CKD Management

1. General Measures (Lifestyle & Dietary Therapy)

2. Blood Pressure Control 

3. Glycemic Control 

4. RAAS Blockade (Disease-Modifying Therapy)

5. SGLT2 Inhibitors 

6. Management of Complications 

A. Anemia of CKD

 DOSING 

1. Epoetin Alfa

• Route: SC (preferred) / IV
• Initial dose:
• 50–100 IU/kg 3 times/week
• Adjustment:
• Increase by 25% if Hb rise <1 g/dL in 4 weeks
• Reduce if Hb rises too fast (>1 g/dL in 2 weeks)

2. Darbepoetin Alfa

• Route: SC / IV
• Initial dose:
• 0.45 mcg/kg once weekly
  OR
• 0.75 mcg/kg every 2 weeks
• Long-acting → better compliance

 ESA CONVERSION 

• 200 IU epoetin ≈ 1 mcg darbepoetin

PRE-ESA WORKUP (MANDATORY BEFORE START)

MUST CORRECT:

• Iron deficiency:
• Ferritin ≥100 ng/mL (ND-CKD)
• Ferritin ≥200 ng/mL (dialysis)
• TSAT ≥20%
• Vitamin B12 & folate
• Ongoing blood loss
• Infection/inflammation

 IRON + ESA = CORE CONCEPT

 ESA therapy fails without iron

• Functional iron deficiency:
• Adequate stores but poor utilization
• IV iron often required in CKD

 ESA HYPORESPONSIVENESS

Causes (VERY IMPORTANT)

• Iron deficiency (most common)
• Inflammation (↑ hepcidin)
• Infection
• Malnutrition
• Hyperparathyroidism
• Aluminum toxicity
• ACE inhibitors / ARBs (mild effect)

 ADVERSE EFFECTS 

1. Hypertension (MOST COMMON)

• Due to:
• ↑ blood viscosity
• Vasoconstriction

2. Thromboembolism

• DVT
• Stroke
• Dialysis access thrombosis

3. Pure Red Cell Aplasia (PRCA)

• Rare but serious
• Due to anti-EPO antibodies

4. Others

• Seizures (rare, early therapy)
• Flu-like symptoms

 CONTRAINDICATIONS

• Uncontrolled hypertension
• Active malignancy (relative, case-dependent)
• History of PRCA

 MONITORING 

• Hb:
• Every 2–4 weeks initially
• Iron status:
• Ferritin, TSAT
• BP monitoring
• Dose titration based on Hb response

B. Hyperkalemia

 1. SODIUM POLYSTYRENE SULFONATE (SPS)

• Cation exchanged: Na⁺ for K⁺
• Site: Colon

 Mechanism

• Resin binds K⁺ in colon → excreted in stool
• Releases Na⁺ → systemic absorption

 Dose

• 15–60 g orally or rectally
• Repeat every 4–6 hrs

 Onset Slow (2–6 hours) → NOT for emergencies

 Adverse Effects 

• Intestinal necrosis (life-threatening)
• Especially with sorbitol
• Constipation / diarrhea
• Sodium overload → edema, HTN
• Hypokalemia

 Guidelines (KDIGO, nephrology societies): avoid routine use

 2. PATIROMER

• Exchanges: Ca²⁺ for K⁺
• Site: Colon

 Mechanism

• Binds K⁺ → releases Ca²⁺
• Works mainly in distal colon

 Dose

• Start: 8.4 g once daily
• Max: 25.2 g/day

 Onset

• ~7 hours (slow)
• Not for emergency hyperkalemia

 Adverse Effects

• Hypomagnesemia (IMPORTANT EXAM POINT)
• Constipation
• Mild GI symptoms

 Drug Interaction

• Binds other drugs → give 3 hours apart

 Role

• Chronic hyperkalemia
• CKD patients on:
• ACE inhibitors
• ARBs
• MRAs

 Allows continuation of RAAS inhibitors (very important concept)

 3. SODIUM ZIRCONIUM CYCLOSILICATE (SZC)

• Exchanges: Na⁺ + H⁺ for K⁺
• Site: Entire GI tract

 Mechanism

• Selectively traps K⁺ (high specificity)
• Works throughout GI tract

 Dose

• Initial: 10 g TDS for 48 hours (acute correction)
• Maintenance: 5–15 g OD

 Onset

• Fastest binder (~1 hour)
   Can be used in subacute/early hyperkalemia

 Adverse Effects

• Edema (Na⁺ load)
• Mild GI symptoms

 Role

• Acute + chronic hyperkalemia
• Better than SPS

C. Metabolic Acidosis

 Why is acidosis harmful?

• Bone buffering → osteodystrophy
• Muscle breakdown → sarcopenia
• ↑ progression of CKD
• ↑ mortality

Hence correction is disease-modifying, not just symptomatic

 DOSING 

Initial dose:0.5–1 mEq/kg/day in divided doses

Practical regimen:

• 500–650 mg tablet = ~6–8 mEq HCO₃⁻
• Typical:
• 500 mg TDS → mild acidosis
• Titrate based on HCO₃⁻ levels

 HCO₃⁻ deficit=0.5×body weight×(24−current HCO₃⁻)

 Give gradually (oral), not full correction immediately

 Strong evidence: CKD patients on bicarbonate have slower GFR decline

D. CKD–Mineral Bone Disorder (CKD-MBD)

 Dietary Phosphate Restriction 

 Target Intake

• 800–1000 mg/day (KDIGO recommendation)

 Foods to Restrict 

1. High-phosphate natural foods

• Dairy:
• Milk, cheese, paneer, yogurt
• Protein sources:
• Red meat, organ meat, egg yolk
• Nuts & seeds:
• Almonds, peanuts, sunflower seeds
• Legumes:
• Beans, lentils

2. MOST IMPORTANT: Hidden phosphate 

• Processed foods:
• Packaged meats, sausages
• Instant foods
• Cola beverages (phosphoric acid)
• Bakery products (phosphate additives)

 PHOSPHATE BINDERS 

 WHY PHOSPHATE BINDERS?

