INTRODUCTION — For patients with chronic kidney disease (CKD), the decision of when to start chronic dialysis is made in collaboration between the nephrologist and patient. Although dialysis effectively treats the signs and symptoms of uremia and fluid overload (some of which may be life threatening), it is a lifelong therapy that is associated with discomfort, inconvenience, and some risk for the patient.
Thus, dialysis should be started when the benefit from relieving uremic signs and symptoms is thought to outweigh its risk and associated effect on quality of life, but not before this time.
Preparation for dialysis is integrated into the overall care of the patient with advanced CKD. Ideally, the decision to initiate dialysis is made long after the patient has undergone an evaluation for kidney transplantation, identified their preferred dialysis modality, and has a functioning dialysis access in place. Referral of patients for evaluation for kidney transplantation should occur when the estimated glomerular filtration rate falls below 30 mL/min/1.73 m2, with every attempt to identify living donors prior to the need for dialysis. (See "Kidney transplantation in adults: Evaluation of the potential kidney transplant recipient".)
This topic reviews the indications for chronic dialysis for patients with end-stage kidney disease (ESKD). Other issues related to the care of the CKD patient and to options of renal replacement therapy are discussed elsewhere. (See "Overview of the management of chronic kidney disease in adults" and "Evaluating patients for chronic peritoneal dialysis and selection of modality".)
The indications for acute dialysis are discussed elsewhere. (See "Kidney replacement therapy (dialysis) in acute kidney injury in adults: Indications, timing, and dialysis dose", section on 'Urgent indications'.)
OUR APPROACH — Our decision to start dialysis is based upon the presence of end-stage kidney disease (ESKD)-related signs and symptoms, the estimated glomerular filtration rate (eGFR), and the rate of decline of the eGFR. These factors must be considered together. The GFR can be estimated using either the Modification of Diet in Renal Disease (MDRD) formula or the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. These formulas are used by most clinical laboratories and give similar results at low eGFR ranges.
Our approach is largely consistent with the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines [1], the 2014 Canadian Society of Nephrology guidelines [2], the European guidelines [3], and the 2015 Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines [4].
The indications for starting dialysis are the same for patients starting hemodialysis and peritoneal dialysis. Logistics surrounding the initiation of peritoneal dialysis are unique, however, and are discussed below. (See 'Peritoneal dialysis' below.)
Our general approach is as follows:
●Patients with eGFR >15 mL/min/1.73 m2 – We generally do not initiate chronic dialysis for such patients, even when they have possible symptoms related to ESKD. While some symptoms of kidney disease may be present in patients with eGFR >15 mL/min/1.73 m2, they usually can be managed by medical therapy, and dialysis is rarely required. When patients with eGFR >15 mL/min/1.73 m2 present with symptoms of ESKD, other causes should be excluded or treated before considering dialysis. Specific signs and symptoms are discussed below. (See 'Signs and symptoms' below.)
●Asymptomatic patients with eGFR 5 to 15 mL/min/1.73 m2 – We closely follow such patients (eg, monthly) for the emergence of ESKD-related signs and symptoms but do not initiate dialysis in the absence of signs or symptoms. (See 'Signs and symptoms' below.)
●Patients with eGFR 5 to 15 mL/min/1.73 m2 with signs or symptoms that could be due to ESKD – Among such patients, we exclude other causes of signs and symptoms and try to treat medically (ie, without dialysis), if possible, especially if the eGFR is >10 mL/min/1.73 m2 (see 'Signs and symptoms' below). We initiate dialysis for those patients whose signs and symptoms are refractory to medical therapy. An important exception is patients who have absolute indications for dialysis, including uremic pericarditis, pleuritis, or encephalopathy; such patients should be started on dialysis without delay. (See 'Absolute indications' below.)
As the eGFR declines below 10 mL/min/1.73 m2, patients often develop symptoms of ESKD that no longer can be treated medically and require dialysis [3].
