| Abstract|| |
Glomerulonephritis (GN) is the most common cause of end-stage renal disease in Nepal. The aim of the present study is to determine the clinical presentation and histological pattern of GN with and without immunofluorescence (IF). It is a retrospective analysis of all GN patients with kidney biopsy at the Bir Hospital from January 2000 to April 2009. The clinical presentation, blood pressure, urine analysis, 24-h urinary protein, biochemistry, hemoglobin, antinuclear antibody, anti-ds DNA, light microscopy (LM) and IF findings of kidney biopsies were computed from hospital records. SPSS package was used for analysis. A total of 398 patients [LM 204 (51%) and LM plus IF 194 (49%] were analyzed. The mean age of the study patients was 28 ± 13.6 years (range 7-74); males comprised 52.8% and females 47.2% of the patients; 51% were between 16 and 30 years of age. The common clinical presentations included nephrotic syndrome (NS), seen in 69% of the patients, followed by acute nephritic syndrome, seen in 14.4% of the patients. Kidney biopsy without IF showed mesangial proliferative GN (MesPGN) in 21.1%, membranoproliferative GN (MPGN) in 18.6%, membranous nephropathy (MN) in 14.2%, minimal change disease (MCD) in 12.3% and focal and segmental glomerulosclerosis (FSGS) in 9.8% of the cases. With IF, MCD was seen in 23.2%, FSGS in 18%, MN in 11.9%, IgA nephropathy in 9.8%, MesPGN in 8.2%, MPGN in 4.1% and crescentic GN in 3.1% of the cases. Lupus nephritis in the cases GN was most common in young adults, with the majority presenting with NS. MCD and FSGS were the most common glomerular lesions; over-diagnosis of MesPGN and MPGN by LM could be due to exclusion of IgA nephropathy.
|How to cite this article:|
Khakurel S, Agrawal R K, Hada R. Pattern of glomerular disease in Nepal: A single-center experience. Saudi J Kidney Dis Transpl 2015;26:833-8
|How to cite this URL:|
Khakurel S, Agrawal R K, Hada R. Pattern of glomerular disease in Nepal: A single-center experience. Saudi J Kidney Dis Transpl [serial online] 2015 [cited 2019 Jun 16];26:833-8. Available from: http://www.sjkdt.org/text.asp?2015/26/4/833/160249
| Introduction|| |
The incidence and prevalence of glomerular diseases vary in different parts of the world. The incidence of various types of primary glomerulonephritis (GN) has been reported to vary between 0.2 and 2.5/100,000/year.  Most countries base the incidence on kidney biopsy performed within the period of evaluation in a given population. The pattern of glomerular diseases also varies throughout the world, with IgA nephropathy being the leading cause worldwide.  Increasing incidence of focal and segmental glomerulosclesosis (FSGS)  and declining incidence of membranoproliferative GN (MPGN),  from 0.7/100,000/year in 1970 to 0.2/100,000/year in 1990, has been noted in recent years. Although glomerular disease is reported as the most common cause of endstage renal disease in Nepal,  its exact incidence and prevalence is not known. Immunofluorescence (IF) evaluation of kidney biopsy has been accessible only since 2004. The pattern of glomerular disease has been analyzed in a previous study, the findings based mainly on light microscopy.  In that study, it was reported that membranous GN (MN) and MPGN were reported as the most common causes of GN. The aim of the present study is to analyze the pattern of glomerular diseases in Nepal, including its clinical features, and compare the biopsy findings with and without IF.
| Materials and Methods|| |
This retrospective analysis of all GN patients and their kidney biopsy findings was performed at the Bir Hospital, from January 2000 to April 2009. Kidney biopsies with inadequate specimen, transplant biopsies and biopsies without GN were excluded.
The demographic pattern, clinical presentation, blood pressure, urine analysis, 24-h urinary protein, biochemistry, hemoglobin, antinuclear antibody (ANA), anti-ds DNA, hepatitis B surface antigen (HbSAg), human immunodeficiency virus (HIV), anti-hepatitis C virus (HCV) antibody and biopsy reports were computed from hospital records.
All kidney biopsies were performed with a shot gun biopsy needle under local anesthesia after ultrasound marking. Initially, all biopsies were studied in the Bir Hospital laboratory with light microscopy (LM) only, stained with hematoxylin-eosin (H&E), periodic acid-Schiff (PAS) and Masson's Trichome (MT) in all and congo red staining in some cases. Since 2004, it became possible to send the biopsy samples to a private laboratory in India with IF facility. The IF panel included IgA, IgG, IgM, C3 and C1q.
