Abstract
Glomerulonephritis (GN) relating to bacterial infections is discussed in this chapter. While a portion of the chapter is dedicated to discussing classic poststreptococcal GN, an emphasis is placed on other subtypes of infection-related GN, including those due to staphylococcal infections and those associated with endocarditis. The varied clinical presentations, histologic features, and outcomes are presented, along with a discussion of the differential diagnosis and diagnostic pitfalls.
Keywords
infection, postinfectious glomerulonephritis, hypocomplementemia, streptococcal, staphylococcal, endocarditis, nephritic syndrome, proliferative glomerulonephritis, nephritogenic infection-related glomerulonephritis
In previous editions, this chapter was titled “Postinfectious Glomerulonephritis,” which aptly describes classic poststreptococcal glomerulonephritis (PSGN) but is a misnomer for the increasingly recognized forms of glomerulonephritis (GN) that are manifestations of ongoing infection. Indeed, infection has a much broader role in the development of GN, sometimes serving as a trigger for a variety of common autoimmune responses including lupus, antineutrophil cytoplasmic antibody (ANCA) vasculitis, and IgA nephropathy. This chapter addresses both classic PSGN as well as forms of GN resulting from active bacterial infections. Glomerular disease due to viral hepatitis and HIV are discussed elsewhere. The change in the title from “Postinfectious” to “Infection-Related Glomerulonephritis (IRGN)” is meant to draw attention to the changing epidemiology of IRGN and to emphasize that infection may be ongoing at the time of the development of GN, which is important for guiding therapy.
Clinical Features
The clinical presentation of IRGN is variable, ranging from a complete lack of symptoms to a rapidly progressive GN. When symptomatic, 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 22.1 ).
| Onset of Nephritic Syndrome | Infection Site | Bacterial Organisms | Low C3 | Prognosis | |
|---|---|---|---|---|---|
| Children | After infection (typical latency 1–4 weeks) | Pharyngitis skin (impetigo) | Predominantly streptococcal | ≈90% of cases | Excellent (>90% make a full recovery) |
| Adults | During ongoing infection | Highly variable, including respiratory tract, skin, heart, urinary tract, bone, oral/dental | Staphylococcal ≥ streptococcal, gram-negative organisms | 30%–80% of cases | Guarded, with residual CKD common; elderly patients and those with diabetic nephropathy show full recovery in <25% of cases |
In classic PSGN, symptomatic children usually present with acute nephritic syndrome characterized by hematuria, proteinuria, hypertension, edema, oliguria, and variable elevation of serum creatinine. The urinary sediment is usually active, with dysmorphic red 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 usually 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 macroscopic 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 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 estimate that between 9.5 and 28.5 cases of PSGN occur 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 such as 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 renal disease (ESRD). 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.
Histopathology
A spectrum of histologic findings can be seen in IRGN, and biopsy findings are influenced by the associated organism and site and duration of infection.
Light microscopy can reveal a wide range of proliferative glomerular lesions ( Fig. 22.1 ). The most common finding in acute IRGN, including PSGN, is that of diffuse endocapillary proliferation, with significant numbers of infiltrating neutrophils. While occasional cellular crescents may be seen with these diffuse proliferative GNs, crescent formation in >50% of glomeruli is uncommon. More subacute or remote cases of IRGN may show only focal endocapillary proliferation, or simply a mesangial proliferative appearance. In longer standing ongoing infections, such as shunt nephritis, a membranoproliferative pattern with large subendothelial deposits can be seen. Necrotizing and crescentic histology, similar to what can be seen in ANCA vasculitis, is increasingly recognized as a pattern of IRGN associated with endocarditis. In the adult population, acute GN may be superimposed on chronic conditions such as diabetic nephropathy, and this can alter the histologic appearance.
