| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2002;106:1777.)
© 2002 American Heart Association, Inc.
Clinical Investigation and Reports |
From the Trial Coordination Center (H.L.H., W.H.v.G., D.J.v.V.), Department of Cardiology, and the Department of Internal Medicine (R.O.B.G.), Division of Nephrology (P.E.d.J.), University Hospital of Groningen, Groningen, the Netherlands; the Departments of Health Sciences (V.F.) and Clinical Pharmacology (G.F.H.D., W.H.v.G., D.d.Z.), University of Groningen, Groningen, the Netherlands; the Department of Internal Medicine (W.M.T.J.), Martini Hospital of Groningen, Groningen, the Netherlands; and Julius Center for Health Sciences and Primary Care (D.E.G.), University Medical Center, Utrecht, the Netherlands.
Correspondence to Prof Dr P.E. de Jong, Department of Internal Medicine, Division of Nephrology, University Hospital of Groningen, PO Box 30.001, 9700 RB Groningen, Netherlands. E-mail p.e.de.jong{at}int.azg.nl
| Abstract |
|---|
|
|
|---|
Methods and Results In the period 1997 to 1998, all inhabitants of the city of Groningen, the Netherlands, aged between 28 and 75 years (n=85 421) were sent a postal questionnaire collecting information about risk factors for CV disease and CV morbidity and a vial to collect an early morning urine sample for measurement of urinary albumin concentration (UAC). The vital status of the cohort was subsequently obtained from the municipal register, and the cause of death was obtained from the Central Bureau of Statistics. Of these 85 421 subjects, 40 856 (47.8%) responded, and 40 548 could be included in the analysis. During a median follow-up period of 961 days (maximum 1139 days), 516 deaths with known cause were recorded. We found a positive dose-response relationship between increasing UAC and mortality. A higher UAC increased the risk of both CV and non-CV death after adjustment for other well-recognized CV risk factors, with the increase being significantly higher for CV mortality than for non-CV mortality (P=0.014). A 2-fold increase in UAC was associated with a relative risk of 1.29 for CV mortality (95% CI 1.18 to 1.40) and 1.12 (95% CI 1.04 to 1.21) for non-CV mortality.
Conclusions Urinary albumin excretion is a predictor of all-cause mortality in the general population. The excess risk was more attributable to death from CV causes, independent of the effects of other CV risk factors, and the relationship was already apparent at levels of albuminuria currently considered to be normal.
Key Words: follow-up studies mortality risk factors
| Introduction |
|---|
|
|
|---|
| Methods |
|---|
|
|
|---|
All participants gave written informed consent. The PREVEND study was approved by the local medical ethics committee and was conducted in accordance with the guidelines of the Declaration of Helsinki.
Urinary Albumin Measurements
Urinary albumin excretion was measured as UAC in a morning urine sample. UAC was determined by a commercial immunoturbidimetry assay with a sensitivity of 2.3 mg/L and interassay and intra-assay coefficients of variation of 4.4% and 4.3%, respectively (BNII, Dade Behring Diagnostica). Microalbuminuria was defined as a UAC between 20 and 200 mg/L, and macroalbuminuria was defined as a UAC >200 mg/L.11
Mortality Data
From the time of recruitment, the vital status of the participants was checked through the municipal register. The cause of death was obtained by linking the number of the death certificate to the primary cause of death as coded by a physician from the Central Bureau of Statistics. Causes of death were coded according to the 10th revision of the International Classification of Diseases. Cause-specific end points used in the analyses were CV disorders, and the remaining codes were those from non-CV causes.
Survival time for the participants was defined as the period from the date of the urine collection of the participant to the date of death from any cause or September 2000, until which date information about specific causes of death follow-up information was available. If a person had moved to an unknown destination, the date on which the person was dropped from the municipal registry was used as the census date.
Statistical Analysis
To study the effects of albumin excretion on mortality, we fitted Cox proportional hazards models to the data. Two competing death causes were distinguished: CV and non-CV. Apart from UAC, the following available explanatory variables for CV and non-CV death were entered in the regression analysis: sex, age, presence of diabetes mellitus, use of antihypertensive drugs, use of lipid-lowering drugs, smoking, family history of CVD, previous myocardial infarction, and previous stroke. We used competing risk analysis, which allowed us to compare the effects of explanatory variables on either CV or non-CV death.12 P-splines were used to explore the functional form of effects of continuous variables age and UAC. Results are summarized by hazard (risk) ratios, with CIs based on robust standard error estimates, by plotting the adjusted hazard ratio as a function of UAC and by plotting cause-specific cumulative incidence functions for specific covariate values.12 A value of P<0.05 (2-sided) was used as the nominal level of statistical significance. We used the statistical package S-Plus 6 (2001, Insightful Co) for the analysis.
| Results |
|---|
|
|
|---|
Table 1 shows the baseline characteristics of the study cohort at the time of inclusion stratified into CV and non-CV mortality. Compared with those who survived, those who died were older, more likely to be male, and more likely to have had a history of diabetes, hypertension, hyperlipidemia, smoking, or a (parental) history of CV disease. Moreover, those who died from CV causes had the highest prevalences of these risk factors.
|
Urinary Albumin Excretion and Mortality
Crude incidence rates per 1000 person-years for all-cause, CV, and non-CV mortality by different UACs are shown in Table 2. There was a clear dose-response relationship between UAC and all-cause, CV, and non-CV mortality (P for trend<0.001).
