Acute Kidney Injury (AKI) and Chronic Kidney Disease (CKD): Complete Clinical Guide

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PART 1: ACUTE KIDNEY INJURY (AKI)

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1.1 Definition

• Rise in serum creatinine (SCr) ≥0.3 mg/dL within 48 hours, OR
• Rise in SCr ≥50% (1.5× baseline) within 7 days, OR
• Urine output <0.5 mL/kg/h for >6 hours

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1.2 Staging (KDIGO)

• Risk → Injury → Failure → Loss (RRT >4 weeks) → End-stage (RRT >3 months)

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1.3 Causes and Classification

A. Prerenal AKI (~55-60%)

• Volume depletion: hemorrhage, vomiting, diarrhea, burns, third spacing
• Reduced cardiac output: heart failure, cardiogenic shock, massive PE
• Vasodilation/sepsis: septic shock, hepatorenal syndrome
• Medications: NSAIDs (inhibit prostaglandin-mediated afferent dilation), ACE inhibitors/ARBs (efferent arteriole dilation reduces GFR), calcineurin inhibitors, contrast agents
• Renal artery stenosis / renal vein thrombosis

• BUN:Cr ratio >20:1
• Urine Na <20 mEq/L
• FeNa <1% (FeNa = UNa × SCr / SNa × UCr × 100)
• FeUrea <35% (more useful if diuretics on board)
• Urine osmolality >500 mOsm/kg
• Hyaline casts on urinalysis

B. Intrinsic AKI (~35-40%)

• Aminoglycosides (gentamicin, tobramycin) - delayed 3-5 days
• Vancomycin
• Amphotericin B
• Cisplatin, ifosfamide
• Radiocontrast agents
• Myoglobin (rhabdomyolysis), hemoglobin (hemolysis)
• NSAIDs, calcineurin inhibitors

C. Postrenal AKI (~5-10%)

• Intrarenal: uric acid crystals (tumor lysis), oxalate crystals (ethylene glycol), myeloma casts, acyclovir/methotrexate crystals
• Ureteral: bilateral stones, retroperitoneal fibrosis, external compression (tumor, lymphadenopathy, gravid uterus)
• Bladder outlet: BPH, prostate cancer, bladder cancer, neurogenic bladder, anticholinergic drugs
• Urethral: stricture, phimosis

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1.4 Pathophysiology of Ischemic ATN

1. Initiation phase: Ischemia → ATP depletion → loss of cell polarity → Na+/K+-ATPase moves to apical surface → loss of brush border
2. Extension phase: Continued ischemia → endothelial injury → vascular congestion → inflammation (neutrophil and T-cell infiltration)
3. Maintenance phase: Tubular cell necrosis/apoptosis → cast formation → tubular obstruction → backleak of filtrate → oliguria
4. Recovery phase: Tubular cell regeneration → polyuria (tubular regeneration precedes concentrating ability)

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1.5 Clinical Features

• Oliguria (<400 mL/day) or anuria (<100 mL/day) in 50%; non-oliguric in the rest (better prognosis)
• Polyuria in recovery phase or postrenal AKI after relief
• Uremic symptoms: nausea, vomiting, fatigue, confusion, asterixis (uremic encephalopathy)
• Fluid overload: edema, pulmonary edema, hypertension
• Flank pain (obstructive, renal infarction)

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1.6 Diagnosis of AKI

• Urinalysis + microscopy: casts, RBCs, WBCs, protein
• Urine Na, Cr → calculate FeNa and FeUrea
• Urine osmolality
• Urine protein:creatinine ratio

• BMP (BUN, Cr, electrolytes)
• CBC (anemia, thrombocytopenia in TMA)
• Complement levels, ANCA, anti-GBM, ANA, SPEP (if GN suspected)
• CK, LDH, haptoglobin (rhabdomyolysis, hemolysis)
• Blood cultures if sepsis suspected
• Peripheral smear (schistocytes for TMA/HUS/TTP)

