CLINICAL EPIDEMIOLOGY

Association of Albuminuria and Cancer Incidence

Lone Jørgensen, Ivar Heuch, Trond Jenssen and Bjarne K. Jacobsen
JASN May 2008, 19 (5) 992-998; DOI: https://doi.org/10.1681/ASN.2007060712

Abstract

Albuminuria, which is associated with noncardiovascular mortality, might be a result of altered vascular permeability caused by cytokines and other tumor cell products. The aim of this population-based, longitudinal study was to examine whether elevated albumin-to-creatinine ratio (ACR) is associated with cancer incidence. A total of 5425 participants without diabetes or previous cancer in the Tromsø Study were followed; 590 had a first diagnosis of cancer during 10.3 yr of follow-up. The ACR at baseline significantly correlated with the incidence of cancer, even after adjustment for age, gender, body mass index, physical activity, and smoking (P < 0.001). Participants with ACR in the highest quintile were 8.3- and 2.4-fold more likely to receive a diagnosis of bladder cancer and lung cancer, respectively, compared with those with ACR in the lowest quintile after similar adjustments. It is concluded that albuminuria is associated with cancer incidence in individuals without a history of diabetes, macroalbuminuria, or previous cancer and that it might confer risks of varying magnitude for different types of cancer.

Microalbuminuria was originally regarded as an early sign of nephropathy in patients with diabetes, but numerous studies have found that microalbuminuria also predicts all-cause mortality even in individuals without diabetes.1,2 Independent of diabetes, albuminuria has been related to atherosclerosis,3–7 to an increased risk for cardiovascular diseases, and to mortality caused by cardiovascular disease.8–11 It is therefore thought to reflect not only dysfunction of the glomeruli but also generalized vascular dysfunction.

Albuminuria has also been observed in individuals with different kinds of cancers, such as lung, breast, renal cell, colon/rectal, and non-Hodgkin's lymphoma.12–23 Some studies have indicated that the degree of albuminuria reflects the severity of the disease, with higher levels in patients with metastatic disease and a large tumor burden12,15,16; therefore, albuminuria has been suggested to be a nonspecific marker of malignancy reflecting a microvascular response (and altered glomerular permeability) to tumor cell products such as cytokines.12,24

In a recent longitudinal, population-based study of community-dwelling elderly individuals, markers of chronic kidney dysfunction were found to predict noncardiovascular mortality (e.g., cancer mortality).25 In another population-based study, urinary albumin excretion also predicted mortality caused by noncardiovascular disease, which could mostly be attributed to malignant neoplasms.9 Although there may be several explanations for these findings, we hypothesized that albuminuria may be related to cancer incidence. Albumin-to-creatinine ratios (ACR) were measured in 5425 individuals who did not have diabetes and were then followed for 10.3 yr with regard to a first diagnosis of cancer. To the best of our knowledge, no previous study has examined this research topic.

RESULTS

The 5425 individuals who did not have diabetes and were followed with regard to cancer incidence (2545 women, 2880 men) all had participated in the fourth Tromsø survey in 1994/1995, in which the baseline measurements, including measurements of ACR, had been performed. At that time, they were 25 to 84 yr of age and had no previous diagnosis of cancer.

The baseline characteristics of the study group according to ACR quintiles are presented in Table 1. Significant differences between groups were found with respect to age, gender, systolic BP, diastolic BP, ever use of medication for hypertension, glycated hemoglobin, serum creatinine, current use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, prevalent cardiovascular disease, smoking habits, fibrinogen, and white blood cell (WBC) count.

View this table:
Table 1.

Characteristics of the participants at baseline in 1994 by ACR quintilesa

During the 49,120 person-years of follow-up, 590 individuals had a first ever diagnosis of cancer. Among the individuals who had no cancer diagnosis during follow-up, 397 died and 45 emigrated. The mean follow-up time was 9.1 yr (range 47 d to 10.3 yr).

