By Steven Z. Fadem, MD, FACP

You leave the doctor’s office after hearing the bad news, “There is something wrong with your kidneys. One of your tests was abnormal. We are going to have to do some additional studies.” Racing through your mind are the thoughts of stories you once read about the horrors of dialysis. You recall tales of people in foreign countries who sell and buy kidneys. You panic as you think about a life of illness. Then, you decide to compose yourself and fight. Just what do you do next?  

Fighting a chronic illness, be it cancer, kidney disease or any other condition requires education. This article will help with what you need to know about chronic kidney disease (CKD). For a fuller and richer understanding, you should refer to several outstanding resources presented at the end of this article. But first...  

You may not even have chronic kidney disease  

Chronic kidney disease is defined as kidney damage or a decrease in kidney function that lasts over three months. Kidney function is measured by the GFR - glomerular filtration rate, and is simply calculated from a formula that uses your age, race, gender and serum creatinine level.1 Patients who have a GFR less than 60 cc/min/1.73 m2 for more than three months are defined as having chronic kidney disease even in the absence of detectable kidney damage. When kidney damage, as defined by pathologic abnormalities in blood, urine tests or on diagnostic imaging studies, persists it indicates chronic kidney disease even at higher GFR levels (60 to 89 mL/min/1.73 m2). There are several circumstances when the kidneys function poorly for a short time. Dehydration, acute viral illness and/or medications are the most common reasons for the kidneys being temporarily damaged. Certain medications such as the non-steroidal anti-inflammatory drugs (NSAIDS) or select antibiotics can briefly diminish kidney function. Kidney stones, obstruction and the contrast media used in x-rays may also cause reversible damage to the kidneys.  

Three months later - Your GFR is less than 60 cc/min  

You are not alone with CKD. It is common, affecting as many as one in nine individuals in America. It has multiple causes, ranging from diabetes and hypertension to glomerulonephritis (an inflammation of the glomerulus or filter, i.e. lupus nephritis) and hereditary or urological diseases. Despite its varied origins, kidney disease progresses as the number of nephrons (filtering units) diminish. In many instances, the rate at which nephrons die can be lessened and even halted. It is often possible to slow the progression of kidney disease at its earliest stages.  

What are the stages? How is kidney disease classified?  

The National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI) Clinical Practice Guidelines on Chronic Kidney Disease offer the following classifications2:  

• Stage 1 - GFR = 90 cc/min/1.73m2
Kidney damage with normal or high GFR

• Stage 2 - GFR - 60 to 89 cc/min/1.73m2
Kidney damage with mild decreased GFR

• Stage 3 - GFR - 30 to 59 cc/min/1.73m2
Moderately decreased GFR

• Stage 4 - GFR - 15 to 29 cc/min/1.73m2
Severely decreased GFR

• Stage 5 - GFR - < 15 cc/min/1.73m2
Kidney failure  

This classification is universal, and enables providers to develop a specific action plan based upon the stage of disease. The important concept here is that we must take action. Doing nothing leads to the one certainty we wish to avoid - kidney failure. There are risk factors associated with the loss of kidney function (the rate of GFR decline) that predict when kidneys will fail. Our action plan goal will be to identify and reduce these factors. We will follow the GFR closely to determine how effective our efforts are.

The Action Plan 

Stage 1 CKD

The NKF/KDOQI Guidelines recommend that once CKD has been established and staged, an action plan be developed. At this point, and after the diagnosis is made, treatment may focus on the underlying condition. Since cardiac events are common in kidney disease, efforts to treat atherosclerosis are integrated into the plan. Diabetes is the most common cause of kidney disease; it is in a category of its own. Non-diabetic kidney disease can be classified by its involvement in the kidney’s internal anatomy. Does it involve the filter (glomerulus), the tubules (tubulointerstitial disease) or the vasculature (vasculitis, ischemia or hypertension)? Cystic kidney disease and transplant-related disease round out the classification. In glomerular disease, a biopsy may be necessary to make a more definitive pathological diagnosis.  

Clinical research trials are looking intensely at the mechanisms related to CKD, and are focusing on prevention as well as treatment. The clinical trials and consensus reports published in recent years have given us startling insights into the relationship between hypertension, diabetes and the endpoints of renal and cardiac disease.3-10 In clinical practice, we follow the same tactic, aggressively treat blood pressure, keep diabetes under control2 and add a medicinal to reduce the adverse blood vessel constrictor effects of angiotensin. We strive to reduce the major risk factors associated with heart disease, among which are inflammation, cholesterol, obesity, cigarette smoking and a sedentary lifestyle.

