Serum Creatinine And Cystatin C in Diagnosis And Evaluation Of Degree Of Renal Function Damage in Patients With Chronic Kidney Disease

Oct 14, 2022

Abstract: 

Objective: To investigate the application value of serum creatinine(Scr)and cystatin C(Cys—C)in the diagnosis and evaluation of the degree of renal function damage in patients with chronic kidney disease(CKD).

Methods: A total of 173 CKD patients admitted between June 2014 and June 2016 were selected as the observation group, and other 173 healthy people taking the physical examination at the same time were selected as a control group. Scr and Cys—C levels were analyzed and compared in two groups. In the observation group, positive rates of Scr and Cys—C, and diagnostic abilities of Scr and Cys—C, Scr and Cys—C levels in patients with different CKD stages were also analyzed and compared. Results: Serum levels of Scr and Cys—C in the observation group were significantly higher than those in the control group(P<0.01). Cys-C positive rate was significantly higher than that of Scr in the observation group(P<0.01).ROC curve analysis showed that values of area under the curve, specificity, and odds plot of Cys—C were significantly higher than those of Scr(P<0.05). 

Serum levels of Scr and Cys—C were gradually increased with increasing CKD stage in the observation group(P<0.01). Conclusion Both Scr and Cys—C can diagnose and evaluate renal function damage in CKD patients, but Cys—C has better specificity and accuracy, and therefore it can be used as a reliable indicator for diagnosing renal function in CKD patients. 

Keywords: Kidney disease, chronic; Serum creatinine; Cystatin C; Kidney function tests; Diagnosis

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Chronic kidney disease (CKD) is a common disease in nephrology, and its clinical characteristics are high prevalence, high mortality, many complications, and high medical costs, it has become a public health problem in the world'1. . . The main causes of CKD include Renal vascular disease, renal tubular injury, and various secondary and primary glomerulonephritis. For CKD patients, early detection and timely intervention can effectively reduce the occurrence of complications, thereby improving prognosis and improving survival rate. 41.

Glomerular filtration rate (GFR) is an important indicator to measure the kidney, and it is also a key indicator for the diagnosis and staging of CKD"1. The traditional GFR evaluation standard is mainly based on the renal clearance rate of exogenous markers. There are many drawbacks, so it is not suitable for routine application ∞1. Studies have shown that serum creatinine (Scr) is the most widely used indicator for clinical evaluation of GFR, with certain sensitivity and accuracy, but there are still many influencing factors. 7… The role of cystatin c (cystatin C, Cys-C) in the early diagnosis of renal disease and evaluation of renal function changes has been paid more and more attention, and it can be used as an effective indicator to reflect GFR. . This study explores the relationship between Scr and Cys-C. The application value of CKD in the diagnosis and assessment of the degree of renal damage. The report is as follows.

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1 Material and methods

1.1 General data 173 CKD patients admitted to Xianyang Central Hospital from June 2014 to June 2016 were selected as the observation group.

①Inclusion criteria: 20-70 years old; all meet the diagnostic criteria for CKD in the 2012 Clinical Practice Guidelines for the Assessment and Management of CKD developed by the Kidney Disease Improvement Global Outcomes Organization (KDIGO) ¨…: History of kidney transplantation and imaging findings Structural abnormality, abnormal histological examination, electrolyte and other abnormalities caused by renal tubular disease, abnormal urinary sediment or albuminuria, etc., if any of the above is present, it can be judged as kidney damage, and it lasts for >3 months; GFR declines , and<60 appearing="" for="">3 months; CKD can be diagnosed if one of kidney damage or GFR decline is satisfied.

②Exclusion criteria: combined with hypothyroidism or hyperthyroidism, renal failure, liver cirrhosis and other serious chronic diseases

Patients with severe cardiac insufficiency, autoimmune diseases, primary liver diseases, infections or ketoacidosis; patients with muscle atrophy, limb insufficiency, etc. affecting endogenous creatinine; patients with acute renal failure; patients with a history of renal replacement therapy ; Those who took glucocorticoids within 1 month before enrollment; women who were breastfeeding or pregnant. In the observation group, there were 96 males and 77 females; the age was (47.84-6.3) years old; the etiology included 44 cases of hypertensive nephropathy, 47 cases of nephrotic syndrome, 41 cases of diabetic nephropathy, 17 cases of IgA nephritis, and lupus nephropathy. 11 cases of nephropathy, 13 cases of other factors. GFR (eGFR) was calculated by the simplified formula of dietary modification for kidney disease, and the standard staging developed by KDIGO ¨…,

①CKD stage 1: 31 cases with eGFR≥90 ml/(rain·1.73m2); ②CKD stage 2: 36 cases with eGFR 60~89 ml/(rain·1.73m2); ③CKD stage 3: 30~59 ml/(rain ·1.73m2) 38 cases; ④CKD stage 4: eGFR 15~29 ml/(rain·1.73m2) 39 cases; ⑤

CKD stage 5: 29 cases with eGFR≤15 ml/(min·1.73m2). And 173 healthy people who underwent physical examination during the same period were selected as the control group, including 93 males and 80 females; aged (47.94-6.2) years old. There was no significant difference in gender and age between the two groups (P>0.05), and they were comparable.

