Indications For Initiation of Dialysis in Chronic Kidney Disease

Indications for initiation of dialysis in chronic kidney disease
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Nuhad Ismail, MD
Section Editor
Steve J Schwab, MD
Deputy Editor
Theodore W Post, MD
Last literature review version 18.2: May 2010 | This topic last updated: May 11, 2010
INTRODUCTION The decision to initiate dialysis in a patient with chronic kidney disease
(CKD) involves the consideration of subjective and objective parameters by the physician and the
patient. These parameters are often modulated by the patient's perception of his or her quality of
life and by possible anxiety about starting new therapy that is technologically complex.
INDICATIONS There are a number of clinical indications to initiate dialysis in patients with
CKD. These include [1-3]:
Pericarditis or pleuritis (urgent indication)
Progressive uremic encephalopathy or neuropathy, with signs such as confusion, asterixis,
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 acidosis, hypercalcemia, hypocalcemia, and hyperphosphatemia
Persistent nausea and vomiting
Weight loss or signs of malnutrition
However, these indications are potentially life-threatening and the patient is generally known to
have advanced CKD. As a result, most nephrologists agree that delaying initiation of dialysis until
one or more of these complications is present may put the patient at unnecessary jeopardy.
Only one study has reported the outcomes of patients with CKD who initiated dialysis only after
the onset of symptoms due to uremia. In this prospective cohort study of 233 consecutive
patients with advanced uremia, 151 were elective starters on dialysis, while 82 initially declined
dialysis [4]. Among the initial refusers, 55 percent developed a uremic emergency, while 48
percent were eventually established on maintenance dialysis. Compared with the elective
starters, one year mortality was significantly higher among the initial refusers (18 versus 7
percent). However, these results are confounded by lack of randomization and by three deaths
among the initial refusers, which resulted from treatment withdrawal.
Relative indications Since an important goal of dialysis is to enhance the quality of life as
well as to prolong survival, it is therefore important to consider less acute indications for dialysis.
These relative indications include anemia that is refractory to erythropoietic stimulating agents
and iron treatment, decreased attentiveness and cognitive tasking, depression, persistent pruritus
or the restless leg syndrome.
Unfortunately, the expressions of these signs and symptoms are variable in patients with slowly
progressive renal disease. The following are some of the factors that may contribute to this
variability.
Some patients accommodate to these symptoms and downgrade their sense of wellbeing as
renal failure progresses.
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Many of the medications given to patients with CKD have side effects that mimic uremic
symptoms. As examples, oral iron therapy often leads to nausea and centrally-acting
antihypertensive drugs can induce drowsiness independent of the degree of renal failure.
On the other hand, partial correction of anemia by erythropoietin may improve the patient's
sense of wellbeing without affecting the extent of uremia.
These factors illustrate the need to identify more objective markers of renal failure to lessen the
subjective component of the decision to initiate dialysis.
POSSIBLE INDICATIONS FOR EARLY DIALYSIS A number of factors have been proposed
as possible indications for early institution of maintenance dialysis. The two most widely
evaluated have been estimation of the glomerular filtration rate (GFR) and assessment of
nutritional status.
Estimation of GFR Although the filtration rate provides the best measure of functioning renal
mass, there are problems with each of the available tests used to measure the GFR. As an
example, many nephrologists previously used a target plasma creatinine concentration above 10
mg/dL (884 mol/L) [5,6]. However, progressive renal failure is frequently associated with
marked changes in the generation and elimination of creatinine [7]. In particular, inadequate
diet, increased tubular secretion of creatinine, and low muscle mass often limit the rise in the
plasma creatinine concentration, thereby masking the true degree of renal failure.
Use of the creatinine clearance is also limited in this setting. (See "Calculation of the creatinine
clearance".) The creatinine clearance generally overestimates the GFR due to increased tubular
creatinine secretion. Some patients with a seemingly "normal" plasma creatinine concentration
(<1.5 mg/dL or 132 mol/L) may have a GFR determined by inulin clearance as low as 20 to 25
mL/min/1.73 m [7]. One study, for example, evaluated 80 patients with CKD and a mean GFR of
22 mL/min [8]. The creatinine clearance was nearly twice the level of the inulin clearance.
