Racial and Ethnic Disparities in Kidney Replacement Therapies Among Adults With Kidney Failure: An Observational Study of Variation by Patient Age.

RATIONALE & OBJECTIVE: Non-Hispanic Black and Hispanic patients present with kidney failure at younger ages than White patients. Younger patients are also more likely to receive transplants and home dialysis than in-center hemodialysis (ICHD), but it is unknown whether racial and ethnic disparities in treatment differ by age. We compared use of kidney replacement therapies between racial and ethnic groups among patients with incident kidney failure overall and by age. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 830,402 US adult (age >21 years) patients initiating kidney failure treatment during the period of 2011-2018. EXPOSURES: Patient race and ethnicity (non-Hispanic Black, non-Hispanic White, Hispanic, or other) and age group (22-44, 45-64, 65-74, or 75-99 years). OUTCOME: Treatment modality (transplant, peritoneal dialysis [PD], home hemodialysis [HHD], or ICHD) as of day 90 of treatment. ANALYTICAL APPROACH: Differences in treatment modalities were quantified for patient subgroups defined by race and ethnicity and by age. Log-binomial regression models were fit to estimate adjusted risk ratios. RESULTS: 81% of patients were treated with ICHD, 3.0% underwent transplants (85% preemptive, 57% living-donor), 10.5% were treated with PD, and 0.7% were treated with HHD. Absolute disparities in treatment were most pronounced among patients aged 22-44 years. Compared with non-Hispanic White patients, whose percentages of treatment with transplant, PD, and HHD were 10.9%, 19.0%, and 1.2%, respectively, non-Hispanic Black patients were less commonly treated with each modality (unadjusted percentages, 1.8%, 13.8%, and 0.6%, respectively), as were Hispanic patients (4.4%, 16.9%, and 0.5%, respectively; all differences P < 0.001). After adjustment, the largest relative disparities were observed for transplant among the 22-44-year age group; compared with non-Hispanic White patients, the adjusted risk ratios for non-Hispanic Black and Hispanic patients were 0.21 (95% CI, 0.19-0.23) and 0.47 (95% CI, 0.43, 0.51), respectively. LIMITATIONS: Race and ethnicity data not self-reported. CONCLUSIONS: Among adults with incident kidney failure, racial and ethnic disparities in transplant and home dialysis use are most pronounced among the youngest adult patient age group.

Epidemiology of COVID-19 Infection in Hospitalized End-Stage Kidney Disease Patients in a Predominantly African-American Population.

BACKGROUND: End-stage kidney disease patients on dialysis are particularly susceptible to COVID-19 infection due to comorbidities, age, and logistic constraints of dialysis making social distancing difficult. We describe our experience with hospitalized dialysis patients with COVID-19 and factors associated with mortality. METHODS: From March 1, 2020, to May 31, 2020, all dialysis patients admitted to 4 Emory Hospitals and tested for COVID-19 were identified. Sociodemographic information and clinical and laboratory data were obtained from the medical record. Death was defined as an in-hospital death or transfer to hospice for end-of-life care. Patients were followed until discharge or death. RESULTS: Sixty-four dialysis patients with COVID-19 were identified. Eighty-four percent were African-American. The median age was 64 years, and 59% were males. Four patients were on peritoneal dialysis, and 60 were on hemodialysis for a median time of 3.8 years, while 31% were obese. Fever (72%), cough (61%), and diarrhea (22%) were the most common symptoms at presentation. Thirty-three percent required admission to intensive care unit, and 23% required mechanical ventilation. The median length of stay was 10 days, while 11 patients (17%) died during hospitalization and 17% were discharged to a temporary rehabilitation facility. Age >65 years (RR 13.7, CI: 1.9-100.7), C-reactive protein >100 mg/dL (RR 8.3, CI: 1.1-60.4), peak D-dimer >3,000 ng/mL (RR 4.3, CI: 1.03-18.2), bilirubin >1 mg/dL (RR 3.9, CI: 1.5-10.4), and history of peripheral vascular disease (RR 3.2, CI: 1.2-9.1) were associated with mortality. Dialysis COVID-19-infected patients were more likely to develop thromboembolic complications than those without COVID-19 (RR 3.7, CI: 1.3-10.1). CONCLUSION: In a predominantly African-American population, the mortality of end-stage kidney disease patients admitted with COVID-19 infection was 17%. Age, C-reactive protein, D-dimer, bilirubin, and history of peripheral vascular disease were associated with worse survival.

