|Year : 2017 | Volume
| Issue : 5 | Page : 1057-1063
|A “Mini-Epidemic” of anti-glomerular basement membrane disease: Clinical and epidemiological study
Umesh Lingaraj, Shivaprasad Sasivehalli Mallappa, Rajiv Elkal Neminah, Satishkumar Madakala Mohan, Leelavathi Venkatesh, Sreedhara Chikkanayakanahalli Gurusiddaiah, Niranjan Manibally Rachaiah
Department of Nephrology, Institute of Nephrourology, Victoria Hospital Campus, Bengaluru, Karnataka, India
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|Date of Web Publication||21-Sep-2017|
| Abstract|| |
Acute glomerulonephritis due to anti-glomerular basement membrane (anti-GBM) antibody disease is rare, estimated to occur in fewer than one case per million population and accounts for less than 20% of rapidly progressive glomerulonephritis. The prevalence among patients evaluated for potential glomerular disease is lower. It accounts for fewer than 3% of all kidney biopsies done with crescentic glomerulonephritis. Cases of anti-GBM disease occurring in a cluster have rarely been reported. All biopsy proven anti-GBM disease cases were collected from January 2015 to March 2015 at our Institute. All cases were analyzed for demographic and clinical profile, pathological findings, treatment received and for any common environmental antigenic source. A total of 11 new biopsy proven anti-GBM cases were seen within a span of three months. Age group varied from 17–80 years. Seven were males and four were females. All were dialysis dependent at presentation. Seven had active cellular crescents, and four had fibrocellular. Only one patient was a smoker and none had a history of exposure to any forms of hydrocarbons. The peak seen from January 2015 to March 2015 does not correlate with any of seasonal occurrence of infections in southern India. Although there was clustering of cases to southern territories of Karnataka state, no common etiological agents could be identified. No patient had any previous urological surgeries. All patients received methylprednisolone with plasmapheresis 5–7 sessions and cyclophosphamide. All 11 patients were dialysis dependent at the end of three months. We conclude anti-GBM disease cannot be regarded as a rare cause of renal failure and lung hemorrhage. The occurrence of such epidemic within a short period suggests a possible unidentified environmental factor like infection or occupational agents as inciting agents. Identification of such inciting agents could help us in instituting appropriate preventing measures.
|How to cite this article:|
Lingaraj U, Mallappa SS, Neminah RE, Mohan SM, Venkatesh L, Gurusiddaiah SC, Rachaiah NM. A “Mini-Epidemic” of anti-glomerular basement membrane disease: Clinical and epidemiological study. Saudi J Kidney Dis Transpl 2017;28:1057-63
|How to cite this URL:|
Lingaraj U, Mallappa SS, Neminah RE, Mohan SM, Venkatesh L, Gurusiddaiah SC, Rachaiah NM. A “Mini-Epidemic” of anti-glomerular basement membrane disease: Clinical and epidemiological study. Saudi J Kidney Dis Transpl [serial online] 2017 [cited 2019 Oct 24];28:1057-63. Available from: http://www.sjkdt.org/text.asp?2017/28/5/1057/215128
| Introduction|| |
Anti-glomerular basement membrane (Anti-GBM) antibody disease is a disorder in which circulating antibodies are directed against an antigen intrinsic to the GBM, thereby resulting in acute or rapidly progressive glomerulo-nephritis (RPGN) that is typically associated with crescent formation. There are no good data on the population incidence and prevalence. Acute glomerulonephritis due to anti-GBM antibody disease is rare, estimated to occur in fewer than one case per million population. In case series published before the 1980s, anti-GBM antibody disease accounted for less than 20% of cases of RPGN., Early recognition is of paramount importance as it rapidly leads to end-stage renal disease (ESRD). Two parameters which have long been regarded as reliable predictors of adverse outcome: an elevated serum creatinine at presentation or anuria and the percentage of crescents in biopsy specimens.
