Bones can break, muscles can atrophy,glands can loaf, even the brain can go tosleep without immediate danger tosurvival.• But not!... should kidneys fail.... neitherbone, muscle, nor brain could carry on.“Homer Smith”
Introduction.3/18/2013Dr. Abrar Ali Katpar@1st NephrologySymposium & Workshop on WorldKidney Day at KKH-Hail.3
Most critical decision to make along the course ofchronic renal insufficiency. Negative psychological impact on patients. Important socioeconomic implications. When to start - subject to much controversy.3/18/2013Dr. Abrar Ali Katpar@1st NephrologySymposium & Workshop on WorldKidney Day at KKH-Hail.4Initiation of dialysis.
Free of uremic symptoms. To control volume overload, acid-base andelectrolyte disorders. And to provide a clearance of uremic toxins enoughto allow an adequate dietary protein and caloricintake. When residual renal function fails to maintain allthese vital functions, we have a solid argument forstarting dialysis therapy.3/18/2013Dr. Abrar Ali Katpar@1st NephrologySymposium & Workshop on WorldKidney Day at KKH-Hail.5Goals of dialysis
K/DOQI3/18/2013Dr. Abrar Ali Katpar@1st NephrologySymposium & Workshop on WorldKidney Day at KKH-Hail.6GUIDELINE 1When to Initiate Dialysis–Kt/Vurea Criterion (Opinion)Unless certain conditions are met, patients should be advised to initiate some form of dialysiswhen the weekly renal Kt/Vurea (Krt/Vurea) falls below 2.0. The conditions that may indicatedialysis 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 adequatenutrition include a lean body mass >63%, subjective global assessment score indicative ofadequate nutrition and a serum albumin concentration in excess of the lower limit for thelab, 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 kidneycreatinine clearance that varies between 9 to 14 mL/min/1.73 m2. Urea clearance should benormalized to total body water (V) and creatinine clearance should be expressed per 1.73 m2 ofbody surface area. The GFR, which is estimated by the arithmetic mean of the urea andcreatinine clearances, will be approximately 10.5 mL/min/1.73 m2 when the Krt/Vurea isabout 2.0.
3/18/2013Dr. Abrar Ali Katpar@1st NephrologySymposium & Workshop on WorldKidney Day at KKH-Hail.7Early 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 inRenal Disease estimated GFR [eGFR]> 10 ml/min per 1.73m2) account for over 50percent of new dialysis starts. This trend to an early start is based on conventionalwisdoms regarding benefits of dialytic clearance, that albumin levels are nutritionalmarkers, and early dialytic therapy is justified to improve nutrition especially indiabetics and that waiting until low levels of eGFRmay be dangerous. In order tojustify early dialysis treatment, the therapy must provide a morbidity, mortality, orquality of life benefit. The current review examines whether early dialysis initiationprovides any of these benefits and whether the conventional wisdoms that havepromoted this early dialysis trend are valid. Utilizing this information and theresults of recent large observational studies and the randomized controlledInitiating Dialysis Early and Late (IDEAL) study, we suggest that dialysis initiationis justified at GFR levels of 5–9 ml/min/1.73m2, if accompanied by uremiasymptoms or fluid management issues.
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.3/18/2013Dr. Abrar Ali Katpar@1st NephrologySymposium & Workshop on WorldKidney Day at KKH-Hail.8Complications That May Prompt Initiation ofKidney Replacement Therapy.
The key question is whether we have to start dialysisprior to, or after the overt development of theseuremic signs and symptoms1. The beneficial effects that dialysis can offer to thepre-dialysis renal failure patient.2. The potential complications of dialysis, and thechanges in the way of life that many patients have toendure, are factors which should temper thisdecision.3/18/2013Dr. Abrar Ali Katpar@1st NephrologySymposium & Workshop on WorldKidney Day at KKH-Hail.9When to Initiate??
