Impact of Bioelectrical Impedance-Guided Fluid Management and Vitamin D Supplementation on Left Ventricular Mass in Patients Receiving Peritoneal Dialysis: A Randomized Controlled Trial.

RATIONALE & OBJECTIVE: Hypervolemia and vitamin D deficiency occur frequently in patients receiving peritoneal dialysis and may contribute to left ventricular (LV) hypertrophy. The effect of bioelectrical impedance analysis (BIA)-guided volume management or vitamin D supplementation on LV mass among those receiving peritoneal dialysis is uncertain. STUDY DESIGN: Two-by-two factorial randomized controlled trial. SETTING & PARTICIPANTS: Sixty-five patients receiving maintenance peritoneal dialysis. INTERVENTION: BIA-guided volume management versus usual care and oral cholecalciferol 50,000 U weekly for 8 weeks followed by 10,000 U weekly for 44 weeks or matching placebo. OUTCOME: Change in LV mass at 1 year measured by cardiac magnetic resonance imaging. RESULTS: Total body water decreased by 0.9 + 2.4 (SD) L in the BIA group compared with a 1.5 ± 3.4 L increase in the usual care group (adjusted between-group difference: -2.4 [95% CI, -4.1 to -0.68] L, P = 0.01). LV mass increased by 1.3 ± 14.3 g in the BIA group and decreased by 2.4 ± 37.7 g in the usual care group (between-group difference: +2.2 [95% CI, -13.9 to 18.3] g, P = 0.8). Serum 25-hydroxyvitamin D concentration increased by a mean of 17.2 ± 30.8 nmol/L in the cholecalciferol group and declined by 8.2 ± 24.3 nmol/L in the placebo group (between-group difference: 28.3 [95% CI, 17.2-39.4] nmol/L, P < 0.001). LV mass decreased by 3.0 ± 28.1 g in the cholecalciferol group and increased by 2.0 ± 31.2 g in the placebo group (between-group difference: -4.5 [95% CI, -20.4 to 11.5] g, P = 0.6). LIMITATIONS: Relatively small sample size with larger than expected variation in change in LV mass. CONCLUSIONS: BIA-guided volume management had a modest impact on volume status with no effect on the change in LV mass. Vitamin D supplementation increased serum vitamin D concentration but had no effect on LV mass. FUNDING: Unrestricted Baxter International extramural grant and the Kidney Foundation of Canada. TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCT01045980.

Combined preoperative plasma exchange and red blood cell exchange transfusion in a renal transplant patient with protein S deficiency and hemoglobin SC disease.

BACKGROUND: Protein S deficiency is associated with increased risk of venous thromboembolism, complicating the perioperative management of such patients. We present a patient with sickle cell disease (Hb SC genotype) and inherited protein S deficiency who underwent a living-donor renal transplant. To minimize thrombotic risk and sickle cell complications, both plasma exchange and red blood cell (RBC) exchange transfusion were performed pre-operatively. METHODS AND MATERIALS: Plasma exchange was utilized to increase protein S levels and to reduce the risk of post-operative venous thromboembolism, including allograft thrombosis, while RBC exchange was performed to reduce the risk of acute post-operative sickle cell disease complications. RESULTS: With the use of combined pre-operative plasma exchange and RBC exchange transfusion, this patient with protein S deficiency and Hb SC underwent a successful renal transplant without acute sickle cell complications or thrombotic complications. CONCLUSIONS: This case demonstrates the potential use of pre-operative plasma exchange in patients with protein S deficiency undergoing high thrombotic risk procedures.

Circulating heparin-like anticoagulants: Case report and review of literature.

