Researchers Identify Biomarkers For Chronic Kidney Disease

Even though present in trace amounts, D-amino acid levels in patients can be measured to provide prognostic information of chronic kidney disease. 

Asian Scientist Newsroom | August 8, 2016 | Health 

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AsianScientist (Aug. 8, 2016) - Researchers in Japan have found that measuring D-amino acid levels in patients can help doctors to identify chronic kidney disease patients at high-risk for progression to end-stage kidney disease. Their research findings were published in Scientific Reports. 

Chronic kidney disease is a critical health problem and can lead to end-stage kidney disease. Additionally, the risk of cardiovascular diseases and death increases with the progression of chronic kidney disease. There is currently no effective method to determine the prognosis of chronic kidney disease. 

On the other hand, D-amino acids are increasingly recognized as potential biomarkers in several diseases. Although D-amino acids are usually only present in trace amounts in the body, recent technological advancements have enabled us to measure D-amino acids with much higher sensitivity. 

Led by Drs. Tomonori Kimura and Yoshitaka Isaka from the Department of Nephrology at Osaka University, the research group measured D-amino acid levels in the blood of chronic kidney disease patients and followed their prognoses. 16 out of 21 D-amino acids were detected in the blood of these patients. 

Further analyses revealed that D-serine and D-asparagine were associated with the progression of chronic kidney disease. Furthermore, the risk of progression to end-stage kidney disease was elevated two- to four-fold in patients with higher levels of these two types of D-amino acids. 

The researchers hope that the results of the present study will provide a new method for clinicians to identify chronic kidney disease patients at high-risk for progression to end-stage kidney disease. This method is also applicable to diseases like cardiovascular disease, diabetes mellitus and hypertension, the researchers said, as the prognoses of these diseases are strongly influenced by chronic kidney disease progression. 

The article can be found at: Kimura et al. (2016) Chiral Amino Acid Metabolomics for Novel Biomarker Screening in the Prognosis of Chronic Kidney Disease. 

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Source: Osaka University. 

http://www.asianscientist.com/2016/08/health/biomarkers-d-amino-acids-chronic-kidney-disease/

What Your Kidneys May Be Telling You

December 2013

Don't miss these subtle warnings...

Are your kidneys working normally? If you're like most people, you probably don't really know.

About one in every nine American adults suffers from chronic kidney disease (CKD). But many of these people have no idea that they're affected until they develop cardiovascular disease due to kidney disease…or have kidney failure or even end-stage renal disease, necessitating dialysis treatments or a kidney transplant.

What's new: With up to 44 million people in the US potentially affected by CKD—a startling number that rivals the diabetes epidemic—scientists now are developing new ways to detect and fight this problem.


What you need to know…

WHO'S AT RISK

If you have early-stage kidney disease, chances are you won't experience any pain and may, in fact, feel fine. Any signs that do appear are likely to be vague (for example, a slight increase in frequency of urination or becoming fatigued more easily) and even may resemble those triggered by other conditions, such as prostate enlargement or anemia.

Anyone can develop kidney disease, but it's long been known that people who are over age 60 and/or those who have high blood pressure, diabetes or heart disease are at increased risk. People who have a family history of kidney disease, especially in a parent or sibling, are also at increased risk for CKD.

But certain other risk factors are often overlooked. These include obesity, a history of kidney stones and rheumatologic conditions such as lupus. Acute kidney injury, caused by such conditions as dehydration, infection or trauma, also may lead to CKD.

BEYOND THE USUAL RED FLAGS

The classic red flags for CKD may include slight changes in typical urine output (either more or less) and swelling of the ankles, feet or eye area due to fluid retention.

Surprising signs: Foamy urine that resembles foam on the surface of eggs as they are beaten can indicate an abundance of protein in the urine, a sign of kidney damage.

Other unusual symptoms that may, for unknown reasons, signal CKD include nonspecific muscle pains (especially at night) or dry, itchy skin (anywhere on the body) without obvious skin disease.

GETTING THE RIGHT TESTS

If you have any of the risk factors for CKD or symptoms, as described above, you should have certain screening tests at least once a year.

