Medication Safety Principles and Practice in CKD : Clinical Journal of the American Society of Nephrology

Journal Logo

Nephropharmacology for the Clinician

Medication Safety Principles and Practice in CKD

Whittaker, Chanel F.1; Miklich, Margaret A.2; Patel, Roshni S.3; Fink, Jeffrey C.4

Author Information
Clinical Journal of the American Society of Nephrology 13(11):p 1738-1746, November 2018. | DOI: 10.2215/CJN.00580118
  • Open



Moliere, the 17th century playwright wrote, “Nearly all men die of their remedies, and not of their illnesses.” Many therapeutic drugs used as remedies are kidney-relevant, meaning they require clearance or metabolism by the kidney or have potential for nephrotoxicity (1,2). One important barrier to medication safety is CKD is often under-recognized (3,4). Failure to recognize patients with CKD is a lost opportunity to minimize patient safety threats related to medications. A study alerting providers of medication orders requiring modifications because of impaired kidney function revealed 14% of all orders were for kidney-relevant medications (5). Of these, about 15% were flagged with an initial prescription error. Others have found a higher proportion of medication orders with potential nephrotoxicity, or orders not properly modified for kidney function, which are therefore associated with high risk of adverse events for both kidney-relevant and nonkidney-relevant medications in CKD (6,7).

Adverse medication-related outcomes in CKD can be classified as those leading to kidney damage, including AKI, accelerated kidney function loss, and ESKD, as well as other metabolic complications, including hyperkalemia, hypercalcemia, hypoglycemia, and bleeding, among others (8). Omitted therapies, such as failure to initiate erythropoiesis-stimulating agents (ESAs) for severe anemia, can also be considered safety events. A substantial proportion of the burden of illness in patients with CKD relates to such safety complications, and may be prevented with improved attention to this population’s special care needs.

Safe medication use in CKD is a complex process involving determination of kidney function, consideration of changes in drug pharmacokinetics (PK) and pharmacodynamics (PD) as kidney function declines, and judicious use of therapies to manage uremic complications and other comorbid conditions (9).

The US Food and Drug Administration (FDA) guidance for dosing recommendations accounting for kidney function were not issued until 1998. Although initial FDA guidance called for direct measurement of GFR using a tracer such as iothalamate, the 2000s witnessed the validation and implementation of estimating equations to assess kidney function (9). Yet, estimates of kidney function on the basis of creatinine clearance (e.g., the Cockcroft–Gault equation) and GFR (e.g., the CKD Epidemiology Collaboration equation) can differ substantially from direct measurement of kidney function. These discrepancies can lead to misguided dosing recommendations for certain drugs (10). However, direct measurement of kidney function is often not practical; hence, a Kidney Disease Improving Global Outcomes (KDIGO) consensus panel recommended that clinicians’ refer to a valid equation for determination of eGFR (9). Dosing adjustments should be made on the basis of clinically observed drug response and toxicity, as well as drug levels, when measurable.

Altered drug PK/PD profiles in CKD may warrant modified dosing or drug discontinuation (8,9,11). Drug absorption in the gastrointestinal (GI) tract may be impaired by medications that alter gastric pH (e.g., proton pump inhibitors) and comorbid conditions that cause edema (e.g., congestive heart failure [CHF]) or GI losses common in CKD (e.g., diarrhea) (11). The volume of distribution of water-soluble drugs may also be increased in the setting of edema. Uremia in CKD can also alter the volume of distribution of plasma/tissue protein-bound drugs, which can significantly affect therapeutic and safety outcomes of narrow therapeutic range medications (e.g., digoxin) (11). Changes in hepatic or nonrenal clearance of commonly used medications, such as antibiotics and antihypertensives, have also been observed in CKD (12). All mechanisms of kidney excretion are impaired in CKD, including glomerular filtration, tubular secretion, and reabsorption (11). Progressive decline in kidney function results in changes in clearance, therapeutic effect, and risk of toxicity of many drugs eliminated through the kidneys.

Medication Safety in CKD and Related Complications

In addition to a medication’s nephrotoxic effects, patients with CKD are also susceptible to other adverse effects with agents routinely used in the management of CKD and comorbid conditions. Examples include anticholinergic (e.g., histamine-1 receptor antagonists), sedative (e.g., codeine, diazepam), and hypoglycemic (e.g., glyburide) effects, as well as electrolyte abnormalities (e.g., renin-angiotensin-aldosterone system [RAAS] blockers, sulfamethoxazole-trimethoprim, mineralocorticoid receptor antagonists, calcium- and magnesium-containing antacids). Agents with particular pertinence to patients with CKD are discussed below.


Thiazide and loop diuretics are commonly used for natriuresis and BP control with a reduced GFR. This is especially important in advanced CKD, where extracellular volume excess is a concern and BP becomes more salt-sensitive. Loop diuretics are the preferred agents at GFR<30 ml/min per 1.73 m2, but more potent thiazide diuretics also can be used, often in combination with loop diuretics. Injudicious diuretic use can increase the risk of AKI in vulnerable patients with CHF, ascites, or other edematous states, especially with superimposed volume depletion (13). Loop and thiazide diuretics are also associated with a range of electrolyte disturbances, including hypokalemia, hypomagnesemia, and hypochloremic metabolic alkalosis (14,15). Additional metabolic derangements include hyperuricemia, and at higher doses of thiazide diuretics, glucose intolerance and hyperlipidemia (13).

RAAS Blockers as a Double-Edged Sword

RAAS blockers are essential to CKD treatment and although not overtly nephrotoxic, under certain clinical circumstances they have the potential for harm (16). Practitioners may construe physiologic reductions in GFR with RAAS blockers as justification to avoid these agents with advanced CKD; however, RAAS blockers have demonstrated benefit in early as well as later stages of CKD (17). Hazards from RAAS blockers are most prominent in conditions where the kidney is autoregulation-dependent, including CHF, active diuresis, and other illnesses with attendant volume depletion (16).

Hypotension with RAAS blockers is common among elderly patients, and episodes of AKI across the range of severity are not infrequent among nursing home patients treated with RAAS blockers (16,18). AKI is also more common with treatment with RAAS blockers during high summer temperatures and with volume depletion, and can also occur with bilateral renal artery stenosis or unilateral stenosis with a solitary kidney (19). Patients with CHF on angiotensin-converting enzyme inhibitors develop a greater rate of AKI with intensified diuretic regimens than their counterparts on lower doses or no diuretics (20). Adding a nonsteroidal anti-inflammatory drug (NSAID) to an RAAS blocker and diuretic can amplify the risk of AKI, and has been described as a “triple whammy.” (21) Similar conditions may increase the risk of AKI when more than one RAAS blocker are used together, or in combination with sodium-glucose cotransporter 2 in patients with CKD and diabetes (22,23). An increase in AKI admissions have been reported and correspond with a rise in RAAS blocker prescriptions across geographic regions. AKI admissions increased as much as 15% because of an increase in RAAS blocker prescriptions (24).


