Quantification and Dosing of Renal Replacement Therapy in Acute Kidney Injury: A Reappraisal.

BACKGROUND/AIMS: Delivered dialysis therapy is routinely measured in the management of patients with end-stage renal disease; yet, the quantification of renal replacement prescription and delivery in acute kidney injury (AKI) is less established. While continuous renal replacement therapy (CRRT) is widely understood to have greater solute clearance capabilities relative to intermittent therapies, neither urea nor any other solute is specifically employed for CRRT dose assessments in clinical practice at present. Instead, the normalized effluent rate is the gold standard for CRRT dosing, although this parameter does not provide an accurate estimation of actual solute clearance for different modalities. METHODS: Because this situation has created confusion among clinicians, we reappraise dose prescription and delivery for CRRT. RESULTS: A critical review of RRT quantification in AKI is provided. CONCLUSION: We propose an adaptation of a maintenance dialysis parameter (standard Kt/V) as a benchmark to supplement effluent-based dosing of CRRT. Video Journal Club "Cappuccino with Claudio Ronco" at http://www.karger.com/?doi=475457.

Safety of low-molecular-weight heparin compared to unfractionated heparin in hemodialysis: a systematic review and meta-analysis.

BACKGROUND: Low molecular weight heparins (LMWH) have been extensively studied and became the treatment of choice for several indications including pulmonary embolism. While their efficacy in hemodialysis is considered similar to unfractionated heparin (UFH), their safety remains controversial mainly due to a risk of bioaccumulation in patients with renal impairment. The aim of this systematic review was to evaluate the safety of LMWH when compared to UFH for extracorporeal circuit (ECC) anticoagulation. METHODS: We used Pubmed, Embase, Cochrane central register of controlled trials, Trip database and NICE to retrieve relevant studies with no language restriction. We looked for controlled experimental trials comparing LMWH to UFH for ECC anticoagulation among end-stage renal disease patients undergoing chronic hemodialysis. Studies were kept if they reported at least one of the following outcomes: bleeding, lipid profile, cardiovascular events, osteoporosis or heparin-induced thrombocytopenia. Two independent reviewers conducted studies selection, quality assessment and data extraction with discrepancies solved by a third reviewer. Relative risk and 95% CI was calculated for dichotomous outcomes and mean weighted difference (MWD) with 95% CI was used to pool continuous variables. RESULTS: Seventeen studies were selected as part of the systematic. The relative risk for total bleeding was 0.76 (95% CI 0.26-2.22). The WMD calculated for total cholesterol was -28.70 mg/dl (95% CI -51.43 to -5.98), a WMD for triglycerides of -55.57 mg/dl (95% CI -94.49 to -16.66) was estimated, and finally LDL-cholesterol had a WMD of -14.88 mg/dl (95% CI -36.27 to 6.51). CONCLUSIONS: LMWH showed to be at least as safe as UFH for ECC anticoagulation in chronic hemodialysis. The limited number of studies reporting on osteoporosis and HIT does not allow any conclusion for these outcomes. Larger studies are needed to evaluate properly the safety of LMWH in chronic hemodialysis.

IgD heavy-chain deposition disease: detection by laser microdissection and mass spectrometry.

Monoclonal Ig deposition disease (MIDD) is a rare complication of monoclonal gammopathy characterized by deposition of monoclonal Ig light chains and/or heavy chains along the glomerular and tubular basement membranes. Here, we describe a unique case of IgD deposition disease. IgD deposition is difficult to diagnose, because routine immunofluorescence does not detect IgD. A 77-year-old man presented with proteinuria and renal failure, and kidney biopsy analysis showed a nodular sclerosing GN with extensive focal global glomerulosclerosis, tubular atrophy, and interstitial fibrosis. Immunofluorescence was negative for Ig deposits, although electron microscopy showed deposits in the glomeruli and along tubular basement membranes. Laser microdissection of glomeruli and mass spectrometry of extracted peptides showed a large spectra number for IgD, and immunohistochemistry showed intense glomerular and tubular staining for IgD. Together, these findings are consistent with IgD deposition disease. Bone marrow biopsy analysis showed 5% plasma cells, which stained for IgD. The patient was treated with bortezomib and dexamethasone, which resulted in improvement of hematologic parameters but no improvement of renal function. The diagnosis of IgD deposition disease underscores the value of laser microdissection and mass spectrometry in further evaluating renal biopsies when routine assessment fails to reach an accurate diagnosis.

Outcomes of integrated home dialysis care: a multi-centre, multi-national registry study.

