Urinary B-cell-activating factor of the tumour necrosis factor family (BAFF) in systemic lupus erythematosus.

INTRODUCTION: We examined the clinical relevance of urinary concentrations of B-cell-activating factor of the tumour necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL) in systemic lupus erythematosus (SLE). METHODS: We quantified urinary BAFF (uBAFF) by enzyme-linked immunosorbent assay in 85 SLE, 28 primary Sjögren syndrome (pSS), 40 immunoglobulin A nephropathy (IgAN) patients and 36 healthy controls (HCs). Urinary APRIL (uAPRIL) and monocyte chemoattractant protein 1 (uMCP-1) were also quantified. Overall and renal SLE disease activity were assessed using the Systemic Lupus Erythematosus Disease Activity Index 2000. RESULTS: uBAFF was detected in 12% (10/85) of SLE patients, but was undetectable in HCs, IgAN and pSS patients. uBAFF was detectable in 28% (5/18) of SLE patients with active nephritis vs 5/67 (7%) of those without ( p = 0.03), and uBAFF was significantly higher in active renal patients ( p = 0.02) and more likely to be detected in patients with persistently active renal disease. In comparison, uAPRIL and uMCP-1 were detected in 32% (25/77) and 46% (22/48) of SLE patients, respectively. While no difference in proportion of samples with detectable uAPRIL was observed between SLE, HCs and IgAN patients, both uAPRIL and uMCP-1 were significantly detectable in higher proportions of patients with active renal disease. CONCLUSIONS: uBAFF was detectable in a small but a significant proportion of SLE patients but not in other groups tested, and was higher in SLE patients with active renal disease.

Gaps and barriers in health-care provision for co-morbid diabetes and chronic kidney disease: a cross-sectional study.

BACKGROUND: Patients with diabetes and chronic kidney disease (CKD) are a complex subset of the growing number of patients with diabetes, due to multi-morbidity. Gaps between recommended and received care for diabetes and chronic kidney disease (CKD) are evident despite promulgation of guidelines. Here, we document gaps in tertiary health-care, and the commonest patient-reported barriers to health-care, before exploring the association between these gaps and barriers. METHODS: This cross-sectional study recruited patients with diabetes and CKD (eGFR < 60 mL/min/1.73 m2) across 4 large hospitals. For each patient, questionnaires were completed examining clinical data, recommended care, and patient-reported barriers limiting health-care. Descriptive statistics, subgroup analyses by CKD stage and hospital, and analyses examining the relationship between health-care gaps and barriers were performed. RESULTS: 308 patients, of mean age 66.9 (SD 11.0) years, and mostly male (69.5%) and having type 2 diabetes (88.0%), participated. 49.1% had stage 3, 24.7% stage 4 and 26.3% stage 5 CKD. Gaps between recommended versus received care were evident: 31.9% of patients had an HbA1c ≥ 8%, and 39.3% had a measured blood pressure ≥ 140/90 mmHg. The commonest barriers were poor continuity of care (49.3%), inadequate understanding/education about CKD (43.5%), and feeling unwell (42.6%). However, barriers associated with a failure to receive items of recommended care were inadequate support from family and friends, conflicting advice from and poor communication amongst specialists, the effect of co-morbidities on self-management and feeling unmotivated (all p < 0.05). CONCLUSIONS: Barriers to health-care varied across CKD stages and hospitals. Barriers associated with a deviation from recommended care were different for different items of care, suggesting that specific interventions targeting each item of care are required.

BK Virus Associated Nephropathy, a Cause of Early Renal Allograft Dysfunction: A Single Centre Study.

