scholarly journals La proteína KIM-1, un biomarcador asociado a la enfermedad renal

2022 ◽  
Vol 10 (19) ◽  
pp. 20-27
Author(s):  
Emmanuel Reyes-Uribe ◽  
Marco Antonio Hernández-Bedolla ◽  
Joel Salazar-Flores ◽  
Erandis Dheni Torres-Sánchez
Keyword(s):  
T Cell ◽  
Kidney Injury ◽  
El Sistema ◽  
Kidney Injury Molecule 1 ◽  
Domain 4

La enfermedad renal o de riñón es una anormalidad funcional de los riñones que tiene implicaciones en la salud. El daño agudo de riñón y la enfermedad renal crónica presentan una elevada incidencia en México y representan un problema de salud pública con repercusiones económicas importantes. El diagnóstico oportuno de la enfermedad renal tendría un efecto positivo en la eficacia del tratamiento y en el pronóstico de la enfermedad. KIM-1(Kidney Injury Molecule-1) es una glicoproteína que actúa como receptor para fosfatidilserina y TIM-4 (T-Cell Immunoglobulin and Mucin Domain-4); aunque se expresa en diferentes células y tejidos, su expresión se produce principalmente en células del epitelio tubular proximal de las nefronas. En personas sanas KIM-1 no se expresa, pero durante el daño en las células epiteliales tubulares, se sobreexpresa y su fracción soluble es secretada en orina y/o filtrada a la sangre, lo que aumenta su concentración y permite su detección en estos fluidos; por esta razón, se ha propuesto como un biomarcador de daño renal. En fases tempranas, KIM-1 tiene una función protectora ante el insulto renal, pero su expresión sostenida en células del epitelio tubular se ha asociado con la enfermedad renal crónica y la fibrosis renal. En esta revisión, describimos la estructura de KIM-1, su expresión y su función tanto en el sistema inmunológico como en la enfermedad renal.

Tim-1 promotes cisplatin nephrotoxicity

2011 ◽  
Vol 301 (5) ◽  
pp. F1098-F1104 ◽  
Author(s):  
Yuji Nozaki ◽  
David J. Nikolic-Paterson ◽  
Hideo Yagita ◽  
Hisaya Akiba ◽  
Stephen R. Holdsworth ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Kidney Injury ◽  
Mucin 1 ◽  
Antibody Treatment ◽  
Cisplatin Nephrotoxicity ◽  
Renal Tubular Cells ◽  
Kidney Injury Molecule 1

Nephrotoxicity is a frequent complication of cisplatin-based chemotherapy, in which T cells are known to promote acute kidney injury. In this study, we examined the role of T cell immunoglobulin mucin 1 (Tim-1) in cisplatin-induced acute kidney injury using an inhibitory anti-Tim-1 antibody. Tim-1 acts to modulate T cell responses, but it is also expressed by damaged proximal tubules in the kidney, where it is known as kidney injury molecule-1 (Kim-1). Anti-Tim-1 antibodies attenuated cisplatin nephrotocity, with less histologic damage, improved renal function, and fewer leukocytes infiltrating the kidney compared with control antibody-treated mice. Renal NF-κB activation and apoptosis were reduced, and proinflammatory renal cytokine and chemokine mRNA expression was decreased. Renal Kim-1 expression was reduced, consistent with the diminished kidney injury after anti-Tim-1 antibody treatment. Furthermore, anti-Tim-1 antibodies reduced early systemic CD4+ and CD8+ T cell activation, apoptosis, and cytokine production. To determine whether the protective actions of anti-Tim-1 antibodies were due to effects on renal tubular cells, cisplatin nephrotoxicity was studied in Rag1−/− mice. Anti-Tim-1 antibodies did not affect renal dysfunction or histologic damage in Rag1−/− mice, showing that the benefits of inhibiting Tim-1 come from T cell effects. As Tim-1 plays an important role in promoting cisplatin nephrotoxicity, inhibiting Tim-1 may be a therapeutic strategy to prevent cisplatin-induced acute kidney injury.

Effects of prophylactic administration of glutamine on CD4+ T cell polarisation and kidney injury in mice with polymicrobial sepsis

2019 ◽  
Vol 122 (6) ◽  
pp. 657-665 ◽  
Author(s):  
Yu-Chen Hou ◽  
Jin-Ming Wu ◽  
Kuen-Yuan Chen ◽  
Po-Da Chen ◽  
Cing-Syuan Lei ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
T Cell ◽  
Late Phase ◽  
Kidney Injury ◽  
Polymicrobial Sepsis ◽  
Control Group ◽  
T Cell Apoptosis ◽  
Inflammatory Protein ◽  
Kidney Injury Molecule 1

