Development of PD in lower-income countries: a rational solution for the management of AKI and ESKD.

It is estimated that >50% of patients with end-stage kidney disease (ESKD) in low-resource countries are unable to access dialysis. When hemodialysis is available, it often has high out-of-pocket expenditure and is seldom delivered to the standard recommended by international guidelines. Hemodialysis is a high-cost intervention with significant negative effects on environmental sustainability, especially in resource-poor countries (the ones most likely to be affected by resultant climate change). This review discusses the rationale for peritoneal dialysis (PD) as a more resource and environmentally efficient treatment with the potential to improve dialysis access, especially to vulnerable populations, including women and children, in lower-resource countries. Successful initiatives such as the Saving Young Lives program have demonstrated the benefit of PD for acute kidney injury. This can then serve as a foundation for later development of PD services for end-stage kidney disease programs in these countries. Expansion of PD programs in resource-poor countries has proven to be challenging for various reasons. It is hoped that if some of these issues can be addressed, PD will be able to permit an expansion of end-stage kidney disease care in these countries.

Symptom Burden and Its Impact on Quality of Life in Patients With Moderate to Severe CKD: The International Chronic Kidney Disease Outcomes and Practice Patterns Study (CKDopps).

RATIONALE & OBJECTIVE: Recent evidence suggests people with nondialysis chronic kidney disease (ND-CKD) experience a substantial burden of symptoms, but informative large-scale studies have been scarce. We assessed the prevalence of symptoms and the association of overall symptom burden with quality of life in patients with moderate to severe CKD. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: 4,430 patients with ND-CKD stages 3-5 enrolled in the Chronic Kidney Disease Outcomes and Practice Patterns Study (CKDopps) in Brazil, France, and the United States between 2013 and 2021. EXPOSURE: 13 individual patient-reported symptoms from the Kidney Disease Quality of Life Short Form (KDQOL-SF) questionnaire and an overall symptom burden score (low, intermediate, and high). OUTCOME: Physical and mental component summary scores (PCS and MCS) of the KDQOL-SF. ANALYTICAL APPROACH: Adjusted prevalence ratios and generalized estimating equations. RESULTS: Patients (mean age, 68 years; 40% women; mean baseline estimated glomerular filtration rate [eGFR], 30mL/min/1.73m2) were very much to extremely bothered by numerous symptoms ("soreness in muscles," 23%; "washed out or drained," 21%; "cramps, shortness of breath, dry skin, diminished sex life, or numbness in hands or feet," 14%-17%). The adjusted prevalences of "cramps," "washed out or drained," "lack of appetite," "nausea/upset stomach," and "sex life" were greater with more severe CKD and in women (except for "sex life"). A high overall symptom burden was more common in women, in France, and in patients with severe albuminuria and various comorbidities, but not with lower eGFR. The PCS and MCS scores were 13.4 and 7.7 points lower, respectively, for high versus low overall symptom burden. LIMITATIONS: Generalizability limited to patients under nephrology care, residual confounding, and inaccurate Brazilian translation of some symptoms. CONCLUSIONS: The high symptom burden observed in this large cohort of ND-CKD patients across 3 diverse countries and its strong association with poorer health-related quality of life should inform clinical management of and clinical research in CKD. PLAIN-LANGUAGE SUMMARY: Little is known about symptoms in patients with non-dialysis-dependent chronic kidney disease (ND-CKD). In the Chronic Kidney Disease Outcomes and Practice Patterns Study, which enrolled 4,430 patients with CKD stages 3-5 in Brazil, France, and the United States, patients most often reported soreness in muscles, feeling washed out or drained, cramps, shortness of breath, dry skin, altered sex life, and numbness in hands or feet. Cramps, feeling washed out or drained, lack of appetite, and nausea were more often reported at lower levels of kidney function. The overall symptom burden was higher in women than men, in French than in Brazilian or US patients, and in those with severe albuminuria. The higher the symptom burden, the lower were the physical and mental health quality of life scores. The high symptom burden observed in this large cohort of ND-CKD patients across 3 diverse countries and its strong association with poorer health-related quality of life should inform clinical management of and clinical research in CKD.

Spiritual well-being and its relationship with patient characteristics and other patient-reported outcomes in peritoneal dialysis patients: Findings from the PDOPPS.

