Live-donor kidney transplant outcome prediction (L-TOP) using artificial intelligence.

Outcome prediction for live-donor kidney transplantation improves clinical and patient decisions and donor selection. However, the concurrently used models are of limited discriminative or calibration power and there is a critical need to improve the selection process. We aimed to assess the value of various artificial intelligence (AI) algorithms to improve the risk stratification index. We evaluated pre-transplant variables among 66 914 live-donor kidney transplants (performed between 01/12/2007-01/06/2021) from the United Network of Organ Sharing database, randomized into training (80%) and test (20%) sets. The primary outcome measure was death-censored graft survival. We tested four machine learning models for discrimination (time-dependent concordance index, CTD, and area under the ROC curve) and calibration (integrated Brier score, IBS). We used decision curve analysis to assess the potential clinical utility. Among the models, the deep Cox mixture model showed the best discriminative performance (AUC = 0.70, 0.68, and 0.68 at 5, 10, and 13 years post-transplant, respectively). CTD reached 0.70, 0.67, and 0.66 at 5, 10, and 13 years post-transplant. The IBS score was 0.09, indicating good calibration. In comparison, applying the Living Kidney Donor Profile Index (LKDPI) on the same cohort produced a CTD of 0.56 and an AUC of 0.55-0.58 only. Decision curve analysis showed an additional net benefit compared to the LKDPI, 'Treat all' and 'Treat None' approaches. Our AI-based deep Cox mixture model, termed Live-Donor Kidney Transplant Outcome Prediction outperforms existing prediction models, including the LKDPI, with the potential to improve decisions for optimum live donor selection by ranking potential transplant pairs based on graft survival. This model could be adopted to improve the outcomes of paired exchange programs.

A bibliometric analysis of publications in Renal Failure in the last three decades.

Publications in Renal Failure in Science Citation Index Expanded (SCI-EXPANDED) between 1992 and 2021 were analyzed. Six publication indicators: total, independent, collaborative, first author, corresponding author, and single author publications as well as their related citation indicators, were used to compare performances of countries, institutes, and authors. Comparison of the highly cited papers and journal's impact factor (IF) contributors was discussed. In addition, the main research topics in the journal were presented. Results show that China published the most total articles and reviews, as well as the first-author papers and corresponding-author papers in the journal. The Chang Gung Memorial Hospital in Taiwan ranked the top in five publication indicators: total, single-institution, inter-institutionally collaborative, first author, and corresponding-author papers. A low percentage of productive authors emerged as a journal IF contributor. Similarly, only a limited relationship between highly cited papers and IF contributing papers was found. Publications related to hemodialysis, chronic kidney disease, and acute kidney injury were the most popular topic, while meta-analysis was new focus in the last decade in the journal.

Real-world characteristics, modern antidiabetic treatment patterns, and comorbidities of patients with type 2 diabetes in central and Eastern Europe: retrospective cross-sectional and longitudinal evaluations in the CORDIALLY® study.

