Acute kidney injury (AKI) is a complex disorder for which currently there is no accepted definition. Having a uniform standard for diagnosing and classifying AKI would enhance our ability to manage these patients. Future clinical and translational research in AKI will require collaborative networks of investigators drawn from various disciplines, dissemination of information via multidisciplinary joint conferences and publications, and improved translation of knowledge from pre-clinical research. We describe an initiative to develop uniform standards for defining and classifying AKI and to establish a forum for multidisciplinary interaction to improve care for patients with or at risk for AKI. Members representing key societies in critical care and nephrology along with additional experts in adult and pediatric AKI participated in a two day conference in Amsterdam, The Netherlands, in September 2005 and were assigned to one of three workgroups. Each group's discussions formed the basis for draft recommendations that were later refined and improved during discussion with the larger group. Dissenting opinions were also noted. The final draft recommendations were circulated to all participants and subsequently agreed upon as the consensus recommendations for this report. Participating societies endorsed the recommendations and agreed to help disseminate the results. The term AKI is proposed to represent the entire spectrum of acute renal failure. Diagnostic criteria for AKI are proposed based on acute alterations in serum creatinine or urine output. A staging system for AKI which reflects quantitative changes in serum creatinine and urine output has been developed. We describe the formation of a multidisciplinary collaborative network focused on AKI. We have proposed uniform standards for diagnosing and classifying AKI which will need to be validated in future studies. The Acute Kidney Injury Network offers a mechanism for proceeding with efforts to improve patient outcomes.

Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury

Polyomavirus-associated nephropathy (PVAN) is an emerging cause of kidney transplant failure affecting 1-10% of patients. As uncertainty exists regarding risk factors, diagnosis, and intervention, an independent panel of experts reviewed the currently available evidence and prepared this report. Most cases of PVAN are elicited by BK virus (BKV) in the context of intense immunosuppression. No specific immunosuppressive drug is exclusively associated with PVAN, but most cases reported to date arise while the patient is on triple immunosuppressive combinations, often comprising tacrolimus and/or mycophenolate mofetil plus corticosteroids. Immunologic control of polyomavirus replication can be achieved by reducing, switching, and/or discontinuing components of the immunosuppressive regimen, but the individual's risk of rejection should be considered. The success rate of this intervention is increased with earlier diagnosis. Therefore, it is recommended that all renal transplant recipients should be screened for BKV replication in the urine: 1) every three months during the first two years posttransplant; 2) when allograft dysfunction is noted; and 3) when allograft biopsy is performed. A positive screening result should be confirmed in <4 weeks and assessed by quantitative assays (e.g. BKV DNA or RNA load in plasma or urine). Definitive diagnosis of PVAN requires allograft biopsy. If PVAN and concurrent acute rejection is diagnosed, antirejection treatment should be considered, coupled with subsequently reducing immunosuppression. The antiviral cidofovir is not approved for PVAN, but investigational use at low doses (0.25-0.33 mg/kg intravenously biweekly) without probenicid should be considered for refractory cases. Retransplantation after renal allograft loss to PVAN remains a treatment option for patients clearing polyomavirus replication.

Polyomavirus-Associated Nephropathy in Renal Transplantation: Interdisciplinary Analyses and Recommendations

Hyponatraemia, defined as a serum sodium concentration !135 mmol/l, is the most common disorder of body fluid and electrolyte balance encountered in clinical practice. It can lead to a wide spectrum of clinical symptoms, from subtle to severe or even life threatening, and is associated with increased mortality, morbidity and length of hospital stay in patients presenting with a range of conditions. Despite this, the management of patients remains problematic. The prevalence of hyponatraemia in widely different conditions and the fact that hyponatraemia is managed by clinicians with a broad variety of backgrounds have fostered diverse institution- and speciality-based approaches to diagnosis and treatment. To obtain a common and holistic view, the European Society of Intensive Care Medicine (ESICM), the European Society of Endocrinology (ESE) and the European Renal Association – European Dialysis and Transplant Association (ERA–EDTA), represented by European Renal Best Practice (ERBP), have developed the Clinical Practice Guideline on the diagnostic approach and treatment of hyponatraemia as a joint venture of three societies representing specialists with a natural interest in hyponatraemia. In addition to a rigorous approach to methodology and evaluation, we were keen to ensure that the document focused on patient-important outcomes and included utility for clinicians involved in everyday practice.

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Clinical practice guideline on diagnosis and treatment of hyponatraemia

https://www.kidney-international.org/article/S0085-2538(15)52823-8/pdf

Association between obesity and kidney disease: a systematic review and meta-analysis.

