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Kidney fibrosis constitutes the shared final pathway of nearly all chronic nephropathies, but biomarkers for the non-invasive assessment of kidney fibrosis are currently not available. To address this, we characterize five candidate biomarkers of kidney fibrosis: Cadherin-11 (CDH11), Sparc-related modular calcium binding protein-2 (SMOC2), Pigment epithelium-derived factor (PEDF), Matrix-Gla protein, and Thrombospondin-2. Gene expression profiles in single-cell and single-nucleus RNA-sequencing (sc/snRNA-seq) datasets from rodent models of fibrosis and human chronic kidney disease (CKD) were explored, and Luminex-based assays for each biomarker were developed. Plasma and urine biomarker levels were measured using independent prospective cohorts of CKD: the Boston Kidney Biopsy Cohort, a cohort of individuals with biopsy-confirmed semiquantitative assessment of kidney fibrosis, and the Seattle Kidney Study, a cohort of patients with common forms of CKD. Ordinal logistic regression and Cox proportional hazards regression models were used to test associations of biomarkers with interstitial fibrosis and tubular atrophy and progression to end-stage kidney disease and death, respectively. Sc/snRNA-seq data confirmed cell-specific expression of biomarker genes in fibroblasts. After multivariable adjustment, higher levels of plasma CDH11, SMOC2, and PEDF and urinary CDH11 and PEDF were significantly associated with increasing severity of interstitial fibrosis and tubular atrophy in the Boston Kidney Biopsy Cohort. In both cohorts, higher levels of plasma and urinary SMOC2 and urinary CDH11 were independently associated with progression to end-stage kidney disease. Higher levels of urinary PEDF associated with end-stage kidney disease in the Seattle Kidney Study, with a similar signal in the Boston Kidney Biopsy Cohort, although the latter narrowly missed statistical significance. Thus, we identified CDH11, SMOC2, and PEDF as promising non-invasive biomarkers of kidney fibrosis.

Climate change affects the managed water cycle in terms of drought, water quality and the need to manage flood risk in the urban environment. In Scotland, we already experience environmental events consistent with climate projections. Seasonal temperature and rainfall anomalies have seen droughts and floods in parts of the country, and Scottish Water is focussed on delivering water and wastewater services resilient to more extreme and variable conditions. Working with others and managing our landscapes are vital to climate change adaptation in water catchments and to sustainably drain our cities. Carbon emissions from services are high—water collection, treatment and supply, and the collection, treatment and recycling of wastewater are asset and energy-intensive processes. Scottish Water has committed to deliver net zero emissions across operational and investment activities by 2040 through reducing power consumption, generating renewable electricity, reducing the emission intensity of investment and increasing the carbon stored in its landholdings.

The transition from hunting to herding transformed the cold, arid steppes of Mongolia and Eastern Eurasia into a key social and economic center of the ancient world, but a fragmentary archaeological record limits our understanding of the subsistence base for early pastoral societies in this key region. Organic material preserved in high mountain ice provides rare snapshots into the use of alpine and high altitude zones, which played a central role in the emergence of East Asian pastoralism. Here, we present the results of the first archaeological survey of melting ice margins in the Altai Mountains of western Mongolia, revealing a near-continuous record of more than 3500 years of human activity. Osteology, radiocarbon dating, and collagen fingerprinting analysis of wooden projectiles, animal bone, and other artifacts indicate that big-game hunting and exploitation of alpine ice played a significant role during the emergence of mobile pastoralism in the Altai, and remained a core element of pastoral adaptation into the modern era. Extensive ice melting and loss of wildlife in the study area over recent decades, driven by a warming climate, poaching, and poorly regulated hunting, presents an urgent threat to the future viability of herding lifeways and the archaeological record of hunting in montane zones. Introduction - Mountain zones and the emergence of herding economies in Eastern Eurasia Results - Remote sensing - Pedestrian and horseback survey - Radiocarbon dating and cultural patterns Discussion - Weapon manufacture - Hunting strategies and butchery - Ritual activity - Other cultural activities - Role of mountain zones in emerging pastoral societies - Implications of climate change and poaching Conclusion Methods

