Point-of-Care Ultrasound Use in Nephrology: A Survey of Nephrology Program Directors, Fellows, and Fellowship Graduates.

Rationale & Objective: Adoption of point-of-care ultrasound (POCUS) into nephrology practice has been relatively slow. We surveyed US nephrology program directors, their fellows, and graduates from a single training program regarding current/planned POCUS training, clinical use, and barriers to training and use. Study Design: Anonymous, online survey. Setting & Participants: All US nephrology program directors (n=151), their fellows (academic year 2021-2022), and 89/90 graduates (1980-2021) of the Walter Reed Nephrology Program. Analytical Approach: Descriptive. Results: 46% (69/151) of program directors and 33% (118/361) of their fellows responded. Response rate was 62% (55/89) for Walter Reed graduates. 51% of program directors offered POCUS training, most commonly bedside training in non-POCUS oriented rotations (71%), didactic lectures (68%), and simulation (43%). 46% of fellows reported receiving POCUS training, but of these, many reported not being sufficiently trained/not confident in kidney (56%), bladder (50%), and inferior vena cava assessment (46%). Common barriers to training reported by program directors were not enough trained faculty (78%), themselves not being sufficiently trained (55%), and equipment expense (51%). 64% of program directors and 55% of fellows reported <10% of faculty were able to perform POCUS. 64% of fellows reported having too little POCUS training. 72% of program directors and 77% of graduates felt POCUS should be incorporated into the fellowship curriculum. 59% of fellows and 61% of graduates desired hands-on POCUS training rather than didactic lectures or simulation. Limitations: Loss of respondents as program directors and fellows progressed through the survey. Conclusions: Nephrology program directors, fellows, and graduates surveyed want POCUS training incorporated into the fellowship curriculum. No group felt sufficiently trained to confidently perform POCUS, and the major barrier to training was lack of sufficiently trained faculty. This highlights the need to "train the trainers" before POCUS can be fully integrated into fellowship training and regularly used in nephrology practice.

Fatigability and the Role of Neuromuscular Impairments in Chronic Kidney Disease.

BACKGROUND: The combination of neuromuscular impairments plus psychosocial aspects of chronic kidney disease (CKD) may predispose these patients to greater risk for experiencing increased levels of fatigability. There has been extensive clinical and scientific interest in the problem of fatigue in CKD and end-stage kidney disease (ESKD) patients, whereas less attention has been directed to understanding fatigability. Accordingly, the primary purposes of this review are to (1) discuss fatigue and fatigability and their potential interactions in patients with CKD and ESKD, (2) provide evidence for increased fatigability in CKD and ESKD patients, (3) examine how commonly experienced neuromuscular impairments in CKD and ESKD patients may contribute to the severity of performance fatigability, and (4) highlight preliminary evidence on the effects of exercise as a potential clinical treatment for targeting fatigability in this population. SUMMARY: Fatigue is broadly defined as a multidimensional construct encompassing a subjective lack of physical and/or mental energy that is perceived by the individual to interfere with usual or desired activities. In contrast, fatigability is conceptualized within the context of physical activity and is quantified as the interactions between reductions in objective measures of performance (i.e., performance fatigability) and perceptual adjustments regulating activity performance (i.e., perceived fatigability). We propose herein a conceptual model to extend current understandings of fatigability by considering the interactions among fatigue, perceived fatigability, and performance fatigability. Neuromuscular impairments reported in patients with CKD and ESKD, including reductions in force capacity, skeletal muscle atrophy, mitochondrial dysfunction, abnormal skeletal muscle excitability, and neurological complications, may each contribute to the greater performance fatigability observed in these patients. KEY MESSAGES: Considering the interactions among fatigue, perceived fatigability, and performance fatigability provides a novel conceptual framework to advance the understanding of fatigability in CKD and ESKD patients. Measures of fatigability may provide valuable clinical insights into the overall health status of CKD and ESKD patients. Existing data suggest that CKD and ESKD patients are at greater risk of experiencing increased fatigability, partly due to neuromuscular impairments associated with reduced kidney function. Further investigations are warranted to determine the potential clinical role fatigability measures can play in monitoring the health of CKD and ESKD patients, and in identifying potential treatments targeting fatigability in this patient population.

Physical Activity and Exercise for Cardiorespiratory Health and Fitness in Chronic Kidney Disease.

