Renal Function Tests
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I. RENAL PHYSIOLOGY |
*Functions of the kidneys:
1. Elimination of metabolic and toxic wastes: Neutral or positively charged molecules are more likely to pass through the glomerulus than those negatively charged
2. Maintenance of water (blood pressure), electrolyte, and acid-base balance
3. Secondary endocrine organ (erythropoietin and calcitriol)
*Dynamics:
PCT:80% of filtrate reabsorbed; active & passive absorption
LoH: 6% of filtrate reabsorbed; site of water and salt retention
DCT: 9% of filtrate reabsorbed; variable reabsorption; active secretion
CD: 4% of filtrate reabsorbed; variable water and salt reabsorption
Urine volume: 1% of total filtrate volume
*Hormonal Regulation:
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Hormone |
Effect |
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Antidiuretic Hormone (ADH) |
↑ H2O reabsorption in CD and DCT ↑ urea reabsorption in CD |
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Aldosterone (ALD) |
↑ Na (H2O follows) & Cl reabsorption in DCT in exchange for K, H in CD |
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Parathyroid Hormone (PTH) |
↑ Ca reabsorption & Pi secretion |
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Calcitriol |
↓ Ca reabsorption & Pi secretion |
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*Renin-angiotensin system: Active in low Na, hypotension, and reduced renal blood flow; Angiotensin II stimulates ADH release |
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II. Renal Pathology |
*When is assessment of renal function considered?
1. S&S suggestive of kidney disease (Hx, low birth weight, old age, low kidney mass…)
2. Monitoring diseases with potential kidney complications (UTI, DM, hypertension…)
3. Dose adjustment (many drugs are renally excreted)
*Why is a given analyte a “kidney function test”?
1. Blood/urine levels are regulated solely or mainly by the kidneys
2. Analyte is a known nephrotoxic
*Renal function tests evaluate either glomerular or tubular function:
1. Glomerular: serum creatinine and BUN
2. Tubular: urine pH – urine specific gravity – urine/plasma osmolality
*Results will not be abnormal, and symptoms will not appear, until 60% of function has been lost.
*Serum Creatinine (Cr):
-Creatinine is produced in the muscle from phosphocreatine (high-energy storage reservoir for ATP)
-Thus, creatinine excretion is closely correlated with muscle mass, which is usually related to body weight, and is greater for men than women after the age of 12
-Serum levels increase after a meat-containing meal
-Basis of diagnosis and staging of acute renal failure
*Creatinine Clearance (CrC) and Glomerular Filtration Rate (GFR):
-GFR:
o The amount of filtrate that flows out of glomeruli in both kidneys per minute (120 mL/min about 180 L/day).
o Not valid at the extremes of age, body mass, in pregnancy, or amputees
o Basis of classification in chronic renal disease – may be normal
o GFR falls with age, so does muscle mass, so creatinine remains the same
-To accurately evaluate glomerular function, the true amount of plasma filtered must be measured.
-To do this, we need to measure the clearance of a substance which is:
o Present in plasma at a constant level
o Freely filtered by glomeruli
o Neither reabsorbed nor secreted by tubules
-Creatinine is that substance. In fact, 10% of filtered Cr comes from tubular secretion, but this is only significant in advanced cases wherein GFR is too low (<10 mL/min) so that the proportion secreted constitutes a larger portion of the overall filtered Cr, in which case the CrC is said to overestimate GFR.
-Creatinine Clearance (CrC) is a better marker than creatinine especially for the aged patient in which the muscle mass is decreased and Cr levels become less reliable.
*Blood Urea Nitrogen (BUN):
-In the liver, amino groups and free ammonia are detoxified by the urea cycle into urea. It is the major excretory product of protein metabolism – highest NPN in blood (45-50%)
-In the kidneys:
§ Readily filtered
§ 40-70% passively diffuse in PCT and CD. This reabsorption depends on urine flow rate and hydration state
§ Accounts for 75% of all NPN excreted
-Urea molecular weight = 60 (28 from N2)
-Blood Urea Nitrogen (BUN): Term based on
historic methods that measured nitrogen in
urea – the real concentration of urea
is BUN x (60/28), or BUN x 2.14
-Alternatively, the nitrogen weight (28) is 46.7% of the urea weight (60). So if BUN = 120 mg/L, over 0.467 = 257 mg/L urea
-Blood levels are affected by renal function, protein intake, and protein catabolism
*Prerenal: Decreased blood flow to the kidneys = less urea filtered + slow urine flow = more absorption + normal Cr, all lead to high ratio
-Increased protein catabolism occurs in stress, fever, major
illness, corticosteroid, and GIT hemorrhage (blood is digested).
