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.

The Predialysis Serum Sodium Level Modifies the Effect of Hemodialysis Frequency on Left-Ventricular Mass: The Frequent Hemodialysis Network Trials.

INTRODUCTION: The Frequent Hemodialysis Network (FHN) Daily and Nocturnal trials aimed to compare the effects of hemodialysis (HD) given 6 versus 3 times per week. More frequent in-center HD significantly reduced left-ventricular mass (LVM), with more pronounced effects in patients with low urine volumes. In this study, we aimed to explore another potential effect modifier: the predialysis serum sodium (SNa) and related proxies of plasma tonicity. METHODS: Using data from the FHN Daily and Nocturnal Trials, we compared the effects of frequent HD on LVM among patients stratified by SNa, dialysate-to-predialysis serum-sodium gradient (GNa), systolic and diastolic blood pressure, time-integrated sodium-adjusted fluid load (TIFL), and extracellular fluid volume estimated by bioelectrical impedance analysis. RESULTS: In 197 enrolled subjects in the FHN Daily Trial, the treatment effect of frequent HD on ∆LVM was modified by SNa. When the FHN Daily Trial participants are divided into lower and higher predialysis SNa groups (less and greater than 138 mEq/L), the LVM reduction in the lower group was substantially higher (-28.0 [95% CI -40.5 to -15.4] g) than in the higher predialysis SNa group (-2.0 [95% CI -15.5 to 11.5] g). Accounting for GNa, TIFL also showed more pronounced effects among patients with higher GNa or higher TIFL. Results in the Nocturnal Trial were similar in direction and magnitude but did not reach statistical significance. DISCUSSION/CONCLUSION: In the FHN Daily Trial, the favorable effects of frequent HD on left-ventricular hypertrophy were more pronounced among patients with lower predialysis SNa and higher GNa and TIFL. Whether these metrics can be used to identify patients most likely to benefit from frequent HD or other dialytic or nondialytic interventions remains to be determined. Prospective, adequately powered studies studying the effect of GNa reduction on mortality and hospitalization are needed.

[HYPERTENSION AMONG HEMODIALYSIS PATIENTS, NOT NECESSARILY HYPERVOLEMIA].

BACKGROUND: Hypertension in dialysis patients is common. In daily practice, it is not always clear whether adjustment of dry weight or vasodilatory medication should be administered and treatment strategy is often based on clinical impression. We used a whole-body bio-impedance based, non-invasive, hemodynamics monitoring technology to acquire hemodynamic data in order to evaluate the incidence and causes of hypertension in dialysis patients. METHODS: Novel noninvasive impedance based technique was used to collect hemodynamic data from patients undergoing chronic hemodialysis in four different dialysis units. Patients were defined as having hypertension if their predialysis systolic or diastolic BP results were >140mmHg or >90 respectively and as hypervolemic if their total body water (TBW) was greater than normal according to the Kushner formula+1SD. Vasoconstriction was defined as total peripheral resistance index (TPRI) greater than 3000 dyn*sec/cm5*m2. RESULTS: Of 144 hemodialysis patients, 81 (56%) were male; mean age was 67.3±12.1 years and 67 (47%) had hypertension. Among the hypertensive patients, only 18(27%) met hypervolemia criteria and thirty (45%) met vasoconstriction criteria (mean TPRI of 4474±1592dyn*sec/cm5*m2). Patients with hypertension due to vasoconstriction had higher vintage (50±45 vs 20±8 months 0=0.018), lower heart rate (71±11 vs 79±11 BPM p=0.002), lower stroke index (28±7 vs 44±8ml/m2 p<0.001) and cardiac index (2.1±0.5 vs 3.5±0.6 p=0<0.001) compared to patients without vasoconstriction. CONCLUSIONS: Vasoconstriction was the main etiology for pre-dialysis hypertension in chronic hemodialysis patients. This calls for individualized, hemodynamic-based therapeutic intervention.

Diagnosis of Acute Kidney Injury in Children Hospitalized in a Sub-Saharan African Unit by Saliva Urea Nitrogen Dipstick Test.

