Rare disease
CASE REPORT
IgA-dominant postinfectious glomerulonephritis induced by methicillin-sensitive Staphylococcus aureus Joana Caetano,1 Fernando Pereira,2 Susana Oliveira,1 José Delgado Alves1,3 1
Department of Medicine 4, Fernando Fonseca Hospital, Amadora, Portugal 2 Department of Nephrology, Fernando Fonseca Hospital, Amadora, Portugal 3 CEDOC – Center for Chronic Diseases of NOVA Medical School, Lisbon, Portugal Correspondence to José Delgado Alves, [email protected] Accepted 26 April 2015
SUMMARY A 56-year-old man with alcohol-associated cirrhosis, arterial hypertension and diabetes, presented with a 1-month history of fever, lumbar back pain and lower limb weakness. MRI revealed a spinal epidural abscess extending from the cervical to the dorsolumbar spine. A methicillin-sensitive Staphylococcus aureus strain was isolated on blood cultures. Meropenem was initially started with no response, and then changed to vancomycin. During treatment, the patient’s condition progressed with anasarca and renal failure with nephrotic-range proteinuria. The renal biopsy showed a membranoproliferative glomerulonephritis with IgA deposition. After completing 2 months of antibiotic therapy the patient recovered from the neurological deficits, with a complete resolution of the abscess and partial recovery of renal function and proteinuria.
Membranoproliferative glomerulonephritis (GN) with dominant mesangial deposition of IgA secondary to Staphylococcus aureus infection is rare and described mainly in case reports. With the increasing prevalence of Staphylococcus infection, this entity must be kept in mind in the differential diagnosis.
The laboratory investigation showed rising serum creatinine from 0.98 to 4.7 mg/dL, high blood urea nitrogen (92.4 mg/dL), hypoalbuminaemia (1.1 g/ dL), a low C3 fraction (64 mg/dL), active urinary sediment with dysmorphic erythrocytes and 24 h proteinuria of 6.6 g. Viral serologies for HIV, and hepatitis B and C, were negative. Antinuclear antibody, anti-double stranded DNA, antineutrophil cytoplasmic antibody, cryoglobulins, serum protein electrophoresis, immunofixation and Bence-Jones proteinuria were negative. Serum cholesterol and the C4 fraction were within the normal range. Renal ultrasound was normal. Renal biopsy showed a mesangial and endothelial hypercellularity associated with glomerular membrane double contours, compatible with membranoproliferative GN, and sparse areas of interstitial fibrosis (figure 1). Immunofluorescence revealed IgA and C3 deposition in a granular pattern, predominantly mesangial, and also focal segmental capillary loop staining. The λ and κ light chains were in similar deposition (figure 2). IgG, IgM and C1q were negative. Electron microscopic study showed subendothelial and subepithelial dense deposits, some with hump characteristics (figure 3).
CASE PRESENTATION
DIFFERENTIAL DIAGNOSIS
A 56-year-old man presented after 1 month of lumbar back pain, fever and lower limb weakness. He had a history of alcohol-associated cirrhosis, arterial hypertension and type 2 diabetes mellitus. On physical examination, he had a high temperature (39°C) and diminished muscle strength in both lower limbs (3/5). General examination was otherwise unremarkable, namely there were no other neurological indications, and no heart murmurs or skin rash. Laboratory analysis showed leucocytosis and elevated C reactive protein. Methicillin-sensitive S. aureus (MSSA) was identified in blood cultures. MRI revealed a spinal epidural abscess extending from the cervical to the dorsolumbar spine. The patient was evaluated by neurosurgery, but was considered as not having indication for surgical intervention. Given the extension of the abscess, treatment with meropenem was started. In a 2-week period, the patient’s general condition further deteriorated, and the antibiotic was changed to vancomycin. After 6 weeks of vancomycin treatment, anasarca developed with ascites, peripheral pitting oedema and hypertension.
