CHAPTER 2. Primary Glomerulonephritis

Transcription

1 2nd Report of the PRIMARY GLOMERULONEPHRITIS CHAPTER 2 Primary Glomerulonephritis Sunita Bavanandan Lee Han Wei Lim Soo Kun 21

2 PRIMARY GLOMERULONEPHRITIS 2nd Report of the 2.1 Introduction This chapter covers the main primary glomerulonephritis that were reported to the MRRB from the years Minimal change disease is the commonest secondary glomerulonephritis in adult contributing 33% of all primary glomerulonephritis in Malaysia. This was followed by focal segmental glomerulosclerosis which contributed about 30% of cases. Ig A nephropathy (19%) is the third commonest primary glomerulonephritis. Idiopathic membranous nephropathy contributed only 11% of all biopsy proven primary glomerulonephritis. The other types of primary glomerulonephritis are relatively uncommon (Table 2.1). Table 2.1: Primary Glomerulonephritis, Histopathological Diagnosis Total n % n % n % n % n % Minimal Change Disease (MCD) Focal Segmental Glomerulosclerosis (FSGS) Ig A nephropathy (Ig AN) Membranous nephropathy (IMN) Membrano-proliferative GN (MPGN) Mesangial Proliferative GN non Ig A Crescentic ANCA Idiopathic Crescentic Unknown Total : Minimal change disease 2.2.1: Introduction Minimal change disease (MCD) is typically characterized by normal appearing glomeruli by light microscopy and the absence of complement or immunoglobulin deposits by immunofluorescence microscopy. Glomerular size is usually normal by standard methods of light microscopy, although enlarged glomeruli may be observed. The characteristic histologic lesion in minimal change disease is diffuse effacement (also called "fusion") of the epithelial foot processes on electron microscopy. Minimal change disease is a major cause of nephrotic syndrome in both children and adults. 22

3 2nd Report of the PRIMARY GLOMERULONEPHRITIS 2.2.2: Patient population and characteristics A total of 389 cases of minimal change disease were reported in The mean age of the patients at the time of biopsy was 29.1 ± 12.8 with a clear predominance in second and third decades of life. The frequencies of age groups 15 to <25, and 25 to <35 were 51% and 23% respectively, which is 74% when combined. However, it is important to bear in mind that children with steroid responsive nephrotic syndrome are usually not biopsied, hence the actual incidence of minimal change disease in the paediatric age group is under-represented. The diagnosis of minimal change disease is relatively rare after 55 years of age and our reported frequency was only about 6% in this age group. There is a higher incidence of minimal change disease in males, with a ratio of 2:1 in the four-year registry data (overall 66% as compared to 34% in the female group (Table (a)). In terms of racial distribution, there was no predilection of any particular ethnic group. The racial group distribution in Malay, Chinese and Indian was 60%, 17% and 6% (Table (a)). This pattern of distribution reflects the ethnic composition of patients admitted to public hospitals. Table 2.2.2(a): Demographic characteristics for MCD, Demographic Characteristics n =389 % Age (years) 29.1 ± 12.8 Race Male Female Malay Gender Chinese Indian 22 6 Others Table (b): Age group at time of biopsy (years) for MCD, Age group Total (years) n % n % n % n % n % 15-< < < < < > Total Figure (b): Age at time of biopsy (years) MCD, Density Age at time of biopsy (years) 23