The urea clearance is an even less accurate measure of GFR. The urea clearance underestimates
the rate of filtration due to a substantial degree of tubular reabsorption. It has been suggested
that, when GFR is less than 15 mL/min, the mean of the creatinine and urea clearance provides a
good estimate of GFR because the errors balance out. (See "Assessment of kidney function:
Serum creatinine; BUN; and GFR".)
Because of the limitations of the conventionally used tests, many investigators have sought more
accurate methods to measure the GFR. Although other markers of GFR, such as the clearance of
125-I-iothalamate, Cr-51-EDTA, 99m-Tc-DTPA, or inulin, are considered to be highly accurate,
they are not widely available and cumbersome to use for regular monitoring of renal function.
Several formulas that utilize easily obtained values have therefore been developed that help
estimate the GFR. These include the Cockcroft-Gault and Modification of Diet in Renal Disease
(MDRD) equations:
The Cockcroft-Gault equation is:
CCr, in mL/min
(140 - age) x lean body weight [kg]
PCr [mg/dL] x 72
This formula takes into account the increase in creatinine production with increasing weight, and
the decline in creatinine production with age. The value obtained must be multiplied by 0.85 in
women who have a smaller muscle mass than men (calculator 1).
Using data from the MDRD study, the following is a simplified MDRD formula [9]:
GFR, in mL/min per 1.73 m2 =
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186.3 x ((serum creatinine) exp[-1.154]) x (Age exp[-0.203]) x (0.742 if female) x (1.21 if

African American)
where exp is the exponential.
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.
Since the MDRD equations were derived from patients with renal failure, they can be reliably used
in those with significant renal dysfunction. The MDRD and Cockroft-Gault equations, however,
appear to generally overestimate the GFR in patients with stage 4 and 5 disease. Both the
abbreviated MDRD formula and the Cockcroft-Gault equations provide similar values within a
wide-range of patient ages. These formulas can only be used in patients with stable renal
function. (See "Assessment of kidney function: Serum creatinine; BUN; and GFR", for a detailed
discussion of these formulas).
The work group for the 2006 K/DOQI guidelines 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). (See 'Summary and recommendations' below.)
A retrospective study in the United States found that the GFR at initiation of dialysis varied with
patient age [10]. Based upon the United States Renal Data Systems database from 1995 to 1999,
the creatinine clearance at initiation was 14.76, 13.38, 11.63, and 11.60 mL/min among those
aged 20 to 44, 45 to 64, 65 to 74, and greater than 75 years, respectively.
Nutritional status Many studies have shown an increased mortality risk associated with
malnutrition in patients on maintenance dialysis [11,12]. As an example, an inverse relationship
has been shown between the plasma albumin concentration and mortality risk in this setting
[13,14]. The risk of death is increased when the plasma albumin concentration is below 3.5 to 4
mg/dL (35 to 40 g/L) (figure 1). (See "Patient survival and maintenance dialysis".)
The United States Renal Data Systems analysis extended this observation by evaluating the
relationship between the plasma albumin concentration at the time of initiation of dialysis and
subsequent survival [14]. The risk of death in patients starting hemodialysis with
hypoalbuminemia was substantially higher than in patients with a normal plasma albumin
concentration (figure 2). This relationship persisted even when diabetic patients, who may have
significant proteinuria, were excluded from the analysis [15]. Worse outcomes in patients with
lower plasma albumin concentrations at the initiation of dialysis have also been noted in patients
with continuous peritoneal dialysis [16].
The significance of hypoalbuminemia in patients with nephrotic syndrome (other than diabetes)
and end-stage renal disease is undetermined at present. In this setting, the low plasma albumin
concentration may not reflect malnutrition.
