Cross-sectional associations of albuminuria among Aboriginal and Torres Strait Islander adults: the eGFR Study.

OBJECTIVE: To describe the detailed associations of albuminuria among a contemporary cohort of Aboriginal and Torres Strait Islander people to inform strategies for chronic kidney disease prevention and management. METHODS: A cross-sectional analysis of Indigenous participants of the eGFR Study. MEASURES: Clinical, biochemical and anthropometric measures were collected (including body-circumferences, blood pressure (BP); triglycerides, HbA1c, liver function tests, creatinine; urine- microscopic-haem, albumin: creatinine ratio (ACR), prescriptions- angiotensin converting enzyme inhibitor or angiotensin receptor II antagonist (ACEI/ARB). Albuminuria and diabetes were defined by an ACR>3.0 mg/mmol, and HbA1c≥48 mmol/mol or prior history respectively. Waist: hip ratio (WHR), and estimated glomerular filtration rate (eGFR) were calculated. ACR was non-normally distributed; a logarithmic transformation was applied (in base 2), with each unit increase in log2-albuminuria representing a doubling of ACR. RESULTS: 591 participants were assessed (71% Aboriginal, 61.6% female, mean age 45.1 years, BMI 30.2 kg/m2 , WHR 0.94, eGFR 99.2 ml/min/1.73m2 ). The overall prevalence of albuminuria, diabetes, microscopic-haem and ACEI/ARB use was 41.5%, 41.5%, 17.8% and 34.7% respectively; 69.3% of adults with albuminuria and diabetes received an ACEI/ARB. Using multivariable linear regression modelling, the potentially modifiable factors independently associated with log2-albuminuria were microscopic-haem, diabetes, WHR, systolic BP, alkaline phosphatase (all positive) and eGFR (inverse). CONCLUSION: Albuminuria is associated with diabetes, central obesity and haematuria. High ACEI/ARB prescribing for adults with diabetes and albuminuria was observed. Further understanding of the links between fat deposition, haematuria and albuminuria is required.

Bilirubin concentration is positively associated with haemoglobin concentration and inversely associated with albumin to creatinine ratio among Indigenous Australians: eGFR Study.

Low serum bilirubin concentrations are reported to be strongly associated with cardio-metabolic disease, but this relationship has not been reported among Indigenous Australian people who are known to be at high risk for diabetes and chronic kidney disease (CKD). HYPOTHESIS: serum bilirubin will be negatively associated with markers of chronic disease, including CKD and anaemia among Indigenous Australians. METHOD: A cross-sectional analysis of 594 adult Aboriginal and Torres Strait Islander (TSI) people in good health or with diabetes and markers of CKD. Measures included urine albumin: creatinine ratio (ACR), estimated glomerular filtration rate (eGFR), haemoglobin (Hb) and glycated haemoglobin (HbA1c). Diabetes was defined by medical history, medications or HbA1c≥6.5% or ≥48mmol/mol. Anaemia was defined as Hb<130g/L or <120g/L in males and females respectively. A multivariate regression analysis examining factors independently associated with log-bilirubin was performed. RESULTS: Participants mean (SD) age was 45.1 (14.5) years, and included 62.5% females, 71.7% Aboriginal, 41.1% with diabetes, 16.7% with anaemia, 41% with ACR>3mg/mmol and 18.2% with eGFR<60mL/min/1.73m2. Median bilirubin concentration was lower in females than males (6 v 8µmol/L, p<0.001) and in Aboriginal than TSI participants (6 v 9.5µmol/L, p<0.001). Six factors explained 35% of the variance of log-bilirubin; Hb and cholesterol (both positively related) and ACR, triglycerides, Aboriginal ethnicity and female gender (all inversely related). CONCLUSION: Serum bilirubin concentrations were positively associated with Hb and total cholesterol, and inversely associated with ACR. Further research to determine reasons explaining lower bilirubin concentrations among Aboriginal compared with TSI participants are needed.

Associations of serum adiponectin with markers of cardio-metabolic disease risk in Indigenous Australian adults with good health, diabetes and chronic kidney disease.