BACKGROUND: BK virus associated nephropathy (BKVN) is an important cause of early graft dysfunction in renal transplant recipients. The present study was carried out to determine the burden of BKVN in a single renal transplant centre in Australia. METHOD: A retrospective analysis of de novo renal transplant recipients from 2010 to 2013 was performed to identify biopsy proven BKVN. Estimated glomerular filtration rate (eGFR) was compared at baseline, at BKVN diagnosis and 3 and 12 months postdiagnosis. RESULT: Of the 317 de novo renal transplants recipients in the study period, 20 (6.3%) developed BKVN. The mean age was 54.8 ± 13.1 years and 13 (65%) were male. The mean time from transplant to BKVN was 8.7 ± 6.7 months with 17 (85%) diagnosed within 12 months. Four recipients each were diagnosed BKVN on 3 and 12 month surveillance biopsy. Six (30%) had normal eGFR at diagnosis. Mean eGFR at diagnosis was 38.8 ± 19.2 ml/min/1.73 m2, which was significantly lower (p < 0.01) than that at baseline (50.3 ± 16.4 ml/min/1.73 m2). eGFR improved numerically at 3 and 12 months post-diagnosis, however the difference was not significant. One patient had graft failure, 19 months after diagnosis. CONCLUSION: BKVN generally occurs in first post-transplant year and is an important cause of early graft dysfunction. Surveillance biopsy helps in detecting subclinical BKVN.

Vancomycin-resistant enterococci colonization does not increase mortality in end-stage kidney failure: a case-control study.

BACKGROUND: Vancomycin-resistant enterococci (VRE) colonization is a frequent occurrence in patients with renal failure. Understanding the impact of VRE colonization on this group of patients has considerable clinical applicability. AIM: To understand whether VRE colonization in renal patients has an impact on number of admissions to hospital, length of stay, and mortality. METHODS: A retrospective case-control study of renal dialysis patients was performed between 2000 and 2010. Cases were 134 VRE-colonized patients requiring renal replacement therapy and matched controls were 137 non-colonized patients with the same baseline characteristics. Matched cases and controls were analysed for differences in number of admissions, length of stay, and mortality. FINDINGS: There was no difference in mortality between colonized and non-colonized patients (hazard ratio: 1.14; 95% confidence interval: 0.78-1.69; P = 0.49). Length of stay for colonized patients was 7.29 days compared with 4.14 days (P < 0.001). The number of admissions for VRE-colonized patients was not significantly different compared with controls (9.34 vs 8.33, P = 0.78). CONCLUSION: VRE colonization did not increase mortality in renal patients but did contribute to increased length of stay.

Cinacalcet reduces plasma intact parathyroid hormone, serum phosphate and calcium levels in patients with secondary hyperparathyroidism irrespective of its severity.

AIMS: To evaluate the relationship between the severity of secondary hyperparathyroidism (SHPT) - defined in terms of baseline plasma intact parathyroid hormone (iPTH) level - and the magnitude of response to cinacalcet. MATERIALS AND METHODS: In this post hoc analysis, data were pooled from three randomized, placebo-controlled trials in which dialysis patients with iPTH ≥ 300 pg/ml were dose-titrated with cinacalcet or placebo in addition to conventional treatment to achieve iPTH ≤ 250 pg/ml. In 953 patients analyzed (cinacalcet, 545; placebo, 408), baseline iPTH levels were categorized in 100 pg/ml intervals (300 - ≥ 1,000 pg/ml), and the impact of baseline iPTH on changes in iPTH, phosphate (P), calcium (Ca) and calcium- phosphate product (Ca × P) was evaluated. RESULTS: Cinacalcet reduced iPTH (47% reduction), P (9%), Ca (7%), and Ca × P (15%) across all subgroups. For patients receiving cinacalcet, the mean percentage reduction from baseline in iPTH varied from 35 to 55%, being consistently decreased across the severity subgroups. The mean absolute change in iPTH was more pronounced in patients with higher baseline iPTH levels, particularly in the ≥ 1,000 pg/ml subgroup vs. the other subgroups. However, as baseline iPTH levels increased, iPTH ≤ 250 pg/ml was achieved in fewer patients. A trend towards greater absolute change from baseline was observed for P in patients with more severe disease (iPTH ≥ 800 pg/ml) treated with cinacalcet compared with patients with less severe disease (iPTH 300 - < 800 pg/ml). CONCLUSIONS: Cinacalcet lowers plasma iPTH and serum P, Ca and Ca × P levels in dialysis patients with SHPT, regardless of disease severity. Patients with more severe disease experienced greater reductions in PTH and P, but fewer achieved iPTH ≤ 250 pg/ml by the efficacy assessment phase. Use of cinacalcet when baseline PTH is lower may result in more stable control of SHPT and help to control bone and mineral alterations.

Advanced chronic kidney disease, cardiovascular events and the effect of diabetes: data from the Atherosclerosis and Folic Acid Supplementation Trial.

