Evaluation of chemotherapeutic effect and prognosis of serum and urine IGFBP7 and TIMP-2 in multiple myeloma with renal injury

Abstract:Objective To assess the utility of serum/urinary insulin-like growth factor binding protein 7(IGFBP7) and tissue inhibitor of metalloproteinases-2(TIMP-2) in predicting chemotherapy response and prognosis in myeloma with renal injury.Methods A total of 328 patients with multiple myeloma and renal injury admitted to Linfen People's Hospital from June 2018 to June 2023 were enrolled. All patients received chemotherapy with the BTD(bortezomib + thalidomide + dexamethasone) regimen. Serum and urinary levels of IGFBP7 and TIMP-2 were measured before chemotherapy. After chemotherapy, patients were divided into a remission group and a non-remission group based on efficacy. Follow-up was conducted for 12 months, and patients were divided into a death group and a survival group based on prognosis. Multivariate Cox regression analysis was used to identify factors influencing the prognosis of patients with multiple myeloma and renal injury. Receiver operating characteristic(ROC) curve analysis was performed to evaluate the value of serum and urinary IGFBP7 and TIMP-2 in assessing chemotherapy efficacy and predicting prognosis.Results All patients completed 4 cycles of chemotherapy. There were 135 non-remission cases and 193 remission cases. Serum and urinary levels of IGFBP7 and TIMP-2 in the non-remission group were significantly higher than those in the remission group(t/P=29.113/<0.001, 21.386/<0.001, 27.663/<0.001, 23.716/<0.001). During follow-up, 5 patients were lost to follow-up, and 35 died. Serum and urinary levels of IGFBP7 and TIMP-2 in the death group were significantly higher than those in the survival group(t/P=14.298/<0.001、17.110/<0.001, 17.088/<0.001, 22.987/<0.001). The area under the curve(AUC) of serum IGFBP7, TIMP-2 and urine IGFBP7, TIMP-2 in predicting the efficacy of chemotherapy in patients with multiple myeloma complicated with renal injury was 0.771, 0.760, 0.811, 0.770, respectively. The AUC of combined prediction was 0.885, 0.811, which was higher than that of IGFBP7 and TIMP-2 alone(P<0.05). The AUC of serum IGFBP7, TIMP-2 and urine IGFBP7, TIMP-2 in predicting the prognosis of patients with multiple myeloma complicated with renal injury were 0.679,0.715,0.786,0.794, respectively. The AUC of combined prediction was 0.887,0.895, which was higher than that of IGFBP7 and TIMP-2 alone(P<0.05).The value of urinary IGFBP7 and TIMP-2 in predicting the efficacy of chemotherapy and poor prognosis in patients with multiple myeloma complicated with renal injury was greater than that of serum IGFBP7 and TIMP-2.Non-remission of chemotherapy, high FLC-κ/λ, high serum and urine IGFBP7 and TIMP-2 were risk factors for poor prognosis in patients with multiple myeloma complicated with renal injury[HR(95%CI)=2.803(1.503-5.229),1.384(1.103-1.737), 1.668(1.036-2.687),1.511(1005-2.272),2.164(1.207-3.891),1.868(1.086-3.215) ].Conclusion Urinary IGFBP7/TIMP-2 are superior to serum markers for monitoring therapeutic efficacy and survival in myeloma-associated kidney injury.