Year : 2007 | Volume
: 18 | Issue : 4 | Page : 556--564
Prevalence and Clinical Findings of Biopsy-Proven Glomerulonephritidis in Iran
Afsoon Emami Naini1, Ali Amini Harandi1, Shahrzad Ossareh2, Ahad Ghods2, Bahar Bastani3,
1 Division of Nephrology, Isfahan University of Medical Sciences and Health Services, Isfahan, Iran
2 Division of Nephrology, Iran University of Medical Sciences and Health Services, Tehran, Iran
3 Division of Nephrology, Department of Internal Medicine, Saint Louis University Health Sciences Center, Saint Louis, Missouri, USA
Afsoon Emami Naini
Department of Nephrology, Noor Hospital, Isfahan University of Medical Sciences, Isfahan
Epidemiological data of renal diseases is population-based and have great geographic variability. Due to the lack of a national renal data registry system, there is no information on the prevalence rate, and clinical and laboratory features of various glomerulonephritidis (GNs) in Iran. In a retrospective cross sectional study, we analyzed 462 adult renal biopsies in Tehran, Iran. We determined the prevalence rate and the frequency of different clinical and laboratory findings in patients with different GNs. We also compared our results with the reports from other countries. There were 267 (57.8%) males and 195 (42.2%) females. The mean (± SD) age was 33.6 ± 15.7 (range, 13-75) years. A total of 55 biopsies, which had revealed pathologies other than GNs, were excluded. Among the remaining 407 biopsies, membranous glomerulopathy (MGN) was the most common GN (23.6%), followed by IgAN (13.5%), membranoproliferative GN (MPGN) (11.5%), systemic lupus nephritis (SLE-GN) (10.6%), focal and segmental glomerulosclerosis (FSGS) (10.3%), and minimal change disease (MCD) (9.8%). Our study shows that MGN is the most common form of GN, followed by IgAN, MPGN, SLEGN, FSGS and MCD in adult patients in Iran. A multi-center study with a larger sample size is needed for more comprehensive data in Iranian population.
|How to cite this article:|
Naini AE, Harandi AA, Ossareh S, Ghods A, Bastani B. Prevalence and Clinical Findings of Biopsy-Proven Glomerulonephritidis in Iran.Saudi J Kidney Dis Transpl 2007;18:556-564
|How to cite this URL:|
Naini AE, Harandi AA, Ossareh S, Ghods A, Bastani B. Prevalence and Clinical Findings of Biopsy-Proven Glomerulonephritidis in Iran. Saudi J Kidney Dis Transpl [serial online] 2007 [cited 2019 Jul 23 ];18:556-564
Available from: http://www.sjkdt.org/text.asp?2007/18/4/556/36512
Glomerulonephritidis (GNs) remain the third most common cause of end-stage renal failure.  Epidemiological data of renal diseases is population-based and has great variability according to the geographic area, socioeconomic condition, race, indication for biopsy, and differences in genetic susceptibility and environmental exposure.,,, Due to the lack of a nationwide renal data registry system, there is no information on the frequency of different GNs in Iran. Furthermore, the great variability of clinical manifestations confounds the determination of a definitive diagnosis based on the clinical features alone,  and thus, kidney biopsy remains the gold standard test for the diagnosis of GNs. However, this procedure is invasive, has some associated morbidity, and in some circumstances may be contraindicated. Due to the great variety of glomerular diseases the approach to these patients heavily relies on the clinical, laboratory and pathologic findings. In this study we analyzed the clinical and laboratory findings of 407 adult patients whose native kidney biopsies had revealed different forms of GNs, over a 3-year period in Tehran, Iran. We also compare our results with the reports from other countries.
Materials and Methods
In a retrospective cross sectional study, we analyzed 462 renal biopsies performed in Tehran, Iran. The biopsies had been performed in an adult referral university medical center. The indications for renal biopsy were: idiopathic nephrotic syndrome; rapidly progressive renal failure; evaluation and followup for collagen diseases, predominantly SLE with proteinuria; abnormal urine sediment or reduced renal function; glomerular proteinuria of unknown etiology accompanied by abnormal urine sediment or persistent proteinuria of >1 gm/day; persistent or recurrent glomerular hematuria with proteinuria more than 500 mg/day or acute renal failure (ARF) of unknown etiology with normal kidney size and no obstruction. 
We determined the frequency of different clinical and laboratory findings in these patients. Renal biopsies were processed for light and immunofluorescence microscopy in all specimens. In all cases, sections were stained with Hematoxylin and Eosin (H and E), Masson's trichrome, periodic acid-Schiff (PAS), and Silver Jone's stain.
