Drug stewardship in chronic kidney disease to achieve effective and safe medication use

Abstract

People living with chronic kidney disease (CKD) often experience multimorbidity and require polypharmacy. Kidney dysfunction can also alter the pharmacokinetics and pharmacodynamics of medications, which can modify their risks and benefits; the extent of these changes is not well understood for all situations or medications. The principle of drug stewardship is aimed at maximizing medication safety and effectiveness in a population of patients through a variety of processes including medication reconciliation, medication selection, dose adjustment, monitoring for effectiveness and safety, and discontinuation (deprescribing) when no longer necessary. This Review is aimed at serving as a resource for achieving optimal drug stewardship for patients with CKD. We describe special considerations for medication use during pregnancy and lactation, during acute illness and in patients with cancer, as well as guidance for the responsible use of over-the-counter drugs, herbal remedies, supplements and sick-day rules. We also highlight inequities in medication access worldwide and suggest policies to improve access to quality and essential medications for all persons with CKD. Further strategies to promote drug stewardship include patient education and engagement, the use of digital health tools, shared decision-making and collaboration within interdisciplinary teams. Throughout, we position the person with CKD at the centre of all drug stewardship efforts.

Figure 1.

Suggested approach to GFR evaluation for drug dosing. While Cystatin-C may not be available in all geographic areas, this algorithm describes the approach to the evaluation of GFR and how it can be applied to drug dosing. *Consider eGFRcys rather than eGFRcr-cys in otherwise healthy populations with decreased creatinine generation due to reduced muscle mass or decreased creatinine secretion or extra-renal elimination due to use of specific medications. ** Use eGFRcr or eGFRcr-cys depending on discordance between eGFRcr and eGFRcys.

Figure 2.

Algorithms proposing decision making process for medications that may carry contraindications in people with CKD. Panel A (upper panel) discusses steps for medications directly related to the management of CKD (e.g., ACE-inhibitors), while Panel B (lower panel) discusses steps for medications prescribed for other indications than CKD (e.g., metformin, antibiotics)

Figure 3.

Selected herbal remedies and dietary supplements with evidence of nephrotoxicy, grouped by continent where case reports come from. From 2024 KDIGO guidelines on CKD screening, detection and management.

Figure 4.

Suggested steps in the process of medication review. From the 2024 KDIGO guidelines on CKD screening, detection, and management

Figure 5.

Impact of acute illness on medication management in CKD. Patients with CKD use chronic therapies to prevent long term morbidity mortality (e.g., hypertension management, diabetes management). When an acute illness occurs, chronic medications may be continued, dose adjusted, or discontinued. New medications which are renally active may be introduced alongside devices to support management of the acute illness. As the patient’s condition stabilises and they transition from acute care to the post-acute care setting, the modifications to their medication program may unintentionally or intentionally persist; The vignette illustrates a case example of a patient with CKD and diabetes, with a history of neuropathy and coronary artery disease that present to the hospital with a myocardial infarction, cardiogenic shock, and type 1 cardiorenal syndrome. Chronic therapies such as RASi, SGLT2i, and loop diuretics would typically be held in favor of acute interventions to stabilise the shock including vasopressor therapy. Reduced GFR would prompt dose adjustment for medications eliminated by kidney like gabapentin to limit oversedation. As the patient’s condition stabilises, therapies like diuretics may be reintroduced to facilitate decongestion. At the point of discharge, drugs may or may not be resumed depending on resolution of ongoing kidney dysfunction, and existence of new comorbidities. There may also be inadvertent medication errors at care transition due to the plethora of changes which occurred as a function of the acute event. Abbreviations: CKD: Chronic kidney disease; RASi: Renin Angiotensin System inhibitor; SGLT2i: Sodium Glucose Co-transporter 2 Inhibitors.

Figure 6.

Essential steps for appropriate sick day rule implementation This figure shows the steps which have to be undertaken correctly by patients for sick day rules to be implemented as intended. Patients need to be able to recognise a dehydrating illness, identify the medication(s) to hold, stop the medication(s), and understand the medication(s) should be restarted after they recover. From the 2024 KDIGO guidelines on CKD screening, detection and management