BACKGROUND: The 'integrated home dialysis' model involving initiation of peritoneal dialysis (PD) first followed by home haemodialysis (HHD) has previously been proposed as an optimal form of dialysis that maximizes the advantages of both modalities. While this model has great potential, its clinical outcomes, especially compared with direct HHD initiation, remain uncertain. METHODS: All incident home dialysis patients from the Australia and New Zealand Dialysis and Transplant (ANZDATA) registry between 2000 and 2012 were included. Propensity score matching was performed to evaluate patients initially treated with PD followed by HHD ('PD + HHD'), PD without subsequent transition to HHD ('PD only') and HHD without subsequent transition to PD ('HHD only'). The composite primary outcome was death and home dialysis technique failure (defined as transfer to facility haemodialysis for 90 days). Groups were compared using a Cox proportional hazards model. RESULTS: The 2:1 matched cohort included 84 patients in the 'PD + HHD' group, 168 patients in the 'HHD only' group and 168 patients in the 'PD only' group. Compared with the 'PD + HHD' group, death and home dialysis technique failure was similar for patients treated with 'HHD only' [hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.52-1.62; P = 0.77] and higher for those treated with 'PD only' (HR 3.22, 95% CI 1.97-5.25; P < 0.001). CONCLUSION: Patients treated with PD first followed by HHD had a risk of death and home dialysis technique failure that was comparable to those treated with HHD as the only home dialysis modality and inferior to those treated with PD as the only home dialysis modality. These results support the 'integrated home dialysis model' in patients who initiate dialysis with PD.

An economic evaluation of rt-PA locking solution in dialysis catheters.

In a recent randomized trial, weekly recombinant tissue plasminogen activator (rt-PA), 1 mg per lumen, once per week, and twice-weekly heparin as a locking solution (rt-PA/heparin) resulted in lower risks of hemodialysis catheter malfunction and catheter-related bacteremia compared with thrice-weekly heparin (heparin alone). We collected detailed costs within this trial to determine how choice of locking solution would affect overall health care costs, including the cost of locking solutions and all other relevant medical costs over the course of the 6-month trial. Nonparametric bootstrap estimates were used to derive 95% confidence intervals (CIs) and mean cost differences between the treatment groups. The cost of the locking solution was higher in patients receiving rt-PA/heparin, but this was partially offset by lower costs for managing complications. Overall, the difference in unadjusted mean cost for managing patients with rt-PA/heparin versus heparin alone was Can$323 (95% CI, -$935 to $1581; P=0.62). When the costs were extrapolated over a 1-year time horizon using decision analysis, assuming ongoing rt-PA effectiveness, the overall costs of the strategies were similar. This finding was sensitive to plausible variation in the frequency and cost of managing patients with catheter-related bacteremia, and whether the benefit of rt-PA on catheter-related bacteremia was maintained in the long term. In summary, we noted no significant difference in the mean overall cost of an rt-PA/heparin strategy as a locking solution for catheters compared with thrice-weekly heparin. Cost savings due to a lower risk of hospitalization for catheter-related bacteremia partially offset the increased cost of rt-PA.

Prevention of dialysis catheter malfunction with recombinant tissue plasminogen activator.

BACKGROUND: The effectiveness of various solutions instilled into the central venous catheter lumens after each hemodialysis session (catheter locking solutions) to decrease the risk of catheter malfunction and bacteremia in patients undergoing hemodialysis is unknown. METHODS: We randomly assigned 225 patients undergoing long-term hemodialysis in whom a central venous catheter had been newly inserted to a catheter-locking regimen of heparin (5000 U per milliliter) three times per week or recombinant tissue plasminogen activator (rt-PA) (1 mg in each lumen) substituted for heparin at the midweek session (with heparin used in the other two sessions). The primary outcome was catheter malfunction, and the secondary outcome was catheter-related bacteremia. The treatment period was 6 months; treatment assignments were concealed from the patients, investigators, and trial personnel. RESULTS: A catheter malfunction occurred in 40 of the 115 patients assigned to heparin only (34.8%) and 22 of the 110 patients assigned to rt-PA (20.0%)--an increase in the risk of catheter malfunction by a factor of almost 2 among patients treated with heparin only as compared with those treated with rt-PA once weekly (hazard ratio, 1.91; 95% confidence interval [CI], 1.13 to 3.22; P = 0.02). Catheter-related bacteremia occurred in 15 patients (13.0%) assigned to heparin only, as compared with 5 (4.5%) assigned to rt-PA (corresponding to 1.37 and 0.40 episodes per 1000 patient-days in the heparin and rt-PA groups, respectively; P = 0.02). The risk of bacteremia from any cause was higher in the heparin group than in the rt-PA group by a factor of 3 (hazard ratio, 3.30; 95% CI, 1.18 to 9.22; P = 0.02). The risk of adverse events, including bleeding, was similar in the two groups. CONCLUSIONS: The use of rt-PA instead of heparin once weekly, as compared with the use of heparin three times a week, as a locking solution for central venous catheters significantly reduced the incidence of catheter malfunction and bacteremia. (Current Controlled Trials number, ISRCTN35253449.).

