The multidimensional nature of renal disease: rates and associations of albuminuria in an Australian Aboriginal community.

BACKGROUND: An epidemic of end-stage renal disease (ESRD) is accompanying the rising rates of hypertension, type 2 diabetes and cardiovascular disease among Aborigines in the Northern Territory of Australia. Incidence rates are now 21 times those of nonAboriginal Australians and are doubling every four years. We describe the rates and associations of renal disease in one remote community, which has a current ESRD incidence of 2700 per million, and cardiovascular mortality among the highest in Australia. METHODS: Between 1992 and 1995 a community-wide screening program was conducted, in which the urinary albumin/creatinine ratio (ACR) was used as the chief renal disease marker. More than 90% of the population ages five and older participated. RESULTS: Albuminuria was evident in early childhood and increased dramatically with age; 26% of adults had microalbuminuria and 24% had overt albuminuria. All renal failure developed out of a background of overt albuminuria. ACR was significantly correlated with the presence of scabies at screening, with a history of poststreptococcal glomerulonephritis, which is epidemic and endemic in the community, with increasing body wt, blood pressure, glucose, insulin and lipid levels, and with evidence of heavy drinking. ACR was also significantly and inversely correlated with birth weight. As a result of its association with deteriorating hemodynamic and metabolic profiles, increasing ACR was also correlated with increasing cardiovascular risk score. Direct observations showed, and multivariate models predicted, progressive amplification of ACR when multiple risk factors were present simultaneously. Albuminuria also clustered in families. CONCLUSION: Renal disease in this population is multifactorial, with risk factors related to whole-of-life nutrition, metabolic and hemodynamic profiles, infections, health behaviors, and possibly a family predisposition. Its relationship to low birth weight, and its associations with deteriorating metabolic and hemodynamic profiles, suggest that renal disease is, in part, a component of Syndrome X, which explains the simultaneous increase in metabolic, cardiovascular and renal disease in Aboriginal people. The family clustering might have both environmental and genetic causes, and is under further investigation. Most of the identified risk factors arise out of poverty, disadvantage and accelerated lifestyle change, and the current epidemic can be explained by the confluence of many risk factors in the last few decades. The introduction of effective and sustained programs to address social, economic and educational inequities in all Aboriginal communities, and of screening and renal- and cardiovascular-protective treatment programs for those already afflicted are matters of great urgency.

A health profile of adults in a Northern Territory aboriginal community, with an emphasis on preventable morbidities.

We conducted a brief health survey of adults in an isolated Northern Territory Aboriginal community, whose standardised mortality rates are the second highest in Australia. The screen revealed high rates of smoking and excessive drinking, of preventable infections and their sequelae, and of hypertension, insulin resistance, diabetes and renal disease. The infectious morbidities were more pronounced and the life-style morbidities almost entirely new since a health screen in 1957. Most morbidities were strongly associated with identifiable risk factors, such as overweight, smoking, excessive drinking, skin sores and scabies, all of which which are amenable to modification. Problems with food supply and pricing, poor food choices and diversion of money to cigarettes, beer and gambling all contributed to poor nutrition. Low birthweight probably compounds the risk for serious adult disease associated with these environmental influences. This profile highlights the failure of current systems to deal with health needs. Improvements in infrastructure, education and employment, and reinvigoration of preventive and primary health care programs, assumption of responsibility for health by the community and by individuals themselves, and better management of existing morbidities are essential to rectifying this shameful situation.

Community mental health teams: development in community care.

This article discusses research undertaken in an area of South Wales on the functioning of community mental health teams, which took place during the closure of two large psychiatric hospitals and the development of the Welsh Office strategy for mental illness. Key findings relate to the lack of clarity of the role of team coordinators, the absence of individual performance review systems, the diversities in referral systems and caseloads. An attempt was made to develop a performance matrix in relation to individual teams.

Markers for cardiovascular and renal morbidity: expectations for an intervention programme in an Australian aboriginal community.

1. Australian Aborigines have high rates of both cardiovascular mortality and renal failure and the usual male dominance in these conditions is respectively reduced and effaced. 2. In one Aboriginal community, we have demonstrated a strong association between albuminuria and cardiovascular risk factors and a relationship of both with insulin resistance, which is more pronounced in females than males. 3. We propose that albuminuria is a component of Syndrome X and that reduction in levels of albuminuria should prove to be a useful marker of effectiveness in treatment programmes targeting cardiovascular risk as well as renal disease.

Sneddon's syndrome, anti-cardiolipin antibody and glomerular thrombosis.