We report a case of a 56-year-old woman with a history of idiopathic thrombocytopenic purpura (ITP) following splenectomy on mycophenolate mofetil (MMF), who developed moderate bleeding after stopping MMF. Her laboratory testing suggested the presence of an abnormal circulating heparin-like anticoagulant with demonstrable anti-Xa activity. She was initially treated with antifibrinolytic therapy and was subsequently started on MMF alongside intravenous immunoglobulin, which significantly improved her bleeding symptoms. The presence of abnormal circulating heparin-like anticoagulants is a rare cause of coagulopathy. Few cases exist in the literature, with nearly all occurring in the setting of hematologic or solid-organ malignancy. The mechanism by which these endogenous anticoagulants develop is unclear. Clinical manifestations range from mild bleeding and bruising to life-threatening hemorrhage refractory to conventional therapy. Diagnosis of a heparin-like anticoagulant is based on coagulation testing as well as exclusion of other exogenous anticoagulants, acquired inhibitors, and/or factor deficiencies.

Using bioimpedance analysis to assess intensive care unit patients with sepsis in the post-resuscitation period: a prospective multicentre observational study.

PURPOSE: Clinicians lack well-validated, non-invasive, objective tools to guide volume management in the post-resuscitative period. Bioimpedance analysis (BIA) represents a novel method for guiding fluid management. We studied the relationship of BIA vector length (VL), an indicator of volume status, to the need for mechanical ventilation in patients with sepsis. METHODS: This is a multicentre prospective observational study at four Canadian ICUs. We examined adult patients admitted to the ICU within 72 hr of a sepsis diagnosis. Patients underwent daily BIA measurements for 30 days, until discharge from the ICU, or until death. Our primary outcome was the ongoing need for invasive mechanical ventilation, and we examined the association with VL using a generalized estimating equation. Our secondary analyses were targeted to determine an association between VL and other measures of volume status and acute kidney injury (AKI). RESULTS: We enrolled 159 patients from four centres over 27 months. The mean (standard deviation [SD]) age was 64 (15) yr with a mean (SD) APACHE (acute physiology, age, chronic health evaluation) II score of 25 (10); 57% (n = 91) were male. A 50-unit (ohm·m) increase in VL over any time period was associated with a 30% decrease in the probability of requiring invasive mechanical ventilation (P < 0.03). Volume expansion, indicated by a shorter VL, correlated with higher edema scores (r = - 0.31; P < 0.001) and higher net 24-hr fluid balance (r = - 0.27, P < 0.001). Patients with AKI had a shorter overall VL (r = - 0.23; P = 0.003). CONCLUSIONS: An increase in VL over time is associated with a decrease in probability of requiring invasive mechanical ventilation. Vector length correlates with other commonly used volume assessment methods in post-resuscitation patients with sepsis.

Comparison of the effects of standard vs low-dose prolonged-release tacrolimus with or without ACEi/ARB on the histology and function of renal allografts.

Targeting the renin-angiotensin system and optimizing tacrolimus exposure are both postulated to improve outcomes in renal transplant recipients (RTRs) by preventing interstitial fibrosis/tubular atrophy (IF/TA). In this multicenter, prospective, open-label controlled trial, adult de novo RTRs were randomized in a 2 × 2 design to low- vs standard-dose (LOW vs STD) prolonged-release tacrolimus and to angiotensin-converting enzyme inhibitors/angiotensin II receptor 1 blockers (ACEi/ARBs) vs other antihypertensive therapy (OAHT). There were 2 coprimary endpoints: the prevalence of IF/TA at month 6 and at month 24. IF/TA prevalence was similar for LOW vs STD tacrolimus at month 6 (36.8% vs 39.5%; P = .80) and ACEi/ARBs vs OAHT at month 24 (54.8% vs 58.2%; P = .33). IF/TA progression decreased significantly with LOW vs STD tacrolimus at month 24 (mean [SD] change, +0.42 [1.477] vs +1.10 [1.577]; P = .0039). Across the 4 treatment groups, LOW + ACEi/ARB patients exhibited the lowest mean IF/TA change and, compared with LOW + OAHT patients, experienced significantly delayed time to first T cell-mediated rejection. Renal function was stable from month 1 to month 24 in all treatment groups. No unexpected safety findings were detected. Coupled with LOW tacrolimus dosing, ACEi/ARBs appear to reduce IF/TA progression and delay rejection relative to reduced tacrolimus exposure without renin-angiotensin system blockade. ClinicalTrials.gov identifier: NCT00933231.

