Paediatric Long Case Discussions

When taking a history for a child with known asthma, the goal is to assess control, identify triggers, check for comorbidities, and evaluate management and adherence.

• Assessment of Asthma Control (GINA Guidelines):
  • Daytime Symptoms: How often in the past 4 weeks? (More than twice a week is uncontrolled).
  • Night-time Waking: Any night waking due to asthma? (Any is a sign of poor control).
  • Reliever Use: How often is the reliever (e.g., Salbutamol) needed? (More than twice a week is uncontrolled).
  • Activity Limitation: Does asthma limit play, sports, or daily activities? (Any limitation is a sign of poor control).
• Triggers and Comorbidities:
  • Triggers: Inquire about exposure to common triggers: viral infections (colds), dust mites, pet dander (dog, cat), cockroaches, pollen, passive smoking, and changes in weather.
  • Atopic History (The “Atopic March”): Ask about symptoms of other atopic conditions like Allergic Rhinitis (sneezing, runny/blocked nose), Eczema (atopic dermatitis), and food allergies.
• History of Exacerbations:
  • Frequency and severity of past asthma attacks.
  • History of hospitalizations, emergency room visits, or ICU admissions.
  • Previous need for oral or IV steroids.
• Management and Adherence:
  • Current Medications: Names of all inhalers (preventer and reliever), doses, and frequency.
  • Inhaler Technique: Ask the parent/child to demonstrate their technique. Ask about the use and cleaning of a spacer device.
  • Adherence: How often are doses missed? What are the barriers to taking medication (e.g., forgetfulness, cost, fears about side effects)?
• Social and Family History:
  • Home Environment: Smoking in the household, presence of pets, dampness or mold.
  • Family History: Asthma, allergies, or eczema in parents or siblings.
  • Impact: Effect on school attendance, family life, and psychosocial well-being.

The physical examination aims to identify signs of current respiratory distress, chronic changes, complications, and associated atopic features.

• General Examination:
  • Vitals & Respiratory Distress: Check respiratory rate, heart rate, and SpO2. Look for signs of increased work of breathing (subcostal/intercostal retractions, nasal flaring, use of accessory muscles).
  • Growth Parameters: Plot height and weight on a growth chart. Long-term use of corticosteroids, especially oral steroids, can affect growth. A calorie deficit may indicate chronic, severe disease.
  • Atopic Stigmata: Look for signs of atopy which increase the likelihood of asthma:
    • Eyes: Allergic shiners (dark circles under the eyes), Dennie-Morgan lines (creases below the lower eyelids).
    • Nose: Transverse nasal crease from the “allergic salute,” pale or bluish nasal mucosa.
    • Skin: Signs of active or past eczema (flexural lichenification).
  • Clubbing: Absence of clubbing is expected. Its presence would suggest an alternative diagnosis like cystic fibrosis or bronchiectasis.
• Respiratory System Examination:
  • Inspection: Look for chest wall deformities like Harrison’s sulci (a groove at the lower margin of the thorax) or pectus excavatum, which can be seen in chronic, poorly controlled asthma.
  • Auscultation: Listen for polyphonic, expiratory wheeze. A silent chest during an acute attack is an ominous sign. Check air entry globally. Listen for crepitations, which might suggest a concurrent infection (pneumonia) or a complication.
• Assessment of Inhaler Technique:
  • This is a critical part of the “examination.” Ask the patient to demonstrate how they use their inhaler and spacer. Check for common errors like not shaking the canister, poor coordination, inhaling too quickly, or not holding their breath.

Poor control is multifactorial. A systematic approach is needed to identify the cause(s):

• Issues with Management:
  • Incorrect Inhaler Technique: The most common reason. The drug does not reach the lungs effectively.
  • Poor Adherence/Compliance: Patient not taking the preventer medication regularly as prescribed.
  • Inadequate Treatment: The prescribed dose or type of medication may be insufficient for the severity of their asthma (e.g., needs a step-up in GINA guidelines).
• Environmental/External Factors:
  • Ongoing Trigger Exposure: Unidentified or unavoidable exposure to allergens (pets, dust mites, pollen) or irritants (tobacco smoke).
  • Comorbidities: Untreated associated conditions that can worsen asthma, such as:
    • Allergic Rhinitis: Inflammation in the upper airways can worsen inflammation in the lower airways.
    • Gastroesophageal Reflux Disease (GERD): Microaspiration of stomach acid can trigger bronchospasm.
    • Obesity: A pro-inflammatory state that can lead to more severe, difficult-to-treat asthma.
• Diagnostic Uncertainty:
  • Incorrect Diagnosis: The patient’s symptoms (wheeze, cough) might be due to another condition, such as vocal cord dysfunction, cystic fibrosis, or bronchiectasis.
• Psychosocial Factors:
  • Family stress, lack of understanding of the disease, or adolescent rebellion can lead to poor adherence.