Sneddon's syndrome, cerebrovascular thrombosis and livedo reticularis, is often a variant of the "primary" anti-phospholipid syndrome (PAPS). We report a woman with PAPS, presenting as Sneddon's syndrome, with renal impairment and glomerular thrombosis on renal biopsy. An IgG anti-cardiolipin antibody (aCL) was identified. The aCL was purified by affinity chromatography, gel filtration chromatography and ion-exchange chromatography, assayed in a modified ELISA and found to be of the type that requires the plasma protein beta 2-GPI to bind aCL. As beta 2-GPI has anticoagulant properties it is postulated that its interaction with aCL has a pathogenic role in the thrombotic lesions associated with aCL.

Streptococcal infection and renal disease markers in Australian aboriginal children.

OBJECTIVE: To demonstrate an association between markers of streptococcal infection and markers of glomerulonephritis in Aboriginal children. DESIGN: A cross-sectional study of Aboriginal children of school age. SETTING: Three Aboriginal communities in the Northern Territory--two, coastal and one, desert. PARTICIPANTS: Sixty children, randomly selected from the school roll, were studied in each community; thus there were 180 children in total, aged 5-17 years. Midstream urine and venous blood was collected and swabs were taken from the pharynx and from impetiginous skin lesions or axillary skin in the absence of impetigo. Clinical records were examined for evidence of past glomerulonephritis. MAIN OUTCOME MEASURES: Swabs were cultured for beta-haemolytic streptococci and isolates were grouped; serum was tested for titres of antistreptolysin O (ASO) and antideoxyribonuclease B (anti-DNaseB). Protein and creatinine levels were measured in urine, and a ratio of protein to creatinine (UPC) of more than 50 mg protein per mmol creatinine was taken as a measure of significant proteinuria. Urine was examined microscopically for glomerular haematuria (greater than 10 red blood cells per microL with at least 20% dysmorphic red cells). RESULTS: Group A beta-haemolytic streptococci were isolated from the throat swabs of two children and from skin swabs of 25 (13.9%) children; 20 of these were from impetiginous lesions and five from normal axillary skin. beta-Haemolytic streptococci of group C or G were grown from the throat swabs of 13 (8.1%) children. The median titre of ASO (256 IU) was raised compared with a reference level, and the median titre of anti-DNaseB (3172 IU) was particularly high; ASO titres were significantly higher in 31 children with impetigo than in 149 children without impetigo. Significant proteinuria was present in 7 (3.9%) children and glomerular haematuria in 16 (8.9%). Glomerular haematuria was present in 2/7 (28%) children with proteinuria, 4/21 (19%) children with a past history of post-streptococcal glomerulonephritis, in 5/31 (16%) of those with impetigo and in 4/25 (16%) of those with positive skin cultures. However, none of these prevalences was significantly greater than the prevalence of glomerular haematuria among the other children. The prevalence of proteinuria differed significantly between communities and increased significantly with age. Furthermore, the differences in childhood proteinuria observed between communities in this study were parallel with community differences in the prevalence of proteinuria in a related study of adults. CONCLUSIONS: Group A streptococci are important causes of impetigo in Aboriginal children. Streptococcal skin infection may contribute to glomerular haematuria, proteinuria and persistent glomerulonephritis in Aboriginal children, and possibly to chronic glomerulonephritis in adult life. Public health programs are needed to reduce the prevalence of impetigo and group A streptococcal infections in Aboriginal communities; longitudinal studies are needed to test the relationship between streptococcal skin infection in Aboriginal children and chronic renal disease in later life.

Bone histoquantitative findings and histochemical staining reactions for aluminium in chronic renal failure patients treated with haemodialysis fluids containing high and low concentrations of aluminium.

A total of 112 undecalcified bone biopsies from 67 patients under treatment for chronic renal failure by maintenance haemodialysis was available for retrospective study. The patients were divided into three groups. Group I (15 cases) had been dialysed for the majority of the time in their own homes with a fluid containing a low concentration of aluminium. Group II (28 cases) had been dialysed exclusively in hospital (prior to 1978) with a fluid containing a high concentration of aluminium and group III (24 cases) had been treated exclusively in hospital (from 1978 onwards) with a fluid of low aluminium concentration. The tissues from these groups were subjected to histoquantitative assessment and stained by a histochemical technique to demonstrate aluminium salt. In group II, 71.4% of cases showed positive aluminium staining reactions (at the osteoid/mineralised tissue interface) compared to 26.6% in group I and 37.5% in group III. Staining reactions were also more extensive in group II cases. The osteoid volume was significantly increased and the calcification front extents significantly decreased in group II compared to both groups I and III. A comparison of histochemically positive with negative cases in each group showed a significantly increased osteoid volume and significantly decreased calcification fronts in the positive cases. It was, therefore, concluded that haemodialysis against a fluid containing a high concentration of aluminium leads to intraosseous aluminium accumulation of greater degree in a larger number of patients than a fluid with low aluminium content and that there is an accompanying osteomalacia manifest by an increase in osteoid volume together with diminution in the extent of the calcification fronts.

