Tests of Tubular Function

• tubular dysfunction rarely happens on its own through inherited conditions such as cystinurea (inability to acidify urine), often its secondary to other conditions of the kidneys like nephrotoxic drugs (cells lining the tubules are very sensitive especially in the loop of Henley), acute kidney injury (AKI), and decreased glomerular function (increasing urea and creatinine)
• acute tubular necrosis can occur through tubule cells being damages by toxins become concentrated in the tubular fluid causing direct damage or through ischemia reducing blood flow and blood oxygen content supplied from the peritubular capillaries
• renal tubular function does not have a test which can be easy and quantitatively performed and so indirect tests are used to measure the presence of substance in urine which should be reabsorbed by the kidneys such as glucose - glucose in urine is often due to uncontrolled diabetes not tubular dysfunction.
• the ability for a patient to produce a concentrated urine can be tested to measure renal tubular function. other tests load plasma with substance normally excreted by tubule and measured the concentration in urine for example the acid load test.
• most frequently affected function of the tubules is the ability to concentrate urine. to asses tubular function measure the patients urine concentration by osmolarity and compare with their plasma osmolarity
• ADH influences water balance and is essential for water reabsorption. it opens pores in the collecting duct to allow water to move out - ADH present means small volume of concentrated urine
• osmolarity is the number of solute particles per unit weight of water (mmol/kg)
• urine osmolarity is directly proportional to osmotic work done by the kidney therefore is a correct measure of concentrating power
• urine specific gravity (dipstick test) is usually proportional to osmolality but gives increased results if their is glycosurea or proteinurea
• normal urine:plasma is 3:1 when the ratio is less than or equal to 1 it means that renal tubules are not reabsorbing water
• normal urine osmolality is 50-1250mmol/kg depending on how much water has been drunk and or excreted.
• normal plasma osmolality is 250-300mmol/kg
• kidneys lose the ability to concentrate urine at a relatively late stage in CKD, patients with polyurea due to CKD are unable to produce a dilute or concentrated urine due to the lack of functioning loops of Henley meaning that medullary hyperosmolarity is not maintained so ADH mechanism wot work - will still be produced just not work.
• fluid deprivation test or tenacity test is used in an attempt to find the cause of excessive polyuria. it is extremely unpleasant for the patient and requires close supervision as it can be hazardous if there is a severe inability to retain water
• fluid deprivation tests will never be done on individuals who have:

  • CKD - know to expect polyurea so no need to test
  • uncontrolled DM - know why they have polyuria due to the osmotic pull of glucose
  • if urine osmolality is high (>8000mosmol/kg) in an early morning urine as this is adequate evidence of the kidney's concentrating ability
• during the fluid deprivation test the patient is weighed every 2 hours and the test is stopped if weight loss of 3-5% occurs or if >3L of urine is passed. test is stopped if excess fluid loss occurs
• the fluid deprivation test involves complete fluid deprivation over a 24hr period usually starting at 10pm with blo0od and urine samples taken from 8am-3pm the next day and measured for osmolality
• normally there is no increase in plasma osmolality (kidneys respond normally osmolality will be 800mmol/kg), whereas urine osmolality rises to 800mosmol/kg or higher. if rising plasma osmolality is seen it means that their is either a failure to secrete ADH or a failure to respond to ADH at a distal nephron within the collecting duct
• rising plasma osmolality within the fluid deprivation test rewuires a DDAVP test to be perfomed
• DDAVP test starts at the end of the fluid deprivation test where the patient is allowed a moderate amount of water to drink. an injection of synthetic analogue of AVP (DDAVP) is administered and urine samples are collected hourly for 3 hours with osmolality being measured.
• DDAVP test helps distinguish between hypothalamic-pituitary, psychogenic, and renal causes of polyurea
• patients with diabetes insipidus of a hypothalamic-pituitary origin produce insufficient vasopressin (ADH). therefore the respond to DDAVP test but not the fluid deprivation test.
• typical osmolality results for diabetes insipidus individuals are

  • fluid-deprivation test : plasma >300mmol/kg and urine 200-400mmol/kg
  • DDAVP test : urine >700mmol/kg
• patients with psychogenic diabetes insipidus should respond normally to both tests as they just drink a lot of water
• patients with polyurea of renal origin fail to respond to both tests so urine osmolality is <400mmol/kg and plasma osmolality increases after fluid deprivation. this is due to their tubules being unable to respond normally to ADH due to poor medullary osmotic gradient.
• metabolic acidosis is where the pH of blood and ECF is higher than expected and can be caused by chronic renal failure, uncontrolled diabetic ketoacidosis, salicylic poisoning
• if the patient has persistent unexplained metabolic acidosis it could be due to renal tubular acidosis as a result of diminished tubular secretion of hydrogen ions in to the renal tubule
• urine is normally acidic if it alkaline it could be due to a vegan diet (generally less acid from diet) or UTI (bacteria use urease to break down urea into ammonia which readily gives up its hydrogen ion)
• acid load test is a test that measures the amount of acid in the urine. the patient begins the test by orally taking ammonium chloride within a gelatin capsule and their urine samples are then collected for 8hrs
• with normal renal function the pH of at least 1 sample should be pH <5.3 if not it can be due to:

  1. type I distal renal tubular acidosis
  2. type II proximal renal tubular acidosis
• type I distal renal tubular acidosis is the inability to maintain hydrogen ion gradient across distal tubule and collecting ducts. it is usually inherited , but can be acquired. patients urine rarely falls below pH6
• type II proximal renal tubular acidosis is caused by a decreased capacity to reabsorb bicarbonate ions in the proximal tubule. (could be due to Fanconis' syndrome) the bicarbonate ion is the main buffer in plasma so a decrease causes a metabolic acidosis in blood stream. their urine pH may fall below pH 5.3 in the test and so require an assessment of their renal threshold for bicarbonate.
• specific proteinurea indicated tubular dysfunction and is an abnormal presence of small proteins in a patients urine - specifically beta 2 and alpha 1 microglobulin which are small proteins that are filtered at the glomeruli and usually reabsorbed by tubular cells. the increase in urine concentration indicates renal tubular cell damage.
• aminoacidurea is when amino acids are present in the urine in excessive amounts when they should be fully reabsorbed in proximal tubules
• aminoacidurea can be caused by :

  1. [plasma] exceeded renal threshold - occurs in PKU and inherited condition
  2. acquired damage/failure of proximal tubules - most common cause
  3. failure of specific reabsorptive mechanism in the proximal convulated tubules (rare) - such as cystinurea a hereditary condition
• fanconis syndrome is where there are multiple defects of tubular functions particularly within the convoluted tubules. this can be inherited as seen in cystinosis or secondary to other disorders such as heavy metal poisoning or multiple myeloma (cancerous condition)
• fanconis syndrome causes an excessive urinary loss of amino acids phosphate glucose and sometimes bicarbonate ions
• renal stones are more common in hot climates as dehydration causes an increase in the concentration of urine
• renal stone or calculus causes severe pain and discomfort and is common cause of obstruction in the urinary tract. it consists of material that has came out of solution and precipitated in the kidney, urethra, or bladder
• seeding process of renal; stones is the process in which layering occurs and the stones gradually get larger - it can be triggered by debris and bacteria in urine