Henoch-Schönlein purpura nephritis in children: incidence, pathogenesis and management.

BACKGROUND: Henoch-Schönlein purpura (HSP) is one of the most common vasculitides in children. It is manifested by skin purpura, arthritis, abdominal pain, renal involvement, etc. Typically, HSP is considered to be self-limiting, although renal involvement (HSP purpura nephritis, HSPN) is the principal cause of morbidity from this disease. For this reason, it is important to clarify the mechanism of onset and clinical manifestations of HSPN and to ascertain the most appropriate treatment for HSPN. In this article, we review the updated pathophysiology and treatment strategies for HSPN. DATA SOURCES: We searched databases including PubMed, Elsevier and Wanfang for the following key words: Henoch-Schönlein purpura, nephritis, mechanism and treatment, and we selected those publications written in English that we judged to be relevant to the topic of this review. RESULTS: Based on the data present in the literature, we reviewed the following topics: 1) the possible pathogenesis of HSPN: several studies suggest that immunoglobulin A immune complexes deposit in the mesangium and induce renal injury; 2) multiple-drug treatment for HSPN: although there have been few evidence-based treatment strategies for HSPN, several studies have suggested that immunosuppressive drugs and multiple drug combination therapy were effective in ameliorating proteinuria and histological severity. CONCLUSIONS: HSPN is a severe disease of childhood. To better understand this disease, detailed investigations into the pathogenesis of HSPN and prospective randomized controlled treatment studies on children with severe HSPN are needed.

Serial non-invasive assessment of antibody induced nephritis in mice using positron emission tomography.

Mouse models of experimental anti-glomerular basement membrane (anti-GBM) nephritis provide an analytical tool for studying spontaneous lupus nephritis. The potential of Positron Emission Tomography (PET) was evaluated using 2-deoxy-2-[(18)F]fluoro-d-glucose (FDG) as a probe to monitor the progression of anti-GBM induced nephritis in a mouse model. The imaging results were compared to conventional measures of renal function and pathological changes. Serum and urinary vascular cell adhesion molecule-1 (VCAM-1) levels were used as measures of endothelial cell activation and inflammation. Following a challenge with anti-glomerular antibodies, mice exhibited peak changes in serum creatinine, proteinuria, and glomerulonephritis score at 14 days post-challenge (p.c.). In contrast, VCAM levels peaked at day 7 p.c. On dynamic PET images (0-60 min) of day 7, kidneys of the anti-GBM nephritis mice demonstrated a unique pattern of FDG uptake. Compared to the time activity curve (TAC) prior to challenge, a rightward shift was observed after the challenge. By day 10 p.c., kidney FDG uptake was lower than baseline and remained so until the study ended at 21 days p.c. During this time frame measures of renal dysfunction remained high but VCAM-1 levels declined. These changes were accompanied by an increase in kidney volume as measured by Computed Tomography (CT) and intra-abdominal fluid collection. Our results suggest that FDG-PET-CT can be used as a non-invasive imaging tool to longitudinally monitor the progression of renal disease activity in antibody mediated nephritis and the magnitude of renal FDG retention correlates better with early markers of renal inflammation than renal dysfunction.

The role of renin-angiotensin-aldosterone system in the progression of chronic kidney disease.

The renin-angiotensin-aldosterone system (RAAS) is a well known regulator of blood pressure (BP) and determinant of target-organ damage. It controls fluid and electrolyte balance through coordinated effects on the heart, blood vessels, and Kidneys. Angiotensin II (AII) is the main effector of the RAAS and exerts its vasoconstrictor effect predominantly on the postglomerular arterioles, thereby increasing the glomerular hydraulic pressure and the ultrafiltration of plasma proteins, effects that may contribute to the onset and progression of chronic renal damage. AII may also directly contribute to accelerate renal damage by sustaining cell growth, inflammation, and fibrosis. Interventions that inhibit the activity of the RAAS are renoprotective and may slow or even halt the progression of chronic nephropathies. ACE inhibitors and angiotensin II receptor antagonists can be used in combination to maximize RAAS inhibition and more effectively reduce proteinuria and GFR decline in diabetic and nondiabetic renal disease. Recent evidence suggests that add-on therapy with an aldosterone antagonist may further increase renoprotection, but may also enhance the risk hyperkalemia. Maximized RAAS inhibition, combined with intensified blood pressure control (and metabolic control in diabetics) and amelioration of dyslipidemia in a multimodal approach including lifestyle modifications (Remission Clinic), may achieve remission of proteinuria and renal function stabilization in a substantial proportion of patients with proteinuric renal disease. Ongoing studies will tell whether novel drugs inhibiting the RAAS, such as the renin inhibitors or the vasopeptidase inhibitors, may offer additional benefits to those who do not respond, or only partially respond, to this multimodal regimen.