Figure 1 and Table 2 show that the age- and gender-adjusted risk for cancer increased with increasing levels of ACR, at least in the three upper quintiles of the range for ACR. The trend was slightly attenuated after further adjustments for smoking habits (never smokers, previous smokers/<10 cigarettes per day, previous smokers/≥10 cigarettes per day, current smokers/<10 cigarettes per day, current smokers/10 to 19 cigarettes per day, or current smokers/≥20 cigarettes per day), body mass index, and physical inactivity. ACR was also included in an analysis as a continuous variable (ACR logarithmically transformed). For a 1-SD higher value for the log-transformed ACR, the age- and gender-adjusted relative risk (RR) for cancer was 1.19 (P < 0.001) and was 1.16 (P < 0.001) after further adjustments. These results were essentially the same with adjustment for pack-years as an indicator of smoking habits.

Figure 1.
Figure 1.

Estimated age- and gender-adjusted proportion of the cohort without a diagnosis of cancer as a function of follow-up time.

View this table:
Table 2.

RR for cancer at all sites in relation to ACR quintilesa,b

The risk for cancer in individuals with microalbuminuria (ACR 2.5 to 25 mg/mmol; n = 449) was examined specifically. In these individuals, the risk relative to individuals without microalbuminuria was 1.38 (95% confidence interval 1.08 to 1.77) after multiple adjustments.

Specific analyses were performed with further adjustments for estimated GFR, systolic BP, ever use of medication for hypertension, or current use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers; however, the relationship was very similar after these adjustments. For a 1-SD higher value for the log-transformed ACR, the RR for cancer was 1.17 (P < 0.001).

To ensure that severe illness or undiagnosed cancer at the start of follow-up did not influence our results, we performed separate analyses among the individuals who were cancer-free and alive 4 yr after the baseline examination. This analysis included 5058 individuals, 357 of whom received a diagnosis of cancer during follow-up. Table 3 displays the results; it also shows the RR for cancer within the first 4 yr after the baseline measurements. Evidently, exclusion of the first 4 yr of follow-up did not have any major impact on the relationship between ACR and total cancer incidence. Figure 1 also suggests that the relationship was present throughout the follow-up period.

View this table:
Table 3.

RR for cancer at all sites in relation to ACR at different periods of follow-upa

Albuminuria is a result of endothelial dysfunction in the urinary system, and increased ACR may therefore be specifically related to cancers of the kidney and the bladder; however, even after the exclusion of kidney and bladder cancer, the RR for cancer comparing the highest and the lowest quintiles was 1.41 (95% confidence interval 1.07 to 1.84; P = 0.004 for trend) after multiple adjustments.

Table 4 displays the distribution of the most frequent cancers (≥35 cases) that occurred during follow-up (colon/rectal, breast, lung, prostate, and bladder) and the RR for cancer of these sites in relation to ACR level. In addition, results for renal cancer are included. ACR was significantly associated with bladder and lung cancer; tended to be associated with renal cancer; but showed no relationship with colon/rectal, breast, or prostate cancer.

View this table:
Table 4.

RR for selected cancer sites in relation to ACR quintiles and per 1-SD increase in log (ACR)a

Fibrinogen and WBC count were measured in addition to ACR in 5184 individuals. ACR (log-transformed) correlated significantly (P < 0.001) with these markers of inflammation (r = 0.14 and r = 0.06, respectively). Fibrinogen and WBC count correlated with each other (r = 0.21, P < 0.001). The relationship between ACR and cancer risk was very similar with and without the inclusion of fibrinogen and WBC count in the model. For a 1-SD higher value for the log-transformed ACR, the RR for cancer was 1.16 (P < 0.001), after adjustments for age, gender, body mass index, physical inactivity, and smoking habits, and 1.15 (P < 0.001), after further adjustments for fibrinogen and WBC count. In the 5000 individuals with measurements of glycated hemoglobin available, the relationship between ACR and cancer risk was similar after adjustment for glycated hemoglobin (data not shown). Exclusion of 342 individuals with glycated hemoglobin levels ≥6.0% hardly influenced the results (RR 1.17 and 1.18 for each 1-SD increase in the log-transformed ACR, before and after the exclusion).

