Neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, and periostin: Novel urinary biomarkers in diabetic nephropathy

doi:10.5527/wjn.v13.i4.98880

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Dec 25, 2024 (publication date) through Nov 8, 2024

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World Journal of Nephrology

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2220-6124

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Observational Study

World J Nephrol. Dec 25, 2024; 13(4): 98880
Published online Dec 25, 2024. doi: 10.5527/wjn.v13.i4.98880

Table 1 Characteristics of the study population, n (%)

Parameter	Control (n = 40)	Normoalbuminuria (n = 40)	Microalbuminuria (n = 40)	Macroalbuminuria (n = 40)	P value
Mean age in years (SD)	52.83 (7.65)	49.63 (8.76)	51.05 (6.54)	53.73 (10.71)	0.144
Male	25 (62.5)	23 (57.5)	28 (70)	26 (65)	0.704
Smoking habit	4 (10)	4 (10)	4 (10)	5 (12.5)	0.978
Alcohol consumption	7 (17.5)	8 (20)	9 (22.5)	7 (17.5)	0.932
Mean duration of diabetes mellitus in years (SD)	-	2.23 (2.41)⁴^,⁵	5.98 (7.08)⁶	8.55 (6.76)	< 0.001
Mean body mass index (SD) (kg/m²)	24.43 (3.4)	24.8 (3.7)	24 (4.29)	23.8 (3.58)	0.656
Mean systolic blood pressure (SD)	118.8 (10.83)¹^,²^,³	124.88 (8.7)⁵	128.78 (10.11)	132.08 (13.8)	< 0.001
Mean diastolic blood pressure (SD)	78.75 (7.21)²^,³	81.3 (6.91)	84.63 (7.52)	85.18 (10.06)	0.001

¹Significance difference between control and normoalbuminuria.

²Significance difference between control and microalbuminuria.

³Significance difference between control and macroalbuminuria.

⁴Significance difference between normoalbuminuria and microalbuminuria.

⁵Significance difference between normoalbuminuria and macroalbuminuria.

⁶Significance difference between microalbuminuria and macroalbuminuria.

Data are n (%) unless indicated otherwise.

Table 2 Blood parameters and urine biomarkers of the study population

Parameter	Control (n = 40)	Normoalbuminuria (n = 40)	Microalbuminuria (n = 40)	Macroalbuminuria (n = 40)	P value
Urea	24.75 ± 6.78	24.23 ± 6.56	22.58 ± 10.19⁶	28.63 ± 13.52	0.042
Creatinine	0.75 ± 0.43¹^,²^,³	0.85 ± 0.36	0.83 ± 0.45	1.18 ± 0.5	< 0.001
Fasting blood sugar	92.75 ± 8.32¹^,²^,³	173.88 ± 83.01	199.7 ± 56.15	202.78 ± 102.01	< 0.001
Postprandial blood sugar	138.55 ± 15.02¹^,²^,³	268.85 ± 117.93⁴^,⁵	337.48 ± 97.98	326.9 ± 118.48	< 0.001
Glycated hemoglobin	5.03 ± 0.15¹^,²^,³	8.53 ± 2.07	9.5 ± 1.66	9.35 ± 2.52	< 0.001
Estimated glomerular filtration rate	117.08 ± 30.0¹	111.18 ± 27.3⁵	110.88 ± 39.9⁶	77 ± 27.48	< 0.001
Urine albumin creatinine ratio	5.35 ± 6.49¹^,²^,³	11.13 ± 6.63⁴^,⁵	150.58 ± 81.4⁶	1612.55 ± 2064.23	< 0.001
Neutrophil gelatinase-associated lipocalin (µg/L)	3.75 ± 2.43¹^,²^,³	5.28 ± 2.59⁴^,⁵	6.85 ± 2.81⁶	9.15 ± 2.02	< 0.001
Kidney injury molecule-1 (ng/mL)	0.7 ± 0.64¹^,²^,³	1.33 ± 0.57⁴^,⁵	1.85 ± 1.16⁶	2.45 ± 0.9	< 0.001
Periostin (ng/mL)	29.25 ± 13.15¹^,²^,³	41.8 ± 24.17⁴^,⁵	53.65 ± 14.57⁶	64.6 ± 9.1	< 0.001

¹Significance difference between control and normoalbuminuria.

