Aging Kidney Research Articles

S1361 Association of Non-Alcoholic Fatty Liver Disease and Metabolic-Associated Fatty Liver Disease with Duration of Hospital Stay in Covid-19 Patients: A Systematic Review and Meta-Analysis

Introduction: With the ongoing SARS-CoV-2 pandemic there is a need to evaluate and investigate risk factors for COVID-19. Age, dyslipidemia, obesity, cardiovascular disease, and chronic kidney disease are established risk factors that lead to worse outcomes in COVID-19 Patients. The association between Non-Alcoholic fatty liver disease (NAFLD) and Metabolic Associated fatty liver disease (MAFLD) and COVID-19 infection is still in debate The discrepancies in the literature may be due to confounding factors, a small study population, and heterogeneity. We conducted a systematic review and meta-analysis to investigate the impact of NAFLD/MAFLD on the duration of hospital stay in COVID-19 patients. Methods: A systematic review of literature databases Pubmed, Cochrane, Embase, Science Direct, and Web of Science was conducted from January 2022- to May 2022. Observational studies or clinical trials that studied hospital stay outcomes in COVID-19 patients were included. Studies that assessed NAFLD/MAFLD using lab assessment (FIB-4, APRI, FIBROSIS score, HSI index, etc), non-invasive imaging (Elastography, Liver Ultrasound, or CT scan, MR elastography, Liver stiffness measurement), or liver biopsy were included. The protocol of the study was registered in Prospero (CRD42022313259) and PRISMA guidelines were followed (Figure). The meta-analysis was performed using RevMan software on studies for hospital length of stay. Mean differences were generated to describe the overall effect size using random effect models. Results: A total of 4,381 patients from eight studies were included in the qualitative analysis. A total of 909 patients in the NAFLD group and 3472 patients in the Non-NAFLD group. A qualitative synthesis showed that the mean difference in the hospital length of stay was 2.49 days between the NAFLD and NON-NAFLD groups and a 95% Confidence interval (95%CI) of 0.96- 4.02. (Figure) I2 = 61%.This denotes on an average ∼2.5 days additional hospital stay among NAFLD/MAFLD patients with COVID-19. Conclusion: Our meta-analysis suggests that NAFLD patients remain in the hospital for a longer period than NON-NAFLD patients. Fatty Liver disease is a risk factor that leads to increased severity of COVID-19 infection.Figure 1.: PRISMA Flowchart outlining the study search and Forest Plot, meta-analysis of Hospital length of stay in COVID-19 with Fatty Liver disease.

Short-term blood pressure variability and outcomes in non-dialysis chronic kidney disease.

BackgroundBlood pressure variability (BPV) is associated with cardiovascular and all-cause mortality, and has been demonstrated in dialysis patients, but has been poorly studied and remains controversial in non-dialysis chronic kidney disease (CKD) patients. We investigated the effect of short-term BPV on prognosis in this population.MethodsA total of 245 stage 1–4 CKD patients with 24-h ambulatory blood pressure recordings were recruited. BPV was evaluated by standard deviation, coefficient of variation, and variation independent of the mean, respectively. All subjects were followed up to the composite end-point event or until January 15, 2020. Patients were divided into two groups based on 24-h median variation independent of the mean, and demographics, laboratory indicators and echocardiogram results were compared. Logistic regression was used to analyze the risk factors for increased BPV. Multivariate Cox regression and Kaplan-Meier survival analysis were used to explore the relationship between BPV and renal prognosis and major cardiovascular events.ResultsThe mean age was 42.07 ± 12.66 years, with 141 males (57.55%). Multivariate Logistic regression analysis showed that high BMI (OR 1.110, P = 0.017), hyperkalemia (OR 2.227, P = 0.040), increased left ventricular end-diastolic diameter (OR 1.103, P = 0.010) and hypertension (OR 2.525, P = 0.002) were independent risk factors for high BPV. Kaplan-Meier survival analysis showed that renal and cardiovascular outcomes were better in the low BPV group than in the high BPV group (P = 0.006; P = 0.002). After adjusting for age, sex and traditional kidney related risk factors, BPV were not independently associated with renal outcomes. High BPV (HR 4.662, P = 0.017) was the main independent risk factor for major cardiovascular events in CKD.ConclusionsIn non-dialysis CKD, short-term BPV was associated with major cardiovascular disease but not renal progression. BMI, hypertension, potassium balance, and left ventricular end-diastolic diameter influenced short-term BPV.