DISCUSSION

In this population-based study of individuals without diabetes and macroalbuminuria, increasing levels of ACR were associated with an increased incidence of cancer, especially bladder and renal cancer. To the best of our knowledge, no previous study has examined the incidence of cancer in relation to ACR levels in individuals without diabetes of a general population; however, the associations between ACR and cancer risk seem to be in line with the results of studies of individuals on dialysis, who have higher cancer rates than the general population.26,27 Moreover, cystatin C, a marker of chronic kidney dysfunction, has been related to noncardiovascular mortality, including cancer mortality, in community-dwelling elderly individuals. Individuals with prevalent cancer were not excluded, however, in these analyses.25 Two other population-based studies, one of the Norfolk population (United Kingdom)28 and one of the inhabitants of Groningen (Netherlands),9 examined albuminuria as a risk factor for noncardiovascular mortality. The results were conflicting with regard to mortality. The study from Groningen found that death as a result of malignant neoplasms could explain most of the increased noncardiovascular mortality risk, whereas the Norfolk study found no association with cancer death. In both studies, only one single spot-urine sample was analyzed, which leads to larger random errors in the assessment of albuminuria.29 Moreover, the Norfolk study measured albumin concentrations from frozen urine samples, which underestimates the real values and therefore may limit the ability to predict mortality.30

At present, we have no complete explanation for why higher levels of ACR are associated with the risk for cancer. ACR, which is related to renal and endothelial dysfunction, is frequently increased with inflammation,31,32 and inflammation has been hypothesized to increase the risk for cancer.33 Inflammatory markers, such as WBC count and fibrinogen, have been found to be associated with an increased risk for cancer mortality in individuals without cancer at baseline.34–36 Because inflammatory markers were positively related to the ACR level of our participants (Table 1), inflammation might have been a potential explanation for the association with cancer incidence; however, ACR predicted cancer incidence independent of WBC count and fibrinogen.

Albuminuria has been observed in individuals after the detection of various types of cancers.12–23 The underlying mechanisms are not known, but albuminuria has been regarded as a paraneoplastic phenomenon (clinical syndromes involving nonmetastatic systemic effects that accompany malignant disease) and a reflection of an inflammatory process. Theoretically, increased glomerular permeability and, thus, albuminuria could be linked to the presence of neoplastic cells through elevated levels of cytokines. A study of patients with non-Hodgkin's lymphoma showed that urinary albumin excretion was strongly associated with proinflammatory cytokines and suggested that lymphoma cells secrete cytokines that modulate renal leakage of albumin.14 In animal models, TNF-α, a cytokine involved in systemic inflammation, has been shown to increase glomerular albumin permeability.37 In patients with inflammatory bowel disease, TNF-α seems to be important in the pathogenesis of microalbuminuria, possibly through TNF-induced damage to the glomerular basement membrane.38 Conversely, albuminuria could also be mediated through decreased tubular reabsorption of filtered albumin.39 Indeed, TGF-β may inhibit the megalin-cubilin–mediated endocytosis of albumin in tubular cells in vitro.40 There is a need for other studies to examine the relationship between ACR and cancer incidence, and if the results are reproduced, then studies examining potential underlying mechanisms are warranted.

In our study, the strength of the associations between ACR and cancer risk persisted largely unchanged when the analysis was restricted to cancers that appeared ≥4 yr after the baseline examination. This observation reduces the likelihood that the relationship between ACR and cancer incidence was mainly due to early, undiagnosed disease; however, we still cannot totally rule out the possibility that the ACR levels may have been influenced by preclinical disease, especially in case of cancers with a long latency period (≥4 yr).

This study indicated that ACR predicts cancer at specific sites. There was a statistically significant relationship with bladder and lung cancer but no relationship with prostate cancer. Smoking was clearly a possible confounder, because it is a widely known predictor of the same cancer sites as those predicted by ACR and is related to ACR as well. Nevertheless, ACR was associated with bladder and lung cancer independent of smoking.