 WHEN TO START? (KDIGO GUIDELINES)

• Start when:
• Persistent hyperphosphatemia
• Usually CKD G4–G5 (sometimes earlier)

Targets:

• Target goal is serum phosphorus ≤5.5 mg/dL
• Avoid:
• Hypercalcemia
• Positive calcium balance

CLASSIFICATION OF PHOSPHATE BINDERS

 CALCIUM-BASED BINDERS

Drugs:

• Calcium carbonate
• Calcium acetate

Mechanism:

• Bind dietary phosphate in gut → form insoluble calcium phosphate
• Excreted in feces

Dose:

• Calcium carbonate: 500–1500 mg TDS with meals
• Calcium acetate: more potent (less elemental Ca load)

Disadvantages 

 Hypercalcemia
 Vascular calcification
 Adynamic bone disease

Contraindications:

• Hypercalcemia
• Low PTH (adynamic bone disease)
• Extensive vascular calcification

Restrict total elemental calcium intake <1500 mg/day

 NON-CALCIUM BASED BINDERS

 A. Sevelamer

Types:

• Sevelamer hydrochloride
• Sevelamer carbonate

Mechanism:

• Non-absorbed polymer
• Binds phosphate via anion exchange

Dose:800–1600 mg TDS with meals(Dietary phosphate enters gut only after meal),Titrate dose; increase by 400-800 mg per meal at 2-week intervals as necessary to achieve target serum phosphorus levels

Additional benefits:

↓ LDL cholesterol
No hypercalcemia
↓ vascular calcification progression

Side effects:

• GI: bloating, constipation
• Metabolic acidosis (HCl form)

Indications:

 Preferred in:

• Hypercalcemia
• Vascular calcification
• Adynamic bone disease

 B. Lanthanum carbonate

Mechanism:

• Binds phosphate → insoluble lanthanum phosphate

Dose:500–1000 mg TDS (chewable)

Side effects:

• GI upset
• Tissue deposition (long-term safety debated)

 C.  Iron-based binders

• Ferric citrate
• Sucroferric oxyhydroxide

Mechanism:

• Iron binds phosphate → insoluble complex

Advantages:

✔ ↓ phosphate
✔ Treats anemia (iron absorption)
✔ Low pill burden (especially sucroferric)

Side effects:

• Dark stools
• Iron overload (rare)
• GI upset

 D. Aluminum-based binders (OBSOLETE)

Drug:

• Aluminum hydroxide

Why avoided?

 Aluminum toxicity:

• Encephalopathy
• Osteomalacia
• Microcytic anemia

 Use only short-term in severe hyperphosphatemia

CALCITRIOL (1,25-DIHYDROXY VITAMIN D₃)

 BASIC CONCEPT

• Calcitriol = Active form of Vitamin D
• Chemical name: 1,25-dihydroxycholecalciferol
• Final activation step occurs in kidney via:
• 1-alpha hydroxylase

 In CKD:

• ↓ kidney function → ↓ enzyme activity → ↓ calcitriol
  → core driver of secondary hyperparathyroidism

 PHYSIOLOGY & SYNTHESIS

Stepwise pathway:

1. Skin: 7-dehydrocholesterol → Vitamin D₃ (UV light)
2. Liver: → 25-OH vitamin D (calcidiol)
3. Kidney: → Calcitriol

Stimulators:

• ↓ Calcium
• ↓ Phosphate
• ↑ PTH

Inhibitors:

• ↑ Phosphate
• ↑ FGF-23

INDICATIONS 

1. CKD–MBD (MOST IMPORTANT)

• Secondary hyperparathyroidism
• CKD stage 3–5 (selective use)
• Dialysis patients (IV preferred)

KDIGO UPDATE 

• Not routinely used in early CKD (G3–G4)
• Reserved for:
• Severe progressive hyperparathyroidism

 Overuse → vascular calcification risk

DOSING

Oral:

• 0.25–1 mcg/day

Dialysis (IV):

• 0.5–2 mcg 3 times/week

 Adjust based on:

• PTH
• Calcium
• Phosphate

ADVERSE EFFECTS 

1. Hypercalcemia (MOST IMPORTANT)

• Weakness
• Confusion
• Arrhythmias

2. Hyperphosphatemia

• Due to ↑ gut absorption

3. Vascular & Soft Tissue Calcification

• Coronary artery calcification
• Valvular calcification

4. Adynamic Bone Disease

• From over-suppression of PTH

 CONTRAINDICATIONS

• Hypercalcemia
• Hyperphosphatemia (uncontrolled)
• Low PTH (adynamic bone disease)

DRUG INTERACTIONS

• Thiazides → ↑ hypercalcemia risk
• Digoxin → ↑ arrhythmia risk (due to Ca)
• Phosphate binders → modify effect

COMPARISON WITH OTHER VITAMIN D FORMS

 NEWER ANALOGUES 

1. Paricalcitol

2. Doxercalciferol

 Advantages:

• Less hypercalcemia
• Less hyperphosphatemia

 Preferred in:

• CKD with high Ca/phosphate risk