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Hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) share the morphologic lesion of thrombotic microangiopathy (TMA), characterized by platelet thrombi occluding the microvasculature. The HUS and TTP syndromes overlap clinically (1–9). Recent evidence indicates differing pathogenesis (see below): TTP is more common in adults, and is characterized by fever, bleeding, hemolytic anemia, renal failure, and neurologic impairment. Hemolytic uremic syndrome is characterized by acute renal failure, nonimmune hemolytic anemia, and thrombocytopenia, and it is most common in infants and small children. The renal manifestations at presentation include hematuria and low-grade proteinuria with elevated creatinine in severe cases. Intravascular hemolysis is evident by increased bilirubin and lactate dehydrogenase (LDH), reticulocytosis, and low haptoglobin. Both HUS and TTP cause thrombocytopenia, but in our experience, and that of others, this may not be detected by the time a renal biopsy is performed, especially in the transplant setting (10).

Diabetic nephropathy is a clinical syndrome in a patient with diabetes mellitus that is characterized by persistent albuminuria, worsening proteinuria, hypertension, and progressive renal failure (1,2). Approximately a third of patients with type 1 insulin-dependent diabetes mellitus (IDDM) and type 2 non-insulin-dependent diabetes mellitus (NIDDM) develop diabetic nephropathy (2). The pathologic hallmark of diabetic nephropathy is diabetic glomerulosclerosis that results from a progressive increase in extracellular matrix in the glomerular mesangium and glomerular basement membranes. Diabetic glomerulosclerosis is the leading cause of endstage renal disease in the United States, Europe, and Japan (1).

Acute interstitial nephritis (AIN) may be the result of indirect injury by drugs, reaction to systemic infections, direct renal infection (viral and selected bacteria), humoral immune responses (anti-tubular basement membrane disease), hereditary and metabolic disorders, and obstruction and reflux in the acute stages. Similar changes can also be observed in the kidney in systemic diseases such as lupus erythematosus and in transplant rejection. Acute tubulointerstitial nephritis also occurs to varying degrees in association with glomerulonephritides. This section is largely confined to the drug-induced, reactive, idiopathic and immunologic disorders inducing AIN. Acute interstitial nephritis usually presents with acute renal failure, often oliguric; it is sometimes associated with systemic manifestations such as arthralgia fever, eosinophilia and rash, typically as a consequence of drug hypersensitivity (1–3).

Chronic interstitial nephritis represents a large and diverse group of disorders characterized primarily by interstitial fibrosis with mononuclear leukocyte infiltration and tubular atrophy (1–3). The chronic damage is unrelated to underlying glomerular or vascular processes. Among the many causes of chronic interstitial nephritis are high-grade vesicoureteral reflux, urinary obstruction, chronic bacterial infections, Sjögren’s syndrome, drugs (lithium, Chinese herbs), radiation, and Balkan nephropathy (3). Although the pathologic aspects by light microscopy have the abovementioned features in common, historical information, imaging data, familial history, and gross pathology features may help to distinguish one disease from another. Because it was once widely considered that most chronic interstitial nephritis represented chronic infection, the term chronic pyelonephritis was commonly used for this group of disorders (1,2). However, chronic pyelonephritis is a rare entity (4).

Acute tubular necrosis (ATN) is a pathologic process that manifests clinically as acute renal failure. Although the term implies cellular death (necrosis), it should be appreciated that frank necrosis is not a constant finding; evidence of sublethal cellular injury is common. Furthermore, there is often a lack of clinical-pathologic correlation, with severe acute renal failure sometimes associated with trivial morphologic findings (1,2).

Patients with Bence Jones cast nephropathy usually present with acute renal failure (less commonly with chronic renal failure) and Bence Jones proteinuria. It has been known for many years that intravenous radiocontrast media, dehydration, infections, and the use of nonsteroidal antiin- fl ammatory drugs may induce the precipitation of renal tubular light chain casts and result in acute renal failure, which is reversible in only a small percent of affected patients. A less common manner of presentation is the acquired Fanconi syndrome. This is most often associated with intracellular crystals in plasma cells and tubular cells; the crystals represent the abnormal light chain (2,3).

Patients with plasma cell dyscrasias may have other forms of renal disease than light chain cast nephropathy. These include the closely related systemic disorders amyloidosis (AL type) and light chain deposit disease (1–7). In the kidneys, although both of these conditions clinically and pathologically affect primarily glomeruli, there is important and often constant involvement of tubular basement membranes, interstitium, and arteries. On rare occasions, the intact monoclonal protein (light and heavy chains) or heavy chain alone may deposit in renal basement membranes and systemically. Consequently, these disorders, originally considered solely of abnormal light chain pathogenesis and termed by some as light chain deposit diseases or nephropathies, are more correctly termed and thought of as monoclonal immunoglobulin deposition diseases (5). Evaluation of immunoglobulin synthesis by bone marrow cells has determined incomplete light chains and/or heavy chain fragments (8).

Amyloidosis (AL type) is conceptually similar to light chain deposit disease in many respects (1). It represents the systemic deposition of a structurally altered light and/or heavy chain and is more common than light chain deposit disease. Amyloid may also be due to deposition of other proteins that form beta-pleated sheets. Most patients with glomerular amyloid present with heavy proteinuria and approximately 50% have concurrent renal insufficiency. Interstitial or vascular (nonglomerular) amyloid morphologically is similar to amyloid in other locations; in the absence of glomerular amyloid, its detection requires a reasonably high level of suspicion on the part of the pathologist. Isolated interstitial amyloid is usually manifested by some degree of renal insufficiency; “pure” vascular amyloid may be clinically silent or may be associated with renal functional impairment.

Other abnormal substances may infiltrate the glomeruli and cause signifi - cant dysfunction. Perhaps among the more important of these is the lesion known as fibrillary glomerulonephritis (Fig. 19.1) (1–3). The light microscopy of glomeruli indicates variable increase in mesangial cellularity and irregularly thickened capillary walls. Crescents may be present (1,4). Immunofluorescence is positive, with coarse linear/confl uent granular immunoglobulin G (IgG), C3, and one or both light chains. This disorder is ultrastructurally defined and is characterized by the accumulation of fibrils that are roughly 10 to 20 nm in diameter and are throughout the mesangial matrix and basement membranes in a manner very similar to amyloid (1). Indeed, the fi brils bear striking similarity to amyloid. In contrast, however, the infiltrate is Congo red negative, unlike amyloid (5).

The renal transplant biopsy remains the gold standard for the diagnosis of episodes of graft dysfunction that occur in 10% to 30% of patients after transplantation. In a prospective trial at the Massachusetts General Hospital, the biopsy diagnosis changed the patient management as based on the prebiopsy clinical diagnosis in 42% of graft dysfunction episodes (39% in the first month, 56% in the first year, and 39% after 1 year); in 19% unnecessary immunosuppression was avoided (1). The present review is updated from prior publications by the author (2,3). My preferred pathologic classification of the diseases of renal allografts is given in Table 20.1.