Detection of decline in estimated glomerular filtration rate in patients with type 2 diabetes by cystatin C-based equations

Table 1 Criteria for diagnosis of diabetes

Tests	Results
Fasting plasma glucose (fasting is defined as no caloric intake for at least eight hours)1	≥ 126 mg/dL (7.0 mmol/L)
Or, 2-hour plasma glucose during OGTT (the test should be performed as described by the World Health Organization, using a glucose load containing the equivalent of 75-g anhydrous glucose dissolved in water)1	≥ 200 mg/dL (11.1 mmol/L)
Or, HbA1c (the test should be performed in a laboratory using a method that is NGSP certified and standardized to the DCCT assay)1	≥ 6.5% (48 mmol/mol)
Or, in a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose	≥ 200 mg/dL (11.1 mmol/L)

¹In the absence of unequivocal hyperglycemia, diagnosis requires two abnormal test results from the same sample or in two separate test samples.

OGTT: Oral glucose tolerance test; HbA1c: Glycated hemoglobin; NGSP: National Glycohemoglobin Standardization Program; DCCT: Diabetes Control and Complications Trial.

Table 2 Estimated glomerular filtration rate equations

Names	Equations
Cock-Croft Gault (mL/min)	eGFR = [(140-age) × weight]/(72 × Scr) (× 0.85 if female)
MDRD (mL/min/1.73 m²)	eGFR = 186 × (Scr)-1.154 × (age)-0.203 × (0.742 if female) × (1.210 if African American)
CKD-EPI 2021 creatinine (mL/min/1.73 m²)	Female	Scr ≤ 0.7	eGFR = 142 × (Scr/0.7)-0.241 × 0.9938age × 1.012
		Scr > 0.7	eGFR = 142 × (Scr/0.7)-1.200 × 0.9938age × 1.012
	Male	Scr ≤ 0.9	eGFR = 142 × (Scr/0.9)-0.302 × 0.9938age
		Scr > 0.9	eGFR = 142 × (Scr/0.9)-1.200 × 0.9938age
CKD-EPI 2012 cystatin C (mL/min/1.73 m²)	Female	Scys ≤ 0.8	eGFR = 133 × (Scys/0.8)– 0.499 × 0.996age × 0.932
		Scys > 0.8	eGFR = 133 × (Scys/0.8)– 1.328 × 0.996age × 0.932
	Male	Scys ≤ 0.8	eGFR = 133 × (Scys/0.8)– 0.499 × 0.996age
		Scys > 0.8	eGFR = 133 × (Scys/0.8)– 1.328 × 0.996age
CKD-EPI 2021 creatinine-cystatin C (mL/min/1.73 m²)	Female	Scr ≤ 0.7	Scys ≤ 0.8	eGFR = 135 × (Scr/0.7)-0.219 × (Scys/0.8)-0.323 × 0.9961age × 0.963
			Scys > 0.8	eGFR = 135 × (Scr/0.7)-0.219 × (Scys/0.8)-0.778 × 0.9961age × 0.963
		Scr > 0.7	Scys ≤ 0.8	eGFR = 135 × (Scr/0.7)-0.544 × (Scys/0.8)-0.323 × 0.9961age × 0.963
			Scys > 0.8	eGFR = 135 × (Scr/0.7)-0.544 × (Scys/0.8)-0.778 × 0.9961age × 0.963
	Male	Scr ≤ 0.9	Scys ≤ 0.8	eGFR = 135 × (Scr/0.9)-0.144 × (Scys/0.8)-0.323 × 0.9961age
			Scys > 0.8	eGFR = 135 × (Scr/0.9)-0.144 × (Scys/0.8)-0.778 × 0.9961age
		Scr > 0.9	Scys ≤ 0.8	eGFR = 135 × (Scr/0.9)-0.544 × (Scys/0.8)-0.323 × 0.9961age
			Scys > 0.8	eGFR = 135 × (Scr/0.9)-0.544 × (Scys/0.8)-0.778 × 0.9961age

Age (year); weight (kg).

eGFR: Estimated glomerular filtration rate; Scr: Serum creatinine (mg/dL); MDRD: Modification of Diet in Renal Disease; CKD-EPI: Chronic Kidney Disease Epidemiology Collaboration; Scys: Serum cystatin C (mg/L).