When interpreting the plasma albumin concentration, it is important to be aware of the specific
assay used by the clinical laboratory. The two most commonly used methods are the bromcresol
green (BCG) and bromcresol purple (BCP) dyebinding methods. BCG binds other proteins and
therefore overestimates the albumin concentration. This error does not occur with the BCP
method, the results of which compare closely with the reference immunonephelometric method
[17,18].
Another marker of nutritional status at the time of dialysis initiation is the plasma creatinine
concentration. The creatinine level reflects muscle mass as well as renal function. Thus, a patient
requiring dialysis at a lower than usual plasma creatinine concentration has a reduced muscle
mass and may be malnourished. Data from the USRDS are consistent with this hypothesis as the
late mortality rate was increased in patients with a plasma creatinine concentration below 10
mg/dL (884 mol/L) at the start of dialysis (figure 2) [14]. In comparison, the BUN level did not
show a correlation with mortality risk.
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These data strongly suggest that malnutrition, as evidenced by a low plasma albumin and/or
creatinine concentration at initiation of dialysis for symptomatic uremia, is an important
prognostic variable. Other markers of malnutrition also may prove useful, including the plasma
concentrations of transferrin, somatomedin C, prealbumin, and cholesterol [19]. (See
"Assessment of nutritional status in end-stage renal disease".) In patients treated with CAPD, for
example, low serum prealbumin concentrations (<30 mg/dL) have been associated with increased
mortality risk [20]. A similar finding has been shown with maintenance hemodialysis (relative risk
of mortality was 4.4 when the plasma prealbumin concentration was less than 15 mg/dL) [9].
A simple determinant of nutritional status that can be easily monitored is protein intake,
assuming that the patient is not on a low protein diet. Patients with CKD on an unrestricted diet
tend to decrease their protein intake as the renal failure progresses. The magnitude of this effect
was demonstrated in a report that evaluated 90 patients with CKD who received no dietary
intervention [21-23]. A direct correlation was noted between the dietary protein intake and the
creatinine clearance (Ccr):
1.1 g/kg per day at a Ccr above 50 mL/min
0.85 g/kg per day between 25 and 50 mL/min
0.70 g/kg per day between 10 and 25 mL/min
0.54 g/kg per day below 10 mL/min
These changes, which presumably reflect anorexia induced by renal failure, question the safety of
restricting protein intake in patients with a creatinine clearance below 25 mL/min.
These decrements in dietary protein intake can be followed by assessing daily urinary urea
nitrogen and nonurea nitrogen losses. If daily intake is relatively constant and the patient is in a
steady state (as evidenced by a stable BUN and body weight), then urinary nitrogen excretion is
roughly equal to nitrogen intake. The former can be estimated from [24]:
Urinary nitrogen excretion
Urine urea nitrogen
Nonurea nitrogen
Nonurea nitrogen excretion is relatively constant, averaging 30 mg/kg per day.

Each gram of nitrogen is derived from 6.25 grams of protein. Thus,
Estimated protein intake
6.25 (Urine urea nitrogen + 30 mg/kg)
If, for example, 24-hour urine urea nitrogen excretion is 8.2 grams in a 60 kg woman excreting
3.5 g of protein per day, then:
Estimated protein intake
6.25 (8.2 + 1.8)
62.5 grams
Thus, protein intake is approximately 1 g/kg per day. Moderate urinary protein loss can be
ignored, but each gram excreted above 5 g/day should be added to the above formula.
A useful measurement of protein metabolism is the protein equivalent of nitrogen appearance
(eg, excretion) normalized using the ideal body weight (nPNA) which is equivalent to the
normalized protein catabolic rate. Values below 0.8 g/kg per day are considered indicative of a
malnourished state. (See "Protein catabolic rate in maintenance dialysis".)
Effect of dialysis Although the initiation of dialysis improves appetite in symptomatic uremia,
there is a paucity of data showing that it is clearly associated with an improvement in nutritional
status. Two observational studies reported that initiation of dialysis was associated with clear
improvement in nutritional indices:
Over a one year period, different nutritional indices were evaluated every three months after
dialysis initiation among 50 hemodialysis patients [25]. Marked improvements were observed in
the serum albumin, serum prealbumin, nPNA, fat mass, and others. The degree of improvement
was dependent upon nutrition at baseline, with the lower the baseline value the lower its value at
one year.