Chronic Phase Survival Rate in Stroke Patients With Severe Functional Limitations According to the Frequency of Rehabilitation Treatment

ObjectiveTo investigate the chronic phase survival rate according to the frequency of rehabilitation treatment in the acute and subacute phases in stroke patients with severe functional limitations. DesignA retrospective longitudinal cohort study. SettingPopulation-based study using the Korean National Health Insurance Database from 2007 to 2018. ParticipantsWe enrolled 593 patients who experienced stroke in 2009 with national disability registration (NDR) grade of 3 or less (N=593). InterventionNot applicable. Main Outcome MeasuresThe frequencies of rehabilitation treatment within 24 months after stroke were categorized into none, 1-50, 51-200, 201-400, and >400 treatments based on requests made to the Health Insurance Review and Assessment Service. As a dependent variable, we assessed all-cause mortality from 24 to 120 months after stroke. ResultsThe study enrolled 283 patients in NDR grade 1 (the most severe), 158 in grade 2, and 152 in grade 3. Groups with more severe functional limitations showed a lower chronic phase survival rate (P<.001). The groups with higher frequencies of rehabilitation treatment in the acute and subacute phases showed a higher chronic phase survival rate (P<.001). In the Cox regression analysis, a higher degree of functional limitation, lower frequency of rehabilitation treatment, older age, male sex, and chronic kidney disease were independent risk factors for chronic phase mortality in stroke patients with severe functional limitations. ConclusionsA high frequency of rehabilitation treatment in the acute and subacute phases was associated with the long-term survival of stroke patients with severe functional limitations.

Induction of ferroptosis selectively eliminates senescent tubular cells

The accumulation of senescent cells is an important contributor to kidney aging, chronic renal disease, and poor outcome after kidney transplantation. Approaches to eliminate senescent cells with senolytic compounds have been proposed as novel strategies to improve marginal organs. While most existing senolytics induce senescent cell clearance by apoptosis, we observed that ferroptosis, an iron-catalyzed subtype of regulated necrosis, might serve as an alternative way to ablate senescent cells. We found that murine kidney tubular epithelial cells became sensitized to ferroptosis when turning senescent. This was linked to increased expression of pro-ferroptotic lipoxygenase-5 and reduced expression of anti-ferroptotic glutathione peroxidase 4 (GPX4). In tissue slice cultures from aged kidneys low dose application of the ferroptosis-inducer RSL3 selectively eliminated senescent cells while leaving healthy tubular cells unaffected. Similar results were seen in a transplantation model, in which RSL3 reduced the senescent cell burden of aged donor kidneys and caused a reduction of damage and inflammatory cell infiltration during the early post-transplantation period. In summary, these data reveal an increased susceptibility of senescent tubular cells to ferroptosis with the potential to be exploited for selective reduction of renal senescence in aged kidney transplants.

Tuberculosis and diabetes: increased hospitalisations and mortality associated with renal impairment.

Diabetes mellitus (DM) triples a person's risk of active tuberculosis (TB) and is associated with increased mortality. It is unclear whether diabetes status and/or the associated renal dysfunction is associated with poor TB outcomes in New Zealand, which has high diabetes screening. To characterise the population of TB-DM and TB-alone to assess the effect of diabetes status and renal function on hospitalisation and mortality. Clinical records from all adult patients diagnosed with TB in Auckland over a 6-year period (2010-2015) were reviewed. Baseline demographics, clinical presentation and microbiological data were assessed to compare the rates of hospitalisation and mortality between those with TB-DM and TB-alone. Statistical significance was defined as P < 0.05. A total of 701 patients was identified with TB; 120 (17%) had an unknown diabetes status and were excluded, and 135 had co-existing diabetes. The TB-DM and TB-alone groups had similar distribution of TB site and proportions of Mycobacterium tuberculosis culture positivity. Univariate analysis showed TB-DM patients had statistically significantly higher proportions of acute hospitalisation and mortality. Multivariate logistic regression showed only a reduced estimated glomerular filtration rate (eGFR) accounted for the higher rates of hospitalisation, with the odds of hospitalisation increasing by 2% for every unit decrease in eGFR. The odds of mortality increased by 6% for every year increase in age, and the odds of mortality increased by 3% for every unit reduction in eGFR. Diabetes is associated with higher TB hospitalisation and mortality; however, this is likely mediated by increased age and chronic kidney disease.

