Chronic Kidney Disease
Clinical Snapshot
Chronic kidney disease (CKD) is defined by KDIGO as abnormalities of kidney structure or function, present for at least 3 months, with implications for health. This is met by either a glomerular filtration rate (GFR) under 60 mL/min/1.73m², or by any marker of kidney damage — albuminuria, urine sediment abnormalities, electrolyte or other abnormalities from tubular disorders, structural abnormalities on imaging, histological abnormalities, or a history of kidney transplantation — each sustained for at least 3 months.[1] CKD is staged, not simply diagnosed, using the CGA framework: Cause, GFR category (G1 through G5), and Albuminuria category (A1 through A3). This staging drives every subsequent decision in this chapter — which drugs to start, how often to monitor, and when to refer — so it is worth learning as a framework, not memorizing as a table.
Diabetes mellitus and hypertension are the leading causes of CKD; glomerulonephritis, polycystic kidney disease, and obstructive/interstitial disease account for most of the remainder. A large share of CKD progression is genuinely modifiable by medication therapy pharmacists directly manage or influence — RAAS inhibitor and SGLT2 inhibitor renoprotection, blood pressure control, glycemic control, nephrotoxin avoidance, and correct dose adjustment of every renally-cleared drug as function declines. CKD is also, deliberately, covered end-to-end in this chapter through to dialysis: the same eGFR-based staging and drug-dosing logic that applies at CKD G3a applies — in a more extreme and less forgiving form — to a patient on hemodialysis, and pharmacists remain just as central to safe medication management at that end of the spectrum.
Recognize the Condition
Early CKD (G1-G3a) is frequently entirely asymptomatic and is identified on routine bloodwork or urinalysis rather than through symptoms — this is exactly why proactive testing in at-risk patients, not a wait-for-symptoms approach, is how most CKD is actually caught in time to intervene.
Leading causes of CKD
Identifying the underlying cause (the "C" in CGA) matters because it changes both the specific treatment and the referral threshold.
Diabetic kidney disease
The single leading cause of CKD. Classically presents with slowly progressive albuminuria, often with concurrent diabetic retinopathy. SGLT2 inhibitors and, where indicated, finerenone are specifically evidence-based here (see Choose Initial Treatment).
Hypertensive nephrosclerosis
Long-standing, often poorly-controlled hypertension causing progressive glomerular and vascular injury. Usually produces milder albuminuria than diabetic kidney disease. Blood pressure control is the central intervention.
Glomerulonephritis
An inflammatory or immune-mediated process (IgA nephropathy, lupus nephritis, ANCA-associated vasculitis, membranous nephropathy, and others). Suggested by hematuria, red cell casts, and disproportionate albuminuria/proteinuria relative to GFR. Needs nephrology referral and often a kidney biopsy to guide immunosuppressive therapy.
Polycystic kidney disease
The most common inherited cause of CKD, typically autosomal dominant. Progressive cyst growth and kidney enlargement; family history is the key clue. Tolvaptan can slow progression in selected patients under nephrology direction.
Obstructive / interstitial disease
Chronic urinary obstruction (benign prostatic hyperplasia, nephrolithiasis, retroperitoneal fibrosis) or chronic tubulointerstitial injury (chronic nephrotoxin exposure, reflux nephropathy, chronic pyelonephritis). Often reversible in part if the obstruction is relieved or the exposure stopped.
Symptoms and signs by stage
- G1-G3a: Usually asymptomatic. May have hypertension or mild edema; the only clue is often an abnormal eGFR or albumin-to-creatinine ratio (ACR) on routine testing.
- G3b-G4: Fatigue, mild edema, nocturia, and early laboratory complications become more common — anemia, secondary hyperparathyroidism, and mild metabolic acidosis.
- G5 (uremic symptoms): Nausea, anorexia, pruritus, restless legs, cognitive slowing, muscle cramps, and — at the more severe end — pericarditis, encephalopathy, or a bleeding tendency from uremic platelet dysfunction. These are the symptoms that ultimately drive the decision to start dialysis (see Choose Initial Treatment).
- Signs pointing to a specific cause: hematuria and edema (glomerulonephritis), palpable flank masses (polycystic kidney disease), or hesitancy/a palpable bladder (obstruction).
Risk Factors
- Diabetes mellitus — the leading cause of CKD; annual ACR and eGFR screening is standard of care in diabetes for exactly this reason.
- Hypertension, both as a cause and a consequence of CKD.
- Cardiovascular disease — atherosclerotic coronary, cerebral, or peripheral vascular disease shares risk factors with CKD and each accelerates the other.
- Family history of kidney failure or a hereditary kidney disease (polycystic kidney disease, Alport syndrome).
- Unexplained anemia — CKD is a common, under-recognized cause and should prompt an eGFR check.[2]
- Older age — GFR declines gradually with normal aging even without disease, but the threshold for calling this CKD is unchanged.
- A prior episode of acute kidney injury — an independent risk factor for de novo CKD and for accelerated progression of pre-existing CKD (see the Acute Kidney Injury chapter).
- Obesity, and a history of low birth weight or a solitary kidney (reduced nephron mass).
- Recurrent urinary tract obstruction, nephrolithiasis, or chronic urinary tract infection.
