Bisphosphonates for preventing bone disease in kidney transplant recipients: a meta-analysis of randomized controlled trials.

An estimated 60% of kidney transplant recipients have mineral bone disease and about 0.5% break their hip within the first year after transplantation. We conducted a systematic review of benefits and harms of bisphosphonates in kidney transplant recipients. We searched CENTRAL (Issue 5, 2015) for randomized controlled trials in all languages and screened the reference list of an earlier Cochrane review. One reviewer identified the trials, extracted all data, and assessed risk of bias. Meta-analysis used a random effects model, with results expressed as risk ratios (RR) or mean differences (MD) with 95% confidence intervals (CI). Bisphosphonates have uncertain effects on death (RR 0.45, CI 0.04-4.69) and vertebral fractures (RR 0.58, CI 0.24-1.43, I(2) 0%). Bisphosphonates moderately to importantly reduce the loss of vertebral bone mineral density (MD 5.98%, CI 3.77-8.18% change from baseline in g calcium/cm² at 12 months, I(2) 91%) and femoral bone mineral density (MD 5.57%, 3.12-8.01% change from baseline in g calcium/cm² at 12 months, I(2) 69%). At this stage, insufficient evidence exists to support routine use of bisphosphonates to reduce fracture risk after kidney transplantation. Data on important health outcomes are lacking, surrogate outcomes poorly reflect bone quality in kidney transplant recipients, and serious adverse events are not studied and reported systematically.

Serum urea concentration is probably not related to outcome in ICU patients with AKI and renal replacement therapy.

BACKGROUND: Acute kidney injury (AKI) is a common complication in patients admitted to the intensive care unit (ICU). Among other variables, serum urea concentrations are recommended for timing of initiation of renal replacement therapy (RRT). The aim of this study was to evaluate whether serum urea concentration or different serum urea concentration cutoffs as recommended in the literature were associated with in-hospital mortality at time of initiation of RRT for AKI. METHODS: This is a retrospective single- centre study during a 3-year period (2004-07), in a 44-bed tertiary care centre ICU of adult AKI patients who were treated with RRT. RESULTS: Three hundred and two patients were included: 68.9% male, median age 65 years and an APACHE II score of 21. The overall in-hospital mortality was 57.9%. Non-survivors were older (67 versus 64 years, P = 0.016) and had a higher APACHE II score (22 versus 20, P < 0.001). At time of initiation of RRT, they were more severely ill and had a lower serum urea concentration compared to survivors (130 versus 141 mg/dL, P = 0.038). Serum urea concentration, as well as the different historical serum urea concentration cut-offs had low area under the curves for the receiver operating characteristic curve for prediction of mortality. In multivariate analysis, age, and at time of initiation of RRT, potassium, SOFA score with exclusion of points for AKI and RIFLE class were associated with mortality, but serum urea concentration and the different cut-offs were not. CONCLUSIONS: This retrospective study suggests that serum urea concentration and serum urea concentration cut-offs at time of initiation of RRT have no predictive value for in-hospital mortality in ICU patients with AKI.

Epidemiology of infection in critically ill patients with acute renal failure.