The higher serum adiponectin concentrations observed in females are often attributed to differences in adiposity or sex hormones. There is little data describing adiponectin in Indigenous Australians, and no studies examining its association with cardio-metabolic disease risk markers and chronic kidney disease (CKD). AIM: To describe the relationship of serum adiponectin with cardio-metabolic disease risk markers and kidney function in a community-based sample of Indigenous Australian adults, with particular reference to sex-specific differences. METHODS: A cross-sectional analysis of a community-based volunteer sample of 548 Indigenous Australian adults (62% female), stratified into five cardio-metabolic risk groups ranging from good health (strata-1) to high cardio-metabolic risk and low measured glomerular filtration rate (mGFR, <60ml/min/1.73m2) (strata-5). We examined serum adiponectin concentrations with cardio-metabolic risk markers, albuminuria and mGFR. RESULTS: Indigenous Australian females had a lower than expected adiponectin concentration (3.5µg/ml), which was higher than males in strata 1-4 (as in other populations), but not in strata-5 (mGFR<60, p=0.19), and higher leptin: adiponectin ratio than other populations (7.8ng/µg - strata-1, healthy females; 12.2ng/µg - strata-3, females with diabetes and mGFR≥90). Female-gender, HDL-cholesterol (positive), mGFR and waist: hip ratio (WHR) (inverse) were independently associated with log-adiponectin when mGFR≥60; when mGFR<60, female-gender was associated with 0.27 units lower log-adiponectin. CONCLUSION: Female-gender was not associated with higher adiponectin concentrations in Indigenous Australians with mGFR<60ml/min/1.73m2. High WHR was frequent in both genders, and inversely associated with adiponectin. Longitudinal studies are needed to examine relationships of serum adiponectin, obesity and cardiovascular disease events in Indigenous Australians.

Performance of formulas for estimating glomerular filtration rate in Indigenous Australians with and without Type 2 diabetes: the eGFR Study.

AIMS: It has been proposed that the Chronic Kidney Disease Epidemiology Collaboration formula estimates glomerular filtration rate more accurately than the Modification of Diet in Renal Disease formula. With the very high incidence of diabetes and end-stage kidney disease in Indigenous Australians, accurate estimation of glomerular filtration rate is vital in early detection of kidney disease. We aimed to assess the performance of the Chronic Kidney Disease Epidemiology Collaboration, Modification of Diet in Renal Disease and Cockcroft-Gault formulas in Indigenous Australians with and without diabetes. METHODS: Indigenous Australians with (n = 224) or without (n = 340) Type 2 diabetes had a reference glomerular filtration rate measure using plasma disappearance of iohexol (measured glomerular filtration rate) over 4 h. Serum creatinine was measured by an enzymatic method. Performance was assessed by bias (measured glomerular filtration rate - estimated glomerular filtration rate) and accuracy (percentage of estimated glomerular filtration rate within 30% of measured glomerular filtration rate). RESULTS: The median measured glomerular filtration rate (interquartile range) in participants with or without diabetes was 97 (68-119) and 108 (90-122) ml min(-1)  1.73 m(-2) , respectively. The Chronic Kidney Disease Epidemiology Collaboration formula had smaller bias and greater accuracy than the Modification of Diet in Renal Disease and Cockcroft-Gault formulas overall, for participants both with and without diabetes. However, for estimated glomerular filtration rate > 90 ml min(-1)  1.73 m(-2) , the Chronic Kidney Disease Epidemiology Collaboration formula had greater bias in participants with diabetes, underestimating measured glomerular filtration rate by 7.4 vs. 1.0 ml min(-1)  1.73 m(-2) in those without diabetes. The Chronic Kidney Disease Epidemiology Collaboration formula was less accurate across the whole range of estimated glomerular filtration rates in participants with vs. those without diabetes (87.1% vs. 93.3%). CONCLUSIONS: The Chronic Kidney Disease Epidemiology Collaboration formula outperforms the Modification of Diet in Renal Disease and Cockcroft-Gault formulas overall in Indigenous Australians with and without diabetes. However, the Chronic Kidney Disease Epidemiology Collaboration formula has greater bias in people with diabetes compared with those without diabetes, especially in those with normal renal function.

