Paraproteins

Introduction

This section of the book focuses on paraprotein-related kidney disorders. In this chapter, we describe a general overview of paraproteins and their adverse effects on the kidneys with emphasis on proximal tubule disorders. In the following chapters, detailed discussions on other types of paraprotein-mediated kidney disorders, including cast nephropathy, monoclonal immunoglobulin light chain (AL) amyloidosis, light and heavy chain diseases, etc., are provided.

Paraprotein basics

Paraproteins are monoclonal light chains (LCs), heavy chains, or intact immunoglobulins detected in the serum or urine in abnormal quantities. The majority of the paraproteinemia-associated kidney disorders result from free monoclonal light chains (FLC), as these immunoglobulin fragments have relatively unrestricted access to kidneys and kidney tubules. There is an expanding spectrum of kidney disorders caused by either direct effects of FLCs on kidney cells or by deposition of intact immune globulins or their fragments in the glomeruli or along the kidney tubules ( Box 6.1 ).

Paraproteins are produced by plasma cells or B cells, and their presence in blood or urine indicates clonal proliferation of either of these cell lines, that is, multiple myeloma (plasma cells), or lymphomas (B cells). Thus paraproteinemias are typically associated with cancer of these cell lines. In some cases, however, the workup for their clonal origin may not meet the criteria for cancer and there may be no overt kidney disorder, a condition referred to as monoclonal gammopathy of unknown significance ( MGUS ). Upon closer scrutiny, many MGUS cases are found to have renal abnormalities, although without an obvious cancer identifiable as their source. Such conditions are termed monoclonal gammopathy of renal significance ( MGRS ). In most cases of MGRS, the initial diagnosis is suspected when a kidney disorder is diagnosed in the presence of monoclonal gammopathy, or when a kidney biopsy is reported to show monoclonal immunoglobulin deposition, and when clonal workup fails to meet the criteria for the diagnosis of overt multiple myeloma or a B cell tumor. ^{, ,} Paraproteins, whether produced by a cancer, such as myeloma, lymphoma, or leukemia, or by a small clone that does not meet the criteria for cancer, often affect the kidneys by various mechanisms that include disruption of transport systems, triggering inflammatory reactions in the kidney, ^{, , , –} cast formation, ^, or kidney deposition of organized or unorganized monoclonal proteins. ^{, , –} Renal involvement in paraproteinemia always implies a worse prognosis. ^,