This paper discusses a unique introduction of modular screens into the design of a deep water horizontal open hole injector completion offshore Nigeria and describes the complete quality assurance/quality control (QA/QC) and operational procedures of the first global deployment of modular screens with sliding sleeves. The Egina field, initially designed without a provision for mechanical or hydraulic isolation of panels, provided an opportunity to introduce a means of accomplishing isolation with modular screens and mechanical actuated sliding sleeves. This application provides the operator with the ability to (1) selectively inject into different intervals using mechanical intervention and (2) address erosion concerns on a high rate water injector without compromising the current upper completion (UC) and existing wellhead design. The paper details the successful installation, excellent completion equipment functionality, and well results. The operator's geosciences team targeted two separate reservoir panels in the Egina field for water injection. However, commingled injection into both panels would result in an early water breakthrough at one of the supported producers, causing a large loss in oil recovery. The current design for Egina does not provide a means of temporarily isolating the heel section while allowing communication into the toe during injection. Rather than drilling two separate water injectors at significantly higher costs, the completion team identified a solution combining the two targets into a single well while maintaining the ability to temporarily access, isolate, or isolate one interval. The team introduced a viable means to selectively inject by adding modular screens with integral sliding sleeves. The revised completion design used existing materials applied on earlier completions, which maintained complete compatibility with the UC and the existing wellhead configuration. Modular screens have long been used in cased hole gravel pack applications where multi-zone selectivity has been necessary. Applying this technology to a horizontal open hole scenario allowed the team to selectively inject into one interval and then return later to subsequently inject into the next interval using sliding sleeves. Injection rates vary based upon the number of sliding sleeves opened or closed. The subject well was run with a modified lower completion (LC) incorporating modular screens in the upper interval and standard wire-wrapped screens in the lower interval with a swell packer providing isolation of the two. This modified completion design allows for an adjustable rate for either individual or commingled injection through a mechanical intervention, and it provides a completion that can be deployed and installed in an efficient manner without any operational issues. Successful installation and injectivity testing have proven the completion concept, and have helped in providing a technical solution allowing the operator to recover the 3-Mbbl oil stake associated with water injection into the upper interval. The sliding sleeves incorporated into the system were manipulated opened and closed with no issues, and injectivity tests were performed with excellent results.

Providing optimal end-stage kidney disease (ESKD) management requires an adequately trained and sufficiently staffed workforce, including doctors, nurses, and patient care technicians (PCTs). The growing need for ESKD services for a surging population of dialysis-dependent patients has made obvious a workforce crisis affecting nephrology. For a multitude of reasons, the physician workforce supply available to provide dialysis care has failed to expand commensurate with patients need in recent years. Of most importance, fewer US trainees are choosing to enter nephrology, and fewer international medical graduates are available to fill training program rosters. Equally important but less frequently cited are occupational shortages of trained dialysis nurses and PCTs. This article brings attention to this complex workforce shortage and addresses the limited information available regarding how it might constitute a barrier to optimal dialysis care.

Background Combination therapy with isosorbide dinitrate (ISD) and hydralazine (HY) reduces heart failure mortality. The safety and tolerability in individuals requiring maintenance hemodialysis (HD) is unknown. Methods Single-center, randomized, placebo-controlled, double-blind pilot trial to explore safety and tolerability of ISD/HY in maintenance HD. Participants were randomized to placebo or combination ISD/HY. Dose was escalated over 3 weeks from ISD 10 mg/HY 10 mg to ISD 40 mg/HY 75 mg three times per day with the maximum tolerated dose maintained for the subsequent 21 weeks. Primary endpoints included adverse events, adverse events precluding further treatment with study medication, serious hypotension (i.e., requiring hospitalization or emergency room visit), and recurrent intra-dialytic hypotension. Efficacy signals included change in mitral annular E’ velocity by tissue Doppler echocardiography and change in left ventricular coronary flow reserve on positron emission tomography. Results A total of 17 individuals were randomized to ISD/HY (N=7) or placebo (N=10). All participants assigned to ISD/HY completed dose escalation to 40/75 mg, but dose reductions were required in two participants. No participants discontinued therapy. There were no serious hypotension events. Recurrent intradialytic hypotension was less frequent with ISD/HY (0.47 events/patient-year) than placebo (1.83 events/patient-year, P=0.04). In contrast, nausea (ISD/HY, 1.90 events/patient-year; placebo, 0.50 events/patient-year, P=0.03) was significantly more frequent, and headache and diarrhea were numerically but not significantly more frequent with ISD/HY. Adverse events were more frequent with ISD/HY (11.4 events/patient-year) than placebo (6.31 events/patient-year). We did not detect between-group differences in the change in E’ (P=0.34); ISD/HY showed a mean increase of 0.6 cm/s (SD 1.1), and placebo showed a mean decrease of 0.04 cm/s (SD 0.9). Changes in coronary flow reserve were minimal, −0.3 (0.2) with ISD/HY and −0.03 (0.5) in the placebo group, P=0.19. Conclusions ISD/HY appears to be well tolerated in patients being treated with maintenance HD, but headache and gastrointestinal side effects occur more frequently with ISD/HY compared with placebo.