Crusted scabies in a renal transplant recipient treated with daily ivermectin: A case report and literature review.

Crusted scabies is a rare disease variant associated with T-cell dysregulation. Transplant patients are at risk of developing crusted scabies as a consequence of their immunosuppressive regimens. We report a case of crusted scabies presenting with recurrent septicemia in a 65-year-old renal transplant recipient, treated with daily ivermectin for 7 days after initial failure of weekly ivermectin dosing. A literature review of crusted scabies in transplant recipients consisting of 19 cases reports was summarized. Pruritus was common, and initial misdiagnosis was frequent. Most were treated with topical therapy, with one-third receiving ivermectin. Three of seven cases presenting with a concomitant infection died. Crusted scabies is commonly misdiagnosed in transplant recipients owing to its rarity, varied appearance, and different skin distributions. It should be considered in the differential diagnosis of transplant recipients presenting with rash and pruritus, given its association with secondary infection and subsequent mortality.

WNT signaling is required for peritoneal membrane angiogenesis.

The wingless-type mouse mammary tumor virus integration site family (WNT) signaling pathway is involved in wound healing and fibrosis. We evaluated the WNT signaling pathway in peritoneal membrane injury. We assessed WNT1 protein expression in the peritoneal effluents of 54 stable peritoneal dialysis (PD) patients and WNT-related gene expression in ex vivo mesothelial cell cultures from 21 PD patients. In a transforming growth factor-ß (TGF-ß)-mediated animal model of peritoneal fibrosis, we evaluated regulation of the WNT pathway and the effect of WNT inhibition on peritoneal fibrosis and angiogenesis. WNT1 and WNT2 gene expression were positively correlated with peritoneal membrane solute transport in PD patients. In the mouse peritoneum, TGF-ß-induced peritoneal fibrosis was associated with increased expression of WNT2 and WNT4. Peritoneal ß-catenin protein was significantly upregulated after infection with adenovirus expressing TGF-ß (AdTGF-ß) along with elements of the WNT signaling pathway. Treatment with a ß-catenin inhibitor (ICG-001) in mice with AdTGF-ß-induced peritoneal fibrosis resulted in attenuation of peritoneal angiogenesis and reduced vascular endothelial growth factor. Similar results were also observed with the WNT antagonist Dickkopf-related protein (DKK)-1. In addition to this, DKK-1 blocked epithelial-mesenchymal transition and increased levels of the cell adhesion protein E-cadherin. We provide evidence that WNT signaling is active in the setting of experimental peritoneal fibrosis and WNT1 correlates with patient peritoneal membrane solute transport in PD patients. Intervention in this pathway is a possible therapy for peritoneal membrane injury.

Plasma exchange to remove HIT antibodies: dissociation between enzyme-immunoassay and platelet activation test reactivities.

Repeated therapeutic plasma exchange (TPE) has been advocated to remove heparin-induced thrombocytopenia (HIT) IgG antibodies before cardiac/vascular surgery in patients who have serologically-confirmed acute or subacute HIT; for this situation, a negative platelet activation assay (eg, platelet serotonin-release assay [SRA]) has been recommended as the target serological end point to permit safe surgery. We compared reactivities in the SRA and an anti-PF4/heparin IgG-specific enzyme immunoassay (EIA), testing serial serum samples in a patient with recent (subacute) HIT who underwent serial TPE precardiac surgery, as well as for 15 other serially-diluted HIT sera. We observed that post-TPE/diluted HIT sera-when first testing SRA-negative-continue to test strongly positive by EIA-IgG. This dissociation between the platelet activation assay and a PF4-dependent immunoassay for HIT antibodies indicates that patients with subacute HIT undergoing repeated TPE before heparin reexposure should be tested by serial platelet activation assays even when their EIAs remain strongly positive.