Managing COVID-19-positive Solid Organ Transplant Recipients in the Community: What a Community Healthcare Provider Needs to Know.

BACKGROUND: The current surge of coronavirus 2019 (COVID-19) cases in certain parts of the country has burdened the healthcare system, limiting access to tertiary centers for many. As a result, COVID-19-positive Solid Organ Transplant (SOT) recipients are increasingly being managed by local healthcare providers. It is crucial for community providers to understand disease severity and know if COVID-19-impacted SOT recipients have a different clinical course compared with COVID-19-negative SOT recipients with a similar presentation. METHODS: We conducted a retrospective analysis on SOT recipients suspected to have COVID-19 infection tested during March 14, 2020-April 30, 2020. Patients were followed from time of testing to May 31, 2020. RESULTS: One hundred sixty SOT recipients underwent testing: 22 COVID-19 positive and 138 COVID-19 negative. COVID-19-positive patients were more likely to have rapid progression of symptoms (median 3 vs 6 d, P = 0.002), greater hospitalizations (78% vs 64%, P < 0.017), and need for intensive care unit care (45% vs 17%, P < 0.001) Severe COVID-19 infection was not observed in patients on Belatacept for immunosuppression (30% vs 87%,P = 0.001). COVID- 19 positive patients in the intensive care unit were more likely to have multifocal opacities on radiological imaging in comparison to those admitted to the medical floor (90% vs 11%). Survival probability was similar in both cohorts. CONCLUSION: COVID-19-infected SOT recipients have a propensity for rapid clinical decompensation. Local providers need to be work closely with transplant centers to appropriately triage and manage COVID-19 SOT recipients in the community.

Acute Kidney Injury in a Patient on Tenofovir Alafenamide Fumarate After Initiation of Treatment for Hepatitis C Virus Infection.

HIV treatment with tenofovir alafenamide fumarate (TAF) has decreased renal toxicity compared with tenofovir disoproxil fumarate in clinical trials. We report the case of a patient with HIV/HCV coinfection who was started on a TAF-based HIV regimen and developed acute kidney injury that worsened with the addition of sofosbuvir-ledipasvir.

Serious Fall Injury History and Adverse Health Outcomes After Initiating Hemodialysis Among Older U.S. Adults.

Background: Although older adults with predialysis chronic kidney disease are at higher risk for falls, the prognostic significance of a serious fall injury prior to dialysis initiation has not been well described in the end-stage renal disease population. Methods: We examined the association between a serious fall injury in the year prior to starting hemodialysis and adverse health outcomes in the year following dialysis initiation using a retrospective cohort study of U.S. Medicare beneficiaries ≥ 67 years old who initiated dialysis in 2010-2012. Serious fall injuries were defined using diagnostic codes for falls plus an injury (fracture, joint dislocation, or head injury). Health outcomes, defined as time-to-event variables within the first year of dialysis, included four outcomes: a subsequent serious fall injury, hospital admission, post-acute skilled nursing facility (SNF) utilization, and mortality. Results: Among this cohort of 81,653 initiating hemodialysis, 2,958 (3.6%) patients had a serious fall injury in the year prior to hemodialysis initiation. In the first year of dialysis, 7.6% had a subsequent serious fall injury, 67.6% a hospitalization, 30.7% a SNF claim, and 26.1% died. Those with versus without a serious fall injury in the year prior to hemodialysis initiation were at higher risk (hazard ratio, 95% confidence interval) for a subsequent serious fall injury (2.65, 2.41-2.91), hospitalization (1.11, 1.06-1.16), SNF claim (1.40, 1.30-1.50), and death (1.14, 1.06-1.22). Conclusions: For older adults initiating dialysis, a history of a serious fall injury may provide prognostic information to support decision making and establish expectations for life after dialysis initiation.

Chronic kidney disease induces autophagy leading to dysfunction of mitochondria in skeletal muscle.

