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,

Kidney disease leads to clinically relevant disturbances in glucose and insulin homeostasis, but the pathophysiology in moderate-severe CKD remains incompletely defined. In a cross-sectional study of 59 participants with nondiabetic CKD (mean eGFR =37.6 ml/min per 1.73 m 2 ) and 39 healthy control subjects, we quantified insulin sensitivity, clearance, and secretion and glucose tolerance using hyperinsulinemiceuglycemic clamp and intravenous and oral glucose tolerance tests. Participants with CKD had lower insulin sensitivity than participants without CKD (mean[SD] 3.9[2.0] versus 5.0 [2.0] mg/min per mU/ml; P,0.01). Insulin clearance correlated with insulin sensitivity (r=0.72; P,0.001) and was also lower in participants with CKD than controls (876 [226] versus 998 [212] ml/min; P,0.01). Adjustment for physical activity, diet, fat mass, and fatfree mass in addition to demographics and smoking partially attenuated associations of CKD with insulin sensitivity (adjusted difference, 20.7; 95% confidence interval, 21.4 to 0.0 mg/min per mU/ml) and insulin clearance (adjusted difference, 285; 95% confidence interval, 2160 to 210 ml/min). Among participants with CKD, eGFR did not significantly correlate with insulin sensitivity or clearance. Insulin secretion and glucose tolerance did not differ significantly between groups, but 65% of participants with CKD had impaired glucose tolerance. In conclusion, moderate-severe CKD associated with reductions in insulin sensitivity and clearance that are explained, in part, by differences in lifestyle and body composition. We did not observe a CKD-specific deficit in insulin secretion, but the combination of insulin resistance and inadequate augmentation of insulin secretion led to a high prevalence of impaired glucose tolerance.

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BackgroundThe discovery of nondiabetic kidney disease (NDKD) in an individual patient with diabetes may have significant treatment implications. Extensive histopathologic data in this population are lacking, but they may provide insights into the complex pathogenesis of diabetic nephropathy (DN) and reveal specific phenotypes for the development of targeted therapies. This study seeks to elucidate the clinical and laboratory parameters associated with the spectrum of kidney histopathologic features in patients with diabetes.MethodsThis study is a retrospective analysis of 399 kidney biopsies assessed from 2014 to 2016 at the University of Washington among patients with diabetes. More comprehensive clinical data were evaluated in a subset of 79 participants.ResultsOf the 399 biopsies reviewed, 192 (48%) had a primary diagnosis of DN (including 26 with an additional diagnosis), and 207 (52%) had a primary diagnosis of NDKD (including 67 who also had DN). Retinopathy (sensitivity: 0.86; specificity: 0.81; OR, 27.1; 95% CI, 6.8 to 107.7) and higher levels of proteinuria (7.6 versus 4.1 g/d; P=0.004) were associated with DN, whereas a physician description of AKI was associated with a lower risk of DN (OR, 0.13; 95% CI, 0.04 to 0.38). The four most prevalent diagnoses in participants with NDKD were FSGS in 39, nephrosclerosis in 29, IgA nephropathy in 27, and acute tubular injury in 21.ConclusionsAmong patients with diabetes who undergo kidney biopsy in the Pacific Northwest, approximately half have DN, and half have NDKD. Retinopathy and more severe proteinuria were associated with DN, and AKI was a more common descriptor in NDKD.PodcastThis article contains a podcast at https://www.asnonline.org/media/podcast/K360/2020_11_25_KID0003962020.mp3