Comparison of oral and intravenous alfacalcidol in chronic hemodialysis patients.

BACKGROUND: Activated vitamin D is the mainstay of treatment for secondary hyperparathyroidism (SHPT) in chronic hemodialysis patients. However, the optimal route of administration is still debated. The aim of our study was to compare efficacy of oral vs intravenous (IV) administration of alfacalcidol in hemodialysis. A secondary objective was to determine the cost-effectiveness advantage of oral administration. METHODS: Eighty-eight chronic hemodialysis patients receiving IV alfacalcidol three times a week were included in the study. All were switched to the same dose of alfacalcidol given orally three times a week during the hemodialysis session. A budget impact analysis was performed. RESULTS: Mean patient age was 64 years old and 43% were males. The mean alfacalcidol dose administered was 2.1 µg three times a week. After three months, serum parathormone (PTH) levels decreased from 80 to 59 pmol/L (p = 0.001) and total serum calcium levels increased from 2.34 to 2.40 mmol/L (p = 0.002). After six months, total serum calcium levels were still significantly higher. Alfacalcidol dosage was significantly decreased during study period; the mean reduction was 0.44 µg per dose. Finally, oral administration was associated with an annual cost reduction of 197 678$CAN and an annual nursing time reduction of 25 days. CONCLUSION: Our findings support that switching IV to oral administration of alfacalcidol during hemodialysis sessions may lead to a similar control of SHPT with lower doses of activated vitamin D. This is a good strategy for optimizing compliance and may allow a dose reduction because of a greater efficacy to suppress PTH. Oral administration also has significant cost-effectiveness advantages.

Magnitude of discordance between registry data and death certificate when evaluating leading causes of death in dialysis patients.

BACKGROUND: Discordance between dialysis registry and death certificate reported death has been demonstrated. Since cause of death is measured using registry data in dialysis patients and death certificate data in the general population, comparisons of cause of death proportions between dialysis patients and the general population may be biased. Our aim was to compare the proportion of deaths attributed to cardiovascular disease (CVD), malignancy, and infections between patients receiving dialysis and the general population using death certificates for both, and to quantify the magnitude of discrepancy between registry and death certificate estimates in dialysis patients. METHODS: A retrospective cohort study of 5858 patients initiating maintenance dialysis between 2001 and 2007 was conducted. Cause of death was obtained from both registry and death certificate data for dialysis patients, and from death certificate data for the general population. RESULTS: Compared to the general population, use of death certificate data in dialysis patients resulted in smaller differences in the proportion of deaths attributed to CVD or infection than that from the registry. In the general population, the proportion of deaths due to CVD is 29.3% for men and 28.2% for women, and the proportion of deaths due to infection is 3.3% for men and 3.6% for women. For men, the proportion of deaths in dialysis patients due to CVD using registry data is 41.5%, compared with a proportion of 32.1% using death certificate data. Similarly for women, the proportion of deaths due to CVD using registry data is 35.2% and that using death certificate data 24.3%. The proportion of deaths due to infection in dialysis patients follows the same pattern: for men, the proportion of deaths due to infection using registry data is 9.9% and that from death certificate data at 5.0%; while for women the proportions are 11.6% and 4.8%, respectively. CONCLUSIONS: While absolute cause-specific mortality rates did differ, evaluation of causes of death using death certificate in dialysis patients in Quebec revealed that they do not have substantially different proportion of death due to CVD or infections than the general population. Infections appeared to be a frequent complication leading to death, suggesting that infections are an important target to consider for reducing mortality in dialysis populations.

Effect of cinacalcet availability and formulary listing on parathyroidectomy rate trends.