Distribution of volumes of individual glomeruli in kidneys at autopsy: association with age, nephron number, birth weight and body mass index.

BACKGROUND: Glomerular hypertrophy occurs in a number of normal and pathological states. Glomerular volume in kidneys at autopsy is usually indirectly derived from estimates of total glomerular mass and nephron number, and provides only a single value per kidney, with no indication of the range of volumes of glomeruli within the kidney of any given subject. We review findings of the distribution of volumes of different glomeruli within subjects without kidney disease, and their correlations with age, nephron number, birth weight and body mass index (BMI). METHODS: The study describes findings from autopsy kidneys of selected adult white males from the Southeast USA who had unexpected deaths, and who did not have renal scarring or renal disease. Total glomerular (nephron) number and total glomerular volume were estimated using the disector/fractionator combination, and mean glomerular volume (Vglom) was derived. The volumes of 30 individual glomeruli (IGV) in each subject were determined using the disector/Cavalieri method. IGV values were compared by categories of age, nephron number, birth weight and BMI. RESULTS: There was substantial variation in IGV within subjects. Older age, lower nephron number, lower birth weight and gross obesity were associated with higher mean IGV and with greater IGV heterogeneity. High Vglom and high IGVs were associated with more glomerulosclerosis. However, amongst the generally modest numbers of sclerosed glomeruli, the pattern was uniformly of ischemic collapse of the glomerular tuft. There was no detectable focal segmental glomerular tuft injury. DISCUSSION: In this series of people without overt renal disease, greater age, nephron deficit, lower birth weight and obesity were marked by glomerular enlargement and greater glomerular volume heterogeneity within individuals.

Recent patterns in chronic disease mortality in remote living Indigenous Australians.

BACKGROUND: Despite the well-recognised Indigenous-non-Indigenous health disparity, some reports suggest improvements in Indigenous mortality. Our aim was to quantify Indigenous mortality in Outer Regional (OR), Remote (R), and Very Remote (VR) areas in New South Wales, Queensland, South Australia, Western Australia, and the Northern Territory and changes in mortality from 1998 to 2005. METHODS: We calculated rates, standardized mortality ratios (SMRs) and percentage change in annual rates of Indigenous cardiovascular, diabetes and renal mortality mentioned anywhere on the death certificate by using ICD-10 codes and the 2001 total Australian population as the reference population. RESULTS: In 1998-2001, Indigenous SMRs for all-cause mortality were 241%, 421% and 220% in OR, R and VR, respectively. In 2001-03, corresponding SMRs were 202%, 331% and 176%. Percentage changes (95% confidence interval) in annual all-cause mortality were -3.0% (-5.3%, -0.7%) in OR, -4.2% (-7.4%, -0.9%) in R and -0.5 (-9.1%, -0.7%) in VR. In 2002-2005, compared with 1998-2001, changes in the number of Indigenous deaths were -147, -195, and -197 in OR, R and VR, respectively. Similar patterns and trends were observed for cardiovascular mortality. CONCLUSIONS: Mortality was elevated about 2-fold in OR, 4-fold in R and 2-fold in VR areas. The downward trend in mortality regardless of remoteness of residence was partly attributable to a decrease in the absolute number of deaths. These patterns were observed for each of the states/territories individually.

Lessons in ethnonephrology.

Only recently has the nephrology community moved beyond a fairly singular focus on terminal kidney failure to embrace population-based studies of earlier stages of disease, its markers and risk factors, and of interventions. Observations in developing countries, and in minority, migrant, and disadvantaged groups in westernized countries, have promoted these developments. We are only beginning to interpret renal disease in the context of public health history, social and health transitions, changing population demography, and competing mortality. Its intimate relationships to other health issues are being progressively exposed. Perspectives on the multideterminant etiology of most disease and the pedestrian nature of most risk factors are maturing. We are challenged to reconcile epidemiologic patterns with morphology in diseased renal tissue, and to consider structural markers, such as nephron number and glomerular size, as determinants of disease susceptibility. New work force models are mandated for population-based studies and intervention programs. Intervention programs need to be integrated with other chronic disease initiatives and nested in a matrix of systematic primary care, and although flexible to changing needs, must be sustained over the long term. Cross-disciplinary collaboration is essential in designing those programs, and in promoting them to health-care funders. Substantial expansion and restructuring of the discipline is needed for the nephrology community to participate effectively in those processes.

