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Official reprint from UpToDate®
www.uptodate.com
©2010 UpToDate®
Authors
Theodore W Post, MDBurton D Rose, MD
Section Editor
Gary C Curhan, MD, ScDDeputy Editor
Alice M Sheridan, MD
Overview of the management of chronic kidney disease inadults
Last literature review version 18.3: Setembro 2010 | This topic last updated: Outubro 8,2010
INTRODUCTION — All patients with renal disease (whether acute or chronic) should undergo an
assessment of renal function by estimating the glomerular filtration rate (GFR). This
measurement is used clinically to evaluate the degree of renal impairment, to follow the course
of the disease, and to assess the response to therapy. An attempt must also be made to obtaina specific diagnosis. The first step in this process is a careful urinalysis. (See "Assessment of
kidney function: Serum creatinine; BUN; and GFR" and "Diagnostic approach to the patient with
acute or chronic kidney disease" and "Urinalysis in the diagnosis of renal disease".)
An overview of the general issues involved in the management of the patient with chronic kidney
disease, including modalities to slow the rate of progression, will be presented here. The specific
therapy of patients with particular renal diseases is discussed separately in the appropriate topic
reviews.
NATURAL HISTORY OF RENAL DISEASE — The initial injury to the kidney may result in a
variety of clinical manifestations, ranging from asymptomatic hematuria to renal failure requiringdialysis. Many individuals fully recover and subsequently suffer from little or no sequelae.
Poststreptococcal glomerulonephritis in children, for example, most frequently has a long-term
benign prognosis. By comparison, some patients, such as those with lupus nephritis, experience
repeated and chronic insults to the renal parenchyma, thereby resulting in lasting damage.
Furthermore, others in whom the initial disease is either inactive or cured may still develop
progressive renal disease due to hemodynamic and other mechanisms.
In addition to variations in the activity of the individual diseases, these different manifestations
are partly due to how the kidney responds to injury. The kidney is able to adapt to damage by
increasing the filtration rate in the remaining normal nephrons, a process called adaptive
hyperfiltration. As a result, the patient with mild renal insufficiency often has a normal or near-normal serum creatinine concentration. Additional homeostatic mechanisms (most frequently
occurring within the renal tubules) permit the serum concentrations of sodium, potassium,
calcium, and phosphorous and the total body water to also remain within the normal range,
particularly among those with mild to moderate renal failure. (See "Assessment of kidney
function: Serum creatinine; BUN; and GFR".)
Adaptive hyperfiltration, although initially beneficial, appears to result in long-term damage to
the glomeruli of the remaining nephrons, which is manifest by proteinuria and progressive renal
insufficiency. This process appears to be responsible for the development of renal failure among
those in whom the original illness is either inactive or cured [1]. The institution of measures to
help prevent this process, such as antihypertensive therapy with an angiotensin convertingenzyme inhibitor or an angiotensin II receptor blocker, may slow progressive disease and even
preserve renal function. If these modalities are effective, the benefit is likely to be greatest if
begun before a great deal of irreversible scarring has occurred. (See "Secondary factors and
progression of chronic kidney disease".)
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The gradual decline in function in patients with chronic kidney disease (CKD) is initially
asymptomatic. However, as previously mentioned, different signs and symptoms may be
observed with advanced renal dysfunction, including volume overload, hyperkalemia, metabolic
acidosis, hypertension, anemia, and bone disease. The onset of end-stage renal disease results
in a constellation of signs and symptoms referred to as uremia.
Manifestations of the uremic state include anorexia, nausea, vomiting, pericarditis, peripheral
neuropathy, and central nervous system abnormalities (ranging from loss of concentration and
lethargy to seizures, coma, and death). No direct correlation exists between the absolute serumlevels of blood urea nitrogen (BUN) or creatinine, and the development of these symptoms. Some
patients have relatively low levels (eg, a BUN of 60 mg/dL [21.4 mmol/L] in an older patient) but
are markedly symptomatic, while others have marked elevations (eg, a BUN of 140 mg/dL [50
mmol/L]) but remain asymptomatic. To continue life, uremic patients require the institution of
renal replacement therapy with hemodialysis, peritoneal dialysis, or renal transplantation. (See
"Uremic toxins".)
Not all individuals have progressive loss of kidney function. Some studies show a high rate of
progression, while others report relatively stable disease [2-4]. The rate of progression of
chronic kidney disease from one major stage to another varies based upon the underlying
disease, presence or absence of comorbid conditions, treatments, socioeconomic status,
individual genetics, ethnicity, and other factors.
Using epidemiologic data, general estimates for the rate of transition from a GFR between 15 to
60 mL/min per 1.73 m2 to end stage disease may be approximately 1.5 percent per year, while
the rate of transition from a GFR above 60 to below 60 mL/min per 1.73 m2 may be
approximately 0.5 percent per year [5,6].
The combination of both a low GFR plus dipstick positive proteinuria, versus either parameter
alone, is associated with a significantly increased risk of progressive renal disease. This was
shown in a retrospect ive study of the association between these measures and the 25 year
incidence of end-stage renal disease of middle aged men originally studied in the Multiple RiskFactor Intervention Study (MRFIT) [7]. The presence of 1+ dipstick proteinuria, 2+ dipstick
proteinuria, estimated GFR less than 60 mL/min per 1.73m2, and a low GFR plus 2+ proteinuria
was associated with hazard ratios of 3.1, 15.7, 2.4, and 41, respectively, for the development of
ESRD over a 25-year period.
DEFINITIONS AND CLASSIFICATION — The definition and classification of chronic kidney
disease may help identify affected patients, possibly resulting in the early institution of effective
therapy. To achieve this goal, guidelines were proposed from the National Kidney Foundation of
the United States through its Kidney Disease Outcomes Quality Initiat ive (K/DOQI) program [8].
These guidelines have been reviewed and accepted internationally [9-11].
The K/DOQI working group defined chronic kidney disease in adults as:
Evidence of structural or functional kidney abnormalities (abnormal urinalysis, imaging
studies, or histology) that persist for at least three months, with or without a decreased
GFR (as defined by a GFR of less than 60 mL/min per 1.73 m2). The most common
manifestation of kidney damage is persistent albuminuria, including microalbuminuria.
OR
Decreased GFR, with or without evidence of kidney damage.
Based upon these definitions, the following is the recommended classification of chronic kidney
disease by stage [8,12-16] along with the estimated prevalence in adults in the United States of
each stage, as determined by a National Health and Nutrition Examination Survey (NHANES)
performed in 1999 to 2004 [15]:
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Stage 1 disease is defined by a normal GFR (greater than 90 mL/min per 1.73 m2) and
persistent albuminuria (5.7 percent of the total United States population)
Stage 2 disease is a GFR between 60 to 89 mL/min per 1.73 m2 and persistent albuminuria
(5.4 percent)
Stage 3 disease is a GFR between 30 and 59 mL/min per 1.73 m2 (5.4 percent)
Stage 4 disease is a GFR between 15 and 29 mL/min per 1.73 m2 (0.4 percent for stages 4and 5)
Stage 5 disease is a GFR of less than 15 mL/min per 1.73 m2 or end-stage renal disease
(0.4 percent for stages 4 and 5)
Compared with 1988 to 1994, the overall prevalence of CKD stages 1 to 4 significantly increased
in the period 1999 to 2004 (13.1 versus 10.0 percent) [16].
The GFR was estimated in this survey using the simplified or abbreviated Modification of Diet in
Renal Disease (MDRD) study equation [8,12]. For small changes in serum creatinine, which may
be c linically significant, the measurements are most reliable if performed in the same laboratory.
By comparison, changes in serum creatinine of ±0.3 mg/dL measured in different laboratories may
represent variations in the assay rather than the GFR [17]. Because of this, there is an ongoing
effort to standardize serum creatinine measurements.
Websites are available to aid in the calculation of the GFR through different formulas. These
include: http://www.kidney.org/professionals/KDOQI/gfr_calculator.cfm and
nephron.com/mdrd/default.html
The K/DOQI guidelines consider a chronic estimated GFR (eGFR) of less than 60 mL/min per 1.73
m2 as a definition of chronic kidney disease. We feel this is too restrictive because it will
miscategorize some patients with clear evidence of loss of renal function as not having chronic
kidney disease. As an example, a patient whose serum creatinine concentration increases (as
measured in the same laboratory) slowly on sequential measurements from 0.8 to 1.2 mg/dL (71
to 106 micromol/L) clearly has chronic kidney disease even though the GFR may only have fallen
from 120 to 80 mL/min and the serum creatinine concentration still remains within the normal
range for the laboratory.
