Human renal proximal tubule epithelial cells stained for gamma gtp

   

 

       

 

 

 

The kidney is a key organ of the urinary system, which plays a pivotal role in many physiological processes such as the maintenance of homeostasis, the excretion of nitrogen waste and the secretion of endocrine factors.  Nephron -- the structural and functional unit of kidney -- is a highly complex organ comprised of convoluted tubules, the cortical collecting ducts, the calyxes, and the renal pelvis.  The epithelial cells (renal epithelial cells) located in the tubules and ducts differ in their physiology and morphology and exert critical functions in the kidney.1  Renal cells in the proximal tubule play physiological roles in the re-absorption of small molecular weight proteins, peptides and glucose via receptors present on the villi of their luminal surface2. This localization and biological role exposes these cells to numerous challenging stimuli in the event of any up-stream pathology, with excessive protein, glucose, toxins, advanced glycation end products (AGEs) and bacterial products all being able to perturb normal Renal epithelial cell physiology.3   

 

Image Courtesy of Wikimedia

Lonza's Human Renal Cells include cells isolated from various normal human kidney tissue specific to each cell type. Human Renal Proximal Tubule Cells are isolated from the proximal tubule. Human Renal Epithelial Cells (HRE) comprise cells from the cortex and glomerular region. Human Renal Cortical Cells (HRCE) are from proximal and distal tubule. Human Mesangial Cells (HMC) are isolated from the renal glomerulus and modified smooth muscle cells between capillaries.

 

In vitro renal epithelial cell culture systems are considered to be the most valuable tool for studying renal physiology, nephrotoxicity studies, drug transporter studies, disease models, renal transplantation models, cancer models, co-culture models, 3D cell culture models, cytokine production, glomerulonephritis, prostaglandin activity, & cellular function and differentiation, gene expression profiling. Refer to our select references highlighting different applications of Lonza's renal cells.

 

Renal Drug Transporters

Renal transporter human cells are promising tools that  provide crucial cell-based assay models to study the absorption, distribution, metabolism, excretion, and toxicity properties of compounds. The kidney is a vital organ for the elimination of therapeutic drugs and their metabolites. Renal drug transporters, which are primarily located in the renal proximal tubules, play an important role in tubular secretion and reabsorption of drug molecules in the kidney4. Renal clearance is a major pathway of drug elimination, involves a variety of transporters predominantly expressed in the proximal tubule, and they work in tandem to eliminate drugs from the blood circulation to the urine. Major renal transporters include organic cation transporter 2 (hOCT2) and organic anion transporters 1 (hOAT1) and 3 (hOAT3). Transporter-mediated drug–drug interactions (DDIs) are increasingly recognized as an important modifier  of the pharmacokinetics and pharmacodynamics of drugs. One such study was done using Lonza’s Human Renal Proximal Tubule Epithelial Cells, where the effect of Cobicistat (COBI) on the cytotoxicity of  Tenofovir (TFV) in renal cell cultures was examined to elucidate renal drug-drug interaction between these two components5.

 

Nephrotoxicity

Exposure to drugs and chemicals often results in toxicity to living organisms.  Kidneys may be much more susceptible than other organs to the toxic effects of a variety of chemicals. Certain classes of drugs are known to cause renal failure by preferential accumulation within the proximal tubule cells. In vitro studies have been conducted to evaluate the direct toxicity effect of certain drugs on human renal proximal tubule epithelial cells.

 

Renal cell carcinoma (RCC)

RCC accounts for approximately 2% of all cancers worldwide and its incidence has increased by 2–3% in the last decade, with even higher rates in developed countries.  RCC is a renal cortical tumor typically characterized by malignant proximal convoluted tubular epithelium. Gene expression studies have been conducted with RCC cell lines and normal human renal cells from Lonza to understand and identify different cancer biomarkers for RCC.

 

 

References

1. Cynthia Van der Hauwaert , Grégoire Savary , Viviane Gnemmi , François Glowacki , Nicolas Pottier, Audrey Bouillez, Patrice Maboudou, Laurent Zini, Xavier Leroy, Christelle Cauffiez, Michaël Perrais , Sébastien Aubert. Isolation and Characterization of a Primary Proximal Tubular Epithelial Cell Model from Human Kidney by CD10/CD13 Double Labeling. PLoS One (2013); 8(6): e66750

2. Deepak Nihalani & Katalin Susztak, Sirt1–Claudin-1 crosstalk regulates renal function, Nature Medicine (2013); 19, 1371–1372

3. Sampangi S, Kassianos AJ, Wang X, Beagley KW, Klein T, Afrin S. The Mechanisms of Human Renal Epithelial Cell Modulation of Autologous Dendritic Cell Phenotype and Function. PLoS ONE (2015); 10(7): e0134688

4. Jia Yin, Joanne Wang. Renal drug transporters and their significance in drug–drug interactions. Acta Pharmceutica Sinca B (2016); 6(5): 363–373

5. Kirsten M. Stray, Rujuta A. Bam, Gabriel Birkus, Jia Hao, Eve-Irene Lepist, Stephen R. Yant, Adrian S. Ray, Tomas Cihlar.  Evaluation of the effect of cobicistat on the in vitro renal transport and cytotoxicity potential of tenofovir. Antimicrobial Agents and Chemotherapy (2013); 57(10): 4982-4989