Chronic kidney disease (CKD) causes loss of lean body mass by multiple mechanisms. This study examines whether autophagy-mediated proteolysis contributes to CKD-induced muscle wasting. We tested autophagy in the muscle of CKD mice with plantaris muscle overloading to mimic resistance exercise or with acupuncture plus low-frequency electrical stimulation (Acu/LFES) treatment. In CKD muscle, Bnip3, Beclin-1, and LC3II mRNAs and proteins were increased compared with those in control muscle, indicating autophagosome-lysosome formation induction. Acu/LFES suppressed the CKD-induced upregulation of autophagy. However, overloading increased autophagy-related proteins in normal and CKD muscle. Serum from uremic mice induces autophagy formation but did not increase the myosin degradation or actin break down in cultured muscle satellite cells. We examined mitochondrial biogenesis, copy number, and ATP production in cultured myotubes, and found all three aspects to be decreased by uremic serum. Inhibition of autophagy partially reversed this decline in cultured myotubes. In CKD mice, the mitochondrial copy number, biogenesis marker peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), mitochondrial transcription factor A (TFAM), and mitochondrial fusion marker Mitofusin-2 (Mfn2) are decreased. Both muscle overloading and Acu/LFES increased mitochondrial copy number, and reversed the CKD-induced decreases in PGC-1α, TFAM, and Mfn2. We conclude that the autophagy is activated in the muscle of CKD mice. However, myofibrillar protein is not directly broken down through autophagy. Instead, CKD-induced upregulation of autophagy leads to dysfunction of mitochondria and decrease of ATP production.

Serious Fall Injuries Before and After Initiation of Hemodialysis Among Older ESRD Patients in the United States: A Retrospective Cohort Study.

BACKGROUND: Because initiation of dialysis therapy often occurs in the setting of acute illness and may signal worsening health and functional decline, we examined whether rates of serious fall injuries among older hemodialysis patients differ before and after dialysis therapy initiation. STUDY DESIGN: Retrospective cohort study of claims data from the 2 years spanning dialysis therapy initiation among patients initiating dialysis therapy in 2010 to 2012. SETTING & PARTICIPANTS: Claims from 81,653 Medicare end-stage renal disease beneficiaries aged 67 to 100 years. PREDICTOR: Post- versus pre-dialysis therapy initiation periods, defined as on or after versus before dialysis therapy initiation. OUTCOMES: Serious fall injuries were defined using diagnostic codes for falls in combination with fractures, brain injuries, or joint dislocation. Incidence rate ratios (overall and stratified) for post- versus pre-dialysis therapy initiation periods were estimated using generalized estimating equation models with a negative binomial link. RESULTS: Overall, 12,757 serious fall injuries occurred in the pre- and post-dialysis therapy initiation periods. Annual rates of serious fall injuries were 64.4 (95% CI, 62.7-66.2) and 107.8 (95% CI, 105.4-110.3) per 1,000 patient-years, respectively, in the pre- and post-dialysis therapy initiation periods (incidence rate ratio, 1.62; 95% CI, 1.56-1.67). Relative rates of serious fall injuries in the post- vs pre-dialysis initiation periods were of greater magnitude among patients who were younger (<75 years), had pre-end-stage renal disease nephrology care, had albumin levels > 3g/dL, were able to walk and transfer, did not need assistance with activities of daily living, and were not institutionalized compared with relative rates among their counterparts. LIMITATIONS: Potential misclassification due to the use of claims data and survival bias among those initiating hemodialysis therapy. CONCLUSIONS: Among older Medicare beneficiaries receiving hemodialysis, serious fall injuries are common, the post-dialysis initiation period is a high-risk time for falls, and dialysis therapy initiation may be an important time to screen for fall risk factors and implement multifactorial fall prevention strategies.

Association of Reduced eGFR and Albuminuria with Serious Fall Injuries among Older Adults.

