Disaster preparedness for people with kidney disease and kidney healthcare providers.

PURPOSE OF REVIEW: Man-made and natural disasters become more frequent and provoke significant morbidity and mortality, particularly among vulnerable people such as patients with underlying kidney diseases. This review summarizes strategies to minimize the risks associated with mass disasters among kidney healthcare providers and patients affected by kidney disease. RECENT FINDINGS: Considering patients, in advance displacement or evacuation are the only options to avoid harmful consequences of predictable disasters such as hurricanes. Following unpredictable catastrophes, one can only rely upon educational initiatives for disaster risk mitigation. Preparatory initiatives before disasters such as training courses should target minimizing hazards in order to decrease morbidity and mortality by effective interventions during and early after disasters. Retrospective evaluation of previous interventions is essential to identify adverse consequences of disaster-related health risks and to assess the efficacy of the medical response. However, preparations and subsequent responses are always open for ameliorations, even in well developed countries that are aware of disaster risks, and even after predictable disasters. SUMMARY: Adverse consequences of disasters in patients with kidney diseases and kidney healthcare providers can be mitigated by predisaster preparedness and by applying action plans and pragmatic interventions during and after disasters. Preparing clear, practical and concise recommendations and algorithms in various languages is mandatory.

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.

Harmonizing acute and chronic kidney disease definition and classification: report of a Kidney Disease: Improving Global Outcomes (KDIGO) Consensus Conference.

Kidney disease is an important public health problem. Both acute kidney injury (AKI) and chronic kidney disease have been well defined and classified, leading to improved research efforts and subsequent management strategies and recommendations. For those patients with abnormalities in kidney function and/or structure who meet neither the definition of AKI nor chronic kidney disease, there remains a gap in research, care, and guidance. The term acute kidney diseases and disorders, abbreviated to acute kidney disease (AKD), has been introduced as an important construct to address this. To expand and harmonize existing definitions and to ultimately better inform research and clinical care, Kidney Disease: Improving Global Outcomes (KDIGO) organized a consensus workshop. Multiple invitees from around the globe, representing both acute and chronic kidney disease researchers and experts, met virtually to examine existing data, and discuss key concepts related to AKD. Despite some remaining unresolved questions, conference attendees reached general consensus on the definition and classification of AKD, management strategies, and research priorities. AKD is defined by abnormalities of kidney function and/or structure with implications for health and with a duration of ≤3 months. AKD may include AKI, but, more importantly, also includes abnormalities in kidney function that are not as severe as AKI or that develop over a period of >7 days. The cause(s) of AKD should be sought, and classification includes functional and structural parameters. Management of AKD is currently based on empirical considerations. A robust research agenda to enable refinement and validation of definitions and classification systems, and thus testing of interventions and strategies, is proposed.

A call for harmonization of European kidney care: dialysis reimbursement and distribution of kidney replacement therapies.

BACKGROUND: We compare reimbursement for haemodialysis (HD) and peritoneal dialysis (PD) in European countries to assess the impact on government healthcare budgets. We discuss strategies to reduce costs by promoting sustainable dialysis and kidney transplantation. METHODS: This was a cross-sectional survey among nephrologists conducted online July-December 2016. European countries were categorized by tertiles of gross domestic product per capita (GDP). Reimbursement data were matched to kidney replacement therapy (KRT) data. RESULTS: The prevalence per million population of patients being treated with long-term dialysis was not significantly different across tertiles of GDP (P = 0.22). The percentage of PD increased with GDP across tertiles (4.9, 8.2, 13.4%; P < 0.001). The HD-to-PD reimbursement ratio was higher in countries with the highest tertile of GDP (0.7, 1.0 versus 1.7; P = 0.007). Home HD was mainly reimbursed in countries with the highest tertile of GDP (15, 15 versus 69%; P = 0.005). The percentage of public health expenditure for reimbursement of dialysis decreased across tertiles of GDP (3.3, 1.5, 0.7%; P < 0.001). Transplantation as a proportion of all KRT increased across tertiles of GDP (18.5, 39.5, 56.0%; P < 0.001). CONCLUSIONS: In Europe, dialysis has a disproportionately high impact on public health expenditure, especially in countries with a lower GDP. In these countries, the cost difference between PD and HD is smaller, and home dialysis and transplantation are less frequently provided than in countries with a higher GDP. In-depth evaluation and analysis of influential economic and political measures are needed to steer optimized reimbursement strategies for KRT.