The K/DOQI guidelines have also suggested that microalbuminuria alone that persists for more
than three months falls within the definition of chronic kidney disease in patients without
diabetes. We do not agree that microalbuminuria without a reduction in GFR or some other
abnormality necessarily reflects renal disease. It correlates best with generalized endothelial
dysfunction and is clearly associated with an increase in cardiovascular risk. (See"Microalbuminuria and cardiovascular disease".) The K/DOQI clinical practice guidelines for CKD,
as well as other K/DOQI guidelines, can be accessed through the National Kidney Foundation's
web site at www.kidney.org/professionals/kdoqi/guidelines.cfm.
Some experts also feel that the presence of a low GFR alone should not necessarily be
considered a sign of progressive disease, particularly in older patients [18]. There are many
elderly patients who have substantial reductions in GFR who do not develop end-stage renal
disease in their lifetime [19]. Additional discussion related to the epidemiology of chronic kidney
disease and screening recommendations is presented separately. (See "Epidemiology of chronic
kidney disease and sc reening recommendations".)
ASSOCIATION WITH CARDIOVASCULAR DISEASE, END-STAGE RENAL DISEASE, AND
MORTALITY — There is a large body of evidence that patients with CKD have a substantial
increase in cardiovascular risk that can be in part explained by an increase in traditional risk
factors such as hypertension, diabetes, and the metabolic syndrome. CKD alone is also an
independent risk factor for cardiovascular disease. Among patients with CKD, the risk of death,
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particularly due to cardiovascular disease, is much higher than the risk of eventually requiring
dialysis. This is discussed separately. (See "Chronic kidney disease and coronary heart disease".)
Close attention to the prevention and management of cardiovascular disease should occur
among patients identified with chronic renal dysfunction [20]. As an example, the increased
intake of calcium (which is commonly given to treat hyperphosphatemia and may result in a high
calcium-phosphorus product) may enhance coronary arterial calcification. Although controversial,
this is thought by some to be associated with the development of coronary atherosclerosis, and
is related to the presence and/or consequences of elevated serum phosphorus, calcium, andparathyroid hormone levels. (See 'Hyperphosphatemia' below and "Vascular calcification in
chronic kidney disease".)
These and other observations have suggested that chronic kidney disease should be considered
a coronary equivalent and that aggressive risk factor reduction should be part of standard
therapy of patients with chronic kidney disease. (See "Chronic kidney disease and coronary
heart disease".)
Patients with CKD are also at increased risk for the development of end-stage renal disease
(ESRD) as well as all-cause mortality. In some subsets of individuals with CKD, the risk of ESRD
exceeds the risk of mortality. As an example, in an analysis of the African American Study of
Kidney Disease and Hypertension (AASK), follow-up of 764 participants for over 11 years found
that the rate of ESRD significantly surpassed the rate of total mortality (3.9/100 patient-years
versus 2.2/100 patient-years, respect ively) [21].
ASSOCIATION WITH NON-CARDIOVASCULAR DISEASE — Patients with CKD are at increased
risk for a variety of non-cardiovascular diseases, including infection and malignancy [22-24].
Careful attention should be paid to preventive measures such as influenza and pneumococcal
immunization, and age-appropriate screening for malignancy [25]. (See "Overview of preventive
medicine in adults".)
GENERAL MANAGEMENT OF CHRONIC KIDNEY DISEASE — The general management of the
patient with chronic kidney disease involves the following issues [26]:
Treatment of reversible causes of renal dysfunction
Preventing or slowing the progression of renal disease
Treatment of the complications of renal dysfunction
Identification and adequate preparation of the patient in whom renal replacement therapy
will be required
Reversible causes of renal dysfunction — In addition to exacerbation of their original renal
disease, patients with chronic renal disease with a recent decrease in renal function may be
suffering from an underlying reversible process, which if identified and corrected may result in
the recovery of function.
Decreased renal perfusion — Hypovolemia (such as vomiting, diarrhea, diuretic use,
bleeding), hypotension (due to myocardial dysfunction or pericardial disease), infection (such as
sepsis), and the administration of drugs which lower the GFR (such as nonsteroidal
antiinflammatory drugs [NSAIDs] and ACE inhibitors) are common causes of potentially reversible
declines in renal function.
The normal response to renal hypoperfusion is to lower the urine sodium concentration (less than
25 meq/L) and the fractional excretion of sodium (less than 1 percent in patients with advanced
renal failure) to very low levels. However, the superimposition of a prerenal process among
patients with chronic kidney disease may not result in the expected low values since the tubulesin the diseased kidney are unable to reabsorb sodium so efficiently. As a result, hypovolemia in
these patients should be diagnosed by the history and physical examination, including the
presence of relative hypotension, a low jugular venous pressure, and poor skin turgor. In this
setting, a judicious trial of fluid repletion may result in the return of renal function to the
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previous baseline. (See "Fractional excretion of sodium in acute kidney injury (acute renal
failure)".)
Administration of nephrotoxic drugs — The administration of drugs or diagnostic agents
that adversely affect renal function are a frequent cause of worsening renal function. Among
patients with chronic kidney disease, common offenders include aminoglycoside antibiotics
(particularly with unadjusted doses), nonsteroidal antiinflammatory drugs, and radiographic
contrast material, particularly in diabetics. The administration of such drugs should therefore be
avoided or used with caution in patients with underlying chronic kidney disease. (See"Manifestations of and risk factors for aminoglycoside nephrotoxicity" and "NSAIDs: Acute kidney
injury (acute renal failure) and nephrotic syndrome" and "Pathogenesis, clinical features, and
diagnosis of contrast-induced nephropathy".)
Certain drugs also interfere with either creatinine secretion or the assay used to measure the
serum creatinine. These include cimetidine, trimethoprim, cefoxitin, and flucytosine. In these
settings, there will be no change in GFR; the clinical clue that this has occurred is the absence
of a concurrent elevation in the blood urea nitrogen (BUN). (See "Drugs that elevate the serum
creatinine concentration".)
Urinary tract obstruction — Urinary tract obstruction should always be considered in the
patient with unexplained worsening renal function although, in the absence of prostatic disease,
it is much less common than decreased renal perfusion. Patients with slowly developing
obstruction typically have no changes in the urinalysis, no symptoms referable to the kidney,
and initially maintain their urine output. Given this lack of c linical clues, renal ultrasonography is
often performed to exclude urinary tract obstruction in patients with an unexplained elevation in
the serum creatinine. (See "Diagnosis of urinary tract obstruction and hydronephrosis".)
Slowing the rate of progression — Studies in experimental animals and humans suggest that
progression in chronic kidney disease may be due at least in part to secondary factors that are
unrelated to the ac tivity of the initial disease. The major factors are thought to be
intraglomerular hypertension and glomerular hypertrophy (which are primarily responsible for theadaptive hyperfiltration described above), leading to glomerular scarring (glomerulosc lerosis).
Additional causes may include hyperlipidemia, metabolic acidosis, and tubulointerstitial disease.
(See "Secondary factors and progression of chronic kidney disease".)
The major histologic manifestation of hemodynamically-mediated renal injury is secondary focal
segmental glomerulosclerosis [27]. Thus, proteinuria typically occurs in patients with progressive
chronic kidney disease, even in primary tubulointerstitial diseases such as reflux nephropathy.
Multiple studies in humans have been performed investigating the effect of treating secondary
factors on the progression of renal disease. There is clear evidence in diabetic nephropathy and
nondiabetic chronic kidney diseases that the administration of angiotensin converting enzyme
(ACE) inhibitors or angiotensin II receptor blockers (ARBs) slows the progression of chronic
kidney disease, with the greatest benefit in patients with higher degrees of proteinuria (figure
1) [28]. The possible efficacy of dietary protein restriction is less clear. (See "Antihypertensive
therapy and progression of nondiabetic chronic kidney disease" and "Protein restriction and
progression of chronic kidney disease".)