BACKGROUND AND OBJECTIVES: Falls are common and associated with adverse outcomes in patients on dialysis. Limited data are available in earlier stages of CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We analyzed data from 8744 Reasons for Geographic and Racial Differences in Stroke Study participants ≥65 years old with Medicare fee for service coverage. Serious fall injuries were defined as a fall-related fracture, brain injury, or joint dislocation using Medicare claims. Hazard ratios (HRs) for serious fall injuries were calculated by eGFR and albumin-to-creatinine ratio (ACR). Among 2590 participants with CKD (eGFR<60 ml/min per 1.73 m(2) or ACR≥30 mg/g), cumulative mortality after a serious fall injury compared with age-matched controls without a fall injury was calculated. RESULTS: Overall, 1103 (12.6%) participants had a serious fall injury over 9.9 years of follow-up. The incidence rates per 1000 person-years of serious fall injuries were 21.7 (95% confidence interval [95% CI], 20.3 to 23.2), 26.6 (95% CI, 22.6 to 31.3), and 38.3 (95% CI, 31.2 to 47.0) at eGFR levels ≥60, 45-59, and <45 ml/min per 1.73 m(2), respectively, and 21.3 (95% CI, 20.0 to 22.8), 31.7 (95% CI, 27.5 to 36.5), and 42.2 (95% CI, 31.3 to 56.9) at ACR levels <30, 30-299, and ≥300 mg/g, respectively. Multivariable adjusted HRs for serious fall injuries were 0.91 (95% CI, 0.76 to 1.09) and 1.09 (95% CI, 0.86 to 1.37) for eGFR=45-59 and <45 ml/min per 1.73 m(2), respectively, versus eGFR≥60 ml/min per 1.73 m(2) and 1.31 (95% CI, 1.11 to 1.54) and 1.81 (95% CI, 1.30 to 2.50) for ACR=30-299 and ≥300 mg/g, respectively, versus ACR<30 mg/g. Among participants with CKD, cumulative 1-year mortality rates among patients with a serious fall and age-matched controls were 21.0% and 5.5%, respectively. CONCLUSIONS: Elevated ACR but not lower eGFR was associated with serious fall injuries. Evaluation for fall risk factors and fall prevention strategies should be considered for older adults with elevated ACR.

Critical Care for Multiple Organ Failure Secondary to Ebola Virus Disease in the United States.

OBJECTIVE: This report describes three patients with Ebola virus disease who were treated in the United States and developed for severe critical illness and multiple organ failure secondary to Ebola virus infection. The patients received mechanical ventilation, renal replacement therapy, invasive monitoring, vasopressor support, and investigational therapies for Ebola virus disease. DATA SOURCES: Patient medical records from three tertiary care centers (Emory University Hospital, University of Nebraska Medical Center, and Texas Health Presbyterian Dallas Hospital). STUDY SELECTION: Not applicable. DATA EXTRACTION: Not applicable. DATA SYNTHESIS: Not applicable. CONCLUSION: In the severe form, patients with Ebola virus disease may require life-sustaining therapy, including mechanical ventilation and renal replacement therapy. In conjunction with other reported cases, this series suggests that respiratory and renal failure may occur in severe Ebola virus disease, especially in patients burdened with high viral loads. Ebola virus disease complicated by multiple organ failure can be survivable with the application of advanced life support measures. This collective, multicenter experience is presented with the hope that it may inform future treatment of patients with Ebola virus disease requiring critical care treatment.

The Use of TKM-100802 and Convalescent Plasma in 2 Patients With Ebola Virus Disease in the United States.

BACKGROUND: The current West Africa Ebola virus disease (EVD) outbreak has resulted in multiple individuals being medically evacuated to other countries for clinical management. METHODS: We report two patients who were transported from West Africa to the United States for treatment of EVD. Both patients received aggressive supportive care measures, as well as an investigational therapeutic (TKM-100802) and convalescent plasma. RESULTS: While one patient experienced critical illness with multi-organ failure requiring mechanical ventilation and renal replacement therapy, both patients recovered without serious long-term sequelae to date. CONCLUSIONS: It is unclear what role the experimental drug and convalescent plasma had in the recovery of these patients. Prospective clinical trials are needed to delineate the role of investigational therapies in the care of patients with EVD.

Underreporting of nursing home utilization on the CMS-2728 in older incident dialysis patients and implications for assessing mortality risk.

BACKGROUND: The usage of nursing home (NH) services is a marker of frailty among older adults. Although the Centers for Medicare & Medicaid Services (CMS) revised the Medical Evidence Report Form CMS-2728 in 2005 to include data collection on NH institutionalization, the validity of this item has not been reported. METHODS: There were 27,913 patients ≥ 75 years of age with incident end-stage renal disease (ESRD) in 2006, which constituted our analysis cohort. We determined the accuracy of the CMS-2728 using a matched cohort that included the CMS Minimum Data Set (MDS) 2.0, often employed as a "gold standard" metric for identifying patients receiving NH care. We calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for the CMS-2728 NH item. Next, we compared characteristics and mortality risk by CMS-2728 and MDS NH status agreement. RESULTS: The sensitivity, specificity, PPV and NPV of the CMS-2728 for NH status were 33%, 97%, 80% and 79%, respectively. Compared to those without the MDS or CMS-2728 NH indicator (No MDS/No 2728), multivariable adjusted hazard ratios (95% confidence interval) for mortality associated with NH status were 1.55 (1.46 - 1.64) for MDS/2728, 1.48 (1.42 - 1.54) for MDS/No 2728, and 1.38 (1.25 - 1.52) for No MDS/2728. NH utilization was more strongly associated with mortality than other CMS-2728 items in the model. CONCLUSIONS: The CMS-2728 underestimated NH utilization among older adults with incident ESRD. The potential for misclassification may have important ramifications for assessing prognosis, developing advanced care plans and providing coordinated care.