BACKGROUND: Spiritual well-being (SWB), an individual's understanding of the meaning and purpose of life, may help patients with chronic or terminal illnesses cope with their diseases. This study aimed to assess SWB in patients on peritoneal dialysis (PD), as well as its relationship with patient characteristics and patient-reported outcomes (PRO). METHODS: The data were obtained from questionnaires that formed part of the PD Outcomes and Practice Patterns Study (PDOPPS). Measures used in this study were SWB scores derived from the WHO quality of life, spirituality, religiousness and personal beliefs (WHOQOL-SRPB) tool including 32 items from eight facets; physical (PCS) and mental component summary (MCS) scores of the 12-Item Short-Form Health Survey (SF-12), Center of Epidemiologic Studies Depression Scale-10 (CES-D-10) scores, burden of kidney disease scores and functional status scores. RESULTS: Overall, 529 out of 848 participants (62%) completely responded to the questionnaires and were included in the analysis. Over two-thirds of PD patients (70%) had moderate or higher SWB scores. The SWB scores were significantly lower in patients with age >65 years and unemployed status. SWB scores positively correlated with higher PCS, MCS, burden of kidney disease scores and functional status scores, while negatively correlated with depression scores by CES-D-10 scale. Patients who reported significant depressive symptoms (CES-D-10 score ≥ 10) had significantly lower SWB scores. CONCLUSION: Better SWB was significantly associated with better health-related QOL (HRQOL) and the absence of depressive symptoms. SWB may be an essential consideration in the delivery of high-quality PD.

High Oxalate Concentrations Correlate with Increased Risk for Sudden Cardiac Death in Dialysis Patients.

BACKGROUND: The clinical significance of accumulating toxic terminal metabolites such as oxalate in patients with kidney failure is not well understood. METHODS: To evaluate serum oxalate concentrations and risk of all-cause mortality and cardiovascular events in a cohort of patients with kidney failure requiring chronic dialysis, we performed a post-hoc analysis of the randomized German Diabetes Dialysis (4D) Study; this study included 1255 European patients on hemodialysis with diabetes followed-up for a median of 4 years. The results obtained via Cox proportional hazards models were confirmed by competing risk regression and restricted cubic spline modeling in the 4D Study cohort and validated in a separate cohort of 104 US patients on dialysis after a median follow-up of 2.5 years. RESULTS: A total of 1108 patients had baseline oxalate measurements, with a median oxalate concentration of 42.4 µM. During follow-up, 548 patients died, including 139 (25.4%) from sudden cardiac death. A total of 413 patients reached the primary composite cardiovascular end point (cardiac death, nonfatal myocardial infarction, and fatal or nonfatal stroke). Patients in the highest oxalate quartile (≥59.7 µM) had a 40% increased risk for cardiovascular events (adjusted hazard ratio [aHR], 1.40; 95% confidence interval [95% CI], 1.08 to 1.81) and a 62% increased risk of sudden cardiac death (aHR, 1.62; 95% CI, 1.03 to 2.56), compared with those in the lowest quartile (≤29.6 µM). The associations remained when accounting for competing risks and with oxalate as a continuous variable. CONCLUSIONS: Elevated serum oxalate is a novel risk factor for cardiovascular events and sudden cardiac death in patients on dialysis. Further studies are warranted to test whether oxalate-lowering strategies improve cardiovascular mortality in patients on dialysis.

First-in-Human Experience With Peritoneal Direct Sodium Removal Using a Zero-Sodium Solution: A New Candidate Therapy for Volume Overload.

BACKGROUND: Loop diuretics have well-described toxicities, and loss of response to these agents is common. Alternative strategies are needed for the maintenance of euvolemia in heart failure (HF). Nonrenal removal of sodium directly across the peritoneal membrane (direct sodium removal [DSR]) with a sodium-free osmotic solution should result in extraction of large quantities of sodium with limited off-target solute removal. METHODS: This article describes the preclinical development and first-in-human proof of concept for DSR. Sodium-free 10% dextrose was used as the DSR solution. Porcine experiments were conducted to investigate the optimal dwell time, safety, and scalability and to determine the effect of experimental heart failure. In the human study, participants with end-stage renal disease on peritoneal dialysis (PD) underwent randomization and crossover to either a 2-hour dwell with 1 L DSR solution or standard PD solution (Dianeal 4.25% dextrose, Baxter). The primary end point was completion of the 2-hour dwell without significant discomfort or adverse events, and the secondary end point was difference in sodium removal between DSR and standard PD solution. RESULTS: Porcine experiments revealed that 1 L DSR solution removed 4.1±0.4 g sodium in 2 hours with negligible off-target solute removal and overall stable serum electrolytes. Increasing the volume of DSR solution cycled across the peritoneum increased sodium removal and substantially decreased plasma volume (P=0.005). In the setting of experimental heart failure with elevated right atrial pressure, sodium removal was ≈4 times greater than in healthy animals (P<0.001). In the human proof-of-concept study, DSR solution was well tolerated and not associated with significant discomfort or adverse events. Plasma electrolyte concentrations were stable, and off-target solute removal was negligible. Sodium removal was substantially higher with DSR (4.5±0.4 g) compared with standard PD solution (1.0±0.3 g; P<0.0001). CONCLUSIONS: DSR was well tolerated in both animals and human subjects and produced substantially greater sodium removal than standard PD solution. Additional research evaluating the use of DSR as a method to prevent and treat hypervolemia in heart failure is warranted. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03801226.