Several studies found that diabetes is associated with a variety of cancers, and in a recent study showing that diabetes predicted cancer mortality, the authors suggested that insulin resistance and hyperinsulinemia may play a role in the pathogenesis of cancer.41 Because ACR is associated with diabetes, this could provide a possible link between ACR and cancer. In our study, however, we excluded individuals with diabetes, yet many individuals with type 2 diabetes are not aware that they have the disease. It is therefore reassuring that adjustments for glycated hemoglobin or the exclusion of individuals with glycated hemoglobin ≥6.0% (and thus possible cases of diabetes) did not influence our findings.

This study has several strengths. It is a longitudinal, population-based study comprising a large group of individuals with a high attendance rate. Urine samples from the first morning urine from three consecutive days were used to assess albuminuria. A strict definition of albuminuria was used, in that urine samples from all patients were cultured, and patients with bacteriuria were excluded from the analysis. A major limitation of this study is the small number of site-specific cancer cases, and to confirm or refute our results, studies with more statistical power are warranted.

The number of cases in our study was approximately 15% lower than expected on the basis of the national data; however, because individuals with diabetes and macroalbuminuria were excluded and because severely ill individuals are usually underrepresented in population studies, a lower cancer incidence was not unexpected. Although the attendance rate in our study was high (76% of the eligible population), selection bias may have been present; however, if this selection bias should invalidate our findings, then the incidence of cancer would have to be very strongly associated with lower levels of ACR among the nonparticipants. We believe that this is unlikely and that it is more plausible that nonparticipation may have weakened the true relationship between ACR and cancer incidence. Information about cancer incidence was collected in November 2005. It is thus possible that a few cancer cases diagnosed in 2004 had not yet been recorded in the registry, but the likelihood of delayed notification of cancer is regarded to be unrelated to the exposure variable considered.

We conclude that there is a relationship between increasing ACR levels and cancer incidence in individuals without diabetes or macroalbuminuria. The relationship seems to be site specific, but larger samples are needed to examine this topic further. Moreover, studies examining potential underlying mechanisms are required.

CONCISE METHODS

The Tromsø Study is a population-based, longitudinal study with repeated health surveys of inhabitants in the municipality of Tromsø, Norway. Originally a cardiovascular study, it now focuses on several chronic and lifestyle-related conditions such as atherosclerosis and diabetes. The regional ethical committee approved the study, and the participants have given informed consent. At the fourth survey in 1994/1995, all inhabitants aged 55 to 74 yr and 5 to 10% random samples of the other 5-yr birth cohorts older than 24 yr were invited to participate in the survey. In the age groups 25 to 54, 55 to 74, and 75 to 84 yr, 1751, 7158, and 148 individuals were eligible for measurement of albuminuria and 1205, 5617, and 80, respectively, participated (76% of the eligible population).

Among the 6902 individuals who attended the examination, 110 either withdrew their data or had missing measurements of the ACR. We excluded 239 individuals who reported diabetes and/or use of medication for diabetes, 851 with bacteriuria or hematuria on any day when urine samples were collected or macroalbuminuria (ACR >25 mg/mmol), and 277 who had a diagnosis of cancer before this survey took place. Thus, 5425 individuals were included in these analyses.

Participants were asked which medication they had used during the past week. Information about smoking habits (never smokers; previous smokers; current smokers; and, for previous and current smokers, number of cigarettes smoked per day), drinking habits (alcohol users versus abstainers), prevalent diabetes, cardiovascular disease (angina pectoris, previous myocardial infarction, stroke), treatment for hypertension, and physical activity was collected from self-administered questionnaires.42 We categorized the individuals into six groups according to their smoking habits: Never smokers, previous smokers/<10 cigarettes per day, previous smokers/≥10 cigarettes per day, current smokers/<10 cigarettes per day, current smokers/10 to 19 cigarettes per day, or current smokers/≥20 cigarettes per day.

