BackgroundReports from centers treating patients with coronavirus disease 2019 (COVID-19) have noted that such patients frequently develop AKI. However, there have been no direct comparisons of AKI in hospitalized patients with and without COVID-19 that would reveal whether there are aspects of AKI risk, course, and outcomes unique to this infection.MethodsIn a retrospective observational study, we evaluated AKI incidence, risk factors, and outcomes for 3345 adults with COVID-19 and 1265 without COVID-19 who were hospitalized in a large New York City health system and compared them with a historical cohort of 9859 individuals hospitalized a year earlier in the same health system. We also developed a model to identify predictors of stage 2 or 3 AKI in our COVID-19.ResultsWe found higher AKI incidence among patients with COVID-19 compared with the historical cohort (56.9% versus 25.1%, respectively). Patients with AKI and COVID-19 were more likely than those without COVID-19 to require RRT and were less likely to recover kidney function. Development of AKI was significantly associated with male sex, Black race, and older age (>50 years). Male sex and age >50 years associated with the composite outcome of RRT or mortality, regardless of COVID-19 status. Factors that were predictive of stage 2 or 3 AKI included initial respiratory rate, white blood cell count, neutrophil/lymphocyte ratio, and lactate dehydrogenase level.ConclusionsPatients hospitalized with COVID-19 had a higher incidence of severe AKI compared with controls. Vital signs at admission and laboratory data may be useful for risk stratification to predict severe AKI. Although male sex, Black race, and older age associated with development of AKI, these associations were not unique to COVID-19.

Background Animal models of kidney disease have linked metabolic acidosis with renal damage. The role of low serum bicarbonate levels in kidney disease progression in humans has not been studied. Study Design Retrospective cohort study. Setting & Participants: Adults visiting a medical clinic in the Bronx, NY from 01/01/01 to 12/31/03 were included in the study (n=5,422) and followed until 6/30/07 Predictor Serum bicarbonate levels Outcomes Kidney disease progression was defined as either a decline in the estimated glomerular filtration rate (eGFR) by 50% or reaching an eGFR of <15 ml/min/1.73m2 (n=337). Measurements Patients’ baseline demographics, comorbidities, laboratory data and socioeconomic status were recorded. Serial outpatient serum creatinines were collected (median, 5 measurements/ person). Results The mean age was 52 years, 69% were women, 45% were African-American, 31% were Hispanic, 21% had diabetes mellitus, 41% had hypertension, and 9% had a baseline eGFR <60 ml/min/1.73m2. Kidney disease progressed by the definition above in 337 patients (6.2%). Compared to the reference group (bicarbonate level 25-26 mEq/L), the hazard ratio for progression after adjustment for potential confounders was 1.54 (95% CI 1.13-2.09) for bicarbonate levels ≤22 mEq/L, 0.97 (95% CI 0.70-1.35) for levels 23-24 mEq/L and 1.14 (95% CI 0.84-1.55) for levels ≥27 mEq/L. (Global p-value for inclusion of serum bicarbonate in the model, 0.01). These results remained similar when using different definitions of the outcome (an eGFR decline by 30%, 1288 outcomes (24%)) or doubling of serum creatinine (268 outcomes (4.9%)). Limitations Data used in study was collected for clinical, not research, purposes. Conclusions Low serum bicarbonate is associated with the progression of kidney disease, independent of baseline eGFR and other clinical, demographic and socioeconomic factors. Prospective studies are needed to confirm this relationship and to evaluate the efficacy of alkali supplements for slowing progression.

BackgroundThe level of body-mass index (BMI) associated with the lowest risk of death remains unclear. Although differences in muscle mass limit the utility of BMI as a measure of adiposity, no study has directly examined the effect of muscle mass on the BMI-mortality relationship.MethodsBody composition was measured by dual-energy x-ray absorptiometry in 11,687 participants of the National Health and Nutrition Examination Survey 1999–2004. Low muscle mass was defined using sex-specific thresholds of the appendicular skeletal muscle mass index (ASMI). Proportional hazards models were created to model associations with all-cause mortality.ResultsAt any level of BMI ≥22, participants with low muscle mass had higher body fat percentage (%TBF), an increased likelihood of diabetes, and higher adjusted mortality than other participants. Increases in %TBF manifested as 30–40% smaller changes in BMI than were observed in participants with preserved muscle mass. Excluding participants with low muscle mass or adjustment for ASMI attenuated the risk associated with low BMI, magnified the risk associated with high BMI, and shifted downward the level of BMI associated with the lowest risk of death. Higher ASMI was independently associated with lower mortality. Effects were similar in never-smokers and ever-smokers. Additional adjustment for waist circumference eliminated the risk associated with higher BMI. Results were unchanged after excluding unintentional weight loss, chronic illness, early mortality, and participants performing muscle-strengthening exercises or recommended levels of physical activity.ConclusionsMuscle mass mediates associations of BMI with adiposity and mortality and is inversely associated with the risk of death. After accounting for muscle mass, the BMI associated with the greatest survival shifts downward toward the normal range. These results provide a concrete explanation for the obesity paradox.