Recognition and management of community-acquired acute kidney injury in low-resource settings in the ISN 0by25 trial: A multi-country feasibility study.

BACKGROUND: Acute kidney injury (AKI) is increasingly encountered in community settings and contributes to morbidity, mortality, and increased resource utilization worldwide. In low-resource settings, lack of awareness of and limited access to diagnostic and therapeutic interventions likely influence patient management. We evaluated the feasibility of the use of point-of-care (POC) serum creatinine and urine dipstick testing with an education and training program to optimize the identification and management of AKI in the community in 3 low-resource countries. METHODS AND FINDINGS: Patients presenting to healthcare centers (HCCs) from 1 October 2016 to 29 September 2017 in the cities Cochabamba, Bolivia; Dharan, Nepal; and Blantyre, Malawi, were assessed utilizing a symptom-based risk score to identify patients at moderate to high AKI risk. POC testing for serum creatinine and urine dipstick at enrollment were utilized to classify these patients as having chronic kidney disease (CKD), acute kidney disease (AKD), or no kidney disease (NKD). Patients were followed for a maximum of 6 months with repeat POC testing. AKI development was assessed at 7 days, kidney recovery at 1 month, and progression to CKD and mortality at 3 and 6 months. Following an observation phase to establish baseline data, care providers and physicians in the HCCs were trained with a standardized protocol utilizing POC tests to evaluate and manage patients, guided by physicians in referral hospitals connected via mobile digital technology. We evaluated 3,577 patients, and 2,101 were enrolled: 978 in the observation phase and 1,123 in the intervention phase. Due to the high number of patients attending the centers daily, it was not feasible to screen all patients to assess the actual incidence of AKI. Of enrolled patients, 1,825/2,101 (87%) were adults, 1,117/2,101 (53%) were females, 399/2,101 (19%) were from Bolivia, 813/2,101 (39%) were from Malawi, and 889/2,101 (42%) were from Nepal. The age of enrolled patients ranged from 1 month to 96 years, with a mean of 43 years (SD 21) and a median of 43 years (IQR 27-62). Hypertension was the most common comorbidity (418/2,101; 20%). At enrollment, 197/2,101 (9.4%) had CKD, and 1,199/2,101 (57%) had AKD. AKI developed in 30% within 7 days. By 1 month, 268/978 (27%) patients in the observation phase and 203/1,123 (18%) in the intervention phase were lost to follow-up. In the intervention phase, more patients received fluids (observation 714/978 [73%] versus intervention 874/1,123 [78%]; 95% CI 0.63, 0.94; p = 0.012), hospitalization was reduced (observation 578/978 [59%] versus intervention 548/1,123 [49%]; 95% CI 0.55, 0.79; p < 0.001), and admitted patients with severe AKI did not show a significantly lower mortality during follow-up (observation 27/135 [20%] versus intervention 21/178 [11.8%]; 95% CI 0.98, 3.52; p = 0.057). Of 504 patients with kidney function assessed during the 6-month follow-up, de novo CKD arose in 79/484 (16.3%), with no difference between the observation and intervention phase (95% CI 0.91, 2.47; p = 0.101). Overall mortality was 273/2,101 (13%) and was highest in those who had CKD (24/106; 23%), followed by those with AKD (128/760; 17%), AKI (85/628; 14%), and NKD (36/607; 6%). The main limitation of our study was the inability to determine the actual incidence of kidney dysfunction in the health centers as it was not feasible to screen all the patients due to the high numbers seen daily. CONCLUSIONS: This multicenter, non-randomized feasibility study in low-resource settings demonstrates that it is feasible to implement a comprehensive program utilizing POC testing and protocol-based management to improve the recognition and management of AKI and AKD in high-risk patients in primary care.

Serum biomarkers of iron stores are associated with worse physical health-related quality of life in nondialysis-dependent chronic kidney disease patients with or without anemia.

