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PURPOSE OF REVIEW: Although initially kidney involvement in COVID-19 infection was felt to occur relatively infrequently, this has proved not to be the case. In critically ill patients with COVID-19, multiorgan failure including acute kidney injury (AKI) is common and is associated with an increased risk of mortality and morbidity. This review focuses briefly on the epidemiology and pathophysiology of COVID-19 associated AKI as well as options for management. RECENT FINDINGS: The risk factors for AKI are common to both noncovid-related AKI and COVID-19 associated AKI. Kidney injury in COVID-19 associated AKI may arise through several mechanisms, including not only direct effects on the kidney leading to tubular injury but also through the effects of treatment of multiorgan failure complicating infection. During surge conditions, the use of kidney replacement therapy has embraced all modalities including the use of peritoneal dialysis. The use of blood purification techniques has been proposed, but to date, the results are variable. SUMMARY: COVID-19 associated AKI is common, affecting approximately a quarter of patients hospitalized with COVID-19. Glomerular injury can occur, but in the main tubular injury seems most likely leading to AKI, which should be managed following clinical pathways informed by accepted guidelines.

Purpose of review Hepatorenal syndrome (HRS) is encountered frequently in patients with end-stage liver disease and remains an important cause of morbidity and mortality in this patient population. This review will focus and provide updates on pathophysiology, assessment of kidney function, new definitions, and treatment and prevention of HRS. Recent findings Pathophysiology of HRS has been elucidated more recently and in addition to hemodynamic changes, the role of systemic inflammatory response contributes significantly to this process. Assessment of kidney function in patients with liver cirrhosis remains challenging. Novel glomerular filtration rate equations have been developed in patients with liver disease to better estimate kidney function and changes made in the definition of acute kidney injury (AKI), which are more aligned with KDIGO criteria for AKI. Vasoconstrictors, especially terlipressin, along with albumin remain the mainstay of pharmacological treatment of HRS-AKI. Biomarkers have been useful in differentiating ATN from HRS at an early stage. Summary HRS remains a significant cause of morbidity and mortality for patients with end-stage liver disease. Newer understanding of mechanisms in development and pathophysiology of HRS have helped with elucidation of the disease process.

BACKGROUND: Accuracy of glomerular filtration rate estimating (eGFR) equations has significant implications in cirrhosis, potentially guiding simultaneous liver kidney allocation and drug dosing. Most equations adjust for Black race, partially accounted for by reported differences in muscle mass by race. Patients with cirrhosis, however, are prone to sarcopenia which may mitigate such differences. We evaluated the association between baseline eGFR and incident acute kidney injury (AKI) in patients with cirrhosis with and without race adjustment. METHODS: We conducted a retrospective national cohort study of veterans with cirrhosis. Baseline eGFR was calculated using multiple eGFR equations including Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), both with and without race adjustment. Poisson regression was used to investigate the association between baseline eGFR and incident AKI events per International Club of Ascites criteria. RESULTS: We identified 72,267 patients with cirrhosis, who were 97.3% male, 57.8% white, and 19.7% Black. Over median follow-up 2.78 years (interquartile range 1.22-5.16), lower baseline eGFR by CKD-EPI was significantly associated with higher rates of AKI in adjusted models. For all equations this association was minimally impacted when race adjustment was removed. For example, removal of race adjustment from CKD-EPI resulted in a 0.1% increase in the association between lower eGFR and higher rate of AKI events per 15mL/min/1.73m(2) change (p

Kidney involvement in patients with coronavirus disease 2019 (COVID-19) is common, and can range from the presence of proteinuria and haematuria to acute kidney injury (AKI) requiring renal replacement therapy (RRT; also known as kidney replacement therapy). COVID-19-associated AKI (COVID-19 AKI) is associated with high mortality and serves as an independent risk factor for all-cause in-hospital death in patients with COVID-19. The pathophysiology and mechanisms of AKI in patients with COVID-19 have not been fully elucidated and seem to be multifactorial, in keeping with the pathophysiology of AKI in other patients who are critically ill. Little is known about the prevention and management of COVID-19 AKI. The emergence of regional ‘surges’ in COVID-19 cases can limit hospital resources, including dialysis availability and supplies; thus, careful daily assessment of available resources is needed. In this Consensus Statement, the Acute Disease Quality Initiative provides recommendations for the diagnosis, prevention and management of COVID-19 AKI based on current literature. We also make recommendations for areas of future research, which are aimed at improving understanding of the underlying processes and improving outcomes for patients with COVID-19 AKI., COVID-19-associated AKI (COVID-19 AKI) is associated with high mortality and is an independent risk factor for all-cause in-hospital death in patients with COVID-19. This Consensus Statement from the Acute Disease Quality Initiative provides recommendations for the diagnosis, prevention and management of COVID-19 AKI and for areas of future research, with the aim of improving understanding of the underlying processes and outcomes for patients with COVID-19 AKI.