Life-threatening asthma is a medical emergency requiring immediate and aggressive treatment.

Features (any of the following):

• General Appearance: Drowsy, confused, or exhausted state.
• Airway: A “silent chest” on auscultation (due to severe bronchoconstriction and poor air movement).
• Breathing: Weak respiratory effort, cyanosis, SpO2 < 92%.
• Circulation: Bradycardia or hypotension.
• PEFR: < 33% of predicted or personal best.

Emergency Management:

1. Immediate High-Flow Oxygen: Administer via a non-rebreather mask to maintain SpO2 > 94%.
2. Back-to-Back Nebulized Bronchodilators:
   • Salbutamol: Nebulized with oxygen.
   • Ipratropium Bromide: An anticholinergic, given together with Salbutamol for synergistic effect.
3. Systemic Corticosteroids:
   • IV Hydrocortisone or oral Prednisolone immediately. Steroids take several hours to work but are crucial to reduce airway inflammation. A typical IV Hydrocortisone dose for a child is 4 mg/kg.
4. Second-Line Therapies (if not responding):
   • IV Magnesium Sulfate: Acts as a bronchodilator. Given as a slow infusion.
   • IV Aminophylline/Salbutamol: Considered if the patient is still deteriorating. Requires cardiac monitoring and careful administration in an HDU/ICU setting.
5. Intubation and Ventilation: If the patient develops respiratory arrest, coma, or continues to deteriorate despite maximal therapy. This is a last resort.

Pneumothorax is a rare but serious complication of severe asthma exacerbations.

Bedside Clinical Diagnosis:

• Sudden Deterioration: A patient with severe asthma suddenly worsens, often with sharp, pleuritic chest pain.
• Asymmetrical Chest Examination:
  • Inspection: Reduced chest movements on the affected side.
  • Palpation: Tracheal deviation away from the affected side (in tension pneumothorax). Reduced chest expansion on the affected side.
  • Percussion: Hyper-resonant percussion note over the affected area.
  • Auscultation: Diminished or absent breath sounds on the affected side.

Confirmation:

• Erect Chest X-ray: This is the gold standard for confirmation. It will show a visceral pleural line with a lack of lung markings peripheral to it. In a tension pneumothorax, there will also be contralateral mediastinal shift and flattening of the hemidiaphragm.

Management involves treating both the infection and the asthma exacerbation it has triggered.

• Supportive Care: Oxygen, hydration, and antipyretics as needed.
• Asthma Management: Administer bronchodilators (e.g., nebulized Salbutamol) and systemic corticosteroids as you would for a standard exacerbation. The infection is the trigger, but the underlying airway inflammation and bronchoconstriction must be treated.
• Antibiotics:
  • Causative Organisms: In community-acquired pneumonia (CAP), the most common bacterial pathogens are Streptococcus pneumoniae, followed by atypical organisms like Mycoplasma pneumoniae in older children.
  • Choice of Antibiotic: Oral Amoxicillin is typically the first-line treatment for uncomplicated CAP. If an atypical pneumonia is suspected, a macrolide like Azithromycin or Clithromycin would be added. For hospitalized patients, IV Benzylpenicillin or Co-amoxiclav is often used.

Investigating an allergy to house dust mites (HDM) is important in patients with poorly controlled asthma, as HDM is a major indoor allergen.

• Skin Prick Test (SPT): This is the most common, rapid, and sensitive method. A small drop of HDM allergen extract is placed on the skin (usually the forearm), and the skin is lightly pricked. A positive reaction is a wheal-and-flare response appearing within 15-20 minutes, which is larger than the negative control (saline).
• Specific IgE Blood Test (e.g., RAST or ImmunoCAP): This blood test measures the amount of IgE antibodies specific to HDM in the patient’s blood. It is a useful alternative when skin testing cannot be done (e.g., patient has severe eczema or is on antihistamines).