Reduced nephron number and glomerulomegaly in Australian Aborigines: a group at high risk for renal disease and hypertension.

Aborigines in remote areas of Australia have much higher rates of renal disease, as well as hypertension and cardiovascular disease, than non-Aboriginal Australians. We compared kidney findings in Aboriginal and non-Aboriginal people in one remote region. Glomerular number and mean glomerular volume were estimated with the disector/fractionator combination in the right kidney of 19 Aborigines and 24 non-Aboriginal people undergoing forensic autopsy for sudden or unexpected death in the Top End of the Northern Territory. Aborigines had 30% fewer glomeruli than non-Aborigines--202,000 fewer glomeruli per kidney, or an estimated 404,000 fewer per person (P=0.036). Their mean glomerular volume was 27% larger (P=0.016). Glomerular number was significantly correlated with adult height, inferring a relationship with birthweight, which, on average, is much lower in Aboriginal than non-Aboriginal people. Aboriginal people with a history of hypertension had 30% fewer glomeruli than those without--250,000 fewer per kidney (P=0.03), or 500,000 fewer per person, and their mean glomerular volume was about 25% larger. The lower nephron number in Aboriginal people is compatible with their susceptibility to renal failure. The additional nephron deficit associated with hypertension is compatible with other reports. Lower nephron numbers are probably due in part to reduced nephron endowment, which is related to a suboptimal intrauterine environment. Compensatory glomerular hypertrophy in people with fewer nephrons, while minimizing loss of total filtering surface area, might be exacerbating nephron loss. Optimization of fetal growth should ultimately reduce the florid epidemic of renal disease, hypertension, and cardiovascular disease.

Hypertension, glomerular number, and birth weight in African Americans and white subjects in the southeastern United States.

Low nephron number has been related to low birth weight and hypertension. In the southeastern United States, the estimated prevalence of chronic kidney disease due to hypertension is five times greater for African Americans than white subjects. This study investigates the relationships between total glomerular number (Nglom), blood pressure, and birth weight in southeastern African Americans and white subjects. Stereological estimates of Nglom were obtained using the physical disector/fractionator technique on autopsy kidneys from 62 African American and 60 white subjects 30-65 years of age. By medical history and recorded blood pressures, 41 African Americans, and 24 white subjects were identified as hypertensive and 21 African Americans and 36 white subjects as normotensive. Mean arterial blood pressure (MAP) was obtained on 81 and birth weights on 63 subjects. For African Americans, relationships between MAP, Nglom, and birth weight were not significant. For white subjects, they were as follows: MAP and Nglom (r=-0.4551, P=0.0047); Nglom and birth weight (r=0.5730, P=0.0022); MAP and birth weight (r=-0.4228, P=0.0377). For African Americans, average Nglom of 961 840+/-292 750 for normotensive and 867 358+/-341 958 for hypertensive patients were not significantly different (P=0.285). For white subjects, average Nglom of 923 377+/-256 391 for normotensive and 754 319+/-329 506 for hypertensive patients were significantly different (P=0.03). The data indicate that low nephron number and possibly low birth weight may play a role in the development of hypertension in white subjects but not African Americans.

Chronic kidney disease management--what can we learn from South African and Australian efforts?

