Kidneys form a pair of organs, which perform many im- portant functions.
Functions of Kidney
1. Excretion of urea and other wastes, such as acids, bas- es, toxins, drug metabolites, urea, creatinine.
2. Maintaining water balance.
3. Excretion of sodium (effect on blood pressure). 4. Excretion of potassium (effect on heart).
5. Excretion of hydrogen ions (maintenance of pH). 6. Activation of vitamin D (effect on bone).
7. Production of erythropoietin (effect on red blood cells). 8. Filtration: About 180 liters/day of water with all sodi-
um, chloride, sugar and amino acids.
9. Reabsorption: About 178.5 liters reabsorbed; all glu- cose and amino acids reabsorbed; most of sodium and chloride reabsorbed.
Classification of Renal Function Tests
To Screen for Kidney Disease
1. Complete urine analysis. 2. Plasma urea and creatinine. 3. Plasma electrolytes.
To Assess Renal Function
To assess glomerular function: Following are to be done:
a. Glomerular filtration rate. b. Clearance tests.
c. Glomerular permeability. d. Proteinuria.
To assess tubular function:: Following are to be done:
a. Reabsorption studies. b. Secretion tests.
c. Concentration and dilution tests. d. Renal acidification.
Complete urine analysis: The complete urine analysis is giv-
en in Table 13.1.
Table 13.1: Urine analysis Test and normal
range Interpretations
Specific gravity
(1.015–1.025) Low: Renal tubular acidosis, diabetes insipidus, polydipsia High: Excess water loss due to diarrhea, vomiting, diabetes mellitus (DM), glomerulonephritis
pH (4.5–8) Low: Increased protein diet, acidosis High: Decreased protein diet
Blood Glomerulonephritis, trauma of urinary tract stones, hemoglobinuria
Protein
(< 150 mg/day) Fever, exercise, proteinuria, glomerulonephritis, urinary tract infection (UTI), tubular diseases Glucose Diabetes mellitus, renal glycosuria,
Fanconi’ s syndrome Ketone bodies Diabetes mellitus, starvation Bilirubin Hepatitis, obstructive jaundice Urobilinogen Concentrated urine, hepatitis,
intravascular hemolysis Bile salts Obstructive jaundice
Plasma urea and creatinine: The estimation of urea is done
by: the following: 1. Urease method.
2. Glutamate dehydrogenase (GLDH) method. 3. Diacetyl monoxime method (DAM).
Normal serum urea level: The normal value is 20–40
mg/dL.
Blood urea nitrogen: Sometimes used as a measurement of
urea since 1½ molecular weight of urea contains nitrogen. The normal range of blood urea nitrogen (BUN) is 5–25 mg/dL.
High BUN > 80 mg/dL, indicates impaired renal function.
Normal serum urea = BUN × 2.14.
Causes for increased blood urea
1. Prerenal conditions:
a. Dehydration: Severe vomiting, intestinal obstruc- tion, diarrhea.
b. Diabetic coma and severe burns. c. Fever and severe infections. 2. Renal diseases: a. Acute glomerulonephritis. b. Nephrosis. c. Malignant hypertension. d. Chronic pyelonephritis. 3. Postrenal causes:
a. Stones in the urinary tract. b. Enlarged prostate.
c. Tumors of bladder.
Causes for decreased blood urea
a. During pregnancy. b. Liver diseases. c. Protein malnutrition.
Clinical Correlation
1. Azotemia: Increase in the blood levels of non-protein
nitrogen (NPN) is referred to as azotemia and is the hallmark of kidney failure.
2. Uremic syndrome: Clinical syndrome that develops
due to nitrogen retention due to renal failure.
Mnemonic:
Blood urea nitrogen (BUN): Creatinine elevation: Causes ABCD:
• Azotemia (prerenal)
• Bleeding [gastrointestinal (GI)] • Catabolic status
• Diet (high protein parenteral nutrition)
Estimation of serum creatinine: Done by Jaffe’s method.
1. Normal range (Table 13.2): a. Adult males: 0.7–1.4 mg/dL. b. Adult females: 0.6–1.3 mg/dL. c. Children: 0.4–1.2 mg/dL.
Plasma electrolytes: Are as given below:
1. Estimation of electrolytes (Na+ and K+):
a. Flame photometry.
b. By ion selective electrode method.
Chapter 13: Clinical Chemistry 133
2. Normal range:
a. Sodium: 135–150 mmol/L. b. Potassium: 3.5–5 mmol/L.
Table 13.2: Factors that increase and decrease serum creatinine Factors reducing
serum creatinine Factors increasing serum creatinine
Low muscle mass Old age Females Males
Malnutrition Renal diseases: • Glomerulonephritis • Pyelonephritis • Renal failure • Urinary obstruction
Glomerular Function
When the blood is perfused through the Bowman’s capsule, an ultrafiltrate of the blood is produced in glomerulus, while the cells and proteins are retained in the blood. The sieves of the glomeruli are such that hemoglobin is passed through to be excreted in urine, but albumin is retained in blood. Therefore, the earliest manifestation in the abnormal func- tion of the glomeruli is appearance of albumin in urine.
