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 ~  Abstract
 ~ Introduction
 ~ Case Report
 ~ Discussion
 ~  References
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  Table of Contents  
CASE REPORT
Year : 2019  |  Volume : 37  |  Issue : 4  |  Page : 587-589
 

A rare association of Mycobacterium tuberculosis infection of kidney and urinary tract with immunoglobulin A nephropathy


1 Department of Pathology, Madras Medical Mission, Chennai, Tamil Nadu, India
2 Department of Nephrology, Madras Medical Mission, Chennai, Tamil Nadu, India
3 Department of Urology, Madras Medical Mission, Chennai, Tamil Nadu, India
4 Department of Microbiology, Madras Medical Mission, Chennai, Tamil Nadu, India

Date of Submission24-Jan-2020
Date of Acceptance30-Jan-2020
Date of Web Publication18-May-2020

Correspondence Address:
Georgi Abraham
Department of Nephrology, Madras Medical Mission, Chennai - 600 037, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijmm.IJMM_19_482

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 ~ Abstract 


Mycobacterium tuberculosis(MTB)-related secondary immunoglobulin A (IgA) nephropathy is reported in a 72-year-old male patient. The patient was diagnosed to have MTB infection of the kidney and genitourinary tract which was diagnosed by the demonstration of the organism by GeneXpert Ultra and culture. Concurrent kidney biopsy showed IgA nephropathy. The patient responded to urethral double-J stenting and four-drug antituberculous therapy with improvement of kidney function and resolution of MTB. IgA nephropathy can present as primary glomerulonephritis or secondary to MTB infection.


Keywords: Genitourinary tuberculosis, immunoglobulin A nephropathy, obstructive uropathy


How to cite this article:
Pradeep I, Anupama SH, Koshy P, Kurien A, Rohit A, Mathew M, Parthasarathy R, Abraham G. A rare association of Mycobacterium tuberculosis infection of kidney and urinary tract with immunoglobulin A nephropathy. Indian J Med Microbiol 2019;37:587-9

How to cite this URL:
Pradeep I, Anupama SH, Koshy P, Kurien A, Rohit A, Mathew M, Parthasarathy R, Abraham G. A rare association of Mycobacterium tuberculosis infection of kidney and urinary tract with immunoglobulin A nephropathy. Indian J Med Microbiol [serial online] 2019 [cited 2020 May 27];37:587-9. Available from: http://www.ijmm.org/text.asp?2019/37/4/587/284518





 ~ Introduction Top


India which is the second most populous country accounts for 25% of the global burden of Mycobacterium tuberculosis (MTB) infection.[1] In a study from the United Kingdom, genitourinary MTB accounts for 5% of cases of non-pulmonary tuberculosis (TB) in ethnic minorities, mostly those from the Indian subcontinent.[2] Chronic kidney disease (CKD) is an emerging health-care burden in India.[3] Although diabetic nephropathy is the major cause of CKD, immunoglobulin A (IgA) glomerulonephritis is the most common biopsy-proven glomerular disease.[4] The most common pathological diagnosis of TB-associated glomerulonephritis is IgA nephropathy (IgAN). Due to its atypical presentation, the diagnosis of TB-associated IgAN is challenging.[4] Primary MTB in IgA nephropathy (IgAN) as a leading cause of CKD in the Asia-Pacific region is attributed to differences in geographic prevalence of disease-specific susceptibility genes and environmental factors including infections.[5]

The pathogenesis of IgAN is a 'multi-hit' process with increased production of galactose- deficient IgA1 and subsequent antibody and immune complex formation which thereby deposit in the mesangium producing abnormal mucosal response and glomerular injury.[6]In lieu of the above findings, screening for infectious aetiology is mandatory in the clinical settings of the diagnosis of IgAN. Herein, we present a case of genitourinary MTB infection-associated IgAN with atypical clinical presentation. There has been no previous reports of TB-associated IgAN from India.