Chronic kidney disease (CKD) is associated with an increased risk for cardiovascular disease (CVD), major adverse CVD events, and cardiovascular mortality. Low levels of physical activity and reduced cardiorespiratory fitness further compound the health consequences in this patient population. Aerobic exercise alone and the combination of aerobic and resistance exercise have beneficial effects for improving aerobic capacity while resistance exercise alone improves strength and skeletal muscle health. Given the prevalence of CVD in CKD patients and limited treatment options targeting traditional and non-traditional CVD risk factors in this population, the incoroporation of physical activity and exercise into the care of CKD seems critical for improving patient outcomes. Therefore, the purpose of this narrative review is to discuss the evidence of physical activity and exercise in CKD patients and the effects on cardiovascular outcomes and fitness.

Social Support, Caregivers, and Chronic Kidney Disease.

The morbidity and mortality associated with chronic kidney disease remains unacceptably high. Psychosocial issues in CKD patients are frequently overlooked yet are often modifiable risk factors for mortality. Addressing patient perception of social support can potentially improve patient outcomes.

Comparative Efficacy of Therapies for Treatment of Depression for Patients Undergoing Maintenance Hemodialysis: A Randomized Clinical Trial.

Background: Although depression is common among patients receiving maintenance hemodialysis, data on their acceptance of treatment and on the comparative efficacy of various therapies are limited. Objective: To determine the effect of an engagement interview on treatment acceptance (phase 1) and to compare the efficacy of cognitive behavioral therapy (CBT) versus sertraline (phase 2) for treating depression in patients receiving hemodialysis. Design: Multicenter, parallel-group, open-label, randomized controlled trial. (ClinicalTrials.gov: NCT02358343). Setting: 41 dialysis facilities in 3 U.S. metropolitan areas. Participants: Patients who had been receiving hemodialysis for at least 3 months and had a Beck Depression Inventory-II score of 15 or greater; 184 patients participated in phase 1, and 120 subsequently participated in phase 2. Intervention: Engagement interview versus control visit (phase 1) and 12 weeks of CBT delivered in the dialysis facility versus sertraline treatment (phase 2). Measurements: The primary outcome for phase 1 was the proportion of participants who started depression treatment within 28 days. For phase 2, the primary outcome was depressive symptoms measured by the Quick Inventory of Depressive Symptoms-Clinician-Rated (QIDS-C) at 12 weeks. Results: The proportion of participants who initiated treatment after the engagement or control visit did not differ (66% vs. 64%, respectively; P = 0.77; estimated risk difference, 2.1 [95% CI, -12.1 to 16.4]). Compared with CBT, sertraline treatment resulted in lower QIDS-C depression scores at 12 weeks (effect estimate, -1.84 [CI, -3.54 to -0.13]; P = 0.035). Adverse events were more frequent in the sertraline than the CBT group. Limitation: No randomized comparison was made with no treatment, and persistence of treatment effect was not assessed. Conclusion: An engagement interview with patients receiving maintenance hemodialysis had no effect on their acceptance of treatment for depression. After 12 weeks of treatment, depression scores were modestly better with sertraline treatment than with CBT. Primary Funding Source: Patient-Centered Outcomes Research Institute, Dialysis Clinic, Kidney Research Institute, and National Institute of Diabetes and Digestive and Kidney Diseases.

Thrombotic Microangiopathies with Rheumatologic Involvement.

Thrombotic microangiopathies are heterogeneous disorders characterized by microangiopathic hemolytic anemia with thrombocytopenia and renal injury. There are a variety of causes, including metabolic disorders, infections, medications, complement disorders, pregnancy, malignancy, and autoimmune disorders. This review focuses on renal thrombotic microangiopathy in the setting of rheumatologic diseases. Systemic lupus erythematosus is the most common autoimmune disease associated with thrombotic microangiopathy. Other etiologies include scleroderma renal crisis and antiphospholipid antibody syndrome, which can be primary or secondary to autoimmune diseases including systemic lupus erythematosus. There have also been case reports of thrombotic microangiopathy in the setting of rheumatoid arthritis and dermatomyositis.

Anxiety in Patients Treated with Hemodialysis.

Anxiety is a common yet frequently overlooked psychiatric symptom in patients with ESRD treated with hemodialysis (HD). Anxiety is characterized by disruptive feelings of uncertainty, dread, and fearfulness. A variety of common medical complaints may be manifestations of an anxiety disorder, including palpitations, tremors, indigestion, numbness/tingling, nervousness, shortness of breath, diaphoresis, and fear. It is essential for the clinician to rule out specific medical conditions, including cardiovascular, pulmonary, and neurologic diseases, before ascribing these symptoms to an anxiety disorder. In addition, there is considerable overlap between the symptoms of anxiety and those of depression and uremia. This psychiatric condition has a significant adverse impact on patients' perception of quality of life. Little is known regarding the prevalence and impact of anxiety disorders in patients with ESRD treated with HD; however, many of the seemingly irrational behaviors of patients, or behaviors which place them in conflict with staff and physicians, such as behavioral noncompliance, may be the expression of an underlying anxiety disorder. In this review, we present three clinical vignettes, highlighting the impact of anxiety disorders in patients with ESRD treated with HD.

