Kidney function, two complimentary evaluations

Serum and urine testing

Robert L. Stout, Ph.D

.

Tests of kidney function

• Measured glomerular filtration rate.

• Urinalysis • Serum creatinine and blood urea nitrogen.

• Estimated glomerular filtration rate, eGFR.

Measured glomerular filtration rate

• Only on patients with known kidney disease to determine severity.

• Requires injection of a tag; radioactive, non-metabolizable sugar or dye.

• Collect samples and determine clearance rate.

Urine protein and urine creatinine

• The kidneys filter the blood to remove metabolites, waste material(s), salts, and water.

• The kidneys also recover water, glucose, salts and amino acids from the forming urine.

• This process concentrates the urine while recovering important building material for the body.

Proteinuria

• The kidneys loose about 100-150mg of protein per day. • On average about 1.0 to 1.5 gram of creatinine is produced per day depending on your muscle mass.

• Depending on your hydration state most people produce about 1 to 1.5 liters of urine per day.

Protein creatinine ratio

• It is both inconvenient and impractical to collect all the urine produced during a day. • Urine concentration varies widely depending on the hydration state. • The urine protein creatinine ratio allows an accurate measure of the average protein loss per day and is reported by all laboratories .

Fulks M, Stout RL, Dolan VF. Urine Protein/Creatinine Ratio as a Mortality Risk Predictor in Non-Diabetics with Normal Renal Function.

J. Insurance Medicine

. 2012;43:76-83

Serum creatinine a measure of renal function

• Serum creatinine values are the result of 2 opposing factors – Production is driven by muscle mass; men have higher creatinine values than women of the same age.

– Elimination is driven by filtration in the kidneys; as we age the kidneys have decreased capacity for filtration.

Aging and serum creatinine

• Normal aging is accompanied by a decrease in muscle mass.

• Normal aging is also accompanied by a decrease in kidney filtration and elimination of creatinine.

• Insurance product pricing accounts for the increasing mortality associated with normal aging.

• Underwriters need an objective measure of “age based normal renal function”.

Sex, age and mean serum creatinine

Upper range of expected value for creatinine

The samples

• A blood sample and urine may be collected anytime that is convenient for an applicant and paramedical examiner.

• The serum sample is allowed to clot and then centrifuged to separate the liquid portion (serum) from the clot, trapped cells and fibrin .

Things that can go wrong.

• For the urine, the only big problem is sample mix-up.

• In contrast, if the serum sample is not centrifuged within 2 hours there is a risk for, – Glycolysis, the catabolism of glucose in the sample – Hemolysis, the rupture of red cells and release of hemoglobin into the serum.

Hemolysis and glycolysis

• How do these effect the serum creatinine value?

• Which is the best indicator that something has gone wrong?

• If there was a problem can the underwriter still reliably proceed with the review?

Serum glucose (glycolysis) and creatinine

Glycolysis

Hemolysis and serum creatinine

Serum creatinine set at 1.45mg/dL

GLUCOSE Glycolysis Total Serum <= 1.45

<= 10 11-20 21 - 30 31 - 40 41 - 50 51 - 60 61 - 70 71+ 82.19% 93.90% 96.75% 97.56% 98.59% 98.88% 99.16% 99.09% 224584 Creatinine 1.46+ 17.81% 6.10% 3.25% 2.44% 1.41% 1.12% 0.84% 0.91% 4849 % high 1.04% 0.12% 0.07% 0.07% 0.05% 0.06% 0.09% 0.62% 2.11% % total 5.80% 2.00% 2.20% 2.80% 3.70% 5.50% 10.20% 67.80% 229433

Serum creatinine set at 1.45mg/dL

GLUCOSE Glycolysis Total Serum <= 1.45

<= 10 82.19% 11-20 93.90% 21 - 30 96.75% 31 - 40 97.56% 41 - 50 98.59% 51 - 60 98.88% 61 - 70 71+ 99.16% 99.09% 224584 17.81% 6.10% 3.25% 2.44% 1.41% 1.12% 0.84% 0.91% 4849 Creat 1.46+ 1.04

% 0.12% 0.07% 0.07% 0.05% 0.06% 0.09% 0.62% 2.11% % high 5.80% 2.00% 2.20% 2.80% 3.70% 5.50% 10.20% 67.80% 229433 % TOTAL

Enzymatic and Jaffe creatinine

Jaffe serum creatinine>1.5 evaluated by 2 methods

Estimated glomerular filtration rate

• Half a dozen different equations.

– The Mayo equation (Rule) and the CKD EPI equations are the most common.

• They both work, however, they do not have the same mortality risk ranges.

– If you use the tables from reinsurance most use the Mayo.

National Kidney Disease Education Program 2014

Be wary of Trojan horses

• In the insurance industry all current assessments of kidney function rely on a serum creatinine.

• Jaffe serum creatinine results in samples with low glucose values are not reliable. You can directly substitute an enzymatic creatinine into the eGFR calculation.

Case study

• Female 62yo, non-smoker, chemistry all normal except glucose is 0 and creatinine is 1.4mg/dL.

– eGFR = 38 ml/min/1.73m

2 • Enzymatic creatinine was 0.9mg/dL – eGFR=69 ml/min/1.73m

2

Case study

• Male 62yo, 6’4”, 340lb, all normal except glucose is 0 and creatinine is 1.4mg/dL, urine 0.25pro/creatinine • Enzymatic creatinine was 1.4mg/dL – Both eGFR is 51ml/min/1.73m

2 – Corrected for body surface area 71ml/min • 25% of applicants with proteinuria have normal eGFR

Questions?????