Hybrid breeding in wheat has the potential to boost yields. An efficient hybrid seed production system requires elite pollinators; however, such germplasm is limited among modern cultivars. Piko, a winter wheat (Triticum aestivum L.) cultivar, has been identified as a superior pollinator and has been used in Europe. Piko has favourable pollinator traits for anther extrusion, anther length, pollen mass and hybrid seed set. However, the genetic factors responsible for Piko’s favourable traits are largely unknown. Here, we report on the genetic analysis of a Piko-derived F2 mapping population. We confirmed that Piko’s Rht-D1a allele for tall stature is associated with large anthers and high anther extrusion. However, Rht-D1 was not found to be associated with anther filament length, confirmed by near isogenic lines. Piko’s photoperiod sensitive Ppd-B1b allele shows an association with increased spike length, more spikelets and spike architecture traits, while the insensitive Ppd-B1a allele is linked with high anther extrusion and larger anthers. We identified an anther extrusion quantitative trait locus (QTL) on chromosome 6A that showed significantly biased transmission of the favourable Piko allele amongst F2 progenies. The Piko allele is completely absent in the distal 6AS region and the central 6A region revealed a significantly lower ratio (

Although control of chronic glycemia in the population with diabetes and end-stage renal disease (ESRD) has been extensively studied in recent years, the unique problems of short-term glycemic management in acutely ill patients undergoing dialysis have received little attention. Bally et al. evaluated the role of a "closed-loop" (glucose sensor/algorithm tablet device/insulin pump) system in a cohort of hospitalized patients with type 2 diabetes receiving hemodialysis. Compared with usual care, the intervention group had superior glycemic control without increased hypoglycemic events. Additional studies are warranted.

A major operator manages multiple, multi-well deep water projects in West Africa. For two such projects in Congo and Nigeria, it was determined that sand control was necessary and a standalone screen (SAS) completion was an efficient and cost-effective means for providing sand control for the majority of wells in both projects. This paper describes a new and unique feature of the SAS completion, called the Dual Isolation Assembly (DIA) that addresses many challenges and its application in Nigeria on the Egina Project. Standard SAS completions incorporate a circulation path down the workstring, through the float shoe, and back to surface through the work string by casing annulus for circulation, pressure maintenance, and removal of the filter cake at the operation's conclusion. The capability to wash down through the toe of the system while running in the well requires washpipe seals inside the float shoe, which incorporates spring-loaded valves that open during pumping but close when pumping stops. In addition to the wash-down capability, the washpipe incorporates a shifter for closing an uphole isolation valve with the ability to reopen the valve, if necessary. For an injector well, the flow path into the formation is through the sand control screens and float shoe from the inside. The path is the opposite for a producer well, which flows from the formation to inside the screen while the float shoe is closed. Because of the different natures of the flow paths, the float shoe is continuously exercised in an injector well as a result of injection fluid starts and stops. During injection, if the opening pressure of the float shoe spring is exceeded, it could stay open over time, causing loss of integrity of the float shoe. When pumping stops, the flow path into the screen through the float shoe could heave formation particles back into the wellbore as a result of the reservoir being energized upon injection shutdown. The DIA provides secondary and permanent isolation of the float shoe, as requested by the operator, and is capable of shifting a barrier isolation valve installed in the lower completion to comply with the operator's barrier policy for deepwater wells. The DIA and lower completion design allows the operator to safely place a filter-cake breaker treatment in the openhole after setting a lower completion packer. In addition to fulfilling the requirements of these SAS completions, the DIA design addresses other potential challenges, such as hydraulic locks and any potential swabbing while manipulating the service tools. This paper describes the evolution of the DIA design and full quality assurance/quality control (QA/QC) and operational procedures, which led to the successful deployment and excellent functionality of the DIA in 12 completions run to date in Nigeria.

