Renal Function & Renal Failure

• Kidney Functions include:

  1. Regulation of blood pressure
  2. Regulation of RBC production through the release of erythropoietin 
  3. Regulation of bone-mineral-metabolism
  4. Excretion of metabolic waste products and water
  5. Influence blood pH and acid-base metabolism.
• Kidney dysfunctions can be glomerular or tubular in source and primary (polycystic kidneys, tumors) or more commonly secondary (high blood pressure, diabetes) in origin
• Glomerular dysfunctions occur through selective impairment of glomerular function - filtration of blood
• Tubular dysfunction occurs through the impairment of one or more tubular functions - tubular reabsorption, tubular secretion
• Kidneys regulate extracellular fluid (ECF) volume and electrolyte composition to compensate for daily variations in water and food intake
• Kidneys form urine - where potentially toxic waste products of metabolism are excreted e.g. urea, hydrogen ions and drug metabolites
• Kidneys are endocrine organs which produce several hormones e.g. erythropoietin (produces RBC), calcitriol (produces calcium), renin (controls blood pressure)
• Kidneys are subject to control by other hormones such as Antidiuretic hormone (ADH - controls water balance), aldosterone (increases sodium reabsorption and potassium secretion), and parathyroid hormone (maintains calcium balance)
• Diagram of kidney

  A) Capsule

  B) Cortex

  C) Medulla

  
• Filtration occurs at the glomerulus where the proximal tubule collects filtrate from the blood by size water can go through but protein platelets and cells will remain.
• Reabsorption then occurs reclaiming glucose, sodium, and amino acids back into the blood.
• Secretion of toxins and excess ions (urea, hydrogen ions and potassium ions) into the distal tubule
• Glomerular Filtration rate (GFR) is how much filtrate is produced in a given time and is an important measure of glomerular function. GFR is directly related to body size so males normally have a higher GFR than females. Normal GFR is approximately between 120-140ml/min but depends on normal renal blood flow and pressure (no clogs etc.)
• GFR normally declines by roughly 10% per decade after 35, due to the loss of functional nephrons so can provide an index of the number of functioning glomeruli and estimate the degree of renal impairment.
• GFR = the maximum rate at which plasma can be cleared of any substance into urine. Accurate measurement requires determination of con. in plasma and urine of a substance filtered at the glomerulus, but not reabsorbed or secreted by the tubules - the con. of plasma must remain constant throughout urine collection.
• GFR measurement:

  U - urinary con. (mmol/l)

  V - vol. urine (l/24hr)

  P - [plasma] of substance
• GFR measurement:

  U - urinary con. (mmol/l)

  V - vol. urine (l/24hr)

  P - [plasma] of substance

  $Clearance =$$UV/P =$$mlmin^-1$
• Clearance is the vol. of plasma which would have to be completely "cleared" of the substance in the time specified to give the amount seen in urine
• Creatinine is a waste product of metabolism in muscle tissue and is excreted by the kidneys.
• Muscle mass doesn't normally change much so levels of creatinine in the blood in any individual are normally steady making it good to measure for clearance.
• Creatinine clearance = the volume of plasma that is cleared of creatine per unit of time. This is a standard practice test although it does give a slightly higher GFR than the patient has as small amounts of creatinine are secreted by the renal tubule - this is only a problem if renal failure becomes severe as the overestimation of creatinine is due to a large proportion of excreted creatinine derived from secretion
• Sampling often requires a 24hr collection time (less can underestimate the true GFR) and first urine should be discarded as bladder should be empty when sampling starts
• plasma is produced if an anti-coagulant is present in the blood collection tube, serum is when the blood has clotted in the tube (plasma-fibrinogen)
• Plasma/serum [creatinine] and [urea] both are nitrogenous waste materials that can be used to measure glomerular function however this is a more insensitive test. - GFR must fall to roughly half the normal value before a significant increase in serum [creatinine] will be apparent therefore normal levels in this test don't mean an absence of disease.
• plasma creatinine and urine tests are useful as they don't decline with age
• A progressive rise (2 or 3 times per week or increased rise within months) in plasma [creatinine] indicates declining renal function so good for monitoring an individual.
• plasma [creatinine] is lower in women and lower in children or those with lower muscle mass. And increases after vigorous exercise
• Estimated GFR (eGFR) is now used instead of creatinine clearance and the formulae are based on plasma [creatinine], age, sex, weight and various demographics - often use the Cockcroft and gault equation.
• urea is a nitrogenous waste material filtered at the glomeruli, therefore plasma [urea] is an inferior test as 50% or more are reabsorbed through tubules - so con. increases at low urine flow rates (dehydration) and with blood loss
• plasma [urine] is affected by dietary protein intake (increases with more protein) as well as GI bleeding (ulcer etc). patients have low plasma [urine] due to anorexia, malabsorption of nutrients and liver failure (cirrhosis)
• patients with high plasma [urine] (uraemia) are indicated to have pre-renal, renal, and post-renal disease
• proteinuria is the abnormal presence of protein in urine in excess of 2000mg/day (normal levels are <25mg/day) and indicative of damage to the glomerular membrane (glomerular disfunction). it is measured using a dipstick test which is not the most sensitive but does pick up when large damage has occured
• albumin is a relatively small protein and when found in urine (microalbuminuria) indicate slight glomerular dysfunction. When immunoglobulins are found they indicate severe glomerular dysfunction
• Nephrotic syndrome is the loss of very large amounts of protein in the urine (severe proteinuria) with the glomerular damage allowing the loss of 2-30g/day of protein
• the main protein loss in nephrotic syndrome is albumin (the main plasma protein) which leads to hypoalbuminemia, oedema (swelling in tissues) and secondary hyperaldosteronism.
• the cause of nephrotic syndrome include glomerulonephritis (inflammation of glomeruli), SLE (systemic lupus erythematosus), and diabetic nephropathy
• renal failure is the cessation of kidney function - can be either acute or chronic
• acute kidney injury (AKI) is when your kidneys fail over a period of hours or days, there are many causes of this but it is reversible and can be treated
• chronic kidney disease (CKD) develops over months/years and eventually leads to end stage kidney disease (ESKD) - it is irreversible. CKD can also be called chronic renal failure (CRF) in long term patients
• AKI can arise form various problems affecting the kidney and or their circulation - must keep perfusion (passage of fluid to an organ/tissue though he blood or lymphatic system)