.9% of Trials Committee of the Hospital Central de Asturias. Informed consent those with IFG. In the patients with diabetes, BP was controlled of the patient was obtained in all cases. (Ͻ130/80 mmHg) in 11.5% of cases. BMI was higher in patients with abnormalities in glucose values as compared with normo- Study Protocol glycemic patients. A progressive increment in fasting plasma Demographic and clinical data were obtained for each patient. Phys- glucose, by definition, and in triglycerides was observed from ical examination that included weight, height, body mass index (BMI), and SBP and diastolic BP (DBP) measurements was carried out on the the NFG to the diabetes groups. HDL cholesterol, however, visit day. Sitting SBP and DBP were measured according to the Spanish followed an inverse association. Hypertension Society guidelines (24), after 5 min of rest and with the cuff fitted to the perimeter of the arm. Three readings were taken, and UAE the mean value of the last two was accepted as valid. The prevalence of abnormal UAE (Ն3.4 mg/mmol) was Serum glucose levels, creatinine levels, and the lipid profile were 54.5%, which increased across the spectrum of glucose abnor- determined in blood samples that were obtained after at least8hof malities (39.7, 46.2, 48.6, and 65.6% for normoglycemic, low- fasting. Glucose status was stratified as NFG, IFG, and diabetes, as range IFG, high-range IFG, and diabetes, respectively). In a described previously. In addition, patients with IFG were subdivided multiple regression analysis, UAE was positively related to the into two groups, those with fasting glucose of between 100 and 109.9 SBP (P ϭ 0.003) and inversely to the GFR (P Ͻ 0.001). In mg/dl (low-range IFG) and the remainder between 110 and 125.9 normoalbuminuric patients, GFR values did not differ among mg/dl (high-range IFG), based on the current and the former criteria 2 the glucose categories: 76.7, 76.8, 75.9, and 74.6 ml/min per 1.73 for IFG. GFR was estimated as ml/min per 1.73 m according to the 2 abbreviated Modification of Diet in Renal Disease (MDRD) study equa- m for NFG, low-range and high-range IFG, and diabetes, tion (16), which includes serum creatinine level, age, and gender. Race respectively. In contrast, in those with abnormal UAE, GFR was was not applicable in our study because all of the patients were white. significantly lower in the diabetes group (67.9 ml/min per 1.73 Patients were stratified according to the GFR categories of the Kidney m2) as compared with the other two groups (74.7, 74.4, and 74.3 Disease Outcomes Quality Initiative guidelines (25). ml/min per 1.73 m2; P Ͻ 0.01 for each comparison). A single first-morning urine albumin/creatinine ratio was measured using Bayer reagent strip Microalbustix (Leverkusen, Germany), a GFR semiquantitative method. Abnormal UAE was defined as an albumin/ Most of the patients had a GFR between 60 and 90 ml/min per Ն Ն creatinine ratio 3.4 mg/mmol (equivalent to 30 mg/g). According 1.73 m2 (3623 [58.2%]). Renal insufficiency (GFR Ͻ60 ml/min per to the manufacturer, the Bayer Microalbustix test has a sensitivity of 1.73 m2) was present in 1361 (21.8%) of the patients, but only 298 90% and a specificity of 88% for the albumin/creatinine ratio. As (4.8%) patients had a GFR Յ45 ml/min. The main characteristics defined in the protocol, urine samples with creatinine concentrations of Յ10 mg/dl were ruled out because they were considered too diluted. of the patients in the various GFR categories are shown in Table 2. Patients with the lowest GFR more frequently were older and Statistical Analyses women and had diabetes. Although the selection criteria estab- The variables are presented as frequency (95% confidence interval lished a misbalanced number of study patients (more patients [CI]), mean (SD), or median (25th to 75th percentiles) according to the selected by inclusion criteria in the IFG group), the trend associ- distribution of the variable. ANOVA was used for comparisons among ation between the glucose category and the GFR spectrum can be groups. The association between qualitative variables was evaluated observed. The proportion of normoglycemic patients decreases S238 Journal of the American Society of Nephrology J Am Soc Nephrol 17: S236–S245, 2006

Table 1. General characteristics of the study population grouped by glucose metabolism statusa

Glucose Status Characteristic P NFG Low-Range IFG High-Range IFG Diabetes (n ϭ 1128) (n ϭ 591) (n ϭ 1902) (n ϭ 2598)

Age (yr) 61.7 Ϯ 10.7 63.5 Ϯ 9.8 62.8 Ϯ 10.1 64.9 Ϯ 9.0 Ͻ0.0001 Male gender (%) 48.6 46.5 51.3 50.4 0.1542 BMI (kg/m2) 28.3 Ϯ 4.1 30.5 Ϯ 4.9 29.9 Ϯ 4.5 30.2 Ϯ 4.6 0.0050 Fasting glucose (mg/dl) 92.1 Ϯ 8.4 105.3 Ϯ 2.9 117.3 Ϯ 4.3 151.9 Ϯ 36.1 Ͻ0.0001 Total cholesterol (mg/dl) 211.6 Ϯ 34.6 211.0 Ϯ 34.2 214.4 Ϯ 34.5 209.3 Ϯ 37.6 0.0002 HDL cholesterol (mg/dl) 54.7 Ϯ 12.9 54.4 Ϯ 12.9 52.7 Ϯ 13.4 51.0 Ϯ 12.6 0.0025 LDL cholesterol (mg/dl) 133.5 Ϯ 31.7 131.2 Ϯ 31.0 133.6 Ϯ 30.3 128.2 Ϯ 32.5 0.0383 Triglycerides (mg/dl) 133.5 Ϯ 54.0 140.4 Ϯ 61.2 151.0 Ϯ 63.8 162.5 Ϯ 66.2 0.0001 Creatinine (mg/dl) 0.94 Ϯ 0.2 0.98 Ϯ 0.2 0.96 Ϯ 0.2 1.03 Ϯ 0.3 Ͻ0.0001 UAE (mg/mmol creatinine) 8.7 Ϯ 18.9 7.6 Ϯ 15.0 8.5 Ϯ 16.2 13.5 Ϯ 27.6 Ͻ0.0001 UAE (mg/mmol creatinine) Ͻ0.0001 Ͻ3.4 (%) 60.3 53.8 53.4 34.4 Ն3.4 (%) 39.7 46.2 48.6 65.6 BP (mmHg) SBP 139.3 Ϯ 14.7 139.7 Ϯ 13.5 141.4 Ϯ 13.0 141.9 Ϯ 14.1 0.0122 DBP 82.1 Ϯ 8.6 81.7 Ϯ 8.6 83.3 Ϯ 8.4 81.6 Ϯ 8.6 0.7404 eGFR (ml/min per 1.73 m2) Ͻ0.0001 Ͼ90 (%) 23.4 8.9 35.5 32.4 60 to 90 (%) 18.6 10.2 31.5 40.2 60 to 45 (%) 12.7 8.4 27.1 51.8 Յ45 (%) 10.4 8.7 16.8 64.1

aBMI, body mass index; DBP, diastolic BP; eGFR, estimated GFR; IFG, impaired fasting glucose; NFG, normal fasting glucose; SBP, systolic BP; UAE, urinary albumin excretion.