Hyperkalemia and hypokalemia are common safety concerns for patients with CKD because they can lead to altered cardiac electro-conduction, arrhythmias, and sudden death (25–30). Hyperkalemia can occur with RAAS blocker use, especially when two are used in combination, or with other drugs including potassium-sparing diuretics, NSAIDs, or trimethoprim-sulfamethoxazole (31). Less commonly, heparin can cause hyperkalemia in the setting of AKI, or when used with other agents that increase the risk of hyperkalemia (32). It is also important to note that hypokalemia can develop with unsupervised diuretic use (33).

Several tactics in response to hyperkalemia can shift potassium from the extracellular to intracellular space (e.g., insulin and glucose, β-agonist therapy, and bicarbonate in the setting of acidosis), but definitive therapies remove total body potassium. These treatments includes diuresis, which may have limited effectiveness and the potential for metabolic or hemodynamic complications. Cation exchange resins, such as sodium polystyrene sulfate, have limited evidence for efficacy in potassium removal, and have associated concerns for toxic effects including bowel necrosis (34). However, this complication is uncommon, with unclear linkage to oral versus rectal administration (35). The cation exchange resin patiromer has introduced an alternative for chronic treatment of hyperkalemia, and can be used in conjunction with RAAS blockers (36). However, patiromer has been associated with hypomagnesemia and altered absorption of some common drugs (37). Mineralocorticoid agonists may have modest effectiveness in reducing serum potassium, especially in hyperkalemic patients on dialysis (38). Dialysis remains the gold standard for potassium removal, but should be used sparingly, except for patients with ESKD (25). Treatment and prevention of hypokalemia includes reduction in diuretic use, sodium restriction, and liberalization of patients’ diets to include potassium-rich foods. Consideration of potassium-sparing diuretics and RAAS blockers, where appropriate, should also be considered (33).

Treatments for Anemia in CKD

Anemia management in CKD is a balance between optimizing erythropoiesis and minimizing adverse effects associated with therapeutic agents that treat anemia (39,40). Use of ESAs along with iron supplementation to treat anemia are important elements in CKD care (40). Despite extensive experience with these agents, many questions remain regarding optimal and safe therapeutic end points (39–41).

Iron supplementation (oral or intravenous) is usually the first step in anemia management (40,42). However, oral iron use is often limited because of suboptimal efficacy and GI intolerance (43,44). Intravenous iron is more efficacious at correcting iron deficiency, improving hemoglobin levels, and reducing ESA use and blood transfusions, but is often underutilized because of clinician apprehension of infusion-related reactions and iron overload (42,43). Anaphylaxis most commonly occurs with high molecular weight iron dextran, whereas severe or life-threatening reactions are rare with nondextran formulations, such as iron sucrose and sodium ferric gluconate complex (42,45). Commentaries have postulated that aggressive iron supplementation and overload in conjunction with ESA use may increase the risk of safety events (46). The upper limits of iron stores is clinically undefined, but studies suggest that adverse effects related to iron overload are not likely to occur at ferritin levels below 1200–2000 ng/ml (42,45). However, the KDIGO guidelines take a conservative stance with regard to upper limits of iron stores, and do not recommend routine use of iron supplementation when transferrin saturation and ferritin levels are adequate (40).

Controversy continues over appropriate ESA use, and there are safety concerns about optimal treatment targets in CKD (47–50). Generally, trials evaluating aggressive treatment targets with epoetin alfa have been successful at achieving hemoglobin targets, but demonstrate a higher rate of arteriovenous fistula thrombosis, myocardial infarction, death, and CHF-related hospitalizations. Comparable results have been reported with darbepoetin alfa (48). Apart from a modest improvement in quality of life with higher hemoglobin targets, aggressive treatment has been associated with an increased risk of stroke, venous thromboembolism, and death in patients with an active malignancy (40). Hence, the benefits of targeting higher hemoglobin levels with ESAs are limited by significant toxicity signals (50,51). As part of best practices identified by the American Society of Nephrology’s “Choosing Wisely” campaign, an individualized patient approach to ESA use is recommended to alleviate symptoms while maintaining conservative hemoglobin targets and minimizing the need for transfusions (52). Specifically, ESAs should be avoided in asymptomatic patients who are predialysis, with hemoglobin levels >10 g/dl. When treatment is warranted, ESAs should be used judiciously, along with close monitoring of hemoglobin and anemia symptoms.

Treatments for CKD–Mineral and Bone Disorder

CKD–mineral and bone disorder (CKD–MBD) is a complex condition characterized by phosphate, calcium, vitamin D, and parathyroid hormone (PTH) abnormalities (53). Pharmacotherapeutic interventions have primarily focused on correcting laboratory disturbances with the intent of reducing long-term complications. Paradoxically, drug therapy for CKD–MBD has the potential to accelerate disease progression if not used appropriately.

Maintaining phosphorus and calcium homeostasis in CKD is associated with decreased kidney and cardiovascular risk (54). Phosphate binders are the recommended first-line therapy in CKD to correct hyperphosphatemia (55). However, binders do not significantly improve phosphorus levels or delay the progression of coronary artery calcification in the predialysis CKD population (56–59). The updated 2017 KDIGO guidelines de-emphasize targeting precise calcium and phosphate levels, but endorse the initiation and adjustment of therapy on the basis of “persistent and progressively” abnormal individual levels in the context of overall trends in CKD–MBD biomarkers (55,57).

Noncalcium-based binders may have less effect on calcium balance and cardiovascular endpoints (60). Specifically, novel iron-based phosphate binders are effective alternatives to managing hyperphosphatemia and minimizing risk of hypercalcemia, and have an added benefit of improving iron stores (61). When cost limits choice to calcium-based binders, the dosing should be tailored to the individual patient’s dietary calcium intake to maintain a neutral calcium balance (59). Calcium-containing binders should be considered primarily in patients with CKD with low calcium intake. Calcium-based products should be avoided in patients with adequate (800–1000 mg/d) or excessive intake. Examples of surreptitious calcium intake include over-the-counter antacids, and patiromer used in the treatment of hyperkalemia.