• Renal ultrasound: first-line to exclude obstruction, assess kidney size
• CT KUB (non-contrast): stones, obstructive uropathy

• NGAL (Neutrophil Gelatinase-Associated Lipocalin) - rises 2-6 hours after injury
• KIM-1 (Kidney Injury Molecule-1) - proximal tubular injury
• IL-18 - ischemic ATN
• Cystatin C - better GFR marker than creatinine in non-steady state
• [TIMP-2] × [IGFBP-7] - KDIGO-endorsed for predicting AKI progression

• Normal/hyaline casts → prerenal
• Muddy brown granular + tubular epithelial cell casts → ATN
• RBC casts, dysmorphic RBCs → glomerulonephritis
• WBC casts, eosinophiluria → AIN
• Oxalate crystals → ethylene glycol toxicity
• Uric acid crystals → tumor lysis syndrome

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1.7 Management of AKI

General Principles

1. Identify and treat the underlying cause
2. Optimize hemodynamics - maintain MAP ≥65 mmHg
3. Correct fluid and electrolyte imbalances
4. Discontinue all nephrotoxic medications
5. Dose-adjust all renally cleared medications (creatinine overestimates GFR in non-steady state)
6. Early nephrologist consultation

A. Prerenal AKI

• Isotonic crystalloid (0.9% saline or balanced crystalloid - Ringer's lactate, Plasma-Lyte) preferred over colloids
• Blood loss → packed red blood cells
• Avoid hydroxyethyl starch (increased AKI risk, no longer available for inpatients)
• 0.9% saline can worsen hyperchloremic acidosis → prefer Plasma-Lyte/Lactated Ringer's in acidosis; 0.9% saline acceptable in metabolic alkalosis
• Oliguria alone is NOT an indication for fluids - only give if intravascular hypovolemia is confirmed

• Rule out SBP (paracentesis with cell count and culture)
• IV Albumin: 25-50 g, maximum 100 g/day
• Vasoconstrictors: Norepinephrine or Terlipressin (vasopressin analogue)
• Or Midodrine (α1-adrenergic agonist) + Octreotide (somatostatin analogue) + IV albumin
• Definitive: orthotopic liver transplantation

B. Intrinsic AKI - Specific Therapies

C. Postrenal AKI

• Bladder outlet obstruction: Foley catheter → expect post-obstructive diuresis (monitor volume and replace ~50% of output to prevent severe dehydration)
• Ureteral obstruction: Percutaneous nephrostomy or ureteral stent
• Prompt relief can prevent permanent structural damage

D. Supportive Management

• Hypervolemia: restrict fluid and sodium
• Furosemide: bolus 200 mg IV → drip 10-40 mg/h
  • If patient responds to 60 mg IV bolus → convert to 10 mg/h continuous infusion
  • Reassess at 60 minutes; if no response, escalate dose
  • Loop diuretics do NOT improve natural history but may reduce need for dialysis
• Add thiazide (Metolazone 2.5-5 mg/d) for diuretic resistance (synergistic with loop diuretics)
• Low-dose dopamine - NOT recommended for AKI prevention/treatment (risk of arrhythmias and bowel ischemia outweighs benefit)

• Treat only if pH <7.20 AND HCO3 <15 mmol/L
• Sodium bicarbonate IV (oral for chronic AKI/CKD transition)
• Avoid overcorrection (risk: metabolic alkalosis, hypocalcemia, hypokalemia, volume overload)

• Phosphate binders with meals: calcium carbonate, calcium acetate, sevelamer, lanthanum carbonate, aluminum hydroxide (short-term only)

• Symptomatic only: Calcium gluconate 10% 10-20 mL IV slowly (monitor ionized calcium, not total, if hypoalbuminemia)

