early vs late dialysis

Bones can break, muscles can atrophy, glands can loaf, even the brain can go to sleep without immediate danger to survival. • But not!... should kidneys fail....

neither bone, muscle, nor brain could carry on.

“Homer Smith”

Early vs late Initiation

of Dialysis

Dr. Abrar Ali KatparNephrology

KKH-Hail

Dr. Abrar Ali Katpar@1st Nephrology Symposium & Workshop on World Kidney Day at KKH-Hail.

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Introduction.

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Most critical decision to make along the course

of chronic renal insufficiency. Negative psychological impact on patients. Important socioeconomic implications. When to start - subject to much controversy.

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Initiation of dialysis.


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Free of uremic symptoms. To control volume overload, acid-base and

electrolyte disorders. And to provide a clearance of uremic toxins

enough to allow an adequate dietary protein and caloric intake. When residual renal function fails to

maintain all these vital functions, we have a solid argument for starting dialysis therapy.

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Goals of dialysis


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K/DOQI

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GUIDELINE 1When to Initiate Dialysis–Kt/Vurea Criterion (Opinion)Unless certain conditions are met, patients should be advised to initiate some form of dialysis when the weekly renal Kt/Vurea (Krt/Vurea) falls below 2.0. The conditions that may indicate dialysis is not yet necessary even though the weekly Krt/Vurea is less than 2.0 are:

1. Stable or increased edema-free body weight. Supportive objective parameters for adequate nutrition include a lean body mass >63%, subjective global assessment score indicative of adequate nutrition and a serum albumin concentration in excess of the lower limit for the lab, and stable or rising; and2. Nutritional indications for the initiation of renal replacement therapy.3. Complete absence of clinical signs or symptoms attributable to uremia.

A weekly Krt/Vurea of 2.0 approximates a kidney urea clearance of 7 mL/min and a kidney creatinine clearance that varies between 9 to 14 mL/min/1.73 m2. Urea clearance should be normalized to total body water (V) and creatinine clearance should be expressed per 1.73 m2 of body surface area. The GFR, which is estimated by the arithmetic mean of the urea and creatinine clearances, will be approximately 10.5 mL/min/1.73 m2 when the Krt/Vurea is about 2.0.


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Early Start of Dialysis: A Critical ReviewSteven Rosansky*, Richard J. Glassock†, William F. Clark‡AbstractSummary In the US, patients who initiate dialysis “early” (at Modification of Diet in Renal Disease estimated GFR [eGFR]> 10 ml/min per 1.73m2) account for over 50 percent of new dialysis starts. This trend to an early start is based on conventional wisdoms regarding benefits of dialytic clearance, that albumin levels are nutritional markers, and early dialytic therapy is justified to improve nutrition especially in diabetics and that waiting until low levels of eGFRmay be dangerous. In order to justify early dialysis treatment, the therapy must provide a morbidity, mortality, or quality of life benefit. The current review examines whether early dialysis initiation provides any of these benefits and whether the conventional wisdoms that have promoted this early dialysis trend are valid. Utilizing this information and the results of recent large observational studies and the randomized controlled Initiating Dialysis Early and Late (IDEAL) study, we suggest that dialysis initiation is justified at GFR levels of 5–9 ml/min/1.73m2, if accompanied by uremia symptoms or fluid management issues.


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Intractable ECV overload Hyperkalemia Metabolic acidosis Hyperphosphatemia Hypercalcemia or hypocalcemia Anemia Neurological dysfunction (eg, neuropathy, encephalopathy) Pleuritis or pericarditis Otherwise unexplained decline in functioning or well-being Gastrointestinal dysfunction (eg, nausea, vomiting, diarrhea,

gastroduodenitis) Weight loss or other evidence of malnutrition Hypertension.

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Complications That May Prompt Initiation of Kidney Replacement Therapy.


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The key question is whether we have to start

dialysis prior to, or after the overt development of these uremic signs and symptoms

1. The beneficial effects that dialysis can offer to the pre-dialysis renal failure patient.

2. The potential complications of dialysis, and the changes in the way of life that many patients have to endure, are factors which should temper this decision.

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When to Initiate??


