Kidney function test

Functions of kidney

• Maintenance of homeostasis: responsible for water, electrolyte and acid-base balance • Excretion of metabolic waste products: end products of protein and nucleic acids e.g. urea, creatinine, uric acid etc.

• Retention of substances vital to the body: glucose, amino acids etc.

• Hormonal function: Erythropoietin, calcitriol, renin etc

Formation of urine

• Urine is formed by the help of nephrons • About 1 million nephrones are present in one kidney • Nephron contains bowmen’s capsule, proximal convoluted tubule, loop of henle, distal convoluted tubule and collecting tubule • blood supply high-1200ml/min • 120-125ml/min is filtered which is known as glomerular filtration rate (GFR)

Formation of urine

Process of urine formation basically involves two steps • Glomerular filtration: formation of ultrafiltrate – waste materials of plasma are filtered • Tubular reabsorption: formation of pure urine – PCT & DCT retain water and most of the soluble constituents of the glomerular filtrate by reabsorption

• Renal threshold of a substance is the concentration in blood beyond which it is excreted in urine • Renal threshold for glucose is 180mg/dL • Tubular maximum (Tm): maximum capacity of the kidneys to absorb a particular substance • Tm for glucose is 350 mg/min

Renal function tests

• Glomerular function tests: all the clearance tests (innulin, creatinine, urea) • Tubular function test: urine concentration or dilution test or urine acidification test • Analysis of blood/serum: blood urea, serum creatinine, protein and electrolytes • Urine examination: simple routine examination of urine for volume, pH, proteins, blood, ketone bodies, glucose

Why Test Renal Function?

• To identify renal dysfunction.

• To diagnose renal disease.

• To monitor disease progress.

• To monitor response to treatment.

• To assess changes in function that may impact on therapy (e.g. Digoxin, chemotherapy).

Renal Functions

• Production of urine – Elimination of metabolic end products (Urea/Creatinine) – Elimination of foreign materials (Drugs) – Control of volume & composition of ECF • Water and electrolyte balance • Acid/Base status • Endocrine Functions • Vit D, Erpo, Renin

Signs and Symptoms of Renal Failure

• Symptoms of Uraemia

(nausea, vomiting, lethargy)

• Disorders of Micturation

(frequency, nocturia, dysuria)

• Disorders of Urine volume

(polyuria, oliguria, anuria)

• Alterations in urine composition

(haematuria, proteinuria, bacteriuria, leukocytouria, calculi)

• Pain • Oedema

(hypoalbuminaemia, salt and water retention)

Biochemical Tests of Renal Function

• • •

Urinalysis

– Appearance – Specific gravity and osmolality – pH – Glucose – Protein – Urinary sediments?

Measurement of GFR

– Clearance tests – Plasma creatinine

Tubular function tests

Role of Biochemical Testing

• Presentation of patients: • • •

Routine urinalysis Symptom or physical sign Systemic disease with known renal component.

• Effective management of renal disease depends upon establishing a definitive diagnosis: • •

Detailed clinical history Diagnostic imaging and biopsy

• Role of biochemistry: •

Rarely establishes the cause

• •

Screening for damage Monitoring progression.

Urinalysis 1

• Fresh sample = Valid sample.

• Appearance: – Blood – Colour

(haemoglobin, myoglobin,)

– Turbidity

(infection, nephrotic syndrome

• Specific gravity : – Normal is 1.0002-1.030

• pH: – Normal =acidic, except after meal

Urinalysis 2

• •

Glucose

– Increased glucose – Low renal threshold or other tubular disorders

Proteinuria

– Normal < 200 mg/24h. Urine sticks (+)ve if ≥300mg/L – Causes: •

overflow (raised plasma Low MW Proteins, Bence Jones, myoglobin)

• •

glomerular leak decreased tubular reabsorption of protein (RBP, Albumin)

•

protein renal origin

Causes of colouration in urine

Blue Green Pink-Orange Red Methylene Blue Haemoglobin Pseudomonas Riboflavin Myoglobin Porphyrins Rifampicin Red-brown-black Haemoglobin Myoglobin Phenolpthalein Red blood cells Homogentisic Acid L –DOPA Melanin Methyldopa

Urinalysis 3

•

Urine sediments

– Microscopic examination of sediment from freshly passed urine.

• Looking for cells, casts (Tamm-Horsfall protein), fat droplets • Red Cell casts - haematuria - glomerular disease • White cell cast + polymorphs + bacteriuria = pylonephrites • Acute glomerulnephritis = haematuria, cells, casts

Measurement of Glomerular

Filtration

Rate (GFR )

• GFR is essential to renal function • Most frequently performed test of renal function.

• Measurement is based on concept of clearance: -

“The determination of the volume of plasma from which a substance is removed by glomerular filtration during it’s passage through the kidney”

Determination of Clearance

• Clearance = (UxV)/P

Where, U is the urinary concentration of substance V is the rate of urine formation (mL/min) P is the plasma concentration of substance

• Units

=

volume/unit time (mL/min) • If clearance = GFR then substance should have the properties: – freely filtered by glomerulus – glomerulus = sole route of excretion from the body (no tubular secretion or reabsorbtion) – Non-toxic and easily measurable

Properties of Agents used to Determine GFR

Property Not Protein Bound Freely Filtered Urea

Yes Yes

No secretion or absorbtion Constant endogenous production rate Easily Assayed

Flow related reabsorption No Yes

Creatinine

Yes Yes Some secretion Yes Yes

Inulin

Yes Yes Yes No No

Inulin GFR

• Gold Standard • Plant polysacharide • Complex procedure – Bolus dose followed by constant infusion – Timed urines, with bloods taken midpoint of collection periods, for inulin assay.

– GFR is taken as the mean for each period.

• 1-2%/day of muscle creatine converted to creatinine • Amount produced relates to muscle mass • Freely filtered at the glomerulus • Some tubular excretion.

Creatinine Clearance

• Timed urine collection for creatinine measurement (usually 24h) • Blood sample taken within the period of collection.

• Normal range = 120-145ml/min

Problems: -

• Practical problems of accurate urine collection and volume measurement.

• Within subject variability = 11%

Plasma Creatinine Concentration

Difficulties: • Concentration depends on balance between input and output.

• Production determined by muscle mass which is related to age, sex and weight.

• High between subject variability but low within subject.

• Concentration inversely related to GFR.

– Small changes in creatinine within and around the reference limits = large changes in GFR.

Effect of Muscle Mass on Serum Creatinine

Creatinine Input Plasma Pool Content Kidney Output

Normal Muscle Mass Normal Muscle Mass Increased Muscle Mass Reduced Muscle Mass Normal Kidneys Diseased Kidneys Normal Kidneys Diseased Kidneys

Acute Renal Failure

Metabolic features: • Retention of: – Urea & creatinine – Na & water – potassium with hyper kalaemia – Acid with metabolic acidosis Classification of Causes: • Pre-renal – reduced perfusion • Renal – inflammation – infiltration – toxicity • Post-renal – obstruction

Pre-renal versus intrinsic ARF

Test Result

Pre-renal Renal Urea & Creatinine Disproportionate rise in Urea Protein in urine Uncommon Tend to rise together Present on dipstick testing