Management of Hypertension in Chronic Kidney Disease
Blood Pressure Targets Based on Albuminuria Status
For CKD patients with significant albuminuria (≥30 mg/day or ACR ≥30 mg/g), target blood pressure <130/80 mmHg using standardized office measurement. 1, 2 This lower target provides optimal cardiovascular and renal protection in the presence of proteinuria. 2
For CKD patients without significant albuminuria, target blood pressure <140/90 mmHg. 2, 3 Lower targets have not demonstrated additional kidney or cardiovascular benefit in this population. 2, 3
When standardized automated office blood pressure measurement is used (5-minute rest, average of three readings), a systolic target <120 mmHg may be considered for cardiovascular protection, though the renal benefit at this level is less certain. 1, 2 This aggressive target applies only to standardized measurement technique—applying it to routine office readings will lead to overtreatment. 1, 2
For IgA nephropathy with proteinuria >1 g/day specifically, consider an even tighter goal of 125/75 mmHg. 1
Stepwise Pharmacologic Management
First-Line Therapy: ACE Inhibitors or ARBs
Initiate an ACE inhibitor as first-line therapy for all CKD patients with albuminuria ≥300 mg/day (or ACR ≥300 mg/g). 1, 2, 3 This is a strong (1B) recommendation from KDIGO. 1
For moderately increased albuminuria (30-300 mg/day or ACR 30-300 mg/g), either an ACE inhibitor or ARB is suggested as first-line therapy. 1, 2
If an ACE inhibitor is not tolerated (e.g., due to cough), substitute an ARB—the renal and cardiovascular benefits are comparable. 2, 3
Titrate the ACE inhibitor or ARB to the maximum approved dose that the patient can tolerate, as trial benefits were achieved at these doses. 1, 2, 3 For example, losartan should be titrated to 100 mg daily if tolerated. 4
For CKD patients without significant albuminuria, initial therapy can include a dihydropyridine calcium-channel blocker, a thiazide diuretic, or an ACE inhibitor/ARB—any of these classes is reasonable. 2, 3 ACE inhibitors do not confer additional renoprotective benefit over calcium-channel blockers or thiazides when albuminuria is absent. 2
Second-Line Therapy: Diuretics or Calcium-Channel Blockers
Add a thiazide-type diuretic (chlorthalidone or indapamide preferred over hydrochlorothiazide) when eGFR >30 mL/min/1.73 m² and blood pressure remains uncontrolled on ACE inhibitor/ARB monotherapy. 2, 3 Thiazide-like agents provide superior cardiovascular event reduction. 2
For CKD stage 4 (eGFR 15-29 mL/min/1.73 m²) or stage 5, switch to a loop diuretic instead of a thiazide. 2, 3, 5
Alternatively, add a long-acting dihydropyridine calcium-channel blocker (amlodipine 5-10 mg daily or nifedipine extended-release) as second-line therapy. 2, 3
A single-pill fixed-dose combination of the ACE inhibitor/ARB plus the chosen second agent is strongly recommended to improve adherence. 2
Third-Line Therapy: Triple Combination
If blood pressure remains uncontrolled on dual therapy, add the third class not yet used (the remaining thiazide-like diuretic or calcium-channel blocker), creating an ACE-inhibitor + CCB + thiazide regimen. 2 A single-pill triple combination is preferred. 2
Most CKD patients require three or more antihypertensive agents to achieve target blood pressure. 2, 3
Resistant Hypertension: Mineralocorticoid Receptor Antagonists
For resistant hypertension (uncontrolled on three agents including a diuretic), add a mineralocorticoid receptor antagonist (spironolactone or eplerenone) with close monitoring for hyperkalemia. 2, 3
Beta-blockers may be added when there are compelling indications such as coronary artery disease or heart failure, but are not recommended as first-line agents in CKD with proteinuria. 2, 3
Critical Contraindications
NEVER combine an ACE inhibitor with an ARB (dual RAS blockade)—this is a strong (1B) contraindication from KDIGO because it increases hyperkalemia, hypotension, and acute kidney injury without added benefit. 2, 3, 5
Avoid triple therapy that adds a direct renin inhibitor to an ACE inhibitor + ARB. 2
Monitoring Protocol After Initiating or Titrating RAS Inhibitors
Check serum creatinine, potassium, and eGFR 2-4 weeks after starting or increasing the dose of an ACE inhibitor or ARB. 2, 3
Continue the RAS inhibitor unless serum creatinine rises >30% within 4 weeks—a rise up to 30% is expected and reflects the intended hemodynamic effect on intraglomerular pressure. 2, 3, 6 This initial eGFR dip is reversible and should not be interpreted as treatment failure. 3
If creatinine rises >30% and persists, investigate for volume contraction, nephrotoxic agents (NSAIDs), or renovascular disease before discontinuing the RAS inhibitor. 3, 5
Manage hyperkalemia with potassium-wasting diuretics, potassium binders (e.g., patiromer, sodium zirconium cyclosilicate), or dietary potassium restriction (<2-3 g/day) rather than stopping the RAS inhibitor. 2, 6
Discontinue or reduce the ACE inhibitor/ARB only if hyperkalemia is uncontrolled despite measures, the patient develops symptomatic hypotension, or the creatinine increase >30% persists after excluding other causes. 2, 3
