The use of belimumab in three cases of refractory lupus nephritis.

In recent trials for the treatment of systemic lupus erythematosus (SLE), belimumab (BLM), in addition to standard immunosuppression, has been shown to improve renal and nonrenal outcomes. We report our experience using BLM in three cases of refractory lupus nephritis (LN), where renal remission was not achieved using cyclophosphamide, mycophenolate mofetil and other immunosuppressive medications. In two of the three cases, BLM therapy led to a partial remission of LN, improvement in serological markers of SLE and disease activity, which permitted a reduction in prednisolone dosing. Treatment with efficacious therapies early in the course of LN is a desirable therapeutic strategy, to achieve early remission of proteinuria and curtail the development of irreversible chronic renal damage. Further studies are needed to provide information on the effectiveness of BLM for maintenance of remission, prevention of flares and monitoring for long-term complications of B-cell modulation.

Medical student psychological distress and academic performance.

INTRODUCTION: The impact of medical student psychological distress on academic performance has not been systematically examined. This study provided an opportunity to closely examine the potential impacts of workplace and study related stress factors on student's psychological distress and their academic performance during their first clinical year. METHODS: This one-year prospective cohort study was performed at a tertiary hospital based medical school in Melbourne, Australia. Students completed a questionnaire at three time points during the year. The questionnaire included the validated Kessler psychological distress scale (K10) and the General Health Questionnaire-28 (GHQ-28), as well as items about sources of workplace stress. Academic outcome scores were aggregated and correlated with questionnaire results. RESULTS: One hundred and twenty six students participated; 126 (94.7%), 102 (76.7%), and 99 (74.4%) at time points one, two, and three, respectively. 33.1% reported psychological distress at time point one, increasing to 47.4% at time point three. There was no correlation between the K10 scores and academic performance. There was weak negative correlation between the GHQ-28 at time point three and academic performance. Keeping up to date with knowledge, need to do well and fear of negative feedback were the most common workplace stress factors. CONCLUSIONS: Poor correlation was noted between psychological distress and academic performance.

Acute Tubular Necrosis and Thrombocytopenia Associated With Rifampin Use: Case Report and Review.

A case of rifampin-induced acute tubular necrosis requiring hemodialysis in a patient receiving thrice-weekly rifampin with daily dapsone for retreatment of relapsed Hansen's disease is reported. The patient had positive rifampin-dependent antiplatelet antibodies. Case reports of acute renal failure associated with the use of rifampin are summarized.

Predictors of infection requiring hospitalization in patients with systemic lupus erythematosus: a time-to-event analysis.

OBJECTIVES: To evaluate the predictors of serious infection in patients with systemic lupus erythematosus (SLE). METHODS: Serious infections were identified in SLE patients in a prospectively-followed single centre cohort. Associations of serious infection with disease-related variables and medication use were analysed using Cox and related regression models. RESULTS: 346 patients were followed for a mean (SD) of 6.6 (3.7) years. 86 episodes of serious infection were observed, with an incidence rate of 3.8 episodes per 100 person-years. Patients who had serious infection had higher baseline SLE Damage Index (SDI) and Charlston Comorbidity Index (CCI); they were also more likely to have high disease activity status (HDAS), and higher disease activity in multiple clinical domains, higher flare rates, higher time-adjusted prednisolone dose exposure, and less time in lupus low disease activity state (LLDAS). Patients who have received cyclophosphamide, rituximab and mycophenolate were more likely to have experienced serious infection. After multivariable adjustment in Cox regression analysis, cyclophosphamide, higher SDI score, and higher disease activity were associated with an increased hazard of first serious infection. History of previous serious infection conferred the highest risk. Lymphopenia was also a modest but statistically significant predictor of serious infection. CONCLUSION: History of previous serious infection was the strongest predictor of serious infection in our SLE cohort. This study also suggests that clinical factors such as damage accrual, disease activity, and choice of immunosuppressant, can each have an independent risk in predicting serious infection particularly the first episode.

Body composition in home haemodialysis versus conventional haemodialysis: a cross-sectional, matched, comparative study.

