Association of Residual Urine Output with Mortality, Quality of Life, and Inflammation in

Incident Hemodialysis

The Choices for Healthy Outcomes in caring for End-Stage Renal Disease (CHOICE) Study

Peter Schrier, MDJournal Club

Hofstra North Shore LIJ School of Medicine2011

Outline

• Residual Renal Function– What it is– Why it matters

• Peritoneal Dialysis Data• Hemodialysis Data• CHOICE Study

Residual Renal Function

• Small Solute Clearance (measured GFR)

• Volume Clearance (Urine output/volume)

• Endocrine Kidney (ESA usage, hemoglobin)

Residual Renal Function

AY-M Wang & K-N Lai, Kidney International (2006) 69, 1726–1732

Residual Renal Function

• Mortality– All-cause mortality– Cardiovascular

• Quality of Life– Overall QoL– Fewer diet restrictions– Less volume restriction– Others (sleep, pain,

perceived disease burden, etc.)

RKF and Morality in PD

• Effects of Increased Peritoneal Clearances on Mortality Rates in Peritoneal Dialysis: ADEMEX, a Prospective, Randomized, Controlled Trial– 965 person, multicenter, prospective, randomized

controlled trial– Follow-up at least 2 years– RCT was to measure mortality with standard PD dose vs.

more intense PD dose with greater pCrCl (peritoneal creatinine clearance)

– Looked at other factors that correlated with mortality, including rCrCl (renal creatinine clearance)

RKF and Mortality in PD

RKF and Morality in PD

• The relative importance of residual renal function compared with peritoneal clearance for patient survival and quality of life: An analysis of the Netherlands cooperative study on the adequacy of dialysis (Necosad)-2– 413 person, multicenter, prospective,

observational, cohort study of incident PD patients– Mortality with increased rGFR (renal GFR = RKF) vs.

increased pCrCl (peritoneal creatinine clearance)

NECOSAD-2- Am J Kidney Dis. 2003;41(6):1293- 1302.

RKF and Mortality in PD

NECOSAD-2- Am J Kidney Dis. 2003;41(6):1293- 1302.

RKF and Morality in PD

• Relative Contribution of Residual Renal Function and Peritoneal Clearance to Adequacy of Dialysis: A Reanalysis of the CANUSA Study– 680 person, multicenter, prospective cohort study – 2-year follow-up– Reanalysis of data– Mortality with increased rGFR (renal GFR = RKF) vs.

increased pCrCl (peritoneal creatinine clearance) vs. urine output

CANUSA- J Am Soc Nephrol 12: 2158–2162, 2001

RKF and Morality in PD

CANUSA- J Am Soc Nephrol 12: 2158–2162, 2001

RKF and Morality in PD

CANUSA- J Am Soc Nephrol 12: 2158–2162, 2001

RKF and Mortality in HD

• Residual renal function and mortality in hemodialysis patients– 114 person, single center, prospective cohort

study– 2-year follow-up– Mortality in patients with vs without RKF– Residual renal function defined as producing

> 100cc urine / 24 hour urine collection– Patients included all current patients at the

single hemodialysis center who agreed to participate and RFK was assessed at study initiation only Shemin- Am J

Kidney Dis. 2001;38(1):85-90.

RKF and Mortality in HD

Shemin- Am J Kidney Dis. 2001;38(1):85-90.

RKF and Mortality in HD

Shemin- Am J Kidney Dis. 2001;38(1):85-90.

RKF and Mortality in HD

• Relative Contribution of Residual Renal Function and Different Measures of Adequacy to Survival in Hemodialysis Patients: An analysis of the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD)-2– 740-person, prospective, observational

multicenter cohort study– Incident ESRD patients– Median follow-up 1.7 years

J Am Soc Nephrol 15: 1061–1070, 2004

RKF and Mortality in HD

Figure 1. The effect of single-pool Kt/Vurea (sp-dKt/Vurea) on mortality by presence of residual renal function (rKt/Vurea = 0 [“anurics’” versus rKt/Vurea >0). The rKt/Vurea and sp-dKt/Vurea were included as time-dependent variables. The relative risks are adjusted for age, Davies’ comorbidity score, primary kidney disease, subjective global assessment, and body mass index.

J Am Soc Nephrol 15: 1061–1070, 2004

RKF and Mortality in HD

J Am Soc Nephrol 15: 1061–1070, 2004

RKD and Mortality in Dialysis

Pearl and Bargman, Am J Kidney Dis 53:1068-1081

Quality of Life (QoL) in PD

NECOSAD-2- Am J Kidney Dis. 2003;41(6):1293- 1302.

CHOICE STUDY

• 734 patients from 81 clinics nationally• Prospective, observational cohort study• Incident dialysis patients– New onset of long-term dialysis– Baseline at within after initiation of therapy

• Goal: Determine association of urine output with mortality, quality of life, and inflammation in incident HD patients

Assessment of RKF

• Urine output used as a surrogate for RKF• Questionnaire at baseline and one year– “Do you produce at least one full cup (250cc) of

urine daily?”– Urine output was measured in 42% of patients

and was found to correlate well with reported production of 250cc/day

Baseline Characteristics of Study

Baseline Characteristics of Study

Baseline Characteristics of Study

All-Cause Mortality

e Clinical and treatment factors in addition to demographic characteristics: smoking history (ever smoked), pulse pressure, body mass index, primary cause of kidney failure (diabetes, hypertension, glomerulonephritis, or other), Index of Coexistent Disease score (0-3), cardiovascular disease, congestive heart failure, left ventricular hypertrophy, diabetes, and serum albumin level (at baseline or year 1).

All-Cause Mortality

All-cause Mortality by baseline urine output

All-cause Mortality by one-year urine output

Cardiovascular Mortality

e Clinical and treatment factors in addition to demographic characteristics: smoking history (ever smoked), pulse pressure, body mass index, primary cause of kidney failure (diabetes, hypertension, glomerulonephritis, or other), Index of Coexistent Disease score (0-3), cardiovascular disease, congestive heart failure, left ventricular hypertrophy, diabetes, and serum albumin level (at baseline or year 1).

Cardiovascular Mortality

Cardiovascular Disease mortality by baseline urine

output

Cardiovascular Disease mortality by one-year urine

output

Mortality and Change in Urine Output

Quality of Life (QoL)

EPO Dose Requirements

Improvements

• CVD Mortality– Not enough power? Many variables were very

close to statistical significance

• Definition of Residual Renal Function– Subjective urine output of >250cc rather arbitrary.

Maybe we are mislabeling those with ~100 cc urine output/day as not having RKF when they do enjoy its protective effects

Improvements

• More nit-picking than real concerns– Diuretics shouldn’t increase RKF even though they

do increase urine output (unless volume is the issue!)

– EPO usage was only calculated at baseline and 6 months, much earlier than the study stopped follow-up. Maybe not the best measure of residual endocrine kidney function

Conclusions

• Residual Renal Function, especially the maintenance of existing residual renal function, has important prognostic value

• Future studies may be useful to assess interventions aimed at preserving residual renal function

• As nephrologists, it is our responsibility to be advocates for the last few cc’s of GFR; they may be the difference between life and death…

• …or certainly a keg-stand and a picnic