Renal biopsy findings among Indigenous Australians: a nationwide review.

Australia's Indigenous people have high rates of chronic kidney disease and kidney failure. To define renal disease among these people, we reviewed 643 renal biopsies on Indigenous people across Australia, and compared them with 249 biopsies of non-Indigenous patients. The intent was to reach a consensus on pathological findings and terminology, quantify glomerular size, and establish and compare regional biopsy profiles. The relative population-adjusted biopsy frequencies were 16.9, 6.6, and 1, respectively, for Aboriginal people living remotely/very remotely, for Torres Strait Islander people, and for non-remote-living Aboriginal people. Indigenous people more often had heavy proteinuria and renal failure at biopsy. No single condition defined the Indigenous biopsies and, where biopsy rates were high, all common conditions were in absolute excess. Indigenous people were more often diabetic than non-Indigenous people, but diabetic changes were still present in fewer than half their biopsies. Their biopsies also had higher rates of segmental sclerosis, post-infectious glomerulonephritis, and mixed morphologies. Among the great excess of biopsies in remote/very remote Aborigines, females predominated, with younger age at biopsy and larger mean glomerular volumes. Glomerulomegaly characterized biopsies with mesangiopathic changes only, with IgA deposition, or with diabetic change, and with focal segmental glomerulosclerosis (FSGS). This review reveals great variations in biopsy rates and findings among Indigenous Australians, and findings refute the prevailing dogma that most indigenous renal disease is due to diabetes. Glomerulomegaly in remote/very remote Aboriginal people is probably due to nephron deficiency, in part related to low birth weight, and probably contributes to the increased susceptibility to kidney disease and the predisposition to FSGS.

CKD in Aboriginal Australians.

Chronic kidney disease (CKD) is one component of a spectrum of chronic disease in Aboriginal Australians. CKD is marked by albuminuria, which predicts renal failure and nonrenal natural death. Rates vary greatly by community and region and are much higher in remote areas. This reflects the heterogeneous characteristics and circumstances of Aboriginal people. CKD is multideterminant, and early-life influences (notably low birth weight), infections (including poststreptococcal glomerulonephritis), metabolic/hemodynamic parameters, and epigenetic/genetic factors probably contribute. CKD is associated intimately with cardiovascular risk. Albuminuria progresses over time, with a high incidence of new onset of pathologic levels of albuminuria in all age groups. All the usual morphologic findings are found in renal biopsy specimens. However, glomerular enlargement is notable in individuals from remote regions, but not those living closer to population centers. Glomerulomegaly probably represents compensatory hypertrophy caused by low nephron number, which probably underlies the accentuated susceptibility to renal disease. In the last decade, health care services have been transformed to accommodate systematic chronic disease surveillance and management. After a relentless increase for 3 decades, rates of Aboriginal people starting renal replacement therapy, as well as chronic disease deaths, appear to be stabilizing in some regions. Official endorsement of these system changes, plus ongoing reductions in the incidence of low birth weight and infections, hold promise for continued better outcomes.

Effect of pravastatin on kidney function and urinary protein excretion in autosomal dominant polycystic kidney disease.

OBJECTIVE: Autosomal dominant polycystic kidney disease (ADPKD) is progressive, resulting in end-stage kidney failure in most patients. Experimental and clinical studies have suggested that statins may slow the progression of chronic kidney disease in general and ADPKD specifically. MATERIAL AND METHODS: This randomized open-label clinical trial was conducted to assess the effect of pravastatin 20 mg on kidney function and urinary protein excretion in patients with ADPKD. Sixty patients were initially recruited but 49 of these received either pravastatin 20 mg or no treatment for 2 years. Trial visits were conducted every 3 months, assessing kidney function by estimated glomerular filtration rate and 24 h urine creatinine clearance and urinary protein excretion. RESULTS: There were no significant (p > 0.05) changes in markers of kidney function or urinary protein excretion between groups over the 2 years despite a significant fall in total serum cholesterol in pravastatin-treated patients (p = 0.029). CONCLUSION: This trial found that taking 20 mg pravastatin for 2 years had no significant effect on kidney function or urinary protein excretion in patients with ADPKD. The lack of statistical power limits the external validity of these findings. A larger, longer duration study using a higher dose of a more potent statin is required.

