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Granulomatous interstitial nephritis: a chameleon in a globalized world.

Aleckovic-Halilovic M, Nel D, Woywodt A - Clin Kidney J (2015)

View Article: PubMed Central - PubMed

Affiliation: Department of Nephrology, Dialysis and Transplantation , University Clinical Hospital Tuzla , Tuzla , Bosnia and Herzegovina.

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Two articles in this issue deal with granulomatous acute interstitial nephritis (GIN), a rare disorder seen in 0.5–0.9% of native and 0.6% of transplant renal biopsies... Other inflammatory cells, such as natural killer (NK) cells, which produce interferon (INF)-γ, are also involved... Glucocorticosteroids exert their beneficial effect on granulomas by repression of NF-κB-related gene transcription with lymphocyte apoptosis... In reporting tuberculosis as the predominant cause of GIN in their series from India, Agrawal and colleagues provide a worthwhile reminder that things may be very different elsewhere... Sarcoidosis, in an advanced stage, may be characterized by marked interstitial fibrosis, although in the literature varying amounts of fibrosis are seen in many different causes of GIN... Others found the presence of eosinophils not helpful in diagnosing a drug-related aetiology... This is not helped by the fact that tubulitis is a common feature of rejection and interstitial nephritis and differentiating acute interstitial nephritis from rejection in a graft is notoriously difficult... Another aetiology one does not want to miss is surely oxalosis, and biopsies should be examined closely for crystals... Another reason to be meticulous in this regard is the fact that a diagnosis of idiopathic GIN will usually mandate a trial of steroids—in the absence of anti-tuberculous therapy this is unlikely to be of any help if tuberculosis is the cause of GIN... In this issue of CKJ, Agrawal et al. add that multiplex PCR for tubercular DNA is a useful and reliable diagnostic tool for supporting diagnosis of GIN due to tuberculosis, with some previous pessimistic results on PCR most probably being attributable to old specimens... It is difficult to come up with any evidence-based recommendations for treatment of GIN, given that the disease is rare and also heterogenous... In drug-associated GIN, withdrawal of the offending drug may result in rapid recovery of renal function... Across all causes of GIN the renal prognosis appears to be favourable: in one of the largest series so far Joss and co-workers reported that only 1 out of 18 patients required dialysis, although most patients did not recover fully... In Jules Verne's Around the World in 80 Days, Phileas Phogg remarks that he could have shortened the trip (by a meagre 2 days) by not passing through India... However, like Phogg we benefit from the experience from India, in this case the emphasis on infectious causes of GIN.

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Stepwise diagnostic approach to GIN. EBV, Epstein-Barr virus; LAM, lipoarabinomannan antigen.
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SFV092F1: Stepwise diagnostic approach to GIN. EBV, Epstein-Barr virus; LAM, lipoarabinomannan antigen.