BACKGROUND: The prevalence of chronic kidney disease is on the rise. Our objective is to describe two programs to improve the awareness and management of hypertension, renal disease, and diabetes in remote Australian Aboriginal and urban and periurban South African communities. We focus on how the Australian Aboriginal and South African Chronic Disease Outreach Programs have worked together. METHODS: The establishment of prevention programs in developing countries is a challenge. The paper evaluates these challenges, including accessing international aid. The programs advocate that regular integrated checks for chronic disease and their risk factors are essential elements of regular adult health care. Programs should be run by primary health workers, following algorithms for testing and treatment, and a backup provided by nurse coordinators. Constant evaluation is essential to develop community health profiles and adapt program structure. RESULTS: Both programs are discussed, including how they are organized to deliver preventative and treatment strategies. The challenges and adaptations required are outlined. CONCLUSIONS: It is the aim of the international kidney community to prevent chronic kidney disease. The South African and Australian groups highlight the need for a systematic and sustained approach to the management of chronic diseases to achieve this goal.

Body size measurements as predictors of type 2 diabetes in Aboriginal people.

OBJECTIVE: To investigate waist circumference, waist-to-hip ratio, body mass index (BMI), weight and hip circumference as risk factors for type 2 diabetes in Aboriginal Australians. DESIGN: Community-based cross-sectional study. SUBJECTS: In total, 915 Australian Aboriginal adults (age: 18-74 y) from a remote Aboriginal community in the Northern Territory of Australia. MEASUREMENTS: Body size measurements included waist circumference, waist-to-hip ratio, BMI, weight and hip circumference. Diabetes status was determined according to medical history and fasting and 2-h postload plasma glucose values. Logistic regression was used to calculate odds ratio for diabetes associated with 1 standard deviation (s.d.) increase in a body size measurement. The areas under the ROC curves of five body size measurements were calculated and compared. RESULTS: Risk of diabetes increased with increasing levels of body size. ORs (95% CI) for diabetes with adjustment for age and sex were 2.16 (1.75, 2.66), 1.80 (1.49, 2.17), 1.41 (1.17, 1.71), 1.81 (1.51, 2.19) and 1.84 (1.50, 2.24) associated with 1 s.d. increase in waist circumference, BMI, weight, waist-to-hip ratio, and hip circumference, respectively. The area under the ROC curve for waist circumference was significantly higher than those for other measurements. CONCLUSION: Waist circumference is the best body size measurement in predicting diabetes in Aboriginal people.

Waist circumference, body mass index, hip circumference and waist-to-hip ratio as predictors of cardiovascular disease in Aboriginal people.

OBJECTIVE: To investigate waist circumference (WC), waist-hip ratio, hip circumference and body mass index (BMI) as risk factors for cardiovascular disease in Aboriginal Australians. METHODS: This cohort study included 836 adults aged 20-74 y in a remote Aboriginal community. WC, waist-hip ratio, hip circumference and BMI were obtained from a screening program. The participants were followed for up to 10 y for cardiovascular events. A Cox regression model was used to calculate the rate ratio (RR) and 95% confidence interval (CI) for the first-ever cardiovascular event (fatal and nonfatal). RESULTS: RRs for the first-ever cardiovascular event were 1.31 (95% CI: 1.11, 1.54), 1.29 (95% CI: 1.09,1.53), 1.28 (95% CI: 1.08, 1.52) and 1.10 (95% CI: 0.93, 1.30) per standard deviation increase in WC, BMI, hip circumference and waist-hip ratio, respectively, after adjustment for diabetes mellitus, total cholesterol, systolic blood pressure and smoking status. WC, BMI and hip circumference were significantly associated with cardiovascular risk, independent of other cardiovascular risk factors. Dividing each of the four parameters into quartiles, WC had the highest likelihood statistics (12.76) followed by BMI (11.45), hip circumference (10.57) and waist-hip ratio (3.15) for predicting first CV events. CONCLUSION: WC, BMI and hip circumference are associated with cardiovascular outcome, independent of traditional risk factors. However, WC appears to be a better predictor for cardiovascular risk than other parameters. Waist-hip ratio is not as useful as other measurements.

The natural history of renal disease in Australian Aborigines. Part 1. Changes in albuminuria and glomerular filtration rate over time.