 

Don't overlook this test: A urinalysis, sometimes dubbed the "dipstick" test, checks more than a dozen components in urine, such as pH level, protein, glucose, nitrites and ketones. The presence of urine protein, in particular, offers an immediate clue that kidney damage may have occurred. If your doctor doesn't ask you for a urine sample to perform a urinalysis during your yearly checkup, talk to him/her about getting the test. Routine tests to screen for kidney disease…

• Serum creatinine and estimated glomerular filtration rate (eGFR). The latter test estimates how well your kidneys are filtering blood. As kidney disease worsens, your level of creatinine goes up and your eGFR goes down. An eGFR of less than 60 (for three months or longer) indicates CKD.
• Urinary albumin-to-creatinine ratio (UACR). Albumin, a protein in the blood that passes through the kidneys' microscopic filtering cells, signals kidney damage. The lower the number the better, with a normal UACR being less than 30.

Important: Exercising strenuously or eating a lot of meat before a test could raise creatinine levels, erroneously signaling a problem. Herbal supplements containing creatinine also can falsely elevate levels. This naturally occurring substance, which helps muscles make energy, often is taken by weight lifters.

AVOIDING CKD

High blood pressure and diabetes cause more than two-thirds of CKD cases in the US. Modifying those risk factors through lifestyle changes, such as limiting sodium and sugar intake, losing weight and taking prescribed medications, is crucial.

The hidden dangers: Daily use of over-the-counter nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (Advil) or naproxen (Aleve), can increase one's risk for CKD over time by constricting the blood vessels in the kidneys. For this reason, people who have CKD should avoid NSAIDs. Many herbal supplements contain compounds that can be toxic to the kidneys. Be sure to discuss these products with your doctor before using them, especially if you have CKD. For more on this, go to Kidney.org and search "Herbs.

If you need an imaging test that requires the use of dyes that contain iodine—these are used as contrast agents for computed tomography (CT) and other imaging scans—discuss your CKD risk with your doctor.

If your kidney function is normal, the dyes typically won't harm you. But these contrast agents can be toxic to the kidneys, causing acute injury to the organs if kidney function is already compromised. If this type of scan is needed by a person with advanced CKD, serum creatinine levels should be monitored before and after the scan. These patients also need to stay well-hydrated, and their kidney function must be closely followed to minimize the risks of contrast agents.

Source: Rajiv Saran, MD, professor of medicine and associate director of the University of Michigan's Kidney Epidemiology and Cost Center in Ann Arbor. He's also a principal investigator on a national chronic kidney disease surveillance system (CDC.gov/ckd), a project funded by the Centers for Disease Control and Prevention (CDC) and in partnership with the University of California, San Francisco.

http://www.bottomlinepublications.com/content/article/health-a-healing/what-your-kidneys-may-be-telling-you