The history in a known thalassemia patient focuses on the adequacy of current therapy, monitoring for complications, and assessing quality of life.

• Transfusion History:
  • Frequency: How often are transfusions required? A shortening interval (e.g., from every 4 weeks to every 3 weeks) is a key indicator of developing hypersplenism.
  • Pre-transfusion Haemoglobin: What are his typical Hb levels before transfusion? The goal is to keep it above 9-9.5 g/dL to prevent complications and ensure adequate growth.
  • Transfusion Reactions: Any history of febrile, allergic, or delayed transfusion reactions?
• Iron Chelation Therapy:
  • Drug and Dose: Which chelator is he on (e.g., Deferasirox, Desferrioxamine, Deferiprone)? What is the dose?
  • Adherence: This is critical. For oral chelators, ask about missed doses. For Desferrioxamine, ask about the number of nights the subcutaneous pump is used.
  • Side Effects: Inquire about common side effects (e.g., gastrointestinal upset with Deferasirox, auditory/visual toxicity with Desferrioxamine).
• Monitoring for Complications of Iron Overload:
  • Endocrine: Ask about growth and puberty (short stature, delayed puberty are common). Symptoms of hypothyroidism or diabetes.
  • Cardiac: Any symptoms of heart failure like exercise intolerance, shortness of breath, or palpitations? (Iron-induced cardiomyopathy is the leading cause of death).
  • Liver: Any abdominal pain or jaundice? (Iron deposition leads to fibrosis and cirrhosis).
• General Health and Development:
  • Growth: Review growth charts. Poor growth can be due to chronic anemia, iron overload, or endocrinopathies.
  • Schooling and Activities: Assess impact on daily life.
  • Dietary Advice: Have they received advice to avoid iron-rich foods?
• Family and Social Context:
  • Understanding of the inheritance pattern (autosomal recessive).
  • Inquire about plans for future children and the availability of prenatal diagnosis.
  • Discuss the status of the Bone Marrow Transplant (BMT) workup, including donor search.

The examination looks for signs of chronic anemia, extramedullary hematopoiesis, and complications of iron overload.

• General Examination:
  • Pallor and Jaundice: Signs of anemia and hemolysis.
  • Growth Parameters: Essential for monitoring disease control and endocrine health.
  • Thalassemic Facies: (Frontal bossing, maxillary prominence, depressed nasal bridge). Caused by bone marrow expansion from ineffective erythropoiesis. Well-transfused patients may have minimal facies.
  • Pubertal Staging (Tanner): To assess for delayed puberty.
• Abdominal Examination:
  • Hepatosplenomegaly: Palpate for the liver and spleen. Splenomegaly is due to both extramedullary hematopoiesis and the removal of abnormal red cells. Increasing spleen size is a sign of hypersplenism.
• Cardiovascular System:
  • Look for signs of high-output cardiac failure (due to anemia) or cardiomyopathy (due to iron overload), such as a flow murmur, gallop rhythm (S3), or elevated JVP.
• Endocrine System:
  • Assess for signs of hypothyroidism (e.g., goiter) or other endocrine issues.

An increasing transfusion requirement (i.e., a shortening interval between transfusions needed to maintain the target pre-transfusion Hb) is the hallmark of hypersplenism.

• Mechanism of Hypersplenism:
  1. The spleen, enlarged due to its role in extramedullary hematopoiesis and clearing defective RBCs, becomes overactive.
  2. It begins to sequester and destroy not only the patient’s abnormal red cells but also the transfused donor red cells at an accelerated rate.
  3. This leads to a shorter survival of transfused RBCs, causing the patient’s hemoglobin to drop more quickly and requiring more frequent transfusions.
  4. Hypersplenism can also lead to thrombocytopenia and leukopenia (pancytopenia).
• Management: If hypersplenism becomes severe (causing a massive increase in transfusion needs or symptomatic pancytopenia), a splenectomy may be considered.

Excess iron from repeated transfusions is toxic as the body has no natural way to excrete it. It deposits in and damages various organs.