HIV-associated immune complex kidney disease.

The introduction in the late 20(th) century of combination antiretroviral therapy (cART) to treat patients infected with HIV has changed the natural history of the disease from an acute illness that rapidly culminates in death, to a chronic condition that can be managed with medications. Over the past decade the epidemiology of kidney disease in US patients infected with HIV has changed, perhaps because of the increased availability and use of cART. Patients with HIV infection exhibit unique immunologic characteristics, including immunodeficiency and dysregulation of immunoglobulin synthetic responses and T-cell function, which can result in glomerular immune complex deposition and subsequent kidney injury. This Review examines the differential diagnoses of HIV-associated immune complex kidney diseases (HIVICD), and discusses the clinical manifestations and mechanisms underlying their development. We address the issues associated with treatment, clinical outcomes, and research needs to enhance our ability to diagnose and optimally treat patients with HIVICD.

Quality of life and mental health related to timing, frequency and dose of hemodialysis.

The perceived quality of life (QOL) and mental health of dialysis patients can have a significant impact on clinical outcomes in the end-stage renal disease (ESRD) population. There is growing interest in increasing dialysis frequency, dose and duration to achieve more adequate dialysis clearance, particularly of middle molecules. Over the past decade, there has been an interest in earlier initiation of dialysis; however, the results of the IDEAL study call this practice into question, and showed no difference in QOL scores between the early-start and later start dialysis patients. There are inconsistent results regarding the impact of increased dialysis frequency and dose on patients' perceived health-related QOL (HRQOL). Some studies of daily nocturnal dialysis patients show a positive impact on QOL, while others show no significant difference. The disparate outcomes may be partly related to differences in the demographic characteristics of the study populations and the specific questionnaires used to measure HRQOL. Additional research is necessary to determine whether changes in dialysis frequency, timing, and dose can positively or negatively impact patients' perceptions of their QOL and mental health.

Long-term sequelae of acute kidney injury in the ICU.

PURPOSE OF REVIEW: Acute kidney injury (AKI) in the ICU is associated with adverse outcomes. We review the long-term consequences of AKI in ICU patients. RECENT FINDINGS: Observational studies show associations between AKI and mortality, prolonged length of ICU stay, dependence on mechanical ventilation, the development and progression of chronic kidney disease (CKD), and need for permanent renal replacement therapy. Few studies evaluate ICU AKI outcomes specifically, and data on long-term outcomes of survivors from this population are sparse. Little information exists comparing AKI in ICU and non-ICU settings, and prospective study designs to address such questions are problematic. AKI in the ICU should be distinguished from AKI in other clinical settings, as the underlying pathophysiology, severity of illness, and risk for permanent sequelae may be different. AKI and CKD are not mutually exclusive, but are part of a clinical spectrum in which AKI can potentiate the risk for CKD and pre-existing CKD increases risks of AKI. SUMMARY: Further research is necessary to delineate the mechanisms by which AKI may lead to CKD, and to understand how CKD enhances the risk for developing AKI. Whereas restrospective observational studies of this population exist, prospective clinical studies and trials evaluating the long-term clinical outcomes of AKI specifically in ICU patients are needed.

Idiopathic membranous nephropathy: clinical and histologic prognostic features and treatment patterns over time at a tertiary referral center.

BACKGROUND: Idiopathic membranous nephropathy (i-MN) is a leading cause of nephrotic syndrome in adults and results in end-stage renal disease in approximately one third of patients. There are few large, long-term US studies evaluating clinical and histologic prognostic factors in i-MN. METHODS: We describe 132 patients with biopsy-proven i-MN who were followed for a mean period of 68 months at our tertiary referral center from 1977 to 2009, and we analyzed clinical and histologic features that predicted renal outcomes. RESULTS: The presence of hypertension and treating physician's decision to institute immunosuppression were negative predictors of attaining complete or partial remission. Among clinical variables, impaired renal function (eGFR <60 ml/min/1.73 m(2)) at time of presentation was the only variable at presentation associated with an increased risk of reaching end-stage renal disease. The use of statins and RAAS blockers were protective. The choice of corticosteroids as the initial immunosuppressive agent by referring physicians decreased over time but even in the most recent era (2000-2008) was significant (33%). CONCLUSION: Renal function at presentation and non-white race were the main predictors of a worse renal outcome. Corticosteroid therapy is still being adopted as first-line therapy in a significant number of patients in this era. The development of guidelines may help clarify the treatment strategies of i-MN.

