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.

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.

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.

The effects of deoxyspergualin on lymphocytes and monocytes in vivo and in vitro.

It has been suggested that deoxyspergualin, a new immunosuppressant, may be immunosuppressive via a purely antimonocyte action. As this appears to be unlikely, this study examines the effect of deoxyspergualin on lymphocyte and monocyte function in vivo and in vitro. It is demonstrated that deoxyspergualin inhibits human lymphocyte proliferation in response to mitogens and allogeneic stimulation. Furthermore, it is demonstrated that this inhibition occurs no matter whether the monocytes or lymphocytes are treated with the drug. The drug appears to have a more significant effect on the lymphocyte component; rhIL-2 appears partly to overcome the deoxyspergualin-induced inhibition of lymphocyte proliferation in response to allogeneic stimulation. In a rat renal transplant model, deoxyspergualin-treated animals demonstrated a moderate interstitial infiltrate in their transplant kidneys that comprised approximately 50% each of macrophages and lymphocytes. There was significantly less activation (e.g. IL-2R expression) in the treated kidney infiltrates compared to rejected controls. Thus deoxyspergualin is an agent with immunosuppressive effects on both lymphocytes and monocytes and would appear to have more marked effects on lymphocytes.

The effects of OKT3 therapy on infiltrating lymphocytes in rejecting renal allografts.

OKT3 antibody therapy is effective in the treatment of renal allograft rejection. However its exact mode of action is unknown. Following OKT3 administration, peripheral blood lymphocytes fail to express the CD3 antigen, although other membrane antigens are relatively preserved. In this way the lymphocytes are unable to respond to foreign antigens. It is not known whether this modulation of CD3 on lymphocytes occurs within the rejecting allograft. Ten patients who received OKT3 therapy for steroid-resistant renal allograft rejection were studied. The aim of the study was to examine whether OKT3 antibody therapy altered the degree or the relative composition of the inflammatory infiltrate and to assess whether OKT3 treatment resulted in modulation of CD3 on intragraft lymphocytes. The study involved immunoperoxidase examination of biopsy material and flow cytometric analysis of peripheral blood lymphocytes obtained before and during treatment with OKT3 antibody. The results show that the total number of infiltrating leukocytes decreased after 5 days of treatment (3215 +/- 700 cells/l. 0 mm2 of tissue before vs. 1730 +/- 635 at day 5; P less than 0.001). The relative proportions of macrophages, total lymphocytes, CD4 +ve and CD8 +ve cells did not alter during therapy. Despite marked modulation of peripheral blood lymphocytes (CD3/CD2 ratio 0.89 +/- 0.13 before vs. 0.10 +/- 0.11 during treatment, P less than 0.001), there was no evidence of modulation of intragraft lymphocytes (CD3/CD2 ratio 0.98 +/- 0.14 before vs. 0.90 +/- 0.21 during treatment, P = NS). Although OKT3 antibody therapy is effective clinically at improving renal allograft rejection, this study demonstrates that it does not appear to cause modulation of the CD3 antigen on intragraft lymphocytes.

Phenotypic definition of primed T cells in human renal allografts. Use of the CD45R marker.

Immunohistological studies indicate that T cells and macrophages are the major components of human kidney allograft infiltrates. Recent work has demonstrated a division of T lymphocytes into 2 subpopulations with distinct functions on the basis of their expression of the CD45R antigen (CD45R+ "naive" and CD45R- "memory" T cells). This study analyzes CD45R expression on circulating T cells and T cells infiltrating renal allografts in patients undergoing rejection and/or cyclosporine nephrotoxicity. The percentage of circulating T cells that expressed CD45R in patients with rejecting (63 +/- 4) or stable grafts (66 +/- 3) was not different from values obtained for normal donors (62 +/- 3). In contrast, the percentage of T cells expressing CD45R infiltrating rejecting grafts was 21 +/- 2 and was not affected by the stage of rejection; in patients with CsA toxicity the value was 22 +/- 6. The reduced proportion of T cells that expressed CD45R in the allograft may reflect a change in status from the naive state due to alloantigenic stimulation (which can be demonstrated in vitro) and/or a propensity of memory T cells to enter or be retained in an allograft.

Deoxyspergualin suppresses local macrophage proliferation in rat renal allograft rejection.

Deoxyspergualin (DSP) is a potent immunosuppressive drug that is able to both prevent and reverse acute allograft rejection. Although there is good evidence that DSP can inhibit T and B lymphocyte responses, the effect of this drug upon monocyte function is controversial. In the current study, substantial local proliferation of inflammatory macrophages (41.6 +/- 5.5% of ED1+ cells) within acutely rejecting rat renal allografts was identified by expression of the proliferating cell nuclear antigen. Treatment of animals with DSP not only reduced macrophage accumulation within the tissue, but it also significantly inhibited local proliferation of macrophages within the graft (26.4 +/- 5.6% of ED1+ cells, P < 0.05 vs. untreated). This appeared to be, at least in part, a direct effect of DSP upon macrophages since the drug also inhibited growth of 2 monocytic cell lines (RC-2A and U937) in vitro. However, DSP treatment had no effect upon LPS-induced monocyte IL-1 beta, TNF alpha, and IL-6 mRNA and protein production, indicating that this drug is not a general inhibitor of monocyte function. In conclusion, this study has demonstrated that local proliferation of macrophages within the kidney is a prominent feature of acute allograft rejection and that inhibition of this response is one mechanism whereby DSP exerts its potent immunosuppressive actions.