*Renal: Low urea + normal Cr = low ratio
*Postrenal: Obstruction of urine flow by calculi, bladder/prostate tumor, or severe infection. High urea + Cr = high ratio
*Serum Uric Acid:
-Principle waste product of purine (A & G) metabolism in the liver
-Excretion:
*Renal (70%): Freely filtered, secreted and reabsorbed continuously and only 6-12% make it out in the urine (98-100% reabsorbed in PCT)
*GIT (30%): Gut bacteria
-Dissolved as monosodium urate, which is relatively insoluble in plasma at pH 7, and so at high concentrations (> 6.8 mg/dL) urate crystals deposit easily in joints and tissue causing painful inflammation (i.e. gout)
-Hyperuricemia:
1. Chronic renal disease - impaired filtration and secretion
2. Hemolytic or megaloblastic anemia
3. Preeclampsia
4. Lactic acidosis - competition for binding sites with lactate
5. High purine intake
6. Increased tissue catabolism due to starvation
9. Proliferative processes
10. Gout
11. Inherited carbohydrate disorders (GSD-I & fructose
intolerance)
12. Lesch-Nyhan syndrome
-Hypouricemia:
1. Severe liver disease
2. Defective tubular reabsorption
Sodium (Na+)
-Main extracellular cation, whose main function is maintaining oncotic pressure.
-Hypernatremia is caused by renal loss of water such as in nephrogenic diabetes insipidus. Serum osmolality and urinary Na differentiate renal from nonrenal loss of water
-Hyponatremia is caused by water retention and salt loss as in acute uremia, renal tubular acidosis (RTA), nephrotic syndrome (edema), and CKD. Hyponatermia is associated with severe polyuria, hyperosmolar urine and high urinary Na except in edema
Potassium (K+)
-Main intracellular cation; 95% in cells, 5% in blood (narrow RR). This is maintained by the Na/K pump
-Hyperkalemia is caused by impaired renal excretion as in acute/chronic renal failure
-Hypokalemia is caused by excessive renal loss as in renal tubular acidosis
Chloride
Hyperchloremia is seen in RTA
Hypochloremia is seen in salt-losing nephritis
Often asociated with hyponatremia
Magnesium
Hypermagensemia is seen in uremia
Hypomagnesemia is seen in acute pancreatitis
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III. Common Kidney Diseases |
*Glomerulonephritis:
-Diffuse inflammation that affects the structure and function of the glomerulus.
-It may result from a wide array of causes (infections “group A strept”, autoimmunity “SLE”…)
-Lab:
1. ↓ GFR (↑Cr)
2. ↑ BUN & Uric acid
3. ↑ BUN/Cr ratio (>20:1)
4. Proteinuria (mild/moderate) & Hematuria (RBC casts highly suggestive) –↓ A/G ratio
5. Hypertension and localized edema (Na and water retention)
6. Metabolic acidosis (retention of Pi, S, AAs, H, and other acids)
7. ↓ Ca (due to loss of albumin) stimulates PTH
8. Anemia and CHF
*In chronic cases:
9. Polyuria (early); Oliguria (late)
10. SG fixed at 1.010 (late)
11. ↓ Na & ↑ K
12. ↓ BUN/Cr ratio (<10:1)
13. Isosthenuria
14. Proteinuria (Massive)
*Nephrotic Syndrome:
-The integrity of basement glomerular membrane and tubular epithelium is compromised resulting in large porous openings
-It appears as an endpoint of previous conditions such as acute/chronic glomerulonephritis, SLE, nephrotoxicity, infections, allograft rejection, diabetic nephropathy, or carcinomas
-The prognosis is usually poor
-Lab:
o Massive edema (Why? – Severe proteinuria = oncotic pressure drop)
o Thrombosis (loss of coagulation factors)
o ↓ Albumin (<3 g/dL) & γ-globulins (immunodeficiency “loss of Abs”)
o ↑ α2 & β-globulins (IDA “transferrin loss”; copper deficiency “ceruloplasmin loss”)
o ↓ A/G ratio
o ↓ Ca & Na
o Oliguria, severe proteinuria (> 3.5 g/day) & Hematuria
o Hyperlipidemia & OFB’s (Why? – 1. loss of albumin stimulates hepatic lipoprotein synthesis 2. loss of LP synthesis regulatory factors = low LPs = high chol.)
*Kidney Stones:
-A stone (i.e. calculus [pl. –li]) is a concretion (hard, solid mass) of precipitated minerals or organic materials. Some chemicals in urine tend to crystallize in a concentrated form and precipitate into a solid deposit attached to the kidney or ureter walls
-Risk: Underlying metabolic conditions (RTA, hyperparathyroidism, and medullary sponge kidney); dehydration; sedentary lifestyle; high Ca, urate, and oxalate; low Mg; low urine SG
-Lead to urinary flow obstruction and muscle spasm (oliguria, hematuria, and pyuria)
-Most pass freely, and some require surgery (renal failure or infection)
-Lab analysis determines the chemical makeup, which is necessary for treatment plans:
o Ca oxalate – Most common type
o Ca phosphate – Hyperparathyroidism and RTA
o Struvite (Magnesium Ammonium Phosphate) – Bacterial UTI
o Uric Acid (radiolucent) – Low pH
-Confirmation: Radiology
-Urine culture to exclude infection (either as a differential cause of the patient's pain, or secondary to the presence of a stone) is always a good idea