Baseline Kidney Research Articles

Association between different dementia diagnosis and kidney function decline: A Swedish registry study

AbstractBackgroundPopulation studies have shown that chronic kidney disease(CKD) and CKD progression are associated with dementia, particularly Alzheimer’s dementia(AD) and vascular dementia(VD). However, the impact of different brain pathogenesis on these associations is not known.MethodObservational study of patients with recently diagnosed dementia disorders from the Swedish Dementia Registry(SveDem) 2007‐2018 linked with complete information of kidney function tests [estimated glomerular filtration rate(eGFR)] over time from the Stockholm CREAtinine Measurements(SCREAM) registry. The study exposure were different dementia diagnosis [AD, VD, mixed dementia, dementia with Lewy Bodies(DLB) and Parkinson’s disease dementia(PDD), frontotemporal dementia(FTD), unspecified dementia(UNS) and other dementia types]. The study outcome was CKD progression, defined as the composite of a sustained eGFR decline of>30% from baseline, initiation of kidney replacement therapy or death attributed to kidney disease. We performed competing risk analyses where death from non‐renal causes was considered as competing events for CKD progression. Confounders included demographics, comorbidities, and baseline kidney function.ResultWe included 20,618 patients, of whom, 6,452(31%) had AD, 7,012(34%) had mixed dementia, 3,987(19%) had VD, 764(4%) had DLB or PDD, 312(2%) had FTD, and 2,091(10%) patients were diagnosed with unspecified or other dementia diagnoses. The mean age was 80 years (60%female). During median follow‐up time of 2.5 (IQR1.0‐4.5) years, 2,225(11%) events of CKD progression occurred, along with 8,684(42%) non‐renal deaths. After adjusting for confounders and accounting for competing risks, a higher risk of CKD progression compared to patients with AD was observed for patients with VD [sub‐HR, 95%CI 1.19;1.05‐1.34], mixed (1.13;1.02‐1.26), UNS or other dementia types (1.13;0.96‐1.32), while patients with DLB or PDD dementia had 46% lower risk of CKD progression (0.54;0.39‐0.76), and those with FTD showed no difference compared to AD (0.99;0.64‐1.51).ConclusionVD and mixed dementia (vs AD diagnosis) were associated with a higher risk of CKD progression, whereas DLB or PDD dementia were associated with lower risk of CKD progression. Since DLB and PDD dementia involve less and VD and mixed dementia more vascular pathology, this suggests that vascular mechanisms may play an important role in the brain‐kidney axis. Future studies are needed to explore this hypothesis.

398-P: KIM-1 and TNFR 1 and Associations with Early Diabetic Nephropathy Histology

Aim: GFR and urine albumin excretion (UAE) are prevailing measures used to detect and monitor diabetic nephropathy (DN) . We tested whether serum kidney injury molecule-1 (KIM-1) and tumor necrosis factor receptor-1 (TNFR1) , markers of DN progression, are associated with DN renal structural parameters in persons with TIDM. Methods: We measured KIM-1 and TFNR1 in 285 participants from the Renin Angiotensin System Study (RASS) . Participants had T1DM for 2-20 yrs and were free of any clinical DN. Baseline iGFR and kidney biopsies were obtained. We used linear regression to estimate cross-sectional associations of markers with renal structural measures. Results: Mean age was 30 ± yrs; mean iGFR was 125 ± 18 ml/min/1.73 m2; median UAE was 5 (IQR 4- 7) . Higher KIM-1 was associated with significantly greater mesangial fraction volume [Vv (Mes/glom) ] and the tubular atrophy (table 1) . Higher TNFR1 was associated with significantly higher Vv (Mes/glom) and glomerular basement membrane (GBM) width. Neither iGFR nor UAE were significantly associated with lesions. Conclusion: Serum KIM-1 and TNFR1 were associated with higher values for Vv (Mes/glom) , GBM, and tubular atrophy in persons with T1DM and normal kidney function, suggesting relevance as markers of early DN structural changes prior to UAE elevation or GFR decline. KIM-1 is specific to the tubules, highlighting the importance of characterizing the natural history of tubular functions in DN. Disclosure F.Tian: None. D.Prince: None. A.Doria: Research Support; Novo Nordisk Foundation. M.Mauer: None. B.Kestenbaum: Consultant; Reata Pharmaceuticals, Inc. Funding T32

