Renal function tests renal failure dialysis and diuretics

Renal Physiology

Renal Function Tests, Renal Failure, Dialysis and Diuretics

Properties and composition of normal urine, renal function tests, renal failure, dialysis, kidney transplantation and diuretics.

01

Properties and Composition of Normal Urine

Properties of Urine

Property Normal Value / Description
Volume 1,000 to 1,500 mL/day
Reaction Slightly acidic with pH of 4.5 to 6
Specific gravity 1.005 to 1.030
Osmolarity 1,200 mOsm/L
Color Normally straw colored
Odor Fresh urine has light aromatic odor. If stored for some time, odor becomes stronger due to bacterial decomposition.

Composition of Urine

Urine consists of water and solids. Solids include organic and inorganic substances.

Solids Excreted in Urine

Organic Substances Quantity (mmol/day) Inorganic Substances Quantity (mmol/day)
Urea 400 Sodium 200
Uric acid 4 Potassium 50
Creatinine 10 Calcium 5
Ammonia 40 Chloride 200
Phosphate 25
Sulfate 50
02

Renal Function Tests

Renal function tests are the group of tests that are performed to assess the functions of kidney.

Types of Renal Function Tests

  1. Examination of urine alone.
  2. Examination of blood alone.
  3. Examination of blood and urine.
03

Examination of Urine: Urinalysis

Routine examination of urine or urinalysis is a group of diagnostic tests performed on the sample of urine.

Urinalysis is done by:

  1. Physical examination.
  2. Microscopic examination.
  3. Chemical analysis.

A. Physical Examination of Urine

  1. Volume.
  2. Appearance.
  3. Reaction.
  4. Specific gravity.
  5. Color.
  6. Odor.

B. Microscopic Examination of Urine

Microscopic examination reveals the presence of red blood cells, pus cells, epithelial cells, casts and crystals which suggests renal pathology.

C. Chemical Analysis of Urine

Chemical analysis of urine helps to determine the presence of abnormal constituents of urine or presence of normal constituents in abnormal quantity. Both the findings reveal the presence of renal abnormality.

Chemical analysis is done to determine the following substances:

  1. Glucose.
  2. Protein, particularly albumin.
  3. Ketone bodies.
  4. Bilirubin.
  5. Urobilinogen.
  6. Bile salts.
  7. Blood.
  8. Hemoglobin.
  9. Nitrite.
04

Examination of Blood

Level of plasma proteins, urea, uric acid and creatinine are determined in blood. Blood level of these substances is altered in renal failure.

Estimation of Plasma Proteins

Normal Values

Plasma Protein Normal Value
Total proteins 7.3 g/dL (6.4 to 8.3 g/dL)
Serum albumin 4.7 g/dL
Serum globulin 2.3 g/dL
Fibrinogen 0.3 g/dL

Level of plasma proteins is altered during renal failure.

Estimation of Urea, Uric Acid and Creatinine

Normal Values

Substance Normal Value
Urea 25 to 40 mg/dL
Uric acid 2.5 mg/dL
Creatinine 0.5 to 1.5 mg/dL

Blood level of above substances increases in renal failure.

05

Examination of Blood and Urine

Plasma Clearance

Plasma clearance is defined as the amount of plasma that is cleared of a substance in a given unit of time.

It is also known as renal clearance. It is based on Fick’s principle.

Measurement of Clearance

Determination of clearance value for certain substances helps to assess the following renal functions:

  1. Glomerular filtration rate.
  2. Renal plasma flow.
  3. Renal blood flow.

To determine plasma clearance of a particular substance, measurement of following factors is required:

  1. Volume of urine excreted.
  2. Concentration of the substance in urine.
  3. Concentration of the substance in blood.

Formula to Calculate Clearance Value

C = UV / P

Where:

  • C = Clearance.
  • U = Concentration of the substance in urine.
  • V = Volume of urine flow.
  • P = Concentration of the substance in plasma.
06

Measurement of Glomerular Filtration Rate

A substance that is completely filtered but neither reabsorbed nor secreted should be used to measure glomerular filtration rate (GFR).

Inulin is a substance that is completely filtered. And, it is neither reabsorbed nor secreted. So, inulin is the ideal substance used to measure GFR.

Inulin Clearance

A known amount of inulin is injected into the body. After sometime, the concentration of inulin in plasma and urine and the volume of urine excreted are estimated.