Calcitriol and other vitamin D receptor antagonists (VDRA) suppress parathyroid gland activity in advanced stages of CKD (55). However, there may be a negative shift in the risk–benefit profile for VDRAs in predialysis CKD because their use is associated with increased risk of hypercalcemia with no significant benefit to cardiac function (62). The current guidelines recommend avoiding routine use of VDRAs before ESKD (55). When therapy is warranted, VDRAs should be used conservatively and only with evidence that intact PTH levels are progressively and/or persistently elevated.

Calcimimetics are also efficacious at suppressing PTH secretion in CKD–MBD (55,63). This class of agents is commonly associated with hypocalcemia in patients with ESKD and patients who are predialysis, however, the clinical significance of this expected safety event is unclear (55). Calcimimetics are not recommended in CKD GFR categories 3a-5 (G3a–G5) when the patient is not on dialysis, but are limited to use in CKD category G5 when the patient is on dialysis (55). Additionally, the guidelines recommend an individualized approach to managing hypocalcemia on the basis of severity of symptoms and calcium levels.

Antihyperglycemic Agents in CKD

Poorly controlled type 2 diabetes (T2DM) mellitus can lead to microvascular complications, including nephropathy, as >40% of patients with T2DM have CKD (64). Slowing the progression of nephropathy through glycemic control is of paramount importance in clinical management.

Metformin remains the first-line treatment for T2DM, given its hemoglobin A1c lowering potential, oral administration, neutral effect on body weight, and cardiovascular outcome and all-cause mortality benefit (65). Historically, metformin was contraindicated in patients with a serum creatinine level of ≥1.5 or ≥1.4 mg/dl for men and women, respectively, given that the drug is eliminated through the kidneys and can increase the risk of lactic acidosis (66). However, this is an exceedingly rare complication and most patients with mild-to-moderate kidney impairment safely tolerate metformin (66). Nonetheless, although the incidence remains low, the risk of lactic acidosis or elevated lactate concentrations increases with metformin use with declining kidney function, especially when higher doses are used. In 2016, the FDA required changes to metformin labeling to expand its use in patients with impaired kidney function (Table 1) (67). The guidelines also recommend using GFR to estimate kidney function rather than serum creatinine to determine whether a patient is a safe candidate for metformin.

Table 1. - Cautionary notes for prescribing in people with CKD
Medication Comments
Narrow therapeutic index drugs
 Aminoglycosides Nephrotoxic (acute tubular necrosis, AKI). Ototoxic. Therapeutic drug monitoring recommended.
 Digoxin Increased for digoxin toxicity including arrhythmias. Therapeutic drug monitoring recommended.
 Lithium Diabetes insipidus, interstitial disease. Avoid concomitant use of thiazide diuretics and NSAIDs, maintain hydration. Therapeutic drug monitoring recommended.
 Phenytoin Low albumin will affect bound concentration. Monitor free phenytoin level.
 Tacrolimus Vasoconstriction, nephrotoxicity. Avoid concomitant use of CYP 3A4 inhibitors. Therapeutic drug monitoring recommended.
 Warfarin Increased risk of bleeding. Close INR monitoring recommended.
 NSAIDs Hemodynamically mediated kidney injury, sodium and/or potassium retention, interstitial nephropathy. Avoid with concomitant use of diuretics or RAAS inhibitors, maintain hydration, consider alternate analgesic.
 Meperidine Active metabolite, normeperidine, increases risk of seizure. Avoid.
 Morphine Active metabolites, increased drug effect.
Contrast agents
 Iodinated contrast media Nephrotoxic. Use lowest dose, maintain hydration with saline, can consider N-acetylcysteine or sodium bicarbonate, avoid concomitant nephrotoxins, avoid use of high-osmolarity agents, avoid use of gadolinium-containing contrast media.
Bowel preparation
 Phosphate-containing bowel preparation Increased risk for phosphate nephropathy and electrolyte disturbances. Avoid phosphate-based preparations.
 Licorice Increased risk of sodium and water retention, hypokalemia, hypertension. Avoid use.
 Noni juice Increased risk of hyperkalemia. Avoid use.
 St. John’s wort CYP inducer. Increased risk of drug interactions. Avoid use.
Ginkgo biloba Increased risk of bleeding. Avoid use.
 Ephedra alkaloids (ma huang) May potentiate hypertension. Avoid use.
Excerpted from the 2012 Kidney Disease Improving Global Outcomes Guidelines on the management of CKD (77). NSAIDs, nonsteroidal anti-inflammatory drugs; CYP 3A4, cytochrome p450 3A4; INR, International Normalized Ratio; RAAS, renin-angiotensin-aldosterone system; CYP, cytochrome p450.

The American Diabetes Association advocates considering both efficacy and safety profiles when selecting an agent to add to metformin (65). Patients with T2DM and CKD are at an increased risk for hypoglycemia, and some agents pose a higher risk of hypoglycemia than others. Sulfonylureas and insulin have a higher risk for hypoglycemia than other drug classes. Within the sulfonylurea class, glyburide is not recommended for use in CKD because it is hepatically metabolized with active metabolites excreted by the kidney (68). Glimepiride is metabolized in the liver into two major metabolites, and clinical trials have demonstrated a reduced elimination of these metabolites with kidney impairment; therefore, to reduce the risk of hypoglycemia, the drug should be initiated at a low dose in patients with T2DM and CKD. Glipizide is also metabolized by the liver but into inactive metabolites excreted by the kidney; hence, it is the preferred sulfonylurea agent for use in CKD.

Thiazolidinediones are highly metabolized by the liver and require no dose adjustments in CKD (68). Despite this, the thiazolidinedione class of agents is often avoided because of a propensity for fluid retention and edema in CKD.

Two classes of incretins available for the treatment of T2DM have grown in use over the last decade: dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists. All dipeptidyl peptidase-4 inhibitors agents can be safely used in all stages of CKD, and ESKD on dialysis (69). Certain agents in this class are eliminated through the kidneys, such as alogliptin, saxagliptin, and sitagliptin, and require a dose adjustment with lower GFRs. Linagliptin is eliminated through a hepatobiliary route and does not require adjustment, offering an advantage over the other members in the class (70).