Medical Tests for Kidneys

Medical Tests Made Easy

By Jay Wish, MD Introduction Patients with kidney disease need to understand the meaning of the many tests that are performed to measure kidney function, to assess the complications of kidney disease and to determine the response to treatment. This article addresses some of the tests that are most commonly performed on patients with chronic kidney disease (CKD), explaining the rationale for the tests and the implications if the tests falls outside a normal or target range. It is important for each patient with kidney disease to discuss the results of his or her own tests with their nephrologist. Tests of Kidney Function The blood urea nitrogen (BUN) is a normal product of the breakdown of proteins, both in the diet and in the body. Normal kidneys excrete urea efficiently, so the BUN level rarely exceeds 20 in patients without kidney disease. The BUN level will rise above the normal range when the ability of the kidneys to excrete urea is impaired or in situations where protein breakdown is increased (such as a high-protein diet or damage to cells). A decrease in BUN during dialysis is the most commonly used test to measure dialysis adequacy. Serum creatinine is the most commonly used test of kidney function and is more accurate than the BUN since its level is not affected by dietary protein intake. Serum refers to the liquid part of the blood, and the tests described below using the term “serum” just mean that they are blood tests. Creatinine is a normal product of muscle breakdown, and is produced at approximately the same rate every day in each person. Creatinine is normally excreted by the kidneys. A normal serum creatinine level for an adult is around 1 (0.6-1.2). Using only serum creatinine as a test of kidney function has been shown in many patients to underestimate the degree of kidney disease. Other formulas which use serum creatinine along with patient characteristics such as age, weight, gender and race are much more accurate in determining kidney function. Creatinine clearance is a measure of kidney function that can be determined from a 24-hour urine collection and a simultaneous blood sample, or it can be calculated from a formula based on serum creatinine and the patient’s age, weight and gender. The creatinine clearance test has recently fallen out of favor because it tends to overestimate kidney function as compared to glomerular filtration rate (GFR) also, because the collection of a 24-hour urine sample tends to be cumbersome and often inaccurate since it may fail to capture the entire urine output of the patient over a 24-hour period. Glomerular filtration rate (GFR) has become the “gold standard” test for the measurement of kidney function. It is the basis for the classification of the stages of CKD endorsed by the National Kidney Foundation (NKF). Another advantage of GFR is that it is expressed in terms of a value for a standard sized individual, making it possible to predict what the consequences of abnormal kidney function will be on populations of individuals irrespective of the size of a particular person. The most accurate way to determine GFR is by a kidney scan, but this is expensive and cumbersome, and is generally reserved for research protocols. It is possible to get a reasonably accurate measurement of GFR with a formula that uses the patient’s serum creatinine, age, gender and race. The GFR is also used by the Center for Medicare Services (CMS) to determine the threshold at which dialysis is initiated and by the United Network for Organ Sharing (UNOS) to determine when a patient becomes eligible for a kidney transplant. The NKF’s staging classification of CKD is shown in Table 1 with a description of the action that is recommended at each stage. If you have CKD and are not yet on dialysis, you should ask your doctor what your GFR is, then you can determine what stage you fall into and what the recommendations for further evaluation and treatment of your kidney disease and its complications are at that stage. If you are on peritoneal dialysis, the dose of peritoneal dialysis administered to you takes into account any residual kidney function you might have, and this is based on a GFR as well. Table 1: NKF Staging of CKD Stage Description Glomerular Filtration Rate (GFR) Action 0 At increased risk >90% Screening, risk reduction 1 Chronic kidney damage with normal or increased GFR >90% Diagnosis and treatment of comorbidities, slowing progression and CVD risk 2 Mild decrease in GFR 60-89% Estimating progression 3 Moderate decrease in GFR 30-59% Evaluation and treatment of complications 4 Severe decrease in GFR 15-29% Preparation for renal replacement therapy 5 Kidney failure <15% - or dialysis RRT if uremia present Anemia in Renal Disease Virtually all patients with CKD will develop anemia due to decreased production of erythropoietin (EPO) by the kidneys. EPO is a hormone produced by normal kidneys that stimulates the bone marrow to make an adequate number of red blood cells assuring oxygen delivery to all tissues. With increasing damage to the kidneys, the production of EPO decreases, so the bone marrow produces fewer red blood cells and anemia develops. Red blood cells carry oxygen to the tissues by binding the oxygen to hemoglobin which contains iron. The initial evaluation of anemia should include tests of iron, as well as certain vitamins that are required for hemoglobin production. Tests should also check for small amounts of blood leaking out in the stool. The most commonly used test to diagnose anemia is the hemoglobin level in the blood. A decreased level of hemoglobin in the blood impairs the ability to deliver oxygen to the tissues, and leads to symptoms including weakness, fatigue and shortness of breath. More importantly, a low hemoglobin level puts an additional strain on the heart, since the heart has to pump more blood in order to keep up with the oxygen demands of the tissues in the body. This may lead to cardiac complications including