Matrix metalloproteinase 9 is associated with peritoneal membrane solute transport and induces angiogenesis through ß-catenin signaling.

Background: For patients using peritoneal dialysis (PD), the peritoneal membrane can develop fibrosis and angiogenesis, leading to ultrafiltration failure, chronic hypervolemia and increased risk of technique failure and mortality. Matrix metalloproteinases (MMPs), and specifically the gelatinases (MMP2 and MMP9), may be involved in peritoneal membrane injury. Methods: From stable PD patients, mesothelial cells were assayed for MMP gene expression. MMP9 was overexpressed in mouse peritoneum by adenovirus, and MMP9 -/- mice were subjected to transforming growth factor ß (TGF-ß)-induced peritoneal fibrosis. Results: MMP9 mRNA expression correlated with peritoneal membrane solute transport properties. Overexpression of MMP9 in the mouse peritoneum induced submesothelial thickening and angiogenesis. MMP9 induced mesothelial cell transition to a myofibroblast phenotype measured by increased alpha smooth muscle actin and decreased E-cadherin expression. Angiogenesis was markedly reduced in MMP9 -/- mice treated with an adenovirus expressing active TGF-ß compared with wild-type mice. TGF-ß-mediated E-cadherin cleavage was MMP9 dependent, and E-cadherin cleavage led to ß-catenin-mediated signaling. A ß-catenin inhibitor blocked the angiogenic response induced by AdMMP9. Conclusions: Our data suggest that MMP9 is involved in peritoneal membrane injury possibly through cleavage of E-cadherin and induction of ß-catenin signaling. MMP9 is a potential biomarker for peritoneal membrane injury and is a therapeutic target to protect the peritoneal membrane in PD patients.

Gremlin promotes peritoneal membrane injury in an experimental mouse model and is associated with increased solute transport in peritoneal dialysis patients.

The peritoneal membrane becomes damaged in patients on peritoneal dialysis (PD). Gremlin 1 (GREM1) inhibits bone morphogenic proteins (BMPs) and plays a role in kidney development and fibrosis. We evaluated the role of gremlin in peritoneal fibrosis and angiogenesis. In a cohort of 32 stable PD patients, GREM1 concentration in the peritoneal effluent correlated with measures of peritoneal membrane damage. AdGrem1, an adenovirus to overexpress gremlin in the mouse peritoneum, induced submesothelial thickening, fibrosis, and angiogenesis in C57BL/6 mice, which was associated with decreased expression of BMP4 and BMP7. There was evidence of mesothelial cell transition to a mesenchymal phenotype with increased α smooth muscle actin expression and suppression of E-cadherin. Some of the GREM1 effects may be reversed with recombinant BMP7 or a pan-specific transforming growth factor ß (TGF-ß) antibody. Neovascularization was not inhibited with a TGF-ß antibody, suggesting a TGF-ß-independent angiogenic mechanism. Swiss/Jackson Laboratory (SJL) mice, which are resistant to TGF-ß-induced peritoneal fibrosis, responded in a similar fashion to AdGrem1 as did C57BL/6 mice with fibrosis, angiogenesis, and mesothelial-to-mesenchymal transition. GREM1 was associated with up-regulated TGF-ß expression in both SJL and C57BL/6 mice, but SJL mice demonstrated a defective TGF-ß-induced GREM1 expression. In summary, GREM1 induces fibrosis and angiogenesis in mouse peritoneum and is associated with increased solute transport in these PD patients.

Estimated GFR reporting influences recommendations for dialysis initiation.