Urine samples from the first morning urine from three consecutive days were used to assess microalbuminuria. Albumin and creatinine were measured by turbidimetry on a Cobas Mira S with kits from ABX Diagnostics (Parc Euromedecine, Montpellier, France). The ACR (mg albumin/mmol creatinine) was computed, and the mean of the three ratios was used in the analyses. The between-assay coefficient of variation for all determinations of albumin, creatinine, and the ACR was <4% throughout the range of concentrations. Serum creatinine was measured by the HiCo Creatinine Jaffé method with a kinetic colorimetric assay on automated clinical chemistry analyzers (Boehringer-Mannheim, Mannheim, Germany), and estimated GFR was calculated using the abbreviated (four-variable) Modification of Diet in Renal Disease equation.43 Measurements of height, body weight, BP, glycated hemoglobin, fibrinogen, and counts of WBC were done as described previously.44

Case Identification and Follow-up Time

Information on death and emigration was gathered by linkage to Statistics Norway (Oslo, Norway). Individuals who received a diagnosis of cancer during follow-up were identified by linkage to the Cancer Registry of Norway. In Norway, registration of cancer is mandatory by law, and the registration is considered almost complete (97.6%, for solid tumors). The unique national 11-digit identification number of every Norwegian citizen ensured linkage of data from the Tromsø Study with the Cancer Registry. Thus, no person in Norway is lost to follow-up. All cancer diagnoses are thoroughly checked by the Cancer Registry of Norway according to a standard procedure. As noted previously, 277 individuals with a diagnosis of cancer at baseline were excluded from all analyses.

Follow-up time was assigned from the date of the baseline examination to date of the first diagnosis of cancer (n = 590) or to date of censoring (death [n = 397]; emigration [n = 45]; or end of follow-up [n = 4393], December 31, 2004). In the analyses for selected cancer sites (colon and rectum, lung, breast, prostate, kidney, bladder), follow-up time was assigned from the date of the baseline examination to the date of that specific cancer diagnosis or to date of censoring (death; emigration; other cancers; or end of follow-up, December 31, 2004).

Statistical Analyses

Differences between the baseline characteristics of the participants were tested using general linear models, and trends over the groups were tested using multiple regression analyses. The participants were divided into groups according to quintiles of ACR.

We estimated the RR for cancer among individuals at different ACR levels by use of Cox regression analysis. When ACR was included in an analysis as a continuous variable, the value was logarithmically transformed [log (ACR + 0.1)]. Adjustments were done for age, gender, body mass index, smoking, and physical inactivity. Additional adjustments were done for fibrinogen and WBC count in a separate analysis, for glycated hemoglobin in another, and for other relevant factors in a third.

The Cox analysis also generated curves, adjusted for age and gender and taking censoring into account, describing the proportion of the cohort that had not received a diagnosis of cancer as a function of follow-up time. Two-sided P < 0.05 was considered statistically significant. The data were analyzed using SPSS 14.0 for Windows (SPSS, Chicago, IL).

DISCLOSURES

None.

Acknowledgments

The study was financed through the Norwegian Research Council.

Footnotes

  • Published online ahead of print. Publication date available at www.jasn.org.

