Chronic kidney disease drug dosing

Hydralazine may cause a dose-related, reversible lupus-like syndrome, which is more common in slow acetylators. Lupus-like reactions can usually be avoided by using total daily doses of less than 200 mg. Other hydralazine side effects include dermatitis, drug fever, peripheral neuropathy, hepatitis, and vascular headaches. For these reasons, hydralazine has limited usefulness in the treatment of hypertension. However, it may be useful in patients with severe chronic kidney disease and in kidney failure. 

Calcineurin inhibitor nephrotoxicity presents as two distinct forms of renal injury. Acute nephrotoxicity is a dose-dependent, hemodynamically mediated disorder, not accompanied by particular or permanent structural changes which is reversible with decrease or discontinuation of the offending drug. On the other hand, calcineurin inhibitor-induced chronic nephrotoxicity is an insidious lesion, characterized by an irreversible and progressive renal interstitial fibrosis, which may cause important impairment in renal function and even stage 5 chronic kidney disease. 

ACE inhibitors are well tolerated in most patients but are not absent of side effects. ACE inhibitors decrease aldosterone and can increase potassium serum concentrations. Usually the increase in potassium is small, but hyperkalemia is possible. It is seen primarily in patients with chronic kidney disease or diabetes mellitus and in those on concomitant ARBs, nonsteroidal anti-inflammatory drugs, potassium supplements, or potassium-sparing diuretics. Judicious monitoring of potassium and serum creatinine values within 4 weeks of starting or increasing the dose of an ACE inhibitor often can identify these abnormalities before they evolve into more serious complications. 

The GFR remains the single best index of functioning renal mass. As renal mass declines in the presence of age-related loss of nephrons or coexisting disease states such as hypertension or diabetes, there is aprogressive decline in GFR. The GFR can be used to predict the time to onset of ESKD as well as the risk of complications of chronic kidney disease. Furthermore, accurate assessment of GFR in clinical practice allows proper dosing of drugs excreted renally in order to maximize therapeutic efficacy and avoid potential drug toxicity. 

Acute renal insufficiency usually improves with dose reduction, and treatment of contributing illness or the discontinuation of interacting drugs. Chronic kidney disease is usually irreversible, but progressive toxicity may be limited by discontinuation of cyclosporine therapy or dose reduction, with the continuation of other immunosuppressants (e.g., prednisone or azathioprine). 

Cinacalcet is available in 30-, 60-, and 90-mg tablets. Optimal doses have not been defined. The recommended starting dose for treatment of secondary hyperparathyroidism in patients with chronic kidney disease on dialysis is 30 mg once daily, with a maximum of 180 mg/day. For treatment of parathyroid carcinoma, a starting dose of 30 mg twice daily is recommended, with a maximum of 90 mg four times daily. The starting dose is titrated upward every 2 to 4 weeks to maintain the PTH level between 150 and 300 pg/mL (secondary hyperparathyroidism) or to normalize serum calcium (parathyroid carcinoma). The principal adverse event with cinacalcet is hypocalcemia. Thus, the drug should not be used if the initial serum calcium concentration is less than 8.4 mg/dL serum calcium and phosphorus concentrations should be measured within 1 week, and PTH should be measured within 4 weeks after initiating therapy or after changing dosage. 

Patients with anemia secondary to chronic kidney disease are ideal candidates for epoetin alfa therapy. The response in predialysis, peritoneal dialysis, and hemodialysis patients is dependent on the severity of renal failure, erythropoietin dose and route of administration, and iron availability. The subcutaneous route of administration is preferred to the intravenous route because absorption is slower and the amount of drug required is reduced by 20 to 40%. 

Munar MY, Singh H Drug dosing adjustments in patients with chronic kidney disease. Am Fam Physician 2007 75 1487-1496. 

Adefovir dipivoxil (4) was initially developed as a treatment for HIV, but the FDA in 1999 rejected the drug due to concerns about the severity and frequency of kidney toxicity when dosed at 60 or 120 mg, respectively. However, 4 was effective at a much lower dose of 10 mg for the treatment of chronic hepatitis B in adults with evidence of active viral replication and either evidence of persistent elevations in serum alanine aminotransferases (primarily ALT) or histologically active disease. It works by blocking reverse transcriptase, an enzyme that is crucial for the HBV to reproduce in the body. Overall, the efficacy of 4 against wild-type and lamivudine (2)-resistant HBV and the delayed emergence of 4-resistance during monotherapy contribute to the durable safety and efficacy observed in a wide range of chronic hepatitis B patients. ... 

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