Comprehensive Management of Chronic Kidney Disease
Foundation: Lifestyle Modifications for All CKD Patients
Every patient with CKD requires a foundation of lifestyle interventions before layering pharmacologic therapies. 1
- Dietary sodium restriction to <2 g/day (<90 mmol/day) enhances blood pressure control and slows CKD progression 2
- Target BMI 20-25 kg/m² through weight management strategies 2
- Complete tobacco cessation is mandatory; counsel on reducing secondhand smoke exposure 1
- Regular physical activity as part of comprehensive risk reduction 1
Blood Pressure Management: Targets and First-Line Agents
Blood Pressure Targets by Albuminuria Status
For patients with albuminuria ≥30 mg/g (≥3 mg/mmol), target systolic BP <120 mmHg when tolerated using standardized office measurement. 1, 2
- For albuminuria <30 mg/g: Target BP ≤140/90 mmHg 2
- For albuminuria ≥30 mg/g: Target BP ≤130/80 mmHg, with consideration of <120 mmHg systolic when tolerated 2
- Use standardized office BP measurement techniques—routine office measurements alone can lead to overtreatment when targeting intensive lowering 2
RAS Inhibitor Therapy (ACEi or ARB)
Start an ACEi or ARB at maximum approved dose for all CKD patients with albuminuria, regardless of diabetes status. 1
Specific Indications by Albuminuria and Diabetes Status:
- CKD with severely increased albuminuria (A3, >300 mg/g) WITHOUT diabetes: Start RASi (Grade 1B recommendation) 1
- CKD with moderately increased albuminuria (A2, 30-300 mg/g) WITHOUT diabetes: Start RASi (Grade 2C recommendation) 1
- CKD with moderately-to-severely increased albuminuria (A2 or A3) WITH diabetes: Start RASi (Grade 1B recommendation) 1
- CKD with normal to mildly increased albuminuria (A1): Consider RASi for specific indications like hypertension or heart failure with reduced ejection fraction 1
Critical RASi Dosing and Monitoring:
- Administer the highest approved dose tolerated—proven benefits were achieved at target doses in trials 1, 3
- Check serum creatinine and potassium within 2-4 weeks of initiation or dose increase 1
- Continue RASi unless creatinine rises >30% within 4 weeks of initiation or dose increase 1
- Continue RASi even when eGFR falls below 30 mL/min/1.73 m²—only consider dose reduction at eGFR <15 mL/min/1.73 m² if symptomatic hypotension, uncontrolled hyperkalemia, or uremic symptoms develop 1, 3
Managing RASi Side Effects:
Hyperkalemia associated with RASi should be managed by measures to reduce serum potassium rather than immediately stopping the RASi. 1
- Consider dietary potassium restriction 1
- Add diuretics if appropriate 1
- Consider sodium bicarbonate 1
- Consider GI cation exchangers 1
- Reduce dose or stop RASi only as last resort 1
Additional Antihypertensive Agents
- Add long-acting dihydropyridine calcium channel blocker or thiazide-like diuretic if BP remains uncontrolled on RASi 3
- Often all three classes (RASi, CCB, diuretic) are needed to attain BP targets 1
Critical Contraindications in BP Management
Never combine ACEi + ARB + direct renin inhibitor—this triple combination increases adverse events without benefit. 1, 3
- Avoid dual RASi therapy (ACEi + ARB) due to increased risk of hyperkalemia, hypotension, and acute kidney injury without additional benefit 1, 3, 4
- Do not coadminister aliskiren with losartan in patients with diabetes 4
- Avoid aliskiren with losartan in patients with renal impairment (GFR <60 mL/min) 4
SGLT2 Inhibitors: Foundational Therapy for Kidney and Cardiovascular Protection
All patients with type 2 diabetes, CKD, and eGFR ≥20 mL/min/1.73 m² should be treated with an SGLT2 inhibitor (Grade 1A recommendation). 1
Expanded Indications Beyond Diabetes:
SGLT2 inhibitors are now recommended for adults with CKD even without diabetes in the following scenarios (Grade 1A recommendation): 1
- eGFR ≥20 mL/min/1.73 m² with urine ACR ≥200 mg/g (≥20 mg/mmol), OR
- Heart failure, irrespective of albuminuria level
For adults with eGFR 20-45 mL/min/1.73 m² with urine ACR <200 mg/g (<20 mg/mmol), consider SGLT2 inhibitor (Grade 2B recommendation). 1
SGLT2 Inhibitor Continuation and Monitoring:
- Once initiated, continue SGLT2i even if eGFR falls below 20 mL/min/1.73 m² unless not tolerated or kidney replacement therapy is initiated 1
- Withhold SGLT2i during prolonged fasting, surgery, or critical medical illness when patients may be at greater risk for ketosis 1
- The reversible decrease in eGFR on initiation is generally not an indication to discontinue therapy—SGLT2i initiation does not necessitate alteration of CKD monitoring frequency 1
Glycemic Management in Diabetic CKD
Glycemic Monitoring
Use HbA1c to monitor glycemic control in patients with diabetes and CKD (Grade 1C recommendation). 1
- Monitor HbA1c twice per year for stable patients; up to 4 times per year if glycemic target not met or after therapy change 1
- HbA1c accuracy declines with advanced CKD (G4-G5), particularly in dialysis patients—consider glucose management indicator (GMI) from continuous glucose monitoring when HbA1c is not concordant with measured glucose 1
- Daily glycemic monitoring with CGM or SMBG may help prevent hypoglycemia when using antihyperglycemic therapies associated with hypoglycemia risk 1