BACKGROUND: Guidelines from 2016 onwards recommend early use of SGLT2i or GLP-1 RA for patients with type 2 diabetes (T2D) and cardiovascular disease (CVD), to reduce CV events and mortality. Many eligible patients are not treated accordingly, although data are lacking for Central and Eastern Europe (CEE). METHODS: The CORDIALLY non-interventional study evaluated the real-world characteristics, modern antidiabetic treatment patterns, and the prevalence of CVD and chronic kidney disease (CKD) in adults with T2D at nonhospital-based practices in CEE. Data were retrospectively collated by medical chart review for patients initiating empagliflozin, another SGLT2i, DPP4i, or GLP-1 RA in autumn 2018. All data were analysed cross-sectionally, except for discontinuations assessed 1 year ± 2 months after initiation. RESULTS: Patients (N = 4055) were enrolled by diabetologists (56.7%), endocrinologists (40.7%), or cardiologists (2.5%). Empagliflozin (48.5%) was the most prescribed medication among SGLT2i, DPP4i, and GLP-1 RA; > 3 times more patients were prescribed empagliflozin than other SGLT2i (10 times more by cardiologists). Overall, 36.6% of patients had diagnosed CVD. Despite guidelines recommending SGLT2i or GLP-1 RA, 26.8% of patients with CVD received DPP4i. Patients initiating DPP4i were older (mean 66.4 years) than with SGLT2i (62.4 years) or GLP-1 RA (58.3 years). CKD prevalence differed by physician assessment (14.5%) or based on eGFR and UACR (27.9%). Many patients with CKD (≥ 41%) received DPP4i, despite guidelines recommending SGLT2is owing to their renal benefits. 1 year ± 2-months after initiation, 10.0% (7.9-12.3%) of patients had discontinued study medication: 23.7-45.0% due to 'financial burden of co-payment', 0-1.9% due to adverse events (no patients discontinued DPP4i due to adverse events). Treatment guidelines were 'highly relevant' for a greater proportion of cardiologists (79.4%) and endocrinologists (72.9%) than diabetologists (56.9%), and ≤ 20% of physicians consulted other physicians when choosing and discontinuing treatments. CONCLUSIONS: In CORDIALLY, significant proportions of patients with T2D and CVD/CKD who initiated modern antidiabetic medication in CEE in autumn 2018 were not treated with cardioprotective T2D medications. Use of DPP4i instead of SGLT2i or GLP-1 RA may be related to lack of affordable access, the perceived safety of these medications, lack of adherence to the latest treatment guidelines, and lack of collaboration between physicians. Thus, many patients with T2D and comorbidities may develop preventable complications or die prematurely. Trial registration NCT03807440.

Outcomes of Interleukin-2 Receptor Antagonist Induction Therapy in Standard-Risk Renal Transplant Recipients Maintained on Tacrolimus: A Systematic Review and Meta-Analysis.

INTRODUCTION: The additive benefit of interleukin-2 receptor antagonist (IL2-RA) induction in standard-risk kidney transplant recipients, while maintained on tacrolimus-based immunosuppressive therapy, is uncertain. METHODS: We divided the studies included in this meta-analysis into 2 groups: group A (included studies that used same dose of tacrolimus in both arms of each study) and group B (included studies that compared patients who received induction therapy and low-dose tacrolimus vs. those who received no-induction therapy and high dose of tacrolimus). RESULTS: In group A, 11 studies were included (n = 2,886). IL2-RA induction therapy was not associated with significant differences in comparison to no-induction therapy in terms of acute rejection rates at 6 months post-transplant (risk ratio = 1.12 and 95% confidence interval [CI] range: 0.94-1.35) or graft survival at 1 year post-transplant (risk ratio = 0.78 and 95% CI range: 0.45-1.36). In group B, 2 studies were included (n = 669). There was no difference between both arms in terms of acute rejection rates (risk ratio = 0.62, with 95% CI range: 0.33-1.14) or graft survival (risk ratio = 1 and 95% CI range: 0.57-1.74). CONCLUSION: IL2-RA induction therapy does not improve outcomes in patients maintained on tacrolimus-based immunotherapy in standard-risk population.

How We Got Where We Are in Blood Pressure Targets.

PURPOSE OF REVIEW: While we started clinical trials evaluating the benefit of lowering systolic BP's >160 mm Hg and diastolic BPs of <130 mm Hg, the latest guideline suggests a target of <130/80 mm Hg in those with hypertension. This article summarizes exactly how we got to where we are looking over the last half-century. RECENT FINDINGS: Our understanding of systolic and diastolic blood pressure targets to improve cardiovascular outcomes has changed substantially over the past 5 decades. Regarding diastolic blood pressure targets to improve cardiovascular outcomes, initially the VA1 in 1967 had set the goal to <115 mmHg. Over time, several studies including the VA2, Hypertension Optimal Treatment (HOT), and United Kingdom Prospective Diabetes Study Group 38 (UKPDS38) highlighted even greater cardiovascular benefit with lower diastolic targets <80 mmHg, especially in diabetic patients. Of equal importance, multiple studies have focused the attention to systolic blood pressure targets. Starting in 1948 with the Framingham study, passing through the Systolic Hypertension in the Elderly Program (SHEP), Syst-Eur and Syst-China trials, all have set the systolic blood pressure goal <150 mmHg. Most recently, the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial showed an improved cardiovascular outcome with a systolic blood pressure target <140 mmHg in patients with type 2 diabetes, while the Systolic Blood Pressure Intervention Trial (SPRINT) in non-diabetic patients moved it closer to 120 mmHg. There is "no one size fits all" when it comes to blood pressure targets to improve cardiovascular outcomes. To progress our understanding of individual blood pressure goals, future studies might develop a more standardized approach to highlight characteristics such as design and end point definitions while allowing clinical practitioners greater latitude to adapt guideline recommendations to individual patient characteristics and clinical needs.

