How to manage complications in patients with Chronic Kidney Disease (CKD) stages 3-5?

Management of Chronic Kidney Disease Complications (Stages 3-5)

All patients with CKD stages 4-5 must be referred immediately to nephrology, while stage 3 patients require systematic management of cardiovascular risk, blood pressure, proteinuria, and metabolic complications to prevent progression. 1, 2

Blood Pressure Management

Target systolic blood pressure <120 mmHg when tolerated using standardized office measurement. 1, 2

• Use ACE inhibitors or ARBs as first-line therapy for blood pressure control and proteinuria reduction 1, 2
• Monitor serum creatinine and potassium within 2-4 weeks of starting or adjusting ACE inhibitor/ARB doses 2
• Continue ACE inhibitor/ARB unless creatinine rises >30% within 4 weeks of initiation 2
• Never combine ACE inhibitor with ARB due to increased hyperkalemia and acute kidney injury risk 2
• Manage hyperkalemia with dietary restriction and potassium binders rather than discontinuing ACE inhibitor/ARB 2
• Add loop diuretics (not thiazides) for volume overload in stages 3-5 3, 2
• Restrict dietary sodium to <2g per day 1, 2

The 2025 KDIGO guidelines represent a shift toward more intensive blood pressure control, though this carries a moderate strength of recommendation (2B) due to concerns about tolerability in frail patients. 1

Proteinuria Reduction

Reducing proteinuria/albuminuria is a primary treatment goal that directly correlates with slowing CKD progression. 2

• ACE inhibitors or ARBs are the cornerstone of proteinuria management 1, 2
• Target reduction in urinary albumin excretion as a surrogate marker for disease progression 2

Cardiovascular Risk Reduction

Treat all adults ≥50 years with CKD using statin or statin/ezetimibe combination therapy. 2

• Choose statin-based regimens to maximize absolute LDL cholesterol reduction 2
• Consider PCSK-9 inhibitors for patients with established indications 2
• Use low-dose aspirin for secondary prevention in patients with established ischemic cardiovascular disease 2
• Encourage plant-based "Mediterranean-style" diet in addition to lipid-modifying therapy 2

Cardiovascular disease is the leading cause of death in CKD patients, making aggressive cardiovascular risk management more important than focusing solely on kidney function. 4, 5

Diabetes Management (if applicable)

Start SGLT2 inhibitor if patient has type 2 diabetes and eGFR ≥20 mL/min/1.73 m². 2

• Continue SGLT2 inhibitor even if eGFR falls below 20 mL/min/1.73 m² unless dialysis initiated 2
• Use glipizide as preferred sulfonylurea due to lack of active metabolites 2
• Consider DPP-4 inhibitors (sitagliptin, saxagliptin, linagliptin) with appropriate dose adjustments 2
• Insulin requires careful dose adjustment due to reduced renal clearance 2
• Target HbA1c should be determined every 3 months in patients not meeting goals 1

Dietary Management

Maintain protein intake of 0.8 g/kg body weight/day in adults with CKD stages 3-5. 1

• Avoid high protein intake >1.3 g/kg/day in adults at risk of progression 1
• In motivated patients at risk of kidney failure, consider very low-protein diet (0.3-0.4 g/kg/day) supplemented with essential amino acids or ketoacid analogs under close supervision 1
• Do not restrict protein in children with CKD due to growth impairment risk 1
• In older adults with frailty and sarcopenia, consider higher protein and calorie targets 1
• Advise higher consumption of plant-based foods compared to animal-based foods and lower consumption of ultra-processed foods 1

Mineral and Bone Disorder

Monitor serum calcium and phosphorus every 3-6 months in stage 4-5 CKD. 2

• Monitor PTH every 6-12 months 2
• Measure alkaline phosphatase annually or more frequently if PTH elevated 2
• Measure 25(OH)D levels and correct deficiency using general population treatment strategies 2

Anemia Management

Perform complete blood count at least monthly after initial stabilization in stage 4-5 CKD. 2

• Assess and treat anemia by removing underlying causes first 2
• Use erythropoiesis-stimulating agents (ESAs) only to reduce need for RBC transfusions, not to target hemoglobin >11 g/dL 6, 7
• Targeting hemoglobin >11 g/dL increases mortality, myocardial infarction, stroke, and thromboembolism risk 6, 7
• For CKD patients on dialysis: start darbepoetin alfa 0.45 mcg/kg IV/SC weekly or 0.75 mcg/kg every 2 weeks 6
• For CKD patients not on dialysis: start darbepoetin alfa 0.45 mcg/kg IV/SC at 4-week intervals 6

Volume Overload Management

Use loop diuretics for leg swelling and volume overload in CKD stage 3-5. 3

• Monitor weight regularly to track fluid status and treatment response 3
• Assess blood pressure at every clinical contact 3
• Check serum electrolytes frequently due to hypokalemia risk with loop diuretics 3
• Excessive diuresis can precipitate acute kidney injury in patients with reduced renal reserve 3
• Dietary sodium restriction enhances diuretic efficacy 3

Metabolic Complications Monitoring

Monitor for hyperkalemia, metabolic acidosis, and electrolyte abnormalities regularly. 3, 2, 4

• These complications become more prevalent when GFR falls below 60 mL/min/1.73 m² 3
• Renal function (serum creatinine, eGFR) should be monitored regularly 3

Medication Safety

Avoid nephrotoxic agents including NSAIDs, COX-2 inhibitors, and contrast media. 2, 4

• Adjust drug dosing for many antibiotics and oral hypoglycemic agents 4
• Avoid allopurinol in patients receiving azathioprine 2
• For contrast-enhanced procedures: use hydration with normal saline, low-osmolar or iso-osmolar contrast media, and minimize contrast volume 1
• Consider short-term high-dose statin therapy before contrast procedures 1
• Hydration with sodium bicarbonate may be considered before contrast administration 1

Screening for Other Complications

Perform comprehensive dilated eye examination annually in diabetic patients with CKD. 1

• Visual foot inspection at each healthcare visit 1
• Comprehensive foot examination with Semmes-Weinstein monofilament testing, 128-Hz tuning fork, and pedal pulse evaluation annually 1
• Refer high-risk patients to foot and/or vascular specialists annually 1

Nephrology Referral Criteria

Refer immediately to nephrology for:

• All CKD stage 4-5 patients (eGFR <30 mL/min/1.73 m²) 1, 2, 8
• Refractory edema despite adequate diuretic therapy 3
• Rapid decline in kidney function (>20% decrease in eGFR) 3
• Severe electrolyte abnormalities difficult to manage 3
• Albuminuria ≥300 mg per 24 hours 4
• Uremic symptoms, BUN >100 mg/dL, or altered mental status 2
• Refractory volume overload, severe hyperkalemia, uremic encephalopathy, pericarditis, or severe metabolic acidosis (pH <7.2) 2

Early referral to nephrology improves outcomes, reduces costs, and allows timely preparation for dialysis or transplantation. 2, 8, 9

Preparation for Renal Replacement Therapy (Stage 4-5)

Begin structured pre-dialysis education program when stage 4 is reached. 2

• Patient education about renal replacement therapy options should begin immediately, as progression rates are unpredictable 2
• Evaluate for preemptive kidney transplantation including living donor assessment 2
• Create arteriovenous fistula in advance for patients likely to require hemodialysis 2
• For patients interested in peritoneal dialysis, delay AVF creation and focus on PD catheter planning 2