Cultured Human Kidney Cells Improve Chronic Kidney Injury

Chronic kidney disease (CKD) is extremely expensive to treat and also leads to additional complications, such as heart and circulatory troubles. In general, when you have CKD, your life is a drag. ~13% of the worldwide population has CKD and in the US alone, the estimated Medicare costs for the treatment of this disease is $42 million.

There are drugs that can treat CKD, but these drugs (statins, angiotensin 2 receptor blockers and angiotensin converting enzyme (ACE) inhibitors, and erythropoietin to improve anemia) must be given for some time and at high doses before their effects become apparent.

The hormone erythropoietin (EPO) is made by the kidneys, and EPO signals to the bone marrow to produce more red blood cells. Recombinant versions of EPO are given to anemia patients, and have also been used illicitly in aerobic athletics to artificially boost red blood cell production (e.g., Floyd Landis, Lance Armstrong, etc.). However, EPO has another function in CKD in that EPO administration seems to protect the kidney from damage caused by low oxygen delivery. EPO production is quite low in CKD patients and this might play a role in the problems encountered by CKD patients.

The laboratory of James Yoo from the Institute for Regenerative Medicine at Wake Forest University has investigated the ability of cultured, human kidney cells that express EPO to improve kidney structure and function in a rodent model of CKD.

In this experiment, Yoo and his coworkers cut off the blood supply to the kidneys of hairless rats and then fed them the antibiotic gentimicin for a day (five doses). 8-10 weeks after this treatment, kidney function was reduced and the rats had all the signs of CKD.

Next, Yoo and others injected into the kidneys of these rats cultured human kidney cells. One group of rats received injections of buffer into their kidneys, some received cultured human kidney cells, and another group received cultured kidney cells that had been engineered to express EPO. These kidney cells came from a discarded organ from a 51-year-old human organ donor.

The kidneys of these rats were assayed for function and structure. One of the features of CKD is lots of protein in the urine. When the levels of protein in the urine of these rats was examined 1, 4, and 12 weeks after they had received infusions of the kidney cells, along with other markers of kidney damage, the levels of protein in the urine were high in the rats injected with buffer, lower in those injected with cultured kidney cells, and much mower in those injected with the EPO-expressing kidney cells. Also, hemoglobin levels (hemoglobin is the protein in red blood cells that ferries oxygen from the lungs to the tissues) were significantly higher in the rats injected with EPO-expressing kidney cells.

Next, Yoo and his colleagues examined the kidneys for inflammation and scarring. Scarring is relatively easy to detect because there are tissue stains that will highlight scarring (e.g., Masson’s Trichome stain). Once again, the buffer injected kidneys were loaded with scars, the kidney cell-injected kidneys had much less scarring and the rats injected with EPO-expressing kidney cells had even less scarring in most of the kidney. Also the presence of inflammatory cells in the kidney, which is indicative of cell damage, was significantly lower in kidneys injected with either type of cultured kidney cell. As an added bonus, Yoo’s group examined the markers of kidney cell damage (8-OHdG) and these were lower in the kidneys injected with cultured human kidney cells.

Did the injected cells hang around in the kidneys and contribute to the kidney? The answer seems to be, only a bit. When the rat kidneys were checked for human cells 12 weeks after injection, very few human kidney cells were found.

These experiments suggest that cultured kidney cells, particularly EPO-expressing ones, can initiate regeneration in damaged kidneys. While this experimental protocol requires adjustment and tweaking, it suggests a potential therapeutic strategy for treating CKD patients.