Automated reporting of estimated GFR (eGFR) with serum creatinine measurement is now common. We surveyed nephrologists in four countries to determine whether eGFR reporting influences nephrologists' recommendations for dialysis initiation. Respondents were randomly allocated to receive a survey of four clinical vignettes that included either serum creatinine concentration only or serum creatinine and the corresponding eGFR. For each scenario, the respondent was asked to rank his or her likelihood of recommending dialysis initiation on a modified 8-point Likert scale, ranging from 1 ("definitely not") to 8 ("definitely would"). Analysis of the 822 eligible responses received showed that the predicted likelihood of recommending dialysis increased by 0.55 points when eGFR was reported (95% confidence interval, 0.33 to 0.76), and this effect was larger for eGFRs >5 ml/min per 1.73 m(2) (P<0.001). Subgroup analyses suggested that physicians who had been in practice ≥13 years were more affected by eGFR reporting (P=0.03). These results indicate that eGFR reporting modestly increases the likelihood that dialysis is recommended, and physicians should be aware of this effect when assessing patients with severe CKD.

Point-of-care-ultrasound for the assessment of post-renal transplant recipients.

INTRODUCTION: Postoperative imaging for deceased donor renal transplants is often delayed, as these surgeries occur after-hours. These delays can be critical in identifying immediate complications. To our knowledge, there are no formal training programs for point-of-care ultrasound (POCUS) in this setting; therefore, we aimed to develop and evaluate a feasible and practical POCUS curriculum for the assessment of a renal transplant graft. METHODS: Urology and nephrology transplant physicians completed a three-hour online course, followed by a five-hour hands-on seminar for sonographic scanning. Simulated patients with transplanted kidneys were used. Course material was developed with licensed ultrasound technologists based on Sonography Canada national competency profiles. Pre- and post-course surveys focused on user confidence, while pre- and post-course multiple-choice questionnaires assessed theoretical knowledge. RESULTS: Twelve participants were included, six of whom were urologists. Theoretical knowledge in POCUS improved significantly (p<0.001). Confidence in manipulation of ultrasound controls, Doppler imaging, and POCUS of the transplant kidney also improved (all p<0.001, d>2.0). Participants indicated an increased likelihood of POCUS use in clinical practice and that training should be integrated into a transplant fellowship. CONCLUSIONS: We introduced a novel and guideline-based POCUS curriculum that leveraged local ultrasound educators and found improved theoretical knowledge and skill confidence in our cohort of transplant physicians. This course will serve as the first step toward a validated competency-based training system for POCUS use in the immediate post-renal transplant setting, and likely will be incorporated into the training of the modern transplant physician.

Mercury-associated nephrotic syndrome: a case report and systematic review of the literature.

Kidney injury from mercury is known to cause dose-related tubular dysfunction and idiosyncratic nephrotic syndrome according to various case reports. Motivated by a patient with subacute-onset nephrotic syndrome, histologic features of secondary focal segmental glomerulosclerosis, and concurrent mercury toxicity, we conducted a systematic review to explore renal histologic changes in patients with toxic mercury exposures and nephrotic syndrome. Data were extracted from a patient's clinical record. MEDLINE/Ovid was searched from 1950 to November 2010 using a prespecified search strategy. Two nephrology textbooks and the UpToDate online database also were searched. Inclusion criteria were studies of humans with nephrotic syndrome, nephrotic-range proteinuria, or kidney biopsy results reported. There were no exclusion criteria. We identified 27 other reports of 42 patients with nephrotic syndrome or nephrotic-range proteinuria. Of the 26 individuals, including our patient, who underwent kidney biopsy, histology showed glomerular disease in 21. Of these 20 biopsies, 4 showed minimal change disease and 15 showed membranous glomerulonephritis. Mercury exposure can lead to various glomerular lesions; we emphasize the importance of a careful occupational and dietary history in elucidating a cause for the undetermined nephrotic syndrome.

Canadian Society of Nephrology guidelines for the management of patients with ESRD treated with intensive hemodialysis.

