CHAPTER 3. Secondary Glomerulonephritis
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1 CHAPTER 3 Secondary Glomerulonephritis Rosnawati Yahya Liew Yew Foong 59
2 3.1: Introduction This chapter covers the main secondary glomerulonephritis that were reported to the MRRB from the year Lupus nephritis is the commonest secondary glomerulonephritis in adult contributing to 84% of all total secondary glomerulonephritis in Malaysia. Diabetic nephropathy contributed about 11%. Other causes of secondary glomerulonephritis are relatively uncommon (Table 3.1). Table 3.1: Causes of secondary glomerulonephritis in adult, Total n % n % n % n % n % n % n % Type of secondary GN Other infection Lupus nephritis Henoch Schoenlein Purpura HUS/TTP* Amyloidosis Systemic vasculitis Post infectious GN Polyarteritis nodosa Malignancy Light/heavy chain disease Diabetic nephropathy Anti-GBM antibody disease Immunotactoid glomerulopathy Multiple myeloma Idiopathic Crescentic GN Not available/missing Total * Hemolytic uraemic syndrome/thrombotic thrombocytopenic purpura 60
3 3.2: Lupus Nephritis 3.2.1: Introduction Lupus nephritis is the commonest secondary glomerulonephritis in Malaysia. This section describes lupus nephritis in adult population (defined as more than 15 years of age) : Patient population and characteristics There was a total of 1372 biopsy-proven lupus nephritis in 1691 patients reported in the period of 1st January 2005 until 31st December : Age at time of biopsy The mean age of adult patients with lupus nephritis at the time of biopsy was ± years (range: years). The most predominant age group was between 15 to 25 years old, which accounted for 38% of cases. The onset of lupus above the age of 45 was uncommon and constituted about 10.5% of cases (Table & Figure ). Table (a): Age group at time of biopsy (years), Year Total n Mean Standard Deviation Median Interquartile range Minimum Maximum Figure : Age group at time of biopsy (years),
4 : Gender distribution Lupus nephritis predominantly affects females with female: male ratio of 7.26: 1. Figure : Gender distribution, : Racial Distribution Fifty-eight percent of patients with lupus nephritis were Malays, 29.8% were Chinese, 4% were Indian and 8.1 % were of other races (mainly indigenous population of Malaysia). Figure : Racial distribution,
5 3.2.3: Clinical presentation In adult patients with lupus nephritis, 36% presented with urine abnormalities, 11% with nephritic syndrome, 31% with nephrotic syndrome and 12% presented with a combination of nephritic and nephrotic picture. There has been an increased in incidence in the latter presentation in recent years. Data were missing in about 11% of cases (Figure 3.2.3). At the time of presentation, % had impaired renal function (defined by egfr by modified MDRD of less than 60 ml/min/1.72m2). The incidence of hypertension increased almost two fold from 2007 to 2008 (Figure (a) & (b). Figure 3.2.3: Clinical presentation by year, Figure (a): Hypertension by year, Figure (b) Impaired renal function by year,
6 : Clinical Presentation by age Urine abnormalities were the commonest clinical presentation of lupus nephritis in all age group. This was followed by nephrotic syndrome (Table & Figure (a)). The prevalence of hypertension was between 20-25% across all age groups (Figure (b)). The prevalence of impaired kidney function (e-gfr of < 60ml/min/1.73 m2) was higher in older age groups (Figure (c)). Table (a): Clinical presentation by age group, <25 25-<35 35-<45 45-<55 55-<65 65 Total n % n % n % n % n % n % n % Age group (years) Urine abnormality Nephritic syndrome Nephrotic syndrome Nephrotic-Nephritic Not available/missing TOTAL Figure (a): Clinical presentation by age group,
7 Figure (b) Hypertension by age group Figure (c): Impaired renal function by age group, : Clinical presentation by gender There were no differences in the clinical presentation, prevalence of hypertension and proportion of patients with impaired renal function between the two genders (Figure (a,b & c)). Figure (a): Clinical presentation by gender, Figure (b): Hypertension by gender, Figure (c): Impaired renal function by gender,