BACKGROUND: Recent trends in parathyroidectomy rates are not known. Our objective was to investigate the trend in parathyroidectomy rates between 2001 and 2010, and to evaluate if the availability and reimbursement of cinacalcet modified that trend. METHODS: Using a provincial administrative database, we included all adult patients receiving chronic dialysis treatments between 2001 and 2010 (incident and prevalent) in a time series analysis. The effect of cinacalcet availability on parathyroidectomy bimonthly rates was modeled using an ARIMA intervention model using different cut-off dates: September 2004 (Health Canada cinacalcet approval), January 2005, June 2005, January 2006, June 2006 (date of cinacalcet provincial reimbursement), and January 2007. RESULTS: A total of 12 795 chronic dialysis patients (mean age 64 years, 39% female, 82% hemodialysis) were followed for a mean follow-up of 3.3 years. During follow-up, 267 parathyroidectomies were identified, translating to an average rate of 7.0 per 1000 person-years. The average parathyroidectomy rate before cinacalcet availability was 11.4 /1000 person-years, and 3.6 /1000 person-years after cinacalcet public formulary listing. Only January 2006 as an intervention date in the ARIMA model was associated with a change in parathyroidectomy rates (estimate: -5.58, p = 0.03). Other intervention dates were not associated with lower parathyroidectomy rates. CONCLUSIONS: A reduction in rates of parathyroidectomy was found after January 2006, corresponding to cinacalcet availability. However, decreased rates may be due to other factors occurring simultaneously with cinacalcet introduction and further studies are needed to confirm these findings.

Protocolized intensive care unit management of analgesia, sedation, and delirium improves analgesia and subsyndromal delirium rates.

BACKGROUND: Sedatives and analgesics, in doses that alter consciousness in the intensive care unit (ICU), contribute to delirium and mortality. Pain, agitation, and delirium can be monitored in ICU patients. These symptoms were noted before (PRE) and after (POST) a protocol to alleviate undesirable symptoms. Analgesia and sedation levels, the incidence of coma, delirium, length of stay (LOS), discharge location, and mortality were then compared. We hypothesized that the likely reduction in iatrogenic coma would result in less delirium, because these 2 morbid conditions seem to be linked. METHODS: All patients were consecutively admitted to an ICU PRE-protocol (August 2003 to February 2004, 610 patients) and POST-protocol (April 2005 to November 2005, 604 patients). Between February 2004 and April 2005, we piloted and taught individualized nonpharmacologic strategies and titration of analgesics, sedatives, and antipsychotics based on sedation, analgesia, and delirium scores. We measured the following outcomes: coma, delirium, LOS, mortality, and discharge location. RESULTS: The POST group benefited from better analgesia, received less opiates (90.72 + or - 207.45 vs 22.93 + or - 40.36 morphine equivalents/d, P = <0.0001), and, despite comparable sedation, had shorter duration of mechanical ventilation. Medication-induced coma rates (18.1%vs 7.2%, P < 0.0001), ICU and hospital LOS, and dependency at discharge were lower in the POST-protocol group. Subsyndromal delirium was significantly reduced; delirium was similar. The 30-day mortality risk in the PRE cohort was 29.4% vs 22.9% in the POST cohort (log-rank test, P = 0.009). CONCLUSION: Educational initiatives incorporating systematic management protocols with nonpharmacologic measures and individualized titration of sedation, analgesia, and delirium therapies are associated with better outcomes.

Successful treatment of encapsulating peritoneal sclerosis with immunosuppressive therapy.

Encapsulating peritoneal sclerosis is a rare, but potentially lethal, complication of peritoneal dialysis. Treatment of patients with encapsulating peritoneal sclerosis is controversial. Conservative treatment carries a poor outcome, and immunosuppressive drugs are now used frequently. Most commonly, these immunosuppressive regimens include steroids with or without azathioprine or cyclosporine. Mycophenolate mofetil is a reversible DNA synthesis inhibitor that frequently replaces azathioprine in renal transplantation because of its improved immunosuppressive potency and better side-effect profile. We report 3 cases of encapsulating peritoneal sclerosis in continuous ambulatory peritoneal dialysis patients for which an association of prednisone and mycophenolate mofetil significantly modified the evolution of the disease. All 3 patients showed significant improvement within a month and are still alive more than 2 years after the diagnosis of encapsulating peritoneal sclerosis. None experienced a relapse or abdominal symptoms, and body weights are stable. This is the first report of 3 cases of successful treatment of patients with encapsulating peritoneal sclerosis with prednisone and mycophenolate mofetil.

A practice-related risk score (PRS): a DOPPS-derived aggregate quality index for haemodialysis facilities.

