Nephritic syndrome is a clinical manifestation of inflammatory injury affecting the renal glomeruli, characterized by haematuria, proteinuria, reduced glomerular filtration rate (GFR), hypertension, and oedema. It results from inflammation of the glomerular structures, causing disruption of the filtration barrier and impaired kidney function.

Glomerular diseases represent a broad group of clinicopathological disorders that may progress to glomerulosclerosis and eventually end-stage kidney disease (ESKD). These disorders may occur as:

• Primary renal diseases, where the kidney is the main site of pathology.

• Secondary renal diseases, resulting from systemic conditions such as autoimmune disorders, infections, or other systemic illnesses.

Nephritic syndrome requires careful evaluation to determine the underlying cause because treatment depends on the specific glomerular disease identified. Empirical treatment without appropriate investigation may delay diagnosis of potentially serious conditions.

Epidemiology

Nephritic syndrome occurs worldwide and affects individuals of all ages, although the underlying causes vary according to age, geographic region, infection burden, and prevalence of systemic diseases.

In children, acute post-streptococcal glomerulonephritis remains an important cause of acute nephritic syndrome, particularly in areas with high rates of streptococcal infections. In adults, nephritic syndrome is more frequently associated with autoimmune diseases, vasculitis, infections, and other glomerular disorders.

Delayed diagnosis may lead to persistent kidney damage, chronic kidney disease, and end-stage kidney disease.

Risk Factors

Common risk factors include:

• Recent streptococcal infection.

• Autoimmune diseases such as systemic lupus erythematosus (SLE).

• Vasculitis.

• Chronic infections.

• Hepatitis B and hepatitis C infection.

• HIV infection.

• Diabetes mellitus.

• Family history of kidney disease.

• Exposure to certain medications associated with immune-mediated kidney injury.

• Previous episodes of glomerulonephritis.

Pathophysiology

Nephritic syndrome results from inflammatory injury to the glomeruli, usually mediated by immune mechanisms. Inflammation damages the glomerular capillary wall, allowing leakage of red blood cells and proteins into urine.

The inflammatory process reduces filtration capacity, resulting in:

• Reduced GFR.

• Retention of sodium and water.

• Increased blood pressure.

• Development of oedema.

Persistent inflammation may cause scarring of glomeruli (glomerulosclerosis), progressive loss of kidney function, and eventual end-stage kidney disease.

Clinical Presentation

Clinical features include:

• Haematuria.

• Proteinuria.

• Reduced GFR and effects of reduced kidney function.

• Hypertension.

• Oedema.

Patients may present with:

• Painless visible haematuria.

• Turbid, bloody, or brownish urine.

• Facial and peripheral oedema.

• Reduced urine output (oliguria).

• Difficulty in breathing due to fluid overload.

• Fatigue.

• Headache due to hypertension.

Severe presentations may include:

• Hypertensive encephalopathy.

• Reduced level of consciousness.

• Convulsions.

• Severe fluid overload.

Diagnostic Criteria

Nephritic syndrome is suspected in patients presenting with:

• Haematuria.

• Proteinuria.

• Reduced kidney function.

• Hypertension.

• Oedema.

Confirmation requires laboratory evaluation and, in selected cases, kidney biopsy to determine the specific underlying glomerular disease.

Differential Diagnosis

Conditions that should be considered include:

1. Nephrotic syndrome

   • Characterized by heavy proteinuria, hypoalbuminaemia, and generalized oedema.

2. Acute kidney injury (AKI)

   • May present with reduced urine output and rising creatinine but requires evaluation for the underlying cause.

3. Urinary tract infection

   • May cause haematuria and urinary abnormalities.

4. Renal calculi (kidney stones)

   • Can cause visible haematuria and flank pain.

5. Malignancy of the urinary tract

   • Particularly in adults with unexplained haematuria.

6. Acute pyelonephritis

   • Kidney infection causing haematuria, fever, and renal impairment.

7. Hypertensive nephropathy

   • Kidney injury associated with severe uncontrolled hypertension.