|
Table 3 summarizes the results of the Cox regression analysis adjusted for age and sex. Both CV and non-CV deaths were found to be associated with the presence or absence of diabetes mellitus, hyperlipidemia, smoking, myocardial infarction, and UAC level. CV deaths were also associated with a history of stroke. The effect of age on the logarithmic hazard was found to be linear; the effect of UAC was linear after logarithmic transformation of UAC. A higher UAC increased the risk of both types of death, with the increase being significantly higher for the CV deaths (P=0.009). The inclusion in the regression model of the other CV risk factors did not substantially alter the relationship between UAC and CV and non-CV death. In this mutually adjusted model, a 2-fold increase in UAC (ie, from 5 to 10 mg/L or 20 to 40 mg/L) was associated with a 1.29 higher risk for CV death and 1.12 higher risk for non-CV death (P=0.014). Smokers tended to have an increased risk for non-CV death (P=0.039). The effects of the level of UAC on the cause-specific hazards for CV and non-CV mortality, adjusted for all the risk factors as shown in Table 3, are presented in Figure 1. The solid line curves corresponding to the log-linear functional form lie within the dotted CI curves. This supports reasonability of the chosen model, although the (P-splinebased) CI curves obviously do not exclude the existence of a more complex functional relation. The increase in risk associated with an increase in UAC is steeper for CV deaths than for non-CV deaths.
|
|
To show the effects of UAC within the currently used reference ranges, cause-specific cumulative incidence functions using the Cox model were calculated for 2 UAC levels well below the lower border of the definition of microalbuminuria. The curves represent the cumulative incidence functions of CV and non-CV mortality for a nonhypertensive, nonhyperlipidemic, nondiabetic, nonsmoking 50-year-old male without a history of myocardial infarction or stroke, with UAC levels set equal to the 25th percentile (3.8 mg/L) and to the 75th percentile (9.8 mg/L). The 2-year cumulative incidence of CV mortality for a UAC of 3.8 mg/L is 0.12%, and that for a UAC of 9.8 mg/L is 0.15%, whereas for non-CV mortality, these figures are 0.21% and 0.24%, respectively (Figure 2).
|
| Discussion |
|---|
|
|
|---|
Microalbuminuria is associated with an increased risk of renal and CV morbidity and all-cause mortality in diabetic patients, in patients with hypertension, and in elderly subjects.18 We found a stronger relationship between albuminuria and mortality from CV causes compared with non-CV causes in an unselected cohort derived from the population at large. In view of this finding, albuminuria appears to be a marker of generalized vascular disease and indicates an incremental risk for CV mortality not only in CV-compromised subjects. The precise cause underlying this mechanism is unknown. It is possible that the glomerular albumin leak reflects a widespread atherosclerosis-mediated capillary vasculopathy.1315 Dysfunction of the coagulation and fibrinolytic systems has also been suggested as a possible link between microalbuminuria and CV disease. In diabetic and nondiabetic subjects, microalbuminuria has been associated with changes in von Willebrand factor, fibrinogen, thrombomodulin, and plasminogen activator inhibitor-1.1618 However, urinary albumin excretion is associated with several other risk factors that may themselves be linked with mortality. These include diabetes mellitus, hyperglycemia, hypertension, renal dysfunction, dyslipidemia, hyperhomocystinemia, dietary protein, smoking, and markers of an acute-phase response. A critical question within this context is whether the relationship between urinary albumin excretion and mortality is due to an association of urinary albumin excretion with other predictors of mortality. If albuminuria and the other prognostic factors share a common causal pathway, adjustment for these factors may attenuate the relationship between albuminuria and mortality. However, even after adjustment for these factors, albuminuria remains a relatively strong predictor after full adjustment, suggesting an independent additive component in the relationship between albuminuria and mortality from CV causes.
We also observed an association, although less strong, between albuminuria and non-CV mortality. The incidence of non-CV mortality could mostly be attributed to death due to malignant neoplasms. An elevated urinary albumin excretion in patients with malignancies has been reported previously.19 Interestingly, although the precise underlying mechanism is unknown, it has been speculated that in this type of patient, the increased urinary albumin loss appears to be more of an isolated renal phenomenon than to be related to endothelial dysfunction, because a normal endothelial function was observed, as demonstrated by the transcapillary escape rate of albumin, which suggests an overall unaffected capillary permeability.
The present study adds considerable data to the available information on urinary albumin excretion as a vascular risk factor because we have used the full range of UAC in studying the relationship with mortality and did not cluster UAC levels into several categories. Several objections could be raised about categorizing UAC, including the following: (1) a step function is biologically implausible because estimating the risk of categories ignores the possibility that actual risk varies smoothly with the exposure of the risk factor; (2) high-risk individuals will be submerged in a pool of lower-risk members, thereby diluting the effect size; (3) there may be a significant loss of power, especially when the effects are concentrated at the end of the UAC scale; and (4) cutoff point bias may be introduced when cutoff points are selected to maximize effect size.
It has been suggested in selected patient populations that even modestly raised albuminuria values, within what hitherto has been considered the normal range, are associated with a future risk of CV events.3,5,20 Our finding of a dose-response relationship between UAC and the risk of mortality extends such a suggestion to the general population. Therefore, we suggest that the lower limit defining a "pathological" albuminuria seems appropriate.