BACKGROUND: Iron deficiency (ID) is a common condition in nondialysis-dependent chronic kidney disease (NDD-CKD) patients that is associated with poorer clinical outcomes. However, the effect of ID on health-related quality of life (HRQoL) in this population is unknown. We analyzed data from a multinational cohort of NDD-CKD Stages 3-5 patients to test the association between transferrin saturation (TSAT) index and ferritin with HRQoL. METHODS: Patients from Brazil (n = 205), France (n = 2015) and the USA (n = 293) in the Chronic Kidney Disease Outcomes and Practice Patterns Study (CKDopps, 2013-2019) were included. We evaluated the association of TSAT and ferritin (and functional and absolute ID, defined as TSAT ≤20% and ferritin ≥300 or <50 ng/mL) on pre-specified HRQoL measures, including the 36-item Kidney Disease Quality of Life physical component summary (PCS) and mental component summary (MCS) as the primary outcomes. Models were adjusted for confounders including hemoglobin (Hb). RESULTS: TSAT ≤15% and ferritin <50 ng/mL and ≥300 ng/mL were associated with worse PCS scores, but not with MCS. Patients with composite TSAT ≤20% and ferritin <50 or ≥300 ng/mL had lower functional status and worse PCS scores than those with a TSAT of 20-30% and ferritin 50-299 ng/mL. Patients with a lower TSAT were less likely to perform intense physical activity. Adjustment for Hb only slightly attenuated the observed effects. CONCLUSIONS: Low TSAT levels, as well as both low TSAT with low ferritin and low TSAT with high ferritin, are associated with worse physical HRQoL in NDD-CKD patients, even after accounting for Hb level. Interventional studies of iron therapy on HRQoL among NDD-CKD individuals are needed to confirm these findings.

Strategic plan for integrated care of patients with kidney failure.

There is a huge gap between the number of patients worldwide requiring versus those actually receiving safe, sustainable, and equitable care for kidney failure. To address this, the International Society of Nephrology coordinated the development of a Strategic Plan for Integrated Care of Patients with Kidney Failure. Implementation of the plan will require engagement of the whole kidney community over the next 5-10 years.

Symptoms of Secondary Hyperparathyroidism in Patients Receiving Maintenance Hemodialysis: A Prospective Cohort Study.

RATIONALE & OBJECTIVE: Although multiple lines of evidence suggest a negative impact of secondary hyperparathyroidism on patients with kidney failure treated by hemodialysis, it is uncertain whether patients can detect associated symptoms. The objective was to determine whether changes in parathyroid hormone (PTH) levels are associated with changes in symptoms within this patient population. STUDY DESIGN: Prospective cohort. SETTING & PARTICIPANTS: 165 adults with hyperparathyroidism secondary to kidney failure diagnosed, a range of dialysis vintages, and receiving regular hemodialysis from a US single-provider organization. EXPOSURE: Change in PTH levels over 24 weeks. OUTCOMES: 19 putative symptoms of secondary hyperparathyroidism measured up to 4 times using a self-administered questionnaire that assessed severity on a 5-level ordinal scale. ANALYTICAL APPROACH: Longitudinal associations between changes in PTH levels and symptom severity were assessed using generalized additive models. RESULTS: The 165 participants studied represented 81% of enrollees (N=204) who had sufficiently complete data for analysis. Mean age was 56 years and 54% were women. Increases in PTH levels over time were associated (P<0.1) with worsening of bone aches and stiffness, joint aches, muscle soreness, overall pain, itchy skin, and tiredness, and the effects were more pronounced with larger changes in PTH levels. LIMITATIONS: Findings may have been influenced by confounding by unmeasured comorbid conditions, concomitant medications, and multiple testing coupled with a P value threshold of 0.10. CONCLUSIONS: In this exploratory study, we observed that among patients with secondary hyperparathyroidism, increases in PTH levels over time were associated with worsening of 1 or more cluster of symptoms. Replication of these findings in other populations is needed before concluding about the magnitude and shape of these associations. If replicated, these findings could inform clinically useful approaches for measuring patient-reported outcomes related to secondary hyperparathyroidism.

Barriers to optimal peritoneal dialysis.

Peritoneal dialysis in the United States is underutilized when compared to the experience in other developed countries. The reasons for this are multifactorial and include government regulatory issues, the priority of dialysis facilities, and education and training of nephrology trainees and patients. The challenges to expanding PD in the United States are discussed and strategies to overcome the barriers are outlined.

Increasing access to integrated ESKD care as part of universal health coverage.

