Membranoproliferative glomerulonephritis and Pott's disease

Abstract

The reports of glomerular lesions of kidney due to tuberculosis are sparse. A 48-year-old gentleman, presented with swelling of feet of 3 months duration. As he had renal impairment, proteinuria and normal-sized kidneys, he was subjected to renal biopsy. The light microscopy and immunofluorescence revealed the diagnosis was membrano-proliferative glomerulonephritis. During hospital stay, the patient complained fever and stiffness at thoracic spine. The MRI of thoraco-lumbo-sacral spine revealed paravertebral abscess at D11–D12. The pus aspirated was positive for Mycobacterium tuberculosis. He was started on anti-tuberculous medication. After 8 weeks of therapy, the serum creatinine was 1.5 mg/dL and 24 h urine protein 250 mg.

Tuberculous involvement in the genitourinary tract is well reported in literature. However, reports of glomerular lesions due to tuberculosis are sparse. We report a patient with an association of tuberculosis and membranoproliferative glomerulonephritis.

A 48-year-old man presented to our institute with complaints of swelling of the feet of 3 months duration. He also had a history of facial puffiness and oliguria. There was no history of haematuria or pyuria. He had no history of passing stones in the urine. There was history of prolonged frothiness of urine. On examination, blood pressure was 140/90 mmHg, he had paedal oedema, and facial puffiness. He had no history of hypertension or diabetes mellitus. Cardiovascular, respiratory and abdomen examinations were unremarkable. Results of other investigations were blood urea, 17.5 mmol/L (50 mg/dL); serum creatinine, 166.2 µmol/L (1.88 mg/dL); serum sodium, 134 mmol/L (134 mEq/L); serum potassium, 3.9 mmol/L (3.9 mEq/L); total serum protein, 60 g/L (6 g/dL); serum albumin, 30 g/L (3 g/dL); haemoglobin, 115 g/dL (11.5 g/dL); 24-h urine protein, 1400 mg; urine albuminm 3+; red blood cells, 10–12/hpf; white blood cells, 10–12/hpf; ultrasound abdomen, right kidney: 11.3 × 5.1 cm and left kidney 10.2 × 4.8 cm, anti dsDNA, C- ANCA and P- ANCA: negative, C 3: 620 (reference range: 970–1576 mg/L), C 4: 79 (reference range: 102–445 mg/L).

As he had renal impairment, proteinuria and normal-sized kidneys, he was subjected to renal biopsy. Three linear grey-white soft tissue bits were reported with 10 glomeruli, all of them showing an increase in mesangial cell proliferation and mesangial matrix. There was lobular accentuation in all of them (Figure 1 and Supplementary Figure 1), a few of them showing neutrophil and lymphocyte infiltration. Tubules showed red blood cell casts. There was focal moderate interstitial lymphomononuclear infiltrate. Blood vessels were unremarkable. Immunofluorescence (IF) showed granular deposition of C3 in the capillary walls, outlining the lobular structure of the glomerulus. In addition IgG was also found, but was of less intensity. IgM, IgA, C1q and light chains were absent. The diagnosis was membranoproliferative glomerulonephritis. During the hospital stay, one day after renal biopsy patient complained fever. Blood and urine cultures were sterile. Chest radiograph was normal. The ultrasound of the abdomen did not reveal any abnormality. After a week he complained of backache and stiffness at the thoracic spine. Examination revealed muscle spasms and rigidity. The radiographs of the thoracolumbar spine were unremarkable, but the MRI of thoracolumbosacral spine revealed paravertebral abscess (osteitis, discitis and abscess) at D11-D12. CT-guided aspiration of the spinal lesion revealed pus. The pus was interspread with many neutrophils few macrophages, lymphocytes and many fine fibrinous threads with entangled leucocytes. Ziehl Neelsen stain showed acid-fast bacilli confirming the diagnosis of Pott's disease (Figure 2). He was started on anti-tuberculous medication. The anti-tuberculous medication included isoniazid (5 mg/kg per day), rifampin (10 mg/kg per day), pyrazinamide (10 mg/kg per day) and ethambutol (5 mg/kg per day). After 2 weeks of the anti-tuberculous medication, there was improvement in pain and stiffness, but the paedal oedema and facial puffiness persisted. During this phase, he was given ramipril (5 mg bds). He was not started on steroids or other immunosuppressants. He was followed up at 2-week intervals. After 8 weeks of therapy, the pain in the back disappeared, as well as the paedal oedema and facial puffiness. The serum creatinine was 1.5 mg/dL and 24-h urine protein 250 mg.