4 PRIMARY GLOMERULONEPHRITIS 2nd Report of the 2.2.3: Clinical presentation The mean level of 24 hours urine protein was 6.4 ± 5.1g/day. Nephrotic syndrome, as expected, was the most common presentation (81%). Other presentations were asymptomatic urine abnormality (10%), nephritic syndrome (3%) and nephritic-nephrotic syndrome (3%) (Table & Figure 2.2.3(a)). Majority of blood pressures were normal during presentation (88%) (Table 2.2.3(b)). Most patients do not have any documented renal impairment, 58% have egfr 90 ml/min/1.73m 2 while 23% have egfr between 60 to 89 ml/min/1.73m 2. One fifth of patients have significant renal impairment (egfr less than 60 ml/min/1.73m 2 ) (Table (c)). Table (a): Clinical presentation for MCD, Clinical Presentations Total n % n % n % n % n % Asymptomatic urine abnormality Nephritic syndrome Nephrotic syndrome Nephritic-Nephrotic syndrome Missing Total Figure (a): Clinical presentation for MCD, Table (b): Presence of hypertension in MCD, Hypertension n % Present 35 9 Absent Missing 13 3 Total Table (c): Renal function in MCD by year, GFR (ml/min/1.73m 2 ) Total n % n % n % n % n % < Total

5 2nd Report of the PRIMARY GLOMERULONEPHRITIS : Clinical presentation by age Nephrotic syndrome consistently predominates as the clinical presentation throughout all age groups (Table ). However, the presence of hypertension increases with increasing age (Figure (b)). Table : Clinical presentation by age group for MCD, Clinical Presentations 15- <25 25-<35 35-<45 45-<55 55-<65 > 65 Total n % n % n % n % n % n % n % Asymptomatic urine abnormality Nephritic syndrome Nephrotic syndrome Nephritic-Nephrotic syndrome Missing Total Figure (b): Hypertension by age group for MCD,

6 PRIMARY GLOMERULONEPHRITIS 2nd Report of the : Clinical presentation by gender There are basically no differences between genders in terms of clinical presentation and renal function at presentation (Table (a & b)). Both genders have relatively well preserved with renal function with less than 20% have egfr < 60 ml/min/1.72 m 2 (Figure (b)). The prevalence of hypertension was higher in female than male (13% vs. 7%) (Figure (c)). Table (a): Clinical presentation by gender for MCD, Clinical Presentations Male Female n % n % Asymptomatic urine abnormality Nephritic syndrome Nephrotic syndrome Nephritic-Nephrotic syndrome Missing Total Table (b): Renal function by gender for MCD, egfr (ml/min/1.73m 2 ) Male Female n % n % < Total Figure (b): Impaired renal function by gender for MCD, Figure (c): Hypertension by gender for MCD,

7 2nd Report of the PRIMARY GLOMERULONEPHRITIS 2.2.4: Renal function at presentation About three-quarter of patients below 35-years-old have well-preserved renal function (egfr >60ml/ min/1.73m 2 ). This is in contrast to the older age group, e.g. those aged above 55 years where % have already suffered significant renal impairment (egfr < 60ml/min/1.73m 2 ) on presentation (Table & Figure 2.2.4). Table 2.2.4: Renal function at presentation by age group for MCD, egfr (ml/min/1.73m 2 ) Total n % n % n % n % n % n % n % > < Total Figure 2.2.4: Renal function at presentation by age group for MCD,

8 PRIMARY GLOMERULONEPHRITIS 2nd Report of the 2.3: Focal Segmental Glomerulosclerosis 2.3.1: Introduction Focal segmental glomerulosclerosis is defined on histologic criteria by segmental capillary obliteration with increased mesangial matrix deposition, intra-capillary hyaline deposits and focal adhesions of the capillary tuft to Bowman s capsule : Patient Population and Characteristics A total of 355 cases of FSGS were reported in our four-year registry data. The mean age at the time of biopsy was 32.5 ± 13.5 (Table (a)). The first three decades of life were the predominant age groups in this type of renal disease. After the age of 55, the frequency rate was only 8% compared to other age groups (Table & Figure (b)). FSGS was slightly more common in males (57%) compared to females (43%) (Table 2.3.2(a)). The distribution according to ethnicity was 62% in Malays, 16% in Chinese, 7% in Indians and 15% in others (Table 2.3.2(a)). Table (a): Demographic characteristics for FSGS, Demographic Characteristics n=355 % Age (years) 32.5 ± 13.5 Gender Male Female Malay Race Chinese Indian 26 7 Others Table (b): Age group at time of biopsy (years) for FSGS, Age group (years) Total n % n % n % n % n % 15-< < < < < > Total Figure (b): Age at time of biopsy (years) for FSGS, Density Age at time of biopsy (years)

