Page 950 - Clinical Immunology_ Principles and Practice ( PDFDrive )

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Immunological Renal Diseases

Meryl Waldman, Howard A. Austin III, James E. Balow

Compelling clinical, pathological, and experimental data indicate Urinary RBCs that result from glomerular or tubulointerstitial
that most forms of glomerular diseases manifest some element of pathology are more likely to appear dysmorphic (abnormal shapes
1
immune-mediated injury. Major advances in our understanding and sizes, fragmented); when these dysmorphic RBCs, called
of the etiology and pathogenesis of the various glomerular diseases acanthocytes, are present, it is usually appropriate to refer the
have occurred in the past decade. However, the primary events patient to nephrology for further evaluation. Erythrocyte and/or
or inciting factors that trigger the host immune responses and leukocyte casts are indicative of glomerulonephritis (or interstitial
secondary pathways that are directly or indirectly pathogenic nephritis). Cellular casts can be formed from erythrocytes and/
to the kidney are still not fully elucidated. In some conditions, or leukocytes that enter the tubular lumen because of glomerular
normal or allergic immune responses to exogenous infectious or tubular inflammation (Fig. 68.1).
agents or drugs can lead to incidental nephropathic injury (e.g.,
postinfectious glomerulonephritis, serum sickness). In the case PROTEINURIA
of autoimmune diseases, nephropathic processes range from loss
of self-tolerance to specific constitutive renal tissues (e.g., anti- Glomerular proteinuria results from a loss of the size-selective
glomerular basement membrane [GBM] disease) or to extrarenal and/or charge-selective properties of the glomerular capillary
tissues and cells (e.g., antineutrophil cytoplasmic autoantibodies wall and disruptions of the glomerular epithelial cells (podocytes),
[ANCAs]). Other mechanisms include excessive and unregulated allowing plasma proteins (especially albumin) to leak into the
polyclonal immune responses that produce nephritogenic immune filtrate. Tubulointerstitial nephropathy often leads to impaired
1,2
complexes (e.g., lupus nephritis). Recent advances have begun tubular absorption of other normally filtered low-molecular-
to uncover candidate antigens involved in the pathogenesis of weight proteins; this so-called tubular proteinuria exhibits a
immune-mediated renal diseases (e.g., some subsets of mem- characteristic pattern on urine protein electrophoresis (low
branous nephropathy [MN]). But it has become increasingly fraction of albumin), rarely exceeds 2 g/day, and is often associated
apparent that the immune system does not operate in isolation with other manifestations of tubular dysfunction.
and that there are extraordinarily complex interactions among Estimates of proteinuria are based on 24-hour urine collections
vast networks involving components of native and adaptive or on the protein/creatinine or albumin/creatinine concentration
immune systems, humoral and cell-mediated immune systems, ratios in random urine samples. Normally, these ratios should
small-molecular-weight mediators derived from lymphoid be <0.1. Filtration of abnormal plasma proteins can be responsible
and other cell types, complement factors and their regulatory for proteinuria (e.g., multiple myeloma or monoclonal immu-
proteins, other inflammatory and coagulation system pathways, noglobulin [Ig] light-chain disease). This type of proteinuria
microvascular biology, and tissue repair, as well as sclerosis and (paraproteinuria) may be undetected by albumin-sensitive dipstick
fibrosis reactions. Underlying this constellation are associated screening. Paraproteinemia may also be undetected or under-
genetic risk factors that modulate these responses and predispose estimated by standard plasma electrophoresis; however, an assay
to a nephritogenic response. Rapidly evolving molecular and for serum free light chains is more sensitive for detection of low
genetic technologies with the tools of modern systems biology levels of circulating light chain paraproteins. Identification of
and bioinformatics will continue to unravel these complex specific Ig-derived paraproteinuria usually requires urine immu-
interactions. 3 nofixation electrophoresis (Fig. 68.2)
Appropriate evaluation of patients with immune-mediated
kidney diseases requires particular attention to the findings of NEPHROTIC SYNDROME
urinalysis, assessment of the type and amount of proteinuria,
tests of renal functions, and renal biopsy. Urine microscopy also Nephrotic syndrome is characterized by substantial degrees of
plays a pivotal role in the assessment of urinary disorders. proteinuria (>3.5 g/day or protein to creatinine ratio >2.5)
resulting in hypoalbuminemia, edema, hyperlipidemia, and
HEMATURIA lipiduria. The degree of proteinuria can offer a helpful diagnostic
clue because some immune-mediated conditions with typically
Red blood cells (RBCs) that emanate from lesions of the calices, diffuse glomerular disease (e.g., MN, systemic lupus erythematosus
ureters, bladder, or urethra tend to maintain their normal mor- [SLE]) are more likely than others with typically focal disease
phology; when nondysmorphic RBCs are present, it is usually (e.g., IgA nephropathy, ANCA-associated glomerulonephritis)
appropriate to refer the patient to urology for further evaluation. to be associated with nephrotic syndrome.

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