Follow-Up Schedule
Schedule clinic visits every 6-8 weeks until the blood pressure target is safely achieved. 2, 3
Once the target is reached, follow up every 3-6 months based on medication regimen and patient stability. 2, 3
Implement home blood pressure monitoring during medication titration to prevent hypotension (systolic <110 mmHg) and to detect masked hypertension, which occurs in up to 30% of CKD patients. 2, 5
Repeat a basic metabolic panel 2-4 weeks after adding or adjusting any agent that affects electrolytes or renal function. 2, 3
Monitor eGFR, serum creatinine, and urine albumin-to-creatinine ratio at least annually (typically 2-4 times per year for CKD stage 3 or higher). 2, 3 A reduction in albuminuria signals effective therapy. 2
Assess patients for symptoms of hypotension such as fatigue, light-headedness, or dizziness at each visit. 2, 3
Lifestyle Modifications
Limit dietary sodium to <2 g/day (≈5 g salt) because CKD patients with albuminuria are often salt-sensitive. 2, 3
Restrict protein intake to ≈0.8 g/kg/day for CKD stages 3-5 and avoid high-protein diets >1.3 g/kg/day. 2, 3
Encourage at least 150 minutes per week of moderate-intensity physical activity. 2
Advise tobacco cessation. 2, 3
Promote maintenance of a healthy body weight appropriate for age and comorbidities. 2
Patient Education: Sick-Day Management
Instruct patients to hold or reduce antihypertensive doses during acute illnesses with vomiting, diarrhea, or reduced oral intake to prevent volume depletion and acute kidney injury. 2, 3
Teach patients to watch for symptoms of hypotension such as fatigue, light-headedness, or dizziness. 2, 3
Advise patients not to use salt substitutes containing potassium without consulting their physician, as these can precipitate hyperkalemia on ACE inhibitor/ARB therapy. 6
Special Populations and Nuances
CKD Stage 3b-4 (eGFR 15-44 mL/min/1.73 m²)
Target <140/90 mmHg for CKD stage 4, as there is insufficient high-quality data for more aggressive targets in advanced CKD. 5 Most major trials, including SPRINT, excluded patients with advanced CKD. 5
Caution is warranted with intensive blood pressure lowering in advanced CKD, as the risk of acute kidney injury is higher than in earlier CKD stages. 5
Among older individuals with advanced CKD, diastolic blood pressure is often low due to increased arterial stiffness, making aggressive systolic blood pressure lowering potentially problematic. 5
Diabetic CKD
Apply the same blood pressure targets and treatment principles as non-diabetic CKD: <130/80 mmHg for albuminuria ≥30 mg/day, <140/90 mmHg without albuminuria. 2, 3
Use an ACE inhibitor or ARB as first-line therapy for diabetic CKD with albuminuria ≥30 mg/day. 2, 3
Incorporate diabetes-specific therapies such as SGLT2 inhibitors and GLP-1 receptor agonists, which provide additional cardiovascular and renal protection. 2
Elderly or Frail Patients
Community-dwelling adults ≥65 years can safely target systolic blood pressure <130 mmHg if tolerated. 3 A SPRINT subgroup analysis showed that frail elderly patients (≥75 years) also benefit from lower systolic blood pressure targets, even among those with the slowest gait speed. 3
Age alone should not preclude appropriate blood pressure control, but monitor closely for symptomatic postural hypotension. 2, 3
Black Patients with CKD
For Black patients with CKD and albuminuria, initiate an ACE inhibitor or ARB as first-line therapy. 5
For Black patients with CKD without albuminuria, initial therapy should include a thiazide diuretic or calcium-channel blocker, with an ACE inhibitor or ARB added if proteinuria is present. 5
Use the race-free CKD-EPI equation (2021) for estimating eGFR in Black patients, eliminating the previous race multiplier. 2 This may reclassify some Black patients to more advanced CKD stages, prompting earlier interventions. 2
Women of Childbearing Age
Discontinue ACE inhibitors or ARBs in women considering pregnancy or who become pregnant, as these agents are teratogenic. 2, 6
Common Pitfalls to Avoid
Do not apply the <120 mmHg target to routine office blood pressure measurements—it requires standardized automated measurement (5-minute rest, average of three readings). 1, 2, 3 Applying it to typical office readings yields higher values and leads to overtreatment. 1
Do not discontinue an ACE inhibitor/ARB for a creatinine rise <30%—this reflects the intended hemodynamic effect and is expected. 2, 3, 6
Never combine an ACE inhibitor with an ARB, as this increases harm without benefit. 2, 3, 5
A blood pressure of <140/90 mmHg is insufficient for patients with albuminuria ≥30 mg/day—a lower target <130/80 mmHg must be pursued. 2, 3
Do not withhold antihypertensive therapy solely because of a small drop in eGFR—stable kidney function is expected even with modest eGFR declines. 2
Recognize that the initial eGFR dip after starting RAS blockade is expected and reversible; it should not be interpreted as treatment failure. 3
Avoid initiating ACE inhibitor/ARB in patients with abrupt-onset nephrotic syndrome (e.g., minimal change disease) because of the risk of acute kidney injury. 3