Background and aims Among patients with cirrhosis awaiting liver transplantation, prediction of wait-list (WL) mortality is adjudicated by the Model for End Stage Liver Disease-Sodium (MELD-Na) score. Replacing serum creatinine (SCr) with estimated glomerular filtration rate (eGFR) in the MELD-Na score may improve prediction of WL mortality, especially for women and highest disease severity. Approach and results We developed (2014) and validated (2015) a model incorporating eGFR using national data (n = 17,095) to predict WL mortality. Glomerular filtration rate (GFR) was estimated using the GFR assessment in liver disease (GRAIL) developed among patients with cirrhosis. Multivariate Cox proportional hazard analysis models were used to compare the predicted 90-day WL mortality between MELD-GRAIL-Na (re-estimated bilirubin, international normalized ratio [INR], sodium, and GRAIL) versus MELD-Na. Within 3 months, 27.8% were transplanted, 4.3% died on the WL, and 4.7% were delisted for other reasons. GFR as estimated by GRAIL (hazard ratio [HR] 0.382, 95% confidence interval [CI] 0.344-0.424) and the re-estimated model MELD-GRAIL-Na (HR 1.212, 95% CI 1.199-1.224) were significant predictors of mortality or being delisted on the WL within 3 months. MELD-GRAIL-Na was a better predictor of observed mortality at highest deciles of disease severity (≥ 27-40). For a score of 32 or higher (observed mortality 0.68), predicted mortality was 0.67 (MELD-GRAIL-Na) and 0.51 (MELD-Na). For women, a score of 32 or higher (observed mortality 0.67), the predicted mortality was 0.69 (MELD-GRAIL-Na) and 0.55 (MELD-Na). In 2015, use of MELD-GRAIL-Na as compared with MELD-Na resulted in reclassification of 16.7% (n = 672) of patients on the WL. Conclusion Incorporation of eGFR likely captures true GFR better than SCr, especially among women. Incorporation of MELD-GRAIL-Na instead of MELD-Na may affect outcomes for 12%-17% awaiting transplant and affect organ allocation.

Acute kidney injury (AKI) and chronic kidney disease (CKD) are important drivers of morbidity and mortality in patients with cirrhosis before and after liver transplantation (LT). In this review, we examine the role of novel kidney biomarkers for early recognition of kidney injury. Studies are limited by lack of reference standards, heterogeneous definitions of outcomes and biomarker cutoffs, and inconsistent diagnostic performance. Overall, a change in biomarker is more relevant than an absolute cutoff. Cystatin C and urinary neutrophil gelatinase-associated lipocalin (uNGAL) are the most studied candidate biomarkers and identify AKI or progression of AKI earlier than serum creatinine (sCr). Kidney injury molecule 1 and liver-type fatty acid-binding protein (L-FABP) also show potential. NGAL and interleukin 18 may play a role in differentiating acute tubular necrosis from other forms of AKI. Combining novel biomarkers with the Model for End-Stage Liver Disease score may assist prognosis. Persistent elevations in select markers (eg, NGAL) can portend irreversible injury. Several pretransplantation markers (including sCr) predict posttransplantation kidney dysfunction. Pretransplantation assessment of clinical factors (eg, age, diabetes) and novel markers (osteopontin and tissue inhibitor of metalloproteinases 1 [TIMP-1]) may predict renal kidney recovery after LT. Intraoperative changes in biomarkers predict early post-LT AKI. Prediction of CKD remains difficult, although a combination of biomarkers (eg, beta-2 microglobulin, CD40) is promising. Novel biomarkers have yet to replace sCr in guideline-based evaluation and management of kidney dysfunction in patients with cirrhosis. We propose a theoretical framework for practical incorporation of these biomarkers that considers patient characteristics (risk for irreversible injury), markers of functional and structural change, and assessment of the AKI-CKD continuum to identify patients at the highest risk for progressive kidney disease before and after LT.

Acute kidney injury (AKI) in cirrhosis consists of varying phenotypes, with hepatorenal syndrome (HRS) representing a single entity. Prompt recognition and diagnosis of AKI cause identifies appropriate therapeutic measures. This review provides an overview of AKI definitions, highlights challenges in quantifying renal impairment in cirrhosis, lists novel diagnostic AKI biomarkers, and summarizes transplantation implications.Biomarkers (neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, interleukin-18, and liver-type fatty acid-binding protein) may assist in the identification of underlying acute tubular necrosis. Of these, neutrophil gelatinase-associated lipocalin is the most promising; however, significant overlap occurs among AKI phenotypes, with diagnostic values yet to be defined. Mainstay treatment of HRS consists of albumin and vasopressors. Acute-on-chronic liver failure grade independently predicts response to terlipressin treatment. Many end-stage liver disease patients with AKI have underlying chronic kidney disease with important implications on pre and postliver transplantation mortality. Simultaneous liver-kidney transplant candidacy is based on low likelihood of renal recovery.Novel biomarkers may assist in identification of acute tubular necrosis and persistent/severe AKI. Norepinephrine has been suggested to be inferior to terlipressin, with additional research required. Increasing acute-on-chronic liver failure grade correlates with lower likelihood of vasopressor response in HRS. Severe preliver transplantation AKI confers significantly worse postliver transplantation renal outcomes.

Item does not contain fulltext AKI is a global concern with a high incidence among patients across acute care settings. AKI is associated with significant clinical consequences and increased health care costs. Preventive measures, as well as rapid identification of AKI, have been shown to improve outcomes in small studies. Providing high-quality care for patients with AKI or those at risk of AKI occurs across a continuum that starts at the community level and continues in the emergency department, hospital setting, and after discharge from inpatient care. Improving the quality of care provided to these patients, plausibly mitigating the cost of care and improving short- and long-term outcomes, are goals that have not been universally achieved. Therefore, understanding how the management of AKI may be amenable to quality improvement programs is needed. Recognizing this gap in knowledge, the 22nd Acute Disease Quality Initiative meeting was convened to discuss the evidence, provide recommendations, and highlight future directions for AKI-related quality measures and care processes. Using a modified Delphi process, an international group of experts including physicians, a nurse practitioner, and pharmacists provided a framework for current and future quality improvement projects in the area of AKI. Where possible, best practices in the prevention, identification, and care of the patient with AKI were identified and highlighted. This article provides a summary of the key messages and recommendations of the group, with an aim to equip and encourage health care providers to establish quality care delivery for patients with AKI and to measure key quality indicators.

