Abstract

Abstract Background and Aims Serum creatinine (SCr), serum cystatin C (SCyc) and estimating GFR (eGFR) calculated by calculation formula are the most popular parameters to estimate renal function in clinical setting. Reference intervals (RIs) of these important indices are very essential for prompt and precise clinical diagnosis, treatment and management especially for early asymptomatic chronic kidney injury or acute kidney injury. There are few reports on RI for these renal function indices in Chinese healthy population. Hence, it is important to establish the RIs for Chinese. Our study was performed to determine the RIs of SCr, SCyc and eGFR in healthy adult population in South China in large sample size by age and sex group. Method Apparently healthy Chinese ethnic individuals without diagnosis of chronic diseases and medications according to the record of our hospital's outpatient service system, aged between 18 and 89 years old and performed health screening in Sun-Yat Sen Memorial Hospital in the last 5 years from Jan 01, 2014 to Dec 31, 2019 were recruited into this study. Individuals with abnormality of urinary system checked with ultrasound, abnormal dipstick urine test including proteinuria, hematuria, urinary infection and low urine osmolality, ALT or AST exceeds the upper limit of reference levels, fasting blood sugar>7.0 mmol/l, Hb<110 g/L or dyslipidemia, gout or hyperuricemia were excluded. Results A total of 3480 healthy individuals (female 1645 and male 1835) were enrolled in this study (Table 1). We analyzed the median, 2.5 and 97.5 percentile of SCr, SCysc and eGFR in each age group by sex. The RIs for SCr with respect to age (Table 2) (ranges of 18-29, 30-39, 40-49, 50-59 and 60+ years) were 52.00-87.47, 52.20-82.80, 53.00-86.00, 63.78-88.20 and 53.80-95.20μmol/L for females, and 72.38–112.00, 73.00–111.00, 71.00–112.00, 69.00-114.82 and 70.00-113.00μmol/L for males, respectively. Meanwhile, the RIs for SCysc with respect to age (Table 3) (ranges of 18–29, 30–39, 40–49, 50-59 and 60+ years) were 0.51-1.00, 0.47-1.03, 0.49-1.13, 0.51-1.19 and 0.63-1.25 mg/L for females, and 0.57-1.10, 0.57-1.23, 0.57-1.21, 0.60-1.28 and 0.67-1.39 mg/L for males, respectively. The levels of Scr in female were significantly lower than male (P<0.001) and remained relatively stable across different age group both in male and female (Figure 1). However, our results showed that the levels of SCyc were abruptly increased from 50 years old in healthy population especially in female, and the differences between male and female disappeared in more than 60 years old age group (Figure 2). The medians of reference GFRs(CKD-EPI2012Scr-SCy) (Table 4) are 108.68, 104.25, 97.80, 91.11 and 82.89 mL/min/1.73 m2 for males, and 113.35, 111.64, 104.74, 92.22 and 77.72 for females, in healthy adult aged 18-29, 30-39, 40-49, 50-59 and 60+ years, respectively. Our results showed that higher eGFR and lower decline rate per year of eGFR in female compared with male whose age were under 40 years old, as shown in Figure 3. However, thereafter, the decline rate of eGFR was faster in female than male, which shown as 0.77 in 40-49, 1.39 in 50-59 and 1.12 mL/min/1.73 m2 per year in over 60 years old in female and 0.65 mL/min/1.73 m2 in 40-49, 0.74in 50-59 and 0.82 mL/min/1.73 m2 per year in more than 60 years old in male. The levels of eGFR in female were decreased and lower than male after 60 years old. Similar trend was confirmed by CKD-EPI2009Scr. Conclusion In conclusion, this study provides sex and age specific normal reference values for SCr, SCyc and eGFR of healthy adult population in South China. Our results remind clinicians should consider the important effects of sex and age when evaluate the real renal function of patients and local RIs should be established in clinical setting.

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