Keeping kidney function flowing
SUSAN SIMMONS HOLCOMB ARNP,BC, PHD
Nursing Made Incredibly Easy!
September/October 2004
Volume 2 Number 5
Pages 30 - 40
Abstract
Chronic renal insufficiency is an increasingly common problem, with over-the-counter nonsteroidal antiinflammatory drugs, low-carbohydrate diets, and a growing elderly population possibly fueling the rise. Find out
what you can do to educate patients about renal insufficiency, prevent it from developing, and halt its progress
when it does occur.
THE KIDNEYS ARE TRULY a dynamic duo, with a vital role to play in daily functioning. They're among our most
important excretory organs, and they're instrumental in reabsorption, which helps the body maintain water,
electrolyte, and acid-base balances. The kidneys also help regulate blood pressure by way of the reninangiotensin-aldosterone system. In fact, without kidneys, we'd die within days.
That's why you need to act quickly if a patient develops renal insufficiency: You want to protect him from
progressing to renal failure.
Let's learn more about kidney function and what happens when the renal system goes awry.
The body's filter
To understand renal disease, you first need to know how normal kidneys function. Each kidney is comprised of
four elements: the cortex, the medulla, the renal pelvis, and the nephrons. Nephrons—considered the “heart” of
the kidney—are further divided into the renal corpuscle and the renal tubules.
The renal arteries bring blood to the kidneys. The 1 million nephrons in each kidney have the job of filtering the
blood to form urine, excreting toxins and other wastes, and returning the filtered blood to the renal veins to put
it back into the general circulation. So you can see how important the nephrons are to our health!
Damaged nephrons will die, triggering hypertrophy in the remaining nephrons to compensate. Unfortunately,
hypertrophied nephrons don't work as well as the original cell structure, causing renal insufficiency.
Who's at risk?
The incidence of renal disease is on the rise, affecting about 12 million people in the United States. An
estimated 10 million of them have renal insufficiency.
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The etiology of renal insufficiency varies. It's most common in the elderly, so the incidence of renal failure
increases with age. Other populations at risk include non-whites (especially African Americans, Hispanics, and
Native Americans), men, people with diabetes, and those with hypertension.
Figure. No caption available.
Diabetes and hypertension, in fact, are at the root of about two-thirds of all renal insufficiency cases. Diabetes
is the leading cause of renal insufficiency regardless of ethnicity, except in African Americans, who are more
likely to develop renal insufficiency because of hypertension. In some cases, renal disease may result from
antibody-mediated or cell-mediated immunologic problems or from certain medications, such as sulfa antibiotics
for infection or allopurinol for gout.
Typically, the etiology of renal insufficiency tells you a lot about the pathology of the patient's renal disease
(see Causes of Renal Disease). Disease of the kidneys can be classified as glomerular disease, vascular disease,
tubulointerstitial disease, and cystic disease. Primary glomerular disease affects the glomerular capillaries of the
kidney; secondary glomerular disease stems from a systemic cause, such as lupus, which affects the glomeruli
of the kidney. Vascular disease is due to circulatory disease, usually outside the kidney, or is systemic, such as
renal artery stenosis or hypertension.
Tubulointerstitial disease is caused by drugs or infection and affects the function of the nephron. Affecting
600,000 people in the United States, cystic disease is inherited. Cysts form in the renal tubules, displacing
healthy kidney tissue. Signs and symptoms typically appear in 40 to 60 year olds. Determining the patient's
type of renal insufficiency will help identify the best course of treatment.
The numbers game
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Figure. No caption available.
The patient's serum creatinine level is often used to diagnose renal insufficiency: greater than 1.5 mg/dl is
considered renal insufficiency; greater than 2.0 mg/dl is considered renal failure. But that doesn't tell the whole
story.
The mean normal serum creatinine level is 0.96 mg/dl for women and 1.17 mg/dl for men—which means using
1.5 mg/dl as the marker for renal insufficiency doesn't take into account gender differences.
What's more, renal damage doesn't suddenly occur when the serum creatinine reaches 1.5 mg/dl; it could be
going on well before that point. So clearly, serum creatinine level isn't an adequate evaluation of renal function.