INTRODUCTION: Acute kidney injury in pediatric patients (pAKI) is common in developing countries and leads to significant morbidity and mortality. Most nephrology services in developing countries are only in larger cities and for that reason many cases remain undiagnosed. We evaluated the performance of a saliva urea nitrogen (SUN) dipstick to diagnose pAKI in Sudan. METHODS: We collected demographic and clinical information, serum creatinine (SCr), blood urea nitrogen (BUN), SUN, and urine output (UO) in children with pAKI. pAKI was diagnosed based on different criteria (Risk, Injury, Failure, Loss of kidney function, and end-stage kidney disease, Acute Kidney Injury Network and Kidney Disease Improving Global Outcomes). We also recorded hospital and 3-months' mortality and progression to chronic kidney disease (CKD) as outcomes. RESULTS: We studied 81 patients (mean age 10.7 ± 7 years, 51.9% females) and divided them by age into (a) neonates (<120 days; n = 21; 25.9%); (b) -infants (120-365 days; n = 18; 25.9%); and (c) children (>365 days; n = 42; 53.1%). Diagnosis using different pAKI definitions resulted in differences in AKI staging. SUN reliably reflected BUN over the entire study period, regardless of treatment modality or pAKI severity. Neither pAKI staging, SUN, BUN, nor SCr were associated with mortality or progression to CKD. UO predicted all-cause mortality during the 3-months follow-up. CONCLUSION: Diagnosis of pAKI using different criteria differs in triage and staging. SUN reflects BUN particularly at higher BUN levels and allows monitoring of treatment responses. Despite the lack of predictive power of SUN to predict hard outcomes, measurement of SUN by dipstick can be used to identify, screen, and monitor pediatric patients with pAKI.

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.

Monitoring of Intraperitoneal Fluid Volume during Peritoneal Equilibration Testing using Segmental Bioimpedance.

BACKGROUND: Ultrafiltration failure and fluid overload are common in peritoneal dialysis (PD) patients. Knowledge of intraperitoneal volume (IPV) and time to peak IPV during a dwell would permit improved PD prescription. This study aimed to utilize trunk segmental bioimpedance analysis (SBIA) to quasi-continuously monitor IPV (IPVSBIA) during the peritoneal dwell. METHODS: IPVSBIA was measured every minute using lower-trunk SBIA (Hydra 4200; Xitron Technologies Inc., CA, USA) in 10 PD patients during a standard 240-min peritoneal equilibration test (PET). The known dialysate volume (2 L) rendered IPVSBIA calibration and calculation of instantaneous ultrafiltration volume (UFVSBIA) possible. UFVSBIA was defined as IPVSBIA - 2 L. RESULTS: Based on dialysate-to-plasma creatinine ratio, 2 patients were high, 7 high-average, and 1 low-average transporters. Technically sound IPVSBIA measurements were obtained in 9 patients (age 59.0 ± 8.8 years, 7 females, 5 African Americans). Drained ultrafiltration volume (UFVdrain) was 0.47 ± 0.21 L and correlated (r = 0.74; p < 0.05) with end-dwell UFVSBIA (0.55 ± 0.17 L). Peak UFVSBIA was 1.04 ± 0.32 L, it was reached 177 ± 61 min into the dwell and exceeded end-dwell UFVSBIA by 0.49 ± 0.28 L (95% CI: 0.27-0.7) and UFVdrain by 0.52 ± 0.31 L (95% CI: 0.29-0.76), respectively. CONCLUSION: This pilot study demonstrates the feasibility of trunk segmental bioimpedance to quasi-continuously monitor IPVSBIA and identify the time to peak UFVSBIA during a standard PET. Such new insights into the dynamics of intraperitoneal fluid volume during the dwell may advance our understanding of the underlying transport physiology and eventually assist in improving PD treatment prescriptions.

The effect of increased frequency of hemodialysis on vitamin C concentrations: an ancillary study of the randomized Frequent Hemodialysis Network (FHN) daily trial.