Figure 1 Glomerulus showing a lobular appearance with marked mesangial and endocapillary proliferation and infiltrating leucocytes. A segmental double contour of the glomerular membrane can be seen. Periodic acid-Schiff, ×200.
BACKGROUND
To cite: Caetano J, Pereira F, Oliveira S, et al. BMJ Case Rep Published online: [ please include Day Month Year] doi:10.1136/ bcr-2014-208513
INVESTIGATIONS
In this case, the clinical presentation of anasarca and renal failure with nephrotic range proteinuria and an active urinary sediment with dysmorphic erythrocytes, suggested an intrinsic renal disease.
Caetano J, et al. BMJ Case Rep 2015. doi:10.1136/bcr-2014-208513
1
Rare disease their lumina1 and (2) acute interstitial nephritis, with diffuse interstitial infiltrates consisting of lymphocytes, polymorphonuclear cells and macrophages. In some cases, eosinophils, IgE and epithelioid cell granulomas are also present.2 On this basis, the biopsy of our patient, which showed a membranoproliferative GN, was not compatible with vancomycin-induced nephrotoxicity.
TREATMENT Vancomycin was maintained for two more weeks to complete antibiotic treatment and prednisone was initiated (1 mg/kg/day), with a subsequent reduction.
OUTCOME AND FOLLOW-UP
Figure 2 Coarsely granular, global glomerular capillary wall and mesangial staining for IgA. Anti-IgA immunofluorescence, ×200. Primary renal disease capable of this clinical presentation included minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, membranoproliferative GN, fibrillar GN and postinfectious GN. Systemic diseases such as autoimmune diseases, including lupus, vasculitis and cryoglobulinaemia, amyloidosis, deposition light chain disease, hepatitis C or B virus infection and HIV infection should also be excluded. GN associated with liver cirrhosis, namely IgA nephropathy, consisting of mesangial proliferation and mesangial IgA deposits, due to impaired hepatic clearance of immune complexes, should also be considered in this case. Other conditions that could contribute to renal failure, but would not explain the nephrotic proteinuria, were progression of hepatic dysfunction with ascites and hepatorenal syndrome, although there were no other signs of liver dysfunction such as hepatic encephalopathy or jaundice, and vancomycin renal toxicity. Vancomycin-induced nephrotoxicity has two possible pathological findings: (1) acute tubular necrosis, a very rare condition, consisting of tubular necrosis and hyaline or epithelial casts in
Figure 3 Transmission electron microscopy showing subepithelial deposits (arrows), the upper one with hump characteristics. Also shown are scattered subendothelial deposits (arrow heads) ×3000. 2
After treatment, there was complete resolution of the neurological deficits, together with complete disappearance of the spinal abscess (revaluated by MRI scan). There was also a partial recovery of renal function (creatinine 1.5 mg/dL) and 24 h proteinuria reduction to 2.2 g, with no need of haemodialysis. Repeated blood cultures were negative for MSSA.