A major operator with two large projects in Africa has been using a unique subassembly design, called the dual-isolation assembly (DIA), positioned on the bottom or toe of an open hole stand-alone screen (SAS) completion. The main objective of the DIA is to enhance the circulation process for washdown capabilities and provide efficient management and removal of the filter cake for the subsequent improvement of injectivity rates by lowering formation skin values on the injector wells. After providing high-rate washdown through the float shoe at the toe of the completion, the DIA provides a means of circulating a filter cake removal treatment for the open hole. Once the filter cake treatment has been circulated sufficiently, the service tools are retrieved from the completion to surface. For an injector well, the flow path into the formation would be through the sand-control screens and the float shoe from the inside. Since the float shoe incorporates spring-loaded valves that would normally open during injection and close when pumping stops, it is beneficial to lock the valves out of service to prevent long term spring fatigue that could cause the valves to remain open at some point during the life of the well, allowing flow back of formation material inside the screens. After treatment of the open hole, an additional function of the DIA is to close the barrier isolation valve to isolate the formation while the filter cake treatment is activating. As a continuation of an earlier paper (Roane, et al. 2018), the DIA has met all expectations on all 19 wells where it has been implemented in Africa. Due to enhanced procedures, the mechanical skins have averaged 2.5 and injectivity indices have averaged above 140 (B/D/psi) on these wells. Installation times have continually improved during the project due to following best practices. In addition to fulfilling the requirements of these standalone screen (SAS) completions, the DIA design addresses other potential challenges, such as the prevention of hydraulic locks and formation swabbing, which can be detrimental and problematic to open hole completions. Other characteristics of the DIA that benefit open hole management were realized during the course of the project, such as the capability of the DIA to wash through the interior of the isolation barrier valve prior to closing the valve. Once closed, the valve can be re-opened and re-closed as required. An important aspect of the physical attributes of the DIA that benefits logistics and running speed of the completion is its compact design allowing it to be completely assembled in the shop and shipped to location, such that it is a single pickup and makeup on the rig floor. This benefit has been exhibited by continual improvement in completion installation times throughout the project.

The Egina project has delivered best-in-class upper and lower completions, utilizing deep water completion experiences, global best practices, and lessons learned using a "factory" approach providing robust completion processes. Continuous improvement throughout the completion process was achieved through process optimization practices that contributed to the overall success of the project. Lower completion (LC) times have been reduced by 60 % between the first and 26th well, while reducing upper completion (UC) times by 40 % for the same wells. Well construction durations, including drilling and completion, currently averages 24 days per well, with lower and upper completion operating efficiencies (OE), and run reliabilities (RR), exceeding 98 %. Mechanical skins average approximately 2.5, while productivity/injectivity indices recorded 26 wells, during initial flowback and injection testing, average around 150 B/D/psi (325 m3/D/bar). Standardized completion designs identified the fundamental process tasks and estimated cycle times associated with those tasks. A disciplined process approach was maintained to help minimize potential risks—by using Failure Mode, Effects, and Criticality Analysis (FMECA) and Failure Risk Analysis (FRA)—during all stages of the project, anticipating requirements and potential issues. Implementation of lessons learned from previous deep water operations during the project was fundamental to design optimization and the allocation of local resources. Following in the spirit of a "factory" approach in executing the completions, all times for tasks and subtasks were captured from the onset of project inception, allowing the project team to establish benchmark task times, while demonstrating continuous improvement throughout the project. The project has delivered best-in-class completions, leveraging deep water completion experiences and referencing global best practices and lessons learned. Fundamental tasks for both the lower and upper completions were identified as the areas where the most significant efficiency improvements could be gained. The team developed a data tracking process to help ensure tasks and subtasks were monitored during the completion process, allowing the project to establish best practices. Statistical analysis of lower and upper completion tasks and subtasks was constantly monitored, with results communicated to the team. Since project kickoff, lower completion run rates have been reduced by 60 % between the first and 26th well, while reducing upper completion rates by 40 %. Well construction durations currently average 24 days per well, and lower and upper completion operating efficiencies and run reliabilities exceed 98 %. The project established Key Performance Indicators (KPIs) for fundamental tasks monitored during the completion process, establishing benchmark metrics for each while monitoring continuous improvement. Reviews of these tasks within the completion process for completed wells have helped identify the improvement of best practices and lessons learned, at the task and subtask level, which have been applied to future completion activities in Nigeria and additionally shared within the operator’s global deep water operations.