BACKGROUND: The Dialysis Outcomes and Practice Patterns Study (DOPPS) database was used to develop and validate a practice-related risk score (PRS) based on modifiable practices to help facilities assess potential areas for improving patient care. METHODS: Relative risks (RRs) from a multivariable Cox mortality model, based on observational haemodialysis (HD) patient data from DOPPS I (1996-2001, seven countries), were used. The four practices were the percent of patients with Kt/V > or =1.2, haemoglobin > or =11 g/dl (110 g/l), albumin > or =4.0 g/dl (40g/l) and catheter use, and were significantly related to mortality when modelled together. DOPPS II data (2002-2004, 12 countries) were used to evaluate the relationship between PRS and mortality risk using Cox regression. RESULTS: For facilities in DOPPS I and II, changes in PRS over time were significantly correlated with changes in the standardized mortality ratio (SMR). The PRS ranged from 1.0 to 2.1. Overall, the adjusted RR of death was 1.05 per 0.1 points higher PRS (P < 0.0001). For facilities in both DOPPS I and II (N = 119), a 0.2 decrease in PRS was associated with a 0.19 decrease in SMR (P = 0.005). On average, facilities that improved PRS practices showed significantly reduced mortality over the same time frame. CONCLUSIONS: The PRS assesses modifiable HD practices that are linked to improved patient survival. Further refinements might lead to improvements in the PRS and will address regional variations in the PRS/mortality relationship.

Transfusion Management of Incident Dialysis Patients in Canada: A Prospective Observational Study.

BACKGROUND: Several studies have demonstrated harm associated with using erythropoiesis-stimulating agents (ESA) to achieve higher hemoglobin (Hb) levels. Subsequently, more conservative use of ESAs has changed anemia therapy in patients with chronic renal failure. OBJECTIVE: The objectives were to identify transfusion rates in hemodialysis (HD) patients during the first year of therapy, to identify factors associated with the probability of transfusion, describe reasons for the transfusions, and identify the Hb values associated with each transfusion. An exploratory objective was to describe the age of red blood cell transfusions. DESIGN: This was a multicenter prospective observational cohort study. SETTING: There were 12 study sites in 5 Canadian provinces. The study was performed from 2012 to 2014. METHODS: The study patients were adult incident chronic HD patients in these centers. Patients with acute kidney injury, peritoneal dialysis, and planned transfer to satellite units were excluded. Patients had to receive at least 1 month of chronic HD to be eligible. Data for 3 months prior to HD were obtained by retrospective chart review. Prospectively, charts were reviewed monthly for 12 months for data abstraction. RESULTS: There were 314 patients enrolled and 79.9% completed 12 month follow-up. Ninety-four (29.9%) patients received at least 1 unit of blood. During the first 90 days, the transfusion episode rate was 148.4 per 100 patient-years compared with 62.6 per 100 patient-years post 90 days. The most frequent indication was a low Hb value (92%) with gastrointestinal bleeding, surgical blood loss, and fatigue accounting for 9.9%, 8.6%, and 4.5%, respectively. Some patients had >1 indication. The mean Hb values prior to transfusion episodes ranged from 75.3 to 78.6 g/L. Cox regression analysis on time to first transfusion and time to first hospitalization/death both showed an association with inpatient initiation of HD. Some 37.5% initiated HD as an inpatient and differed from those starting as an outpatient. They had less predialysis care and laboratory data suggested more inflammation. The mean and median ages of the blood units transfused were 24.9 (SD = 10.0) and 23 days (interquartile range = 17-33). CONCLUSIONS: This work reported the blood transfusion rate in incident HD patients in Canada during a period associated with conservative ESA prescription. The major indication for transfusion was a low Hb rather than clinical symptoms. Initiation of HD as an inpatient was independently associated with the probability of receiving a blood transfusion. These findings require further investigation.

