Frequency of primary glomerular disease in northeastern China

Most frequently reported Chinese renal biopsy data have originated from southeastern China. The present study analyzed the renal biopsy data from northeastern China. The records of 1550 consecutive native patients who were diagnosed with primary glomerular diseases (PGD) after renal biopsy at our hospital during 2005-2009 were used. These patients were divided into four age groups for stratified analysis: <15, 15-44, 45-59, and ≥60 years old. Among PGD, minimal change disease (MCD) was the most common histologically diagnosed disease (30.7%), followed by IgA nephropathy (IgAN), mesangial proliferative glomerulonephritis (MsPGN), membranous nephropathy (MN), membranoproliferative glomerulonephritis (MPGN), focal segmental glomerulosclerosis (FSGS), and endocapillary proliferative glomerulonephritis (EnPGN). MCD was the disease most frequently observed (43.7%) in the <15-year-old group. MsPGN was the most common disease in the elderly group (38.1%). MsPGN was more prevalent in females (27.8%), whereas MCD was more prevalent in males (35.3%). Primary glomerular diseases constituted the most commonly encountered group of diseases with a high prevalence of MCD, which predominantly affected males and young adults. The prevalence of MCD was high in northeastern China. Further study is necessary to expand the epidemiologic data available for renal disease in China.


Introduction
Chronic kidney disease (CKD) is a worldwide public health problem with increasing incidence and prevalence, poor outcome and high associated costs (1).Glomerulonephritis and hypertension are the most common causes of CKD in developing countries.Primary glomerular disease (PGD) is the leading cause of CKD in China (2,3).Common causes of PGD include minimal change nephrotic syndrome (minimal change disease, MCD) and its variants, membranous glomerulonephritis, or membranoproliferative glomerulonephritis (MPGN) (4).The patterns of PGD differ by country and are also changing over time within countries.These patterns are probably changing because of better infection control, changes in environmental pollution, increasing awareness of the disease, and increases in life expectancy (5).In studies from East Asia, IgA nephropathy (IgAN) and non-IgA mesangial proliferative glomerulonephritis (MsPGN) are the most common types of PGD.In most European studies, IgAN and membranous nephropathy (MN) are the common types of PGD.In the USA, the incidence of focal segmental glomerulosclerosis (FSGS), which appears to be the most frequent

O N L I N E P R O V I S I O N A L
PGD type, is increasing (6,7).A renal biopsy is required for a definitive diagnosis and has been performed routinely in China for the last 20 years.Most reported renal biopsy data originate from southeastern China, which includes Shanghai, Nanjing and Hong Kong (4,(8)(9)(10).Epidemiologic PGD data for the northeastern region are rarely reported.This article presents the epidemiological data from renal biopsies performed in Heilongjiang Province (east longitude 121°13'-135°05'; north latitude 43°22'-53°24').Because many patients reside in different regions of the country, these data might supplement the previously published data related to the epidemiology of renal disease in China.

Patients
The medical records of 1550 patients with PGD diagnosed by renal biopsy were collected from the First Clinical Medical College, Harbin Medical University, Heilongjiang Province, during the period from January 2005 to December 2009.Subjects resided in all 13 regions of Heilongjiang Province (454,000 km 2 ).Of the 1550 patients, 728 (47.0%) were males, and 822 (53.0%) were females.Their average age was 35.1 ± 12.5 (6 to 75) years.The indications for renal biopsy were as follows: 1) nephrotic syndrome (NS; proteinuria ≥3.5 g/day with or without hypoalbuminemia); 2) chronic nephritic syndrome (CGN; proteinuria 1-3.5 g/day and a >3-month history of hematuria); 3) acute nephritic syndrome (AGN; hematuria, red blood cell casts and a <3-month history of proteinuria <3.5 g/day); 4) rapidly progressive glomerulonephritis syndrome (RPGN; AGN with acute deterioration of renal function, such as a 2-fold increase in the serum creatinine concentration or a 50% decrease in creatinine clearance), and 5) asymptomatic urinary abnormality (AUA; proteinuria <1.0 g/day and hematuria found in routine check-ups, without edema, hypertension or abnormal renal function).The indications for a renal biopsy did not change during the entire observation period.All biopsy specimens were prepared and examined by the same group of clinicians and technicians.As previously described, the analysis included light microscopy, immunohistology, and electron microscopy (3).Renal biopsy specimens were fixed with 10% neutral buffer formalin and embedded in paraffin using standard procedures.In addition, 2-mm thick sections were stained with hematoxylin and eosin (HE), periodic acid-Schiff reagent (PAS), silver methenamine, and Masson's trichrome.Immunofluorescence techniques were performed using fluorescence-labeled rabbit anti-human IgG, IgM, IgA, C3, C4, and C1q antibodies.All specimens were examined by two experienced pathologists.A final diagnosis was made for each patient on the basis of the clinical and histological investigations.