OBJECTIVES: Critically ill patients with infection are at increased risk for developing acute renal failure (ARF), and ARF is associated with an increased risk for infection. Both conditions are associated with prolonged length of stay (LOS) and worse outcome; however, little data exist on the epidemiology of infection in this specific cohort. Therefore, we investigated the occurrence of infection in a cohort of critically ill patients with ARF treated with renal replacement therapy (RRT). In addition, we assessed whether this infection worsened outcome. DESIGN: Retrospective cohort study. SETTING: General intensive care unit (ICU) in an academic tertiary care center comprising a 22-bed surgical ICU, eight-bed cardiac surgery ICU, 14-bed medical ICU, and six-bed burn center. PATIENTS: Six hundred forty-seven consecutive critically ill patients with ARF treated with RRT, admitted between 2000 and 2004. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: total of 519 (80.2%), 193 (29.8%), 66 (10.2%), and ten (1.5%) patients developed one, two, three, and four episodes of infection, respectively. Of 788 episodes of infection observed, 364 (46.2%) occurred before, 318 (40.3%) during, and 106 (13.4%) after discontinuation of RRT. Pneumonia (54.3%) was most frequent, followed by intra-abdominal (11.9%) and urinary tract infections (9.7%). Infections were caused by Gram-negative organisms in 33.7%, Gram-positive organisms in 21.6%, and yeasts in 9.8%. Patients with infection had higher mortality (p = 0.04) and longer ICU and hospital LOS. They needed more vasoactive therapy and spent more time on mechanical ventilation and RRT (all p < 0.001) than patients without infection. After adjustment for potential confounders, Acute Physiology and Chronic Health Evaluation II score, age, mechanical ventilation, and vasoactive therapy were associated with worse outcome, but infection was not. CONCLUSIONS: Infection occurred in four fifths of critically ill patients with ARF treated with RRT and was in an unadjusted analysis associated with longer LOS and higher mortality. After correction for other covariates, infection was no longer associated with in-hospital mortality.

Health implications of antimicrobial resistance for patients with acute kidney injury and bloodstream infection.

Studies have produced conflicting findings on outcomes for patients with antimicrobial-resistant infection. This study evaluated whether infection with an antimicrobial-resistant organism affects outcome in critically ill patients with acute kidney injury treated with renal replacement therapy and whose clinical course is complicated with a nosocomial bloodstream infection. We found that infection with an antimicrobial-resistant organism did not adversely affect clinical outcome in this specific cohort, which already has a high mortality rate.

Severe lactic acidosis in critically ill patients with acute kidney injury treated with renal replacement therapy.

PURPOSE: Severe lactic acidosis (SLA) is frequent in intensive care unit (ICU) patients with acute kidney injury (AKI) treated with renal replacement therapy (RRT). The aim of the study is to describe the epidemiology of SLA in this setting. MATERIALS AND METHODS: An observational single-center cohort analysis was performed on AKI patients treated with RRT. At initiation of RRT, SLA patients (serum lactate concentration>5 mmol/L and pH<7.35) were compared with non-SLA patients. RESULTS: Of the 454 patients dialyzed during the study period, 342 patients matched inclusion criteria (116 with and 226 patients without SLA). In SLA patients, lactate stabilized/decreased in 69.7% at 4 hours (P=.001) and in 81.8% during the period of 4 to 24 hours (P<.001) after initiation of RRT. Mortality during this 24-hour period was 31.0%. Intensive care unit mortality was 83.6% compared with 47.3% in non-SLA patients. Initial lactate concentration was not related to ICU mortality in SLA patients. CONCLUSIONS: Severe lactic acidosis was frequent in AKI patients treated with RRT. Severe lactic acidosis patients were more severely ill and had higher mortality compared with patients without. During the first 24 hours of RRT, a correction of lactate concentration and acidosis was observed. In SLA patients, lactate concentration at initiation of RRT was not able to discriminate between survivors and nonsurvivors.

Diagnostic performance of combined specific urinary proteins and urinary flow cytometry in urinary tract pathology.

BACKGROUND: Urinalysis comprises three techniques: urinary flow cytometry, test strip analysis and determination of specific urinary proteins. We investigated the diagnostic possibilities of combining these methods for a cohort of patients with a variety of well-documented urological and nephrological pathology. METHODS: Urinary samples from 407 in- and out-patients with nephrological or urological pathology were retrospectively included in our study. Test strip analysis (URISYS 2400), urinary flow cytometry (UF-100) and urinary protein analysis [albumin, total protein, alpha1-microglobulin (A1M), alpha2-macroglobulin (A2M)] were performed. RESULTS: In discriminating upper and lower urinary tract infections, A1M and A1M/log(white blood cells) can be used, whereas pathological casts only give poor discrimination. The ratio A2M/log(red blood cells; RBC) allows differentiation between cystitis and pyelonephritis, while glomerular diseases can be recognised by the log(RBCxurinary total protein). Combining A2M and urinary albumin allows the determination of acute prostatitis. CONCLUSIONS: Using combined parameters provided by various urinalysis techniques, ratios can be proposed with diagnostic value for classifying renal and urological conditions. Possible integration in computer-based knowledge systems may offer valuable information for clinicians dealing with these pathologies.