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Among 97 patients initiating maintenance dialysis therapy, multiple nutritional indices,

including predialysis serum albumin, iron, transferrin saturation, creatinine, and the nPNA,
significantly increased over the first six months of therapy, with many indices continuing to
increase at study end [26]. In addition, dietary intake, as shown by the nPNA, directly correlated
with serum albumin value.
Given that dialysis was initiated based upon varying criteria, these studies do not address the
question of whether early or late initiation of dialysis is optimal. However, these results support
the view that dialysis initiation improves nutritional parameters in the first year after beginning
renal replacement therapy.
DOES EARLY DIALYSIS OR REFERRAL IMPROVE OUTCOME? There is conflicting evidence
concerning the effect of the early initiation of dialysis on survival. One study that compared
patients who began dialysis early (creatinine clearance >10 mL/min) with those started late
(creatinine clearance <4 mL/min) reported that patients with early dialysis had a higher 12-year
survival rate (85 versus 51 percent), as well as fewer hospital days per year (5 versus 11), and a
higher likelihood of working fulltime (75 versus 49 percent) [27].
However, other subsequent reports have not found a significant survival benefit with early
initiation:
In a prospective multicenter cohort study, mortality after the initiation of dialysis was
examined among 253 patients with known residual renal function, 94 (37 percent) of whom
started therapy later than that recommended by the DOQI guidelines [28]. There was a
nonsignificant trend toward improved survival among timely starters (an estimated survival
increase of 2.5 months in the first three years of dialysis); however, this was balanced by at least
4.1 months of extra time free of dialysis among the late initiators, suggesting that the apparent
gain in survival time was due to lead-time bias.
A retrospective Scottish study attempted to account for lead-time bias by evaluating survival
from the time at which patients had a creatinine clearance of 20 mL/min [29]. Early or late
initiation was defined as beginning dialysis with a creatinine clearance that was either higher or
lower than the median creatinine clearance obtained for all patients initiating dialysis (8.3
mL/min). Early initiation did not provide a survival benefit and was associated with increased
mortality; a Cox proportional hazards model found a 10 percent increased risk of death with every
1 mL/min increase in renal function at dialysis initiation.
A retrospective study evaluated the effect of comorbidity on mortality and early initiation of
dialysis [30]. An increased risk of death was associated with greater GFR at dialysis initiation
among all populations studied. After adjusting for all covariates, the general dialysis population
with a GFR greater than 10 mL/min per 1.73 m2 when beginning dialysis, compared to those with
a GFR less than 5 mL/min per 1.73 m2, had a 42 percent increased risk of death. Similar
increased risks with increased GFR were observed among the older and healthier populations (25
and 39 percent, respectively). The underlying reasons for these observations are unclear.
Although a survival benefit is unproven, there may be two additional advantages to early dialysis:
control of hypertension, and increased dietary intake [31]. Reversal of volume overload with
dialysis often leads to a reduction in blood pressure, which is typically volume-dependent in CKD.
(See "Hypertension in kidney disease".)
Perhaps more important, patients on dialysis patients require at least 1 g/kg of protein per day to
replace dialysis losses and maintain nitrogen balance. Thus, early institution of dialysis can allow
a more liberal diet in terms of both food and fluid.
No truly randomized study of early versus late initiation of dialysis for end-stage renal disease
has yet been performed. An ongoing trial, the IDEAL study, has been designed to determine
whether the timing of dialysis initiation has an effect upon survival [32]. Recruited patients will
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be randomly assigned to dialysis initiation at GFRs (as determined by the Cockcroft-Gault

equation) of either 10 to 14 mL/min per 1.73 m2 or 5 to 7 mL/per per 1.72, with outcomes
including morbidity and mortality at three years post-randomization.
