Regional citrate anticoagulation in continuous venovenous hemofiltration in critically ill patients with a high risk of bleeding

Regional citrate anticoagulation in continuous venovenous hemofiltration in critically ill patients with a high risk of bleeding.BackgroundSystemic heparinization is associated with a high rate of bleeding when used to maintain patency of the extracorporeal circuit during continuous renal replacement therapy (CRRT) in critically ill patients. Regional anticoagulation can be achieved with citrate, but previously described techniques are cumbersome and associated with metabolic complications.MethodsWe designed a simplified system for delivering regional citrate anticoagulation during continuous venovenous hemofiltration (CVVH). We evaluated filter life and hemorrhagic complications in the first 17 consecutive patients who received this therapy at our institution. Blood flow rate was set at 180ml/min. Ultrafiltration rate was maintained at 2.0 liters/hr and citrate-based replacement fluid (trisodium citrate 13.3mm, sodium chloride 100mm, magnesium chloride 0.75mm, dextrose 0.2%) was infused proximal to the filter to maintain the desired fluid balance. Calcium gluconate was infused through a separate line to maintain a serum-ionized calcium level of 1.0 to 1.1mm.ResultsAll patients were critically ill and required mechanical ventilation and vasopressor therapy. Systemic heparin anticoagulation was judged to be contraindicated in all of the patients. A total of 85 filters were used, of which 64 were lost because of clotting, with a mean life span of 29.5 ± 17.9hours. The remaining 21 filters were discontinued for other reasons. Control of fluid and electrolyte balance and azotemia was excellent (mean serum creatinine after 48 to 72hr of treatment was 2.4 ± 1.2mg/dl). No bleeding episodes occurred. Two patients, one with septic shock and the other with fulminant hepatic failure, developed evidence for citrate toxicity without a significant alteration in clinical status. Nine patients survived (52.9%).ConclusionOur simplified technique of regional anticoagulation with citrate is an effective and safe form of anticoagulation for CVVH in critically ill patients with a high risk of bleeding

Comparison of aneroid and oscillometric blood pressure measurements in children.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.Limited data exist on the comparison of blood pressure (BP) measurements using aneroid and oscillometric devices. The purpose of the study was to investigate the difference in BP obtained using oscillometric and aneroid BP monitors in 9- to 10-year-old children. A total of 979 children were divided into group O, which underwent two oscillometric BP readings followed by two aneroid readings, and group A, which had BP measured in the reverse order. No significant difference was found between the mean (±standard deviation) of the two systolic BP readings obtained using the oscillometric and aneroid devices (111.5±8.6 vs 111.3±8.1 mm Hg; P=.39), whereas the mean diastolic BP was lower with the oscillometric monitor (61.5±8.0 vs 64.5±6.8 mm Hg; P<.001). A significant downward trend in BP was observed with each consecutive measurement, and agreement between the two monitors was limited. Multiple BP measurements are, therefore, recommended before the diagnosis of elevated BP or hypertension is made with either method.Landspitali - The National University Hospital of Iceland Research Fun

Impact of nephrolithiasis on kidney function.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.Kidney stone disease has been associated with reduced kidney function and chronic kidney disease (CKD). The objective of the study was to examine kidney function, body mass index (BMI) and the prevalence of cardiovascular disease, hypertension and diabetes in recurrent kidney stone formers.A cross-sectional, case-control study comparing measures of kidney function, BMI and comorbid conditions was conducted in 195 kidney stone patients aged 18 to 70 years with recurrent clinical stone events and 390 age- and gender-matched controls. Wilcoxon-Mann-Whitney, chi-square tests and analysis of covariance were used to compare serum creatinine (SCr) and estimated glomerular filtration rate (eGFR) between the groups.The median age of stone formers was 51 (range, 19-70) years and 108 (55 %) were males. Seventy patients (36 %) had experienced 2-4 clinical stone events, 41 (21 %) 5-10 episodes and 84 (43 %) more than 10. The median SCr was 75 (41-140) μmol/L in the stone formers and 64 (34-168) μmol/L in the control group (p < 0.001). The mean eGFR was 87 ± 20 and 104 ± 22 mL/min/1.73 m(2) in the stone formers and controls, respectively (p < 0.001). After adjustment for body size and comorbid conditions, the difference in SCr and eGFR between cases and controls remained highly significant (p < 0.001). The prevalence of CKD was 9.3 % among stone formers compared with 1.3 % in the control group (P < 0.001). Hypertension and diabetes were significantly more prevalent among the cases that also had higher BMI than controls.Recurrent kidney stone formers have a significantly lower level of kidney function and a markedly higher prevalence of CKD than age- and gender-matched control subjects. The observed deleterious effect of kidney stones on kidney function appears to be independent of comorbid conditions.Landspitali University Hospital Research Fun