All age groups are affected, but the peak incidence is in the third decade in young men with a second peak in the sixth and seventh decades affecting men and women equally.,, Lung hemorrhage is more common in younger men, while isolated renal disease is more frequent in elderly with near equal gender distribution.,
There is short-lived production of circulating autoantibodies directed against an antigen intrinsic to the GBM in response to an unknown inciting stimulus. The principal target for the anti-GBM antibodies (which are typically IgG 1 and 3 but sometimes IgA or IgM) is the NC1 domain of the alpha-3 chain of type IV collagen [alpha-3 (IV) chain], one of six genetically distinct gene products found in basement membrane collagen.,
Environmental factors have long been implicated to play a role in triggering the disease. A number of case reports of clusters of patients with anti-GBM disease implicate an infective agent; however, no clear viral association has been identified., A few case reports have found causal relationship linking anti-GBM disease to hydrocarbon exposure, thus implicating occupational exposure as a trigger. Some reports followed lithotripsy, and ureteric obstruction, suggesting that antigen released from a mechanically damaged kidney may initiate disease in susceptible individuals. Regardless of the role of environmental factors in initiating the autoimmune attack, the environment plays a critical role in determining whether anti-GBM antibodies cause lung injury. Pulmonary hemorrhage occurs in nearly all current cigarette smokers, while it is very rare in nonsmokers.
There is increasing evidence that genetic factors affect the susceptibility to anti-GBM antibody disease. Patients with HLA-DR15 and DR4 appear to be at increased risk, while those with DR1 and DR7 are at lesser risk. The association with DR15 has been confirmed in Chinese and Japanese patients. More specific molecular analysis of DRß chains has found that a particular six amino acid motif common to DRw15 and DR4 may confer disease susceptibility. This motif is not seen in DR1 and is uncommon in blacks, who also have a lower incidence of anti-GBM antibody disease.
We are reporting a “Mini-Epidemic” of 11 anti-GBM disease occurring within a short time period of just three months in our tertiary care center with particular review of any possible etiological factors in these cases.
| Methods|| |
Study design, population and setting
Clinical, Epidemiological, and pathological details were prospectively collected and analyzed from January 2015 to March 2015 in a state run tertiary care center after initial observation of occurrence of anti-GBM disease in clusters. Clinical and epidemiological information were obtained directly from the cases with a detailed enquiry into their presenting symptoms, preceding illness and any possible etiological agents like viral illness, occupational exposures including the demographical profiles.
Pathological findings were analyzed using light microscopy and immunofluorescent stains.
Immunofluorescent stains were performed with antibodies against IgG, IgM, IgA, the complement components c3 and c1q, and Kappa and lambda.
| Statistical Analysis|| |
Values are expressed as mean ± standard deviation. Statistical analysis was conducted with Student’s t test.
| Results|| |
A total of 11 cases occurred within a short period of three months from January 2015 to March 2015. Seven were males and four females. The age range was 18 to 80 years (mean = 48 years). Although there was clustering of cases to southern territories of Karnataka. We attributed this to their proximity to our referral center [Figure 1]. No common inciting or etiological agents could be identified. There was no similarity in their occupation, with one patient being painter. Four cases were diagnosed in January and March, with February showing three cases. Three patients had preceding fever which was unexplained and of short duration, one having upper respiratory illness. None of the patients had any previous urological procedures in the past. None of these patients had pulmonary hemorrhage.
|Figure 1: Point prevalence of the cases: Clustering of cases to southern territories of the geographical area.|
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Clinical profile of patients is presented in [Table 1]. Ten patients had serum creatinine more than 5.5 mg/dL, and all were dialysis dependent at presentation. Eight had anuria on admission. One patient had serum creatinine of 1.5 mg/dL with nephrotic range proteinuria and biopsy showed 100% active cellular crescents. Subsequently, he progressed to ESRD in spite of all therapeutic measures. Eight patients received pulse methylprednisolone followed by oral steroids along with cyclophos-phamide and plasmapheresis. Plasmapheresis was given on alternate days for 14 days. None of them recovered, and all reached ESRD. Three were readmitted with infections, two with pulmonary and one with catheter infection. Three patients were not considered for any immunosuppressive therapy in view of their anuric state and dialysis dependency.