Successful delivery of RRT in Ebola virus disease.

AKI has been observed in cases of Ebola virus disease. We describe the protocol for the first known successful delivery of RRT with subsequent renal recovery in a patient with Ebola virus disease treated at Emory University Hospital, in Atlanta, Georgia. Providing RRT in Ebola virus disease is complex and requires meticulous attention to safety for the patient, healthcare workers, and the community. We specifically describe measures to decrease the risk of transmission of Ebola virus disease and report pilot data demonstrating no detectable Ebola virus genetic material in the spent RRT effluent waste. This article also proposes clinical practice guidelines for acute RRT in Ebola virus disease.

miR-182 attenuates atrophy-related gene expression by targeting FoxO3 in skeletal muscle.

Skeletal muscle atrophy occurs in response to a variety of conditions including chronic kidney disease, diabetes, cancer, and elevated glucocorticoids. MicroRNAs (miR) may play a role in the wasting process. Activation of the forkhead box O3 (FoxO3) transcription factor causes skeletal muscle atrophy in patients, animals, and cultured cells by increasing the expression of components of the ubiquitin-proteasome and autophagy-lysosome proteolytic systems. To identify microRNAs that potentially modulate the atrophy process, an in silico target analysis was performed and miR-182 was predicted to target FoxO3 mRNA. Using a combination of immunoblot analysis, quantitative real-time RT-PCR, and FoxO3 3'-UTR luciferase reporter genes, miR-182 was confirmed to regulate FoxO3 expression in C2C12 myotubes. Transfection of miR-182 into muscle cells decreased FoxO3 mRNA 30% and FoxO3 protein 67% (P < 0.05) and also prevented a glucocorticoid-induced upregulation of multiple FoxO3 gene targets including MAFbx/atrogin-1, autophagy-related protein 12 (ATG12), cathepsin L, and microtubule-associated protein light chain 3 (LC3). Treatment of C2C12 myotubes with dexamethasone (Dex) (1 µM, 6 h) to induce muscle atrophy decreased miR-182 expression by 63% (P < 0.05). Similarly, miR-182 was decreased 44% (P < 0.05) in the gastrocnemius muscle of rats injected with streptozotocin to induce diabetes compared with controls. Finally, miR-182 was present in exosomes isolated from the media of C2C12 myotubes and Dex increased its abundance. These data identify miR-182 as an important regulator of FoxO3 expression that participates in the control of atrophy-inducing genes during catabolic diseases.

Docosahexaenoic acid prevents palmitate-induced activation of proteolytic systems in C2C12 myotubes.

Saturated fatty acids like palmitate contribute to muscle atrophy in a number of conditions (e.g., type II diabetes) by altering insulin signaling. Akt is a key modulator of protein balance that inhibits the FoxO transcription factors (e.g., FoxO3) which selectively induce the expression of atrophy-inducing genes (atrogenes) in the ubiquitin-proteasome and autophagy-lysosome systems. Conversely, omega-3 polyunsaturated fatty acids have beneficial effects on insulin signaling and may preserve muscle mass. In an earlier report, the omega-3 fatty acid docosahexaenoic acid (DHA) protected myotubes from palmitate-induced atrophy; the mechanisms underlying the alterations in protein metabolism were not identified. This study investigated whether DHA prevents a palmitate-induced increase in proteolysis by restoring Akt/FoxO signaling. Palmitate increased the rate of protein degradation, while cotreatment with DHA prevented the response. Palmitate reduced the activation state of Akt and increased nuclear FoxO3 protein while decreasing its cytosolic level. Palmitate also increased the messenger RNAs (mRNAs) of two FoxO3 atrogene targets, the E3 ubiquitin ligase atrogin-1/MAFbx and the autophagy mediator Bnip3. DHA attenuated the effects of palmitate on Akt activation, FoxO3 localization and atrogene mRNAs. DHA, alone or in combination with palmitate and decreased the ratio of LC3B-II:LC3B-I protein as well as the rate of autophagosome formation, as indicated by reduced LC3B-II protein in the presence of 10 mmol/L methylamine, suggesting an independent effect of DHA on the macroautophagy pathway. These data indicate that palmitate induces myotube atrophy, at least in part, by activating multiple proteolytic systems and that DHA counters the catabolic effects of palmitate by restoring Akt/FoxO signaling.