BACKGROUND: End-stage kidney disease registry data have reported increased mortality in patients with diabetes as compared with those without. Here we examine whether diabetes is independently associated with an increased risk of major cardiovascular events and death in patients with advanced chronic kidney disease (CKD). METHODS: Data from 315 participants with CKD in the Atherosclerosis and Folic Acid Supplementation Trial (ASFAST) were assessed. Primary end-points were fatal or non-fatal cardiovascular events, including myocardial infarction, stroke, unstable angina, coronary revascularisation and peripheral vascular events assessed both jointly and separately using Cox-proportional hazard models. RESULTS: Twenty-three per cent reported diabetes. Median follow up was 3.6 years. In those with diabetes, an increased risk for major cardiovascular events was observed, crude hazard ratio (HR) 2.87 (95% confidence interval (CI) 2.11-3.90). After adjustment for age, gender, smoking, systolic blood pressure, body mass index, past ischaemic heart disease and use of preventive therapies, diabetes was associated with an HR of 1.83 (1.28-2.61) for major cardiovascular events. The risk for peripheral vascular events was also increased, adjusted HR 6.31 (2.61-15.25). For all-cause death, major coronary and stroke events, the risk in those with diabetes was not significantly increased (all-cause death, adjusted HR 1.31 (95% CI 0.80-2.14); major coronary events, adjusted HR 1.26 (95% CI 0.64-2.49); and major stroke events, adjusted HR 1.28 (95% CI 0.55-2.99)). CONCLUSIONS: Diabetes significantly increases the risk of major cardiovascular events, especially peripheral vascular events in patients with advanced CKD. Trials of multifactorial management of cardiovascular risk factors are required to determine if outcomes for this population may be improved.

Arterial calcification and stiffness in chronic kidney disease.

1. Patients with chronic kidney disease (CKD) demonstrate a high burden of vascular disease. This vascular disease is unusual by way of a preponderance of medial calcification. Further, traditional cardiovascular risk factors fail to fully explain the high cardiovascular event rate in this population. 2. The present review examines the problem of medial calcification and arterial stiffness evident in patients with CKD and explores evidence for its existence and the potential pathological process involved. Many factors are emerging as potential culprits in this disease entity, although the specific roles of components such as fetuin-A, matrix Gla protein, osteopontin and fibroblast growth factor-23 have yet to be determined. Calcium and phosphate balance remains integral to the pathological process. 3. Pulse wave velocity has proven to be a useful tool to assess and follow arterial stiffness in CKD patients and is discussed. 4. Finally, techniques aimed at reducing or reversing arterial calcification and stiffness are discussed, with as yet no definitive answers available.

Erythrocyte oxidative stress in clinical management of diabetes and its cardiovascular complications.

Diabetes mellitus is a chronic disease in its own right and is also regarded as a cardiovascular risk factor as well as a cardiovascular disease, due to its ability to progress to a stage of cardiovascular co-morbidity. The pathophysiology of cardiovascular complications in diabetes is reported to involve hyperglycaemia-induced oxidative stress. The erythrocyte has an array of endogenous antioxidants involved in quenching oxidant production and the exponential chain reactions in diabetes. When the erythrocyte is oxidatively stressed, as demonstrated by depleted reduced glutathione and/or increased malondialdehyde in its cell membrane, the risk of diabetes progression and its cardiovascular sequelae, including atherosclerosis and coronary artery disease, is increased. Virtually all studies that determined erythrocyte malondialdehyde and glutathione in diabetes show consistently increased and reduced levels, respectively. Furthermore, cardiovascular complications of diabetes are reported to commence at the prediabetes stage. Current coronary artery disease screening programmes based on the presence of two or more risk factors are failing to identify those with increased risk of diabetes and cardiovascular complications, thereby limiting early interventions. Screening that includes erythrocyte oxidative stress determination may provide an additional marker for both preclinical and advanced disease. In this review, a concise description of the involvement of erythrocyte oxidative stress in diabetes mellitus and its cardiovascular sequelae is presented. Antioxidant action and interaction in the erythrocyte are also described, with emphasis on why current coronary artery disease screening markers cannot be regarded as erythrocyte oxidative stress markers.

Associations of hemodialysis dose and session length with mortality risk in Australian and New Zealand patients.