REFERENCES

  1. ↵
    Karalliedde J, Viberti G: Microalbuminuria and cardiovascular risk. Am J Hypertens 17 : 986 –993, 2004
    OpenUrlCrossRefPubMed
  2. ↵
    Sarnak MJ, Levey AS, Schoolwerth AC, Coresh J, Culleton B, Hamm LL, McCullough PA, Kasiske BL, Kelepouris E, Klag MJ, Parfrey P, Pfeffer M, Raij L, Spinosa DJ, Wilson PW: Kidney disease as a risk factor for development of cardiovascular disease: A statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. Circulation 108 : 2154 –2169, 2003
    OpenUrlFREE Full Text
  3. ↵
    Bigazzi R, Bianchi S, Nenci R, Baldari D, Baldari G, Campese VM: Increased thickness of the carotid artery in patients with essential hypertension and microalbuminuria. J Hum Hypertens 9 : 827 –833, 1995
    OpenUrlPubMed
  4. Furtner M, Kiechl S, Mair A, Seppi K, Weger S, Oberhollenzer F, Poewe W, Willeit J: Urinary albumin excretion is independently associated with carotid and femoral artery atherosclerosis in the general population. Eur Heart J 26 : 279 –287, 2005
    OpenUrlCrossRefPubMed
  5. Jørgensen L, Jenssen T, Johnsen SH, Mathiesen EB, Heuch I, Joakimsen O, Fosse E, Jacobsen BK: Albuminuria as risk factor for initiation and progression of carotid atherosclerosis in non-diabetic persons: The Tromsø Study. Eur Heart J 28 : 363 –369, 2007
    OpenUrlCrossRefPubMed
  6. Leoncini G, Sacchi G, Ravera M, Viazzi F, Ratto E, Vettoretti S, Parodi D, Bezante GP, Del Sette M, Deferrari G, Pontremoli R: Microalbuminuria is an integrated marker of subclinical organ damage in primary hypertension. J Hum Hypertens 16 : 399 –404, 2002
    OpenUrlCrossRefPubMed
  7. ↵
    Mykkanen L, Zaccaro DJ, O'Leary DH, Howard G, Robbins DC, Haffner SM: Microalbuminuria and carotid artery intima-media thickness in nondiabetic and NIDDM subjects. The Insulin Resistance Atherosclerosis Study (IRAS). Stroke 28 : 1710 –1716, 1997
    OpenUrlAbstract/FREE Full Text
  8. ↵
    Gerstein HC, Mann JF, Yi Q, Zinman B, Dinneen SF, Hoogwerf B, Halle JP, Young J, Rashkow A, Joyce C, Nawaz S, Yusuf S: Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals. JAMA 286 : 421 –426, 2001
    OpenUrlCrossRefPubMed
  9. ↵
    Hillege HL, Fidler V, Diercks GF, van Gilst WH, de Zeeuw D, van Veldhuisen DJ, Gans RO, Janssen WM, Grobbee DE, de Jong PE: Urinary albumin excretion predicts cardiovascular and noncardiovascular mortality in general population. Circulation 106 : 1777 –1782, 2002
    OpenUrlAbstract/FREE Full Text
  10. Klausen K, Borch-Johnsen K, Feldt-Rasmussen B, Jensen G, Clausen P, Scharling H, Appleyard M, Jensen JS: Very low levels of microalbuminuria are associated with increased risk of coronary heart disease and death independently of renal function, hypertension, and diabetes. Circulation 110 : 32 –35, 2004
    OpenUrlAbstract/FREE Full Text
  11. ↵
    Romundstad S, Holmen J, Kvenild K, Hallan H, Ellekjær H: Microalbuminuria and all-cause mortality in 2,089 apparently healthy individuals: A 4.4-year follow-up study. The Nord-Trøndelag Health Study (HUNT), Norway. Am J Kidney Dis 42 : 466 –473, 2003
    OpenUrlCrossRefPubMed
  12. ↵
    Pedersen LM, Milman N: Microalbuminuria in patients with lung cancer. Eur J Cancer 34 : 76 –80, 1998
    OpenUrlCrossRefPubMed
  13. Pedersen LM, Johnsen HE: Microalbuminuria is associated with impaired glomerular permselectivity in lymphoma patients. Scand J Clin Lab Invest 65 : 477 –484, 2005
    OpenUrlCrossRefPubMed
  14. ↵
    Pedersen LM, Sørensen PG: Mediators of inflammation correlate with microalbuminuria in patients with non-Hodgkin's lymphoma. Br J Haematol 121 : 275 –279, 2003
    OpenUrlCrossRefPubMed