BACKGROUND: Reports on vitamin C in HD patients have shown effects of vitamin C deficiency in association with scurvy symptoms. Dialyzability of water soluble vitamins is high, and substantial losses in those who are dialyzed more frequently were hypothesized. The randomized FHN Daily Trial compared the effects of in-center HD six versus three times per week. We studied baseline correlations between vitamin C and potentially associated parameters, and the effect of more frequent HD on circulating vitamin C concentrations. METHODS: We studied vitamin C levels at baseline and months, 3, 5 and 11. Patients enrolled between 2007 and 2009 into the randomized FHN Daily trial in the East Coast consortium were approached for participation. Predialysis plasma samples were processed with metaphosphoric acid and frozen at - 70 °C for measurement with HPLC. Regression models between baseline log-transformed vitamin C and hemoglobin, CRP, eKt/V, ePCR and PTH, and a linear mixed-effects model to estimate the effect size of more frequent HD on plasma vitamin C, were constructed. RESULTS: We studied 44 subjects enrolled in the FHN Daily trial (50 ± 12 years, 36% female, 29% Hispanics and 64% blacks, 60% anuric). Vitamin C correlated significantly with predialysis hemoglobin (r = 0.3; P = 0.03) and PTH (r = - 0.3, P = 0.04), respectively. Vitamin C did not significantly differ at baseline (6×/week, 25.8 ± 25.9 versus 3×/week, 32.6 ± 39.4 µmol/L) and no significant treatment effect on plasma vitamin C concentrations was found [- 26.2 (95%CI -57.5 to 5.1) µmol/L at Month 4 and - 2.5 (95%CI -15.6 to 10.6) µmol/L at Month 12. CONCLUSIONS: Based on data from this large randomized-controlled trial no significant effect of the intervention on circulating plasma vitamin C concentrations was found, allaying the concerns that more frequent HD would affect the concentrations of water-soluble vitamins and adversely affect patient's well-being. Correlations between vitamin C and hemoglobin and PTH support the importance of vitamin C for normal bone and mineral metabolism, and anemia management.

Non-invasive hemodynamic profiling of patients undergoing hemodialysis - a multicenter observational cohort study.

BACKGROUND: Intradialytic blood pressure (BP) measurement is currently the main parameter used for monitoring hemodynamics during hemodialysis (HD). Since BP is dependent on cardiac output and total peripheral resistance, knowledge of these parameters throughout the HD treatment would potentially be valuable. METHODS: The use of a novel non-invasive monitoring system for profiling hemodynamic response patterns during HD was explored: a whole-body bio-impedance system was used to assess cardiac index (CI), total peripheral resistance index (TPRI), cardiac power index (CPI) among other parameters in chronic HD patients from 4 medical centers. Measurements were made pre, during and post dialysis. Patients were grouped into 5 hemodynamic profiles based on their main hemodynamic response during dialysis i.e. high TPRI; high CPI; low CPI; low TPRI and those with normal hemodynamics. Comparisons were made between the groups for baseline characteristics and 1-year mortality. RESULTS: In 144 patients with mean age of 67.3 ± 12.1 years pre-dialysis hemodynamic measurements were within normal limits in 35.4% but only 6.9% overall remained hemodynamically stable during dialysis. Intradialytic BP decreased in 65 (45.1%) in whom, low CPI (47 (72.3%)) and low TPRI (18 (27.7%) were recorded. At 1-year follow-up, mortality rates were highest in patients with low CPI (23.4%) and low TPRI (22.2%). CONCLUSIONS: Non-invasive assessment of patients' response to HD provides relevant hemodynamic information that exceeds that provided by currently used BP measurements. Use of these online analyses could potentially improve the safety and performance standards of dialysis by guiding appropriate interventions, particularly in responding to hypertension and hypotension.

Hemodynamic response to fluid removal during hemodialysis: categorization of causes of intradialytic hypotension.