Treatment of chronic kidney disease (CKD) can slow its progression to end-stage renal disease (ESRD). However, the therapies remain limited. Blood pressure control using angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) has the greatest weight of evidence. Glycemic control in diabetes seems likely to retard progression. Several metabolic disturbances of CKD may prove to be useful therapeutic targets but have been insufficiently tested. These include acidosis, hyperphosphatemia, and vitamin D deficiency. Drugs aimed at other potentially damaging systems and processes, including endothelin, fibrosis, oxidation, and advanced glycation end products, are at various stages of development. In addition to the paucity of proven effective therapies, the incomplete application of existing treatments, the education of patients about their disease, and the transition to ESRD care remain major practical barriers to better outcomes.

SummaryBackground and objectives Metabolic acidosis contributes to muscle breakdown in patients with CKD, but whether its treatment improves functional outcomes is unknown. The choice of dose and tolerability of high doses remain unclear. In CKD patients with mild acidosis, this study evaluated the dose-response relationship of alkali with serum bicarbonate, its side effect profile, and its effect on muscle strength. Conclusions NaHCO 3 supplementation produces a dose-dependent increase in serum bicarbonate and improves lower extremity muscle strength after a short-term intervention in CKD patients with mild acidosis. Long-term studies are needed to determine if this finding translates into improved functional status.

Steroid use is independently associated with 25(OH)D deficiency in this nationally representative cohort limited by cross-sectional data. It suggests the need for screening and repletion in patients on chronic steroids.

Background and objectives Muscle wasting is common among patients with ESRD, but little is known about differences in muscle mass in persons with CKD before the initiation of dialysis. If sarcopenia was common, it might affect the use of body mass index for diagnosing obesity in people with CKD. Because obesity may be protective in patients with CKD and ESRD, an accurate understanding of how sarcopenia affects its measurement is crucial.Design, setting, participants, & measurements Differences in body composition across eGFR categories in adult participants of the National Health and Nutrition Examination Survey 1999-2004 who underwent dual-energy x-ray absorptiometry were examined. Obesity defined by dual-energy x-ray absorptiometry versus body mass index and sarcopenia as a contributor to misclassification by body mass index were examined.Results Sarcopenia and sarcopenic obesity were more prevalent among persons with lower eGFR (P trend ,0.01 and P trend ,0.001, respectively). After multivariable adjustment, the association of sarcopenia with eGFR was U-shaped. Stage 4 CKD was independently associated with sarcopenia among participants $60 years old (adjusted odds ratio, 2.58; 95% confidence interval, 1.02 to 6.51 for eGFR=15-29 compared with 60-89 ml/min per 1.73 m 2 ; P for interaction by age=0.02). Underestimation of obesity by body mass index compared with dualenergy x-ray absorptiometry increased with lower eGFR (P trend ,0.001), was greatest among participants with eGFR=15-29 ml/min per 1.73 m 2 (71% obese by dual-energy x-ray absorptiometry versus 41% obese by body mass index), and was highly likely among obese participants with sarcopenia (97.7% misclassified as not obese by body mass index).Conclusions Sarcopenia and sarcopenic obesity are highly prevalent among persons with CKD and contribute to poor classification of obesity by body mass index. Measurements of body composition beyond body mass index should be used whenever possible in the CKD population given this clear limitation.

Introduction In pre-dialysis chronic kidney disease (CKD), the association of muscle mass with mortality is poorly defined, and no study has examined outcomes related to the co-occurrence of low muscle mass and excess adiposity (sarcopenic-obesity). Methods: We examined abnormalities of muscle and fat mass in adult participants of the National Health and Nutrition Examination Survey 1999–2004. We determined whether associations of body composition with all-cause mortality differed between participants with CKD compared to those without. Results CKD modified the association of body composition with mortality (p=0.01 for interaction). In participants without CKD, both sarcopenia and sarcopenic obesity were independently associated with increased mortality compared with normal body composition (hazard ratio (HR) 1.44 (95%CI 1.07–1.93) and 1.64 (95%CI 1.26–2.13), respectively). These associations were not present among participants with CKD. Conversely, obese persons had the lowest adjusted risk of death, with an increased risk among those with sarcopenia (HR 1.43 (95%CI 1.05–1.95)) but not sarcopenic-obesity (p=0.003 for interaction by CKD status; HR 1.21 (95%CI 0.89–1.65)), compared with obesity. Conclusion Sarcopenia associates with increased mortality regardless of eGFR, but excess adiposity modifies this association among people with CKD. Future studies of prognosis and weight loss and exercise interventions in CKD patients should consider muscle mass and adiposity together rather than in isolation.