AbstractThe present study investigated the effects of glutamine (GLN) pretreatment on CD4+ T cell polarisation and remote kidney injury in mice with gut-derived polymicrobial sepsis. Mice were randomly assigned to three groups: normal control fed with American Institute of Nutrition (AIN)-93G diet and two sepsis groups provided with either AIN-93G-based diet or identical components, except part of casein was replaced by GLN. Mice were given their respective diets for 2 weeks. Then, mice in the sepsis groups were performed with caecal ligation and puncture and were killed 72 h after the surgery. Blood, spleens and kidneys were collected for further examination. The results showed that sepsis resulted in decreased circulating and splenic total T lymphocyte and CD4+ T cell percentages, whereas IL-4-, and forkhead box p3 (Foxp3)-expressing CD4+ T cells percentages were up-regulated. Compared with the sepsis control group, pretreatment with GLN maintained blood T and CD4+ T cells and reduced percentages of IL-4- and Foxp3-expressing CD4+ T cells. Also, a more pronounced activation and increased anti-apoptotic Bcl-2 gene expression of splenic CD4+ T cells were observed. Concomitant with the decreased plasma IL-6, keratinocyte-derived chemokine (KC) levels, the gene expression of KC, macrophage inflammatory protein-2 and renal injury biomarker kidney injury molecule-1 (Kim-1) were down-regulated when GLN was administered. These findings suggest that antecedent of GLN administration elicit a more balanced blood T helper cell polarisation, sustained T cell populations, prevented splenic CD4+ T cell apoptosis and attenuated kidney injury at late phase of polymicrobial sepsis. GLN may have benefits in subjects at risk of abdominal infection.

Endogenous Tim-1 promotes severe systemic autoimmunity and renal disease MRL-Faslpr mice

2014 ◽  
Vol 306 (10) ◽  
pp. F1210-F1221 ◽  
Author(s):  
Yuji Nozaki ◽  
A. Richard Kitching ◽  
Hisaya Akiba ◽  
Hideo Yagita ◽  
Koji Kinoshita ◽  
...  
Keyword(s):  
T Cell ◽  
Cellular Proliferation ◽  
Kidney Injury ◽  
Skin Lesions ◽  
Mucin 1 ◽  
Leukocyte Accumulation ◽  
Systemic Autoimmunity ◽  
Cell Alterations ◽  
Kidney Injury Molecule 1 ◽  
Antibody Levels

The T-cell immunoglobulin mucin 1, also known as kidney injury molecule-1, modulates CD4+ T-cell responses and is also expressed by damaged proximal tubules within the kidney. Both Th subset imbalance (Th1/Th2/Th17) and regulatory T-cell and B-cell alterations contribute to the pathogenesis of autoimmune disease. This study investigated the effects of an inhibitory anti-T-cell immunoglobulin mucin 1 antibody (RMT1–10) in lupus-prone MRL- Fas lpr mice. MRL- Fas lpr mice were treated with RMT1–10 or a control antibody intraperitoneally twice weekly from 3 mo of age for 16 wk. RMT1–10 treatment significantly improved survival, limited the development of lymphadenopathy and skin lesions, preserved renal function and decreased proteinuria, reduced serum anti-DNA antibody levels, and attenuated renal leukocyte accumulation. Th1 and Th17 cellular responses systemically and intrarenally were reduced, but regulatory T and B cells were increased. RMT1–10 treatment also reduced glomerular immunoglobulin and C3 deposition and suppressed cellular proliferation and apoptosis. Urinary excretion and renal expression of kidney injury molecule-1 was reduced, reflecting diminished interstitial injury. As RMT1–10 attenuated established lupus nephritis, manipulating immune system T-cell immunoglobulin mucin 1 may represent a therapeutic strategy in autoimmune diseases affecting the kidney.

scholarly journals T Cell Expression and Release of Kidney Injury Molecule-1 in Response to Glucose Variations Initiates Kidney Injury in Early Diabetes

2021 ◽  
Author(s):  
Josephine M. Forbes ◽  
Domenica A. McCarthy ◽  
Andrew J. Kassianos ◽  
Tracey Baskerville ◽  
Amelia J. Fotheringham ◽  
...  
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
T Cell ◽  
High Risk ◽  
Kidney Disease ◽  
Kidney Injury ◽  
Glycemic Variability ◽  
Low Risk ◽  
Kidney Injury Molecule 1