8 : Clinical Presentation by histopathology There were no clear correlation between histopathological findings and clinical presentation. However, class IV and class IV+V were more likely to present with symptomatic renal disease, with 58.8% had symptomatic renal disease at presentation. In comparison, those with class II, only 43.3% had symptomatic renal disease (Table & Figure (a)). The prevalence of hypertension was higher in class IV & IV+V lupus nephritis (Figure (b)). The prevalence of impaired kidney function correlated with histopathological findings. The proportion of patients with e-gfr < 60 ml/min/1.72 m 2 were 44.2%, 21.8%, 19.7% and 10.5% in class IV or IV+V, class III or V+III, class V and class II respectively (Figure (c)). Table (a): Clinical presentation by histopathology in lupus nephritis, I II III & III + V IV & IV + V V & II + V VI Total n % n % n % n % n % n % n % Clinical Presentations Urine abnormality Nephritic syndrome Nephrotic syndrome Nephrotic nephritic syndrome Not available/missing Total * 26 cases are missing on lupus subclass Figure (a): Clinical presentation by histopathology in lupus nephritis,
9 Figure (b) Hypertension by histopathology, Figure (c): Impaired renal function by histopathology, : Renal function at presentation. Thirty-four percent of all patients have impaired renal function (defined as e-gfr < 60ml/min/1.73 m2) at the time of presentation and 6.3% percent had e-gfr < than 15 ml/min (Table ) : Renal function at presentation by age group The frequency of impaired renal function increases after the age of 35. Between 27-33% has e-gfr less than 60 ml/min below the age of 35 and rises to 39% in the age group of 35 to 45 and 54.6% in age group of 45 to 55 (Table & Figure ). Table : Renal function by age group in lupus nephritis, e-gfr (ml/min/1.73m 2 ) 15-<25 25-<35 35-<45 45-<55 55-<65 >65 Total n % n % n % n % n % n % n % < to < to < to < > Missing* Total Figure : Renal function by age group in lupus nephritis,
10 : Renal function at presentation by gender There were no differences in the renal function at presentation between the two genders (Figure ). Figure : Renal function at presentation by gender, : Renal function at presentation by histopathology Class IV and V+IV have worse renal function than class III or class V+III in the proliferative group (Table ). Table : Renal function at presentation by histopathology, Total I II III & III + V IV & IV + V V & II + V VI Others n % n % n % n % n % n % n % e-gfr (ml/min/1.72m 2 ) < > Missing** Total * 26 cases are missing on lupus subclass 68
11 3.2.5: Histopathological diagnosis There were a total of 1665 adult biopsies with a diagnosis of lupus nephritis. Data on the lupus subclass were incomplete in 18 cases. The distribution of histopathological class based on WHO or ISN/RPS classification is summarized in table Class IV and IV+V are the predominant biopsy findings accounting for 57.8 % of patients diagnosed with lupus nephritis, followed by class III and III+V which contributes about 21.5%. There was little class I and VI lupus nephritis reported to the registry. Table 3.2.5: Histopathological diagnosis in lupus nephritis by year, Total n % n % n % n % n % n % n % WHO or ISN/ RPS classification Class I Class II Class III and III+V Class IV and IV+V Class V and II+V Class VI Others Total * 26 cases are missing on lupus subclass 69
12 : Histopathological diagnosis by age In adults, class IV or V+IV were the most predominant lesion in all age groups. However, the frequency of class IV and IV+V were less with increasing age (Table ). Table : Histopathological diagnosis by age group in lupus nephritis, <25 25-<35 35-<45 45-<55 55-<65 >65 Total n % n % n % n % n % n % n % Histopathology Class I Class II Class III and III+V Class IV and IV+V Class V and II+V Class VI Others Total * 26 cases are missing on lupus subclass 70