from those with GFR Ͼ90 ml/min per 1.73 m2 to those with Յ45 with a higher prevalence among those with higher UAE. Uri- ml/min per 1.73 m2; a similar trend is found for patients with IFG. nary albumin excretion was inversely related to GFR, and an In contrast, the proportion of diabetes increases as the GFR de- abnormal UAE increases the risk for renal insufficiency (GFR clines. For each GFR category, UAE values increase as well as the Յ60 ml/min per 1.73 m2) by 89%. This association between percentage of patients with abnormal UAE, although the incre- abnormal UAE and renal insufficiency was more evident in ment is steeper for the diabetes group as compared with the other patients with diabetes as compared with those with NFG and glucose categories (Table 3). IFG. Likewise, for each GFR category, UAE values increased as The factors that were related to GFR Յ60 ml/min per 1.73 m2 well as the percentage of patients with abnormal UAE, al- were analyzed in a multiple logistic regression analysis. Abnor- though the values were higher for the diabetes group as com- mal UAE, presence of glucose abnormalities, and uncontrolled pared with patients with NFG and those with IFG. Figures for BP were related independently to the low GFR. UAE Ն3.4 patients with IFG, both low range and high range, were be- mg/mmol increased the risk by 87% (OR 1.87; 95% CI 1.61 to tween those of NFG and diabetes. 2.17), IFG and diabetes by 30% (OR 1.30; 95% CI 1.05 to 1.62), In this study, the prevalence of abnormal UAE was greater and BP Ն140/90 mmHg or Ն130/80 if diabetes by 23% (OR than that observed in other cross-sectional surveys (26). This 1.23; 95% CI 1.04 to 1.45). When each of the glucose status probably is due to the method used for measuring UAE and the categories was included separately in the model, abnormal characteristics of the study population. It has been reported that UAE and diabetes were the only significant determinants of a single UAE assessment may increase by at least one fifth the renal insufficiency. An elevated UAE (Ն3.4 mg/mmol) in- prevalence of abnormal UAE (27). Selecting patients with both creased the risk by 86% (OR 1.86; 95% CI 1.60 to 2.17) and hypertension and glucose disorders also increases the preva- diabetes by 62% (OR 1.62; 95% CI 1.29 to 2.04). lence, because high BP and glucose values are among the most important causes of UAE elevation (28). In addition, mean age Discussion and BMI in our study population was higher than in other In this large cohort of hypertensive patients from primary surveys, two factors that also have been associated with abnor- care, the proportion of patients with abnormal UAE was 54.5%, mal UAE. and 21.8% had renal insufficiency. This study shows a clear The prevalence of renal insufficiency was 21.8%, although it association between UAE and frequency of renal insufficiency might be slightly overestimated as a result of the use of the J Am Soc Nephrol 17: S236–S245, 2006 Relationship between GFR and UAE S239

Table 2. General characteristics of the study population grouped by eGFR

eGFR (ml/min per 1.73 m2) Characteristic P Ͼ90 ͓90 to 60 ͓60 to 45 Յ45 (n ϭ 1243) (n ϭ 3623) (n ϭ 1063) (n ϭ 298)

Age (yr) 57.2 Ϯ 8.8 64.3 Ϯ 9.7 67.4 Ϯ 8.1 68.0 Ϯ 8.0 Ͻ0.0001 Male gender (%) 81.3 47.9 26.1 29.2 Ͻ0.0001 BMI (kg/m2) 29.6 Ϯ 4.4 29.8 Ϯ 4.6 30.1 Ϯ 4.5 29.9 Ϯ 4.7 0.1158 Fasting glucose (mg/dl) 129.7 Ϯ 30.7 132.2 Ϯ 31.7 136.6 Ϯ 32.0 143.3 Ϯ 37.7 Ͻ0.0001 Total cholesterol (mg/dl) 210.8 Ϯ 36.4 210.8 Ϯ 35.2 212.4 Ϯ 36.1 217.6 Ϯ 40.0 0.0123 HDL cholesterol (mg/dl) 52.4 Ϯ 12.6 52.9 Ϯ 12.9 51.8 Ϯ 13.4 51.3 Ϯ 13.2 0.0528 LDL cholesterol (mg/dl) 130.6 Ϯ 31.3 130.7 Ϯ 31.2 131.8 Ϯ 31.9 136.1 Ϯ 36.8 0.0482 Triglycerides (mg/dl) 150.2 Ϯ 63.8 148.1 Ϯ 62.5 158.7 Ϯ 65.2 175.1 Ϯ 69.9 Ͻ0.0001 Creatinine (mg/dl) 0.80 Ϯ 0.1 0.95 Ϯ 0.2 1.17 Ϯ 0.2 1.63 Ϯ 0.3 Ͻ0.0001 UAE (mg/mmol creatinine) 9.8 Ϯ 21.5 9.7 Ϯ 20.4 12.6 Ϯ 25.3 17.4 Ϯ 31.2 0.0070 UAE (mg/mmol creatinine) Ͻ0.0001 Ͻ3.4 (%) 49.6 49.6 37.2 18.5 Ն3.4 (%) 50.4 50.4 62.8 81.5 BP (mmHg) SBP 140.8 Ϯ 12.9 140.7 Ϯ 13.8 142.2 Ϯ 13.9 144.4 Ϯ 16.0 0.0004 DBP 83.5 Ϯ 8.2 81.9 Ϯ 8.5 81.7 Ϯ 8.8 82.4 Ϯ 9.4 0.00026 Glucose status Ͻ0.0001 normal (%) 23.3 18.6 12.7 10.4 low-range IFG (%) 20.1 18.4 15.5 10.5 high-range IFG (%) 24.3 22.8 30.0 15.5 diabetes (%) 32.4 40.2 51.8 64.1

Table 3. UAE and prevalence of abnormal UAE (Ͼ3.4 mg/mmol) grouped by glucose status and eGFR

eGFR (ml/min per 1.73 m2) Glucose Status P Ͼ90 ͓90 to 60 ͓60 to 45 Յ45 (n ϭ 1243) (n ϭ 3623) (n ϭ 1063) (n ϭ 298)

UAE (mg/mmol creatinine)a Ͻ0.0001 normal 2.3 (1.1 to 5.6) 2.3 (1.1 to 6.8) 2.3 (1.7 to 6.8) 4.5 (1.7 to 8.5) low-range IFG 2.3 (1.7 to 6.8) 2.3 (1.7 to 4.5) 3.4 (1.7 to 7.6) 5.0 (2.3 to 13.3) high-range IFG 3.2 (1.7 to 6.8) 2.3 (1.7 to 6.8) 3.4 (1.7 to 8.5) 6.8 (3.4 to 18.2) diabetes 3.4 (1.7 to 6.8) 4.5 (1.7 to 9.1) 6.8 (2.3 to 9.1) 8.5 (4.5 to 18.2) UAE (mg/mmol creatinine) Ն3.4 Ͻ0.0001 normal 37.4 38.2 41.9 62.1 low-range IFG 46.5 42.2 53.3 70.8 high-range IFG 50.0 44.1 58.0 77.5 diabetes 58.4 61.8 71.6 87.4

aData are median (25th to 75th percentiles).

