Overview
Definition:
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by widespread inflammation and autoantibody production affecting various organ systems
Pediatric lupus nephritis (LN) is a common and serious manifestation of childhood SLE, leading to significant morbidity and potential progression to end-stage renal disease.
Epidemiology:
SLE affects approximately 1 in 10,000 to 1 in 20,000 children globally
LN is present in 50-75% of children with SLE at diagnosis, making it one of the most frequent and critical organ involvements
It is more prevalent in girls and often presents in adolescence.
Clinical Significance:
Lupus nephritis in children poses a significant threat to long-term renal function and overall survival
Early diagnosis, accurate classification of nephritis, and prompt, evidence-based management are crucial to preserve kidney function, prevent irreversible damage, and improve patient outcomes, which is vital for DNB and NEET SS preparation.
Clinical Presentation
Symptoms:
Hematuria (gross or microscopic)
Proteinuria (mild to nephrotic range)
Edema and hypertension
Fatigue and malaise
Joint pain and swelling
Rash (malar, discoid)
Fever
Abdominal pain
Seizures or psychosis (CNS involvement).
Signs:
Hypertension
Peripheral edema
Pallor due to anemia
Malar rash, photosensitivity, discoid lesions
Arthritis/arthralgia
Serositis (pleuritis, pericarditis).
Diagnostic Criteria:
Diagnosis of SLE relies on the Systemic Lupus International Collaborating Clinics (SLICC) classification criteria or the American College of Rheumatology (ACR) revised criteria, which involve clinical and immunological findings
Lupus nephritis diagnosis is confirmed by kidney biopsy.
Diagnostic Approach
History Taking:
Detailed history of constitutional symptoms (fever, weight loss), mucocutaneous manifestations, musculoskeletal complaints, neurological symptoms, hematological issues, and renal symptoms (edema, changes in urine)
Family history of autoimmune diseases
Medication history.
Physical Examination:
Thorough examination including vital signs (BP monitoring), assessment for edema, skin and mucous membrane inspection for characteristic rashes, joint examination for synovitis, cardiovascular and respiratory system evaluation for serositis.
Investigations:
Urinalysis with microscopy (hematuria, casts - red blood cell, granular)
24-hour urine protein excretion or urine protein-to-creatinine ratio
Serum creatinine and glomerular filtration rate (GFR)
Complete blood count (anemia, leukopenia, thrombocytopenia)
Autoantibodies: Antinuclear antibody (ANA) is essential, anti-dsDNA, anti-Sm, complement levels (C3, C4 – often low in active LN)
Kidney biopsy: The gold standard for diagnosis, classification, and guiding treatment
Histopathological findings determine the class of lupus nephritis.
Differential Diagnosis:
Other causes of glomerulonephritis (e.g., IgA nephropathy, post-infectious GN)
Henoch-Schonlein purpura nephritis
Nephrotic syndrome of other etiologies
Systemic vasculitis affecting kidneys.
Nephritis Classification And Biopsy
Class I Minimal Mesangial Nephritis:
Normal appearing glomeruli by light microscopy (LM)
mesangial immune deposits by immunofluorescence (IF) or electron microscopy (EM)
Usually asymptomatic or mild proteinuria/hematuria.
Class Ii Mesangial Proliferative Nephritis:
Mesangial expansion and proliferation by LM
mesangial immune deposits by IF/EM
Mild to moderate proteinuria, microscopic hematuria.
Class Iii Focal Nephritis:
Focal proliferation (segmental) in <50% of glomeruli by LM
mesangial and/or endothelial/capillary wall immune deposits
Active urinary sediment (hematuria, proteinuria, casts)
Requires prompt treatment.
Class Iv Diffuse Nephritis:
Diffuse proliferation (global or segmental) in >50% of glomeruli by LM
diffuse global immune deposits along capillary walls and in mesangium
Most severe form, often presents with significant proteinuria, hematuria, renal insufficiency, hypertension
High risk of progression to ESRD.
Class V Membranous Nephritis:
Diffuse thickening of glomerular basement membrane by LM due to subepithelial immune deposits
IF shows granular capillary wall deposits
Presents with nephrotic syndrome
Can coexist with class III or IV (IV-V, III-V).