Glucose-Lowering Medications
For type 2 diabetes with CKD, the medication hierarchy is: SGLT2i (first-line) + metformin (if eGFR ≥30), then add GLP-1 RA if needed to achieve glycemic targets. 1
- Metformin may be given when eGFR ≥30 mL/min/1.73 m² 1
- GLP-1 receptor agonists are preferred additional glucose-lowering drugs if SGLT2i and metformin are insufficient to meet glycemic targets or if unable to use SGLT2i or metformin 1
- For patients choosing not to do daily glycemic monitoring, select antihyperglycemic agents with lower hypoglycemia risk and dose appropriately for eGFR level 1
Nonsteroidal Mineralocorticoid Receptor Antagonists
For adults with type 2 diabetes, eGFR >25 mL/min/1.73 m², normal serum potassium, and albuminuria >30 mg/g (>3 mg/mmol) despite maximum tolerated RASi, add a nonsteroidal MRA (Grade 2A recommendation). 1
- Nonsteroidal MRA (finerenone) is most appropriate for adults with type 2 diabetes at high risk of CKD progression and cardiovascular events, as demonstrated by persistent albuminuria despite other standard-of-care therapies 1
- Nonsteroidal MRA may be added to RASi + SGLT2i for treatment of type 2 diabetes and CKD 1
- To mitigate hyperkalemia risk, select patients with consistently normal potassium 1
- Steroidal MRA may be used for resistant hypertension but carry higher hyperkalemia risk 1
Lipid Management
All patients with type 1 or type 2 diabetes and CKD should be treated with a moderate- or high-intensity statin. 1
- Add ezetimibe, PCSK9 inhibitor, or icosapent ethyl if indicated based on ASCVD risk and lipid levels 1
Cardiovascular Disease Management
The level of care for ischemic heart disease offered to people with CKD should not be prejudiced by their CKD (Grade 1A recommendation). 2
- Persons with CKD are more likely to have a cardiovascular event than to progress to end-stage renal disease 2
- Use antiplatelet agents for clinical ASCVD 1
- Aspirin should be used lifelong for secondary prevention; may be considered for primary prevention in high ASCVD risk 1
Monitoring Strategy and Frequency
Annual monitoring of eGFR and albuminuria for patients at standard risk of progression; more frequent monitoring for higher-risk individuals. 2
Risk-Based Monitoring Frequency:
The frequency of monitoring varies from once per year (low risk) to 4 times or more per year (every 1-3 months for high risk) according to risks of CKD progression and complications 1
- Define progression as decline in GFR category accompanied by ≥25% drop in eGFR from baseline, or sustained decline in eGFR of ≥5 mL/min/1.73 m²/year 2
- Regular risk factor reassessment every 3-6 months for glycemia, albuminuria, BP, CVD risk, and lipids 1
Nephrology Referral Criteria
Patients at high risk of CKD progression should be promptly referred to a nephrologist: 5
- eGFR <30 mL/min/1.73 m² 5
- Albuminuria ≥300 mg per 24 hours 5
- Rapid decline in eGFR 5
- Use the Kidney Failure Risk Equation to identify patients at high risk of progressive kidney disease and kidney failure to guide referrals 6
Monitoring for CKD Complications
Patients require monitoring for: 5
- Hyperkalemia (especially with RASi, MRA, or combination therapies) 1
- Metabolic acidosis 5
- Hyperphosphatemia 5
- Vitamin D deficiency 5
- Secondary hyperparathyroidism 5
- Anemia 5
Drug Interactions and Nephrotoxin Avoidance
NSAIDs and CKD
In elderly, volume-depleted, or compromised renal function patients, coadministration of NSAIDs with ARBs may result in deterioration of renal function, including possible acute renal failure. 4
- Monitor renal function periodically in patients receiving losartan and NSAID therapy 4
- NSAIDs may attenuate the antihypertensive effect of ARBs 4
- Avoid nonsteroidal anti-inflammatory drugs as potential nephrotoxins 5
Other Drug Considerations
- Adjust dosing for many antibiotics and oral hypoglycemic agents based on eGFR 5
- Monitor serum lithium levels during concomitant use with ARBs due to risk of lithium toxicity 4
- Coadministration with drugs that raise serum potassium may result in hyperkalemia—monitor potassium 4
Acute Kidney Injury Risk
All people with CKD are considered to be at increased risk of AKI (Grade 1A recommendation). 2
- CKD remains an independent risk factor for AKI even after adjustment for comorbid conditions 2
- When evaluating creatinine rise >30% on RASi, review for causes of AKI, correct volume depletion, and reassess concomitant medications (diuretics, NSAIDs) before discontinuing RASi 1
- Consider renal artery stenosis if creatinine rises significantly 1
Common Pitfalls to Avoid
Do not discontinue RASi prematurely for modest creatinine increases (<30% rise within 4 weeks) or manageable hyperkalemia—these medications provide critical renal and cardiovascular protection. 2
Do not use routine office BP measurements alone when targeting intensive BP lowering to <120 mmHg—this can lead to overtreatment and adverse events; use standardized measurement techniques. 2
Do not delay SGLT2i initiation in eligible patients—uptake has been slow, particularly in CKD without type 2 diabetes, despite strong evidence for kidney and cardiovascular protection. 7