KIM-1 as a potential serological/urinological tumor-associated marker of renal cell carcinoma and chemotherapy nephrotoxicity

Solokhina, M. P.; Сергеева, Н. С.; Маршутина, Н. В.; Алентов, И. И.; Kanukoev, K. Yu.; Nyushko, K. M.; Alekseev, B. Ya.; Каприн, А. Д.

doi:10.17650/1726-9776-2019-15-3-132-142

Cited by 4 publications

(4 citation statements)

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“…Кроме того, по результатам ряда экспериментальных работ, выявлено, что экспрессия KIM-1 может повышаться при других злокачественных новообразованиях. С другой стороны, KIM-1 может принимать участие в регенерации почечных канальцев после ОПП (нефропротекция) [12]. В основной группе была выше коморбидность, что также могло оказать влияние на развитие патологии почек, и как следствие, увеличение уровня KIM-1.…”

Section: таблица 4 частота и структура ургентных осложнений госпитального периода у пациентов с окс в зависимости от наличия или отсутствunclassified

“…В клинических исследованиях KIM-1 показал себя как чувствительный и специфичный биомаркер для диагностики ОПП, индуцированного противоопухолевой терапией, рентгеноконтрастными препаратами (РКП) (констраст-индуцированное ОПП (КИ-ОПП)), а также после кардиохирургических вмешательств [2,10,11]. Имеются данные, что KIM-1 повышается у больных с ХБП и является одним из маркеров почечно-клеточного рака [12]. В настоящий момент нет достаточного количества данных для широкого использования KIM-1 в практике, в связи с чем необходимо дальнейшее исследование возможностей применения биомаркера, в том числе при ОКС в сочетании с ОЗ.…”

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Features of Acute Coronary Syndrome in Combination with Oncological Diseases in Elderly and Senile Patients

Михайлова¹,

Пивоваров²,

Пивоварова³

2021

Arhivʺ vnutrennej mediciny

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Relevance. The presence of oncological diseases, high polymorbidity in elderly and senile patients can lead to a complicated course of acute coronary syndrome, including the development of acute kidney injury and/or chronic kidney disease, which contributes to a deterioration of the immediate and long-term prognosis and an increase in mortality.The research purposes. To study the course of acute coronary syndrome depending on the presence or absence of oncological diseases in elderly and senile people and to identify clinical and laboratory-instrumental features.Materials and methods. The study included 200 patients (men — n=122 (61 %), women — n=78 (39 %), Me age — 69 (65;77) years). The patients were divided into two groups: 1) the main group — acute coronary syndrome in combination with oncological diseases (n=100) (men — n=61 (61 %), women — n=39 (39 %), Me age — 69 (65;77) years); 2) the comparison group — acute coronary syndrome without oncological diseases (n=100). The groups were formed by the copy-pair method in a ratio of 1:1 by gender and age. All patients were evaluated for anamnesis parameters, the total number of diseases, the Charlson comorbidity index, the main clinical and laboratory-instrumental parameters and the development of complications. We collected an average portion of morning urine on the first day of hospitalization to determine the content of KIM-1 (pg/ml) in 40 patients of the main group and 47 from the comparison group. We collected daily urine on the 2nd day of hospital treatment to determine the level of K+, Na+, Cl-, uric acid and albumin.The results. Patients of the main group, according to the anamnesis, were more often diagnosed with stable angina (p = 0.042), diabetic kidney disease (p = 0.017), chronic kidney disease (p = 0.013) and anemia (p = 0.008). In addition, these patients had a higher Charleson comorbidity index [8 (6; 9) and 5 (4; 6) points; p <0.001] and a total number of diseases [6 (5; 7) and 4 (3; 5); p <0.001]. Patients with oncological diseases with the development of acute coronary syndrome more often complained of shortness of breath (p=0.008) and heart rhythm disturbance (p=0.004). In patients of the main group a lower left ventricular ejection fraction was diagnosed [51.0 (44; 55) and 54 (48; 57), p=0.013]. Acute kidney injury was more frequently diagnosed in the study group than in the comparison group (p <0.001), including acute kidney injury by “basal” creatinine (p=0.005), acute kidney injury by creatinine dynamics (p=0.047), and acute kidney injury by chronic kidney disease (p=0.003). The KIM-1 leel in patients of the main group was higher [921.0 (425.1; 1314.8) and 658.0 (345.6; 921.4) pg/ml; p=0.011]. In patients with acute kidney injury, in contrast to patients without acute kidney injury, a higher level of KIM-1 was detected [999.2 (480.8;1314.1) and 663.1 (360.5;905.2) pg/ml; p=0.008]. Patients with acute coronary syndrome and oncological diseases in the hospital were more likely to develop urgent complications (p=0.005), including death (p=0.024) and acute heart failure (p <0.001). They also had a higher incidence of early post-infarction angina (p=0.018) and anemia (p=0.005).Conclusions. Our study found that patients in the main group had a higher Charlson comorbidity index, a greater number of diseases, including stable angina, diabetic kidney disease, chronic kidney disease, and anemia. These patients with the development of acute coronary syndrome more often complained of shortness of breath and heart rhythm disturbance. Patients with oncological diseases were more often diagnosed with acute kidney damage, including “basal” creatinine, creatinine dynamics, and chronic kidney disease. The level of KIM-1 in the urine was higher in this group of patients. Patients of the main group in the hospital were more likely to develop urgent complications, including acute heart failure and death. There was also a high incidence of early post-infarction angina and anemia.