MDRD equation to calculate GFR (29). Several studies have function behaved as expected. The mean age was greater examined the difference between this method and the corre- among patients with lower GFR values, and the prevalence of sponding gold standard: derived GFR calculated by isotopic diabetes was higher as compared with the other groups. Not techniques (30–32). In the range of normal values, with true only diabetes but also a previous stage, such as the IFG, in- GFR Ͼ60 ml/min, the GFR may be underestimated by up to creased the risk for renal insufficiency. Likewise, uncontrolled 28% when the formula is applied. As true glomerular filtration hypertension was associated with low GFR. There were no decreases, the differences become smaller, reaching an under- differences, however, in the degree of obesity, with mean val- estimation of 6% when the true GFR is Ͻ30 ml/min (31). ues Ͼ29 kg/m2 in all of the groups. The factors that were associated with a worsening in renal Patients with the lowest GFR more frequently were older and S240 Journal of the American Society of Nephrology J Am Soc Nephrol 17: S236–S245, 2006 women and had diabetes. Although increased age and the Abarca Bujan Benjamı´n, Abordan Chanat Ruchdi Omar, Acosta Me´n- presence of diabetes have been widely accepted as conditions dez Juan M., Acosta Socorro Antonio, Adelantado Pozuelo Esther, that are associated with renal insufficiency, the high rate in Afonso Navarro Carmen, Agote Cuesta Gabriel, Aguado Mori Ana women is less recognized, but it is in agreement with previous Cristina, Agudo Codujo´n Beatriz, Aguilar Huertas Eva, Aguilera Zu- bizarreta Eulalia, Aguilo´ Furio´ Sara, Aguirre Min˜ana Teresa, A´ lamo surveys of renal insufficiency using the MDRD equation. Differ- Domı´nguez Anı´bal, Alba Dı´az A´ ngel, Albert Cun˜at Vicente, Albors ences between genders in the prevalence of GFR Ͻ60 ml/min are Valls Alberto, Alegret Crespi Santiago, Alegria Alonso Ramo´n, Alfaro noteworthy, with a higher prevalence in women as compared Alonso Guillermo, Alfaya Carrera Juan Jose, Allut Vidal Germa´n, with men. This also has been observed in other large-scale studies Almela Tejedo Teresa, Alonso Atienza Ma Del Carmen, Alonso Del Ͻ (32–34). The differences in the prevalence of GFR 60 ml/min Pino Elena, Alonso Dı´az-Marta Manuel, Alonso Fernandez Lola, between genders increases across the age range: The older the Alonso Matia Rafael, Alonso Quintanilla Carmelo, Alonso Patricio, higher (33). This contradicts that more men than women receive Altarriba Cano Ma Luisa, Altuna Zuriarrain Manuel, Alvarado Tato treatment for ESRD, and it seems that the higher prevalence of Antonio M., A´ lvarez Blanco Antonio, A´ lvarez De Monrego Carina, renal failure in women results from the excessive dominance of A´ lvarez Fernandez Hortensia, A´ lvarez Garcı´a Antonio, A´ lvarez Guisa- age and gender in the equation. sola Fernando, A´ lvarez Mejorada Enrique, A´ lvarez Sanchez Ignacio, ´ ´ ´ The relationship between GFR and UAE was analyzed. Alvarez Taboas Jorge, Alvarez Valero Jesu´s, Alvarez Vicente Juan Lower GFR was observed in patients with abnormal UAE, Carlos, Alvear Garcı´a Martin Jorge, Amhed Loufty Kheder, Amigo Nu´n˜ezMa Elena, Amurrio Olartua Juan Ma, Andre´s Pauls Inmaculada, mainly in patients with diabetes. Likewise, as the GFR declined, Andre´s Mayor Ma Jose´, Andre´s Santos Esther, Andreu Amoros Juan the UAE values, as well as the prevalence of abnormal UAE, Luis, Angel Cavada Miguel, Angora Mazuecos Francisco, Anguiano increased, and both shared common causative factors: High BP Calvo Jose´, Angulo Gonzalez Javier, Angulo Vallejo Ester, Angulo and abnormal glucose. Despite that this is a cross-sectional Yuste Enrique, Antolin Llinares, Asuncio´n, Anton Ortega Javier, Anto´n study, it seems that the presence of UAE increases the risk for Castello´ Jose´ Luis, Anto´n Garcı´a Francisco, An˜el Rodrı´guez Rosa, renal function worsening, as has been demonstrated in a fol- Aramburu Aramburu Pedro, Arancegi Marticorena Izaskun, Arayo low-up study (35). In patients who are prone to developing an Sola Inmaculada, Arbesu´Prieto Jose´, Arde´vol Gonza´lez Ro´mulo, Are- increment in UAE, the impact over time of both BP values and nas Mosqueda Julia´n, Arias Go´mez Ma Jesus, Arias Salgado-Robsy Ana abnormal glucose lead to a faster GFR decline than in those Marı´a, Ariza Herna´ndez Andre´s, Arlandis Puig Antonio, Arnal a who maintain normal values of UAE. Another factor that may Sanchez Jose, Aroca Sanz M Luisa, Arocas Pe´rez Ricardo, Arribas a a contribute to the association between abnormal UAE and low Aguirregavirı´a F. Javier, Arrieta M Jesu´s, Arrondo Beguiristain M ´ GFR is that during antihypertensive treatment and for a given Angeles, Arroyo Azpa Concepcio´n, Arteaga Herrera Domingo, Arteche Legorburu Miguel A´ ngel, Artigues Llull Isabel, Arujo Marisol, Arza BP, UAE values in patients with renal insufficiency resist re- Arteaga Alicia, Ascanio Leo´n Bele´n, Asenjo Cabrera Irene, Asenjo duction. Martin Amparo, Asensi Pen˜arrocha Isabel, Atienza Gaona Jose Juan, The main strengths of the present study lies in the large Atxotegi Loizate Laura, Auza Jose´ Javier, Avile´s Martı´nez Francisco number of patients analyzed in the cross-sectional survey and a Javier, Ayala Mun˜oz Francisco, Ayensa Esparza Javier, Aznar Ladro´n large representation of the glucose metabolism status catego- De Guevara Ma Jose, Azorı´n Sanz Francisco Javier, Baamonde ries. However, its limitations are that the sample size is not Mosquera Leopoldo, Badiola Elu Jose Luis, Badosa Sanuy Ana, Baeza population based and that selection bias by the participating Romero Manuel, Baixarias Tibau Joaquim, Bajo Garcia Julia´n, Balaguer physicians cannot be completely ruled out. This, however, does Montesinos Francisco, Balanzategi Garmendia Inmaculada, Ballester not invalidate the main goal of the study, which was to examine Berenguer Jose´ Vicente, Ballester Dı´az Trinidad Margarita, Ballester a the relationship between GFR and UAE in various glucose Orti Javier, Ban˜o´n Garcı´a Raquel, Ban˜os Martı´nez M Soledad, Ban˜os a conditions. Another limitation of the study was that creatinine Merino Isabel, Ban˜ Gago M Jesu´s, Barbeito Zaldua Edurne, Barcelo´ Bartolome´, Barges Ponce Vicente, Barras Gala´n Domingo, Barreiro measurement was not calibrated with reference standards by Mourentans Carlos, Barrera Pe´rez Manuel, Barrera Torres Vicente, all of the participating physicians. Finally, an unresolved ques- Barruso Bares Carlos, Bartolome´ Resano Javier, Bartolome´ Resano tion is whether the poorer prognosis for cardiovascular out- Rafael, Baudet Dejean Chantal, Beaus Alonso Jose´Luis, Becerra Becerra comes that are associated with UAE and GFR overlaps or is Alberto, Belayos Jime´nez Enrique, Belenguer Ma´rquez J.Maria, Belen- additive. Only prospective studies can help us to resolve this guer Prieto Rafael, Belles Calvo Amadeo, Belmonte Santamarı´a Julia key issue. Elena, Beltra´n Juana Jose, Benavides Ferna´ndez Encarnacio´n, Benedicto Acebo Rosa, Benedito Garcı´a Esther, Bengoa Goiri Ainhoa, Bengoetxea Conclusion Zorrilla Juan, Benı´tez Ortiz Juan Pedro, Benı´tez Rivero Javier, Benito De There is a close relationship between abnormal UAE and La Cruz Jose´-Luis, Benlloch Guillem Jose´Blas, Berciano Ma´rquez Edu- renal insufficiency in patients with essential hypertension. This ardo, Bermejo Enjuto Carmen, Bermejo Garcia Begon˜, Bermejo Guille´n was more marked in patients with diabetes and was moderate Gonzalo, Bernad Guerrero Amparo, Bernal Soto Jose Antonio, Bernat Gil Luis Marcial, Besada Gesta Ricardo, Bethencourt Marante Jorge, in patients in the highest IFG range The clinical relevance of this Bijedick Snejada, Bilbao Armas In˜aki, Blanco Aparicio Javier, Blanco relationship needs to be established in terms of temporal trend, Arias Ana, Blanco Perdigo´n Luis, Blanco Ramos Cristina, Blanco Ro- treatment changes, and impact on risk. drı´guez Rube´n, Bocos Ruiz Jose´Ignacio, Bolinches Gandia Juan Jose, Bonet Garcia Jorge, Bordallo Huidobro Juan Ramo´n, Bordas Ignacio, Acknowledgments Borges Mesa Ofelia, Borrachero Carmen, Borras Palle Carlos, Botella This study was supported by a Grant from Bristol-Myers Squibb. Gregori Ana, Bouzas Formoso Fernando, Bravo Bricien Ma Luz, Bravo The following investigators participated in the MAGAL Study: Valverde Antonio, Brime Secades Jose´ Manuel, Brito Brito Elisenda, J Am Soc Nephrol 17: S236–S245, 2006 Relationship between GFR and UAE S241

