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

Hyponatremia is frequently encountered in patients with heart failure (HF), and its association with adverse outcomes is well-established in this population. While hyponatremia is an independent marker for severity of HF, it is not certain whether it has a causal impact on the progression of the disease. There are no universally accepted consensus guidelines regarding therapeutic strategies for HF-associated hyponatremia and volume overload; current societal guidelines do not address management of this complication. Whereas thiazide diuretics are known to induce or worsen hyponatremia in this setting through a number of mechanisms, loop diuretics can be considered a readily available first-line pharmacologic therapy. Consistent with pathophysiology of the disease and mechanisms of action of loop diuretics, available clinical evidence supports such an approach provided that patients can be closely monitored. Use of vasopressin receptor antagonists is an emerging therapeutic strategy in this setting, and the efficacy of these agents has so far been shown in a number of clinical studies. These agents can be reserved for patients with HF in whom initial appropriate loop diuretic therapy fails to improve serum sodium levels.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/clc.20791

Hyponatremia in heart failure: revisiting pathophysiology and therapeutic strategies.

Congestion represents the primary reason for hospitalization of patients with heart failure and is associated with adverse outcomes. Fluid overload has been shown to be inadequately addressed in a significant subset of these patients in part due to lack of robust, reliable, and readily available biomarkers for objective assessment and monitoring of therapy. Natriuretic peptides have long been used in this setting, often in conjunction with other assessment tools such as imaging studies. Patients presenting with concomitant cardiac and renal dysfunction represent a unique population with regard to congestion in that the interactions between the heart and the kidney can affect the utility and performance of biomarkers of fluid overload. Herein, we provide an overview of the currently available evidence on the utility of natriuretic peptides in these patients and discuss the clinical conundrum associated with their use in the setting of renal dysfunction. We highlight the potential divergence in the role of natriuretic peptides for assessment of volume status in a subset of patients with renal dysfunction who receive renal replacement therapy and call for future research to elucidate the utility of the biomarkers in this setting.

/pdf/natriuretic-peptides-as-biomarkers-for-congestive-states-the-10hon0oo14.pdf

Natriuretic Peptides as Biomarkers for Congestive States: The Cardiorenal Divergence

BK virus nephropathy (BKVN) is increasingly recognized as a major cause of renal allograft failure. Recent reports demonstrate that prompt reduction of immunosuppression upon detection of persistent viremia can be associated with resolution of viremia, with minimal risk of acute rejection (AR). However, these experiences in general have occurred in centers with low baseline risks of AR. It is possible that a finer balance between overimmunosuppression and the risk of AR may exist in centers that routinely transplant patients with higher risk of AR. Thus the risk/benefit of this strategy may be altered in these centers. We report a case of antibody-mediated rejection that followed reduction of immunosuppression for BKVN diagnosed more than 3 months after the onset of viremia. This rejection episode resulted in a greater decrease in graft function than the initial BKVN episode. Issues relevant to the management of these patients are discussed, including the need for improved immune monitoring assays to determine more accurately the balance between infection and rejection.

Immunosuppression reduction for BK virus nephropathy: a case for caution.

Ultrafiltration (UF) has emerged as an alternative therapy for acute decompensated heart failure (ADHF) due to its physiological benefits such as improvement in neurohormonal activation. We performed a systematic review and a meta-analysis to evaluate the efficacy, safety, and the impact on outcomes for UF therapy as compared to conventional medical treatment. The PubMed and Cochrane databases were searched from inception to December 2015 for randomized controlled trials that examined UF therapy in ADHF and used diuretic-based regimens as the control group. In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, we explored the impact on weight change, fluid removal, renal function, rehospitalization rate, and mortality. Mantel–Haenszel odds ratio (OR) was calculated for dichotomous data and weighted mean difference (WMD) for continuous data. Seven studies with a total of 771 patients met our selection criteria. UF therapy led to greater weight loss (WMD 1.35, 95 % CI 0.49–2.21, p < 0.01) and fluid removal (WMD 1.81, 95 % CI 1.01–2.62, p = <0.01) while the impact of UF on renal function was comparable with medical treatment (WMD 0.06, 95 % CI −0.11 to 0.22, p = 0.48), UF decreased heart failure rehospitalization rate (OR 0.60, 95 % CI 0.37–0.98, p = 0.04) but did not change mortality (OR 1.03, 95 % CI 0.68–1.57, p = 0.89). Compared with diuretic-based medical treatment, UF therapy is more efficient in decongestion of patients with ADHF. It does not have a deleterious impact on renal function and can improve heart failure-related rehospitalization rate, albeit without conferring a survival benefit.

