Elsevier

Journal of Diabetes and its Complications

Volume 28, Issue 6, November–December 2014, Pages 779-784
Journal of Diabetes and its Complications

Systolic blood pressure as a predictor of incident albuminuria and rapid renal function decline in type 2 diabetic patients

https://doi.org/10.1016/j.jdiacomp.2014.08.002Get rights and content

Abstract

Aims

Albuminuria and a reduced estimated glomerular filtration rate (eGFR) are known risk factors of poor cardiovascular outcomes in diabetic patients. We here aimed to investigate the determinants of incident albuminuria and rapid progression of renal dysfunction in patients with type 2 diabetes.

Methods

Type 2 diabetic outpatients (n = 215) with a mean baseline eGFR of 87 ± 20 mL min 1 1.73 m 2 were followed for 12 months. Urinary albuminuria was defined according to the urine albumin-to-creatinine ratio (UACR).

Results

Among 132 patients with normoalbuminuria at baseline, 20 (15.2%) progressed to a more advanced stage of albuminuria within 1 year, and 20.5% of the 215 patients experienced a rapid decline in eGFR (eGFR reduction > 5 mL min 1 1.73 m 2 year 1). After adjusting for potential confounders, both baseline UACR and systolic blood pressure (SBP) were found to be significant independent factors for incident albuminuria and a rapid decline of eGFR in separate models. Using receiver operating characteristic curves, systolic blood pressures of 132 and 138 mmHg were found to predict incident albuminuria and a rapid decline of eGFR, respectively.

Conclusions

In addition to baseline UACR, SBP is one of the most powerful modifiable independent risk factors for incident albuminuria and a rapid renal function decline in type 2 diabetic patients without symptomatic cardiovascular disease.

Introduction

The prevalence of diabetic renal disease is growing at an alarming rate worldwide and has imposed a high burden of disease-related morbidity and mortality in the recent decades (Huang et al., 2012, Jindal et al., 2013, Reeves et al., 2012). Diabetic nephropathy shares many risk factors with cardiovascular disease (Luo et al., 2010, Sheen et al., 2013), and usually occurs in conjunction with various metabolic abnormalities, such as hyperglycemia (Coresh et al., 2003, Ritz, 2008), dyslipidemia (Chawla et al., 2010, Lee et al., 2009), or overweight/obesity (Inker et al., 2014, Jindal et al., 2013); hypertension (Coresh et al., 2003, Haroun et al., 2003, Whelton et al., 1996); and smoking (Ritz, 2008). Traditionally, two biomarkers, namely the glomerular filtration rate (GFR) and albuminuria, have been used for the diagnosis, severity classification, and outcome prediction of chronic kidney disease (CKD). In fact, based on the Kidney Disease: Improving Global Outcomes (KDIGO) 2012 Clinical Practice Guidelines, both the estimated GFR (eGFR) and albuminuria are required for assessing the progression and identifying the stage of CKD (Inker et al., 2014), and previous studies have demonstrated that an eGFR decline is a prognostic marker for the outcomes of systemic disease-related nephropathy (Drury et al., 2011, Weng et al., 2014). Moreover, a low eGFR has been demonstrated to be associated with progressive arterial stenosis and stiffening (Bertomeu et al., 2008, Bouchi et al., 2011, Kshirsagar et al., 2004, Meguro et al., 2009, Nakamura et al., 2010, Sheen et al., 2012).

Albuminuria is considered to be an early sign of renal damage in diabetic patients (Seaquist & Ibrahim, 2010), and is an established marker for predicting the progression of renal function, adverse cardiovascular outcomes, and mortality in patients with diabetes and nephropathy (Halbesma et al., 2006, Holtkamp et al., 2011, Stephen et al., 2014). Previous studies, such as UKPDS (Retnakaran, Cull, Thorne, Adler, & Holman, 2006), have investigated the factors predicting progression of renal function in type 2 diabetes; however, the progression rate of diabetic kidney disease is highly variable. In most cases, diabetic kidney disease progresses over decades, and rapid renal function progression can lead to renal failure within months (Levey & Coresh, 2012). The potential causes of variations in the progression rate of renal function in type 2 diabetic patients are still undetermined.

Therefore, we here aimed to evaluate the potential determinants of incident albuminuria and rapid decline of eGFR in type 2 diabetic outpatients.

Section snippets

Study population

We retrospectively analyzed data obtained from an outpatient clinic of a community hospital in central Taiwan. Type 2 diabetic patients who regularly visited the outpatient department, underwent ankle-brachial index (ABI) examinations between October 2008 and August 2009, and had measured their renal function every 6 months and urinary albumin-to-creatinine ratio (UACR) annually for at least 1 year were reviewed. Patients were excluded if they were undergoing dialysis or had been diagnosed with

Results

Table 1A shows the baseline clinical characteristics of the study population. Twenty (15.2%) of the 132 patients with normoalbuminuria at baseline progressed to a more advanced stage of albuminuria during the 1-year follow up. These patients had significantly higher mean values of SBP and PP, presented with higher baseline UACR, and were taking sulfonylurea more frequently than those who did not develop incident albuminuria (Table 2). Table 3 illustrates the results of the multivariate logistic

Discussion

In the present study, we demonstrated that SBP was an independent factor associated with both incident albuminuria and a rapid decline of eGFR in type 2 diabetic outpatients without apparent cardiovascular complications during a 1-year follow-up.