DISCUSSION IgA-dominant acute postinfectious GN (APIGN) secondary to Staphylococcus infections is a rare clinical entity that has been recently described, mainly through case reports.3 Koyama et al4 first described it in 1995, in 10 patients with methicillinresistant S. aureus (MRSA) infection. It is characterised by glomerular IgA deposits on immunofluorescence, resembling IgA nephropathy, and a diffuse proliferative GN with subepithelial hump-shaped electron dense deposits, similar to poststreptococcal GN.5 Although the first case reports were associated with MRSA infection, MSSA can also cause this type of GN (reported in 18% of patients), with the same clinical, histological and laboratory features.3 6 IgA-dominant APIGN is most frequent in elderly male patients (average age at diagnosis of 60 years), and diabetes mellitus is the most common underlying condition (55%).7 The most frequent sites of infection are the skin (cellulitis, surgical wound infections, skin abscesses), deep-seated abscesses, and lung, joint and heart infections (infective endocarditis).3 7 The pathogenic mechanisms of this GN are not well understood.5 Koyama et al, proposed a role for bacterial superantigens (enterotoxins C and A, and toxic shock syndrome toxin). These superantigens bind directly to major histocompatibility class II molecules, stimulating T cells, cytokine production and polyclonal activation of IgG and IgA, with formation of immuneocomplexes.4 The same group also identified a S. aureus cell envelope antigen designated ‘probable adhesion’ in the glomeruli, in co-localisation with the IgA deposits, in patients with IgA nephropathy and IgA-dominant APIGN, but not in nonimmune complex types of GN, suggesting a potential role of this superantigen in the induction of IgA nephropathy.8 The hypothesis put forward by Koyama has been supported with evidence that IgA can activate alternative as well as lectin complement pathways, hence explaining the deposits found in kidney biopsies in this context.9–11 Roos et al12 demonstrated the presence of mesangial deposition of mannose-binding lectin in IgA nephropathy, as a marker for lectin pathway activation, and that this deposition was associated with more severe renal injury. The clinical, laboratory and histological presentation in our case are in accordance with the literature. The majority of patients present with acute renal failure, with a rise of serum Caetano J, et al. BMJ Case Rep 2015. doi:10.1136/bcr-2014-208513
Rare disease creatinine (range 1.2–14.5 mg/dL), and concomitant haematuria and proteinuria (nephrotic range in 40% of patients).5 7 Hypocomplementaemia is also present in the majority of patients (69%).7 Staphylococcus infection can be coexistent with the renal disease, but the renal manifestations can occur after the resolution of the infection, more often within a 10-week period.13 14 The histological features of the renal biopsy on light microscopy consist of an endocapillary proliferative and exudative GN in 63% of the reported cases, and a mesangial proliferative GN in 33%.7 Electron microscopic studies show large subepithelial humps, which decrease as the disease progresses.5 Immunofluorescence analysis shows a dominant granular IgA glomerular staining, with or without a weaker staining for IgG and/or IgM.5 7 There is also high-intensity glomerular staining for C3, which is stronger than IgA in the majority of cases. C1q staining is uncommon and usually of weak intensity.7 This type of GN must be distinguished from IgA nephropathy due to the differences in prognosis and treatment between the two entities.3 IgA nephropathy affects younger individuals and may have a wide range of presentations, from isolated haematuria to nephritic or nephrotic syndrome, but does not typically cause hypocomplementaemia. The renal biopsy aspects are also different, with endocapillary proliferation, stronger staining for C3 rather than for IgA, equal or stronger staining for λ chains compared with κ and subepithelial humps, favouring IgA-dominant APIGN.3 5 7 Treatment of IgA-dominant APIGN is based on antibiotics for the underlying infection, which were used in all cases reported, sometimes with a concomitant use of steroids. The role of
steroids to treat this condition remains unclear.5 8 Immunosuppression with corticoids can be considered after the infection is controlled, if there is progression of the renal disease, as in our patient.14 15 Predictors of long-term prognosis are not well defined, and patients can progress to end-stage renal disease (41% in some series).7 Hypertension, diabetes mellitus and fibrosis on kidney biopsy seem to be related to a poorer prognosis and deterioration of renal function.3 8 Acknowledgements The authors thank Dr Sílvia Coelho for the contribution to this study. Contributors All the authors contributed to conception of the work and acquisition of data. JC and FP participated in drafting of the manuscript. JDA and SO revised the manuscript critically for important intellectual content. All the authors approved the final version to be published. Competing interests None declared. Patient consent Obtained. Provenance and peer review Not commissioned; externally peer reviewed.
REFERENCES 1 2 3
4
5 6
7
Learning points
8
▸ IgA-dominant acute postinfectious glomerulonephritis (APIGN) is a rare disease, but has been increasingly associated with a higher prevalence of staphylococcal-associated infections. ▸ Although less frequent, methicillin-sensitive Staphylococcus aureus infection can induce IgA-dominant APIGN similar to methicillin-resistant S. aureus. ▸ IgA-dominant APIGN should be considered in patients with rapidly progressive acute renal injury, haematuria and proteinuria. ▸ Worsening of renal function can occur even after the infection has been treated. ▸ IgA-dominant APIGN must be distinguished from IgA nephropathy by the clinical context (eg, infection) and the kidney biopsy.