This article updates the Heart Failure Association of the European Society of Cardiology (ESC) 2007 classification of advanced heart failure and describes new diagnostic and treatment options for these patients. Recognizing the patient with advanced heart failure is critical to facilitate timely referral to advanced heart failure centres. Unplanned visits for heart failure decompensation, malignant arrhythmias, co-morbidities, and the 2016 ESC guidelines criteria for the diagnosis of heart failure with preserved ejection fraction are included in this updated definition. Standard treatment is, by definition, insufficient in these patients. Inotropic therapy may be used as a bridge strategy, but it is only a palliative measure when used on its own, because of the lack of outcomes data. Major progress has occurred with short-term mechanical circulatory support devices for immediate management of cardiogenic shock and long-term mechanical circulatory support for either a bridge to transplantation or as destination therapy. Heart transplantation remains the treatment of choice for patients without contraindications. Some patients will not be candidates for advanced heart failure therapies. For these patients, who are often elderly with multiple co-morbidities, management of advanced heart failure to reduce symptoms and improve quality of life should be emphasized. Robust evidence from prospective studies is lacking for most therapies for advanced heart failure. There is an urgent need to develop evidence-based treatment algorithms to prolong life when possible and in accordance with patient preferences, increase life quality, and reduce the burden of hospitalization in this vulnerable patient population.

Advanced heart failure : a position statement of the Heart Failure Association of the European Society of Cardiology

Nearly all reported cases of PVN in the literature are caused by BKvirus (BKV). PVN has therefore traditionally been considered somehow synonymous with BKV nephropathy. However, some facts should be reviewed regarding the etiologic agent responsible for PVN: F|rst, the three polyomaviruses, namely BKV, JC virus (JCV), and Simian virus-40 (SV40), are very similar in structure, with 70^72%DNA sequence homology. Second, JCV has been shown as a co-infectious agent in the kidney of a subset of renal transplant recipients with established BKVnephropathy (1); molecular evidence of co-infection with BKVand SV40 has also been shown in some renal transplant recipients with established PVN (2). Third, BKV and SV40 have been reported to cause progressive multifocal leukoencephalopathy, although the overwhelming majority of cases are caused by JCV (3). These facts indicate that these three polyomaviruses, which share many structural similarities, might also be capable of inducing similar pathologic patterns. The hypothesis that JCV and SV40 could induce PVN independent of BKVwould not then seem surprising. Indeed, recent ¢ndings are in agreement with this hypothesis. Our team has recently reported a case of JCV-induced allograft nephropathy in a renal transplant recipient in the absence of BKV (4), and very recently SV40 has been reported as the single agent causing PVN without any biological stigmata of BKV or JCV infection (5). These reports indicate that nonBKV PVN, though rare, does exist.

Polyomaviruses and transplant patients: new concepts.