Recent technological advances have led to the development of small wearable microelectronic sensors (accelerometers) that detect motion, gravitational acceleration, and velocity with six degrees of freedom (forward-backward, updown, and side-to-side plus rotational vectors). We have used these motion sensors to create new analytical tools called biokinetographs (BKGs). BKGs allow for more precise screening, diagnosing, monitoring, assessment and predicting of function of elderly people as they ambulate using sophisticated analysis of the unique electronic motion signature of each person. Remarkable visual differences in “functional walking signatures” are evident on the BKGs between fallers and non-fallers. This presentation will summarize our current efforts to translate this new technology into novel clinical and research tools for improving function, reducing injurious falls, and diagnosing orthopedic and neurological conditions for elderly people.

The ESRD program provides medical care to a diverse and medically complex patient population. The care for the ESRD patient population has become increasingly benchmarked with process of care measures. These measures include dialysis adequacy, anemia, nutrition, and vascular access outcomes. These process-related dialysis measures may not improve the care of the individual patient as care relates to the individual's goals and values. There is also evidence that these process measures may not be causally related to quality of life, hospitalization, and survival. The adoption of patient-reported outcomes may shift the balance toward more patient-centered care. However, the extent to which mandated measures of health-related quality of life and patient satisfaction result in improved outcomes remains unclear.

Motivated by issues in detonation stability, we study existence of block-diagonalizing transformations for ordinary differential semiclassical limit problems arising in the study of high-frequency eigenvalue problems. Our main results (i) establish existence of block-diagonalizing transformations in a neighborhood of infinity for analytic-coefficient ordinary differential equations (ODEs), and (ii) establish by a series of counterexamples sharpness of our hypotheses and conclusions on the existence of block-diagonalizing transformations near a finite point. In particular, we show that, in general, bounded transformations exist only locally, answering a question posed by Wasow in the 1980s, and, under the minimal condition of spectral separation, for ODEs with analytic rather than $C^\infty$ coefficients. The latter issue is connected with quantitative comparisons of $C^\omega$ versus $C^\infty$ stationary phase estimates.

The validity of hemoglobin A1c (HgbA1c) is undergoing increasing scrutiny in the advanced CKD/ESRD (chronic kidney disease/end-stage renal disease) population, where it appears to be discordant from other glycemic indices. In the Glycemic Indices in Dialysis Evaluation (GIDE) Study, we sought to assess correlation of HgbA1c with casual glucose, glycated albumin, and serum fructosamine in a large group of diabetic patients on dialysis. From 26 dialysis facilities in the United States, 1758 diabetic patients (hemodialysis = 1476, peritoneal dialysis = 282) were enrolled in the first quarter of 2013. The distributions of HgbA1c and the other glycemic indices were analyzed. Intra-patient coefficients of variation and correlations among the four glycemic indices were determined. Patients with low HgbA1c values were both on higher erythropoietin (ESA) doses and more anemic. Serum glucose exhibited the highest intra-patient variability over a 3-month period; variability was modest among the other glycemic indices, and least with HgbA1c. Statistical analyses inclusive of all glycemic markers indicated modest to strong correlations. HgbA1c was more likely to be in the target range than glycated albumin or serum fructosamine, suggesting factors which may or may not be directly related to glycemic control, including anemia, ESA management, and iron administration, in interpreting HgbA1c values. These initial results from the GIDE Study clarify laboratory correlations among glycemic indices and add to concerns about reliance on HgbA1c in patients with diabetes and advanced kidney disease.

STRIDER: Semi-Autonomous Tracking Robot with Instrumentation for Data-Acquisition and Environmental Research, a semi-autonomous aquatic vessel, was envisioned for automated water sampling, data collection, and depth profiling to document water quality variables related to agricultural run-offs. Phase-I of the STRIDER project included the capability for STRIDER to collect water samples and water quality data on the surface of water bodies. This paper discusses the Phase-II efforts of the project, in which the previous design of STRIDER was adapted to extend its capabilities to include monitoring, depth profiling, and visualization of in-situ water quality data at various depths as well as collect water samples at each depth for bacterial analysis. At present, the vessel has been utilized for navigation to specified locations using remote control for collecting water quality data and water samples from the surface, as well as 2 feet and 4 feet below the surface at multiple UMES ponds. In a series of preliminary trial runs with the supervision of UMES faculty members and collaborators from the United States Department of Agriculture (USDA), STRIDER successfully collected 48 water samples for bacterial analysis at different locations and depths of ponds on the UMES campus. Design alternatives are being explored for more efficient water sampling capabilities.

