Infection-Related Glomerulonephritis

Clinical Features

The clinical presentation of IRGN is variable, ranging from asymptomatic, incidentally discovered urinary abnormalities to a rapidly progressive GN requiring kidney replacement therapy. Clinical findings include hematuria, which can be either microscopic or gross; proteinuria, which is usually subnephrotic but can be in the nephrotic range; and variable degrees of hypertension, edema, and glomerular filtration rate (GFR) loss. The presentation and outcomes in children are often different from those in adults ( Table 23.1 ).

In classic PSGN, symptomatic children usually present with acute nephritic syndrome characterized by hematuria, proteinuria, hypertension, edema, oliguria, and variable elevation of the serum creatinine. The urinary sediment is usually active, with dysmorphic red blood cells, red blood cell casts, and leukocyturia. Hypocomplementemia is very common, with decreased C3 in up to 90% of cases and, to a lesser extent, depleted levels of C4. There is usually a “latent” period between the resolution of the streptococcal infection and the acute onset of the nephritic syndrome. This period is often 7 to 10 days after oropharyngeal infections and 2 to 4 weeks after skin infections. Serologic markers of a recent streptococcal infection include elevated antistreptolysin O (ASO), antistreptokinase, antihyaluronidase, and antideoxyribonuclease B (anti-DNase B) levels. Elevation of these four markers has a yield of approximately 80% in documenting recent streptococcal infection.

In adults, most cases of IRGN no longer follow streptococcal infection, and the GN often coexists with the triggering infection. In cases of ongoing active infection, other clinical manifestations related to the specific infectious disease are common. Sites of infection can include the upper and lower respiratory tract, skin/soft tissue, bone, teeth/oral mucosa, heart, deep abscesses, shunts, and indwelling catheters. GFR loss and the nephrotic syndrome are more common in adults than in children, whereas gross hematuria is less commonly seen. Hypocomplementemia is only seen in 30% to 80% of these patients. Adults more commonly present with kidney failure and with complications of hypervolemia, including decompensated heart failure. Up to 50% of adults with IRGN may require dialysis, and mortality may approach 20%.

Epidemiology

The incidence of PSGN has declined throughout most of the world over the past several decades due to improvements in hygiene, sanitation, and infection control, but still remains a health concern in many developing countries. An effort by Carpentis and colleagues to evaluate the incidence of PSGN using 11 population-based studies suggests that approximately 472,000 cases of PSGN occur worldwide annually, resulting in approximately 5000 deaths (1% of total cases). Approximately 97% of these cases of PSGN occur in less developed countries. Other estimates of the burden of PSGN in the developing world range between 9.5 and 28.5 cases of PSGN per 100,000 individuals per year.

In industrialized countries, much of the burden of IRGN has shifted to adults, with a lower proportion attributed to PSGN. IRGN associated with other microorganisms, including Staphylococcus species and gram-negative bacteria, are increasingly recognized, mainly in the adult population. In these cases, coexistence of the glomerular disease and the infection is common, and classic clinical findings of low complement levels may be absent. The clinical course and prognosis of these newly recognized forms are also different, with more patients developing progressive chronic kidney disease (CKD), sometimes to end-stage kidney disease (ESKD). Diabetes is the most commonly recognized comorbidity and is associated with poor outcomes. Other common comorbidities seen in patients with IRGN include malignancy, immunosuppression, AIDS, alcoholism, cirrhosis, malnutrition, and IV drug use. The elderly population is especially prone to IRGN, with patients over 65 years of age accounting for about 34% of IRGN cases in the developed world, increased from only 4% to 6% of recognized IRGN 40 years ago.