When to Initiate Dialysis : K t/V urea Criterion (Opinion)patients should be advised to initiate some form ofdialysis when the weekly renal Kt/V urea < 2.0. Unless:1. Stable or increased edema-free body weight.2. No Nutritional indications3. Complete absence of clinical signs or symptoms attributableto uremia. A weekly Kt/V urea of 2.0 approximates a kidney ureaclearance of 7 mL/min and a kidney creatinine clearancethat varies between 9 to 14 mL/min/1.73 m 2.3/18/2013Dr. Abrar Ali Katpar@1st NephrologySymposium & Workshop on WorldKidney Day at KKH-Hail.10KDOQI.. Timing of Therapy
patients with chronic kidney failure (e.g, GFR < 15 to20 ml/min) who are not undergoing maintenancedialysis, if protein-energy malnutrition (PEM)develops or persists despite vigorous attempts tooptimize protein and energy intake and there is noapparent cause for malnutrition other than lownutrient intake, initiation of maintenance dialysis ora renal transplant is recommended (Opinion).3/18/2013Dr. Abrar Ali Katpar@1st NephrologySymposium & Workshop on WorldKidney Day at KKH-Hail.11KDOQI.. Timing of Therapy
Timing of therapy: When patients reach stage 5 CKD(estimated GFR < 15 mL/min/1.73 m2),nephrologists should evaluate the benefits, risks, anddisadvantages of beginning kidney replacementtherapy. Particular clinical considerations and certaincharacteristic complications of kidney failure mayprompt initiation of therapy before stage 5 (B) AJKD VOL 48, NO 1, SUPPL 1, JULY 20063/18/2013Dr. Abrar Ali Katpar@1st NephrologySymposium & Workshop on WorldKidney Day at KKH-Hail.12KDOQI.. Timing of TherapySecond update of the Clinical Practice Guidelines (CPGs) &Clinical Practice Recommendations (CPRs)
3/18/2013Dr. Abrar Ali Katpar@1st NephrologySymposium & Workshop on WorldKidney Day at KKH-Hail.13
Bonomini et al, 1985 Reported that an early start of dialysis wasassociated with reduced mortality & morbidity. Among a subset of patients who were subsequentlytransplanted, there was a survival advantage forthose started dialysis early (n=50) vs later (n=96), aswell as less vascular calcification, bacterialinfection, dyslipidemia and hospitalization!3/18/2013Dr. Abrar Ali Katpar@1st NephrologySymposium & Workshop on WorldKidney Day at KKH-Hail.14Early initiation – Believers..
CANUSA Study (McCusker et al 1996) PD Significantly poorer survival for patients with lower levelsof renal function when starting dialysis The mean creatinine clearance at the start of dialysis for allpatients 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 forhigher total (residual plus dialysis) Kt/V up to 2.0, andpossibly up to 2.33/18/2013Dr. Abrar Ali Katpar@1st NephrologySymposium & Workshop on WorldKidney Day at KKH-Hail.15Early initiation – Believers..
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 lessresidual renal function at start of dialysis, althoughthese patients were also significantly older and hadsignificantly more co-morbidity. Hospitalization length of stay was greater amongthose with residual Kt/V <1.05 at time of initiation ofdialysis.3/18/2013Dr. Abrar Ali Katpar@1st NephrologySymposium & Workshop on WorldKidney Day at KKH-Hail.16Early initiation – Believers..
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 creatinineclearance > 10 ml/min had an 88% 10- year survivalwhen compared to 55% in those initiated at acreatinine clearance of < 10 ml/min (mean 4 ml/min)3/18/2013Dr. Abrar Ali Katpar@1st NephrologySymposium & Workshop on WorldKidney Day at KKH-Hail.17Early initiation – Believers..