- Autoimmune disease (systemic lupus erythematosus, ANCA-associated vasculitis) and other causes of glomerulonephritis.
- Regular use of nephrotoxic medications, including chronic NSAID use and long-term lithium or calcineurin inhibitor therapy.
- Smoking — an independent, modifiable risk factor for CKD onset and progression.
- Indigenous ethnicity in the Canadian context — First Nations peoples are specifically identified by the Canadian Society of Nephrology as a high-risk population warranting proactive testing, reflecting both a higher burden of diabetes and hypertension and documented inequities in access to nephrology care and transplantation that pharmacists should be alert to when supporting these patients.[2]
Red Flags & Refer
Refer to nephrology for any of the following — referral is based on these triggers, not on having reached a specific "final" stage, and earlier referral consistently produces better outcomes than late referral.[2][1]
- eGFR under 30 mL/min/1.73m² (CKD G4 or G5), at any albuminuria category.
- Very high albuminuria — ACR over 60 mg/mmol (approximately over 300 mg/24h / A3 category), or a positive urine protein dipstick confirmed on 2 of 3 samples.[2]
- A progressive, sustained decline in eGFR — a persistent drop of more than 5 mL/min/1.73m²/year, or a sustained drop to a lower GFR category, confirmed on repeat testing rather than acted on from a single value.
- Unexplained or persistent hematuria, especially with red cell casts or dysmorphic red cells — raises concern for glomerulonephritis.
- Suspected hereditary kidney disease (a family history of kidney failure, or imaging findings suggestive of polycystic kidney disease).
- Inability to achieve treatment targets despite optimized primary-care management — uncontrolled hypertension on 3 or more agents, refractory hyperkalemia, or CKD-mineral bone disorder/anemia not responding to standard measures.[2]
- Acute kidney injury superimposed on CKD, or any abrupt, otherwise-unexplained fall in eGFR.
- A high predicted risk of kidney failure using a validated risk equation (e.g., the 4-variable Kidney Failure Risk Equation) — KDIGO's 2024 update specifically recommends using this alongside GFR/albuminuria category, since 2 patients in the same category can have materially different actual risk; a 5-year predicted kidney failure risk of roughly 3-5% or higher is a reasonable referral trigger, and a 2-year risk over 10% should prompt interdisciplinary/multidisciplinary CKD clinic involvement where available.[1]
Assessment & Diagnosis
The CGA classification
Every CKD diagnosis should be recorded as Cause – GFR category – Albuminuria category (e.g., "diabetic kidney disease, G3b A2") rather than as a single "stage" number — this is the actual KDIGO framework, and both the GFR and albuminuria categories independently and multiplicatively affect risk.[1] The Canadian Society of Nephrology formally reviewed and welcomed this GFR/albuminuria-category staging system — including the G3a/G3b split and the routine addition of albuminuria categories at every GFR level — as the framework Canadian nephrology practice should follow.[3]
| GFR category | eGFR (mL/min/1.73m²) | Term |
|---|---|---|
| G1 | ≥90 | Normal or high (only CKD if a damage marker is also present) |
| G2 | 60-89 | Mildly decreased (only CKD if a damage marker is also present) |
| G3a | 45-59 | Mildly to moderately decreased |
| G3b | 30-44 | Moderately to severely decreased |
| G4 | 15-29 | Severely decreased |
| G5 | <15 (or on dialysis) | Kidney failure |
| Albuminuria category | ACR | Term |
|---|---|---|
| A1 | <3 mg/mmol (<30 mg/g) | Normal to mildly increased |
| A2 | 3-30 mg/mmol (30-300 mg/g) | Moderately increased |
| A3 | >30 mg/mmol (>300 mg/g) | Severely increased |
The KDIGO risk heat-map
Combining the GFR and albuminuria category gives the overall risk of progression, cardiovascular events, and mortality — this grid, introduced in 2012, remains the structural basis of the 2024 update.[1]
| GFR category | A1 (normal-mild) | A2 (moderate) | A3 (severe) |
|---|---|---|---|
| G1 (≥90) | Low risk | Moderately increased risk | High risk |
| G2 (60-89) | Low risk | Moderately increased risk | High risk |
| G3a (45-59) | Moderately increased risk | High risk | Very high risk |
| G3b (30-44) | High risk | Very high risk | Very high risk |
| G4 (15-29) | Very high risk | Very high risk | Very high risk |
| G5 (<15) | Very high risk | Very high risk | Very high risk |
Monitoring frequency (see Monitoring & Follow-Up) and referral urgency both scale directly with this risk grid — a G1-G2 A1 patient with no other damage marker does not actually have CKD by definition and needs no special follow-up, while a G3a A3 patient is already at "very high risk" despite a relatively preserved GFR, purely because of the albuminuria.
Estimating GFR
Use a validated equation with serum creatinine (a race-free CKD-EPI-family equation is standard). Where the result will directly drive a clinical decision — a boundary between GFR categories, transplant or dialysis planning, or dosing of a narrow-therapeutic-index or clearance-critical medication — KDIGO's 2024 update recommends using a combined creatinine-cystatin C equation (eGFRcr-cys) in preference to creatinine alone, since it is more accurate and less affected by muscle mass.[1][4] For medication dosing specifically, use a body-surface-area-indexed eGFR (standardized eGFR × the patient's actual BSA ÷ 1.73m²) rather than the standardized value used for staging, since drug clearance tracks the patient's actual filtration, not the value normalized to an average body size.[4]
History, examination, and initial workup
- Duration of the abnormality (the 3-month criterion is essential to distinguish CKD from AKI or acute kidney disease), and the trajectory of eGFR/ACR over time.