• Total energy: 20-30 kcal/kg/day
• Protein:
  • Non-catabolic, no dialysis: 0.8-1.0 g/kg/day
  • On dialysis: 1.0-1.5 g/kg/day
  • Hypercatabolic on CRRT: up to 1.7 g/kg/day
• Supplement water-soluble vitamins and trace elements

• ESAs not effective (delayed onset; marrow resistance in critical illness)
• DDAVP (Desmopressin) 0.3 mcg/kg IV for uremic bleeding
• GI prophylaxis: PPI or H2 blocker (note: PPIs themselves can cause AIN)
• VTE prophylaxis: avoid LMWH and factor Xa inhibitors in severe AKI (unpredictable PK); prefer unfractionated heparin

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1.8 Renal Replacement Therapy (RRT) in AKI

Absolute/Emergent Indications (AEIOU mnemonic):

• Acidosis - severe metabolic acidosis refractory to bicarbonate (pH <7.10)
• Electrolyte - hyperkalemia refractory to medical therapy
• Intoxication - methanol, ethylene glycol, salicylates, lithium (dialyzable)
• Overload - fluid overload refractory to diuretics (pulmonary edema)
• Uremia - uremic encephalopathy, uremic pericarditis, uremic bleeding

Timing:

• No benefit to early (preemptive based on creatinine threshold) vs standard (symptom-driven) initiation - initiate for uremic complications or metabolic emergencies
• Late initiation carries risk of complications

Modalities:

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PART 2: CHRONIC KIDNEY DISEASE (CKD)

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2.1 Definition

• GFR markers: eGFR <60 mL/min/1.73m²
• Kidney damage markers: albuminuria (ACR ≥30 mg/g), abnormal urine sediment, electrolyte abnormalities from tubular disorders, structural abnormalities on imaging, history of kidney transplant, pathological abnormalities on biopsy

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2.2 Staging (KDIGO 2012)

By GFR (G stages):

By Albuminuria (A categories):

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2.3 Epidemiology and Causes

1. Diabetic nephropathy (DKD) - most common cause (~40%)
2. Hypertensive nephrosclerosis - second most common
3. Glomerulonephritis - IgA nephropathy (most common worldwide), FSGS, membranous nephropathy
4. Polycystic kidney disease (ADPKD) - most common hereditary CKD
5. Renovascular disease - renal artery stenosis, hypertensive nephrosclerosis
6. Reflux nephropathy / chronic pyelonephritis
7. Obstruction - chronic obstructive uropathy
8. Drug nephrotoxicity - analgesic nephropathy (NSAIDs), calcineurin inhibitors
9. Systemic diseases - SLE, amyloidosis, myeloma, sarcoidosis
10. AKI to CKD transition - increasingly recognized as a significant pathway

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2.4 Pathophysiology of CKD Progression

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2.5 Clinical Features and Complications of CKD

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2.6 Diagnosis and Monitoring of CKD

• eGFR from serum creatinine (CKD-EPI 2021 equation preferred; race-free)
• Urine albumin:creatinine ratio (UACR) - on first morning void
• Urine protein:creatinine ratio
• Renal ultrasound - kidney size (small = chronic fibrosis; large = DKD, amyloid, infiltrative)
• Serum BMP, phosphate, calcium, PTH, HCO3, CBC, iron studies
• Lipid panel, HbA1c, fasting glucose

• GFR <30 mL/min/1.73m²
• UACR ≥300 mg/g
• Rapid GFR decline >5 mL/min/year or category change with ≥5 mL/min loss
• Unexplained hematuria + significant proteinuria
• Refractory hypertension
• Metabolic complications difficult to manage