Background: Intradialytic hypotension is a clinically significant problem, however, the hemodynamics that underlie ultrafiltration and consequent hypotensive episodes has not been studied comprehensively. Methods: Intradialytic cardiac output, cardiac power and peripheral resistance changes from pretreatment measurements were evaluated using a novel regional impedance cardiographic device (NICaS, NI Medical, Peta Tikva, Israel) in 263 hemodialysis sessions in 54 patients in dialysis units in the USA and Brazil with the goal of determining the various hemodynamic trends as blood pressure decreases. Results: Hypotensive episodes occurred in 99 (13.5%) of 736 intra- and postdialytic evaluations. The hemodynamic profiles of the episodes were categorized: (i) The cardiac power index significantly decreased in 35% of episodes by 36%, from 0.66 [95% confidence interval (CI) 0.60-0.72] to 0.43 (95% CI 0.37-0.48) [w/m2] with a small reduction in the total peripheral resistance index. (ii) The total peripheral resistance index significantly decreased in 37.4% of episodes by 33%, from 3342 (95% CI 2824-3859) to 2251 (95% CI 1900-2602) [dyn × s/cm5 × m2] with a small reduction in the cardiac power index. (iii) Both the cardiac power index and total peripheral resistance index significantly decreased in 27.3% of episodes, the cardiac power index by 25% from 0.63 (95% CI 0.57-0.70) to 0.48 (95% CI 0.42-0.53) [w/m2] and the total peripheral resistance index by 23% from 2964 (95% CI 2428-3501) to 2266 (95% CI 1891-2642). Conclusions: The hemodynamic profiles clearly define specific hemodynamic mechanisms of cardiac power reduction and/or vasodilatation as underlying intradialytic hypotensive episodes. A reduction in cardiac power (reduction of both blood pressure and cardiac output) could be the result of preload reduction due to a high ultrafiltration rate with not enough refilling or low target weight. A reduction in peripheral resistance (reduction in blood pressure and increase in cardiac output) could be the result of relative vasodilatation as arteries do not contract to compensate for volume reduction due to autonomous dysfunction. As both phenomena are independent, they may appear at the same time. Based on these results, a reduction of ultrafiltration rate and an increase in target weight to improve preload or immediate therapeutic actions to increase peripheral resistance are rational measures that could be taken to maintain blood pressure and prevent hypotensive ischemic complications in dialysis patients.

The value of non-invasive measurement of cardiac output and total peripheral resistance to categorize significant changes of intradialytic blood pressure: a prospective study.

BACKGROUND: Blood pressure (BP) is currently the main hemodynamic parameter used to assess the influence of fluid removal during hemodialysis session. Since BP is dependent on cardiac output (CO) and total peripheral resistance (TPRI), investigating these parameters may help to better understand the influence of fluid removal on patient's hemodynamics. We used a novel non-invasive whole-body bio-impedance cardiography device, recently validated in hemodialysis patients, to examine mechanisms of intradialytic hemodynamics in a Chinese dialysis population. METHODS: Chronic hemodialysis patients in Sichuan Provincial People's Hospital were enrolled. Demographic data and dialysis prescriptions were collected. Hemodynamic measurements were made pre-treatment, every 20 min during treatment and immediately after treatment in each random dialysis session. These included blood pressure, cardiac index (CI), total peripheral resistance (TPRI) and cardiac power index (CPI). Patients were divided into 5 hemodynamic groups as per their major hemodynamic response to fluid removal: low CPI, low TPRI, high TPRI, High CPI and those with normal hemodynamics. RESULTS: Twenty-seven patients were enrolled, with 12 (44.4%) males. The average age was 65 ± 12 y. The average body mass index (BMI) was 23.7 ± 3.9 kg/m2. 12 (44.4%) patients were diabetic. Three hundred twenty-four hemodynamic measurements were made. Weight, BMI, total fluid removal, pretreatment systolic BP, CI, TPRI and CI differed significantly among the 5 hemodynamic groups.11.1% of patients had low CPI, 25.9% had low TPRI, 18.5% had high CPI, 3.7% had high TPRI and 40.7% had normal hemodynamics. Hemodynamic differences among the 5 subgroups were significant. CONCLUSION: This technology provides multi-dimensional insight into intradialytic hemodynamic parameters, which may be more informative than blood pressure only. Using hemodynamic parameters to describe patients' status is more specific and accurate, and could help to work out specific and effective therapeutic actions according to underlying abnormalities.

Effect of Change in Fluid Status Evaluated by Bioimpedance Techniques on Body Composition in Hemodialysis Patients.