- Diabetes and hypertension history and control, cardiovascular history, and family history of kidney disease.
- Full medication review specifically for nephrotoxin exposure — prescription, over-the-counter, and herbal/supplement products (see Drug Tables).
- Volume status, blood pressure, and signs pointing to a specific cause (edema, rash, palpable flank masses, a palpable bladder).
- Baseline labs: serum creatinine/eGFR, urine ACR, electrolytes, and — once G3a or beyond — calcium, phosphate, PTH, and a CBC with iron studies to screen for early CKD-mineral bone disorder and anemia.
- Renal ultrasound when the cause is unclear, when obstruction or polycystic kidney disease is suspected, or before a nephrotoxic contrast study in a patient with reduced eGFR.
- Kidney biopsy, arranged by nephrology, when glomerulonephritis or another process needing histological diagnosis is suspected.
Treatment Targets
- Slow progression toward kidney failure — blood pressure control, RAAS inhibition and SGLT2 inhibition in albuminuric CKD, glycemic control in diabetes, and correction of metabolic acidosis.
- Reduce cardiovascular risk, which exceeds the risk of progressing to kidney failure for most CKD patients — statin therapy where indicated, smoking cessation, and standard cardiovascular risk-factor management.
- Prevent and treat CKD's own complications as they arise — CKD-mineral bone disorder, anemia, hyperkalemia, and metabolic acidosis — rather than waiting for them to become severe.
- Avoid every avoidable nephrotoxic exposure, and correctly dose-adjust every renally-cleared medication to the patient's current level of kidney function, reassessed as that function changes.
- Refer to nephrology at the appropriate trigger point (see Red Flags & Refer) — not too early to burden a stable patient, and not so late that RRT planning is rushed.
- Plan renal replacement therapy proactively once it is anticipated — modality education, timely vascular access creation, and transplant referral where appropriate — rather than starting dialysis emergently.
- Once on dialysis, manage the medication issues specific to that population: nephrotoxin avoidance (now with essentially no reserve renal function), dialyzability-aware dosing and timing, and the practical realities of a fluid- and diet-restricted, multi-visit-per-week treatment schedule.
Choose Initial Treatment
First: RAAS inhibition. Start an ACE inhibitor or ARB (never both together — dual RAAS blockade increases hyperkalemia and AKI risk without added benefit) in every patient with CKD and albuminuria, regardless of blood pressure. Titrate to the highest approved and tolerated dose, not just a dose that controls blood pressure — the albuminuria-lowering, renoprotective effect is dose-dependent.[1][4] An initial eGFR decline of up to about 30% is expected and acceptable within the first 4 weeks; do not stop or reduce the dose for this alone. Check serum creatinine and potassium 2-4 weeks after starting or increasing the dose.[4]
Then: add an SGLT2 inhibitor. Add an SGLT2 inhibitor (e.g., empagliflozin or dapagliflozin) on top of a maximized RAAS inhibitor for type 2 diabetes with CKD at an eGFR of 20 mL/min/1.73m² or above, for CKD with heart failure with reduced ejection fraction, and for non-diabetic CKD with an eGFR of 20 or above and an ACR of 200 mg/g (roughly 20 mg/mmol) or higher.[1][4] As with RAAS inhibitors, expect and tolerate an initial eGFR dip. If tolerated, continue the SGLT2 inhibitor through disease progression all the way to dialysis initiation or transplant — do not stop it simply because eGFR has fallen further.[4] Hold it temporarily during acute dehydrating illness per sick-day (SADMANS) counselling — see the Acute Kidney Injury chapter.
Then, in type 2 diabetes with persistent albuminuria: add finerenone. Finerenone, a nonsteroidal mineralocorticoid receptor antagonist, is added on top of a maximized RAAS inhibitor (with or without an SGLT2 inhibitor) in type 2 diabetes with CKD and persistent albuminuria.[1][4] Do not start if serum potassium is above 5.0 mmol/L; recheck potassium and eGFR within about 4 weeks of starting or increasing the dose — hyperkalemia is its most common clinically significant adverse effect.[4] Finerenone is not a substitute for a steroidal MRA (spironolactone/eplerenone) in heart failure with reduced ejection fraction — the two have not been shown interchangeable for that indication.
Blood pressure: target a standardized office systolic blood pressure under 120 mmHg in most adults with CKD, individualized upward for frailty, symptomatic orthostatic hypotension, or limited life expectancy.[1][4] Most patients need 3 or more antihypertensive agents to reach target; a RAAS inhibitor should be part of that regimen whenever albuminuria is present.
Glycemic control: individualize the HbA1c target by CKD stage, hypoglycemia risk, and comorbidity — commonly under 7% in earlier CKD, relaxed toward 7.5-8% in advanced CKD or with significant hypoglycemia risk.[4] An SGLT2 inhibitor and, increasingly, a GLP-1 receptor agonist are preferred glucose-lowering agents in CKD given their independent cardiorenal benefit, on top of standard glycemic management.
