Management of Chronic Kidney Disease (CKD)

Classification - KDIGO 2012

• A1: <30 mg/g - Normal to mildly increased
• A2: 30-300 mg/g - Moderately increased
• A3: >300 mg/g - Severely increased

1. Slowing CKD Progression

Blood Pressure Control

• Target BP: <130/80 mmHg in CKD patients (especially with proteinuria)
• ACE inhibitors (ACEi) or ARBs are first-line in:
  • Diabetic CKD with albuminuria
  • Non-diabetic CKD with proteinuria >500 mg/day
  • Both reduce intraglomerular hypertension and proteinuria
• Avoid combination ACEi + ARB (increased risk of AKI and hyperkalemia without additional benefit)
• ACEi/ARBs cause a predictable early ~20-30% rise in creatinine, which is acceptable; discontinue if rise >30%

SGLT-2 Inhibitors (Major Recent Advance)

• Dapagliflozin, empagliflozin, canagliflozin have demonstrated robust kidney-protective effects in both diabetic and non-diabetic CKD (DAPA-CKD, EMPA-KIDNEY trials)
• Mechanism: reduce glomerular hyperfiltration via tubuloglomerular feedback, reduce albuminuria, modest BP-lowering
• Indicated for CKD with eGFR ≥20 + albuminuria ≥200 mg/g (regardless of diabetes status per current guidelines)
• A 2025 systematic review (Ammar et al., Pharmacotherapy 2025, PMID 40152479) highlights SGLT-2 inhibitors and GLP-1 agonists as key updates in CKD management

GLP-1 Receptor Agonists

• Semaglutide, liraglutide: benefit extends beyond glycemic control - reduce proteinuria, CV risk, and slow CKD progression in diabetic patients
• Now included in multi-drug cardiorenal protection protocols

Non-steroidal Mineralocorticoid Receptor Antagonist (nsMRA)

• Finerenone: approved for CKD in type 2 diabetes with albuminuria; reduces risk of kidney failure, CV events, and hospitalization
• Advantage over spironolactone: selective for mineralocorticoid receptor, lower risk of gynecomastia and hyperkalemia

2. Dietary and Lifestyle Modifications

• Sodium restriction: <2 g/day for all CKD patients with hypertension or heart failure
• Protein restriction: Moderate restriction (0.6-0.8 g/kg/day) may slow progression in advanced CKD (G4-G5), though evidence for strict restriction in early CKD is limited; excessive restriction risks malnutrition
• Potassium restriction: 60 mEq/day in patients with hyperkalemia (common in G4-G5 and with ACEi/ARB use)
• Phosphate restriction: Low-phosphate diet in G3b-G5 to prevent mineral bone disease
• Fluid: Not routinely restricted (may cause hypernatremia if excessive); restrict only in dilutional hyponatremia or ESKD oligo/anuria
• Smoking cessation: Smoking accelerates CKD progression
• Weight management: High BMI is an independent risk factor for progression
• Avoid nephrotoxins: NSAIDs, aminoglycosides, iodinated contrast agents; hold metformin if eGFR <30
• Washington Manual of Medical Therapeutics

3. Management of CKD Complications

A. Anemia

• Cause: Relative erythropoietin (EPO) deficiency + iron deficiency + chronic inflammation
• Screening: Monitor Hb annually from G3a, twice yearly from G4-G5
• Diagnosis: Hb <13.0 g/dL (males), <12.0 g/dL (females)
• Management:
  1. Rule out other causes: iron deficiency, B12, folate deficiency
  2. Iron supplementation first - oral or IV (IV preferred in dialysis patients and those with intolerance)
  3. ESAs (erythropoietin alfa, darbepoetin): start when Hb <10.0 g/dL after correcting iron; target Hb 10-12 g/dL (avoid >13 - increased stroke/thrombosis risk)
  4. HIF-PHI (Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors) - e.g., daprodustat, roxadustat: newer oral agents that stimulate endogenous EPO synthesis; approved in several countries; suitable when ESAs fail or IV access is difficult
• Do NOT start ESAs until iron deficiency is corrected
• Comprehensive Clinical Nephrology, 7th Ed.

B. CKD-Mineral and Bone Disorder (CKD-MBD)

• Begins at G3b; characterized by:
  • Hyperphosphatemia
  • Vitamin D deficiency (reduced 1,25-dihydroxyvitamin D3 production)
  • Secondary hyperparathyroidism (elevated PTH)
  • Bone disease (osteitis fibrosa cystica) + vascular calcification
• Monitoring: Serum calcium, phosphate, PTH, alkaline phosphatase from eGFR <45 (G3b+)
• Management:
  1. Dietary phosphate restriction + phosphate binders:
     • Calcium-based (calcium carbonate, calcium acetate) - first line but caution re: hypercalcemia
     • Non-calcium binders: sevelamer, lanthanum carbonate (preferred in dialysis patients to avoid calcium loading)
     • Ferric citrate (also provides iron)
  2. Active Vitamin D analogues: calcitriol, paricalcitol - suppress PTH; caution with hypercalcemia and hyperphosphatemia
  3. Calcimimetics: cinacalcet - reduces PTH by increasing sensitivity of parathyroid gland to calcium; used in dialysis patients with secondary hyperparathyroidism; etelcalcetide (IV form for HD patients)
  4. Parathyroidectomy: for severe, refractory secondary hyperparathyroidism
• Comprehensive Clinical Nephrology, 7th Ed.

