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  Table of Contents    
CASE REPORT  
Year : 2015  |  Volume : 58  |  Issue : 3  |  Page : 374-376
Acute postinfectious glomerulonephritis with a large number of crescents caused by Mycoplasma pneumoniae


1 Division of Nephrology, Renmin Hospital, Wuhan University, Wuhan, Hubei, China
2 Division of Dermatology, Wuhan City Hospital No. 3 & Tongren Hospital of Wuhan University, Wuhan, Hubei, China

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Date of Web Publication14-Aug-2015
 

   Abstract 

Mycoplasma pneumoniae-induced acute postinfectious glomerulonephritis has various pathological changes and relatively poor prognosis. It often occurs in children, barely in adults. Currently, no clear treatment guidelines have been established for its treatment using glucocorticoid and immunosuppressive. In this study, we report an adult who admitted to our hospital due to fever and gross hematuria. The patient presented with nephritic syndrome and renal failure and confirmed to have M. pneumoniae infection by serum detection and acute postinfectious glomerulonephritis with a large number of crescents by renal biopsy. He was given glucocorticoid, immunosuppressive agent combined with hemodialysis as well as other supportive treatment. Three months later, his renal function became normal, urine protein level decreased to 0.4 g/24 h, and the C3 complement increased to normal level. In conclusion, glucocorticoid and immunosuppressive treatment should be given to patients with M. pneumoniae-infection induced glomerulonephritis after confirmed to have a large number of crescents by renal biopsy and the treatment could improve the prognosis.

Keywords: Crescent, Mycoplasma pneumoniae, postinfectious glomerulonephritis

How to cite this article:
Chen X, Xu W, Du J, Wang H. Acute postinfectious glomerulonephritis with a large number of crescents caused by Mycoplasma pneumoniae. Indian J Pathol Microbiol 2015;58:374-6

How to cite this URL:
Chen X, Xu W, Du J, Wang H. Acute postinfectious glomerulonephritis with a large number of crescents caused by Mycoplasma pneumoniae. Indian J Pathol Microbiol [serial online] 2015 [cited 2020 Jun 6];58:374-6. Available from: http://www.ijpmonline.org/text.asp?2015/58/3/374/162907



   Introduction Top


Postinfectious glomerulonephritis is an immunologic response of kidney to nonrenal infection, often with streptococci, but also with virus, mycoplasma, and parasite. [1] Its incidence is declining in most industrialized countries but remains high in some less developed regions. Mycoplasma pneumoniae-associated acute glomerulonephritis (AGN) often occurs in children and is manifested in renal biopsy with various pathological changes such as membranoproliferative glomerulonephritis (MPGN), endocapillary proliferative glomerulonephritis (EPGN), minimal change disease, and so on. [2] Its pathogenesis remains unclear although is thought to be an immune complex-mediated nephritis due to circulating immune complexes containing either mycoplasmal or autologous antigens.

In this paper, we report a case of acute M. pneumoniae-associated glomerulonephritis in a 46-year-old male characterized by severe endo- and extracapillary proliferation. He was treated with combined therapy of steroid and immunosuppressive agents and obtained satisfactory outcome.


   Case Report Top


A 46-year-old male admitted to the Department of Nephrology because of painless gross hematuria and edema. Twenty days prior to the admission, he:

  1. Started to developed a fever (37.8°C) that lasted for 24 h and was associated with nonproductive cough,
  2. He had received venous cefoperazone sodium, and
  3. Although his body temperature returned to normal, the anasarca hyposarca and gross hematuria persisted until admission. At the admission time, he had body temperature of 36.9°C, pulse rate of 84 beats/min, respiratory rate of 18/min, and blood pressure of 145/95 mmHg.