Age 50 or older with CKD G3a-G5 not on dialysis: start a statin, or a statin/ezetimibe combination, regardless of baseline LDL-cholesterol — the absolute cardiovascular risk in this group justifies treatment without requiring a lipid threshold to be crossed first.
Age 18-49 with CKD: start a statin if there is known coronary disease, diabetes, a prior ischemic stroke, or an estimated 10-year risk of coronary death or myocardial infarction over 10%.
Already on dialysis: continue a statin already established before dialysis started, but do not routinely start a new statin purely for cardiovascular prevention once a patient is dialysis-dependent — trial evidence in this specific population has not shown the expected benefit.
Treat hyperkalemia rather than reflexively reducing or stopping an evidence-based RAAS inhibitor, SGLT2 inhibitor, or finerenone — losing a renoprotective drug is itself a harm to be weighed against the hyperkalemia.[4] Work through, in order: review and stop other hyperkalemia-contributing drugs where possible (NSAIDs, potassium-sparing diuretics used outside a deliberate MRA/finerenone indication, non-selective beta-blockers, trimethoprim); review dietary potassium intake; optimize diuretic therapy (a loop diuretic promotes kaliuresis); and add a potassium binder (patiromer or sodium zirconium cyclosilicate) specifically to enable continuation of the renoprotective drug.[4] Only reduce or stop the RAAS inhibitor/finerenone itself if hyperkalemia remains refractory to all of the above.
Metabolic acidosis: start oral sodium bicarbonate when serum bicarbonate is persistently low (roughly under 22 mmol/L) to correct the acidosis, with the goal of slowing CKD progression and improving nutritional and bone health.[1]
Base the decision to initiate dialysis on the development of uremic signs or symptoms, volume overload, or metabolic derangement refractory to medical management — not on reaching a fixed eGFR number in an otherwise well patient. Starting dialysis pre-emptively in an asymptomatic patient does not improve outcomes and adds treatment burden without benefit; the modern practice is a symptom- and complication-driven start, arrived at through a proactive planning process (modality education, timely vascular access) so that the start, when it happens, is not an emergency.
Non-Pharmacologic Treatment
- Sodium restriction (roughly under 2 g/day, i.e., under 90 mmol/day, sodium) to support blood pressure and albuminuria control — one of the most effective non-drug interventions available.
- Individualized dietary counselling as CKD advances — potassium and phosphate restriction guided by actual lab values (not applied reflexively before there is evidence of a problem), and protein moderation in advanced CKD to reduce uremic symptom burden, balanced against the real risk of malnutrition, especially once a patient is on dialysis and protein needs rise again.
- Smoking cessation — an independent, modifiable driver of CKD progression and cardiovascular risk.
- Regular physical activity and weight management as tolerated.
- Nephrotoxin avoidance in daily life — routine avoidance of NSAIDs, caution with herbal/supplement products of uncertain content, and the same sick-day medication-holding counselling (SADMANS) taught in the Acute Kidney Injury chapter, since a sick-day AKI on top of CKD is a major driver of permanent stepwise loss of function.
- Immunization: hepatitis B vaccination (ideally before dialysis or transplant is needed, since response is better with preserved kidney function), annual influenza vaccine, pneumococcal vaccination, and COVID-19 vaccination per current recommendations — CKD and dialysis patients are at increased risk of severe infection.
- Vein preservation: once CKD reaches G4-G5, avoid routine venipuncture and IV cannulation in the non-dominant forearm to preserve the vessels needed for a future arteriovenous fistula — a small, easily-missed counselling point with a real long-term consequence if ignored.
- Structured modality education (in-centre hemodialysis, home hemodialysis, peritoneal dialysis, pre-emptive transplant, or conservative kidney management without dialysis) well before kidney failure is reached, so the choice is the patient's own rather than made under emergency conditions.
- Fluid restriction, individualized and typically only needed once oliguric or on dialysis — not appropriate to impose earlier without a specific indication.
Special Populations
Pregnancy
CKD in pregnancy carries a materially higher risk of preeclampsia, preterm delivery, and accelerated maternal loss of kidney function. ACE inhibitors, ARBs, finerenone, and SGLT2 inhibitors are all contraindicated in pregnancy and should be stopped before conception is attempted where feasible, or as soon as pregnancy is confirmed; labetalol, nifedipine (extended-release), and methyldopa are the standard antihypertensive alternatives. Statins are also generally avoided in pregnancy. Because normal pregnancy increases GFR, interpret creatinine against pregnancy-adjusted expectations rather than the standard non-pregnant reference range (see the Acute Kidney Injury chapter for the same principle applied acutely). Pregnancy in a patient with advanced CKD or on dialysis needs joint nephrology/obstetric management from the outset.
Breastfeeding
Labetalol, nifedipine, and enalapril/captopril (specifically, at usual doses, once past the newborn period) are generally considered compatible with breastfeeding. Statins are typically avoided. Confirm the compatibility of any other CKD-specific medication against current lactation references before assuming it is safe, rather than extrapolating from the pregnancy contraindication alone.