Ureteral Strictures Following Ureteroscopy for Kidney Stone Disease: A Population-based Assessment.

As the prevalence of urolithiasis increases and ureteroscopy is used more frequently, the risks of uncommon complications such as ureteral stricture may become more notable. Our objective is to assess the rate and associated risk factors of ureteral stricture formation in patients undergoing ureteroscopy. Utilizing the IBM MarketScan research database, we evaluated data from 2008 to 2019 and compared ureteral stricture rates and their management following ureteroscopy to subjects who had shock wave lithotripsy. Shock wave lithotripsy was used as a comparison group to represent the rate of stricture from stone disease alone. A third group of those having both shock wave lithotripsy and ureteroscopy was included. Patients and secondary procedures were identified using Current Procedural Terminology, and International Classification of Diseases-9 and -10 codes. A total of 329,776 patients received ureteroscopy, shock wave lithotripsy, or shock wave lithotripsy+ureteroscopy between 2008 and 2019. Stricture developed in 2.9% of patients after ureteroscopy, 1.5% after shock wave lithotripsy, and 2.6% after shock wave lithotripsy+ureteroscopy. In the multivariable model, rates of stricture were 1.7-fold higher after ureteroscopy vs shock wave lithotripsy (OR:1.71, 95% CI 1.62-1.81). Preoperative hydronephrosis, age, prior stones/intervention, and concurrent kidney and ureteral stones were associated with increased risk of stricture. Of those with strictures incurred after ureteroscopy, 35% required drainage, 21% had endoscopic intervention, 4.8% required reconstructive surgery, and 1.7% underwent nephrectomy. Ureteral stricture rate after ureteroscopy of nearly 3% was higher than expected and approximately twice the rate attributable to stone disease alone. Factors associated with the stone as well as instrumentation were found to be risk factors. The morbidity of stricture disease following ureteroscopy was significant.

Upregulated PD-1 signaling antagonizes glomerular health in aged kidneys and disease.

With an aging population, kidney health becomes an important medical and socioeconomic factor. Kidney aging mechanisms are not well understood. We previously showed that podocytes isolated from aged mice exhibit increased expression of programmed cell death protein 1 (PD-1) surface receptor and its 2 ligands (PD-L1 and PD-L2). PDCD1 transcript increased with age in microdissected human glomeruli, which correlated with lower estimated glomerular filtration rate and higher segmental glomerulosclerosis and vascular arterial intima-to-lumen ratio. In vitro studies in podocytes demonstrated a critical role for PD-1 signaling in cell survival and in the induction of a senescence-associated secretory phenotype. To prove PD-1 signaling was critical to podocyte aging, aged mice were injected with anti–PD-1 antibody. Treatment significantly improved the aging phenotype in both kidney and liver. In the glomerulus, it increased the life span of podocytes, but not that of parietal epithelial, mesangial, or endothelial cells. Transcriptomic and immunohistochemistry studies demonstrated that anti–PD-1 antibody treatment improved the health span of podocytes. Administering the same anti–PD-1 antibody to young mice with experimental focal segmental glomerulosclerosis (FSGS) lowered proteinuria and improved podocyte number. These results suggest a critical contribution of increased PD-1 signaling toward both kidney and liver aging and in FSGS.