CONTEXTE: Plusieurs études ont fait état de lésions associées à l'utilisation d'agents stimulant l'érythropoïèse (ASE) pour hausser le taux d'hémoglobine (Hb). Dès lors, une utilisation plus conservatrice des ASE a modifié le traitement de l'anémie chez les patients atteints d'insuffisance rénale chronique. OBJECTIFS DE L'ÉTUDE: L'étude visait à i) établir les taux de transfusion sanguine chez les patients hémodialysés au cours de la première année de traitement; ii) cerner les facteurs associés à la probabilité de recourir à une transfusion sanguine; iii) connaître les raisons de la transfusion; et iv) caractériser le taux d'hémoglobine au moment de l'intervention. En outre, un objectif exploratoire consistait à déterminer l'âge des érythrocytes transfusés. TYPE D'ÉTUDE: Il s'agit d'une étude de cohorte observationnelle prospective multicentrique. CADRE DE L'ÉTUDE: L'étude s'est tenue entre 2012 et 2014 sur douze sites répartis dans cinq provinces canadiennes. MÉTHODOLOGIE: Les patients adultes hémodialysés des centres participants ont été recrutés pour l'étude. Ont été exclus les patients atteints d'insuffisance rénale aiguë, les patients traités par dialyse péritonéale et les patients à être transférés vers une unité satellite. Pour être admissible, le patient devait recevoir un traitement d'hémodialyse continu pendant au moins un mois. On a rétrospectivement tiré des dossiers médicaux les données des trois mois précédant l'hémodialyse, puis on a extrait les données des dossiers médicaux chaque mois sur un an. RÉSULTATS: Un total de 314 patients a participé à l'étude et 79,9 % d'entre eux ont complété les 12 mois de suivi. Sur cette période, 94 patients (29,9 %) ont reçu au moins une transfusion sanguine. Au cours des 90 premiers jours, le taux d'épisodes transfusionnels était de 148,4 pour 100 années-patients, comparativement à 62,6 pour 100 années-patients pour le reste de l'étude. La raison la plus fréquente de recourir à une transfusion était un faible taux d'Hb (92 % des cas); les cas de saignements gastro-intestinaux, de perte de sang périchirurgicale et de fatigue comptaient quant à eux pour 9,9 %, 8,6 % et 4,5 % respectivement. Certains patients cumulant plus d'une indication. Le taux d'Hb moyen prétransfusion variait de 75,3 à 78,6 g/L. Une analyse de régression de Cox sur le temps écoulé jusqu'à la première transfusion et jusqu'à la première hospitalisation (ou le décès) du patient a montré une corrélation avec l'initiation d'un traitement d'hémodialyse chez les patients hospitalisés. Les sujets qui avaient initié leur traitement d'hémodialyse alors qu'ils étaient hospitalisés (37,5 %) ont reçu moins de soins prédialyse et présentaient davantage d'inflammation que les sujets qui avaient commencé leurs traitements d'hémodialyse en tant que patient externe. Enfin, l'âge moyen et l'âge médian des érythrocytes transfusés étaient de 24,9 jours (ÉT : 10,0) et de 23 jours (EIQ : 17 à 23). CONCLUSION: Notre étude a permis de connaître le taux de transfusions sanguines dans une population de patients hémodialysés canadiens au cours d'une période correspondant à une prescription conservatrice d'ASE. On a observé que la principale raison de transfusion était un faible taux d'Hb et non des symptômes cliniques. Enfin, une hémodialyse amorcée en cours d'hospitalisation a été associée à une probabilité accrue de transfusion sanguine. Nos constatations devraient faire l'objet d'études plus approfondies.

Association of Neutrophil-to-Lymphocyte Ratio With Inflammation and Erythropoietin Resistance in Chronic Dialysis Patients.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) was widely studied as a prognostic marker in various medical and surgical specialties, but its significance in nephrology is not yet established. OBJECTIVE: We evaluated its accuracy as an inflammation biomarker in a dialysis population. DESIGN SETTING: Single-center retrospective study. PATIENTS: The records of all 550 patients who were treated with hemodialysis (HD) or peritoneal dialysis (PD) from September 2008 to March 2011 were included. MEASUREMENTS: NLR was calculated from the monthly complete blood count. METHODS: Association between NLR and markers of inflammation (C-reactive protein [CRP], serum albumin, and erythropoietin resistance index [ERI]) was measured using Spearman coefficient. RESULTS: In total, 120 patients were eligible for the correlation analyses. We found a positive correlation between NLR and CRP (all patients: r = 0.45, P < .001; HD: r = 0.47, P < .001; PD: r = 0.48, P = .13). NLR and albumin were inversely correlated (r = -0.51, P < .001). Finally, high NLR was associated with a nonsignificant increased ERI, but we have not demonstrated a direct correlation. LIMITATIONS: CRP and albumin are not measured routinely and were ordered for a specific clinical reason leading to an indication bias. Also, no relationship with clinical outcome was established. CONCLUSIONS: NLR seems to be a good inflammatory biomarker in dialysis in addition to being easily available. However, controlled studies should be conducted to properly assess and validate NLR levels that would be clinically significant and relevant, as well as its prognostic significance and utility in a clinical setting.