How to increase kidney transplant activity throughout Europe-an advocacy review by the European Kidney Health Alliance.

Kidney transplantation offers better outcomes and quality of life at lower societal costs compared with other options of renal replacement therapy. In this review of the European Kidney Health Alliance, the current status of kidney transplantation throughout Europe and suggestions for improvement of transplantation rates are reported. Although the European Union (EU) has made considerable efforts in the previous decade to stimulate transplantation activity, the discrepancies among European countries suggest that there is still room for improvement. The EU efforts have partially been neutralized by external factors such as economic crises or legal issues, especially the illicit manipulation of waiting lists. Hence, growth in the application of transplantation throughout Europe virtually remained unchanged over the last few years. Continued efforts are warranted to further stimulate transplantation rates, along with the current registration and data analysis efforts supported by the EU in the Effect of Differing Kidney Disease Treatment Modalities and Organ Donation and Transplantation Practices on Health Expenditure and Patient Outcomes project. Future actions should concentrate on organization, harmonization and improvement of the legal consent framework, population education and financial stimuli.

A swan song for Kt/Vurea.

Dialyzer clearance of urea multiplied by dialysis time and normalized for urea distribution volume (Kt/Vurea or simply Kt/V) has been used as an index of dialysis adequacy since more than 30 years. This article reviews the flaws of Kt/V, starting with a lack of proof of concept in three randomized controlled hard outcome trials (RCTs), and continuing with a long list of conditions where the concept of Kt/V was shown to be flawed. This information leaves little room for any conclusion other than that Kt/V, as an indicator of dialysis adequacy, is obsolete. The dialysis patient might benefit more if, instead, the nephrology community concentrates in the future on pursuing the optimal dialysis dose that conforms with adequate quality of life and on factors that are likely to affect outcomes more than Kt/V. These include residual renal function, volume status, dialysis length, ultrafiltration rate, the number of intra-dialytic hypotensive episodes, interdialytic blood pressure, serum potassium and phosphate, serum albumin, and C reactive protein.

Haste makes waste-Should current guideline recommendations for initiation of renal replacement therapy for acute kidney injury be changed?

There is broad consensus among guideline organizations that renal replacement therapy (RRT) should not be delayed in case of life-threatening conditions. However, in case of severe acute kidney injury (AKI) without these conditions, it is unclear whether immediate RRT has an advantage over delayed RRT. Two recently published randomized controlled trials (AKIKI and ELAIN) with seemingly opposite results have reignited the discussion whether guideline recommendations on initiation strategies in severe AKI should be adapted. This editorial discusses RRT initiation strategies in severe AKI, based on recent literature and highlights the potential advantages and disadvantages of immediate vs delayed start. Overall, evidence in favor of immediate compared to delayed strategies is sparse and there is wide heterogeneity across studies making it difficult to draw firm conclusions. RRT should not be delayed in case of refractory hyperkalemia, severe metabolic acidosis or pulmonary edema resistant to diuretics. In all other cases, a delayed strategy seems justified and might enhance renal recovery. RRT is not a "it doesn't hurt to try" technique and can expose the patient to a higher risk of bleeding, hemodynamic problems, under-dosing of antibiotics, loss of nutrients, catheter-related complications and the uncertain effects of blood-membrane interactions. There is no compelling reason to change current guideline recommendations and research focus should shift toward the development of algorithms as a decision aid tool for RRT initiation in severe AKI.