●Patients with eGFR <5 mL/min/1.73 m2 – We and most other nephrologists initiate dialysis for most patients (who plan to do so) when eGFR is ≤5 mL/min/1.73 m2, regardless of the absence or presence of ESKD-related signs or symptoms. At such a markedly reduced eGFR, most patients will have signs and symptoms, which are difficult to treat medically. Furthermore, we believe that, at this eGFR, the risks of the patient requiring emergent dialysis initiation or having severe complications of ESKD are unacceptably high without elective dialysis initiation. (See 'Estimated glomerular filtration rate' below.)
Despite the general approach defined above, the decision of when to initiate dialysis remains complex, and there is large variability in the timing of dialysis initiation between patients. This is because uremic symptoms are often vague and nonspecific, and loss of kidney function is highly variable and may occur rapidly in up to 20 percent of patients. As an example, in a national cohort study of 23,349 United States veterans requiring dialysis, 4804 (21 percent) of the patients experienced an abrupt decline as their kidney failure progressed [5]. In the Chronic Renal Insufficiency Cohort (CRIC) Study, 8.5 percent had an abrupt decline leading to dialysis. Risk factors for decline included cardiovascular disease, diabetes, and cancer [6].
The 2012 KDIGO guidelines suggest that dialysis be initiated when there are signs or symptoms attributable to kidney failure (such as serositis, acid-base or electrolyte disorders not easily corrected medically, pruritus), an inability to control volume status or blood pressure, a progressive deterioration in nutritional status that is refractory to dietary interventions, or cognitive impairment [1]. The KDIGO guidelines state that such signs and symptoms often but not invariably occur when the eGFR is between 5 and 10 mL/min/1.73 m2.
The 2014 Canadian Society of Nephrology guidelines recommend monitoring and actively treating symptoms when the eGFR declines below 15 mL/min/1.73 m2 [2]. The guidelines recommend commencing dialysis in asymptomatic patients when the eGFR declines to below 6 mL/min/1.73 m2 or when symptoms occur [2].
European guidelines suggest that, in patients with a GFR <15 mL/min/1.73 m2, dialysis should be considered when symptoms are present, while recognizing that the majority of patients will be symptomatic and need to start dialysis with GFR in the range of 6 to 9 mL/min/1.73 m2 [3].
The 2015 KDOQI guidelines suggest that the decision to start dialysis should be based on uremic signs and symptoms, evidence of protein-energy wasting, and the ability to medically manage metabolic abnormalities and volume overload and not based upon the level of kidney function [4].
SIGNS AND SYMPTOMS — Uremia-related signs and symptoms may develop when the estimated glomerular filtration rate (eGFR) is 10 to 15 mL/min/1.73 m2 but usually are not disabling until the eGFR is <10 mL/min/1.73 m2 [7]. Signs and symptoms that provide an indication for dialysis may be classified as absolute (see 'Absolute indications' below) or common. (See 'Common indications' below.)
The severity of symptoms varies substantially among patients. Younger patients and patients without other comorbid conditions tend to tolerate lower eGFR levels without developing as many symptoms.
Among patients who have uremic symptoms despite an eGFR that is consistently >10 mL/min/1.73 m2, a nuclear determination of GFR or a 24-hour urine for measurement of urea and creatinine clearance may be performed in order to provide a more accurate estimate of the GFR. While the GFR estimation equations have been found to be extremely reliable for clinical purposes in the vast majority of patients, occasionally the GFR estimation may not accurately reflect the true GFR. As an example, among patients who have extremely low muscle mass, the eGFR by Modification of Diet in Renal Disease (MDRD) may overestimate the true GFR. (See "Assessment of kidney function", section on 'Measurement of GFR with plasma clearance'.)
Absolute indications — Patients who have absolute indications for dialysis should be initiated on dialysis without delay. Absolute indications to start chronic dialysis include the following [8-10]:
●Uremic pericarditis or pleuritis.
●Uremic encephalopathy – True uremic encephalopathy (ie, significant alterations in cognitive function in a patient without other causes) is a rare condition that usually does not occur with eGFR >5 mL/min/1.73 m2. Emergent dialysis is indicated. Progressive loss of cognitive function in patients with other underlying conditions (such as dementia, history of strokes, etc) may be an indication for a trial of renal replacement therapy for several weeks to see if cognitive decline improves.