Pediatrics
Pediatric CKD staging uses age-appropriate estimating equations (e.g., the bedside Schwartz equation) rather than the adult CKD-EPI-family equations in this chapter. Growth, nutrition, and developmental impact are central concerns distinct from adult CKD management, and every aspect of drug dosing and RRT planning should be individualized under pediatric nephrology direction rather than extrapolated from the adult recommendations above.
Older adults
Reduced renal reserve, higher rates of polypharmacy, and a higher prevalence of frailty combine to make dose adjustment and nephrotoxin avoidance especially important in this group. Individualize blood pressure targets upward where frailty or orthostatic symptoms are limiting factors. Conservative kidney management — active symptom-focused care without dialysis — is a legitimate, guideline-recognized choice for some frail older patients with advanced CKD, and should be presented as a genuine option during modality education rather than an implicit failure to treat.
Indigenous patients in Canada
First Nations peoples in Canada carry a disproportionate burden of the leading causes of CKD (diabetes and hypertension) and have been shown to face inequities in timely referral, vascular access creation, and transplant listing. The Canadian Society of Nephrology specifically flags this population for proactive CKD testing; pharmacists supporting these patients should be alert to both the higher baseline risk and the added importance of not letting systemic access barriers further delay guideline-indicated referral or renoprotective therapy.[2]
Monitoring & Follow-Up
Monitoring frequency
Frequency scales with the KDIGO risk heat-map — low-risk CKD (or a patient not meeting CKD criteria at all) needs only routine primary care follow-up, while very-high-risk categories (G4-G5, or any G3b-G5 with A3 albuminuria) warrant review roughly every 3-4 months or more often, and always with active nephrology involvement.[1] Recheck eGFR and ACR at least annually in low-to-moderate risk CKD, and more often — often every 3-6 months — as risk increases or after any medication change likely to affect kidney function.
What to monitor
- Serum creatinine/eGFR and urine ACR, at the frequency above.
- Serum potassium and creatinine within 2-4 weeks of starting or up-titrating a RAAS inhibitor, SGLT2 inhibitor, or finerenone, and periodically thereafter.
- Calcium, phosphate, PTH, and alkaline phosphatase starting at G3a, with frequency increasing through G3b-G5 (see Drug Tables for CKD-mineral bone disorder management once an abnormality is found).
- Hemoglobin, ferritin, and transferrin saturation starting at G3a, or sooner if anemia is otherwise unexplained.
- HbA1c and a lipid profile at standard intervals for a patient with diabetes or on a statin, respectively; routine re-checking of lipids purely to titrate a statin already started for the ≥50/eGFR<60 indication is not required.
- Blood pressure at every visit, with home monitoring encouraged.
- A full medication reconciliation at every CKD-related visit — this is the single best opportunity to catch a nephrotoxin that has crept back in, a dose that was never adjusted for a falling eGFR, or a drug that could now be simplified or stopped.
On dialysis
Dialysis-specific monitoring (dialysis adequacy, dry weight assessment, and vascular access surveillance) is managed by the dialysis unit, but medication reconciliation at every clinic and dialysis-unit encounter remains a core pharmacist contribution — this population's regimen changes frequently and is unusually vulnerable to accumulation errors, and dialyzability-aware dosing/timing decisions benefit from a dedicated renal-program pharmacy reference rather than a general renal dosing table alone[5] (see Drug Tables).
Common Errors to Avoid
- Stopping or reducing a RAAS inhibitor for an initial eGFR decline that is within the expected, acceptable range (up to about 30%) — this discards real renoprotective benefit for a change that does not itself indicate harm.[4]
- Combining an ACE inhibitor and an ARB together — no added renoprotective benefit, and a clearly increased risk of hyperkalemia and AKI.
- Continuing metformin or other drugs with an absolute low-eGFR cutoff without checking current renal function against that cutoff (see Drug Tables).
- Treating a single high-normal phosphate or PTH value reflexively rather than confirming a genuine trend first.
- Starting a new statin purely for primary cardiovascular prevention in a patient already dialysis-dependent.
- Over-correcting hemoglobin with an ESA to a normal range — trial evidence links normalizing hemoglobin in CKD with an increased risk of stroke and cardiovascular events, not improved outcomes.[7]
- Using NSAIDs, or missing chronic NSAID use on medication reconciliation, in a patient with reduced eGFR.
- Forgetting sick-day (SADMANS) medication-holding counselling in a CKD patient during an intercurrent dehydrating illness — the same principles that prevent AKI in a healthy kidney matter even more with reduced renal reserve.
- Referring too late — waiting for symptoms to appear at G5 rather than referring at the triggers in Red Flags & Refer, which leaves no time for modality education or vascular access planning.
- Missing the vein-preservation counselling point in G4-G5 CKD, compromising a future arteriovenous fistula site.
- Giving a phosphate binder without food, or separated from meals — it only works when taken with the meal whose phosphate it is meant to bind (see Drug Tables).
- Continuing a drug that is materially removed by hemodialysis on its usual outpatient schedule without adjusting the dose or timing around dialysis sessions once a patient starts dialysis.