Overall, data suggest that early initiation may decrease the likelihood of malnutrition, increase
the rate of rehabilitation, and improve longterm patient survival.
Possible value of early referral A related issue to the criteria for the initiation of dialysis is
the timing of referral of patients with chronic renal failure to a nephrologist. Referral occurs at
variable levels of renal function, but often late in the course of progressive renal failure, just
before or even after the onset of symptomatic uremia. Late referral reflects in part the absence of
clear criteria for the initiation of dialysis.
However, early referral affords the opportunity to assess the rate of progression of renal disease
and to exclude any reversible causes of a declining GFR. It may also improve patient outcome.
This is discussed in detail separately. (See "Late referral to nephrologists of patients with chronic
kidney disease".)
INITIATION OF DIALYSIS AND DIALYSIS DISEQUILIBRIUM An important potential
complication of the initiation of dialysis is the dialysis disequilibrium syndrome. This disorder,
which appears to be related in part to a rapid reduction in the plasma osmolality due to urea
removal, can produce a variety of symptoms including headache, nausea, vomiting, blurring of
vision, muscle twitching, disorientation, tremor, and seizures. Patients with underlying neurologic
disease or marked azotemia are at increased risk. (See "Dialysis disequilibrium syndrome", for a
discussion of this syndrome).
INFORMATION FOR PATIENTS Educational materials on this topic are available for patients.
(See "Patient information: Dialysis or kidney transplantation which is right for me?" and
"Patient information: Hemodialysis" and "Patient information: Peritoneal dialysis".) We encourage
you to print or e-mail these topic reviews, or to refer patients to our public web site,
www.uptodate.com/patients, which includes these and other topics.
SUMMARY AND RECOMMENDATIONS There are a number of clinical indications to initiate
dialysis in patients with CKD. These include [1-3]:
Pericarditis or pleuritis (urgent indication)
Progressive uremic encephalopathy or neuropathy, with signs such as confusion, asterixis,
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 acidosis, hypercalcemia, hypocalcemia, and hyperphosphatemia.
Persistent nausea and vomiting
Weight loss or signs of malnutrition
However, these indications are potentially life-threatening. They occur
when the patient has very advanced CKD, such as may be observed in those who present with
severe uremia and have not had prior medical contact. For patients under medical care, delaying
initiation of dialysis until one or more of these complications is present may put the patient at
unnecessary jeopardy; dialysis should therefore be initiated well before these indications have
developed. Patients with CKD or disease should therefore be closely followed and the GFR
estimated.
We therefore strongly consider initiation of dialysis when the approximate GFR is below 10 to 15
mL/min, especially in elderly patients and diabetics. (See "Assessment of kidney function: Serum
creatinine; BUN; and GFR", for a detailed discussion relating to measurements of GFR and the
various estimation equations for patients with markedly decreased renal function).
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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 [2,3]. 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 declining 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 [33].
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REFERENCES
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Daugirdas, JT, Blake, PG, Ing, TS (Eds). Lippincott Williams & Wilkins, Philadelphia 2007.
2. K/DOQI Clinical Practice Guidelines for Peritoneal Dialysis Adequacy. Am J Kidney Dis 2006;
47(Suppl 4):S1.
3. K/DOQI Clinical Practice Guidelines and Clinical Practice Recommendations 2006 Updates
Hemodialysis adequacy Peritoneal Dialysis Adequacy Vascular Access. Am J Kidney Dis 2006;
48(Suppl 1):S1.
4. Tang, SC, Ho, YW, Tang, AW, et al. Delaying initiation of dialysis till symptomatic
uraemia--is it too late?. Nephrol Dial Transplant 2007; 22:1926.
5. Man, NK. Initiation of dialysis: when?. Nippon Jinzo Gakkai Shi 1992; 34:1.
6. Obrador, GT, Arora, P, Kausz, A, et al. Level of renal function at the initiation of dialysis in
the U.S. end-stage renal disease population. Kidney Int 1999; 56:2227.