Physical examination showed that he had mild anemia and impressive double low limb edema. Urinalysis demonstrated that his macroscopic hematuria and proteinuria was up to 5.3 g/24 h. Blood chemistry studies indicated that his urea was 15.66 mmol/l, creatinine was 601 μmol/l, serum total protein was 48.7 g/l, albumin was 24.6 g/l, hemoglobin was 9.5 g/dl, platelets was 176,000/μl, white blood cell count was 7440/μl, C-reactive protein was 6.6 mg/l, rheumatoid factor was <9.94 IU/mL (normal range: 0-15), ASO was 75.8 IU/ml (normal range: 0-200), and erythrocyte sedimentation rate was 5 mm/h (normal range: 0-15). In addition, he had normal serum immunoglobulin (Ig)G of 8.74 g/l (normal range: 8-16), IgA of 2.61 g/l (normal range: 0.76-3.9) and IgM of 0.80 g/l (normal range: 0.76-3.9), but enhanced IgE of 1530 IU/ml (normal range: 0-378) and reduced complement component 3 (C3) of 0.647 (normal range: 0.81-1.6). He was negative for antinuclear antibody, antineutrophil cytoplasmic antibody (ANCA), anti-glomerular basement membrane (anti-GBM) antibody and anti-extractable nuclear antigen antibody, hepatitis B surface antigen (HBsAg),  Treponema pallidum Scientific Name Search tibody, hepatitis C virus -IgG, human immunodeficiency virus-Ag/Ab, cytomegalovirus (CMV)-IgM, CMV-IgG and Epstein-Barr virus -DNA, but positive to HBsAb. He had normal tumor markers such as serum AFU, total prostate specific antigen (tPSA), complex PSA, CA125, CA199, carcinoembryonic antigen, Ferritin, alpha-fetoprotein, CA724 and squamous cell carcinoma, as well as normal chest X-ray and electrocardiogram results. The renal ultrasound scan showed enlarged hyperechoic kidneys (left: 16.0 cm × 6.8 cm × 5.4 cm, right: 15.6 cm × 6.4 cm × 5.2 cm).

A polymerase chain reaction (PCR) analysis for detecting serum M. pneumoniae was positive, and the repeat studies of the complement fixation reaction for M. pneumoniae showed a significant increase in the serum titer. Both results supported the diagnosis that he was recently infected with M. pneumoniae. Thus, he was intravenously given macrolides.

A percutaneous renal biopsy was performed on March 18, 2014 (26 days after fever) to explore the cause of proteinuria. The examination under light microscopy revealed:

  1. 20 glomeruli with diffuse global mesangial matrix and cellular and endocapillary proliferation; among which, 8 had cell-fibrous crescents and one had segment fibrous crescent [Figure 1]a-c;
    Figure 1: Renal pathology showed acute postinfectious glomerulonephritis with a large number of crescents. (a) Periodic acid-Schiff staining showing global mesangial matrix, cellular and endocapillary proliferation, and a big crescent formation (×400); (b) periodic acid-silver metheramine staining showing segmental duplication of Bowman's capsule (×400); (c) masson trichrome staining showing discrete glomerular glomerular basement membrane and mesangial deposits (×400); (d-f) immunofluorescence staining showing highly positive for immunoglobulin A (IgA), IgG and C3 in a broken, wide and band-like pattern with some coarse granularity areas along capillary loops and mesangium, respectively. Segmental IgA, IgG, and C3 staining were also observed in the mesangium (×400)


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  2. Protein and red blood cells (RBCs) in tubules and vacuolar and granular degeneration as well as multifocality tubular atrophy in tubular epithelial cells;
  3. Interstitial edema and focal fibrosis, and
  4. No obvious changes of artery blood vessels.


Immunofluorescence revealed that the patient had IgA (+), trace IgM, C3 (+++), IgG (+), C4 (–) and C1q (–) in a coarse granular pattern with mesangial and capillary distribution [Figure 1]d-f, and inconspicuous staining for IgM along the glomerular capillary walls in a granular pattern. In addition, the patient showed negative staining for HBsAg and hepatitis B core antigen. The suspected diagnosis was endo-and extracapillary proliferative glomerulonephritis. Ultrastructural studies showed endo-and extracapillary proliferation, high-density deposits of mesangial matrix and GBM.