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2.7 Management of CKD

A. Slowing Progression

• ACE inhibitors (first-line) or ARBs - dual benefit: lower BP + reduce intraglomerular pressure + antiproteinuric:
  • Ramipril 2.5-10 mg/day
  • Lisinopril 5-40 mg/day
  • Enalapril 5-40 mg/day (ACEi)
  • Losartan 25-100 mg/day
  • Irbesartan 150-300 mg/day
  • Valsartan 80-320 mg/day (ARBs)
  • Monitor: Expect up to 30% rise in SCr (acceptable and indicates drug is working); check K+ and Cr at 1 week after any dose change
  • Do NOT combine ACEi + ARB (increased risk of hyperkalemia and AKI without mortality benefit)
• Loop diuretics preferred over thiazides when GFR <30 mL/min (thiazides lose efficacy)
• Dihydropyridine CCBs (amlodipine) as adjunct

• Dapagliflozin 10 mg/day (DAPA-CKD trial - reduced CKD progression by 39%, regardless of diabetes status)
• Empagliflozin 10 mg/day (EMPA-KIDNEY trial)
• Canagliflozin 100 mg/day (CREDENCE trial - diabetic CKD)
• Indicated when eGFR ≥20-25 mL/min/1.73m² (continue even if eGFR falls below threshold during treatment)
• Reduce albuminuria, intraglomerular pressure, and cardiovascular events
• KDIGO 2024 recommends as foundational therapy alongside RAAS inhibition

• Target HbA1c ~7% (KDOQI guideline) to prevent microvascular complications and CKD progression
• SGLT2 inhibitors preferred (as above)
• GLP-1 receptor agonists (semaglutide, liraglutide) also show renoprotective effects in diabetic CKD
• Metformin: safe down to eGFR ≥30; hold if eGFR <30 or around contrast/surgery

• 10-20 mg/day in diabetic CKD with UACR ≥30 mg/g
• Reduces CKD progression and cardiovascular events (FIDELIO-DKD, FIGARO-DKD trials)
• Used in triple combination: RAAS inhibitor + SGLT2 inhibitor + Finerenone

B. Dietary Modifications

C. Complication Management

• Evaluate when Hb <13 g/dL (men) or <12 g/dL (women) with eGFR <60
• Target Hb: 9-11 g/dL (do NOT target >11.5; associated with increased cardiovascular mortality)
• Iron supplementation (always first):
  • Oral iron: ferrous sulfate 325 mg TID - limited by GI side effects and reduced absorption in CKD
  • IV iron preferred for dialysis patients or when oral ineffective:
    • Iron sucrose (Venofer): 200-300 mg IV infusion × 3-5 doses
    • Ferric carboxymaltose (Injectafer): up to 750 mg IV, can repeat in 7 days
    • Ferumoxytol: 510 mg IV, repeat in 3-8 days
• Erythropoiesis-Stimulating Agents (ESAs):
  • Only start if Hb <10 g/dL after addressing iron deficiency; goal is to reduce transfusions
  • Epoetin alfa (rHuEPO): SC/IV 50-100 units/kg 3×/week (HD patients); NDD-CKD: 10,000-40,000 units SC once weekly
  • Darbepoetin alfa: 0.45 mcg/kg SC/IV every 4 weeks (NDD-CKD); can dose every 2-4 weeks for HD patients
  • SC route 20-30% more efficient than IV (pharmacokinetics)
  • Monitor Hb every 1-2 weeks during initiation, every 3 months when stable
  • Hypertension occurs in 20-30% with ESA - treat rather than stop ESA
  • Do NOT target Hb >13 g/dL (TREAT, CHOIR trials - increased stroke and CV mortality)
  • HIF-PHI inhibitors (newer): Roxadustat, daprodustat - oral ESA alternatives; stimulate endogenous EPO production; approved in some countries
• Blood transfusions: Avoid if possible (sensitization risk pre-transplant); reserve for symptomatic severe anemia

• Evaluate: serum Ca, PO4, PTH, 25-OH vitamin D at G3 and above
• Target: PTH within 2-9× upper normal limit in dialysis patients