If these modalities are to be effective, the benefit is likely to be greatest if begun before a great
deal of irreversible scarring has occurred. Thus, protective therapy has the greatest impact if it
is initiated relatively early in the course, before the serum creatinine concentration exceeds 1.2
(106 micromol/L) and 1.5 mg/dL (133 micromol/L) in women and men, respectively, or the GFR is
less than 60 mL/min per 1.73 m2. At this point, most patients have already lost more than one-half of their GFR. Waiting until the disease progresses further diminishes the likelihood of a
successful response.
The following recommendations are consistent with JNC 7 and the K/DOQI Clinical Practice
Guidelines on hypertension and antihypertensive agents in chronic kidney disease [29-31].
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Aggressive goals are recommended for both proteinuria and blood pressure. Antihypertensive
therapy is given for both renal protection and cardiovascular protection, since chronic kidney
disease is associated with a marked increased in cardiovascular risk. (See 'Association with
cardiovascular disease, end-stage renal disease, and mortality' above and "Chronic kidney
disease and coronary heart disease".)
A reduction in protein excretion to less than 500 to 1000 mg/day; recognizing the difficulty
of achieving such a goal in many patients, we recommend a minimum reduction of at least
60 percent of baseline values.
A reduction in blood pressure to less than 130/80 mmHg. However, evidence from the
Modification of Diet in Renal Disease study, the AASK trial, and a meta-analysis from the
ACE inhibition and Progressive Renal Disease (AIPRD) study group suggest that an even
lower systolic pressure may be more effective in slowing progressive renal disease in
patients with a spot urine total protein-to-creatinine ratio ≥1000 mg/g (which represents
protein excretion of greater than 1000 mg/day) [28]. Caution is advised about lowering the
systolic blood pressure below 110 mmHg. (See "Measurement of urinary protein excretion".)
These aggressive goals will, in most patients, require therapy with multiple drugs. Our
recommendations concerning drug therapy are discussed separately. (See "Antihypertensive
therapy and progression of nondiabetic chronic kidney disease".)
ACE inhibitors and ARBs can cause a decline in renal function and a rise in plasma potassium that
typically occur soon after the onset of therapy. An elevation in serum creatinine of as much as
30 to 35 percent above baseline that stabilizes within the first two to four months of therapy is
considered acceptable and not a reason to discontinue therapy with these drugs [29,32].
However, a repeat plasma creatinine and potassium should be measured within three to five
days. (See "Antihypertensive therapy and progression of nondiabetic chronic kidney disease".)
In patients with nonproteinuric renal disease, most often a tubulointerstitial disease, none of the
above drugs has been shown to slow progression of the renal disease and therapy is limited toblood pressure control.
Other therapeutic modalities also may offer some renal protection:
The optimal level of protein intake has also not been determined but it may be reasonable
to restrict intake to 0.8 to 1.0 g/kg per day of high biologic value protein, with the lower
value used in patients with progressive chronic kidney disease. Some recommend even
lower levels, such as 0.6 to 0.75 g/kg per day of high value protein, with close supervision
and dietary counseling [33]. (See "Protein restriction and progression of chronic kidney
disease".)
Both hyperlipidemia and metabolic acidosis should be treated, in part because there is
some evidence that they may enhance the rate of progression of the renal disease (see
below). (See "Statins and chronic kidney disease".)
Smoking cessation should be encouraged, with smoking stoppage being associated with a
reduced rate of progression of chronic kidney disease [34]. In an increasing number of
studies, smoking also appears to correlate with an enhanced risk of developing kidney
disease (primarily nephrosclerosis) as well as increasing the rate of progression among
those with existing CKD [35].
Treatment of the complications of renal dysfunction — A wide range of disorders maydevelop as a consequence of the loss of renal function. These include disorders of fluid and
electrolyte balance, such as volume overload, hyperkalemia, metabolic acidosis, and
hyperphosphatemia, as well as abnormalities related to hormonal or systemic dysfunction, such
as anorexia, nausea, vomiting, fatigue, hypertension, anemia, malnutrition, hyperlipidemia, and
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bone disease. Attention needs to be paid to all of these issues.
One recommended diet, including suggest ions for protein, fat, mineral, water, and vitamin intake,
is presented in Tables 1 and 2 (table 1 and table 2). This should be modified based upon the
needs of the individual patient.
Volume overload — Sodium and intravascular volume balance are usually maintained via
homeostatic mechanisms until the GFR falls below 10 to 15 mL/min. However, the patient with
mild to moderate chronic kidney disease, despite being in relative volume balance, is less able to
respond to rapid infusions of sodium and is therefore prone to fluid overload.
Patients with chronic kidney disease and volume overload generally respond to the combination
of dietary sodium restriction and diuretic therapy, usually with a loop diuretic given daily. Some
investigators have also c laimed that limiting sodium intake may also help decrease progression of
chronic kidney disease by lowering intraglomerular pressure [36]. (See "Optimal dosage and side
effects of loop diuretics" and "Treatment of refractory edema in adults".)
Hyperkalemia — The ability to maintain potassium excretion at near normal levels is
generally maintained in patients with renal disease as long as both aldosterone secretion and
distal flow are maintained [37,38]. Thus, hyperkalemia generally develops in the patient who is
oliguric or who has an additional problem such as a high potassium diet, increased tissuebreakdown, or hypoaldosteronism (due in some cases to the administration of an ACE inhibitor or
ARB) [39]. Impaired cell uptake of potassium also may contribute to the development of
hyperkalemia in advanced chronic kidney disease. (See "Causes of hyperkalemia".)
Hyperkalemia due to ACE inhibitor or ARB therapy is most likely to occur in patients in whom the
serum potassium concentration is elevated or in the high normal range prior to therapy. This is
discussed in detail separately. (See "Treatment and prevention of hyperkalemia".)
In addition to treating hyperkalemia, there are several measures that can help prevent
hyperkalemia in patients with chronic kidney disease. These include ingestion of a low potassium
diet (eg, less than 40 to 70 meq/day [1500 to 2700 mg/day]) and avoiding, if possible, the useof drugs that raise the serum potassium concentration such as nonsteroidal antiinflammatory
drugs [40]. Nonselective beta-blockers make the postprandial rise in the serum potassium
concentration but do not produce persistent hyperkalemia. (See "Sympathetic ac tivity and
potassium balance" and "Patient information: Low potassium diet".)
Metabolic acidosis — There is an increasing tendency to retain hydrogen ions among
patients with chronic kidney disease [41-43]. This can lead to a progressive metabolic acidosis
with the serum bicarbonate concentration tending to stabilize between 12 and 20 meq/L, and
rarely falling below 10 meq/L [42,44].
Previously, exogenous alkali was not usually given to treat the generally mild metabolic acidosis(arterial pH generally above 7.25) in asymptomatic adults with chronic kidney disease. This was
primarily due to concerns related to the exacerbation of volume expansion and hypertension.
However, these concerns appear to be overstated.
There are three major reasons why treatment of the acidemia may be desirable in patients with
chronic kidney disease. (See "Pathogenesis and treatment of metabolic acidosis in chronic kidney
disease".)
Bicarbonate supplementation may slow the progression of chronic kidney disease [45].
Bone buffering of some of the excess hydrogen ions is associated with the release of
calcium and phosphate from bone, which can worsen the bone disease. (See 'Renal
osteodystrophy' below.)
Uremic acidosis can increase skeletal muscle breakdown and diminish albumin synthesis,
leading to loss of lean body mass and muscle weakness. The administration of bicarbonate
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increases serum albumin and the lean body mass [45].
We recommend alkali therapy to maintain the serum bicarbonate concentration above 23 meq/L
[45-50]. If alkali is given, sodium bicarbonate (in a daily dose of 0.5 to 1 meq/kg per day) is the
agent of choice. Sodium citrate (citrate is rapidly metabolized to bicarbonate) may be used in
patients who are unable to tolerate sodium bicarbonate, since it does not produce the bloating
associated with bicarbonate therapy [47]. Sodium citrate should be avoided in the rare patient
who may be taking aluminum-containing antacids since it markedly enhances intestinal aluminum
absorption [51,52].