CONTEXTE: La qualité de marqueur pronostique du ratio neutrophiles/lymphocytes a fait l'objet d'études approfondies dans plusieurs disciplines médicales et spécialités chirurgicales. En revanche, son importance n'est toujours pas établie dans le domaine de la néphrologie. OBJECTIF DE L'ÉTUDE: Nous avons voulu évaluer l'efficacité du ratio neutrophiles/lymphocytes comme biomarqueur de l'inflammation chez une population de patients dialysés. MODÈLE DE L'ÉTUDE: Il s'agit d'une étude rétrospective restreinte à un seul établissement. PARTICIPANTS: Les dossiers médicaux des 550 patients ayant été traités par hémodialyse (HD) ou par dialyse péritonéale (DP) entre septembre 2008 et mars 2011 ont été retenus pour cette étude. MESURES: Le ratio neutrophiles/lymphocytes a été calculé à partir de la formule sanguine complète prélevée mensuellement. MÉTHODOLOGIE: On a utilisé le coefficient de Spearman pour mesurer la corrélation entre le ratio neutrophiles/lymphocytes et certains marqueurs de l'inflammation : la protéine C-réactive, l'albumine sérique et l'index de résistance à l'érythropoïétine (IRE). RÉSULTATS: De tous les dossiers médicaux retenus, seuls 120 patients étaient admissibles à l'analyse de corrélation. Nous avons pu établir une corrélation positive entre le ratio neutrophiles/lymphocytes et la protéine C-réactive (r=0,45; p<0,001 pour l'ensemble des patients, r=0,47; p<0,001 chez les patients en HD, et r=0,48; p=0,13 chez les patients sous DP), alors que la corrélation était inversée dans le cas de l'albumine sérique (r=0,51; p<0,001). Nous avons également observé qu'un ratio neutrophiles/lymphocytes élevé était associé à une élévation non significative de l'IRE, sans toutefois établir une corrélation directe. LIMITES DE L'ÉTUDE: Règle générale, l'albumine sérique et la protéine C-réactive ne sont mesurées que lorsqu'une raison d'ordre clinique le demande, ce qui pourrait signaler un biais. De plus, aucun lien n'a été établi entre le ratio neutrophiles/lymphocytes et les devenirs cliniques des patients. CONCLUSION: Le calcul du ratio neutrophiles/lymphocytes semble être un bon indicateur de l'état inflammatoire chez les patients dialysés. Qui plus est, les données nécessaires pour évaluer ce ratio sont faciles à obtenir. Néanmoins, des études contrôlées devraient être menées pour déterminer les valeurs de ratio neutrophiles/lymphocytes qui seraient significatives du point de vue clinique, de même que pour établir l'importance du ratio neutrophiles/lymphocytes sur le plan du pronostic et sa pertinence dans un cadre clinique.

Conversion of oral alfacalcidol to oral calcitriol in the treatment of secondary hyperparathyroidism in chronic hemodialysis patients.

PURPOSE: The optimal vitamin D3 therapy for the treatment of secondary hyperparathyroidism (SHPT) in chronic hemodialysis patients is still controversial. Recent studies suggest that uremia in end-stage renal disease is associated with enzymatic hepatic dysfunction altering 25-hydroxylation of vitamin D3. The goal of our study was to compare the efficacy of calcitriol, the fully hydroxylated active form of vitamin D3, to alfacalcidol which needs 25-hydroxylation to be effective, for the treatment of SHPT in chronic hemodialysis patients. METHODS: We retrospectively reviewed 45 chronic hemodialysis patients who were switched from oral alfacalcidol to oral calcitriol for the treatment of SHPT. Parathyroid hormone (PTH), serum calcium and serum phosphorus levels were compared pre- and post-conversion using paired Student's t tests. RESULTS: The mean dose of active vitamin D3 decreased from 3.50 mcg/week at baseline to 2.86 mcg (P < 0001) after the switch from alfacalcidol to calcitriol. PTH significantly decreased from 94.4 to 82.6 pmol/L (-11.8 pmol/L, P = 0.02). The mean corrected calcium increased from 2.17 to 2.25 mmol/L (+0.08 mmol/L, P < 0.001) without any clinically significant hypercalcemia, and phosphorus levels were stable. Results were similar in a subgroup of patients (n = 17) for whom the medication was administrated during the hemodialysis session, ensuring a complete compliance. CONCLUSIONS: According to our study, calcitriol in equal dosage is more effective than alfacalcidol in lowering serum PTH level in chronic hemodialysis patients. This suggests that calcitriol may be the optimal active vitamin D3 for the treatment of SHPT in chronic hemodialysis patients.

Prevention of catheter lumen occlusion with rT-PA versus heparin (Pre-CLOT): study protocol of a randomized trial [ISRCTN35253449].