The clinical presentation of patients was further analyzed in the IF group; SPSS package was used for analysis. Hypertension was defined as blood pressure ≥ 140/90 mm Hg or use of anti-hypertensive medications. Renal impairment was defined as serum creatinine ≥ 1.5 mg/dL. Glomerulosclerosis, tubular atrophy and tubulo-interstitial changes on kidney biopsy were noted as none (0%), mild (<25%), moderate (25-50%) and severe (>50%).
| Results|| |
A total of 398 patients were analyzed; only LM was used in 204 patients (51%), and both LM and IF were used in 194 patients (49%). The mean age was 28 ± 13.6 years (range 7- 74), with 51% being between 16 and 30 years [Figure 1]; 52.8% were males and 47.2% were females. There was a slight male preponderance, with notable exception being in patients with lupus nephritis (LN), in which 90% of the cases were female. The clinical presentation was nephrotic syndrome (NS) in 69%, nephritic syndrome in 14.4%, acute renal failure in 3.1%, rapidly progressive GN (RPGN) in 3.1%, chronic kidney disease (CKD) in 5.2%, isolated proteinuria ± hematuria in 4.6% and hypertension in 0.5%. Renal impairment was present in 41.2% of the cases, hypertension in 49% and hemoglobin ≤10 g/dL in 20%, at presentation.Analysis of histopathology findings in the group with IF showed minimal change disease (MCD) in 23.2%, FSGS in 18%, MN in 11.9% and IgA nephropathy in 9.8% of the cases, while histopathology without IF showed mesangial proliferative GN (MesPGN) as the predominant glomerular disease, seen in 21.1% of the patients, followed by MPGN in 18.6% and MN in 14.2% of the patients; IgA nephropathy was undiagnosed [Table 1].
|Table 1: Comparison of glomerular histopathology with or without immunofluorescence.|
Click here to view
Further analysis within the IF group showed primary glomerular disease in 142 patients (73.2%) and secondary glomerular disease in 52 patients (26.8%). The etiology of primary GN was MCD in 45 cases (31.6%), FSGS in 35 (24.6%), MN in 22 (15.4%), MesPGN in 15 (10.5%), MPGN in six (4.2%) and IgA nephropathy in 19 cases (13.3%).
LN, seen in 29 patients (54.7%), was the most common cause of secondary GN, with class IV LN seen in 74.5%, class II in 9.8%, class V in 7.8% and class III and VI LN seen in 3.9% of the cases each. ANA was present in all these patients and anti-dsDNA was present in 55.5% of the patients with LN. Infectionassociated GN was present in 18 patients (34.6%), with MesPGN in one case, MPGN in two (recurrent ear infection, 1 and hepatitis B infection, 1), diffuse endocapillary proliferative GN (DPGN) in six and immune complex vasculitis and crescentic GN in eight cases. Three patients had Henoch-Scholein purpura (HSP) nephritis, one had MN related to rheumatoid arthritis and two had amyloidosis. Analysis of primary GN in various age groups [Table 2] revealed that FSGS was the most common glomerular lesion in children up to 15 years, while MCD was the most commonly seen glomerular disease in the age group of 16-45 years. MN was not seen in children, but was the most common GN seen in patients above 45 years of age.
|Table 2: Distribution of primary glomerulonephritis in the various age groups (immunofluorescence only).|
Click here to view
The clinical presentations of various histopathological types of GN with IF were further analyzed [Table 3]. NS (69%) was the most common presentation, followed by nephritic presentation (14.4%).
|Table 3: Clinical presentation of various histological types of glomerulonephritis with immunofluorescence.|
Click here to view
Renal impairment was present in 41.2% of the cases, of whom 31.9% had acute kidney injury (AKI) and 9.3% of the cases had CKD. Pre-renal AKI was the cause of renal impairment in eight cases (17.6%), MCD in nine cases (25.7%), FSGS in one case (4.3%), MN in two cases (12.5%), MesPGN in four cases (13.8%), LN in one case (5.3%) and IgA nephropathy and amyloidosis in one case each (4.3%).
Moderate to severe glomerulosclerosis on biopsy was most marked in IgA nephropathy and MPGN, while tubulo-interstitial nephritis was most marked in LN [Table 4].
|Table 4: Percentage of moderate to severe histological changes seen on kidney biopsy in various glomerular lesions.|
Click here to view
| Discussion|| |
Our study indicates that GN predominantly affected the younger age group population, with almost equal sex distribution, with the most notable exception being LN. The most common GN noted in the age group <15 years was FSGS, which was probably because most steroid-responsive children did not undergo biopsy. MCD remained the most common GN in the age group of 15-45 years, followed by FSGS. The prevalence of MCD in our study was similar to the report from Korea (24.8%),  while a declining incidence of MCD has been reported from India,  China  and Pakistan.  The incidence of FSGS, on the other hand, has been reported to be rising worldwide, including the US.  FSGS was reported to be the most common primary GN (29%) , and the most common cause of NS (39%) among adults in Pakistan. 