BACKGROUND: The purpose of this study was to describe changes over time in albuminuria and glomerular filtration rate (GFR) in a cohort of Australian Aborigines from a community with high rates of renal disease and renal failure. METHODS: Participants were 486 adult community members (20+ years at first exam) who were screened for renal disease and related factors on at least two occasions (mean 2.7 occasions), at least a year apart, between 1990 and 1997. Renal function was assessed by the albumin:creatinine ratio (ACR; g/mol) on a random urine specimen and by the GFR estimated from the Cockcroft-Gault formula. Evolution over time was expressed as the average annual changes in these parameters. RESULTS: On baseline examination, 70% of participants had albuminuria (ACR 1.1+ g/mol) There was a significant net increase in ACR and a fall in GFR in the cohort over time. Among individuals, however, changes were strongly correlated with ACR levels at baseline. There was no loss of GFR in persons with normal renal parameters at baseline and a rapid loss of GFR in those with substantial levels of albuminuria at baseline. Other factors significantly correlated with progression of ACR included age, baseline body mass index and systolic blood pressure, the presence of diabetes (or levels of fasting glucose), and elevated levels of serum gamma glutamyl transferase. Factors significantly associated with loss of GFR included body mass index, diabetes, systolic and diastolic blood pressures, microscopic hematuria, and marginally high cholesterol levels. CONCLUSION: Albuminuria progresses and GFR is lost over time in individuals in this community, at rates that are strongly dependent on levels of pre-existing albuminuria. Much loss of GFR and all renal failure should be avoided by preventing the development of albuminuria and minimizing its progression. This depends on improving the weight, blood pressure, and metabolic profile of the entire community and reducing infections. Modification of the course in people with established disease depends on vigorous control of blood pressure and the metabolic profile and the specific use of angiotensin-converting enzyme inhibitors.

The natural history of renal disease in Australian Aborigines. Part 2. Albuminuria predicts natural death and renal failure.

BACKGROUND: The purpose of this study was to describe the relationship of albuminuria and glomerular filtration rate (GFR) with natural death and renal failure in an Australian Aboriginal community with high rates of renal disease. METHODS: Study subjects were 825 adults (18+ years, mean 33.6 years) or 88% of adults in a remote community who participated in a health screening program offered between 1990 and 1997. The urinary albumin:creatinine ratio (ACR; g/mol) was used as the renal disease marker. Participants were followed for 1.0 to 9.8 years (mean 5.8 years) until renal failure, death, the start of systematic antihypertensive/renal-protective treatment or June 30, 2000. RESULTS: Sixty-five people reached a terminal end point of renal failure or natural death. Sixteen people developed terminal renal failure, all of whom had an ACR of 34+ at baseline exam. There were 49 other natural deaths, which were also strongly correlated with increasing ACR and decreasing GFR over a wide range. This was observed in people without diabetes and in people with normal and elevated blood pressures. It applied to deaths associated with cardiovascular disease and to deaths without an assigned primary or underlying cardiovascular or renal cause. With adjustment for age, the association with death was more robust with ACR than GFR. When compared with people with an ACR <3.4, the hazard ratio (HR; 95% CI) for nonrenal natural death of persons with an ACR 3.4 to 33 was 3.0 (1.1 to 8.4), with an ACR 34 to 99, it was 5.4 (1.8 to 15.9), and with an ACR 100+, it was 6.5 (2.0 to 21). Regression equations predicted that each tenfold increase in the ACR was associated with a 3.7-fold increase in all-cause natural death: a> 400-fold increase in renal deaths, a 4-fold increase in cardiovascular deaths, and a 2.2-fold increase in nonrenal noncardiovascular deaths. Eighty-four percent of all-cause natural death was associated with pathologic albuminuria. CONCLUSION: All renal failure develops out of a background of persistent albuminuria in this population. More important, albuminuria and, inversely, GFR are powerful markers of risk for nonrenal natural death, including, but not restricted to, cardiovascular deaths. Most of the risk for premature death can be assessed by a simple urine test, and interventions that prevent development and progression of albuminuria and loss of GFR should not only prevent renal insufficiency, but powerfully reduce mortality from natural causes as well.