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Features of Acute Coronary Syndrome in Combination with Oncological Diseases in Elderly and Senile Patients

Михайлова¹,

Пивоваров²,

Пивоварова³

2021

Arhivʺ vnutrennej mediciny

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“…В последние годы в качестве потенциального биологического маркера ПКР рассматривается белок KIM-1 (kidney injury molecule 1), который относят к группе ранних маркеров повреждения проксимальных почечных канальцев [2,3]. Повышение экспрессии KIM-1 в клетках проксимального отдела нефрона индуцируется при острой и хронической ишемии почки и при токсическом воздействии различной природы [4].…”

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“…Повышение экспрессии KIM-1 в клетках проксимального отдела нефрона индуцируется при острой и хронической ишемии почки и при токсическом воздействии различной природы [4]. Молекула KIM-1 представляет собой трансмембранный гликопротеин, и предполагают, что благодаря способности служить рецептором сигналов, поступающих от погибающих клеток, и непосредственной связи с цитоплазматическими сигнальными белками, он вовлечен в молекулярные механизмы, направленные на поддержание жизнеспособности и восстановление почечного эпителия [2][3][4].…”

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KIM-1 (kidney injury molecule 1) in the urine of renal cell carcinoma patients

et al. 2020

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Objective: to assess the potential clinical significance of KIM-1 (kidney injury molecule 1) as a urinological marker for kidney cancer.Materials and methods. An enzyme-linked immunosorbent assay was used to assess urinary KIM-1 (uKIM-1 — kidney injury molecule 1) levels in 67 patients with renal cell carcinoma (RCC) and 36 healthy volunteers (a control group).Results. Both in patients and in healthy individuals, uKIM-1 levels were age independent. A difference between mean uKIM-1 values in RCC patients (2.4 ± 0.2 ng/ml) and the control group (0.7 ± 0.1 ng/ml) was statistically significant (p <0.0001). In RCC patients the higher uKIM-1 level was observed at more advanced clinical disease stages: the values increasedfrom 2.0 ± 0.2 ng/ml at the stage I and 3.0 ± 0.5 ng/ml at the stage II—III to 4.4 ± 1.2 ng/ml at the stage IV. In the group of patients with stage IRCC, most representative by the number of cases (n = 44) the uKIM-1 levels correlated with the tumor size and were increased in patients with different histological subtypes of the tumor, including clear cell, papillary and chromophobe RCC. After nephrectomy, a monotonous decrease in uKIM-1 level was observed, and after 6 days its values approached the mean value in the control group. Two days after kidney resection, uKIM-1 increased and then decreased, remaining elevated after 6 days.Conclusion. This study demonstrates that uKIM-1 can be attributed to potentially significant urine tumor-associated markers of RCC.

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Clinical implication of kidney injury molecule (KIM-1) in blood plasma of renal-cell cancer patients

Герштейн¹,

Naberezhnov²,

Alferov³

et al. 2021

Onkourologiâ

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Background. The most important task in the field of renal-cell cancer (RCC) treatment results improvement is the search and validation of the markers for its early diagnostics still absent in the clinical practice. It was established that even before the onset and/or detection of RCC the level of kidney injury molecule-1 (KIM-1) in blood plasma did increase.Objective of the study — comparative evaluation of KIM-1 levels in blood plasma of practically healthy persons, RCC cancer, benign kidney tumor patients, patients with non-oncological renal pathologies, and analysis of its role in RCC diagnostics and prognosis.Materials and methods. 125 RCC (age 33—81 years), 14 — benign kidney neoplasms (29—84 years) patients, 90patients with chronic nephritis (28—82 years) and 68 practically healthy persons (18—71 years) were included in the study. Plasma KIM-1 content was measured using Human Serum TIM-1/KIM-1/HAVCR Quantikine® ELISA kit (R&D Systems Biotechne®, USA).Results. KIM-1 level in blood plasma of RCC and chronic nephritis patients was significantly higher than in control (medians 305, 282 and 37.8pg/ml respectively, p <0.0001). The rate of KIM-1 elevation over cut-offvalue 90pg/ml corresponding to the upper 95 % confidence interval of control in RCC patients comprised 79.2 %, in patients with nephritis — 83 %, in those with benign renal tumors — 50 %. Specificity in relation to healthy control was 96 %. KIM-1 level highly significantly increased with RCC progression, and already at stage I was 4.3-fold higher by median than in control (p <0.0001). Sensitivity of stage I—IIRCC detection at cut-off 90pg/ml comprised 75 %; stage III—IV — 94 %. The highest plasma KIM-1 levels were detected in papillary cancer patients (median 644pg/ml), that was more than 2-fold higher than in clear-cell and 32-fold higher than in chromophobic RCC. Plasma KIM-1 median level was 7-fold higher in patients with G3 4RCC than in those with G12 (p <0.0001). At the cut-off KIM-1 value of 163pg/ml, corresponding to the median at stage I, significant differences in 3.5-years overall survival both in the total group: 49 % at high, 95 % at low marker level (p <0.01), and at stage I RCC: 62 % and 100 % respectively (p <0.05) — were revealed.Conclusion. Plasma KIM-1 may become the first highly sensitive marker for the early detection of RCC, but it does not allow differentiating between oncologic and non-oncologic renal pathologies. Increased basal plasma KIM-1 is an unfavorable prognostic factor irrespective of the stage of tumor progression.

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KIM-1 as a potential serological/urinological tumor-associated marker of renal cell carcinoma and chemotherapy nephrotoxicity

Cited by 4 publications

References 69 publications

Features of Acute Coronary Syndrome in Combination with Oncological Diseases in Elderly and Senile Patients

Features of Acute Coronary Syndrome in Combination with Oncological Diseases in Elderly and Senile Patients

KIM-1 (kidney injury molecule 1) in the urine of renal cell carcinoma patients

Clinical implication of kidney injury molecule (KIM-1) in blood plasma of renal-cell cancer patients

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