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.

Epidemiology of acute kidney injury in children worldwide, including developing countries.

In this review we summarize the world-wide epidemiology of acute kidney injury (AKI) in children with special emphasis on low-income countries, notably those of the sub-Saharan continent. We discuss definitions and classification systems used in pediatric AKI literature. At present, despite some shortcomings, traditional Pediatric Risk Injury Failure Loss and End Stage Kidney Disease (pRIFLE) and Kidney Disease Improving Global Outcomes (KDIGO) systems are the most clinically useful. Alternative definitions, such as monitoring serum cystatin or novel urinary biomarkers, including cell cycle inhibitors, require more long-term studies in heterogenous pediatric AKI populations before they can be recommended in routine clinical practice. A potentially interesting future application of some novel biomarkers could be incorporation into the "renal angina index", a concept recently introduced in pediatric nephrology. The most reliable epidemiological data on AKI in children come from high-outcome countries and are frequently focused on critically ill pediatric intensive care unit populations. In these patients AKI is often secondary to other systemic illnesses or their treatment. Based on a recent literature search performed within the framework of the "AKI 0by25" project of the International Society of Nephrology, we discuss the scarce and often inaccurate data on AKI epidemiology in low-income countries, notably those on the African continent. The last section reflects on some of the many barriers to improvement of overall health care in low-income populations. Although preventive strategies for AKI in low-income countries should essentially be the same as those in high-income countries, we believe any intervention for earlier detection and better treatment of AKI must address all health determinants, including educational, cultural, socio-economic and environmental factors, specific for these deprived areas.

Statins for the prevention of contrast-induced acute kidney injury.

PURPOSE OF REVIEW: To highlight the most recently published meta-analyses on the role of statins in the prevention of contrast-induced acute kidney injury (CI-AKI) and to formulate recommendations for clinical practice. RECENT FINDINGS: Nine meta-analyses were published on this topic from January 2015 to April 2016. Significant clinical heterogeneity between studies, regarding study population, treatment protocol, concomitant preventive strategies or dosage and duration of statin therapy was observed. In addition, the definition of CI-AKI was not uniform throughout all studies, and a number of other clinically meaningful endpoints, such as length of hospital stay in patients who developed CI-AKI, as well as adverse events, were rarely analyzed. SUMMARY: Despite some promising results, it is premature to adapt the existing guidelines and implement the preprocedural use of statins in daily clinical practice. At present, low volumes of iso-osmolar or low-osmolar intravascular contrast and adequate intravascular hydration in high-risk patients remain the cornerstone for the prevention of CI-AKI. There is a need for additional well designed randomized controlled trials to clarify these issues and assess the risk vs benefit of statin use for the purpose of CI-AKI prevention.

Cost of renal replacement: how to help as many as possible while keeping expenses reasonable?

The treatment of kidney diseases consumes a substantial amount of the health budget for a relatively small fraction of the overall population. If the nephrological community and society do not develop mechanisms to contain those costs, it will become impossible to continue assuring optimal outcomes and quality of life while treating all patients who need it. In this article, we describe several mechanisms to maintain sustainability of renal replacement therapy. These include (i) encouragement of transplantation after both living and deceased donation; (ii) stimulation of alternative dialysis strategies besides classical hospital haemodialysis, such as home haemodialysis, peritoneal dialysis or self-care and necessitating less reimbursement; (iii) promotion of educational activities guiding the patients towards therapies that are most suited for them; (iv) consideration of one or more of cost containment incentives such as bundling of reimbursement (if not affecting quality of the treatment), timely patient referral, green dialysis, start of dialysis based on clinical necessity rather than renal function parameters and/or prevention of CKD or its progression; (v) strategically planned adaptations to the expected growth of the ageing population in need of renal replacement; (vi) the necessity for support of research in the direction of helping as large as possible patient populations for acceptable costs; and (vii) the need for more patient-centred approaches. We also extend the discussion to the specific situation of kidney diseases in low- and middle-income countries. Finally, we point to the dramatic differences in accessibility and reimbursement of different modalities throughout Europe. We hope that this text will offer a framework for the nephrological community, including patients and nurses, and the concerned policy makers and caregivers on how to continue reaching all patients in need of renal replacement for affordable expenses.