The global nephrology community recognizes the need for a cohesive strategy to address the growing problem of end-stage kidney disease (ESKD). In March 2018, the International Society of Nephrology hosted a summit on integrated ESKD care, including 92 individuals from around the globe with diverse expertise and professional backgrounds. The attendees were from 41 countries, including 16 participants from 11 low- and lower-middle-income countries. The purpose was to develop a strategic plan to improve worldwide access to integrated ESKD care, by identifying and prioritizing key activities across 8 themes: (i) estimates of ESKD burden and treatment coverage, (ii) advocacy, (iii) education and training/workforce, (iv) financing/funding models, (v) ethics, (vi) dialysis, (vii) transplantation, and (viii) conservative care. Action plans with prioritized lists of goals, activities, and key deliverables, and an overarching performance framework were developed for each theme. Examples of these key deliverables include improved data availability, integration of core registry measures and analysis to inform development of health care policy; a framework for advocacy; improved and continued stakeholder engagement; improved workforce training; equitable, efficient, and cost-effective funding models; greater understanding and greater application of ethical principles in practice and policy; definition and application of standards for safe and sustainable dialysis treatment and a set of measurable quality parameters; and integration of dialysis, transplantation, and comprehensive conservative care as ESKD treatment options within the context of overall health priorities. Intended users of the action plans include clinicians, patients and their families, scientists, industry partners, government decision makers, and advocacy organizations. Implementation of this integrated and comprehensive plan is intended to improve quality and access to care and thereby reduce serious health-related suffering of adults and children affected by ESKD worldwide.

Measurement properties of the Short Form-36 (SF-36) and the Functional Assessment of Cancer Therapy - Anemia (FACT-An) in patients with anemia associated with chronic kidney disease.

BACKGROUND: Anemia is a common and debilitating manifestation of chronic kidney disease (CKD). Data from two clinical trials in patients with anemia of CKD were used to assess the measurement properties of the Medical Outcomes Survey Short Form-36 version 2 (hereafter SF-36) and the Functional Assessment of Cancer Therapy-Anemia (FACT-An). The Vitality and Physical functioning domains of the SF-36 and the FACT-An Total, Fatigue and Anemia subscales were identified as domains relevant to CKD-associated anemia. METHODS: A total of 204 patients aged 18-80 years were included in the analyses that included internal consistency (Cronbach's alpha), test-retest reliability (intraclass correlation coefficients [ICCs]), convergent and known-groups validity, responsiveness, and estimates of important change. RESULTS: Both the SF-36 and the FACT-An had strong psychometric properties with high internal consistency (Cronbach's alpha: 0.69-0.93 and 0.79-0.95), and test-retest reliability (ICCs: 0.64-0.83 and 0.72-0.88). Convergent validity, measured by correlation coefficients between similar concepts in SF-36 and FACT-An, ranged from 0.52 to 0.77. Correlations with hemoglobin (Hb) levels were modest at baseline; by Week 9, the correlations with Hb were somewhat higher, r = 0.23 (p < 0.05) for SF-36 Vitality, r = 0.22 (p < 0.05) for FACT-An Total, r = 0.26 (p < 0.001) for FACT-Fatigue and r = 0.22 (p < 0.01) for Anemia. Correlations with Hb at Week 13/17 were r = 0.28 (p < 0.001) for SF-36 Vitality and r = 0.25 (p < 0.05) for Role Physical; FACT-An Total correlation was r = 0.33 (p < 0.0001), Anemia was r = 0.28 (p < 0.001), and Fatigue was r = 0.30 (p < 0.001). The SF-36 domains and Component Summary scores (p < 0.05-p < 0.0001) demonstrated ability to detect change. For the FACT-An, significant differences (p < 0.05-p < 0.0001) were observed between responder and non-responder change scores: important change score estimates ranged from 2 to 4 for Vitality and 2-3 for Physical functioning. Important change scores were also estimated for the FACT-An Total score (6-9), the Anemia (3-5), and Fatigue subscale (2-4). CONCLUSIONS: Both the SF-36 Vitality and Physical function scales and the FACT-An Total, Fatigue and Anemia scales, are reliable and valid measures for assessing health-related quality of life in anemia associated with CKD.

Patients receiving frequent hemodialysis have better health-related quality of life compared to patients receiving conventional hemodialysis.