Each of the six available glucagon-like peptide-1 receptor agonists differ in their recommendations for use in CKD, partly because of the paucity of data evaluating use with impaired kidney function. Exenatide and exenatide extended release should be avoided in patients with a creatinine clearance <30 ml/min because both are eliminated through the kidneys, whereas lixisenatide should not be used for patients with a creatinine clearance of <15 ml/min (70). Other agents, such as albiglutide, dulaglutide, and semaglutide, are not associated with kidney elimination and do not require a dose adjustment with impaired kidney function. Liraglutide is not eliminated through the kidneys but does carry a cautionary recommendation for use with any degree of kidney impairment (70,71). Liraglutide is also unique in this class because its use has been specifically evaluated in patients with CKD stage 3, revealing no negative effects on kidney function, and in patients with CKD stage 4, showing a slower progression of diabetic kidney disease (72,73). Finally, there have been postmarketing reports of both acute kidney failure and worsening of CKD in both patients with and without reduced kidney function for several agents in this class (70). The majority of these are in patients experiencing GI adverse effects, and the drug class carries a warning to monitor kidney function in patients with CKD who report severe GI symptoms.

The sodium-glucose cotransporter 2 inhibitors are oral agents for treatment of T2DM targeting kidney tubular glucose reabsorption. Efficacy of these agents can be affected by kidney function and specific dosing recommendations are summarized in Table 2 (74).

Table 2. - Dosing recommendations for select drug therapies by CKD stage
Drug Class Drug CKD Staging by GFR Category (ml/min per 1.73 m2)
Stage 1 (>90) Stage 2 (89–60) Stage 3a (59–45) Stage 3b (44–30) Stage 4 (29–15) Stage 5 (<15)
Biguanide Metformin R R R DA a X X
Sulfonylureas Glipizide R R R R R R
Glimepiride R R R R R C
Glyburide R R C C C C
Thiazolidinediones Pioglitazone R R R R R R
Rosiglitazone R R R R R R
DPP4 inhibitors Alogliptin R R DA DA DA DA
Linagliptin R R R R R R
Saxagliptin R R R DA DA DA
Sitagliptin R R R DA DA DA
SGLT2 inhibitors Canagliflozin R R DA X X X
Dapagliflozin R R X X X X
Empagliflozin R R R X X X
Ertugliflozin R R X X X X
Direct oral anticoagulants for indications: VTE/atrial fibrillation Apixaban R/DA b R/DA b R/DA b R/DA b R/DA b C/DA b
Dabigatran R/R R/R R c /R c R c /R c C/DA d C/C
Edoxaban R/X e R/R DA f /DA f DA/DA DA/DA X/X
Rivaroxaban R/R R/R R/DA f R/DA X/DA X/C
ARB/neprilysin inhibitor Sacubitril/Valsartan R R R R DA g DA g
Antiretrovirals TDF R R DA f DA DA DA
Emtricitabine R R DA f DA DA DA
Lamivudine R R DA f DA DA DA
Elvitegravir/Cobicistat/ R R h X f X X X
TDF/Emtricitabine i R R X j X j X j X j
Tenofovir Alafenamide/ R R R R X X
Tenofovir Alafenamide/Emtricitabine
Tenofovir Alafenamide
Direct-acting antihepacivirals Ledipasvir/Sofosbuvir R R R R C k C k
Ombitasvir/Paritaprevir/Ritonavir R R R R R R
R, can be safely recommended at normal doses; DA, dose adjustment required for use; X, use not recommended; C, no manufacturer specific recommendation for use or dose adjustment, use with caution; DPP4, dipeptidyl peptidase-4; SGLT2, sodium-glucose cotransporter 2; ARB, angiotensin receptor blocker; VTE, venous thromboembolism; TDF, tenofovir disoproxil fumarate; CrCl, creatinine clearance; P-gp, P-glycoprotein.
aMetformin should not be initiated in patients with an eGFR between 30 and 45 ml/min per 1.73 m2.
bApixaban requires dose adjustment in atrial fibrillation if two of the following characteristics are met: serum creatinine ≥1.5 mg/dl, body weight ≤60 kg, age ≥80 years.
cDabigatran requires dose adjustment in both VTE and atrial fibrillation for CrCl 30–50 ml/min with coadministration of P-gp inhibitors.
dAvoid dabigatran use in atrial fibrillation for CrCl <30 ml/min with coadministration of P-gp inhibitors.
eAvoid edoxaban use in atrial fibrillation for CrCl >95 ml/min because of increased risk of ischemic stroke.
fRequires no dose adjustment for CrCl 51–59 ml/min (edoxaban in VTE and atrial fibrillation, rivaroxaban in atrial fibrillation, ceftazidime/avibactam, ceftolozane/tazobactam, tenofovir disoproxil fumarate) or CrCl 50–59 ml/min (emtricitabine, lamivudine, elvitegravir/cobicistat/tenofovir disoproxil/emtricitabine) or eGFR 50–59 ml/min per 1.73 m2 (meropenem/vaborbactam).
gDose adjustment required for initial dose.
hAvoid initiating Elvitegravir/Cobicistat/Emtricitabine/TDF in CrCl <70 ml/min.
iDose adjustment may be used for TDF/Emtricitabine in CrCl 30–49 ml/min.
jUse individual components. Dose adjustment for TDF and Emtricitabine for kidney function.
kNo dose adjustments have been provided by the manufacturer in CrCl <30 ml/min.

Finally, all available insulin preparations can be used in patients with CKD. However, because the kidney is responsible for 30%–80% of insulin removal, patients should be monitored for hypoglycemia due to decreased insulin elimination as kidney function declines (75). Insulin requirements should be tailored to meet individual needs, and no specific dose adjustment is recommended.

Anticoagulant Agents in CKD

Many patients with CKD require anticoagulation for comorbid conditions and treatment with vitamin K antagonist or direct oral anticoagulants (DOACs). However, caution is warranted with DOAC use in CKD because these agents are partly eliminated by the kidneys (76). Unaltered dosing can result in an increased risk of bleeding. Although all DOACs can be used with impaired kidney function, the recommendations for dose adjustment are dependent on indication and kidney function. Of note, DOACs should be avoided in ESKD given the lack of data evaluating the efficacy and safety of these agents (76). Low molecular weight heparin should also be administered at a reduced dose with lower GFRs, and avoided in ESKD.

Medication Reconciliation and Deprescribing in CKD

Several approaches have been proposed to address medication safety hazards in CKD (8,11,77) Much of the focus is on adherence to appropriate prescribing guidelines, medication reconciliation, evidence-based agent selection, dose modifications on the basis of altered kidney function and drug PK/PD, and monitoring of drug therapy response and kidney function (8,9,11). Special attention is also required for CKD drug dosing with many over-the-counter medications and dietary supplements (i.e., herbal supplements, nonherbal supplements, and vitamins) (78). However, it is difficult to provide dosing and management recommendations for many herbals and vitamins with unknown toxicities.

