Chronic Kidney Disease for the NP Exam: KDIGO Staging, Albuminuria, Kidney-Protective Drugs and Dose Adjustment

Chronic kidney disease is defined by KDIGO as abnormal kidney structure or function present for more than 3 months, and it is always staged on two axes: GFR category (G1 to G5) and albuminuria category (A1 to A3). The provider's job after staging is threefold. Start kidney-protective therapy (an ACE inhibitor or ARB at the highest tolerated dose when albuminuria is present, and an SGLT2 inhibitor for most patients with an eGFR of 20 or more), adjust every renally cleared drug to the current GFR, and refer when KDIGO 2024 criteria are met. Monitoring follows the same logic: check blood pressure, creatinine and potassium within 2 to 4 weeks of any change in kidney-active therapy, and continue it unless creatinine rises by more than 30%.

Assessment: confirming CKD

KDIGO 2024 practice points shape the first visit:

• Test both markers. Anyone at risk (diabetes, hypertension, cardiovascular disease, family history, prior acute kidney injury) gets an eGFR and a urine albumin-to-creatinine ratio (ACR). Dipstick protein is not enough.
• Repeat abnormal results. An incidental low eGFR, raised ACR or hematuria is repeated to confirm. A single low eGFR may be acute kidney injury.
• Prove chronicity. More than 3 months of abnormality, shown by repeat testing, earlier results, imaging (small kidneys, thin cortex) or history.
• Find the cause. Diabetes and hypertension are the common causes, but the history should cover NSAIDs and other nephrotoxins, urinary obstruction, autoimmune disease, hereditary kidney disease and recurrent stones. Urinalysis with microscopy and kidney ultrasound are standard early tests.

Estimating GFR

KDIGO 2024 recommends creatinine-based eGFR for initial assessment, using a validated equation without a race term; in the United States that is the 2021 CKD-EPI equation. When cystatin C is available, a combined creatinine-cystatin C equation is recommended in situations where creatinine-based eGFR is less accurate: low or high muscle mass, amputation, frailty, malnutrition, liver disease, or when the result will change a treatment decision.

Measuring albuminuria

The preferred test is a urine ACR, ideally on a first-morning sample. Exercise, fever, infection, menstruation and marked hyperglycemia can raise it temporarily, so abnormal values are confirmed.

KDIGO staging

A complete stage names the cause, the G category and the A category, for example "diabetic kidney disease, G3a A2." Risk of progression and cardiovascular events rises with both axes, which is why KDIGO's heat map uses them together.

Monitoring frequency

KDIGO 2024 asks for eGFR and ACR at least annually in everyone with CKD, and more often in those at higher risk of progression when the result will change management. Two thresholds help decide whether a change is real:

• An eGFR change of more than 20% on a later test exceeds expected variability and warrants evaluation.
• A doubling of ACR exceeds laboratory variability and warrants evaluation.

For people in G3 to G5, KDIGO recommends a validated risk equation such as the Kidney Failure Risk Equation (KFRE) to estimate the absolute risk of kidney failure.

Kidney-protective therapy

Blood pressure

KDIGO 2024 suggests a target systolic blood pressure below 120 mm Hg, when tolerated, using standardized office measurement.

ACE inhibitors and ARBs (renin-angiotensin system inhibitors)

Practice points the exam targets:

• Use the highest approved dose that is tolerated, because trial benefit came at those doses.
• Check blood pressure, creatinine and potassium within 2 to 4 weeks of starting or increasing the dose.
• Continue unless creatinine rises by more than 30% within 4 weeks. A smaller rise reflects the expected hemodynamic effect.
• Treat hyperkalemia with measures that lower potassium (dietary review, diuretics, potassium binders) before reducing or stopping the drug.
• Reduce or stop for symptomatic hypotension, uncontrolled hyperkalemia despite treatment, or to ease uremic symptoms at an eGFR below 15.
• Continue even when eGFR falls below 30.

SGLT2 inhibitors

Once started, an SGLT2 inhibitor can be continued below an eGFR of 20 unless not tolerated or dialysis begins. The early, reversible dip in eGFR is not a reason to stop, and starting one does not change the monitoring schedule. Withhold it during prolonged fasting, surgery or critical illness because of ketoacidosis risk.

Other agents

• Nonsteroidal mineralocorticoid receptor antagonist (finerenone): suggested for adults with type 2 diabetes, an eGFR above 25, normal potassium and an ACR above 30 mg/g despite a maximally tolerated ACE inhibitor or ARB. Monitor potassium after starting.
• GLP-1 receptor agonist: recommended in type 2 diabetes with CKD when glycemic targets are not met on metformin and an SGLT2 inhibitor, choosing an agent with proven cardiovascular benefit.
• Statins: adults 50 and older with an eGFR below 60, not on dialysis, receive a statin or statin plus ezetimibe.

Drug dosing in CKD

KDIGO 2024 treats medication safety as part of CKD care:

• Consider GFR whenever a drug is cleared by the kidney.
• Creatinine-based eGFR is appropriate for dosing in most people. Where precision matters (narrow therapeutic range, toxicity, unreliable creatinine), use a creatinine-cystatin C equation or measured GFR.
• At extremes of body size, an eGFR not indexed to body surface area may be needed for narrow-range drugs.
• Review over-the-counter drugs and supplements; NSAIDs are the classic nephrotoxin.
• Before elective surgery, consider pausing metformin, ACE inhibitors, ARBs and SGLT2 inhibitors 48 to 72 hours ahead, with a clear plan to restart.

eGFR or creatinine clearance?