The K/DOQI clinical practice guidelines for nutrition in CRF, as well as other K/DOQI guidelines,
can be accessed through the National Kidney Foundation's web site at
www.kidney.org/professionals/kdoqi/guidelines.cfm.
Hyperphosphatemia — A tendency toward phosphate retention begins early in renal
disease, due to the reduction in the filtered phosphate load. Although this problem is initially mild
with hyperphosphatemia being a relatively late event, phosphate retention is intimately related
to the common development of secondary hyperparathyroidism. (See "Pathogenesis of renal
osteodystrophy".)
From the viewpoint of calcium and phosphate balance, the hypersecretion of parathyroid
hormone (PTH) is initially appropriate, since PTH can correct both hyperphosphatemia and
hypocalcemia. As a result, phosphate balance and a normal serum phosphate concentration are
generally maintained in patients with a GFR of greater than 30 mL/min [53]. The price paid is
secondary hyperparathyroidism and the development of renal osteodystrophy. (See
"Pathogenesis of renal osteodystrophy".)
Dietary phosphate restrict ion may limit the development of secondary hyperparathyroidism in
patients with chronic kidney disease. An intake of about 800 mg/day may be desirable and is
recommended by the K/DOQI guidelines in patients with elevated phosphate and/or PTH levels.
However, it can be accomplished only by limiting protein intake which is not acceptable to manypatients (even though it may provide some protection against progressive renal disease). (See
"Protein restriction and progression of chronic kidney disease".)
Once the GFR falls below 25 to 30 mL/min, the addition of oral phosphate binders are usually
required to prevent hyperphosphatemia [53,54]. The K/DOQI guidelines recommend that serum
phosphorus levels should be between 2.7 and 4.6 mg/dL (0.87 and 1.49 mmol/L) among patients
with stage 3 and 4 chronic kidney disease, and between 3.5 and 5.5 mg/dL (1.13 and 1.78
mmol/L) among those with end-stage renal disease (or stage 5 disease) [54]. The serum
calcium-phosphorus product should also be maintained at <55 mg2/dL2. This is best achieved by
controlling serum levels of phosphorus within the target range. (See "Treatment of
hyperphosphatemia in chronic kidney disease".)
One of the preferred agents to bind intestinal phosphate is calcium salts, of which one of the
most widely used is calcium carbonate. Another calcium salt, calcium acetate, may be a more
efficient phosphate binder than calcium carbonate. In patients with stage 3 to 5 CKD, the
K/DOQI guidelines suggest that total elemental calcium intake (including both dietary calcium
intake and calcium-based phosphate binders) should not exceed 2,000 mg/day. Phosphate
binders are most effective if taken with meals to bind dietary phosphate.
Hypercalcemia is a common complication of this regimen, particularly in patients also treated
with calcitriol to protect against the development of renal osteodystrophy (see 'Renal
osteodystrophy' below). Thus, careful monitoring of the serum calcium concentration isessential.
The nonabsorbable agent sevelamer, which contains neither calcium nor aluminum, is a cationic
polymer that binds phosphate through ion exchange. Sevelamer controls the serum phosphate
concentration without inducing hypercalcemia. It may be best used in patients who cannot
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tolerate calcium-based phosphate binders (eg, due to hypercalcemia or constipation) or have
persistent hyperphosphatemia. It may also be used in combination therapy with calcium-
containing antacids among those with serum phosphate levels consistently above target levels
despite single-agent binder therapy. (See "Treatment of hyperphosphatemia in chronic kidney
disease".)
Lanthanum, a rare earth element, also has significant phosphate binding properties. Although no
significant clinical adverse effects have yet been reported, the long-term safety of lanthanum,
particularly its possible effect on bone and other organs, remains unclear. (See "Treatment of hyperphosphatemia in chronic kidney disease".)
Most other phosphate binders should be avoided:
Aluminum hydroxide, the previous standard, because of the gradual induction of aluminum
toxicity
Magnesium-containing antacids (such as magnesium hydroxide), because of the risk of
hypermagnesemia and the frequent development of diarrhea
Calcium citrate, since it markedly increases intestinal aluminum absorption
Unfortunately, all of the phosphate binders have a limited phosphorous binding capacity. Thus,
phosphate-binding compounds will be effective in lowering serum phosphorous levels only if the
dietary restrictions for phosphorus are continued simultaneously.
The increased intake of calcium may enhance coronary arterial calcification in this setting. This
is thought by some to be associated with the development of coronary atherosclerosis, and may
be related to the presence and/or consequences of elevated serum phosphorus, calcium, and
parathyroid hormone levels. Detailed discussions of these issues, including specific K/DOQI
guidelines, can be found separately. (See "Vascular calcification in chronic kidney disease".) The
K/DOQI clinical practice guidelines for bone metabolism and disease in CKD, as well as other
K/DOQI guidelines, can be accessed through the National Kidney Foundation's web site at
www.kidney.org/professionals/kdoqi/guidelines.cfm.
Renal osteodystrophy — Changes in mineral metabolism and bone structure are an almost
universal finding with progressive chronic kidney disease [55]. The principal types of renal bone
disease include osteitis fibrosa, osteomalacia, and adynamic bone disease. (See "Pathogenesis of
renal osteodystrophy".)
Osteitis fibrosa results from secondary hyperparathyroidism. Although an exact relationship is
unclear, parathyroid hormone levels appear to increase when renal function decreases beyond a
certain threshold value, with evidence suggesting that hormone levels begin to rise when the
creatinine clearance is less than 40 to 70 mL/min [8,56].
To help guide preventive measures, parathyroid hormone levels should therefore be assessed
among such patients, as hormonal abnormalities are one of the earliest markers of abnormal bone
mineral metabolism with progressive chronic kidney disease. Prevention and/or treatment of
osteitis fibrosis in patients with predialysis chronic kidney disease are primarily based upon
dietary phosphate restriction, the administration of oral phosphate binders, and the
administration of calcitriol (or vitamin D analogs) to directly suppress the secretion of
parathyroid hormone.
Calcitriol (1,25-dihydroxyvitamin D), the most active metabolite of vitamin D, is principally
synthesized in the kidney. Circulating calcitriol levels begin to fall when the GFR is less than 40mL/min and are typically markedly reduced in subjects with end-stage renal disease. In addition
to the loss of functioning renal mass, calcitriol production is also reduced by phosphate
retention. (See "Pathogenesis of renal osteodystrophy".)
Calcimimetics are agents that allosterically increase the sensitivity of the calcium-sensing
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receptor in the parathyroid gland to calcium. The calcium-sensing receptor is the principal factor
regulating parathyroid gland parathyroid hormone secretion and hyperplasia. The separate target
offers the potential to suppress parathyroid hormone secretion by mechanisms complementary
and potentially synergistic with vitamin D analogues that target the vitamin D receptor. Although
not approved for patients with CKD not yet on dialysis, cinacalcet, the only currently available
calcimimetic, is an emerging option in the treatment of secondary hyperparathyroidism in
predialysis pat ients with CKD.
Target serum levels for PTH as well as the approach to the management of this issue arediscussed separately. (See "Management of secondary hyperparathyroidism and mineral
metabolism abnormalities in adult predialysis patients with chronic kidney disease".)
Hypertension — Hypertension is present in approximately 80 to 85 percent of patients with
chronic kidney disease [57]. Treating hypertension can both slow the progression of proteinuric
CKD and reduce the rate of cardiovascular complications. (See "Chronic kidney disease and
coronary heart disease", section on 'Blood pressure control' and "Hypertension in kidney
disease".)
The desired degree of blood pressure control can usually be safely achieved with combined
therapy which usually begins with an ACE inhibitor or angiotensin II receptor blocker (also given
to slow disease progression as noted above) and a diuretic. Issues surrounding the treatment of
hypertension among patients with diabetic nephropathy are discussed in detail separately. (See
"Treatment of hypertension in patients with diabetes mellitus".)
Volume expansion, often in the absence of overt edema, contributes to the elevation in blood
pressure in most forms of chronic kidney disease. As a result, before other medications are
added, the dose of diuretics should be increased until the blood pressure is normalized or the
patient has attained "dry weight" which, in the presence of persistent hypertension, is defined
as the weight at which further fluid loss will lead either to symptoms (fatigue, orthostatic
hypotension) or to decreased tissue perfusion as evidenced by an otherwise unexplained
elevation in the BUN and plasma creatinine concentration. (See "Hypertension in kidneydisease".)
