CKD Management

1. General Measures (Lifestyle & Dietary Therapy)

Recommendation

Reason 

Salt restriction <5 g/day NaCl (~2 g Na⁺)

↓ sodium → ↓ volume overload → ↓ BP → slows CKD progression

Protein intake 0.6–0.8 g/kg/day (non-dialysis CKD)

↓ nitrogenous waste → ↓ uremic toxin generation → ↓ hyperfiltration injury

Weight control BMI 20–25

Obesity → hyperfiltration + insulin resistance

Exercise ≥150 min/week moderate

Improves CV health + insulin sensitivity

Smoking cessation

Smoking → endothelial dysfunction + accelerates CKD


2. Blood Pressure Control 

Aspect

Details

Exam Insight

Target BP

<130/80 mmHg

Most important modifiable factor

First-line drugs

ACE inhibitors / ARBs

Especially if A2/A3 albuminuria

Add-on drugs

CCBs, diuretics

Loop diuretics in advanced CKD

Monitoring

Creatinine & K⁺ after initiation(Creatinine rise ≤30% acceptable)



3. Glycemic Control 

Aspect

Recommendation

HbA1c target

~7% (individualized)

SGLT2 inhibitors

Dapagliflozin, Empagliflozin

GLP-1 agonists

Liraglutide, Semaglutide

Insulin

Required in advanced CKD


4. RAAS Blockade (Disease-Modifying Therapy)

Drug Class

Mechanism

ACE inhibitors(First-line)

Efferent arteriole dilation → ↓ intraglomerular pressure

ARBs(Alternative if ACEi intolerance)

RAAS blockade


5. SGLT2 Inhibitors 

Feature

Details

Mechanism

Drugs

Dapagliflozin, Empagliflozin

↑ Na delivery to macula densa → afferent constriction

Renal benefit

↓ CKD progression

Hemodynamic + anti-inflammatory effects

CV benefit

↓ heart failure hospitalization

Osmotic diuresis + ↓ preload

When to use

eGFR ≥20 (latest guidelines)

Continue even if GFR falls


6. Management of Complications 

A. Anemia of CKD

Parameter

Reason / Mechanism

Target Hb –10–11.5 g/dL(CHOIR trial

TREAT trial)

Avoid overcorrection → thrombosis risk

IV iron preferred (ferritin <100–300, TSAT <20%)

CKD → functional iron deficiency

ESA therapy- Epoetin alfa, darbepoetin

Replace ↓ Erythropoietin

Caution Avoid Hb >11.5–12

↑ stroke, CV events

 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

Management Step

Details

Mechanism

Dietary restriction

↓ K⁺ intake

Prevents accumulation

Loop diuretics

Furosemide

↑ renal K⁺ excretion

Potassium binders

Patiromer, sodium zirconium

GI K⁺ removal


 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

Aspect

Details

Threshold

HCO₃⁻ <22 mEq/L

Treatment

Oral sodium bicarbonate

Benefit

Slows CKD progression

 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)

Component

Treatment

Hyperphosphatemia

Dietary restriction + phosphate binders

Phosphate binders

Calcium carbonate, sevelamer

Vitamin D analogues

Calcitriol

Calcimimetics

Cinacalcet-Activates calcium-sensing receptor (CaSR) on parathyroid gland

“Tricks” gland into sensing high calcium
→ ↓ PTH secretion


 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

Feature

Calcitriol

Cholecalciferol

Active?

Yes

No

Kidney activation needed

No

Yes

Onset

Rapid

Slow

Use in CKD

Preferred

Less useful

 NEWER ANALOGUES 

1. Paricalcitol

2. Doxercalciferol

 Advantages:

  • Less hypercalcemia
  • Less hyperphosphatemia

 Preferred in:

  • CKD with high Ca/phosphate risk


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