Half of the mortality in diabetes is seen in individuals <50 years of age and commonly predicted by the early onset of kidney disease (DKD). In Type 1 diabetes, increased uACR (urinary albumin-creatinine ratio) during adolescence defines this risk, but the pathological factors responsible remain unknown. We postulated that early in diabetes, glucose variations contribute to kidney injury molecule- 1 (KIM-1) release from circulating T cells, elevating uACR and DKD risk. <p>DKD risk was assigned in youth with type 1 diabetes [n=100; 20.0±2.8 yrs; M:F-54:46, HbA<sub>1C</sub>-66.1(12.3) mmol/mol; diabetes duration-10.7±5.2 yrs; BMI-24.5(5.3) kg.m<sup>-2</sup>] and 10 year historical uACR, HbA<sub>1C</sub> and random blood glucose concentrations collected retrospectively. Glucose fluctuations in the absence of diabetes were also compared to streptozotocin diabetes in <i>Apolipoprotein E-/-</i> mice. Kidney biopsies were used to examine infiltration of KIM-1 expressing T cells in DKD and compared with other chronic kidney disease.</p> <p>Individuals at high risk for DKD had persistent elevations in uACR (uACR<sub>AUC0-10yrs</sub>, 29.7±8.8 vs 4.5±0.5; <i>P</i><0.01 vs low risk) and early kidney dysfunction including ~8.3ml.min<sup>-1</sup>.1.73m<sup>-2</sup> higher estimated glomerular filtration rates (eGFR<sub>SCHWARTZ</sub>; <i>P<sub>adj</sub></i> <0.031 vs low risk) and plasma KIM-1 concentrations (~15% higher vs low risk;<i> P</i><0.034). High risk individuals had greater glycemic variability and increased peripheral blood T cell KIM-1 expression, particularly on CD8+ T cells. These findings were confirmed in a murine model of glycemic variability both in the presence and absence of diabetes. KIM-1+ T cells were also infiltrating kidney biopsies from individuals with DKD. Healthy primary human proximal tubule epithelial cells exposed to plasma from high risk youth with diabetes showed elevated collagen IV and SGLT2 expression, alleviated with KIM-1 blockade. Taken together, these studies suggest that glycemic variations confer risk for DKD in diabetes via increased CD8+ T cell production of KIM-1.<b><br> </b></p>

T cell expression and release of kidney injury molecule-1 in response to glucose variations initiates kidney injury in early diabetes.

Diabetes ◽  
2021 ◽  
pp. db201081
Author(s):  
Josephine M. Forbes ◽  
Domenica A. McCarthy ◽  
Andrew J. Kassianos ◽  
Tracey Baskerville ◽  
Amelia J. Fotheringham ◽  
...  
Keyword(s):  
T Cell ◽  
Kidney Injury ◽  
Early Diabetes ◽  
Kidney Injury Molecule 1 ◽  
Cell Expression

scholarly journals T Cell Expression and Release of Kidney Injury Molecule-1 in Response to Glucose Variations Initiates Kidney Injury in Early Diabetes

2021 ◽  
Author(s):  
Josephine M. Forbes ◽  
Domenica A. McCarthy ◽  
Andrew J. Kassianos ◽  
Tracey Baskerville ◽  
Amelia J. Fotheringham ◽  
...  
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
T Cell ◽  
High Risk ◽  
Kidney Disease ◽  
Kidney Injury ◽  
Glycemic Variability ◽  
Low Risk ◽  
Kidney Injury Molecule 1

Half of the mortality in diabetes is seen in individuals <50 years of age and commonly predicted by the early onset of kidney disease (DKD). In Type 1 diabetes, increased uACR (urinary albumin-creatinine ratio) during adolescence defines this risk, but the pathological factors responsible remain unknown. We postulated that early in diabetes, glucose variations contribute to kidney injury molecule- 1 (KIM-1) release from circulating T cells, elevating uACR and DKD risk. <p>DKD risk was assigned in youth with type 1 diabetes [n=100; 20.0±2.8 yrs; M:F-54:46, HbA<sub>1C</sub>-66.1(12.3) mmol/mol; diabetes duration-10.7±5.2 yrs; BMI-24.5(5.3) kg.m<sup>-2</sup>] and 10 year historical uACR, HbA<sub>1C</sub> and random blood glucose concentrations collected retrospectively. Glucose fluctuations in the absence of diabetes were also compared to streptozotocin diabetes in <i>Apolipoprotein E-/-</i> mice. Kidney biopsies were used to examine infiltration of KIM-1 expressing T cells in DKD and compared with other chronic kidney disease.</p> <p>Individuals at high risk for DKD had persistent elevations in uACR (uACR<sub>AUC0-10yrs</sub>, 29.7±8.8 vs 4.5±0.5; <i>P</i><0.01 vs low risk) and early kidney dysfunction including ~8.3ml.min<sup>-1</sup>.1.73m<sup>-2</sup> higher estimated glomerular filtration rates (eGFR<sub>SCHWARTZ</sub>; <i>P<sub>adj</sub></i> <0.031 vs low risk) and plasma KIM-1 concentrations (~15% higher vs low risk;<i> P</i><0.034). High risk individuals had greater glycemic variability and increased peripheral blood T cell KIM-1 expression, particularly on CD8+ T cells. These findings were confirmed in a murine model of glycemic variability both in the presence and absence of diabetes. KIM-1+ T cells were also infiltrating kidney biopsies from individuals with DKD. Healthy primary human proximal tubule epithelial cells exposed to plasma from high risk youth with diabetes showed elevated collagen IV and SGLT2 expression, alleviated with KIM-1 blockade. Taken together, these studies suggest that glycemic variations confer risk for DKD in diabetes via increased CD8+ T cell production of KIM-1.<b><br> </b></p>

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