On normalizing of urinary KIM-1 level to urine creatinine in patients with renal cell cancer

KIM-1 (kidney injury molecule 1), a marker of acute kidney injury, is produced by epithelial cells of renal proximal tubules. Elevated KIM-1 levels in urine and plasma are associated with renal cell carcinoma (RCC). The aim of this study was to compare the significance of non-normalized uKIM-1 values and those normalized to urine creatinine, as urinary biomarkers in RCC. The uKIM-1, urine creatinine and their ratio (uKIM-1/Cre) were studied in 118 RCC patients and 58 apparently healthy subjects. The median of uKIM-1 in the healthy group was 0.71 ng/ml (1st and 3rd quartiles were 0.35 and 1.23, respectively) and in RCC patients it was 2.36 (1.43; 5.93) ng/ml. The medians of uKIM-1/Cre were 0.77 (0.49; 1.18) and 2.42 (1.41; 4.61) ng/mgCre, respectively. Stage I RCC is statistically significantly different from stages II-III and stage IV using uKIM-1/Cre values (p = 0.0056 and p = 0.0012, respectively); using uKIM-1 values significant differences occur only when comparing stages I and IV (p = 0.015). In both healthy individuals and RCC patients, uKIM-1/Cre levels were slightly lower in subgroups younger than 50 years than in subgroups older than 50 years, whereas a similar trend was observed for uKIM-1 only in patients. In healthy men and male patients, uKIM-1 levels were higher than in the corresponding groups of women (the differences were not statistically significant), but the use of uKIM-1/Cre values eliminated the gender differences. A high correlation was found between the concentrations of uKIM-1 and urine creatinine in three healthy subjects followed up for 3 weeks (Spearman’s correlation coefficients were 0.758, 0.825 and 0.933, respectively). The data obtained are clear evidence of the need for normalization uKIM-1 to urine creatinine in RCC patients.

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

Cancer Urology ◽

10.17650/1726-9776-2020-16-3-21-28 ◽

2020 ◽

Vol 16 (3) ◽

pp. 21-28

Author(s):

K. Yu. Kanukoev ◽

N. S. Sergeeva ◽

T. A. Karmakova ◽

N. V. Marshutina ◽

M. P. Solokhina ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Kidney Injury ◽

Stage Iv ◽

Mean Value ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Kidney Injury Molecule 1 ◽

Disease Stages

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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Abstract 5195: Kidney injury molecule-1: a novel therapeutic target in renal cell carcinoma.

10.1158/1538-7445.am2013-5195 ◽

2013 ◽

Cited By ~ 19

Author(s):

Venkata Sabbisetti ◽

Rupal Bhatt ◽

Swetha Ramadesikan ◽

Joseph Bonventre

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Therapeutic Target ◽

Renal Cell ◽

Kidney Injury ◽

Kidney Injury Molecule 1 ◽

Novel Therapeutic

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Phase II Trial of Autologous Tumor Vaccination, Anti-CD3-Activated Vaccine-Primed Lymphocytes, and Interleukin-2 in Stage IV Renal Cell Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2003.08.023 ◽

2003 ◽

Vol 21 (5) ◽

pp. 884-890 ◽

Cited By ~ 69

Author(s):

Alfred E. Chang ◽

Qiao Li ◽

Guihua Jiang ◽

Donna M. Sayre ◽

Thomas M. Braun ◽

...