Clinical Decision Algorithm
Drug Tables
How to use this table: Doses are adult doses and require patient-specific confirmation (renal/hepatic function, weight, allergy history). Pediatric dosing is weight-based per the current product monograph unless stated. Drug pricing is intentionally omitted. Select any drug name to open its complete Pharmasist Drug Database page.
General principles of renal drug dosing in CKD
- Use a body-surface-area-indexed eGFR (standardized eGFR × the patient's actual BSA ÷ 1.73m²), not the staging eGFR, when the number will directly set a dose — the staging value is normalized to an average body size and is not the right input for a dosing calculation.
- Where a dosing decision is genuinely finely balanced (a boundary between dose bands, transplant/dialysis planning, or a narrow-therapeutic-index drug), prefer a combined creatinine-cystatin C eGFR equation over creatinine alone if available — it is more accurate and less confounded by muscle mass.
- Loading doses are generally not reduced for reduced kidney function — they depend on volume of distribution, not clearance. It is the maintenance dose or the dosing interval that usually needs adjustment.
- Use therapeutic drug monitoring wherever it is available for narrow-therapeutic-index, renally-cleared drugs (vancomycin, aminoglycosides, digoxin) rather than adjusting by estimated function alone.
- Reassess every renally-cleared drug's dose again whenever eGFR changes materially — CKD is progressive, and a dose that was correct a year ago may no longer be.
- Consult the current product monograph or an institutional renal dosing reference for the individual drug in question; do not extrapolate one drug's adjustment to another drug in the same class.
Nephrotoxin Stewardship — Avoid or Use With Caution in CKD
"Nephrotoxin stewardship" means actively weighing the benefit of each agent below against its risk to a kidney with reduced reserve, substituting a safer alternative where one exists, and using the lowest effective dose/duration when a listed agent is genuinely needed.
| Drug / class | Renal concern in CKD | Recommended action | Comments |
|---|---|---|---|
| NSAIDs / COX-2 inhibitors | Hemodynamically-mediated further decline in GFR; sodium/fluid retention worsening blood pressure control | Avoid regular use; use acetaminophen for analgesia where appropriate | The most common preventable nephrotoxin exposure pharmacists encounter. Also see naproxen and celecoxib. |
| Proton pump inhibitors | Observational association with incident CKD and progression with long-term use | Use the lowest effective dose for the shortest appropriate duration; substitute an H2-receptor antagonist where clinically adequate | Not a reason to withhold a genuinely indicated PPI, but a reason to periodically reassess ongoing need. |
| Metformin | Risk of lactic acidosis accumulation as clearance falls | Continue at full dose eGFR ≥45; reduce dose 30-44; do not start below 45 and stop below 30 | Reassess at every eGFR check as CKD progresses — a dose appropriate at G3a may not be at G3b. |
| Aminoglycosides | Direct nephrotoxicity, especially with prolonged courses | Reserve for situations with no adequate less-nephrotoxic alternative; dose and monitor by level | Also see tobramycin and amikacin. |
| Iodinated contrast media | Contrast-associated AKI risk, greatest at eGFR ≤30 | Proceed when clinically indicated; individualize prophylaxis only at eGFR ≤30 | See the Acute Kidney Injury chapter for the full current (2022 Canadian Association of Radiologists) prevention framework. |
| Digoxin | Renally cleared; accumulation risk as eGFR falls | Reduce dose/maintenance interval for reduced eGFR; use levels to guide dosing | Toxicity risk compounded by the electrolyte disturbances (hypokalemia, hypomagnesemia) common in CKD. |
| Enoxaparin and other low-molecular-weight heparins | Renally cleared; accumulation increases bleeding risk at low eGFR | Dose-reduce at eGFR <30; consider unfractionated heparin instead if eGFR is very low or unstable | Confirm the current product-specific renal dosing threshold before use. |
| Direct oral anticoagulants | Variable renal clearance by agent; accumulation risk | Use a renally-appropriate agent and dose (apixaban has the most data at very low eGFR); avoid agents with predominantly renal clearance at very low eGFR | Also see rivaroxaban. Confirm the current eGFR cutoff in the product monograph before use or continuation. |
| Opioids (morphine, codeine, meperidine) | Active/toxic metabolite accumulation causing sedation, confusion, or seizures (meperidine) | Avoid meperidine entirely; use morphine/codeine cautiously at reduced dose/frequency or avoid; fentanyl and hydromorphone are generally better-tolerated alternatives | Also see hydromorphone and fentanyl. |
| Gabapentin and pregabalin | Renally cleared; accumulation causes sedation, ataxia, or myoclonus/encephalopathy | Reduce dose and/or dosing frequency proportional to eGFR; reduce further and dose after hemodialysis on dialysis days once on HD | Also see pregabalin. A frequently missed cause of otherwise-unexplained confusion in CKD. |
| Allopurinol | Renally cleared; a fixed low empiric dose under-treats while too-rapid uptitration risks toxicity | Start low and titrate the dose upward to a target urate level, monitoring for hypersensitivity, rather than leaving it fixed at a low renal-adjusted starting dose indefinitely | Also see febuxostat as an alternative not requiring the same renal dose adjustment. |
| Sulfamethoxazole/trimethoprim | Trimethoprim blocks renal potassium secretion, raising hyperkalemia risk on top of CKD/RAAS-inhibitor therapy | Use an alternative agent where feasible in advanced CKD, or monitor potassium closely if used | A commonly missed drug-disease interaction, especially in a patient already on a RAAS inhibitor. |
| Herbal and unregulated supplement products | Unpredictable content and a history of nephrotoxin contamination (e.g., aristolochic acid) | Ask specifically about herbal/supplement use at every medication reconciliation; discourage unregulated products in CKD | Patients frequently do not volunteer these unless asked directly. |
CKD-Mineral and Bone Disorder — Phosphate Binders, Vitamin D, and Calcimimetics
Monitor calcium, phosphate, and PTH as a trend over serial measurements, not by single values, and treat the whole picture rather than one number in isolation.