8. Diabetic kidney disease

   • Chronic kidney damage associated with diabetes and albuminuria.

9. Tubulointerstitial nephritis

   • Inflammatory kidney disease affecting renal tubules and interstitium.

Investigations

Investigations aim to confirm nephritic syndrome, assess kidney function, and identify the underlying cause.

Basic investigations

• Serum creatinine.

• Blood urea nitrogen (BUN) / urea.

• Urinalysis:

  • Dipstick testing.

  • Microscopy.

• Confirmation and quantification of proteinuria using:

  • Urine albumin-creatinine ratio (UACR).

  • Urine protein-creatinine ratio (UPCR).

• Urine culture.

• Complete blood count.

Specialized investigations

At tertiary hospital level:

• Kidney biopsy and histological examination.

• Antinuclear antibody (ANA).

• Anti-double stranded DNA antibodies (anti-dsDNA).

• Rheumatoid factor (RF).

• Complement levels (C3 and C4).

• Syphilis screening:

  • Venereal Disease Research Laboratory (VDRL).

  • Rapid plasma reagin (RPR).

Additional investigations should be guided by clinical suspicion.

Management

Management aims to:

• Treat the underlying cause.

• Control fluid overload.

• Manage hypertension.

• Prevent complications.

• Preserve kidney function.

The definitive treatment depends on the specific cause of nephritis. A diagnosis such as acute post-streptococcal nephritis or another glomerular disease should not be assumed without appropriate investigation.

Non-pharmacological Treatment

General measures include:

• Administer oxygen if respiratory distress is present.

• Nurse the patient in semi-Fowler's position when respiratory symptoms occur.

• Restrict dietary salt intake.

• Restrict potassium-containing foods and fluids.

• Restrict fluid intake to approximately:

  • 10 mL/kg/day plus visible fluid losses.

• Monitor:

  • Urine output.

  • Blood pressure.

  • Body weight.

  • Electrolytes.

  • Kidney function.

Pharmacological Treatment

Treatment depends on the clinical condition and underlying cause.

Fluid overload

For patients with fluid overload:

• Furosemide 80 mg intravenous bolus.

Response should be monitored carefully, particularly urine output, blood pressure, and electrolyte levels.

Hypertension

If:

• Diastolic blood pressure is greater than 100 mmHg, or

• Systolic blood pressure is above 150 mmHg,

Administer:

• Amlodipine 5 mg orally as a stat dose before referral.

Continue additional antihypertensive therapy according to hypertension management guidelines while considering contraindications and kidney function.

Referral

Refer patients to a nephrologist or higher-level facility when:

• Nephritic syndrome is suspected.

• Kidney biopsy is required.

• Kidney function is deteriorating.

• Severe hypertension is present.

• Hypertensive encephalopathy occurs.

• Significant proteinuria or haematuria persists.

• Dialysis may be required.

Patients with suspected glomerular disease should receive specialist assessment because treatment depends on the specific pathological diagnosis.

Complications

Potential complications include:

• Acute kidney injury.

• Severe hypertension.

• Hypertensive encephalopathy.

• Pulmonary oedema.

• Electrolyte abnormalities.

• Chronic kidney disease.

• End-stage kidney disease.

• Cardiovascular complications.

• Death.

Prognosis

The prognosis depends on the underlying glomerular disease, severity of kidney injury, response to treatment, and presence of complications.

Some causes, such as acute post-infectious glomerulonephritis, may resolve completely, while others, including autoimmune or rapidly progressive glomerular diseases, may progress to chronic kidney disease or end-stage kidney disease if not diagnosed and treated promptly.

Prevention

Preventive measures include:

• Early diagnosis and treatment of infections.

• Effective management of autoimmune diseases.

• Control of hypertension and diabetes.

• Avoidance of nephrotoxic medications.

• Early evaluation of persistent haematuria and proteinuria.

• Regular monitoring of kidney function in high-risk individuals.

• Early referral for suspected glomerular disease.