Acute kidney injury in critically ill cancer patients: an update.

Patients with cancer represent a growing group among actual ICU admissions (up to 20 %). Due to their increased susceptibility to infectious and noninfectious complications related to the underlying cancer itself or its treatment, these patients frequently develop acute kidney injury (AKI). A wide variety of definitions for AKI are still used in the cancer literature, despite existing guidelines on definitions and staging of AKI. Alternative diagnostic investigations such as Cystatin C and urinary biomarkers are discussed briefly. This review summarizes the literature between 2010 and 2015 on epidemiology and prognosis of AKI in this population. Overall, the causes of AKI in the setting of malignancy are similar to those in other clinical settings, including preexisting chronic kidney disease. In addition, nephrotoxicity induced by the anticancer treatments including the more recently introduced targeted therapies is increasingly observed. However, data are sometimes difficult to interpret because they are often presented from the oncological rather than from the nephrological point of view. Because the development of the acute tumor lysis syndrome is one of the major causes of AKI in patients with a high tumor burden or a high cell turnover, the diagnosis, risk factors, and preventive measures of the syndrome will be discussed. Finally, we will briefly discuss renal replacement therapy modalities and the emergence of chronic kidney disease in the growing subgroup of critically ill post-AKI survivors.

Selecting a strategy for prevention of contrast-induced nephropathy in clinical practice: an evaluation of different clinical practice guidelines using the AGREE tool.

BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) is a potential complication of radio-contrast investigations. Many organisations have published guidance documents on the prevention of CI-AKI. Our aim is to explore the scope, content, consistency, practicality in clinical practice and reasons for eventual underlying discrepancies of these documents. METHODS: We searched the literature for guidance documents developed to guide prevention of CI-AKI up to 09/2014. Four reviewers appraised guideline quality using the 23-item AGREE-II instrument, which rates reporting of the guidance development process across six domains: scope and purpose, stakeholder involvement, rigour of development, clarity of presentation, applicability and editorial independence. Total scores were calculated as standardised averages by domain. RESULTS: Twenty-four guidance documents were evaluated. The guidance documents were produced by radiologists (N = 7), intensivists (N = 2), nephrologists (N = 6) or multidisciplinary teams (N = 9). One document did not mention the background of the authors. Only guidance documents (N = 15) that were not mere adaptations of existing guidelines were evaluated more in depth, using the AGREE tool. Overall, quality was mixed: only one clinical practice guidance document obtained an average score of >50% for all domains. The evidence was rated in a systematic way in only 11, and only 7 graded the strength of the recommendations. The Kidney Diseases Improving Global Outcomes guideline was the only one recommended without adaptions by all assessors. The guidance documents agreed in recommending pre-hydration as the main preventive measure, but there was difference in recommended total volumes, composition, rate and duration of the infused solutions. There was no consensus on the use of NaHCO3, with eight recommending it, six considering it and one not. Five guidance documents mentioned oral pre-hydration as a possibility, and none recommended N-acetylcysteine as solitary preventive measure. More recent guidance documents recommend avoiding hypertonic contrast media, but did not recommend preference of iso-osmolar over low-osmolar contrast media. Most guidance documents recognised pre-existing chronic kidney disease, diabetes, age and cardiovascular comorbidity as risk factors. CONCLUSIONS: There seems to be a relative consensus on the need for adequate pre-hydration to avoid CI-AKI, but recommendations to define at-risk populations for whom these measures should be applied and how they should be implemented differ substantially. Based on accumulating evidence, more recent guidelines do not recommend iso-osmolar over low-osmolar contrast media, whereas all recommend avoiding hypertonic agents.