• Ergocalciferol (Vitamin D2): 50,000 IU PO weekly or biweekly for 8-12 weeks (if 25-OH VitD <5 ng/mL), then monthly maintenance
• Cholecalciferol (Vitamin D3): 2000-4000 IU/day; maintenance 1000-2000 IU/day

• Dietary restriction to 800-1000 mg/day
• Phosphate binders (take with meals):
  • Calcium carbonate: 500-1500 mg (200 mg elemental Ca/500 mg tab) TID with meals; total elemental calcium <1500 mg/day
  • Calcium acetate (Phoslo): 667 mg (169 mg elemental Ca) 2-4 caps TID with meals
  • Sevelamer carbonate (Renvela): 800-1600 mg TID with meals (non-calcium, non-absorbable; also lowers LDL)
  • Lanthanum carbonate (Fosrenol): 500-1000 mg TID with meals (non-calcium)
  • Ferric citrate (Auryxia): 2 tabs (2 g) TID with meals (also treats iron deficiency in dialysis patients)
  • Sucroferric oxyhydroxide (Velphoro): 500 mg TID with meals (dialysis patients)
  • Aluminum hydroxide: Effective but risk of aluminum toxicity - use only short-term

• If PTH remains elevated after vitamin D repletion and phosphate control:
  • Calcitriol (1,25-OH2 vitamin D3): 0.25-1 mcg/day PO or 0.5-4 mcg IV 3×/week (HD)
  • Paricalcitol (Zemplar): 1-5 mcg/day PO or 0.04-0.1 mcg/kg IV 3×/week
  • Doxercalciferol (Hectorol): 1-5 mcg/day PO
  • Monitor Ca closely - risk of hypercalcemia

• Cinacalcet (Sensipar): 30-180 mg/day PO (start 30 mg, titrate monthly)
  • Dialysis patients only - not for pre-dialysis CKD
  • Can cause significant hypocalcemia; monitor Ca
  • Usually combined with active vitamin D analogue
• Etelcalcetide (Parsabiv): IV calcimimetic for HD patients; 5 mg IV 3×/week

• Target: serum HCO3 ≥22 mEq/L
• Sodium bicarbonate tablets: 650 mg (7.7 mEq HCO3) or 1300 mg (15.5 mEq) - start 650-1300 mg BID-TID; titrate to HCO3 ≥22 mEq/L
• Benefit: slows CKD progression, reduces muscle wasting, improves bone health
• Alkali-rich diet (fruits and vegetables) is an alternative for mild acidosis

• Dietary K+ restriction
• Optimize RAAS inhibitors (lower dose rather than discontinue if possible)
• Patiromer (Veltassa): 8.4 g PO once daily (takes ~7 hours to work; not for acute emergency); maintenance 8.4-25.2 g/day
• Sodium zirconium cyclosilicate (Lokelma): 10 g TID × 48 hours for acute; 5-10 g/day maintenance (onset 1-2 hours)
• Fludrocortisone occasionally used in hyperkalemic renal tubular acidosis (type IV RTA)

• KDIGO 2013: Statin ± ezetimibe for all CKD patients age ≥50 with GFR <60 who are not on dialysis
• Rosuvastatin 10-20 mg/day (renally safe; dose adjustment for GFR <30)
• Atorvastatin 10-40 mg/day
• Ezetimibe 10 mg/day (if statin intolerant or in combination)
• No LDL target-based dose escalation recommended (KDIGO guideline)
• Dialysis patients: statins not started de novo (AURORA,4D trials - no benefit in established ESKD)

• Low-dose aspirin in established CVD
• BP control, diabetes management, smoking cessation
• Exercise and weight loss

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2.8 Preparation for Renal Replacement Therapy

• Uremic symptoms (encephalopathy, pericarditis, nausea/vomiting, anorexia)
• Hyperkalemia refractory to medical management
• Persistent extracellular volume overload despite diuretics
• Refractory metabolic acidosis
• Uremic bleeding diathesis
• eGFR <10 mL/min/1.73m² (with symptoms; no absolute creatinine or GFR threshold - symptom-driven)