Therapy directed at stabilizing diabetes, hypertension and lupus nephritis has the added importance of reducing damage to other target organs. Damage to these other organs affects the well-being of the patient, and requires equal attention.  

Current recommendations suggest that the systolic blood pressure target for treatment be 130 mm/Hg and the diastolic 80 mm/Hg in patients with chronic kidney disease.3 People with diabetes may require a lower level of blood pressure control, such as 130/75. In patients whom CKD and proteinuria greater than 1 gm/24 hr are present, especially African Americans, the blood pressure should be kept at 125/75 mm/Hg.4 Evidence exists that higher blood pressure values are directly associated with kidney damage, and therapy with two or more medications may be required.  

There is direct evidence that smoking is a promoter of kidney disease.5 The progression to atherosclerosis may accelerate renal deterioration through the development of ischemic kidney disease, but additionally it contributes to heart, stroke and peripheral vascular disease.  

The management of cholesterol and elevated triglycerides requires arranging for optimal nutrition support and the use of medications. Obesity, as defined by a body mass index greater than 30, is a major risk factor for diabetes, heart disease and hypertension.6 Inflammation is a risk factor for heart disease, and subtle causes such as helicobacter (an infection that involves the stomach) and gingival disease should be addressed. Now is the time to develop good exercise habits, and continue them throughout the duration of the disease.  

Although protein restriction can help retard the progression of disease,7,8 it is very difficult to follow, and is limited as a useful tool. Secondly, efforts to restrict dietary intake of saturated fat, unrefined sugars and carbohydrates often leave little alternatives. We ask patients not to overindulge in protein intake and to use good judgment.

In many instances, kidney disease runs in the family, and relatives should be screened for kidney disease. A serum creatinine, blood pressure reading, urinalysis and urine microalbumin should be performed.    

Stage 2 CKD

As renal function deteriorates, physicians will need to review the patient’s medication list to assure that dosing has been suitably adjusted. It is rare at this stage to see anemia or indicators of metabolic bone disease. The practice plan outlined in Stage 1 CKD should be continued in those patients who progress. This action plan also includes calculating the progression of disease.  

Stage 3 CKD

By this stage, the chances of reversing kidney disease are small, but the fight continues as we try to ward off its complications, especially anemia and metabolic bone disease. The kidney cells produce erythropoietin. This hormone, known as a cytokine, stimulates the production and maturation of red blood cells, small bodies containing hemoglobin and iron that transport oxygen to and away from the tissues. When the kidneys fail, the production of erythropoietin decreases, leading to anemia, with a subsequent fall in hemoglobin. By the time the GFR reaches 60 cc/min/1.73m2 kidney patients are at risk to develop anemia.  

A symptom of anemia is fatigue. With the decrease in oxygenated blood, the heart must work harder to deliver enough oxygen to the tissues. Over time, this extra workload weakens the heart. Anemia associated with CKD is easily treated with regular injections of recombinant human erythropoietin. These injections should start when the hemoglobin starts to decline, not when the patient requires dialysis. The early management of anemia may help reduce the workload on the heart. It is certain to reduce fatigue and improve the quality of life. Thus, in addition to hypertension and the factors above, patients should be evaluated and managed for anemia.9

As the kidney fails, several other metabolic consequences occur. Calcium is a vital mineral that every muscle requires to contract. The body closely guards the level of calcium in the system. The kidney activates vitamin D, a vitamin vital for the intestinal absorption of calcium. In the absence of active vitamin D, the parathyroid glands in the neck secrete a hormone that reabsorbs calcium from the bone. The elevation in parathyroid hormone (hyperparathyroidism) can be controlled by first making sure that the precursors to vitamin D are present. When necessary, early management of hyperparathyroidism can be achieved by prescribing a medication similar to vitamin D.10  

Stage 4 CKD

By the time the GFR reaches 25 cc/min/1.73m2, the albumin levels start to fall, and the ability to secrete or buffer the acids that result from the breakdown of body nutrients may lead to symptoms, subtle at first, but contributors to a nutritional wasting state. During this phase of kidney disease, it is necessary to monitor the serum bicarbonate and the serum albumin levels.11 The serum albumin is an indicator of nutritional status. Our goal will be to keep this value greater than four grams/dL. Sometimes, dialysis is necessary in order to achieve this objective. Since dialysis therapy is inevitable, it is best to be prepared. Some people are fortunate, and have a loved one or good friend willing to donate a kidney. Now is the time to have one’s nephrologist arrange this.  

