By Mary Ann Arndt, MD; Prabhleen Singh, MD; Scott C. Thomson, MD

Chronic kidney disease (CKD) is a term used to describe impaired kidney function, due to several conditions that can affect kidneys. Normal kidney function involves removing body waste, maintaining salt and mineral balance, stimulating red blood cell production and supporting bone health. Therefore, CKD leads to complications, such as high blood pressure due to salt and water retention, anemia (low red blood cell count), weak bone structure and overall poor health status.

Your primary care physician or nephrologist makes the diagnosis, and determines the severity of CKD by performing tests on the blood and/or urine. The presence of too much protein in the urine always indicates kidney disease, although CKD can occur even without protein in the urine. Blood in the urine may also indicate kidney disease, although there are many other causes of blood in the urine. The most common way to test for CKD is to measure the amount of creatinine in the blood plasma. Creatinine is a natural substance made by the body each day and removed by the kidneys. In CKD, the kidney filters less blood so the creatinine level rises. There are standard formulae for estimating how much blood the kidney actually filters based on the creatinine level. This common measure of kidney function is referred to as the estimated glomerular filtration rate or eGFR.

CKD is highly prevalent in the United States, as approximately 20 million adults have the diagnosis and another 20 million are at risk to develop this within their natural lifetime. Risk factors for developing kidney disease include diabetes, high blood pressure and family history of kidney disease. Early diagnosis is important in order to begin therapy to slow the progression of the disease and prevent its complications.

The eGFR is further used to define the stages of CKD:
                                        Stage                       eGFR ml/min/1.73m2
Mild                                   2                                   60-89
Moderate                           3                                   30-59
Severe                               4                                   15-29
Kidney Failure                    5                                     <15

There are many causes of kidney disease, most of which are rare. Nowadays, most cases of CKD are attributed to diabetes and/or high blood pressure. Only 1/3 of patients with diabetes will ever develop classic diabetic kidney disease, or diabetic nephropathy. Those who develop diabetic nephropathy are eventually destined for total kidney failure. But in spite of the poor ultimate outlook for these patients, kidney survival may be extended for many years by aggressively lowering the blood pressure, controlling the blood sugar, and taking steps to lessen the amount of protein in the urine. In contrast to those with diabetic nephropathy, most patients with CKD are not destined to develop total kidney failure in their natural lifetime. This group includes many older diabetics who develop CKD as a consequence of high blood pressure or atherosclerosis, rather than diabetic nephropathy. Regardless of the original cause of kidney disease, CKD renders the kidney more vulnerable to further damage from high blood pressure. Therefore, it is the standard of care to treat high blood pressure more aggressively in patients with CKD.

Cardiovascular Disease
Disease of blood vessels of the heart, brain, legs and other organs is referred to as cardiovascular disease (CVD) or heart disease. CVD involves build-up of cholesterol within the vessels forming a plaque, which leads to blockage of the blood supply. When blood supply is blocked, heart attack and stoke can result. CVD also includes left ventricular hypertrophy (LVH), a condition in which the heart muscle thickens in response to long-standing high blood pressure and anemia. LVH limits the heart from functioning at full capacity, sometimes resulting in heart failure.

Kidney disease patients are at especially high risk for developing CVD and for having heart disease be the cause of their death. For example, an elderly person with stable mild to moderate disease is twice as likely to die from CVD as an elderly person with normal kidneys. The risk of CVD is even greater in young people with kidney disease. The American Heart Association now recognizes CKD to be a risk factor independent of the other risks such as smoking and high cholesterol. The risk for cardiovascular events is also known to increase with worsening kidney disease.

Aware of the high risk of heart disease in kidney patients, physicians are compelled to prescribe what they can to lower that risk. Optimal control of blood pressure and blood sugar is not only vital to prevent or slow the progression of kidney disease, but also to prevent heart disease. Studies have determined the goal blood pressure for patients with kidney disease is 130/80.