Defining the role of ultrafiltration therapy in acute heart failure: a systematic review and meta-analysis.

Sir, Asahi et al. [1] recently reviewed the previously published cases of valacyclovir neurotoxicity (VAN) in your journal. They found a strong association between VAN and renal failure; all reported cases in the literature had some degree of renal dysfunction. Whilst the majority of these patients were receiving maintenance hemodialysis for end-stage renal disease (ESRD), there are only few reports on the correlation between changes in serum levels of valacyclovir and neurological status of the patient with regards to this modality of renal replacement therapy [2,3]. A 49-year-old woman with a history of ESRD on maintenance hemodialysis for 3 years was diagnosed with shingles of the left T4 dermatome. She was prescribed valacyclovir 1000 mg three times a day. After a total dose of 4000 mg, the patient was noted to be disoriented, confused, agitated, and hallucinating. On presentation to the emergency department, blood pressure was 170/85 mmHg, pulse 110, and temperature 36.7 C. She was found to be delirious, incoherent, oriented only to self, and following simple brief commands. There was no nuchal rigidity, reflexes were 1+ symmetrical, and she had no focal neurological deficits. Laboratory studies were unremarkable except for high blood urea nitrogen and creatinine and non-contrasted CT scan of the brain did not reveal any acute changes. VAN was suspected based on the history of recent initiation of valacyclovir, of which the dose was not adjusted for the degree of renal function. A serum valacyclovir level of 7.4 mcg/ml (normal: 2–4 mcg/ml) supported the diagnosis (measured via high-pressure liquid chromatography). The medication was stopped and the decision was made for emergent hemodialysis using a high-flux filter for two consecutive sessions of 4-h duration, separated by 12 h. The serum valacyclovir level decreased to 1.6 mcg/ml after the first hemodialysis treatment. Interestingly, the patient s mental status significantly improved in the middle of the second session and returned to baseline by the end of the treatment; the serum level of valacyclovir was found to be 0.83 mcg/ml at that time and did not rebound afterward (Fig. 1). Valacyclovir is the prodrug for acyclovir and is generally considered safe and efficacious. Administration of valacyclovir results in a twofold higher bioavailability compared with oral acyclovir. It is eliminated primarily by the kidneys through both glomerular filtration and tubular secretion. Therefore, the half-life of the drug is significantly prolonged in the presence of renal failure, increasing the possibility of serious adverse effects such as neurotoxicity. VAN includes a wide spectrum of neuropsychiatric disturbances ranging fromdizziness to coma [1]. Because the drug is readily dialyzable, high-flux and high-efficiency hemodialysis will provide rapid clearance of the drug. This observation adds to the previously published reports suggesting the role of hemodialysis in significant reduction in serum valacyclovir levels and improvement in symptoms [1,3]. We propose that only adjusted dose of valacyclovir should cautiously be used in patients with renal dysfunction, and that hemodialysis represents an efficient management strategy for rapid elimination of the drug in the setting of VAN.

Amir Kazory

Papers

Hyponatremia in heart failure: revisiting pathophysiology and therapeutic strategies.

Natriuretic Peptides as Biomarkers for Congestive States: The Cardiorenal Divergence

Immunosuppression reduction for BK virus nephropathy: a case for caution.

Defining the role of ultrafiltration therapy in acute heart failure: a systematic review and meta-analysis.

Valacyclovir neurotoxicity can be effectively managed by hemodialysis.