End-Stage Renal Failure (ESRF)

1. Definition

End-Stage Renal Failure (ESRF), also called End-Stage Kidney Disease (ESKD), is the irreversible final stage (stage 5) of chronic kidney disease (CKD), defined by a glomerular filtration rate (GFR) <15 mL/min/1.73 m² or the requirement for renal replacement therapy (RRT) to sustain life (dialysis or kidney transplantation).

2. Causes

Cause Category	Specific Conditions
Diabetic nephropathy	Longstanding uncontrolled diabetes mellitus
Hypertensive nephrosclerosis	Chronic hypertension
Glomerular diseases	Chronic glomerulonephritis, lupus nephritis
Tubulointerstitial disease	Reflux nephropathy, chronic pyelonephritis
Hereditary diseases	Polycystic kidney disease, Alport syndrome
Obstructive uropathy	BPH, stones, tumors
Drug/toxin-related	NSAIDs, lithium, aminoglycosides

3. Risk Factors

Diabetes mellitus (type 1 or 2)
Hypertension
Cardiovascular disease
Family history of CKD
Smoking
Obesity
Dyslipidemia
Recurrent urinary tract infections
Age > 60 years
Exposure to nephrotoxic agents
Proteinuria

4. Types / Classifications

KDIGO CKD Staging (Stage 5 = ESRF)

Stage	eGFR (mL/min/1.73 m²)	Description
5	<15	Kidney failure (ESRF)

By RRT Status

Hemodialysis-dependent ESRF
Peritoneal dialysis-dependent ESRF
Transplant-eligible ESRF
Conservative (non-dialysis) ESRF

5. Pathogenesis

Progressive nephron loss due to underlying pathology → reduced GFR
Compensatory hyperfiltration in remaining nephrons → further damage
RAAS activation → hypertension, glomerular sclerosis
Uremic toxin accumulation → systemic toxicity
Electrolyte imbalances and acid-base disturbances
Erythropoietin deficiency → anemia
Impaired phosphate/calcium regulation → secondary hyperparathyroidism

6. Clinical Features

Symptoms

Acute/Decompensated ESRF:

Dyspnea (fluid overload)
Nausea, vomiting, anorexia
Decreased urine output
Confusion, lethargy (uremia)

Chronic ESRF:

Pruritus
Fatigue
Restless leg syndrome
Muscle cramps
Sexual dysfunction
Menstrual irregularities

Physical Examinations

General Examination:

Parameter	Findings
GCS	Reduced in severe uremia
Bedside	Dialysis access, uremic frost, pallor
Vital signs	Hypertension common; hypotension in late stages
Hands	Pale palms (anemia), flapping tremor (asterixis)
Face	Periorbital edema, hyperpigmentation

System-Based Examination:

Cardiovascular

Volume overload signs: elevated JVP, displaced apex
Pericardial rub (uremic pericarditis)
Hypertension

Respiratory

Crackles: pulmonary edema
Pleural effusion

Abdominal

Distension (ascites from hypoalbuminemia)
Tender kidneys (polycystic kidney disease)

Neurological

Peripheral neuropathy
Asterixis
Confusion in advanced uremia

Special Tests

Uremic encephalopathy signs: cognitive decline, poor concentration

7. Organ & System Complications

System	Complication
Cardiovascular	LVH, ischemic heart disease, pericarditis
Hematologic	Normocytic normochromic anemia, platelet dysfunction
Neurologic	Uremic encephalopathy, peripheral neuropathy
Endocrine/Metabolic	Secondary hyperparathyroidism, bone disease
Respiratory	Pulmonary edema, pleural effusion
Dermatologic	Pruritus, uremic frost, hyperpigmentation
GI	Nausea, gastritis, anorexia
Immunologic	Increased infection susceptibility

8. Diagnostic Investigations

Test	Expected Findings
Serum creatinine	Elevated
eGFR	<15 mL/min/1.73 m²
Blood urea nitrogen (BUN)	Elevated
Electrolytes	Hyperkalemia, hyperphosphatemia, hypocalcemia
Arterial blood gas	Metabolic acidosis (low HCO₃⁻)
CBC	Normocytic normochromic anemia
Urinalysis	Proteinuria, hematuria, isosthenuria
Renal ultrasound	Small, echogenic kidneys in chronic ESRD

9. Other Relevant Investigations

Test	Expected Findings
Parathyroid hormone (PTH)	Elevated (secondary hyperparathyroidism)
Vitamin D levels	Low
Ferritin, transferrin saturation	Variable; evaluate iron status
ECG	Tall T waves (hyperkalemia), LVH, prolonged QT
Chest X-ray	Pulmonary congestion, cardiomegaly
Bone density scan (if indicated)	Low BMD (renal osteodystrophy)

10. Treatment

Curative/Definitive:

Kidney transplantation

Empirical:

Antihypertensives (ACEi/ARB if tolerated)
Erythropoiesis-stimulating agents (ESAs) for anemia
Phosphate binders
Vitamin D analogs

Supportive:

Dialysis (hemodialysis or peritoneal dialysis)
Sodium/fluid restriction
Dietary phosphate and potassium restriction
Iron supplementation
Bicarbonate for acidosis

Palliative:

Conservative management in non-transplant candidates
Symptom control: pain, dyspnea, pruritus, fatigue
Advance care planning and hospice

11. Long Term Effects / Complications of Treatment

Treatment	Complication	Monitoring Investigations	Expected Results
Hemodialysis	Access site infection, hypotension	Dialysis adequacy (Kt/V), CBC	Target Kt/V >1.2
Peritoneal dialysis	Peritonitis	Peritoneal fluid WBC count	<100 cells/µL
ESA therapy	Hypertension, thromboembolism	BP, Hb every 2–4 weeks	Hb target 10–11.5 g/dL
Phosphate binders	Hypercalcemia	Serum calcium, phosphate	Ca 2.1–2.5 mmol/L, PO₄ 0.9–1.5 mmol/L
Transplantation	Graft rejection, infection, malignancy	Creatinine, immunosuppressive drug levels	Stable creatinine, therapeutic drug levels

12. Surveillance

Surveillance Tool	Frequency
Renal panel (U&E, eGFR)	Monthly or more often if unstable
CBC	Every 1–3 months (anemia monitoring)
PTH, calcium, phosphate	Every 3–6 months
Iron studies	Every 3–6 months on ESA
Dialysis adequacy (Kt/V)	Every 3 months (hemodialysis)
Echocardiogram	Annually
Bone density scan	Every 1–2 years (if CKD-MBD present)

13. References

Malaysia Clinical Practice Guidelines
- Management of Chronic Kidney Disease, Ministry of Health Malaysia, 2nd Edition (Updated 2018)
- https://www.moh.gov.my
UK NHS/NICE Guidelines
- NICE NG203: Chronic kidney disease: assessment and management
- https://www.nice.org.uk/guidance/ng203
UpToDate
- “Overview of the management of chronic kidney disease in adults”
- “Dialysis-related complications”
- “Kidney transplantation in adults: Overview of immunosuppression”