BACKGROUND: Nutritional status predicts outcome in dialysis populations. Increased dialysis time and/or frequency reportedly improves nutritional status. We examined the impact of more intensive dialysis on body composition. METHODS: A cross-sectional, matched study comparing home haemodialysis (HHD) patients (>15 h/week, n = 28) and conventional haemodialysis (CHD) patients (<15 h/ week, n = 28), matched for age, sex, length of time on dialysis and diabetes, was performed. We measured total body protein (TBP) by in vivo neutron activation, total body fat (TBF) and skeletal muscle mass (SKMM) by dual-energy x-ray absorptiometry (DEXA) and biochemical and inflammatory parameters. Visceral (VFA) and subcutaneous fat areas (SFA) were determined from computed tomography. RESULTS: There was no significant difference in TBP (10.2 +/- 1.9 kg CHD versus 10.8 +/- 1.8 kg HHD, P = 0.18) or SKMM (25.6 +/- 5.6 kg CHD versus 26.2 +/- 4.2 kg HHD). TBF was not different (27.7 +/- 10.7 kg CHD versus 27.8 +/- 16.0 kg HHD), although the HHD group had greater VFA (182.0 +/- 105.6 cm(2) versus 173.8 +/- 90.1 cm(2)) and lower SFA (306.7 +/- 176.4 cm(2) versus 309.7 +/- 138.1 cm(2)), the difference was not statistically significant. Albumin concentrations were significantly increased in the HHD group (37.5 +/- 3.56 g/L versus 35.18 +/- 4.11 g/L, P = 0.03), whilst phosphate concentrations (1.57 +/- 0.41 mmol/LHHD versus 1.92 +/- 0.62 mmol/ LCHD, P = 0.02) and inflammatory parameters were lower. There was a positive relationship between hours of dialysis and TBP (beta = 0.08; P = 0.03). CONCLUSION: Surrogate nutritional markers and inflammatory parameters improved with more intensive dialysis, but this was not reflected by improved body composition. Further prospective studies are required to confirm whether more intensive dialysis affects body composition, and whether this impacts on metabolic risk and clinical outcome.

Reduction in beta2-microglobulin with super-flux versus high-flux dialysis membranes: results of a 6-week, randomized, double-blind, crossover trial.

BACKGROUND: Uremic toxicity is a major concern in the dialysis population. There is keen interest in techniques that increase the removal of larger uremic molecules. We examined the short-term impact of a new, more porous, super-flux Helixone membrane (FX-E) versus the conventional high-flux Helixone membrane (FX-60) on beta(2)-microglobulin (beta2M) reduction and nutritional and inflammatory parameters. STUDY DESIGN: Randomized, double blind, crossover, pilot trial. SETTING & PARTICIPANTS: A single freestanding dialysis center. 30 stable hemodialysis patients. INTERVENTION: Patients were treated with FX-60 and FX-E membranes for a treatment period of 6 weeks each, with a 2-week washout period in between. OUTCOME & MEASUREMENTS: Primary outcome was change in beta2M concentrations from baseline to end of treatment. Serum samples were obtained predialysis and postdialysis at 0, 2, and 6 weeks, and dialysate albumin samples were collected continuously throughout dialysis sessions. RESULTS: Mean postdialysis beta2M concentrations at the end of 6 weeks of treatment were 6.73 mg/L for FX-E versus 8.22 mg/L for FX-60, which was significantly lower overall by 0.69 mg/L (95% confidence interval [CI], -1.09 to -0.29; P = 0.001). beta2M reduction ratios were greater overall with FX-E by 4.83% (95% CI, 2.78 to 6.89; P < 0.001), with mean values of 57% for FX-60 versus 66% for FX-E at the end of treatment. Median dialysate albumin loss with FX-E was 1.23 g (range, 0.22 to 4.83 g) compared with 0.17 g (range, 0.0017 to 2.69 g) with FX-60, which was greater by 1.52 g (95% CI, 1.11 to 1.93; P < 0.001). Serum albumin concentrations were slightly lower with FX-E by 0.1 g/dL (0.55 g/L; 95% CI, -1.04 to -0.07; P = 0.03), but prealbumin concentrations were not significantly different at 8.53 mg/L (95% CI, -23.76 to 6.71; P = 0.3). There were no differences in inflammatory cytokine concentrations or small-solute removal. LIMITATIONS: Short-term pilot study. CONCLUSION: In this stable dialysis population, removal of beta2M was more efficient with the Helixone super-flux FX-E membrane, with only a small decrease in albumin concentrations despite increased albumin loss. Large trials with longer treatment periods are required to evaluate the impact of the FX-E membrane on clinical outcomes.

Are traditional risk factors valid for assessing cardiovascular risk in end-stage renal failure patients?

AIM: Cardiovascular diseases (CVD) are the major cause of morbidity and mortality in end-stage renal failure (ESRF). Establishing whether traditional risk factors are valid predictors of CVD in ESRF is important in order to devise preventive and interventional strategies for the ESRF populations. METHODS: In this retrospective cohort study, a cohort of patients on dialysis were examined between September 2000 and February 2001. Only those without previous CVD events at baseline were included. For each individual, 5 year CVD risk was calculated using the New Zealand 5 year CVD risk prediction charts based on the Framingham Heart Study prognostic algorithm. The subsequent 5 year CVD outcome for each patient was determined and the observed rate of first CVD events was compared to the predicted risk. Relation of individual risk factors with the CVD outcome was also assessed. RESULTS: Of the patients, 274 were without previous CVD events at baseline and 27% experienced CVD events during the subsequent 5 years. Observed CVD risk was more than twofold that of predicted risk although there was a linear correlation between the two. Among individual risk factors, increasing age, diabetes and smoking were significantly related to the incidence of the CVD events but, unlike in the general population, systolic blood pressure, total cholesterol/high-density lipoprotein ratio and body mass index were not significantly related to CVD events. CONCLUSION: The very high incidence of CVD in ESRF patients suggest that non-traditional risk factors present in the uraemic state are independent risk factors for CVD in ESRF patients. Nevertheless, the application of traditional cardiovascular risk profiles does allow risk stratification of the ESRF population.

