Renal Function Flashcards
Kidney Function
pH balance
Urea excretion
Erythropoietin production
Vitamin D metabolism
Aldosterone
When sodium levels or BP decreases, renin is secreted from juxtaglomerular cells.
Renin causes a cascade of events that eventually causes release of aldosterone from adrenal cortex.
Aldosterone increases sodium reabsorption by increasing sodium chamels.
Vasopressin (ADH)
Released from posterior pituitary to increase water permeability & reabsorption.
Inserts aquaporin-2 water channels in luminal membrane of collecting duct cells.
Glomerular Filtration Rate
Assesses how well glomerulus filters waste products.
Measure serum creatinine levels to calculate GFR.
Creatinine is a waste product formed from muscle activity.
[Creatinine] (pmol/mI) × Urine flow (ml/min) ÷ [Creatinine in plasma] (pmol/mI)
Plasma creatinine concentration is influenced by muscle mass, resulting in lower levels in children, pregnancy and individuals with wasting diseases. Also increased by high meat intake & exercise.
Urine collection
GFR measurement involves collecting urine every twenty-four hours, at the same time every day.
While this method is inexpensive, noninvasive, and can be done by patients themselves, errors such as missed samples, overhydration, or dehydration can significantly affect accuracy.
Additionally, GFR estimations using creatinine levels, which are relatively stable over time, are not always precise.
Measuring GFR
GFR is a more sensitive indicator of early renal damage as it changes significantly before plasma creatinine levels.
However, plasma creatinine measurement is more precise, easier to perform, and adequate for monitoring renal disease progression or detecting rejection after kidney transplantation.
Causes of elevated creatinine
Elevated plasma creatinine can result from impaired renal perfusion (due to low blood pressure, reduced blood volume, or renal artery narrowing), loss of functioning nephrons (e.g., glomerulonephritis, linked to antibody-mediated damage or the accumulation of immune complexes in the glomeruli), or increased pressure in the nephron from obstructions like prostatic enlargement or kidney.
Urea measurement
Urea is the final breakdown product of amino acids, formed in the liver when nitrogen from ammonia combines with other chemicals.
Kidneys normally filter 90% of urea produced, so this acts as a biomarker for kidney and liver function.
Levels typically range from 2.5 to 6.6 mmol/L.
Elevated plasma urea levels indicate reduced kidney perfusion, kidney disease, or urinary obstruction, as these conditions cause impairment of kidney function, leading to accumulation of urea in blood.
High protein intake or increased protein breakdown can raise plasma urea without affecting the kidneys, while liver failure, low protein intake, or water retention can lower urea levels.
Proximal tubule
The proximal tubules of the kidneys reabsorb filtered glucose, an essential energy source stored as glycogen when in excess.
Glucosuria is when urine contains glucose.
If blood glucose levels are normal, but there is glucose in urine, it indicates proximal tubular dysfunction.
If blood glucose levels are elevated and there is glucose in urine, it indicates diabetes mellitus.
In type 1 diabetes, a lack of insulin prevents glucose storage as glycogen, while in type 2 diabetes, insulin resistance leads to excess glucose in the blood.
This glucose reaches the kidneys, where it can be detected through dipstick tests.
Chronic high glucose levels can damage the glomerulus and nephrons, increasing blood viscosity and impairing kidney filtration.
This can result in toxin and waste accumulation, raising the risk of renal complications, particularly in individuals with insulin resistance.
Distal tubular function (specific gravity)
Distal tubular function is assessed through urine concentration tests, primarily measuring specific gravity (SG) and osmolality.
SG compares the mass of 1 ml of urine to 1 ml of water, while osmolality reflects the number of solute particles per kilogram, typically 285 mmol/kg in serum.
Normal early morning values include an osmolality >800 mmol/kg and SG >1.02. Deviations from these values may indicate distal tubular dysfunction.
However, SG is less reliable in cases of proteinuria, as high protein concentrations significantly affect urine density, reducing their diagnostic value.
Distal tubular function (osmolality)
Distal tubular function is evaluated using tests such as injecting a synthetic vasopressin analogue and measuring urine osmolality hourly for three hours.
Normally, osmolality increases due to enhanced water reabsorption driven by aquaporin expression in the distal tubules, leading to more concentrated urine.
Dysfunction in the distal tubules impairs the kidney’s ability to dilute the filtrate and reabsorb water effectively.
Additionally, distal tubular function can be assessed by monitoring the kidney’s ability to maintain pH balance, as an excess of protons in the urine may indicate tubular dysfunction.
Albumin for renal function
Protein in urine is physiologically harmful but serves as a key indicator of kidney dysfunction.
Albumin, a large protein (60 kDa), should not pass through the glomerular filter due to its size.
If it does, it is typically reabsorbed, as producing albumin requires significant energy.
Microalbuminuria (30–300 mg/24h) is where small amounts of albumin are found in urine, often detected with immunoassay sticks.
It is associated with diabetic nephropathy, where high blood glucose damages kidney nephrons, causing glomerular slits to lose structure and become porous, allowing albumin leakage.
Macroalbuminuria (>300 mg/24h) suggests severe nephron damage, commonly seen in uncontrolled type 2 diabetes.
It is detected using colorimetric dipsticks, where specific antibodies bind to albumin for measurement.
Dipsticks for urine tests
Urine dipsticks are basic, cost-effective diagnostic tools used to detect pathological conditions in urine.
They typically consist of up to 10 chemical pads or reagents that react to substances in the urine when immersed.
The test is qualitative, providing positive or negative results rather than precise concentrations.
The intensity or density of the colour change corresponds approximately to the concentration of the substance being tested.
Acute Kidney Injury (AKI)
Acute Kidney Injury (AKI) is a rapid onset of kidney failure or damage that occurs within a few hours or days, leading to the retention of urea, creatinine, and hydrogen ions.
It is often characterized by oliguria (low urine output of <400 ml/24h in adults) and hyperkalemia (increased plasma potassium levels).
AKI causes a build-up of waste products in the blood and disrupts the kidneys’ ability to maintain fluid balance.
It is common among hospitalized patients, particularly the elderly and critically ill.
Uncomplicated AKI has a mortality rate of 5-10%, but more severe cases require immediate medical attention.
Dialysis becomes necessary in end-stage kidney failure when kidney function declines to less than 15%, as it helps remove waste, salt, and excess water to maintain body balance.
Markers for AKI
Markers for AKI are important for early detection to reduce mortality.
Plasma creatinine levels can be delayed, so significant damage may occur before it’s detected.
Neutrophil gelatinase-associated lipocalin (NGAL) is a promising marker, as it is released into the urine within 2 hours of ischemic or nephrotoxic kidney damage.
Specific cut-offs for creatinine concentrations and urine output help determine kidney function stage.