| Drug | Dosage / use | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Calcium carbonate | Use: With meals, dosed to the phosphate content of that meal | Hypercalcemia; constipation | Reduces absorption of many oral drugs taken concurrently | A calcium-containing phosphate binder — limit total elemental calcium intake to avoid vascular calcification risk. |
| Sevelamer | Use: With meals, dosed to the phosphate content of that meal | GI upset; does not cause hypercalcemia | Reduces absorption of many oral drugs — separate dosing where interaction is significant | Preferred where calcium load should be limited (e.g., vascular calcification, hypercalcemia risk). |
| Lanthanum | Use: With meals, dosed to the phosphate content of that meal | GI upset; chewable formulation requires adequate chewing | Reduces absorption of many oral drugs — separate dosing where interaction is significant | A non-calcium-containing binder alternative to sevelamer. |
| Calcitriol | Use: Per current PTH trend and calcium/phosphate status | Hypercalcemia; hyperphosphatemia if used without adequate phosphate control | Additive hypercalcemia risk with calcium supplements/binders | Reserve for CKD G4-G5 with severe, progressive hyperparathyroidism — not routine in earlier CKD not on dialysis. |
| Alfacalcidol | Use: Per current PTH trend and calcium/phosphate status | Hypercalcemia; hyperphosphatemia if used without adequate phosphate control | Additive hypercalcemia risk with calcium supplements/binders | An alternative active vitamin D analog to calcitriol; same reservation for G4-G5 with progressive hyperparathyroidism. |
| Vitamin D3 (cholecalciferol) | Use: Per measured 25(OH)D level, repeated per baseline value and response | Hypercalcemia at high doses | Additive hypercalcemia risk with active vitamin D analogs/calcium supplements | Used to correct nutritional 25(OH)D (calcidiol) deficiency/insufficiency — a distinct goal from active vitamin D analog therapy above. |
| Cinacalcet | Use: Titrated to PTH trend and calcium status | Hypocalcemia; GI upset | Reduce or stop if hypocalcemia develops, accounting for concurrent medications | A calcimimetic used for PTH lowering, typically in dialysis-dependent CKD (G5D). |
Anemia of CKD — Iron and Erythropoiesis-Stimulating Agents
Correct iron deficiency before or alongside starting an ESA — an iron-deficient patient will not respond adequately to an ESA regardless of dose. Investigate anemia rather than attributing it to CKD by default.
| Drug | Dosage / use | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Ferrous sulfate (oral iron) | Use: A therapeutic trial when TSAT ≤30% and ferritin ≤500 mcg/L | GI upset, constipation; poor tolerability limits use | Reduced absorption with concurrent phosphate binders, antacids, and some other oral drugs — separate dosing | A reasonable initial trial in non-dialysis CKD; oral absorption is often inadequate once on dialysis. |
| Iron sucrose (IV iron) | Use: Per institutional IV iron protocol, guided by TSAT/ferritin | Hypotension with rapid infusion; rare hypersensitivity | None significant | Preferred over oral iron in dialysis-dependent CKD given poor oral absorption and the convenience of IV access during a dialysis session. |
| Ferric carboxymaltose (IV iron) | Use: Per institutional IV iron protocol, guided by TSAT/ferritin | Hypophosphatemia (agent-specific); rare hypersensitivity | None significant | An alternative IV iron formulation allowing larger single-dose administration. |
| Epoetin alfa | Use: Titrated to an individualized hemoglobin target, not a normal-range hemoglobin | Hypertension; increased thromboembolic risk, especially if hemoglobin is over-corrected | None significant | Start once hemoglobin approaches/falls below approximately 100 g/L, individualized; do not target a normal hemoglobin. |
| Darbepoetin alfa | Use: Titrated to an individualized hemoglobin target, not a normal-range hemoglobin | Hypertension; increased thromboembolic risk, especially if hemoglobin is over-corrected | None significant | A longer-acting erythropoiesis-stimulating agent allowing less frequent dosing than epoetin alfa. |
Potassium and Acidosis Management
Used specifically to enable continuation of a RAAS inhibitor, SGLT2 inhibitor, or finerenone (potassium binders) or to slow progression and improve nutritional/bone status (sodium bicarbonate) — see Choose Initial Treatment for the full stepwise approach.