Complications:

• Heart: Dilated cardiomyopathy, arrhythmias, heart failure. This is the leading cause of mortality.
• Liver: Transaminitis, hepatic fibrosis, cirrhosis, and an increased risk of hepatocellular carcinoma.
• Endocrine Glands:
  • Pituitary: Hypogonadotropic hypogonadism (leading to delayed puberty and infertility).
  • Pancreas: Diabetes mellitus (damage to beta cells).
  • Thyroid/Parathyroid: Hypothyroidism and hypoparathyroidism.
  • Adrenals: Adrenal insufficiency.
• Bones: Osteoporosis and osteopenia.

Monitoring:

• Serum Ferritin: A blood test done every 3 months. It’s an indicator of total body iron stores but can be affected by inflammation. The goal is to keep it < 1000 ng/mL.
• Liver Iron Concentration (LIC): The gold standard is a liver biopsy, but this is invasive.
• MRI T2*: A non-invasive imaging technique that has become the standard of care for quantifying iron deposition in the heart (cardiac T2*) and liver (liver T2*). This is crucial for guiding chelation therapy to prevent cardiac complications. An annual MRI is recommended.
• Annual Endocrine Screening: Oral glucose tolerance test (for diabetes), thyroid function tests, calcium/phosphate levels, and assessment of growth and puberty.
• Annual Cardiac Assessment: Echocardiogram and ECG to assess cardiac function.

The goal of chelation is to bind excess iron and excrete it from the body.

1. Desferrioxamine (DFO):
   • Use: Given as a slow subcutaneous infusion via a portable pump, typically overnight for 8-12 hours, 5-7 nights a week. It can also be given intravenously.
   • Side Effects: Local skin reactions, auditory (high-frequency hearing loss) and visual toxicity, growth retardation with high doses. Poor compliance is a major issue due to the burdensome administration.
2. Deferasirox (Exjade, Asunra):
   • Use: A once-daily oral medication. Comes as a dispersible tablet that is mixed in water or juice.
   • Side Effects: Gastrointestinal disturbances (nausea, diarrhea, abdominal pain) are common. Can cause a non-progressive rise in creatinine and elevated liver enzymes, requiring regular monitoring of renal and liver function.
3. Deferiprone (L1):
   • Use: An oral medication taken three times a day. It is particularly effective at removing iron from the heart. Often used in combination with DFO or Deferasirox for patients with significant cardiac iron overload.
   • Side Effects: Agranulocytosis/neutropenia (a serious drop in white blood cells) is a major risk, requiring weekly blood count monitoring. Also causes arthropathy (joint pain) and GI upset.

The only established permanent cure for Thalassemia Major is Allogeneic Haematopoietic Stem Cell Transplantation (HSCT), often referred to as a Bone Marrow Transplant (BMT).

• Principle: The patient’s own defective bone marrow is ablated (destroyed) using high-dose chemotherapy. They are then infused with healthy hematopoietic stem cells from a compatible donor. These donor cells migrate to the bone marrow, engraft, and start producing normal, healthy red blood cells.
• Donor Source: The best outcome is with an HLA-matched sibling donor. Other sources include matched unrelated donors (MUD) from international registries or haploidentical (half-matched) family donors.
• Risks and Complications:
  • Graft-versus-Host Disease (GVHD): Donor immune cells attack the recipient’s body. Can be acute or chronic.
  • Graft Failure/Rejection: The donor cells fail to engraft or are rejected by the patient’s body.
  • Infections: The patient is severely immunocompromised for a period and is at high risk of life-threatening infections.
  • Toxicity from Conditioning: The chemotherapy/radiotherapy regimen has its own short-term and long-term side effects, including infertility and risk of secondary cancers.
• Future Therapies:
  • Gene Therapy: This is an emerging curative option. The patient’s own hematopoietic stem cells are harvested, corrected in the lab using a viral vector to insert a functional beta-globin gene, and then re-infused into the patient. This avoids the risks of GVHD. It is currently available in clinical trials and has recently received regulatory approval in some regions.

The history in a child with known nephrotic syndrome is aimed at assessing disease activity, monitoring for complications of the disease and its treatment, and evaluating the family’s ability to manage the condition.