Complications of portal hypertension, including ascites, gastrointestinal bleeding, hepatic hydrothorax, and hepatic encephalopathy, are associated with significant morbidity and mortality. Despite few high-quality randomized controlled trials to guide therapeutic decisions, transjugular intrahepatic portosystemic shunt (TIPS) creation has emerged as a crucial therapeutic option to treat complications of portal hypertension. In North America, the decision to perform TIPS involves gastroenterologists, hepatologists, and interventional radiologists, but TIPS creation is performed by interventional radiologists. This is in contrast to other parts of the world where TIPS creation is performed primarily by hepatologists. Thus, the successful use of TIPS in North America is dependent on a multidisciplinary approach and technical expertise, so as to optimize outcomes. Recently, new procedural techniques, TIPS stent technology, and indications for TIPS have emerged. As a result, practices and outcomes vary greatly across institutions and significant knowledge gaps exist. In this consensus statement, the Advancing Liver Therapeutic Approaches group critically reviews the application of TIPS in the management of portal hypertension. Advancing Liver Therapeutic Approaches convened a multidisciplinary group of North American experts from hepatology, interventional radiology, transplant surgery, nephrology, cardiology, pulmonology, and hematology to critically review existing literature and develop practice-based recommendations for the use of TIPS in patients with any cause of portal hypertension in terms of candidate selection, procedural best practices and, post-TIPS management; and to develop areas of consensus for TIPS indications and the prevention of complications. Finally, future research directions are identified related to TIPS for the management of portal hypertension.

Accurate estimation of kidney function in cirrhosis is crucial for prognosis and decisions regarding dual-organ transplantation. We performed a systematic review/meta-analysis to assess the performance of creatinine-based and cystatin C (CysC)-based eGFR equations compared with measured GFR (mGFR) in patients with cirrhosis. A total of 25 studies (n = 4565, 52.0 years, 37.0% women) comprising 18 equations met the inclusion criteria. In all GFR equations, the creatinine-based equations overestimated GFR (standardized mean difference, SMD, 0.51; 95% confidence interval [CI], 0.31-0.71) and CysC-based equations underestimated GFR (SMD, -0.3; 95% CI, -0.60 to -0.02). Equations based on both creatinine and CysC were the least biased (SMD, -0.14; 95% CI, -0.46 to 0.18). Chronic kidney disease-Epi-serum creatinine-CysC (CESC) was the least biased but had low precision and underestimated GFR by -3.6 mL/minute/1.73 m2 (95% CI, -17.4 to 10.3). All equations significantly overestimated GFR (+21.7 mL/minute/1.73 m2 ; 95% CI, 17.7-25.7) at GFR

Hepatorenal syndrome (HRS) is a form of acute kidney injury (AKI) occurring in patients with advanced cirrhosis and is associated with significant morbidity and mortality. The pathophysiology underlying HRS begins with increasing portal pressures leading to the release of vasodilatory substances that result in pooling blood in the splanchnic system and a corresponding reduction in effective circulating volume. Compensatory activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system and release of arginine vasopressin serve to defend mean arterial pressure but at the cost of severe constriction of the renal vasculature, leading to a progressive, often fulminant form of AKI. There are no approved treatments for HRS in the United States, but multiple countries, including much of Europe, use terlipressin, a synthetic vasopressin analogue, as a first-line therapy. CONFIRM (A Multi-Center, Randomized, Placebo Controlled, Double-Blind Study to Confirm Efficacy and Safety of Terlipressin in Subjects With Hepatorenal Syndrome Type 1), the third randomized trial based in North America evaluating terlipressin, met its primary end point of showing greater rates of HRS reversal in the terlipressin arm. However, due to concerns about the apparent increased rates of respiratory adverse events and a lack of evidence for mortality benefit, terlipressin was not approved by the Food and Drug Administration (FDA). We explore the history of regulatory approval for terlipressin in the United States, examine the results from CONFIRM and the concerns they raised, and consider the future role of terlipressin in this critical clinical area of continued unmet need.

Acute kidney injury (AKI) is a common condition following liver transplantation (LT). It negatively impacts patient outcomes by increasing the chances of developing chronic kidney disease and reducing graft and patient survival rates. Multiple definitions of AKI have been proposed and used throughout the years, with the International Club of Ascites definition being the most widely now used for patients with cirrhosis. Multiple factors are associated with the development of post-LT AKI and can be categorized into pre-LT comorbidities, donor and recipient characteristics, operative factors, and post-LT factors. Many of these factors can be optimized in an attempt to minimize the risk of AKI occurring and to improve renal function if AKI is already present. A special consideration during the post-LT phase is needed for immunosuppression as certain immunosuppressive medications can be nephrotoxic. The calcineurin inhibitor tacrolimus (TAC) is the mainstay of immunosuppression but can result in AKI. Several strategies including use of the monoclonoal antibody basilixamab to allow for delayed initiation of tacrolimus therapy and minimization through combination and minimization or elimination of TAC through combination with mycophenolate mofetil or mammalian target of rapamycin inhibitors have been implemented to reverse and avoid AKI in the post-LT setting. Renal replacement therapy may ultimately be required to support patients until recovery of AKI after LT. Overall, by improving renal function in post-LT patients with AKI, outcomes can be improved.

Postoperative acute kidney injury (PO-AKI) is a common complication of major surgery that is strongly associated with short-term surgical complications and long-term adverse outcomes, including increased risk of chronic kidney disease, cardiovascular events and death. Risk factors for PO-AKI include older age and comorbid diseases such as chronic kidney disease and diabetes mellitus. PO-AKI is best defined as AKI occurring within 7 days of an operative intervention using the Kidney Disease Improving Global Outcomes (KDIGO) definition of AKI; however, additional prognostic information may be gained from detailed clinical assessment and other diagnostic investigations in the form of a focused kidney health assessment (KHA). Prevention of PO-AKI is largely based on identification of high baseline risk, monitoring and reduction of nephrotoxic insults, whereas treatment involves the application of a bundle of interventions to avoid secondary kidney injury and mitigate the severity of AKI. As PO-AKI is strongly associated with long-term adverse outcomes, some form of follow-up KHA is essential; however, the form and location of this will be dictated by the nature and severity of the AKI. In this Consensus Statement, we provide graded recommendations for AKI after non-cardiac surgery and highlight priorities for future research., The development of acute kidney injury (AKI) after major non-cardiac surgery is associated with substantial long-term morbidity and mortality. This joint Consensus Statement from the Acute Disease Quality Initiative and the PeriOperative Quality Initiative provides recommendations for the definition, prevention and management of postoperative AKI.

