Chronic Kidney Disease

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.

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.

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).

• 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]

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]

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]

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.

• 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.

• 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.

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 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).

1. eGFR continues to decline despite optimized therapy: confirm true adherence, re-screen for a missed reversible cause (obstruction, volume depletion, an unrecognized nephrotoxin, NSAID use), confirm the RAAS inhibitor is actually at the highest tolerated dose, and add an SGLT2 inhibitor (and finerenone, if indicated) if not already used. Refer to nephrology if not already under their care.
2. Hyperkalemia remains refractory despite dietary review, stopping other contributing drugs, diuretic optimization, and a potassium binder: involve nephrology before reducing or stopping the RAAS inhibitor/finerenone, since that step trades away proven renoprotection.^[4]
3. Blood pressure remains above target on 3 or more agents including a RAAS inhibitor and a diuretic: reassess adherence and volume status, screen for a secondary cause, and refer if not already done — resistant hypertension in CKD is itself a referral trigger.
4. PTH remains above target despite phosphate control and vitamin D/analog therapy: reassess for uncorrected hyperphosphatemia or hypocalcemia as the driver before escalating to or adding a calcimimetic, guided by the trend over serial measurements rather than a single value.^[6]
5. Anemia does not respond to an ESA and adequate iron stores: investigate for ESA hyporesponsiveness — occult bleeding, unrecognized inflammation or infection, undertreated hyperparathyroidism, vitamin B12/folate deficiency, or true iron deficiency despite seemingly adequate ferritin (an unreliable marker during inflammation) — rather than simply escalating the ESA dose further.^[7]
6. Uremic symptoms emerge or volume overload becomes refractory to diuretics despite maximized medical therapy: this is the trigger to finalize dialysis initiation, not a reason to intensify diuretic dosing indefinitely.

• 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.

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.

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.

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.

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.

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.