Childhood post-streptococcal glomerulonephritis as a risk factor for chronic renal disease in later life.

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 remote 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 1992-1998. RESULTS: Overt albuminuria (ACR > 34 mg/mmol) was present at follow-up in 13% of the PSGN group, 8% of the abnormal urine group, and 4% of the control group. The odds ratio (OR) for overt albuminuria in those with a history of PSGN compared with the control group, adjusted for age and sex, was 6.1 (95% CI, 2.2-16.9). Haematuria (>trace) was present in 21% of the PSGN group compared with 7% of the control group (adjusted OR, 3.7; 95% CI, 1.8-8.0). There were no significant differences between the groups in blood pressure, serum creatinine level or calculated GFR. CONCLUSION: In this population, a history of PSGN in childhood is a risk factor for albuminuria and haematuria in later life.

Cyclosporine in patients with steroid-resistant membranous nephropathy: a randomized trial.

BACKGROUND: A clinical trial of cyclosporine in patients with steroid-resistant membranous nephropathy (MGN) was conducted. Although MGN remains the most common cause of adult-onset nephrotic syndrome, its management is still controversial. Cyclosporine has been shown to be effective in cases of progressive MGN, but it has not been used in controlled studies at an early stage of the disease. METHODS: We conducted a randomized trial in 51 biopsy-proven idiopathic MGN patients with nephrotic-range proteinuria comparing 26 weeks of cyclosporine treatment plus low-dose prednisone to placebo plus prednisone. All patients were followed for an average of 78 weeks, and the short- and long-term effects on renal function were assessed. RESULTS: Seventy-five percent of the treatment group versus 22% of the control group (P < 0.001) had a partial or complete remission of their proteinuria by 26 weeks. Relapse occurred in 43% (N = 9) of the cyclosporine remission group and 40% (N = 2) of the placebo group by week 52. The fraction of the total population in remission then remained almost unchanged and significant different between the groups until the end of the study (cyclosporine 39%, placebo 13%, P = 0.007). Renal function was unchanged and equal in the two groups over the test medication period. In the subsequent follow-up, renal insufficiency, defined as doubling of baseline creatinine, was seen in two patients in each group, but remained equal and stable in all of the other patients. CONCLUSION: This study suggests that cyclosporine is an effective therapeutic agent in the treatment of steroid-resistant cases of MGN. Although a high relapse does occur, 39% of the treated patients remained in remission and were subnephrotic for at least one-year post-treatment, with no adverse effect on filtration function.

Glomerular size and glomerulosclerosis in Australian aborigines.

We have previously described the prevalence of glomerulomegaly in biopsy specimens from Australian Aborigines with renal disease, a phenomenon documented in a number of other indigenous populations. Many of the biopsy specimens showed variable degrees of focal and segmental glomerulosclerosis (FSGS). Correlations between glomerular size and FSGS have been described in various animal models, as well as studies of humans. The aim of this study is to determine whether a relation exists between glomerular volume and severity of FSGS in biopsy specimens from Australian Aboriginals in the Northern Territory and Aboriginal inhabitants of the Tiwi Islands (Bathurst Island and Melville Island, Northern Territory, Australia). Consecutive clinical biopsy specimens were obtained from 78 non-Tiwi and 72 Tiwi Aboriginals. Glomerular volume was estimated using the stereological method of Weibel and Gomez. FSGS was graded from 0 to 4; 0 indicates no sclerosis and 4 indicates severe sclerosis. A biphasic relationship between glomerular size and severity of FSGS was identified. As the severity of FSGS increased from grade 0 to grade 3, glomerular size also increased. For both populations studied, glomeruli scored as grades 1, 2, and 3 were approximately 50% (P< 0.001), 65% (P< 0.001), and 100% (P< 0.001) larger than normal glomeruli, respectively. However, in glomeruli with grade 4 FSGS, glomerular size decreased to the size of normal glomeruli. These results show a biphasic relationship between severity of FSGS and glomerular size in Australian Aborigines.