GFR-Based Stages (KDIGO 2024)

Albuminuria-Based Categories (Heat Map)

Clinical Pearl: Combination of GFR + albuminuria stage predicts progression risk. A patient with G3a/A3 (eGFR 45–59 + UACR >300 mg/g) has higher risk than G3a/A1 despite same GFR.

Key Assessments at CKD Diagnosis

• Urine albumin-to-creatinine ratio (UACR) (gold standard; repeat if initial >300 mg/g)
• Blood pressure (home BP preferred; target <120 mmHg systolic)
• Metabolic panel: K, PO₄, HCO₃⁻, Ca, Mg
• Bone-specific markers: Alkaline phosphatase, PTH, 25-OH vitamin D
• Lipid panel
• Hemoglobin/hematocrit (baseline for anemia management)
• Renal imaging (ultrasound or CT to assess echogenicity, size, exclude hydronephrosis)

Tier 1: SGLT2 Inhibitors (Universal Therapy)

Recommendation: For patients with eGFR ≥20 mL/min/1.73 m² AND either T2D or albuminuria (UACR >30 mg/g).

Key Evidence: - DAPA-CKD trial [2]: Dapagliflozin 10 mg daily in CKD (with/without DM) - Primary outcome: 61% RRR in composite of ≥50% GFR decline, ESRD, or renal death - Secondary outcome: 71% RRR in cardiovascular death or HF hospitalization - Mean follow-up: 2.4 years

• EMPA-KIDNEY trial: Empagliflozin 10 mg daily in CKD (non-diabetes cohort ≥50% of subjects)
  • Primary outcome: 39% RRR in composite of CKD progression or CV death
  • All-cause mortality: 25% RRR

Mechanism: Proximal tubule glucose/sodium reabsorption inhibition → natriuresis, reduced intraglomerular pressure, anti-inflammatory effects.

Dosing: - Dapagliflozin: 10 mg daily (empagliflozin: 10 mg daily) - Continue even if eGFR falls below 20 mL/min/1.73 m² - Caution: genitourinary infections (5–8% increased incidence); counsel patients on symptoms

Side Effects: Euglycemic DKA (rare, <1%), genital infections, volume depletion (caution in elderly).

Tier 2: RAAS Blockade (ACE-I/ARB)

Recommendation: Initiate ACE inhibitor or ARB if albuminuria present (UACR ≥30 mg/g) [1].

Mechanism: Block aldosterone and angiotensin II → reduce proteinuria, lower intraglomerular pressure, anti-inflammatory.

Target: Maximum tolerated dose (not just minimum therapeutic dose).

Monitoring: SCr and K⁺ 7–14 days after initiation or dose change. - Expected SCr rise up to 30% acceptable (due to afferent arteriole dilation) - If K⁺ >5.5 mEq/L, reduce dose or add potassium-lowering agent

Caution: - Triple whammy: ACE-I/ARB + NSAID + diuretic → acute renal failure - Contraindicated: Pregnancy, prior angioedema, K⁺ >6.0 mEq/L

Tier 3: Finerenone (Non-Steroidal Mineralocorticoid Receptor Antagonist)

Recommendation: For patients with CKD + T2D or CKD + albuminuria, on stable ACE-I/ARB ± SGLT2i.

Key Evidence: - FIDELIO-DKD trial [3]: Finerenone 10 mg daily (titrate to 20 mg) in CKD + T2D - Primary outcome: 18% RRR in composite of ≥40% GFR decline, ESRD, or renal death - Cardiovascular outcome: 14% RRR

• FIGARO-DKD trial: Finerenone in earlier-stage CKD + T2D
  • Consistent benefit across CKD stages G2–G4

Mechanism: Selective MRA (non-steroidal, avoids hyperkalemia of spironolactone) → anti-inflammatory, reduces fibrosis.

Dosing: Start 10 mg daily; titrate to 20 mg daily based on tolerability.

Monitoring: K⁺ and SCr at baseline, 4 weeks, 12 weeks, then 6–12 months.

Side Effects: Hyperkalemia (more common if eGFR <30; incidence 10–15%), volume depletion, hypotension.

Tier 4: GLP-1 Receptor Agonists (If Diabetes + Obesity)

Recommendation: For T2D patients with CKD who require glucose control and have weight loss indication.

