Relationships among Non-Neoplastic Histopathological Features, Kidney Function, Proteinuria, and Other Clinical Factors in Patients Undergoing Nephrectomy.

Introduction: The non-neoplastic kidney parenchyma from nephrectomies is often overlooked in routine examinations. We aimed to evaluate the associations between global glomerulosclerosis (GS), interstitial fibrosis (IF), or arteriosclerosis (AS) and estimated glomerular filtration rate (eGFR), dipstick proteinuria, and other clinical factors. Methods: We performed a cross-sectional analysis of 781 patients with nephrectomy. We used regression models with and without interaction factors. The tested exposures were GS, IF, or AS, and the outcome measures were GFR and dipstick proteinuria. Results: In multivariable analyses, increasing degrees of GS, IF, or AS were significantly associated with lower eGFR and proteinuria (p < 0.05 for each). Obesity and hypertension (HTN) modified the association between eGFR and degrees of GS, whereas proteinuria and cardiovascular disease (CVD) modified the association between eGFR and degrees of AS (p for interaction <0.05). Compared with GS <10%, GS >50% was associated with lower eGFR in patients with (-45 mL/min/1.73 m2) than without (-19 mL/min/1.73 m2) obesity, and GS >50% was associated with lower eGFR in patients with (-31 mL/min/1.73 m2) than without (-16 mL/min/1.73 m2) HTN. Compared with AS <26%, AS >50% was associated with lower eGFR in patients with (-11 mL/min/1.73 m2) than without (-6 mL/min/1.73 m2) proteinuria, and AS >50% was associated with lower eGFR in patients with (-23 mL/min/1.73 m2) than without (-7 mL/min/1.73 m2) CVD. Conclusion: Greater degrees of each GS, IF, and AS are independently associated with proteinuria and lower eGFR. Obesity, HTN, proteinuria, and CVD modify the relationship between eGFR and specific histopathological features of nephrosclerosis.

One-year all-cause mortality in hospitalized patients with COVID-19 and end-stage renal disease undergoing hemodialysis.

INTRODUCTION: Patients with end-stage renal disease (ESRD) on dialysis and COVID-19 infection have an increased risk of in-hospital mortality, but whether these patients have a higher long-term mortality risk is unknown. MATERIALS AND METHODS: Retrospective chart review of 958 patients admitted with COVID-19 infection or those with ESRD admitted for any other reason between February 2020 and August 2020. We collected data on demographics, comorbidities, laboratory tests, and mortality. The primary outcome was all-cause 1-year mortality. The secondary outcome was in-hospital mortality. We used primarily logistic regression models to assess the mortality risk. RESULTS: In total, 651 patients without ESRD with COVID-19 (COVID+ESRD-), 259 with ESRD without COVID-19 (ESRD+COVID-), and 48 with ESRD with COVID-19 (COVID+ESRD+) were hospitalized between February 2020 and August 2020. Patients were followed after discharge until September 2021. The all-cause 1-year mortality rates were 24% in patients with COVID+ESRD-, 22% in ESRD+COVID- patients, and 40% in those with COVID+ESRD+ (p < 0.05). Compared to the COVID+ESRD- group, the unadjusted and adjusted odds ratio (OR) for all-cause 1-year mortality in the COVID+ESRD+ group was 2.13 (95% confidence interval (CI), 1.16 - 3.91) and 2.15 (95% CI,1.12 - 4.14), respectively. The unadjusted and adjusted OR for all-cause in-hospital mortality in the COVID+ESRD+ group was 1.79 (95% CI, 0.92 - 3.49); and 1.79 (95% CI, 0.88 - 3.65), respectively. We found no statistically significant difference between the COVID+ESRD- and ESRD+COVID- groups for both in-hospital and 1-year mortality (p > 0.05). CONCLUSION: Patients with COVID+ESRD+ have significantly higher odds for all-cause 1-year mortality compared to COVID+ESRD- patients. Future studies should investigate the mechanisms of long-term mortality risk in ESRD patients with COVID-19 infection.

Depressive symptoms exacerbate disability in older adults: A prospective cohort analysis of participants in the MemAID trial.