Example:

Concentration of inulin in urine = 125 mg/dL

Plasma concentration = 1 mg/dL

Volume of urine output = 1 mL/min

Glomerular filtration rate = UV / P

= (125 × 1) / 1

= 125 mL/min

Measurement of Renal Plasma Flow

To measure renal plasma flow, a substance which is filtered and secreted but not reabsorbed should be used.

Such a substance is para-aminohippuric acid (PAH). PAH clearance indicates the amount of plasma passed through kidneys.

A known amount of PAH is injected into the body. After sometime, the concentration of PAH in plasma and urine and the volume of urine excreted are estimated.

Example:

Concentration of PAH in urine = 66 mg/dL

Plasma concentration = 0.1 mg/dL

Volume of urine output = 1 mL/min

Renal plasma flow = UV / P

= (66 × 1) / 0.1

= 660 mL/min
07

Measurement of Renal Blood Flow

To determine renal blood flow, value of following two factors is necessary:

  1. Renal plasma flow.
  2. Percentage of plasma volume in the blood.

1. Renal Plasma Flow

Renal plasma flow is measured by using PAH clearance.

2. Percentage of Plasma Volume in the Blood

Percentage of plasma volume is indirectly determined by using PCV.

For example, if PCV is 45%, plasma volume in the blood is 100 − 45 = 55%, i.e., 55 mL plasma is present in every 100 mL blood.

Formula

Renal blood flow = Renal plasma flow / % of plasma in blood
Example:

Renal plasma flow = 660 mL/min

Amount of plasma in blood = 55%

Renal blood flow = 660 / (55/100)

= 1,200 mL/min
08

Renal Failure

Renal failure refers to failure of excretory functions of kidney. It is usually characterized by decrease in glomerular filtration rate (GFR).

Renal failure may be either acute or chronic.

Complications of Renal Failure

Renal failure is always accompanied by other complications, such as:

  1. Deficiency of calcitriol (activated vitamin D) resulting in reduction of calcium absorption from intestine and hypocalcemia. Deficiency of calcitriol and hypocalcemia may cause secondary hyperparathyroidism in some patients.
  2. Deficiency of erythropoietin resulting in anemia.
  3. Disturbances in acid-base balance.

Acute Renal Failure

Acute renal failure is the temporary loss of kidney function.

It occurs abruptly or suddenly. It is often reversible within few days to few weeks.

Acute renal failure may result in sudden life-threatening reactions in the body with the need for emergency treatment.

Common Causes of Acute Renal Failure

  1. Pyelonephritis: Inflammation of kidney involving glomeruli, tubules and interstitium.
  2. Acute glomerulonephritis: Inflammation of glomeruli.
  3. Damage of renal tissues: By poisons like lead, mercury and carbon tetrachloride.
  4. Renal ischemia: Inadequate blood supply to kidney.
  5. Acute tubular necrosis: Necrosis of tubular cells in kidney.
  6. Severe transfusion reactions: Refer Chapter 19 for transfusion reactions.
  7. Sudden fall in blood pressure: Due to conditions such as hemorrhage, diarrhea, severe burns and cholera.
  8. Blockage of ureter: Caused by formation of calculi (renal stone) or tumor.

Treatment for Acute Renal Failure

Acute renal failure can be treated in most of the cases if diagnosed early. Cause of the condition is determined and treatment is carried out accordingly.

Treatment involves use of medications, change in diet and dialysis if necessary.

Chronic Renal Failure

Chronic renal failure is the progressive, long standing and irreversible impairment of renal functions.

Last stage of chronic renal failure is called end stage renal disease (ESRD).

Common Causes of Chronic Renal Failure

  1. Chronic glomerulonephritis: Long-term inflammation of glomeruli.
  2. Polycystic kidney disease (PKD): Development of clusters of cysts in kidneys.
  3. Renal calculi.
  4. Urethral constriction.
  5. Hypertension.
  6. Atherosclerosis.
  7. Tuberculosis.
  8. Slow poisoning by drugs or metals.

Treatment for Chronic Renal Failure

Chronic renal failure is treated by dialysis or kidney transplant.

09

Dialysis and Artificial Kidney

Dialysis is a procedure to remove waste materials and toxic substances and to restore normal volume and composition of body fluid in severe renal failure.

It is also called hemodialysis.