9 2nd Report of the PRIMARY GLOMERULONEPHRITIS 2.3.3: Clinical Presentation The mean level of 24 hours urine protein was 4.6±3.7g/day. Nephrotic syndrome was the most common reported clinical presentation (65%). Other reported presentations were asymptomatic urine abnormality (21%), nephritic syndrome (6%) and nephritic-nephrotic syndrome (3%) (Table & Figure 2.3.3(a)). The majority of patients (79%) have normal blood pressure during the initial presentation (Table (b)). Table (a): Clinical presentation for FSGS, Clinical Presentations Total n % n % n % n % n % Asymptomatic urine abnormality Nephritic syndrome Nephrotic syndrome Nephritic-Nephrotic syndrome Missing Total Figure (a): Clinical presentation for FSGS, Table (b): Hypertension in FSGS, Hypertension n % Present Absent Missing 11 3 Total

10 PRIMARY GLOMERULONEPHRITIS 2nd Report of the : Clinical presentation by age Nephrotic syndrome consistently predominates as the clinical presentation throughout all age groups particularly in the very young (below 25 years) and those above 55 (Table & Figure (a)). years. The prevalence of hypertension increases with increasing age (Figure (b)). Table (a): Clinical presentation by age group for FSGS, Age group (years) Asymptomatic urine abnormality > 65 Total n % n % n % n % n % n % n % Nephritic syndrome Nephrotic syndrome Nephritic-Nephrotic syndrome Missing Total Figure (a): Clinical presentation by age group for FSGS, Figure (b): Hypertension by age group for FSGS,

11 2nd Report of the PRIMARY GLOMERULONEPHRITIS : Clinical presentation by gender From the 4 years of collected data, nephrotic syndrome appears more common in males and more females present as asymptomatic urine abnormality (Table & Figure (a)). There was no difference in the prevalence of hypertension in both genders (Figure (b)). Table (a): Clinical presentation by gender for FSGS, Clinical Male Female Presentations n % n % Asymptomatic urine abnormality Nephritic syndrome Nephrotic syndrome Nephritic-Nephrotic syndrome Missing Total Figure (a): Clinical presentation by gender for FSGS, Figure (b): Hypertension by gender in FSGS,

12 PRIMARY GLOMERULONEPHRITIS 2nd Report of the 2.3.4: Renal function at presentation About 59% have normal or well-preserved renal function (egfr >60 ml/min/1.73m 2 ) on presentation. There were 21% of cases with egfr range of ml/min/1.73m 2, 11 % were ml/min/1.73m 2 and 5% were <15 ml/min/1.73m 2 (Table 2.3.4). Table 2.3.4: Impaired renal function in FSGS by year, egfr (ml/min/1.73m 2 ) Total n % n % n % n % n % < Total : Renal function at presentation by age There was a higher risk of renal impairment with increasing age (Table & Figure ) Table : Renal function at presentation by age group for FSGS, egfr (ml/min/1.73m 2 ) 15- <25 25-<35 35-<45 45-<55 55-<65 >65 Total n % n % n % n % n % n % n % > < Total Figure : Impaired renal function at presentation by age group for FSGS,