Mentions: GIN is rarely expected as a biopsy finding and often comes as a bit of a surprise. At this point the underlying cause will be either obvious or at least likely in a sizeable proportion of patients, i.e. those with known sarcoidosis, tuberculosis or an exposure to medication within a relevant time frame. What to do if at this point the cause is still enigmatic? Based on our experience and our understanding of the literature we would suggest a stepwise (but not dogmatic) approach (Figure 1). Good dialogue with the nephropathologist should be the starting point. No histological pattern is diagnostic of any of the main causes of GIN but, as detailed above, important pointers can be obtained from the number and phenotype of granulomas and the inflammatory infiltrate. Further testing of the biopsy specimen should be discussed at this point. History-taking needs to include a meticulous drug history, and also focus on signs and symptoms of tuberculosis or sarcoidosis. Travel, occupational history and risk factors for HIV infection are also of interest. A thorough clinical examination should include skin, eyes, lymph nodes and genitals. The assessment should be completed by HIV test, chest X-ray, serum calcium, angiotensin converting enzyme (ACE) and ANCA. At this point, the most likely diagnosis will be either drug-associated, sarcoidosis, tuberculosis or it will remain entirely unclear. Drug-induced cases are probably the most straightforward. If sarcoidosis appears likely then the next step should be to liaise with a respiratory physician to establish the diagnosis. In comparison, the situation is much more challenging if tuberculosis is suspected. Good dialogue with the renal pathologist needs to continue and further staining and testing should be guided by local availability and expertise. Another reason to be meticulous in this regard is the fact that a diagnosis of idiopathic GIN will usually mandate a trial of steroids—in the absence of anti-tuberculous therapy this is unlikely to be of any help if tuberculosis is the cause of GIN. A good example of this potentially lethal pitfall is a case described by Walker and co-workers who report a fatal case of disseminated histoplasmosis in a patient with GIN treated with steroids [29]. Histological features may be atypical, especially in patients who are immunocompromised, be it due to HIV infection or as a transplant patient or following chemotherapy. Culture of biopsy specimens is worthwhile, but results may take weeks [21]. It is therefore essential to initiate evaluation for bacterial, mycobacterial, fungal and viral infections as soon as possible to prevent any delay in definitive treatment and to look closely for evidence of tuberculosis elsewhere. More sophisticated tests, such as molecular testing for Mycobacterium tuberculosis, immunohistochemical techniques, enzyme-linked immunosorbent assay tests for mycobacterial antigens in serum or the urine should be used according to local availability or expertise. In this issue of CKJ, Agrawal et al. add that multiplex PCR for tubercular DNA is a useful and reliable diagnostic tool for supporting diagnosis of GIN due to tuberculosis [2], with some previous pessimistic results on PCR most probably being attributable to old specimens [13]. What to do if a case appears truly idiopathic? Going through the list of causes [1, 3] one last time would seem like a good idea, with consideration of re-testing if there is substantial evidence for one of the rarer causes. Vigilance is certainly warranted in that manifestations of underlying disease may well appear later on.Fig. 1.


Granulomatous interstitial nephritis: a chameleon in a globalized world.

Aleckovic-Halilovic M, Nel D, Woywodt A - Clin Kidney J (2015)

Stepwise diagnostic approach to GIN. EBV, Epstein-Barr virus; LAM, lipoarabinomannan antigen.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4581397&req=5

SFV092F1: Stepwise diagnostic approach to GIN. EBV, Epstein-Barr virus; LAM, lipoarabinomannan antigen.
Mentions: GIN is rarely expected as a biopsy finding and often comes as a bit of a surprise. At this point the underlying cause will be either obvious or at least likely in a sizeable proportion of patients, i.e. those with known sarcoidosis, tuberculosis or an exposure to medication within a relevant time frame. What to do if at this point the cause is still enigmatic? Based on our experience and our understanding of the literature we would suggest a stepwise (but not dogmatic) approach (Figure 1). Good dialogue with the nephropathologist should be the starting point. No histological pattern is diagnostic of any of the main causes of GIN but, as detailed above, important pointers can be obtained from the number and phenotype of granulomas and the inflammatory infiltrate. Further testing of the biopsy specimen should be discussed at this point. History-taking needs to include a meticulous drug history, and also focus on signs and symptoms of tuberculosis or sarcoidosis. Travel, occupational history and risk factors for HIV infection are also of interest. A thorough clinical examination should include skin, eyes, lymph nodes and genitals. The assessment should be completed by HIV test, chest X-ray, serum calcium, angiotensin converting enzyme (ACE) and ANCA. At this point, the most likely diagnosis will be either drug-associated, sarcoidosis, tuberculosis or it will remain entirely unclear. Drug-induced cases are probably the most straightforward. If sarcoidosis appears likely then the next step should be to liaise with a respiratory physician to establish the diagnosis. In comparison, the situation is much more challenging if tuberculosis is suspected. Good dialogue with the renal pathologist needs to continue and further staining and testing should be guided by local availability and expertise. Another reason to be meticulous in this regard is the fact that a diagnosis of idiopathic GIN will usually mandate a trial of steroids—in the absence of anti-tuberculous therapy this is unlikely to be of any help if tuberculosis is the cause of GIN. A good example of this potentially lethal pitfall is a case described by Walker and co-workers who report a fatal case of disseminated histoplasmosis in a patient with GIN treated with steroids [29]. Histological features may be atypical, especially in patients who are immunocompromised, be it due to HIV infection or as a transplant patient or following chemotherapy. Culture of biopsy specimens is worthwhile, but results may take weeks [21]. It is therefore essential to initiate evaluation for bacterial, mycobacterial, fungal and viral infections as soon as possible to prevent any delay in definitive treatment and to look closely for evidence of tuberculosis elsewhere. More sophisticated tests, such as molecular testing for Mycobacterium tuberculosis, immunohistochemical techniques, enzyme-linked immunosorbent assay tests for mycobacterial antigens in serum or the urine should be used according to local availability or expertise. In this issue of CKJ, Agrawal et al. add that multiplex PCR for tubercular DNA is a useful and reliable diagnostic tool for supporting diagnosis of GIN due to tuberculosis [2], with some previous pessimistic results on PCR most probably being attributable to old specimens [13]. What to do if a case appears truly idiopathic? Going through the list of causes [1, 3] one last time would seem like a good idea, with consideration of re-testing if there is substantial evidence for one of the rarer causes. Vigilance is certainly warranted in that manifestations of underlying disease may well appear later on.Fig. 1.