heart failure and heart attacks. The lower limit of a normal hemoglobin level is 12 in menstruating females and 13.5 in males and postmenopausal females. Hematocrit is the percentage volume of blood occupied by the red cells after the blood is centrifuged, and is approximately three times the hemoglobin level. It’s not as accurate a test as is measuring the hemoglobin directly. The lower limit of normal hematocrit for menstruating females is 36 and for males and postmenopausal females is 41. The two major tests to diagnose iron deficiency are transferrin saturation (TSAT) and serum ferritin. TSAT is a measure of the iron that is carried in the blood that can be delivered to the bone marrow to be incorporated into new red blood cells. When patients are treated with EPO-like drugs, it accelerates red blood cell production to a higher than normal level, so a higher than normal TSAT is required to keep up with the demand for iron by the bone marrow. The target TSAT for patients with CKD who are being treated with EPO-like drugs is 20–50 percent. Serum ferritin is another test of iron and correlates with the amount of iron that your body holds in storage. This is not iron that is in the blood or is available to the bone marrow for production of new red blood cells. It is important for patients receiving EPO-like drugs to maintain adequate iron stores so that the body does not run out of iron as new red blood cells are produced. Unfortunately, the serum ferritin may also be elevated in the setting of inflammation, independent of iron stores, so sometimes an elevated serum ferritin can be difficult to interpret by your physician. If you are an anemic patient with CKD whose TSAT is less than 20 percent or whose serum ferritin is less than 100, you should be treated with an oral or intravenous iron supplement to get your TSAT and serum ferritin back into the target range. The presence of iron deficiency will make it more difficult for your anemia to be corrected even if you are given an EPO-like agent. Vitamin deficiencies may also contribute to anemia in patients with CKD, especially if you are not eating a balanced diet. The two most important vitamins for red blood cell production are vitamin B12 and folic acid. The levels of these vitamins in the blood should be measured as part of a complete evaluation of anemia, and these vitamins should be replaced if they are deficient. Reticulocytes are the youngest red blood cells in your circulation, one or two days old, and can be identified because they take on a special stain in the blood analyzer machine. Measurement of these newest red blood cells can be helpful in determining whether anemia is due to an underproduction of red blood cells or due to the loss or destruction of existing red blood cells. Patients with anemia in the setting of CKD, because they are deficient in EPO, have an underproduction of red blood cells and, therefore, a low reticulocyte count. If your reticulocyte count is elevated, then consideration should be given as to whether your anemia might be due, in part, to the loss or destruction of red blood cells in addition to EPO deficiency. Many patients with CKD have abnormalities in blood clotting which may lead to a low-grade loss of red blood cells in the gastrointestinal tract through the stools. Therefore, a complete evaluation of anemia should include a test for hidden blood in the stool that can be done by your physician in his/her office. If blood is present in the stool, then it is important for this to be followed up by additional tests to determine whether or not this represents a condition that needs to be treated more extensively. Tests of Bone Disease Bone disease often occurs in patients with CKD. This is due to the inability of the kidneys to completely excrete phosphorus from the blood and due to the inability of the kidneys to convert vitamin D to its active form. Both of these problems lead to a decrease in serum calcium levels, which stimulates the parathyroid gland in the neck to make a hormone, called parathyroid hormone (PTH). This hormone raises the serum calcium level back towards normal by breaking down bone and releasing calcium from the bone. Treatment and prevention of bone disease in patients with CKD is directed at treating the elevated serum phosphorus with phosphate binders and dietary phosphate restriction, and providing the active form of vitamin D with a medication. This can be administered either orally or intravenously on dialysis. Therefore, it is important to periodically monitor the effectiveness of this therapy by measuring serum calcium, serum phosphorus and serum PTH levels. The target range for serum calcium in patients with CKD is 8.4-9.5. A low serum calcium level should be avoided because it stimulates the parathyroid gland to make more PTH and to accelerate bone disease. On the other hand, high serum calcium levels may lead to the deposition of calcium in soft tissues and vessels, increasing the risk of heart attacks, strokes and other forms of cardiovascular disease. The target range for serum phosphorus in patients with CKD is 3.5-5.5. Almost all patients with CKD will require dietary phosphorus restriction and/or phosphate binders to maintain serum phosphorus levels within the target range. Although elevated serum phosphorus levels generally do not produce symptoms other than itching, it is extremely important for you to monitor your serum phosphorus levels. Working with your physician and dietitian to modify your diet and phosphate therapy as needed to keep the serum phosphorus level within the target range will help. Parathyroid hormone (PTH) levels correlate with the development of bone disease in patients with CKD, and should be measured periodically. Elevated PTH levels can be treated in two ways: the administration of an activated form of vitamin D either orally or intravenously and with a newer drug called cinacalcet which directly suppresses the release of PTH from the parathyroid gland. The most commonly used