9
Caetano J, et al. BMJ Case Rep 2015. doi:10.1136/bcr-2014-208513
10
11 12
13
14 15
Shah-Khan F, Scheetz MH, Ghossein C. Biopsy-proven acute tubular necrosis due to vancomycin toxicity. Int J Nephrol 2011;2011:436856. Wai AO, Lo AM, Abdo A, et al. Vancomycin-induced acute interstitial nephritis. Ann Pharmacother 1998;32:1160–4. Wehbe E, Salem C, Simon JF, et al. IgA-dominant Staphylococcus infection-associated glomerulonephritis: case reports and review of the literature. NDT Plus 2011;4:181–5. Koyama A, Kobasyashi M, Yamaguchi N, et al. Glomerulonephritis associated with MRSA infection: a possible role of bacterial superantigen. Kidney Int 1995;47:207–16. Gaut JP, Liapis H. IgA dominant post-infectious glomerulonephritis: pathology and insights into disease mechanisms. Diagn Histopathol 2013;19:175–81. Handa T, Ono T, Watanabe H, et al. Glomerulonephritis induced by methicillin-sensitive Staphylococcus aureus infection. Clin Exp Nephrol 2003;7:247–9. Nasr S, D’Agati V. IgA-dominant postinfectious glomerulonephritis: a new twist on an old disease. Nephron Clin Pract 2011;119:c18–25; discussion –26. Koyama A, Sharmin S, Sakurai H, et al. Staphylococcus aureus cell envelope antigen is a new candidate for the induction of IgA nephropathy. Kidney Int 2004;66:121–32. Roos A, Bouwman LH, Gijlswijk-Jansen DJ, et al. Human IgA activates the complement system via the mannan-binding lectin pathway. J Immunol 2001;167:2861–8. Endo M, Ohi H, Ohsawa I, et al. Glomerular deposition of mannose-binding lectin (MBL) indicates a novel mechanism of complement activation in IgA nephropathy. Nephrol Dial Transplant 1998;13:1984–90. Oartwijn BD, Eijgenraam JW, Rastaldi MP, et al. The role of secretory IgA and complement in IgA nephropathy. Semin Nephrol 2008;28:58–65. Roos A, Rastaldi MP, Calvaresi N, et al. Glomerular activation of the lectin pathway of complement in IgA nephropathy is associated with more severe renal disease. J Am Soc Nephrol 2006;17:1724–34. Satoskar A, Nadasdy G, Plaza JA, et al. Staphylococcus aureus infection-associated glomerulonephritis mimicking IgA nephropathy. Clin J Am Soc Nephrol 2006;1:1179–86. Okuyama S, Wakui H, Maki N, et al. Successful treatment of post-MRSA infection glomerulonephritis with steroid therapy. Clin Nephrol 2008;70:344–7. Chen YR, Wen YK. Favorable outcome of crescentic IgA nephropathy associated with methicillin-resistant Staphylococcus aureus infection. Ren Fail 2011;33:96–100.
