Use of Primary Isolates From Human Kidney to Study the Molecular Aspects of Blood Pressure Regulation

Henrik Dimke

High blood pressure (hypertension) is a major health problem affecting an increasing portion of the population. In fact, it is estimated that hypertension will affect up to 1.56 billion people by the year 2025. The Danish Heart Association estimates that approximately 950,000 Danes have high blood pressure, a disease with many complications, affecting both the quality of life and overall mortality. The kidneys play critical roles in a number of essential physiological processes. As such, the kidney is especially important for the maintenance of blood pressure, due to its ability to adjust the reabsorption of salt from the filtrate back into the blood. The importance of understanding how the human kidney regulates blood pressure is reflected in the dominant diseases of our society. Changes in renal electrolyte transport processes that reclaim salt from the filtrate are disturbed to varying degree in most hypertensive conditions.

The project aims to implement the use of primary isolated tissue from the human kidney to study the molecular aspects of blood pressure maintenance and hypertension. In particular, primary isolated tissue from donated kidneys obtained from patients undergoing nephrectomy, due to renal carcinomas, will be utilized. The use of these isolates would substantially reduce the number of animals needed for study, as we can replace the experiments on mouse isolates with those from the human kidney. Importantly, the tissue utilized from human kidney would normally be discarded after nephrectomy.

Almost all studies on these mechanisms are derived from laboratory animals, mainly rats and mice. Practically, this requires a large quota of experimental animals. Additionally, these models do not always reflect the physiological and pathophysiological responses seen in humans. In fact, the mouse kidney differs in its resistance to nephrotoxic drugs and in its responses to hypertensive compounds and pathogenic mutations. Due to this variability, many findings cannot be extrapolated to humans. A better understanding of how the human kidney function, could increase understanding of the pathological mechanisms that promote hypertension and may help the treatment of this highly prevalent disease.


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