The optimal combination of hemodialysis (HD) dose and session length remains uncertain, and previous studies have not conclusively shown session length to be an important independent determinant of patient mortality. The objective of this study was to examine associations between HD dose and session length with mortality risk using data from the Australian and New Zealand Dialysis and Transplant Registry. Analyses were performed using a prospective inception cohort comprising all incident adult patients treated by thrice-weekly maintenance HD, who commenced renal replacement therapy with HD between 1 April 1997 and 31 March 2004. In all, 6593 patients were identified, of whom 4193 had sufficient data for multivariate analyses. HD dose (single pool fractional clearance of urea, Kt/V) and session length were included in analyses as those recorded 12 months after HD inception to reduce confounding by residual renal function. The outcome examined was patient mortality. Survival analyses included Kaplan-Meier calculations of survival and Cox regression for multivariate analyses. Covariates in Cox models included patient demographics, co-morbid medical conditions at HD inception, and HD operating parameters. After adjustment for covariates and each other, Kt/V of 1.30-1.39 and session length of 4.5-4.9 h were associated with the lowest mortality risk. There was no interaction between HD dose and session length. Thus, the optimal combination for mortality appears to be Kt/V of > or = 1.3 and session length of > or = 4.5 h. These data suggest a randomized controlled trial to test these hypotheses, and support the inclusion of criteria relating to session length in definitions of adequate HD practice.

Treatment for lupus nephritis.

BACKGROUND: Lupus nephritis is the renal manifestation of systemic lupus erythematosus (SLE) - a disease mainly affecting young women with substantial morbidity and mortality. It is classified by the World Health Organization (WHO) criteria I - VI based on histology. WHO Class IV is a diffuse proliferative glomerulonephritis which has the worst prognosis without treatment, with a reported 17% five year survival in the era 1953-1969. This survival was 82% in the early 1990's and continues to improve. An important factor behind this has been the use of cytotoxics such as cyclophosphamide in addition to steroids. OBJECTIVES: To assess the benefits and harms of different treatments in biopsy-proven proliferative lupus nephritis (LN). SEARCH STRATEGY: We searched the Cochrane Renal Group's specialised register (January 2003), the Cochrane Central Register of Randomised Controlled Trials (CENTRAL - The Cochrane Library issue 1, 2003), MEDLINE (1966 - 31 January 2003), EMBASE (1980 - 31 January 2003) and handsearched reference lists of retrieved articles. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs comparing treatments for PLN in both adult and paediatric patients with Class III, IV, Vc, Vd lupus nephritis were included. All treatments were considered. DATA COLLECTION AND ANALYSIS: Data was extracted and quality assessed independently by two reviewers, with differences resolved by discussion. Dichotomous outcomes are reported as relative risk (RR) and measurements on continuous scales are reported as weighted mean differences (WMD) with 95% confidence intervals. Subgroup analysis by study quality, drug type and drug route have been performed where possible to explore reasons for heterogeneity. MAIN RESULTS: Of 920 articles identified, 25 were RCTs suitable for inclusion, which enrolled 915 patients. The majority compared cyclophosphamide or azathioprine plus steroids versus steroids alone. Cyclophosphamide plus steroids reduced the risk of doubling of serum creatinine (RR 0.59, 95% CI 0.40 to 0.88) compared to steroids alone but had no impact on mortality (RR 0.98, 95% CI 0.53 to 1.82). The risk of ovarian failure was significantly increased (RR 2.18, 95% CI 1.10 to 4.34). Azathioprine plus steroids reduced the risk of all cause mortality compared to steroids alone (RR 0.60, 95% CI 0.36 to 0.99), but did not alter renal outcomes. Neither therapy was associated with increased risk of major infection. No benefit was found with addition of plasma exchange to cyclophosphamide or azathioprine plus steroids for mortality ( RR 0.71, 95% CI 0.50 to 1.02), doubling of serum creatinine (RR 0.17, 95% CI 0.02 to 1.26) or end-stage renal failure (RR 1.24, 95% CI 0.60 to 2.57). There was also no increased risk of major infection (RR 0.69, 95% CI 0.35 to 1.37). REVIEWER'S CONCLUSIONS: Until future RCTs of newer agents are completed, the current use of cyclophosphamide combined with steroids remains the best option to preserve renal function in proliferative LN. The smallest effective dose and shortest duration of treatment should be used to minimise gonadal toxicity, without compromising efficacy.