3
Rare disease Copyright 2015 BMJ Publishing Group. All rights reserved. For permission to reuse any of this content visit http://group.bmj.com/group/rights-licensing/permissions. BMJ Case Report Fellows may re-use this article for personal use and teaching without any further permission. Become a Fellow of BMJ Case Reports today and you can: ▸ Submit as many cases as you like ▸ Enjoy fast sympathetic peer review and rapid publication of accepted articles ▸ Access all the published articles ▸ Re-use any of the published material for personal use and teaching without further permission For information on Institutional Fellowships contact [email protected] Visit casereports.bmj.com for more articles like this and to become a Fellow
4
Caetano J, et al. BMJ Case Rep 2015. doi:10.1136/bcr-2014-208513
CASE REPORT
IgA-dominant postinfectious glomerulonephritis induced by methicillin-sensitive Staphylococcus aureus Joana Caetano,1 Fernando Pereira,2 Susana Oliveira,1 José Delgado Alves1,3 1
Department of Medicine 4, Fernando Fonseca Hospital, Amadora, Portugal 2 Department of Nephrology, Fernando Fonseca Hospital, Amadora, Portugal 3 CEDOC – Center for Chronic Diseases of NOVA Medical School, Lisbon, Portugal Correspondence to José Delgado Alves, [email protected] Accepted 26 April 2015
SUMMARY A 56-year-old man with alcohol-associated cirrhosis, arterial hypertension and diabetes, presented with a 1-month history of fever, lumbar back pain and lower limb weakness. MRI revealed a spinal epidural abscess extending from the cervical to the dorsolumbar spine. A methicillin-sensitive Staphylococcus aureus strain was isolated on blood cultures. Meropenem was initially started with no response, and then changed to vancomycin. During treatment, the patient’s condition progressed with anasarca and renal failure with nephrotic-range proteinuria. The renal biopsy showed a membranoproliferative glomerulonephritis with IgA deposition. After completing 2 months of antibiotic therapy the patient recovered from the neurological deficits, with a complete resolution of the abscess and partial recovery of renal function and proteinuria.
Membranoproliferative glomerulonephritis (GN) with dominant mesangial deposition of IgA secondary to Staphylococcus aureus infection is rare and described mainly in case reports. With the increasing prevalence of Staphylococcus infection, this entity must be kept in mind in the differential diagnosis.
The laboratory investigation showed rising serum creatinine from 0.98 to 4.7 mg/dL, high blood urea nitrogen (92.4 mg/dL), hypoalbuminaemia (1.1 g/ dL), a low C3 fraction (64 mg/dL), active urinary sediment with dysmorphic erythrocytes and 24 h proteinuria of 6.6 g. Viral serologies for HIV, and hepatitis B and C, were negative. Antinuclear antibody, anti-double stranded DNA, antineutrophil cytoplasmic antibody, cryoglobulins, serum protein electrophoresis, immunofixation and Bence-Jones proteinuria were negative. Serum cholesterol and the C4 fraction were within the normal range. Renal ultrasound was normal. Renal biopsy showed a mesangial and endothelial hypercellularity associated with glomerular membrane double contours, compatible with membranoproliferative GN, and sparse areas of interstitial fibrosis (figure 1). Immunofluorescence revealed IgA and C3 deposition in a granular pattern, predominantly mesangial, and also focal segmental capillary loop staining. The λ and κ light chains were in similar deposition (figure 2). IgG, IgM and C1q were negative. Electron microscopic study showed subendothelial and subepithelial dense deposits, some with hump characteristics (figure 3).
CASE PRESENTATION
DIFFERENTIAL DIAGNOSIS
A 56-year-old man presented after 1 month of lumbar back pain, fever and lower limb weakness. He had a history of alcohol-associated cirrhosis, arterial hypertension and type 2 diabetes mellitus. On physical examination, he had a high temperature (39°C) and diminished muscle strength in both lower limbs (3/5). General examination was otherwise unremarkable, namely there were no other neurological indications, and no heart murmurs or skin rash. Laboratory analysis showed leucocytosis and elevated C reactive protein. Methicillin-sensitive S. aureus (MSSA) was identified in blood cultures. MRI revealed a spinal epidural abscess extending from the cervical to the dorsolumbar spine. The patient was evaluated by neurosurgery, but was considered as not having indication for surgical intervention. Given the extension of the abscess, treatment with meropenem was started. In a 2-week period, the patient’s general condition further deteriorated, and the antibiotic was changed to vancomycin. After 6 weeks of vancomycin treatment, anasarca developed with ascites, peripheral pitting oedema and hypertension.