3/18/2013Dr. Abrar Ali Katpar@1st NephrologySymposium & Workshop on WorldKidney Day at KKH-Hail.18Early initiationHowever,early initiation of dialysis exposepatients : complications ofdialysis, unnecessary lifestylerestriction, potential increasedcost, patient fatigue.No RCTs - Confounding influencesin other studies include referraltime bias, age, co-morbidity, patientcompliance and starting time bias.Lead time bias.Early initiation - skeptics - lead time biasIn the context of initiation of dialysis, lead-time bias refers tothe effect whereby measuring survival from the start ofdialysis increases apparent survival of those started with moreresidual renal function i.e., earlier in the course of thedisease, than those who start dialysis with less residual renalfunctionWhen to initiate dialysis: effect of proposed US guidelines onsurvival.Korevaar et al. Lancet 2001 Sep 29; 358(9287):1046-1050In NECOSAD study (Korevaar et al.) estimated the effects oflead-time bias on dialysis survival by using predictionsoftware based on the Finnish Cancer Registrytimely initiation - associated with a small survival benefit of 2.5monthsHowever, the extra time free of dialysis for “late starters ” wasonly 4.1 monthsThis study suggested that any perceived survival benefit fromearly start could be accounted for by lead-timeEarly initiation - skeptics – QOL(Korevaar et al 2002)(Evaluation of DOQI guidelines: Early start of dialysistreatment is not associated with better health-relatedquality of life. Am J Kidney Dis 2002; 39:108- 1 15)Prospective cohort study from Holland38% of 237 incident dialysis patients commenceddialysis late, as defined by the K/DOQI guidelines.Compared with patients who have timely initiation,the HRQOL among late starters was worse during thefirst 6 months after initiation, but no different at 12monthsEarly 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, comparingearly (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 associatedwith an increased risk of death in multivariate Coxmodel (hazard ratio 1.27 for each 5 ml/min increase)• “ reflect an erroneous GFR estimation by MDRDformula”• Concluded that the data do not support earlyinitiation of dialysisEarly initiation of dialysis increases risk of mortality?Kazmi et al – Am J Kidney Dis. 2005 Nov;46(5):887-96undertook an evaluation of the impact of comorbidityon the association between GFR at initiation and deathResults: greater GFR at initiation associated with agreater risk for death in all populationsPatients in the general dialysis population whoinitiated dialysis therapy at a GFR >10 mL/min/1.73m2 had a 42% increased risk for death compared withpatients with a GFR < 5 mL/min/1.73 m2 at initiationof dialysis therapy after adjusting for all covariatesAdditional research required.
(IDEAL) TRIALThe Initiating Dialysis Early and Late 1. Enrollment, Randomization, and Follow-up.3/18/2013Dr. Abrar Ali Katpar@1st NephrologySymposium & Workshop on WorldKidney Day at KKH-Hail.19Definite answer?
The data for time to the initiation of dialysis (Panel A) were censored at the time ofdeath, transplantation, or withdrawal of consent or at the time a patient transferred to anonparticipating 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%.3/18/2013Dr. Abrar Ali Katpar@1st NephrologySymposium & Workshop on WorldKidney Day at KKH-Hail.202. Kaplan–Meier Curves for Time to the Initiationof Dialysis and for Time to Death.
3/18/2013Dr. Abrar Ali Katpar@1st NephrologySymposium & Workshop on WorldKidney Day at KKH-Hail.21Primary and Secondary Outcomes, Including Adverse Events
3/18/2013Dr. Abrar Ali Katpar@1st NephrologySymposium & Workshop on WorldKidney Day at KKH-Hail.22Effect of the Timing of Dialysis Initiationin SubgroupsThe forest plot shows thehazard ratio (and 95%confidence intervals) forthe primary outcome ofdeath from any cause,with early initiation ascompared with lateinitiation of dialysis,according to each of theprespecified subgroups.The body-mass index(BMI) is the weight inkilograms divided by thesquare of the height inmeters. GFR C–G denotesglomerular filtration rateestimated with theCockcroft–Gault equation,and GFR MDRD theglomerular filtration rateestimated with theModification of Diet inRenal Disease equation.
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.3/18/2013Dr. Abrar Ali Katpar@1st NephrologySymposium & Workshop on WorldKidney Day at KKH-Hail.23Study Outcomes
3/18/2013Dr. Abrar Ali Katpar@1st NephrologySymposium & Workshop on WorldKidney Day at KKH-Hail.24When to initiate dialysis?Rosansky and colleagues addresses the issueof when is the appropriate time to start dialysis.This study raises questions about the increasinglycommon practice of an early start to dialysis.The title of the paper appropriately is "Early Start ofHemodialysis May Be Harmful."The higher the GFR at the time dialysis wasstarted, the higher the subsequent mortality and, in thisstudy, first year mortality. Patients who started dialysiswith GFRs in the 5-10 mL/min range had substantiallylower mortality than those who started dialysis at eachsuccessively higher level of GFR, including 10-15 mL/minand over 15 mL/min.
Adhere to best practice…….3/18/2013Dr. Abrar Ali Katpar@1st NephrologySymposium & Workshop on WorldKidney Day at KKH-Hail.25
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.org3/18/2013Dr. Abrar Ali Katpar@1st NephrologySymposium & Workshop on WorldKidney Day at KKH-Hail.26References
Thank you3/18/2013Dr. Abrar Ali Katpar@1st NephrologySymposium & Workshop on WorldKidney Day at KKH-Hail.27