Brito Ma Jesu´s, Buendı´a Romero Alejandro, Bueno Lozano Mercedes, Jesus, Domı´nguez Deben Daniel, Domı´nguez Pe´rez Juan A., Dosantos Buitrago Vera Carmen, Burgui Eslava Antonio, Busselo Lete Luis Hernandez Javier, Echeverria Arruabarrena Juan, Eguinoa Villanueva Miguel, Bustamante Caso Maria Luisa, Caaman˜o Mata Juan, Cabal Jose´Luis, Eiris Cambre M.Jesu´s, Ekek Jannura Miguel, El Kak Chaaban Garcia Alberto, Cabaleiro Ubeira Dolores, Caballero Millan Pilar, Ca- Raffat, Eliche Vilchez Julia´n, Elorriaga Campos Angel, Elorriaga ballero Montanary Leo´nides, Cabanes Martı´n Teodorico, Cabanilla Urquijo Eguzkin˜e, Elorza Olabegoya Itziar, Elvira Perez Eladio, Enci- Valenzuela Antonio, Cacho A´ ngel, Cal Martı´nez Pablo, Calatayud Car- noso Sa´nchez Candelaria, Enrriquez De Terry Alfonso, Epaizabal Mu- reres Ma Del Carmen, Calatayud Climent Enrique, Calatayud Climent jika Xabier, Erdozain Corpas Juan Pedro, Erlanz Abad Arturo, Escobar Enrique, Caldeiro Jime´nez Jose´Ma, Caldero´n Alva Juan, Calduch Her- Moreno Cesar, Espinosa Barrientos Lourdes, Estarriol Jime´nez Carlos, rera Lourdes, Calero Gonzalez Cloria, Callado Ramo´n Mariano, Calleja Esteban Gaitero Juan Pedro, Esteban Marquez Juan Jose´, Estebanez Delgado Ma A´ ngeles, Calvillo Navarro A´ ngel, Calvin˜o Carballo Auxina Alberto, Esteve Fuster Vicente, Este´vez Ardit Anabel, Este´vez Ramo´n, Calvo Hornillos Mercedes, Calvo Quintela Laura, Calzada Gil Gonza´lez Pablo, Etxeberria Uribesalgo Carmelo, Etxevarria Etxevaria Manuel, Camarena Rodrı´guez Jose´Ma, Campos Martos Ignacio, Can- Juan Ignacio, Etxezarreta Crespo Ramon, Ezpeleta Albuixech Leo- dau Marcos Rafael, Candela Maetzu Macarena, Caneda Carmen, Ca- nardo, Farouk Hendi Malas Mohamer, Farreres Pı´ Concepcio´, Faus neiro Lo´pez Ana Maria, Caniego Monreal A´ ngel, Cano Aparicio Pere, Mascarell Emilia, Fenoll Pascual Federico, Fenoy Soriano Angel, Fer- Cano Espı´n Agustina, Cantera Valls Nieves, Can˜as Gonzalez Juan, na´ndez Benitez Carlos, Fernandez Cabello Ma Luisa, Fernandez Can˜a- Capdevila Falguera Dolors, Carballal Martı´nez Angelines, Carballo das Enrique, Fernandez Fernandez Carmen, Fernandez Fernandez Le- Albarate Jose Luis, Carballo Garcia Jose Juan, Carcas Sansuan Jose´Luis, andro, Fernandez Fernandez Luis, Fernandez Gomez Jose, Fernandez Carcedo Sua´rez Virgilio, Ca´rdenas Joyanes Ma Dolores, Cardona Ros- Hernandez Jose A´ ngel, Ferna´ndez Lo´pez Jose´Manuel, Fernandez Mar- sello Federico, Carmona Segado Jose Manuel, Carrasco Go´mez Conso- tinez Angel, Fernandez Martinez Juncal, Fernandez Moyano Fernando, lacio´n, Carrasco Herrera Jesu´s, Carrasco Pineda Marcos, Carretero Fernandez Peleteiro Jose Manuel, Fernandez Seoane Antonio, Fernan- Ramos Raquel, Carretero Salvador Olegario, Carrillo Lourdes, Carrio dez Silva Ma Jesus, Fernandez Villaverde Jose Maria, Fernandez Yebra Garcia Guillermo, Carrio´n Valero Lucinio, Carvajal Trujillo Nicomedes, Esther, Ferna´ndez Arienza Jose´, Ferna´ndez Barrial Manuel, Ferna´ndez Casal Ardines Eliecer, Casal Osorio Antonio, Casal Redondo Fernando, Can˜averas Ma Isabel, Ferna´ndez Escalada Eugenio, Ferna´ndez Garcia Casanova Carlos, Casanueva A´ lvarez Rosa Ma, Cascan Martı´n Jose Ma, Elisa, Ferna´ndez Garcia Jose Maria, Ferna´ndez Gonza´lez Angeles, Fer- Castan˜o Gonza´lez Mercedes, Castell Victoria, Castello Esteve Luis, na´ndez Gonza´lez Manuel, Ferna´ndez Gutie´rrez Maria A´ ngeles, Ferna´n- Castillejo Orozco Ana E, Castresana Arrate Ma Victoria, Castro Blanco dez Mourin˜o Ma Jesu´s, Ferna´ndez Prieto Dulce, Ferna´ndez Roces Ra- Isabel, Catala´n Macia´ Jose´, Cato´n Valde´s Manuel, Cavero Clerencia monita, Ferna´ndez Rodriguez Jose´Antonio, Ferna´ndez Sa´nchez Carlos, Elena, Cazador Romero Pilar, Cebreiro Navalon Antonio, Cebrian Ferna´ndez Simo´n Felisa, Ferrandiz Miquel Joaquin, Ferrandiz Miquel Montolio Francisco, Cebrian Picazos Adolfo, Cejudo Serrano Rosa, Joaquin, Ferreiro Alonso Pablo, Ferreiro Guri Jose Antonio, Ferrer Celades Moliner Pilar, Cenoz Osinaga Juan Carlos, Cerdan Oliver Bascun˜ana Pedro, Ferrer Tomas Ramon, Fiallega Otero Rafael, Flores Miguel, Cereceda Pecilla Ricardo, Cervantes Chaves Alfredo, Cervera Hernandez Miguel Angel, Flores Holguera Antonio, Flo´rez Garcia Jose´, Moscardo