Two classes of blood pressure medications, angiotensin converting enzyme inhibitors (ACEs) and angiotensin receptor blockers (ARBs), have been shown to offer a protective benefit for the kidneys and the heart over and above their ability to lower blood pressure. In patients with CKD, ACEs and ARBs are often prescribed to treat both hypertension and to reduce urinary protein. Patients receiving ACEs and ARBS require close monitoring of blood chemistries, especially the potassium level, as the potassium can increase in patients with kidney disease. Additionally, these medications cause a slight decline in kidney function, the eGFR, though is not detrimental in the long term. In very few patients, the medications are not tolerated well, due to persistently elevated potassium or a more severe decline in kidney function.

In patients with more severe kidney disease, imbalance commonly develops in the hormones that regulate calcium and phosphorus. This often leads to deposition of these minerals in blood vessel walls, which causes the vessels to become stiff and, thus, contributing to CVD. The current approach to treating patients with CKD is to manipulate the diet and medications, as needed, to prevent excess phosphorus from accumulating in the body and to normalize the vitamins and hormones that regulate calcium and phosphorus.

The kidney is responsible for signaling the bone marrow to make red blood cells. As such, many kidney patients become anemic. Severe anemia places stress on the heart, which must pump more blood to deliver the same amount of oxygen. Potent medications are available to correct the anemia of CKD. These are a mainstay of treatment for patients on dialysis and those with severe anemia from advanced CKD. However, using these medications to correct mild anemia in kidney patients has not proven beneficial.

Elevated cholesterol is another CVD risk factor that can improve with therapy. Treatment with medications that reduce levels of LDL cholesterol, the bad cholesterol, can improve the blockage formation within blood vessels. Along with these medications, patients can participate in management by making lifestyle changes, such as with exercise, weight loss, stop smoking and following a low salt diet, and by keeping a record of blood pressures and blood sugars to be reviewed at doctor visits. Patients with more severe kidney disease may also require following a low potassium and low phosphorus diet.

Conclusions and Recommendations
Kidney disease is a common condition among the aging population. Most patients with kidney disease will never develop complete kidney failure. Instead, kidney patients have an increased risk of stroke, heart attack or heart failure. This risk can be reduced and the progression of CKD can be slowed by lowering blood pressure, controlling diabetes and reducing urinary protein. Kidney disease patients are more likely to preserve their well-being if they take a pro-active role by understanding the progression of kidney and heart disease can be modified and consistently apply those measures of known benefit.

References
_{Go Alan, et al. Chronic Kidney Disease and the Risks of Death, Cardiovascular Events, and Hospitalization. NEJM 2004; 351:1296-305.
Menon Vandana, et al. The Epidemiology of Chronic Kidney Disease Stages 1 to 4 and Cardiovascular Disease: A High-Risk Combination. AJKD 2005;45:223-232.
Coresh Josef, et al. Prevalence of Chronic Kidney Disease and Decreased Kidney Function in the Adult US Population: Third National Health and Nutrition Examination Survey. AJKD 2003;41:1-12.
Schiffrin Ernesto, et al. Chronic Kidney Disease: Effects on the Cardiovascular System. Circulation 2007;116:85-97.
McCullough Peter, et al. Independent Components of Chronic Kidney Disease as a Cardiovascular Risk State. Archives of Internal Medicine 2007; 167:1122-1129.
Berl Thomas, et al. Kidney-Heart Interactions: Epidemiology, Pathogenesis, and Treatment. CJASN 2006;1:8-18.
Ruggenenti Piero, et al. Kidney Failure Stabilizes after a Two- Decade Increase: Impact on Global (Renal and Cardiovascular) Health. CJASN 2007; 2:146-150.
Singh Ajay K et al. Correction of Anemia with Epoetin Alfa in Chronic Kidney Disease. N Engl J Med. 2006 Nov 16; 355(20):2085-98.}

Mary Ann Arndt, MD; Prabhleen Singh, MD; Scott C. Thomson, MD, are members of the Department of Medicine, University of California, San Diego and Veterans Affairs San Diego Healthcare System. The VA San Diego Healthcare System (VASDHS) provides quality healthcare service to more than 280,000 veterans in the San Diego and Imperial Valley counties.

This article originally appeared in the December 2007 edition of Kidney Beginnings: The Magazine.

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