The present study has a number of limitations, and to appreciate the findings, some issues need to be addressed. We measured UAC only once and without correcting for potential variability in urine concentration. In addition, we were unable to perform detailed measurements of the CV risk factors. Self-reported histories have limitations because a certain degree of misclassification; therefore, bias may occur. Because we do not expect this misclassification to be related to the risk factors or to the morning urinary albumin measurements themselves, misclassification would dilute the estimated effects; ie, it would make the estimated risk ratio closer to 1. Therefore, our analysis may have underestimated the true association between urinary albumin excretion and mortality. The relatively short follow-up could have masked some of the long-term health hazards of an increased urinary albumin excretion. The current large population-based study is not characterized by a high participation rate and, hence, could be subject to selection bias. However, the finding that
40% of all deaths in the present study were classified as being due to CV disease, which is in line with previous prospective studies of subjects of the general population, favors acceptable generalizibility.21 Finally, we did an extensive subgroup analysis on the other investigated risk factors but did not find any significant differences. However, although the total number of studied subjects is very large, the number of subjects who died is relatively small, suggesting that the present study is likely underpowered in its design to reliably detect any differences in subgroups.
We conclude from this large prospective cohort study that albuminuria is an important marker for both CV and non-CV mortality. The use of UAC as a screening tool is made more feasible by more sensitive assays that are commercially available and that appear to be reliable even in the lower ranges. However, mechanisms underlying the increased CV risk of an increased urinary albumin excretion require further elucidation. There may be an important clinical role for albuminuria in CV disease screening that is analogous to the role of blood pressure and lipid screening. Because albuminuria is a modifiable risk marker, because studies of secondary prevention have shown that blood pressurelowering drugs effectively reduce the albumin excretion rate, and because ACE inhibitors seem to be particularly effective, the current observation may lead to new therapeutic strategies in the prevention of CV disease.
| Acknowledgments |
|---|
| Footnotes |
|---|
| Appendix |
|---|
|
|
|---|
Received May 13, 2002; revision received July 17, 2002; accepted July 17, 2002.
| References |
|---|
|
|
|---|
2. Jager A, Kostense PJ, Ruhe HG, et al. Microalbuminuria and peripheral arterial disease are independent predictors of cardiovascular and all-cause mortality, especially among hypertensive subjects: five-year follow-up of the Hoorn Study. Arterioscler Thromb Vasc Biol. 1999; 19: 617624.
3. Damsgaard EM, Froland A, Jorgensen OD, et al. Microalbuminuria as predictor of increased mortality in elderly people. BMJ. 1990; 300: 297300.
4. Dinneen SF, Gerstein HC. The association of microalbuminuria and mortality in non-insulin-dependent diabetes mellitus: a systematic overview of the literature. Arch Intern Med. 1997; 157: 14131418.
5. Yudkin JS, Forrest RD, Jackson CA. Microalbuminuria as predictor of vascular disease in non-diabetic subjects: Islington Diabetes Survey. Lancet. 1988; 2: 530533.[Medline] [Order article via Infotrieve]
6. Roest M, Banga JD, Janssen WM, et al. Excessive urinary albumin levels are associated with future cardiovascular mortality in postmenopausal women. Circulation. 2001; 103: 30573061.
7. Borch-Johnsen K, Feldt-Rasmussen B, Strandgaard S, et al. Urinary albumin excretion: an independent predictor of ischemic heart disease. Arterioscler Thromb Vasc Biol. 1999; 19: 19921997.
8. Gerstein HC, Mann JF, Pogue J, et al. Prevalence and determinants of microalbuminuria in high-risk diabetic and nondiabetic patients in the Heart Outcomes Prevention Evaluation Study: the HOPE Study Investigators. Diabetes Care. 2000; 23 (suppl 2): B35B39.[Medline] [Order article via Infotrieve]
9. Hillege HL, Janssen WM, Bak AA, et al. Microalbuminuria is common, also in a nondiabetic, nonhypertensive population, and an independent indicator of cardiovascular risk factors and cardiovascular morbidity. J Intern Med. 2001; 249: 519526.[CrossRef][Medline] [Order article via Infotrieve]
10. Pinto-Sietsma SJ, Janssen WM, Hillege HL, et al. Urinary albumin excretion is associated with renal functional abnormalities in a nondiabetic population. J Am Soc Nephrol. 2000; 11: 18821888.
11. Bangstad HJ, Try K, Dahl JK, et al. New semiquantitative dipstick test for microalbuminuria. Diabetes Care. 1991; 14: 10941097.[Abstract]
12. Therneau TM, Grambsch P, Grambsch PM. Modeling Survival Data: Extending the Cox Model. New York, NY: Springer-Verlag; 2000.
13. Deckert T, Kofoed EA, Norgaard K, et al. Microalbuminuria. Implications for micro- and macrovascular disease. Diabetes Care. 1992; 15: 11811191.[Abstract]
14. Pedrinelli R, Penno G, DellOmo G, et al. Microalbuminuria and transcapillary albumin leakage in essential hypertension. Hypertension. 1999; 34: 491495.