Evidence: GLP-1 RAs reduce proteinuria by ~20% independent of glucose lowering [4]. CREDENCE trial showed canagliflozin + GLP-1 RA additive benefit.

Advantage: Weight loss (unlike other antihyperglycemics), reduced cardiovascular events.

Monitor: Pancreatitis risk (low but real), retinopathy changes if diabetic.

Target Blood Pressure

KDIGO 2024 Recommendation: - Without albuminuria: <120 mmHg systolic (SBP) with home BP monitoring [1] - With albuminuria: <120 mmHg SBP with home BP monitoring

Rationale: SPRINT trial (non-diabetic CKD) showed 25% RRR in ESRD/death with intensive (SBP <120) vs standard (<140) BP targets.

Home Blood Pressure Monitoring

Preferred over office BP (office readings overestimate; home BP more predictive of progression).

Protocol: - Measure in morning (before medications) and evening - Record 3 readings, separated by 1–2 minutes, on 3+ days/week - Use validated automated device (avoid aneroid manometers) - Target: Mean SBP 110–120 mmHg

Antihypertensive Strategy

First-line (for CKD with albuminuria): 1. ACE-I or ARB (proteinuria reduction) 2. Add SGLT2i (cardiac + renal benefit) 3. Add finerenone if persistent albuminuria/progression

Add second agent if BP target not met: - Calcium channel blocker (amlodipine, diltiazem): reduces proteinuria, no adverse metabolic effects - Thiazide-type diuretic (chlorthalidone, hydrochlorothiazide): caution in K⁺ disturbances

Avoid (or use with extreme caution): - Direct vasodilators (hydralazine) as monotherapy: reflex tachycardia, hypertensive tolerance - Alpha-blockers: no renal protection; increased HF risk

Chronic Kidney Disease–Mineral Bone Disorder (CKD-MBD)

Pathophysiology: Phosphate retention → FGF23 elevation → secondary hyperparathyroidism → vascular calcification, bone disease.

Management: - Dietary PO₄ restriction: Target <1000 mg/day (G3–G4), <1200 mg/day (G5) - Phosphate binders (if G4–G5 or serum PO₄ >4.5 mg/dL): - Calcium-based (calcium carbonate, acetate): cheap; risk of vascular calcification - Non-calcium (sevelamer, patiromer, lanthanum): more expensive; preferred if Ca high or vascular disease present - Active vitamin D analogs (if PTH elevated): Calcitriol 0.25 μg 2–3×/week (G4–G5 with hyperparathyroidism) - Monitor: Serum Ca, PO₄, PTH every 6–12 months (G3), every 3–6 months (G4), every 1–3 months (G5)

Anemia in CKD

Etiology: Erythropoietin (EPO) deficiency (85%) + chronic inflammation + reduced RBC lifespan.

Hemoglobin Target: 10–11.5 g/dL (KDIGO; higher targets increase thrombotic risk).

Treatment Pathway: 1. Rule out other causes: Iron deficiency, B12/folate deficiency, GI bleeding, hemolysis 2. Iron repletion: Target ferritin 100–800 ng/mL, TSAT 20–50% - Oral iron (ferrous sulfate 325 mg daily) if TSAT <20% - IV iron (iron sucrose 100–200 mg × 3/week HD) for dialysis patients or IV-dependent 3. EPO-stimulating agents (ESA): If Hgb <10 despite iron repletion - Epoetin alfa, darbepoetin alfa (IV or SC) - Goal: Hgb 10–11.5 g/dL (avoid overcorrection → thrombosis risk) - Monitor: Blood pressure, thrombotic events 4. HIF-prolyl hydroxylase inhibitors (newer agents): - Roxadustat, daprodustat (oral; mimic hypoxia response) - Advantage: Oral; may reduce RBC transfusions; less hypertension - Caution: Thromboembolic risk; avoid if prior VTE/stroke

Metabolic Acidosis

Mechanisms: Reduced ammonia excretion, impaired H⁺ secretion, accumulation of organic acids.

Target pH: HCO₃⁻ ≥22 mEq/L [5].