• Arteriovenous fistula (AVF) - "fistula first" (best patency, lowest infection)
• AV graft (less ideal but acceptable)
• Tunneled dialysis catheter (last resort due to infection risk)
• Refer for AVF creation at GFR ~20-25 (needs 3-6 months to mature)

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2.9 AKI-CKD Connection

• AKI predisposes to CKD - even a single episode of AKI accelerates CKD progression
• CKD is the major risk factor for AKI - patients with CKD have 10× higher AKI risk
• After apparent recovery of AKI, monitor:
  • SCr and eGFR at 3 months
  • UACR at 3 months
  • Blood pressure
  • If abnormal at 3 months → classified as CKD; if normal → reassess at 6 months

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Summary Table: Key Doses at a Glance

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Sources

• Brenner and Rector's The Kidney, 2-Volume Set - Tables 29.2, 29.6; AKI staging, pathophysiology
• Harrison's Principles of Internal Medicine 22E (2025) - AKI and CKD management, supportive care
• Washington Manual of Medical Therapeutics - CKD staging, dietary management, mineral bone disease with doses
• National Kidney Foundation Primer on Kidney Diseases, 8e - ESA dosing, anemia management
• Comprehensive Clinical Nephrology, 7th Edition - CKD complication targets, RRT criteria, metabolic acidosis
• Campbell-Walsh-Wein Urology - Diuretic dosing in AKI
• PubMed: PMID 39190304 (AKI electronic alert systems meta-analysis, 2024)

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Clinical pearl: AKI and CKD are not isolated disorders - they form a bidirectional continuum. Every patient with AKI should be followed at 3 months for CKD, and every patient with CKD should be monitored for AKI risk factors. The foundations of CKD treatment in 2025 are: RAAS inhibition + SGLT2 inhibitor + finerenone (in diabetic CKD) - the "triple therapy" approach.This is a complete clinical guide based on authoritative nephrology textbooks (Brenner & Rector, Harrison's 22E, Washington Manual, NKF Primer, Comprehensive Clinical Nephrology). Here's a quick orientation to the guide above:

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What's Covered

• Definition - KDIGO criteria (SCr rise ≥0.3 mg/dL in 48h, or ≥50% in 7 days, or urine output <0.5 mL/kg/h)
• Staging - KDIGO Stages 1-3 with SCr and UO criteria; RIFLE comparison
• 3-category classification - Prerenal (~55%), Intrinsic (ATN, GN, AIN, vascular), Postrenal (~10%)
• Pathophysiology of ischemic ATN (4 phases), vulnerable nephron segments
• Diagnosis - urinalysis, FeNa/FeUrea, biomarkers (NGAL, KIM-1, cystatin C), urine sediment interpretation
• Management with doses - fluids, hyperkalemia ladder (calcium gluconate → insulin/dextrose → patiromer/ZS-9), furosemide dosing, nutrition targets, uremic bleeding
• RRT - AEIOU indications, IHD vs CRRT vs SLED vs PD

• Definition - structural or functional abnormality >3 months
• KDIGO staging - G1-G5 by eGFR + A1-A3 by albuminuria
• Causes - DKD (40%), hypertensive nephrosclerosis, GN, ADPKD, APOL1 genetics
• Pathophysiology - hyperfiltration, proteinuria-driven fibrosis, RAAS activation
• Complications - anemia, CKD-MBD, metabolic acidosis, hyperkalemia, CVD (each with management and doses)
• Slowing progression - ACEi/ARB + SGLT2 inhibitors (dapagliflozin/empagliflozin) + finerenone ("triple therapy" in DKD)
• Mineral bone disease - step-by-step: native vitamin D → phosphate binders → active vitamin D → cinacalcet (dialysis only)
• RRT planning - indications, modalities, vascular access timing