15. Taddei S, Virdis A, Mattei P, et al. Lack of correlation between microalbuminuria and endothelial function in essential hypertensive patients. J Hypertens. 1995; 13: 10031008.[Medline] [Order article via Infotrieve]
16. Agewall S, Fagerberg B, Attvall S, et al. Microalbuminuria, insulin sensitivity and haemostatic factors in non-diabetic treated hypertensive men: Risk Factor Intervention Study Group. J Intern Med. 1995; 237: 195203.[Medline] [Order article via Infotrieve]
17. Clausen P, Feldt-Rasmussen B, Jensen G, et al. Endothelial haemostatic factors are associated with progression of urinary albumin excretion in clinically healthy subjects: a 4-year prospective study. Clin Sci (Colch). 1999; 97: 3743.[Medline] [Order article via Infotrieve]
18. Kario K, Matsuo T, Kobayashi H, et al. Activation of tissue factor-induced coagulation and endothelial cell dysfunction in non-insulin-dependent diabetic patients with microalbuminuria. Arterioscler Thromb Vasc Biol. 1995; 15: 11141120.
19. Pedersen LM, Terslev L, Sørensen PG, et al. Urinary albumin excretion and transcapillary escape rate of albumin in malignancies. Med Oncol. 2000; 17: 117122.[Medline] [Order article via Infotrieve]
20. Gerstein HC, Mann JF, Yi Q, et al. Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals. JAMA. 2001; 286: 421426.
21. Konings-Dalstra JAA, Reitsma JB. Hart- en vaatziekten in Nederland 1999, cijfers over ziekte en sterfte. Den Haag, Nederlands: Hartstichting; 1999.
This article has been cited by other articles:
![]() |
S. De Cosmo, N. Motterlini, S. Prudente, F. Pellegrini, R. Trevisan, A. Bossi, G. Remuzzi, V. Trischitta, P. Ruggenenti, and on behalf of the BENEDICT Study Group Impact of the PPAR-{gamma}2 Pro12Ala Polymorphism and ACE Inhibitor Therapy on New-Onset Microalbuminuria in Type 2 Diabetes: Evidence From BENEDICT Diabetes, December 1, 2009; 58(12): 2920 - 2929. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Nitsch, D. A. Lawlor, R. Patel, C. Carson, and S. Ebrahim The association of renal impairment with all-cause and cardiovascular disease mortality Nephrol. Dial. Transplant., November 30, 2009; (2009) gfp607v1. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Sabanayagam, J. Lee, A. Shankar, S. C. Lim, T. Y. Wong, and E. S. Tai C-reactive protein and microalbuminuria in a multi-ethnic Asian population Nephrol. Dial. Transplant., November 13, 2009; (2009) gfp591v1. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. E. Schmieder Hypertension and Diabetes: What are the pros to treating early surrogates? Diabetes Care, November 1, 2009; 32(suppl_2): S294 - S297. [Full Text] [PDF] |
||||
![]() |
M. C. Odden, I. B. Tager, R. T. Gansevoort, S. J. L. Bakker, R. Katz, L. F. Fried, A. B. Newman, R. B. Canada, T. Harris, M. J. Sarnak, et al. Age and cystatin C in healthy adults: a collaborative study Nephrol. Dial. Transplant., September 11, 2009; (2009) gfp474v1. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. H. Jafar, Z. Qadri, and S. Hashmi Prevalence of microalbuminuria and associated electrocardiographic abnormalities in an Indo-Asian population Nephrol. Dial. Transplant., July 1, 2009; 24(7): 2111 - 2116. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. K. Mottl, S. Vupputuri, S. A. Cole, L. Almasy, H. H.H. Goring, V. P. Diego, S. Laston, N. Shara, E. T. Lee, L. G. Best, et al. Linkage Analysis of Albuminuria J. Am. Soc. Nephrol., July 1, 2009; 20(7): 1597 - 1606. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Dhaun, I. M. MacIntyre, V. Melville, P. Lilitkarntakul, N. R. Johnston, J. Goddard, and D. J. Webb Blood Pressure-Independent Reduction in Proteinuria and Arterial Stiffness After Acute Endothelin-A Receptor Antagonism in Chronic Kidney Disease Hypertension, July 1, 2009; 54(1): 113 - 119. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Anderson, J. B. Halter, W. R. Hazzard, J. Himmelfarb, F. M. Horne, G. A. Kaysen, J. W. Kusek, S. G. Nayfield, K. Schmader, Y. Tian, et al. Prediction, Progression, and Outcomes of Chronic Kidney Disease in Older Adults J. Am. Soc. Nephrol., June 1, 2009; 20(6): 1199 - 1209. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. J Lamb, F. MacKenzie, and P. E Stevens How should proteinuria be detected and measured? Ann Clin Biochem, May 1, 2009; 46(3): 205 - 217. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Vogt, D. de Zeeuw, A. J. J. Woittiez, and G. Navis Selective cyclooxygenase-2 (COX-2) inhibition reduces proteinuria in renal patients Nephrol. Dial. Transplant., April 1, 2009; 24(4): 1182 - 1189. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. van der Velde, N. Halbesma, F. T. de Charro, S. J.L. Bakker, D. de Zeeuw, P. E. de Jong, and R. T. Gansevoort Screening for Albuminuria Identifies Individuals at Increased Renal Risk J. Am. Soc. Nephrol., April 1, 2009; 20(4): 852 - 862. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Tanaka, K. Doi, R. Maeda-Mamiya, K. Negishi, D. Portilla, T. Sugaya, T. Fujita, and E. Noiri Urinary L-Type Fatty Acid-Binding Protein Can Reflect Renal Tubulointerstitial Injury Am. J. Pathol., April 1, 2009; 174(4): 1203 - 1211. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. T. Gansevoort and E. Ritz Hermann Senator and albuminuria--forgotten pioneering work in the 19th century Nephrol. Dial. Transplant., March 1, 2009; 24(3): 1057 - 1062. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. T. Gansevoort and P. E. de Jong The Case for Using Albuminuria in Staging Chronic Kidney Disease J. Am. Soc. Nephrol., March 1, 2009; 20(3): 465 - 468. [Full Text] [PDF] |