Table 3 Chronic kidney disease stages

Terms	eGFR (mL/min/1.73 m2)
Normal or high	≥ 90
Mildly decreased	60-89
Mildly to moderately decreased	45-59
Moderately to severely decreased	30-44
Severely decreased	15-29
Kidney failure	< 15

eGFR: Estimated glomerular filtration rate.

Table 4 Clinical and laboratory characteristics of the study subjects

Characteristics		Type 2 diabetic		P value	Characteristics	Type 2 diabetic		P value
		Yes (n = 47)	No (n = 46)			Yes (n = 47)	No (n = 46)
Gender n, (%)	Male	15 (31.9)	18 (39.1)	0.47	HbA1c (%)	7.3 ± 1.7	5.8 ± 0.93	< 0.011
	Female	32 (68.1)	28 (60.9)		Glucose (mmol/L)	7.2 ± 2.7	5.5 ± 0.6	< 0.011
Average age (years)		71 ± 1.0	71 ± 1.2	0.82	Total cholesterol (mmol/L)	5.6 ± 0.9	5.6 ± 1.2	0.8
Weight (kg)		59.4 ± 13.4	57.3 ± 9.3	0.4	Triglycerides (mmol/L)	2.3 ± 0.9	2.1 ± 1.3	0.6
BMI (kg/m2)		24.3 ± 4.4	23.0 ± 2.7	0.08	HDL-C (mmol/L)	1.1 ± 0.27	1.1 ± 0.3	0.8
SBP (mmHg)		133 ± 14.2	129.7 ± 10.6	0.2	LDL-C (mmol/L)	3.6 ± 0.9	3.6 ± 1.0	1
DBP (mmHg)		82.2 ± 4.5	81.4 ± 5.0	0.4	Uric acid (μmol/L)	330 ± 75.6	315 ± 68.4	0.3
Scr (µmol/L)		84.9 ± 26.3	77.9 ± 20.1	0.15	Scys (mg/L)	1.3 ± 0.4	1.22 ± 0.3	0.3
ACR (mg/g)		17.4 (3.9 – 8632.3)2	13.5 (4 – 252.8)2	0.11

¹Student’s t-test.

²Median (minimum – maximum).

BMI: Body mass index; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; Scr: Serum creatinine; ACR: Albumin/creatinine ratio; HbA1c: Glycated hemoglobin; HDL-C: High-density lipoprotein cholesterol; LDL-C: Low-density lipoprotein cholesterol; Scys: Serum cystatin C.

Table 5 Estimated glomerular filtration rate values and its correlation with serum cystatin C concentration

eGFR (mL/min/1.73 m2)	Type 2 diabetes		P value	Correlation between eGFR values and Scys
	Yes (n = 47)	No (n = 46)		r	P1 value
Cockcroft-Gault	64.7 ± 22.5	67.3 ± 20.6	0.56	-0.47	< 0.01
MDRD	72 ± 0.19	80 ± 0.17	0.06	-0.59	< 0.01
CKD-EPI 2021 creatinine	102.8 ± 32.8	109.1 ± 30.9	0.34	-0.59	< 0.01
CKD-EPI 2012 cystatin C	55.6 ± 17.1	58.7 ± 15.4	0.35	-0.86	< 0.01
CKD-EPI 2021 creatinine-cystatin C	66.8 ± 14.6	70.4 ± 13.8	0.23	-0.91	< 0.01

¹Pearson’s correlation coefficient.

eGFR: Estimated glomerular filtration rate; MDRD: Modification of Diet in Renal Disease; CKD-EPI: Chronic Kidney Disease Epidemiology Collaboration; Scys: Serum cystatin C.