Reduction of proteinuria by rosiglitazone in non-diabetic renal disease.

AIM: To investigate the effect of a thiazolidinedione on proteinuria in patients with non-diabetic renal disease. METHODS: In an open-label randomized cross-over study, 40 adults with chronic non-diabetic renal disease completed the study. In a random fashion, one group was treated for 4 months with 4 mg of rosiglitazone first followed by a 4-month period of standard treatment. The opposite order was used for the second group. RESULTS: Baseline urinary protein excretion rate was 1.45 g/24 h. On rosiglitazone, there was a drop of urinary protein level of 0.24 g/24 h (P=0.045). In contrast, there was a trend for proteinuria to increase during the control period (0.12 g/24 h, P=0.18). The urine protein level on rosiglitazone was lower than on usual treatment (0.36 g/24 h, P=0.002, 95% CI 0.15-0.58). There was a similar beneficial effect on systolic blood pressure which was reduced by rosiglitazone by 7.8 mmHg (P=0.006, 95% CI 2.6-13.1). Although average fasting glucose was only 5.8 mmol/L, there was a significant Spearman correlation between fasting glucose and a reduction in urinary protein levels (r=0.34, P=0.045). CONCLUSION: It is concluded that thiazolidinediones may have a role in the management of non-diabetic proteinuria of various aetiologies. In this study the average body mass index was 28.9 kg/m2. It will be important to repeat these studies in non-overweight subjects with non-diabetic proteinuria and in addition to trial maximal therapeutic doses of the thiazolidenedione.

The investigation of hematuria.

Persistent microscopic hematuria is present in about 6% of the population, but probably only a small minority have hematuria that does not originate from the glomerulus. Careful analysis of phase-contrast urine microscopy by a skilled observer is critically important in the investigation of hematuria. In glomerular disease, urine microscopy often is second only to renal biopsy examination in helping make a diagnosis. Glomerular and nonglomerular hematuria are distinguished easily on phase-contrast urine microscopy or by an automated peripheral blood cell counter. However, urine microscopy provides additional information about casts and other features that may enable such disparate diagnoses as Fabry's disease, sickle cell disease, and cystine calculi to be made. Macroscopic nonglomerular hematuria is of particular significance because it is much more likely than microscopic hematuria to be associated with malignancy. Macroscopic hematuria originating from the glomerulus indicates the presence of crescentic disease, which requires urgent assessment by renal biopsy examination. We advocate a renal biopsy examination in any individual with a persisting urinary erythrocyte count greater than 100,000/mL. Thirty percent of patients with isolated microscopic hematuria have mesangial immunoglobulin A glomerulonephritis (IgAN) shown on biopsy examination and 20% to 40% of these patients will progress to renal failure without treatment.

A report with consensus statements of the International Society of Nephrology 2004 Consensus Workshop on Prevention of Progression of Renal Disease, Hong Kong, June 29, 2004.

This report summarizes the discussions of the International Society of Nephrology (ISN) 2004 Consensus Workshop on Prevention of Progression of Renal Disease, which was held in Hong Kong on June 29, 2004. Three key areas were discussed during the workshop: (1) screening for chronic kidney disease; (2) evaluation and estimating progression of chronic kidney disease; and (3) measures to prevent the progression of chronic kidney disease. Fifteen consensus statements were made in these three areas, as endorsed by the participants of the workshop. The ISN can make use of and take reference to these statements in formulating its policy for tackling chronic kidney disease, a disease with significant global impact.

Dual blockade of the renin-angiotensin system compared with a 50% increase in the dose of angiotensin-converting enzyme inhibitor: effects on proteinuria and blood pressure.