Jose B, Chumilla Checa Celia, Cifuentes Go´mez Pedro, Cir- Florit Anglada Antonio, Font Servera Jose, Forcada Lozano Eugenio, apozu Mendivil Juan, Cobo Domı´nguez Concepcio´n, Cobo Rodrigo Formento Tirado Aurelio, Fraga Cabado Jose´, Fraga Carballo Carmen, Ammonia, Codesido Blanco Teresa, Colomer Escuder Teresa, Colomer Fraga Gonzalez Camila, Franco Martinez Generosa, Fransi Galiana Lloret Mireya, Colomina Sarrio´ Pilar, Comas Samper Jose Manuel, Amparo, Frasquet Todolı´ Concha, Fuentes Fernandez Fernando, Fu- Concheiro Coello Gonzalo, Contrera Enrique, Contreras Torres Juan A, entes Vigil Jose´, Fuster Bellido Toma´s, Gabriel Escribano Ma A´ ngeles, Copeiro Del Villar Martı´nez Ana, Corell Dolz Jose´, Coronado Reyes Gacto Fernandez Socorro, Gadea Vicente Pilar, Gaga Garcia Alfredo, Pedro, Corralez Hava Joaquin, Correa Armero Rosario, Corte´s Oliva Gago Ferna´ndez Carlos, Gainza De Los Rios Luis, Gaisa´n Tome´Car- Anna, Cortilla Santamaria Albert, Cozar Hernandez Antonio, Crespo men, Gala´n Velasco Jose´ Antonio, Galarreta Calvo Javier, Galarza Basterra Javier, Crespo Gargallo Antonio, Crespo Jimenez Floreal, Cre- Amorrortu Ana, Galdamez Nun˜ez Ana Ma, Galindo Tobal Francisca, spo Martı´nez Francisco, Crespo Rodrı´guez Rufina, Criado Gonzalez Gallardo Alonso Fernando, Gallego Berciano Pilar, Gallego Garcia Car- Luis, Cristobal Torras Joan, Cruz Villegas Inmaculada, Cubas Cubells men, Gallo Trebol Fernando, Gallo Jaime, Gamarra Ortiz Javier, Carmen, Cuende Chamorro Maria Jesu´s, Cuerpo A´ lvarez Francisco, Gamero Perez Florencio, Gandia Moya Carmen, Garay Orte Jon, Ga- Cueto Bulnes Ignacio, Cumplido Pe´rez Antonio, Damas Manuel, Dap- rayoa Arraiza Javier, Garcia Andre´s Luis Enrique, Garcia Blas Miguel, ena Baro´n Cristina, Davila Brun Carlos, De Diego Sierra David, De Garcia Cabarcos Juan Antonio, Garcia Campo Urbano, Garcia Cantos Felipe Medina Ricardo, De Frutos Marcos Concha, De La Fuente Fer- Elena, Garcia Castellanos Natividad, Garcia Cuadros Marta, Garcia De na´ndez Teodoro, De La Fuente Marin˜o Rosa, De La Torre Edo Jorge, De Francisco Ana, Garcia Exposito Esmeralda, Garcia Falide Nieves, Gar- La Vega Cuya´s Arturo, De La Villa De Diego Ricardo, De Miguel cia Gallego Francisco, Garcia Gonzalez Carmen, Garcia Lombardero Villamediana Begon˜a, De Simo´n Gutie´rrez Rau´l, Debon Belda Manuel, Jose Maria, Garcia Machado Ma Luisa, Garcia Martinez Jose Joaquı´n, Dehesa Terreros Jose´, Del A´ lamo Alonso Alberto, Del Alba Carballo Garcia Molinos Juan R, Garcia Nadal Ignacio, Garcia Ortiz Jose Pablo, Maria Rosa, Del Amo Rodrı´guez Concha, Del Amo Carmen, Del Garcia Ortiz Luis, Garcia Ortiz Teresa, Garcia Panero Maria Luisa, Campo Aguado Concepcion, Del Carmen Elcuaz Julia´n, Del Castillo Garcia Perez Rafael, Garcia Pe´rez Fina, Garcia Pindado Ma A´ ngeles, Martı´nez Ma Jose´, Del Jesu´s Clemente Amelia, Del Rivero Llano En- Garcia Prades Pascuala, Garcia Ramo´n Elpidio, Garcia Romanos Fer- rique, Dela´s Go´mez Enrique, Delfin Va´zquez Marta, Delgado nando, Garcia Sanchez Dolores, Garcia Sanchez Sofia, Garcia Serrano Dominguez Benito, Diaz Bernabe´Jose´Ramo´n, Diaz Fernandez Ma Del Angel, Garcia Sierra Alberto, Garcia Suarez Victor Ignacio, Garcia Carmen, Diaz Gomez Juan Manuel, Diaz Milla´n Almudena, Diaz Olea Valverde Concepcion, Garcia Velasco Guillermo, Garcia Velasco Pilar, Emilia, Diaz Roger Teresa, Dı´az Andre´s Ma Luisa, Dı´az Eraso Mont- Garcı´a Palacios Carmen, Garcı´a Vilamea Jose´ Carlos, Garcia-Reyes serrat, Dı´az Jime´nez Jesu´s, Dı´az Luis Carmen, Dieguez Estevez Ramos Mercedes, Gardoki Elorriaga Jose A., Garicano Lasa Critina, Agapito, Diez Blanco Felipe, Diez Garcia Manuel, Diez Ruiz Ana, Dı´ez Garrido Marcos Cecilio, Garrote Florencio Timotea, Garrote Gutierrez Cantalapiedra Eladio, Dı´ez Cantarero Adolfo, Dimas Nun˜ez Fernando, Luis, Gascon Boto Fatima, Gasso Jime´nez Jose´ Manuel, Gazquez In- Divison Garrote Juan Antonio, Do´iaz Ruisanchez Enrique, Domingo maculada, Genoves Esplugues Andres Vicente, Gerpe Rodriguez Os- Platero Concepcion, Domingo Sancho Cesar, Dominguez Gonzalez car, Gijon Conde Teresa, Gil Correa Leopoldo, Gil Gil Cecilio, Gil S242 Journal of the American Society of Nephrology J Am Soc Nephrol 17: S236–S245, 2006

