IgA Nephropathy in Cirrhosis; Incidence, Pathogenesis, and Clinical Significance: Literature Review

Abstract

Purpose: Increased serum IgA levels are found in the vast majority of cirrhotic patients with resulting glomerular IgA deposition in many of these patients. Many theories are available to explain this association but the clinical significance behind this glomerular deposition remains a mystery. The aim of this review is to evaluate the incidence, pathogenesis, and clinical significance of glomerular IgA deposition in cirrhosis. Methods: An extensive literature review was conducted of studies about the dysregulation of IgA immune complex (IC) clearance in cirrhotic patients and their deposition in the glomeruli with a focus on the clinical significance behind that. Results: Numerous studies described renal histology in cirrhosis (as revealed by biopsies at the time of liver transplantation or autopsies post-mortem) in addition to describing the kidney function by measuring serum creatinine whether at the time of the biopsy/autopsy or in the preceding few months. These studies reported glomerular IgA deposition rate of 50-90% making cirrhosis by far the most common cause of secondary IgA nephropathy (IgAN). There are two most accepted theories behind this high rate of glomerular deposition. The clearance theory focuses on the role of the liver in clearing IgA IC through the asialoglycoprotein receptor on the hepatocytes and the Fc receptor on Kupffer cells. The second theory in turn focuses more about the portacaval shunting that occurs with portal hypertension which shunts these IC and thus escaping the liver. Now, the clinical importance of secondary IgAN in cirrhotics remains the biggest dilemma. All studies reviewed agree that most patients are asymptomatic (>90%). If the disease becomes clinically active, hematuria is the most common presenting sign/symptom (exactly as primary IgAN) while nephrotic range proteinuria is much less common. Most studies also agree that the disease remains stable over many years with very few patients reported to progress to end stage renal disease (ESRD) over years. Nonetheless, most studies remark that the activity of urine sediments predicts glomerular and mesangial cell injury. Conclusion: Second IgAN is the most common histological renal finding observed in cirrhotic patients although this seems to represent a stable histologic diagnosis that can rarely (<10% of cases) progress to apparent clinically significant renal disease and much less likely to progress to ESRD over many years.