Most patients with end-stage kidney disease value their health-related quality of life (HRQoL) and want to know how it will be affected by their dialysis modality. We extended the findings of two prior clinical trial reports to estimate the effects of frequent compared to conventional hemodialysis on additional measures of HRQoL. The Daily Trial randomly assigned 245 patients to receive frequent (six times per week) or conventional (three times per week) in-center hemodialysis. The Nocturnal Trial randomly assigned 87 patients to receive frequent nocturnal (six times per week) or conventional (three times per week) home hemodialysis. All patients were on conventional hemodialysis prior to randomization, with an average feeling thermometer score of 70 to 75 (a visual analog scale from 0 to 100 where 100 is perfect health), an average general health scale score of 40 to 47 (a score from 0 to 100 where 100 is perfect health), and an average dialysis session recovery time of 2 to 3 hours. Outcomes are reported as the between-treatment group differences in one-year change in HRQoL measures and analyzed using linear mixed effects models. After one year in the Daily Trial, patients assigned to frequent in-center hemodialysis reported a higher feeling thermometer score, better general health, and a shorter recovery time after a dialysis session compared to standard thrice-weekly dialysis. After one year in the Nocturnal Trial, patients assigned to frequent home hemodialysis also reported a shorter recovery time after a dialysis session, but no statistical difference in their feeling thermometer or general health scores compared to standard home dialysis schedules. Thus, patients receiving day or nocturnal hemodialysis on average recovered approximately one hour earlier from a frequent compared to conventional hemodialysis session. Patients treated in an in-center dialysis facility reported better HRQoL with frequent compared to conventional hemodialysis.

Recognition and management of acute kidney injury in the International Society of Nephrology 0by25 Global Snapshot: a multinational cross-sectional study.

BACKGROUND: Epidemiological data for acute kidney injury are scarce, especially in low-income countries (LICs) and lower-middle-income countries (LMICs). We aimed to assess regional differences in acute kidney injury recognition, management, and outcomes. METHODS: In this multinational cross-sectional study, 322 physicians from 289 centres in 72 countries collected prospective data for paediatric and adult patients with confirmed acute kidney injury in hospital and non-hospital settings who met criteria for acute kidney injury. Signs and symptoms at presentation, comorbidities, risk factors for acute kidney injury, and process-of-care data were obtained at the start of acute kidney injury, and need for dialysis, renal recovery, and mortality recorded at 7 days, and at hospital discharge or death, whichever came earlier. We classified countries into high-income countries (HICs), upper-middle-income countries (UMICs), and combined LICs and LMICs (LLMICs) according to their 2014 gross national income per person. FINDINGS: Between Sept 29 and Dec 7, 2014, data were collected from 4018 patients. 2337 (58%) patients developed community-acquired acute kidney injury, with 889 (80%) of 1118 patients in LLMICs, 815 (51%) of 1594 in UMICs, and 663 (51%) of 1241 in HICs (for HICs vs UMICs p=0.33; p<0.0001 for all other comparisons). Hypotension (1615 [40%] patients) and dehydration (1536 [38%] patients) were the most common causes of acute kidney injury. Dehydration was the most frequent cause of acute kidney injury in LLMICs (526 [46%] of 1153 vs 518 [32%] of 1605 in UMICs vs 492 [39%] of 1260 in HICs) and hypotension in HICs (564 [45%] of 1260 vs 611 [38%%] of 1605 in UMICs vs 440 [38%] of 1153 LLMICs). Mortality at 7 days was 423 (11%) of 3855, and was higher in LLMICs (129 [12%] of 1076) than in HICs (125 [10%] of 1230) and UMICs (169 [11%] of 1549). INTERPRETATION: We identified common aetiological factors across all countries, which might be amenable to a standardised approach for early recognition and treatment of acute kidney injury. Study limitations include a small number of patients from outpatient settings and LICs, potentially under-representing the true burden of acute kidney injury in these areas. Additional strategies are needed to raise awareness of acute kidney injury in community health-care settings, especially in LICs. FUNDING: International Society of Nephrology.

Association between changes in quality of life and mortality in hemodialysis patients: results from the DOPPS.