Mun˜oz Julio, Gil Prats Pedro, Gil Tocados Guadalupe, Gil Velez Jaime, billo De On˜ate Margarita, Lopez Abietar Ma Isabel, Lopez Abril Juan, Gili Juan, Gime´nez Gonza´lez Manuel, Gobierno Herna´ndez Jesu´s, Lopez Aisa Blanca, Lopez Andrino Juan Carlos, Lopez Bazo Pedro, Godoy Garcı´a Isidro, Goenaga Badiola Eugenia, Goikoetxea Arrillaga Lopez Cambeses Pilar, Lopez Cambeses Rosario, Lo´pez Castan˜eda Alejandro, Golpe Dı´az Marcos, Gomez Abellas Enrique, Gomez Agui- Elvia, Lopez Castro Antonio Jose´, Lopez De Coca Fernandez-Valencia naga Juan Manuel, Gomez Albadalejo Eduardo, Gomez Criado Maria Enrique, Lopez De La Calle Fernando, Lopez De La Fuente Elena, Soledad, Gomez Dacal Maria Dolores, Gomez Galvez Cayetano, Gomez Lopez Diaz Jesus, Lopez Hernandez Antonio, Lopez Leza Simon, Garcia Beatriz, Gomez Queipo Belen, Gomez Rodriguez Adela, Gomez Lopez Lopez Francisco, Lopez Martinez Mario, Lopez Moreno Ma Del Saez Miguel A´ ngel, Gomez Sal Esther, Gomez Vazquez Jose Luis, Carmen, Lopez Mun˜oz Felix, Lopez Rodriguez Isidro, Lopez Rodriguez Gomez Sonsoles, Go´mez Del Rı´o Marı´a Zulema, Go´mez Marcos Man- Jesus, Lopez Serrano Beatriz, Lopez Vazquez Luis Miguel, Lo´pez Cre- uel A´ ngel, Go´mez Marı´n Elisa, Gonzalez Aller Manuel, Gonza´lez spo Yolanda, Lo´pez De La Fuente F. Javier, Lo´pez Galindo Pedro Luis, Acun˜a Eduardo, Gonzalez Alvarez Antonio, Gonzalez Candela Rosa, Lo´pez Mun˜oz Manuel, Lo´pez Ortiz Franciso, Lo´pez Ruiz Teresa, Lopez Gonzalez Espadas Ricardo, Gonzalez Gordillo Soledad, Gonzalez Her- Perez Jose Manuel, Lopez-Cozar Fernandez Carmen, Lo´pez Carmen, na´ndez Luis, Gonzalez Loureiro Patricia, Gonzalez Lujan Jose´ Luis, Lorente Lopez Enrique, Lorente Mayor Juan, Lorenzo Lorenzo Jesus Gonzalez Marcos Juanjo, Gonzalez Martin Carmen Teresa, Gonzalez Francisco, Lorenzo Salido Francisco, Lozano Chilet Inmaculada, Lucas Perez Carmen, Gonzalez Perez Ma Jesu´s, Gonzalez Ramos Elena, Sa´nchez Roque, Lucero Avin˜a Jose´ Luis, Luengo Agu¨ero Jesus, Luis Gonzalez Reza Emilio, Gonzalez Rodriguez Manuel, Gonzalez Vicente Ruiz Cristina, Luna Estevez Sergio, Luna Estevez Sergio, Luque Jime- Angel, Gonza´lez Aguado Jose´ Manuel, Gonza´lez Casado Ignacio, nez Miguel, Madero Ambrojo Emilio, Maduen˜o Caro Antonio J., Mae- Gonza´lez Delgado Federico, Gonza´lez Ferna´ndez Maximino, Gonza´lez stre Amat Luis, Maestre Amat Luis, Maestro Castellblanque Esperanza, Gago Jose´Antonio, Gonza´lez Garcia Angel, Gonza´lez Garcia Carmen, Maffiotte Carrillo Nicola´s, Mampel Almela Josep, Manzano Martinez Gonza´lez Herna´ndez Jose´A., Gonza´lez Martin Angela, Gonza´lez Mar- Antonio, Marchena Consejero Manuel, Marco Macian Ma Dolores, Mar- tin Carmen Teresa, Gonza´lez Me´ndez Magdalena, Gonza´lez Pozueco cos Bailon Jesus, Marcos Fernandez Fco.Jose, Marcos Olea Javier Luis, Yolanda, Gonza´lez Rodriguez Emilio, Gonzalez-Vals Gonzalez Ma Jose, Marcos Rodriguez Angel, Margeli Ana, Mari Solivellas Bartolome, Gonzalo Ines, Gorostiza Ormaetxea Javier, Gorrocategui Eren˜o Jesus, Marin Castan˜o David, Marı´n Andre´s Fernando, Marı´n Valero Jose´, Granado Sanchez Francisco Jose´, Granja Garra´n Yolanda, Gregori Pel- Marque´s Calvo Inmaculada, Martel Martel Alberto, Martin Alfaro licer Juan-Ignasi, Guerrero Espejo Ma Carmen, Guija Villa Eduardo, Maria Luisa, Martin Gomez Madel Carmen, Martin Martin Pedro, Guillard Marie Martine, Guillen Hernandez Gaspar Elias, Guillot Valls Martin Sanchez Jose, Martı´n Burillo Teresa, Martı´n Garcı´a Lourdes, Alfonso, Guinot Martinez Enrique, Gutierrez Angulo Marisa, Gutierrez Martı´n Garito Enrique, Martı´n Martı´nez Enrique, Martı´n Millana Juan Espinosa de los Montero Juan Antonio, Gutierrez Marin Francisco, Carlos, Martı´n Moros Jose´Ma, Martı´n Portal Alejandro, Martı´n Serrano Gutierrez Moreno Jose Abel, Gutierrez Miguel A´ ngel, Haya Guaita Fernando, Martı´n Soledad Jose´ A, Martincano Jose Luis, Martinez Amparo, Hermosa Hernan Juan Carlos, Hernaiz Valero Susana, Her- Andueza Camino, Martinez Ausin Ma Carmen, Martinez Barrios Jesus, nandez In˜arra Gabriel, Hernandez Manzano Carmen, Hernandez Mar- Martinez Bes Ma Jose´, Martinez Cabrera Ana, Martinez Carrasco Jose tin Francisco Javier, Hernandez Mayle Colette, Herna´ndez Gutie´rrez