All research subjects voluntarily participated in this study and signed informed consent, and this study was approved by the hospital medical ethics committee.

1.2 Detection method

①4ml fasting venous blood was collected from both groups of subjects, placed in a vacuum tube without anticoagulant, and placed at room temperature for 15 minutes. The serum was separated by a centrifuge (Shenzhen Hanvino Instrument and Equipment Co., Ltd., model L.530), and stored in a One 80. C refrigerator pending inspection.

②Scr and Cys-C detection: use automatic biochemical analyzer (Olympus, Japan, model AU680) to determine, Scr is sarcosine oxidase method, Cys-C is particle-enhanced immune turbidimetry, and the kits were purchased from Guangzhou Nat Biotechnology Co., Ltd., the detection steps are strictly in accordance with each

The kit comes with the instruction manual.

③Scr and Cys. The normal reference value range of C: Scr is 44-133 I mountain mol/L, Cys-C is 0.51-1.09 mg/L. ④Notes: Scr and Cys-C are subject to internal quality control each time they are tested, that is, the quality control value should be close to the mean x, and not exceed the range of ±1 standard deviation. The biochemical analyzer selected in this study should take small maintenance, once a week; at the same time, professional engineers should be invited to perform instrument calibration and major maintenance every 3 months to ensure the reliability of the test results.


1.3 Observation indicators

The serum levels of Scr and Cys-C in the two groups were analyzed and compared, and the levels of Scr and Cys in the observation group were compared. The positive rate of C, the diagnostic efficacy of Scr and Cys-C, and the serum levels of Scr and Cys-C in each CKD stage of the observation group.

Among them, Scr>133 i ratio mol/L was positive, Cys-C>1.09 mg/L was positive; ROC curve was used to evaluate the efficacy of Scr and Cys-C in diagnosing CKD ¨1f:

①The area under the curve (AUC) can be used to evaluate the diagnostic value, and AUC>0.5 means it has diagnostic value;

②The curve indicators include sensitivity, specificity and odds product (OP). 1.4 Statistical methods SPSS 20.0 statistical software was used to process the data. Measurement data were expressed as mean 4-standard deviation (x-I-s), using t test and analysis of variance; enumeration data were expressed as rate (%), using x2 test. Take 0=0.05 as the inspection level.

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2 results

2.1 Comparison of serum Scr and Cys-C levels Serum Scr and Cys-C levels of observation group were (306.84 4-22.53) ixmol/L and (3.44 4-0.51) mg/L, respectively. The control group was (85.72±11.36) pLmol/L and (0.78 4-0.12) Ing/L; the serum Scr and Cys-C levels in the observation group were significantly higher than those in the control group (t=115 .266, 66.778.P<0.01).

2.2 Scr and Cys. Comparison of C positive rates in CKD patients, the positive rates of Scr and Cys-C were 83 (47.98%) and 121 (69.94%), respectively, and the positive rate of Cys-C was significantly higher than that of Scr.

()(2=17.247, P<0.01).

2.3 Comparison of the diagnostic efficacy of Scr and Cys-C Scr and Cys-C were used as detection variables, 1=with CKD, 0=without CKD, and the ROC curve for diagnosing CKD was drawn. see picture 1. Cys. The AUC, specificity and OP of C were significantly higher than those of Scr (P<0.05); however, the sensitivity of Scr was similar to that of Cys-

There was no statistically significant difference in C (P>0.05). See Table 1.

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Figure 1 ROC curve of serum creatinine and cystatin C in the diagnosis of chronic kidney disease


2.4 Comparison of serum Scr and Cys-C levels in patients with different CKD stages Serum Scr and Cys-C levels in the observation group showed a gradual upward trend with the increase of CKD stages (P<0.01). See Table 2.

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Table 2 Comparison of serum cystatin and cystatin c levels in patients with chronic kidney disease in different stages (x±s)


3 Discussion

The pathogenesis of CKD is very complex, but early and timely intervention can directly affect the prognosis, so early and effective diagnosis is of great significance. It is generally believed that GFR is the best indicator for evaluating renal function in CKD patients, so accurate GFR evaluation is the key. However, GFR cannot be directly detected, and the filtration rate of a certain filtration marker can only be calculated according to a specific formula. Currently, the most widely used methods include iohexol plasma clearance rate, radionuclide GFR measurement and inulin clearance rate, etc., but they are all exogenous markers. Due to the high price and other deficiencies, it is generally limited to scientific research.