Impact of iron sucrose therapy on leucocyte surface molecules and reactive oxygen species in haemodialysis patients.

BACKGROUND: It has been suggested that iron increases oxidative stress and that an excess of iron contributes to cardiovascular disease and infections in haemodialysis patients. In the present study, the effects of parenterally administered iron on leucocyte surface molecule expression and the production of reactive oxygen species (ROS) were evaluated. METHODS: Ten chronic haemodialysis (HD) patients without iron overload were studied. To each patient, four different regimens were applied: placebo; iron sucrose, either 30 or 100 mg, administered via the outflow dialyser line; and 100 mg of iron sucrose infused via the inflow dialyser line. Blood was sampled at different time points: before, during and after infusion and immediately before the next dialysis session. Levels of CD11b and CD45 expression on granulocytes and of CD11b, CD14 and CD36 on monocytes were determined using flow cytometric analysis. The generation of ROS was quantified using chemiluminescence with and without ex vivo stimulation by phorbol myristate acetate (PMA). RESULTS: No significant differences among the four different treatment regimes were found, neither in chemilumescence activity nor in the expression of CD11b and CD45 on granulocytes, and of CD11b, CD14 and CD36 on monocytes. CONCLUSIONS: Our results suggest that parenteral infusion of iron sucrose during haemodialysis in patients who have no signs of iron overload has no significant effect on the expression of leucocyte surface molecules and does not increase production of ROS.

Outcome in critically ill medical patients treated with renal replacement therapy for acute renal failure: comparison between patients with and those without haematological malignancies.

BACKGROUND: Starting renal replacement therapy (RRT) for acute renal failure in critically ill patients with haematological malignancies is controversial because of the poor outcome and high costs. The aim of this study was to compare the outcome between critically ill medical patients with and without haematological malignancies who received RRT for acute renal failure. METHODS: We retrospectively collected data on all consecutive patients who received RRT for acute renal failure at the Medical Intensive Care Unit (ICU) of a University Hospital between 1997 and 2002, and assessed the impact of the presence of a haematological malignancy on the survival within 6 months after ICU admission by Cox proportional hazard models. RESULTS: Fifty of the 222 (22.5%) consecutive patients with haematological malignancies admitted to the ICU over the study period received RRT for acute renal failure compared with 248 of the 4293 (5.8%) patients without haematological malignancies (P<0.001). Among patients who received RRT, those with haematological malignancies had higher crude ICU (79.6 vs 55.7%, P=0.002) and in-hospital (83.7 vs 66.1%, P=0.016) mortality rates, and a higher mortality at 6 months (86 vs 72%, P=0.018) by Kaplan-Meier estimates compared with those without haematological malignancies. However, after adjustment for the severity of illness and the duration of hospitalization before ICU admission, haematological malignancy by itself was no longer associated with a higher risk of death (hazard ratio 1.04; 95% confidence interval, 0.73-1.54, P=0.78). CONCLUSIONS: Medical ICU patients with haematological malignancies have a higher rate of occurrence of acute renal failure treated with RRT and a higher mortality, compared with those without haematological malignancies. However, the presence of a haematological malignancy by itself is not a reason to withhold RRT in medical ICU patients with acute renal failure.

Studies on dialysate mixing in the Genius single-pass batch system for hemodialysis therapy.