MN was uncommon in children, with the prevalence rising after 30 years, and was the most common GN after 45 years. MPGN was present in 4% of the cases with IF, which is similar to a report from India (4.6%).  Biopsy without IF in the present study, and an earlier biopsy series from Nepal,  gave a misleading picture of the prevalence of MPGN of 18.6% and 21.9%, respectively, which could be due to thick sectioning of the biopsy specimen in the local laboratory. MesPGN constituted 8.2% of all biopsies with IF in contrast to 21% without IF, probably because all cases of IgA nephropathy were included in the latter. A high prevalence of MesPGN has been reported from Bangladesh  and China.  IgA nephropathy, which is the most common GN worldwide, was noted in 9.8% of all biopsies and 13.3% of all primary glomerular diseases. A high prevalence of IgA nephropathy (47% and 45% of all primary glomerular diseases) has been reported from countries like Japan  and China,  respectively. It is the most common GN among adults and also the most common GN causing end-stage renal disease in Australia.  A prevalence of IgA nephropathy of 7- 14% has been reported from South Asian countries like India , and Pakistan,  while a lower prevalence (3.4%) has been reported from Bangladesh.  The actual incidence of IgA nephropathy is probably higher, considering the biopsy practice and the indolent nature of the disease.
A significant proportion of our cases had renal impairment, hypertension and moderate to severe histological changes on biopsy, especially in diseases like IgA nephropathy. Presentation of GN was late as there is no widescale screening program for kidney diseases.
| Conclusion|| |
GN was common in young adults, with the majority presenting as NS, and non-proliferative GN seems to be the most common variety in our set up. Studies without IF gave fallacious reports, leading to misdiagnosis and treatment, emphasizing the need for this facility in Nepal. A screening program for early detection, proper diagnosis and effective treatment will help reduce the burden of CKD in Nepal.
| References|| |
McGrogan A, Franssen CF, de Vries CS. The incidence of primary glomerulonephritis worldwide: A systematic review of the literature. Nephrol Dial Transplant 2011;26:414-30.
Galla JH. IgA nephropathy. Kidney Int 1995; 47:377-87.
Dragovic D, Rosenstock JL, Wahl SJ, Panagopoulos G, DeVita MV, Michelis MF. Increasing incidence of focal segmental glomerulosclerosis and an examination of demographic patterns. Clin Nephrol 2005;63:1-7.
Khakurel S, Agrawal RK, Hada R. Pattern of end stage renal disease in a tertiary care center. JNMA J Nepal Med Assoc 2009;48:126-30.
Aryal G, Kafle RK. Histological spectrum of glomerular disease in Nepal: A seven year retrospective study. Nepal Med Coll J 2008;10: 126-8.
Choi IJ, Jeong HJ, Han DS, et al. An analysis of 4,514 cases of renal biopsy in Korea. Yonsei Med J 2001;42:247-54.
Chandrika BK. Non-neoplastic renal diseases in Kerala, India - Analysis of 1592 cases, a two year retrospective study. Indian J Pathol Microbiol 2007;50:300-2.
Li LS, Liu ZH. Epidemiologic data of renal diseases from a single unit in China: Analysis based on 13,519 renal biopsies. Kidney Int 2004;66:920-3.
Mubarak M, Kazi JI, Naqvi R, et al. Pattern of renal diseases observed in native renal biopsies in adults in a single centre in Pakistan. Nephrology (Carlton) 2011;16:87-92.
Haas M, Spargo BH, Coventry S. Increasing incidence of focal-segmental glomerulosclerosis among adult nephropathies: A 20-year renal biopsy study. Am J Kidney Dis 1995; 26:740-50.
Kazi JI, Mubarak M, Ahmed E, Akhter F, Naqvi SA, Rizvi SA. Spectrum of glomerulonephritides in adults with nephrotic syndrome in Pakistan. Clin Exp Nephrol 2009;13:38-43.
Das RK, Saleh AF, Kabir AN, Talukder SI, Kamal M. Immunofluorescence studies of Renal Biopsies. Dinajpur Med Coll J 2008;1:813.
Koyama A, Igarashi M, Kobayashi M. Natural history and risk factors for immunoglobulin A nephropathy in Japan. Research Group on Progressive Renal Diseases. Am J Kidney Dis 1997;29:526-32.
Briganti EM, Dowling J, Finlay M, et al. The incidence of biopsy-proven glomerulonephritis in Australia. Nephrol Dial Transplant 2001;16: 1364-7.
Bhuyan UN, Dash SC, Srivastava RN, Tiwari SC, Malhotra KK. IgA associated glomerulonephritis. J Assoc Physicians India 1992;40: 310-3.
Chandrika BK. IgA nephropathy in Kerala, India: A retrospective study. Indian J Pathol Microbiol 2009;52:14-6.
Muzaffar S, Azad NS, Kayani N, Pervaz S, Ahmed A, Hasan SH. The frequency of IgA Nephropathy at a single center in Pakistan. J Pak Med Assoc 2003;53:301-5
Department of Nephrology, Kist Medical College, Kathmandu
[Table 1], [Table 2], [Table 3], [Table 4]