Skin autofluorescence of Advanced Glycation End-products and mortality in older adults: The roles of chronic kidney disease and diabetes

Background and aimAdvanced glycation end products are involved in age-related multisystem decline. They accumulate in body tissues with age, diabetes and chronic kidney disease (CKD), and can be measured non-invasively by the skin autofluorescence (SAF). We studied the relation between SAF and later mortality in old adults. Methods and resultsThe SAF was measured using an AGE-Reader in 451 individuals from the general population aged over 75 years, and all-cause mortality was assessed during an average follow-up of 6.4 years. The association between SAF and mortality was analyzed using a multivariate Cox survival model, adjusted for age and gender. Analyses were further adjusted for diabetes and stratified on the presence of CKD due to its interaction with SAF for the risk of mortality.Participants were 82 years old on average (SD 4.1). Their mean SAF was 2.8 AU (SD 0.6). One hundred and forty-four individuals (31.9%) died during the follow-up. Adjusted for age and gender, SAF was associated with an increased risk of all-cause mortality (HR 1.44, 95%CI: 1.14–1.82 for a one-AU increase of SAF). The association was no longer significant after adjustment for diabetes. However, after stratification for the presence of CKD, higher SAF was associated with an increased risk of all-cause mortality in the participants with CKD at baseline (HR 1.68, 95%CI: 1.11–2.55), whereas there was no association among participants without CKD (HR 0.95, 95%CI: 0.63–1.44). ConclusionSkin autofluorescence is associated with increased all-cause mortality in older adults already suffering from CKD.

Geriatric risk and protective factors for serious COVID-19 outcomes among older adults in Shanghai Omicron wave

ABSTRACT Shanghai has been experiencing the Omicron wave since March 2022. Though several studies have evaluated the risk factors of severe infections, the analyses of BA.2 infection risk and protective factors among geriatric people were much limited. This multicentre cohort study described clinical characteristics, and assessed risk and protective factors for geriatric Omicron severe infections. A total of 1377 patients older than 60 were enrolled, with 75.96% having comorbidities. The median viral shedding time and hospitalization time were nine and eight days, respectively. Severe and critical were associated with longer virus clearance time (aOR [95%CI]:0.706 (0.533–0.935), P = .015), while fully vaccinated/booster and paxlovid use shortened viral shedding time (1.229 [1.076–1.402], P = .002; 1.140 [0.019–1.274], P = .022, respectively). Older age (>80), cerebrovascular disease, and chronic kidney disease were risk factors of severe/critical. Fully vaccination was a significant protective factor against severe infections (0.237 [0.071–0.793], P = .019). We found patients with more than two comorbidities were more likely to get serious outcomes. These findings demonstrated that in the elderly older than 60 years old, older age (aged over 80), cerebrovascular disease, and chronic kidney disease were risk factors for severe infection. Patients with more than two comorbidities were more likely to get serious outcomes. Fully vaccinated/booster patients were less likely to be severe and vaccinations could shorten viral shedding time. The limitation of lacking an overall spectrum of COVID-19 infections among elders could be compensated in other larger-scale studies in the future.

Risk Factors for Slow Viral Decline in COVID-19 Patients during the 2022 Omicron Wave

Formulating termination of isolation (de-isolation) policies requires up-to-date knowledge about viral shedding dynamics. However, current de-isolation policies are largely based on viral load data obtained before the emergence of Omicron variant. In this retrospective cohort study involving adult patients hospitalised for COVID-19 between January and February 2022, we sought to determine SARS-CoV-2 viral shedding kinetics and to investigate the risk factors associated with slow viral decline during the 2022 Omicron wave. A total of 104 patients were included. The viral load was highest (Ct value was lowest) on days 1 post-symptom-onset (PSO) and gradually declined. Older age, hypertension, hyperlipidaemia and chronic kidney disease were associated with slow viral decline in the univariate analysis on both day 7 and day 10 PSO, while incomplete or no vaccination was associated with slow viral decline on day 7 PSO only. However, older age was the only risk factor that remained statistically significant in the multivariate analysis. In conclusion, older age is an independent risk factor associated with slow viral decline in this study conducted during the Omicron-dominant 2022 COVID-19 wave. Transmission-based precaution guidelines should take age into consideration when determining the timing of de-isolation.

