HSP Nephritis: Key Symptoms and Renal Involvement Patterns

Henoch-Schönlein purpura (HSP) is a small-vessel vasculitis primarily affecting children but also seen in adults. While it often presents with skin, joint, and gastrointestinal symptoms, kidney involvement—HSP nephritis—is a major concern due to its potential for long-term complications.

Recognizing the symptoms and patterns of renal involvement is crucial for timely diagnosis and management.

Main Symptoms

HSP nephritis presents with urinary abnormalities reflecting glomerular inflammation and vascular injury. Hematuria, often microscopic and detectable only through lab analysis, is the most common finding. In severe cases, gross hematuria gives urine a tea- or cola-colored appearance due to significant red blood cell leakage. This symptom typically appears within weeks of the characteristic purpuric rash.

Proteinuria frequently accompanies hematuria and indicates disease severity. Mild cases may have transient or low-grade proteinuria, while more severe forms present with nephrotic-range proteinuria exceeding 3.5 grams per day. This level of protein loss can lead to hypoalbuminemia and edema, particularly in the lower extremities and around the eyes. Significant proteinuria increases the risk of long-term renal impairment, requiring close monitoring.

Hypertension can develop due to glomerular dysfunction and fluid retention. While mild cases may go unnoticed, sustained hypertension accelerates kidney damage and increases cardiovascular risk. Blood pressure monitoring is essential, especially in patients with persistent proteinuria or declining renal function.

Renal Involvement Patterns

Renal manifestations in HSP nephritis vary from transient urinary abnormalities to progressive glomerular disease. The most common pattern involves isolated hematuria with or without mild proteinuria, often resolving without long-term damage. However, some patients develop persistent proteinuria and declining kidney function, necessitating early identification and risk stratification.

A more concerning pattern is nephrotic syndrome, marked by heavy proteinuria, hypoalbuminemia, and edema. This suggests significant podocyte injury and increased glomerular permeability, which can accelerate disease progression. Patients with nephrotic-range proteinuria face a higher risk of chronic kidney disease (CKD), requiring close surveillance. In some cases, the disease mimics IgA nephropathy, with persistent proteinuria and episodic hematuria.

A rapidly progressive form, though less common, carries the highest risk for renal failure. This pattern is often linked to crescentic glomerulonephritis, where extensive inflammation leads to severe glomerular injury. Histological studies show that patients with more than 50% crescent formation in renal biopsies tend to have an aggressive disease course. Without prompt intervention, these cases can progress to end-stage renal disease (ESRD), requiring dialysis or transplantation.

Diagnostic Parameters

Diagnosing HSP nephritis involves laboratory testing, clinical assessment, and imaging studies. Urinalysis is the primary tool, detecting hematuria, proteinuria, and cellular casts. Red blood cell casts indicate glomerular injury, while proteinuria levels help assess severity. A 24-hour urine protein measurement or spot urine protein-to-creatinine ratio provides precise quantification, guiding prognosis and treatment.

Serum markers assess renal function and systemic involvement. Elevated serum creatinine and decreased estimated glomerular filtration rate (eGFR) indicate impaired kidney function. Hypoalbuminemia, commonly seen in nephrotic-range proteinuria, reflects protein loss and systemic effects. Complement levels, typically normal in HSP nephritis, help differentiate it from other glomerular diseases like lupus nephritis.

Imaging studies, though not always necessary, can provide additional context in complicated cases. Renal ultrasound evaluates kidney size and echogenicity, identifying structural abnormalities or chronic damage. Doppler ultrasonography assesses renal perfusion, particularly in hypertensive patients. Magnetic resonance angiography (MRA) or computed tomography (CT) angiography may be considered if vascular involvement is suspected.

Immune Targets

HSP nephritis is driven by abnormal IgA deposition in the glomeruli, leading to inflammation and tissue damage. IgA1, a subclass of immunoglobulin A, plays a central role due to its altered glycosylation patterns. In affected individuals, circulating IgA1 molecules exhibit reduced galactosylation, making them prone to self-aggregation and immune complex formation. These complexes deposit in the mesangium, triggering inflammation and glomerular injury.

Once deposited, IgA1-containing immune complexes activate mesangial cells, leading to the release of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). This immune activation promotes extracellular matrix expansion, contributing to glomerulosclerosis in severe cases. Complement system activation, particularly through the alternative and lectin pathways, further amplifies kidney damage. Increased levels of complement component C3 and mannose-binding lectin (MBL) in patients with progressive HSP nephritis suggest a role in disease severity.

Biopsy Observations

Renal biopsy is crucial in cases with persistent proteinuria, declining kidney function, or suspected crescentic glomerulonephritis. Histopathological findings provide insight into disease progression and guide treatment decisions. The most characteristic feature is mesangial proliferation, where increased cellularity and matrix expansion reflect ongoing glomerular injury. This pattern closely resembles IgA nephropathy, reinforcing their shared pathophysiology.

Crescent formation is a key histological marker of severe disease and a higher risk of CKD. These crescents, composed of proliferating epithelial and immune cells, indicate an aggressive inflammatory response that can lead to irreversible damage. The proportion of affected glomeruli strongly correlates with prognosis, with more than 50% involvement significantly increasing the likelihood of ESRD. Immunofluorescence microscopy confirms dominant IgA deposition in the mesangium, often accompanied by C3 and, in some cases, fibrinogen. Electron microscopy may reveal electron-dense deposits within the mesangial matrix, reinforcing the immune complex-mediated nature of the disease.