BACKGROUND: Several publications in the past 2 years have demonstrated that combined angiotensin-converting enzyme inhibitors (ACEI) and angiotensin-II receptor antagonist (AIIRA) are more effective in reducing blood pressure and proteinuria in patients with chronic renal disease than ACEI or AIIRA alone. This study compares the effect of increasing the ACEI dose by 50% with that of adding an AIIRA to a standard ACEI dose. METHODS: This study was designed as part of a previous comparison of ACEI with ACEI plus candesartan. Directly after completion of the randomized intervention periods of that study, the dose of ACEI was increased by 50% in all patients. Proteinuria and blood pressure were compared in both groups of patients in the three periods, on standard ACEI, on ACEI plus candesartan and on a dose of ACEI increased by 50%. RESULTS: No significant differences in the primary end-point proteinuria or secondary end-points were observed when the ACEI dose was increased by 50%. Proteinuria was 1.8 g in 24 h on candesartan and ACEI and 2.4 g in 24 h when the ACEI dose was increased by 50% (P<0.02). Systolic blood pressure was 126.6 mmHg on candesartan and ACEI and 134.47 mmHg when the ACEI dose was increased by 50% (P<0.002). Diastolic blood pressure, serum creatinine, urea and potassium were not different between groups. CONCLUSIONS: Standard ACEI plus candesartan is more effective in reducing systolic blood pressure and proteinuria than a 50% increase in ACEI dose. This has implications for the prevention of renal failure in chronic renal disease.

Hypothesis: obesity and the insulin resistance syndrome play a major role in end-stage renal failure attributed to hypertension and labelled 'hypertensive nephrosclerosis'.

About a third of new cases of renal failure in USA are attributed to hypertension despite controversy about the frequency and pathology of so called hypertensive nephrosclerosis. In spite of good documentation that obesity causes renal failure and in spite of the global epidemic of obesity this diagnosis does not feature on most renal failure registries. New documentation that progressive renal failure in hypertension is linked to insulin resistance and analysis of NHANES III data which shows a strong positive significant dose-response relationship between insulin resistance and chronic kidney disease strengthen the view that so called hypertensive nephrosclerosis may be linked more closely to obesity and insulin resistance than to blood pressure. The pathology of the kidney in hypertension has changed. Studies 50 years ago did not show segmental glomerulosclerosis, which has recently been shown to be the key lesion in hypertensive nephrosclerosis. Recent documentation that this is a major mechanism of progression in hypertension together with the fact that similar segmental glomerulosclerosis is the key lesion in obesity and the metabolic syndrome suggests that these factors are more important than hypertension in renal failure attributed to hypertensive nephrosclerosis.

Randomized controlled crossover study of the effect on proteinuria and blood pressure of adding an angiotensin II receptor antagonist to an angiotensin converting enzyme inhibitor in normotensive patients with chronic renal disease and proteinuria.