Gout Screening Identifies a Large Cardiovascular Population at Increased Risk of Mortality.

Gout is prevalent in people with cardiovascular disease, although up to a third of the cases remain unregistered. We aimed to assess whether active gout screening in inpatients with cardiovascular events helps identify patients at higher risk of mortality after discharge. This study included patients admitted for cardiovascular events. Gout was established by records review and clinical interview. After discharge, electronic medical records were reviewed for mortality and cause of death. The association between gout and subsequent mortality was tested using Cox regression models. Of 266 recruited patients, 17 were lost to follow-up, leaving a final sample of 249 patients (93.6%). Thirty-six cases (14.5%) were classified as having gout; 13 of these (36.1%) were identified through the interview. Mean follow-up was 19.9 (SD, 8.6) months. Gout significantly increased the risk of all-cause mortality in the overall sample (hazard ratio [HR], 2.01; 95% confidence interval [CI], 1.13-3.58) and in the subgroup with a prior diagnosis of gout (HR, 2.89; 95% CI, 1.54-5.41). The adjusted HR for all-cause mortality associated with gout was 1.86 (95% CI, 1.01-3.41). Patients with gout carried an increased risk of both cardiovascular and noncardiovascular deaths; age and chronic kidney disease were mortality predictors within the gout population. Gout was an independent predictor of subsequent all-cause mortality in patients admitted for cardiovascular events. Active screening for gout allowed the detection of a larger population at high risk of mortality and could help tailor patient management to minimize the cardiovascular impact.

5-year risk of “adult-onset” chronic diseases during childhood and adolescent transitioning for individuals with cerebral palsy

Epidemiologic evidence documenting risk of chronic diseases as children with cerebral palsy age throughout growth is lacking to inform prevention strategies. The objective was to characterize the 5-year risk of chronic diseases that are typically associated with advanced aging among < 1–13 year olds with cerebral palsy and effects by patient-level factors. This retrospective cohort study used nationwide commercial administrative claims from 01/01/2001–12/31/2018 from children < 1–13 years old with ≥ 5 years of mostly continuous insurance enrollment. The 5-year risk of chronic diseases was examined for the entire cohort with and without cerebral palsy and then by baseline age group (<1–2, 3–5, 6–8, 9–11, 12–13 years old), including cardiorespiratory, metabolic, kidney, and liver diseases, cancer, depression, and osteoarthritis. For cerebral palsy, the association between 5-year chronic disease rate and patient-level factors was assessed using Cox regression. Children with (n = 5,559) vs without (n = 2.3 million) cerebral palsy had a higher 5-year risk of all chronic diseases when comparing the entire cohorts (relative risk, 1.19 to 64.26, all P < 0.05) and most chronic diseases when comparing cohorts for each age group. Among children with cerebral palsy, there were effects by gender, co-occurring intellectual disabilities and/or epilepsy, and wheelchair use for some chronic diseases, which can help to identify at-risk children. This study provides novel epidemiologic evidence of 5-year risk of “adult-onset” chronic diseases for children with cerebral palsy during important developmental stages, and associated patient-level factors (to enhance clinical detection). Findings may inform when to implement prevention strategies and who may be more at risk.

Diminished Tubule Epithelial Farnesoid X Receptor Expression Exacerbates Inflammation and Fibrosis Response in Aged Rat Kidney.

