Describe the structure of a nephron
- The glomerulus: where happens the filtration
- Different tubules and collecting ducts: where urine is secreted
o Proximal tubule
o Loop of Henle
o Distal tubule
o Collecting ducts
Which characteristics are important to undergo renal excretion?
- ionized forma at physiological pH
- Low lipid solubility
Which compounds are eliminated through glomerular filtration and why?
Water, electrolytes and other endogenous compound are excreted in this way. The limit in term of molecular weight is 66000 in order to avoid the elimination of proteins
Which transporters are necessary for the tubula excretion?
ABC drug transporters (P-gp and MRP).
SLC drug transporters (OAT, OCT, MATE) -> minor role
What is a victim drug?
A drug administered at the same time of another one with a higher affinity to the transporters. It’s no longer able to be excreted so it remain in the blood and may create toxicity
Give some examples of drugs that undergo tubular excretion
- Antidiabetic drug metformin
- Antineoplastic drug methotrexate
- Weak acid (penicillin, salicylates, phenobarbital, glucoronoconjugates and sulphoconjugates
- Weak basis (morphine)
Despite glomerular filtration and tubular secretion, the renal clearance of a xenobiotic may be relatively low, why?
due to the occurrence of important reabsorption mechanisms:
- Active or facilitated reabsorption, occurs in proximal tubules and involves in almost all cases electrolytes (Na+/K+), sugars, aminoacids, lactate, vitamins…
- Passive reabsorption: mainly occurs in both distal tubules and collecting ducts, according to chemical lipophilicity, pKa and urinary pH, etc.
Which factors affect renal clearance?
- Higher plasma concentration, higher renal clearance
- The more a given compound is lipophilic, the more it is excreted
- The extent of plasma protein binding: if they’re bound, they’re excreted in a longer time.
This is less important for drug excreted through tubular excretion - The extent of drug ionization, Pka and pH.
The pH of urine depends on the diet, omnivorous and carnivorous have urine with pH around 5.5-6.5, herbivores (and probably vegans) have a pH around 7-8. Weak acids are best reabsorbed in animals with acid urine, and weak bases are normally absorbed better in a basic environment. - Renal diseases: the associated reduction in the rate of glomerular filtration and tubular secretion will prolong the body persistence of drugs. Adjustments in drug dosages is necessary.
Definition of renal clearance
Renal clearance is the volume of plasma completely cleared by the kidneys via the urine per unit of time.
