Associations between Renal Hyperfiltration and Serum Alkaline Phosphatase

<div><p>Renal hyperfiltration, which is associated with renal injury, occurs in diabetic or obese individuals. Serum alkaline phosphatase (ALP) level is also elevated in patients with diabetes (DM) or metabolic syndrome (MS), and increased urinary excretion of ALP has been demonstrated in patients who have hyperfiltration and tubular damage. However, little was investigated about the association between hyperfiltration and serum ALP level. A retrospective observational study of the 21,308 adults in the Korea National Health and Nutrition Examination Survey IV-V databases (2008–2011) was performed. Renal hyperfiltration was defined as exceeding the age- and sex-specific 97.5^th percentile. We divided participants into 4 groups according to their estimated glomerular filtration rate (eGFR): >120, 90–119, 60–89, and <60 mL/min/1.73 m². The participants with eGFR >120 mL/min/1.73 m² showed the highest risk for MS, in the highest ALP quartiles (3.848, 95% CI, 1.876–7.892), compared to the lowest quartile. Similarly, the highest risk for DM, in the highest ALP quartiles, was observed in participants with eGFR >120 ml/min/1.73 m² (2.166, 95% CI, 1.084–4.329). ALP quartiles were significantly associated with albuminuria in participants with eGFR ≥ 60 ml/min/1.73m². The highest ALP quartile had a 1.631-fold risk elevation for albuminuria with adjustment of age and sex. (95% CI, 1.158-2.297, P = 0.005). After adjustment, the highest ALP quartile had a 1.624-fold risk elevation, for renal hyperfiltration (95% CI, 1.204–2.192, <i>P</i> = 0.002). In addition, hyperfiltration was significantly associated with hemoglobin, triglyceride, white blood cell count, DM, smoking, and alcohol consumption (<i>P</i><0.05). The relationship between serum ALP and metabolic disorders is stronger in participants with an upper-normal range of eGFR. Higher ALP levels are significantly associated with renal hyperfiltration in Korean general population.</p></div

Distribution of estimated glomerular filtration rate by sex and age.

<p>The 97.5th percentiles are shown in 10-year age groups. Hyperfiltration was defined as an estimated glomerular filtration rate (eGFR) over the age- and sex-specific 97.5th percentile.</p

Associations of glomerular hyperfiltration among serum alkaline phosphatase quartiles in participants with an estimated glomerular filtration rate ≥ 60 ml/min/1.73 m².

<p>*The odds ratios of serum alkaline phosphatase quartiles were adjusted by age, sex, diastolic blood pressure, glucose, body mass index, alanine aminotransferase, aspartate aminotransferase, hemoglobin, white blood cell count (WBC), ferritin, triglyceride, diabetes (DM), metabolic syndrome, angina, current smoking, and alcohol consumption.</p><p>Associations of glomerular hyperfiltration among serum alkaline phosphatase quartiles in participants with an estimated glomerular filtration rate ≥ 60 ml/min/1.73 m².</p

Associations between serum alkaline phosphatase quartiles and diabetes according to the estimated glomerular filtration rate (eGFR).

<p>*The odds ratios of serum alkaline phosphatase quartiles were adjusted by age, sex, systolic blood pressure, body mass index, hemoglobin, cholesterol, current smoking, alcohol, hypertension, myocardial infarction, stroke, and malignancy.</p><p>Associations between serum alkaline phosphatase quartiles and diabetes according to the estimated glomerular filtration rate (eGFR).</p

Associations of albuminuria among serum alkaline phosphatase quartiles in participants with eGFR ≥ 60 ml/min/1.73m².

<p>Associations of albuminuria among serum alkaline phosphatase quartiles in participants with eGFR ≥ 60 ml/min/1.73m².</p

Age, sex, and age- and sex-adjusted demographic and clinical characteristics of the Korean population, age 19 years and older, in the 2011 KNHANES according to albuminuria.

<p>Data are expressed as means with SEM. Abbreviations: albuminuria, microalbuminuria or macroalbuminuria; NA, normoalbuminuria; mA, microalbuminuria; MA, macroalbuminuira; BMI, body mass index; obesity, BMI ≥25 kg/m² or more; BP, blood pressure; hypertension, systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg or use of antihypertensive medications irrespective of BP; FPG, fasting plasma glucose; diabetes, fasting plasma glucose ≥7.0 mmol/L or current anti-diabetes medication or a previous diagnosis of diabetes by a physician; LDL-C, low density lipoprotein-cholesterol; TG, triglyceride; eGFR, estimated glomerular filtration rate; ACR, albumin-creatinine ratio.</p><p>Age, sex, and age- and sex-adjusted demographic and clinical characteristics of the Korean population, age 19 years and older, in the 2011 KNHANES according to albuminuria.</p

Odds ratio for albuminuria in each quartile of estimated 24-h urine sodium with the first quartile as a control.

<p>Model 1: adjusted for age and sex.</p><p>Model 2: adjusted for age, sex, diabetes, hypertension, and obesity.</p><p>Model 3: Model 2 after excluding eGFR <60 ml/min/1.73 m² (n = 4964).</p><p>Odds ratio for albuminuria in each quartile of estimated 24-h urine sodium with the first quartile as a control.</p

Prevalence of albuminuria according to the estimated 24-h urinary Na excretion.

<p>Model 1, no adjustments;</p><p>Model 2, adjusted for age and sex;</p><p>Model 3, adjusted for diabetes, hypertension, obesity, and the variables in Model 2.</p><p>Prevalence of albuminuria according to the estimated 24-h urinary Na excretion.</p

Associations of sodium intake with obesity, metabolic disorder, and albuminuria according to age

<div><p>Sodium intake is associated with obesity and metabolic disorder in the general population. However, sodium intake is significantly reduced according to the decrease of energy intake in older adults although the prevalence of obesity is higher than younger adults. We evaluate the association of sodium excretion (UNa) with blood pressure, obesity, metabolic disorders, and albuminuria according to age. An observational study using data from the Korean National Health and Nutrition Examination Survey IV-V (2008–2011) was performed (N = 18,146). The 24 hour UNa was estimated from a single fasting urine sample.Participants aged≥75 years showed the highest risk for hypertension (HTN) in the highest quartile of UNa (1.769, 95% CI, 1.174–2.665), and the risks for HTN increased with advancing age. Obesity was not associated with UNa in participants aged≥75 years, and hypertriglyceridemia and body fat were not related to UNa in participants aged≥65 years, although these values were significantly associated with UNa in participants aged<65 years. Impaired fasting glucose (IFG) and insulin resistance (IR) were associated with UNa only in participants aged 20–39 years. The highest quartile of UNa showed a 3.777 fold increased risk for albuminuria in those aged 20–39 years (95% CI, 1.130–12.630), and a 1.885 fold increased risk (95% CI, 1.156–3.075) among participants aged 40–64 years. In participants aged≥65 years, albuminuria was not associated with UNa. In contrast with HTN, UNa was not associated with albuminuria, obesity, hypertriglyceridemia, IFG, and IR in older adults despite a strong association in younger adults.</p></div

Adjusted risks of albuminuria^* according to sodium excretion in each age group.

<p>Adjusted risks of albuminuria^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0188770#t002fn001" target="_blank">*</a>} according to sodium excretion in each age group.</p