What, then, is a better indicator of renal insufficiency? The answer is the glomerular filtration rate (GFR), also
known as creatinine clearance. Renal insufficiency can be diagnosed when the patient's GFR is 30 to 60
ml/min/1.73 m2; chronic renal insufficiency is identified when the GFR has been less than 60 ml/min/1.73 m 2
for at least 3 months (normal GFR in the range of 100 to 140 ml/min/1.73 m2). Chronic renal failure is
identified when the GFR falls to 15 to 30 ml/min/1.73 m2. End-stage renal failure is characterized by a GFR of
less than 15 ml/min/1.73 m2 (see Stages of Renal Disease).
Of course, every rule has its exceptions, and measuring GFR is one of them. Sub-stantial kidney damage can
occur without a change in the GFR, which tells us that some people's kidneys are better able to compensate for
structural damage than others. Also, normal GFR varies with age, gender, and body size. Children reach adult
values for GFR by about age 2. Women usually have GFR values that are 8% lower than men. In young
adulthood, defined as ages 20 to 30, GFR begins to decline by approximately 1 ml/min/1.73 m 2 per year. That
means an expected GFR by age 70 is 70 ml/min/1.73 m2. See Creatinine Clearance Calculation for more
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information.
That's a surprise!
Figure. No caption available.
Health care providers aren't typically looking for renal insufficiency unless the patient is at high risk for the
disease. In many cases, it's discovered accidentally with routine laboratory work when the creatinine and blood
urea nitrogen are abnormally elevated. Specific tests will then be done to confirm or rule out renal insufficiency
(see Tests of Renal Function).
Proteinuria is an important marker for progression of renal disease; it also appears to be a marker for
cardiovascular disease. So you'll closely monitor the patient with renal disease for protein in the urine. Early in
the disease, large protein molecules won't be noted, so watch the patient's microalbumin instead. In the past,
24-hour urine collections for microalbumin measurements were recommended. The problem was that these
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were time consuming and weren't always done correctly.
Now the recommendation is to do spot (untimed) collections. When you do this, keep in mind that urinary
protein excretion varies throughout the day—which means the ratio of protein to creatinine will also vary
according to the time of day. A first morning specimen most closely correlates with a 24-hour protein excretion,
making it preferred over randomly timed specimens to monitor proteinuria and albuminuria.
Dehydration increases protein excretion; volume overload reduces protein in the urine. Obtaining a protein-tocreatinine or albumin-to-creatinine ratio can give you a more accurate picture. But even that isn't a simple fix:
Creatinine excretion is usually higher in men than women, so the normal values for albumin-to-creatinine ratios
will be lower in men than in women. Other factors that may influence protein/albumin measurement in the
urine include hematuria, exercise, and infection.
Asymptomatic…at first
Initially, patients with renal insufficiency are asymptomatic. But as the disease progresses toward renal failure,
symptoms can develop, including fatigue, nausea, anorexia, nocturia, pruritus, erectile dysfunction, restless leg
syndrome, insomnia, confusion, and changes in taste, especially a metallic taste. Hypocalcemia,
hyperphosphatemia, and an elevated parathyroid hormone level can result in osteomalacia. In addition, salt
and water retention can manifest as edema, increased blood pressure, ascites, congestive heart failure, and
pericardial effusion.
Neurologically, changes in the patient's electrolyte, fluid, and acid-base balances can be noted as asterixis,
confusion, lethargy, orthostatic hypotension, gastroparesis, diminished deep tendon reflexes, hypesthesia, and
paresthesias. Anemia may result in pallor, shortness of breath, or chest pain.
We don't really know why, but any degree of renal insufficiency—even mild disease—is associated with a
marked increase in cardiovascular mortality. Cardiovascular disease is the leading cause of death in patients
with renal failure; in fact, cardiovascular disease is more prevalent in renal patients than in the general
population.
This increased risk for cardiovascular disease is independent of other comorbid factors, like diabetes,
hypertension, and hyperhomocystinemia. The risk rises even more in the presence of these comorbid
conditions, however. And it increases as the GFR declines, proteinuria increases, and anemia develops.
Trouble's brewing
Complications of renal disease seem to develop and progress from a declining GFR. Besides cardiovascular
problems, other complications include anemia, malnutrition, osteoporosis, and neuropathy. In renal failure,
complications are manifested and referred to as uremia or uremic syndrome. These complications may or may
not exist, or may present in varying degrees, before overt failure occurs.