||||
![]() |
M. I. Yilmaz, J. Axelsson, A. Sonmez, J. J. Carrero, M. Saglam, T. Eyileten, K. Caglar, A. Kirkpantur, T. Celik, Y. Oguz, et al. Effect of Renin Angiotensin System Blockade on Pentraxin 3 Levels in Type-2 Diabetic Patients With Proteinuria Clin. J. Am. Soc. Nephrol., March 1, 2009; 4(3): 535 - 541. [Abstract] [Full Text] [PDF] |
||||
![]() |
WRITING GROUP MEMBERS, D. Lloyd-Jones, R. Adams, M. Carnethon, G. De Simone, T. B. Ferguson, K. Flegal, E. Ford, K. Furie, A. Go, et al. Heart Disease and Stroke Statistics--2009 Update: A Report From the American Heart Association Statistics Committee and Stroke Statistics Subcommittee Circulation, January 27, 2009; 119(3): e21 - e181. [Full Text] [PDF] |
||||
![]() |
C. Sabanayagam, A. Shankar, S. M. Saw, S. C. Lim, E S. Tai, and T. Y. Wong Socioeconomic status and microalbuminuria in an Asian population Nephrol. Dial. Transplant., January 1, 2009; 24(1): 123 - 129. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. E. Kjeldsen, T. A. Aksnes, R. H. Fagard, and G. Mancia CHAPTER 13 Hypertension ESC Textbook of Cardiovascular Medicine, January 1, 2009; 2(1): med-9780199566990-chapter - med-9780199566990-chapter. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. H. Brantsma, S. J. L. Bakker, H. L. Hillege, D. de Zeeuw, P. E. de Jong, R. T. Gansevoort, and for the PREVEND Study Group Cardiovascular and renal outcome in subjects with K/DOQI stage 1-3 chronic kidney disease: the importance of urinary albumin excretion Nephrol. Dial. Transplant., December 1, 2008; 23(12): 3851 - 3858. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Lin, R. J. Glynn, N. Rifai, J. E. Manson, P. M. Ridker, D. M. Nathan, and D. A. Schaumberg Inflammation and Progressive Nephropathy in Type 1 Diabetes in the Diabetes Control and Complications Trial Diabetes Care, December 1, 2008; 31(12): 2338 - 2343. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. S. A. Naderi and R. F. Reilly Primary Care Approach to Proteinuria J Am Board Fam Med, November 1, 2008; 21(6): 569 - 574. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. J. Lambers Heerspink, A. H. Brantsma, D. de Zeeuw, S. J. L. Bakker, P. E. de Jong, R. T. Gansevoort, and for the PREVEND Study Group Albuminuria Assessed From First-Morning-Void Urine Samples Versus 24-Hour Urine Collections as a Predictor of Cardiovascular Morbidity and Mortality Am. J. Epidemiol., October 15, 2008; 168(8): 897 - 905. [Abstract] [Full Text] [PDF] |
||||
![]() |
W. A. K. M. Windt, R. H. Henning, A. C. A. Kluppel, Y. Xu, D. de Zeeuw, and R. P. E. van Dokkum Myocardial infarction does not further impair renal damage in 5/6 nephrectomized rats Nephrol. Dial. Transplant., October 1, 2008; 23(10): 3103 - 3110. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. J. McQueen and A. C. Don-Wauchope Requesting and Interpreting Urine Albumin Measurements in the Primary Health Care Setting Clin. Chem., October 1, 2008; 54(10): 1595 - 1597. [Full Text] [PDF] |
||||
![]() |
E. Crowe, D. Halpin, P. Stevens, and on behalf of the Guideline Development Group Early identification and management of chronic kidney disease: summary of NICE guidance BMJ, September 29, 2008; 337(sep29_1): a1530 - a1530. [Full Text] |
||||
![]() |
A. M. Abbatecola, M. Barbieri, M. R. Rizzo, R. Grella, M. T. Laieta, E. Quaranta, A. M. Molinari, M. Cioffi, P. Fioretto, and G. Paolisso Arterial Stiffness and Cognition in Elderly Persons With Impaired Glucose Tolerance and Microalbuminuria J. Gerontol. A Biol. Sci. Med. Sci., September 1, 2008; 63(9): 991 - 996. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. H. Brantsma, S. J.L. Bakker, D. de Zeeuw, P. E. de Jong, R. T. Gansevoort, and for the PREVEND Study Group Extended Prognostic Value of Urinary Albumin Excretion for Cardiovascular Events J. Am. Soc. Nephrol., September 1, 2008; 19(9): 1785 - 1791. [Abstract] [Full Text] [PDF] |
||||
![]() |
M S O'Neill, A V Diez-Roux, A H Auchincloss, T G Franklin, D R Jacobs Jr, B C Astor, J T Dvonch, and J Kaufman Airborne particulate matter exposure and urinary albumin excretion: the Multi-Ethnic Study of Atherosclerosis Occup. Environ. Med., August 1, 2008; 65(8): 534 - 540. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Mimran and G. du Cailar Dietary sodium: the dark horse amongst cardiovascular and renal risk factors Nephrol. Dial. Transplant., July 1, 2008; 23(7): 2138 - 2141. [Full Text] [PDF] |