Chaperone-mediated autophagy in the kidney: the road more traveled.

Chaperone-mediated autophagy (CMA) is a lysosomal proteolytic pathway in which cytosolic substrate proteins contain specific chaperone recognition sequences required for degradation and are translocated directly across the lysosomal membrane for destruction. CMA proteolytic activity has a reciprocal relationship with macroautophagy: CMA is most active in cells in which macroautophagy is least active. Normal renal proximal tubular cells have low levels of macroautophagy, but high basal levels of CMA activity. CMA activity is regulated by starvation, growth factors, oxidative stress, lipids, aging, and retinoic acid signaling. The physiological consequences of changes in CMA activity depend on the substrate proteins present in a given cell type. In the proximal tubule, increased CMA results from protein or calorie starvation and from oxidative stress. Overactivity of CMA can be associated with tubular lysosomal pathology and certain cancers. Reduced CMA activity contributes to protein accumulation in renal tubular hypertrophy, but may contribute to oxidative tissue damage in diabetes and aging. Although there are more questions than answers about the role of high basal CMA activity, this remarkable feature of tubular protein metabolism appears to influence a variety of chronic diseases.

Preparing for renal replacement therapy in patients with the Ebola virus disease.

The Ebola virus disease (EVD) is a serious illness characterized by fever, severe vomiting and diarrhea, and, in severe cases, multi-organ failure requiring mechanical ventilation and renal replacement therapy. The current outbreak has centered in West Africa and affected over 15,000 individuals. EVD is transmitted by direct contact with blood or other infectious bodily fluid, and as such, numerous heath care workers caring for patients with EVD have become infected. During the current outbreak, a number of patients have received advanced supportive care for EVD in Europe and North America and therefore survived. Now, many hospitals in Europe and North America are planning to accept care for patients with EVD. In this review, we discussed the key issues related to the planning and delivery of advanced supportive care in patients with EVD with a focus on the factors necessary to provide renal replacement therapy (RRT). Since success in the treatment of patients with EVD rests on both patient outcome and prevention of transmission of disease to health care workers, we extensively discussed the modes of Ebola virus transmission and recommended protocols to protect health care workers. Experience now indicates that with appropriate planning and protocols, it is possible to successfully treat EVD patients with advanced supportive care (mechanical ventilation and RRT) while avoiding transmission to health care providers. Video Journal Club "Cappuccino with Claudio Ronco" at http://www.karger.com/?doi=371530.

Prevention and treatment of protein energy wasting in chronic kidney disease patients: a consensus statement by the International Society of Renal Nutrition and Metabolism.

Protein energy wasting (PEW) is common in patients with chronic kidney disease (CKD) and is associated with adverse clinical outcomes, especially in individuals receiving maintenance dialysis therapy. A multitude of factors can affect the nutritional and metabolic status of CKD patients requiring a combination of therapeutic maneuvers to prevent or reverse protein and energy depletion. These include optimizing dietary nutrient intake, appropriate treatment of metabolic disturbances such as metabolic acidosis, systemic inflammation, and hormonal deficiencies, and prescribing optimized dialytic regimens. In patients where oral dietary intake from regular meals cannot maintain adequate nutritional status, nutritional supplementation, administered orally, enterally, or parenterally, is shown to be effective in replenishing protein and energy stores. In clinical practice, the advantages of oral nutritional supplements include proven efficacy, safety, and compliance. Anabolic strategies such as anabolic steroids, growth hormone, and exercise, in combination with nutritional supplementation or alone, have been shown to improve protein stores and represent potential additional approaches for the treatment of PEW. Appetite stimulants, anti-inflammatory interventions, and newer anabolic agents are emerging as novel therapies. While numerous epidemiological data suggest that an improvement in biomarkers of nutritional status is associated with improved survival, there are no large randomized clinical trials that have tested the effectiveness of nutritional interventions on mortality and morbidity.