Considering the proliferative properties of glomerular lesions and M. pneumoniae infection, the patient was given oral azithromycin for 10 days and three methylprednisolone pulses administration at 1 g/1.73 m 2 body surface area/dose followed by oral prednisone at 1 mg/kg/day. In addition, he also received intravenous (iv) cyclophosphamide (CTX) (500 mg/m 2 ) per half month, and 11 times of hemodialysis. [Table 1] summarizes his biological data and treatment.
Table 1: Laboratory data and treatment at presentation and follow-up


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Blood and urine studies showed he had persistent heavy proteinuria and a low total serum protein level. Although his renal function was slightly improved after treatment, his serum creatinine level remained high (291 μmol/l). One month after admission, his proteinuria was 1.62 g/24 h, blood urea was 14.7 mmol/l, serum creatinine was 235 μmol/l and serum complement C3 returned to normal. He was discharged with no edema and no need for hemopurification. After 1-month, he was still treated with oral prednisone at 1 mg/kg/day and iv CTX at 500 mg/m 2 every half month. At the 6 th month of prednisone and CTX treatment, his renal function was normal, and proteinuria remained stable at around 0.28 g/24 h. CTX treatment was then stopped and oral prednisone was tapered to maintenance dose of 0.3 mg/(kg.day).


   Discussion Top


The patient's clinical presentation was compatible with acute postinfectious glomerulonephritis (AGN), showing manifestation of gross hematuria, proteinuria, and renal insufficiency after upper respiratory infection. AGN is usually caused by group A beta-hemolytic Streptococcus but can be caused by other infections such as virus, mycoplasma, and parasite. Most AGN patients can recover in a short period. However, the patient reported here had abnormal renal function. Further PCR analyses indicated that he was infected with M. pneumoniae. Although his ASO was in the normal range, the serum C3 at poststreptococcal glomerulonephritis was decreased. And the renal biopsy results proved that he had postinfectious glomerulonephritis with manifestation of endothelial cell proliferation. The diagnosis of AGN in our case was supported by the sudden onset gross hematuria, proteinuria, renal biopsy results as well as RBC casts that confirmed that hematuria was glomerular originated.

Acute postinfectious glomerulonephritis caused by M. pneumoniae is rare and often occurred in children, [3] barely in adults. Renal biopsy of these patients has revealed type 1 and type 2 MPGN, endocapillary proliferative glomerulonephritis and minimal change disease in children [3] and crescentic glomerulonephritis in adults. [4],[5],[6] In addition, animal model indicated that M. pneumoniae infection could induce IgA nephropathy. [7]

The following diseases were considered in the diagnosis procedure but eventually were excluded by comparing and analyzing the clinical presentation and renal pathology:

  1. Poststreptococal glomerulonephritis. Although the clinical presentation of our patient was compatible with poststreptococal glomerulonephritis, the patient had normal ASO and showed no glomerular inflammatory cells infiltration in renal pathological examination and no hump-like electron-dense deposits in the subepithelium in ultrastructural studies;
  2. IgA nephropathy. IgA nephropathy is tended to occur in children and young males. Patients with IgA nephropathy often have mesangial cells proliferation and mesangial matrix expansion, but not endothelial cell proliferation in renal pathological examination, and IgA, not C3 and others as the main immune complex deposition in mesangial matrix, which were not compatible with the renal pathology of our patient;
  3. Crescentic glomerulonephritis. There are three types of crescentic glomerulonephritis, namely anti-GBM (+), immunecomplex type, and ANCA (+). Our patient was negative to anti-GBM and ANCA and had crescents in less than half of the glomeruli (9/20) in renal pathological examination;
  4. C3 glomerulonephritis. Patients with C3 glomerulonephritis often had subendothelial and/or mesangial electron-dense deposits, and isolated glomerular C3 deposits, but not Ig or C1q deposits in renal pathological examination. [8],[9] However, our patient had not only C3 deposits but also IgA and IgG deposits.