The KDIGO guidelines provide a starting point for evaluating medication appropriateness for commonly used medications in CKD (Table 1). Since publication of the guidelines, a number of new agents used in management of common comorbid conditions entered the market. Of these new agents, we have identified several drug classes and selected agents that may require dose adjustment or deprescription in CKD, detailed in Table 2. Decision-support platforms such as Micromedex and Lexicomp offer easily accessible monographs of prescription and over-the-counter medications to guide agent selection and dosing. The Natural Medicine Comprehensive Database is a useful resource to consider the safety of herbals, dietary supplements, vitamins, and other and nutraceuticals in CKD.

In addition to adherence to prescription guidelines, deprescribing is gaining attention for identifying and eliminating inappropriate medications. Deprescribing can be defined as “the systematic process of identifying and discontinuing drugs in instances in which existing or potential harms outweigh existing or potential benefits.” (79) Studies involving deprescribing or drug therapy reviews in kidney disease have centered on the hemodialysis population, and deprescribing guidance for patients with predialysis CKD are lacking (80,81). Despite the paucity of guidelines for this population, health care providers can apply general principles of deprescribing in CKD (8,11,79).

A range of drug classes are candidates for deprescription in CKD. NSAIDs are priority for deprescribing in CKD because of potential adverse effects such as worsening of CKD, fluid retention, hyperkalemia, BP, and AKI (52,77,82). NSAIDs, including cyclooxygenase-2 inhibitors should be avoided in hypertension, CHF, and CKD of all causes (52). Other candidate drug classes for deprescribing in CKD include proton pump inhibitors, for which growing evidence indicates potential kidney and nonkidney-related harm with prolonged usage (83).

A general approach to medication assessment and deprescribing is proposed in Table 3. As outlined in the table, one should review the indication for each individual agent to determine whether the potential for harm outweighs the evidence for efficacy. For example, RAAS blockers, which can lead to hyperkalemia and AKI, should undergo a harm versus benefit evaluation, especially in patients where the benefits of treatment targets are unknown or equivocal.

Table 3. - Approach to medication assessment and deprescribing in CKD (8,9,11,77,79)
Step Comments
1. Assess kidney function Determine GFR to evaluate kidney function for drug dosing
Direct measurement of GFR may be necessary for dosing narrow therapeutic or toxic range drugs
2. Medication history Collect complete medication list:
 Include all prescription, over-the-counter and dietary supplements (including herbal, nonherbal, and vitamin supplements)
Collect history of drug allergies/sensitivities; adjustment or discontinuation of medication due to impaired kidney function or toxicity
3. Medication review Is the drug nephrotoxic or contraindicated in CKD or at a specific GFR level?
Is the drug or drug metabolite’s half-life prolonged in CKD?
Is the risk of adverse effects or drug–drug interactions increased in CKD?
Does this drug have a narrow therapeutic or toxic range?
4. Adjust regimen Prescribing:
 Calculate/adjust dose on the basis of Food and Drug Administration-approved product labeling, drug pharmacokinetic characteristics, and the patient’s GFR
 Refer to peer-reviewed literature recommendations if limited information in product labeling
 Patients should consult with pharmacist or health professional before initiating over-the-counter medications or dietary supplements
 Discuss rationale and plan with patient and care team
 Deprescribe one medication at a time, consider agents with greatest harm and least benefit, consider patient preferences
5. Drug therapy monitoring Document and monitor for signs efficacy, toxicity, and change in symptoms with initiation or discontinuation of agent
Revise regimen on the basis of acute (e.g., intercurrent illness) or chronic changes/decline in patient’s health status and/or kidney function

Finally, given the complexity of medication management of the CKD population, there is strong justification for the involvement of an interprofessional team that includes pharmacists to prevent, identify, and resolve potential or actual medication-related problems (84,85). Although much of the evidence supporting pharmacist involvement in medication reconciliation and management is in the hemodialysis population, these best practices may also be extrapolated to the predialysis population.


Medication management in CKD offers unique challenges, but presents providers with opportunities to enhance care quality to this high-risk population. Implementing strategies to evaluate the heavy medication burden of many patients with CKD, considering the risks and benefits of all prescribed agents, and deprescribing when indicated may improve patient outcomes. The implications of reduced kidney function in a disease population with a range of comorbidities are substantial, and recognizing these can have a significant effect on care management of patients with CKD, and has the potential to reduce much of their morbidity and mortality.


This work was supported by Baltimore Veterans Affairs Patient Safety Center of Inquiry which is funded by the Veterans Affairs National Patient Center for Patient Safety in White River Junction, Vermont.


C.F.W. received financial support from the Veterans Affairs National Center for Patient Safety, Patient Safety Center of Inquiry.