Randomized, placebo-controlled trial of intramuscular vitamin B12 for the treatment of hyperhomocysteinaemia in dialysis patients.

BACKGROUND: Plasma homocysteine is elevated in patients with end-stage renal disease (ESRD) and is a risk factor for cardiovascular disease. Folic acid has been shown to partially reduce homocysteine levels in dialysis patients. It is not known whether vitamin B12 reduces homocysteine independent of folic acid in patients who are not vitamin B12 deficient. AIM: To determine whether 1 mg vitamin B12 lowers homocysteine in stable, chronic, haemodialysis patients independent of folic acid. METHODS: Twenty-eight haemodialysis patients were randomized to receive three doses of 1 mg vitamin B12 or 1 mL saline placebo in a double-blind fashion at 1-month intervals. Fasting plasma total homocysteine, folic acid, red-cell folate, vitamin B12 and haemoglobin levels were determined prior to each dose and 4 weeks after the final injection. The study was powered to detect a 30% reduction in homocysteine over the 3 months. RESULTS: Both the two groups were well matched with respect to total homocysteine levels, folic acid, red-cell folate and vitamin B12 levels. Serum vitamin B12 levels were significantly higher in the treatment group compared to placebo (217.7 pmol/L; 95% confidence interval (CI) 103.0-332.5; P < 0.001) at the end of the trial but homocysteine levels were not significantly different (3.08 micromol/L; 95% CI -4.44-10.61; P= 0.406). CONCLUSIONS: The administration of intramuscular vitamin B12 over a 3-month period does not result in any reduction of plasma homocysteine levels in haemo-dialysis patients independent of folate status, however reductions of <30% cannot be excluded by the present study. High-dose folic acid remains the treatment of choice in reducing homocysteine, but whether this results in a reduction in cardiovascular events remains to be determined.

Epidemiology and blood flow surveillance of the native arteriovenous fistula: a review of the recent literature.

Vascular access placement is a key management issue for hemodialysis patients. Despite being well regarded as the access of first choice, the native arteriovenous fistula (AVF) remains underutilized in the United States. The first part of this review examines recent epidemiology studies addressing patient factors associated with the use of the synthetic arteriovenous graft as opposed to the native fistula. Female gender and older age are consistently associated with a higher frequency of graft use. Diabetes, peripheral vascular disease, and body mass index were associated with graft use in some but not all of the studies. Recent evidence also suggests an independent survival advantage for patients dialyzing via native fistulae especially for infection-related mortality. The second part reviews evidence surrounding the recommendations for blood flow surveillance of the native fistula. The hemodynamic features of the native fistula are examined and differences from synthetic grafts are highlighted. Clinical studies assessing the use of blood flow surveillance to prevent the sudden thrombosis of native fistulae are reviewed. Blood flow thresholds for further investigation are yet to be determined definitely for AVF and randomized studies should be performed to assesses the impact on AVF thrombosis rates.

Development of a capture ELISA for the detection of antibodies to enteropathogenic Escherichia coli (EPEC) in rabbit flocks using intimin-specific monoclonal antibodies.

A capture enzyme-linked immunosorbent assay (cELISA) was developed using intimin-specific monoclonal antibodies to detect specific antibody in rabbits that have been in contact with enteropathogenic Escherichia coli (EPEC). Sera from 121 EPEC-negative, minimum-disease-level (MDL) rabbits were used for negative controls, and sera from 25 MDL rabbits, experimentally infected with EPEC of bio-/serotype 3-/O15, for positive controls. These were used to determine a cut-off value for a positive cELISA result. The value selected gave the test a sensitivity of 80.0% and a specificity of 98.4% on an individual level. At this value, a flock level sensitivity and specificity of 79.2 and 85.2%, respectively were calculated for a flock with a prevalence of seven per cent, if 40 animals were tested, and a minimum of two reactors were obtained. The test characteristics improve with increasing prevalence. To evaluate the diagnostic potential of the cELISA, sera from 40 to 50 slaughter rabbits per flock from 25 rabbit flocks with bacteriologically determined EPEC status were tested. The results demonstrated that this test can be a useful tool to determine the EPEC status of a rabbitry, provided that it is used at regular intervals.

