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.

/pdf/clinical-practice-guideline-on-diagnosis-and-treatment-of-509w3449ob.pdf

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

To the editor, Aortic stenosis is one of the most common cardiac degenerative valvular diseases with an estimated prevalence of 1.3% in patients aged between 65 and 74 years and 2.8–4.6% in those aged 75 or more [1, 2]. Transcatheter aortic valve replacement (TAVR) has emerged as a viable option for the treatment of patients with aortic stenosis who are not suitable candidates for surgical aortic valve replacement (SAVR). Acute kidney injury (AKI) is considered an established postoperative complication that is associated with a significant increase in the risk of mortality [3]. We sought to explore the available evidence on the risk of AKI after TAVR as compared with SAVR. We searched the articles cited in PubMed database from years 2000 to 2017 using key words “aortic stenosis” and “transcatheter aortic valve replacement”, and those evaluating the role of TAVR in management of aortic stenosis were reviewed. Randomized controlled trials (RCT) that contained data on comparative impact of TAVR and SAVR on renal function were selected [4–7]. Relevant data including baseline renal function, definition of AKI, and incidence of AKI were extracted and compared (Table 1). Using Altman formula, the relative risk (RR) of AKI, its standard error, and 95% confidence intervals (CI) were extracted and compared for each study. A total of 113 citations were reviewed and after exclusion of duplicate studies, 4 RCTs with 3310 participants (1640 TAVR and 1584 SAVR) were included. The weighted mean age was 81.6 years and 55.2% were men. There existed substantial variation across studies in the degree of baseline renal function and the definition of AKI. Two studies defined AKI as the need for renal replacement therapy [4, 5], one as an increase in serum creatinine greater than 50% of the baseline [6], and the other as KDIGO stage 2–3 [7]. The incidence of AKI was reported between 2.9–5.8% and 0–13.5% for TAVR and SAVR, respectively. Three main studies (including 98% of the included patients) reported lower incidence of AKI with TAVR compared to SAVR. Two studies [6, 7] reached statistical significance (RR 0.43, 95% CI 0.27–0.69, and RR 0.41, 95% CI 0.22–0.74, respectively) and one [5] did not (RR 0.96, 95% CI 0.53–1.74). The RR of AKI could not be calculated from the smallest study [4] that included 70 patients because there were no cases of AKI in the SAVR group. The limited number of RCTs that have compared TAVR and SAVR used diverse definitions for post-procedural renal complications. Currently available evidence suggests that the two options for treatment of aortic stenosis might portend distinct impact on renal function; TAVR is associated with lower RR of AKI compared to SAVR. Future prospective studies with pre-defined renal endpoints are needed to confirm these findings and evaluate the impact of baseline renal function on the incidence of post-procedural renal complications. Author contributions All the authors had access to the data and contributed to writing of the manuscript.

Distinct renal outcomes for transcatheter aortic valve replacement and surgical repair.

Polyomavirus in a Lung Transplant Patient

In contrast to significant advances in the management of patients with chronic heart failure over the past few years, there has been little change in how patients with acute heart failure are treated. Symptoms and signs of fluid overload are the primary reason for hospitalization of patients who experience acute decompensation of heart failure. Intravenous loop diuretics remain the mainstay of therapy in this patient population, with a significant subset of them showing suboptimal response to these agents leading to incomplete decongestion at the time of discharge. Combination diuretic therapy, i.e., using loop diuretics along with an add-on agent, is a widely applied strategy to counter renal sodium avidity through sequential blockade of sodium absorption within renal tubules. The choice of the second diuretic is affected by several factors including the site of action, the anticipated secondary effects, and the available evidence on their efficacy and safety. While current guidelines recommend combination diuretic therapy as a viable option to overcome suboptimal response to loop diuretics, it is also acknowledged that this strategy is not supported by strong evidence and remains an area of uncertainty. The recent publication of landmark studies has regenerated the interest in sequential nephron blockade. Herein, we provide an overview of the results of the key studies on combination diuretic therapy in the setting of acute heart failure and discuss their findings primarily with regards to the impact on renal sodium avidity and cardiorenal outcomes.

Combination Diuretic Therapy to Counter Renal Sodium Avidity in Acute Heart Failure: Trials and Tribulations.