These absolute indications are rarely observed today since dialysis is usually started prior to their development.
Common indications — Common signs and symptoms that provide an indication for dialysis initiation, but are not considered absolute indications, include:
●Declining nutritional status
●Persistent or difficult to treat volume overload
●Fatigue and malaise
●Mild cognitive impairment
●Refractory acidosis, hyperkalemia, and hyperphosphatemia
These indications are discussed individually below:
●Declining nutritional status – We generally initiate dialysis in patients with an eGFR <15 mL/min/1.73 m2 who have anorexia, weight loss, or poor caloric intake that is not adequately treated by conservative measures. Anorexia, nausea, and weight loss are the most common reasons to initiate dialysis.
With declining eGFR, symptoms of anorexia and weight loss are usually the first uremic symptoms to appear. Loss of appetite for meat is a frequent early symptom and sign [11-14]. In a study of 90 patients with CKD who received no dietary intervention, a direct correlation was noted between the dietary protein intake and the creatinine clearance [12]:
•1.1 g/kg per day at a clearance above 50 mL/min/1.73 m2
•0.85 g/kg per day between 25 and 50 mL/min/1.73 m2
•0.70 g/kg per day between 10 and 25 mL/min/1.73 m2
•0.54 g/kg per day below 10 mL/min/1.73 m2
After development of anorexia and weight loss, patients may then develop early morning nausea, followed by frequent nausea and vomiting.
Evaluation of anorexia and malnutrition requires careful history (including dietary protein intake), physical examination, and laboratory studies.
Although the history is very important, it is sometimes difficult to obtain an accurate history about these symptoms. Sometimes, patients and family members realize that anorexia is a key factor in the decision about dialysis, and they may not provide accurate information in order to delay or avoid dialysis.
Following the patient's edema-free weight is helpful, especially when followed over a number of months. A decline in serum albumin also signifies worsening nutritional status. Some nephrologists may also follow urinary nitrogen excretion as a marker of protein intake, although this is rarely done in clinical practice.
In addition, clinicians must be aware of a number of other potential causes of these symptoms. As an example, diabetic gastroparesis causes similar symptoms and should be diagnosed, evaluated, and treated, if present. (See "Diabetic autonomic neuropathy of the gastrointestinal tract", section on 'Management'.)
A number of medications that are started at the time of kidney failure may also cause nausea. As an example, iron supplements frequently cause gastric symptoms. Phosphate binders, alkali replacement in the form of sodium citrate or sodium bicarbonate, and some antihypertensive medications may cause nausea. Changing to intravenous iron and alternative phosphate binders and antihypertensive medications may alleviate the nausea.
●Persistent volume overload – Sodium retention worsens as kidney function deteriorates. Volume overload can lead to refractory hypertension and recurring hospital admissions for congestive heart failure. Judicious use of diuretics is often effective in the treatment of volume overload among patients with low eGFR. Diuretics should not be withheld to prevent a rise in the blood urea nitrogen (BUN) and serum creatinine level. Instead, the patient should be diuresed to euvolemia or at least to a volume status that, in the clinician's judgment, is well tolerated by the patient, and the BUN and serum creatinine level evaluated at this volume status.
●Fatigue and malaise – Worsening fatigue and malaise develop as kidney function declines. In one study of patients with autosomal dominant tubulointerstitial kidney disease, which is typically an asymptomatic cause of chronic kidney disease (CKD), fatigue was reported by 15 percent of unaffected family members, 20 percent of affected individuals with stage 2 CKD, 45 percent of those with stage 3 CKD, and 55 percent with stage 4 CKD [15]. It is important for the clinician to rule out other causes such as anemia or depression. (See "Treatment of anemia in patients on dialysis" and "Diagnosis of iron deficiency in chronic kidney disease".)