Kidney involvement in patients with coronavirus disease 2019 (COVID-19) is common, and can range from the presence of proteinuria and haematuria to acute kidney injury (AKI) requiring renal replacement therapy (RRT; also known as kidney replacement therapy). COVID-19-associated AKI (COVID-19 AKI) is associated with high mortality and serves as an independent risk factor for all-cause in-hospital death in patients with COVID-19. The pathophysiology and mechanisms of AKI in patients with COVID-19 have not been fully elucidated and seem to be multifactorial, in keeping with the pathophysiology of AKI in other patients who are critically ill. Little is known about the prevention and management of COVID-19 AKI. The emergence of regional 'surges' in COVID-19 cases can limit hospital resources, including dialysis availability and supplies; thus, careful daily assessment of available resources is needed. In this Consensus Statement, the Acute Disease Quality Initiative provides recommendations for the diagnosis, prevention and management of COVID-19 AKI based on current literature. We also make recommendations for areas of future research, which are aimed at improving understanding of the underlying processes and improving outcomes for patients with COVID-19 AKI.

COVID-19, the infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has resulted in a global pandemic with unprecedented health, societal and economic impact The disease often manifests with flu-like symptoms and is dominated by pulmonary complications, but widely diverse clinical manifestations involving multiple organ systems can result We posit that viral tropism and the aberrant host immune response mediate the protean findings and severity in this disease In general, extrapulmonary manifestations are a harbinger of or contemporaneously associate with disease progression, but in the case of some extrapulmonary findings (GI and dermatologic), may track with milder disease The precise underlying pathophysiological mechanisms remain incompletely elucidated, and additional immune phenotyping studies are warranted to reveal early correlates of disease outcomes and novel therapeutic targets This article is protected by copyright All rights reserved

Background & Aim The goal of organ allocation is to distribute a scarce resource equitably to the sickest patients. In the United States, the Model for End-stage Liver Disease (MELD) is used to allocate livers for transplantation. Patients with greater MELD scores are at greater risk of death on the waitlist and are prioritized for liver transplant (LT). The MELD is capped at 40 however, and patients with calculated MELD scores >40 are not prioritized despite increased mortality. We aimed to evaluate waitlist and post-transplant survival stratified by MELD to determine outcomes in patients with MELD >40. Methods Using United Network for Organ Sharing data, we identified patients listed for LT from February 2002 through to December 2012. Waitlist candidates with MELD ⩾40 were followed for 30days or until the earliest occurrence of death or transplant. Results Of 65,776 waitlisted patients, 3.3% had MELD ⩾40 at registration, and an additional 7.3% had MELD scores increase to ⩾40 after waitlist registration. A total of 30,369 (46.2%) underwent LT, of which 2,615 (8.6%) had MELD ⩾40 at transplant. Compared to MELD 40, the hazard ratio of death within 30days of registration was 1.4 (95% CI 1.2–1.6) for patients with MELD 41–44, 2.6 (95% CI 2.1–3.1) for MELD 45–49, and 5.0 (95% CI 4.1–6.1) for MELD ⩾50. There was no difference in 1- and 3-year survival for patients transplanted with MELD >40 compared to MELD=40. A survival benefit associated with LT was seen as MELD increased above 40. Conclusions Patients with MELD >40 have significantly greater waitlist mortality but comparable post-transplant outcomes to patients with MELD=40 and, therefore, should be given priority for LT. Uncapping the MELD will allow more equitable organ distribution aligned with the principle of prioritizing patients most in need. Lay summary: In the United States (US), organs for liver transplantation are allocated by an objective scoring system called the Model for End-stage Liver Disease (MELD), which aims to prioritize the sickest patients for transplant. The greater the MELD score, the greater the mortality without liver transplant. The MELD score, however, is artificially capped at 40 and thus actually disadvantages the sickest patients with end-stage liver disease. Analysis of the data advocates uncapping the MELD score to appropriately prioritize the patients most in need of a liver transplant.

Baroreflex activation therapy is a novel technique for treating patients with resistant hypertension. Although short-term studies have demonstrated that it lowers blood pressure, long-term results have not yet been reported. The aim of the present study is to assess the long-term efficacy and safety of baroreflex activation therapy. Long-term follow-up data were analyzed from all patients who had been included in 1 of the 3 trials that focused on treatment-resistant hypertensive patients. Altogether, 383 patients were available for analysis: 143 of these had completed 5 years of follow-up and 48 patients had completed 6 years of follow-up. In the entire cohort, office systolic blood pressure fell from 179±24 mm Hg to 144±28 mm Hg ( P P P After a follow-up of 6 years, baroreflex activation therapy maintains its efficacy for persistent reduction of office blood pressure in patients with resistant hypertension without major safety issues.