||||
![]() |
E. Rademacher, M. Mauer, D. R. Jacobs Jr, B. Chavers, J. Steinke, and A. Sinaiko Albumin Excretion Rate in Normal Adolescents: Relation to Insulin Resistance and Cardiovascular Risk Factors and Comparisons to Type 1 Diabetes Mellitus Patients Clin. J. Am. Soc. Nephrol., July 1, 2008; 3(4): 998 - 1005. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Danziger Importance of Low-Grade Albuminuria Mayo Clin. Proc., July 1, 2008; 83(7): 806 - 812. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. G. Ramos and K. Olden The Prevalence of Metabolic Syndrome Among US Women of Childbearing Age Am J Public Health, June 1, 2008; 98(6): 1122 - 1127. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. C. Astor, S. I. Hallan, E. R. Miller III, E. Yeung, and J. Coresh Glomerular Filtration Rate, Albuminuria, and Risk of Cardiovascular and All-Cause Mortality in the US Population Am. J. Epidemiol., May 15, 2008; 167(10): 1226 - 1234. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Jorgensen, I. Heuch, T. Jenssen, and B. K. Jacobsen Association of Albuminuria and Cancer Incidence J. Am. Soc. Nephrol., May 1, 2008; 19(5): 992 - 998. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. J. Postma, C. Boersma, and R. T. Gansevoort Pharmacoeconomics in nephrology: considerations on cost-effectiveness of screening for albuminuria Nephrol. Dial. Transplant., April 1, 2008; 23(4): 1103 - 1106. [Full Text] [PDF] |
||||
![]() |
R. P. Obermayr, C. Temml, M. Knechtelsdorfer, G. Gutjahr, J. Kletzmayr, S. Heiss, A. Ponholzer, S. Madersbacher, R. Oberbauer, and R. Klauser-Braun Predictors of new-onset decline in kidney function in a general middle-european population Nephrol. Dial. Transplant., April 1, 2008; 23(4): 1265 - 1273. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. E. de Jong and R. T. Gansevoort Fact or fiction of the epidemic of chronic kidney disease--let us not squabble about estimated GFR only, but also focus on albuminuria Nephrol. Dial. Transplant., April 1, 2008; 23(4): 1092 - 1095. [Full Text] [PDF] |
||||
![]() |
B.C. Astor, S. Yi, L. Hiremath, T. Corbin, V. Pogue, B. Wilkening, G. Peterson, J. Lewis, J.P. Lash, F. Van Lente, et al. N-Terminal Prohormone Brain Natriuretic Peptide as a Predictor of Cardiovascular Disease and Mortality in Blacks With Hypertensive Kidney Disease: The African American Study of Kidney Disease and Hypertension (AASK) Circulation, April 1, 2008; 117(13): 1685 - 1692. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Cirillo, M. P. Lanti, A. Menotti, M. Laurenzi, M. Mancini, A. Zanchetti, and N. G. De Santo Definition of Kidney Dysfunction as a Cardiovascular Risk Factor: Use of Urinary Albumin Excretion and Estimated Glomerular Filtration Rate Arch Intern Med, March 24, 2008; 168(6): 617 - 624. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. M. Connolly, R. Cunningham, P. T. McNamee, I. S. Young, and A. P. Maxwell Troponin T is an independent predictor of mortality in renal transplant recipients Nephrol. Dial. Transplant., March 1, 2008; 23(3): 1019 - 1025. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. E. de Jong, M. van der Velde, R. T. Gansevoort, and C. Zoccali Screening for Chronic Kidney Disease: Where Does Europe Go? Clin. J. Am. Soc. Nephrol., March 1, 2008; 3(2): 616 - 623. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. D. Hanevold, J. S. Pollock, and G. A. Harshfield Racial Differences in Microalbumin Excretion in Healthy Adolescents Hypertension, February 1, 2008; 51(2): 334 - 338. [Abstract] [Full Text] [PDF] |
||||
![]() |
Writing Group Members, W. Rosamond, K. Flegal, K. Furie, A. Go, K. Greenlund, N. Haase, S. M. Hailpern, M. Ho, V. Howard, et al. Heart Disease and Stroke Statistics--2008 Update: A Report From the American Heart Association Statistics Committee and Stroke Statistics Subcommittee Circulation, January 29, 2008; 117(4): e25 - e146. [Full Text] [PDF] |
||||
![]() |
S. Nguyen, C. McCulloch, P. Brakeman, A. Portale, and C.-y. Hsu Being Overweight Modifies the Association Between Cardiovascular Risk Factors and Microalbuminuria in Adolescents Pediatrics, January 1, 2008; 121(1): 37 - 45. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. D. Solomon, J. Lin, C. G. Solomon, K. A. Jablonski, M. M. Rice, M. Steffes, M. Domanski, J. Hsia, B. J. Gersh, J. M. O. Arnold, et al. Influence of Albuminuria on Cardiovascular Risk in Patients With Stable Coronary Artery Disease Circulation, December 4, 2007; 116(23): 2687 - 2693. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. M. van de Wal, P. van der Harst, W. B. Gerritsen, F. van der Horst, T. H. Plokker, R. T Gansevoort, W. H van Gilst, and A. A Voors Plasma matrix metalloproteinase-9 and ACE-inhibitor-induced improvement of urinary albumin excretion in non-diabetic, microalbuminuric subjects Journal of Renin-Angiotensin-Aldosterone System, December 1, 2007; 8(4): 177 - 180. [Abstract] [PDF] |
