RENAL DATA FROM ASIA - AFRICA
|Year : 2015 | Volume
| Issue : 5 | Page : 1057-1063
|Spectrum of IgA nephropathy in a single center
Uttara Das1, Kaligotla Venkata Dakshinamurty1, Aruna Prayaga2, Megha Uppin2
1 Department of Nephrology, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad, Andhra Pradesh, India
2 Department of Pathology, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad, Andhra Pradesh, India
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|Date of Web Publication||7-Sep-2015|
| Abstract|| |
Immunoglobulin A (IgA) nephropathy (IgAN) is the most common biopsy-proven primary glomerular disease in the world and a major contributor to the worldwide burden of endstage renal failure, with a wide geographical variation. To determine the incidence, clinical profile and histological pattern of IgAN in our institute, we reviewed all the patients who had native kidney biopsies with the diagnosis of primary IgAN during the period from 1998 to 2009 in the context of the clinical features. A total of 116 patients with IgAN were finally analyzed; 85 (73%) of the patients were male, the mean age of the patients was 29.2 ± 12.2 (range 10-70) years and the mean duration of disease was 10.4 ± 18.7 months (median: 2 months). Hypertension was present in 74 (63.2%) cases. Gross hematuria was rare. The most common clinical presentation was nephrotic syndrome, followed by chronic renal failure. The mean proteinuria level was 2.5 ± 2.3 g/day (median: 1.7 g/day) and the mean serum creatinine level was 3.04 ± 3.3 mg/dL (median:1.7 mg/dL). The morphological sub-classification (Haas): Class I was the most common (44.4%), followed by class V (23%). IgA co-deposition with C3 and lambda was the most common finding in the immunofluorescence study. The glomerular filtration rate decreased with advanced histological damage. The incidence of IgAN was 7.5%, which is lower as compared with studies from elsewhere. IgAN in our population had a more severe clinical presentation.
|How to cite this article:|
Das U, Dakshinamurty KV, Prayaga A, Uppin M. Spectrum of IgA nephropathy in a single center. Saudi J Kidney Dis Transpl 2015;26:1057-63
|How to cite this URL:|
Das U, Dakshinamurty KV, Prayaga A, Uppin M. Spectrum of IgA nephropathy in a single center. Saudi J Kidney Dis Transpl [serial online] 2015 [cited 2020 May 31];26:1057-63. Available from: http://www.sjkdt.org/text.asp?2015/26/5/1057/164612
| Introduction|| |
Primary immunoglobulin A (IgA) nephropathy (IGAN) is defined as the presence of IgAdominant glomerular deposition in the absence of systemic or other non-renal diseases. It is the most common biopsy-proven primary glomerular disease in the world. ,
There is a wide geographical variation existing around the globe, with incidence varying from 2-52%. In some countries such as Japan, China, Singapore, Hong Kong and Australia, the statistics show that nearly half of the biopsy-proven primary glomerular disease is IgAN. ,,,, In the European countries, IgAN accounts for 10-20% of the total kidney biopsies.  In the United States, this disease is common in certain areas.  The incidence is dependent, to a large extent, on variations in the policies of renal biopsy among different countries. 
Similarly, clinical features also vary from mild to severe forms. The most common presentations include synpharyngitic macroscopic hematuria, microscopic hematuria with proteinuria and hypertension and chronic renal failure. The relatively rare presentations include malignant hypertension, acute nephritic syndrome, acute renal failure and nephrotic syndrome. 
Observations show high diversity on light microscopic features ranging widely from minimal histological lesions to severe diffuse proliferative lesions.
IgAN used to be considered benign in the classic descriptions. However, in India, it is not well characterized. Very few documented studies are available about this disease in India so far. ,,,,,,, Results from these studies prove that IgAN in India probably has a severe form of renal involvement.
The aim of our study was to estimate the incidence of IGAN in our institute and the spectrum of its clinical presentation besides the correlation with the histopathological classification.
| Materials and Methods|| |
A total of 1708 renal biopsies were analyzed retrospectively from 1998 to 2009; 148 cases were excluded due to incomplete data or inadequate biopsies. Of the remaining 1560 biopsies, IgAN was diagnosed in 116 cases. Patients' data were collected documenting age, sex, duration of disease, clinical presentation, blood pressure, serum creatinine, 24-h urine protein, urinalysis, serology, virology at the time of biopsy from biopsy reports, requisition forms and discharge summery records. Considering the mode of presentation and laboratory findings, the clinical syndrome was classified into nephrotic syndrome (NS), nephritic syndrome, rapidly progressive renal failure, acute kidney injury, chronic renal failure and abnormal urinalysis.
Diagnosis of IgAN was based on immunofluorescence microscopy showing mesangial IgA deposition as the predominant or codominant immunoglobin and on the lack of clinical or laboratory evidence of systemic lupus erythematosus, Henoch-Schonlein purpura or liver cirrhosis. 