Table 6 The agreements between estimated glomerular filtration rate equations

Equations		CKD-EPI 2021 creatinine-cystatin C (mL/min/1.73m2)		Kappa coefficients (P1 value)
		< 60	≥ 60
Cockcroft-Gault (mL/min/1.73 m2)	< 60	19	20	0.43 (P < 0.001)
	≥ 60	4	50
MDRD (mL/min/1.73 m2)	< 60	15	3	0.66 (P < 0.001)
	≥ 60	8	67
CKD-EPI 2021 creatinine (mL/min/1.73 m2)	< 60	9	0	0.49 (P < 0.001)
	≥ 60	14	70
CKD-EPI 2012 cystatin C (mL/min/1.73 m2)	< 60	19	20	0.44 (P < 0.001)
	≥ 60	4	50

¹Kappa statistic.

MDRD: Modification of Diet in Renal Disease; CKD-EPI: Chronic Kidney Disease Epidemiology Collaboration.

Table 7 Related factors that affect the estimated glomerular filtration rate decline in elderly diabetic patients

Characteristics (n, %)		eGFR decline			P value	Characteristics (n, %)					eGFR decline				P value
		Yes (n = 14)	No (n = 33)								Yes (n = 14)		No (n = 33)
Gender	Male	4 (26.7)	11 (73.3)		0.7	BMI			Normal		6 (28.6)		15 (71.4)		0.2
	Female	10 (31.2)	22 (68.8)						Overweight, obese		8 (30.8)		18 (69.2)
Hypertension	Yes	6 (35.3)	11 (64.7)		0.53	Uric acid			Increased		1 (10.0)		9 (90.0)		0.15
	No	8 (26.7)	22 (73.3)						Normal		13 (35.1)		24 (64.9)
ACR	Increased	5 (35.7)	9 (27.3)		0.6	Triglycerides			Increased		9 (31.0)		20 (69.0)		0.24
	Normal	9 (64.3)	24 (72.7)						Normal		5 (27.8)		13 (72.2)
HDL-C	Decreased	9 (39.1)	14 (60.9)		0.18	LDL-C			Increased		11 (26.8)		30 (73.2)		0.26
	Normal	5 (20.8)	19 (79.2)						Normal		3 (50.0)		3 (50.0)
The relationship of declined eGFR and the correlation of eGFR with glucose, HbA1c, total cholesterol, and exercise (n = 47)
Characteristics				Declined eGFR								eGFR (mL/min/1.73 m2)
				OR			95%CI			Pa value		r		Pb value
Glucose (mmol/L)				1.6			1.1-2.5			0.04		-0.46		0.001
HbA1c (%)				1.7			1.1-2.6			0.013		-0.47		0.001
Total cholesterol (mmol/L)				0.24			0.06-0.9			0.029		0.341		0.019
Exercise (regular, irregular)				0.16			0.03-0.81			0.017		N/A		N/A
Multivariate logistic regression between glucose, HbA1c, total cholesterol, exercise and declined eGFR (n = 47)
Characteristics				Declined eGFR
				β			OR			95%CI		Pc value
Glucose (mmol/L)				-0.203			0.816			0.550-1.212		0.315
HbA1c (%)				-0.456			0.634			0.330-1.217		0.171
Total cholesterol (mmol/L)				1.141			3.130			1.000-9.793		0.05
Exercise (regular, irregular)				2.844			17.178			1.409-209.369		0.026
Multiple linear regression between glucose, HbA1c, total cholesterol and eGFR values (n = 47)
Characteristics				eGFR (mL/min/1.73 m2)
				β			r			r2		Pd value
Glucose (mmol/L)				-2.248			-0.366			0.13		0.026
HbA1c (%)				-1.591			-0.162			0.02		0.332
Total cholesterol (mmol/L)				4.503			1.949			3.79		0.058

^aChi-square test.

^bPearson’s correlation coefficient.

^cMultivariate logistic regression.

^dMultiple linear regression.

r²: Square of the correlation coefficient.

eGFR: Estimated glomerular filtration rate; ACR: Albumin/creatinine ratio; HDL-C: High-density lipoprotein cholesterol; BMI: Body mass index; LDL-C: Low-density lipoprotein cholesterol; HbA1c: Glycated hemoglobin; OR: Odds ratio; CI: Confidence interval.