Luis, Martinez Castellanos Mar, Martinez Correcher Francisca, Mar- Juana Isabel, Herna´ndez Ollero Ma Dolores, Herna´ndez Perlines Ma tinez Eizagirre Jose Manuel, Martinez Fernandez Montserrat, Martinez Vicenta, Hernando Mendivil Itziar, Hernando Zapatero Carlos, Her- Galvan Luis Alfonso, Martinez Garcia Candido, Martinez Garcia nani Bengoa Marta, Herraiz Rodriguez Ramo´n, Herrera Pelaez Anto- Eladio, Martinez Gonzalez Esteban, Martinez Gonza´lez Mercedes, Mar- nio, Herrera Valladolid Carmen, Herrero Ballestar Jose Vte, Herrero- tinez Hermosilla Alicia, Martinez Jativa Teresa, Martinez Lahuerta Juan zorriqueta Ma Jesu´s, Hervias Saiz Francisco Jose´, Hevia Rodriguez Jose´, Martinez Linuesa Remedios, Martinez Martinez Jose Ma, Martinez Eduardo, Hidalgo Herrera Manuel, Homar Isern Bernardino, Hortal Montero Juan Alberto, Martinez Nun˜ez Elisa, Martinez Orozco Marino, Gutierrez Felicidad, Iban˜ez Bernabeu Vicente, Iban˜ez Gomez Patricia, Martinez Quess Dulce, Martinez Quilez Javier, Martinez Ramos Fco, Ibarra Corbillo´n Angel, Ibeas Cristina, Iglesias Clemente Jose´M., Igle- Martinez Sanchez Luis, Martinez Vidal Angel, Martinez Vindel Juan sias Perez Eugenia, Iglesias Retamar Rafael, Igual Fraile Dimas, Ilizarri Carlos, Martı´nez Guerola Carmen, Martı´nez Pardo Inmaculada, Mar- Ollauri Miren, Indurain Ordun˜a Santos, In˜igo Espinosa Pedro A., Isidro tı´nez Pardo Rafael, Martı´nez Quintas Marı´a Jose´, Martı´nez Vazquez Ortega Joan, Iturralde Iriso Jesus, Iturri Gaztelu Ana, Iznaola Sanchez Constantino, Martn Martin Araceli, Martorell Adsuara Vicente, Martos Pedro Juan, Izquierdo Lopez Enrique, Izquierdo Sanz Jose Ramo´n, Calzado Jose´, Martos Garcia Emilio, Mateo Cabrejas Jesu´s Javier, Ma- Izquierdo Yan˜ez Ma Jose´, Jalon Monzon Mercedes, Jamil Ala Ramzi, teos Mateos Jesu´s, Mateos Perez Mar, Matilla Alvarez Carmen, Maya Jesu´s Casado Maria, Jimenez Perez Ramon, Jime´nez Franco Julio, Jime´- Teresa, Mazquiara´n Mendia Martı´n, Medina Castan˜o Antonio, Medina nez Paredes Javier, Jime´nez Redondo Jose´Ramo´n, Jorge Bravo Maria Cuenca Pedro, Medina Engler Berta, Medrano Gonzalez Maite, Megias Teresa, Jorge Rodriguez Fco.Jose, Jorques Navarro Juan Daniel, Jover Boils Araceli, Mejı´as Gonza´lez Santiago, Mejuto Bernabe´Francisco J., Barber Juan Manuel, Juan Armas Julia, Juanes De La Pen˜a Adria´n, Mellizo Moya Angel, Mena Garcia Juan, Mena Sastre Francisco Javier, Jurado Toro Alberto, Labrador Gonzalez Alberto, Labrador Esther, Mencı´a De Castro Gaspar, Mencı´a Herreras Jose´Ma, Mendez Gomez Lado Llerena Angel, Lado Lopez Manuel, Laencina Lo´pez Salvador, Begon˜a, Mendez Martinez Carmen, Mendez San Pedro Tomas, Mend- Lafuente Gutie´rrez Jose Luis, Laguna Isabel, Lalanza Lasheras Juan ieta Ruiz Ma A´ ngeles, Mendiguren Navascues Arantxa, Mendinueta Jose, Lamelas Garcia Jose A., Landin Vicun˜a Concha, Laporta Crespo Fernandez Carmen, Menedez Tamargo Jose Manuel, Mene´ndez Felix, Lara Moles Jesu´s, Larrinaga Kortabitarte Aitor, Lasarte Calderay Piquero Manuel, Mengual Moll, Vicente, Merino Mun˜oz Marta, Mesa Jose E., Lasheras Ferna´ndez Yolanda, Lazaro Rivera Mariano, Lazo Pedrero Carlos, Mesquida Jero´nima, Mestre Llugany Joan, Mialdea Naudin Victor, Leal Correa Bartolme, Lebrero Sa´nchez Encarnacio´n, Lozano Maria Jose´, Milian Beser Susana, Minchero Arroyo Alberto, Ledo Cabaleiro Jose´Marı´a, Letona Antia Lurdes, Lin˜ares Stolle Manuel, Minguez Villar Jose´ Carlos, Minguijon Barea Concha, Minin˜o Couto Lite Dı´az Annabel, Lizarribar Sans Marta, Llario Sanjua´n Miguel, Llido Gerardo, Minuesa Cortijo Francisco Javier, Miquel Mira Ma Jose, Mira Vicedo Ricardo, Llinares Moreno Vicente, Lliteras Fleixas Gabriel, Castejo´n Luis Alfredo, Miranda Ruiz Francisco, Modrego Navarro An- Llorens Edo Fernando, Llorente Martin Carmen, Lloscos Llavador Ger- gel, Molina Contreras Moises, Monfort Saez Rogelio, Monraba Capella man, Llull Sarralde Micaela, Lobato Delgado Luis Alberto, Lobato Miquel, Monsalve Terro´n Manuel, Montagud Moncho Miguel, Mon- Ferna´ndez Manuel, Lobera Serrano Pedro, Loizaga Horno Juan, Lom- tan˜es Rustullet Carlos, Montero Luengo Juan, Montero Luque Javier, J Am Soc Nephrol 17: S236–S245, 2006 Relationship between GFR and UAE S243

