Nephrologists evaluate the risks, rewards of incremental dialysis
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For years, the kidney community has debated the merits of “adequate” vs. “optimal” dialysis. Of equal contention has been the decision about when to start dialysis, according to recent interviews and published papers.
“There are many factors to consider before starting dialysis,” Steven Rosansky, MD, a nephrologist affiliated with the William Jennings Bryan Dorn Research Center at the Veterans Affairs Medical Center in Columbia, South Carolina, told Nephrology News & Issues. “ For some patients, you can delay using the therapy for years.”
One of the confounding issues in the studies that compare patient survival by predialysis eGFR is that patients who are sicker and have high comorbidity may start dialysis earlier. In an attempt to minimize this confounder, Rosansky and colleagues studied the value of starting dialysis in a healthy, nondiabetic end-stage kidney disease population (n = 81,176). The only reported comorbidity was hypertension, and the patients ranged from 20 to 64 years old and received in-center hemodialysis.
First-year mortality for patients with predialysis serum albumin greater than 3.5 mg/dL by an eGFR less than 5 mL/min/1.73 m2; 5 mL/min/1.73 m2; to 10 mL/min/1.73m2 and greater than 15 mL/min/1.73 m2, was 3.6%, 4.5%, 6.7% and 12.5%, respectively.
“The increased hazard ratio during hemodialysis associated with early start in the healthiest group of patients undergoing dialysis indicates that early start of dialysis may be harmful,” the authors wrote in the Archives of Internal Medicine paper.
Source: Thomas Golper, MD
Rosansky said there are risks to starting dialysis too early, including sudden death, recurrent cardiac ischemia and stroke. Withdrawal from dialysis due to poor quality of life is also common.
“There are too many risks imposed by dialysis compared to the benefits to encourage a patient to start dialysis unless there is a clear clinical indication,” he said.
In an editorial about the paper, Tufts University School of Medicine colleagues Daniel E. Weiner, MD, MS, and Lesley A. Stevens, MD, MS, wrote that other measures should be evaluated before dialysis is initiated. “Careful interpretation of symptoms and signs, eGFR, and other clinical and laboratory data, taking into account the limitations associated with each of these, is essential to making the best decision regarding initiation of dialysis therapy,” they wrote.
Thomas A. Golper, MD, FACP, head of the home dialysis program at Vanderbilt University Medical Center, agrees that using the eGFR to determine when dialysis begins is troublesome.
“I am against the idea of putting a patient on dialysis based on a number,” Golper, who is chair of the Editorial Advisory Board for Nephrology News & Issues, said. “The GFR should be taken out of the picture ... putting patients on dialysis [based on eGFR] has the potential of being harmful.”
Nationally, a large percentage of patients with high eGFRs are being placed on dialysis, although the number is showing some decline (see Table on page 24). According to the United States Renal Data System’s 2018 annual data report (ADR), “mean eGFR at initiation of dialysis in 2016 was 9.7 mL/min/1.73 m2, down from a peak of 10.4 in 2010.” However, “the percentage of incident end-stage renal disease cases starting with eGFR [of at least] 10 mL/min/1.73 m2 rose from 12.9% in 1996 to 42.6% in 2010 but decreased to 38.6% in 2016.”
The mean eGFR at the start of dialysis among incident ESRD patients in 2016 was higher in patients 21 years of age and younger, men, white patients, non-Hispanic patients and those with diabetes as their primary cause of ESRD, according to the ADR.
Guidelines developed by the National Kidney Foundation in 1997, updated in 2006, and guidelines from the Kidney Disease: Improving Global Outcomes (KDIGO) in 2013 recommend starting dialysis in patients with an eGFR less than 15 mL/min per 1.73 m2 and less than 10 mL/min/1.73 m2, respectively. But both guidelines recommend using symptoms of uremia to determine the timing.
“We suggest that dialysis be initiated 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,” according to KDIGO’s Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. “This often but not invariably occurs in the GFR range between 5 [mL/min/1.73 m2] and 10 mL/min/1.73 m2.”
Rajnish Mehrotra, MD, interim head of the division of nephrology at the University of Washington School of Medicine, said determining when a patient is ready for dialysis should include a comprehensive assessment – and input from the patient.
“The key symptoms I look for in people I am following over time include anorexia, a decrease in the level of energy, weight loss, lower extremity swelling or shortness of breath,” Mehrotra said. “In addition, patients may present with nausea, vomiting, and confusion, but they are infrequent as a trigger for the decision to start dialysis. Finally, there are laboratory variables such as difficult-to-medically manage hyperkalemia that can trigger the decision to start dialysis.
“I do not believe eGFR is an accurate tool to determine when to initiate dialysis,” Mehrotra said. “In patients with low measured GFR, differences in eGFR reflect differences in muscle mass. At the same measured GFR, people with low muscle mass have lower serum creatinine and higher eGFR than people with higher muscle mass. The eGFR is imprecise and similarly problematic whether the patient is to start on in-center or home dialysis.”
Residual kidney function
One of the benefits of starting patients earlier on dialysis can be to preserve residual kidney function (RKF). Patients who still have urine output may not need dialysis three times a week. Starting them incrementally might be of value in extending kidney health.