Statistical analysis
Data were stored in a database file (Excel 2007).All statistical analyses were performed using the SPSS software (SPSS 11.0, USA).Categorical variables were analyzed using chi-square and Fisher exact tests.Continuous variables were analyzed using the Student t-test.Statistical significance was defined as P < 0.05.

The prevalence of PGD in males and females
As shown in Table 2, the proportions of MsPGN and MCD differed between males and females.MsPGN was more prevalent among females (27.8%) than among males (18.9%;P < 0.01) and MCD was more prevalent among males (35.3%) than among females (26.6%;P < 0.01).Among females, there was no significant difference between the proportions of MCD, IgAN and MsPGN (26.6, 25.4, and 27.8%, respectively).

Discussion
In the present study, we analyzed the clinical and pathological data of 1550 patients who were diagnosed with PGD between 2005 and 2009 in northeastern China.We found that MCD was the most common form of PGD (30.7%), followed by IgAN, MsPGN, MN, FSGS, and MPGN.
MCD is diagnosed when a patient has nephrotic syndrome.The renal biopsy reveals little or no change in the structure of the glomeruli or the surrounding tissues as assessed by light microscopy.MCD has a variable geographic distribution and is more common in Asia than in North America or Europe (11).In Korea (12) and Thailand (13), MCD accounts for 26.6 and 45.8%, respectively, of PGD.MCD may occur at any age, but is most common in childhood (14).The predominance of young adults has also been observed in Asian studies of patients with a mean age of 27-31 years (15,16).In addition, a slight male predominance is noted more frequently among Asian patients (male:female = 1.2-2.0:1)than among Western patients (male:female = 0.5-1.3:1)(17).In our study, MCD was the most common PGD in the <15-yearold group (43.7%).The mean age of adult-onset MCD was relatively younger (30.9 years) compared to the other PGD forms (30.9 years), and 80% of patients were less than 40 years old.The male-to-female ratio of MCD patients was 1.33, the same value reported in previous studies.
IgA nephropathy is one of the most common forms of glomerulonephritis, accounting for approximately 45% of primary glomerulonephritis cases in China (3).Few epidemiologic studies have examined the incidence of primary IgA nephropathy in various populations in the world.There is a marked regional difference in the frequency of IgA nephropathy among PGD patients.IgA nephropathy occurs with the highest frequency in Asian countries (Japan and China) (3,8,18) and is less common in North America and Europe (USA and Italy) (19,20).Genetic factors are thought to underlie the development of IgAN in Asia because the incidence of IgAN is much higher in Asia than in Western countries.In our study, Heilongjiang Province showed a low IgAN prevalence (24.5%) compared to other regions of China (3,8,18).Heilongjiang is located in Northeastern China, which is an area with unique geographical features and climate conditions.Winter lasts more than 6 months in this region.Economic growth and standards of living are lower than in the Southeastern region of China, which includes cities such as Shanghai, Nanjing, and Hong Kong.With the improvement in living conditions, people lifestyle and dietary changes may have an impact on the incidence of IgAN.
Our results show that NS was the most common clinical presentation of PGD (60.6% of patients).This finding is consistent with previous studies, in which NS has been demonstrated to be the most common renal syndrome (6,13).However, the clinicopathologic presentations of PGD vary in different regions.In Heilongjiang province, MCD is the most common cause of NS and IgAN is the leading cause of AUA, AGN, and CGN.Clinical practice shows that the same pathological type can have different clinical manifestations, and vice versa.Although renal biopsy can provide information about the type and severity of renal diseases, the diagnosis of PGD should be closely integrated with clinical and the pathological diagnosis in order to rule out a systemic or genetic disease and to obtain the correct diagnosis.
This report, which is based on data from a 5-year period, provides information on renal diseases diagnosed by renal biopsy.This is the first systematic report that focused on data from northeastern China, and the data presented complement reported data on the epidemiology of renal disease in China.

Table 2 .
Gender distribution of primary glomerular diseases.