Principle of Artificial Kidney

Principle of artificial kidney is the diffusion of solutes from an area of higher concentration to area of lower concentration, through a semipermeable membrane.

Artificial Kidney

Artificial kidney is a machine that is used to carry out hemodialysis during renal failure.

Patient’s arterial blood is passed continuously or intermittently through the artificial kidney and then back to the body.

Peritoneal Dialysis

In some cases, patient’s peritoneal membrane is used as a semipermeable membrane. This technique is called peritoneal dialysis.

It is also used to treat the patients suffering from renal failure.

10

Kidney Transplantation

Kidney or renal transplantation is the surgical procedure to place the healthy kidney into the renal failure patients.

Transplanted kidney takes over the functions of diseased kidney and the patient needs no further dialysis.

Healthy kidney is taken from either a live donor or a deceased donor.

Kidney transplantation is the treatment of choice for patients suffering from end stage renal disease (ESRD).

11

Diuretics

Diuretics or diuretic agents are the substances which enhance urine formation and output.

Diuretics increase the excretion rate of water, sodium and chloride through urine.

Diuretics increase the urine formation by influencing any of the processes involved in urine formation.

Diuretics are commonly called water pills.

Uses of Diuretics

Diuretics are generally used for treatment of disorders involving increase in extracellular fluid volume such as:

  1. Hypertension.
  2. Congestive cardiac failure.
  3. Edema.

Diuretic agents prevent the above disorders by increasing the urinary output and reducing extracellular fluid (ECF) volume.

Abuses and Complications of Diuretics

Nowadays, diuretics are misused to reduce body weight and keep the body slim. Even people suffering from eating disorders attempt to reduce body weight by misusing diuretics.

Prolonged use of diuretics leads to complications such as syndrome of diuretic-dependent sodium retention, characterized by edema.

Adverse effects depend upon the type of diuretic agents used.

Adverse Effects of Diuretics

  1. Dehydration.
  2. Electrolyte imbalance.
  3. Potassium deficiency.
  4. Headache.
  5. Dizziness.
  6. Renal damage.
  7. Cardiac arrhythmia.
  8. Heart palpitations.

Types of Diuretics

1. Osmotic Diuretics

Osmotic diuretics are the substances that induce osmotic diuresis.

When injected in large quantities into the body, these substances increase the osmotic pressure in the tubular fluid.

Increased osmotic pressure in the tubular fluid, in turn, reduces water reabsorption.

It leads to excretion of excess of water through urine.

Elevated blood sugar level in diabetes can also cause osmotic diuresis in the same manner.

Examples: Mannitol, sucrose and glucose.

2. Diuretics Which Inhibit Reabsorption of Electrolytes

Diuretics of this type inhibit the active reabsorption of electrolytes like sodium and potassium from the tubular fluid.

Inhibition of electrolyte reabsorption causes loop diuretics.

Loop Diuretics

Loop diuretics are the substances that inhibit electrolyte reabsorption in Henle’s loop.

Loop diuretics inhibit sodium and chloride reabsorption from thick ascending limb of Henle’s loop.

So, the osmotic pressure in tubular fluid increases, leading to diuresis.

Examples: Furosemide and torasemide.

3. Diuretics Which Inhibit Action of Aldosterone

Some diuretics inhibit sodium reabsorption and potassium excretion in the distal convoluted tubule and collecting duct, by inhibiting the action of aldosterone.

These substances are also called the potassium-retaining diuretics or aldosterone antagonists.

Examples: Spironolactone and eplerenone.

4. Diuretics Which Inhibit Activity of Carbonic Anhydrase

Some diuretics inhibit the activity of carbonic anhydrase in proximal convoluted tubules and result in osmotic diuresis.

Such diuretic agents are called carbonic anhydrase inhibitors.

Example: Acetazolamide.

5. Diuretics Which Increase Glomerular Filtration Rate

Some xanthines (alkaloids, used as mild stimulants) cause diuresis by increasing the glomerular filtration rate and to some extent by decreasing the sodium reabsorption.

Examples: Caffeine and theophylline.

6. Diuretics Which Inhibit Secretion of ADH

Some diuretics produce diuresis by inhibiting the secretion of ADH.

Examples: Water and ethanol.

7. Diuretics Which Inhibit ADH Receptors

Some diuretics cause diuresis by inhibiting receptors of antidiuretic hormone, thereby preventing the activity of hormone.

Example: Antagonists of V2 receptors.