BACKGROUND: Proteinuria and hypertension have independent deleterious effects on the progression of chronic renal disease. The objectives of this study were to determine whether the addition of Candesartan, an angiotensin II receptor antagonist, would reduce proteinuria and blood pressure in normotensive patients with chronic renal disease already receiving an angiotensin converting enzyme inhibitor (ACEI). METHODS: This was an open randomized controlled crossover study conducted in a private consultant practice in Melbourne. Sixty patients, aged 23-75, who had chronic renal disease and stable proteinuria over 0.5 g in 24 h and were receiving an ACEI, were enrolled in the study. The patients were randomized to have 8 mg of Candesartan added in the first or second of two 12-week study periods. The primary end point was urine protein excretion, which was measured every 2 weeks for the 24-week period. Secondary end points included systolic and diastolic blood pressure, serum creatinine, urea and potassium levels. Candesartan was added against a background of standard care, which included other blood pressure lowering therapy. RESULTS: Lower urine protein excretion 2.4 vs 2.0 g in 24 h (P<0.04, difference 0.45, CI 0.01, 0.9) and lower levels of systolic blood pressure 134 vs 128 mmHg (P<0.001, difference 6.4, CI 3.2, 9.6) and diastolic blood pressure 82 vs 80 mmHg (P<0.008, difference 2.7, CI 0.7, 4.6) were observed when Candesartan, 8 mg, was added to a regimen, which included an ACEI. No rise in serum creatinine occurred but there was a significant rise in urea, during the Candesartan arm of the study, from 12.3 to 13.8 mmol/l (P<0.001). The addition of 8 mg of Candesartan in normotensive patients with chronic renal disease receiving ACEI appeared safe and was not accompanied by adverse effects apart from postural hypotension in three patients and a serum potassium level of 6.3 mmol/l in one. CONCLUSIONS: In a private consulting practice setting, the addition of 8 mg of Candesartan in normotensive patients with chronic renal disease and proteinuria receiving an ACEI reduced proteinuria and blood pressure. The combination of Candesartan and ACEI appeared safe in this setting and may offer additional protection in preventing progression in chronic renal disease. Although the reduction of proteinuria was small (0.45 g/24 h) this reflected in part a lack of response in diabetic nephropathy and in part a marked rise in proteinuria after ceasing Candesartan in patients who did not complete the Candesartan arm of the study.

Pharmacological management of membranous nephropathy.

When steroids and immunosuppressive drugs were the only available pharmacological agents used to treat membranous nephropathy, nephrologists were polarized into two groups, those supporting therapy on the basis of the results achieved in controlled trials and those opposed to therapy who contended that the side-effects of therapy were too severe to consider in a disease with a relatively benign course. These two groups are drawing closer as treatments with lesser side-effects emerge. The demonstration that proteinuria accelerates progressive kidney failure in all renal diseases led to a major focus on control of proteinuria. Angiotensin-converting enzyme inhibitors, diuretics and angiotensin II receptor antagonists all play a role. Older methods of treatment that reduce proteinuria are being resurrected. A major development is the demonstration in a randomized study that cyclosporin A is effective in membranous nephropathy. Therefore, although there has been no major recent breakthrough or novel therapeutic agent used in membranous nephropathy, a range of new methods of controlling proteinuria provide some compromise between therapeutic enthusiasm and conservative management in this common disorder.

The fifth freedom.

Women in developing countries suffer considerable morbidity and mortality due to inability to control their own fertility and lack of access to family planning services. Over 500,000 deaths each year are related to pregnancy. Two thirds of these maternal deaths could be prevented by providing contraception to those women who wish to use it in developing countries. There is no tenable ethical defence of cultural and religious behaviour which denies a women a choice as to whether she will undertake a pregnancy or not. Implementaion of the principles of the programme of action from the 1994 Cairo Population Conference would, through empowering women to control their own fertility, have a huge impact on maternal health in the developing world. [Kincaid-Smith is president of the World Medical Association].

Características do infiltrado inflamatório renal na nefropatia de refluxo / Characteristics of the renal inflamatory infiltrates in reflux nephropathy

Este trabalho objetivou caracterizar, in situ, o infiltrado inflamatório da nefropatia de refluxo. Para tal, estudamos rins de ratos infectados experimentalmente com Escherichia coli e espécimes renais humanos obtidos por biópsia renal ou nefrectomia. A caracterizaçäo das células mononucleares foi feita pela técnica de imunoperoxidase em quatro etapas, utilizando-se anticorpos monoclonais na primeira etapa. Observamos que a nefrite tubulointersticial era constituída de 72,1% de linfocitos T, dos quais 79,7 - 88,2% eram células T auxiliares e 11, 7-20,3% linfócitos T citotóxicos supressores. O restante do infiltrado inflamatório (27,9%) constituiu-se de monócitos-macrófagos (18%) e linfócitos B e/ou células "nulas" (10%)