 ~ Case Report Top


A male doctor aged 72 years, known hypertensive with previous history of stroke and kidney function impairment, presented with dysuria and fever off and on for 1 month. Physical examination was unremarkable with blood pressure (BP) 140/76 mmHg. A routine chest X-ray did not show evidence of pulmonary TB. Routine urine examination showed trace albuminuria 1+ with leucocyturia and microscopic haematuria. Serum creatinine was 2.21 mg/dL (reference range: 0.6–1 mg/dl). Serology for hepatitis B and C was negative. Ultrasound followed by a computed tomography of kidneys, ureters and bladder imaging showed left-sided hydronephrosis, hydroureter and irregular bladder wall thickening suggestive of obstructive uropathy [Figure 1]. Cystoscopy showed thickened and oedematous trigone and lateral wall. While doing the cystoscopy, a right-sided percutaneous kidney biopsy was performed. Urine was collected from the left ureter and a double-J (DJ) stent was placed. Kidney biopsy showed mesangioproliferative glomerulonephritis with granular mesangial IgA deposition (M1E0S0T0-C0). Bladder biopsy from trigone and left ureteric orifice showed necrotising granulomatous inflammation [Figure 2]. Ziehl–Neelsen stain and Auramine O stain of urine from the left kidney did not show acid-fast bacilli (AFB). GeneXpert ultra on urine specimen for MTB was positive with no rifampicin resistance. Urine AFB culture was positive for MTB after 28 days of incubation. He was initiated on four-drug antituberculous therapy (ATT) with rifampicin 600 mg, isoniazid 300 mg, pyrazinamide 1500 mg and levofloxacin 500 mg with Vitamin B6 supplementation. When on ATT, he developed severe drug-induced liver toxicity, which prompted us to discontinue rifampicin, isoniazid and pyrazinamide. He was followed up with weekly liver functions tests. He had a repeat cystoscopy for replacing the stent. ATT was re-introduced, once the bilirubin level reached 4 mg/dl, with reduced dosage.
Figure 1: Computed tomography images showing left hydronephrosis with dilated pelvicalyceal system and hydroureter. Urinary bladder shows irregular mucosal thickening

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Figure 2:(a and b) Kidney biopsy showing immunoglobulin A nephropathy. (c) Urinary bladder biopsy showing epithelioid cell granuloma (H and E, ×200)

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Three months later, DJ stent was replaced. Follow-up serum creatinine was 1.54 mg/dL with urine albumin of 1+, microscopic haematuria and leucocyturia. Six months later, GeneXpert ultra of urine specimen reported MTB detected (very low) with no rifampicin resistance, whereas urine culture from the left kidney for MTB was negative after 6 weeks of incubation.

The patient continues on low-dose three-drug ATT regimen, and this will be continued for a total of 18 months. A repeat kidney biopsy is yet to be performed. He is not on any specific therapy for IgAN, except BP control with diet and antihypertensive medication.


 ~ Discussion Top


In India, with high prevalence of MTB infection, the probability of kidney disease secondary to MTB-related IgAN is unknown. The modes of presentation of IgAN are either as nephrotic syndrome, kidney dysfunction or haematuria. In our patient, the diagnosis was made based on urine findings and histology showing M1E0S0T0-C0, which is a milder form of the disease. The renal survival rate will be good in our patient.[7] A study by Hitoshi Suzuki has underlined the presence of galactose-deficient IgA1 (Gd-IgA1) and Gd-IgA1-specific antibodies as potential markers for early detection and assessment of disease progression in IgAN.[8]

Despite the prevalence of 2 million cases of MTB in India, there is a scarcity of knowledge on the genetic diversity and drug resistance determinants. This patient responded to the first-line drugs suggesting the absence of resistance. Genitourinary MTB diagnosis is a complex challenge as the number of bacilli excreted in the urine is sparse and varies from time to time. The recommendations are the suspected patient should submit first morning sample of the whole voided urine. The number of samples could be as high as ten. A study by Jean-Laurent Casanova analysed data from across the world to discover that individuals possessing two copies of a specific variation to the gene encoding the enzyme TYK2 are at a higher predisposition to develop TB. This study also reported two gene mutations leading to deficiency of the receptor for interleukin (IL-12) and IL-23.[9] Genitourinary TB is one of the most common manifestations of extrapulmonary TB. MTB complex harbours more genetic diversity which has implications in immunogenicity and virulence.[10] There has been a study by Pang et al. that deems GeneXpert superior in the diagnosis of genitourinary TB over culture of urine.[11]