BACKGROUND: The Genius single-pass batch system for hemodialysis contains a closed reservoir and dialysate circuit of 75 L dialysate. The unused dialysate is withdrawn at the top of the reservoir and the spent fluid is reintroduced into the container at the bottom. Although it has been claimed that both fractions remain unmixed during the dialysis session, no direct proof of this assumption has yet been provided. In the present study, we investigated whether contamination of the unused dialysate with uremic solutes occurred and at which time point it began. Two different dialysate temperatures were compared. METHODS: Ten chronic hemodialysis patients were dialyzed twice with the Genius system, with dialysate prepared at 37 degrees C and 38.5 degrees C, respectively. The sessions lasted 270 minutes with blood/dialysate flow set at 300 mL/min. Dialysate was sampled at 5, 60, 180, 210, 225, 230, 235, 240, 255, and 270 minutes both from the inlet and outlet dialysate line and blood was sampled from the arterial line predialysis, after 4 hours, and postdialysis. All samples were tested for osmolality, urea, creatinine, p-cresol, hippuric acid, and indoxyl sulfate. RESULTS: Uremic solutes appeared in the inlet dialysate line between 3 hours 50 minutes and 4 hours 10 minutes after the start of dialysis, corresponding to 68.6 and 74.7 L spent dialysate, respectively (37 degrees C vs. 38.5 degrees C; P = NS). No difference in the amount of removed solutes and in the serum levels was observed between 37 degrees C and 38.5 degrees C. A Kt/V of 1.17 +/- 0.20 and 1.18 +/- 0.26, respectively, was reached with the 37 degrees C and 38.5 degrees C dialysate temperature (P = NS). CONCLUSION: Contamination with uremic solutes occurred at the dialysate inlet only near the end of the session when small quantities of fresh dialysate were left in the container. Differences in dialysate temperature did not result in a different separation between used and unused dialysate, or in differences in removal of toxins or Kt/V.

In vitro study of the potential role of guanidines in leukocyte functions related to atherogenesis and infection.

BACKGROUND: The blunted immune response upon stimulation in chronic renal failure (CRF) is often coupled to a baseline inflammatory status which has been related to atherogenesis. Uremic biologic fluids and several specific uremic retention solutes alter cell-mediated immune responses, as well as the interaction of calcitriol with the immune system. METHODS: The present study evaluated the influence of different guanidino compounds on DNA synthesis, chemiluminescence production, and CD14 expression of undifferentiated and calcitriol-differentiated HL-60 cells. In a second setup, these guanidino compounds were evaluated for their specific effect on normal human leukocyte oxidative burst activity and tumor necrosis factor-alpha (TNF-alpha) expression. RESULTS: First, several guanidino compounds elicited proinflammatory effects on leukocytes. Methylguanidine and guanidine stimulated the proliferation of undifferentiated HL-60 cells and the antiproliferative effect of calcitriol (P < 0.05) was neutralized in the presence of methylguanidine (P < 0.05) and guanidinosuccinic acid (P < 0.05). The phorbol-myristate-acetate (PMA)-stimulated chemiluminescence production of the calcitriol differentiated HL-60 cells was enhanced in the presence of guanidine (P < 0.05). Methylguanidine and guanidinoacetic acid enhanced the lipopolysaccharide (LPS)-stimulated intracellular production of TNF-alpha by normal human monocytes (P < 0.05). Second, several guanidino compounds inhibited the function of leukocytes if they were activated. The PMA-stimulated chemiluminescence production of the calcitriol differentiated HL-60 cells was inhibited by the presence of methylguanidine (P < 0.05), guanidinoacetic acid (P < 0.05) and guanidinosuccinic acid (P < 0.05). After incubation of whole blood in the presence of methylguanidine, the Escherichia coli stimulated oxidative burst activity of the granulocyte population was significantly inhibited (P < 0.05). In addition, guanidinosuccinic acid had an inhibitory effect on the LPS-stimulated intracellular production of TNF-alpha by human monocytes (P < 0.01). CONCLUSION: Guanidino compounds exert proinflammatory as well as anti-inflammatory effects on monocyte/macrophage function. This could contribute to the altered prevalence of cardiovascular disease and propensity to infection in patients with CRF.