Jeffrey M. Turner

Treatment of chronic kidney disease

Treatment of chronic kidney disease (CKD) can slow its progression to end-stage renal disease (ESRD). However, the therapies remain limited. Blood pressure control using angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) has the greatest weight of evidence. Glycemic control in diabetes seems likely to retard progression. Several metabolic disturbances of CKD may prove to be useful therapeutic targets but have been insufficiently tested. These include acidosis, hyperphosphatemia, and vitamin D deficiency. Drugs aimed at other potentially damaging systems and processes, including endothelin, fibrosis, oxidation, and advanced glycation end products, are at various stages of development. In addition to the paucity of proven effective therapies, the incomplete application of existing treatments, the education of patients about their disease, and the transition to ESRD care remain major practical barriers to better outcomes.

Loop Diuretic Efficiency A Metric of Diuretic Responsiveness With Prognostic Importance in Acute Decompensated Heart Failure

Background— Rather than the absolute dose of diuretic or urine output, the primary signal of interest when evaluating diuretic responsiveness is the efficiency with which the kidneys can produce urine after a given dose of diuretic. As a result, we hypothesized that a metric of diuretic efficiency (DE) would capture distinct prognostic information beyond that of raw fluid output or diuretic dose. Methods and Results— We independently analyzed 2 cohorts: (1) consecutive admissions at the University of Pennsylvania (Penn) with a primary discharge diagnosis of heart failure (n=657) and (2) patients in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) data set (n=390). DE was estimated as the net fluid output produced per 40 mg of furosemide equivalents, then dichotomized into high versus low DE based on the median value. There was only a moderate correlation between DE and both intravenous diuretic dose and net fluid output (r2⩽0.26 for all comparisons), indicating that DE was describing unique information. With the exception of metrics of renal function and preadmission diuretic therapy, traditional baseline characteristics, including right heart catheterization variables, were not consistently associated with DE. Low DE was associated with worsened survival even after adjusting for in-hospital diuretic dose, fluid output, in addition to baseline characteristics (Penn: hazards ratio [HR], 1.36; 95% confidence interval [CI], 1.04−1.78; P=0.02; ESCAPE: HR, 2.86; 95% CI, 1.53−5.36; P=0.001). Conclusions— Although in need of validation in less-selected populations, low DE during decongestive therapy portends poorer long-term outcomes above and beyond traditional prognostic factors in patients hospitalized with decompensated heart failure.Background— Rather than the absolute dose of diuretic or urine output, the primary signal of interest when evaluating diuretic responsiveness is the efficiency with which the kidneys can produce urine after a given dose of diuretic. As a result, we hypothesized that a metric of diuretic efficiency (DE) would capture distinct prognostic information beyond that of raw fluid output or diuretic dose. Methods and Results— We independently analyzed 2 cohorts: (1) consecutive admissions at the University of Pennsylvania (Penn) with a primary discharge diagnosis of heart failure (n=657) and (2) patients in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) data set (n=390). DE was estimated as the net fluid output produced per 40 mg of furosemide equivalents, then dichotomized into high versus low DE based on the median value. There was only a moderate correlation between DE and both intravenous diuretic dose and net fluid output (r2≤0.26 for all comparisons), indicating that DE was describing unique information. With the exception of metrics of renal function and preadmission diuretic therapy, traditional baseline characteristics, including right heart catheterization variables, were not consistently associated with DE. Low DE was associated with worsened survival even after adjusting for in-hospital diuretic dose, fluid output, in addition to baseline characteristics (Penn: hazards ratio [HR], 1.36; 95% confidence interval [CI], 1.04−1.78; P =0.02; ESCAPE: HR, 2.86; 95% CI, 1.53−5.36; P =0.001). Conclusions— Although in need of validation in less-selected populations, low DE during decongestive therapy portends poorer long-term outcomes above and beyond traditional prognostic factors in patients hospitalized with decompensated heart failure.

Acute kidney injury as a causal factor in mortality associated with hepatorenal syndrome

PurposeWe examine how acute kidney injury (AKI) contributes to mortality in patients with liver failure.ContentHepatorenal syndrome (HRS) is a form of AKI in cirrhotic patients, which is defined as a purely physiologic derangement in renal function without any effect on renal parenchyma. Recent literature challenges this understanding. Little attention is paid to the presence of renal pathology and inflammatory alterations that occur as a result of HRS and their contribution to morbidity and mortality. In this paper, we propose that any type of AKI in the presence of liver disease is an inflammatory condition. The combination of AKI and liver failure produces a “toxic milieu” of cytokines, chemokines, and nitric oxide pathway metabolites that directly cause endothelial dysfunction affecting multiple organ systems. These global effects contribute to the increased short- and long-term mortality which has been established in the epidemiologic literature.

