A retrospective cohort study of Childhood post-streptococcal glomerulonephritis as a risk factor for chronic renal disease in later life Andrew V White, Wendy E Hoy and David A Mc Credie The Medical Journal of Australia, 2001

Abstract Objective: To test the hypothesis that post-streptococcal glomerulonephritis (PSGN) in childhood is a risk factor for chronic renal disease in later life. Design: Retrospective cohort study Setting: A Aboriginal community in the "Top End" of the Northern Territory that experienced two epidemics of PSGN in 1980 and 1987, respectively.

Participants: 472 people who were aged 2-15 years during either epidemic. They were categorised by clinical features recorded during the epidemics as having clinically defined PSGN (63), "abnormal urine" (haematuria or proteinuria; 86) or controls (323). Outcome measures: Urinary albumin to creatinine ratio (ACR), haematuria (by dipstick urinalysis), blood pressure, serum creatinine level, and calculated glomerular filtration rate (GFR) during community screening in Abstract

INTRODUCTION Although unusual in the rest of Australia, post- streptococcal glomerulonephritis (PSGN) is still common in Aboriginal children living in remote communities, where group A streptococcal pyoderma is endemic. 1 1

PSGN is usually followed by clinical recovery over several days to weeks, and the long-term outlook has generally been regarded as excellent, with no increase in risk of urinary abnormalities or hypertension. However, some studies have suggested an increase in rates of chronic renal impairment after this illness INTRODUCTION

We aimed to test whether a history of PSGN in childhood is a risk factor for later renal dysfunction in Aboriginal Australians living in a remote community. The main outcome measure used, albumin to creatinine ratio, is a sensitive early marker of renal damage. Albuminuria has also been shown to mark early chronic renal disease in this population of Aboriginal Australians, and its progression predicts renal failure, as well as cardiovascular disease and mortality

MATERIALS AND METHODS DESIGN : retrospective cohort study of children from an isolated Aboriginal coastal community in the "Top End" of the Northern Territory of Australia. The community experienced two epidemics of PSGN in 1980 and 1987, respectively, each lasting for three months. 14,15 14,15 POPULATION: – Inclusion criteria pediatric patients ( of age) at the time of either epidemic and who participated in health screening examinations between 1992 and These 472 people represented 98% of the population of the community in the relevant age groups, according to 1996 census estimates

Baseline data Edema, Hypertension and urinary abnormalities on dipstick testing; results were recorded in individuals' medical records in the community. PSGN group had documented oedema (facial swelling or dependent oedema) or hypertension (diastolic pressure 80 mmHg if aged 2-12 years and 85 mmHg if over 12, levels corresponding to the 90th percentile for each age range) 17 plus haematuria greater than trace or proteinuria greater than trace on dipstick urinalysis 17 Abnormal urine group had haematuria greater than trace or proteinuria greater than trace, but no oedema or hypertension Control group comprised children who had normal results on clinical examination and urinalysis (trace or less for blood and protein); children with no symptoms suggesting PSGN, but for whom urinalysis was either not performed or not recorded; and children with no entry in the medical record at the time of the epidemics

Outcome measures Population health screening was undertaken in the community between 1992 and – The albumin to creatinine ratio (ACR) was determined in a random urine sample: normal (< 1.1 mg/mmol), suspicious ( mg/mmol), microalbuminuria ( mg/mmol), overt albuminuria (34 mg/mmol). – Glomerular filtration rate (GFR) was calculated using the formula of Cockroft and Gault. 18 Dipstick urinalysis was also performed (Multistix 10SG, Bayer Diagnostics), and blood pressure and serum creatinine level were measured. 18

Results On follow-up screening, 104 participants (22%) had albuminuria of any degree (micro- or overt; ACR 3.4 mg/mmol), 27 (6%) had overt albuminuria (ACR 34 mg/mmol), and 45 (10%) had haematuria ( trace), while 64 (14%) had haematuria or overt albuminuria.

Results Albuminuria and haematuria were more prevalent in the groups with a history of clinical PSGN or abnormal urine during the PSGN epidemics than in the control group (Box 3). In the abnormal urine group, outcomes at follow-up were similar whether or not haematuria had occurred alone or in the presence of proteinuria during the epidemics.Box 3

Outcomes on follow-up screening, by diagnostic category during post-streptococcal glomerulonephritis (PSGN) epidemics Outcome PSGN (n = 63) Abnormal urine (n = 86) Control (n = 323) ACR 34 mg/mmol Rate13%8%4% Crude odds ratio (95% CI)3.8 ( )2.3 ( )1 Adjusted* odds ratio (95% CI)6.1 ( )1.6 ( )1 PAF (95% CI)24% (5%-40%)8% (-14% to 26%) ACR 3.4 mg/mmol Rate32%30%18% Crude odds ratio (95% CI)2.2 ( )2.0 ( )1 Adjusted* odds ratio (95% CI)3.2 ( )1.4 ( )1 PAF (95% CI)11% (4%-18%)5% (-4% to 14%) Haematuria > trace Rate21%9%7% Crude odds ratio (95% CI)3.4 ( )1.4 ( )1 Adjusted* odds ratio (95% CI)3.7 ( )1.1 ( )1 PAF (95% CI)20% (5%-33%)1% (-14% to 14%) Haematuria > trace or ACR 34 mg/mmol Rate30%16%11% Crude odds ratio (95% CI)3.6 ( )1.6 ( )1 Adjusted* odds ratio (95% CI)4.6 ( )1.2 ( )1 PAF (95% CI)19% (8%-29%)3% (-9% to 13%) ACR = albumin to creatinine ratio. PAF = population-attributable fraction. * Adjusted for age and sex.

DISCUSSION This study indicates that a history of PSGN in childhood is a risk factor for albuminuria and haematuria years later, and suggests that about a quarter of cases of overt albuminuria may be attributable to PSGN in childhood. The incidence of renal disease is high in this population of Aboriginal Australians, 12 and other risk factors for renal disease are also common, including low birth weight, recurrent infectious diseases, diabetes and features of syndrome X. 3,12,20, ,12,20,21 Possibly, it is the combination of insults that leads to high risk for later renal disease. A prospective cohort study would provide the best evidence.

CONCLUSION In summary, we have presented evidence that, in this community, a remote history of PSGN in childhood is a powerful risk factor for renal damage, as evidenced by increased ACR and haematuria. These findings are important as PSGN is still prevalent in children living in Aboriginal communities in Australia. Prevention of PSGN is possible through improvements to housing, economic and living conditions, along with attention to control and treatment of scabies and skin infections. Preventing PSGN may contribute to reducing the incidence of renal disease and renal failure in the future.