Renal Function Tests Overview

Renal Function Tests (RFT)

• Kidney function tests are categorized into four groups: glomerular function, tubular function, urine concentration/dilution, and urine acidification.
• Glomerular function tests include clearance tests using substances like inulin, creatinine, and urea.
• Tubular function tests include urine concentration or dilution tests and urine acidification tests.
• Blood/serum analysis involves assessing blood urea, serum creatinine, proteins, and electrolytes to evaluate renal function.
• Urine examination includes analyzing urine volume, pH, specific gravity, osmolality, and identifying abnormal substances like proteins, blood, ketone bodies, and glucose.
• Clearance is the plasma volume completely cleared of a substance per minute. It's calculated using the formula: C = (UxV)/P, where U is urine concentration, V is urine volume per minute, and P is plasma concentration.
• Glomerular filtration rate (GFR) is the rate at which substances are filtered by the glomeruli, typically 120-125 ml/min in adults.
• Normal GFR results in a filtrate of approximately 175-180 liters per day, with only 1.5 liters excreted as urine. More than 99% of filtrate is reabsorbed.
• Kidney function tests help assess glomerular and tubular function, including filtration rate, reabsorption, and concentration ability.

Kidney Function

• Kidneys maintain homeostasis by regulating water, electrolyte, and acid-base balance.
• They excrete metabolic waste products, like urea, creatinine, uric acid, sulfate, and phosphate, from protein and nucleic acid metabolism.
• Kidneys retain vital biochemical substances like glucose and amino acids.
• Kidneys produce hormones, acting as endocrine organs.
  • Erythropoietin promotes hemoglobin synthesis and red blood cell (erythrocyte) formation.
  • 1,25-Dihydroxycholecalciferol (calcitriol) is the active form of vitamin D, regulating calcium absorption from the gut.
  • Renin is a proteolytic enzyme that stimulates angiotensin II production, which, in turn, leads to aldosterone production, regulating electrolyte balance.
• The functional unit of the kidney is the nephron.
  • A nephron consists of a Bowman's capsule (with blood capillaries), proximal convoluted tubule (PCT), loop of Henle, distal convoluted tubule (DCT), and collecting tubule.
• The blood supply to the kidneys is significant; around 1200 ml of blood (650 ml plasma) flows through them every minute.
• The glomerular filtration rate (GFR) is about 120-125 ml/min.

Formation of Urine

• Glomerular filtration is a passive process; all unbound plasma constituents with a molecular weight below 70,000 are passed into the filtrate.
• The filtrate is similar in composition to plasma, but proteins are almost completely absent.
• Tubular reabsorption is the process by which the renal tubules retain water and most of the dissolved substances in the filtrate. This can be passive or active.
• Renal threshold substances are substances whose excretion depends on their concentration in the blood. At normal levels, they are completely reabsorbed. Examples include glucose, ketone bodies, calcium, and bicarbonate.
• Tubular maximum (Tm) is the maximum capacity of the kidneys to absorb a particular substance. For example, the tubular maximum for glucose is 350 mg/min.

Creatinine Clearance

• Creatinine is a waste product from creatine phosphate, excreted relatively constantly regardless of metabolism or diet.
• Creatinine is primarily filtered by the glomeruli and only minimally secreted by the tubules.
• Creatinine clearance is used to estimate GFR and is calculated using the formula C = (UxV)/P.
• A 24-hour urine collection is typically used to measure creatinine, but a 1-hour urine collection after hydration can also be used.
• Normal creatinine clearance is around 120-145 ml/minute. The values are slightly lower in women.

Urea Clearance

• Urea is a by-product of protein metabolism.
• After glomerular filtration, urea is partially reabsorbed by the renal tubules.
• Urea clearance is less than GFR and is influenced by protein intake in the diet.
• Urea clearance is less sensitive than creatinine clearance for indicating kidney function.
• Maximum urea clearance, when urine output is over 2 ml/minute is about 75 ml/min. Standard urea clearance (when urine output is less than 2 ml/min) is about 54 ml/min. The formula for calculating urea clearance is C_m or C_s= (UxV/P).

Diagnostic Importance

• A decreased creatinine clearance value (below 75% of normal) indicates decreased GFR and suggests renal damage.
• Blood urea (BUN) levels increase noticeably only when clearance falls below 50% of normal.
• Urea clearance values below 75% of normal indicate significant renal damage.
• Blood urea levels are elevated (azotemia) as a hallmark of kidney failure.

Causes of Increased Blood Urea

• Pre-renal causes: dehydration (severe vomiting, diarrhea, intestinal obstruction, burns, fever, infections, diabetic coma).
• Renal diseases: Acute glomerulonephritis, nephrosis, malignant hypertension, chronic pyelonephritis
• Post-renal causes: stones in the urinary tract, enlarged prostate, tumors of the bladder
• Medications: ACE inhibitors, acetaminophen, aminoglycosides, diuretics

Decreased Blood Urea

• Decreased blood urea may occur in pregnancy, starvation, inadequate dietary protein, or hepatic (liver) issues.

Uremia

• Uremia is a terminal stage of kidney failure caused by accumulated toxins.
• Toxins result in carbamoylation of proteins, uremic pericarditis (inflammation of the pericardium), peripheral neuropathy (nerve damage), and renal amyloidosis (protein deposit within the kidney).

Urine Concentration Tests

• Urine concentration tests assess renal tubular function.
• Tests involve measuring urine specific gravity, which relies on solute concentration.
• A specific gravity of 1.020 in early morning urine is considered normal.
• Urine osmolality (concentration of dissolved particles) is also variable, typically ranging from 500-1200 milliosmoles/kg in healthy individuals.

Proteinuria

• Glomerular proteinuria: glomeruli (tiny filters) do not allow proteins above 69,000 molecular weight to pass into urine.
• Damage/disease to glomeruli allows proteins to pass into urine (pathological).
  • Albuminuria (proteinuria due to albumin): Always pathological. Large amounts in nephrosis (kidney disease). Small amounts occur in acute nephritis, strenuous exercise, and pregnancy.
• Overflow proteinuria: elevated levels of small molecular proteins (ex: hemoglobin) in blood exceed kidneys' ability to filter result in abnormal proteins present in urine.
• Tubular proteinuria: occurs with compromised reabsorption mechanisms in damaged nephrons, with smaller molecules passing into urine
• Nephrotic-loss proteinuria: result of number of nephrons decreasing in chronic kidney disease (CKD), leading to increased filtered load of protein as other nephrons try to compensate, regardless of glomerular permeability changes.
• Urogenic proteinuria: inflammation of the urinary tract causes protein secretion into the urinary tract

Microalbuminuria

• It's a significant indicator of kidney damage and is characterized by small amounts of albumin (30-300 mg/day) present in the urine.
• It is not indicated with overt proteinuria.

Other Important Points

• The normal range of albumin-creatinine ratio in urine is less than 23 mg/gm in men and less than 32 mg/gm in women.
• A normal serum creatinine range for adults is 0.7–1.4 mg/dL in males and 0.6–1.3 mg/dL in females.
• Children display a slightly different serum creatinine range.
• Kidney Function tests classify damage to the kidney in stages 1 – 5, depending on GFR value.