Blood pressure targets for hemodialysis patients

The association between blood pressure (BP) and mortality is unique in hemodialysis patients compared with that in the general population. This is because of an altered benefit-risk balance associated with BP reduction in these patients. An adequately designed study comparing BP targets in hemodialysis patients remains to be conducted. The current evidence available to guide dialysis providers regarding treatment strategies for managing hypertension in this population is limited to large observational studies and small randomized controlled trials. In this opinion article, we review these data and discuss the key points regarding BP management for hemodialysis patients. Our aim is to provide a practical opinion regarding BP targets that nephrologists can incorporate into clinical practice, with a focus on moving away from dialysis unit BPs and focusing on out-of-dialysis unit BPs.

We Avoid RAAS Inhibitors in PD Patients with Residual Renal Function.

Preserving residual renal function in patients on peritoneal dialysis (PD) positively impacts mortality. While it is important to avoid nephrotoxic agents in this setting, clinicians should appreciate that inhibitors of the renin‐angiotensin‐aldosterone system (RAAS), including angiotensin converting enzyme inhibitors, and angiotensin receptor blockers are likely to preserve glomerular filtration rate and prolong the time until patients on PD reach anuria, and this may improve mortality in these patients. In addition, RAAS blockade favorably affects the peritoneal membrane by reducing morphologic changes that can lead to ultrafiltration failure. This in turn may delay or prevent modality failure in patients on PD. Thus, clinicians should avoid the impulse to stop RAAS inhibitors in the PD population.

Nutritional Supplements for the Treatment of Hypertension: A Practical Guide for Clinicians

Nutraceuticals are dietary components with pharmacologic properties that can be used to treat various disease states. There is growing interest among patients in the use of nutraceuticals for the management of hypertension; as such, it is important that clinicians are prepared to engage in meaningful discussions with their patients about these substances. Flavonoids, beetroot, garlic, and unsaturated fats have garnered significant attention for their blood pressure lowering properties. We review the clinical evidence and reported mechanisms of action for these substances in an attempt to offer a practical guide for clinicians to engage with patients who are highly motivated to seek out nutraceutical therapies to manage their hypertension.

Barriers to Advance Care Planning in End-Stage Renal Disease: Who is to Blame, and What Can be Done?

Patients with end-stage renal disease experience significant mortality and morbidity, including cognitive decline. Advance care planning has been emphasized as a responsibility and priority of physicians caring for patients with chronic kidney disease in order to align with patient values before decision-making capacity is lost and to avoid suffering. This emphasis has proven ineffective, as illustrated in the case of a patient treated in our hospital. Is this ineffectiveness a consequence of failure in the courtroom or the clinic? Through our own experience we affirm what has been written before: that legal precedent favors intensive treatment in virtually all cases without ‘clear and convincing evidence’ of a patient’s previously declared wishes to the contrary. Equally clear is that more than 20 years of support in the clinical literature suggesting advance care planning early in the course of disease can address challenges in the legal system for those lacking capacity. However, many physicians fail to recognize the need for advance care planning in a timely manner and lack the necessary training to provide it. The need for more training and new tools to recognize opportunities for advance care planning in daily practice remains unmet.

Loop Diuretic EfficiencyCLINICAL PERSPECTIVE

Background— Rather than the absolute dose of diuretic or urine output, the primary signal of interest when evaluating diuretic responsiveness is the efficiency with which the kidneys can produce urine after a given dose of diuretic. As a result, we hypothesized that a metric of diuretic efficiency (DE) would capture distinct prognostic information beyond that of raw fluid output or diuretic dose. Methods and Results— We independently analyzed 2 cohorts: (1) consecutive admissions at the University of Pennsylvania (Penn) with a primary discharge diagnosis of heart failure (n=657) and (2) patients in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) data set (n=390). DE was estimated as the net fluid output produced per 40 mg of furosemide equivalents, then dichotomized into high versus low DE based on the median value. There was only a moderate correlation between DE and both intravenous diuretic dose and net fluid output (r2⩽0.26 for all comparisons), indicating that DE was describing unique information. With the exception of metrics of renal function and preadmission diuretic therapy, traditional baseline characteristics, including right heart catheterization variables, were not consistently associated with DE. Low DE was associated with worsened survival even after adjusting for in-hospital diuretic dose, fluid output, in addition to baseline characteristics (Penn: hazards ratio [HR], 1.36; 95% confidence interval [CI], 1.04−1.78; P=0.02; ESCAPE: HR, 2.86; 95% CI, 1.53−5.36; P=0.001). Conclusions— Although in need of validation in less-selected populations, low DE during decongestive therapy portends poorer long-term outcomes above and beyond traditional prognostic factors in patients hospitalized with decompensated heart failure.Background— Rather than the absolute dose of diuretic or urine output, the primary signal of interest when evaluating diuretic responsiveness is the efficiency with which the kidneys can produce urine after a given dose of diuretic. As a result, we hypothesized that a metric of diuretic efficiency (DE) would capture distinct prognostic information beyond that of raw fluid output or diuretic dose. Methods and Results— We independently analyzed 2 cohorts: (1) consecutive admissions at the University of Pennsylvania (Penn) with a primary discharge diagnosis of heart failure (n=657) and (2) patients in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) data set (n=390). DE was estimated as the net fluid output produced per 40 mg of furosemide equivalents, then dichotomized into high versus low DE based on the median value. There was only a moderate correlation between DE and both intravenous diuretic dose and net fluid output (r2≤0.26 for all comparisons), indicating that DE was describing unique information. With the exception of metrics of renal function and preadmission diuretic therapy, traditional baseline characteristics, including right heart catheterization variables, were not consistently associated with DE. Low DE was associated with worsened survival even after adjusting for in-hospital diuretic dose, fluid output, in addition to baseline characteristics (Penn: hazards ratio [HR], 1.36; 95% confidence interval [CI], 1.04−1.78; P =0.02; ESCAPE: HR, 2.86; 95% CI, 1.53−5.36; P =0.001). Conclusions— Although in need of validation in less-selected populations, low DE during decongestive therapy portends poorer long-term outcomes above and beyond traditional prognostic factors in patients hospitalized with decompensated heart failure.

