Drug dosing consideration in patients with acute and chronic kidney disease—a clinical update from Kidney Disease: Improving Global Outcomes (KDIGO)

Abstract

Drug dosage adjustment for patients with acute or chronic kidney disease is an accepted standard of practice. The challenge is how to accurately estimate a patient's kidney function in both acute and chronic kidney disease and determine the influence of renal replacement therapies on drug disposition. Kidney Disease: Improving Global Outcomes (KDIGO) held a conference to investigate these issues and propose recommendations for practitioners, researchers, and those involved in the drug development and regulatory arenas. The conference attendees discussed the major challenges facing drug dosage adjustment for patients with kidney disease. In particular, although glomerular filtration rate is the metric used to guide dose adjustment, kidney disease does affect nonrenal clearances, and this is not adequately considered in most pharmacokinetic studies. There are also inadequate studies in patients receiving all forms of renal replacement therapy and in the pediatric population. The conference generated 37 recommendations for clinical practice, 32 recommendations for future research directions, and 24 recommendations for regulatory agencies (US Food and Drug Administration and European Medicines Agency) to enhance the quality of pharmacokinetic and pharmacodynamic information available to clinicians. The KDIGO Conference highlighted the gaps and focused on crafting paths to the future that will stimulate research and improve the global outcomes of patients with acute and chronic kidney disease.

Adaptation posologique des médicaments et fonction rénale : quel(s) estimateur(s) faut-il choisir ?

“…Ceci pourrait aboutir notamment à une sous-exposition au mé dicament chez le sujet obè se et à une surexposition chez le sujet trè s maigre. L'utilisation de DFG non indexé est d'ailleurs recommandé e par les KDIGO [11,26], mais aussi par la FDA [7] et l'EMA [6]. Un consensus assez large semble donc se dé gager en faveur de l'utilisation d'une valeur de DFG non indexé e pour l'adaptation posologique.…”

“…Cependant, les autres estimateurs comme les formules MDRD ou CKD-EPI donnent un ré sultat où l'indexation à la SC est inté gré e [14,21,27]. Cela implique donc que l'on « dé sindexe » les ré sultats obtenus par la valeur de SC individuelle [11,26]. Cette procé dure de dé sindexation est en soi discutable et ne pourrait être mathé matiquement valable que pour les SC retrouvé es dans les cohortes qui ont servi au dé veloppement de ces diffé rentes formules [21].…”

“…Les moindres performances de la formule de Cockcroft, auxquelles s'ajoutent des problé matiques analytiques spé cifiques lié es à l'absence de ré é valuation de cette formule avec les nouveaux dosages de cré atinine (voir infra) expliquent que cette formule n'a plus sa place dans les recommandations pour l'estimation du DFG au cours de la MRC. Malgré cela, il persiste indiscutablement un dé bat sur l'utilité de cette formule dans le champ spé cifique de l'adaptation posologique, notamment au sein de la communauté pharmacologique [2,26,33,45,46]. En effet, tout d'abord, il faut bien constater le poids historique indé niable de l'é quation de Cockcroft.…”

Prescribing of anticancer drugs in renal impairment: why can’t we do better?

“…According to the KDIGO (Kidney Disease: Improving Global Outcomes) clinical practice recommendation, physicians should adjust drug dosages primarily according to the approved product labeling; where there is no information in the product label, peer-reviewed literature recommendations should be used (Matzke et al 2011). …”

“…Reliable information on posology adjustments is also the basis for integration into emerging health information technologies, such as electronic clinical decision support systems, which are expected to improve drug prescribing quality, particularly in patients with kidney disease. In 2010, the KDIGO conference brought together 50 experts, including representatives from the EMA and FDA, to propose recommendations for research and regulatory authorities, which remain valid: rigorously conducted renal impairment studies are needed and drug labeling should be improved (Matzke et al 2011). It might be time to take action.…”