• Disease Activity and Relapses:
  • Current Status: Is the child in remission (no proteinuria)? How is this monitored at home (urine dipstick)?
  • Relapse History: How many relapses have occurred in the last year? What typically triggers a relapse (e.g., viral infections)? This helps classify the disease (e.g., infrequent vs. frequent relapser).
  • Response to Steroids: Confirm the diagnosis of Steroid-Dependent NS (relapses while on tapering steroids or within 2 weeks of stopping). Differentiate from Steroid-Resistant NS (failure to achieve remission after 4 weeks of daily high-dose prednisolone).
• Treatment History and Side Effects:
  • Corticosteroids (Prednisolone): Current dose and tapering schedule. Inquire about side effects:
    • Growth: Review growth charts (steroids can cause growth failure).
    • Appearance: Cushingoid features (moon face, weight gain, hirsutism).
    • Bone Health: Any bone pain? (Risk of osteoporosis/avascular necrosis).
    • Mood/Behaviour: Any mood swings, sleep disturbance, or increased appetite?
    • Eyes: Any visual problems? (Risk of cataracts and glaucoma).
  • Steroid-Sparing Agents: Confirm use of drugs like Levamisole or Cyclophosphamide. Ask about any known side effects and monitoring.
• Monitoring for Complications of Nephrotic Syndrome:
  • Infections: Any recent fevers or illnesses? Children with NS are at high risk of serious bacterial infections (especially from encapsulated organisms like S. pneumoniae) due to loss of immunoglobulins and complement factors in the urine. Spontaneous Bacterial Peritonitis (SBP) is a classic complication.
  • Thrombosis: Any signs of blood clots, like a swollen, painful leg (DVT) or sudden shortness of breath (PE)? The risk is high due to loss of anticoagulant proteins (Antithrombin III) and increased synthesis of pro-coagulant factors by the liver.
  • Hypovolemia: During a relapse, ask about symptoms of low circulating volume like abdominal pain, dizziness, or reduced urine output, despite being edematous.
• Vaccination Status: Specifically ask about the Pneumococcal (PCV, PPV23) and Varicella vaccines, as these are crucial for preventing severe infections. Live vaccines are contraindicated while on high-dose immunosuppression.
• Family and Social Context: Assess the family’s understanding of the disease, their ability to monitor urine, manage diet (low salt during relapse), and recognize warning signs.

The examination focuses on identifying signs of current disease activity (edema), complications of the disease, and iatrogenic side effects from treatment.

• General Examination:
  • Edema: Look for periorbital edema (especially in the morning), pitting edema in the legs and sacral area, and ascites or pleural effusions in severe cases.
  • Vitals: Check blood pressure (hypertension can be a complication or a side effect of steroids) and assess for signs of hypovolemia (tachycardia, hypotension) if in relapse.
  • Iatrogenic Cushing’s Syndrome: Look for classic signs from chronic steroid use:
    • Moon facies, “buffalo hump” (dorsocervical fat pad).
    • Central obesity, thin limbs.
    • Abdominal striae (purplish), thin skin, easy bruising.
    • Hirsutism.
  • Growth Parameters: Height and weight are mandatory. Stunting is a major long-term side effect of steroids.
• System Specific Examination:
  • Abdomen: Palpate for ascites (fluid thrill, shifting dullness). Tenderness could suggest Spontaneous Bacterial Peritonitis (SBP).
  • Respiratory: Check for signs of pleural effusion (stony dull percussion note, reduced breath sounds at the bases).
  • Ophthalmological: A formal eye check (slit-lamp examination) is needed periodically to screen for steroid-induced cataracts and glaucoma.

Complications arise from the massive loss of protein in the urine and the resulting physiological changes.

• Infections: This is a major cause of morbidity and mortality.
  • Cause: Loss of immunoglobulins (IgG) and complement components (Factor B) in the urine leads to impaired opsonization and defense against encapsulated bacteria.
  • Common Infections: Spontaneous Bacterial Peritonitis (SBP) with organisms like Streptococcus pneumoniae is classic. Sepsis, cellulitis, and pneumonia are also common.
• Thromboembolism: The risk of both arterial and venous clots is significantly increased.
  • Cause: A hypercoagulable state caused by urinary loss of anticoagulants (Antithrombin III, Protein C & S), increased hepatic synthesis of pro-coagulant factors (Fibrinogen, Factors V & VIII), and hemoconcentration during hypovolemia.
  • Common Sites: Deep Vein Thrombosis (DVT), Pulmonary Embolism (PE), and Renal Vein Thrombosis are well-described.
• Hypovolemia and Acute Kidney Injury (AKI):
  • Cause: Despite massive edema (third spacing of fluid), the intravascular volume can be severely depleted due to low plasma oncotic pressure. This can be exacerbated by diuretic use or sepsis.
  • Consequence: Reduced renal perfusion can lead to pre-renal AKI.
• Hyperlipidemia:
  • Cause: A reactive response by the liver to low serum albumin, leading to increased synthesis of lipoproteins (cholesterol, triglycerides).
  • Consequence: Puts patients at long-term risk of atherosclerosis.