What have we learned from clinical trials on prevention?

The incidence of end-stage renal disease is increasing at an alarming rate. While diabetes is now the most common cause of renal failure, hypertension commonly coexists, exacerbating renal damage and the other vascular complications of diabetes. Clinical trials have shown the benefits of intervention strategies that target not only the retardation of renal disease, but also the primary prevention of the conditions known to cause renal damage. These strategies include: lifestyle modification programs to prevent diabetes and hypertension; aggressive treatment of established hypertension; combination antihypertensive regimens; and the use of angiotensin-converting-enzyme inhibitors and angiotensin II receptor blockers for additional renoprotection beyond that of blood pressure control. In addition, albuminuria and proteinuria have emerged as powerful predictors of progression of renal disease. The present paper reviews the results of available clinical trials and meta-analyses on these interventional strategies, and highlights the potential of albuminuria and proteinuria in predicting renal and cardiovascular outcomes.

Wegener's granulomatosis in pregnancy: a novel approach to management.

Wegener's granulomatosis rarely is diagnosed in women of childbearing age and is, thus, uncommonly encountered in pregnancy. Although conventional treatment with steroids and cyclophosphamide controls disease activity in 90% of patients, the associated teratogenicity of such a regimen warrants careful consideration in pregnancy. We describe successful remission induction with the use of intravenous immunoglobulin and steroids alone in a woman diagnosed with de novo Wegener's granulomatosis during the first trimester of pregnancy.

Longitudinal body composition changes due to dialysis.

BACKGROUND AND OBJECTIVES: Nutritional status remains a powerful predictor of outcome in the dialysis population. High body mass index (BMI) seems protective, but which body compartment (fat or lean mass) confers this protection remains unclear. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a longitudinal study (n = 60; n = 46 completed) examining changes in body composition in incident peritoneal dialysis (PD) and hemodialysis (HD) patients over 12 months. We measured total body protein (TBP) by in vivo neutron activation, expressed as nitrogen index (NI), and lean body mass (LBM) and total body fat (TBF) by dual-energy x-ray absorptiometry. Visceral and subcutaneous fat areas (SFAs) were determined from computed tomography. Comparisons were made between different BMI groups and dialysis modalities. RESULTS: No significant change was found in TBP, NI, or TBF. The obese group (BMI >30) had an increase in all mean LBM parameters with a significant increase in NI compared with normal-weight and the overweight group. This increase in NI remained significant after multivariate analysis ß coefficient (0.08). PD patients had the greatest increase in TBF, with a significant increase in visceral fat (VFA:SFA ratio ß coefficient = 0.23). CONCLUSIONS: Obese patients showed preservation of TBP compared with normal- and overweight patients, suggesting that energy storage as fat mass is of value in the dialysis population.

Comparison of biochemical, haematological and volume parameters in two treatment schedules of nocturnal home haemodialysis.

BACKGROUND: The biochemical, haemodynamic, clinical and nutritional benefits of nocturnal home haemodialysis (NHHD) compared with 4 h, three times per week conventional haemodialysis are well known and accrue by increasing dialysis time and frequency either for 8 h alternate night per week (NHHD3.5) or for 8 h six nights per week (NHHD6). However, there are little data comparing NHHD3.5 with NHHD6. METHOD AND RESULTS: Thirteen patients on NHHD6 were compared with 21 patients on NHHD3.5, all with similar demographic profiles. Pre- and post-dialysis phosphate (PO4) control was ideal between the groups. However, all NHHD6 needed PO4 supplementation compared with 4/21 (19%) NHHD3.5. In the present study, 8/21 (38%) NHHD3.5 needed PO4 binders whereas none was required with NHHD6. The pre-haemoglobin (Hb) 122.8 g/L (NHHD6) versus 124.9 g/L (NHHD3.5) and the pre-albumin 38.31 g/L (NHHD6) versus 37.71 g/L (NHHD3.5) were not significantly different. NHHD6 had significantly lower pre-blood urea and creatinine (10.16 vs 19.54 mmol/L and 437.0 vs 812.3 micromol/L, respectively). Less interdialytic urea and creatinine fluctuation were also noted in NHHD6. Of major significance was the significantly lower ultra filtration rate and intradialytic weight gains (mean +/- SEM) of NHHD6 (249 +/- 76 mL/h and 2.0 +/- 0.65 kg) versus NHHD3.5 (425 +/- 168 mL/h and 2.9 +/- 1.2 kg). CONCLUSION: The authors conclude that NHHD6 offers the optimum biochemical, volume and clinical outcome, but NHHD3.5 has additional appeal to providers seeking home-based therapy cost advantages and consumable expenditure control. A flexible dialysis programme should offer all the time and frequency options of NHHD but in particular, should support NHHD at a frequency sympathetic to the clinical rehabilitation and lifestyle aspirations of individual patients.