●Mild cognitive impairment – Cognitive impairment may develop in older adults as kidney function worsens. It is often useful to ask a patient's spouse or other family member about possible signs of cognitive impairment in the patient since reports from the patient may not be reliable. It is extremely important to exclude progressive dementia in such patients. (See "Evaluation of cognitive impairment and dementia".)
For such patients, a three- to four-week trial of dialysis may be warranted to see if it improves mental faculties. Alternatively, in the patient with dementia, conservative management of kidney failure without dialysis may be indicated. (See "Kidney palliative care: Withdrawal of dialysis", section on 'Indications for withdrawal of dialysis'.)
●Refractory acidosis, hyperkalemia, and hyperphosphatemia – Patients may develop marked acidosis that is difficult to treat medically. Patients may not be able to tolerate large enough oral doses of sodium bicarbonate or sodium citrate to reach target serum bicarbonate values. (See "Pathogenesis, consequences, and treatment of metabolic acidosis in chronic kidney disease", section on 'Therapeutic approach'.)
Hyperkalemia may also develop and become persistent, despite conservative measures to prevent its occurrence, such as dietary restriction. (See "Overview of the management of chronic kidney disease in adults", section on 'Hyperkalemia'.)
Hyperphosphatemia may require dietary restriction and/or the initiation of binders (see "Management of hyperphosphatemia in adults with chronic kidney disease", section on 'Nondialysis chronic kidney disease patients'). Hyperphosphatemia usually does not occur until eGFR <15 mL/min/1.73 m2 and often occurs close to the need for dialysis.
Although dietary restriction and phosphate binders are often effective in the prevention of severe hyperkalemia and hyperphosphatemia, their presence increases the rationale for starting dialysis.
ESTIMATED GLOMERULAR FILTRATION RATE — There is no minimum estimated glomerular filtration rate (eGFR) that provides an absolute indication to begin dialysis in the absence of symptoms. Some patients, especially those who are young and have few comorbidities, may remain relatively asymptomatic despite an estimated glomerular filtration rate (eGFR) <10 mL/min/1.73 m2.
However, although there is no minimum eGFR that defines an absolute need for dialysis, we and most nephrologists initiate dialysis when the eGFR decreases below 5 mL/min/1.73 m2. Most patients will be symptomatic at such a low eGFR. However, even in the absence of symptoms, the risk that a sudden and unexpected health event (such as stroke, myocardial infarction, gastrointestinal bleeding, pneumonia, congestive heart failure) will result in emergent dialysis increases at such a low eGFR.
In general, estimates of GFR provided by the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations are adequate for monitoring kidney function in the later stages of CKD, particularly since we do not use the eGFR alone to determine when to begin dialysis (with the exception of patients with an eGFR <5 mL/min/1.73 m2). A comparison between estimation equations was provided by one study that included 409 patients starting dialysis [16]. The mean eGFR at the start of dialysis was 8 mL/min/1.73 m2 using the corrected Cockroft-Gault equation, 6 mL/min/1.73 m2 using the MDRD equation, and 6 mL/min/1.73 m2 using the CKD-EPI equation.
In the Initiating Dialysis Early and Late (IDEAL) study, the only trial in which survival was compared among patients initiating dialysis at two different thresholds of eGFR, found that the survival was comparable between groups [7]. In this study, 828 patients with an eGFR between 10 and 15 mL/min/1.73 m2 (as determined by the Cockcroft-Gault equation) were randomly assigned to dialysis initiation when the eGFR was either 10 to 14 mL/min/1.73 m2 or 5 to 7 mL/min/1.73 m2. Using the MDRD equation, this corresponded to approximately 8 to 13 mL/min/1.73 m2 for the early-start group versus 3 to 5 mL/min/1.73 m2 for the late-start group. The median time to the initiation of dialysis was 2 and 7 months in the early- and late-start groups, respectively. At a median follow-up of nearly four years, the survival was similar between the groups (62 and 63 percent), as were the number of cardiovascular events, infections, and dialysis complications.