Barorefiex activation therapy (BAT) is a device-based therapy for patients with treatment-resistant hypertension. In a randomized, controlled trial, the first-generation system significantly reduced blood pressure (BP) versus sham. Although an open label validation study of the second-generation system demonstrated similar BP reductions, controlled data are not presently available. Therefore, this investigation compares results of first- and second-generation BAT systems. Two cohorts of first-generation BAT system patients were generated with propensity matching to compare against the validation group of 30 second-generation subjects. The first cohort was drawn from the first-generation randomized trial sham group and the second cohort from the active therapy group. Safety and efficacy were compared for the second-generation group relative to the first generation. At 6 months, second-generation BAT outperformed first-generation sham systolic BP reduction by 20 +/- 28 mm Hg (mean +/- standard deviation, P = .008), while BP reduction in first- and second-generation active groups was similar. At 12 months, efficacy was comparable between all three groups after the sham group had received 6 months of therapy; 47% of second-generation patients achieved goal systolic BP of 140 mm Hg or less after 12 months, comparable to 50% of patients at goal in the first-generation group (P > .999). Implant procedure time, system/procedural safety, and pulse generator longevity improved with the second-generation system. Propensity-matched cohort analysis of the first- and second-generation BAT systems suggests similar therapeutic benefit and superior BP reduction of the second-generation system relative to sham control. Implantation procedure duration and perioperative safety were improved with the second-generation device. These findings should be validated in a prospective randomized trial. (C) 2016 The Authors. Published by Elsevier Inc. on behalf of American Society of Hypertension.

Acute kidney injury (AKI) is very common in critically ill cirrhotic patients. The most common phenotypes are prerenal failure, acute tubular necrosis (ATN), and hepatorenal syndrome (HRS). Early distinction between ATN and HRS is important as vasopressors are justified in patients with HRS. Biomarkers can be useful in differentiating ATN from HRS at an early stage; however, a substantial proportion of patients may be misclassified. In the long term, posttransplant glomerular filtration rate is lower in patients transplanted with pretransplant renal dysfunction. Since kidney biopsy is impractical in cirrhosis, novel biomarkers are needed to assess more precisely the potential for kidney recovery after liver transplantation alone. Combined liver and kidney transplantation is an option but criteria have to be refined.

Background Chronic kidney disease (CKD) is disproportionately more prevalent in rural and underserved areas globally, and the epidemiological factors contributing to this phenomenon are poorly understood. Here, we aim to identify several preventable factors contributing towards CKD in the city of Phalodi, a rural city located in the Indian state of Rajasthan. # Methods The qualitative and quantitative data obtained in this study comes from interviews with doctors, nurses, hospital administrators, and patients at the dialysis clinic in Phalodi. This region was selected because of its known increased prevalence of CKD, and its long-standing relation with Discovering Dialysis. # Results Several preventable factors were identified as contributors towards the increased prevalence of CKD: 1) Nimesulide abuse is fairly common in rural areas because it is affordable and effective, but it is highly nephrotoxic and hepatotoxic; 2) Kidney stones caused by the quantity and quality of rural water contribute towards both nimesulide abuse and CKD; 3) Lack of accessibility to healthcare for preventative measures and disease management exacerbate the severity of kidney disease; 4) Lack of transportation to dialysis centers limits the number of patients that can afford to receive dialysis treatment. # Conclusions This study demonstrates that several factors can be targeted to reduce the prevalence of CKD in rural India. Namely, legislation should focus on reducing nimesulide use, providing access to clean and available water, and increasing transportation to medical centers that can provide preventative care.

Renal dysfunction is a common, life-threatening complication occurring in patients with liver disease. Hepatorenal syndrome (HRS) has been defined as a purely "functional" type of renal failure that often occurs in patients with cirrhosis in the setting of marked abnormalities in arterial circulation, as well as overactivity of the endogenous vasoactive systems.4,5 In 2007, the International Club of Ascites (ICA) classified HRS into types 1 and 2 (HRS-1 and HRS-2).5 HRS-1 is characterised by a rapid deterioration of renal function that often occurs because of a precipitating event, while HRS-2 is a moderate and stable or slowly progressive renal dysfunction that often occurs without an obvious precipitant. Clinically, HRS-1 is characterised by acute renal failure while HRS-2 is mainly characterised by refractory ascites. Nevertheless, after these two entities were first described, new concepts, definitions, and diagnostic criteria have been developed by nephrologists for renal dysfunction in the general population and hospitalised patients. In particular, the definitions and characterisation of acute kidney injury (AKI), acute kidney disease and chronic kidney disease have been introduced/refined.6 Accordingly, a debate among hepatologists of the ICA led to a complete revision of the nomenclature and diagnosistic criteria for HRS-1, which was renamed HRS-AKI.7 Additionally, over recent years, greater granularity has been gained regarding the pathogenesis of HRS; it is now increasingly recognised that it is not a purely "functional" entity with haemodynamic derangements, but that systemic inflammation, oxidative stress and bile salt-related tubular damage may contribute significantly to its development. That is, HRS has an additional structural component that would not only make traditional diagnostic criteria less reliable, but would explain the lack of response to pharmacological treatment with vasoconstrictors plus albumin that correlates with a progressive increase in inflammation. Because classification, nomenclature, diagnostic criteria and pathogenic theories have evolved over the years since the traditional classification of HRS-1 and HRS-2 was first described, it was considered that all these novel aspects be reviewed and summarised in a position paper. The aim of this position paper authored by two hepatologists (members of ICA) and two nephrologists involved in the study of renal dysfunction in cirrhosis, is to complete the re-classification of HRS initiated by the ICA in 2012 and to provide an update on the definition, classification, diagnosis, pathophysiology and treatment of HRS.

