Clinicians push for a conservative path forward on initiating dialysis
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A search in the medical literature or for information directed to patients on when treatment for kidney failure should begin is not likely to yield a consensus.
Surprisingly, after nearly 50 years of performing dialysis, the kidney community is not in agreement as to when that first treatment should begin.
“Determining the right time to initiate dialysis is complex,” Jay B. Wish, MD, professor of clinical medicine at Indiana University School of Medicine and chief medical officer for dialysis at Indiana University Health in Indianapolis, told Healio/Nephrology News & Issues. “Many patients don’t require dialysis until their eGFR is less than 5 [mL/min/1.73 m2], especially if they’re relatively asymptomatic.”
Wish and other sources interviewed for this Cover Story said a conservative approach to starting patients on dialysis – later rather than sooner – will lead to better long-term outcomes for patients.
“Dialysis initiation is rarely ‘too late’ and rarely causes harm if delayed, especially if this is done under the guidance of nephrologists and dietitians who watch patients closely under well-defined conservative management,” Kamyar Kalantar-Zadeh, MD, MPH, PhD, chief of the division of nephrology, hypertension and kidney transplantation at University of California-Irvine, told Healio/Nephrology News & Issues. “The prevailing culture of ‘earlier is better’ for dialysis initiation has not been shown to provide benefits to the patient or society.”
Practice guidelines
The National Kidney Foundation recommends dialysis should start when kidneys have begun to fail and patients have shortness of breath or fatigue, experience muscle cramps, nausea or vomiting. Kidney Disease Improving Global Outcomes (KDIGO) guidelines call for initiating dialysis when one or more of the following are present:
- symptoms or signs attributable to kidney failure (serositis, acid-base or electrolyte abnormalities, pruritus);
- inability to control volume status or blood pressure;
- a progressive deterioration in nutritional status refractory to dietary intervention; or
- cognitive impairment.
“This often but not invariably occurs in the GFR range between 5 [mL/min/1.73 m2] and 10 mL/min/1.73 m2,” according to the guidelines.
“The key message is that determining when to initiate kidney replacement therapy, whether dialysis, transplantation or any other therapy for kidney failure, should not rest on the eGFR number alone,” John Davis, CEO for KDIGO, told Healio/Nephrology News & Issues, “but one should consider the constellation of the severity of patient symptoms presented to the clinician.”
Guidelines published by the Canadian Society of Nephrology cite an eGFR of 6 mL/min/1.73 m2 to start dialysis, “but it isn’t an evidence-based lower limit,” Paul Komenda, MD, FRCPC, MHA, FACP, a professor of medicine at Max Rady College of Medicine and director of the Chronic Disease Innovation Centre at the University of Manitoba, told Healio/Nephrology News & Issues.
Komenda added: “If a patient is not symptomatic, has good quality of life and acceptable metabolic parameters, there should be no lower limit. Of course, patient reliability, ability to monitor them and a definite plan for elective initiation of dialysis does come into play.”
Wish said clinicians should remain flexible about starting dialysis when seeing symptoms of pending kidney failure or reviewing results from lab tests. “There is no one-size-fits-all eGFR threshold for initiating dialysis, and the decision to start should be based on a combination of eGFR and symptoms and/or additional lab abnormalities, such as hyperkalemia and acidosis, that are attributable to the kidney failure and would be expected to respond to dialysis,” Wish, co-chair of the Editorial Advisory Board for Nephrology News & Issues, said. “There is no advantage to ‘early’ initiation in terms of survival, and hemodialysis can accelerate the decline in residual kidney function.”
Early vs. late start
The Initiating Dialysis Early and Late (IDEAL) study, published more than a decade ago, showed little change in survival when starting dialysis early. In that study, Bruce A. Cooper, MB, BS, PhD, and colleagues randomized 828 patients at 32 centers in Australia and New Zealand to either early start or late start dialysis. The early start group began dialysis treatment when the eGFR dropped to 10 mL/min/1.73 m2 to 14 mL/min/1.73 m2 and the late start group began dialysis when the eGFR decreased to 5 mL/min/1.73 m2 to 7 mL/min/1.73 m2. The primary outcome for the study was death from any cause.
The results, after a median follow-up of 3.59 years, showed “there was no significant difference between the groups in the frequency of adverse events (cardiovascular events, infections, or complications of dialysis),” Cooper and colleagues wrote in the New England Journal of Medicine. “In this study, planned early initiation of dialysis in patients with stage [5] chronic kidney disease was not associated with an improvement in survival or clinical outcomes.”
Deciding when to start dialysis “is a combination of art and science,” Graham Abra, MD, a clinical assistant professor in the division of nephrology at Stanford University and senior director of medical clinical affairs at Satellite Healthcare, said. “I typically don’t start most patients on dialysis until their eGFR is less than 10 mL/min/1.73 m2 and significant symptoms that are impacting their quality of life are present,” Abra, an associate editor for Healio/Nephrology News & Issues, said. “In the outpatient nephrology clinic, the majority of patients I start do not begin because of hyperkalemia or volume overload (shortness of breath, significant edema), which we can usually control with potassium binders and diuretics. We will start them on dialysis if there are significant uremic symptoms (fatigue, sleep disturbances, restless leg syndrome, pruritus, nausea, or vomiting with weight loss, coupled with progressive and more difficult to control mineral bone disease and anemia.”