||||
![]() |
D. J. Magliano, K. R. Polkinghorne, E. L.M. Barr, Q. Su, S. J. Chadban, P. Z. Zimmet, J. E. Shaw, and R. C. Atkins HPLC-Detected Albuminuria Predicts Mortality J. Am. Soc. Nephrol., December 1, 2007; 18(12): 3171 - 3176. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Sheehan, S.-W. Tsaih, B. L. King, C. Stanton, G. A. Churchill, B. Paigen, and K. DiPetrillo Genetic analysis of albuminuria in a cross between C57BL/6J and DBA/2J mice Am J Physiol Renal Physiol, November 1, 2007; 293(5): F1649 - F1656. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Whaley-Connell, B. S. Pavey, K. Chaudhary, G. Saab, and J. R. Sowers Review: Renin-angiotensin-aldosterone system intervention in the cardiometabolic syndrome and cardio-renal protection Therapeutic Advances in Cardiovascular Disease, October 1, 2007; 1(1): 27 - 35. [Abstract] [PDF] |
||||
![]() |
M. S. MacGregor How common is early chronic kidney disease?: A Background Paper prepared for the UK Consensus Conference on Early Chronic Kidney Disease Nephrol. Dial. Transplant., September 1, 2007; 22(suppl_9): ix8 - ix18. [Full Text] [PDF] |
||||
![]() |
R. T. Gansevoort, H. Lambers, and E. C. Witte Methodology of screening for albuminuria Nephrol. Dial. Transplant., August 1, 2007; 22(8): 2109 - 2111. [Full Text] [PDF] |
||||
![]() |
T. H. Jafar, N. Chaturvedi, J. Hatcher, and A. S. Levey Use of albumin creatinine ratio and urine albumin concentration as a screening test for albuminuria in an Indo-Asian population Nephrol. Dial. Transplant., August 1, 2007; 22(8): 2194 - 2200. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. E. Weiner, H. Tighiouart, E. F. Elsayed, J. L. Griffith, D. N. Salem, A. S. Levey, and M. J. Sarnak The Framingham Predictive Instrument in Chronic Kidney Disease J. Am. Coll. Cardiol., July 17, 2007; 50(3): 217 - 224. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Jorgensen, T. Jenssen, L. Ahmed, A. Bjornerem, R. Joakimsen, and B. K. Jacobsen Albuminuria and Risk of Nonvertebral Fractures Arch Intern Med, July 9, 2007; 167(13): 1379 - 1385. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. L. Schiffrin, M. L. Lipman, and J. F.E. Mann Chronic Kidney Disease: Effects on the Cardiovascular System Circulation, July 3, 2007; 116(1): 85 - 97. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. Ingelsson, J. Sundstrom, L. Lind, U. Riserus, A. Larsson, S. Basu, and J. Arnlov Low-grade albuminuria and the incidence of heart failure in a community-based cohort of elderly men Eur. Heart J., July 2, 2007; 28(14): 1739 - 1745. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Nakayama, H. Metoki, H. Terawaki, T. Ohkubo, M. Kikuya, T. Sato, K. Nakayama, K. Asayama, R. Inoue, J. Hashimoto, et al. Kidney dysfunction as a risk factor for first symptomatic stroke events in a general Japanese population--the Ohasama study Nephrol. Dial. Transplant., July 1, 2007; 22(7): 1910 - 1915. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. W. B. Nanayakkara, C. van Guldener, P. M. ter Wee, P. G. Scheffer, F. J. van Ittersum, J. W. Twisk, T. Teerlink, W. van Dorp, and C. D. A. Stehouwer Effect of a Treatment Strategy Consisting of Pravastatin, Vitamin E, and Homocysteine Lowering on Carotid Intima-Media Thickness, Endothelial Function, and Renal Function in Patients With Mild to Moderate Chronic Kidney Disease: Results From the Anti-Oxidant Therapy in Chronic Renal Insufficiency (ATIC) Study Arch Intern Med, June 25, 2007; 167(12): 1262 - 1270. [Abstract] [Full Text] [PDF] |
||||
![]() |
Authors/Task Force Members:, G. Mancia, G. De Backer, A. Dominiczak, R. Cifkova, R. Fagard, G. Germano, G. Grassi, A. M. Heagerty, S. E. Kjeldsen, et al. 2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) Eur. Heart J., June 11, 2007; (2007) ehm236v1. [Full Text] [PDF] |
||||
![]() |
R. C. Ozsoy, W. A. van der Steeg, J. J. P. Kastelein, L. Arisz, and M. G. Koopman Dyslipidaemia as predictor of progressive renal failure and the impact of treatment with atorvastatin Nephrol. Dial. Transplant., June 1, 2007; 22(6): 1578 - 1586. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. K. Bello, D. de Zeeuw, M. E. Nahas, A. H. Brantsma, S. J. L. Bakker, P. E. de Jong, and R. T. Gansevoort Impact of weight change on albuminuria in the general population Nephrol. Dial. Transplant., June 1, 2007; 22(6): 1619 - 1627. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. E. Schmieder, C. Delles, A. Mimran, J. P. Fauvel, and L. M. Ruilope Impact of Telmisartan Versus Ramipril on Renal Endothelial Function in Patients With Hypertension and Type 2 Diabetes Diabetes Care, June 1, 2007; 30(6): 1351 - 1356. