Glomerulonephritis acute postinfectious N08.0

Acute, immune-mediated, post-infectious inflammation of the renal glomerula, which particularly affects children between the ages of 5 and 15 (Wang D et al. 2017).

The main causes are streptogenic infections of the oropharynx (angina tonsillaris, pharyngitis), skin and bones (erysipelas, impetigo, possibly osteomyelitis, etc.).

Also possible in bacterial endocarditis, infections of ventriculo-atrial or ventriculo-jugular shunts.

Less common pathogens are bacterial pathogens that do not belong to the streptococcus genus, such as staphylococci. (Note: Various authors regard "post-staphylococcal glomerulonephritis" as a separate, IgA-mediated entity. Glassock RJ et al. 2015), viruses (e.g. HBV, parvovirus B19 - Marco H et al. 2016), parasites, rickettsiae, fungi and malaria pathogens.

In adults, leading infection precursors (staphylogenic) are skin infections, followed by pneumonia and urinary tract infections.

In addition to staphylococci, streptococci and gram-negative germs are the main causes (Nasr SH et al. 2011).

In rare cases, scabies infections were the triggering cause in adults. (Wang D et al. 2017)

Rather rare in developed countries, of significant relevance in developing countries (Kambham N 2012) or among certain indigenous peoples (Ramanathan G et al. 2017). For adults: m:w=2.8:1.

Unknown; it is postulated that microbial antigens bind to the glomerular basement membrane; they activate the alternating complement pathway directly or by binding circulating IgG antibodies and induce a site-specific, initially neutrophilic, later neutrophilic/monocytic inflammation. Furthermore, infection-associated circulating immune complexes can be deposited on the glomerular basement membrane, which then also induces a focal, granulocytic/monocytic inflammation. Such a process can also be observed analogously in capillaries of the skin (principle of leukocytoclastic vasculitis, clinical picture of palpable purpura).

Other known antigens that play a role in the pathogenesis of PIGN are the "nephritis-associated plasmin receptor" (NAPlr) and the "streptococcal pyrogenic exotoxin B" (SPeB). Both antigens, which are characterized by an affinity for glomerular proteins, are also able to activate the alternative complement pathway (Balasubramanian R et al.2017).

About 5-10 % of patients with streptococcal pharyngitis and about 25 % of patients with impetigo develop PIGN.

50% of cases of PIG in children and adolescents are completely asymptomatic or are not clinically diagnosed. The other half of patients become symptomatic after a latency phase of 6-21 days (rarely longer, up to 6 weeks). Typically, after a normal post-infectious convalescence phase, the patient feels clearly ill again; however, fever is rare.

• Obligatory symptoms are: microhaematuria + proteinuria (< 3.0 g / 24 h)

Optional symptoms are:

• Edema (especially periorbital), hypertension
• Headache, aching limbs, pain in the lumbar region (renal capsule tension)
• Macrohaematuria (urine becomes dark brown, smoky or purely bloody; detectable in approx. 50 % of cases)
• Neurological symptoms: epileptic seizures, somnolence (cerebral edema)
• Complicative: hypertensive crisis with dyspnea and pulmonary edema. In 1-2 % of patients with severe hypertension, renal failure with fluid overload and heart failure may occur (pulmorenal syndrome with hematuria and hemoptysis).
• Rarely, a nephrotic syndrome (proteinuria > 3.0-3.5 g / 24 h) may persist after the acute phase has subsided.

Urine status: usually moderate proteinuria (0.5-2.0 g / 24 h), dysmorphic erythrocytes, leukocytes, possibly erythrocyte, leukocyte granulocyte cylinders and renal tubule cells.

Serum creatinine: may initially rise rapidly.

ASL: elevated in 50 %

Imaging: Sonography: large swollen kidneys

Immunology:

• Complement: C3- decreased during the active phase. Normalization in 80 % of PIGN cases within 6-8 weeks. C1q, C2 and C4 levels are usually normal.
• Cryoglobulins: Cryoglobulinemia is rare and is usually transient (a few months).
• Anti-DNAse-B (=ADB titer) increased in 90% of cases of streptococcal infections (impetigo contagiosa) of the skin.

Enlarged and hypercellular glomeruli, initially with neutrophilic, later with mononuclear infiltrates. Cellular proliferation and edema of the glomeruli are possible; crescent formation (due to proliferation of Bowman's capillary epithelium); severe narrowing of the capillary clearing. Mesangial spaces often considerably enlarged due to edema formation; they contain neutrophil cells and cell debris.