Practice patterns
How clinicians determine the right time to start dialysis may not be linked to clinical indicators or symptoms. It can be tied to changes in decision-making by large health care systems.
Chi-yuan Hsu, MD, MSc, chief of the division of nephrology at University of California-San Francisco Health, and colleagues from Kaiser Permanente Northern California, looked at when dialysis was initiated among patients with kidney disease treated at Kaiser, a large, integrated health care delivery system.
During an 18-year period, they found the number of patients started on chronic dialysis at any given level of kidney function increased over time, a change in practice patterns consistent with that in the United States and other countries.
“Overall, we estimated that incidence of ESKD could have potentially been 16% lower if there were no changes in system-level practice patterns or other factors besides timing of initiation of long-term dialysis from the initial 3-year interval (2001-2003) to the final 3-year interval (2016-2018) assessed in this study,” Hsu and colleagues wrote in a JAMA Internal Medicine article. “Choices regarding the timing of dialysis initiation should be made on a patient-by-patient basis to maximize the net benefit for individual patients with kidney disease.”
In an interview with Healio/Nephrology News & Issues, Hsu said eGFR is helpful in determining the right time to start dialysis, but other factors need to be reviewed.
“The key point is that the likelihood of starting dialysis at any given level of [low] kidney function/eGFR has gone up rapidly,” he said. “We think it is the comparison across years that is the most important one in our study – less so the absolute eGFR level reported since we captured that in a way different from the rest of the literature.”
The potential 16% decrease in the number of cases in the study of Kaiser patients “is approximately two-thirds of the targeted 25% reduction in new ESKD cases by 2030, as called for in the 2019 White House Advancing American Kidney Health initiative,” Hsu said. “I think this has tremendous implication in this era with dialysis providers and other companies moving toward increasing management of advanced CKD as part of value-based care and away from fee-for-service providers of chronic dialysis.”
New tools
Komenda said he and colleagues at the Chronic Disease Innovation Centre are developing a set of devices to virtually monitor patients pre-dialysis with “very low” GFRs to help determine when to initiate dialysis.
“We ask patients weekly about their symptoms, as well as monitor blood pressure, track walking steps, weight and oxygen saturation so we can get a better sense of how they are doing between monthly visits,” Komenda, a member of the Editorial Advisory Board for Healio/Nephrology News & Issues, said.
Vishal Duggal, MD, and colleagues looked at other factors besides laboratory data that might offer help in determining when to initiate dialysis.
“Current guidelines for nephrology referral are based on laboratory criteria,” Duggal, a post-doctoral fellow in medical informatics at the Center for Health Policy and the Center for Primary Care and Outcomes Research at the VA Palo Alto Health Care System, and colleagues wrote in a recent issue of the American Journal of Kidney Diseases. “Despite the availability of guidelines to facilitate recognition of CKD, there has been little progress in reducing the burden of CKD or improving preparation of those who progress to kidney failure.”
The researchers looked at patient data from the Veterans Affairs (VA) and Department of Defense (DOD), organizations that have developed clinical practice guidelines for CKD management, including suggested “potential indications” for nephrology referral based on laboratory values. “Recently, these guidelines were updated to reflect a diminished emphasis on laboratory-based indications and an increased emphasis on assessing the risk of progression,” the authors wrote. “ ... We sought to estimate the effect on nephrology referral volume if providers were to refer all patients who met a laboratory-based indication for nephrology referral.”
In the study, researchers found the volume of new outpatient nephrology referrals would more than double if all patients meeting potential indications for nephrology referral in VA/DOD CKD guidelines had been referred.
“If a minimum kidney failure risk of 1% over 2 years were applied to all new patients meeting laboratory-based potential referral indications, the number of patients targeted for nephrology referral would be reduced from 66,276 to an estimated 38,229 patients, a 42.3% reduction,” Duggal and colleagues wrote. “Alternatively, referral based only on predicted risk would result in a similar number of patients identified for referral at a predicted risk threshold of 2% or higher. The application of more stringent risk thresholds would identify progressively fewer patients.”
The message, Hsu said, is that starting chronic dialysis too early does not improve outcomes but imposes significant burdens on patients. “I think based on the landmark IDEAL clinical trial and a number of observational studies, we can be more conservative and start dialysis a bit later than what we are doing now.”
- References:
- Cooper B, et al. New Engl Jrnl Med. 2010;doi:10.1056/NEJMoa1000552.
- Duggal V, et al. Am Jrnl of Kid Dis. 2021;doi:10.1053/j.ajkd.2021.06.028.
- Hsu C, et al. JAMA Intern Med. 2020;doi:10.1001/jamainternmed.2020.5009.
- KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. https://kdigo.org/wp-content/uploads/2017/02/KDIGO_2012_CKD_GL.pdf. Published January 2013. Accessed Sept. 27, 2022.
- www.healio.com/news/nephrology/20200611/nephrologists-evaluate-the-risks-rewards-of-incremental-dialysis.
- For more information:
- Graham Abra, MD, can be reached at graham.abra@gmail.com.
- Chi-yuan Hsu, MD, MSc, can be reached at chi-yuan.hsu@ucsf.edu.
- Paul Komenda, MD, FRCPC, MHA, FACP, can be reached at paulkomenda@yahoo.com.
- Kamyar Kalantar-Zadeh, MD, MPH, PhD, can be reached at kkz@hs.uci.edu.
- Jay B. Wish, MD, can be reached at jaywish@earthlink.net.
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