INTRODUCTION: Urinary neutrophil gelatinase-associated lipocalin (NGAL) has shown promise in differentiating acute tubular necrosis (ATN) from other types of acute kidney injuries (AKIs) in cirrhosis, particularly hepatorenal syndrome (HRS). However, NGAL is not currently available in clinical practice in North America. METHODS: Urinary NGAL was measured in a prospective cohort of 213 US hospitalized patients with decompensated cirrhosis (161 with AKI and 52 reference patients without AKI). NGAL was assessed for its ability to discriminate ATN from non-ATN AKI and to predict 90-day outcomes. RESULTS: Among patients with AKI, 57 (35%) had prerenal AKI, 55 (34%) had HRS, and 49 (30%) had ATN, with a median serum creatinine of 2.0 (interquartile range 1.5, 3.0) mg/dL at enrollment. At an optimal cutpoint of 244 μg/g creatinine, NGAL distinguished ATN (344 [132, 1,429] μg/g creatinine) from prerenal AKI (45 [0, 154] μg/g) or HRS (110 [50, 393] μg/g; P < 0.001), with a C statistic of 0.762 (95% confidence interval 0.682, 0.842). By 90 days, 71 of 213 patients (33%) died. Higher median NGAL was associated with death (159 [50, 865] vs 58 [0, 191] μg/g; P < 0.001). In adjusted and unadjusted analysis, NGAL significantly predicted 90-day transplant-free survival (P < 0.05 for all Cox models) and outperformed Model for End-Stage Liver Disease score by C statistic (0.697 vs 0.686; P = 0.04), net reclassification index (37%; P = 0.008), and integrated discrimination increment (2.7%; P = 0.02). DISCUSSION: NGAL differentiates the type of AKI in cirrhosis and may improve prediction of mortality; therefore, it holds potential to affect management of AKI in cirrhosis.

Patients with cirrhosis are prone to develop acute kidney injury (AKI) due to a number of causes, including bacterial infections with or without septic shock, hypovolemia, administration of nephrotoxic drugs, and intrinsic kidney diseases, among others. Most importantly, patients with advanced cirrhosis develop a distinctive cause of AKI, characterized by rapidly progressive glomerular filtration rate loss associated with marked disturbances in circulatory function in the absence of obvious pathologic abnormalities in the kidneys, known as hepatorenal syndrome (HRS). Decreased kidney function results from intense renal vasoconstriction secondary to the complex circulatory changes of cirrhosis with splanchnic vasodilatation and effective hypovolemia. Beyond activation of vasoactive systems, factors including impaired renal blood flow autoregulation and systemic inflammation may play a role in the development of HRS. Most patients improve with albumin and vasopressors; however, the prognosis of HRS remains very poor. Novel biomarkers may be helpful in distinguishing HRS from other causes of AKI in patients with cirrhosis.

The original version of this article omitted an initial from the name of contributing author Patrick S. Kamath, who was listed as Patrick Kamath. The article has now been corrected.

Acute kidney injury (AKI) occurs in 7% to 18% of hospitalized patients and complicates the course of 50% to 60% of those admitted to the intensive care unit, carrying both significant mortality and morbidity.[1][1] Even though many cases of AKI are reversible within days to weeks of occurrence, data

Since the implementation of the Model of End-stage Liver Disease score-based allocation system, the number of transplant candidates with impaired renal function has increased. The aims of this review are to present new insights in the definitions and predisposing factors that result in acute kidney injury (AKI), and to propose guidelines for the prevention and treatment of postliver transplantation (LT) AKI. This review is based on both systematic review of relevant literature and expert opinion. Pretransplant AKI is associated with posttransplant morbidity, including prolonged post-LT AKI which then predisposes to posttransplant chronic kidney disease. Prevention of posttransplant AKI is essential in the improvement of long-term outcomes. Accurate assessment of baseline kidney function at evaluation is necessary, taking into account that serum creatinine overestimates glomerular filtration rate. New diagnostic criteria for AKI have been integrated with traditional approaches in patients with cirrhosis to potentially identify AKI earlier and improve outcomes. Delayed introduction or complete elimination of calcineurin inhibitors during the first weeks post-LT in patients with early posttransplant AKI may improve glomerular filtration rate in high risk patients but with higher rates of rejection and more adverse events. Biomarkers may in the future provide diagnostic information such as etiology of AKI, and prognostic information on renal recovery post-LT, and potentially impact the decision for simultaneous liver-kidney transplantation. Overall, more attention should be paid to pretransplant and early posttransplant AKI to reduce the burden of late chronic kidney disease.

Estimation of glomerular filtration rate (eGFR) in patients with liver disease is suboptimal in the presence of renal dysfunction. We developed a model for GFR assessment in liver disease (GRAIL) before and after liver transplantation (LT). GRAIL was derived using objective variables (creatinine, blood urea nitrogen, age, gender, race, and albumin) to estimate GFR based on timing of measurement relative to LT and degree of renal dysfunction (www.bswh.md/grail). The measured GFR (mGFR) by iothalamate clearance (n = 12,122, 1985-2015) at protocol time points before/after LT was used as reference. GRAIL was compared with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD-4, MDRD-6) equations for mGFR < 30 mL/min/1.73 m2 . Prediction of development of chronic kidney disease (mGFR < 20 mL/min/1.73 m2 , initiation of chronic dialysis) and listing or receipt of kidney transplantation within 5 years was examined in internal cohort (n = 785) and external validation (n = 68,217, 2001-2015). GRAIL had less bias and was more accurate and precise as compared with CKD-EPI, MDRD-4, and MDRD-6 at time points before/after LT for low GFR. For mGFR < 30 mL/min/1.73 m2 , the median difference (eGFR-mGFR) was GRAIL: 5.24 (9.65) mL/min/1.73 m2 as compared with CKD-EPI: 8.70 (18.24) mL/min/1.73 m2 , MDRD-4: 8.82 (17.38) mL/min/1.73 m2 , and MDRD-6: 6.53 (14.42) mL/min/1.73 m2 . Before LT, GRAIL correctly classified 75% as having mGFR < 30 mL/min/1.73 m2 versus 36.1% (CKD-EPI), 36.1% (MDRD-4), and 52.8% (MDRD-6) (P < 0.01). An eGFR < 30 mL/min/1.73 m2 by GRAIL predicted development of CKD (26.9% versus 4.6% CKD-EPI, 5.9% MDRD-4, and 10.5% MDRD-6) in center data and needing kidney after LT (48.3% versus 22.0% CKD-EPI versus 23.1% MDRD-4 versus 48.3% MDRD-6, P < 0.01) in national data within 5 years after LT. Conclusion: GRAIL may serve as an alternative model to estimate GFR among patients with liver disease before and after LT at low GFR.