The age-associated functional decline of the kidney is accompanied by structural changes including glomerular sclerosis and interstitial fibrosis. Aging kidneys also exhibit increased vulnerability in stressful environmental conditions. In this study, we assessed the differences in responses between young and aged animals to folic acid (FA)-induced renal fibrosis. To monitor the effects of aging on FA-induced kidney fibrosis, we administered FA (250 mg/kg) to young (6-month old) and aged (20-month old) rats. The development of severe fibrosis was only detected in aged rat kidneys, which was accompanied by increased kidney injury and inflammation. Furthermore, we found that FA-treated aged rats had significantly lower farnesoid X receptor (FXR) expression in the tubular epithelial cells than the rats not treated with FA. Interestingly, the extent of inflammation was severe in the kidneys of aged rat, where the FXR expression was low. To explore the role of FXR in kidney inflammation, in vitro studies were performed using NRK52E kidney tubule epithelial cells. NF-κB activation by lipopolysaccharide treatment induces chemokine production in NRK52E cells. The activation of FXR by obeticholic acid significantly reduced the transcriptional activity of NF-κB and chemokine production. In contrast, FXR knockdown increased LPS-induced chemokine production in NRK52E cells. Finally, FXR-knockout mice that were administered FA showed increased inflammation and severe fibrosis. In summary, we demonstrated that diminished FXR expression in the epithelial cells of the renal tubules exacerbated the fibrotic response in aged rat kidneys by upregulating pro-inflammatory NF-κB activation.

Associations of maternal and foetoplacental factors with prehypertension/hypertension in early childhood.

To evaluate whether characterization of maternal and foetoplacental factors beyond birthweight can enable early identification of children at risk of developing prehypertension/hypertension. We recruited 693 mother-offspring dyads from the GUSTO prospective mother-offspring cohort. Prehypertension/hypertension at age 6 years was identified using the simplified paediatric threshold of 110/70 mmHg. We evaluated the associations of pregnancy complications (gestational diabetes, excessive/inadequate gestational weight gain, hypertensive disorders of pregnancy), foetal growth deceleration (decline in foetal abdominal circumference at least 0.67 standard deviations between second and third trimesters), high foetoplacental vascular resistance (third trimester umbilical artery systolic-to-diastolic ratio ≥90th centile), preterm birth, small-for-gestational age and neonatal kidney volumes with risk of prehypertension/hypertension at age 6 years, after adjusting for sex, ethnicity, maternal education and prepregnancy BMI. Pregnancy complications, small-for-gestational age, preterm birth, and low neonatal kidney volume were not associated with an increased risk of prehypertension/hypertension at age 6 years. In contrast, foetal growth deceleration was associated with a 72% higher risk [risk ratio (RR) = 1.72, 95% confidence interval (CI) 1.18-2.52]. High foetoplacental vascular resistance was associated with a 58% higher risk (RR = 1.58, 95% CI 0.96-2.62). Having both these characteristics, relative to having neither, was associated with over two-fold higher risk (RR = 2.55, 95% CI 1.26-5.16). Over 85% of the foetuses with either of these characteristics were born appropriate or large for gestational age. Foetal growth deceleration and high foetoplacental vascular resistance may be helpful in prioritizing high-risk children for regular blood pressure monitoring and preventive interventions, across the birthweight spectrum.

Quality of Care Among Patients with Diabetes and Cerebrovascular Disease. Insights from The Diabetes Collaborative Registry

BackgroundAlthough secondary cardiovascular prevention is a focus among patients with type 2 diabetes (T2D) and coronary artery disease (CAD) or peripheral artery disease (PAD), the application of guideline-recommended therapy in T2D patients and isolated cerebrovascular disease (CeVD) remains unknown. MethodsIn a US outpatient registry, T2D patients with established cardiovascular disease from 2014-2018 were categorized as: isolated CeVD, CeVD plus CAD or PAD, or isolated CAD/PAD. In each group, we determined the proportion with optimal secondary prevention (hemoglobin [Hb]A1C <8%, blood pressure <130/80 mm Hg, use of antithrombotics, use of statins, non-smoking/cessation counseling, and use of glucose-lowering medications with cardioprotective effects (sodium-glucose cotransporter [SGLT]-2 inhibitors, glucagon-like peptide [GLP]-1 receptor agonists, thiazolidinediones [TZDs]). Hierarchical Poisson regression was used to estimate relative rate of achieving each target across groups, adjusted for age and chronic kidney disease (where relevant). ResultsOur study included 727,467 T2D outpatients with cardiovascular disease (isolated CeVD [n = 99,777], CeVD plus CAD/PAD [n = 158,361], isolated CAD/PAD [n = 469,329]). Compared with isolated CAD/PAD patients, isolated CeVD patients more often had an HbA1c <8% (adjusted relative risk [aRR] 1.10; 95% confidence interval [CI], 1.08-1.11) but less often had a blood pressure of ≤130/80 mm Hg (aRR 0.93; 95% CI, 0.92-0.94) or were prescribed antithrombotics (0.84; 95% CI, 0.83-0.85), statins (0.86; 95% CI, 0.85-0.87), GLP-1 agonists (0.75; 95% CI, 0.73-0.78), SGLT2 inhibitors (0.73; 95% CI, 0.71-0.76), and TZDs (aRR 0.76; 95% CI, 0.73-0.78). ConclusionAmong T2D patients, those with isolated CeVD had the lowest rates of secondary cardiovascular prevention goals attainment. More focus is needed on secondary prevention in patients with CeVD.