OBJECTIVE: This prospective study uses calf bioimpedance spectroscopy (cBIS) to guide the attainment of dry weight (DWcBIS) in chronic hemodialysis (HD) patients. The primary aim of this study was to evaluate whether body composition is altered when fluid status is reduced to DWcBIS. METHODS: Target post-HD weight was gradually reduced from baseline (BL) until DWcBIS was achieved. DWcBIS was defined as the presence of both flattening of the curve of extracellular resistance and the attainment calf normalized resistivity in the normal range during the dialysis treatment. Extracellular volume (ECV), intracellular volume, and total body water (TBW) were measured using whole body BIS (Hydra 4200). Fluid overload, lean body mass, and fat mass were calculated according to a body composition model. RESULTS: Seventy-three patients enrolled and 60 completed the study (55 ± 13 years, 49% male). Twenty-eight patients (25% diabetes) achieved DWcBIS, whereas 32 patients (47% diabetes) did not. Number of treatment measurements were 16 ± 10 and 12 ± 13 studies per patient in the DWcBIS and non-DWcBIS groups, respectively. Although significant decreases in body weight and ECV were observed, lean body mass and FM did not differ significantly in both groups from BL to the end of study. ECV, ECV/TBW, and fluid overload were higher in the non-DWcBIS than in the DWcBIS group both at BL and at the end of study. Ratios of intradialytic changes in calf normalized resistivity, ECV, and ECV/TBW to ultrafiltration volume were significantly lower in diabetic than in non-diabetic patients. CONCLUSIONS: This study shows that decreasing fluid status by gradual reduction of post-HD weight in both DWcBIS and Non-DWcBIS groups did not affect body composition significantly over a period of about 4 weeks.

Limited reduction in uremic solute concentrations with increased dialysis frequency and time in the Frequent Hemodialysis Network Daily Trial.

The Frequent Hemodialysis Network Daily Trial compared conventional three-times weekly treatment to more frequent treatment with a longer weekly treatment time in patients receiving in-center hemodialysis. Evaluation at one year showed favorable effects of more intensive treatment on left ventricular mass, blood pressure, and phosphate control, but modest or no effects on physical or cognitive performance. The current study compared plasma concentrations of uremic solutes in stored samples from 53 trial patients who received three-times weekly in-center hemodialysis for an average weekly time of 10.9 hours and 30 trial patients who received six-times weekly in-center hemodialysis for an average of 14.6 hours. Metabolomic analysis revealed that increased treatment frequency and time resulted in an average reduction of only 15 percent in the levels of 107 uremic solutes. Quantitative assays confirmed that increased treatment did not significantly reduce levels of the putative uremic toxins p-cresol sulfate or indoxyl sulfate. Kinetic modeling suggested that our ability to lower solute concentrations by increasing hemodialysis frequency and duration may be limited by the presence of non-dialytic solute clearances and/or changes in solute production. Thus, failure to achieve larger reductions in uremic solute concentrations may account, in part, for the limited benefits observed with increasing frequency and weekly treatment time in Frequent Hemodialysis Daily Trial participants.

Impact of fluid status and inflammation and their interaction on survival: a study in an international hemodialysis patient cohort.

In hemodialysis patients extracellular fluid overload is a predictor of all-cause and cardiovascular mortality, and a relation with inflammation has been reported in previous studies. The magnitude and nature of this interaction and the effects of moderate fluid overload and extracellular fluid depletion on survival are still unclear. We present the results of an international cohort study in 8883 hemodialysis patients from the European MONDO initiative database where, during a three-month baseline period, fluid status was assessed using bioimpedance and inflammation by C-reactive protein. All-cause mortality was recorded during 12 months of follow up. In a second analysis a three-month baseline period was added to the first baseline period, and changes in fluid and inflammation status were related to all-cause mortality during six-month follow up. Both pre-dialysis estimated fluid overload and fluid depletion were associated with an increased mortality, already apparent at moderate levels of estimated pre-dialysis fluid overload (1.1-2.5L); hazard ratio 1.64 (95% confidence interval 1.35-1.98). In contrast, post-dialysis estimated fluid depletion was associated with a survival benefit (0.74 [0.62-0.90]). The concurrent presence of fluid overload and inflammation was associated with the highest risk of death. Thus, while pre-dialysis fluid overload was associated with inflammation, even in the absence of inflammation, fluid overload remained a significant risk factor for short-term mortality, even following improvement of fluid status.

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.