13 2nd Report of the PRIMARY GLOMERULONEPHRITIS : Renal function at presentation by gender There were basically no differences between genders in terms of renal function. Table : Renal function at presentation according to gender for FSGS, egfr (ml/min/1.73m 2 ) Male Female n % n % > < Total Figure : Renal function at presentation according to gender for FSGS, : Idiopathic Membranous Nephropathy (IMN) Introduction Membranous nephropathy is characterised by subepithelial immune deposits with spikes and thickening of the basement membrane Patient population and characteristics Over the four-year period from , 125 cases of Idiopathic membranous nephropathy (IMN) were reported to the registry. The mean age at biopsy was , with a range between 19 and 80.8 years (Table & Figure 2.4.2). Overall, there were slightly more males than females. The racial distribution was 44% in Malays, 40% in Chinese, 6 % in Indians and 10% in others (Table 2.4.2). Table 2.4.2: Demographic characteristics for IMN, Demographic characteristics n=125 % Age (years) Gender Race years Male Female Malay Chinese Indian 8 6 Other Figure 2.4.2: Age at time of biopsy (years) for IMN,

14 PRIMARY GLOMERULONEPHRITIS 2nd Report of the 2.4.3: Clinical presentation The majority of patients (70%) presented with overt nephrotic syndrome. The median level of proteinuria was 3.5 g/day with a range from g/day. Asymptomatic urinary abnormalities, nephritic-nephrotic syndrome, and nephritic syndrome were found in 22%, 3% and 2% respectively (Table & Figure 2.4.3(a)). Hypertension was found in 21% of cases (Table (c)) and 37% presented with egfr< 60mls/min (Table 2.4.3(c)). Table (a): Clinical presentation for IMN, Clinical Presentations Total n % n % n % n % n % Asymptomatic urine abnormality Nephritic syndrome Nephrotic syndrome Nephritic-Nephrotic syndrome Missing Total Figure (a): Clinical presentation for IMN, Table (b): Hypertension in IMN, Hypertension n % Present Absent Missing 2 2 Total Table 2.4.3(c): Renal function in IMN, egfr (ml/min/1.73m 2 ) n % > < Total

15 2nd Report of the PRIMARY GLOMERULONEPHRITIS : Clinical presentation by age Nephrotic syndrome remained the commonest clinical presentation across all age groups, and older patients were less likely to be biopsied for asymptomatic urinary abnormalities (Table & Figure (a)). Comparison with respect to incidence of hypertension is limited by the relatively smaller numbers of patients at both extremes of age. Table (a): Clinical presentation by age group for IMN, Age group (years) Asymptomatic urine abnormality > 65 Total n % n % n % n % n % n % n % Nephritic syndrome Nephrotic syndrome Nephritic-Nephrotic syndrome Missing Total Figure (a): Clinical presentation by age group for IMN, Table (b): Hypertension by age group for IMN, Hypertension >65 Total n % n % n % n % n % n % n % Present Absent Missing Total

16 PRIMARY GLOMERULONEPHRITIS 2nd Report of the : Clinical presentation by gender There were no significant differences in gender with respect to clinical presentation. Figure (a): Clinical presentation by gender for IMN, Table (b): Hypertension by gender for IMN, Male Female Hypertension n % n % Present Absent Missing Total : Renal function at presentation : Renal function at presentation by age Majority of cases (62%) had egfr > 60 ml/min/1.73m 2 at presentation. There were 27 % of cases with egfr range of ml/min/1.73m 2, 8% in the ml/min/1.73m 2 and 3% in the < 15 ml/min/1.73m 2 (Table & Figure (a)). The proportion of patients with egfr < 60 ml/min/1.73m 2. Increase with age (Figure (b)). Table (a): Renal function at presentation by age group for IMN, egfr (ml/min/1.73m 2 ) > 65 Total n % n % n % n % n % n % n % > < Total Figure (a): Renal function at presentation by age group for IMN, Figure (b): Impaired renal function by age group for IMN,