BACKGROUND: Maintaining independence in older age is an important aspect of quality of life. We investigated depressive symptoms as an important modifiable risk factor that may mediate the effects of physical and cognitive decline on disability. METHODS: We prospectively analyzed data from 223 adults (age 50-85; 117 controls and 106 with type-2 diabetes) over 48 weeks who were participating in a clinical trial "Memory Advancement by Intranasal Insulin in Type 2 Diabetes." Data from self-reported disability (World Health Organization Disability Assessment Schedule) and depressive symptoms (Geriatric Depression Scale) were obtained from baseline, week 25, and week 48 visits. Cognition (Mini-mental status examination) and medical comorbidities (Charlson Comorbidity Index) were assessed at baseline. Longitudinal analysis assessed the extent to which change in depressive symptoms predicted worsening disability. Mediation analyses were performed to determine the extent to which depressive symptoms accounted for disability associated with worse cognition, walking speed, and comorbidities. RESULTS: At baseline, depressive symptoms, cognition, and walking speed were within normal limits, but participants had a high 10-year risk of cardiovascular mortality. Depressive symptoms were related to disability at baseline (p<0.001), and longitudinally (p<0.001). Cognition, walking speed, and comorbidities were associated with disability at baseline (p-values = 0.027-0.001). Depressive symptoms had a large mediating effect on disability longitudinally: the indirect effect on disability via depression accounts for 51% of the effect of cognition, 34% of the effect of mobility, and 24% of the effect of comorbidities. CONCLUSIONS: Depressive symptoms substantially exacerbated the effects of worsening cognition, gait speed, and comorbidities on disability. In our sample, most individuals scored within the "normal" range of the Geriatric Depression Scale, suggesting that even subclinical symptoms can lead to disability. Treating subclinical depression, which may be under-recognized in older adults, should be a public health priority to help preserve independence with aging.

MemAID: Memory advancement with intranasal insulin vs. placebo in type 2 diabetes and control participants: a randomized clinical trial.

BACKGROUND: This study aimed at assessing the long-term effects of intranasal insulin (INI) on cognition and gait in older people with and without type 2 diabetes mellitus (T2DM). METHODS: Phase 2 randomized, double-blinded trial consisted of 24 week treatment with 40 IU of INI (Novolin® R, off-label use) or placebo (sterile saline) once daily and 24 week follow-up. Primary outcomes were cognition, normal (NW), and dual-task (DTW) walking speeds. Of 244 randomized, 223 completed baseline (51 DM-INI, 55 DM-Placebo, 58 Control-INI, 59 Control-Placebo; 109 female, 65.8 ± 9.1; 50-85 years old); 174 completed treatment (84 DM, 90 Controls); 156 completed follow-up (69 DM). RESULTS: DM-INI had faster NW (~ 7 cm/s; p = 0.025) and DTW on-treatment (p = 0.007; p = 0.812 adjusted for baseline difference) than DM-Placebo. Control-INI had better executive functioning on-treatment (p = 0.008) and post-treatment (p = 0.007) and verbal memory post-treatment (p = 0.004) than Control-Placebo. DM-INI increased cerebral blood flow in medio-prefrontal cortex (p < 0.001) on MRI. Better vasoreactivity was associated with faster DTW (p < 0.008). In DM-INI, plasma insulin (p = 0.006) and HOMA-IR (p < 0.013) decreased post-treatment. Overall INI effect demonstrated faster walking (p = 0.002) and better executive function (p = 0.002) and verbal memory (p = 0.02) (combined DM-INI and Control-INI cohort, hemoglobin A1c-adjusted). INI was not associated with serious adverse events, hypoglycemic episodes, or weight gain. CONCLUSION: There is evidence for positive INI effects on cognition and gait. INI-treated T2DM participants walked faster, showed increased cerebral blood flow and decreased plasma insulin, while controls improved executive functioning and verbal memory. The MemAID trial provides proof-of-concept for preliminary safety and efficacy and supports future evaluation of INI role to treat T2DM and age-related functional decline.

Tilt Test: A Review.

SUMMARY: This review recapitulates the head-up tilt test, which is commonly used for evaluation of orthostatic syndromes and dysautonomia. Tilt test evaluates autonomic system responses to orthostatic stress. Established tilt testing includes monitoring of heart rate and blood pressure; adding capnography and cerebral blood flow monitoring expands its diagnostic yield and allows assessing cerebral blood flow regulation. Common syndromes detectable by the tilt test are neurally mediated syncope (vasodepressor, cardiovagal, or mixed), orthostatic hypotension, postural orthostatic tachycardia syndrome, hypocapnic cerebral hypoperfusion, and orthostatic cerebral hypoperfusion syndrome. This review describes relevant physiology, tilt test protocols, diagnostic criteria for orthostatic syndromes, grading test results, diagnostic accuracy, limitations of the tilt test, and safety considerations.