On light microscopy, all patients had severe crescentic and necrotizing glomerulonephritis, with crescent formation in more than 50% of glomeruli. Glomerular changes were characterized by segmental or global necrosis of the capillary tufts with disruption of the GBM and Bowman capsule. Intratubular red cell casts were present in all the cases.
| Discussion|| |
In this study, we have an extremely rare occurrence of 11 cases of anti-GBM disease within a short-time period of three months. The usual reported incidence in general population is about 0.5 to 1 case per million per year, which usually considered as a extremely rare disease. Male to female ratio was 1.75:1 with slight male predominance. Mean age was 45 years, range between 17 and 80 years. The most striking is the clustering of cases within a short period, three consecutive months as compared to other months.
The possibility of a seasonal clustered incidence in anti-GBM disease was proposed by some authors. Savage et al in their retrospective analysis of about 71 cases reported a peak incidence of anti-GBM disease in the spring and early summer, which almost similar to our finding. Perez et al described four cases of Goodpasture’s syndrome during winter. However, the same seasonal clustering could not get statistical significance in one of the largest retrospective analysis of anti-GBM diseases by Fischer et al.
There are many reports showing casual linkage between influenza and anti-GBM disease. South India demonstrates a peak in the cooler season, during rains – August onward. The timing of this clustering does not coincide with the influenza peak in South India [Table 2] and [Figure 2], as the peak varies with the altitude and others geographical conditions. Only one of our patients had flu-like illness, but the majority had no features of any preceding viral illness.
Several anecdotal reports have linked anti-GBM disease to hydrocarbon exposure, with review of all cases suggesting a causal link., There have been case reports of anti-GBM disease following lithotripsy,, and ureteric obstruction, suggesting that antigen released from a mechanically damaged kidney may initiate disease in susceptible individuals. None of our patients had occupational exposure to hydrocarbons, nor there was any urolo-gical procedure [Table 1].
Regardless of the role of environmental factors in initiating the autoimmune attack, the environment plays a critical role in determining whether anti-GBM antibodies cause lung injury. Pulmonary hemorrhage occurs in nearly all current cigarette smokers, while it is very rare in nonsmokers. Only one of our patients was a smoker [Table 1]; there was no pulmonary involvement in any of these cases.
It is well known that the prognosis of untreated anti-GBM disease is dismal. One-year patient survival in anti-GBM disease between 75% and 90%. However, renal recovery is less common and depends on renal function at the start of treatment. Several series show that most patients starting treatment with a crea-tinine of less than 500 μmol/L (5.5 mg/dL) will recover renal function, but that recovery is rare in patients with an initial creatinine of more than 500 μmol/L. The patients who presented with creatinine <500 μmol/L had an excellent outcome at one year, with 100% surviving and 95% retaining independent renal function. Of those with a creatinine greater than 500 μmol/L but not requiring dialysis immediately, 83% survived 1 year, and independent renal function was maintained in 82% of survivors. However, the outcome was not as good in dialysis-dependent patients, with 65% surviving 1-year, and only 8% of those survivors retaining independent renal function.
| Conclusion|| |
Anti-GBM disease cannot be regarded as a rare cause of renal failure and lung hemorrhage. With the occurrence of such epidemics within a short period of time, suggest a possible unidentified environmental factor like infection or occupational agents as inciting agents. Identification of possible inciting agents could help us in instituting appropriate preventing measures.
Conflict of interest: None.
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Department of Nephrology, Institute of Nephrourology, Victoria Hospital Campus, Bengaluru, Karnataka
[Figure 1], [Figure 2]
[Table 1], [Table 2]
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