In chronic renal disease, anemia commonly occurs at some point and progresses as the disease worsens if not
appropriately treated. Anemia is related primarily to erythropoietin deficiency. Other causes include iron
deficiency, blood loss, and deficiencies of folate or vitamin B12.
An independent predictor of cardiovascular disease in patients with renal insufficiency, anemia leads to left
ventricular hypertrophy (LVH) in these patients. One study found that almost 40% of patients with renal
insufficiency had LVH when they were diagnosed with renal disease. LVH probably developed as the body tried
to compensate for the drop in oxygenation related to anemia by making the heart muscle bigger to pump out
more blood.
Changes in bone development, including osteoporosis, are another potential complication of chronic renal
insufficiency. If vitamin D synthesis decreases, parathyroid hormone secretion can increase. Watch out for
changes in the calcium-phosphorus ratio and hyperparathyroidism. These problems lead to calcification of the
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blood vessels, worsening cardiovascular disease. Because phosphorus isn't excreted appropriately in patients
with renal disease, the increased serum phosphorus level directly affects vitamin D synthesis. In renal disease,
calcium isn't as readily absorbed from the gastrointestinal tract. The combination of low calcium, high
phosphorus, and low vitamin D levels results in secondary hyperparathyroidism from stimulation of parathyroid
hormone (PTH) synthesis and proliferation of parathyroid cells.
Bone changes usually begin when the patient's GFR reaches 60 ml/min/1.73 m2 or less. Suspect bone changes
with an elevated PTH level. Keep a close eye on the PTH, ionized calcium, magnesium, phosphorus, and alkaline
phosphatase levels.
Danger ahead
Besides the warning signs and symptoms of renal diseases that we've discussed, stay alert for other possible
red flags, including encephalopathy, peripheral neuropathy, and sleep disorders. Unfortunately, we don't fully
understand why neuropathies develop in these patients. Increased levels of urea, creatinine, and PTH, as well
as changes in electrolyte, fluid, and acid-base balances may be the culprits because they interfere with nerve
function. Symptoms associated with encephalopathy can range from fatigue, insomnia, and impaired memory
and concentration to convulsions and coma. Peripheral neuropathy symptoms may include itching, burning,
muscle cramps, and muscle weakness. The patient may also experience autonomic changes, such as a cardiac
arrhythmia, orthostatic hypotension, and depressed gastrointestinal motility. On physical examination, findings
may include decreased or loss of deep tendon reflexes, muscle wasting, and changes in sensitivity to pain and
touch.
Renal disease also causes acid-base disturbances. In the early stages of the disease, you'll see a mild increase
in the chloride level, with a normal anion gap and metabolic acidosis. When the GFR is less than 20
ml/min/1.73 m2, the chloride level drops and the patient develops metabolic acidosis with an abnormal anion
gap.
You'll find that malnutrition is common in patients with renal disease. It's speculated that they lose their
appetite from both metabolic and hormonal changes, leading to decreased nutrient intake and malnutrition.
Many patients feel nauseated from gastrointestinal changes, or they may find that food just doesn't taste good
any more, so they don't want to eat.
Metabolic acidosis, combined with a reduced protein intake, can put the body in the position of needing to break
down its own protein stores. Metabolic acidosis also squelches albumin synthesis, which is necessary to
maintain muscle mass.
Declining renal function can adversely affect insulin and growth hormone—two other factors needed for growth
and repair. As GFR decreases, the C-reactive protein level increases, making the need for nutrition for repair
even greater.
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Figure. No caption available.
The treatment goals for a patient with renal disease should include treating the underlying disease, slowing
progression of renal disease, treating and preventing complications, and referring the patient to a nephrologist.
If hypertension is the cause of renal disease, treating it can slow or halt the progression of renal disease.
According to the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood
Pressure (JNC 7), the target blood pressure for patients with renal insufficiency is 125/75 mm Hg. The JNC 7
guidelines advocate angiotensin-converting enzyme inhibitors (ACE-Is) as the first-line treatment of
hypertension in patients with renal disease. These drugs lower intraglomerular pressure via the reninangiotensin-aldosterone system and lower proteinuria, preserving renal function.
