تقييم جزيء إصابة الكلى في المصل-1 ومثبط الأنسجة للميتالوبروتينيز-2 كعلامات تشخيصية في مرض الكلى المزمن في محافظة كربلاء

Assessing Serum Kidney Injury Molecule-1 and Tissue Inhibitor of Metalloproteinase-2 as Diagnostic Markers in Chronic Kidney Disease in Kerbala Governorate

Abstrat

Chronic Kidney Disease (CKD) is a progressive condition characterized by
irreversible loss of renal function, driven by multiple etiologies including
diabetes, hypertension, ischemic injury, and glomerulonephritis. Early
detection of tubular injury is critical to delay progression to end-stage renal
disease (ESRD) requiring dialysis or transplantation.
The current study was a case-control study involving 88 subjects: 58 CKD
patients (29 pre-dialysis stages, 29 on dialysis) and 30 healthy controls, (aged
30–70 years) was conducted. Blood samples were analyzed using ELISA to
measure Serum Kidney Injury Molecule-1 (KIM-1), Tissue Inhibitor of
Metalloproteinases-2 (TIMP-2), other biochemical markers such as serum
creatinine, serum urea, sodium and potassium concentration, calcium,
vitamin D3 and parathyroid hormone (PTH) levels. Ethical approval and
informed consent were obtained. There were no statistically significant
differences in age or BMI among the three groups (p value > 0.05). Males
represented 60% and females 40% of all participants. The most affected age
group was ≥ 60 years (58.1%). Additionally, a majority of CKD patients had
comorbid hypertension (72.3%) and type 2 diabetes mellitus (53%). A
significant proportion of patients (over 66%) lacked regular physical activity,
highlighting the need for lifestyle interventions. KIM-1 (is a kidney
biomarker in the current study) levels were significantly elevated on dialysis
patients compared to pre-dialysis and controls (p-value was 0.001)., but
showed no significant difference between pre-dialysis patients and controls
(p = 0.897). KIM-1 was higher in smokers, correlated positively with serum
creatinine, and negatively with eGFR, but was not influenced by age, sex,
BMI, or comorbidities such as diabetes and hypertension. ROC analysis
II
demonstrated fair diagnostic accuracy for dialysis patients versus controls
(AUC = 0.751), with a cut-off of 0.48 ng/mL yielding 79% sensitivity and
67% specificity. Serum TIMP-2 levels were significantly higher in CKD
patients than in healthy controls (p = 0.004), These findings indicate the
potential diagnostic relevance of TIMP-2 in distinguishing CKD patients
from healthy individuals. When comparing disease stages, TIMP-2 levels
increased progressively across the groups, being lowest in controls, slightly
higher in pre-dialysis patients, and highest in dialysis patients. This trend was
statistically significant (p = 0.001). Further subgroup analysis demonstrated
that CKD patients with diabetes had significantly elevated TIMP-2 levels
compared to non-diabetic patients (p = 0.027). TIMP-2 showed a stronger
correlation with renal dysfunction than KIM-1. ROC analysis indicated
moderate discriminatory power for dialysis patients versus controls, the AUC
increased to 0.715, with 76% sensitivity and 60% specificity. For
differentiating pre-dialysis patients from controls, the AUC was 0.634 with
65% sensitivity and 60% specificity.
In conclusion, KIM-1 and TIMP-2 may serve as useful indicators of kidney
damage, especially in advanced stages of CKD. The findings suggest that the
combined use of KIM-1 an TIMP-2 represents a promising approach for
improving the evaluation and diagnosis of chronic kidney disease (CKD).
KIM-1’s specificity for proximal tubule injury and TIMP-2’s ability to track
disease progression across CKD stages highlight their complementary roles.
Integrating these biomarkers, particularly in combination with others, may
enhance early detection. Further longitudinal studies are warranted to validate
their prognostic value and clinical applicability in diverse patient groups.