Published online ahead of print. Publication date available at


1. Henrich WL, Anderson RJ: Drug use in renal failure. Postgrad Med 64: 153–163, 1978
2. Reed WE Jr, Sabatini S: The use of drugs in renal failure. Semin Nephrol 6: 259–295, 1986
3. Stevens LA, Fares G, Fleming J, Martin D, Murthy K, Qiu J, Stark PC, Uhlig K, Van Lente F, Levey AS: Low rates of testing and diagnostic codes usage in a commercial clinical laboratory: Evidence for lack of physician awareness of chronic kidney disease. J Am Soc Nephrol 16: 2439–2448, 2005
4. Coresh J, Byrd-Holt D, Astor BC, Briggs JP, Eggers PW, Lacher DA, Hostetter TH: Chronic kidney disease awareness, prevalence, and trends among U.S. adults, 1999 to 2000. J Am Soc Nephrol 16: 180–188, 2005
5. Chertow GM, Lee J, Kuperman GJ, Burdick E, Horsky J, Seger DL, Lee R, Mekala A, Song J, Komaroff AL, Bates DW: Guided medication dosing for inpatients with renal insufficiency. JAMA 286: 2839–2844, 2001
6. Corsonello A, Pranno L, Garasto S, Fabietti P, Bustacchini S, Lattanzio F: Potentially inappropriate medication in elderly hospitalized patients. Drugs Aging 26[Suppl 1]: 31–39, 2009
7. Blix HS, Viktil KK, Moger TA, Reikvam A: Use of renal risk drugs in hospitalized patients with impaired renal function--an underestimated problem? Nephrol Dial Transplant 21: 3164–3171, 2006
8. Brown C: Prescribing principles for patients with chronic kidney disease. Pharm Pract (Granada) 18: 23–24, 2008
9. Matzke GR, Aronoff GR, Atkinson AJ Jr, Bennett WM, Decker BS, Eckardt KU, Golper T, Grabe DW, Kasiske B, Keller F, Kielstein JT, Mehta R, Mueller BA, Pasko DA, Schaefer F, Sica DA, Inker LA, Umans JG, Murray P: Drug dosing consideration in patients with acute and chronic kidney disease-a clinical update from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 80: 1122–1137, 2011
10. Stevens LA, Nolin TD, Richardson MM, Feldman HI, Lewis JB, Rodby R, Townsend R, Okparavero A, Zhang YL, Schmid CH, Levey AS; Chronic Kidney Disease Epidemiology Collaboration: Comparison of drug dosing recommendations based on measured GFR and kidney function estimating equations. Am J Kidney Dis 54: 33–42, 2009
11. Kappel J, Calissi P: Nephrology: 3. Safe drug prescribing for patients with renal insufficiency. CMAJ 166: 473–477, 2002
12. Nolin TD: Altered nonrenal drug clearance in ESRD. Curr Opin Nephrol Hypertens 17: 555–559, 2008
13. Brater DC: Diuretic therapy. N Engl J Med 339: 387–395, 1998
14. Wilcox CS: Metabolic and adverse effects of diuretics. Semin Nephrol 19: 557–568, 1999
15. Palmer BF: Metabolic complications associated with use of diuretics. Semin Nephrol 31: 542–552, 2011
16. Schoolwerth AC, Sica DA, Ballermann BJ, Wilcox CS; Council on the Kidney in Cardiovascular Disease and the Council for High Blood Pressure Research of the American Heart Association: Renal considerations in angiotensin converting enzyme inhibitor therapy: A statement for healthcare professionals from the Council on the Kidney in Cardiovascular Disease and the Council for High Blood Pressure Research of the American Heart Association. Circulation 104: 1985–1991, 2001
17. Hou FF, Zhang X, Zhang GH, Xie D, Chen PY, Zhang WR, Jiang JP, Liang M, Wang GB, Liu ZR, Geng RW: Efficacy and safety of benazepril for advanced chronic renal insufficiency. N Engl J Med 354: 131–140, 2006
18. Tomlinson LA, Holt SG, Leslie AR, Rajkumar C: Prevalence of ambulatory hypotension in elderly patients with CKD stages 3 and 4. Nephrol Dial Transplant 24: 3751–3755, 2009
19. Toto RD, Mitchell HC, Lee HC, Milam C, Pettinger WA: Reversible renal insufficiency due to angiotensin converting enzyme inhibitors in hypertensive nephrosclerosis. Ann Intern Med 115: 513–519, 1991
20. Packer M, Lee WH, Medina N, Yushak M, Kessler PD: Functional renal insufficiency during long-term therapy with captopril and enalapril in severe chronic heart failure. Ann Intern Med 106: 346–354, 1987
21. Lapi F, Azoulay L, Yin H, Nessim SJ, Suissa S: Concurrent use of diuretics, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers with non-steroidal anti-inflammatory drugs and risk of acute kidney injury: Nested case-control study. BMJ 346: e8525, 2013
22. Hahn K, Ejaz AA, Kanbay M, Lanaspa MA, Johnson RJ: Acute kidney injury from SGLT2 inhibitors: Potential mechanisms. Nat Rev Nephrol 12: 711–712, 2016
23. Palevsky PM, Zhang JH, Seliger SL, Emanuele N, Fried LF; VA NEPHRON-D Study: Incidence, severity, and outcomes of AKI associated with dual renin-angiotensin system blockade. Clin J Am Soc Nephrol 11: 1944–1953, 2016
24. Tomlinson LA, Abel GA, Chaudhry AN, Tomson CR, Wilkinson IB, Roland MO, Payne RA: ACE inhibitor and angiotensin receptor-II antagonist prescribing and hospital admissions with acute kidney injury: A longitudinal ecological study. PLoS One 8: e78465, 2013
25. Montford JR, Linas S: How dangerous is hyperkalemia? J Am Soc Nephrol 28: 3155–3165, 2017
26. Snitker S, Doerfler RM, Soliman EZ, Deo R, St Peter WL, Kramlik S, Fischer MJ, Navaneethan S, Delafontaine P, Jaar BG, Ojo A, Makos GK, Slaven A, Weir MR, Zhan M, Fink JC; for CRIC Study Investigators: Association of QT-prolonging medication use in CKD with electrocardiographic manifestations [published online ahead of print August 9, 2017]. Clin J Am Soc Nephrol doi:10.2215/CJN.12991216
27. Lewis EJ, Hunsicker LG, Bain RP, Rohde RD; The Collaborative Study Group: The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. N Engl J Med 329: 1456–1462, 1993
28. Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, Remuzzi G, Snapinn SM, Zhang Z, Shahinfar S; RENAAL Study Investigators: Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 345: 861–869, 2001
29. Einhorn LM, Zhan M, Hsu VD, Walker LD, Moen MF, Seliger SL, Weir MR, Fink JC: The frequency of hyperkalemia and its significance in chronic kidney disease. Arch Intern Med 169: 1156–1162, 2009
30. Nakhoul GN, Huang H, Arrigain S, Jolly SE, Schold JD, Nally JV Jr, Navaneethan SD: Serum potassium, end-stage renal disease and mortality in chronic kidney disease. Am J Nephrol 41: 456–463, 2015