Interdialytic Weight Gain: Trends, Predictors, and Associated Outcomes in the International Dialysis Outcomes and Practice Patterns Study (DOPPS).

BACKGROUND: High interdialytic weight gain (IDWG) is associated with adverse outcomes in hemodialysis (HD) patients. We identified temporal and regional trends in IDWG, predictors of IDWG, and associations of IDWG with clinical outcomes. STUDY DESIGN: Analysis 1: sequential cross-sections to identify facility- and patient-level predictors of IDWG and their temporal trends. Analysis 2: prospective cohort study to assess associations between IDWG and mortality and hospitalization risk. SETTING & PARTICIPANTS: 21,919 participants on HD therapy for 1 year or longer in the Dialysis Outcomes and Practice Patterns Study (DOPPS) phases 2 to 5 (2002-2014). PREDICTORS: Analysis 1: study phase, patient demographics and comorbid conditions, HD facility practices. Analysis 2: relative IDWG, expressed as percentage of post-HD weight (<0%, 0%-0.99%, 1%-2.49%, 2.5%-3.99% [reference], 4%-5.69%, and ≥5.7%). OUTCOMES: Analysis 1: relative IDWG as a continuous variable using linear mixed models; analysis 2: mortality; all-cause and cause-specific hospitalization using Cox regression, adjusting for potential confounders. RESULTS: From phase 2 to 5, IDWG declined in the United States (-0.29kg; -0.5% of post-HD weight), Canada (-0.25kg; -0.8%), and Europe (-0.22kg; -0.5%), with more modest declines in Japan and Australia/New Zealand. Among modifiable factors associated with IDWG, the most notable was facility mean dialysate sodium concentration: every 1-mEq/L greater dialysate sodium concentration was associated with 0.13 (95% CI, 0.11-0.16) greater relative IDWG. Compared to relative IDWG of 2.5% to 3.99%, there was elevated risk for mortality with relative IDWG≥5.7% (adjusted HR, 1.23; 95% CI, 1.08-1.40) and elevated risk for fluid-overload hospitalization with relative IDWG≥4% (HRs of 1.28 [95% CI, 1.09-1.49] and 1.64 [95% CI, 1.27-2.13] for relative IDWGs of 4%-5.69% and ≥5.7%, respectively). LIMITATIONS: Possible residual confounding. No dietary salt intake data. CONCLUSIONS: Reductions in IDWG during the past decade were partially explained by reductions in dialysate sodium concentration. Focusing quality improvement strategies on reducing occurrences of high IDWG may improve outcomes in HD patients.

Osmotic Pressure in Clinical Medicine with an Emphasis on Dialysis.

Since the beginning of life of the first multicellular organisms, the preservation of a physiologic milieu for every cell in the organism has been a critical requirement. A particular range of osmolality of the body fluids is essential for the maintenance of cell volume. In humans the stability of electrolyte concentrations and their resulting osmolality in the body fluids is the consequence of complex interactions between cell membrane functions, hormonal control, thirst, and controlled kidney excretion of fluid and solutes. Knowledge of these mechanisms, of the biochemical principles of osmolality, and of the relevant situations occurring in disease is of importance to every physician. This comprehensive review summarizes the major facts on osmolality, its relation to electrolytes and other solutes, and its relevance in physiology and in disease states with a focus on dialysis-related considerations.

Interplay of volume, blood pressure, organ ischemia, residual renal function, and diet: certainties and uncertainties with dialytic management.

Extracellular fluid volume overload and its inevitable consequence, hypertension, increases cardiovascular mortality in the long term by leading to left ventricular hypertrophy, heart failure, and ischemic heart disease in dialysis patients. Unlike antihypertensive medications, a strict volume control strategy provides optimal blood pressure control without need for antihypertensive drugs. However, utilization of this strategy has remained limited because of several factors, including the absence of a gold standard method to assess volume status, difficulties in reducing extracellular fluid volume, and safety concerns associated with reduction of extracellular volume. These include intradialytic hypotension; ischemia of heart, brain, and gut; loss of residual renal function; and vascular access thrombosis. Comprehensibly, physicians are hesitant to follow strict volume control policy because of these safety concerns. Current data, however, suggest that a high ultrafiltration rate rather than the reduction in excess volume is related to these complications. Restriction of dietary salt intake, increased frequency, and/or duration of hemodialysis sessions or addition of temporary extra sessions during the process of gradually reducing postdialysis body weight in conventional hemodialysis and discontinuation of antihypertensive medications may prevent these complications. We believe that even if an unwanted effect occurs while gradually reaching euvolemia, this is likely to be counterbalanced by favorable cardiovascular outcomes such as regression of left ventricular hypertrophy, prevention of heart failure, and, ultimately, cardiovascular mortality as a result of the eventual achievement of normal extracellular fluid volume and blood pressure over the long term.

