Immunoglobulin A Nephropathy

Introduction

Immunoglobulin A nephropathy (IgAN) is the most common glomerulonephritis in the world, with a global incidence of 2.5 per 100,000 per year. It was first identified in 1968 by French nephrologist Dr. Jacques Berger and was therefore historically called Berger’s disease.

IgAN was initially considered a benign self-limiting disease, but epidemiological studies suggest that 20% to 40% of patients will develop renal failure within 10 to 20 years of diagnosis.

Epidemiology and pathogenesis

Onset is typically during the second and third decades with a 2:1 male-to-female predominance in the United States. The etiology of IgAN is unknown, but has been attributed to a dysregulated immune response of T cells to viral, bacterial, and dietary antigens that activate mucosal plasma cells to produce polymeric IgA.

Clinical manifestations

Classically, patients present with gross hematuria after an upper respiratory tract infection. Others present with microscopic glomerular hematuria, proteinuria in the non-nephrotic range, and decreased renal function. With

Less commonly, patients present with rapidly progressive glomerulonephritis manifesting with acute kidney injury and hypertension, with or without nephrotic syndrome.

Laboratory and histological features

Unfortunately, there is no serological test for the diagnosis of IgAN, including serum antibody levels. A definitive diagnosis requires a kidney biopsy, which may not be necessary in all cases. Histological findings range from mild mesangial expansion to diffuse proliferation with crescents.

Prognosis of kidney disease progression

Doctors have used several clinical surrogates to predict patients’ progression to kidney failure. Risk factors include proteinuria greater than 0.5 to 1 g/day, hypertension, reduced glomerular filtration rate, and persistent microscopic hematuria. Many of these surrogates affect a physician’s decision to biopsy a patient with suspected IgAN.

Differential diagnosis

Mesangial IgA deposition has been identified in up to 16% of renal allograft donors. IgA is primarily catabolized by hepatocytes, and chronic liver disease can lead to increased circulating IgA1 and increased nonpathogenic mesangial deposition.

Glomerulonephritis associated with staphylococcus aureus infection is a well-described entity that may have similar clinical features, including multisystem manifestations of small vessel vasculitis and renal biopsy pathology.

IgA vasculitis (previously known as Henoch-Schönlein purpura) is a systemic small vessel vasculitis associated with leukocytoclastic vasculitis of the skin, abdominal pain, and arthralgias.

Management without immunosuppression

Conservative strategies that may reduce disease progression include sodium intake of less than 2 g/day, weight control, smoking cessation, regular activity, and avoidance of nonsteroidal anti-inflammatory drugs. Clinicians should aim for blood pressure less than 130/80 mm Hg and proteinuria less than 1 g/day by maximally blocking the renin-angiotensin system (RAS) with angiotensin-converting enzyme inhibitors or blockers. angiotensin receptors.

Sodium-glucose cotransporter 2 inhibitors have recently been approved by the US Food and Drug Administration (FDA) for patients with or without diabetes and with a glomerular filtration rate (GFR) greater than or equal to 25 ml/min/1.73 m2 body surface area after showing reductions in chronic kidney disease (CKD) progression in the DAPA-CDK (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease) study.

The study randomized 270 patients with IgA nephropathy. Subgroup analysis demonstrated that dapagliflozin decreased the risk of CKD progression by 1.2 ml/min/1.73 m2 per year and reduced the urinary albumin-to-creatinine ratio by 26%.

Immunosuppression

A trial of oral glucocorticoids may be indicated if more than 1 g of proteinuria persists for 3 or more months after the maximum non-immunosuppressive dose has been tried or if the patient is already at high risk for kidney disease. Glucocorticoid therapy and other immunosuppressive medications have been studied with conflicting results.

In the STOP-NIgA trial (Supportive therapy versus immunosuppressive treatment of progressive IgA nephropathy) patients with CKD stages 1 to 3 and proteinuria less than 3.5 g/day treated with immunosuppression had no differences in the reduction of GFR and were at increased risk of serious infections.

The NeflgArd Part A trial randomized 199 patients with IgAN to maximal RAS blockade and targeted-release formulation of budesonide 16 mg/day or placebo for 9 months and demonstrated a 27% reduction in proteinuria and a difference in proteinuria preservation. GFR of 3.87 ml/min/1.73m2 compared to placebo. As expected, there were more side effects in the treatment group and, despite using a targeted-release steroid, patients experienced glucocorticoid-related systemic adverse effects.