  15. ↵
    Pedersen LM, Milman N: Prevalence and prognostic significance of proteinuria in patients with lung cancer. Acta Oncol 35 : 691 –695, 1996
    OpenUrlPubMed
  16. ↵
    Pedersen LM, Sørensen PG: Increased urinary albumin excretion rate in breast cancer patients. Acta Oncol 39 : 145 –149, 2000
    OpenUrlCrossRefPubMed
  17. Pedersen LM, Sørensen PG: Clinical significance of urinary albumin excretion in patients with non-Hodgkin's lymphoma. Br J Haematol 107 : 889 –891, 1999
    OpenUrlCrossRefPubMed
  18. Pedersen LM, Sørensen PG: Urinary albumin excretion is a predictor of response to treatment and disease progression in low-grade non-Hodgkin's lymphoma. Leuk Lymphoma 45 : 547 –551, 2004
    OpenUrlCrossRefPubMed
  19. Sawyer N, Wadsworth J, Wijnen M, Gabriel R: Prevalence, concentration, and prognostic importance of proteinuria in patients with malignancies. BMJ (Clin Res Ed) 296 : 1295 –1298, 1988
    OpenUrlAbstract/FREE Full Text
  20. Roumen RM, Wijnen MH: Proteinuria: A frequent paraneoplastic phenomenon in colorectal cancer? Eur J Cancer 34 : 206 –207, 1998
    OpenUrlCrossRefPubMed
  21. Puolijoki H, Mustonen J, Pettersson E, Pasternack A, Lahdensuo A: Proteinuria and haematuria are frequently present in patients with lung cancer. Nephrol Dial Transplant 4 : 947 –950, 1989
    OpenUrlPubMed
  22. Georgiannos SN, Weston PM, Goode AW: Correlation between albuminuria and positively charged amino acids in gastrointestinal cancer. Int Surg 80 : 49 –52, 1995
    OpenUrlPubMed
  23. ↵
    Vaglio A, Buzio L, Cravedi P, Pavone L, Garini G, Buzio C: Prognostic significance of albuminuria in patients with renal cell cancer. J Urol 170 : 1135 –1137, 2003
    OpenUrlCrossRefPubMed
  24. ↵
    Pedersen LM, Terslev L, Sørensen PG, Stokholm KH: Urinary albumin excretion and transcapillary escape rate of albumin in malignancies. Med Oncol 17 : 117 –122, 2000
    OpenUrlPubMed
  25. ↵
    Fried LF, Katz R, Sarnak MJ, Shlipak MG, Chaves PH, Jenny NS, Stehman-Breen C, Gillen D, Bleyer AJ, Hirsch C, Siscovick D, Newman AB: Kidney function as a predictor of noncardiovascular mortality. J Am Soc Nephrol 16 : 3728 –3735, 2005
    OpenUrlAbstract/FREE Full Text
  26. ↵
    Iseki K, Osawa A, Fukiyama K: Evidence for increased cancer deaths in chronic dialysis patients. Am J Kidney Dis 22 : 308 –313, 1993
    OpenUrlCrossRefPubMed
  27. ↵
    Birkeland SA, Løkkegaard H, Storm HH: Cancer risk in patients on dialysis and after renal transplantation. Lancet 355 : 1886 –1887, 2000
    OpenUrlCrossRefPubMed
  28. ↵
    Yuyun MF, Khaw KT, Luben R, Welch A, Bingham S, Day NE, Wareham NJ: Microalbuminuria independently predicts all-cause and cardiovascular mortality in a British population: The European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk) population study. Int J Epidemiol 33 : 189 –198, 2004
    OpenUrlCrossRefPubMed
  29. ↵
    Mogensen CE, Vestbo E, Poulsen PL, Christiansen C, Damsgaard EM, Eiskjaer H, Frøland A, Hansen KW, Nielsen S, Pedersen MM: Microalbuminuria and potential confounders: A review and some observations on variability of urinary albumin excretion. Diabetes Care 18 : 572 –581, 1995
    OpenUrlFREE Full Text
  30. ↵
    Brinkman JW, de Zeeuw D, Gansevoort RT, Duker JJ, Kema IP, de Jong PE, Bakker SJ: Prolonged frozen storage of urine reduces the value of albuminuria for mortality prediction. Clin Chem 53 : 153 –154, 2007
    OpenUrlFREE Full Text
  31. ↵
    Jager A, van H, V, Kostense PJ, Emeis JJ, Nijpels G, Dekker JM, Heine RJ, Bouter LM, Stehouwer CD: C-reactive protein and soluble vascular cell adhesion molecule-1 are associated with elevated urinary albumin excretion but do not explain its link with cardiovascular risk. Arterioscler Thromb Vasc Biol 22 : 593 –598, 2002
