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.

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.

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.

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.

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.

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.

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.

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.

Cytokine patterns and survival in haemodialysis patients.

BACKGROUND: Increased pro-inflammatory cytokine levels are associated with decreased survival. We performed factor analyses to determine if pro-inflammatory and anti-inflammatory cytokines in haemodialysis (HD) patients load onto one or two discrete factors and assessed if patients with a specific pattern of high pro-inflammatory cytokines have decreased survival compared to patients with a high anti-inflammatory cytokine pattern. METHODS: We evaluated 231 HD patients and analyzed them based on the three most common cytokine distribution patterns seen: a high pro-inflammatory group, a high anti-inflammatory group and all others. Survival and Cox regression analyses were performed. RESULTS: Factor analyses of individual cytokines showed that they loaded onto a single factor. Sixty-five patients had a pro-inflammatory pattern of high IL-1, IL-6 and TNF-alpha levels and low anti-inflammatory parameters, including IL-2, IL-4, IL-5, IL-12, CH50 and T-cell number. The next most frequent cytokine pattern was found in 20 patients with high levels of anti-inflammatory parameters. The patients with high pro-inflammatory cytokines had decreased survival compared to patients without a characteristic cytokine pattern. CONCLUSIONS: Further research is needed to better define the underlying causes of increased inflammation among end-stage renal disease patients and to apply anti-inflammatory therapies that may mitigate adverse effects on patient outcomes.

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.

Association of incident gout and mortality in dialysis patients.

Previous studies have shown that gout is associated with an increased risk for cardiovascular mortality in the general population, but this has not been well studied in patients with ESRD. In this study, the incidence of gout and its association with mortality was evaluated in 259,209 patients in the United States Renal Data System. Overall, the incidence of gout in the first year of dialysis was 5% and in the first 5 yr was 15.4%. Independent risk factors for gout in adjusted analyses included black race, older age, female gender, hypertension, ischemic heart disease, congestive heart failure, and alcohol use. Factors associated with a lower risk for gout included a history of diabetes, smoking, and peripheral vascular disease. Time-dependent Cox regression analysis suggested that an episode of gout was independently associated with a 1.5-fold increase in mortality risk (adjusted hazard ratio 1.49; 95% confidence interval 1.43 to 1.55). The mechanisms underlying this association require further study.

Immune complex renal disease and human immunodeficiency virus infection.

Immune complex glomerulonephritis is a common diagnosis in renal biopsy series of human immunodeficiency virus (HIV)-infected patients. There are a variety of glomerulonephritides associated with HIV infection, including IgA nephropathy, membranoproliferative glomerulonephritis, membranous nephropathy, lupus-like glomerulonephritis, immunotactoid glomerulopathy, and fibrillary glomerulonephritis. In addition, HIV-related proteins may be implicated in circulating immune complexes directly related to a response to the infection. In some cases, the relationship of the HIV infection to the glomerulonephritis is unclear. HIV infection is associated with the development of polyclonal hypergammaglobulinemia, which can promote the development of circulating immune complexes. It is not clear if HIV-associated glomerulonephritis is caused by the passive trapping of these circulating immune complexes or the in situ deposition of antibodies binding to HIV viral antigens. Some renal lesions that are seen in the setting of HIV infection more likely may be related to the presence of a co-infection such as hepatitis C virus infection. The optimal therapy for immune complex glomerulonephritis in the setting of HIV infection is unknown. Because of the underlying immunosuppressed state of many HIV-infected patients, caution with traditional cytotoxic therapies is advised. The role of antiretroviral therapy in modifying the course of these renal lesions is unclear.

Acute kidney injury in patients with human immunodeficiency virus infection.