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When to Initiate Dialysis : K t/V urea Criterion

(Opinion) patients should be advised to initiate some form of dialysis when the weekly renal Kt/V urea < 2.0. Unless: 1. Stable or increased edema-free body weight. 2. No Nutritional indications 3. Complete absence of clinical signs or symptoms attributable to uremia.

A weekly Kt/V urea of 2.0 approximates a kidney urea clearance of 7 mL/min and a kidney creatinine clearance that varies between 9 to 14 mL/min/1.73 m 2.

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KDOQI.. Timing of Therapy


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patients with chronic kidney failure (e.g, GFR

< 15 to 20 ml/min) who are not undergoing maintenance dialysis, if protein-energy malnutrition (PEM) develops or persists despite vigorous attempts to optimize protein and energy intake and there is no apparent cause for malnutrition other than low nutrient intake, initiation of maintenance dialysis or a renal transplant is recommended (Opinion).

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KDOQI.. Timing of Therapy


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Timing of therapy: When patients reach stage

5 CKD (estimated GFR < 15 mL/min/1.73 m2), nephrologists should evaluate the benefits, risks, and disadvantages of beginning kidney replacement therapy. Particular clinical considerations and certain characteristic complications of kidney failure may prompt initiation of therapy before stage 5 (B) AJKD VOL 48, NO 1, SUPPL 1, JULY 2006

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KDOQI.. Timing of TherapySecond update of the Clinical Practice Guidelines (CPGs) &

Clinical Practice Recommendations (CPRs)


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Bonomini et al, 1985 Reported that an early start of dialysis was

associated with reduced mortality & morbidity.

Among a subset of patients who were subsequently transplanted, there was a survival advantage for those started dialysis early (n=50) vs later (n=96), as well as less vascular calcification, bacterial infection, dyslipidemia and hospitalization!

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Early initiation – Believers..


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CANUSA Study (McCusker et al 1996) PD

Significantly poorer survival for patients with lower levels of renal function when starting dialysis

The mean creatinine clearance at the start of dialysis for all patients was 38 L/wk (3.8 ml/min)

12 and 24 month survival for those with creatinine clearance <38 L/wk at start of dialysis was 82.1% and 73.6%, respectively, compared with 94.7% and 90.8%, respectively, for those with creatinine clearance >38 L/wk.

In the CANUSA study, there was a survival advantage for higher total (residual plus dialysis) Kt/V up to 2.0, and possibly up to 2.3

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Tattersall et al. ( Am J Nephrol 15: 283 -2

89, 1995) Prospective cohort study of 63 patients in 1991–

92. Demonstrated reduced survival in patients with

less residual renal function at start of dialysis, although these patients were also significantly older and had significantly more co-morbidity.

Hospitalization length of stay was greater among those with residual Kt/V <1.05 at time of initiation of dialysis.

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Schulman G and Hakim RM

Improving outcomes in chronic hemodialysis patients: should dialysis be initiated earlier? Semin Dial 1996; 9(3):225-9

patients initiated on dialysis with a creatinine clearance > 10 ml/min had an 88% 10- year survival when compared to 55% in those initiated at a creatinine clearance of < 10 ml/min (mean 4 ml/min)

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Early initiation However,

early initiation of dialysis expose patients : complications

of dialysis, unnecessary lifestyle restriction, potential

increased cost, patient fatigue.No RCTs - Confounding

influences in other studies include referral time bias, age,

co-morbidity, patient compliance and starting time

bias.Lead time bias.

Early initiation - skeptics - lead time bias In the context of initiation of dialysis, lead-time bias refers to the effect whereby measuring survival from the start of dialysis increases apparent survival of those started with more residual renal function i.e., earlier in the course of the disease, than those who start dialysis with less residual renal function When to initiate dialysis: effect of proposed US guidelines on survival. Korevaar et al. Lancet 2001 Sep 29; 358(9287):1046-

1050 In NECOSAD study (Korevaar et al.) estimated the effects of lead-time bias on dialysis survival by using prediction software based on the Finnish Cancer Registry timely initiation - associated with a small survival benefit of 2.5 months However, the extra time free of dialysis for “late starters ” was only 4.1 months This study suggested that any perceived survival benefit from early start could be accounted for by lead-time

Early initiation - skeptics – QOL(Korevaar et al 2002)

(Evaluation of DOQI guidelines: Early start of dialysis treatment is not associated with better health-related quality of life. Am J Kidney Dis

2002; 39:108- 1 15)Prospective cohort study from Holland 38% of 237 incident dialysis patients

commenced dialysis late, as defined by the K/DOQI guidelines. Compared with patients who

have timely initiation, the HRQOL among late starters was worse during the first 6 months after initiation, but no different at 12 months

Early initiation does not prolong survival?• Impact of timing of initiation of dialysis on mortality.