7. Levey, AS. Measurement of renal function in chronic renal disease. Kidney Int 1990; 38:167.
8. Shemesh, O, Golbetz, H, Kriss, JP, Myers, BD. Limitations of creatinine as a filtration marker
in glomerulopathic patients. Kidney Int 1985; 28:830.
9. Goldwasser, P, Michel, M A, Collier, J, et al. Pre albumin and lipoprotein (a) in
hemodialysis: Relationships with patient and vascular access survival. Am J Kidney Dis
1993; 22:215.
10. Balogun, SA, Balogun, RA, Evans, J. Age-related differences in renal function at onset of
renal replacement therapy in chronic kidney disease stage 5 patients. QJM 2006; 99:595.
11. Acchiardo, SR, Moore, LW, Latour, PA. Malnutrition as the main factor in morbidity and
mortality of dialysis patients. Kidney Int Suppl 1983; 16:199.
12. Lowrie, EG, Lew, NL. Death risk in hemodialysis patients: The predictive value of commonly
measured variables and an evaluation of death rate differences between facilities. Am J
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13. Owen, WF Jr, Lew, NL, Liu, Y, et al. The urea reduction ratio and serum albumin
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14. Comorbid conditions and correlations with mortality riskamong 3,399 incident hemodialysis
patients. Am J Kidney Dis 1992; 20:32.
15. Hakim, RM. Initiation of dialysis. In: Advances in Nephrology, vol 23, Grunfeld, JP, Back, JF,
Kreis, H, Maxwell, MH (Eds), Mosby Yearbook, Chicago 1994.
16. Misra, M, Nolph, KD, Khanna, R, et al. Retrospective evaluation of renal kt/V(urea) at the
initiation of long-term peritoneal dialysis at the University of Missouri: relationships to
longitudinal nutritional status on peritoneal dialysis. ASAIO J 2003; 49:91.
17. Blagg, CR, Liedtke, RJ, Batjer, JD, et al. Serum albumin concentration-related health care
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18. Wick. Albumin methodology. Dial Transplant 1994; 23:282.

19. Hakim, RM, Levin, N. Malnutrition in hemodialysis patients. Am J Kidney Dis 1993; 21:125.
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progression of chronic renal failure. J Am Soc Nephrol 1995; 6:1386.
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24. Maroni, BJ, Steinman, TI, Mitch, WE. A method for estimating nitrogen intake of patients
with chronic renal failure. Kidney Int 1985; 27:58.
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30. Kazmi, WH, Gilbertson, DT, Obrador, GT, et al. Effect of comorbidity on the increased
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Nephrologiques, Funck Brentano, JL, Back, JF, Kreis, H, Grunfeld, JP (Eds), Jean
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GRAPHICS
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Hypoalbuminemia and reduced survival in

hemodialysis
Odds ratio for death, adjusted for age, sex, race, and
underlying disease, according to the plasma albumin
concentration in patients on maintenance hemodialysis.
The likelihood of dying was inversely related to the
plasma albumin concentration, being greatest at a plasma
albumin concentration below 3.0 g/dL (30 g/L). All values
are signficantly different (p<0.001 to 0.03) from the odds
ratio of 1.0 at a normal plasma albumin concentration of
4.0 to 4.4 g/dL (40 to 44 g/L). Data from Owen, WF Jr, Lew,
NL, Liu, Y, et al, N Engl J Med 1993; 329:1001.
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Nutritional parameters predict relative mortality risk at initiation of

dialysis
Relative mortality risk in new patients begun on maintenance hemodialysis in

1986-1987 according to the plasma albumin (left) and creatinine (right)
concentrations. The mortality risk varied inversely with both parameters.
Asterisks refer to values that are significantly different from the reference
ranges of 3.6 to 4.0 g/dL (36 to 40 g/L) for albumin and 10 to 11.9 mg/dL
[884 to 1052 mol/L]) for creatinine. Lower albumin and creatinine levels
presumably reflect the negative impact of malnutrition on patient survival.
Data from United States Renal Data Systems, Am J Kidney Dis 1992; 20(Suppl 2):32.
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