A loop diuretic is recommended for the treatment of hypertension and edema in patients with
chronic kidney disease. The thiazide diuretics in conventional dosage become less effective as
monotherapy when the GFR falls below 20 mL/min. They do, however, produce an additive effect
when administered with a loop diuretic for refractory edema. (See "Treatment of refractory
edema in adults".)
The optimal blood pressure in hypertensive patients with chronic kidney disease is uncertain. The
rate of loss of GFR appears to be more rapid when the mean arterial pressure remains at or
above 100 mmHg (which reflects a diastolic pressure of 80 to 85 mmHg in the absence of systolic hypertension). To slow progression of chronic kidney disease, the optimal blood pressure
depends in part on the degree of proteinuria. (See "Antihypertensive therapy and progression of
nondiabetic chronic kidney disease", section on 'Importance of proteinuria in predicting
response'.)
We recommend a blood pressure goal of less than 130/80 mmHg in patients with protein
excretion exceeding 500 to 1000 mg/day, which is consistent with JNC 7 and the K/DOQI Clinical
Practice Guidelines on hypertension and antihypertensive agents in chronic kidney disease
[29,30]. (See "Antihypertensive therapy and progression of nondiabetic chronic kidney
disease" and 'Slowing the rate of progression' above.)
There is no clear evidence supporting a blood pressure goal less than 130/80 mmHg in patients
with protein excretion below 500 to 1000 mg/day. The data addressing this issue and our
recommendations are presented elsewhere. (See "Antihypertensive therapy and progression of
nondiabetic chronic kidney disease", section on 'Nonproteinuric chronic kidney disease'.)
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Anemia — The anemia of chronic kidney disease is, in most patients, normocytic and
normochromic, and is due primarily to reduced product ion of erythropoietin by the kidney (a
presumed reflection of the reduction in functioning renal mass), and to shortened red cell
survival [58]. Anemia is a common feature in many patients with chronic kidney disease who do
not yet require dialysis, with anemia becoming increasingly common as glomerular filtration rates
(GFRs) decline below 60 mL/min per 1.73 m2 [59,60], particularly among diabetics [61]. As an
example, based upon over 15,000 participants in the NHANES survey, the prevalence of anemia
(Hbg <12 g/dL in men and <11 g/dL in women) increased from 1 percent at an eGFR of 60
mL/min per 1.73 m2 to 9 percent at an eGFR of 30 mL/min per 1.73 m2 and to 33 to 67 percentat an eGFR of 15 mL/min per 1.73 m2 [59]. (See "Erythropoietin for the anemia of chronic kidney
disease among predialysis and peritoneal dialysis pat ients".)
As stated in the 2006 K/DOQI guidelines, the evaluation of anemia in those with CKD should
begin when the Hgb level is less than 12 g/dL in females, and Hgb levels of less than 13.5 g/dL in
adult males [62]. These levels are based on the Hgb levels below the fifth percentile for the
adult general population as noted in the NHANES database [63]. If untreated, the hematoc rit of
patients with advanced chronic kidney disease normally stabilizes at approximately 25 percent in
the absence of bleeding or hemolysis.
The anemia observed with chronic kidney disease is largely diagnosed by excluding non-renalcauses of anemia in the patient with a suitably decreased GFR. The evaluation of patients should
therefore include red blood cell indices, absolute reticulocyte count, serum iron, total iron binding
capacity, percent transferrin saturation, serum ferritin, white blood cell count and differential,
platelet count, and testing for blood in stool. The content of hemoglobin in reticulocytes can
also be assessed. This work-up should be performed prior to administering epoetin alfa (EPO) or
darbepoetin alfa therapy. (See "Approach to the adult patient with anemia".)
Although primarily used in patients with end-stage renal disease, erythropoietic agents, such as
erythropoietin and darbepoetin alfa, also correct the anemia in those with chronic kidney disease
who do not yet require dialysis. (See "Erythropoietin for the anemia of chronic kidney disease
among predialysis and peritoneal dialysis patients".)
An erythropoietic agent should be given to the predialysis patient with CKD and anemia. We
suggest targeting Hgb levels in the range of 10 to 12 g/dL in predialysis patients with CKD. We
do not recommend maintaining Hgb levels above this level in predialysis patients being
administered an erythropoietic agent, since such levels have been associated with adverse
cardiovascular outcomes. In the patient with Hgb levels above 12 g/dL who is receiving an
erythropoietic agent, appropriate measures should be instituted, such as decreasing the dose of
the erythropoietic agent or increasing the dosing interval, to maintain Hgb levels in the range of
10 to 12 g/dL (see "Anemia of chronic kidney disease: Target hemoglobin/hematocrit for patients
treated with erythropoietic agents")
The erythropoietin dose should be approximately 50 to 100 U/kg per week. The 2006 guidelines
suggest that the initial erythropoietic agent dose and dose adjustment be given based upon the
initial and target hemoglobin level, the clinical setting, and the rate of increase of the
hemoglobin level [62].
Although erythropoietin has traditionally been given in two to three doses per week, it is
currently commonly given only once per week (or even less frequently). In practice, most
patients are dosed by unit dosing (eg, a vial), rather than on a U/kg basis. Thus, it would be
reasonable to begin most patients on 10,000 U subcutaneously once weekly. If necessary,
subsequent adjustments are made in interval and/or dose. Initially, to help detect changes in
levels, weekly test ing of the hemoglobin level is recommended. (See "Erythropoietin for theanemia of chronic kidney disease among predialysis and peritoneal dialysis patients".)
There is limited evidence suggesting that an increased mortality in predialysis patients may be
due to high erythropoietin doses. Thus, we suggest that the dose of epoetin alpha generally not
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associated with an adverse cardiovascular prognosis, chronic kidney disease is considered a
coronary heart disease equivalent [66]. (See "Chronic kidney disease and coronary heart
disease".)
Thus, the goal LDL-cholesterol is similar to that in patients with CHD, which has been less than
100 mg/dL (2.6 mmol/L). However, subsequent data has led some experts to recommend a lower
goal of less than 70 mg/dL (1.8 mmol/L). A similar lipid-lowering goal, beginning with statin
therapy, should be administered to patients with chronic kidney disease. (See "Treatment of
lipids (including hypercholesterolemia) in secondary prevention" and "Hyperlipidemia in nephroticsyndrome" and "Chronic kidney disease and coronary heart disease", section on 'Secondary
prevention'.)
Limited data suggest that lipid lowering may have an additional benefit in patients with chronic
kidney disease, which is slowing the rate of progression of the underlying renal disease. (See
"Secondary factors and progression of chronic kidney disease", section on 'Hyperlipidemia' and
"Statins and chronic kidney disease".)
Sexual dysfunction — Significant abnormalities in sexual and reproductive function are
frequently observed in patients with advanced renal disease. As an example, over 50 percent of
uremic men complain of symptoms that include erectile dysfunction, decreased libido, and
marked declines in the frequency of intercourse [67]; in addition, disturbances in menstruation
and fertility are commonly encountered in women with chronic kidney disease, usually leading to
amenorrhea by the time the patient reaches end-stage renal disease. (See "Sexual dysfunction
in uremic women" and "Sexual dysfunction in uremic men".)
An important clinical implication of these abnormalities is that pregnancy which is carried to term
is uncommon in women with a plasma creatinine concentration of 3 mg/dL (265 micromol/L) or
higher [68]. (See "Pregnancy in women with underlying renal disease".)
Treatment of complications of ESRD — Once the patient has reached the stage of near end-
stage renal disease (GFR less than 15 mL/min), signs and symptoms related to uremia begin to
occur, such as malnutrition, anorexia, nausea, vomiting, fatigue, sexual dysfunction, platelet
dysfunction, pericarditis, and neuropathy.
Malnutrition — Malnutrition is common in patients with advanced chronic renal disease
because of a lower food intake (principally due to anorexia), decreased intestinal absorption and
digestion, and metabolic acidosis [69-71]. Among participants ≥60 years of age in the United
States Third National Health and Nutrition Examination Survey (NHANES), a GFR <30 mL/min was
independently associated with malnutrition (odds ratio of 3.6) [70]. Many additional studies have
shown a strong correlation between malnutrition and death in maintenance dialysis patients.