test is called intact PTH (iPTH) which has a target range of 150-300 in patients on dialysis, 70-110 in patients with stage 4 CKD, and 35-70 in patients with stage 3 CKD. PTH levels higher than the target are bad because they are associated with the increased breakdown of bone which leads to loss of bone strength and increased incidence of fractures. If your PTH level is out of the target range for your stage of CKD, you should discuss this with your nephrologist. Other Lab Tests The monitoring of serum potassium levels in patients with more advanced stages of CKD and those on dialysis is important because very high serum potassium levels can lead to cardiac arrest. The level of CKD at which serum potassium levels rise above the normal range varies from individual to individual. Although the upper limit of potassium for the normal population is 5.0, patients with CKD and longstanding high potassium levels can generally tolerate potassium levels as high as the 5.5-6.0 range. Many physicians will become concerned with potassiums in this range and initiate treatment with an agent that removes potassium from the body through the gastrointestinal tract, such as Kayexalate. If your serum potassium level is elevated and you are a CKD patient not yet on dialysis, then your physician should evaluate the drugs you are receiving to determine if any might be contributing to the high potassium levels, and you may benefit from an increased dose of diuretic to augment the excretion of potassium through your urine. You should also examine your diet with a dietitian to determine whether or not you are consuming foods that are high in potassium and change your food choices accordingly. The serum sodium level is a reflection of whether or not there is too much or too little water in the body. Patients with kidney disease have an inability to excrete as much water as normal individuals, so a large water intake may lead to the retention of water in the body which dilutes the serum sodium to a lower than normal level. The normal serum sodium level is 135-145. If the serum sodium level gets down to the low 120’s, the water that has been retained, causes swelling. The symptoms that occur are due to swelling of the brain, which has no place to expand because it is enclosed in the rigid skull cavity. These symptoms include headache, nausea, vomiting and seizures. A restriction of fluid in the diet may be necessary in some patients with CKD to avoid this complication. The serum bicarbonate level usually falls below the normal range in patients with more advanced kidney disease because their kidneys are no longer able to excrete acids at the rate the acids are produced by the body. The bicarbonate on the blood combines with these retained acids and prevents the acids from combining with other molecules that would produce more damage to the body. As more acids are retained, the bicarbonate level falls further, and then the acids start to combine with the phosphorus in bone. When that happens, calcium is released from the bone, and this makes the bone weaker. So it is important for patients to maintain a serum bicarbonate level over 20 to minimize the amount of acid that goes into bone. This may require the administration of an oral bicarbonate supplement or a medication which the body converts to bicarbonate. Table 2: Summary of Commonly Used Tests in Patients with CKD Test Meaning Normal Range Target Range in CKD Blood urea nitrogen (BUN) Level of protein breakdown product Less than 20 Varies by stage, the lower the better in most cases Serum creatinine Level of muscle breakdown product in blood 0.6-1.2 Varies by stage, the lower the better Creatinine clearance Measure of kidney function Greater than 50-70, depending on age Varies by stage, the higher the better Glomerular filtration rate (GFR) Measure of kidney function Greater than 60-90, depending on age Varies by stage, the higher the better Hemoglobin Oxygen carrying capacity of blood Males 13.5-17 Females 12-15 11-12 if on EPO Hematocrit Percent volume of packed red blood cells after blood is centrifuged Males 41-52 Females 36-46 11-12 if on EPO Transferrin saturation (TSAT) Iron in blood available for new red blood cell production by marrow 25-25 25-50 Serum ferritin Iron in storage 20-300 100-800 Serum calcium Needed for bone health 8.5-10.5 8.4-9.5 Serum phosphorus High levels bad for bone and blood vessels 2.4-4.5 3.5-5.5 Parathyroid hormone (iPTH) Maintains serum calcium level and bone health 10-60 35-70 in Stage 3 70-110 in Stage 4 150-300 In Stage 5 Serum potassium High levels can cause abnormal heart rhythms 3.5-5.0 Less than 5.5-6.0 Serum sodium Amount of water in the body (low level means too much water) 135-145 135-145 Serum bicarbonate Ability to prevent accumulation of excess acid 22-30 20-30 Conclusion There are other tests that may be performed on patients with CKD that are beyond the scope of this article. These include x-rays and other imaging studies of the kidneys to evaluate for structural abnormalities of the urinary tract, abnormal blood flow to the kidneys and kidney function, and evaluation of blood vessels including venous mapping and angiography that may be performed as part of your preparation for hemodialysis vascular access placement. Patients with CKD who are not yet on dialysis should understand that many abnormalities may develop which do not produce symptoms but must be treated before complications occur. Knowledge is power to control your destiny. By understanding and responding to abnormalities in your medical tests, you have a much better chance of achieving favorable healthcare outcomes. Jay B. Wish, M.D. is Professor of Medicine at Case Western Reserve University and Medical Director, Hemodialysis Services at the University Hospitals of Cleveland. Dr. Wish is also a member of the AAKP Medical Advisory Board. This article originally appeared in the June/July 2006 issue of Kidney Beginnings: The Magazine, Vol. 5, No. 2.

http://www.aakp.org/aakp-library/Medical-Tests/