Intensive (longer and more frequent) hemodialysis has emerged as an alternative to conventional hemodialysis for the treatment of patients with end-stage renal disease. However, given the differences in dialysis delivery and models of care associated with intensive dialysis, alternative approaches to patient management may be required. The purpose of this work was to develop a clinical practice guideline for the Canadian Society of Nephrology. We applied the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach for guideline development and performed targeted systematic reviews and meta-analysis (when appropriate) to address prioritized clinical management questions. We included studies addressing the treatment of patients with end-stage renal disease with short daily (≥5 days per week, <3 hours per session), long (3-4 days per week, ≥5.5 hours per session), or long-frequent (≥5 days per week, ≥5.5 hours per session) hemodialysis. We included clinical trials and observational studies with or without a control arm (1990 and later). Based on a prioritization exercise, 6 interventions of interest included optimal vascular access type, buttonhole cannulation, antimicrobial prophylaxis for buttonhole cannulation, closed connector devices, and dialysate calcium and dialysate phosphate additives for patients receiving intensive hemodialysis. We developed 6 recommendations addressing the interventions of interest. Overall quality of the evidence was very low and all recommendations were conditional. We provide detailed commentaries to guide in shared decision making. The main limitation was the very low overall quality of evidence that precluded strong recommendations. Most included studies were small single-arm observational studies. Three randomized controlled trials were applicable, but provided only indirect evidence. Published information for patient values and preference was lacking. In conclusion, we provide 6 recommendations for the practice of intensive hemodialysis. However, due to very low-quality evidence, all recommendations were conditional. We therefore also highlight priorities for future research.

Dialysate calcium concentration and mineral metabolism in long and long-frequent hemodialysis: a systematic review and meta-analysis for a Canadian Society of Nephrology clinical practice guideline.

BACKGROUND: Patients treated with conventional hemodialysis (HD) develop disorders of mineral metabolism that are associated with increased morbidity and mortality. More frequent and longer HD has been associated with improvement in hyperphosphatemia that may improve outcomes. STUDY DESIGN: Systematic review and meta-analysis to inform the clinical practice guideline on intensive dialysis for the Canadian Society of Nephrology. SETTING & POPULATION: Adult patients receiving outpatient long (≥5.5 hours/session; 3-4 times per week) or long-frequent (≥5.5 hours/session, ≥5 sessions per week) HD. SELECTION CRITERIA FOR STUDIES: We included clinical trials, cohort studies, case series, case reports, and systematic reviews. INTERVENTIONS: Dialysate calcium concentration ≥1.5 mmol/L and/or phosphate additive. OUTCOMES: Fragility fracture, peripheral arterial and coronary artery disease, calcific uremic arteriolopathy, mortality, intradialytic hypotension, parathyroidectomy, extraosseous calcification, markers of mineral metabolism, diet liberalization, phosphate-binder use, and muscle mass. RESULTS: 21 studies were identified: 2 randomized controlled trials, 2 reanalyses of data from the randomized controlled trials, and 17 observational studies. Dialysate calcium concentration ≥1.5 mmol/L for patients treated with long and long-frequent HD prevents an increase in parathyroid hormone levels and a decline in bone mineral density without causing harm. Both long and long-frequent HD were associated with a reduction in serum phosphate level of 0.42-0.45 mmol/L and a reduction in phosphate-binder use. There was no direct evidence to support the use of a dialysate phosphate additive. LIMITATIONS: Almost all the available information is related to changes in laboratory values and surrogate outcomes. CONCLUSIONS: Dialysate calcium concentration ≥1.5 mmol/L for most patients treated with long and long-frequent dialysis prevents an increase in parathyroid hormone levels and decline in bone mineral density without increased risk of calcification. It seems prudent to add phosphate to the dialysate for patients with a low predialysis phosphate level or very low postdialysis phosphate level until more evidence becomes available.

Vascular access for intensive maintenance hemodialysis: a systematic review for a Canadian Society of Nephrology clinical practice guideline.