Prognostic robustness of serum creatinine based AKI definitions in patients with sepsis: a prospective cohort study.

BACKGROUND: It is unclear how modifications in the way to calculate serum creatinine (sCr) increase and in the cut-off value applied, influences the prognostic value of Acute Kidney Injury (AKI). We wanted to evaluate whether these modifications alter the prognostic value of AKI for prediction of mortality at 3 months, 1 and 2 years. METHODS: We prospectively included 195 septic patients and evaluated the prognostic value of AKI by using three different algorithms to calculate sCr increase: either as the difference between the highest value in the first 24 h after ICU admission and a pre-admission historical (ΔHIS) or an estimated (ΔEST) baseline value, or by subtracting the ICU admission value from the sCr value 24 h after ICU admission (ΔADM). Different cut-off levels of sCr increase (0.1, 0.2, 0.3, 0.4 and 0.5 mg/dl) were evaluated. RESULTS: Mortality at 3 months, 1 and 2 years in AKI defined as ΔADM > 0.3 mg/dl was 48.1 %, 63.0 % and 63.0 % vs 27.7 %, 39.8 % and 47.6 % in no AKI respectively (OR(95%CI): 2.42(1.06-5.54), 2.58(1.11-5.97) and 1.87(0.81-4.33); 0.3 mg/dl was the lowest cut-off value that was discriminatory. When AKI was defined as ΔHIS > 0.3 mg/dl or ΔEST > 0.3 mg/dl, there was no significant difference in mortality between AKI and no AKI. CONCLUSIONS: The prognostic value of a 0.3 mg/dl increase in sCr, on mortality in sepsis, depends on how this sCr increase is calculated. Only if the evolution of serum creatinine over the first 24 h after ICU admission is taken into account, an association with mortality is found.

Influence of severity of illness on neutrophil gelatinase-associated lipocalin performance as a marker of acute kidney injury: a prospective cohort study of patients with sepsis.

BACKGROUND: The role of neutrophil gelatinase-associated lipocalin (NGAL) as a diagnostic marker for acute kidney injury (AKI) in sepsis is still debated. We hypothesized that in sepsis, the performance of serum(s) and urinary(u) NGAL can be negatively impacted by severity of illness and inflammation, and that both uNGAL and sNGAL levels can be increased regardless of presence of AKI. METHODS: One hundred and seven patients with sepsis were included. uNGAL and sNGAL were measured at admission (T0) and 4 hours (T4) and 24 hours later (T24). Transient and intrinsic AKI were respectively defined as AKI according to RIFLE during the first 72 hours that did or did not recover to "no AKI" in the following 72 hours. Patients were classified according to tertiles of CRP and APACHE II score increase. The relationship between sNGAL and uNGAL was assessed by linear regression. RESULTS: Fifty-seven patients developed transient and 22 intrinsic AKI. Prevalence of transient and intrinsic AKI were higher in patients with versus without septic shock (OR (95% CI): 3.3(1.4-8.2)). uNGAL was associated with sNGAL, and this with parallel slopes but different intercepts for AKI (Y = 0.87*X + 314.3, R2 = 0.31) and no AKI (Y = 0.87*X + 20.1, R2 = 0.38). At T4, median uNGAL and sNGAL levels were higher in septic patients with versus without shock but this is independent of AKI ((545 ng/mL vs 196 ng/ml for uNGAL and 474 ng/ml vs 287 ng/ml for sNGAL (both P = 0.003)). Both uNGAL and sNGAL levels increased with tertiles of CRP and APACHE II score increase. CONCLUSIONS: Serum and uNGAL levels are influenced by severity of illness and inflammation, and this was found to be independent of the presence of AKI. There is a strong correlation between sNGAL and uNGAL levels in patients with sepsis, indicating that increased levels of uNGAL can also be due to overspill from the systemic circulation, blurring the discriminative value of NGAL as a biomarker for AKI in patients with sepsis.