Clinical information was obtained from the biopsy requisition forms, and by reviewing the patients' medical records. All data related to the final diagnosis, age, sex, clinical presentation, serum levels of cholesterol, triglyceride, creatinine and complements (C3, C4 and CH50), and the presence of microscopic hematuria, hypertension (systemic blood pressure >140/90 mm Hg), and proteinuria were recorded.
The clinical presentations were classified as the nephrotic syndrome (>3.5 grams proteinuria), nephritic syndrome (active urinary sediment with/without azotemia), ARF, chronic renal failure (CRF, azotemia of >3 months duration), asymptomatic urinary abnormality (AUA), and rapidly progressive GN (RPGN, doubling of serum creatinine over a 3 months period).  Hypertriglyceridemia and hypercholesterolemia were considered if the plasma concentrations were > 200 mg/dl.
Analysis was performed using the statistical package of social science (SPSS)version 10. Mean ± SD values of laboratory data were compared using ANOVA, between different clinicopathological diagnoses. P 1.4 mg/dl, at the time of presentation, is shown in [Table 4]. There was no significant difference in triglyceride concentrations (p=0.27) among different GNs; however, the difference was significant in regard to serum cholesterol, and creatinine concentrations (p , The male : female ratio has been reported as 2:1, with the peak incidence being in the fourth and fifth decades of life. Clinical manifestations of MGN show significant geographic variation. Patients from Australia and Japan have a lower frequency of the nephrotic syndrome, as compared to patients from Europe or North America. Microscopic hematuria and hypertension (HTN) have been reported in 30-50% of the patients at presentation.,, In our series, the mean age of patients with MGN was 43 years, M:F ratio was 1.5:1, there was a high prevalence of the nephrotic syndrome (84.5%) and hyperlipidemia (hypertriglyceridemia 64.6% and hypercholesterolemia 88.5%) at presentation. The high prevalence of the nephrotic syndrome and azotemia in our series may be due to increased severity of the disease among patients seen in our hospital which is a referral center for renal disease in Tehran, Iran. The other clinical manifestations were HTN (38.5%), microscopic hematuria (13.5%), and serum creatinine >1.4 mg/dl (15.6%). The serum complement levels were reduced in only 5% of the patients.
IgAN is now regarded as the most common form of GN in the world.,, Its prevalence rate varies in different geographic regions,  it is most prevalent in Asia (30-40%) and relatively less prevalent in Europe (20%) and North America (10%)., Its incidence varies from two per 10,000 people in France and Germany to between 2.0 and 4.8% of the population in Singapore., The M:F ratio has been reported to be 2:1.  Around 30-40% of these patients present with microscopic hematuria. HTN has been reported in only 8% of the patients at the time of presentation.  IgAN was the second most common GN, after MGN, in our series. The lower prevalence rate of IgAN in our series may be due to our higher threshold for renal biopsy, i.e., exclusion of patients with isolated hematuria and/or proteinuria of 1.4 mg/dl, at the time of renal biopsy.
FSGS comprises 2 to 41% of the primary GNs in the world.  In the past 20 years, the prevalence of primary FSGS has risen from 
FSGS comprises 6-15% of GNs in Europe and 2-11% of GNs in Asia.  FSGS is slightly more common in males (M:F ratio, 1.4:1), with microscopic hematuria occurring in over one half of the patients, and HTN in one third of the patients at presentation. 
In a report by Cattran, half of the adult patients had the nephrotic syndrome, a third had microscopic hematuria, and 35% had HTN at presentation.  In our series, mean age at presentation was 30.4 years, males were almost twice the females, mean protein excretion rate was 5.8 gm/24 hours with 57% of patients presenting with the nephrotic syndrome, 60% had HTN, 19% had microscopic hematuria, 69% hypercholesterolemia, 55% had hypertriglyceridemia and 55% had serum creatinine >1.4 mg/dl at the time of presentation.
MCD is responsible for 10-15% of the primary the nephrotic syndromes in adults.  It has a variable geographic distribution, being more common in Asia than North America or Europe,  and is equally distributed between the two sexes.  In our series, MCD comprised 9.8% of the biopsies. It was slightly more prevalent among males (M:F, 1.3:1), with an average age at presentation of 35 years, mean protein excretion rate of 7.8 gm/24 hours. In our patients, 95% presented with the nephrotic syndrome, 25% had HTN, 12.5% microscopic hematuria, 87.5% hypercholesterolemia, and 17.5% had serum creatinine >1.4 mg/dl at the time of presentation.
Recent studies have focused on the significance of epidemiologic and clinical features of SLE-GN, and report a F:M ratio of 813:1.  The serum complements are usually decreased in the active phase, and often decline before clinical flare up.  In our series, SLE-GN accounted for 10.6% of all GNs; the patients were the youngest (mean age, 24.4 years) among all GNs, there were 10 times more females than males, 65% presented with the nephrotic syndrome, and only 21% presented with a nephritic picture. At the time of biopsy, 53.5% of our patients had HTN, 35% had microscopic hematuria, around two thirds had hyperlipidemia, 51% had serum creatinine >1.4 mg/dl, and around 80% had reduced serum complement levels.
