Towards a rational screening strategy for albuminuria: results from the unreferred renal insufficiency trial

Arjan van der Tol, Wim Van Biesen, Francis Verbeke, Guy De Groote, Frans Vermeiren, Kathleen Eeckhaut, Raymond Vanholder, Arjan van der Tol, Wim Van Biesen, Francis Verbeke, Guy De Groote, Frans Vermeiren, Kathleen Eeckhaut, Raymond Vanholder

Abstract

Background: There remains debate about the screening strategies for albuminuria. This study evaluated whether a screening strategy in an apparently healthy population based on basic clinical and biochemical parameters could be more effective than a strategy where screening for albuminuria is performed unselectively.

Methodology/principal findings: The Unreferred Renal Insufficiency (URI) Study is a cross-sectional study on the prevalence of metabolic risk factors in Belgian workers, volunteering to be screened during a routine yearly occupational check-up. Subjects (n = 295) with treated hypertension, known diabetes, treated dyslipidaemia, cardiovascular and renal disease were excluded. Among 1,191 apparently healthy subjects, 23% had unknown hypertension, 13% had impaired glucose tolerance, 15.4% had normoalbuminuria, 4.2% had microalbuminuria and 0.4% had macroalbuminuria. Subjects with resting heart rate ≥85 bpm, plasma glucose ≥5.6 mmol/L and blood pressure ≥140/90 mmHg were associated with albuminuria of any degree. A strategy where only subjects with at least one of these risk factors (n = 431) were screened for albuminuria, would identify all subjects with macroalbuminuria (5/5), 64% of those with microalbuminuria (32/50), and less than half of those with normoalbuminuria (81/183). An alternative strategy whereby subjects were first screened for presence of albuminuria, and additional cardiovascular risk factors were only measured in subjects positive for albuminuria (n = 238), would identify only 27% (118/431) of the subjects with additional and potentially modifiable cardiovascular risk factors. On the other hand, half of the subjects in this study with albuminuria (120/238, of which 102 had normoalbuminuria), had no additional cardiovascular risk factor at all.

Conclusions: Screening an apparently healthy population directly for albuminuria will result in a high percentage of false positives, mostly measured in the normal range. Screening for microalbuminuria and macroalbuminuria based on presence of additional, potentially modifiable risk factors appears to be more beneficial. Trial registration 2006 NCT00365911.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. The prevalence of albuminuria in…
Figure 1. The prevalence of albuminuria in subjects with at least one vs. none risk factors.