Class Vi Advanced Sclerotic Nephritis:
>90% of glomeruli show obsolescence and fibrosis by LM
Indicates advanced disease and poor prognosis
Treatment may not reverse established damage but aims to prevent further loss.
Management
Initial Management:
Supportive care including fluid and electrolyte balance, blood pressure control (ACE inhibitors or ARBs are first-line for proteinuria/hypertension)
Management of anemia
Nutritional support.
Medical Management:
Induction therapy for active proliferative (Class III/IV) or severe membranous (Class V with significant proteinuria) nephritis: High-dose corticosteroids (e.g., IV methylprednisolone followed by oral prednisone)
Immunosuppressants: Mycophenolate mofetil (MMF) or Azathioprine (AZA) are commonly used
Cyclophosphamide (CYC) is often used for severe or refractory cases, particularly in pulsed IV regimens (e.g., NIH or Euro-Lupus protocol)
Rituximab is an emerging option for refractory cases
Maintenance therapy: Lower-dose corticosteroids with MMF or AZA to maintain remission and prevent relapse.
Surgical Management:
Renal transplantation may be necessary for patients who develop end-stage renal disease (ESRD) due to lupus nephritis.
Supportive Care:
Close monitoring of renal function (GFR, creatinine, urine protein/creatinine), blood pressure, and autoimmune markers (ANA, anti-dsDNA, complement)
Management of comorbidities and infections
Psychological support for the child and family
Vaccination against infections, especially in immunosuppressed individuals
Strict sun protection due to photosensitivity.
Complications
Early Complications:
Hypertensive emergencies
Fluid overload and pulmonary edema
Acute kidney injury (AKI)
Thrombotic events (due to antiphospholipid antibodies or nephrotic syndrome)
Infections due to immunosuppression.
Late Complications:
Chronic kidney disease (CKD) and end-stage renal disease (ESRD)
Hypertension
Increased risk of cardiovascular disease
Osteoporosis secondary to corticosteroid use
Cataracts
Growth retardation
Steroid-induced diabetes
Opportunistic infections.
Prevention Strategies:
Adherence to treatment protocols
Regular follow-up and monitoring
Judicious use of corticosteroids and immunosuppressants
Prompt treatment of infections
Management of risk factors for cardiovascular disease
Screening for osteoporosis and bone health monitoring.
Prognosis
Factors Affecting Prognosis:
Class of lupus nephritis (Class IV and V have poorer prognosis)
Degree of renal impairment at diagnosis
Histological activity and chronicity scores on biopsy
Response to initial therapy
Presence of autoantibodies (e.g., high anti-dsDNA titres)
Socioeconomic factors and adherence to treatment.
Outcomes:
With aggressive, timely treatment, a significant proportion of children can achieve remission and preserve kidney function
However, relapses are common
A subset of patients will progress to ESRD, necessitating dialysis and transplantation
Long-term survival has improved significantly with advances in therapy.
Follow Up:
Lifelong follow-up is essential
Patients require regular clinical and laboratory assessments to monitor for disease activity, renal function, treatment toxicity, and development of long-term complications
Transition to adult care is crucial.
Key Points
Exam Focus:
The ISN/RPS classification of lupus nephritis is critical
Understand the biopsy findings for each class and the associated clinical presentation and treatment implications
Recognize the importance of renal biopsy as the gold standard
Know the induction and maintenance therapy regimens, including common drug classes and examples.
Clinical Pearls:
Always consider lupus nephritis in a child with new-onset proteinuria, hematuria, or nephrotic syndrome, especially with other SLE manifestations
Early referral to pediatric rheumatology and nephrology is paramount
Monitor for silent disease progression
renal biopsy may be indicated even with seemingly stable renal function if there is suspicion of active disease.
Common Mistakes:
Delaying renal biopsy in suspected active nephritis
Inadequate induction therapy for proliferative or severe membranous nephritis
Insufficient monitoring for treatment toxicity or disease relapse
Underestimating the chronic and relapsing nature of lupus nephritis
Failing to manage comorbidities like hypertension and cardiovascular risk factors.