Women's health issues in haemodialysis patients.

OBJECTIVES: To describe reproductive health issues in women with end-stage renal disease (ESRD) treated with haemodialysis. STUDY DESIGN: Cross-sectional survey based on structured interviews. SETTING: Nephrology units of two major metropolitan tertiary referral hospitals in Victoria and their satellite dialysis centres between 1 November 1998 to 30 June 1999. METHODS: Women aged 20 years or over in haemodialysis programs. OUTCOME MEASURES: Menstrual status; prevalence of menstrual and climacteric symptoms; use of gynaecological screening; and prevalence of comorbidities that may benefit from hormone replacment therapy. RESULTS: 48 women completed the survey. They were similar to the 485 women undergoing haemodialysis in Victoria in age (mean age, 55.5 years; range, 20-84 years), years on dialysis (mean age, 3.9 years; range, 1 month-17 years) and primary diagnosis. Eleven of the 15 premenopausal women reported menstrual cycles of 22-35 days, 13 reported common premenstrual symptoms, and six reported dysmenorrhoea that interfered with daily activities. Average age at menopause was 47.7 years (95% CI, 45.6-49.9 years), and six of the 31 postmenopausal women underwent menopause before 45 years. Eight had ever been prescribed hormone replacement therapy (oral in all cases). Over half the women (26) had not had a Pap smear in the last two years, and 12 of those aged over 50 (38%) had not had a mammogram in the same period. CONCLUSION: Despite their risk of early menopause, cardiovascular disease and bone fracture, few women undergoing haemodialysis were offered hormone replacement therapy. Nor were they adequately screened for gynaecological cancers. Women's health issues seem to be neglected among haemodialysis patients.

The antihypertensive hydralazine is an efficient scavenger of acrolein.

Recent work indicates the highly toxic alpha,beta-unsaturated aldehyde acrolein is formed during the peroxidation of polyunsaturated lipids, raising the possibility that it functions as a 'toxicological second messenger' during oxidative cell injury. Acrolein reacts rapidly with proteins, forming adducts that retain carbonyl groups. Damage by this route may thus contribute to the burden of carbonylated proteins in tissues. This work evaluated several amine compounds with known aldehyde-scavenging properties for their ability to attenuate protein carbonylation by acrolein. The compounds tested were: (i) the glycoxidation inhibitors, aminoguanidine and carnosine; (ii) the antihypertensive, hydralazine; and (iii) the classic carbonyl reagent, methoxyamine. Each compound attenuated carbonylation of a model protein, bovine serum albumin, during reactions with acrolein at neutral pH and 37 degrees C. However, the most efficient agent was hydralazine, which strongly suppressed carbonylation under these conditions. Study of the rate of reaction between acrolein and the various amines in a protein-free buffered system buttressed these findings, since hydralazine reacted with acrolein at rates 2-3 times faster than its reaction with the other scavengers. Hydralazine also protected isolated mouse hepatocytes against cell killing by allyl alcohol, which undergoes in situ alcohol dehydrogenase-catalysed conversion to acrolein.

Dialyzer performance in the clinic: comparison of six low-flux membranes.

The aim of this study is to assess the clinical performance of 6 different low-flux dialysis membranes under steady-state conditions in terms of urea and phosphate clearances. Ten stable hemodialysis patients were examined. The following dialyzers were studied, all in 1.5- to 1.6-m2 format: cuprammonium, cellulose acetate, cellulose diacetate, hemophane, polysulfone (low-flux), and polysynthane. The following parameters were examined: urea reduction ratio, phosphate reduction ratio, "instantaneous dialyzer clearance" for urea and phosphate, and total amount of urea and phosphate removed in the dialysate over a 1-week (three dialyses) period. Although there were differences between the membranes, all produced results within a narrow range. There was no one membrane that produced superior clearances in all categories. The cellulose acetate membrane was the least satisfactory membrane. Phosphate clearances were at best one third that of urea clearances. When choosing a low-flux dialysis membrane, urea and phosphate clearances are so similar amongst different membranes that other criteria are likely to have a greater influence on the choice of membrane.

Outcome of a screening program for vancomycin-resistant enterococci in a hospital in Victoria.