Factor D Inhibition Blocks Complement Activation Induced by Mutant Factor B Associated With Atypical Hemolytic Uremic Syndrome and Membranoproliferative Glomerulonephritis

Funding Information: The authors wish to thank Dr Marina Noris and Dr Roberta Donadelli, Istituto di Ricerche Farmacologiche Mario Negri, Bergamo Italy for excellent technical advice for the assay of factor B cleavage by the C3 convertase. Dr Ravi Bhongir and Dr Sandra Jovic, Infection Medicine, Clinical Sciences Lund are acknowledged for their help with the surface plasmon resonance assays. The authors thank Drs Markus Heidenblad, Sofia Saal and Bj?rn Hallstr?m of the Center for Molecular Diagnostics, Region Sk?ne and Clinical Genomics Lund, SciLifeLab, Lund University for next-generation sequencing. Dr Henning Gong carried out part of the mutagenesis study as part of his master?s thesis. The kidney biopsies of Patient 3 were assessed by Dr. Melinda Raki, Department of Pathology, Oslo University Hospital, Oslo Norway, Dr. Sabine Leh, Department of Pathology, Haukeland Univeristy Hospital Bergen, Norway, Professor Sanjeev Sethi and Professor Fernando Fervenza of the Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota. This work was presented in preliminary poster form at the17th Congress of the International Pediatric Nephrology Association, Iguacu Brazil, September 20-24, 2016, at the 6th International Conference ?HUS & related diseases?, Innsbruck, Austria, June 11-13, 2017, the 16th European Meeting of Complement in Human Disease, Copenhagen, Denmark, September 8-12, 2017, the 18th Congress of the International Pediatric Nephrology Association, Venice, Italy October 17-21, 2019. Publisher Copyright: © Copyright © 2021 Aradottir, Kristoffersson, Roumenina, Bjerre, Kashioulis, Palsson and Karpman.Complement factor B (FB) mutant variants are associated with excessive complement activation in kidney diseases such as atypical hemolytic uremic syndrome (aHUS), C3 glomerulopathy and membranoproliferative glomerulonephritis (MPGN). Patients with aHUS are currently treated with eculizumab while there is no specific treatment for other complement-mediated renal diseases. In this study the phenotype of three FB missense variants, detected in patients with aHUS (D371G and E601K) and MPGN (I242L), was investigated. Patient sera with the D371G and I242L mutations induced hemolysis of sheep erythrocytes. Mutagenesis was performed to study the effect of factor D (FD) inhibition on C3 convertase-induced FB cleavage, complement-mediated hemolysis, and the release of soluble C5b-9 from glomerular endothelial cells. The FD inhibitor danicopan abrogated C3 convertase-associated FB cleavage to the Bb fragment in patient serum, and of the FB constructs, D371G, E601K, I242L, the gain-of-function mutation D279G, and the wild-type construct, in FB-depleted serum. Furthermore, the FD-inhibitor blocked hemolysis induced by the D371G and D279G gain-of-function mutants. In FB-depleted serum the D371G and D279G mutants induced release of C5b-9 from glomerular endothelial cells that was reduced by the FD-inhibitor. These results suggest that FD inhibition can effectively block complement overactivation induced by FB gain-of-function mutations.Peer reviewe