31. Seliger SL, Fried LF: Serum potassium in dual renin-angiotensin-aldosterone system blockade. Clin J Am Soc Nephrol 9: 219–221, 2014
32. Oster JR, Singer I, Fishman LM: Heparin-induced aldosterone suppression and hyperkalemia. Am J Med 98: 575–586, 1995
33. Kovesdy CP, Appel LJ, Grams ME, Gutekunst L, McCullough PA, Palmer BF, Pitt B, Sica DA, Townsend RR: Potassium homeostasis in health and disease: A scientific workshop cosponsored by the National Kidney Foundation and the American Society of Hypertension. J Am Soc Hypertens 11: 783–800, 2017
34. Sterns RH, Grieff M, Bernstein PL: Treatment of hyperkalemia: Something old, something new. Kidney Int 89: 546–554, 2016
35. Watson MA, Baker TP, Nguyen A, Sebastianelli ME, Stewart HL, Oliver DK, Abbott KC, Yuan CM: Association of prescription of oral sodium polystyrene sulfonate with sorbitol in an inpatient setting with colonic necrosis: A retrospective cohort study. Am J Kidney Dis 60: 409–416, 2012
36. Weir MR, Bakris GL, Bushinsky DA, Mayo MR, Garza D, Stasiv Y, Wittes J, Christ-Schmidt H, Berman L, Pitt B; OPAL-HK Investigators: Patiromer in patients with kidney disease and hyperkalemia receiving RAAS inhibitors. N Engl J Med 372: 211–221, 2015
37. Garimella PS, Jaber BL: Patiromer for hyperkalemia in diabetic CKD: A new kid on the block. Am J Kidney Dis 67: 545–547, 2016
38. Kim DM, Chung JH, Yoon SH, Kim HL: Effect of fludrocortisone acetate on reducing serum potassium levels in patients with end-stage renal disease undergoing haemodialysis. Nephrol Dial Transplant 22: 3273–3276, 2007
39. Kliger AS, Foley RN, Goldfarb DS, Goldstein SL, Johansen K, Singh A, Szczech L: KDOQI US commentary on the 2012 KDIGO clinical practice guideline for anemia in CKD. Am J Kidney Dis 62: 849–859, 2013
40. Kidney Disease: Improving Global Outcomes: KDIGO clinical practice guideline for anemia in chronic kidney disease. Kidney Int Suppl 2: 279–335, 2012
41. Locatelli F, Nissenson AR, Barrett BJ, Walker RG, Wheeler DC, Eckardt KU, Lameire NH, Eknoyan G: Clinical practice guidelines for anemia in chronic kidney disease: Problems and solutions. A position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 74: 1237–1240, 2008
42. Kovesdy CP, Kalantar-Zadeh K: Iron therapy in chronic kidney disease: Current controversies. J Ren Care 35[Suppl 2]: 14–24, 2009
43. Macdougall IC, Bock AH, Carrera F, Eckardt KU, Gaillard C, Van Wyck D, Roubert B, Nolen JG, Roger SD; FIND-CKD Study Investigators: FIND-CKD: A randomized trial of intravenous ferric carboxymaltose versus oral iron in patients with chronic kidney disease and iron deficiency anaemia. Nephrol Dial Transplant 29: 2075–2084, 2014
44. Macdougall IC: Iron supplementation in the non-dialysis chronic kidney disease (ND-CKD) patient: Oral or intravenous? Curr Med Res Opin 26: 473–482, 2010
45. Hayat A: Safety issues with intravenous iron products in the management of anemia in chronic kidney disease. Clin Med Res 6: 93–102, 2008
46. Remuzzi G, Ingelfinger JR: Correction of anemia--payoffs and problems. N Engl J Med 355: 2144–2146, 2006
47. Singh AK, Szczech L, Tang KL, Barnhart H, Sapp S, Wolfson M, Reddan D; CHOIR Investigators: Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med 355: 2085–2098, 2006
48. Pfeffer MA, Burdmann EA, Chen CY, Cooper ME, de Zeeuw D, Eckardt KU, Feyzi JM, Ivanovich P, Kewalramani R, Levey AS, Lewis EF, McGill JB, McMurray JJ, Parfrey P, Parving HH, Remuzzi G, Singh AK, Solomon SD, Toto R; TREAT Investigators: A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease. N Engl J Med 361: 2019–2032, 2009
49. Drüeke TB, Locatelli F, Clyne N, Eckardt KU, Macdougall IC, Tsakiris D, Burger HU, Scherhag A; CREATE Investigators: Normalization of hemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med 355: 2071–2084, 2006
50. Goldsmith D, Covic A: Time to Reconsider Evidence for Anaemia Treatment (TREAT) = Essential Safety Arguments (ESA). Nephrol Dial Transplant 25: 1734–1737, 2010
51. Palmer SC, Saglimbene V, Mavridis D, Salanti G, Craig JC, Tonelli M, Wiebe N, Strippoli GF: Erythropoiesis-stimulating agents for anaemia in adults with chronic kidney disease: A network meta-analysis. Cochrane Database Syst Rev (12): CD010590, 2014
52. Williams AW, Dwyer AC, Eddy AA, Fink JC, Jaber BL, Linas SL, Michael B, O’Hare AM, Schaefer HM, Shaffer RN, Trachtman H, Weiner DE, Falk AR; American Society of Nephrology Quality, and Patient Safety Task Force: Critical and honest conversations: The evidence behind the “Choosing Wisely” campaign recommendations by the American Society of Nephrology. Clin J Am Soc Nephrol 7: 1664–1672, 2012
53. Moe S, Drüeke T, Cunningham J, Goodman W, Martin K, Olgaard K, Ott S, Sprague S, Lameire N, Eknoyan G; Kidney Disease: Improving Global Outcomes (KDIGO): Definition, evaluation, and classification of renal osteodystrophy: A position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 69: 1945–1953, 2006
54. Chartsrisak K, Vipattawat K, Assanatham M, Nongnuch A, Ingsathit A, Domrongkitchaiporn S, Sumethkul V, Distha-Banchong S: Mineral metabolism and outcomes in chronic kidney disease stage 2-4 patients. BMC Nephrol 14: 14, 2013
55. Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group: KDIGO 2017 clinical practice guideline update for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease–Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl 7: 1–59, 2017
56. Block GA, Wheeler DC, Persky MS, Kestenbaum B, Ketteler M, Spiegel DM, Allison MA, Asplin J, Smits G, Hoofnagle AN, Kooienga L, Thadhani R, Mannstadt M, Wolf M, Chertow GM: Effects of phosphate binders in moderate CKD. J Am Soc Nephrol 23: 1407–1415, 2012
57. Ketteler M, Elder GJ, Evenepoel P, Ix JH, Jamal SA, Lafage-Proust MH, Shroff R, Thadhani RI, Tonelli MA, Kasiske BL, Wheeler DC, Leonard MB: Revisiting KDIGO clinical practice guideline on chronic kidney disease-mineral and bone disorder: A commentary from a Kidney Disease: Improving Global Outcomes controversies conference. Kidney Int 87: 502–528, 2015