(See "Indications for initiation of dialysis in chronic kidney disease".)
It is therefore desirable to monitor the nutritional status of patients with chronic kidney disease.A low plasma concentration of albumin and/or creatinine (which varies with muscle mass as well
as GFR) may be indicative of malnutrition.
To best assess nutritional status, the serum albumin concentration and body weight should be
measured serially; these should be measured approximately every one to three months for those
with estimated GFRs <20 mL/min, and more frequently if necessary for those with GFRs ≤15
mL/min [50]. (See "Assessment of nutritional status in end-stage renal disease".)
The desire to maintain adequate nutrition among patients with chronic renal failure clearly
competes with attempts to slow the progression of renal dysfunction with the use of a low
protein diet. Although the benefits of slowing progressive chronic kidney disease with markeddietary protein restriction remain controversial, it is probably reasonable to restrict intake to 0.8
to 1.0 g/kg of high biologic value protein since this level of restriction avoids protein malnutrition
and may slow progressive disease. In addition, since symptoms and signs of uremic toxicity are
enhanced with high intakes of protein, it is reasonable to prescribe this diet to all patients with a
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GFR below 20 mL/min per 1.73 m2 [72].
Overall, the diet of most patients with chronic kidney disease should provide approximately 30 to
35 kcal/kg per day [72]. One recommended diet, including suggest ions for protein, fat, mineral,
water, and vitamin intake, is presented in the following tables (table 1 and table 2). The K/DOQI
clinical practice guidelines for nutrition in CRF, as well as other K/DOQI guidelines, can be
accessed through the National Kidney Foundation's web site at
www.kidney.org/professionals/kdoqi/guidelines.cfm.
Uremic bleeding — An increased tendency to bleeding is present in both acute and chronic
kidney disease. This appears to correlate most closely with prolongation of the bleeding time,
due primarily to impaired platelet function. (See "Platelet dysfunction in uremia".)
No specific therapy is required in asymptomatic patients. However, correction of the platelet
dysfunction is desirable in patients who are actively bleeding or who are about to undergo a
surgical or invasive procedure (such as a renal biopsy). A number of different modalities can be
used in this setting, including the correction of anemia, the administration of
desmopressin (dDAVP), cryoprecipitate, estrogen, and the initiation of dialysis. (See "Platelet
dysfunction in uremia".)
Pericarditis — Advances in management have decreased the incidence of pericarditis inpatients with chronic kidney disease, but this problem is still associated with significant morbidity
and occasional mortality. (See "Pericarditis in renal failure".)
Fever, pleuritic chest pain, and a pericardial friction rub are the major presentations of uremic
pericarditis. One relatively characteristic feature of uremic pericarditis is that the
electrocardiogram does not usually show the typical diffuse ST and T wave elevation,
presumably because this is a metabolic pericarditis and epicardial injury is uncommon. Thus, the
finding of these abnormalities suggests some other cause for the pericarditis. The occurrence of
pericarditis in a patient with mild to moderate chronic kidney disease is another clue that the
renal disease is probably not responsible.
The development of otherwise unexplained pericarditis in a patient with advanced renal failure is
an indication to institute dialysis (providing there is no circulatory compromise or evidence of
impending tamponade) (see below). Most patients with uremic pericarditis respond rapidly to
dialysis with resolution of chest pain as well as a decrease in the size of the pericardial effusion.
(See "Pericarditis in renal failure".)
Uremic neuropathy — Dysfunction of the central and peripheral nervous system, including
encephalopathy (impaired mental status progressing if untreated to seizures and coma),
polyneuropathy, and mononeuropathy are important complications of end-stage renal disease.
They have become much less common because of the current tendency to earlier initiation of
dialysis.
Sensory dysfunctions, characterized by the restless leg or burning feet syndromes, are frequent
presentations of uremic neuropathy. These complications are usually absolute indications for the
initiation of dialysis. The extent of recovery from uremic neuropathy is directly related to the
degree and extent of dysfunction prior to the initiation of dialysis. (See "Uremic
polyneuropathy".)
Thyroid dysfunction — The kidney normally plays an important role in the metabolism,
degradation, and excretion of several thyroid hormones. It is not surprising therefore that
impairment in kidney function leads to disturbed thyroid physiology. However, the overlap in
symptomatology between the uremic syndrome and hypothyroidism requires a cautiousinterpretation of the tests of thyroid function.
It is usually possible in the individual patient with chronic kidney disease to assess thyroid status
accurately by physical diagnosis and thyroid function testing. The disturbances that can occur
include low serum free and total T3 concentrations and normal reverse T3 and free T4
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concentrations. The serum thyrotropin (TSH) concentration is normal and most patients are
euthyroid. (See "Thyroid function in chronic kidney disease".)
PREPARATION FOR AND INITIATION OF RENAL REPLACEMENT THERAPY — It is important to
identify patients who may eventually require renal replacement therapy since adequate
preparation can decrease morbidity and perhaps mortality. Early identification enables dialysis to
be initiated at the optimal time with a functioning chronic access and may also permit the
recruitment and evaluation of family members for the placement of a renal allograft prior to the
need for dialysis. In addition, the ability of the individual to psychologically accept therequirement of life-long renal replacement therapy is often diminished if inadequate time has
elapsed between the time of recognition of end-stage renal disease and the initiation of dialysis.
Chronic kidney disease progresses at a variable rate due to differences in the clinical course of
the underlying diseases (particularly between individuals) and the recognition that the natural
history of progressive renal disease can be altered by various therapeutic interventions,
particularly strict blood pressure control with an ACE inhibitor or ARB. (See 'Slowing the rate of
progression' above.) As a result, exactly if and when a patient may require dialysis or renal
transplantation is unclear. In addition, some patients refuse renal replacement therapy until the
onset of absolute indications, while others desire early initiation to avoid the complications of
severe chronic kidney disease, such as malnutrition.
Referral to nephrologists — Patients with CKD should be referred to a nephrologist early in the
course of their disease, preferably before the plasma creatinine concentration exceeds 1.2 (106
micromol/L) and 1.5 mg/dL (133 micromol/L) in women and men, respectively, or the eGFR is less
than 60 mL/min per 1.73 m2. These subspecialists are trained to help counsel the patient in
choosing the optimal renal replacement therapy and to manage the many issues associated with
chronic kidney disease [73]. Lower costs and/or decreased morbidity and mortality may be
associated with early referral and care by subspecialists [74-84]. Reasons for later referral may
include disease specific factors, patient and physician dependent causes, and health care
system related factors [85]. (See "Late referral to nephrologists of patients with chronic kidney
disease".)
There are guidelines that advocate early screening for patients at risk of chronic kidney disease.
The NKF-K/DOQI guidelines for CKD recommend that all individuals should be assessed, as part of
routine health examinations, to determine whether they are at increased risk for developing CKD.
The detection of patients with early disease may also facilitate proper care and early referral to
nephrologists. (See "Epidemiology of chronic kidney disease and screening recommendations".)
The K/DOQI clinical practice guidelines for CKD, as well as other K/DOQI guidelines, can be
accessed through the National Kidney Foundation's web site at
www.kidney.org/professionals/kdoqi/guidelines.cfm.
An equally important component of early identification is institution of renoprotective therapy(eg, ACE inhibitor, angiotensin II receptor blocker, and rigorous blood pressure control) as early
as possible after identifying the presence of progressive chronic kidney disease. Protective
therapy has the greatest impact if it is initiated before the plasma creatinine concentration
exceeds 1.2 (106 micromol/L) and 1.5 mg/dL (133 micromol/L) in women and men, respectively,
or the eGFR is less than 60 mL/min per 1.73m2. At this point, most patients have already lost
more than one-half of their GFR. Waiting until the disease progresses further diminishes the
likelihood of a successful response but still should be attempted. (See "Antihypertensive therapy
and progression of nondiabetic chronic kidney disease" and 'Slowing the rate of
progression' above.)