Direct immunofluorescence (DIF): Detection of immune complex deposits, IgG (more rarely IgA) and complement fractions, which are detectable as "humps", small bumps, on the outside of the basement membrane (Mascarenhas R et al. 2016).

Evidence of previous infection, characteristic clinic, laboratory; possibly kidney biopsy (only if retention values increase rapidly and significantly) to rule out RPGN (Rapid Progressive GN).

Rapid progressive glomerulonephritis (retention levels remain high); IgA nephropathy (macrohematuria).

In principle, the treatment of uncomplicated PIGN is conservative or supportive. It includes physical rest, restriction of protein, sodium and fluid intake (Kanjanabuch T et al. 2009). Furthermore: antibiotic therapy (3 mega penicilin/day for 10 days). Further symptom-oriented therapies:

• Possibly focal decontamination under antibiotic protection (usefulness is controversially discussed)
• Edema: diuretic therapy (loop diuretics)
• Hypertension: ACE inhibitors or sartans
• Severe course/complications: glucocorticoids, intermittent dialysis if necessary

Symptomatic therapy with monitoring of kidney function is usually sufficient in children and leads to healing without consequences within 6-8 weeks (!) in 90% of cases (Sethi S et al. 2012); the GFR normalizes during this time. Mild proteinuria can persist for 6-12 months, microhematuria for several years. Renal cell proliferation disappears within weeks, but sclerosis usually persists. In about 50 % of cases, renal function remains impaired. In immunosuppressed patients, this figure is > 50 %.

Adults (often associated with diabetes mellitus) have a significantly worse prognosis than children. 46 % of adult patients become acutely dialysis-dependent (Nasr SH et al. 2011).

In 1 % of children and 10 % of adults, PIGN develops into rapidly progressive glomerulonephritis (rapid progressive GN). The causes of this atypical course are still unclear. Dysregulations of the alternative complement pathway, such as mutations in the genes that code for the complement building blocks and in antibody formation against the C3 convertase, are being discussed (Sethi S et al. 2012).

Early and sufficiently long antibiotic therapy for infections with beta-hemolytic Group A Streptococci.

In principle, PIGN should be considered in children and adolescents with microhaematuria and mild proteinuria (as well as other facultative PIGN symptoms), a history of recent infections (streptococcal tonsillitis, pharyngitis, impetigo or erysipelas) who feel ill again and have reduced performance. Evidence of hypocomplementemia is an essential confirmation. A biopsy can confirm the diagnosis but is rarely necessary. Supportive treatment generally leads to recovery of renal function.

Further note! Immune complex glomerulonephritis can also develop during a persistent infection, e.g. in endocarditis or soft tissue abscesses.

1. Balasubramanian R et al.(2017) Post-infectious glomerulonephritis. Paediatr Int Child Health 37:240-247.
2. Glassock RJ et al (2015) Staphylococcus-related glomerulonephritis and poststreptococcal glomerulonephritis: why defining "post" is important in understanding and treating infection-related glomerulonephritis. At J Kidney Dis. 65:826-832.
3. Kambham N (2012) Postinfectious glomerulonephritis. Adv Anat Pathol 19:338-347.
4. Kanjanabuch T et al (2009) An update on acute postinfectious glomerulonephritis worldwide. Nat Rev Nephrol 5:259-269.
5. Marco H et al (2016) Postinfectious glomerulonephritis secondary to Erythrovirus B19 (Parvovirus B19): case report and review of the literature. Clin Nephrol 85:238-244.
6. Mascarenhas R et al (2016) IgA dominant postinfectious glomerulonephritis. Clin Pediatr (Phila) 55:873-876.

7. Nasr SH et al (2011) Postinfectious glomerulonephritis in the elderly. J Am Soc Nephrol 22:187-195.

8. Ramanathan G et al (2017) Analysis of clinical presentation, pathological spectra, treatment and outcomes of biopsy-proven acute postinfectious glomerulonephritis in adult indigenous people of the Northern Territory of Australia. Nephrology (Carlton) 22:403-411.

9. Sethi S et al (2012) Atypical postinfectious glomerulonephritis is associated with abnormalities in the alternative pathway of complement. Kidney Int 83:293-299
10. Wang D et al (2017) Acute postinfectious glomerulonephritis associated with scabies in the elderly: A case report. Parasitol Int 66:802-805.