Loop Diuretic EfficiencyCLINICAL PERSPECTIVE: A Metric of Diuretic Responsiveness With Prognostic Importance in Acute Decompensated Heart Failure

Background— Rather than the absolute dose of diuretic or urine output, the primary signal of interest when evaluating diuretic responsiveness is the efficiency with which the kidneys can produce urine after a given dose of diuretic. As a result, we hypothesized that a metric of diuretic efficiency (DE) would capture distinct prognostic information beyond that of raw fluid output or diuretic dose. Methods and Results— We independently analyzed 2 cohorts: (1) consecutive admissions at the University of Pennsylvania (Penn) with a primary discharge diagnosis of heart failure (n=657) and (2) patients in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) data set (n=390). DE was estimated as the net fluid output produced per 40 mg of furosemide equivalents, then dichotomized into high versus low DE based on the median value. There was only a moderate correlation between DE and both intravenous diuretic dose and net fluid output (r2⩽0.26 for all comparisons), indicating that DE was describing unique information. With the exception of metrics of renal function and preadmission diuretic therapy, traditional baseline characteristics, including right heart catheterization variables, were not consistently associated with DE. Low DE was associated with worsened survival even after adjusting for in-hospital diuretic dose, fluid output, in addition to baseline characteristics (Penn: hazards ratio [HR], 1.36; 95% confidence interval [CI], 1.04−1.78; P=0.02; ESCAPE: HR, 2.86; 95% CI, 1.53−5.36; P=0.001). Conclusions— Although in need of validation in less-selected populations, low DE during decongestive therapy portends poorer long-term outcomes above and beyond traditional prognostic factors in patients hospitalized with decompensated heart failure.Background— Rather than the absolute dose of diuretic or urine output, the primary signal of interest when evaluating diuretic responsiveness is the efficiency with which the kidneys can produce urine after a given dose of diuretic. As a result, we hypothesized that a metric of diuretic efficiency (DE) would capture distinct prognostic information beyond that of raw fluid output or diuretic dose. Methods and Results— We independently analyzed 2 cohorts: (1) consecutive admissions at the University of Pennsylvania (Penn) with a primary discharge diagnosis of heart failure (n=657) and (2) patients in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) data set (n=390). DE was estimated as the net fluid output produced per 40 mg of furosemide equivalents, then dichotomized into high versus low DE based on the median value. There was only a moderate correlation between DE and both intravenous diuretic dose and net fluid output (r2≤0.26 for all comparisons), indicating that DE was describing unique information. With the exception of metrics of renal function and preadmission diuretic therapy, traditional baseline characteristics, including right heart catheterization variables, were not consistently associated with DE. Low DE was associated with worsened survival even after adjusting for in-hospital diuretic dose, fluid output, in addition to baseline characteristics (Penn: hazards ratio [HR], 1.36; 95% confidence interval [CI], 1.04−1.78; P =0.02; ESCAPE: HR, 2.86; 95% CI, 1.53−5.36; P =0.001). Conclusions— Although in need of validation in less-selected populations, low DE during decongestive therapy portends poorer long-term outcomes above and beyond traditional prognostic factors in patients hospitalized with decompensated heart failure.

Treatment of hyperkalemia

Introduction: The pathophysiology of potassium imbalances has been a dynamic area of medical research over the years. Controversy exists about the effectiveness and safety of various treatment strategies for hyperkalemia. Areas covered: The following discussion reviews potassium homeostasis, highlights common etiologies responsible for hyperkalemia and describes the associated clinical manifestations. An in-depth discussion about treatment strategies focuses on: i) stabilizing myocardial cell membranes, ii) enhancing cellular uptake of potassium and iii) the removal of excess potassium. The data for safety and efficacy of various therapies are reviewed. Expert opinion: Certain aspects of treating hyperkalemia remain controversial. Serum potassium is tightly regulated within a narrow range and precisely assessing the degree of risk associated with a given degree of hyperkalemia can be difficult. For this reason, its important to individualize treatment strategies. Concerns regarding the risks of calcium administration in patients with digitalis toxicity continue to impact practice patterns for hyperkalemia. A review of the literature in this area allows us to apply reasonable caution in these situations. Finally, reviewing the incidence of adverse events associated with low potassium dialysate solutions provides insight into the safety of this practice.