MPGN accounts for a wide range (2% to 49%; average, 12.5%) of GNs world wide; 50% of the patients present with the nephrotic syndrome, and 30% present with mild and asymptomatic proteinuria.  In our series, MPGN accounted for 11.5% of all GNs; average age was 28.6 years, there were slightly more males (M:F ratio, 1.2:1), and almost all patients presented with proteinuria (average of 5.5 gm/day). At presentation, 66% of our patients had the nephrotic syndrome, 13% had a nephritic picture, 60% were hypertensive, 34% had microscopic hematuria, 72.5% were hypercholesterolemic, 57.5% had elevated serum creatinine >1.4 mg/dL, and around one half of our patients were hypocomplementemic. In Iran, the prevalence rate of hepatitis B has been reported to be between 1.1% and 9% in different provinces, , and there has been ten-time higher incidence of hepatitis C among MPGN patients than in normal population.  Unfortunately, we do not have any information on the status of hepatitis B or C of the MGN or MPGN patients in the present study.
The frequency of different GNs in other geographic regions of the world is presented in table 5. ,,,,,,,,,,,,,,,, Unfortunately, many reports lack detailed information about clinical and laboratory indices. IgAN was the most common GN reported in Australia, France, Japan, Italy, Hong Kong, and Saudi Arabia. FSGS was the most common GN in Brazil, Zaire, USA, Saudi Arabia, and Kuwait. MPGN was the most common GN reported in Moscow and China. MGN, which is the most common GN in our series, has been reported as the most common GN in United Arab Emirates, and Macedonia, and is among the top in the USA.
Recent data point to genetic, biologic, and socioeconomic factors that may be contributing to these findings.  The contribution of clinical epidemiology to evidence-based nephrology is not limited to randomized controlled trials.  Epidemiological studies on the prevalence rate, and clinical and laboratory findings can lead to a higher index of suspicion to a particular diagnosis that may lead to timely appropriate therapeutic intervention. Whether empiric epidemiologic data can be used in treating individual patients, and how, remains controversial. Moreover, like other fields in medical research, epidemiology has some methodological limitations that must be taken into account. 
Our study has several shortcomings. We did not elaborate on the remaining variants of GNs, sub-types of MPGN (I or II), and associated conditions such as malignancy or drug consumption. Further studies with larger sample size, and survival analysis of patients are needed for better understanding of the epidemiologic features of GNs in the Iranian population.
|1||Cattran DC. Outcomes research in glomerulonephritidies. Semin Nephrol 2003; 23:340-54.|
|2||Kitiyakara C, Kopp JB, Eggers P. Trends in the epidemiology of focal segmental glomerulosclerosis. Semin Nephrol 2003; 23:172-82.|
|3||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.|
|4||Yahya TM, Pingle A, Boobes Y, Pingle S. Analysis of 490 kidney biopsies: Data from the United Arab Emirates renal diseases Registry. J Nephrol 1998;11: 148-50.|
|5||Briganti EM, Dowling J, Finlay M, et al. The incidence of biopsy-proven glomerulonephritidies in Australia. Nephrol Dial Transplant 2001;16:1364-7.|
|6||Falk RJ, Jennette JC, Nachman PH. Primary Glomerular Disease. In: Brenner BM. Brenner and Rector's The Kidney. Philadelphia: WB Saunders Company; 2004. p. 1293-380.|
|7||Massry SG, Glassock RJ, eds. Massry and Glassock's Textbook of Nephrology. 4 th ed. Lippincott Williams and Wilkins: Philadelphia; 2001. p. 1743.|
|8||Denker BM, Brenner BM. Azotemia and urinary abnormalities. In: Kasper DL, Braunwald E, Fauci A, Hauser S, Longo D, Jameson JL, eds. Harrison's Principles of Internal Medicine: 16th edition: NewYork: McGraw-Hill Book Co; 2005. p. 247.|
|9||Forland M, Spargo BH. Clinico-pathological correlations in idiopathic nephrotic syndrome with membranous nephropathy. Nephron 1969;6:498-525.|
|10||D'amico G. the commonest glomerulonephritidies in the world: IgA nephropathy. Q J Med 1987;64:709-27.|