“There are many benefits to maintaining RKF in patients who have advanced CKD,” Golper said.
He has been successful in extending RKF in both peritoneal dialysis and hemodialysis patients in his Vanderbilt program. He does not believe the dialysis process itself leads to a greater risk of mortality among patients who start with a higher eGFR.
“Recently there has been a concern that starting dialysis ‘early’ has led to a higher mortality,” he wrote in a paper published in Nephrology Dialysis and Transplantation with Mehrotra as co-author. “We think that the mortality associated with starting dialysis at a higher estimated glomerular ltration rate (eGFR) is almost entirely due to nephrologists and patients resorting to dialysis to salvage health and well-being when the symptoms that led to the initiation of dialysis in the rst place may not necessarily be correctable by dialysis,” the nephrologists wrote. “...Patients with the highest eGFR at the time of initiation of dialysis are signicantly more likely to have sarcopenia and the associations reported in some observational studies likely represent the high risk for death in individuals with low muscle mass rather than the risk with the dialysis procedure. The IDEAL study refuted the notion that the dialysis procedure itself is the cause for higher risk for death in individuals who initiate dialysis at higher kidney function.”
Benefits from an early start
Incremental dialysis also provides a psychological benefit for patients who are progressing toward ESKD.
“Just providing some support via incremental dialysis, sometimes two times a week, preserves kidney function and makes patients psychologically feel that their kidneys are still working well,” Kam Kalantar-Zadeh, MD, MPH, PhD, nephrology chief and director of the dialysis program at University of California-Irvine, told Nephrology News & Issues. He typically has between 15% to 25% of patients in his dialysis program on incremental therapy based on eligibility criteria in a consensus paper he wrote with Golper and others in 2014. “Many patients have a fear of dialysis initiation. There is a lot of anxiety. If we can start dialysis gradually one to two times a week, that gives patients more leverage and puts them in control.”
In a recently published paper, he and home dialysis patient Nieltje Gedney wrote: “Patient perspectives on incremental dialysis generally are positive, given the less severe impact on lifestyle and suffering upon transition to dialysis therapy.”
Good nutritional management can also extend RKF.
“Randomized controlled studies have shown that a low or very low protein diet with ketoacid analogs can help to delay the need for renal replacement therapy as well as decrease mortality risk,” Brittany Sparks, RDN, CSR, told Nephrology News & Issues. “Some studies have shown a delay to dialysis by up to 1 year in individuals with stage 5 CKD on a very low protein diet supplemented with ketoanalogs.” Sparks, who has a private nutrition practice, said many of her predialysis patients show improvement in uremic symptoms, such as nausea, malaise and overall energy level when dietary protein levels are reduced.
Dialyzing incrementally also can provide adequate dialysis during emergency situations. During a national shortage of PD solution in 2014, Golper and colleagues advocated the use of incremental PD to reduce the need for dialysate.
“Incremental PD is worthwhile under many circumstances, but in this period of a PD solution shortage, it may be even more important,” they wrote.
More recently, nephrologists proposed the idea of incremental dialysis by reducing in-center hemodialysis treatments from two to three times a week in an effort to limit risks to patients and staff imposed by the COVID-19 pandemic.
Mehrotra told Nephrology News & Issues, “What I have learned over the years is many uremic symptoms are subtle. Patients adapt to a lower level of functioning without realizing it or are unwilling to acknowledge these symptoms as important because of fear of being asked to start dialysis. Weight loss, for example, may be counterbalanced with weight gain from fluid accumulation.
“For all these reasons, the decision on when to start dialysis remains an art form that needs to be individualized for the person. That is the key.” – by Mark E. Neumann
- References:
- Cooper B, et al. New Engl J Med. 2010;doi:10.1056/NEJMoa1000552.
- Gedney N, et al. Sem in Neph. 2018;doi:10.1016/j.semnephrol.2018.05.012.
- Golper T, et al. Nephrology News & Issues. 2014;28(12):28-29.
- Golper T, et al. Nephrol Dial Transplant. 2015;doi:10.1093/ndt/gfv271.
- Kalantar-Zadeh K, et al. Am J Kidney Dis. 2015;doi:10.1053/j.ajkd.2014.04.019.
- Mehrotra R. J Am Soc of Neph.2020;doi:10.1681/ASN.2020040412.
- Meyer TW, et al. J Am Soc of Neph. 2020;doi:10.1681/ASN.2020030361.
- Rosansky S, et al. Arch Intern Med. 2011;doi:10.1001/archinternmed.2010.415
- For more information:
- Thomas A. Golper, MD, FACP, can be reached at thomas.golper@vumc.org.
- Kamyar Kalantar-Zadeh, MD, MPH, PHD, can be reached at kkz@hs.uci.edu.
- Rajnish Mehrotra, MD, can be reached at RMehrotra@Nephrology.washington.edu.
- Steven Rosansky, MD, can be reached at sjrcra@yahoo.com.
- Brittany Sparks, RDN, CSR, can be reached at info@nutritionbybrittany.com.
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