Fig. 1.

H & E ×20, glomerulus with endocapillary proliferation and lobular accentuation.

Fig. 2.

ZN stain 100×, showing acid-fast bacilli.

In our patient, MPGN and tuberculosis of the vertebrae were diagnosed simultaneously. The diagnosis of tuberculosis was indisputable as the acid-fast bacilli were demonstrated in the aspirated pus. Both the tuberculosis and the proteinuria responded to the anti-tuberculous therapy.

There have been five previous reports of membranoproliferative glomerulonephritis associated with tuberculosis [1–5]. These reports are given in Table 1.

Table 1.

Published reports of MPGN in associated with tuberculosis

References	Age in years/sex	Clinical features	Serum creatinine, µmol/L (mg/dL)	Proteinuria (g/day)	Tuberculous lesion	Treatment	Response
[1]a	53/male	Fever, anaemia	556.9 (6.3)	0.95	Urine culture: mycobacterium growth	ATT	Responded
[2]	45/male	Fever, weight loss, hypertension	256.6 (2.9)	1.3	Miliary tuberculosis	ATT and CS	Reponded
[3]	48/male	Haematuria, oedema, hypertension	114.9 (1.3)	8.0	AFB present in sputum	ATT and NSAID	Reponded
[4]	63/male	Nephrotic syndrome	–	3.9	Right upper lobe cavity	ATT	Reponded
[5]	14/female	Fatigue	114.9 (1.3)	–	Lymphadenopthy and lung nodules	Dipirydamole and NSAID	ESRD after ten years

AFB, acid-fast bacilli; ATT, anti-tuberculous therapy; CS, corticosteroids; ESRD, end-stage renal disease.

^aRenal biopsy has revealed dense deposit disease.

The proposed classification of MPGN divides it into immunoglobulin (Ig) mediated and complement mediated. If immunoglobulins are dominant on IF studies, the evaluation should include a work-up for infections, autoimmune disorders and monoclonal gammopathies, including cryoglobulins. If IF studies show predominantly C3 staining, it could be dense-deposit disease or C3 glomerulopathy. In the existing classification, the largest group of conditions associated with MPGN type I has been infections. It has been suggested that type I results from chronic antigenemia and generation of nephritogenic immune complexes (chronic serum sickness-like response). The exact nature of putative antigens in most patients with MPGN type I is unknown. In hepatitis B-induced MPGN type I, the most likely pathogenesis is glomerular mesangial and subendothelial trapping of circulating immune complexes that are at least in part composed of HBV antigens. These HBV-containing immune complexes presumably localize in the glomerulus either as a result of passive trapping of immune complexes or due to local in situ immune complex formation at this site. Other infectious diseases associated with MPGN, such as malaria and schistosomiasis, produce autoantibodies that can cross-react with glomerular constituents such as heparan sulphate. The pathogenesis of MPGN in tuberculosis is not known. Antibody-mediated immunity in Mycobacterium tuberculous infection has been demonstrated at various stages of infection. Such antibodies could also activate complement, which in turn can promote phagocytosis and inflammation. Antibodies can modify the intensity of the inflammatory response, and here their dual nature as pro- and anti-inflammatory molecules is possible. In particular IgM, is likely to have an important role in protection by facilitating an early inflammatory response in tuberculosis. The formation of antigen–antibody complex and stimulation of the classic complement pathway is possible which leads finally to MPGN.

Supplementary data

Supplementary data is available online at http://ndt.oxfordjournals.org.

Conflict of interest statement

None declared.