Lieske, John C.

Objectives: Sarcopenia is associated with a poor prognosis in the ICU. The purpose of this study was to describe a simple sarcopenia index using routinely available renal biomarkers and evaluate its association with muscle mass and patient outcomes. Design: A retrospective cohort study. Setting: A tertiary-care medical center. Patients: High-risk adult ICU patients from October 2008 to December 2010. Interventions: The gold standard for muscle mass was quantified with the paraspinal muscle surface area at the L4 vertebrae in the subset of individuals with an abdominal CT scan. Using Pearson’s correlation coefficient, serum creatinine-to-serum cystatin C ratio was found to be the best performer in the estimation of muscle mass. The relationship between sarcopenia index and hospital and 90-day mortality, and the length of mechanical ventilation was evaluated. Measurements and Main Results: Out of 226 enrolled patients, 123 (54%) were female, and 198 (87%) were white. Median (interquartile range) age, body mass index, and body surface area were 68 (57–77) years, 28 (24–34) kg/m2, and 1.9 (1.7–2.2) m2, respectively. The mean (± sd) Acute Physiology and Chronic Health Evaluation III was 70 (± 22). ICU, hospital, and 90-day mortality rates were 5%, 12%, and 20%, respectively. The correlation (r) between sarcopenia index and muscle mass was 0.62 and coefficient of determination (r 2) was 0.27 (p < 0.0001). After adjustment for Acute Physiology and Chronic Health Evaluation III, body surface area, and age, sarcopenia index was independently predictive of both hospital (p = 0.001) and 90-day mortality (p < 0.0001). Among the 131 patients on mechanical ventilator, the duration of mechanical ventilation was significantly lower on those with higher sarcopenia index (–1 d for each 10 unit of sarcopenia index [95% CI, –1.4 to –0.2; p = 0.006]). Conclusions: The sarcopenia index is a fair measure for muscle mass estimation among ICU patients and can modestly predict hospital and 90-day mortality among patients who do not have acute kidney injury at the time of measurement.

Nephron number may be an important determinant of kidney health but has been difficult to study in living humans. We evaluated 1638 living kidney donors at Mayo Clinic (MN and AZ sites) and Cleveland Clinic. We obtained cortical volumes of both kidneys from predonation computed tomography scans. At the time of kidney transplant, we obtained and analyzed the sections of a biopsy specimen of the cortex to determine the density of both nonsclerotic and globally sclerotic glomeruli; the total number of glomeruli was estimated from cortical volume×glomerular density. Donors 18–29 years old had a mean 990,661 nonsclerotic glomeruli and 16,614 globally sclerotic glomeruli per kidney, which progressively decreased to 520,410 nonsclerotic glomeruli per kidney and increased to 141,714 globally sclerotic glomeruli per kidney in donors 70–75 years old. Between the youngest and oldest age groups, the number of nonsclerotic glomeruli decreased by 48%, whereas cortical volume decreased by only 16% and the proportion of globally sclerotic glomeruli on biopsy increased by only 15%. Clinical characteristics that independently associated with fewer nonsclerotic glomeruli were older age, shorter height, family history of ESRD, higher serum uric acid level, and lower measured GFR. The incomplete representation of nephron loss with aging by either increased glomerulosclerosis or by cortical volume decline is consistent with atrophy and reabsorption of globally sclerotic glomeruli and hypertrophy of remaining nephrons. In conclusion, lower nephron number in healthy adults associates with characteristics reflective of both lower nephron endowment at birth and subsequent loss of nephrons.

Background and objectives eGFR equations have been evaluated in kidney transplant recipients with variable performance. We assessed the performance of the Modification of Diet in Renal Disease equation and the Chronic Kidney Disease Epidemiology Collaboration equations on the basis of creatinine, cystatin C, and both (eGFR creatinine-cystatin C) compared with measured GFR by iothalamate clearance and evaluated their non-GFR determinants and associations across 15 cardiovascular risk factors. Design, setting, participants, & measurements A cross-sectional cohort of 1139 kidney transplant recipients >1 year after transplant was analyzed. eGFR bias, precision, and accuracy (percentage of estimates within 30% of measured GFR) were assessed. Interaction of each cardiovascular risk factor with eGFR relative to measured GFR was determined. Results Median measured GFR was 55.0 ml/min per 1.73 m 2 . eGFR creatinine overestimated measured GFR by 3.1% (percentage of estimates within 30% of measured GFR of 80.4%), and eGFR Modification of Diet in Renal Disease underestimated measured GFR by 2.2% (percentage of estimates within 30% of measured GFR of 80.4%). eGFR cystatin C underestimated measured GFR by −13.7% (percentage of estimates within 30% of measured GFR of 77.1%), and eGFR creatinine-cystatin C underestimated measured GFR by −8.1% (percentage of estimates within 30% of measured GFR of 86.5%). Lower measured GFR associated with older age, women, obesity, longer time after transplant, lower HDL, lower hemoglobin, lower albumin, higher triglycerides, higher proteinuria, and an elevated cardiac troponin T level but did not associate with diabetes, smoking, cardiovascular events, pretransplant dialysis, or hemoglobin A1c. These risk factor associations differed for five risk factors with eGFR creatinine, six risk factors for eGFR Modification of Diet in Renal Disease, ten risk factors for eGFR cystatin C, and four risk factors for eGFR creatinine-cystatin C. Conclusions Thus, eGFR creatinine and eGFR creatinine-cystatin C are preferred over eGFR cystatin C in kidney transplant recipients because they are less biased, more accurate, and more consistently reflect the same risk factor associations seen with measured GFR.

Non‐invasive tests to identify age and early disease‐associated pathology within the kidney are needed. Specific populations of urinary extracellular vesicles (EVs) could potentially be used for such a diagnostic test. Random urine samples were obtained from age‐ and sex‐stratified living kidney donors before kidney donation. A biopsy of the donor kidney was obtained at the time of transplantation to identify nephron hypertrophy (larger glomerular volume, cortex per glomerulus and mean profile tubular area) and nephrosclerosis (% fibrosis, % glomerulosclerosis and arteriosclerosis). Renal parenchymal‐derived EVs in cell‐free urine were quantified by digital flow cytometry. The relationship between these EV populations and structural pathology on the kidney biopsy was assessed. Clinical characteristics of the kidney donors (n=138, age range: 20–70 years, 50% women) were within the normative range. Overall, urine from women contained more EVs than that from men. The number of exosomes, juxtaglomerular cells and podocyte marker–positive EVs decreased (p<0.05) with increasing age. There were fewer total EVs as well as EVs positive for mesangial cell, parietal cell, descending limb of Henle's loop (simple squamous epithelium), collecting tubule‐intercalated cell and monocyte chemoattractant protein‐1 markers (p<0.05) in persons with nephron hypertrophy. The number of EVs positive for intercellular adhesion molecule‐1, juxtaglomerular cell, podocyte, parietal cell, proximal tubular epithelial cell, distal tubular epithelial cell and collecting duct cells were fewer (p<0.05) in persons with nephrosclerosis. EVs carrying markers of cells from the renal pelvis epithelium did not associate with any indices of nephron hypertrophy or nephrosclerosis. Therefore, specific populations of EVs derived from cells of the glomerulus and nephron associate with underlying kidney structural changes. Further validation of these findings in other cohorts is needed to determine their clinical utility.