Steroid-sparing agents are introduced in children who are steroid-dependent or frequent relapsers to reduce the cumulative dose of corticosteroids and mitigate their significant long-term side effects.

Levamisole:

• Mechanism of Action: It is an immunomodulatory agent. Its exact mechanism in nephrotic syndrome is not fully understood, but it is thought to restore depressed T-cell function.
• Indication: It is often used as a first-line steroid-sparing agent in frequent-relapsing and steroid-dependent nephrotic syndrome due to its relatively favorable side-effect profile.
• Administration: Given orally on alternate days.
• Side Effects: Generally well-tolerated. The most serious side effect is neutropenia/agranulocytosis (rare). Other side effects include flu-like symptoms and rash.

Other Steroid-Sparing Agents include:

• Cyclophosphamide: An alkylating agent. More potent but has serious side effects, including bone marrow suppression, hemorrhagic cystitis, and long-term risks of infertility and malignancy.
• Calcineurin Inhibitors (Cyclosporine, Tacrolimus): Effective but are nephrotoxic and can cause hypertension. Require therapeutic drug monitoring.
• Mycophenolate Mofetil (MMF): Increasingly used, with a good safety profile. Main side effects are gastrointestinal.
• Rituximab: A monoclonal antibody against CD20 on B-cells, reserved for very difficult-to-treat cases.

This clinical picture is highly suggestive of intravascular hypovolemia in a child with nephrotic syndrome. It is a medical emergency requiring careful fluid resuscitation.

1. Immediate Assessment (ABC): Secure the airway, check breathing, and assess circulation (heart rate, BP, capillary refill time).
2. Confirm Hypovolemia: The child will be tachycardic and hypotensive despite being edematous. They may have cold peripheries. The abdominal pain is often due to gut ischemia from poor perfusion.
3. Differential Diagnosis of Abdominal Pain: While hypovolemia is likely, one must also consider and rule out Spontaneous Bacterial Peritonitis (SBP). In SBP, the child would likely have a fever, guarding, and rebound tenderness.
4. Management of Hypovolemia:
   • IV Albumin Infusion: The cornerstone of treatment is to restore intravascular oncotic pressure and pull fluid back into the circulation.
   • Administer 20% Salt-Poor Albumin (1 g/kg, which is 5 ml/kg of 20% albumin) as an IV infusion over 4-6 hours.
   • IV Furosemide: A loop diuretic is often given towards the end of or immediately after the albumin infusion (1-2 mg/kg). This promotes diuresis of the excess fluid that has been pulled back into the vascular space, preventing fluid overload and hypertension.
5. Monitoring: Closely monitor heart rate, blood pressure, and urine output throughout the infusion.
6. Caution: Giving diuretics alone to an edematous but hypovolemic child is dangerous and will worsen the intravascular volume depletion, potentially leading to AKI and thrombosis.

Over 85-90% of childhood nephrotic syndrome is due to Minimal Change Disease (MCD), which is highly responsive to steroids. Therefore, a therapeutic trial of steroids is the first step, and biopsy is not done routinely at presentation. A renal biopsy is indicated when the clinical course is atypical, suggesting a diagnosis other than MCD.

Key Indications for Renal Biopsy:

• Atypical Age of Onset:
  • Presentation at age < 1 year (Congenital/Infantile Nephrotic Syndrome).
  • Presentation at age > 12 years.
• Steroid Resistance:
  • Failure to achieve remission after 4 weeks of daily, high-dose prednisolone therapy. This is the most common indication. It suggests an underlying pathology like Focal Segmental Glomerulosclerosis (FSGS) or Membranoproliferative Glomerulonephritis (MPGN).
• Presence of Atypical Features (Nephritic-Nephrotic Picture):
  • Persistent hypertension.
  • Persistent microscopic or gross hematuria.
  • Impaired renal function (elevated creatinine) that does not resolve with remission.
  • Low serum complement (C3) levels.
• Frequent relapsers or steroid dependent patients before starting significant second line agents like calcineurin inhibitors.