The management of hyperglycemia in patients with kidney failure is complex, and the goals and methods regarding glycemic control in chronic kidney disease (CKD) are not clearly defined. Although aggressive glycemic control seems to be advantageous in early diabetic nephropathy, outcome data supporting tight glycemic control in patients with advanced CKD (including end-stage renal disease [ESRD]) are lacking. Challenges in the management of such patients include therapeutic inertia, monitoring difficulties, and the complexity of available treatments. In this article, we review the alterations in glucose homeostasis that occur in kidney failure, current views on the value of glycemic control and issues with its determination, and more recent approaches to monitor or measure glycemic control. Hypoglycemia and treatment options for patients with diabetes and ESRD or earlier stages of CKD also are addressed, discussing the insulin and noninsulin agents that currently are available, along with their indications and contraindications. The article provides information to help clinicians in decision making in order to provide individualized glycemic goals and appropriate therapy for patients with ESRD or earlier stages of CKD.

While hyperglycemia is central to the pathogenesis and management of diabetes mellitus, hypoglycemia and glucose variability also contribute to outcomes. We previously reported on the relationship of glycemic control to outcomes in a large population of diabetic end-stage renal disease (ESRD) patients. Recognizing that ESRD is a risk factor for severe hypoglycemia, we have now analyzed the association between glycosylated hemoglobin A1c (HgbA1c) levels and glycemic variability in those with hypoglycemia. This is a retrospective study of patients with diabetes enrolled in a large hemodialysis program. Hypoglycemia was identified from hospital discharge diagnostic codes. Glycemic variability was assessed by the standard deviation of HgbA1c and glucose levels over time. Hypoglycemia as a discharge diagnosis was documented in 4.1% of patients. Higher baseline HgbA1c was associated with greater risk for hypoglycemia hospitalization, a finding confirmed by time-lagged HgbA1c levels drawn a quarter earlier. Higher baseline HgbA1c categories were also associated with greater variability in HgbA1c levels during the analysis period. Similarly, greater glucose variability was associated with higher mean glucose levels by trend analysis. High, not low, HgbA1c levels are associated with greater risk of severe hypoglycemia, which may derive from glucose variability in the setting of treatment for hyperglycemia. High HgbA1c and glycemic variability are associated with increased risk of hypoglycemia in individuals with diabetes and ESRD.

Hyperglycemia management in chronic kidney disease (CKD) patients presents difficult challenges, partly due to the complexity involved in treating these patients, and partly due to lack of data supporting benefits of tight glycemic control. While hyperglycemia is central to the pathogenesis and management of diabetes, hypoglycemia and glucose variability also contribute to outcomes. Multiple agents with different mechanisms of action are now available; some can lower glucose levels without the risk of hypoglycemia. This article reviews metabolic changes present in kidney impairment/failure, current views about glycemic goals, and treatment options for the diabetic patient with CKD.

Dialysis should not be presumed to be the treatment of choice for all elderly chronic kidney disease stage 5 patients. Nondialysis active medical management, as an alternative to dialysis or palliative care, is a reasonable alternative in select cases. Early referral of CKD 5 elderly patients may lead to early initiation of dialysis, which may not be advantageous; it also provides an opportunity to institute active management as a treatment alternative. The informed decision to proceed with dialysis must involve both an assessment of evidence-based outcomes applicable to the patient, and allowance of patient preference. Prognostic tools are increasingly sought to aid in decision-making for elderly CKD 5 patients. Chronological age alone is not a sufficient predictor of benefit from dialysis treatments, according to observational studies and limited clinical trial data. The survival advantage of dialysis appears to be lost in patients with high levels of comorbidity. Establishing patient preference is an imperfect process, and many patients appear to regret their decision to undergo dialysis. With active medical management, efforts shift from prolonging life to emphasis on symptom control, dietary and medical treatment, and quality of life. Patient survival time can be remarkably long.

