In older adults, measurements of physical performance assess physical function and associate with mortality and disability. Muscle wasting and diminished physical performance often accompany CKD, resembling physiologic aging, but whether physical performance associates with clinical outcome in CKD is unknown. We evaluated 385 ambulatory, stroke-free participants with stage 2-4 CKD enrolled in clinicbased cohorts at the University of Washington and University of Maryland and Veterans Affairs Maryland Healthcare systems. We compared handgrip strength, usual gait speed, timed up and go (TUAG), and 6-minute walking distance with normative values and constructed Cox proportional hazards models and receiver operating characteristic curves to test associations with all-cause mortality. Mean age was 61 years and the mean estimated GFR was 41 ml/min per 1.73 m 2 . Measures of lower extremity performance were at least 30% lower than predicted, but handgrip strength was relatively preserved. Fifty deaths occurred during the median 3-year follow-up period. After adjustment, each 0.1-m/s decrement in gait speed associated with a 26% higher risk for death, and each 1-second longer TUAG associated with an 8% higher risk for death. On the basis of the receiver operating characteristic analysis, gait speed and TUAG more strongly predicted 3-year mortality than kidney function or commonly measured serum biomarkers. Adding gait speed to a model that included estimated GFR significantly improved the prediction of 3-year mortality. In summary, impaired physical performance of the lower extremities is common in CKD and strongly associates with all-cause mortality. CKD is a growing global health problem that affects .25 million US adults. 1 CKD leads to the retention of metabolic waste products and hormonal disturbances that adversely affect multiple target organ systems, including skeletal muscle. A major consequence of loss of skeletal muscle (sarcopenia) is skeletal muscle dysfunction, which is associated with impaired mobility and reduced physical performance. Among general older adult populations, decreased physical performance is independently associated with subsequent disability, fracture, falls, hospitalization, and mortality. [2][3][4] In particular, usual gait speed has been used as an adjunct for risk stratification by quantifying the burden of recognized and unrecognized multisystem comorbidity,

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Patients with chronic kidney disease (CKD) experience substantial loss of muscle mass, weakness and poor physical performance. As kidney disease progresses, skeletal muscle dysfunction forms a common pathway for mobility limitation, loss of functional independence, and vulnerability to disease complications. Screening for those at high-risk of mobility disability by self-reported and objective measures of function is an essential first step in developing an interdisciplinary approach to treatment which includes rehabilitative therapies and counseling on physical activity. Exercise has beneficial effects on systemic inflammation, muscle and physical performance in CKD. Kidney health providers need to identify patient- and care delivery barriers to exercise in order to effectively counsel patients on physical activity. A thorough medical evaluation and assessment of baseline function using self-reported and objective function assessment is essential to guide an effective, individualized exercise prescription to prevent function decline in persons with kidney disease. This review focuses on the impact of kidney disease on skeletal muscle dysfunction in the context of the disablement process and reviews screening and treatment strategies that kidney health professionals can employ in clinical practice to prevent functional decline and disability.

Mitochondria abnormalities in skeletal muscle may contribute to frailty and sarcopenia, commonly present in patients with chronic kidney disease (CKD). Dysfunctional mitochondria are also a major source of oxidative stress and may contribute to cardiovascular disease in CKD. We tested the hypothesis that mitochondrial structure and function worsens with the severity of CKD. Mitochondrial volume density, mitochondrial DNA (mtDNA) copy number, BNIP3, and PGC1α protein expression were evaluated in skeletal muscle biopsies obtained from 27 subjects (17 controls and 10 with CKD stage 5 on hemodialysis). We also measured mtDNA copy number in peripheral blood mononuclear cells (PBMCs), plasma isofurans, and plasma F2‐isoprostanes in 208 subjects divided into three groups: non‐CKD (eGFR>60 mL/min), CKD stage 3–4 (eGFR 60–15 mL/min), and CKD stage 5 (on hemodialysis). Muscle biopsies from patients with CKD stage 5 revealed lower mitochondrial volume density, lower mtDNA copy number, and higher BNIP3 content than controls. mtDNA copy number in PBMCs was decreased with increasing severity of CKD: non‐CKD (6.48, 95% CI 4.49–8.46), CKD stage 3–4 (3.30, 95% CI 0.85–5.75, P = 0.048 vs. non‐CKD), and CKD stage 5 (1.93, 95% CI 0.27–3.59, P = 0.001 vs. non‐CKD). Isofurans were higher in patients with CKD stage 5 (median 59.21 pg/mL, IQR 41.76–95.36) compared to patients with non‐CKD (median 49.95 pg/mL, IQR 27.88–83.46, P = 0.001), whereas F2‐isoprostanes did not differ among groups. Severity of CKD is associated with mitochondrial dysfunction and markers of oxidative stress. Mitochondrial abnormalities, which are common in skeletal muscle from patients with CKD stage 5, may explain the muscle dysfunction associated with frailty and sarcopenia in CKD. Further studies are required to evaluate mitochondrial function in vivo in patients with different CKD stages.

A cross-sectional study was conducted in the Peruvian Amazon to test the hypothesis that a reservoir of asymptomatic malaria parasitemic patients would form the basis for continuing malaria endemicity in the region. Active surveillance yielded a Plasmodium spp. slide-positive prevalence of 4.2% (43 of 1,023) and a polymerase chain reaction (PCR)-positive prevalence of 17.6% (144 of 819). Plasmodium vivax prevalence was 2.9% and 14.2% while Plasmodium falciparum prevalence was 1.3% and 2.6% by microscopy and PCR, respectively. Approximately two-thirds of slidepositive and one-fourth of PCR-positive people were symptomatic. Anemia was associated with slide positivity (P < 0.001) and PCR positivity for P. falciparum (P ‫ס‬ 0.003). Sensitivity of field microscopy and agreement between field and reference laboratory microscopists were low, arguing for using PCR for epidemiologic investigation and malaria control. While these data confirm recent findings from the Brazilian Amazon suggesting that sufficient numbers of asymptomatic malaria parasitemic patients are present to form a persistent reservoir for continuous reinfection within the Peruvian Amazon region, these results also indicate that clinical immunity in human populations can be driven in malaria-endemic regions that do not have high intensity malaria transmission