    OpenUrlAbstract/FREE Full Text
  32. ↵
    Stehouwer CD, Gall MA, Twisk JW, Knudsen E, Emeis JJ, Parving HH: Increased urinary albumin excretion, endothelial dysfunction, and chronic low-grade inflammation in type 2 diabetes: Progressive, interrelated, and independently associated with risk of death. Diabetes 51 : 1157 –1165, 2002
    OpenUrlAbstract/FREE Full Text
  33. ↵
    Coussens LM, Werb Z: Inflammation and cancer. Nature 420 : 860 –867, 2002
    OpenUrlCrossRefPubMed
  34. ↵
    Grimm RH Jr, Neaton JD, Ludwig W: Prognostic importance of the white blood cell count for coronary, cancer, and all-cause mortality. JAMA 254 : 1932 –1937, 1985
    OpenUrlCrossRefPubMed
  35. Friedman GD, Fireman BH: The leukocyte count and cancer mortality. Am J Epidemiol 133 : 376 –380, 1991
    OpenUrlPubMed
  36. ↵
    Yano K, Grove JS, Chen R, Rodriguez BL, Curb JD, Tracy RP: Plasma fibrinogen as a predictor of total and cause-specific mortality in elderly Japanese-American men. Arterioscler Thromb Vasc Biol 21 : 1065 –1070, 2001
    OpenUrlAbstract/FREE Full Text
  37. ↵
    McCarthy ET, Sharma R, Sharma M, Li JZ, Ge XL, Dileepan KN, Savin VJ: TNF-alpha increases albumin permeability of isolated rat glomeruli through the generation of superoxide. J Am Soc Nephrol 9 : 433 –438, 1998
    OpenUrlAbstract
  38. ↵
    Mahmud N, O'Connell MA, Stinson J, Goggins MG, Weir DG, Kelleher D: Tumour necrosis factor-alpha and microalbuminuria in patients with inflammatory bowel disease. Eur J Gastroenterol Hepatol 7 : 215 –219, 1995
    OpenUrlPubMed
  39. ↵
    Pollock CA, Poronnik P: Albumin transport and processing by the proximal tubule: physiology and pathophysiology. Curr Opin Nephrol Hypertens 16 : 359 –364, 2007
    OpenUrlCrossRefPubMed
  40. ↵
    Gekle M, Knaus P, Nielsen R, Mildenberger S, Freudinger R, Wohlfarth V, Sauvant C, Christensen EI: Transforming growth factor-beta1 reduces megalin- and cubilin-mediated endocytosis of albumin in proximal-tubule-derived opossum kidney cells. J Physiol 552 : 471 –481, 2003
    OpenUrlCrossRefPubMed
  41. ↵
    Coughlin SS, Calle EE, Teras LR, Petrelli J, Thun MJ: Diabetes mellitus as a predictor of cancer mortality in a large cohort of US adults. Am J Epidemiol 159 : 1160 –1167, 2004
    OpenUrlCrossRefPubMed
  42. ↵
    Jørgensen L, Singh K, Berntsen GK, Jacobsen BK: A population-based study of the prevalence of abdominal aortic aneurysms in relation to bone mineral density. The Tromsø study. Am J Epidemiol 159 : 945 –949, 2005
    OpenUrlCrossRef
  43. ↵
    Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D: A more accurate method to estimate glomerular filtration rate from serum creatinine: A new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 130 : 461 –470, 1999
    OpenUrlCrossRefPubMed
  44. ↵
    Johnsen SH, Fosse E, Joakimsen O, Mathiesen EB, Stensland-Bugge E, Njølstad I, Arnesen E: Monocyte count is a predictor of novel plaque formation: A 7-year follow-up study of 2610 persons without carotid plaque at baseline the Tromsø Study. Stroke 36 : 715 –719, 2005
    OpenUrlAbstract/FREE Full Text
Back to top

In this issue

View Selected Citations (0)
Print
Download PDF
Email Article
Citation Tools
Request Permissions
Association of Albuminuria and Cancer Incidence
Lone Jørgensen, Ivar Heuch, Trond Jenssen, Bjarne K. Jacobsen
JASN May 2008, 19 (5) 992-998; DOI: 10.1681/ASN.2007060712
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo

Jump to section