| Drug | Dosage / use | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Patiromer | Use: Once daily, separated from other oral medications by ≥3 hours | GI upset (constipation); hypomagnesemia | Binds many oral drugs in the gut — separate administration by at least 3 hours | Onset over several hours; not for acute/emergency hyperkalemia management. |
| Sodium zirconium cyclosilicate | Use: Per product dosing, separated from other oral medications by ≥2 hours | Edema (sodium load); hypokalemia if over-corrected | Reduced absorption of some concurrent oral drugs — separate administration by ≥2 hours | Faster onset than patiromer. |
| Sodium polystyrene sulfonate | Use: Per current product dosing, only where the newer agents are unavailable or not tolerated | GI upset; rare but serious intestinal necrosis, particularly with sorbitol-containing formulations | Binds many oral drugs in the gut — separate administration | Largely superseded by the two agents above where available, given the weaker evidence base and the intestinal necrosis signal. |
| Sodium bicarbonate | Use: Oral, titrated to serum bicarbonate roughly ≥22 mmol/L | Sodium/volume load; can worsen hypertension or edema if excessive | None significant | For persistent metabolic acidosis, not for acute severe acidosis, which is managed as in the Acute Kidney Injury chapter. |
Dialysis-Specific Medication Considerations
The same renal-dosing logic that applies through CKD G3a-G5 continues on dialysis, but with essentially no residual clearance to buffer an error, and with a new variable: whether hemodialysis itself removes a meaningful fraction of the drug. A drug that is significantly cleared by hemodialysis may need a supplemental dose after a session, or its scheduled dose timed to after dialysis rather than before, to avoid dosing into the dialyzer.
| Medication / class | Significantly removed by hemodialysis? | Timing / dose adjustment | Comments |
|---|---|---|---|
| Antihypertensives (e.g., ACE inhibitors, ARBs, beta-blockers) | Varies by agent | Consider holding the dialysis-day morning dose, or dosing after the session, to reduce intradialytic hypotension risk | Individualize by the patient's actual intradialytic blood pressure pattern, not a blanket rule for every agent. |
| Renally-cleared antibiotics (e.g., vancomycin, many beta-lactams) | Yes, for many agents | Time doses to the end of, or immediately after, the hemodialysis session on dialysis days; use levels to guide vancomycin dosing specifically | Confirm dialyzability and the recommended supplemental dose for the specific antibiotic and dialyzer type in current use — this varies by agent and by dialysis membrane. |
| Gabapentin / pregabalin | Yes | Reduced dose, given after hemodialysis on dialysis days, with reduced frequency on non-dialysis days | A common, preventable cause of post-dialysis sedation or myoclonus if not adjusted. |
| Digoxin | Minimally (large volume of distribution limits removal) | Dose by pre-dialysis level, not timed specifically around the session | Electrolyte shifts during dialysis (potassium, calcium) can transiently increase arrhythmia risk independent of the digoxin level itself. |
| Metformin | Not applicable — contraindicated | Do not use | Absolute contraindication once dialysis-dependent, given lactic acidosis risk with minimal-to-no residual renal clearance. |
| Phosphate binders | Not applicable (not systemically absorbed/acting in the gut) | With every meal and substantial snack — timing to food, not to the dialysis schedule, is what matters | The one dialysis-population drug class whose timing is deliberately independent of the dialysis schedule. |
| Erythropoiesis-stimulating agents and IV iron | No (not meaningfully removed) | Commonly given during the dialysis session for practical vascular-access convenience | Timing here is about convenience, not pharmacokinetics. |
| Heparin (circuit anticoagulation) | Used within the extracorporeal circuit itself | Per the dialysis unit's protocol for that session | Interacts with the patient's own home anticoagulant/antiplatelet therapy — reconcile bleeding risk across both. |
| NSAIDs | Not applicable | Avoid | Compounds bleeding risk from circuit heparinization on top of the platelet dysfunction of uremia, with essentially no residual urine output left to protect. |
References
- KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease — Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. Kidney Int 2024;105(4S):S117-S314
- Care and Referral of Adult Patients with Reduced Renal Function: Recommendations from the Canadian Society of Nephrology — Canadian Society of Nephrology (CSN). Canadian Society of Nephrology clinical resource
- Canadian Society of Nephrology Commentary on the KDIGO Clinical Practice Guideline for CKD Evaluation and Management — American Journal of Kidney Diseases (Akbari A, Clase CM, Acott P, Battistella M, et al.; Canadian Society of Nephrology). Am J Kidney Dis 2015;65(2):177-205
- KDIGO 2024 Clinical Practice Guideline on Evaluation and Management of Chronic Kidney Disease: A Primer on What Pharmacists Need to Know — American Journal of Health-System Pharmacy (Awdishu L, Maxson R, Gratt C, Rubenzik T, Battistella M). Am J Health Syst Pharm 2025;82(12):660-671
- Pharmacy & Formulary — Clinical Resources for Renal Medication Management — BC Renal, Provincial Health Services Authority (British Columbia). BC Renal clinical resource, accessed August 2026
- KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) — Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Update Work Group. Kidney Int Suppl 2017;7(1):1-59
- Executive Summary of the KDIGO 2026 Clinical Practice Guideline for the Management of Anemia in Chronic Kidney Disease (CKD) — Kidney International (Babitt JL, Tonelli M, et al.; KDIGO Anemia in CKD Work Group). Kidney Int 2026;109(1):44-56
Professional reference only. Apply clinical judgment and verify patient-specific decisions against current authoritative guidance and product information.