When your patient is taking one of these drugs, you may notice an increase in his serum creatinine level in the
first weeks of therapy. If the creatinine level increases by more than 35%, notify the patient's health care
provider, who'll want to reevaluate the use of an ACE-I. Be aware that the ACE-I can also increase the serum
potassium level, so make sure you closely monitor the patient and his lab work.
Nondihydropyridine calcium channel blockers reduce proteinuria and may be used synergistically with an ACE-I.
Angiotensin-receptor blockers (ARBs) can also reduce proteinuria and lower intraglomerular pressure. ARBs are
an alternative for patients who can't tolerate ACE-Is due to the dry cough or angioedema that an ACE-I can
cause. Some health care providers combine an ACE-I with an ARB to see if the two drugs are synergistic in the
same way as the nondihydropyridine calcium channel blockers and ACE-Is.
Alpha-blockers and beta-blockers seem to have little effect on proteinuria. Conflicting results have been
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reported regarding the efficacy of dihydropyridine calcium channel blockers against proteinuria. Diuretics also
have little effect on proteinuria, but they can be used with an ACE-I or other antihypertensive agent to help
control blood pressure. If the patient's creatinine clearance is above 30 ml/min, thiazide diuretics may be used
for blood pressure control. But if the creatinine clearance is less than 30 ml/min, avoid thiazides and try using
loop diuretics; loop diuretics may reduce edema as well as blood pressure. Avoid using potassium-sparing
diuretics in patients with renal insufficiency because their serum potassium levels may already be elevated.
It's in the blood
You'll need to monitor your at-risk patients for signs of anemia. Treatment is initiated when the hematocrit falls
below 30% of normal and the patient is symptomatic. Many patients receive daily supplements of ferrous
sulfate and folic acid to boost their iron and folic acid stores. Subcutaneous erythropoietin is used to replace
erythropoietin not being synthesized by the kidneys. The goal of therapy with erythropoietin—a glycoprotein
that's normally produced by the kidneys—is to increase the hemoglobin by 1 to 2 g/dl within the first month.
Some patients need it three times a week; some respond to a weekly dose.
Darbepoetin alfa (Aranesp) is a non-natural recombinant protein that can stimulate red blood cell production
the same as erythropoietin. The half-life of darbepoetin is about three times longer than erythropoietin, leading
to less frequent dosing.
When initiating either erythropoietin or darbepoetin, measure the hemoglobin level weekly. Once the
hemoglobin reaches a therapeutic level (11 to 12 g/dl), it can then be monitored less frequently. One adverse
reaction to either erythropoietin or darbepoetin is hypertension. If this occurs, antihypertensives should be
initiated to reduce blood pressure. In rare cases, blood pressure can't be adequately reduced, and treatment
with erythropoietin or darbepoetin must be stopped. If patients are still anemic, as in some rare cases, they
may need an iron supplement or possibly a transfusion.
Pediatric patients with renal insufficiency may need to receive growth hormone (GH) in the form of Nutropin
injections. Adults can also use this product if they have a subnormal response to GH stimulation, as defined by
peak GH level less than or equal to 5 ng/ml.
Chronic renal replacement therapy, such as hemodialysis or peritoneal dialysis, is initiated when the patient's
GFR is less than 10 ml/min; 15 ml/min in individuals with diabetes. Dialysis can be initiated earlier, especially if
serum albumin is less than 4 g/dl. In such cases, the patient would be severely malnourished. More important,
proteins also help maintain a balance of body fluids. When this is compromised, it can affect other areas of the
body, such as the neurologic or cardiac systems.
Diet does matter
Restricting protein in patients with renal insufficiency is controversial. Following a protein-restricted diet of 0.6
to 0.8 mg/kg/day may lower glomerular pressure. Some research suggests protein restriction can delay the
onset of renal insufficiency, and lowering urinary protein to less than 2,500 mg/day can effectively delay
progression of the disease.
As we've discussed, protein excretion in the urine can be measured either by 24-hour urine collection or by
random spot morning urine. The protein/creatinine ratio in a random urine sample shouldn't exceed 200 mg/g.