Two separate cores of renal tissue were obtained for histological evaluations. Automated biopsy guns were used for kidney biopsy to obtain the tissue cores. Analysis included light microscopy (LM) and immunofluorescence (IF) study. However, electron microscopy (EM) was not performed as this facility was not available. For LM, the biopsy specimens were fixed in 10% buffered formalin, embedded in paraffin and cut into 4-micron thickness and prepared by technicians of our institute. Three sections were stained with hematoxylin and eosin, one with periodic acid-Schiff, one with Masson's trichrome and one with Jones silver methanamine. Special stains were used when warranted. Slides were examined by the renal pathologist of our institute. The IF study was performed on the frozen sections using polyclonal antisera (FITC-conjugated Rabbit Antihuman Antisera manufactured by DAKO from Denmark) against human IgG, IgM, IgA, C3, C1q and kappa and lambda light chains.
The LM findings were categorized according to the classification described by Haas et al which is as follows: 
Subclass I: Minimal histological lesion. The glomeruli show no more than a minimal increase in mesengial cellularity without segmental glomerulosclerosis, necrosis or crescent.
Subclass II: Focal and segmental glomerulosclerosis without active cellular proliferation.
Subclass III: Focal proliferation of glomerulonephritis.
Subclass IV: Diffuse proliferation of glomerulonephritis.
Subclass V: ≥ 40% globally sclerotic glomeruli and/or ≥40% tubular atrophy or loss in the cortex was studied from the periodic acid-Schiff-stained sections.
We have not used the recent Oxford classification as ours is a retrospective study. Estimated glomerular filtration rate (eGFR) was calculated in all the study patients by using the Modification of Diet in Renal Disease formula.
The following definitions were used 
- NS: NS was defined as proteinuria >3.5 g/day/1.73 m 2 body surface area with edema and/or hypoalbuminemia (serum albumin <3.5 g/dL), without AKI, with or without hematuria.
- Asymptomatic urinary proteinuria (AUP): Proteinuria without NS was defined as 0.5-1 g/day. All patients in this group were without significant decline in renal function.
- Significant proteinuria: Proteinuria between >1 and <3.5 g/day.
- Hematuria: Microscopic hematuria was defined as >5 erythrocytes/high-power field on microscopic examination of the urine without significant decline in renal function.
- Acute kidney injury: Abrupt onset of failure of renal function that results in retention of nitrogenous waste products.
- Chronic renal failure: End result of a variety of progressive/irreversible renal diseases, accompanied by uremia when elevated serum creatinine (>1.5 mg/dL) persisted for <6 months.
- Acute nephritic syndrome: Defined as hematuria, red cell cast, hypertension, oliguria, edema, proteinuria <3 g/day and reduced GFR of abrupt onset.
- Rapidly progressive renal failure: Defined as renal failure over days/weeks, proteinuria usually <3 g/day with hematuria, red cell cast, blood pressure often normal, may have other features of vasculitis. Hypertension was considered when blood pressure was >140/90 mm Hg.
- Duration of disease: Duration from the onset of signs and symptoms to the date of kidney biopsy.
| Statistical analysis|| |
Simple descriptive statistics such as median and mean ± SD were used for variables such as age, clinical and laboratory features. Percentage is used for categorical data. Graphs were generated with Microsoft excel 2007.
| Results|| |
The incidence of IgAN was 7.5%. Eightyfive patients were male and the mean age of the patients was 29.2 ± 12.2 (range 10-70) years. The mean duration of the disease was 10.4 ± 18.7 months, with a median of two months. The majority of patients (46.8%) were diagnosed within one month of the onset of symptoms; 24.1% in <6 months, 14% cases in 6-12 months and 12% cases after 12 months. The most common clinical presentation and indication for renal biopsy was NS, followed by chronic renal failure (CRF) [Figure 1]. Hypertension was present in 74 (63.2%) cases. The mean proteinuria was 2.5 ± 2.3 g/day, with a median of 1.7 g/day (range 0.034-11.6 g/day). Nephrotic range proteinuria was seen in 25.3% of the cases, significant proteinuria was observed in 41.4% of the cases, AUP was seen in 27.3% of the cases and 6% cases had <200 mg/day proteinuria.
The mean serum creatinine was 3.04 ± 3.3 mg/dL (range 0.4-20 mg/dL), with a median of 1.7 mg/dL. Severe renal insufficiency (RI) (GFR <30 mL/min) was observed in 30% of the cases, moderate RI (30-59 mL/min) in 26.5% of the cases, mild RI (60-89 mL/min) in 23.9% of the cases and normal (≥ 90 mL/ min) in 19.5% of the cases.