Figure 1 Glomerulus showing a lobular appearance with marked mesangial and endocapillary proliferation and infiltrating leucocytes. A segmental double contour of the glomerular membrane can be seen. Periodic acid-Schiff, ×200.
BACKGROUND
To cite: Caetano J, Pereira F, Oliveira S, et al. BMJ Case Rep Published online: [ please include Day Month Year] doi:10.1136/ bcr-2014-208513
INVESTIGATIONS
In this case, the clinical presentation of anasarca and renal failure with nephrotic range proteinuria and an active urinary sediment with dysmorphic erythrocytes, suggested an intrinsic renal disease.
Caetano J, et al. BMJ Case Rep 2015. doi:10.1136/bcr-2014-208513
1
Rare disease their lumina1 and (2) acute interstitial nephritis, with diffuse interstitial infiltrates consisting of lymphocytes, polymorphonuclear cells and macrophages. In some cases, eosinophils, IgE and epithelioid cell granulomas are also present.2 On this basis, the biopsy of our patient, which showed a membranoproliferative GN, was not compatible with vancomycin-induced nephrotoxicity.
TREATMENT Vancomycin was maintained for two more weeks to complete antibiotic treatment and prednisone was initiated (1 mg/kg/day), with a subsequent reduction.
OUTCOME AND FOLLOW-UP
Figure 2 Coarsely granular, global glomerular capillary wall and mesangial staining for IgA. Anti-IgA immunofluorescence, ×200. Primary renal disease capable of this clinical presentation included minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, membranoproliferative GN, fibrillar GN and postinfectious GN. Systemic diseases such as autoimmune diseases, including lupus, vasculitis and cryoglobulinaemia, amyloidosis, deposition light chain disease, hepatitis C or B virus infection and HIV infection should also be excluded. GN associated with liver cirrhosis, namely IgA nephropathy, consisting of mesangial proliferation and mesangial IgA deposits, due to impaired hepatic clearance of immune complexes, should also be considered in this case. Other conditions that could contribute to renal failure, but would not explain the nephrotic proteinuria, were progression of hepatic dysfunction with ascites and hepatorenal syndrome, although there were no other signs of liver dysfunction such as hepatic encephalopathy or jaundice, and vancomycin renal toxicity. Vancomycin-induced nephrotoxicity has two possible pathological findings: (1) acute tubular necrosis, a very rare condition, consisting of tubular necrosis and hyaline or epithelial casts in
Figure 3 Transmission electron microscopy showing subepithelial deposits (arrows), the upper one with hump characteristics. Also shown are scattered subendothelial deposits (arrow heads) ×3000. 2
After treatment, there was complete resolution of the neurological deficits, together with complete disappearance of the spinal abscess (revaluated by MRI scan). There was also a partial recovery of renal function (creatinine 1.5 mg/dL) and 24 h proteinuria reduction to 2.2 g, with no need of haemodialysis. Repeated blood cultures were negative for MSSA.
