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Measuring How Well the Kidney Works—One “Nephron” at a Time

Scientists developed a new method for calculating the average rate that a single kidney nephron filters blood—an important measure of kidney health. The basic functional unit of the kidney is the nephron, which consists of various cells and structures that work together to filter waste products, remove excess fluid from the blood, and balance various body chemicals. Of these structures, the glomerulus is the fundamental filtering apparatus. A common kidney function measurement called the glomerular filtration rate (GFR) is an estimate of blood filtered per minute by all the nephrons within the kidneys. However, calculating single nephron GFR is complicated for a number of reasons: there is substantial individual variation in the number of nephrons per kidney; there is variation in nephron size and in the amount of blood filtered per nephron; and availability of kidney biopsy samples is limited. Researchers have now developed a method for determining single-nephron GFR using biopsies from almost 1,400 people, with ages ranging from 20s to 70s, 58 percent of whom were women. These tiny biopsy samples were collected at the time of transplantation. People who donate their kidneys typically do not have chronic kidney disease or its major risk factors (e.g., diabetes, hypertension).

To calculate single-nephron GFR, the scientists first measured the total GFR and used a three-dimensional imaging technique that can determine the kidney’s volume. Then they obtained a biopsy sample at the time of donation to determine the kidney’s nephron density, as well as the average nephron size. With these measurements in hand, simple calculations revealed the number of nephrons per kidney (average of 860,000) and the single-nephron GFR for each individual. Several critical findings emerged from their analyses of the kidney donor cohort. The single-nephron GFR did not vary significantly by, sex, age (when under 70) or height (when under 6 feet, 2 inches). However, larger nephron size was associated with higher single-nephron GFR, as were hardening of glomeruli or blood vessels beyond what would be normally expected over time. In addition, some participant characteristics were linked to elevated single-nephron GFRs, including obesity, family history of end-stage renal disease, and height (over 6 feet, 2 inches).

Some of the characteristics found to be associated with elevated single-nephron GFR are known risk factors for kidney disease—seemingly contradictory findings, considering the clear association between lower total GFR and kidney disease. However, the scientists explain that some of these risk factors are often also associated with low numbers of nephrons in the kidney. This lower total number of nephrons could in turn cause individual nephrons to compensate by filtering blood at a higher rate, raising the total GFR to a normal level. However, in some people, over time the increased single nephron work load and other risk factors could lead to further nephron losses and kidney function deterioration, leading to eventual declining total GFR and kidney function. Further research would be needed to understand better how these characteristics affect the relationships between single-nephron GFR, total GFR, and kidney health.

The scientists recognize limitations in the study, such as the lack of diversity in the cohort. For example, only 2 percent of participants were Black. Also, the difficult and intensive process of kidney biopsy collection limited the study to donated kidneys. Due to the relatively healthy status of the kidneys selected through the donor screening process, additional research is needed to determine the generalizability of the results to those with reduced kidney function. Despite these limitations, this report establishes the first method for calculating single-nephron GFR from human kidneys, potentially leading to a greater understanding of the link between nephron GFR and overall kidney function and health.

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