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. M.H. Hermans, R. Henry, J. M. Dekker, J. P. Kooman, P. J. Kostense, G. Nijpels, R. J. Heine, and C. D.A. Stehouwer Estimated Glomerular Filtration Rate and Urinary Albumin Excretion Are Independently Associated with Greater Arterial Stiffness: The Hoorn Study J. Am. Soc. Nephrol., June 1, 2007; 18(6): 1942 - 1952. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Marin, P. Rodriguez, S. Tranche, J. Redon, F. Morales-Olivas, A. Galgo, M. A. Brito, J. Mediavilla, J. V. Lozano, C. Filozof, et al. Prevalence of Abnormal Urinary Albumin Excretion Rate in Hypertensive Patients with Impaired Fasting Glucose and Its Association with Cardiovascular Disease J. Am. Soc. Nephrol., December 1, 2006; 17(12_suppl_3): S178 - S188. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. L. Carter, C. R. V. Tomson, P. E. Stevens, and E. J. Lamb Does urinary tract infection cause proteinuria or microalbuminuria? A systematic review Nephrol. Dial. Transplant., November 1, 2006; 21(11): 3031 - 3037. [Full Text] [PDF] |
||||
![]() |
W. A.K.M. Windt, W. B.A. Eijkelkamp, R. H. Henning, A. C.A. Kluppel, P. A. de Graeff, H. L. Hillege, S. Schafer, D. de Zeeuw, and R. P.E. van Dokkum Renal Damage after Myocardial Infarction Is Prevented by Renin-Angiotensin-Aldosterone-System Intervention J. Am. Soc. Nephrol., November 1, 2006; 17(11): 3059 - 3066. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. M.A. van de Wal, R. T. Gansevoort, P. van der Harst, F. Boomsma, H.W. Thijs Plokker, D. J. van Veldhuisen, P. E. de Jong, W. H. van Gilst, and A. A. Voors Predictors of Angiotensin-Converting Enzyme Inhibitor-Induced Reduction of Urinary Albumin Excretion in Nondiabetic Patients Hypertension, November 1, 2006; 48(5): 870 - 876. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. M. Ruilope and J. Segura Predictors of the Evolution of Microalbuminuria Hypertension, November 1, 2006; 48(5): 832 - 833. [Full Text] [PDF] |
||||
![]() |
R. T. Gansevoort, J. Brinkman, S. J. L. Bakker, P. E. De Jong, and D. de Zeeuw Evaluation of Measures of Urinary Albumin Excretion Am. J. Epidemiol., October 15, 2006; 164(8): 725 - 727. [Abstract] [Full Text] [PDF] |
||||
![]() |
W. Lieb, B. Mayer, J. Stritzke, A. Doering, H.-W. Hense, H. Loewel, J. Erdmann, and H. Schunkert Association of low-grade urinary albumin excretion with left ventricular hypertrophy in the general population: The MONICA/KORA Augsburg Echocardiographic Substudy Nephrol. Dial. Transplant., October 1, 2006; 21(10): 2780 - 2787. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. E. Borggreve, H. L. Hillege, B. H. R. Wolffenbuttel, P. E. de Jong, M. W. Zuurman, G. van der Steege, A. van Tol, R. P. F. Dullaart, and on behalf of the PREVEND Study Group An Increased Coronary Risk Is Paradoxically Associated with Common Cholesteryl Ester Transfer Protein Gene Variations That Relate to Higher High-Density Lipoprotein Cholesterol: A Population-Based Study J. Clin. Endocrinol. Metab., September 1, 2006; 91(9): 3382 - 3388. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. D.A. Stehouwer and Y. M. Smulders Microalbuminuria and Risk for Cardiovascular Disease: Analysis of Potential Mechanisms J. Am. Soc. Nephrol., August 1, 2006; 17(8): 2106 - 2111. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. de Zeeuw, H.-H. Parving, and R. H. Henning Microalbuminuria as an Early Marker for Cardiovascular Disease J. Am. Soc. Nephrol., August 1, 2006; 17(8): 2100 - 2105. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Douglas, P. G. O'Malley, and J. L. Jackson Meta-Analysis: The Effect of Statins on Albuminuria Ann Intern Med, July 18, 2006; 145(2): 117 - 124. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. S. Ommen, J. A. Winston, and B. Murphy Medical Risks in Living Kidney Donors: Absence of Proof Is Not Proof of Absence Clin. J. Am. Soc. Nephrol., July 1, 2006; 1(4): 885 - 895. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Tonelli, P. Jose, G. Curhan, F. Sacks, E. Braunwald, M. Pfeffer, and Cholesterol and Recurrent Events (CARE) Trial Inve Proteinuria, impaired kidney function, and adverse outcomes in people with coronary disease: analysis of a previously conducted randomised trial BMJ, June 17, 2006; 332(7555): 1426. [Abstract] [Full Text] [PDF] |
||||
![]() |
I Rietveld, A Hofman, H A P Pols, C M van Duijn, S W J Lamberts, and J A M J L Janssen An insulin-like growth factor-I gene polymorphism modifies the risk of microalbuminuria in subjects with an abnormal glucose tolerance. Eur. J. Endocrinol., May 1, 2006; 154(5): 715 - 721. [Abstract] [Full Text] [PDF] |
||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Circulation Home | Subscriptions | Archives | Feedback | Authors | Help | AHA Journals Home | Search Copyright © 2002 American Heart Association, Inc. All rights reserved. Unauthorized use prohibited. |