Retrospective analysis of nontraumatic subdural hematoma incidence and outcomes in Egyptian patients with end-stage renal disease on hemodialysis.

BACKGROUND: The incidence of subdural hematoma (SDH) in chronic maintenance hemodialysis (CMH) patients may change over time, along with the evolving characteristics of the underlying populations. METHODS: We conducted a retrospective, single-center study at Cairo University hospitals, assessing the incidence, associated risk factors, and outcomes of nontraumatic SDH in CMH patients between January 2006 and January 2019. RESULTS: Out of 1217 CMH patients, nontraumatic SDH was diagnosed in 41 (3.37%) during the study, increasing with the enrollees' age but stable over the observation period and translating into an annual incidence rate of 28 per 1000 patients per year. SDH patients were likely to use central venous catheters, reported pruritis and history of bone fractures, and had higher phosphorus, parathyroid hormone, and alkaline phosphatase values (p < 0.001); however, there was no association with atrial fibrillation or use of anticoagulants. In the SDH cohort (n = 41), six patients did not need surgical intervention and 13 patients died before becoming surgically fit for intervention; mortality correlated with ischemic heart disease (p = 0.033) and the presence of atrial fibrillation or chronic anticoagulation with warfarin (p < 0.0001 for both), among others. Twenty-two patients received surgical operations and of these 2 died postoperatively; overall patient mortality was 12/41 (29.27%) at 30 days and 15/41 (36.59%) at 1 year. CONCLUSION: Our study demonstrated a striking enrichment for underlying comorbidities in those patients developing SDH and a high risk of immediate mortality. The benefit of chronic anticoagulation therapy should be carefully weighed against the risk of CNS bleed in MHD patients.

Immunosuppression in kidney transplant recipients with COVID-19 infection - where do we stand and where are we heading?

The appropriate immunosuppressive regimen in kidney transplant recipients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2/COVID-19) infection remains unclear. The impact of direct virus injury complicated by dysregulated hyperimmune response with overwhelming release of various cytokines in COVID-19 infected subjects contributes to the complexity of management. The largest concern of the practicing clinicians at current time is how to tailor maintenance immune-modulating therapy during active viral infection and the efficacy of the soon-to-be upcoming immunization for COVID-19. This targeted review aims to cover most of the current evidence on the effect of key maintenance immunosuppressive agents in COVID-19 infection and proposes a line of management to specific scenarios on this very rapidly evolving subject.

Varanto: variant enrichment analysis and annotation.

SUMMARY: Genome-wide association studies (GWAS) aim to identify associations of genetic variations such as single-nucleotide polymorphisms (SNPs) to a specific trait or a disease. Identifying common themes such as pathways, biological processes and diseases associations is needed to further explore and interpret these results. Varanto is a novel web tool for annotating, visualizing and analyzing human genetic variations using diverse data sources. Varanto can be used to query a set of input variations, retrieve their associated variation and gene level annotations, perform annotation enrichment analysis and visualize the results. AVAILABILITY AND IMPLEMENTATION: Varanto web app is developed with R and implemented as Shiny app with PostgreSQL database and is freely available at http://bioinformatics.uef.fi/varanto. Source code for the tool is available at https://github.com/oqe/varanto. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Subjective global assessment of nutrition, dialysis quality, and the theory of the scientific method in Nephrology practice.