Many FDA labels give renal dosing by Cockcroft-Gault creatinine clearance: (140 minus age) times weight in kg, divided by (72 times serum creatinine), multiplied by 0.85 for women. FDA's 2024 renal impairment guidance for industry allows either creatinine clearance or eGFR to characterize kidney function in labeling studies. For the exam, follow the measure named in the vignette or the label; for direct oral anticoagulants, the labels and KDIGO's perioperative table use creatinine clearance.

Metformin by eGFR (FDA labeling)

Other drugs that commonly need GFR-based adjustment include DPP-4 inhibitors other than linagliptin, gabapentin and pregabalin, many antibiotics, and direct oral anticoagulants. Confirm each dose against the current label.

Referral to specialist kidney care

KDIGO 2024 lists these circumstances:

• eGFR below 30 mL/min/1.73 m2.
• A 5-year kidney failure risk of more than 3 to 5% on a validated risk equation.
• A sustained fall in GFR of more than 20%, or more than 30% in people starting hemodynamically active therapy.
• Albuminuria with an ACR of 300 mg/g or more in combination with hematuria, a consistent ACR above 700 mg/g, or a 2-fold rise in albuminuria in someone with significant albuminuria.
• Urinary red cell casts, or more than 20 red cells per high-power field, sustained and not readily explained.
• Hypertension refractory to 4 or more antihypertensive agents.
• Persistent abnormalities of serum potassium.
• Uncertain cause, hereditary kidney disease, or recurrent extensive nephrolithiasis.
• Complications: acidosis, anemia, bone disease or malnutrition.

Acute kidney injury or a rapid unexplained decline needs urgent evaluation, and symptoms of uremia, volume overload or severe hyperkalemia need emergency care.

Patient and family education

• CKD is often silent; the blood and urine tests are how progression is tracked.
• Avoid NSAIDs such as ibuprofen and naproxen; acetaminophen within labeled limits is usually preferred.
• Sick-day guidance: during vomiting, diarrhea or poor intake, the provider may advise pausing SGLT2 inhibitors, ACE inhibitors or ARBs, diuretics and metformin, and restarting when eating and drinking normally.
• A small creatinine rise after starting an ACE inhibitor, ARB or SGLT2 inhibitor is expected and does not mean the kidneys are failing.
• Genital hygiene matters with SGLT2 inhibitors because of mycotic infection risk.
• Bring every medicine and supplement to each visit; tell every prescriber about the kidney disease.
• Family members may need screening if the cause is hereditary, and caregivers can help with blood pressure logs.

How the exam tests this

• Staging on one axis. An answer that ignores albuminuria is incomplete; G3a A3 carries more risk than G3b A1.
• Stopping the ACE inhibitor for a small creatinine rise. A rise under 30% within 4 weeks is expected; the answer is to continue.
• Dual blockade. Adding an ARB to an ACE inhibitor for more albuminuria reduction is a classic wrong answer.
• Withholding an SGLT2 inhibitor at an eGFR of 25. It can be started at an eGFR of 20 or more.
• Metformin thresholds. Do not start at 30 to 44; contraindicated below 30. Stopping metformin at an eGFR of 50 is wrong.
• Calling CKD after one value. Chronicity needs more than 3 months.
• Referral reflex. An eGFR of 48 with ACR 150 mg/g and no hematuria does not meet referral criteria; an eGFR below 30 does.

Practice question

A 63-year-old man with type 2 diabetes and hypertension has an eGFR of 48 mL/min/1.73 m2 and a urine ACR of 420 mg/g, both confirmed over 4 months. Urinalysis shows no blood. He takes metformin 1,000 mg twice daily and lisinopril 40 mg daily. Blood pressure is 128/76 mm Hg, potassium is 4.6 mEq/L, and A1c is 7.1%. Which of the following is the most appropriate next step?

• A. Stop metformin because of his eGFR
• B. Add an SGLT2 inhibitor
• C. Add losartan to further reduce albuminuria
• D. Refer to nephrology for an ACR above 300 mg/g

Answer: B. He has G3a A3 diabetic kidney disease on a maximal ACE inhibitor, and KDIGO 2024 recommends an SGLT2 inhibitor for type 2 diabetes with CKD and an eGFR of 20 or more. Metformin (A) can continue at an eGFR of 48; FDA labeling contraindicates it only below 30 and advises against starting it between 30 and 44. Adding losartan (C) creates dual renin-angiotensin blockade, which KDIGO recommends avoiding because of hyperkalemia and acute kidney injury. Referral (D) is not yet required: KDIGO lists an ACR of 300 mg/g or more combined with hematuria, or a consistent ACR above 700 mg/g, and he has neither, though a KFRE estimate could still change that decision.

Key points

Related NPPace guides

• Genitourinary Presentations in Primary Care: BPH, Overactive Bladder, Urethritis and When to Refer
• GERD and H. pylori on the NP Exam: PPI Trials, Alarm Features, Testing and Eradication Regimens
• Irritable Bowel Syndrome in Primary Care: Rome IV Diagnosis, Red Flags and Treatment by Subtype
• How to Read a Primary-Care Vignette Like a Provider: The 5-Step Method
• AANP vs ANCC: Which NP Certification Exam Should You Take?