Choice of renal replacement therapy — Once it is determined that renal replacement therapy
will eventually be required, the patient should be counseled to consider the advantages and
disadvantages of hemodialysis (in-center or at home), peritoneal dialysis (continuous or
intermittent modalities), and renal transplantation (living or deceased donor) [86]. The 2006
K/DOQI guidelines recommend that patients with a GFR less than 30 mL/min per 1.73 m2 should
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be educated concerning these issues [87].
Kidney transplantat ion is the treatment of choice for end-stage renal disease. A successful
kidney transplant improves the quality of life and reduces the mortality risk for most patients,
when compared with maintenance dialysis. To facilitate early transplantation, a 2008 NKF/KDOQI
conference suggested early education and referral to a transplantation center plus the
identification of potential living donors [88].
However, not all patients are appropriate candidates for a kidney allograft because of absolute
and/or relative contraindications to this procedure or the subsequent required medications.
Referral to a transplant program should occur once renal replacement therapy is thought to be
required within the next year [89]. (See "Patient survival after renal transplantation" and
"Evaluation of the potential renal transplant recipient".)
Living donor transplants, if available, have the additional advantage of being performed with
minimal delay, thereby permitting preemptive transplantat ion (transplantation prior to dialysis).
Such patients appear to have improved graft survival compared to those who undergo a period
of dialysis before transplantation [90]. (See "Dialysis issues prior to and after renal
transplantation" and "Risk factors for graft failure in kidney transplantation".)
For these individuals and for those who are suitable transplant recipients but must wait for anavailable kidney, the choice between hemodialysis or peritoneal dialysis is influenced by a number
of considerations such as availability, convenience, comorbid conditions, home situation, age,
gender, and the ability to tolerate volume shifts. (See "Dialysis modality and patient
outcome" and "Choosing a modality for chronic peritoneal dialysis" and "Dialysis in diabetic
nephropathy".)
In the United States, the universal availability of renal replacement therapy forces the
nephrologist to consider its application in every patient in whom it might be indicated. However,
the patient, particularly the elderly and terminally ill, may refuse dialysis, a choice which is
assuming more prominence as patients and physicians grapple with the increasing use of
advance directives, and the laudable goals of death with dignity and life with quality.
Nevertheless, not all nephrologists are willing to recommend no treatment, especially when
dialysis facilities are available with no need to ration therapy. These issues can be a source of
conflict among physicians, patients, and their families. (See "Withdrawal from and withholding of
dialysis".)
Preparation for hemodialysis — Hemodialysis requires a stable access to the bloodstream to
permit dialysis to be performed. (See "Overview of the hemodialysis apparatus".) The access
should generally be placed in the nondominant upper extremity, because of the increased risk of
infection and more severe consequences of arterial steal syndrome with lower extremity grafts.
Venipuncture should therefore be restricted to the arm not chosen for eventual access
placement so that the veins in the other arm will be preserved.
There are three major types of vascular access for maintenance hemodialysis: primary
arteriovenous (AV) fistulas; synthetic arteriovenous fistulas (AV grafts); and double-lumen,
cuffed tunneled catheters. To facilitate placement of a permanent vascular access, the 2008
Society for Vascular Surgery guidelines recommend that patients be referred to an access
surgeon when the patient has late stage 4 CKD, defined by an estimated GFR of less than 20 to
25 mL/min per 1.73 m2 [91]. (See "Chronic hemodialysis vascular access: Types and
placement".)
Primary AV fistulas — Primary AV fistulas are the preferred form of vascular access given
their significantly higher long-term patency rates and lower rate of complications. Since a
primary AV fistula requires months to mature and is the access of choice, patients should be
referred for surgery to attempt access construction when it is estimated that the patient is
within one year of the anticipated need for dialysis as manifested by a GFR less than 25 mL/min,
a plasma c reatinine concentration greater than 4 mg/mL (354 micromol/L), or a rapid rate of
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progression. The 2006 K/DOQI guidelines recommend that a fistula be placed at least six months
prior to the anticipated start of hemodialysis [87].
Primary AV fistulas are typically constructed with an end-to-side vein-to-artery anastomosis of
the cephalic vein and the radial artery. These fistulas have good long-term patency and
infrequently develop infectious complications. A well constructed radial cephalic fistula that
functions for the first six months can be expected to function for up to 20 years.
The evaluation of non-maturing AV fistulas may require an assessment with procedures that
involve the administration of iodinated radiocontrast agents, thereby possibly resulting in
radiocontrast-induced nephropathy and required early dialysis. In one study of 65 endovascular
procedures among 34 patients with stage 4 CKD and nonmaturing AV fistulas, contrast-induced
nephropathy (25 percent increase in serum creatinine concentration) occurred in only 5 percent
of patients at one week post-procedure and no one required acute dialysis [92]. The mean
contrast volume was small (mean of 7.8 mL per procedure).
The administration of gadolinium during magnetic resonance imaging has been linked to an often
severe disease called nephrogenic systemic fibrosis among patients with moderate to severe
renal disease, particularly those requiring dialysis. As a result, it is recommended that
gadolinium-based imaging be avoided, if possible, in patients with an eGFR less than 30 mL/min.
There is no consensus among experts concerning the dec ision to administer gadolinium among
patients with an eGFR between 30 and 60 mL/min. (See "Nephrogenic systemic
fibrosis/nephrogenic fibrosing dermopathy in advanced renal failure".)
Synthetic AV access (bridge grafts) — AV fistulas constructed with synthetic material,
most commonly polytetrafluoroethylene (PTFE), provide excellent vascular access in patients
who fail endogenous AV fistula placement. PTFE has good surgical handling characteristics, and
grafts of this material usually mature in two weeks. Synthetic grafts have a higher long-term
complication rate (eg, infection, thrombosis) than primary fistulas. The 2006 K/DOQI guidelines
recommend that a synthetic graft be placed at least three to six weeks prior to the anticipated
start of hemodialysis [87].
Cuffed tunneled catheters — These central venous catheters, which can be used
immediately after placement, are primarily used as intermediate-duration vascular access to
allow maturation of endogenous fistulas. They can also provide acceptable long-term access in
patients who have exhausted all available sites. Nevertheless, these central venous catheters
are inferior to AV access as long-term access, since they provide lower flows and have higher
rates of infection and other complications. (See "Acute hemodialysis vascular access".)
Preparation for peritoneal dialysis — Peritoneal dialysis catheters, which are placed into the
abdominal cavity, can be used immediately after placement. However, to minimize the risk of
fluid leak, it is preferable to wait at least 10 to 14 days before beginning dialysis. If dialysis is
required less than 10 days following catheter placement, small volume exchanges performed in
the recumbent position can be performed with little risk of leak. (See "Placement and
maintenance of the peritoneal dialysis catheter".)
Preparation for renal transplantation — Preparation for renal transplantation, which principally
involves evaluation of the potential renal transplant recipient and/or the living donor, is
discussed in detail separately. Referral of patients with CKD to a transplant center should occur
when the GFR decreases to less than 30 mL/min or, among diabetics, when the GFR is between
30 to 40 mL/min [93]. (See "Evaluation of the potential renal transplant recipient" and "Living
unrelated donors in renal transplantation".)
Indications for renal replacement therapy — There are a number of clinical indications to
initiate dialysis in patients with chronic kidney disease (CKD). These include [87,94,95]:
Pericarditis or pleuritis (urgent indicat ion)
Progressive uremic encephalopathy or neuropathy, with signs such as confusion, asterixis,
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myoclonus, wrist or foot drop, or, in severe, cases, seizures (urgent indication)
A clinically significant bleeding diathesis attributable to uremia (urgent indication)
Fluid overload refractory to diuretics
Hypertension poorly responsive to antihypertensive medications
Persistent metabolic disturbances that are refractory to medical therapy. These include
hyperkalemia, metabolic ac idosis, hypercalcemia, hypocalcemia, and hyperphosphatemia.
Persistent nausea and vomiting
Evidence of malnutrition
Relative indications for the initiation of dialysis include decreased attentiveness and cognitive
tasking, depression, persistent pruritus or the restless leg syndrome.
We suggest that, among patients with progressive CKD, clinicians must be vigilant for the
presence of symptoms and/or signs of uremia and patients should also be fully informed of any
symptoms of uremia to be able to contact their physicians appropriately. Dialysis should be
considered based upon clinical factors plus the estimated GFR. Dialysis should be initiated in the
patient with symptoms and/or signs due to uremia.