17 2nd Report of the PRIMARY GLOMERULONEPHRITIS : Renal function at presentation by gender Males appear to have worse renal function. Up to 44% of male vs. 31% of females has egfr < 60 ml/ min/1.73m 2 at presentation (Table ). Table : Renal function at presentation according to gender for IMN, egfr Male Female (ml/min/1.73m 2 ) n % n % > < Total : Ig A Nephropathy (IgAN) 2.5.1: Introduction IgAN is defined by the predominant deposition of IgA in the glomerular mesangium although light microscopic appearances and clinical features can vary considerably due to the various patterns of histopathologic injury found in this glomerulonephritis : Patient population and characteristics Two hundred and twenty-three cases of IgA nephropathy were reported to the registry over the 3-year period of data collection. The mean age at biopsy was 33.8 ± 12.5 years and majority of the cases (81%) were between ages 15 to 45 years (Table & Figure (b)). As suggested in the previous report, there is slight female preponderance in our cohort (53% vs. 47%), which is contrary to what has been reported in the literature. The ethnic distribution was Malays (51%), followed by Chinese (28%) and Indians (8%) (Table 2.5.2(a)). Table 2.5.2(a): Demographic characteristics of patients with IgA nephropathy, Demographic Characteristics n=223 % Age (years) 33.8 ± 12.5 Gender Male Female Malay Race Chinese Indian 18 8 Others

18 PRIMARY GLOMERULONEPHRITIS 2nd Report of the Table (b): Age group at time of biopsy (years) for IgA nephropathy, Age group (years) Total n % n % n % n % n % 15-< < < < < < Total Figure (b): Age at time of biopsy (years) for IgA nephropathy, : Clinical presentation Asymptomatic urine abnormalities remains the most common presentation of IgAN (55%). Up to 25% of those who were biopsied had nephrotic syndrome (Table (a)). This figure was much higher than the 5% quoted the literature and this may reflect relatively conservative local practices with regards to investigation of asymptomatic urine abnormalities. However, it might not be reflective of the true picture due to the small patient numbers in this age group (5 patients). Up to 32% of patients were hypertensive at presentation (Table (b)). Table (a): Clinical presentation for IgA nephropathy, Clinical Presentations Total n % n % n % n % n % Asymptomatic urine abnormality Nephritic syndrome Nephrotic syndrome Nephritic-Nephrotic syndrome Missing Total

19 2nd Report of the PRIMARY GLOMERULONEPHRITIS Figure (a): Clinical presentation for IgA nephropathy, Table (b): Hypertension in IgA nephropathy, Hypertension n % Present Absent Missing 10 4 Total : Clinical presentation by age Asymptomatic urine abnormalities is the most common clinical presentation of IgAN in all age groups except in those above the age of 65 years old. This was followed by nephrotic syndrome. Table : Clinical presentation by age group for IgA nephropathy, Age group (years) Asymptomatic urine abnormality 15- <25 25-<35 35-<45 45-<55 55-<65 <65 Total n % n % n % n % n % n % n % Nephritic syndrome Nephrotic syndrome Nephritic-Nephrotic syndrome Missing Total Clinical presentation by gender More females (58%) than male (51%) presented with asymptomatic urine abnormality. Table : Clinical presentation by gender for IgA nephropathy, Clinical Presentations Male Female n % n % Asymptomatic urine abnormality Nephritic syndrome Nephrotic syndrome Nephritic-Nephrotic syndrome Missing Total

20 PRIMARY GLOMERULONEPHRITIS 2nd Report of the 2.5.4: Renal function at presentation : Renal function at presentation by age Most of the younger patients (age less than 45 years) have preserved renal function at presentation. As expected, older patients have greater degree of renal impairment (Table & Figure ). Table : Renal function at presentation by age group for IgA nephropathy, egfr (ml/min/1.73m 2 ) > 65 Total n % n % n % n % n % n % n % > < Total Figure : Renal function at presentation by age group for IgA nephropathy, Figure : Renal function at presentation according to gender for IgA nephropathy, : Renal function at presentation by gender Male tend to have worse renal function compared to female (54% vs. 41%) have egfr less than 60 ml/min/1.73m 2 (Table & Figure ). Table : Renal function at presentation according to gender for IgA nephropathy, egfr Male Female (ml/min/1.73m 2 ) n % n % > < Total