Acute renal failure after peritoneal lavage with mercuric chloride.

A 64-year-old man developed acute renal failure after hemicolectomy during which the peritoneal cavity was irrigated with a 0.2% solution of mercuric chloride. Renal failure was preceded by abdominal pain and hypotension, and followed by adynamic ileus, wound disruption, and a severe peritoneal reaction. The mechanism of this injury, together with the development of renal failure and its management, are discussed.

A controlled trial of labetalol (Trandate), propranolol and placebo in the management of mild to moderate hypertension.

1. Labetalol, a new drug combining alpha-and beta-adrenoceptor blocking properties, has been compared with placebo in a double-blind crossover study of a group of patients with mild to moderate essential hypertension (blood pressure 150/100 to 189/114 mmHg). 2. Labetalol and propranolol lowered blood pressure satisfactorily in the supine position, but labetalol reduced blood pressure more in the erect posture and following exercise and induced less bradycardia. Thus alpha- as well as beta-adrenoceptor blocking actions appear to contribute to blood pressure reduction. 3. Side effects attributable to labetalol were few. The effective dose ratio labetalol: propranolol was 2.5:1 (w/w). 4. Labetalol, a new form of hypotensive agent, merits further controlled assessment of its usefulness in relation to existing drugs.

Renal prostaglandin synthesis in hypertension induced by deoxycorticosterone and sodium chloride in the rat.

1. The role of renal medullary prostaglandin E has been examined in rats with hypertension induced by sodium chloride and deoxycorticosterone (salt-DOC). 2. Synthesis of prostaglandin E was normal in early salt-DOC hypertension. Indomethacin exacerbated the hypertension, and depressed synthesis of prostaglandin E equally in hypertensive and control rats. 3. Synthesis of prostaglandin E was depressed in rats with late salt-DOC hypertension. 4. The results lend support to the concept that prostaglandin E is involved in the regulation of arterial pressure.

Combined alpha- and beta-adrenoreceptor blockade in hypertension: a controlled trial of labetalol (AH 5158) compared with propranolol and placebo.

1. Labetalol (AH 5158) is a new drug which has both alpha- and beta-adrenoreceptor antagonist activity. Labetalol has been compared with propranolol and placebo for the treatment of mild to moderate hypertension (150/100 to 189/114 mmHg), in a double-blind cross-over trial with three 10 week treatment periods. 2. Both drugs reduced blood pressures in nine of the ten patients who have completed the trial. Relative to placebo labetalol caused decreases in supine pressures similar to those caused by propranolol (average -10/-10 and -10/-9 mmHg respectively), with a greater effect on standing (labetalol -20/-19; propranolol -8/-12 mmHg; P less than 0-01) and after exercise (labetolol -27/-18 and propranolol -16/-14 mmHg). 3. Labetalol and propranolol caused a similar fall in supine pulse rate (-11/min and -13/min respectively), but there was less bradycardia on standing (labetalol -11/min; propranolol -18/min; P less than 0-001) and after exercise (labetalol -17/min; propranolol -23/min; P less than 0-001). 4. The average dose ratios of labetalol to propranolol was 2-4:1 (w/w). 5. These results suggest that the effect of labetalol on blood pressure involves both alpha- and beta-adrenoreceptor antagonist properties. 6. Further evaluation of labetalol is warranted as it may have some advantages in respect of producing less bradycardia, improved peripheral blood flow and less effect on airways resistance than 'pure' beta-receptor-blocking agents.

Controlled comparison of labetalol and propranolol in the management of severe hypertension.

1 Labetalol, a new hypotensive drug combining alpha- and beta-adrenoreceptor antagonist properties, has been compared with propranolol in the treatment of severe hypertension (blood pressure 190/115-249/139 mmHg) in a double-blind trial lasting 14 weeks. Additional diuretic therapy was given to both groups of patients. 2 Both drugs caused an effective reduction in blood pressure, bbut labetalol caused a greater fall in pressure in the standing position and after exercise. Two groups of nine patients have each completed the trial so far. Group average pressures for the last 3 weeks of treatment were: for labetalol 137/87 supine, 121/84 standing, and 117/78 mmHg after exercise; and for propranolol, 138/87 supine, 132/93 standing, and 133/94 mmHg after exercise. 3 Group average heart rates were lower in all three positions for those patients treated with propranolol compared with labetalol. 4 The average final dose ratio for labetalol: propranolol was 1.44:1 (w/w). 5 Labetalol initially induced a number of side-effects, predominantly related to alpha-adrenoreceptor blockade, which disappeared by the end of the trial. 6 Labetalol, in conjunction with diuretic therapy, was at least as effective as propranolol in lowering blood pressure in patients with severe hypertension.