Proliferative Glomerulonephritis



Acute glomerulonephritis (AGN) is the most common nephritic syndrome and can be etiolog-ically divided into post-streptoccocal AGN and nonstreptococcal AGN. In either case, the patient usually presents with oliguria, dependent or fa­cial edema, urine that is grossly bloody or “tea-colored” from hemolyzed RBC’s, and a history of a recent or ongoing infectious process. Hyperten­sion is present or develops during the course of the disease in most patients, and the GFR is almost always reduced. Proteinuria is a constant finding but is rarely of sufficient magnitude to produce the nephrotic syndrome. Red blood cell casts are usually present in the urine. Although azotemia is common, the acute renal failure syndrome with uremia occurs in a minority of patients. Complete recovery of renal function after clearing of the in­fectious process is the rule, although some pa­tients are left with a partial impairment of GFR and fewer still progress to chronic renal failure.

Post-streptococcal AGN is most frequent in children and young adults and follows group A, beta-hemolytic streptococcal infections of either the pharynx or skin (pyoderma]. Signs of nephritis usually appear 10 to 20 days after onset of the infection. The antistreptolysin O (ASO) titer is al­most always elevated in streptococcal pharyngitis but is elevated in less than one third of patients with streptococcal pyoderma. Antihyaluronidase titers are usually elevated in the latter patients. Total serum complement activity (CH50) and serum C3 are almost invariably depressed during the acute illness. These return to normal in 3 to 6 weeks as the renal disease disappears. About 2 per cent of patients may have minor urinary sed­iment abnormalities (protein and/or RBC’s) for as long as 7 to 10 years. Progression to chronic renal failure is rare and is usually confined to the older adults who develop AGN.
Nonstreptococcal, postinfectious AGN has been described in association with bacterial endocar­ditis due to coagulase-positive Staphylococcus aureus, with chronically infected ventriculoatrial shunts due to coagulase-negative S. epidermidis, and with pneumococcal pneumonia. Acute viral infections such as type B hepatitis, mumps, var­icella, infectious mononucleosis, and others have also given rise to AGN. The pattern of the AGN is the same as that for post-streptococcal AGN, and the prognosis for complete renal recovery is favorable in these diseases. A similar syndrome of acute nephritis may be seen in association with other disease processes, most notably with sys­temic lupus erythematosus (SLE).

Histologically, these cases are characterized on light microscopy by endothelial and mesangial cell proliferation with leukocyte infiltration. Small crescents of proliferating cells adherent to Bowman’s capsule may be seen. Immunofluores-cent staining is usually strongly positive for IgG and C3 and shows a granular pattern of deposition around capillary loops. The classic electron mi­croscopic finding in post-streptococcal AGN is that of large “humps” of electron-dense deposits in subepithelial spaces (Fig. 34-lD).
Treatment in all of these cases is directed at eradication, where possible, of the infecting or­ganism and management of the consequences of renal injury until recovery occurs. Corticosteroids and immunosuppressive agents are not useful. Edema and hypertension are best managed by salt restriction and diuretic therapy. The azotemia is usually self-limited, but a few patients will re­quire dialysis. A modest anemia does not require treatment or transfusion.

Anaphylactoid purpura is a chronic recurrent disorder that is most common in young children and is occasionally associated with nephritis. It is characterized by repeated attacks of palpable purpura, chiefly in the lower trunk and legs; variable bouts of abdominal pain; and transient arthralgias. An acute nephritic picture with he­maturia, moderate proteinuria, and a modest re­duction in GFR occurs in a number of patients. A few patients develop a rapidly progressive course to renal failure, almost always within the first few years of diagnosis of the purpura. Serum C3 levels are normal, although CH50 activity may be mildly depressed.
Light microscopy varies from fecal, segmental cellular proliferation to diffuse cellular prolifer­ation with extensive crescent formation; the latter lesion is seen most commonly when renal failure occurs. Immunofluorescent staining for mesangial IgA and C3 is prominent. Importantly, dermal cap­illaries of affected or unaffected skin stain strongly for IgA and C3, so that a skin biopsy may be useful in diagnosing the etiology of nephritis in such patients.

The basic disease is self-limiting, disappearing after a few months to years. Complete renal heal­ing is seen in over half of patients who develop nephritis, but about 10 per cent progress to renal failure. Steroids ameliorate extrarenal symptoms but do not appear to alter the renal component of the disease. Recurrence has been noted in trans­plants.

Essential cryoglobulinemia, in which IgG/IgM cryoprecipitates having rheumatoid factor activ­ity occur, may cause an acute nephritic syndrome. Acute renal failure with proteinuria and hema­turia occurs along with purpura, fever, and Ray­naud’s phenomenon. Immunofluorescent micros­copy typically shows IgG.TgM, and C3 in granular masses within the .mesangium and capillary loops. On electron microscopy, large intracapil-lary “thrombi” of the cryoprecipitate may be seen. Lowering the circulating level of cryoprecipitate with plasmapheresis often induces a clinical re­mission of the nephritis.