Incidence of and risk factors of chronic kidney disease: Results of a nationwide study in Iceland

Background - Information on the incidence of chronic kidney disease (CKD) in the general population is scarce. This study examined the incidence and risk factors of CKD stages 1–5 in Iceland, based on multiple markers of kidney damage. Methods - All serum creatinine (SCr) values, urine protein measurements and diagnosis codes for kidney diseases and comorbid conditions for people aged ≥18 years were obtained from electronic medical records of all healthcare institutions in Iceland in 2008–2016. CKD was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria as evidence for kidney damage and/or estimated glomerular filtration rate (eGFR) 3 months. Alternatively, CKD was defined using age-adapted eGFR thresholds. Mean annual age-standardized incidence of CKD was calculated for persons without CKD at study entry. Risk factor assessment was based on International Classification of Diseases diagnosis codes. Incidence was reported per 100 000 population. Results - We retrieved 1 820 990 SCr values for 206 727 persons. Median age was 45 years (range, 18–106) and 47% were men. Mean annual age-standardized incidence of CKD per 100 000 was 649 in men and 694 in women, and 480 in men and 522 in women using age-adapted eGFR thresholds. The incidence reached over 3000 in men and women aged >75 years. Traditional CKD risk factors, such as acute kidney injury, diabetes, hypertension and cardiovascular disease, as well as less well characterized risk factors, including chronic lung disease, malignancy and major psychiatric illness were associated with increased risk of CKD, and the same was true for obesity and sleep apnoea in women. Conclusion - The annual incidence of CKD, with strict adherence to the KDIGO criteria, was <0.7% but markedly lower using age-adapted eGFR thresholds. Apart from acute kidney injury, the observed risk factors comprised chronic and potentially modifiable disorders

Association of eGFR and mortality with use of a joint model: results of a nationwide study in Iceland

Objectives. Prior studies on the association of estimated glomerular filtration rate (eGFR) and mortality have failed to include methods to account for repeated eGFR determinations. The aim of this study was to estimate the association between eGFR and mortality in the general population in Iceland employing a joint model. Methods. We obtained all serum creatinine and urine protein measurements from all clinical laboratories in Iceland in the years 2008–16. Clinical data were obtained from nationwide electronic medical records. eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation and categorized as follows: 0–29, 30–44, 45–59, 60–74, 75– 89, 90–104 and >104 mL/min/1.73 m2. A multiple imputation method was used to account for missing urine protein data. A joint model was used to assess risk of all-cause mortality. Results. We obtained 2 120 147 creatinine values for 218 437 individuals, of whom 84 364 (39%) had proteinuria measurements available. Median age was 46 (range 18–106) years and 47% were men. Proteinuria associated with increased risk of death for all eGFR categories in persons of all ages. In persons ≤65 years, the lowest risk was observed for eGFR of 75–89 mL/min/1.73 m2 without proteinuria. For persons aged >65 years, the lowest risk was observed for eGFR of 60–74 mL/min/1.73 m2 without proteinuria. eGFR of 45–59 mL/min/1.73 m2 without proteinuria did not associate with increased mortality risk in this age group. eGFR >104 mL/min/1.73 m2 associated with increased mortality. Conclusions. These results lend further support to the use of age-adapted eGFR thresholds for defining chronic kidney disease. Very high eGFR needs to be studied in more detail with regard to mortalit

Does treatment with n-3 polyunsaturated fatty acids prevent atrial fibrillation after open heart surgery?