Clinically, endogenous markers are often used to evaluate GFR in patients with renal function tests, and Scr is the most commonly used. Scr generally refers to endogenous creatinine, a product of creatine metabolism. The molecular weight of creatinine is small, it is not bound to protein in the blood, it can be filtered by the glomerulus, and very few can be absorbed in the renal tubule. . Scr is the main indicator of renal function, and its elevated level can reflect renal function damage. However, there are certain limitations, including: ① There are many interference factors, such as muscle content, inflammatory response, exogenous creatinine intake, obesity, exercise, age, height, gender, etc. ② The sensitivity is poor, the decrease of GFR and Scr are a non-linear relationship. Generally, the Scr level of patients will increase slightly when the GFR decrease ratio is >50%; damage, so it is easy to miss the best time for treatment. ③ The renal compensatory function is strong, as long as the unilateral kidney functions to maintain the normal level of Scr; therefore, when the degree of renal damage is greater than 50%, the Scr can be increased. Therefore, Scr is used to evaluate early and mild renal function damage. Not very effective. ④ There is extrarenal excretion phenomenon, studies by Pei Xiaohua and Zhao Weihong have shown that Scr is easily caused by the stomach.

Intestinal bacteria overproduce and degrade; Miranda et al41 also pointed out that after oral administration of freeze-dried lactic acid bacteria in patients with CKD stage 3 and 4, their Scr and blood urea decreased by >10%, which indirectly supports the above point of view. At present, although Scr is an important indicator for evaluating renal injury, its sensitivity to early renal injury is poor, which restricts further clinical application. Therefore, it is urgent to seek more effective markers for early renal injury.

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Cys-C is a basic non-glycosylated protein composed of 122 amino acid residues, carrying a positive charge and a small molecular weight. It is generally distributed in nucleated cells in body fluids and various tissues; all nucleated cells in the whole body are Cys-C can be formed, and can sustain constant transcription and expression with a short half-life. Cys-C can be cleared by glomerular filtration in the circulation, but it is not secreted and excreted by the renal tubule. Although it can be reabsorbed in the proximal convoluted tubule, it can be completely metabolized and decomposed, so that it cannot be returned again. In blood circulation, the kidney is also the only organ that can remove Cys-C in circulation, so the glomerular filtration capacity is the key to determining its serum level. Abnormal functioning or high-dose application of sugar

Corticosteroids can affect Cys. C level. Usually Cys. The concentration of C increases rapidly when the renal function suffers mild damage, which can sensitively reflect the changes in GFR. In recent years, research reports by Lei Yongge et al.'15' and Wei et al. also pointed out that Cys. C has a significant correlation with GFR. Therefore, it can be used as an endogenous and ideal marker for early reflection of GFR changes. At the same time, relevant research also shows that Cys. C also has important clinical significance in assessing progressive deterioration of renal function 7I.

This study showed that the serum Scr and Cys-C levels in the observation group were significantly higher than those in the healthy control group, which was consistent with the report of Feng Min et al., indicating that both Scr and Cys-C had a certain value in the diagnosis of CKD and could be used to reflect the" Renal damage. The positive rate of Cys-C in the observation group was as high as 69.94%, which was significantly higher than that of Scr, which was similar to the results of Huang Cheng'191 study. The C test helps to improve the detection rate and can better reflect the impairment of renal function. Serum levels of Scr and Cys-C in the observation group showed a gradual upward trend with the aggravation of renal function impairment, which was consistent with Lopez. Giacoman and Madero old 0. The reports are similar, indicating Scr and Cys. C can intuitively and accurately reflect the impaired renal function. The ROC curve of this study indicated that Cys. The AUC, specificity and OP of C were significantly higher than those of Scr, but the sensitivity of Scr and Cys-C had no difference, which was the same as that of Yuan Mingsheng. twenty one. The research reports are consistent.

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 It can be seen from the AUC values of Scr and Cys-C that it can effectively support the view that the two have value in diagnosing CKD, and the diagnostic value of Cys-C is higher, and it also shows that the specificity of Cys-C is much higher than that of Scr; it can be seen from the OP value, Cys. The clinical comprehensive application value of C is higher than that of Scr, so it can more accurately reflect the changes of GFR and renal function. In conclusion, both Scr and Cys-C have the value of diagnosing CKD and evaluating renal function damage, but Cys. C has higher specificity and accuracy, so it can be used as a reliable indicator for the diagnosis of renal function in CKD patients.


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