Measuring the workings of the kidneys-one "nephron" at a time | NIDDK

2021-12-14 11:01:35 By : Mr. Yong Hong

Scientists have developed a new method to calculate the average rate at which a single kidney nephron filters blood-an important indicator of kidney health. The basic functional unit of the kidney is the nephron, which is composed of various cells and structures that work together to filter waste, remove excess fluid in the blood, and balance various body chemicals. In these structures, the glomerulus is the basic filtering device. A common measure of kidney function called the glomerular filtration rate (GFR) is an estimate of the blood that all nephrons in the kidney filter every minute. However, calculating the GFR of a single nephron is complicated for many reasons: there are significant individual differences in the number of nephrons per kidney; differences in nephron size and the amount of blood filtered by each nephron; and the availability of kidney biopsy samples Is limited. Researchers have now developed a method to determine the GFR of a single nephron using biopsies from nearly 1,400 people, ranging in age from their 20s to 70s, and 58% of them are women. These tiny biopsy samples were collected at the time of transplantation. People who donate kidneys usually do not have chronic kidney disease or its major risk factors (for example, diabetes, high blood pressure).

To calculate the single nephron GFR, the scientists first measured the total GFR and used a three-dimensional imaging technique that can determine the volume of the kidney. They then obtained a biopsy sample at the time of donation to determine the density of the kidney's nephrons and the average nephron size. With these measurement results, a simple calculation can show the number of nephrons per kidney (860,000 on average) and the GFR of single nephrons per person. Their analysis of the cohort of kidney donors yielded several important findings. There were no significant differences in single nephron GFR in terms of gender, age (under 70 years), or height (under 6 feet 2 inches). However, larger nephron size is associated with higher single nephron GFR, and over time, glomerulus or blood vessel sclerosis exceeds normal expectations. In addition, some of the characteristics of the participants were associated with elevated single nephron GFR, including obesity, family history of end-stage renal disease, and height (over 6 feet 2 inches).

Some of the features found to be associated with elevated GFR in single nephrons are known risk factors for kidney disease-given the clear association between lower total GFR and kidney disease, these findings seem to be contradictory. However, the scientists explained that some of these risk factors are usually also related to the low number of nephrons in the kidney. This lower total number of nephrons, in turn, causes individual nephrons to compensate by filtering blood at a higher rate, thereby raising total GFR to normal levels. However, in some people, over time, an increase in the workload of a single nephron and other risk factors may lead to further loss of nephrons and deterioration of renal function, ultimately leading to a decline in total GFR and renal function. Further research is needed to better understand how these characteristics affect the relationship between single nephron GFR, total GFR, and kidney health.

Scientists recognize the limitations of this study, such as the lack of diversity in the cohort. For example, only 2% of participants were black. In addition, the difficult and intensive process of kidney biopsy collection limits research to donated kidneys. Since the kidneys selected through the donor screening process are in a relatively healthy state, additional research is needed to determine the prevalence of the results for patients with reduced renal function. Despite these limitations, this report establishes the first method of calculating the GFR of a single nephron of the human kidney, which may lead to a deeper understanding of the link between the GFR of the nephron and overall renal function and health.

Denic A, Mathew J, Lerman LO... and Rule AD. Single nephron glomerular filtration rate in healthy adults. N Eng J Med 376: 2349-2357, doi: 10.1056/NEJMoa1614329, 2017.