Albuminuria is traditionally considered an early marker of diabetic nephropathy, and may appear before the reduction of eGFR (Jindal et al., 2013, Seaquist and Ibrahim, 2010). Accordingly, the level of albuminuria is reported to be a better marker than

Acknowledgments

This study was supported by grants from the Taichung Hospital, Ministry of Health and Welfare, Taiwan, and was approved by the Institutional Review Board of the Taichung Hospital (B-100001).

References (55)

  • A.S. Levey et al.

    Chronic kidney disease

    Lancet

    (2012)
  • K.I. Paraskevas et al.

    Renal function impairment in peripheral arterial disease: an important parameter that should not be neglected

    Annals of Vascular Surgery

    (2009)
  • W.H. Sheu et al.

    Predictors of incident diabetes, metabolic syndrome in middle-aged adults: a 10-year follow-up study from Kinmen, Taiwan

    Diabetes Research and Clinical Practice

    (2006)
  • American Diabetes Association

    Summary of revisions for the 2013 clinical practice recommendations

    Diabetes Care

    (2013)
  • G.L. Bakris et al.

    Angiotensin-converting enzyme inhibitor-associated elevations in serum creatinine: is this a cause for concern?

    Archives of Internal Medicine

    (2000)
  • G.L. Bakris et al.

    Effects of blood pressure level on progression of diabetic nephropathy: results from the RENAAL study

    Archives of Internal Medicine

    (2003)
  • L.D. Bash et al.

    Poor glycemic control in diabetes and the risk of incident chronic kidney disease even in the absence of albuminuria and retinopathy: Atherosclerosis Risk in Communities (ARIC) Study

    Archives of Internal Medicine

    (2008)
  • B.J. Biggerstaff

    Comparing diagnostic tests: A simple graphic using likelihood ratios

    Statistics in Medicine

    (2000)
  • R. Bouchi et al.

    Arterial stiffness is associated with incident albuminuria and decreased glomerular filtration rate in type 2 diabetic patients

    Diabetes Care

    (2011)
  • V. Chawla et al.

    Hyperlipidemia and long-term outcomes in nondiabetic chronic kidney disease

    Clinical Journal of the American Society of Nephrology

    (2010)
  • D. de Zeeuw et al.

    Albuminuria, a therapeutic target for cardiovascular protection in type 2 diabetic patients with nephropathy

    Circulation

    (2004)
  • P.L. Drury et al.

    Estimated glomerular filtration rate and albuminuria are independent predictors of cardiovascular events and death in type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study

    Diabetologia

    (2011)
  • B.J. Epstein

    Elevations in serum creatinine concentration: concerning or reassuring?

    Pharmacotherapy

    (2004)
  • N. Halbesma et al.

    Macroalbuminuria is a better risk marker than low estimated GFR to identify individuals at risk for accelerated GFR loss in population screening

    Journal of the American Society of Nephrology

    (2006)
  • M.K. Haroun et al.

    Risk factors for chronic kidney disease: A prospective study of 23,534 men and women in Washington County, Maryland

    Journal of the American Society of Nephrology

    (2003)
  • F.A. Holtkamp et al.

    Albuminuria and blood pressure, independent targets for cardioprotective therapy in patients with diabetes and nephropathy: a post hoc analysis of the combined RENAAL and IDNT trials

    European Heart Journal

    (2011)
  • P.A. James et al.

    2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the eighth joint national committee (JNC 8)

    JAMA : The Journal of the American Medical Association

    (2014)
  • Cited by (10)

    • The modifying effect of kidney function on the association of cadmium exposure with blood pressure and cardiovascular mortality: NHANES 1999–2010

      2018, Toxicology and Applied Pharmacology
      Citation Excerpt :

      Since our study indicates a significant interaction between kidney function and urinary Cd in relation to blood pressure, stratified analysis is appropriate in addressing the modifying effect of kidney function. One possible explanation for the observation that urinary Cd was positively associated with levels of DBP, but inversely related to SBP is that two previous studies found SBP, but not DBP was significantly associated with a rapid decline in eGFR in the general population (Hirayama et al., 2015) or in individuals with type 2 diabetes (Sheen, Lin, Li, Bau, and Sheu, 2014). This possibility is supported by the change in the inverse association between urinary Cd and SBP to a null or positive association after stratification by eGFR.

    View all citing articles on Scopus

    Conflict of Interest: The authors declare no conflicts of interest.

    View full text