In honor of National Kidney Month, this is the first in a two-part story on kidney disease, how it develops, and what research is happening at Joslin to improve treatment and prevent it from developing and progressing. Today’s blog details why kidneys fail in the presence of high blood sugar, and how kidney disease is developed.
Kidneys are the filters of your body, removing the waste and byproducts of your day-to-day life. When they fail, that waste builds up in your body and becomes toxic. Twenty to 40 percent of people with diabetes will develop some degree of kidney disease. A subset of that number will progress to end-stage renal disease, which can only be treated with dialysis or a kidney transplant.
To understand what goes wrong in kidney disease, we first have to understand how these organs function when they’re healthy. There are two kidneys in the body, and each is home to about one million little filters responsible for cleaning waste from the blood. The filters, or nephrons, are made up of two parts; first is the glomerulus, which removes fluid and waste products while preventing blood cells and large molecules from leaving the blood. Each glomerulus is connected to a long tube, called the tubule, which sends the needed minerals back to the bloodstream and removes the waste through urine.
“And so you need all these million tubules in each kidney functioning properly,” says Robert Stanton, M.D., Chief of the Kidney and Hypertension Section at Joslin Diabetes Center and Associate Professor of Medicine at Harvard Medical School. “Over time, as you lose these filters, that’s when you start getting in trouble.” We naturally lose some of these filters through aging. In fact, normal kidney function can continue at up to a 70 percent loss. But high blood sugar from uncontrolled diabetes can speed this process up, leading to lasting and irreversible damage.
High blood sugar affects the body on a cellular level in a number of ways, all of which can lead to complications including kidney disease. One major way high glucose causes damage is by causing oxidative stress. This occurs in two ways. First, it can increase the number of oxidants in the body. Second, it decreases the ability of anti-oxidants to do their jobs. These two problems are related, says Dr. Stanton. “There’s a normal level of oxidants that you need [in your body], so it’s not their fault. They just need to be regulated normally. But the glucose impairs the normal regulation and that is when the levels get too high.”
When they’re not regulated, oxidants change the structures of proteins, sugars and fats so they don’t work properly. “Membranes will get stuck, proteins don’t work well, normal cellular processes break down,” says Dr. Stanton. When cellular processes break down, so do the larger-scale structures that depend on them—like the filters in the kidneys.
High blood sugar also increases your A1C—short for “glycoslated hemoglobin A1C.” When there is too much glucose in the blood, it begins to cling to hemoglobin molecules in red blood cells. The higher the levels, the more it clings to the hemoglobin, and thus the higher the A1C.
“These sugar-coated proteins cause damage to cells in similar ways to oxidants: not operating properly, they actually can cause oxidative stress of their own, and a variety of other issues,” says Dr. Stanton. Oxidants and A1C aside, there are a host of other kidney-related signaling proteins and enzymes whose functions are altered by high blood-sugar.
“All of these contribute to the development and the worsening of people with kidney disease,” says Dr. Stanton. “High blood pressure also damages the kidneys. And a combination of high blood pressure and high sugar eventually leads to damage.”
Kidney disease is on the rise in this country, and it seems to be at least somewhat linked to the rise in cases of diabetes. “Kidney disease as an issue has been exploding over the years,” says Dr. Stanton. “It’s a 20-fold increase in end stage kidney disease over the last 25 years. Now there are about 600 thousand people who are either on dialysis or need a transplant, and the majority of those people have diabetes.”
Kidney function should be monitored in two ways, both of which check filtering ability. The first, called the glomerular filtration rate (GFR), tests how well the glomerulus is working by measuring the level of creatinine in the bloodstream. Creatinine is a byproduct of muscle metabolism, and when kidneys are working it gets filtered out of the system in urine. Detecting too much creatinine in the blood means the kidneys’ filters aren’t doing their jobs. Doctors use that creatinine level to calculate your GFR; a low GFR indicates kidney disease.
The other marker of kidney disease is increased protein in the urine. This protein, called albumin, is supposed to stay in the blood stream. If it’s found in the urine, that’s another marker of a breakdown of the filters.
Getting these tests is good for more than just your kidneys; it’s also important for your heart. “There’s this big risk of developing cardiovascular complications [once you’ve been diagnosed with kidney disease], so we’re trying to remind people that with decreased kidney function you should be also taking your cardiovascular risk very seriously,” says Dr. Stanton. He recommends regular cholesterol checks and keeping any other cardiovascular risk factors under control.
Taking medications, such as ACE inhibitors or beta blockers, can help stabilize kidney disease, but as of now there are no drugs that can recover lost kidney function. “Blood sugar control, blood pressure control and lowering your albumin level with certain medications are protective. But you don’t generally make things better. You usually just stabilize it if you can,” says Dr. Stanton.
Not everyone with diabetes develops kidney disease, and not everyone who develops kidney disease will progress to end stage renal disease.
In part two of this two-part kidney story, find out what Dr. Stanton and his colleagues are discovering in the lab that could help those at risk for developing kidney disease and end-stage renal disease.
For more information about Joslin’s Kidney Clinic or to make an appointment, click here.