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.

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.

The evolution of the interstitial infiltrate in rejecting rat renal allografts: with particular reference to the production of gamma-interferon.

This study aimed to examine the evolution of the leucocytic infiltrate in rat renal allografts in the first 5 days of rejection. Immunohistology was used to assess the absolute numbers of infiltrating leucocytes in the rejecting allografts. The total infiltrate approximately doubled daily from day 1 through to day 4 (370 +/- 15 total leucocytes/mm2 of tissue on day 1 vs 5055 +/- 135 on day 4, p less than 0.05 for all days) and increased only a minor degree on day 5 (5485 +/- 535 leucocytes/mm2, p = n.s.). CD4 positive cells predominated until day 3, after which time CD8 positive cells greatly outnumbered CD4 positive cells (CD4:CD8 ratio day 3 1.83 vs day 5 0.53, p less than 0.05). Gamma-interferon was positive in T cells on day 2 (73% of all T cells) and was slightly positive on day 3 (5% of all T cells) but was negative on days 4 and 5. Activation markers such as IL-2Rs increased markedly from day 3. These findings favour a pivotal role for CD4 positive cells in the early phase of rejection and suggest that the early release of lymphokines by these cells is associated with the recruitment of CD8 positive cells to the allograft and the activation of those leucocytes present.

Two new anti-rat macrophage monoclonal antibodies.

There are relatively few monoclonal antibodies (MAbs) to rat monocyte/macrophages available. We describe here 2 new such antibodies. The first, 109.2, recognizes most rat monocyte/macrophages and all polymorphs. The antigen recognized by this antibody is upregulated by 15 mins exposure to PMA (Phorbol myristate acetate) but down regulated by overnight exposure to LPS (lipopolysaccharide). It is probably an adhesion molecule and is likely to represent the rat equivalent of CD11b. The second antibody, 112.1, recognizes lysozyme in rat macrophages, particularly alveolar macrophages. In addition it also recognizes lysozyme in hen, rabbit and human macrophages. It also recognizes lysozyme in other tissues such as Paneth cells and proximal renal tubular cells.

Total body protein status assessed by different estimates of fat-free mass in adult peritoneal dialysis patients.

OBJECTIVE: To assess the usefulness of fat-free mass (FFM) as an index of total body protein (TBPr) status in continuous ambulatory peritoneal dialysis (CAPD) patients. DESIGN: TBPr was measured by in vivo neutron activation analysis (IVNAA) and expressed as a standardised protein index (PI). FFM was estimated by dual energy X-ray absorptiometry (DXA), whole body counting of total body potassium (TBK), and creatinine kinetics (CK), and expressed as a standardised FFM index (FFMI). FFM was also determined by a criterion method based on four compartment model (4CM) which is defined as the sum of total body water determined by D2O dilution, TBPr determined by IVNAA, bone mineral determined by DXA, and glycogen estimated to be 4.4% of TBPr. Each patient was measured within a four hour period by all methods. SETTING: Body Composition Laboratory, Monash Medical Centre. SUBJECTS: Six male and twelve female CAPD patients (33-77 years). RESULTS: FFMI assessed by DXA and by TBK agreed with measurements of PI on identifying the mean TBPr status of the CAPD group as significantly below a comparable normal reference population (mean Z score: PI = -1.01 (P < 0.05); FFMI by DXA = -0.50 (P < 0.05); FFMI by TBK = -1.24 (P < 0.05)). In contrast, FFMI assessed by CK did not reveal a significantly reduced TBPr status (mean Z score: -0.70 (NS)). Furthermore, significant linear correlations were noted between PI and FFMI estimated by DXA and by TBK (r = 0.57 (P < 0.05) vs r = 0.69 (P < 0.05)) however no significant correlation was observed between PI and FFMI estimated by CK (r = 0.36 (NS)). Moderate variation in FFM hydration did not compromise the ability of DXA, TBK or CK to differentiate between protein deleted, normal and enriched patients. Comparison of FFM estimates between the criterion method and either DXA, TBK or CK revealed no significant bias (+ 1.8 kg vs -2.0 kg vs +0.8 kg) and respective SEE values of 3.8 kg (8.3%), 5.9 kg (14.3%) and 9.6 kg (21.7%). CONCLUSION: The findings of this study indicate that FFM estimated by either DXA or the whole body counting of TBK is a useful index of TBPr status in CAPD patients. However, FFM assessed by CK does not appear to be an appropriate index of TBPr status in CAPD patients.

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.

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.

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.

A call to the international nursing community: put AIDS in developing countries on the agenda.

In some African countries 10%-15% of the middle class may due during the 1990s and at the present time the human infrastructure is being eroded by HIV. Over 90% of home and community care is being supervised by nursing and midwifery personnel in some developing countries. What will happen if these carers become ill or die? Peter Kerr provided a micro view of HIV disease in developing countries in 'Health care crisis in Africa', August ANJ. In this article he discusses the macro implications for developing countries as they encounter the consequences of what is likely to be the most devastating epidemic of this century.

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.