To the Editor, A well-recognized complication of peritoneal dialysis (PD) is the catheter exitsite infection. While the common causative organisms include Staphylococcus species [1], immunocompromised patients are susceptible to atypical or resistant infections and serious complications [2, 3]. This is particularly important as the number of patients initiating dialysis after a failed renal transplant is increasing; hence there is the need for continued immunosuppressive therapy to prevent allosensitization in anticipation of a potential re-transplant. A 60-year-old woman with a history of end-stage renal disease treated with PD presented with a 2-day history of pain, redness, and purulent discharge from the catheter exit site (Fig. 1a). There were no symptoms or signs of tunnel infection or peritonitis. She had a failed renal transplant one and a half years ago and was followed up by a transplant nephrologist who continued treatment with azathioprine 75 mg/day and prednisone 10 mg/day. Three months earlier, she had completed a 9-month antibiotic course for Mycobacterium fortuitumassociated exit-site infection, albeit without modification of her immunosuppression regimen. This time, she was empirically started on oral ciprofloxacin without any improvement, and 3 days later, she experienced a spontaneous extrusion of the external cuff of the PD catheter. Exit-site culture grew extended-spectrum beta-lactamasepositive Escherichia coli resistant to multiple antibiotics. She was treated with intraperitoneal imipenem-cilastatin and it was decided that immunosuppressive agents be reduced (azathioprine 50 mg/day and prednisone 5 mg/day). On doing this, significant clinical improvement was observed within a week (Fig. 1b). This case highlights the importance of the judicious use of immunosuppressive agents after a failed transplant; the expected benefits of such an approach should be carefully balanced against its potentially serious risks. Moreover, the phenomenon of skin changes that occur at the exit-site leading to extrusion of the external cuff is a rare and less well-recognized complication of the exit-site infection [4]. It may indeed start a vicious cycle by further increasing her susceptibility to future PDrelated infections in the background of continued immunosuppression.

Catheter Cuff Extrusion Following Exit-Site Infection in an Immunosuppressed Patient: One Case and Two Lessons.

Accessible online at: www.karger.com/int Sir, We read with great interest the paper of Merlino et al. [1] recently published in your journal. They discuss the monthly monitoring of BK virus infection in 15 renal transplant recipients (RTRs) by serum and urine quantitative polymerase chain reaction assay and conclude on a number of biological and clinical issues. There are some concerns about the methodology of this study that might adversely influence the clinical relevance of results and conclusions. First, regarding the risk of BK virus nephropathy (BKN), it is likely that the patients included in this study do not represent the overall RTR population. These patients were included at a median time of 5 years (ranging from 7 months to 14 years) posttransplant. However, most cases of BKN have been diagnosed about 40 weeks posttransplant [2] and the largest retrospective study on BKN [3] found the mean time of diagnosis to be 12.8 months after transplantation. Immunosuppression that plays a crucial role in the development of this pathology is reduced over time post-transplantation, especially after the first year. Therefore, the patients included in this study have been at significantly less risk for BKN compared to the overall RTR population. This may explain the fact that no correlation has been found between BK viruria and/or viremia and impairment of allograft function, although other authors have previously found a relationship between viral load in plasma and biopsy-proven BKN [2, 4]. The relatively short follow-up period (6 months) may also have added to this effect. Second, considering the median posttransplant time in this study (5 years), there are also other more prevalent pathologies (e.g. chronic allograft dysfunction and calcineurin inhibitor toxicity) that might have contributed to renal impairment in these RTRs. It seems then difficult to discuss the presence or absence of a causal relationship between BK virus infection and allograft dysfunction without considering the potential interaction of these factors. Data on the number of biopsies and their results could be useful in this setting. Finally, the potential role of tacrolimus and cyclosporin in BKN has been compared in these RTRs without taking into consideration other important factors [2] that have been suggested to predispose a patient to BK virus infection (e.g. prior episode of rejection). In our opinion, lack of data on such confounding factors at baseline makes such a comparison impossible. Considering the similar number of RTRs in each group as well as the wide range of post-transplant time, it seems unlikely that the patients were selected in a randomized and consequent manner. The possibility of a selection bias must then be considered while reviewing the results in these two groups.

Amir Kazory

Papers

Distinct renal outcomes for transcatheter aortic valve replacement and surgical repair.

Polyomavirus in a Lung Transplant Patient

Combination Diuretic Therapy to Counter Renal Sodium Avidity in Acute Heart Failure: Trials and Tribulations.

Catheter Cuff Extrusion Following Exit-Site Infection in an Immunosuppressed Patient: One Case and Two Lessons.

Clinical relevance of BK virus quantitative PCR in renal transplantation.