DISCUSSION IgA-dominant acute postinfectious GN (APIGN) secondary to Staphylococcus infections is a rare clinical entity that has been recently described, mainly through case reports.3 Koyama et al4 first described it in 1995, in 10 patients with methicillinresistant S. aureus (MRSA) infection. It is characterised by glomerular IgA deposits on immunofluorescence, resembling IgA nephropathy, and a diffuse proliferative GN with subepithelial hump-shaped electron dense deposits, similar to poststreptococcal GN.5 Although the first case reports were associated with MRSA infection, MSSA can also cause this type of GN (reported in 18% of patients), with the same clinical, histological and laboratory features.3 6 IgA-dominant APIGN is most frequent in elderly male patients (average age at diagnosis of 60 years), and diabetes mellitus is the most common underlying condition (55%).7 The most frequent sites of infection are the skin (cellulitis, surgical wound infections, skin abscesses), deep-seated abscesses, and lung, joint and heart infections (infective endocarditis).3 7 The pathogenic mechanisms of this GN are not well understood.5 Koyama et al, proposed a role for bacterial superantigens (enterotoxins C and A, and toxic shock syndrome toxin). These superantigens bind directly to major histocompatibility class II molecules, stimulating T cells, cytokine production and polyclonal activation of IgG and IgA, with formation of immuneocomplexes.4 The same group also identified a S. aureus cell envelope antigen designated ‘probable adhesion’ in the glomeruli, in co-localisation with the IgA deposits, in patients with IgA nephropathy and IgA-dominant APIGN, but not in nonimmune complex types of GN, suggesting a potential role of this superantigen in the induction of IgA nephropathy.8 The hypothesis put forward by Koyama has been supported with evidence that IgA can activate alternative as well as lectin complement pathways, hence explaining the deposits found in kidney biopsies in this context.9–11 Roos et al12 demonstrated the presence of mesangial deposition of mannose-binding lectin in IgA nephropathy, as a marker for lectin pathway activation, and that this deposition was associated with more severe renal injury. The clinical, laboratory and histological presentation in our case are in accordance with the literature. The majority of patients present with acute renal failure, with a rise of serum Caetano J, et al. BMJ Case Rep 2015. doi:10.1136/bcr-2014-208513
Rare disease creatinine (range 1.2–14.5 mg/dL), and concomitant haematuria and proteinuria (nephrotic range in 40% of patients).5 7 Hypocomplementaemia is also present in the majority of patients (69%).7 Staphylococcus infection can be coexistent with the renal disease, but the renal manifestations can occur after the resolution of the infection, more often within a 10-week period.13 14 The histological features of the renal biopsy on light microscopy consist of an endocapillary proliferative and exudative GN in 63% of the reported cases, and a mesangial proliferative GN in 33%.7 Electron microscopic studies show large subepithelial humps, which decrease as the disease progresses.5 Immunofluorescence analysis shows a dominant granular IgA glomerular staining, with or without a weaker staining for IgG and/or IgM.5 7 There is also high-intensity glomerular staining for C3, which is stronger than IgA in the majority of cases. C1q staining is uncommon and usually of weak intensity.7 This type of GN must be distinguished from IgA nephropathy due to the differences in prognosis and treatment between the two entities.3 IgA nephropathy affects younger individuals and may have a wide range of presentations, from isolated haematuria to nephritic or nephrotic syndrome, but does not typically cause hypocomplementaemia. The renal biopsy aspects are also different, with endocapillary proliferation, stronger staining for C3 rather than for IgA, equal or stronger staining for λ chains compared with κ and subepithelial humps, favouring IgA-dominant APIGN.3 5 7 Treatment of IgA-dominant APIGN is based on antibiotics for the underlying infection, which were used in all cases reported, sometimes with a concomitant use of steroids. The role of
steroids to treat this condition remains unclear.5 8 Immunosuppression with corticoids can be considered after the infection is controlled, if there is progression of the renal disease, as in our patient.14 15 Predictors of long-term prognosis are not well defined, and patients can progress to end-stage renal disease (41% in some series).7 Hypertension, diabetes mellitus and fibrosis on kidney biopsy seem to be related to a poorer prognosis and deterioration of renal function.3 8 Acknowledgements The authors thank Dr Sílvia Coelho for the contribution to this study. Contributors All the authors contributed to conception of the work and acquisition of data. JC and FP participated in drafting of the manuscript. JDA and SO revised the manuscript critically for important intellectual content. All the authors approved the final version to be published. Competing interests None declared. Patient consent Obtained. Provenance and peer review Not commissioned; externally peer reviewed.
REFERENCES 1 2 3
4
5 6
7
Learning points
8
▸ IgA-dominant acute postinfectious glomerulonephritis (APIGN) is a rare disease, but has been increasingly associated with a higher prevalence of staphylococcal-associated infections. ▸ Although less frequent, methicillin-sensitive Staphylococcus aureus infection can induce IgA-dominant APIGN similar to methicillin-resistant S. aureus. ▸ IgA-dominant APIGN should be considered in patients with rapidly progressive acute renal injury, haematuria and proteinuria. ▸ Worsening of renal function can occur even after the infection has been treated. ▸ IgA-dominant APIGN must be distinguished from IgA nephropathy by the clinical context (eg, infection) and the kidney biopsy.