To the Editors: We read with great interest the article of Bartone and colleagues recently published in your Journal. This study compared the effects of ultrafiltration and usual care with or without nesiritide, in the management of patients with acute decompensated heart failure (HF). The authors concluded that ultrafiltration is more effective for volume removal and possibly for prevention of all-cause rehospitalization at short term. Although excited about the interesting findings of this study, we think a few points in the discussion of the results merit consideration. A novel finding was that the rate of ultrafiltration utilized in this study was associated with significant adverse impact on renal function. The ultrafiltration group manifested the greatest increase in serum creatinine level as well as the number of patients whose creatinine level increased by>0.5 mg ⁄dL. To our knowledge, this is the first study that demonstrates deterioration of renal function in patients with HF undergoing ultrafiltration. Indeed, an important reason for the recent interest in use of ultrafiltration has been the possibility of avoiding the deleterious effects of diuretics on renal function. While it is intriguing to hope that ultrafiltration can improve renal function, this has not yet been demonstrated. All previous studies failed to show any beneficial renal effect for ultrafiltration compared with diuretics. Subsequently, Rogers and colleagues showed that the use of ultrafiltration is associated with a decrease in glomerular filtration rate, similar to diuretics. A major factor in the rise in serum creatinine in the study by Bartone and associates may have been the high rate of fluid removal: average 327 mL ⁄h for a mean duration of 37.5 hours. It is not surprising that this rapid rate of ultrafiltration (>7 L ⁄d) resulted in more than twice the weight reduction than diuretics and raises the concern that it caused a physiologically relevant mismatch between the rate of fluid loss and the plasma refill rate, a concept originating in the hemodialysis literature and now extended into that of HF. Thus, the results of the study of Bartone and colleagues are indeed consistent with previous studies suggesting the absence of any beneficial renal effect for ultrafiltration but highlight as well the possibility of adverse effects especially at excessive rates of fluid removal. Moreover, it is unlikely that fluid removal could fully explain the renal dysfunction in these patients. Indeed, as seen in the Figure of the paper, weight loss (a marker for fluid removal) is correlated with the change in serum creatinine only for patients in the diuretic group, and not for ultrafiltration (P=.002 and .7, respectively). Other factors (eg, bioincompatibility of hemofilters) might have played a role in this setting. The authors have tried to compare the elevation of creatinine in the ultrafiltration group with that observed with the use of angiotensin-converting enzyme inhibitors, but there seems to be insufficient pathophysiologic ground for such comparison. Angiotensin-converting enzyme inhibitors increase serum creatinine levels by a fundamentally different mechanism from ultrafiltration. They lower glomerular filtration rate by modification of intraglomerular hemodynamics (ie, attenuating efferent arteriolar resistance), which is believed to portend their numerous beneficial renal effects. These are obviously absent in ultrafiltration, which could cause acute decreases in renal perfusion and function. Finally, the authors indicate that the rise in serum creatinine levels observed in the ultrafiltration group is transient. Since only 2 measurements of creatinine (preultrafiltration and postultrafiltration) have been reported in this paper, there seem to be no data to support the transient nature of the rise in creatinine. In conclusion, we think that results of the study by Bartone and colleagues, while consistent with previous studies, emphasize the potential adverse impact of ultrafiltration on renal function in settings where the optimal rate of fluid removal is not yet clearly defined. There is an urgent need for studies evaluating the safety of this therapeutic strategy prior to potential expansion of its use and indications, a concept that we have previously discussed in detail.—Amir Kazory, MD; Edward A. Ross, MD, Division of Nephrology, Hypertension, and Renal Transplantation, University of Florida, Gainesville, FL

Impact of ultrafiltration on renal function in patients with decompensated heart failure.

Congestion is the most common reason for hospitalization of patients with acute decompensated heart failure (ADHF) and adversely impacts their outcomes. Extracorporeal ultrafiltration (UF) therapy has re-emerged as an effective strategy for decongestion in this setting. This article is intended to discuss key concepts in UF and its technique, provide a brief historical view of UF application for decongestion in ADHF, review the hemodynamic and neurohormonal effects of UF and their positive effects on the pathophysiology of ADHF, discuss the findings of the landmark trials in this field, and explain key findings of these studies as well as the apparent discrepancies in their findings. In a separate section we discuss the intricacies of renal dysfunction in ADHF as it plays a very important role in understanding the current evidence and designing futures clinical trials of UF in ADHF. In the end, the authors provide their perspective on the future role of UF in management of patients with ADHF and congestion.

Extracorporeal ultrafiltration therapy for acute decompensated heart failure.

The mean age of onset of end-stage renal disease (ESRD) in autosomal dominant polycystic kidney disease (ADPKD) is between 56 and 69. Our case represents one of the oldest patients with ADPKD, whose chronic kidney disease (CKD) progression rate could be successfully reduced by optimal risk factor modification.

An 88-year-old patient with ADPKD: underscoring the importance of risk factor modification

Fluid overload has been associated with morbidity and mortality in various clinical scenarios including heart failure and critical illness. It exerts pathologic sequelae in almost all the organ systems. Proper management of patients with fluid overload requires knowledge of the underlying pathophysiology, objective evaluation of volume status, selection of appropriate therapeutic options, and maintenance and modulation of tissue perfusion. There are several methods to appraise volume status but none without limitations. In this review, we discuss the diagnostic utility, prognostic significance, and shortcomings of various bedside tools in the detection of fluid overload and evaluation of hemodynamic status. These include clinical examination, biomarkers, blood volume assessment, bioimpedance analysis, point-of-care ultrasound, and remote pulmonary pressure monitoring. In our opinion, clinicians must adopt a multiparametric approach offsetting the limitations of individual methods to formulate a management plan tailored to patients’ needs.

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Amir Kazory

Papers

Polyomaviruses and transplant patients: new concepts.

Impact of ultrafiltration on renal function in patients with decompensated heart failure.

Extracorporeal ultrafiltration therapy for acute decompensated heart failure.

An 88-year-old patient with ADPKD: underscoring the importance of risk factor modification

Diagnosis of Fluid Overload: From Conventional to Contemporary Concepts