MO515: Mortality Differences Between Men and Women With Chronic Kidney Disease in the Irish Health System: The National Kidney Disease Surveillance Programme

Abstract BACKGROUND AND AIMS Chronic kidney disease is associated with higher mortality compared with the general population, but mortality differences between men and women with CKD are poorly understood. Although the prevalence of CKD is consistently higher in women than in men, emerging studies suggest that men experience poorer survival. The primary goal of this study was to compare mortality rates between men and women in the Irish health system and determine whether kidney function influenced these sex-specific risks. METHOD We created a cohort of 125 890 patients from the National Kidney Disease Surveillance System (NKDSS) to compare mortality rates between men and women. Patients were recruited from 1 January 2005 to 31 December 2010 and followed until 31 December 2013. Kidney function was determined using the CKD-EPI equation, generating estimated glomerular filtration rate (mL/min/1.73 m2) (eGFR). The primary outcome was all-cause mortality from national records provided by the Central Statistics Office (CSO). The principal exposure was participant sex, classified as men or women. Patients were censored at the date of initiation of dialysis or kidney transplantation, death, loss to follow-up or end of follow-up 31 December 2013. Mortality risks were compared using the Fine-Gray approach, which accounted for the competing risks of renal replacement therapy. Adjustments were made for baseline age, kidney function and blood biomarkers, which indicated the presence and severity of clinical disease. RESULTS Of the 125 890 participants, 55.1% were women, with a mean age of 54.1 (SD: 17.7) years. The median follow-up was 7.75 years (IQR: 6.33–8.55), 243 patients (0.19%) patients progressed to RRT and 14 179 patients (11.26%) died. Overall, mortality rates were significantly higher in men than in women (18.4 versus 16.6 deaths/1000 pyrs, respectively). Compared with women, men with CKD experienced significantly higher rates of death and RRT, P < .001 (Figure 1a). With each worsening GFR category, crude mortality rates increased by 18-fold in women compared with 9-fold in men. The P-value for the interaction of sex and GFR with mortality was <0.001. In stratified analyses, the magnitude of the sHR for men versus women decreased with each descending eGFR category from a peak of 2.17 (1.88–2.49) for eGFR >90 mL/min down to 1.21 (0.98–1.49) for eGFR <29 mL/min/1.72 m2 (Table 1) and was no longer significant in the eGFR <29 mL/min/1.72 m² category. CONCLUSION Although women have a higher burden of CKD than men in the Irish health system, the overall risks of death and RRT were far greater in men than in women. However, the excess risk in men diminished with increasing severity of kidney disease such that mortality risks for women approached those of men with advanced kidney disease. While these findings may have a biologic basis, fundamental disparities in care delivery, quality or accessibility between men and women is a far more likely explanation.

Transgelin-2 in Multiple Myeloma: A New Marker of Renal Impairment?

Transgelin is a 22-kDa protein involved in cytoskeletal organization and expressed in smooth muscle tissue. According to animal studies, it is a potential mediator of kidney injury and fibrosis, and moreover, its role in tumorigenesis is emerging in a variety of cancers. The study included 126 ambulatory patients with multiple myeloma (MM). Serum transgelin-2 concentrations were measured by enzyme-linked immunoassay. We evaluated associations between baseline transgelin and kidney function (serum creatinine, estimated glomerular filtration rate—eGFR, urinary markers of tubular injury: cystatin-C, neutrophil gelatinase associated lipocalin—NGAL monomer, cell cycle arrest biomarkers IGFBP-7 and TIMP-2) and markers of MM burden. Baseline serum transgelin was also evaluated as a predictor of kidney function after a follow-up of 27 months from the start of the study. Significant correlations were detected between serum transgelin-2 and serum creatinine (R = 0.29; p = 0.001) and eGFR (R = −0.25; p = 0.007). Transgelin significantly correlated with serum free light chains lambda (R = 0.18; p = 0.047) and serum periostin (R = −0.22; p = 0.013), after exclusion of smoldering MM patients. Patients with decreasing eGFR had higher transgelin levels (median 106.6 versus 83.9 ng/mL), although the difference was marginally significant (p = 0.05). However, baseline transgelin positively correlated with serum creatinine after the follow-up period (R = 0.37; p < 0.001) and negatively correlated with eGFR after the follow-up period (R = −0.33; p < 0.001). Moreover, higher baseline serum transgelin (beta = −0.11 ± 0.05; p = 0.032) significantly predicted lower eGFR values after the follow-up period, irrespective of baseline eGFR and follow-up duration. Our study shows for the first time that elevated serum transgelin is negatively associated with glomerular filtration in MM and predicts a decline in renal function over long-term follow-up.