In an era of evidence-based medicine and dialysis performance measures, there is strong motivation to find specific, objective, quantifiable, and reproducible parameters to characterize the clinical condition of chronic kidney disease patients and to present population-wide statistics that may describe quality of care in dialysis centers. Yet, in the last three decades, several studies demonstrated that while parameters including Kt/V urea, serum phosphorus, parathyroid hormone, serum cholesterol fulfill all these criteria, efforts to optimize these lab parameters failed to improve survival on dialysis. However, subjective assessments of nutrition including subjective global assessment and malnutrition-inflammation score, while not ideally suited for statistical analysis and not optimal from the point of view of scientific methodology due to their general, semi-quantifiable, subjective nature have, nevertheless, proved themselves as some of the strongest predictors of clinical outcomes in the dialysis population. Where does this paradox leave us? We propose that a deeper understanding of relevance of these variables in the dialysis population may improve appreciation of the clinical situation of individual patients and may result in a paradigm shift from dialysis adequacy to quality dialysis.

Dialysis patients who smoke are more hypertensive, more fluid overloaded and take more antihypertensive medications than nonsmokers.

Background: Smoking remains a powerful risk factor for death in end-stage renal disease (ESRD) and so is the presence of fluid overload. The relationship between smoking, blood pressure (BP) control and volume overload is insufficiently explored in patients on maintenance dialysis.Methods: This is a retrospective cross-sectional cohort study, utilizing existing patients' data generated during routine ESRD care, including bimonthly protocol bioimpedance fluid assessment of the volume status.Results: We analyzed the data of 63 prevalent patients receiving thrice weekly maintenance hemodiafiltration treatments at one rural dialysis unit in Hungary. The cohort's mean ± SD age was 61.5 ± 15.3 years; 65% male, 38% diabetic, with a mean arterial blood pressure (MAP) 99.5 ± 16.8 mmHg and Charlson score 3.79 ± 2.04. Of these, 38 patients were nonsmokers and 25 smokers. The nonsmokers' MAP was 94.3 ± 14.0 versus smokers' 105.9 ± 18.9 mmHg (p: .002); nonsmokers took an average 0.73 ± 0.92 antihypertensive medications vs. 1.73 ± 1.21 for smokers (p: .0001). The distribution of taking more antihypertensive medications is skewed toward a higher number among the smokers (2x5 chi square p: .004). By bioimpedance spectroscopy, nonsmokers had an average 10.93 ± 7.65 percent overhydration (OH) over the extracellular space compared to 17.63 ± 8.98 in smokers (p: .005).Conclusions: Smoking may be a significant mediator of not only BP but also of chronic fluid overload in ESRD patents. Additional, larger studies are needed to explore the mechanistic link between smoking and volume overload.

Relationship between rabbit anti-thymocyte globulin and development of PTLD and its aggressive form in renal transplant population.

Introduction: The aim of our study is to explore the relationship of rabbit anti-thymocyte globulin (R-ATG) on development of post-transplant lymphoproliferative disease (PTLD) and its aggressive forms (monomorphic PTLD and Hodgkin lymphoma) in renal transplant recipients.Methodology: All patients diagnosed with PTLD post-renal transplant in the United States' Organ Procurement and Transplantation Network from 2003 till 2013 and followed up till 2017 were retrospectively reviewed. Multi-variable logistic regression analysis assessed association of R-ATG to development of PTLD and its aggressive form.Results: Risk of developing PTLD post renal transplant is 1.35%. In comparison to interleukin-2 blocker induction therapy, R-ATG is associated with increased risk of development of PTLD (Odds Ratio = 1.48, confidence interval ranges from 1.04 to 2.11, p = .02) and is associated with higher risk of development of aggressive PTLD (Odds Ratio = 1.83, confidence interval ranges from 1.001 to 3.34, p = .04).Conclusion: We conclude that R-ATG induction is associated with a higher risk of PTLD and its aggressive form (monomorphic PTLD and Hodgkin lymphoma). Careful monitoring for development of PTLD in renal transplant recipients receiving R-ATG induction therapy is advised.