Glomerular Filtration Rate
1. The renal blood flow is about 700 mL plasma or 1,200 mL of blood, which passes, kidney per minute. 2. The glomerular filtration rate (GFR) is 120–125 mL per
minute in a person with 70 kg body weight.
3. Glomerular filtrate (GF) formed is about 170–180 li- ters per day, out of which only 1.5 liters are excreted as urine. Thus, 99% of GF is reabsorbed (Table 13.3).
Table 13.3: Glomerular filtration rate Segment of
nephron Reabsorption Secretion
Proximal convoluted tubule (PCT) Sodium (85%), chloride (85%), bicarbonate (85%), glucose (100%), amino acids (100%), uric acid, water (obligatory) H+, acids and bases, NH4+, diodrast, hippuric acid Loop of Henle Na+, Cl-, Ca2+, Mg2+ - Distal convoluted tubule (DCT) Na+, Cl-, water (facultative) H+, K+, NH 4+, uric acid
Renal Threshold and Tubular Maximum
The renal threshold of a substance is the plasma level above which the compound is excreted in urine. The maxi- mum reabsorptive capacity of the substances is known as the tubular maximum.
Markers of GFR
Clearance Tests: Measurement of GFR is a general index for
assessment of renal damage. GFR is also affected by age, sex, body size, protein intake and pregnancy. Normal GFR for young adults is 120–130 mL/min/1.73 m2.
Clearance is defined as the volume of blood or plasma completely cleared of a substance per unit time and is ex- pressed as milliliter per minute. It is expressed as milliliter of plasma per minute (not as g or mg).
Clearance estimates the amount of plasma that must have passed through the glomeruli per minute. It is calcu- lated by using the formula:
U × V C = P
where,
U = Concentration of the substance in urine;
P = Concentration of the substance in plasma or serum; V = The mL of urine excreted per minute.
Creatinine clearance test
Volume of plasma (in mL) completely cleared off creatinine per minute.
Creatinine is a waste product, formed from creatine phosphate. This conversion is spontaneous, nonenzymatic and is dependent on total muscle mass of the body. Since the production is continuous, the serum level of creatinine level will not fluctuate much, making creatinine an ideal substance for clearance test.
Normal range of creatinine: As given below:
Adult males: 0.7–1.4 mg/dL. Adult females: 0.6–1.3 mg/dL. Children: 0.4–1.2 mg/dL.
Procedure: As follows:
Give about 500 mL of water to the patient, to promote good urine flow. After about 30 minutes, ask to empty the blad- der and discard the urine. Exactly after 60 minutes, again void the bladder and collect the urine, and note the volume. Take one blood sample for serum creatinine estimation.
Since the value of creatinine level depends on total muscle mass, creatinine clearance corrected for surface area could be calculated as:
U × V × 1.73 C =
P × A
The value up to 75% of average normal range indicates adequate renal function.
Advantages: As follows:
1. Early detection of functional impairment of kidney without overt signs and symptoms.
2. Helpful in long-term monitoring of patients with renal insufficiency under a protein restricted diet.
4. Endogenous substances and a constant serum cre- atinine level are maintained, and hence blood may be collected at any time.
Disadvantages: As follows:
1. Value depends on total muscle mass. A person suffer- ing from muscle wasting diseases, measurement of creatinine clearance is not a reliable indicator of GFR. 2. Very early stages of decreased GFR may not be identi-
fied by creatinine clearance.
3. Prerenal, renal and postrenal causes will influence creatinine clearance.
Creatinine coefficient: It is the urinary creatinine expressed
in mg/kg body weight. The value is elevated in muscular dystrophy. Normal range is 20–28 mg/kg for males and 15–21 mg/kg for females.
Urea clearance test
Milliliter of plasma completely cleared or filtered off urea per minute. Urea is the end product of protein metabo- lism. Urea clearance is less than GFR, because urea is par- ticularly reabsorbed.
Maximum urea clearance: The urea clearance is calculated
by the formula:
U × V
Cm =
P Where,
U = Milligram of urea per mL of urine; P = Milligram of urea per mL of plasma V = Milliliter of urine excreted per minute. Normal value is found to be 75 mL/minute.
Standard urea clearance: If the clearance value is de-
creased when V, the volume of urine is less than 2 mL/ minute, then it is called standard urea clearance.
Normal value is found to be 54 mL/minute and is cal- culated as:
U × √V Cs =
P
Interpretation of urea clearance value: If the value is below
75% of the normal, it is considered to be abnormal, e.g. im- paired renal function.
The clearance value may be abnormal even though the plasma urea values are within normal limits. The plasma urea values will start to rise only when the clearance value falls below 50% of the normal.