Use of Laboratory Tests in Kidney Disease

Use of Laboratory Tests in Kidney Disease Overview ¾ Review functions of the kidney and related tests ¾ Discuss specific tests and issues relating to...
Author: Paulina Miles
2 downloads 0 Views 2MB Size
Use of Laboratory Tests in Kidney Disease

Overview ¾ Review functions of the kidney and related tests ¾ Discuss specific tests and issues relating to interpretation

Tests of kidney function

1

What does a kidney do? ¾ Blood flow to kidney is about 1.2 L/min (1/5 of Cardiac output)

¾ About 10% of blood flow is filtered across the glomerular membrane (100 – 120 ml/min/1.73m2 ƒ Tests: urea, creatinine, creatinine clearance, eGFR, Cystatin C

Glomerulus

Glomerulus Microscopic

2

Tests of kidney function

Kidney Functions – cont’d Selectively secretes into or re-absorbs from the filtrate to maintain ¾ Salt Balance ƒ Tests: Na+, Cl-, K+ Aldosterone, Renin ¾ Acid Base Balance ƒ Tests: pH, HCO3-, NH4+ Acid loading, Urinary Anion Gap

Kidney Functions – cont’d Selectively secretes into or re-absorbs from the filtrate to maintain ¾ Water Balance ƒ Tests: specific gravity, osmolarity, water deprivation testing, Antidiuretic hormone

¾ Retention of nutrients ƒ Tests: proteins, sugar, amino acids, phosphate ¾ Secretes waste products ƒ Tests: urate, oxalate, bile salts

3

Kidney Function – cont’d Endocrine Function Target organ ¾ Parathyroid hormone (Ca++, Mg++) ¾ Aldosterone (salt balance) ¾ ADH (water balance)

Production ¾ Erythropoietin ¾ 1, 25 dihydroxycholecalciferol

Calcium Metabolism

Renin Angiotensin System

4

Aldosterone

ADH

Tests that predict kidney disease ¾ eGFR ¾ Albumin Creatinine Ratio (aka ACR or Microalbumin)

5

Tests of Glomerular Filtration Rate ¾ Urea ¾ Creatinine ¾ Creatinine Clearance ¾ eGFR ¾ Cystatin C

Glomerular Filtration Rate (GFR) ¾ Volume of blood filtered across glomerulus per unit time

¾ Best single measure of kidney function

Glomerular Filtration Rate (GFR) – cont’d ¾ Patient’s remain asymptomatic until there has been a significant decline in GFR

¾ Can be very accurately measured using “goldstandard” technique

6

Glomerular Filtration Rate (GFR) – cont’d Ideal Marker ¾ Produced endogenously at a constant rate ¾ Filtered across glomerular membrane ¾ Neither re-absorbed nor excreted into the urine

Urea ¾ Used historically as marker of GFR ¾ Freely filtered but both re-absorbed and excreted into the urine

¾ Re-absorption into blood increased with volume depletion; therefore GFR underestimated

¾ Diet, drugs, disease all significantly effect Urea production

Urea Increase

Decrease

Volume depletion Ç Dietary protein Corticosteroids Tetracyclines Blood in G-I tract

Volume Expansion Liver disease Severe malnutrition

7

Creatinine ¾ Product of muscle metabolism ¾ Some creatinine is of dietary origin ¾ Freely filtered, but also actively secreted into urine ¾ Secretion is affected by several drugs

Serum Creatinine Increase

Decrease

Male Meat in diet Muscular body type Cimetidine & some other medications

Age Female Malnutrition Muscle wasting Amputation

Creatinine vs. Inulin Clearance

8

Creatinine Clearance ¾ Measure serum and urine creatinine levels and urine volume and calculate serum volume cleared of creatinine ¾ Same issues as with serum creatinine, except muscle mass ¾ Requirements for 24 hour urine collection adds variability and inconvenience

Cystatin C ¾ Cystatin C is a 13 KD protein produced by all cells at a constant rate

¾ Freely filtered ¾ Re-absorbed and catabolized by the kidney and does not appear in the urine

eGFR ¾ Increasing requirements for dialysis and transplant (8 – 10% per year)

¾ Shortage of transplantable kidneys ¾ Large number at risk

9

eGFR – cont’d Stage

Description

GFR ML/min/1.173m2

Prevalence3

1

Kidney Damage with Normal or ↑ GFR

>90

478,500

2

Kidney Damage with Mild ↓ GFR

60 – 89

435,000

3

Moderate ↓ GFR

30 – 59

623,500

4

Severe ↓ GFR

15 – 29

29,000

5

Kidney Failure

60 years

12

Screen High Risk Groups ¾eGFR ¾Urinalysis ¾Albumin / Creatinine Ratio

Follow-up based on Screen Results ¾Kidney Ultrasound ¾Specialist Referral ¾Cardiovascular Risk Assessment ¾Diabetes Control ¾Smoking cessation ¾Hepatitis / Influenza Management

Creatinine Standardization in British Columbia ¾Based on Isotope dilution /mass spectrometry measurements of creatinine standards

¾Permits estimation and correction of creatinine and eGFR bias at the laboratory level.

13

Importance of Standardization ¾Low bias creatinine: ƒ Causes inappropriately increased eGFR ƒ Patients will not receive the benefits of more intensive investigation of treatment.

¾High bias creatinine: ƒ Causes inappropriately decreased eGFR ƒ Patients receive investigations and treatment which is not required. Wastes time, resources and increases anxiety.

High 143.3 Low

116.0

Mean 124.6

14

Poor Creatinine Precision ¾Incorrect categorization of patients with both “normal” and decreased eGFR.

Total Error ¾TE = % bias + 1.96 CV ¾Goal is