View Article: PubMed Central - PubMed

Affiliation: Department of Nephrology, Dialysis and Transplantation , University Clinical Hospital Tuzla , Tuzla , Bosnia and Herzegovina.

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

Two articles in this issue deal with granulomatous acute interstitial nephritis (GIN), a rare disorder seen in 0.5–0.9% of native and 0.6% of transplant renal biopsies... Other inflammatory cells, such as natural killer (NK) cells, which produce interferon (INF)-γ, are also involved... Glucocorticosteroids exert their beneficial effect on granulomas by repression of NF-κB-related gene transcription with lymphocyte apoptosis... In reporting tuberculosis as the predominant cause of GIN in their series from India, Agrawal and colleagues provide a worthwhile reminder that things may be very different elsewhere... Sarcoidosis, in an advanced stage, may be characterized by marked interstitial fibrosis, although in the literature varying amounts of fibrosis are seen in many different causes of GIN... Others found the presence of eosinophils not helpful in diagnosing a drug-related aetiology... This is not helped by the fact that tubulitis is a common feature of rejection and interstitial nephritis and differentiating acute interstitial nephritis from rejection in a graft is notoriously difficult... Another aetiology one does not want to miss is surely oxalosis, and biopsies should be examined closely for crystals... Another reason to be meticulous in this regard is the fact that a diagnosis of idiopathic GIN will usually mandate a trial of steroids—in the absence of anti-tuberculous therapy this is unlikely to be of any help if tuberculosis is the cause of GIN... In this issue of CKJ, Agrawal et al. add that multiplex PCR for tubercular DNA is a useful and reliable diagnostic tool for supporting diagnosis of GIN due to tuberculosis, with some previous pessimistic results on PCR most probably being attributable to old specimens... It is difficult to come up with any evidence-based recommendations for treatment of GIN, given that the disease is rare and also heterogenous... In drug-associated GIN, withdrawal of the offending drug may result in rapid recovery of renal function... Across all causes of GIN the renal prognosis appears to be favourable: in one of the largest series so far Joss and co-workers reported that only 1 out of 18 patients required dialysis, although most patients did not recover fully... In Jules Verne's Around the World in 80 Days, Phileas Phogg remarks that he could have shortened the trip (by a meagre 2 days) by not passing through India... However, like Phogg we benefit from the experience from India, in this case the emphasis on infectious causes of GIN.

No MeSH data available.


Related in: MedlinePlus