The incidence of cytomegalovirus infection after deceased-donor kidney transplantation from hepatitis-C antibody positive donors to hepatitis-C antibody negative recipients.

BACKGROUND: Deceased-donor kidney transplantation (KT) from hepatitis C (HCV)-infected donors into HCV-uninfected recipients (HCV D+/R-) could become standard care in the near future. However, HCV viral replication by viral transmission might lead to a higher incidence of cytomegalovirus (CMV) infection in these recipients. METHODS: A national-registry-based retrospective cohort study was conducted using the Scientific Registry of Transplant Recipients (SRTR) data set. We assessed the incidence of CMV infection in HCV antibody (Ab) negative recipients receiving kidneys from HCV Ab positive (HCVAb D+/R-) and negative (HCVAb D-/R-) donors. The risk of CMV infection was analyzed by Cox regression analysis in a propensity score (PS) matched-cohort of HCVAb D+/R- (n = 950) versus HCVAb D-/R- (n = 950). Sensitivity analysis was also conducted in the entire cohort (n = 181 082). RESULTS: The mean age at baseline was 54 years, 75% were male, and 55% of the patients were African American in PS-matched cohort. Compared to the HCVAb D-/R - patients, recipients with HCVAb D+/R - showed identical probability for the incidence of CMV infection (Hazard Ratio (HR) = 1.00, 95% Confidence Interval (CI): 0.82-1.22). In the sensitivity analysis, compared to the HCVAb D-/R - patients, the HCVAb D+/R - group had a significantly lower risk of CMV infection in the unadjusted analysis (HR = 0.75, 95%CI: 0.65-0.85), while this risk difference disappeared after the adjusted analysis (HR = 0.99, 95%CI: 0.87-1.14). CONCLUSION: The incidence of CMV infection was similar in recipients who received HCVAb D + and HCVAb D - KT. Further studies are needed to assess this association in KT from HCV nucleic acid positive donors.

Incidence and impact of acute kidney injury on patients with implantable left ventricular assist devices: a Meta-analysis.

Background: We aimed to evaluate the acute kidney injury (AKI) incidence and its associated risk of mortality in patients with implantable left ventricular assist devices (LVAD).Methods: A systematic literature search in Ovid MEDLINE, EMBASE, and Cochrane Databases was conducted through January 2020 to identify studies that provided data on the AKI incidence and AKI-associated mortality risk in adult patients with implantable LVADs. Pooled effect estimates were examined using random-effects, generic inverse variance method of DerSimonian-Laird.Results: Fifty-six cohort studies with 63,663 LVAD patients were enrolled in this meta-analysis. The pooled incidence of reported AKI was 24.9% (95%CI: 20.1%-30.4%) but rose to 36.9% (95%CI: 31.1%-43.1%) when applying the standard definition of AKI per RIFLE, AKIN, and KDIGO criteria. The pooled incidence of severe AKI requiring renal replacement therapy (RRT) was 12.6% (95%CI: 10.5%-15.0%). AKI incidence did not differ significantly between types of LVAD (p = .35) or indication for LVAD use (p = .62). While meta-regression analysis did not demonstrate a significant association between study year and overall AKI incidence (p = .55), the study year was negatively correlated with the incidence of severe AKI requiring RRT (slope = -0.068, p < .001). The pooled odds ratios (ORs) of mortality at 30 days and one year in AKI patients were 3.66 (95% CI, 2.00-6.70) and 2.22 (95% CI, 1.62-3.04), respectively. The pooled ORs of mortality at 30 days and one year in severe AKI patients requiring RRT were 7.52 (95% CI, 4.58-12.33) and 5.41 (95% CI, 3.63-8.06), respectively.Conclusion: We found that more than one-third of LVAD patients develop AKI based on standard definitions, and 13% develop severe AKI requiring RRT. There has been a potential improvement in the incidence of severe AKI requiring RRT for LVAD patients. AKI in LVAD patients was associated with increased 30-day and 1 year mortality.