PURPOSE OF REVIEW: To present an overview of the epidemiology and etiology of acute kidney injury (AKI) in patients infected with human immunodeficiency virus (HIV). RECENT FINDINGS: HIV-infected patients are at an increased risk of developing AKI. Potential risk factors for the development of AKI in this patient population include increased HIV viral loads, reduced CD4 cell counts, hepatitis C virus coinfection, a history of diabetes, black race, male gender, and baseline chronic kidney and hepatic disease. Observational studies have found an increased morbidity and mortality in HIV-infected patients who develop AKI. There are diverse etiologies of AKI in HIV-infected patients, with increasing reports of highly active antiretroviral therapy-related nephropathy secondary to tenofovir nephrotoxicity. There have also been recent case reports of HIV-infected patients who develop a unique form of acute interstitial nephritis secondary to diffuse infiltrative lymphocytosis syndrome. SUMMARY: There are a variety of etiologies of AKI in HIV-infected patients. Prompt diagnosis and treatment of AKI is critical to help prevent morbidity and mortality in this patient population.

Quality of life in patients with end-stage renal disease treated with hemodialysis: survival is not enough!

The quality of life (QoL) of end stage renal disease (ESRD) patients is a frequently overlooked yet critical consideration when evaluating the overall medical care of patients. There are a variety of measures used to assess the QoL of ESRD patients. Some of the more frequently used tools include the single-question QoL questionnaire, the 36 Item Short Form Health Survey (SF-36), and the Kidney Disease Quality of Life (KDQoL) questionnaire. The best intervention to improve the QoL of ESRD patients is renal transplantation. The role of erythropoietin and intensification of dialysis dose in improving patients' QoL is undergoing review. We have previously shown relationships between patients' perception of quality of life and depressive affect, perception of burden of illness (IEQ), social support (MSP), pain and sleep disturbances. Further studies should focus on interventions that modify patients' perceptions of these psychosocial parameters with the goal of improving their QoL. Treatment of depression, pain and sleep disorders holds particular promise in this regard.

Depression in patients with chronic renal disease: where are we going?

Depression is quite prevalent in the end-stage renal disease (ESRD) population, with rates as high as 30% in some dialysis centers. There are fewer data on the epidemiology of depression in patients with earlier stages of chronic kidney disease (CKD), but the disease burden may be just as high. Depression may be associated with worse medical outcomes, including increased mortality. Close attention to screening and treating depression in all patients may be necessary. Several instruments have been used to screen for depression. The most common validated depression screening measure in ESRD patients is the Beck Depression Inventory. There are limited data on the appropriate therapy for depression in CKD patients. Psychotherapy combined with antidepressant medications, such as selective serotonin reuptake inhibitors, may be the optimal form of therapy (always in close consultation with mental health professionals). Adverse effects of antidepressant medications should be considered before prescribing these agents, particularly in patients with reduced glomerular filtration rate. Additional studies are necessary to further evaluate the optimal methods to screen for and treat depression in patients with CKD.

Psychosocial aspects of chronic disease: ESRD as a paradigmatic illness.

Psychosocial issues are an understudied yet important concern in the overall health of hemodialysis (HD) patients. Stress is a concomitant of chronic illness and its treatment, and may have meaningful influences on psychological and medical outcomes. This article reviews the influences of psychopathology, social support, family issues, dialysis unit culture, and socioeconomic status on patients treated with center HD. Depressive affect and decreased perception of social support have been linked with mortality in several studies of ESRD patients. Decreased marital satisfaction, disturbances in family dynamics, and lower socioeconomic status (SES) have been associated with poorer health outcomes and can affect patients' perception of social support and depressive affect. Chronically ill ESRD patients who undergo treatment with constant interaction and observation by medical staff are potentially an ideal group for evaluation of the effects of stress and psychosocial factors on outcomes in those with chronic disease, as well as an excellent patient population for intervention to reduce morbidity and mortality. These interactions between potentially modifiable psychosocial risk factors for disease and medical aspects of illness form a paradigm for the study of interventions related to adjustment to chronic illness in the ESRD population.

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.