Chronic renal failure, drug metabolism

Leblond FA, Giroux L, Villeneuve JP, Pichette V (2000) Decreased in vivo metabolism of drugs in chronic renal failure. Drug Metab Dispos 28 1317-1320... 

The renal clearance can be under estimated in the case of renal drug metabolism. The total drug clearance depends on bioavailability. Therefore, the most reliable estimate for the fraction eliminated by the renal route (fren) is given by the normal clearance (Clnorm) and drug clearance in case of acute and/ or chronic renal failure (Clfail), or from half-lives (Tl/2norm) and (Tl/2fail). 

Diazoxide lowers blood pressure within 3 to 5 minutes after rapid intravenous injection, and its duration of action may be 4 to 12 hours. Interestingly, if diazoxide is either injected slowly or infused its hypotensive action is quite modest. This is believed to be due to a rapid and extensive binding of the drug to plasma proteins. Both the liver and kidney contribute to its metabolism and excretion. The plasma half-life is therefore prolonged in patients with chronic renal failure. 

Pichette V, Leblond FA. Drug metabolism in chronic renal failure. Curr Drug Metab. 2003 4 91-103. 

Recombinant human growth hormone (hGH) is a 22-kDa protein drug having 191 amino acids. It has been used to treat a number of conditions, including short stature in children, Turner syndrome, and chronic renal failure. It is said to play an important role in the metabolism of proteins, carbohydrates, and fats as well as electrolytes and hence influences weight and height. It has been reported that hGH secretion in humans is pulsatile, showing low basal serum levels in between peaks. It has been... 

Nephrogenic Diabetes Insipidus. Failure of the kidney to respond to normal or increased concentrations of AVP can cause NDI. In the majority of these patients, AVP is mcapable of stimulating cychc adenosine monophosphate (cAMP) formation. Two causes have been described for this disorder (1) mutation in the vasopressin receptor and (2) mutations in the aquaporin-2 water channels. Hie vasopressin receptor mutation form of NDI is an X-chromosome-linked disorder that mostly affects males. Females are more likely to have the aquaporin-2 water channel gene defect on chromosome 12,ql2-13, which produces an autosomal recessive disease. Acquired forms of NDI may be caused by metabolic disorders (hypokalemia, hypercalcemia, and amyloidosis), drugs (hthium, demeclocycline, and barbiturates), and renal diseases (polycystic disease and chronic renal failure). NDI may also be seen in the absence of these factors (idiopathic). 

Patterson SE, Cohn VH (1984) Hepatic drug metabolism in rats with experimental chronic renal failure. Biochem Pharmacol 33 711-716... 

The use of potentially nephrotoxic drugs requires close monitoring of renal function. The serum creatinine concentration is the most common method utilized to assess renal function but suffers from its lack of sensitivity. In patients with normal baseline renal function substantial renal injury can occur before there is a demonstrable rise in the serum creatinine concentration. A rise in the serum creatinine concentration that just exceeds the normal range may reflect as much as a 50% dechne in the GFR. The failure of the serum creatinine to accurately reflect the degree of renal injury is particularly evident in patients with decreased muscle mass or those with chronic liver failure. Creatinine is produced from the metabolism of creatine in skeletal muscle. In turn, creatine is derived from the liver. In the setting of chronic liver disease or malnourished patients with decreased muscle mass creatinine synthesis becomes impaired. As a result... 

Metformin is contraindicated in patients with heart failure, renal disease, hypersensitivity to metformin, and acute or chronic metabolic acidosis, including ketoacidosis. The drug is also contraindicated in patients older than 80 years and during pregnancy (Pregnancy Category B) and lactation. 

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