Therapeutic hypernatremia management during continuous renal replacement therapy with elevated intracranial pressures and respiratory failure.

Cerebral edema and elevated intracranial pressure (ICP) are common complications of acute brain injury. Hypertonic solutions are routinely used in acute brain injury as effective osmotic agents to lower ICP by increasing the extracellular fluid tonicity. Acute kidney injury in a patient with traumatic brain injury and elevated ICP requiring renal replacement therapy represents a significant therapeutic challenge due to an increased risk of cerebral edema associated with intermittent conventional hemodialysis. Therefore, continuous renal replacement therapy (CRRT) has emerged as the preferred modality of therapy in this patient population. We present our current treatment approach, with demonstrative case vignette illustrations, utilizing hypertonic saline protocols (3% sodium-chloride or, with coexisting severe combined metabolic and respiratory acidosis, with 4.2% sodium-bicarbonate) in conjunction with the CRRT platform, to induce controlled hypernatremia of approximately 155 mEq/L in hemodynamically unstable patients with acute kidney injury and elevated ICP due to acute brain injury. Rationale, mechanism of activation, benefits and potential pitfalls of the therapy are reviewed. The impact of hypertonic citrate solution during regional citrate anticoagulation is specifically discussed. Maintaining plasma hypertonicity in the setting of increased ICP and acute kidney injury could prevent the worsening of ICP during renal replacement therapy by minimizing the osmotic gradient across the blood-brain barrier and maximizing cardiovascular stability.

Correction to: Therapeutic hypernatremia management during continuous renal replacement therapy with elevated intracranial pressures and respiratory failure.

The authors would like to report an error in the formula describing the correction factor for the protein content in the serum/plasma.

Benefits, challenges, and opportunities using home hemodialysis with a focus on Mississippi, a rural southern state.

The prevalence of end-stage renal disease continues to increase in the United States with commensurate need for renal replacement therapies. Hemodialysis continues to be the predominant modality, though less than 2% of these patients will receive hemodialysis in their own home. While home modalities utilizing peritoneal dialysis have been growing, home hemodialysis (HHD) remains underutilized despite studies showing regression in left ventricular mass, improved quality of life, reduced depressive symptoms, and decreased postdialysis recovery time. To increase penetration of HHD will require a proactive approach from both physicians and dialysis networks to address barriers both in the system and on the level of the patients and families. We are reviewing these issues with a focus on the state of Mississippi.

Diffuse membranoproliferative glomerulonephritis with focal sclerosis and renal amyloidosis in an adult male with autosomal dominant dystrophic epidermolysis bullosa: a case report.

Previous reports of glomerular disease in adult patients with autosomal dominant dystrophic epidermolysis bullosa (EB) are limited and include post-infectious glomerulonephritis, IgA nephropathy, amyloidosis, and leukocytoclastic vasculitis. To our knowledge, membranoproliferative glomerulonephritis (MPGN) has not been described before. We report a case of a 39-year-old male with autosomal dominant dystrophic EB, presenting with bilateral leg swelling of one-week duration. There was no other significant past medical history. The physical examination was remarkable for scars and erosions over all body areas, with all extremities with blisters and ulcers covered, absent finger and toenails and bilateral lower extremity edema. Serum creatinine was 0.9 mg/dL, albumin 1.3 g/dL and urine protein excretion 3.7 g/24 h. Viral markers (hepatitis-B, C, and HIV), complement c3 and c4 levels and auto-immune antibody profile all remained negative or within normal limits. Renal ultrasound and echocardiogram were normal. Renal biopsy recovered 14 glomeruli, all with proliferation of mesangial and endothelial cells as well as an expansion of the mesangial matrix, focal segmental sclerosis and amorphous homogeneous deposits demonstrating apple-green birefringence under polarized light with Congo red stain. Our observation emphasizes the importance of recognizing MPGN and secondary amyloidosis in patients with EB, especially with the availability of newer treatment modalities.

The association of overhydration with megafistulas in hemodialysis patients.