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldAIMS: To examine the effect of n-3 polyunsaturated fatty acid (PUFA) treatment on the incidence of post-operative atrial fibrillation (POAF). METHODS AND RESULTS: A prospective, randomized, double-blinded, placebo-controlled trial was conducted in patients admitted for coronary artery bypass grafting and/or valvular repair surgery. The patients received either n-3 PUFA capsules, containing a daily dose of 1240 mg eicosapentaenoic acid and 1000 mg docosahexaenoic acid, or olive oil capsules for 5-7 days prior to surgery and post-operatively until hospital discharge. The endpoint was POAF, defined as an episode detected by continuous electrocardiographic monitoring, lasting >5 min. A total of 170 patients were enrolled in the study, and 168 patients underwent surgery. Their median age was 67 (range 43-82) years, and 79.2% were males. There was no difference in baseline characteristics between the n-3 PUFA group (n = 83) and the placebo group (n = 85), and the incidence of POAF was 54.2 and 54.1% (P = 0.99), respectively. Factors associated with POAF included advanced age, peak post-operative C-reactive protein level, valvular surgery, lower body mass index, and non-smoking, but n-3 PUFA concentration in plasma lipids was not associated with POAF. CONCLUSION: There is no evidence for a beneficial effect of treatment with n-3 PUFA on the occurrence of POAF in patients undergoing open heart surgery

Common and rare variants associated with kidney stones and biochemical traits.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.Kidney stone disease is a complex disorder with a strong genetic component. We conducted a genome-wide association study of 28.3 million sequence variants detected through whole-genome sequencing of 2,636 Icelanders that were imputed into 5,419 kidney stone cases, including 2,172 cases with a history of recurrent kidney stones, and 279,870 controls. We identify sequence variants associating with kidney stones at ALPL (rs1256328[T], odds ratio (OR)=1.21, P=5.8 × 10(-10)) and a suggestive association at CASR (rs7627468[A], OR=1.16, P=2.0 × 10(-8)). Focusing our analysis on coding sequence variants in 63 genes with preferential kidney expression we identify two rare missense variants SLC34A1 p.Tyr489Cys (OR=2.38, P=2.8 × 10(-5)) and TRPV5 p.Leu530Arg (OR=3.62, P=4.1 × 10(-5)) associating with recurrent kidney stones. We also observe associations of the identified kidney stone variants with biochemical traits in a large population set, indicating potential biological mechanism.Rare Kidney Stone Consortium 5U54DK083908-07 National Center for Advancing Translational Sciences (NCATS) Rare Diseases Clinical Research Network (RDCRN) Rare Kidney Stone Consortiu

The association of living donor source with patient and graft survival among kidney transplant recipients in the ERA-EDTA Registry - a retrospective study

In this study we aimed to compare patient and graft survival of kidney transplant recipients who received a kidney from a living-related donor (LRD) or living-unrelated donor (LUD). Adult patients in the ERA-EDTA Registry who received their first kidney transplant in 1998-2017 were included. Ten-year patient and graft survival were compared between LRD and LUD transplants using Cox regression analysis. In total, 14 370 patients received a kidney from a living donor. Of those, 9212 (64.1%) grafts were from a LRD, 5063 (35.2%) from a LUD and for 95 (0.7%), the donor type was unknown. Unadjusted five-year risks of death and graft failure (including death as event) were lower for LRD transplants than for LUD grafts: 4.2% (95% confidence interval [CI]: 3.7-4.6) and 10.8% (95% CI: 10.1-11.5) versus 6.5% (95% CI: 5.7-7.4) and 12.2% (95% CI: 11.2-13.3), respectively. However, after adjusting for potential confounders, associations disappeared with hazard ratios of 0.99 (95% CI: 0.87-1.13) for patient survival and 1.03 (95% CI: 0.94-1.14) for graft survival. Unadjusted risk of death-censored graft failure was similar, but after adjustment, it was higher for LUD transplants (1.19; 95% CI: 1.04-1.35). In conclusion, patient and graft survival of LRD and LUD kidney transplant recipients was similar, whereas death-censored graft failure was higher in LUD. These findings confirm the importance of both living kidney donor types.Peer reviewe