58. Hill KM, Martin BR, Wastney ME, McCabe GP, Moe SM, Weaver CM, Peacock M: Oral calcium carbonate affects calcium but not phosphorus balance in stage 3-4 chronic kidney disease. Kidney Int 83: 959–966, 2013
59. Hill Gallant KM, Spiegel DM: Calcium balance in chronic kidney disease. Curr Osteoporos Rep 15: 214–221, 2017
60. Jamal SA, Vandermeer B, Raggi P, Mendelssohn DC, Chatterley T, Dorgan M, Lok CE, Fitchett D, Tsuyuki RT: Effect of calcium-based versus non-calcium-based phosphate binders on mortality in patients with chronic kidney disease: An updated systematic review and meta-analysis. Lancet 382: 1268–1277, 2013
61. Collister D, Rigatto C, Tangri N: Anemia management in chronic kidney disease and dialysis: A narrative review. Curr Opin Nephrol Hypertens 26: 214–218, 2017
62. Toussaint ND, Damasiewicz MJ: Do the benefits of using calcitriol and other vitamin D receptor activators in patients with chronic kidney disease outweigh the harms? Nephrology (Carlton) 22[Suppl 2]: 51–56, 2017
63. Brancaccio D, Bommer J, Coyne D: Vitamin D receptor activator selectivity in the treatment of secondary hyperparathyroidism: Understanding the differences among therapies. Drugs 67: 1981–1998, 2007
64. Bailey RA, Wang Y, Zhu V, Rupnow MF: Chronic kidney disease in US adults with type 2 diabetes: An updated national estimate of prevalence based on Kidney Disease: Improving Global Outcomes (KDIGO) staging. BMC Res Notes 7: 415, 2014
65. American Diabetes Association: Standards of medical care in diabetes-2017: Summary of revisions. Diabetes Care 40[Suppl 1]: S4–S5, 2017
66. Lipska KJ, Bailey CJ, Inzucchi SE: Use of metformin in the setting of mild-to-moderate renal insufficiency. Diabetes Care 34: 1431–1437, 2011
67. Food and Drug Administration: FDA Drug Safety Communication: FDA Revises Warnings Regarding Use of the Diabetes Medicine Metformin in Certain Patients with Reduced Kidney Function, 2017. Available at: Accessed November 29, 2017
68. Tuttle KR, Bakris GL, Bilous RW, Chiang JL, de Boer IH, Goldstein-Fuchs J, Hirsch IB, Kalantar-Zadeh K, Narva AS, Navaneethan SD, Neumiller JJ, Patel UD, Ratner RE, Whaley-Connell AT, Molitch ME: Diabetic kidney disease: A report from an ADA Consensus Conference. Diabetes Care 37: 2864–2883, 2014
69. Abe M, Okada K: DPP-4 inhibitors in diabetic patients with chronic kidney disease and end-stage kidney disease on dialysis in clinical practice. Contrib Nephrol 185: 98–115, 2015
70. Scheen AJ: Pharmacokinetics and clinical use of incretin-based therapies in patients with chronic kidney disease and type 2 diabetes. Clin Pharmacokinet 54: 1–21, 2015
71. Prasad-Reddy L, Isaacs D: A clinical review of GLP-1 receptor agonists: Efficacy and safety in diabetes and beyond. Drugs Context 4: 212283, 2015
72. Davies MJ, Bain SC, Atkin SL, Rossing P, Scott D, Shamkhalova MS, Bosch-Traberg H, Syrén A, Umpierrez GE: Efficacy and safety of liraglutide versus placebo as add-on to glucose-lowering therapy in patients with type 2 diabetes and moderate renal impairment (LIRA-RENAL): A randomized clinical trial. Diabetes Care 39: 222–230, 2016
73. Mann JFE, Ørsted DD, Brown-Frandsen K, Marso SP, Poulter NR, Rasmussen S, Tornøe K, Zinman B, Buse JB; LEADER Steering Committee and Investigators: Liraglutide and renal outcomes in type 2 diabetes. N Engl J Med 377: 839–848, 2017
74. Andrianesis V, Glykofridi S, Doupis J: The renal effects of SGLT2 inhibitors and a mini-review of the literature. Ther Adv Endocrinol Metab 7: 212–228, 2016
75. Hahr AJ, Molitch ME: Management of diabetes mellitus in patients with chronic kidney disease. Clin Diabetes Endocrinol 1: 2, 2015
76. Lutz J, Jurk K, Schinzel H: Direct oral anticoagulants in patients with chronic kidney disease: Patient selection and special considerations. Int J Nephrol Renovasc Dis 10: 135–143, 2017
77. KDIGO CKD Work Group: Kidney disease: Improving global outcomes (KDIGO) CKD work group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl 3: 1–150, 2013
78. Gabardi S, Munz K, Ulbricht C: A review of dietary supplement-induced renal dysfunction. Clin J Am Soc Nephrol 2: 757–765, 2007
79. Scott IA, Hilmer SN, Reeve E, Potter K, Le Couteur D, Rigby D, Gnjidic D, Del Mar CB, Roughead EE, Page A, Jansen J, Martin JH: Reducing inappropriate polypharmacy: The process of deprescribing. JAMA Intern Med 175: 827–834, 2015
80. Pai AB, Boyd A, Depczynski J, Chavez IM, Khan N, Manley H: Reduced drug use and hospitalization rates in patients undergoing hemodialysis who received pharmaceutical care: A 2-year, randomized, controlled study. Pharmacotherapy 29: 1433–1440, 2009
81. McIntyre C, McQuillan R, Bell C, Battistella M: Targeted deprescribing in an outpatient hemodialysis unit: A quality improvement study to decrease polypharmacy. Am J Kidney Dis 70: 611–618, 2017
82. Schneider V, Lévesque LE, Zhang B, Hutchinson T, Brophy JM: Association of selective and conventional nonsteroidal antiinflammatory drugs with acute renal failure: A population-based, nested case-control analysis. Am J Epidemiol 164: 881–889, 2006
83. Lazarus B, Chen Y, Wilson FP, Sang Y, Chang AR, Coresh J, Grams ME: Proton pump inhibitor use and the risk of chronic kidney disease. JAMA Intern Med 176: 238–246, 2016
84. Pai AB, Cardone KE, Manley HJ, St Peter WL, Shaffer R, Somers M, Mehrotra R; Dialysis Advisory Group of American Society of Nephrology: Medication reconciliation and therapy management in dialysis-dependent patients: Need for a systematic approach. Clin J Am Soc Nephrol 8: 1988–1999, 2013
85. St Peter WL, Wazny LD, Patel UD: New models of chronic kidney disease care including pharmacists: Improving medication reconciliation and medication management. Curr Opin Nephrol Hypertens 22: 656–662, 2013

medication safety; deprescribing; chronic kidney disease; renal drug dosing; Patient Safety; Pharmaceutical Preparations; Multimorbidity; Iatrogenic Disease; Renal Insufficiency, Chronic; Kidney Failure, Chronic; diabetes mellitus; hypertension; Medical Errors; heart failure

Copyright © 2018 by the American Society of Nephrology