Objectives: Diffuse enlargements of arteriovenous dialysis fistulas customarily attributed to either excessive arterial inflow or central outflow stenosis. The relationship between volume status and clinically enlarged (arteriovenous) fistula (CEF) formation in end-stage renal disease (ESRD) patients is not well understood. Methods: We assessed the pre-dialysis bioimpedance spectroscopy-measured percentage of overhydration (OH%) in 13 prevalent dialysis patients with CEF development and negative angiography and compared the results with those of 52 control dialysis patients (CONTR). All patients were prevalent ESRD patients receiving thrice-weekly maintenance hemodiafiltration at an academic outpatient dialysis unit. Results: 10/13 CEF patients had OH% ≥15% as compared to 20/52 control patients (Chi square p: .02). The degree of OH% was 20.2 ± 7.4% among the CEF vs. 14.4 ± 7.1% in the control group (Student's t-test p: .01), representing 4.2 ± 3.2 vs. 2.8 ± 1.6 L of excess fluid pre-dialysis (p: .03). Patients with CEF development took an average of 1.7 ± 1.4 vs. 0.8 ± 0.8 (p: .002) antihypertensive medications compared to the CONTR patients, yet their blood pressure was higher: 156/91 vs. 141/78 mmHg (systolic/diastolic p: .03<.0001). We found no difference in fistula vintage, body mass index, age, diabetes status, or diuretic use. The odds ratio of having a CEF in patients with ≥15% OH status was 5.3 (95% CI: 1.3-21.7; p: .01), the Number Needed to Harm with overhydration was 4. Conclusions: There is an association between bioimpedance spectroscopy-measured overhydrated clinical state and the presence of CEF; either as an increased volume capacitance or as a potential cause.

Common variants in DRD2 are associated with sleep duration: the CARe consortium.

Sleep duration is implicated in the etiologies of chronic diseases and premature mortality. However, the genetic basis for sleep duration is poorly defined. We sought to identify novel genetic components influencing sleep duration in a multi-ethnic sample. Meta-analyses were conducted of genetic associations with self-reported, habitual sleep duration from seven Candidate Gene Association Resource (CARe) cohorts of over 25 000 individuals of African, Asian, European and Hispanic American ancestry. All individuals were genotyped for ∼50 000 SNPs from 2000 candidate heart, lung, blood and sleep genes. African-Americans had additional genome-wide genotypes. Four cohorts provided replication. A SNP (rs17601612) in the dopamine D2 receptor gene (DRD2) was significantly associated with sleep duration (P = 9.8 × 10(-7)). Conditional analysis identified a second DRD2 signal with opposite effects on sleep duration. In exploratory analysis, suggestive association was observed for rs17601612 with polysomnographically determined sleep latency (P = 0.002). The lead DRD2 signal was recently identified in a schizophrenia GWAS, and a genetic risk score of 11 additional schizophrenia GWAS loci genotyped on the IBC array was also associated with longer sleep duration (P = 0.03). These findings support a role for DRD2 in influencing sleep duration. Our work motivates future pharmocogenetics research on alerting agents such as caffeine and modafinil that interact with the dopaminergic pathway and further investigation of genetic overlap between sleep and neuro-psychiatric traits.

Aminoglycoside impregnated cement spacer precipitating acute kidney injury requiring hemodialysis.

The current standard of care for prosthetic joint infection includes two-stage arthroplasty, with antibiotic-impregnated cement spacers (ACS) utilized between the stages. We report a 75-year-old woman with previously normal renal function, who developed acute kidney injury (AKI) secondary to biopsy-proven acute tubular necrosis and acute interstitial nephritis after ACS placement containing tobramycin and vancomycin. Peak tobramycin level measured 25.3 mcg/mL, the highest value reported in the literature after ACS placement. Intermittent hemodialysis was initiated with subsequent full recovery of renal function. This paper reviews the published literature regarding the accumulation, toxicity and removal dynamics of aminoglycoside (AG) antibiotics and vancomycin in renal patients. Obtaining serum AG level should be strongly considered in patients experiencing AKI after ACS. Renal replacement therapy may assist in reducing toxic AG levels.