A new apolipoprotein E mutation, apoE Las Vegas, in a European-American with lipoprotein glomerulopathy.

Lipoprotein glomerulopathy is a rare disease diagnosed by unique histopathologic findings of glomerular capillary dilatation by lipoprotein thrombi. The disease is caused by mutations in apoE, the gene that encodes apolipoprotein E. To date, <80 cases have been reported in the medical literature, nearly all of which are from Japan or China. Only five cases from the United States have previously been reported, of which three patients were of European ancestry. Here, we present the fourth case of lipoprotein glomerulopathy in a European-American man. Whereas prior European-American patients with lipoprotein glomerulopathy were found to have the previously reported apoE Kyoto genotype, the patient presented here was found to have a novel mutation that we have named apoE Las Vegas.

Renal transplantation in familial dysautonomia: report of two cases and review of the literature.

BACKGROUND AND OBJECTIVES: Chronic kidney disease (CKD) is an increasingly recognized complication of familial dysautonomia (FD), a neurodevelopmental disorder with protean systemic manifestations that are the result of sensory and autonomic dysfunction. Progressive renal dysfunction occurs due to chronic volume depletion and cardiovascular lability with supine hypertension and orthostatic hypotension. By age 25, nearly one-half of all patients with FD will have reached stage 3 CKD. Furthermore, dialysis for ESRD in FD patients is associated with multiple complications and poor outcomes. DESIGN, SETTINGS, PARTICIPANTS, & MEASUREMENTS: We report two patients with FD who developed ESRD at ages 27 and 16, respectively, and underwent renal transplantation. Transplant was performed after 3 months on intermittent hemodialysis (HD) in the first case and after 1 month on twice-weekly continuous veno-venous hemodialysis (CVVHD) in the second case. RESULTS: Both patients tolerated surgery well and have maintained good graft function at 20 and 24 months posttransplantation, respectively. Symptomatic and functional improvements have included lower supine BP and increased sensitivity to antihypertensive agents. CONCLUSIONS: As general supportive care improves the lifespan of FD patients, issues related to the management of ESRD will become more important. Renal transplantation provides a viable alternative to dialysis for FD patients with ESRD.

Beneficial effect of rituximab in the treatment of recurrent idiopathic membranous nephropathy after kidney transplantation.

BACKGROUND AND OBJECTIVES: Recurrence of the original kidney disease after renal transplantation is an increasingly recognized cause of allograft loss. Idiopathic membranous nephropathy (iMN) is a common cause of proteinuria that may progress to ESRD. It is known that iMN may recur after kidney transplantation, causing proteinuria, allograft dysfunction, and allograft loss. Limited data regarding the frequency and treatment of recurrent iMN are available. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this single-center study, all patients who had iMN and were receiving a first kidney transplant were included. We retrospectively assessed the incidence of biopsy-confirmed recurrent iMN and compared clinical characteristics of patients with and without recurrence. In addition, the effect of treatment with rituximab on proteinuria and renal allograft function in patients with recurrent iMN was examined RESULTS: The incidence of recurrent iMN was 44%, and recurrences occurred at a median time of 13.6 months after transplantation. Two patterns of recurrence were identified: Early and late. No predictors of recurrence or disease progression could be identified. Treatment with rituximab was effective in four of four patients in stabilizing or reducing proteinuria and stabilizing renal function. CONCLUSIONS: Recurrence of iMN is common even in the era of modern immunosuppression. Rituximab seems to be a valuable treatment option for these patients, although lager studies are needed to confirm our data.

Novel B cell therapeutic targets in transplantation and immune-mediated glomerular diseases.

B cells and antibodies play an important role in the alloresponse to renal grafts as well as in immune-mediated glomerular diseases. In transplantation, greater recognition and improved diagnosis of antibody-mediated rejection have been a catalyst to the introduction of newer drugs and regimens that target B cells, plasma cells, and donor-specific antibodies to improve the outcome associated with antibody-mediated rejection. In immune-mediated renal disease, novel and more selective B cell therapies are gradually modifying the traditional therapeutic approach that consists of steroids and other immunosuppressants. A new era of selective and more effective immunosuppression agents that target the humoral response is finally emerging in transplantation and renal diseases.