In our patient, the kidney biopsy, cystoscopic findings and urine culture from the left ureter cumulatively confirmed the diagnosis of MTB-associated IgAN. The IgAN could also be a chance association in this patient. Renal TB is generally characterised by weight loss, fever and loss of appetite, flank pain and urinary symptoms such as increase in frequency and urgency. However, in our patient with lack of classical symptoms, the diagnosis and management by multidisciplinary approach yielded a favourable response in terms of improving the kidney function. The hepatotoxicity in this elderly patient calls for close monitoring of liver functions and kidney functions to reduce treatment-related morbidity and mortality. As GeneXpert is a DNA-based polymerase chain reaction, the presence of dead bacilli may show false positivity and hence, urine culture for MTB is the gold standard for success with ATT as seen in our case. Hence, this test can be used for diagnostic purposes but not for proof of cure. The evolution and response to treatment with improvement of glomerular filtration rate is a reflection of the remission of MTB [Figure 3]. The secondary IgAN with concurrent TB cure should lead to IgAN remission. However, we will repeat a kidney biopsy, later on, to confirm this association.
Figure 3: Graph showing timeline of disease evolution. MTB: Mycobacterium tuberculosis, ATT: Antituberculosis therapy, AFB: Acid-fast bacilli

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Our report emphasises the need to perform a kidney biopsy to rule out the presence of secondary glomerulonephritis including IgAN in patients with genitourinary TB as the prevalence of MTB infection is relatively high in India.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published, and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 ~ References Top

1.
World Health Organization. Global Tuberculosis Report 2016. Geneva, Switzerland: World Health Organization; 2016.  Back to cited text no. 1
    
2.
Grange JM, Yates MD, Ormerod LP. Factors determining ethnic differences in the incidence of bacteriologically confirmed genitourinary tuberculosis in South East England. J Infect 1995;30:37-40.  Back to cited text no. 2
    
3.
Rajapurkar MM, John GT, Kirpalani AL, Abraham G, Agarwal SK, Almeida AF, et al. What do we know about chronic kidney disease in India:First report of the Indian CKD registry. BMC Nephrol 2012;13:10.  Back to cited text no. 3
    
4.
Wang Y, Tao Y. Tuberculosis-associated IgA nephropathy. J Int Med Res 2018;46:2549-57.  Back to cited text no. 4
    
5.
Kiryluk K, Li Y, Sanna-Cherchi S, Rohanizadegan M, Suzuki H, Eitner F, et al. Geographic differences in genetic susceptibility to IgA nephropathy: GWAS replication study and geospatial risk analysis. PLoS Genet 2012;8:e1002765.  Back to cited text no. 5
    
6.
Magistroni R, D'Agati VD, Appel GB, Kiryluk K. New developments in the genetics, pathogenesis, and therapy of IgA nephropathy. Kidney Int 2015;88:974-89.  Back to cited text no. 6
    
7.
Alexander S, John GT, Korula A, Vijayakumar TS, David VG, Mohapatra A, et al. Protocol and rationale for the first South Asian 5-year prospective longitudinal observational cohort study and biomarker evaluation investigating the clinical course and risk profile of IgA nephropathy: GRACE IgANI cohort. Wellcome Open Res 2018;3:91.  Back to cited text no. 7
    
8.
Suzuki H. Biomarkers for IgA nephropathy on the basis of multi-hit pathogenesis. Clin Exp Nephrol 2019;23:26-31.  Back to cited text no. 8
    
9.
Rockefeller University. Genetic mutation responsible for tuberculosis vulnerability. ScienceDaily. ScienceDaily; 02 January, 2019. Available from: http://www.sciencedaily.com/releases/2019/01/190102112835.htm. [Last accessed on 2020 Mar 16].  Back to cited text no. 9
    
10.
Niemann S, Supply P. Diversity and evolution of Mycobacterium tuberculosis: Moving to whole-genome-based approaches. Cold Spring Harb Perspect Med 2014;4:a021188.  Back to cited text no. 10
    
11.
Pang Y, Shang Y, Lu J, Liang Q, Dong L, Li Y, et al. GeneXpert MTB/RIF assay in the diagnosis of urinary tuberculosis from urine specimens. Sci Rep 2017;7:6181.  Back to cited text no. 11
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]



 

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