BACKGROUND: Practices in vascular access management with intensive hemodialysis may differ from those used in conventional hemodialysis. STUDY DESIGN: We conducted a systematic review to inform clinical practice guidelines for the provision of intensive hemodialysis. SETTING & POPULATION: Adult patients receiving maintenance (>3 months) intensive hemodialysis (frequent [≥5 hemodialysis treatments per week] and/or long [>5.5 hours per hemodialysis treatment]). SELECTION CRITERIA FOR STUDIES: We searched EMBASE and MEDLINE (1990-2011) for randomized and observational studies. We also searched conference proceedings (2007-2011). INTERVENTIONS: (1) Central venous catheter (CVC) versus arteriovenous (AV) access, (2) buttonhole versus rope-ladder cannulation, (3) topical antimicrobial cream versus none in buttonhole cannulation, and (4) closed connector devices among CVC users. OUTCOMES: Access-related infection, survival, hospitalization, patency, access survival, intervention rates, and quality of life. RESULTS: We included 23, 7, and 5 reports describing effectiveness by access type, buttonhole cannulation, and closed connector device, respectively. No study directly compared CVC with AV access. On average, bacteremia and local infection rates were higher with CVC compared with AV access. Access intervention rates were higher with more frequent hemodialysis, but access survival did not differ. Buttonhole cannulation was associated with bacteremia rates similar to those seen with CVCs in some series. Topical mupirocin seemed to attenuate this effect. No direct comparisons of closed connector devices versus standard luer-locking devices were found. Low rates of actual or averted (near misses) air embolism and bleeding were reported with closed connector devices. LIMITATIONS: Overall, evidence quality was very low. Limited direct comparisons addressing main review questions, small sample sizes, selective outcome reporting, publication bias, and residual confounding were major factors. CONCLUSIONS: This review highlights several differences in the management of vascular access in conventional and intensive hemodialysis populations. We identify a need for standardization of vascular access outcome reporting and a number of priorities for future research.

Impact of haemoglobin and erythropoietin dose changes on mortality: a secondary analysis of results from a randomized anaemia management trial.

BACKGROUND: Anaemia is a common complication of chronic kidney disease. A number of studies have identified an adverse association between haemoglobin (Hgb) variability and mortality. To date, no study has evaluated the impact of Hgb variability on mortality in the setting of a uniform Hgb target and erythropoiesis-stimulating agents (ESA) dosing strategy. METHODS: One hundred and fifty-four haemodialysis (HD) patients from a previous randomized anaemia management study were followed up for up to 6 years. The impact of Hgb variability and ESA dosing parameters on subsequent mortality risk were evaluated. RESULTS: More rapid rises in Hgb (Hgb deflect(pos)) and ESA dose increases were independently associated with mortality in multivariate analysis, whereas more rapid Hgb declines (Hgb deflect(neg)) and ESA dose decreases were not. Each gram per litre per week increase in Hgb deflect(pos) was associated with an adjusted hazard ratio (HR) of 1.23 (1.03-1.48), while for every 1000-unit increase in ESA dose, the adjusted HR was 1.12 (1.01-1.24). Factors associated with positive Hgb deflections included frequency and magnitude of ESA dose changes, baseline Hgb, patient weight and presence of an HD catheter. CONCLUSIONS: Rapid Hgb rises and greater average Eprex dose increases were independently associated with a higher mortality risk in HD patients after adjustment for baseline Hgb and Eprex dose. A randomized controlled trial evaluating different ESA dosing strategies in response to individual patient ESA responsiveness is needed.

Association between markers of inflammation, fibrosis and hypervolemia in peritoneal dialysis patients.

BACKGROUND/AIM: Volume expansion in peritoneal dialysis (PD) patients is associated with left ventricular hypertrophy. The link between inflammation and hypervolemia has not been extensively studied. The aim of this study was to determine if an association exists between hypervolemia and markers of inflammation in PD patients. METHODS: In this cross-sectional study of 22 prevalent PD patients, volume was determined by bioelectrical impedance analysis. Serum and peritoneal effluent interleukin-6 (IL-6) and peritoneal transforming growth factor (TGF)-beta(1) were measured. A fast peritoneal equilibration test determined peritoneal transport status. RESULTS: Bioimpedance-derived measures of hypervolemia correlated with peritoneal effluent IL-6 and TGF-beta(1). Peritoneal IL-6 was also associated with high peritoneal transport status. CONCLUSIONS: Markers of inflammation and fibrosis (peritoneal IL-6 and TGF-beta(1)) are associated with markers of hypervolemia.

