The role of extracellular matrix remodeling markers (MMP-2 and TIMP-1) in predicting chronic kidney disease progression after partial laparoscopic nephrectomy

Partial nephrectomy is the treatment of choice for localized renal cell carcinoma. Following organ-sparing surgery, extracellular matrix remodeling processes develop in renal tissue and are regulated by the balance between matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). Conventional assessment of renal function based on serum creatinine levels does not reflect local tissue remodeling processes.
Purpose of the study. To evaluate the dynamics and interrelationship of TIMP‑1, MMP‑2, and serum creatinine levels in patients with renal cell carcinoma after partial laparoscopic nephrectomy, and to determine their association with progression of chronic kidney disease (CKD).
Patients and methods. This prospective study included 633 patients with localized renal cell carcinoma who underwent partial laparoscopic nephrectomy or tumor enucleation. TIMP‑1 and MMP‑2 levels were measured using enzyme-linked immunosorbent assay (ELISA), and serum creatinine was determined by a kinetic colorimetric method preoperatively, on postoperative days 7 and 30, and at 12 and 24 months.
Analysis of CKD progression was performed in a subgroup of patients with complete 24‑month follow-up (n = 119). CKD progression was defined as transition to a higher CKD stage. Correlation analysis, subgroup analysis, and multivariable logistic regression modeling with ROC analysis were performed.
Results. A transient increase in TIMP‑1 levels was observed by postoperative day 7. MMP‑2 demonstrated marked variability, with a peak in median values at 1 month (p < 0.05). A weak positive correlation between TIMP‑1 and MMP‑2 was detected on day 7 (r = 0.10; p = 0.012). No significant association was found between these markers and serum creatinine levels (p > 0.05). At 24 months, higher TIMP‑1 levels were independently associated with CKD progression (OR = 3.6; 95 % CI 1.5–8.7; p = 0.004). The model demonstrated good predictive performance with an AUC of 0.81.
Conclusion. MMP‑2 and TIMP‑1 reflect specific features of postoperative extracellular matrix remodeling and do not correlate with serum creatinine dynamics. Elevated TIMP‑1 levels in the late postoperative period are associated with CKD progression and demonstrate prognostic potential.

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