Association Between Diabetic Retinopathy and Insomnia Risk: A Nationwide Population-Based Study.

BackgroundPrevious studies have suggested a close link between sleep disturbances and diabetic retinopathy (DR). However, to date, no confirmatory findings have been reported. We aimed to explore the risk of insomnia in DR by considering demographic factors and diabetes mellitus (DM)-related variables.MethodsA nationwide population-based cohort of 2,206,619 patients with type 2 diabetes from the Korean National Insurance Service Database was followed up for insomnia incidence. DR, non-proliferative DR (NPDR), and proliferative DR (PDR) were defined according to ICD-10 codes. The interactive effects of sex, age, and DM-related variables were analyzed to evaluate their impact on insomnia risk in DR.ResultsCompared with the non-DR group, insomnia risk was increased in the DR [(adjusted hazard ratio (aHR): 1.125, 95% confidence interval (CI):1.108-1.142), NPDR (aHR:1.117, 95% CI:1.099-1.134), and PDR (aHR:1.205, 95% CI: 1.156-1.256), even after controlling for comorbidities, lifestyle factors, and DM-related variables. The men and youngest age groups (<40 years) were most vulnerable to insomnia risk. Sex, age, DM duration, and chronic kidney disease (CKD) status exerted interactive effects with DR status in increasing the insomnia risk. In the PDR group, sex, age, DM duration, insulin therapy status, and CKD status exerted interactive effects that increased the risk of insomnia.ConclusionInsomnia risk is significantly higher in patients with DR, and clinical attention is warranted.

Risk factors for mortality in kidney transplant recipients with COVID‐19: a single centre experience and case–control study

BackgroundCOVID-19 infection is considered to cause high mortality in kidney transplant recipients (KTR). Old age, comorbidities and acute kidney injury are known risk factors for increased mortality in KTR. Nevertheless, mortality rates have varied across different regions. Differences in age, comorbidities and varying standards of care across geographies may explain some variations. However, it is still unclear whether post-transplant duration, induction therapy, antirejection therapy and co-infections contribute to increased mortality in KTR with COVID-19. The present study assessed risk factors in a large cohort from India.MethodsA matched case–control study was performed to analyze risk factors for death in KTR (N = 218) diagnosed with COVID-19 between April 2020 to July 2021 at the study centre. Cases were KTR who died (non-survivors, N = 30), whereas those who survived were taken as controls (survivors, N = 188).ResultsA high death-to-case ratio of 13.8% was observed amongst study group KTR infected with COVID-19. There was a high incidence (12.4%) of co-infections, with cytomegalovirus being the most common co-infection among non-survivors. Diarrhea, co-infection, high oxygen requirement, and need for mechanical ventilation were significantly associated with mortality on regression analyses. Antirejection therapy, lymphopenia and requirement for renal replacement therapy were associated with worse outcomes.ConclusionsThe mortality was much higher in KTR who required mechanical ventilation and had co-infections. Mortality did not vary with the type of transplant, post-transplant duration and usage of depletion induction therapy. An aggressive approach has to be taken for an early diagnosis and therapeutic intervention of associated infections.