Beddhu et at. JASN 14: 2305-2312, 2003• Post-hoc analysis of the MDRD study,

comparing early (predicted MDRD GFR>7.5 ml/min; N = 1,444) with late (predicted GFR <7.5 ml/min); N = 1,476), higher MDRD GFR at initiation was associated with an increased risk of death in multivariate Cox model (hazard ratio 1.27 for each 5 ml/min increase)

• “ reflect an erroneous GFR estimation by MDRD formula”

• Concluded that the data do not support early initiation of dialysis

Early initiation of dialysis increases risk of mortality?

Kazmi et al – Am J Kidney Dis. 2005 Nov;46(5):887-96

undertook an evaluation of the impact of comorbidity on the association between GFR at initiation and death Results: greater GFR at initiation associated with a greater risk for death in all populationsPatients in the general dialysis population who initiated dialysis therapy at a GFR >10 mL/min/1.73 m2 had a 42% increased risk for death compared with patients with a GFR < 5 mL/min/1.73 m2 at initiation of dialysis therapy after adjusting for all covariates

Additional research required.


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(IDEAL) TRIAL The Initiating Dialysis Early and Late

1. Enrollment, Randomization, and Follow-up.

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Definite answer?


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The data for time to the initiation of dialysis (Panel A) were censored at the time of death, transplantation, or withdrawal of consent or at the time a patient transferred to a nonparticipating hospital, emigrated, or could not be contacted. The curves for

time to death (Panel B) are truncated at 7 years of follow-up and a cumulative hazard of 60%.

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2. Kaplan–Meier Curves for Time to the Initiation of Dialysis and for Time to Death.


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Primary and Secondary Outcomes, Including Adverse Events


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Effect of the Timing of Dialysis Initiation in Subgroups

The forest plot shows the hazard ratio (and 95% confidence intervals) for the primary outcome of death from any cause, with early initiation as compared with late initiation of dialysis, according to each of the prespecified subgroups. The body-mass index (BMI) is the weight in kilograms divided by the square of the height in meters. GFR C–G denotes glomerular filtration rate estimated with the Cockcroft–Gault equation, and GFR MDRD the glomerular filtration rate estimated with the Modification of Diet in Renal Disease equation.


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Primary outcome = death from any cause. Secondary outcomes=

cardiovascular events: cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, transient ischemic attack, new-onset angina

infectious events: death or hospitalization due to any infection-related cause,

complications of dialysis : temporary placement of an access catheter, need for access revision, infection at the access site, fluid and electrolyte disorders requiring hospitalization, additional dialysis.

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Study Outcomes


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When to initiate dialysis?Rosansky and colleagues[1] addresses the issue of when is the appropriate time to start dialysis.

This study raises questions about the increasingly common practice of an early start to dialysis. The title of the paper appropriately is "Early Start of Hemodialysis May Be Harmful."

The higher the GFR at the time dialysis was started, the higher the subsequent mortality and, in this study, first year mortality. Patients who started dialysis with GFRs in the 5-10 mL/min range had substantially lower mortality than those who started dialysis at each successively higher level of GFR, including 10-15 mL/min and over 15 mL/min.


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Adhere to best practice…….

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Conclusions


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AJKD VOL 48, NO 1, SUPPL 1, JULY 2006. http://www.kidney.org/professionals/kdoqi/

guidelines_commentaries.cfm http://ebookee.org/Nephrology-eBook-

Pack_1066049.html http://www.expertconsultbook.com http://patientsafetyauthority.org/ADVISORIES https://www.nephropath.com http://kidney.niddk.nih.gov/kudiseases/pubs/

hemodialysisdose http://www.medscape.org

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References


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Thank you

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early vs late dialysis

Health & Medicine

initiation of dialysis

early dialysis trend

dialysis initiationis

goals of dialysis

early dialysis treatment

nephrologysymposium

worldkidney day

early start