Keyword(s):

Cell Therapy ◽

Lymph Nodes ◽

Tumor Cells ◽

Renal Cell Cancer ◽

Renal Cell ◽

Cell Cancer ◽

Interleukin 2 ◽

Stage Iv ◽

Autologous Tumor ◽

Cytokine Release

Purpose: Previous preclinical and clinical studies have demonstrated that autologous tumor vaccines can induce relatively specific tumor-reactive T cells in draining lymph nodes. The adoptive transfer of these cells can result in tumor regression. Patients and Methods: Patients with stage IV renal cell cancer (RCC) were vaccinated with irradiated autologous tumor cells admixed with Calmette-Guérin bacillus. Approximately 7 days later, vaccine-primed lymph nodes (VPLNs) were harvested and the lymphoid cells secondarily activated with anti-CD3 monoclonal antibody and expanded in interleukin 2 (IL-2). The activated cells were subsequently infused intravenously along with the concomitant administration of bolus IL-2 (360,000 U/kg intravenously × 15 doses). Results: Thirty-nine patients were entered onto the study, of whom 34 completed an initial course of cell therapy consisting of a mean (SEM) number of 4.3 (2.2) × 1010 VPLN cells. Among subjects who received cell therapy, there were nine responses (four complete responses [CRs] and five partial responses [PRs]), for an overall response rate of 27%. The durations of the CRs were > 48, 45, > 35, and 12 months, and the durations of the PRs were > 63, 48, 15, 12, and 4 months. Cultured tumor cells were available to assess in vitro cytokine release of VPLN cells in 24 subjects. The median cytokine release ratio of interferon gamma (IFNγ) to IL-10 for responders and nonresponders was 992 and 5, respectively, which was significantly different (P = .047). Conclusion: The treatment protocol resulted in durable tumor responses in patients with advanced RCC. The ratio of IFNγ and IL-10 cytokines released in response to tumor by the VPLN cells was a significant correlate with tumor response.

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Reduction of Brain Metastasis Following Immunotherapy with Interleukin-2 for Stage IV Renal Cell Cancer

Acta Oncologica ◽

10.3109/02841869709109236 ◽

1997 ◽

Vol 36 (2) ◽

pp. 228-228 ◽

Cited By ~ 4

Author(s):

Giovanni Citterio ◽

Giuseppe Di Lucca ◽

Ugo Scaglietti ◽

Sara Gilberti ◽

Monica Baldini ◽

...

Keyword(s):

Brain Metastasis ◽

Renal Cell Cancer ◽

Renal Cell ◽

Cell Cancer ◽

Interleukin 2 ◽

Stage Iv

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Hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC): Genotype and phenotype characteristics in a cohort of 197 patients.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.1580 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 1580-1580

Author(s):

Ana Beatriz Sanchez-Heras ◽

Adela Castillejo ◽

Juan de Dios García-Diaz ◽

Mercedes Robledo ◽

Alex Teule ◽

...

Keyword(s):

Renal Cell Cancer ◽

Renal Cell ◽

Cell Cancer ◽

Fumarate Hydratase ◽

Stage Iv ◽

Renal Cysts ◽

Loss Of Function ◽

Cancer Syndrome ◽

Pathogenic Variants

1580 Background: HLRCC is a hereditary condition with autosomal dominant inheritance due to germline mutations in the fumarate-hydratase gene ( FH). It is characterized by skin leiomyomas (SLM) in 48-84% of individuals, uterine leiomyomas (ULM) in 30-72%, renal cysts (RCy) and renal cell cancer (RCC) in 15-34%. We aimed to describe the genetics, the clinical features and the potential genotype-phenotype associations in the largest cohort of FH mutation carriers from Spain. Methods: We performed a multicenter, observational, retrospective study of individuals with genetic or clinical diagnosis of HLRCC. We collected clinical information from medical records. We analyzed genetic variants and looked for genotype-phenotype associations. Statistical analyses were performed by IBM-SPSS Statistics-v.22. Results: We included 197 individuals (113 women, 84 men), 74 index cases and 123 relatives. Twenty-seven different variants were detected, 26 pathogenic (12 missense, 5 frameshift, 4 large-deletions, 3 splice-site and 2 nonsense) and 1 variant of unknown significance (missense). Of 182 patients with full skin examination, 64.8% presented SLM (median age 36 years; range 8-85). ULM were diagnosed in 90.3% of 103 women with gynecologic exam (median age 30 years; range 17- 55). Hysterectomy was performed in 62.9% (median age 34 years; range 21-54). Of 153 patients with radiological records, 37.3 % presented RCy. Nineteen patients (10.9%) presented RCC, 11 males and 8 females (median age 37 years; range 10-67). The histological diagnoses were: 14 papillary, of which 10 were type 2; 3 clear cell carcinoma and 2 unclassified carcinoma. Six tumors had stage I, 2 stage II, 3 stage III, 4 stage IV, and 4 not available. The median overall survival among patients at stages 3-4 was 2.9 years [1.3-4.5]. Patients with missense pathogenic variants showed higher risk of developing SLM (p = 0.043) and ULM (p = 0.002) than those with loss of function variants. Conclusions: In our cohort, the frequency of RCC (10.9%) is lower than that published in cohorts of similar sample size. The most frequent histology was the papillary type-2; however, other histological patterns do not exclude HLRCC. Individuals with missense pathogenic variants show higher incidence of SLM and ULM.

