Specific Immune-Related Renal Diseases: IgA Nephropathy

 IgA Nephropathy 

IgA nephropathy or Berger’s disease is the most common cause of glomerulonephritis in the world. Rarely seen in blacks, this dis-ease afflicts mainly Asians and Caucasians. Clinical features include gross hematuria (40–50 percent), microscopic hematuria (30–40 percent), and rarely, renal insuffi-ciency with edema and hypertension (less than 10 percent). These usually occur after a respiratory infection. Minimal protein-uria is noted. IgA nephropathy is made by kidney biopsy only. The hallmark of this disease is mesangial deposition of IgA, which is prominently noted on immuno-fluorescence. This deposition is associated with focal mesangial expansion, which can be seen on light microscopy. Electron microscopy confirms the presence of elec-tron-dense deposits in the mesangium, which correspond to the immune complex deposits. An abnormality in the regula-tion of IgA may exist because of an envi-ronmental stimuli. This is supported by higher circulating levels of IgA in about 50 percent of cases, circulating immune com-plexes that parallel the duration of the dis-ease, and increased number of IgA-specific B and T lymphocytes. Its strong association with respiratory infection has led authori-ties to believe that mucosal immunity plays a role in this disease. Exaggerated muco-sal IgA response or decreased clearance may explain the elevated levels of plasma IgA in this disease. In the glomeruli, IgA-containing immune complexes activate the alternative complement pathway but do not bind C1, which may slow the removal of circulating complexes and thereby pro-mote deposition in the glomeruli.

The role of fibronectin and uteroglobin (an anti-inflammatory protein) in IgA nephropathy remains unclear. Most of the IgA-containing complexes are bound to fibronectin. In experimental animals, uteroglobin–fibronectin heteromerization prevented formation of fibronectin–IgA complexes and binding to glomeruli. Dele-tion of the uteroglobin gene in mice by gene knockout or suppression of the uteroglobin gene by antisense technology has histolog-ical features similar to IgA nephropathy. Interestingly, polymeric but not monomeric IgA binds only to mesangial cells, which stimulate release of IL-6, further leading to mesangial expansion.

 

IgA nephropathy usually follows a benign course, although about 15 per-cent of cases may reach end-stage renal disease at ten years and 20 percent at twenty years. Clinical and histopatho-logical predictors of progression of renal disease include worsening proteinuria (>1 g/day of proteinuria) and biopsy findings of glomerular sclerosis, tubular atrophy, interstitial fibrosis, and crescent forma-tion. Treatment of IgA nephropathy has radically changed over the past decade. Aggressive use of angiotensin-converting enzyme (ACE) with and without angio-tensin-receptor blocker (ARB) is recom-mended to decrease the proteinuria and for their renoprotective properties. Cyto-toxic agents and steroids are reserved for aggressive renal disease.

Comments

Post a Comment

Popular posts from this blog

Hematopoietic Stem Cell Transplantation

Image
  HEMATOPOIETIC STEM CELL TRANSPLANTATION   HSCT involves the infusion of immature blood-forming cells into the circulation of a patient to reconstitute the recipient’s bone marrow. HSCT is a promising form of therapy for patients with certain forms of genetic diseases, specific cancers, and vari-ous blood disorders (Table 18.1). The trans-planted hematopoietic stem cells (HSCs) may come from the patient (autologous HSCT) or from a different stem cell donor (allogeneic HSCT). The field of  clinical HSCT  began in  the late 1940s,  when experiments in mice showed that shielding of the spleen allowed animals to survive oth-erwise lethal total-body irradiation. It was not until the seminal publication by E. Donnall Thomas in the 1957  New England Journal of Medicine , however,   that even transiently successful hema-topoietic transplants were first reported in humans; and at least another decade passed before allogeneic marrow graft-ing really began ...
Read more

Basic Components of the Immune System

Image
  INTRODUCTION It is generally believed that the immune system evolved as the host’s defense against infectious agents, and it is well known that patients with deficiencies in the immune system generally succumb to these infectious diseases. However, as we shall see, it may well play a larger role in the elimina-tion of other foreign substances, including tumor antigens or cells and antibodies that attack self. An immune response may be conve-niently divided into two parts: (1) a specific response to a given antigen and (2) a more nonspecific augmentation to that response. An important feature of the specific response is that there is a quicker response to the antigen during a second exposure to that antigen. It is the memory of the initial response that provides the booster effect.   For convenience, the specific immune response may be divided into two parts: (1) the humoral response and (2) the cellu-lar response to a given antigen. As we shall see, however, both responses a...
Read more

Etiologic Considerations of Rheumatic Fever

Image
  Etiologic Considerations A large body of both immunological and epidemiological evidence has implicated the group A streptococcus in the induction of the disease process. Yet, the precise pathological mechanisms involved in the process remain obscure. At least three main theories have been proposed.   The first theory is concerned with the question of whether persistence of the organism is important. Despite several controversial reports, no investigators have been able to consistently and reproducibly demonstrate live organisms in rheumatic fever joints, cardiac tissues, or valves.   The second theory focuses on whether deposition of toxic products is required. Although an attractive hypothesis, little or no experimental evidence has been obtained to support this concept. Renewed interest in extracellular toxins has recently emerged with the observation that certain strepto-coccal pyrogenic exotoxins (A and C) may act as superantigens. These antigens may stimulate larg...
Read more