Comparing Survival in Patients With Lung Cancer With and Without a History of Common Autoimmune Disease

IntroductionAutoimmune disease has both a predisposing and a protective effect toward malignancy. Though studies have investigated the risk of malignancy in patients with autoimmune disease, there is limited research on how autoimmunity affects survival. MethodsThis study compared survival in patients with lung cancer with and without autoimmune disease. Patients with lung cancer were culled from the Surveillance, Epidemiology, and End Results Medicare databases (2007–2014), and autoimmune diseases were identified using diagnosis codes. ResultsThe overall prevalence of investigated autoimmune diseases among the 112,445 patients was 22.7%. Overall survival (OS) (p < 0.0001) was longer and cancer-specific mortality (CSM) (p < 0.0001) reduced among patients with autoimmune disease. Median OS was 5 months higher. Improved OS and CSM were also apparent in disease stages 1, 3, and 4 in the NSCLC and SCLC subgroups (p < 0.0001) and across most specific autoimmune diseases. After adjusting for the effects of age, sex, race, disease stage, and chronic kidney disease, autoimmune disease was still predictive of higher OS (hazard ratio = 1.23, 95% confidence interval: 1.21–1.25, p < 0.0001) and reduced CSM (hazard ratio = 1.16, 95% confidence interval: 1.14–1.18, p < 0.0001). ConclusionsThe prevalence of rheumatoid arthritis, inflammatory bowel disease, and systemic lupus erythematous was highly enriched compared with the general population. The improvement in OS and CSM was larger in NSCLC than in SCLC, suggesting a larger role for the immune system in NSCLC. Alternate explanations for the improved survival include lead time bias, better access to health care, and a survival or autoimmunity-inducing genetic factor.

Comparison between COVID‑19 outcomes in the first 3 waves of the pandemic: a reference hospital report.

The course of consecutive COVID‑19 waves was influenced by medical and organizational factors. We aimed to assess the outcomes of patients hospitalized for COVID‑19 during the first 3 waves of the pandemic. We performed a retrospective analysis of medical records of all COVID‑19 patients admitted to the University Hospital in Kraków, Poland, a designated COVID‑19 hospital in Małopolska province, between March 1, 2020 and May 31, 2021. The waves were defined as 1, 2, and 3, and covered the periods of March 2020 to July 2020, August 2020 to January 2021, and February 2021 to May 2021, respectively. Patients' characteristics and outcomes for waves 1 through 3 were compared. Data analyses included 5191 patients with COVID‑19. We found differences in age (mean [SD], 60.2 [17.3] years vs 62.4 [16.8] years vs 61.9 [16.1] years, respectively, for waves 1, 2, and 3; P = 0.003), sex distribution (proportion of women, 51.4% vs 44.2% vs 43.6%; P = 0.003), as well as concentrations of inflammatory markers and oxygen saturation (the lowest and the highest for wave 1, respectively; P <0.001). Hospital death rates in subsequent waves were 10.4%, 19.8%, and 20.3% (P <0.001). Despite similarities in patients' characteristics, the length of hospital and intensive care unit stay was shorter for wave 3 than for wave 2. The risk factors for in‑hospital death were: advanced age, male sex, cardiovascular or chronic kidney disease, higher C‑reactive protein level, and hospitalization during the second or third wave. We identified differences in patients' clinical characteristics and outcomes between consecutive pandemic waves, which probably reflect changes in terms of COVID‑19 isolation policy, hospitalization and treatment indications, and treatment strategies.

Drug handling by elderly kidney: a prospective review to senile kidney physiology

Many organs' functional reserve tends to deteriorate as we age. In particular, elderly people have lower lean body mass, serum albumin levels, hepatic perfusion, and filtration rate of residual glomeruli. Furthermore, comorbid processes frequently affect renal patients, who are treated with a variety of medications. Some drug interactions are also altered by the aging process, such as the affinity and number of receptors for certain drugs, as well as cell responses to receptor activation. As a result, Patients with kidney disease who are elderly are more prone to experience adverse drug reactions. The lack of available information on the pharmacokinetic/dynamic profiles of a large number of daily used drugs makes planning a safe pharmacological regimen difficult in this patient group. Finally, many elderly patients are unintentionally disobedient. We will go over the physiological aspects of drug administration in aging kidneys in this literature review.