Background: Cross-sectional health-related quality of life (HR-QOL) measures are associated with mortality in hemodialysis (HD) patients. The impact of changes in HR-QOL on outcomes remains unclear. We describe the association of prior changes in HR-QOL with subsequent mortality among HD patients. Methods: A total of 13 784 patients in the Dialysis Outcomes and Practice Patterns Study had more than one measurement of HR-QOL. The impact of changes between two measurements of the physical (PCS) and mental (MCS) component summary scores of the SF-12 on mortality was estimated with Cox regression. Results: Mean age was 62 years (standard deviation: 14 years); 59% were male and 32% diabetic. Median time between HR-QOL measurements was 12 months [interquartile range (IQR): 11, 14]. Median initial PCS and MCS scores were 37.5 (IQR: 29.4, 46.2) and 46.4 (IQR: 37.2, 54.9); median changes in PCS and MCS scores were -0.2 (IQR: -5.5, 4.7) and -0.1 (IQR: -6.8, 5.9), respectively. The adjusted hazard ratio (HR) for a 5-point decline in HR-QOL score was 1.09 [95% confidence interval (CI): 1.06-1.12] for PCS and 1.05 (95% CI: 1.03-1.08) for MCS. Adjusting for the second QOL score, the change was not associated with mortality: HR = 1.01 (95% CI: 0.98-1.05) for delta PCS and 1.01 (95% CI: 0.98-1.03) for delta MCS. Categorizing the first and second scores as predictors, only the second PCS or MCS score was associated with mortality. Conclusions: In our study, only the most recent HR-QOL score was associated with mortality. Hence, the predictive power of a measurement of HR-QOL is not affected by changes in HR-QOL prior to that measurement; more frequent HR-QOL measurements are needed to improve the prediction of outcomes in HD. Further studies are needed to determine the optimal frequency and appropriate instrument to be used for serial measurements.

Tryptophan and Kynurenine Levels and Its Association With Sleep, Nonphysical Fatigue, and Depression in Chronic Hemodialysis Patients.

OBJECTIVE: Sleep and mood disorders are common in hemodialysis (HD) patients and the pathophysiology is still unclear. Tryptophan (TRP) and its metabolites may play a prominent role in neural pathways related to sleep, fatigue, and depression. Here, we sought to compare the levels of TRP and its metabolites between HD patients and healthy subjects and examine their association with sleep, fatigue, and depression in HD patients. The design was cross-sectional analysis. SUBJECTS: Ninety-nine adult patients on stable thrice weekly HD schedule between September 2011 and March 2014 and 10 healthy controls. INTERVENTION: Venous blood samples were drawn in healthy subjects and immediately before dialysis in chronic HD patients. TRP and kynurenine (KYN) metabolites were measured by high-performance liquid chromatography. The Medical Outcomes Study Sleep Scale, the PROMIS Short form Fatigue, and the Patient Health Questionnaire were administered concurrently. MAIN OUTCOME MEASURE: Sleep, fatigue, and depression as assessed by subjective questionnaire. RESULTS: TRP levels were significantly lower (52.4 ± 15.2 vs. 67.9 ± 3.1 µmol/L; P < .0001) and KYN (3.2 ± 1.2 vs. 1.4 ± 0.1 µmol/L; P < .0001) were significantly higher in the 99 HD patients relative to 10 healthy controls. In HD patients, higher KYN levels were correlated with worse depression and fatigue scores (r2 = 0.23 and 0.21; P ≤ .05, respectively). We found no association between TRP and KYN/TRP ratio with sleep disturbances, fatigue, and depression in HD patients. CONCLUSIONS: Our study indicates disturbed TRP metabolism in HD patients, but low TRP levels were not related with sleep disturbances, depression, and fatigue. In contrast, KYN levels, a metabolite of TRP, were much higher in HD patients compared with controls, and higher KYN associated with depression and fatigue. Further studies exploring the biological and functional consequences of increased TRP catabolism in HD patients are warranted.

Acute Kidney Injury in Low-Resource Settings: Barriers to Diagnosis, Awareness, and Treatment and Strategies to Overcome These Barriers.

Acute kidney injury (AKI) is increasingly recognized as a major health problem worldwide, responsible for an estimated 1.4 million deaths per year. The occurrence of and approach to AKI in low-resource settings (LRS) present special challenges due to often limited health care resources, including insufficient numbers of trained personnel, diagnostic tools, and treatment options. Although the International Society of Nephrology set a goal of eliminating preventable deaths from AKI by 2025, implementation of this program in LRS presents major challenges not only because of the lack of resources, but also because of the lack of awareness of the impact of AKI on patient outcomes, factors that are complicated by the challenge of cognitively dissociating the care of patients with AKI from the care of patients with chronic kidney failure. To better understand how to increase the awareness of AKI and develop strategies to improve the identification and treatment of patients with AKI in LRS, we administered an 18-item web-based questionnaire to physicians actively engaged in providing nephrology care in LRS. A checklist was then developed of meaningful and targeted approaches for implementation, with focus on engaging local and regional stakeholders, developing education programs and appropriate guidelines, enhancing training of health care workers, expanding health care resources, linking with other regional health care projects, and broadening research opportunities.