However, these results do not imply that the initiation of dialysis can be delayed until the eGFR is between 5 and 7 mL/min/1.73 m2 in all patients. The design of the IDEAL study permitted clinicians to initiate dialysis based upon the presence of uremic symptoms and volume overload as well as on the eGFR. As a result, 76 percent of patients assigned to the late-start arm initiated dialysis earlier than planned. This resulted in a mean eGFR of 10 mL/min/1.73 m2 (7 mL/min/1.73 m2 with the MDRD formula) at dialysis initiation for the late-start group, which was only 2 mL/min/1.73 m2 less than the mean eGFR at dialysis initiation for the early-start group (12 mL/min/1.73 m2 or 9 mL/min/1.73 m2 with the MDRD formula). Thus, approximately 88 percent of all enrolled patients had initiated dialysis with an eGFR of approximately 7 mL/min/1.73 m2 (MDRD) or more, either because of symptoms or enrollment in the early dialysis arm.
Thus, in the absence of indications, patients with an MDRD eGFR above 10 mL/min/1.73 m2 do not require dialysis, although many will be placed on dialysis prior to the MDRD eGFR falling below 5 mL/min/1.73 m2. The indications for dialysis, regardless of the eGFR, are discussed above. (See 'Absolute indications' above and 'Common indications' above.)
The IDEAL study was rapidly accepted in the nephrology community. After publication of the IDEAL trial, observational data showed that, compared with pre-publication, fewer patients had an early-start of dialysis post-publication (34 versus 39 percent) [17].
OTHER CONTRIBUTING FACTORS
●Attitude of the nephrologist – The attitude of the nephrologist strongly influences the time of initiation of dialysis, and there is large variability in individual practices. In a retrospective study of patients starting dialysis in 2006 (n = 83,621) in the US Renal Data System, 16 percent of patients initiated dialysis with an estimated glomerular filtration rate (eGFR) ≥15 mL/min/1.73 m2, and 48 percent of patients initiated dialysis with an eGFR of >10 mL/min/1.73 m2. Factors associated with early start included physician graduation from nondomestic medical schools and less provider nephrologist experience [18]. Another study of US Renal Data System data showed that dialysis was initiated earlier in some US geographic regions (in order of earlier start of dialysis): Mountain regions, Midwest, Pacific, Mid-Atlantic, South, and New England [19]. One study suggested that salaried nephrologists at Veterans Affairs (VA) facilities were less likely to initiate dialysis among patients with an eGFR ≥10 mL/min/1.73m2 compared with non-VA nephrologists (who usually received increased financial compensation for each dialysis patient). This study could not exclude confounding factors [20].
For the nephrologist, starting a patient on dialysis at a given eGFR, regardless of symptoms, is often the easiest approach, particularly if the threshold eGFR for dialysis initiation is >10 mL/min/1.73 m2.
Patients who have a very low eGFR (ie, <10 mL/min/1.73 m2) and are not on dialysis require very close follow-up, which is usually labor intensive for the nephrologist. In contrast, the delivery of care in outpatient dialysis units is usually well coordinated and very easy for a nephrologist to administer.
Attitudes regarding the initiation of dialysis have changed over time. Previous clinical guidelines supported the decision to initiate patients at a higher eGFR than is generally recommended today [21,22].
●Older patients – There is no evidence that initiating dialysis earlier in older patients is beneficial [7]. As in other patient groups, treatment with dialysis versus conservative therapy leads to longer survival, though several studies have shown no survival benefit in older patients with high comorbidities [23]. In older patients with many comorbid conditions and decreased quality of life, careful discussions should take place regarding the benefits and hardships of dialysis. (See "Kidney palliative care: Conservative kidney management", section on 'Offering CKM' and "Maintenance dialysis in the older adult", section on 'Decision to initiate maintenance dialysis'.)
●Comorbid conditions – There is no evidence that patients with diabetes [7,24] or cardiovascular disease [7] benefit from earlier initiation of dialysis.