Currently, no unified treatments have been proved by evidence-based medicine for patients with M. pneumoniae-induced acute postinfectious glomerulonephritis. The outcomes for patients who received glucocorticoid and/or immunosuppressor are also not the same. In our case, the patient received hemodialysis after his serum creatinine exceeded 5 mg/dl. In addition, although the patient was negative to ANCA and anti-GBM, antibody, he was given glucocorticoid and CTX treatment after the renal biopsy revealed that he had endothelial cell proliferation and a large number of crescents. Eventually, he regained normal renal function.


   Conclusion Top


Glucocorticoid and CTX treatment of our patient achieved good short-term renal prognosis. The patient needs to be further followed-up to evaluate the long-term outcome of the treatment. Similar to other cases of postinfectious crescentic glomerulonephritis, because of lacking clear treatment guidelines, the severity of the histopathological findings remains the most important factor in determining the intensity of the glucocorticoid and immunosuppressive treatment.

 
   References Top

1.
Kanjanabuch T, Kittikowit W, Eiam-Ong S. An update on acute postinfectious glomerulonephritis worldwide. Nat Rev Nephrol 2009;5:259-69.  Back to cited text no. 1
    
2.
Saïd MH, Layani MP, Colon S, Faraj G, Glastre C, Cochat P. Mycoplasma pneumoniae-associated nephritis in children. Pediatr Nephrol 1999;13:39-44.  Back to cited text no. 2
    
3.
Siomou E, Kollios KD, Papadimitriou P, Kostoula A, Papadopoulou ZL. Acute nephritis and respiratory tract infection caused by Mycoplasma pneumoniae: Case report and review of the literature. Pediatr Infect Dis J 2003;22:1103-6.  Back to cited text no. 3
    
4.
Adra AL, Vigue MG, Dalla Vale F, Ichay L, Raynaud P, Mariani A, et al. Favorable outcome in a case of Mycoplasma pneumoniae-associated crescentic glomerulonephritis. Pediatr Nephrol 2010;25:1765-9.  Back to cited text no. 4
    
5.
Takato H, Yasui M, Waseda Y, Sakai N, Wada T, Fujimura M. A case of microscopic polyangiitis following mycoplasma infection in a patient with MPO-ANCA positive pulmonary fibrosis. Allergol Int 2011;60:93-6.  Back to cited text no. 5
    
6.
Chen AC, Chen CM, Chang HR, Yeo KJ, Tsao SM, Hsiao PC, et al. Complicated acute motor axonal neuropathy with delayed acute respiratory distress syndrome and rapidly progressive glomerulonephritis: A case report. Acta Neurol Taiwan 2013;22:26-31.  Back to cited text no. 6
    
7.
Jiang X, Lv YQ, Zhang JN, Shi YL, Xu FF. Mycoplasma penetrans infection is a potential cause of immunoglobulin A nephropathy: A new animal model. J Nephrol 2013;26:470-5.  Back to cited text no. 7
    
8.
Fakhouri F, Frémeaux-Bacchi V, Noël LH, Cook HT, Pickering MC. C3 glomerulopathy: A new classification. Nat Rev Nephrol 2010;6:494-9.  Back to cited text no. 8
    
9.
Sethi S, Fervenza FC, Zh ang Y, Zand L, Vrana JA, Nasr SH, et al. C3 glomerulonephritis: Clinicopathological findings, complement abnormalities, glomerular proteomic profile, treatment, and follow-up. Kidney Int 2012;82:465-73.  Back to cited text no. 9
    

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Correspondence Address:
Dr. Huiming Wang
Division of Nephrology, Renmin Hospital, Wuhan University, 238 Jiefang Rd, Wuhan, Hubei 430060
China
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Source of Support: This work was supported by grants from the National Science Foundation of China (81370800 to H.Wang.) and the Fundamental Reaserch Funds for the central Universities (2042014kf0093 to X.Chen), Conflict of Interest: The authors declare that they have no competing interests. The authors alone are responsible for the content and writing of the paper.


DOI: 10.4103/0377-4929.162907

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