Among asymptomatic patients with progressive CKD, the t iming of initiation of dialysis is unclear
and there is no specific threshold GFR level that has been established for the initiation of
dialysis. To help avoid the onset of possible life-threatening complications of uremia, the
initiation of dialysis should be considered in the asymptomatic patient with an extremely low GFR,
such as an estimated GFR of approximately 8 to 10 mL/min per 1.73 m2. However, some
clinicians may choose to closely monitor (weekly) asymptomatic patients with progressive CKD
even when the GFR is less than 8 to 10 mL/min per 1.73 m2, with the initiation of dialysis upon
the onset of uremic signs/symptoms. Nevertheless, as noted in the IDEAL trial, the vast majority
of patients are initiated on dialysis because of the onset of uremic symptoms at a GFR of
approximately 10 mL/min per 1.73 m2 or above [96]. All approaches require close followup, early
nephrology referral, and adequate advance dialysis planning (including the presence of a
functioning peritoneal or vascular access and referral for transplantation). A detailed discussion
of the IDEAL trial and indications for dialysis in the patient with CKD can be found elsewhere.(See "Indications for initiation of dialysis in chronic kidney disease".)
The following are some of the more recent National and International Guidelines for the initiation
of dialysis, which were published before the results of the IDEAL trial were reported:
The 2006 National Kidney Foundation Dialysis Outcomes Quality Initiative (K/DOQI) for
peritoneal dialysis and hemodialysis adequacy published guidelines concerning the initiation
of dialysis among patients with renal insufficiency [87,95]. The work group suggested that
the benefits and risks of initiating renal replacement therapy should be considered in
patients with GFR less than 15 mL/min per 1.73 m2 (stage 5 chronic kidney disease).
Initiation of dialysis prior to stage 5 chronic kidney disease may also be required in patients
with certain characteristics and/or complications, such as dec lining health due to the loss
of kidney function.
The 2005 European Best Practice Guidelines for peritoneal dialysis suggest that dialysis be
initiated before the GFR is less than 6 mL/min per 1.73 m2, with consideration of initiation
when the GFR is approximately 8 to 10 mL/min per 1.73 m2 [97].
INFORMATION FOR PATIENTS — Educational materials on this topic are available for patients.
(See "Patient information: Low potassium diet".) We encourage you to print or e-mail this topic,
or to refer patients to our public web site www.uptodate.com/patients, which includes this and
other topics.
SUMMARY AND RECOMMENDATIONS — There are a significant number of general issues
related to the management of patients with chronic kidney disease. These are discussed in the
following sections of this topic review:
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Natural history of chronic kidney disease. (See 'Natural history of renal disease' above.)
The definition and classification of chronic kidney disease. (See 'Definitions and
classification' above.)
Association of chronic kidney disease with cardiovascular disease, end-stage renal
disease, infection, malignancy and mortality. (See 'Association with cardiovascular disease,
end-stage renal disease, and mortality' above and 'Association with non-cardiovascular
disease' above.)
Management of chronic kidney disease, which includes treatment of reversible causes of
renal dysfunction, preventing or slowing the progression of renal disease, treatment of the
complications of renal dysfunction, and the identification and adequate preparation of the
patient in whom renal replacement therapy will be required. (See 'General management of
chronic kidney disease' above and 'Preparation for and initiation of renal replacement
therapy' above.)
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84. Chow, KM, Szeto, CC, Law, MC, et al. Impact of early nephrology referral on mortality andhospitalization in peritoneal dialysis patients. Perit Dial Int 2008; 28:371.
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93. Gaston, RS, Basadonna, G, Cosio, FG, et al. Transplantation in the diabetic patient withadvanced chronic kidney disease: a task force report. Am J Kidney Dis 2004; 44:529.
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95. K/DOQI Clinical Practice Guidelines for Peritoneal Dialysis Adequacy. Am J Kidney Dis 2006;
47(Suppl 4):S1.96. Cooper, BA, Branley, P, Bulfone, L, et al. A randomized, controlled trial of early versus late
initiation of dialysis. N Engl J Med 2010; 363:609.
97. European Best Practice Guidelines for peritoneal dialysis. Nephrol Dial Transplant 2005;20(Suppl 9):3.
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GRAPHICS
ACE inhibitor slows progression of diabeticnephropathy
The effect of the administration of placebo or captopril topatients with type 1 diabetes with overt proteinuria and aplasma creatinine concentration equal to or greater than 1.5mg/dL (132 µmol/L). The likelihood of a doubling of the plasmacreatinine concentration (Pcr) was reduced by more than 50percent in the captopril group. Data from Lewis, EJ, Hunsicker, LG,
Bain, RP, Rohde, RD, N Engl J Med 1993; 329:1456.
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Recommended dietary intake for chronic kidney and end-stage renaldisease patients*
Chronic kidney disease•Maintenancehemodialysis
Protein 0.8 to 1.0 g/kg/day∆ of high biologicalvalue protein
>1.2 to 1.3 g/kg/day
Energy ≥35 kcal/kg/day; if the body weight is greater than 120 percent of normal or the patient is greater than 60 years of age a loweramount may be prescribed
Fat, percent of totalenergy intake
30 to 40 30 to 40
Polyunsaturated-to-saturated ratio (fattyacid ratio)
1.0:1.0 1.0:1.0
Carbohydrate Balance of nonprotein calories
Total fiber, g/day 20 to 25 20 to 25
Minerals, range of intake
Sodium, mg/day <2000 <2000
Potassium, meq/day 40 to 70 40 to 70
Phosphorus, mg/day 600 to 800◊ 600 to 800◊
Calcium, mg/day 1400 to 1600 1400 to 1600
Magnesium, mg/day 200 to 300 200 to 300
Iron, mg/day ≥10 to 18§ ≥10 to 18§
Zinc, mg/day 15 15
Water, mL/day Up to 3000 as tolerated Usually 750 to 1500
* The nutritional intake is adjusted based upon individual needs. This is particularly important
for the carbohydrate, lipid, and mineral contents of the diet.
• GFR <70 mL/min/1.73 m2 with evidence for progression.
∆ Some recommend 0.56 to 0.75 g/kg/day, with 0.35 g/kg/day of high biological value protein.
The protein intake is increased by 1.0 g/day of high biological value protein for each gram per
day of urinary protein loss. This is performed under close supervision and dietary counse ling.
◊ Phosphate binders often are also needed to maintain normal serum phosphorus levels.
§ 10 mg/day for males and nonmenstruating females, 18 mg/day for menstruating females.
Data from:
1. Ahmed, K, Kopple, J. Nutritional management of renal disease. In: Primer on Kidney Diseases,Greenberg, A (Ed). Academic Press, San Diego, CA, 1994, p. 289.2. Ikizler, IA. Nutrition and kidney disease. In: Primer on Kidney Diseases, Greenberg, A (Ed).
Elsevier, Philadelphia, 2005, p. 496.
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Recommended vitamin intake for patients with chronic kidney and end-stage renal disease
Vitamins
Chronic kidneydisease*
Maintenancehemodialysis
Diets to be supplemented with the following quantities
Thiamin, mg/day 1.5 1.1-1.2
Riboflavin, mg/day 1.8 1.1-1.3
Pantothenic acid,mg/day
5 5
Niacin, mg/day 20 14-16
Pyridoxine, mg/day 5 10
Vitamin B12, µg/day 3 2.4
Vitamin C, mg/day 60 75-90
Folic acid mg, day 1 1Vitamin A No addition No addition
Vitamin D • •
Vitamin E, IU/day 15 400-800
Vitamin K None None
The nutritional intake is adjusted based upon individual patient needs. * GFR <70
mL/min/1.73m2 with evidence for progression.
• Vitamin D, given as calcitriol, is adjusted according to phosphate and calcium balance. Data
from:1. Ahmed, K, Kopple, J. Nutritional management of renal disease. In: Primer on Kidney Diseases,
Greenberg, A (Ed). Academic Press, San Diego, CA, 1994, p. 289.2. Tattersall, J, Martin-Malo, A, Pedrini, L, et al. European Best Practice Guidelines on
Haenodialysis. Nephrol Dial Transplant 2007; 22(Suppl 2):62.
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