Mora Breso´ Concha, Mora Dı´az Juan De Dios, Mora Garcia Cristina, Nuria, Prieto Gonzalez Laureano, Prieto Seva Alvaro Jose´, Prieto Car- Morales Abad Manuel A., Morales Colas Ma Luz, Moranco Sengariz Ma men, Prol Ran˜a Manuel, Puchalt Ana Maria, Pucholt Bergara Juan, A´ ngeles, Moreno De Mingo Javier, Moreno Gonzalez Antonia, Moreno Puente Gala´n Oscar, Puente Martinez Antonio, Puente Perez Pablo, Marı´n Germa´n, Moreno Minguez Vicente, Moreno Moreno Ana, Quevedo Rivera Julia, Quiles An˜on Fernando, Quindimil Vazquez Jose Moreno Moreno Jose Manuel, Moreno Beatriz, Moreno Esther, Moro Antonio, Quiros Alvarez Jesu´s, Raga Asins Martin, Raga Casasus Jose´ Jimenez Julia´n, Moro Torija Pilar, Moron Alejandre Angela, Morrell Vicente, Ralla Pablo Jordi, Rama Ferro Jesu´s, Ramia Mulet Jose Luis, Rosario, Mosquera Martı´nez Juan, Mourin˜o Paz Amelia, Moya Cantar- Ramirez Aparicio Antonio, Ramı´rez Perez Carlos, Ramos Aleixades ell Ma Victoria, Moya Santana Rafael, Mulet Sart Monserrat, Munar Adolfo, Ramos Herna´ndez Santiago, Ramos Rodriguez Manuel, Ramos Mateu Juana Ana, Mun˜iz Fontain˜as Manuel, Mun˜iz Villa Candelas, Rafael, Razo´n Angulo Emilio, Real. Balaguer Vicente, Reboso Reyes Mun˜oz Conde Carmen, Mun˜oz Herna´ndez Jose´Gabriel, Mun˜oz Mora Cristina, Recio Ribote Lourdes, Reguillo Diaz Joaquina, Remo´n Soriano Francisco Javier, Mun˜oz Rodriguez Pepe, Mur Martı´ Teresa, Muriel Agustina, Renteria Goirigolzarri Jon, Repiso Moreno Manuel, Requena Velasco Ana, Muruais Gonzalez Jesus, Napal Anaut Ma Olga, Naranjo Solera Juan, Retis Vazquez Julio, Retuerta Garcı´a Ma Dolores, Revert Carrio´n Emilio Diego, Natal Gonza´lez Fernando, Navarro Martinez Algarra Adoracion, Revert Algarra Adoracio´n, Rey Suarez Salvador, Victoria, Navarro Moreno Carlos, Navarro Soler Javier, Navarro Tarin Ribelles Cebrian Julio, Ribes Vicedo Juana, Ricart Cortes Jose Vicente, Ricardo, Navarro Tarin Vicente, Navarro Valero Diego, Navarro Vil- Ridaura Martı´Amparo, Riera Calvo Andre´s, Rios Gomez Prados, Rios lena Manuel, Navascues Beltran German, Navaz Tejeiro Julio, Navaza Rey Teresa, Ripoll Sanchez Jaime, Rivero Macristo, Robres Oliete Mari- Dafonte Ana Maria, Nevado Mun˜oz Rafael, Nicolau Pellicer Carmen, ano, Roca Baeza Ramon, Roca Bosch Jose Luis, Roca Martinez Amparo, Niell Crespi Miguel, Nieto Hortal Pepe, Nogue´s Lobo´n Aurora, Novoa Roca Verdu´Antonio A´ ngel, Roche Del Toro Marciela, Rodilla Alonso Rodriguez Belen, Nu´n˜ez Jorge Carlos, Ocan˜a Cazalilla Carmelo, Ogal- Angel, Rodriguez Bacardit Neus, Rodriguez Fernandez Benito, Rodri- las Raya Fuensanta, Ojea Amoedo Enrique, Olea Carrasco Miriam, Olid guez Fernandez Concepcion, Rodriguez Gallego Concepcion, Rodri- Valle Antonio, Olina Iparragirre Anuska, Olivar Castrillo´n Carmen, guez Garcia Amor, Rodriguez Ledo Pilar, Rodriguez Lopez Elisa, Ro- Olivares Escribano Quintin, Olivera Can˜adas Guadalupe, Olivera driguez Lopez Isabel, Rodriguez Morua Javier, Rodriguez Ortiz De Ramos Ana G., Olmos Diaz Francisco, Ontan˜on Bort Juan Jose, Ordon˜ez Zarate Ma Luisa, Rodriguez Perez Jose Carlos, Rodriguez Quintela Pico´n Roberto, Orgaz Gallego Pilar, Ormad Sebastian Javier, Orribo Jesus, Rodriguez Romo Antonio, Rodriguez Soriano Ma Jose, Rodriguez Rodrı´guez Severiana, Orrun˜o Albizu Luis, Ortega De La Torre Llanos, Tebar Fabiola, Rodriguez Vivar Antonio, Rodrı´guez Alvarez Jesu´s, Ortega Dı´az A´ ngel Felipe, Ortega Motilla Natividad, Ortega Rı´os Fran- Rodrı´guez Bartolome´Emilio, Rodrı´guez Franco Mercedes, Rodrı´guez cisco Javier, Ortin Arronis Jose´Manuel, Ortiz Forcada Josefina, Ortueta Gallego Concepcio´n, Rodrı´guez Pe´rez Ana Denis, Rodrı´guez Portillo Ruiz De Arbulu Jesus, Otaduy Bengoa Santiago, Otero Arias Fernando, Fernando, Rodrı´guez Relucio Angela, Roig Valdivieso Monserrat, Rojo Otero Coto´n Jose´, Otero Lopez Jose Manuel, Otxoa Iban˜ez In˜aki, Oujo Caldero´n Aranzazu, Rolda´n Sanchez Pilar, Romero Conde Antonio, Pujales Juan, Pablos Herrero Eva, Paches Porcar Ma Dolores, Padin Romero Corroto Carmen, Romero De Lama Concepcion, Romero Gar- Montoto Fernando, Padron Chao Antonio, Padro´n Pe´rez Marcos, Pala- cia Cesar, Romero Mera Fernando, Ros Dominguez Jose, Rosell cio Monedero Carmen, Palacios Claramunt Juan Andres, Palacios Del Cruchaga Luis, Rovira Pen˜a Blanca, Rubert Escrig Carmina, Rubiera Cerro Antonio, Palacios Gonzalez Eleazar, Pallare´s Herna´ndez Maria Alvarez Carlos, Rubio Arribas Victor, Rubio Beltran De Guevara Jesus, Pilar, Palma Lafuente Javier, Palomares Ferna´ndez Sixto, Palomo Del Rubio Fernandez Jose Fe´lix, Rubio Gonzalez Manuela, Rubio Guerrero Arco Jesu´s, Panero Juan Vicente, Pappalardo Ordin˜ana Eric, Pappa- Manuel, Rubio Ruiz Jose´Ma, Rubio Villar Montserrat, Rubio Teresa, lardo Ordin˜ana Eric, Pardo Diaz Beatriz, Paredes Martinez Ma Luz, Ruiz Aguilar Gloria, Ruiz Chamorro Manuel, Ruiz Lopez Jesus, Ruiz Paredes Urraca Toma´s, Parra Rodriguez Francisco, Parralejo Cano Pastor Luis, Ruiz Quintero Manuel, Ruiz Quintero Manuel, Ruiz Ramos Francisco, Parrilla Rubio Margarita, Pascual Gil Octavio, Pascual Rosa, Ruiz Roig Joaquina, Ruiz Ruiz Ana Marı´a, Ruiz Vicente Julia´n, Gonza´lez Oscar, Pascual Seara Benito, Pastor Benavent Carmen, Pastor Ruiz Margarita, Ruz Franzi Ignacio, Saavedra Mija´n Juan, Saenz Garcia- Oliver Jose´Francisco, Pastor Pastor Juan, Pastrana Gonzalez Victoria, Baquero Isabel, Saez Azucena, Sa´ez Sifre Salvador, Sagu¨illo Gonzalez Paya Perez Jose´Antonio, Paya´n Godoy Josefa, Pazos Lopez Jose´, Pe- Pedro, Said Heluani Mohamed, Salanova Pen˜alva Alejandro, Salas draz Garcı´a Ma Isabel, Peiro Morant Juan, Pellit Ramil Jose Ignacio, Gonza´lez Toma´s, Salas Herrera Fernando, Salas Hospital Jose Carlos, Penades Vaya Vicente, Pensado Pousa Jose´ Francisco, Pen˜a Forcada Salcedo Peris Teresa, Salguero Chavez Emilio, Salguero Emilio, Salva- Carmen, Pen˜as Merino Antonio, Perales Bolado Javier, Peralta Mun- dor Hernandez Juan, Salvador Herrero Luis, Salvatierra Palacio Ma guı´a Lucı´a, Pereira Aparicio Ma A´ ngeles, Perera Pe´rez Carmen G., Luisa, San Andre´s Herna´ndez Inmaculada, San Juan Perez Begon˜a, Perez Alemany Antonio, Perez Algar Ma Jose´, Perez Alonso Manuel, 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