A successful transplant in the later segment of Stage 4 can preempt dialysis. In hemodialysis the blood is pumped from the body through a plastic filter. Here, it is purified as there is an exchange of toxins and accumulating minerals into specially balanced fluids. The only ways to access the blood are through catheters or through the creation of an arteriovenous access. The catheters are hard on the system; they contribute to abnormal narrowing of the blood vessels that host them, and can easily become infected. There are two types of arteriovenous access, the AV graft and the AV fistula. In the graft, a soft plastic tube is surgically placed under the skin. This usually functions well for a couple of years, but is inferior to the second type of AV access, the AV fistula. Here the artery and the vein are connected and allow to mature. Once mature, they can be easily cannulated.12 Since it takes at least three months for the fistula to mature, it is best to place it early in Stage 4. Its major advantage is that it lasts longer. By placing it during this stage, one can avoid a catheter altogether. The fistula will be ready to use by the time dialysis starts. An alternative to hemodialysis is peritoneal dialysis. Here, the body’s own membrane, the peritoneum, tissue that lines the inside of the abdomen, is used as the filter. A plastic catheter inserted into the abdomen allows a special fluid to both enter and leave the space where toxins and excess metabolites can be exchanged.  This catheter takes between ten days to three weeks to have healed enough to be used. Thus, it too should be placed early when peritoneal dialysis is preferred.  

Stage 5 CKD

By this stage, dialysis or a kidney transplant is generally necessary.

Summary

We now have an overview of what can be done to prepare us to deal with kidney disease. Realizing that a good outcome rests with you regardless of the stage of disease, helps regain a sense of control. Knowledge is a powerful force in coping with chronic disease. The appreciation that there is constant research leading to new advancements gives one hope. Knowing in advance what to expect helps avoid pitfalls. To further your knowledge about kidney disease the following four resources are recommended:  

1. The AAKP Patient Plan©

2. The NIDDK

3. NKF K/DOQI Guidelines

4. The Nephron Information Center  

Stephen Z. Fadem, MD, FACP, serves as a member of AAKP’s Medical Advisory Board and the AAKP Board of Directors. Dr. Fadem is a practicing nephrologist in Houston, Texas.

References:

1. Coresh J, Astor BC, Greene T, Eknoyan G, Levey AS. Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and Nutrition Examination Survey. Am J Kidney Dis 2003; 41:1-12.

2. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Kidney Disease Outcome Quality Initiative. Am J Kidney Dis 2002; 39:S1-246.

3. Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. Jama 2003; 289:2560-72.

4. Hebert LA, Kusek JW, Greene T, et al. Effects of blood pressure control on progressive renal disease in blacks and whites. Modification of Diet in Renal Disease Study Group. Hypertension 1997; 30:428-35.

5. Jungers P, Massy ZA, Khoa TN, et al. Incidence and risk factors of atherosclerotic cardiovascular accidents in predialysis chronic renal failure patients: a prospective study. Nephrol Dial Transplant 1997; 12:2597-602.

6. Brown WW, Peters RM, Ohmit SE, et al. Early detection of kidney disease in community settings: The kidney early evaluation program (KEEP). Am J Kidney Dis 2003; 42:22-35.

7. Levey AS, Greene T, Beck GJ, et al. Dietary protein restriction and the progression of chronic renal disease: what have all of the results of the MDRD study shown? Modification of Diet in Renal Disease Study group. J Am Soc Nephrol 1999; 10:2426-39.

8. Klahr S, Levey AS, Beck GJ, et al. The effects of dietary protein restriction and blood-pressure control on the progression of chronic renal disease. Modification of Diet in Renal Disease Study Group. N Engl J Med 1994; 330:877-84.

9. Eknoyan G, Levey AS, Levin NW, Keane WF. The national epidemic of chronic kidney disease. What we know and what we can do. Postgrad Med 2001; 110:23-9: quiz 8.

10. Friedman TC, Norris KC. The role of vitamin D in mild to moderate chronic kidney disease. Trends Endocrinol Metab 2002; 13:189-94.

11. Kopple JD. The National Kidney Foundation K/DOQI clinical practice guidelines for dietary protein intake for chronic dialysis patients. Am J Kidney Dis 2001; 38:S68-73.

12. Pisoni RL, Young EW, Dykstra DM, et al. Vascular access use in Europe and the United States: results from the DOPPS. Kidney Int 2002; 61:305-16.

This article originally appeared in the December 2003 issue of Kidney Beginnings: The Magazine, Vol. 2, No. 4.

Back