Circulating microvesicle protein is associated with renal transplant outcome.

Renal transplantation is an effective therapy with improved long-term outcomes compared with other therapies for end stage renal disease. Present methods for evaluating kidney allograft function, such as serum creatinine or allograft biopsy, are not sensitive and identify pathological changes only after any potential intervention would be effective. Thus, there is a necessity for biomarkers that would provide early prognostic information about kidney transplant outcomes. Circulating microvesicles represent an attractive source of biomarkers for different diseases including renal failure. We have studied the proteins of the circulating microvesicles from two populations of kidney transplant recipients (n = 20) with poor transplant outcomes (n = 10) or good transplant outcome (n = 10), according to their estimated glomerular filtration rate (eGFR). Microvesicles from age-matched healthy subjects (n = 10) were used as a control. Also, we performed a pilot study to assess the microvesicle protein in kidney transplant recipients before and six months after kidney transplant (n = 6), compared to healthy subjects. Proteomic analysis of microvesicles could discriminate between transplant recipients and healthy subjects, and between transplant patients based on eGFR. Our results shed light on the potential of blood microvesicles to provide a novel tool for the prediction of the outcome of kidney transplants.

Efficacy and safety of non-vitamin K antagonist oral anticoagulants post-kidney transplantation.

BACKGROUND: Novel oral anticoagulants (NOACs) were developed as alternatives to vitamin K antagonists, primarily warfarin, as they do not require routine monitoring and have limited drug-drug and drug-food interactions. However, the efficacy and safety of these agents in kidney transplantation are not well studied. AIM: To assess the profile and safety of NOACs for patients who had kidney transplantation, and to provide recommendations and guidelines on therapeutic strategies in these patients. METHODS: This was a retrospective study carried out among adult patients who were actively on the following NOACs (apixaban, rivaroxaban or dabigatran) in our renal transplantation program from December 2015 to December 2016. The patients were identified primarily through electronic medical record system (patient data linkage). Data on the clinical and laboratory profile of the patients were retrieved and analyzed with SPSS 22.0. RESULTS: Complete data on 42 renal transplant patients were retrieved: 59.5% males, 90.5% were whites and 66.7% were older than 60 years old. The mean duration since renal transplantation of the patients was 8.8 ± 7.4 years. The most common risk factors for the development of end-stage renal disease in the subjects were hypertension (19.0%), polycystic kidney disease (19.0%), followed by diabetic nephropathy (16.7%) and chronic glomerulonephritis (16.7%). The main indications for NOACs use in the cohort were atrial fibrillation in 25 patients (59.5%) and venous thromboembolism in 10 patients (23.8%). Overall, 29 patients (69%) were treated with apixaban, 10 patients (23.8%) with rivaroxaban and 3 patients (7.14%) with dabigatran. No (0%) thromboembolic events were observed during the one-year period, but 3 (7.1%) bleeding events occurred in the cohort consisting of 1 patient treated with rivaroxaban 15 mg daily and 2 patients who received apixaban 2.5 mg twice daily. There were no significant changes in serum tacrolimus level three days after the initiation of NOACs among patients treated with tacrolimus (pre- and post-NOACs tacrolimus levels were 7.2516 and 7.8867 ng/mL, P = 0.55, respectively). Also, after one-year of treatment with NOACs there were no significant changes in the pre- and post-NOACs serum creatinine level (P = 0.772) and estimated glomerular filtration rates (P = 0.232). CONCLUSION: No thromboembolic events or significant changes in renal profile were observed in our cohort of kidney transplant recipients who were treated with NOACs for at least a year. However, a few bleeding events were observed. This calls for further well-planned randomized controlled trials to assess the efficacy and safety of NOACs among renal transplant recipients.