Acute Kidney Injury (AKI) is common complication of acute and chronic liver disease. Hepatorenal syndrome is a severe consequence of advanced cirrhosis and occurs due to intense renal vasoconstriction causing a reduction in renal perfusion and glomerular filtration. The evaluation of renal dysfunction in cirrhosis is challenging because of the poor correlation of commonly used indices of kidney function to glomerular filtration rate. Novel biomarkers hold promise for the early diagnosis and prognosis of acute kidney injury in cirrhosis but are yet in clinical use. Therapies for acute kidney injury include vasoconstrictors, albumin and liver transplantation. Renal replacement therapy should be used as a bridge to liver transplant.

Acute kidney injury (AKI) is a frequent complication of end-stage liver disease, especially in those with acute-on-chronic liver failure, occurring in up to 50% of hospitalized patients with cirrhosis. There is no specific blood or urine biomarker that can reliably identify the cause of AKI in cirrhotic patients. This review examines studies used to assess renal dysfunction in cirrhotic patients including new diagnostic criteria and potential novel biomarkers. Although biomarker development to differentiate the cause of AKI in cirrhosis has promise, the utility of biomarkers to determine irreversible renal dysfunction with liver transplant remains lacking, warranting further investigation.

Resistant hypertension affects 20% to 30% of patients with high blood pressure (BP). It is defined as failure to achieve goal BP despite using at least 3 antihypertensive drugs of different classes, at maximal tolerated doses, one of which must be a diuretic. Persistent suboptimal BP is the most common attributable risk for death worldwide and its prevalence will most likely increase over the next decade. We review the epidemiologic aspects and diagnostic challenges of resistant hypertension, barriers to achieving proper BP control, and causes of secondary hypertension. Lifestyle modification and pharmacologic and device approaches to treatment are discussed.

Purpose of review Hepatorenal syndrome (HRS) does not represent the predominant phenotype of acute kidney injury (AKI) in cirrhosis. Early recognition of HRS helps initiate appropriate therapy. The aims of this review are to present redefinition of AKI, to list new biomarkers, to report recent data on vasopressors in HRS and to propose criteria for simultaneous liver and kidney transplantation (SLKT). Recent findings Urine output, which was not part of the definition of AKI might be reconsidered as it has an independent prognostic value. Biomarkers (NGAL and IL-18) could help identify ATN. However, cut-off values have to be clarified. Vasopressors with albumin represent first option in HRS. Continuous infusion of terlipressin has a better safety profile than intravenous boluses. SLKT should be considered whenever native kidney recovery is unlikely [i.e. prolonged renal replacement therapy (RRT) and/or GFR less than 25 ml/min for 6 weeks prior to transplantation]. Summary New definitions and recent biomarkers may help differentiate HRS from ATN at an earlier stage. Urine output should be reconsidered in the definitions. Even in patients who are not candidates for transplantation, a short trial of RRT is justified whenever needed. SLKT should be considered whenever posttransplant renal recovery is unlikely.

Liver transplantation (LT) for patients with renal dysfunction is frequently complicated by major fluid shifts, acidosis, and electrolyte and coagulation abnormalities. Continuous renal replacement therapy (CRRT) has been previously shown to ameliorate these problems. We describe the safety and clinical outcomes of intraoperative hemodialysis (IOHD) during LT for a group of patients with high Model for End-Stage Liver Disease (MELD) scores. We performed a retrospective study at our institution of patients who underwent IOHD from 2002 to 2012. Seven hundred thirty-seven patients underwent transplantation, and 32% received IOHD. The mean calculated MELD score was 37, with 38% having a MELD score ≥ 40. Preoperatively, 61% were in the intensive care unit, 19% were mechanically ventilated, 43% required vasopressor support, and 80% were on some form of renal replacement therapy at the time of transplantation, the majority being on CRRT. Patients on average received 35 U of blood products and 4.8 L of crystalloids without significant changes in hemodynamics or electrolytes. The average urine output was 450 ml, and the average amount of fluid removal with dialysis was 1.8 L. The 90-day patient and dialysis-free survival rates were 90% and 99%, respectively. One-year patient survival rates based on the pretransplant renal replacement status and the MELD status were not statistically different. This is the first large study to demonstrate the safety and feasibility of IOHD in a cohort of critically ill patients with high MELD scores undergoing LT with good patient and renal outcomes. Liver Transpl 20:756-764, 2014. © 2014 AASLD.

Simultaneous liver and kidney transplantation (SLKT) remains the procedure of choice for patients with both endstage liver disease and kidney failure. Stringent guidelines are needed to avoid unnecessary kidney transplantation. A recent consensus meeting proposed criteria based on the Modified Diet in Renal Disease (MDRD)-6 equation to estimate glomerular filtration rate (GFR). The aims of this study were to compare GFR equations to true GFR in candidates for liver transplantation (LT) and to determine the impact of inaccuracies on the current guidelines for SLKT. Three hundred stable cirrhosis patients evaluated for LT were studied. All patients had iohexol clearance to measure GFR at evaluation under stable conditions. Measured GFR (mGFR) was compared to MDRD-4, MDRD-6, and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. MDRD-6 was the most accurate equation to predict GFR. In the 290 patients with mGFR >30 mL/min/1.73 m2, 15 patients (7%) had estimated GFR (eGFR) ≤40 mL/min/1.73 m2 based on the MDRD-6 equation, defining “discordant” patients. Among them, two underwent SLKT and 13 underwent LT alone. None of those who survived more than 1 year after LT alone (n = 8) developed renal dysfunction thereafter. In multivariate analysis, discordant patients were older (P = 0.03) and had lower sodium level (P = 0.02). Conclusion: The MDRD-6 equation was superior to other equations at identifying cirrhosis patients with true GFR 30 mL/min/1.73 m2, with a potential risk of unnecessary kidney transplantation if applying current U.S. recommendations for SLKT. (Hepatology 2014;59:1514-1521)

