Kidney Diseases caused by Plasma Cell and B-Cell Disorders

A wide spectrum of clinical manifestations may result from the renal involvement with disorders of B-cells (B lymphocytes) and plasma cells. B lymphocytes and plasma cells are responsible cells for providing acquired and active immunity to our body through production of antibodies (immunoglobulins) against infectious organisms. But the disorders related to the function and number of B-cells and plasma cells lead to excessive or incomplete production of immunoglobulin molecules leading to deposition of immunoglobulins or their components in the kidneys. Deposition of immunoglobulins or their light or heavy chains cause a variety of renal disorders affecting glomeruli, extraglomerular blood vessels, tubules and interstitium. Two major classes of such diseases are as under:

A) Glomerular and vascular diseases

Glomerular and vascular diseases caused by B-cell and plasma cell disorders include amyloidosis (AL, AH and AHL type), light chain deposition disease (LCDD), heavy chain deposition disease (HCDD), light & heavy chain deposition disease (LHCDD), cryoglobulinemic glomerulonephritis (type I & II), monoclonal immunotactoid glomerulopathy and proliferative glomerulonephritis with monoclonal IgG deposits.

B) Tubulointerstitial diseases

Cast nephropathy and light chain proximal tubulopathy are the tubulointerstitial diseases caused due to renal involvement in multiple myeloma (Plasma cell disorder).

Important Investigations

Routine urine examination along with microscopy, blood biochemistry to ascertain renal functions and kidney biopsy evaluation by light, fluorescence and electron microscopy is required to establish an accurate diagnosis of renal disorder in patients affected by B-cell and plasma cell disorders.

Amyloidosis: Causes and Detection

Amyloidosis or deposition of amyloid in vital organs could be labeled as chronic pathological state. Amyloid is an abnormal protein derivative and amyloidosis is characterized by extracellular accumulation of this abnormal protein, which could be detected with Congo-Red staining during histological examination of biopsies/tissues. Genesis of amyloid is associated with B-cell (B Lymphocytes) and Plasma-cell disorders or chronic infections like tuberculosis. Renal (kidney) involvement in amyloidosis may affect all compartments of kidneys. Renal glomeruli, extraglomerular blood vessels, uriniferous tubules and even interstitium could be severely affected leading to impairment of renal function and can cause renal failure. Amyloid could be composed of one or more proteins out of around two dozen different monotypic polypeptides, including immunoglobulin light chains (AL type amyloid), immunoglobulin heavy chains (AH type amyloid), amyloid-A-protein (AA type amyloid), prealbumin, b-2 microglobulin, b-amyloid protein, islet amyloid polypeptide, procalcitonin, cystatin-C, apolipoprotein A-1 or A-2, gelsolin, lysozymes etc. Immunoglobulin light chains type (AL type) and amyloid-A-protein (AA type) amyloid mostly affect the kidneys. Almost all the patients with amyloidosis of kidneys have proteinuria (excretion of proteins in urine; >3g/day) and around 70% also have diminished renal function. On electron microscopy amyloid could be resolved as approximately 10 nm thick non branching and randomly arranged fibrils as illustrated in Figure-1.

Figure-1: Electron micrograph showing randomly arranged non-branching fibrils of amyloid in the mesangial area of a renal glomerulus. Original magnification 36000x.

Amyloid-A-protein type (AA type) amyloidosis is most often associated with chronic inflammatory diseases like tuberculosis, osteoarthritis, or rheumatoid arthritis. Some viral infections can also boost amyloidosis. Production of amyloidogenic light chains is associated with B-cell lymphoma, multiple myeloma or plasma-cell dyscrasia. AL and AA type amyloid have identical physicochemical properties. On renal biopsy evaluation we find acidophilic deposits which stain weakly with Periodic acid Schiff's stain or Silver stain. Amyloid stains bright red with Congo-Red stain and shows apple green birefringence by polarized light microscopy. Amyloid deposits could be revealed in the mesangium and peripheral capillary wall of renal glomerulus depending on the chronicity of the disease process. In advanced stages of amyloidosis, the amyloid deposits could be detected in arteries and interstitial tissue of kidneys in addition to glomeruli, by conventional methods and electron microscopy.