References

    1. Kramer A, Stel V, Zoccali C, Heaf J, Ansell D, et al. An update on renal replacement therapy in Europe: ERA-EDTA Registry data from 1997 to 2006. Nephrol Dial Transplant. 2009;24:3557–3566.
    1. ERA-EDTA Registry: ERA-EDTA Registry 2007 Annual report. Academic Medical Center, Amsterdam, the Netherlands, june 2009.
    1. ERA-EDTA Registry: ERA-EDTA Registry 1998 Annual Report. Academic Medical Center, Amsterdam, The Netherlands, May 2003.
    1. The concise 2009 Annual Data Report Atlas of Chronic Kidney Disease & End-Stage Renal Disease in the United States.
    1. Bigazzi R, Bianchi S, Baldari D, Campese VM. Microalbuminuria predicts cardiovascular events and renal insufficiency in patients with essential hypertension. Journal of Hypertension. 1998;16:1325–1333.
    1. Mogensen CE. Microalbuminuria, blood pressure and diabetic renal disease: origin and development of ideas. Diabetologia. 1999;42:263–285.
    1. Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Heart Outcomes Prevention Evaluation Study Investigators. Lancet. 2000;355:253–259.
    1. Keane WF, Zhang Z, Lyle PA, Cooper ME, de Zeeuw D, et al. Risk scores for predicting outcomes in patients with type 2 diabetes and nephropathy: the RENAAL study. Clin J Am Soc Nephrol. 2006;1:761–767.
    1. van der Velde M, Halbesma N, de Charro FT, Bakker SJL, de Zeeuw D, et al. Screening for Albuminuria Identifies Individuals at Increased Renal Risk. Journal of the American Society of Nephrology. 2009;20:852–862.
    1. Hallan SI, Dahl K, Oien CM, Grootendorst DC, Aasberg A, et al. Screening strategies for chronic kidney disease in the general population: follow-up of cross sectional health survey. British Medical Journal. 2006;333:1047–1050.
    1. Fried L. Are we ready to screen the general population for microalbuminuria? J Am Soc Nephrol. 2009;20:686–688.
    1. Romundstad S, Holmen J, Kvenild K, Aakervik O, Hallan H. Clinical relevance of microalbuminuria screening in self-reported non-diabetic/non-hypertensive persons identified in a large health screening - The Nord-Trondelag Health Study (HUNT), Norway. Clinical Nephrology. 2003;59:241–251.
    1. Wilson JM, Jungner YG. [Principles and practice of mass screening for disease]. Bol Oficina Sanit Panam. 1968;65:281–393.
    1. WHO STEPS Surveillance, part 3. Training and Practical Guides, section 3: guide to physical Measurements.
    1. Warram JH, Gearin G, Laffel L, Krolewski AS. Effect of duration of type I diabetes on the prevalence of stages of diabetic nephropathy defined by urinary albumin/creatinine ratio. Journal of the American Society of Nephrology. 1996;7:930–937.
    1. Levey AS, Coresh J, Greene T, Stevens LA, Zhang YL, et al. Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med. 2006;145:247–254.
    1. Genuth S, Alberti KGMM, Bennett P, Buse J, DeFronzo R, et al. Follow-up report on the diagnosis of diabetes mellitus. Diabetes Care. 2003;26:3160–3167.
    1. Hallan SI, Stevens P. Screening for chronic kidney disease: which strategy? J Nephrol. 2010;23:147–155.
    1. Nielen MM, Schellevis FG, Verheij RA. The usefulness of a free self-test for screening albuminuria in the general population: a cross-sectional survey. BMC Public Health. 2009;9:381.
    1. Klausen KP, Scharling H, Jensen JS. Very low level of microalbuminuria is associated with increased risk of death in subjects with cardiovascular or cerebrovascular diseases. Journal of Internal Medicine. 2006;260:231–237.
    1. Klausen K, Borch-Johnsen K, Feldt-Rasmussen B, Jensen G, Clausen P, et al. Very low levels of microalbuminuria are associated with increased risk of coronary heart disease and death independently of renal function, hypertension, and diabetes. Circulation. 2004;110:32–35.
    1. Hillege HL, Fidler V, Diercks GFH, van Gilst WH, de Zeeuw D, et al. Urinary albumin excretion predicts cardiovascular and noncardiovascular mortality in general population. Circulation. 2002;106:1777–1782.
    1. Hillege HL, Janssen WMT, Bak AAA, Diercks GFH, Grobbee DE, et al. Microalbuminuria is common, also in a nondiabetic, nonhypertensive population, and an independent indicator of cardiovascular risk factors and cardiovascular morbidity. Journal of Internal Medicine. 2001;249:519–526.
    1. Arnlov J, Evans JC, Meigs JB, Wang TJ, Fox CS, et al. Low-grade albuminuria and incidence of cardiovascular disease events in nonhypertensive and nondiabetic individuals: the Framingham Heart Study. Circulation. 2005;112:969–975.
    1. Metcalf PA, Scragg RK, Dryson E. Associations between body morphology and microalbuminuria in healthy middle-aged European, Maori and Pacific Island New Zealanders. Int J Obes Relat Metab Disord. 1997;21:203–210.
    1. Klausen KP, Parving HH, Scharling H, Jensen JS. The association between metabolic syndrome, microalbuminuria and impaired renal function in the general population: impact on cardiovascular disease and mortality. Journal of Internal Medicine. 2007;262:470–478.
    1. Heathcote KL, Wilson MP, Quest DW, Wilson TW. Prevalence and duration of exercise induced albuminuria in healthy people. Clin Invest Med. 2009;32:E261–265.
    1. Weir MR, Bakris GL. Should Microalbuminuria Ever Be Considered as a Renal Endpoint in Any Clinical Trial? American Journal of Nephrology. 2010;31:469–470.
    1. Turnbull F. Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomised trials. Lancet. 2003;362:1527–1535.
    1. Ruilope LM, Salvetti A, Jamerson K, Hansson L, Warnold I, et al. Renal function and intensive lowering of blood pressure in hypertensive participants of the hypertension optimal treatment (HOT) study. Journal of the American Society of Nephrology: JASN. 2001;12:218–225.
    1. Walker WG, Neaton JD, Cutler JA, Neuwirth R, Cohen JD. Renal function change in hypertensive members of the Multiple Risk Factor Intervention Trial. Racial and treatment effects. The MRFIT Research Group. JAMA: the journal of the American Medical Association. 1992;268:3085–3091.
    1. Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008;359:1577–1589.
    1. Bohm M, Reil JC, Danchin N, Thoenes M, Bramlage P, et al. Association of heart rate with microalbuminuria in cardiovascular risk patients: data from I-SEARCH. Journal of Hypertension. 2008;26:18–25.
    1. Inoue T, Iseki K, Iseki C, Ohya Y, Kinjo K, et al. Heart rate as a risk factor for developing chronic kidney disease: longitudinal analysis of a screened cohort. Clin Exp Nephrol. 2009;13:487–493.
    1. Facchini FS, Stoohs RA, Reaven GM. Enhanced sympathetic nervous system activity. The linchpin between insulin resistance, hyperinsulinemia, and heart rate. Am J Hypertens. 1996;9:1013–1017.
    1. Gillman MW, Kannel WB, Belanger A, D'Agostino RB. Influence of heart rate on mortality among persons with hypertension: the Framingham Study. Am Heart J. 1993;125:1148–1154.
    1. Palatini P. Elevated heart rate: a “new” cardiovascular risk factor? Progress in cardiovascular diseases. 2009;52:1–5.
    1. Jouven X, Empana JP, Escolano S, Buyck JF, Tafflet M, et al. Relation of heart rate at rest and long-term (>20 years) death rate in initially healthy middle-aged men. The American journal of cardiology. 2009;103:279–283.
    1. Ritz E, Ogata H, Orth SR. Smoking: a factor promoting onset and progression of diabetic nephropathy. Diabetes Metab. 2000;26(Suppl 4):54–63.
    1. Bakris GL, Fonseca V, Katholi RE, McGill JB, Messerli FH, et al. Metabolic effects of carvedilol vs metoprolol in patients with type 2 diabetes mellitus and hypertension: a randomized controlled trial. JAMA. 2004;292:2227–2236.
    1. K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification. American Journal of Kidney Diseases. 2002;39:s1–s266.
    1. Stehouwer CD, Fischer HR, Hackeng WH, den Ottolander GJ. Identifying patients with incipient diabetic nephropathy. Should 24-hour urine collections be used? Arch Intern Med. 1990;150:373–375.
    1. Witte EC, Lambers Heerspink HJ, de Zeeuw D, Bakker SJ, de Jong PE, et al. First morning voids are more reliable than spot urine samples to assess microalbuminuria. J Am Soc Nephrol. 2009;20:436–443.

Source: PubMed

3
Abonnere