Plasma Gelsolin and Its Association with Mortality and Hospitalization in Chronic Hemodialysis Patients.

BACKGROUND: Human plasma gelsolin (pGSN) is an actin-binding protein that is secreted into the extracellular fluid, with the skeletal muscle and myocardial tissues being its major source. Depletion of pGSN has been shown to be related to a variety of inflammatory and clinical conditions. METHODS: pGSN levels were prospectively determined in prevalent maintenance hemodialysis (HD) patients from 3 U.S. dialysis centers. Demographics (age, time since dialysis initiation, race, gender, body height and weight, comorbidities), inflammatory markers (C reactive protein, CRP; interleukin 6, IL-6), free triiodothyronine (fT3), and routine laboratory parameters were obtained. We performed Kaplan-Meier and Cox proportional hazard survival analysis for all-cause and cardiovascular mortality, and recurrent event survival analysis for hospitalization. RESULTS: We studied 153 patients; mean age was 60.5 ± 14.7; 52% were males. The mean pGSN level was 6,617 ± 1,789 mU/ml. In univariate analysis, pGSN was positively correlated with body mass index (r = 0.2, p = 0.01), pre-HD serum albumin (r = 0.247, p = 0.002), and pre-HD serum creatinine (r = 0.381, p < 0.001), and inversely with age (r = -0.286, p < 0.001), CRP (r = -0.311, p < 0.001), and IL-6 (r = -0.317, p < 0.001). In the adjusted analysis, the associations with CRP and creatinine were retained. pGSN levels tended to be lower in patients who died (p = 0.08). There was no association with all-cause or cardiovascular mortality, or all-cause hospitalization. Of note, fT3 was lower in patients who died (p = 0.001). CONCLUSIONS: Even though pGSN was inversely correlated with age, CRP and IL-6, suggesting that inflammation may influence pGSN, lower pGSN levels were not associated with hospitalization, all-cause and cardio-vascular mortality in this patient population.

Correlation between Inflammatory Biomarkers and Red Blood Cell Life Span in Chronic Hemodialysis Patients.

BACKGROUND AND OBJECTIVES: The pathogenesis of anemia in hemodialysis (HD) patients is dependent on multiple factors, with decreased red blood cell life span (RBCLS) being a significant contributor. Although the impact of reduced RBCLS on anemia is recognized, it is still a subject that is not well researched. The objective of this study was to investigate the relationship between RBCLS and inflammatory biomarkers in chronic HD patients. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: RBCLS was calculated from alveolar carbon monoxide concentrations measured by gas chromatography. Interleukins (IL) IL-6, IL-18, IL-10, and high sensitivity C-reactive protein were measured using bead-based multiplex assay. Measurements were carried out at baseline and during follow-up. The associations between RBCLS and inflammatory biomarkers were evaluated using linear mixed effects models. RESULTS: RBCLS measurements were available for 54 HD patients. Their average age was 58.5 ± 14.4 years, 68.5% were males, 48.1% were diabetics, and the HD vintage was 51 ± 48 months. In 4 patients, RBCLS was measured once, while in 50 patients, up to 5 repeated RBCLS measurements were available. RBCLS was 73.2 ± 17.8 days (range 37.7-115.8 days). No association was found between RBCLS and any of the inflammatory biomarkers. Of note, RBCLS was positively correlated with levels of uric acid (p = 0.02) and blood urea nitrogen (BUN; p = 0.01), respectively. CONCLUSION: Our study suggests that inflammation pathways reported by these biomarkers only have a limited role in causing premature RBC death. The positive correlation with uric acid and BUN warrants further studies.

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.