Supplemental Digital Content is available in the text., Background. As the liver transplant (LT) waiting list continues to outpace organ availability, many patients require renal replacement therapy (RRT) before LT. It is unclear which patients will benefit from simultaneous liver kidney (SLK) transplant as opposed to awaiting a Safety Net kidney transplant (KT) post-LT. Methods. In this study, a retrospective analysis of the United Network for Organ Sharing dataset was performed to identify risk factors associated with poor outcome for patients on RRT before LT who were listed for SLK and received either SLK vs LT alone (LTA). Results. Between January 2003 and December 2016, 8971 adult LT recipients were on RRT at the time of LT. 5359 were listed for and received LTA (Group 1). Of 3612 patients listed for SLK, 3414 (38.1%) received SLK (Group 2) and 198 (2.2%) received LTA (Group 3). Overall, Group 3 had lower graft and patient survival post-LT when compared with Groups 1 and 2 (P 60 (P 90 days; P = 0.001) were associated with lower patient survival in Group 3. Conclusions. Among LT recipients on RRT before LT who were listed for SLK, RRT >90 days, and age >60 were associated with poor outcome following LTA. This suggests that programs should carefully weigh the decision to proceed with LTA vs waiting for SLK in this patient population. Future access to Safety Net KT will be an important consideration for these patients moving forward.

Acute-on-chronic liver failure (ACLF) is defined by the occurrence of organ failure(s) other than the liver in patients with cirrhosis. Even though mortality rates are high, there should no longer be reluctance to admit patients with ACLF in the intensive care unit. The prevalence of multidrug-resistant bacteria is high and broad spectrum antibiotics should be initiated as soon as infection is suspected. In patients with circulatory failure, the assessment of circulatory status is challenging due to the hyperkinetic state and an imbalance between the splanchnic and systemic blood volume. Acute kidney injury is common in patients with ACLF. Acute tubular necrosis should be differentiated from hepatorenal syndrome, which justifies vasoconstrictive agents. Renal replacement therapy and mechanical ventilation should be decided on clinical grounds. Recent trials on extracorporeal liver support failed to demonstrate a survival benefit. Aggressive management may serve as a bridge to transplantation provided patients are likely to survive after transplantation.

Acute kidney injury (AKI) at the time of liver transplantation (LT) has been associated with increased morbidity and mortality. In patients with potentially reversible renal dysfunction, predicting whether there will be sufficient return of native kidney function is sometimes difficult. Previous studies have focused mainly on the effect of the severity of renal dysfunction or the duration of pretransplant dialysis on posttransplant outcomes. We performed a retrospective analysis of patients who underwent LT at our center after Model for End-Stage Liver Disease-based allocation so that we could determine the impact of the etiology of AKI [acute tubular necrosis (ATN) versus hepatorenal syndrome (HRS)] on post-LT outcomes. The patients were stratified according to the severity of AKI at the time of LT as described by the Risk, Injury, Failure, Loss, and End-Stage Kidney Disease (RIFLE) classification: risk, injury, or failure. The RIFLE failure group was further subdivided according to the etiology of AKI: HRS or ATN. The patient survival and renal outcomes 1 and 5 years after LT were significantly worse for those with ATN. At 5 years, the incidence of chronic kidney disease (stage 4 or 5) was statistically higher in the ATN group versus the HRS group (56% versus 16%, P < 0.001). A multivariate analysis revealed that the presence of ATN at the time of LT was the only variable associated with higher mortality 1 year after LT (P < 0.001). Our study is the first to demonstrate that the etiology of AKI has the greatest impact on patient and renal outcomes after LT.

Hepatorenal syndrome (HRS) is defined as the occurrence of renal dysfunction in a patient with end-stage liver cirrhosis in the absence of another identifiable cause of renal failure. The prognosis of HRS remains poor, with a median survival without liver transplantation of

Objectives We sought to determine the effect of baroreflex activation therapy (BAT) on systolic blood pressure (SBP) in patients with resistant hypertension. Background The Rheos Pivotal Trial evaluated BAT for resistant hypertension in a double-blind, randomized, prospective, multicenter, placebo-controlled Phase III clinical trial. Methods This was a double-blind randomized trial of 265 subjects with resistant hypertension implanted and subsequently randomized (2:1) 1 month after implantation. Subjects received either BAT (Group A) for the first 6 months or delayed BAT initiation following the 6-month visit (Group B). The 5 coprimary endpoints were: 1) acute SBP responder rate at 6 months; 2) sustained responder rate at 12 months; 3) procedure safety; 4) BAT safety; and 5) device safety. Results The trial showed significant benefit for the endpoints of sustained efficacy, BAT safety, and device safety. However, it did not meet the endpoints for acute responders or procedural safety. A protocol-specified ancillary analysis showed 42% (Group A) versus 24% (Group B) achieving SBP ≤140 mm Hg at 6 months (p = 0.005), with both groups achieving over 50% at 12 months, at which point Group B had received 6 months of BAT. Conclusions A clinically meaningful measure, those achieving a SBP of ≤140 mm Hg, yielded a significant difference between the groups. The weight of the overall evidence suggests that over the long-term, BAT can safely reduce SBP in patients with resistant hypertension. Future clinical trials will address the limitations of this study and further define the therapeutic benefit of BAT.