9
Caetano J, et al. BMJ Case Rep 2015. doi:10.1136/bcr-2014-208513
10
11 12
13
14 15
Shah-Khan F, Scheetz MH, Ghossein C. Biopsy-proven acute tubular necrosis due to vancomycin toxicity. Int J Nephrol 2011;2011:436856. Wai AO, Lo AM, Abdo A, et al. Vancomycin-induced acute interstitial nephritis. Ann Pharmacother 1998;32:1160–4. Wehbe E, Salem C, Simon JF, et al. IgA-dominant Staphylococcus infection-associated glomerulonephritis: case reports and review of the literature. NDT Plus 2011;4:181–5. Koyama A, Kobasyashi M, Yamaguchi N, et al. Glomerulonephritis associated with MRSA infection: a possible role of bacterial superantigen. Kidney Int 1995;47:207–16. Gaut JP, Liapis H. IgA dominant post-infectious glomerulonephritis: pathology and insights into disease mechanisms. Diagn Histopathol 2013;19:175–81. Handa T, Ono T, Watanabe H, et al. Glomerulonephritis induced by methicillin-sensitive Staphylococcus aureus infection. Clin Exp Nephrol 2003;7:247–9. Nasr S, D’Agati V. IgA-dominant postinfectious glomerulonephritis: a new twist on an old disease. Nephron Clin Pract 2011;119:c18–25; discussion –26. Koyama A, Sharmin S, Sakurai H, et al. Staphylococcus aureus cell envelope antigen is a new candidate for the induction of IgA nephropathy. Kidney Int 2004;66:121–32. Roos A, Bouwman LH, Gijlswijk-Jansen DJ, et al. Human IgA activates the complement system via the mannan-binding lectin pathway. J Immunol 2001;167:2861–8. Endo M, Ohi H, Ohsawa I, et al. Glomerular deposition of mannose-binding lectin (MBL) indicates a novel mechanism of complement activation in IgA nephropathy. Nephrol Dial Transplant 1998;13:1984–90. Oartwijn BD, Eijgenraam JW, Rastaldi MP, et al. The role of secretory IgA and complement in IgA nephropathy. Semin Nephrol 2008;28:58–65. Roos A, Rastaldi MP, Calvaresi N, et al. Glomerular activation of the lectin pathway of complement in IgA nephropathy is associated with more severe renal disease. J Am Soc Nephrol 2006;17:1724–34. Satoskar A, Nadasdy G, Plaza JA, et al. Staphylococcus aureus infection-associated glomerulonephritis mimicking IgA nephropathy. Clin J Am Soc Nephrol 2006;1:1179–86. Okuyama S, Wakui H, Maki N, et al. Successful treatment of post-MRSA infection glomerulonephritis with steroid therapy. Clin Nephrol 2008;70:344–7. Chen YR, Wen YK. Favorable outcome of crescentic IgA nephropathy associated with methicillin-resistant Staphylococcus aureus infection. Ren Fail 2011;33:96–100.
3
Rare disease Copyright 2015 BMJ Publishing Group. All rights reserved. For permission to reuse any of this content visit http://group.bmj.com/group/rights-licensing/permissions. BMJ Case Report Fellows may re-use this article for personal use and teaching without any further permission. Become a Fellow of BMJ Case Reports today and you can: ▸ Submit as many cases as you like ▸ Enjoy fast sympathetic peer review and rapid publication of accepted articles ▸ Access all the published articles ▸ Re-use any of the published material for personal use and teaching without further permission For information on Institutional Fellowships contact [email protected] Visit casereports.bmj.com for more articles like this and to become a Fellow
4
Caetano J, et al. BMJ Case Rep 2015. doi:10.1136/bcr-2014-208513