13 : Histopathological diagnosis by gender Class IV and IV+V was the commonest histopathological finding in both genders. Class IV or IV+V occurred in higher frequency in females, whereas class V occurred in higher frequency in males (Table ). Table : Histopathological diagnosis by gender in lupus nephritis, Histopathology Male Female Total n % n % n % Class I Class II Class III and III+V Class IV and IV+V Class V and II+V Class VI Others Total * 26 cases are missing on lupus subclass : Histopathological diagnosis by clinical presentation Urine abnormalities were the most common clinical presentation, followed by nephrotic syndrome. Sixty-eight percent with nephritic-nephrotic, 63.3% with nephrotic syndrome and 65.7% with nephritic syndrome had class IV or class V+IV lupus nephritis. (Table ). Table : Histopathological diagnosis by clinical presentation, Histopathology Urine Nephritic- Not available/ Nephritic Nephrotic Total abnormality Nephrotic Missing n % n % n % n % n % n % Class I Class II Class III and III+V Class IV and IV+V Class V and II+V Class VI Others Total * 26 cases are missing on lupus subclass 71
14 3.2.6: Extra-renal involvement : American Rheumatological Association (ARA) criteria in lupus nephritis. About 2/3 of cases of lupus nephritis fulfilled 4 or more ARA criteria at the time of presentation (Table ). Table : ARA criteria in lupus nephritis, Number of ARA criteria Total n % n % n % n % n % n % < and more Total : ARA criteria in lupus nephritis by age In patients less than 35 years of age, about 2/3 satisfied the ARA criteria for the diagnosis of SLE. However, in the older patients more than 35 years old, there was less proportion of patients fulfill the ARA criteria. There were only 24 patients aged 55 years and above (Figure ). Figure : ARA criteria by age group, : ARA criteria by gender The proportion of patients that fulfilled 4 or more ARA criteria at the time of presentation is slightly more in female than male (63.9% versus 53.7%) (Figure ). Figure : ARA criteria by gender,
15 : ARA criteria by histopathological findings Fulfilling ARA criteria does not predict the severity of renal lesion in lupus nephritis. Figure : ARA criteria by histopathology, : Extra-renal involvement In patients with lupus nephritis, 53% had mucocutaneous involvement, 35% had arthritis, 9% had serositis, 11% had cerebral involvements and 40% had haematological involvements (Table (a)). Mucocutaneous involvement, serositis and especially arthritis were more common in females than in males. Neurological involvements were slightly more common in males (Table & Figure (a)). Of those with mucocutaneous involvement, the frequency of discoid rash was higher in male and there was no difference in the frequency of malar rash, photosensitivity or oral ulcers between the two genders (Table & Figure (b). Table (a): Extra-renal involvement by gender, Other organs involvement Male (n=203) Female (n=1488) Total (n=1691) n % n % n % Mucocutaneous Arthritis Serositis Cerebral Haematological Total *Patients may have 1 or more other organ involvements 73
16 Figure (a): Extra-renal involvement by gender, Table (b): Mucocutaneous involvement by gender in lupus nephritis, Mucocutaneous involvement Male Female Total (n=95) (n=803) (n=898) n % n % n % Malar rash Discoid rash Photosensitivity Oral ulcer Total *Patients may have 1 or more other organ involvements Figure (b): Mucocutaneous involvement by gender in lupus nephritis,
17 3.2.7 Survival in lupus nephritis Patient survival in lupus nephritis Table & Figure shows that patient survival was 92.8% at 1 year and 87.7 % at 3 years from the time of renal biopsy. Table : Patients Survival estimates for death in lupus nephritis Interval (months) SLE patients survival n % survival SE *Missing of 7 censored cases where the outcome date < date of 1st biopsy Event = death; Status as at 31 Dec 2011 or last follow-up Figure : Patients Survival estimates for death in lupus nephritis 75
18 : Renal survival in lupus nephritis Table & Figure shows that renal survival was 98.2% at 1 year and 96.5% at 3 years from the time of renal biopsy. Table : Renal Survival estimates for lupus nephritis Interval (months) SLE patients survival n % survival SE *Missing of 4 censored and 3 event cases where the outcome date < date of 1st biopsy Event = ESRF; Status as at 31 Dec 2011 or died or last follow-up Figure : Renal Survival estimates for lupus nephritis 76
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