²Significance difference between control and microalbuminuria.

³Significance difference between control and macroalbuminuria.

⁴Significance difference between normoalbuminuria and microalbuminuria.

⁵Significance difference between normoalbuminuria and macroalbuminuria.

⁶Significance difference between microalbuminuria and macroalbuminuria.

Data are mean ± SD.

Table 3 Correlation of urinary neutrophil gelatinase-associated lipocalin, kidney injury molecule-1and periostin with other parameters

Parameter	ACR	Neutrophil gelatinase-associated lipocalin	Kidney injury molecule-1	Periostin
Duration of diabetes mellitus	R = 0.457, P ≤ 0.001^b	-	-	-
Creatinine	R = 0.194, P = 0.014^a	R = 0.218, P = 0.006^b	R = 0.270, P = 0.001^b	R = 0.226, P = 0.004^b
Fasting blood sugar	R = 0.182, P = 0.021^a	R = 0.352, P ≤ 0.001^b	R = 0.192, P = 0.015^a	R = 0.376, P ≤ 0.001^b
Postprandial blood sugar	R = 0.248, P = 0.002^b	R = 0.383, P ≤ 0.001^b	R = 0.231, P = 0.003^b	R = 0.449, P ≤ 0.001^b
Glycated hemoglobin	R = 0.225, P = 0.004^b	R = 0.425, P ≤ 0.001^b	R = 0.295, P ≤ 0.001^b	R = 0.406, P ≤ 0.001^b
ACR	-	R = 0.339, P ≤ 0.001^b	R = 0.219, P = 0.005^b	R = 0.302, P ≤ 0.001^b
Estimated glomerular filtration rate	R = -0.292, P ≤ 0.001^b	R = -0.325, P ≤ 0.001^b	R = -0.299, P ≤ 0.001^b	R = -0.275, P ≤ 0.001^b

^aSignifies P < 0.05.

^bSignifies P value < 0.01.

ACR: Albumin creatinine ratio; R: Correlation coefficient.

Table 4 Urine biomarkers as per estimated glomerular filtration rate category in patients with diabetes mellitus (n = 120)

Parameter	Stage 1 (n = 76)	Stage 2 (n = 30)	Stage 3 (n = 11)	Stage 4 (n = 3)	P value
Albumin creatinine ratio	240.17 ± 633.92¹^,²^,³	1078.1 ± 2231.04	1344.09 ± 1420.74	1860 ± 1893.2	0.002
Neutrophil gelatinase-associated lipocalin (µg/L)	6.36 ± 2.79¹^,²^,³	8.27 ± 3.15	8.27 ± 1.79	9.67 ± 2.3	0.003
Kidney injury molecule-1 (ng/mL)	1.67 ± 1.02³	2.1 ± 0.84	2.45 ± 1.12	2.67 ± 0.57	0.017
Periostin (ng/mL)	51.04 ± 20.01²^,³	52.63 ± 19.11	66.82 ± 9.98	69.67 ± 4.5	0.034

¹Significance difference between stage 1 and stage 2.

²Significance difference between stage 1 and stage 3.

³Significance difference between stage 1and stage 4.

Table 5 The performance criteria of the urine markers in prediction of diabetic nephropathy among the study population

Parameter	Area under curve (95%CI)	Sensitivity	Specificity	Cut of value	P value
Albumin creatinine ratio	0.924 (0.882-0.963)	80	90	12.5	< 0.001
Neutrophil gelatinase-associated lipocalin	0.795 (0.725-0.866)	75.8	55	4.5	< 0.001
Kidney injury molecule-1	0.825 (0.757-0.893)	63.3	90	1.5	< 0.001
Periostin	0.833 (0.773-0.894)	80	67.5	37.5	< 0.001

Citation: Varatharajan S, Jain V, Pyati AK, Neeradi C, Reddy KS, Pallavali JR, Pandiyaraj IP, Gaur A. Neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, and periostin: Novel urinary biomarkers in diabetic nephropathy. World J Nephrol 2024; 13(4): 98880
URL: https://www.wjgnet.com/2220-6124/full/v13/i4/98880.htm
DOI: https://dx.doi.org/10.5527/wjn.v13.i4.98880