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Gonadal function in male patients with metastatic renal cell cancer treated with sunitinib: Effects of testosterone replacement on quality of life.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.2_suppl.525 ◽

2016 ◽

Vol 34 (2_suppl) ◽

pp. 525-525

Author(s):

Alberto Dalla Volta ◽

Francesca Valcamonico ◽

Carlo Cappelli ◽

Andrea Delbarba ◽

Vittorio D. Ferrari ◽

...

Keyword(s):

Quality Of Life ◽

Renal Cell ◽

Cell Cancer ◽

Cross Sectional Study ◽

Testosterone Replacement ◽

Sectional Study ◽

Antiangiogenic Effect ◽

Cross Sectional ◽

Male Patients

525 Background: Sunitinib (S) is a standard first line treatment of metastatic renal cell carcinoma (mRCC). Asthenia and fatigue are the most prevalent toxicities but the relevant causes are not fully elucidated. Since endocrine glands are highly vascularized, the potent antiangiogenic effect of S can potentially impair their function. With the exception of hypothyroidism, the endocrine-related side-effects of S have not been extensively explored. Methods: We performed a cross-sectional study in which pituitary, thyroid, parathyroid, adrenal and gonadal functions were assessed in 25 mRCC patients who received 9 months of S therapy. Since a high prevalence of hypogonadism was observed, we subsequently enrolled 16 mRCC male patients in a prospective cohort study in which serum testosterone (T) serum free T, serum FSH and LH were evaluated at baseline and after 6 weeks (1 cycle) of S therapy. In patients eligible for testosterone replacement after andrologic evaluation, a FACT-G questionnaire for quality of life (QoL) assessment was prospectively administered at baseline and after 3 months. Results: In the cross sectional study 15/22 S treated male patients (68%) had serum T below the normal range and 13 of them (87%) presented with low/normal levels of LH. In the prospective study mean T levels (95% CI) were 5.04 ng/ml (3.4 - 6.7) at baseline and 4.1 ng/ml (3 - 5.3) after 6 weeks (p 0.05). The corresponding free T were 91.4 pg/ml (66 – 116.8) and 80.2 pg/ml (65 – 95.3) (p 0.24), respectively. Hypogonadism was observed in 5 (31%) patients at baseline and 10 (63%) patients after 6 weeks of S therapy. In the 5 patients becoming hypogonadic after S therapy, LH was 11.4 mU/ml (3.2 - 19.5) at baseline and 11.5 mUI/ml (0 – 23.5) after 6 weeks. Four patients were addressed to testosterone replacement. QoL significantly improved in 3 of them, with the strongest advantage in the physical comfort area. Conclusions: S therapy induces hypogonadism in a high proportion of male patients with mRCC. Low or inappropriately normal LH levels are consistent with a pituitary origin of the endocrine disorder. Testosterone replacement may improve the QoL and treatment tolerance.

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