Underwriter s Review of Laboratory Data Optimum Re November 2011

Transcription

1 Underwriter s Review of Laboratory Data Optimum Re November 2011 Robert L. Stout, Ph.D., Director and President Clinical Reference Laboratory

2 Today s discussion is on. Serum creatinine, blood urea nitrogen and estimates for glomerular filtration rate. Natriuretic Peptides and regulation of kidney function Nt-ProBNP values in the Insurance applicant population.

3 "The important thing in science is not so much to obtain new facts as to discover new ways of thinking about them. Sir William Bragg ( )

4 Kidney Disease. Kidney disease is an insidious, chronic illness with few early warning signs. In the past 15 years the number of people with end-stage renal disease has tripled. Approximately 500,000 Americans have ESRD, with 12,000,000 others with earlier stages of chronic kidney disease.

5 Stages of Kidney Disease. Stage 1: Kidney damage with normal or increased GFR Stage 2: Kidney damage with mild decreased GFR (60-89ml/min) Stage 3: Moderately decreased GFR (30-59 ml/min) Stage 4: Severely decreased GFR (15-29) Stage 5: Kidney failure with GFR <15ml/min and a need for dialysis or kidney transplant. All values have units of ml/min per 1.73 m 2 body surface area. Source: National Kidney Foundation Practice Guidelines 2003.

6 End Stage Renal Number of kidney transplants performed 2 : 2006: 18, : 17, : 14, : 12, : 10, : 7, : 3,785 Renal Disease US. gov 2009 Disease. Source of organ donations (2006) 2 : From deceased donor: 11,576 From living related donor: 4,000 From spouse/life partner: 824 From living unrelated donor: 1,450

7 Mediated and Direct Effects of Risk Factor. BMI Factor 1 Factor 2 Hypertension Cardiovascular Disease Renal Disease Factor 3 Factor 4 Diabetes Obstructive Disease Genetic and nongenetic Salt Intake

8 Major Risks Factors Associated with Kidney Disease. Diabetes 216,000 55% Hypertension 106,000 27% Glomerular/interstitial nephritis 57,000 14% Cystic and Genetic 14, % All causes 389,000 Primary diagnosis U.S. Renal Data System ; Reported 2009

9 Serum Creatinine. Serum creatinine, BUN and proteinuria have been the standards for screening for kidney disease. The clinical introduction of estimated glomerular filtration rate reporting will for a period confuse this issue.

10 Comparison of BUN and creatinine by age band.

11 % POPULATION Age and Creatinine >1.5mg/dL. PRECENT OF SAMPLES ABNORMAL FOR CREATININE > AGE DECADE >1.5

12 Limitations of Creatinine. Acute kidney failure, the serum creatinine may not be reliable. Muscular or very frail individuals. People taking creatine supplements. Extremes of age, body size, obesity, malnutrition, paraplegia or muscle disease(s). Hemolysis increases the Cr value

13 Serum Creatinine. The test for creatinine is affected by; Positive ^Protein ^Glucose Cephalosporins ^Hemolysis Ascorbic Acid Negative Bilirubin Lipemia

14 MEAN Monthly Variation in Serum Creatinine. CREATININE MONTH OF YEAR CREATININE

15 Urine test help classify kidney disease risk. Urine albumin corrected for hydration identifies 75% of risk. Urine albumin ratio also identifies a risk group with normal egfr and serum creatinine values.

16 Urine albumin(mg)/ g Creatinine. Mortality Mortality AGE SEX < 60 F < M < Ratio AGE SEX 60+ F < M < Ratio

17 Laboratory Tests for Kidney Function. Glomerular filtration rate is a measure of how well the kidney filters the blood and removes metabolites (creatinine and nitrogen) while concentrating the urine. GFR may be measured with 24 hour urine collection or by measuring the rate of removal of an injected neutral drug. The GFR may also be estimated by equation.

18 Estimated Glomerular Fitration Rate (egfr). The Modification of Diet in Renal Disease (MDRD) is a national study of patients with diabetes. MDRD-4 Rule et al. developed a quadratic equation to better fit the GFR data for a mixed group of sick and well patients. But, as with most clinical studies sick people were the target of these studies.

19 egfr Equations. Factors for the estimation of GFR include; AGE SEX Serum Creatinine Race (not included for insurance samples)

20 Insurance Applicant Mortality. Over 9 Million applicants test results were reviewed. The Social Security Master Death Index was compared to applicant Social Security Numbers to identify deceased tested individuals. Receiver Operator Characteristic curves were evaluated to determine best model for identification of mortality.

21 Receiver Operator Characteristics (ROC). ROC area Serum Cre. Creatinine Cockroft- Gault ALL > >0.8 MDRD >0.8 Rule et. al > ,228 dead/9,646,645 tested

22 Cumulative Surviva 12 Year Survival and Rule et al. Rule egfr Cumulative Surviving years

23 HAZARDS RATIO egfr and Applicant Age. HAZARDS RATIO GFR VS AGE > egfr MDRD4

24 Natriuretic Peptides. Natriuretic hormones help control blood volume and blood pressure by regulating the rate of elimination of salt and water by the kidneys. Natriuretic hormones, produced mainly in the ventricular myocardium, are synthesized as prohormones that are cut into their active form by protease(s). All hormones are cleared or catabolized very quickly, including BNP. Nt-proBNP is the amino terminal portion of the pro-hormone.

25 NT-proBNP Levels. The level of Nt-proBNP is increased by stretch or stress on the left ventricle. Remodeling of the ventricular in response to atrial arrhythmia, valve regurgitation, heart failure and ischemia increases Nt-proBNP. Paper by RK Illango list the normal range of values for Nt-proBNP, for insurance applicant blood samples. Illango,RK JIM 2007;39:

26 RK Illango - JIM Elevated Nt-proBNP is a marker for cardiovascular morbidity and mortality even in the absence of systolic and diastolic dysfunction and other prognostic markers. It provides prognostic information above and beyond that provided by conventional risk factors and is independently associated with ischemia in those with stable coronary artery disease.

27 Consideration of NT-proBNP Values. Women have higher values than males. In the ER values greater than 128 are considered to be abnormal. Values greater than 1000 have a high mortality for all age and sex groups. Nt-proBNP values increase with age.

28 NT PROBNP MEAN NT PROBNP and AGE. MEAN NT PRO BNP BY AGE FOR NT PROBNP VALUES LESS THAN 1, You must consider applicant age AGE

29 Summary. BUN may be superior to creatinine in risk stratification in the elderly. All egfr calculations include an age factor an will underestimate GFR in the elderly. Nt probnp will independently identify excess risk in applicants with and without known heart disease. 8/7/2013