●Timing of referral to a nephrologist – The timing of referral of CKD patients to a nephrologist may have an impact on the timing of dialysis initiation. 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 kidney disease, to exclude any reversible causes of a declining GFR, and to permit close follow-up and adequate advance dialysis planning. It may also improve patient outcomes. This is discussed in detail separately. (See "Overview of the management of chronic kidney disease in adults", section on 'Referral to nephrologists'.)
PERITONEAL DIALYSIS — The timing of initiation of peritoneal dialysis is a complex decision that requires coordination between the nephrologist, the patient, and the dialysis center that will perform the training. Unlike a permanent hemodialysis access, which is preferably created weeks to months before dialysis is started, a peritoneal dialysis catheter is generally placed only 10 to 14 days before it is used. After the catheter is placed, however, the patient must be trained to perform dialysis, which is difficult to accomplish if they are uremic. As a result, among patients who require the acute initiation of chronic dialysis, hemodialysis is often initiated first using a temporary hemodialysis catheter, even if peritoneal dialysis is the preferred modality over the long term. The increasing availability of urgent-start peritoneal dialysis (defined as initiation of peritoneal dialysis less than two weeks after peritoneal dialysis catheter is placed) may ultimately change this. (See "Urgent-start peritoneal dialysis".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Dialysis".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Peritoneal dialysis (The Basics)" and "Patient education: Hemodialysis (The Basics)")
●Beyond the Basics topics (see "Patient education: Dialysis or kidney transplantation — which is right for me? (Beyond the Basics)" and "Patient education: Hemodialysis (Beyond the Basics)" and "Patient education: Peritoneal dialysis (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●The decision to start dialysis is based upon the presence of uremia-related signs and symptoms, the estimated glomerular filtration rate (eGFR), and the rate of decline of the eGFR.
Our general approach is as follows:
•Patients with eGFR >15 mL/min/1.73 m2 – We generally do not initiate chronic dialysis for such patients, even when they have possible symptoms related to end-stage kidney disease (ESKD). While some symptoms of kidney disease may be present, they usually can be managed by medical therapy, and dialysis is rarely required.
•Asymptomatic patients with eGFR 5 to 15 mL/min/1.73 m2 – We follow such patients closely (ie, monthly) for the emergence of ESKD-related signs and symptoms but do not initiate dialysis in the absence of signs or symptoms.
•Patients with eGFR 5 to 15 mL/min/1.73 m2 with signs or symptoms that could be due to ESKD – Among such patients, we exclude other causes of signs or symptoms and try to treat medically (ie, without dialysis), if possible. We initiate dialysis for those patients whose signs or symptoms are refractory to medical therapy. An important exception is patients who have absolute indications for dialysis, including uremic pericarditis or pleuritis or uremic encephalopathy; such patients should be initiated on dialysis without delay.
•Patients with eGFR <5 mL/min/1.73 m2 – We and most other nephrologists usually initiate dialysis for most patients (who plan to do so) when eGFR is ≤5 mL/min/1.73 m2, regardless of the absence or presence of ESKD-related signs or symptoms.
Despite the general approach defined above, the decision of when to initiate dialysis remains complex, and there is large variability in the timing of dialysis initiation between patients. This is because uremic symptoms are often vague and nonspecific, and loss of kidney function is highly variable and may occur rapidly. Up to 20 percent of patients may have an unexpected, accelerated loss of kidney function that leads to earlier initiation of dialysis than expected. (See 'Our approach' above.)
●Absolute indications to start chronic dialysis include uremic pericarditis or pleuritis and progressive uremic encephalopathy. (See 'Absolute indications' above.)
●Common signs and symptoms that provide indication for dialysis initiation include declining nutritional status, persistent or difficult-to-treat volume overload, fatigue and malaise, mild cognitive impairment, and refractory laboratory abnormalities including acidosis, hyperkalemia, and hyperphosphatemia. (See 'Common indications' above.)
●Compared with that of hemodialysis, the timing of initiation of peritoneal dialysis is a more complex decision that requires coordination among the nephrologist, the patient, and the dialysis center that will perform the training. (See 'Peritoneal dialysis' above.)