BACKGROUND: Many patients with end-stage renal disease use a central venous catheter for hemodialysis access. A large majority of these catheters malfunction within one year of insertion, with up to two-thirds due to thrombosis. The optimal solution for locking the catheter between hemodialysis sessions, to decrease the risk of thrombosis and catheter malfunction, is unknown. The Prevention of Catheter Lumen Occlusion with rt-PA versus Heparin (PreCLOT) study will determine if use of weekly rt-PA, compared to regular heparin, as a catheter locking solution, will decrease the risk of catheter malfunction. METHODS/DESIGN: The study population will consist of patients requiring chronic hemodialysis thrice weekly who are dialyzed with a newly inserted permanent dual-lumen central venous catheter. Patients randomized to the treatment arm will receive rt-PA 1 mg per lumen once per week, with heparin 5,000 units per ml as a catheter locking solution for the remaining two sessions. Patients randomized to the control arm will receive heparin 5,000 units per ml as a catheter locking solution after each dialysis session. The study treatment period will be six months, with 340 patients to be recruited from 14 sites across Canada. The primary outcome will be catheter malfunction, based on mean blood flow parameters while on hemodialysis, with a secondary outcome of catheter-related bacteremia. A cost-effectiveness analysis will be undertaken to assess the cost of maintaining a catheter using rt-PA as a locking solution, compared to the use of heparin. DISCUSSION: Results from this study will determine if use of weekly rt-PA, compared to heparin, will decrease catheter malfunction, as well as assess the cost-effectiveness of these locking solutions.

Changes in Urinary and Serum Levels of Novel Biomarkers after Administration of Gadolinium-based Contrast Agents.

OBJECTIVE: The aim of our study is to describe the changes in urinary and serum levels of novel biomarkers after gadolinium contrast administration in patients with normal renal function. METHODS: We measured four biomarkers in 28 volunteers: interleukin-18 (IL-18), N-acetyl-glucosaminidase (NAG), neutrophil gelatinase-associated lipocalin, and cystatin C. Urinary and serum samples were collected at 0, 3, and 24 hours following gadolinium administration. RESULTS: Baseline serum creatinine was 57.8 ± 34.5 µmol/L and remained stable. Urinary IL-18 levels increased significantly at three hours (10.7 vs. 7.3 ng/mg creatinine; P < 0.05). Similarly, urinary NAG levels increased significantly at three hours (3.9 vs. 2.2 IU/mg creatinine; P < 0.001). For both these markers, the difference was no longer significant at 24 hours. No statistically significant differences were observed for urinary and serum neutrophil gelatinase-associated lipocalin levels and for serum cystatin C levels. CONCLUSIONS: Urinary IL-18 and NAG levels increased transiently after administration of gadolinium-based contrast agents in patients with normal renal function.

Predictors of Transfer to Home Hemodialysis after Peritoneal Dialysis Completion.

UNLABELLED: ♦ BACKGROUND: The aim of the present study was to evaluate the predictors of transfer to home hemodialysis (HHD) after peritoneal dialysis (PD) completion. ♦ METHODS: All Australian and New Zealand patients treated with PD on day 90 after initiation of renal replacement therapy between 2000 and 2012 were included. Completion of PD was defined by death, transplantation, or hemodialysis (HD) for 180 days or more. Patients were categorized as "transferred to HHD" if they initiated HHD fewer than 180 days after PD had ended. Multivariable logistic regression was used to evaluate predictors of transfer to HHD in a restricted cohort experiencing PD technique failure; a competing-risks analysis was used in the unrestricted cohort. ♦ RESULTS: Of 10 710 incident PD patients, 3752 died, 1549 underwent transplantation, and 2915 transferred to HD, among whom 156 (5.4%) started HHD. The positive predictors of transfer to HHD in the restricted cohort were male sex [odds ratio (OR): 2.81], obesity (OR: 2.20), and PD therapy duration (OR: 1.10 per year). Negative predictors included age (OR: 0.95 per year), infectious cause of technique failure (OR: 0.48), underweight (OR: 0.50), kidney disease resulting from hypertension (OR: 0.38) or diabetes (OR: 0.32), race being Maori (OR: 0.65) or Aboriginal and Torres Strait Islander (OR: 0.30). Comparable results were obtained with a competing-risks model. ♦ CONCLUSIONS: Transfer to HHD after completion of PD is rare and predicted by patient characteristics at baseline and at the time of PD end. Transition to HHD should be considered more often in patients using PD, especially when they fulfill the identified characteristics.