OBJECTIVE: To screen for faecal colonisation with vancomycin-resistant enterococci (VRE) among potentially at-risk patients. DESIGN: Infection control screening program. SETTING: Monash Medical Centre (a tertiary care hospital), Melbourne, Victoria, in the seven months from June 1997. PATIENTS: Patients in the Renal, Oncology and Intensive Care (ICU) Units. MAIN OUTCOME MEASURES: Presence of VRE in a rectal swab or faecal specimen taken at admission and at regular intervals during inpatient stay; presence of vancomycin-resistance genes (vanA, vanB and vanC) assessed by polymerase chain reaction (PCR); genetic clonality of isolates assessed by pulsed-field gel electrophoresis (PFGE). RESULTS: 574 patients (356 renal, 134 ICU and 84 oncology) were screened; 12 were colonised with VRE--nine renal inpatients, two having peritoneal dialysis or incentre haemodialysis, and one ICU patient. Nine isolates were Enterococcus faecalis (seven positive for vanB and two negative for all three resistance genes) and three were Enterococcus faecium (all positive for vanB). Eight were high-level gentamicin resistant. PFGE suggested genetic clonality between the index isolate and five other isolates from renal patients. No specific clinical practice was associated with VRE colonisation. Attempts to clear rectal carriage with oral ampicillin/amoxycillin or bacitracin were of limited success. Although antibiotic prescribing in the Renal Unit was generally consistent with defined protocols, use of vancomycin and third-generation cephalosporins has been further restricted. CONCLUSIONS: Renal inpatients in our institution appear most at risk of VRE colonisation (4.6% overall) and therefore of VRE infection. Routine screening, especially of potentially high-risk patients, should be considered in major Australian hospitals.

Granulomatous glomerulonephritis in intravenous drug users: a report of three cases in oxycodone addicts.

Various well-documented renal lesions are associated with intravenous drug use; however, intraglomerular mesangial granulomas have not been previously described. We report three patients who developed an unusual granulomatous glomerulonephritis and interstitial nephritis after intravenous injection of oxycodone, derived from suppositories. Granulomas were seen in an intraglomerular mesangial and also interstitial location. In both sites, the granulomas were associated with filamentous material, presumably derived from a component of the suppositories. This material was periodic acid-Schiff-positive, but negative with Congo red and silver stains. Ultrastructurally, the filamentous material was seen within the mesangial granulomas and also in a subendothelial location, suggesting derivation from the circulation with subsequent transport across the basement membrane and accumulation in the mesangium, where a granulomatous reaction was elicited. All patients developed a degree of renal failure; two of the patients require hemodialysis 20 and 30 months after presentation.

Total body nitrogen predicts long-term mortality in haemodialysis patients--a single-centre experience.

BACKGROUND: It has been estimated that 30-50% of adult haemodialysis patients have moderate to severe malnutrition. We have previously shown that estimation of total body nitrogen, expressed as a nitrogen index (NI) by in vivo neutron activation analysis (IVNAA) is an accurate tool for estimating total body protein in dialysis patients. It is not clear whether the nitrogen index is predictive of mortality and morbidity in dialysis patients. METHODS: We studied the long-term predictive value of nutritional assessment by IVNAA and serum albumin on mortality and morbidity (including infection episodes requiring hospital admission, ischaemic heart disease (IHD), cerebrovascular or peripheral vascular disease (PVD). Seventy-six chronic haemodialysis patients were initially studied between 1989 and 1991, with a minimum follow-up of 5 years. The mean age of the patients was 48.3 years (range 21-76). Patients were divided into two groups, group I, n = 22, had a NI < or = 0.8 (NI < or = 0.8 represents protein malnutrition) and group II, n = 54, had a NI > 0.8. RESULTS: Fifteen patients in group II died in the follow-up period compared to nine from group I (P < 0.05), but NI < or = 0.8 did not predict vascular or infective morbidity. Serum albumins < or = 35 g/day did predict over all mortality (P < 0.05) as well as infection episodes (P < 0.001). When patients above the age of 50 years were analysed, NI did predict mortality (P < 0.05) but serum albumin did not, while the age of> 50 itself was a strong predictor of mortality (P < 0.001). CONCLUSION: We conclude that NI < or = 0.8 is predictive of long-term mortality. This reinforces the view that low body protein stores are predictive of increased mortality in dialysis patients and that the serum albumin is predictive of mortality because of its reflection of protein stores.