The disproportionate increase in the prevalence of chronic kidney disease (CKD) and end-stage renal disease (ESRD) in the elderly is now recognized as a national and global reality. Among the major contributing factors are the aging of the population, a growing prevalence of CKD, greater access to care, and increased comorbidities. The utilization of renal replacement therapy in the geriatric population has concomitantly increased. It is imposing enormous challenges to the practice of ESRD care, the largest of which may be to determine the best application of clinical performance targets to a population with limitations in life expectancy. Concurrently, increased focus on quality of life will be required. The effective dialysis practitioner will need to adapt to the aging ESRD demographics with an increased focus on physical and mental well-being of the geriatric patient.

Background. Patient groups associated with disparities in health care are usually defined on the basis of race, gender or geographic location. Social Adaptability Index (SAI), calculated based on education, marital status, income, employment and substance abuse, has been strongly associated with clinical outcome in other patient populations and may be used to identify individuals at risk. We used data from the United States Renal Data System to evaluate the role of SAI in survival of patients on dialysis. Methods. We used Cox model analyses to study the association between SAI and patient survival in patients with ESRD on dialysis, as well as in the subgroups based on age, race, sex, comorbidites and diabetic status. Results. We analyzed 3396 patients (age of ESRD onset 56.9 6 16.1 years, 54.2% males, 64.2% white, 30.3% African-American). Mean SAI of the entire population was 7.1 6 2.5 (range 0–12 points). SAI was higher in whites (7.4 6 2.4) than in African-Americans (6.5 6 2.5) (analysis of variance, P

Background and objectives: The benefits and risks of aggressive glycemic control in diabetes mellitus complicated by end-stage kidney failure remain uncertain but have importance because of the large patient population with inferior overall prognosis. Recent large observational studies with differing methodologies reached somewhat contrasting conclusions regarding the association of hemoglobin A1c with survival in diabetic chronic hemodialysis patients. Design, setting, participants, & measurements: This study supplements the authors' previous analysis (which found no correlation) by extending the follow-up period to 3 years and using time-dependent survival models with repeated measures. Among 24,875 nationally distributed study patients, 94.5% had type 2 diabetes, allowing additional analysis in the subset with type 1 diabetes. Data were collected at baseline and every quarter to a maximum of 3 years' follow-up. Results: Adjusted standard and time-dependent Cox models indicated that only extremes of glycemia were associated with inferior survival. There was no effect modification by serum albumin levels, a marker of protein nutrition status, and no trend associated with random glucose measurements in a post hoc analysis. In type 1 diabetic patients, upper extreme hemoglobin A1c values indicated lower survival risk. Conclusions: Sustained extremes of glycemia were only variably and weakly associated with decreased survival in this population. In the absence of randomized, controlled trials, these results suggest that aggressive glycemic control cannot be routinely recommended for all diabetic hemodialysis patients on the basis of reducing mortality risk. Physicians are encouraged to individualize glycemic targets based on potential risks and benefits in diabetic ESRD patients.

Background and objectives: This report summarizes the first phase 1 trial treating patients with microalbuminuric diabetic kidney disease (DKD) using FG-3019, a human monoclonal antibody to connective tissue growth factor (CTGF). CTGF is critically involved in processes of progressive fibrosis, including DKD. This phase 1, open-label, dose-escalation trial evaluated safety, pharmacokinetics, and possible therapeutic effects of FG-3019 on albuminuria, proteinuria, and tubular proteins. Design, setting, participants, and measurements: Microalbuminuric subjects (n = 24) with type 2 (79%) or type 1 (21%) diabetes received 3 or 10 mg/kg FG-3019 dosed intravenously every 14 days for four doses. Albuminuria and safety follow-up were to days 62 and 365, respectively. Results: No infusion was interrupted for symptoms, although 5 of 24 subjects had mild infusion-day adverse events thought to be possibly drug-related. No subject developed anti-FG-3019 antibodies. FG-3019 clearance was lower at 10 mg/kg than at 3 mg/kg, suggesting a saturable elimination pathway. Although this study was not designed for efficacy testing, it was notable that urinary albumin/creatinine ratio (ACR) decreased significantly from mean pretreatment ACR of 48 mg/g to mean post-treatment (day 56) ACR of 20 mg/g (P = 0.027) without evidence for a dose-response relationship. Conclusions: Treatment of microalbuminuric DKD subjects using FG-3019 was well tolerated and associated with a decrease in albuminuria. The data demonstrate a saturable pathway for drug elimination, minimal infusion adverse events, and no significant drug-attributable adverse effects over the year of follow-up. Changes in albuminuria were promising but require validation in a prospective, randomized, blinded study.