If it does, the patient should be referred to a nephrologist for a thorough renal evaluation. Referral is also
indicated when the serum creatinine is 2 mg/dl or more in men and 1.6 mg/dl or more in women.
Strict blood glucose control can also halt progression of renal insufficiency. Hemo-globin A1C levels should be
targeted to less than 7%. In individuals with diabetes who have urine microalbumin excretion of more than 30
mg/day, proteinuria will develop in 5 to 10 years.
Note that a correlation seems to exist between hyperlipidemia and progressive renal insufficiency. Because
hyperlipidemia is a risk factor for cardiovascular disease, keep lipids in check to help alter the course of
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potential complications associated with renal insufficiency. Statins and other cholesterol-lowering medications,
coupled with diet modifications, can be used to manage hyperlipidemia.
Take time to educate patients about renal disease, including the importance of the kidneys and their function.
Provide patients with information on diet and exercise, smoking cessation, and medications to avoid. Remind
them that over-the-counter (OTC) medications shouldn't be taken without approval from their primary care
provider. And instruct patients to notify their primary care provider any time diarrhea or vomiting occurs more
than once; dehydration will worsen renal status.
Figure. No caption available.
Much of the rise in renal disease that we're seeing could be the result of the increase in availability of OTC
nonsteroidal anti-inflammatory drugs (NSAIDs). These drugs affect prostaglandin production, which is
necessary for maintaining renal function. The daily dosage of ibuprofen shouldn't exceed 2400 mg, and these
drugs should be avoided in those with renal disease, patients on ACE-Is, or those who have heart failure.
The popularity of low-carbohydrate diets and their potential contribution to renal insufficiency is another
concern. These diets are high in fat and cholesterol and cause the body to go into ketosis, which clogs the
kidneys, and can lead to renal insufficiency.
Patients with renal disease may also have electrolyte imbalances. Hyperphosphatemia should be treated with
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phosphate binders and dietary phosphate restrictions. Hypo-calcemia should be treated with calcium
supplements. Patients with renal disease should not receive intravenous radiocontrast dye because their
kidneys wouldn't be able to excrete the dye properly.
What you can do
It's crucial for patients with renal insufficiency to be evaluated and followed up by a renal team to reduce
morbidity and mortality. They need to understand the importance of keeping appointments with their health
care providers to prevent or aggressively treat potentially reversible or controllable factors that affect morbidity
and mortality, including anemia, acidosis, hypertension, malnutrition, renal osteodystrophy (defective bone
development), hyperlipidemia, and hyperglycemia. Because this is a chronic disease, family support is
important. With the patient's permission, family members and significant others should be included in patienteducation activities.
Chronic renal insufficiency is an increasingly common problem in the United States. Some of this increase may
be attributed to the growing elderly population. As nurses, we need to educate our patients about the problem
to prevent its development as much as possible. And, we need to be prepared to initiate measures to slow or
halt its progress when it does occur.
Exploring the nephron
Figure. No caption available.
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Figure. No caption available.
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The Cockroft-Gault formula:
Equation (Uncited)
Table. Stages of renal disease.
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Table.
Causes
of renal
disease.
13
Figure. No caption available.
14
Table.
Tests of
renal
function.
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Table.
Proteinuria
and
albuminuria.
Learn more about it
Henry, R., et al.: “Mild Renal Insufficiency is Associated with Increased Cardiovascular
Mortality. The Hoorn Study,” Kidney International. 62(4):1402–1407, October 2002.
Hebert, C.: “Preventing Kidney Failure: Primary Care Physicians Must Intervene Earlier,”
Cleveland Clinic Journal of Medicine. 70(4):337–344, April 2003. Erratum in: Cleveland Clinic
Journal of Medicine. 70(6):501, June 2003.
National High Blood Pressure Education Program. The Severity Report of the Joint National
Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC
7). Fall 2003. http://www.nhlbi.nih.gov/guidelines/hypertension ; accessed February
25, 2004.
Schmitz, P.: “Progressive Renal Insufficiency,” Postgraduate Medicine online. July 2000.
http://postgradmed.com ; accessed February 11, 2004.
Work Group: “NKF-K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation,
Classification, and Stratification.” National Kidney Foundation. 2002.
http://www.kidney.org ; accessed February 24, 2004.
CE Test
Keeping kidney function flowing
Instructions
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