C. Metabolic Acidosis

• Common in G4-G5 due to reduced renal acid excretion
• Target serum bicarbonate: ≥22 mmol/L
• Treatment: Oral sodium bicarbonate (1-2 g 2-3x/day) - may also slow CKD progression
• Sodium citrate is an alternative (avoid in patients taking aluminum-based antacids)
• Note: bicarbonate supplementation adds sodium load - monitor BP

D. Cardiovascular Disease

• CKD patients have markedly increased CV mortality - all patients with CKD should be treated as high CV risk
• Statins: indicated for all CKD patients for CV risk reduction regardless of LDL level
  • Atorvastatin or rosuvastatin preferred; avoid simvastatin in high-dose in CKD (myopathy risk)
  • Evidence supports statin use in non-dialysis CKD; benefit in dialysis is less clear
• BP control (as above)
• Antiplatelet therapy (aspirin): for secondary prevention; balance against bleeding risk in CKD

E. Hyperkalemia

• Common with ACEi/ARB use, G4-G5 GFR decline, and metabolic acidosis
• Management:
  • Dietary restriction
  • Treat metabolic acidosis
  • Newer potassium binders: patiromer and sodium zirconium cyclosilicate (SZC) - allow continuation of ACEi/ARB in hyperkalemic patients (major advance)
  • Avoid or minimize NSAIDs, trimethoprim, heparin

F. Volume Overload and Edema

• Loop diuretics (furosemide): mainstay; may need high doses as GFR declines
• Thiazides (metolazone): can be added synergistically to loop diuretics in resistant cases
• Monitor for hypovolemia and electrolyte disturbances

G. Glycemic Control in Diabetic CKD

• Target HbA1c: ~7-8% (less strict in advanced CKD/elderly due to hypoglycemia risk)
• Metformin: hold when eGFR <30; dose-reduce at eGFR 30-45
• SGLT-2 inhibitors (as above) - cornerstone of diabetic CKD management
• Insulin: dose reduction needed as GFR declines (reduced renal insulin clearance)

4. Drugs to Avoid or Dose-Adjust in CKD

5. Nephrology Referral Indications

• eGFR <30 mL/min/1.73 m² (G4-G5)
• Rapid decline in eGFR (>5 mL/min/year)
• Proteinuria >1 g/day (especially without clear cause)
• Persistent hematuria with proteinuria
• Uncontrolled hypertension despite 3+ agents
• Suspected glomerulonephritis or rare CKD etiology
• CKD in pregnancy

6. Preparation for Renal Replacement Therapy (RRT)

Options:

1. Hemodialysis (HD): Most common. Typically 3 sessions/week, 3-4 hours each. Requires arteriovenous fistula (AVF) - refer for access creation when eGFR ~15-20
2. Peritoneal Dialysis (PD): Uses peritoneal membrane as filter. CAPD (continuous ambulatory) or APD (automated, nocturnal). Offers independence but requires training and intact peritoneum
3. Kidney Transplantation: Best long-term survival and quality of life; requires long-term immunosuppression. Refer for pre-emptive transplant listing at eGFR ~20
4. Conservative/Palliative Management: For elderly/frail patients where dialysis would not improve quality of life; focuses on symptom control

Indications for Initiating Dialysis (AEIOU mnemonic):

• A: Acidosis (metabolic, refractory)
• E: Electrolyte (hyperkalemia, refractory)
• I: Intoxication (methanol, ethylene glycol, salicylates)
• O: Overload (volume, refractory)
• U: Uremia (encephalopathy, pericarditis, bleeding)

7. Monitoring Schedule in CKD

Recent Evidence Updates (2024-2025)

• The Ammar et al. systematic review (Pharmacotherapy 2025) confirms SGLT-2 inhibitors, GLP-1 agonists, and finerenone as pillars of modern CKD management, with combination therapy showing additive cardiorenal protection.
• A 2025 BMJ Open systematic review (Ketema et al., PMID 40908011) found that quality of care in CKD remains suboptimal globally, with under-prescription of ACEi/ARBs and statins a persistent gap.
• Conservative kidney management for advanced CKD (avoiding dialysis in selected patients) is gaining evidence support - Chawla et al., BMC Nephrology 2025 (PMID 40665214).

• The Washington Manual of Medical Therapeutics, Chapter 13
• Comprehensive Clinical Nephrology, 7th Edition, Chapter on CKD Complications
• Brenner and Rector's The Kidney, 2-Volume Set, CKD Classification and Management
• Tietz Textbook of Laboratory Medicine, 7th Edition, General Management of CKD
• KDIGO 2012 Clinical Practice Guideline for CKD Evaluation and Management