Intensive Hemodialysis and Health-Related Quality of Life.

Diminished health-related quality of life (HRQoL) is common in dialysis patients and associated with increased risks for morbidity and mortality. Patients may present limitations in both physical and mental HRQoL. Poor physical HRQoL may be defined by limited physical function, role limitations due to physical health, dissatisfaction with physical ability, and impaired mobility. Sleep disorders such as obstructive sleep apnea, restless legs, and fatigue are typical manifestations of poor physical HRQoL in dialysis patients. Poor mental HRQoL may be defined by depressive thinking, lack of positive affect, anxiety, and feelings of social isolation. The prevalence of depression is high in dialysis patients. Intensive hemodialysis (HD) can positively address HRQoL. In 3 randomized clinical trials, relative to conventional HD, intensive HD increased physical and mental component summary scores from the 36-Item Short-Form Health Survey (SF-36), although individual treatment effects of daily nocturnal HD were not statistically significant. In another large prospective study, initiation of short daily HD therapy was followed after 12 months by improvements in all SF-36 domains, sleep quality, and restless legs symptoms. In a small study of nocturnal HD, apnea and hypopnea episodes per hour decreased by almost 70% after conversion from conventional HD. Intensive HD is also associated with a large reduction in postdialysis recovery time. In contrast, 2 randomized clinical trials failed to demonstrate statistically significant effects of intensive HD on the Beck Depression Inventory score despite a significant decrease in Beck Depression Inventory score in the prospective study of short daily HD. Furthermore, intensive HD may not improve objective physical performance and can increase burden on caregivers in the home setting. In conclusion, intensive HD potentially can address both physical and mental aspects of poor HRQoL relative to conventional HD. However, more studies are needed to understand the effects of intensive HD, including specific schedules, on HRQoL.

The effect of frequent hemodialysis on self-reported sleep quality: Frequent Hemodialysis Network Trials.

BACKGROUND: Many patients who receive maintenance hemodialysis experience poor sleep. Uncontrolled studies suggest frequent hemodialysis improves sleep quality, which is a strong motivation for some patients to undertake the treatment. We studied the effects of frequent in-center ('daily') and nocturnal home hemodialysis on self-reported sleep quality in two randomized trials. METHODS: Participants were randomly assigned to frequent (six times per week) or conventional (three times per week) hemodialysis in the Frequent Hemodialysis Network Daily (n = 245) and Nocturnal (n = 87) Trials. We used the Medical Outcomes Study Sleep Problems Index II (SPI II), a validated and reliable instrument in patients with end-stage renal disease, to measure self-reported sleep quality. The SPI II is scored from 0-100, with a higher value indicating poorer quality of sleep. A mean relative decline in SPI II would suggest improved sleep quality. The primary sleep outcome was the change in the SPI II score over 12 months. RESULTS: In the Daily Trial, after adjustment for baseline SPI II, subjects randomized to frequent as compared with conventional in-center hemodialysis experienced a 4.2 [95% confidence interval (CI) 0.4-8.0] point adjusted mean relative decline in SPI II at 4 months and a 2.6 (95% CI -2.3-7.5) point adjusted mean relative decline at 12 months. In the Nocturnal Trial, subjects randomized to frequent nocturnal as compared with conventional home hemodialysis experienced 2.9 (95% CI -3.4-9.3) and 4.5 (95% CI -3.2-12.2) point mean relative declines at Months 4 and 12, respectively. CONCLUSIONS: Although a possible benefit of frequent in-center hemodialysis was observed at 4 months, neither frequent in-center hemodialysis nor home nocturnal hemodialysis demonstrated significant improvements in self-reported sleep quality compared with conventional hemodialysis at 12 months.

We Use Bioincompatible Peritoneal Dialysis Solutions.

Despite advances in peritoneal dialysis (PD) technique and therapy over the last 40 years, PD therapy for end-stage renal disease (ESRD) in the United States remains underutilized. One of the major factors contributing to this underutilization involves concerns about technique failure. More physiologic PD solutions, with a lower concentration of glucose degradation products and a neutral pH, exist and are readily available in Europe, Asia, and Australia. Several benefits of these biocompatible solutions exist over the conventional solutions including a slower decline in residual renal function and better maintenance of urine volumes. There may also be a beneficial effect of the biocompatible solutions in limiting the increase in peritoneal transport that is characteristic of patients maintained on conventional solutions. It should be of concern to the US nephrology community that biocompatible PD solutions are unavailable in the United States.