|11||Clarkson AR, Woodroffe AJ, Faull RJ. Immunoglobulin A Nephropathy and Henoch-Schonlein purpura. In: Schrier RW. Ed. Disease of the kidney and urinary tract. Philadelphia: Lippincot; 2001. p. 1691-716.|
|12||Sharples PM, Poulton J, White RH. Steroid responsive nephrotic syndrome is more common in Asians. Arch Dis Child 1985; 60:1014-7.|
|13||Appel GB, Radhakrishnan J, D'Agati VD. Secondary Glomerular Disease. In: Brenner BM. Brenner and Rector's The Kidney. Philadelphia: WB Saunders Company; 2004. p. 1381-481.|
|14||Zali MR, Mohammad K, Farhadi A, Masjedi MR, Zargar A, Nowroozi A. Epidemiology of hepatitis B in the Islamic Republic of Iran. East Mediterr Health J 1996;2:290-8.|
|15||Merat S, Malekzadeh R, Rezvan H, Khatibian M. Hepatitis B in Iran. Arch Iran Med 2000;3:192-201.|
|16||Broumand B, Ghaleh-Baghi B, Abbasi M, Bonabi NB. The association between hepatitis C and membranoprolifrative glomerulonephritis. Nephrology 1997;3: S365.|
|17||Mitwalli AH, Al Wakeel JS, Al Mohaya SS, Malik HG. Pattern of glomerular disease in Saudi Arabia. Am J Kidney Dis 1996;27: 797-802.|
|18||Al-Homrany MA. Pattern of renal diseases among adults in Saudi Arabia: A clinicopathologic study. Ethn Dis 1999; 9:463-7.|
|19||Korbet SM, Genchi RM, Borok RZ, Shwartz MM. The racial prevalence of glomerular lesions in nephritic adults. Am J Kidney Dis 1996;27:647-51.|
|20||Chen H, Tang Z, Zeng C, et al. Pathological demography of native patients in a nephrology center in China. Chin Med J (Engl) 2003;116:1377-81.|
|21||Heaf J, Lokkegaard H, Larsen S. The epidemiology and prognosis of glomerulonephritidies in Denmark 1985-1997. Nephrol Dial Transplant 1999;14:1889-97.|
|22||Khoo JJ. Renal biopsies in Johor: A 7-years study. Malays J Pathol 2001;23: 101-4.|
|23||Hurtado A, Escudero E, Stromquist CS, et al. Distinct pattern of glomerular disease in Lima, Peru. Clin Nephrol 2000;53:325-32.|
|24||Polenakovic MH, Grcevska L, Dzikova S. The incidence of biopsy-proven primary glomerulonephritidies in the Republic of Macedonia-long-term follow-up. Nephrol Dial Transplant 2003; 18:26-7.|
|25||El-Reshaid W, El-Reshaid K, Kapoor MM, Madda JP. Glomerulopathy in Kuwait: The spectrum over the past 7 years. Ren Fail 2003;25:619-30.|
|26||Chan KW, Chan TM, Ceng IK. Clinical and pathological characteristics of patients with glomerular diseases at a university teaching hospital: 5-years prospective review. Hong Kong Med J 1999;5:240-4.|
|27||Dzhanaliev BR, Varshavskii VA, Laurinavichus AA. Primary glomerulopathies: Incidence, dynamics and clinical manifestations of morphological variants. Arkh Patol 2002;64:32-5.|
|28||Serov VV, Varshavsky VA, Schill H, Nizze H. Incidence of glomerular diseases in kidney biopsy materials using WHO classification. Zentralbl Allg Pathol 1986;132:471-5.|
|29||Pakasa M, Mangani N, Dikassa L. Focal and segmental glomerulosclerosis in nephrotic syndrome: A new profile of adult nephrotic syndrome in Zaire. Mod Pathol 1993;6:125-8.|
|30||Bahiense-Oliveira M, Saldanha LB, Mota EL, Penna DO, Barros RT, Romao-Junior JE. Primary glomerular diseases in Brazil (1979-1999): Is the frequency of focal and segmental glomerulosclerosis increasing? Clin Nephrol 2004;61:90-7.|
|31||Mazzarolo Cruz HM, Cruz J, Silva AL Jr, Saldanha LB, de Oliveira Penna D. Prevalence of adult primary glomerular diseases: Retrospective analysis of 206 kidney biopsies (1990-1993). Rev Hosp Clin Fac Med Sao Paulo 1996;51:3-6.|
|32||Simon P, Ramee AP, Autuly V, Laruelle E, Charasse C, Cam G, et al. Epidemiology of primary glomerular diseases in a French region. Variations according to period and age. Kidney Int 1994;4: 1192-8.|
|33||Antonovych TT, Sabins SG, Broumand BB. A study of membranoproliferative glomerulonephritis in Iran. Ann Saudi Med 1999;19:505-10.|
|34||Halevy D, Radhakvishnan J, Appel GB. Racial and socioeconomic factors in glomerular disease. Semin Nephrol 2001;21:403-10.|
|35||Frimat L. Contribution of clinical epidemiology to evidence-based nephrology. Nephrologie 2001;22:199-203.|