Renal Function: Clinical Pathology Department Medicine School/hasan Sadikin Hospital

Renal Function Clinical Pathology Department Medicine School/Hasan Sadikin Hospital

Topics 1. 2. 3. 4.

Renal function Glomerular Filtration Rate (GFR) Concept of clearance Measurement of Glomerular Filtration Rate 5. Indicators of Renal Disease

RENAL FUNCTION 1. 2. 3. 4. 5. 6. 7.

Excretion Reabsorption Acid-base homeostasis Water and Sodium metabolism Vascular tone Erythropoiesis Calcium homeostasis

To produce urine, nephrons and collecting ducts perform 3 basic processes: 1. Glomerular filtration 2. Tubular reabsorption 3. Tubular secretion

Glomerular Filtration Rate • The amount of filtrate formed in all renal corpuscles of both kidneys each minute. • In adult male GFR = 125 ml/min; • female = 105 ml/min.

CONCEPT OF CLEARANCE • Renal clearance: volume of plasma that would theoritically have to be “cleared” of the substance in order to account for the amount of the substance excreted in the urine during a given period.

• Relates the rate of urinary excretion of material to the plasma concentration of that material.

CONCEPT OF CLEARANCE

Parameters need to calculate renal clearance of certain substance: - the amount of substance excreted in the urine  calculate from: - concentration of substance in urine (Ux) - volume of urine (V) - plasma concentration of the substance (Px)

CONCEPT OF CLEARANCE

Example: Creatinine • Creatinine is toxic substance produced by muscle and ingested meat. • If a person excreted creatinine 1500g/day, and normal plasma concentration of creatinine is 1 mg/dl (10 mg/L)  he needs 150 L of plasma to cleared creatinine  creatinine clearance = 150 L/day. Ccreat = (Ucreat X Vu)/Pcreat

CONCEPT OF CLEARANCE

Creatinine clearance formula: • Measured • Estimated Creatinine clearance decreased with age

CONCEPT OF CLEARANCE

Creatinine clearance formula: Ucr (mg/dl) X V (mL/min) Measured Ccr = ---------------------------------Pcr (mg/dl) • Ucr = concentration of creatinine in urine • Pcr = concentration of creatinine in plasma • V = volume of 24-hour urine collection

CONCEPT OF CLEARANCE

Creatinine clearance formula: Estimated: (140-age) X weight (kg) Ccr (adult male) = ------------------------------ X 72 Pcr Ccr (adult female) = Ccr (adult male formula) X 0.85

CONCEPT OF CLEARANCE

Creatinine clearance: • Usefull in: – Detecting renal dysfunction – Calculating dose intervals for nephrotoxic drugs – Evaluating the effectiveness of therapy of progressive renal disease

CONCEPT OF CLEARANCE

Increased Ccr: 1. Normal pregnancy: • •

Range 115-185 ml/min  depent on time of gestation, highest at the end of the first 3 semester. Increase in plasma volume  increase GFR  increase Ccr

2. Early diabetic glomerulopathy: •

arteriosclerosis  constriction of efferent arteriole  GFR  damages the glomerulus (hyperfiltration injury)

CONCEPT OF CLEARANCE

Decreased Ccr: 1. Elderly people: •

GFR normally decreases with age  Ccr

2. Acute and chronic renal disease: •

AKI : -

•

Acute Tubular Necrosis (ATN) Rapidly Progressive Glomerulonephritis (RPGN)

CRF : -

Diabetic glomerulopathy Hypertension

MEASUREMENT OF GLOMERULAR FILTRATION RATE 1. With exogenous substances: •

Inulin (gold standard)

2. With endogenous substances: • • •

Creatinine Urea Nitrogen Cystatin C

MEASUREMENT OF GFR

Creatinine: •

Source: – Muscle: creatine/creatine phosphat – Ingested meat

•

Widely used as GFR marker: – Endogenous substance of fairly constant production. – Not bound to plasma protein  filtered freely by the glomerulus. – Not reabsorbed by the renal tubulus – Only a small amount is secreted by the tubulus

MEASUREMENT OF GFR

Creatinine: •

Disadvantages of Cr as GFR marker: – Depend on muscle mass – Also derived from dietary meat

•

Creatinine measurement: Interfering substances: ketones, glucose, fructose, protein, urea and ascorbic acid.

MEASUREMENT OF GFR

Increase serum creatinine: 1. Decreased cardiac output: Congestive heart failure, hemorrhagic shock, volume depletion  COP ↓  GFR ↓  cr ↑

2. Increased muscle mass (body builder) 3. Increased tissue necrosis third-degree burns (cr degradation ↑  cr ↑)

4. Acute glomerulonephritis (GFR ↓  cr ↑)

MEASUREMENT OF GFR

Increase serum creatinine: 5. 6. 7. 8.

Acute or chronic renal failure (GFR ↓) Post renal disease (GFR ↓) Creatine supplements (Cr degradation ↑) 5. ↓) Drug/chemical interference (cephalosporin, diabetes ketoacidosis)

MEASUREMENT OF GFR

Decrease serum creatinine: 1. Increased plasma volume: Normal pregnancy  plasma vol ↑  GFR ↑  cr ↓. 2. Emaciated patient: Cr muscle ↓  cr ↓ 3. Chemical interference: hyperbilirubinemia

MEASUREMENT OF GFR

Urea •

•

Main waste product of Nitrogencontaining chemicals in the body  Urea Nitrogen. Its value as a measure of GFR is not very good: – Depend largely to protein intake (diet) – Reabsorbed in the proximal tubule and inner medullary collecting duct

MEASUREMENT OF GFR

Increased Blood Urea Nitrogen (BUN): 1. 2. 3. 4. 5. 6.

Decreased cardiac output Increased protein intake Increased tissue catabolism Acute glomerulonephritis Acute or chronic renal failure Postrenal disease

MEASUREMENT OF GFR

Decreased Blood Urea Nitrogen (BUN): 1. Increased plasma volume 2. Decreased urea synthesis 3. Decreased protein intake

MEASUREMENT OF GFR

Cystatin C • •

•

Not affected by muscle mass, sex, race Because small size and positive net charge  freely filtered at the glomerulus, and completely reabsorbed in the tubulus. Not widely used  measurement is expensive

INDICATORS OF RENAL DISEASE 1. 2. 3. 4. 5. 6. 7.

Increased of serum creatinine and BUN Decreased creatinine clearance Loss of urine concentration and dilution Proteinuria Hematuria Leucocyturia Presence of renal tubular casts

Reference books 1. Henry’s Clinical Diagnosis and Management by Laboratory Methods. Richard A.McPherson, Matthew R.Pincus. 21st ed, 2007. 2. Laboratory Testing in Clinical Medicine. Edward F.Goljan, Karlis I.Sloka. 2008