The morphological patterns of IgAN as per the Haas sub classification are shown in [Figure 2]. Class 1 (mesangial proliferative glomerular nephritis and minimal change disease) was the most common histological finding, followed by class V; class III was the least common. Cresentic glomerulonephritis was observed in only 6% of the cases.
|Figure 2: The percentage of patients with IgA nephropathy according to the Haas Histological Classification.|
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The patterns of immune deposition in combination are shown in [Figure 3]. IgA co-deposition with C3 and lambda was the most common finding. C1q co-deposition was very rare. Exclusive IgA without any co-deposition was observed only in 20 (17%) cases. In the range of immune deposits, IgA was present in all the cases (100%), followed by C3 in 50.9% of the cases, lambda in 30.2% of the cases, kappa in 20.7% of the cases, IgM in 13.8% of the cases and IgG in 13.8% of the cases.
|Figure 3: Pattern of immune deposition in combination in patients with IgA nephropathy.|
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The GFR dropped with advanced damage and progression of the disease. Significant proteinuria was observed in all the classes; however, nephrotic-range proteinuria was common in class I and class V. Gross hematuria was rare. Rapidly progressive renal failure (RPRF) and CRF were common presenting syndromes in class IV and class V, respectively [Table 1].
| Discussion|| |
The low incidence of IgAN in our study is comparable with other reported series from India and North America, but sharply contrasts with a high incidence in other Asian and Southern European studies. ,,,,,,,,,,, In our study, the primary indications for renal biopsy were NS (30%) and CRF (18%). Very few patients had abnormal urinalysis. Therefore, the actual incidence of IgAN may be high if we prospectively look for proteinuria in school-age children as the study was carried out in Japan. 
There are few unique features in our study as well as other Indian studies where NS was noted to be the most common clinical presentation. However, it accounts for only 5% of all IgAN worldwide. ,,,,,,,,, Similarly hypertension and renal insufficiency were also very common at the time of diagnosis in our IgAN patients. This is in agreement with a study from the USA by Donadio et al, where they observed 47% hypertension, 59% renal insufficiency and 76% significant proteinuria at the time of renal biopsy.  In contrast, these findings were rare in other parts of the world. ,,,,,
The most common ages at presentation in our study were the 2 nd and 3 rd decades of life, with a male predominance, which correlates with almost all studies worldwide except some south Asian countries, where they reported a female predominance. ,,,
Recurrent microscopic/macroscopic hematuria with mild proteinuria were typical presentations in most of the Asian and European studies. ,,,,, The most common clinical feature at the time of biopsy in our as well as other Indian studies is the nephrotic range proteinuria and usually associated with hypertension and renal insufficiency. Macroscopic hematuria is very rare. ,,,,,,, Such severity has been reported occasionally in other studies. ,,,,,,,,,
Most of the studies on progression and outcome from India also reported a rapid progression to end-stage renal disease. , This severe nature of clinical presentation can be explained by the fact that we do not have a proper policy for early detection of urinary abnormality to detect IgAN at early stage and those patients with predictably more severe clinical scenarios actually come to our institution. Our study bears close resemblance with the Mayo Clinic study from the USA.  It is also noted that the NS was also observed as the most common clinical presentation in Thailand and Saudi Arabia. ,
A wide range of pathological patterns were observed in the `renal biopsies-a finding which is comparable with other studies from India and elsewhere. ,,,,,,,,,,,,,,,,,,, A number of histological grading systems were described. We have chosen Haas classification for its simplicity. The most common histological finding in our study was class I followed by class V, however, the least common was the class III. Almost in all studies class I was the most common finding except in Japan, where diffuse proliferative IgAN was reported as the most common feature.  Few recent publications from India showed class V as the most common. , When compared with studies reported from elsewhere, focal and segmental glomerulosclerosis is another common finding in a recent Indian report.  The current and other studies from India also observe a high incidence of cresentic glomerulonephritis, which is rarely observed in reported studies elsewhere.
Exclusive IgA deposits without other codeposits is a rare finding and is observed in less than a quarter of patients in all the reported studies around the globe, including ours. ,,,,,,,,,,,,,,,,,, IgA with C3 is the most common finding in the present series, which is comparable with the other Indian studies. ,,,, C1q and full house are the rarest findings. There is not much difference among other series with regard to the IF findings. ,,,,,,,,,,,,,,,,,,, Weak deposition of C3, IgG and IgM were observed in various combinations.
From our results, it is obvious that there is no difference in the mean age of patients at presentation, duration of the disease and the gender among the sub-classes. NS is common in classes I, IV and V, whereas RPRF is most common in class IV IgAN and CRF are common in class V. In general, the glomerular changes correlated well with the clinical parameters of renal functions in most of the reported series. ,,,,,,,,,,,,,, Studies from Taiwan and China also showed that class IV and class V pathological changes were associated with high levels of serum creatinine, low frequency of gross hematuria and high frequency of hypertension. ,
The data analyzed from the present study showed severe clinical features at presentation. Recent studies from our country are in agreement with the existence of aggressive clinical features and advanced histological changes at presentation. ,,, This difference encountered in Indian studies may be influenced by two factors: (a) the absence of urinalysis screening program in the schools of India and (b) a different policy for kidney biopsy.
We conclude that our study, as all reported studies from India, revealed severe clinical presentation of IgAN characterized by nephrotic-range proteinuria, hypertension, renal insufficiency and advanced histological stages. Studies about prophylactic examination for urinary abnormality in children and adolescents to evaluate its impact on the outcome of IgAN patients are warranted.
Conflict of interest: None
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Department of Nephrology, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad 500 082, Andhra Pradesh
[Figure 1], [Figure 2], [Figure 3]
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