Intervention: - Sodium bicarbonate: Start 0.5–1 g (6–12 mEq) 2–3×/day; increase to target - Newer agents: Sodium citrate, patiromer (potassium-binding agent with alkali effect) - Dietary modifications: Reduce net acid load (limit red meat, processed foods; increase fruits/vegetables)

Benefit: Slows CKD progression by ~30%; reduces bone loss; improves muscle mass.

Timing of Referral to Nephrology

KDIGO Recommendations: - G4 (eGFR 15–29): Refer for CKD management intensification, education, vascular access planning - G5 (eGFR <15): Prepare for renal replacement therapy (RRT) choice and timing

Modality Selection (Patient Education Timing: G3b–G4)

Vascular Access Planning (G4 Stage)

Timing: Initiate access planning when eGFR ~20 mL/min/1.73 m² to allow maturation.

Preferred Hierarchy: 1. Arteriovenous fistula (AVF): Autologous vein-to-artery; lowest infection/stenosis risk; 6–12 weeks maturation - Forearm (cephalic-radial preferred) or upper arm (brachial-axillary) 2. Arteriovenous graft (AVG): Synthetic prosthetic; shorter maturation (2–4 weeks); higher complication rate 3. Central venous catheter (CVC): Temporary access only; highest infection/thrombosis risk; should not be chronic access

Nephrologist’s Role: Refer to vascular surgeon for fistula evaluation; optimize BP, avoid BP draws/IV lines in non-fistula arm.

Advance Care Planning (G4–G5)

• Discuss RRT options (HD vs PD vs conservative care)
• Address goals of care, quality-of-life expectations, family preferences
• Document wishes if progression to G5 and RRT initiation needed
• Palliative care consultation if considering conservative (non-dialytic) management

CKD + Heart Failure

Unique Challenge: Diuretics reduce BP/perfusion → risk of AKI progression; RAAS blockade may worsen hyperkalemia.

Strategy: - SGLT2i: Proven benefit in both HF (reduced mortality) and CKD (slowed progression); use in both - Finerenone: Caution with K⁺; monitor closely - Loop diuretics: Minimum effective dose; target euvolemia - Aldosterone antagonists: Use finerenone instead of spironolactone (less hyperkalemia)

CKD + Diabetes

Evidence: SGLT2i + GLP-1 RA + RAAS blockade synergistic in slowing progression [5].

Goals: - Tight glycemic control (HbA₁c 7–8%); avoid hypoglycemia (↑ CV risk in CKD) - Initiate SGLT2i immediately at DM diagnosis if eGFR ≥20 - Add finerenone if albuminuria persists on ACE-I/ARB + SGLT2i - GLP-1 RA for additional glycemic and cardiometabolic benefit

CKD + Obesity

Advantage: SGLT2i provide weight loss (2–3 kg over 6 months); GLP-1 RA provide greater weight loss (4–8 kg).

Recommendation: Prefer these agents in obese CKD patients; defer to these drugs as primary weight-loss therapy.

Warning 1: Hyperkalemia in Advanced CKD

Combination of RAAS blockade + finerenone + SGLT2i (all K⁺-sparing) can precipitate dangerous hyperkalemia (K⁺ >6.0 mEq/L) in G4–G5.

Management: - Monitor K⁺ at baseline, 1–2 weeks post-initiation, then every 3–6 months - Hold agents if K⁺ >6.0 mEq/L; restart when K⁺ <5.5 mEq/L - Consider potassium binders (patiromer, sodium zirconium cyclosilicate) - Educate on low-K diet (restrict bananas, tomatoes, nuts, salt substitutes)

Warning 2: Acute Decline in GFR on ACE-I/ARB

30% SCr rise acceptable after initiation (due to hemodynamic changes). However, >30% rise or rise >0.5 mg/dL warrants reassessment: - Rule out AKI (dehydration, infections, NSAIDs) - Check renal artery stenosis if sudden decline - Consider dose reduction if marked hyperkalemia

Warning 3: Volume Overload in Dialysis Preparation

Paradoxically, CKD G4 can present with volume expansion (inability to excrete Na + H₂O) while still maintaining systolic hypertension. This requires: - ACE-I/ARB + loop diuretics (to reduce volume + BP) - Sodium restriction (<2000 mg/day) - Fluid restriction if SIADH or severe hyponatremia