Ertugliflozin and Slope of Chronic eGFR: Prespecified Analyses from the Randomized VERTIS CV Trial.

A reduction in the rate of eGFR decline, with preservation of ≥0.75 ml/min per 1.73 m2 per year, has been proposed as a surrogate for kidney disease progression. We report results from prespecified analyses assessing effects of ertugliflozin versus placebo on eGFR slope from the eValuation of ERTugliflozin effIcacy and Safety CardioVascular outcomes (VERTIS CV) trial (NCT01986881). Patients with type 2 diabetes mellitus and established atherosclerotic cardiovascular disease were randomized to placebo, ertugliflozin 5 mg, and ertugliflozin 15 mg (1:1:1). The analyses compared the effect of ertugliflozin (pooled doses, n=5499) versus placebo (n=2747) on eGFR slope per week and per year by random coefficient models. Study periods (weeks 0-6 and weeks 6-52) and total and chronic slopes (week 0 or week 6 to weeks 104, 156, 208, and 260) were modeled separately and by baseline kidney status. In the overall population, for weeks 0-6, the least squares mean eGFR slopes (ml/min per 1.73 m2 per week [95% confidence interval (95% CI)]) were -0.07 (-0.16 to 0.03) and -0.54 (-0.61 to -0.48) for the placebo and ertugliflozin groups, respectively; the difference was -0.47 (-0.59 to -0.36). During weeks 6-52, least squares mean eGFR slopes (ml/min per 1.73 m2 per year [95% CI]) were -0.12 (-0.70 to 0.46) and 1.62 (1.21 to 2.02) for the placebo and ertugliflozin groups, respectively; the difference was 1.74 (1.03 to 2.45). For weeks 6-156, least squares mean eGFR slopes (ml/min per 1.73 m2 per year [95% CI]) were -1.51 (-1.70 to -1.32) and -0.32 (-0.45 to -0.19) for the placebo and ertugliflozin groups, respectively; the difference was 1.19 (0.95 to 1.42). During weeks 0-156, the placebo-adjusted difference in least squares mean slope was 1.06 (0.85 to 1.27). These findings were consistent by baseline kidney status. Ertugliflozin has a favorable placebo-adjusted eGFR slope >0.75 ml/min per 1.73 m2 per year, documenting the kidney function preservation underlying the clinical benefits of ertugliflozin on kidney disease progression in patients with type 2 diabetes mellitus and atherosclerotic cardiovascular disease. US National Library of Medicine, ClinicalTrials.gov NCT01986881. Date of trial registration: November 13, 2013.

MO531IMPACT OF INFLAMMATORY MARKERS IN COGNITIVE IMPAIRMENT IN CHRONIC KIDNEY DISEASE PATIENTS

Abstract Background and Aims Cognitive impairment is an increasingly identified major cause of chronic disability and is commonly found in patients with chronic kidney disease (CKD). Knowledge of the link between kidney dysfunction and impaired cognition may enhance our understanding of risk factors impacting cognitive dysfunction. Our study aimed to evaluate the relation between serum inflammatory markers and the risk of cognitive decline among adults with CKD. Method Forty-six patients predialysis patients CKD stage 5 (mean age 55.6±11.5 years old) accepted to participate in the study. The Montreal Cognitive Assessment (MoCA) scale was administered to patients. Patients with a MoCA global score of 24/30 were considered cognitively impaired. Descriptive analysis was done for the socio-demographic and clinical variables. We measured high-sensitivity C-reactive protein (hs-CRP), ferritin level, albuminemia, and fibrinogen in baseline plasma samples. Results The mean total MoCA score for all the patients was 22.9 ±3.8 points. Thirty-seven patients, 57.7%, were evaluated with CI, where 74.6 % with Mild CI (MCI) and 25.4% with severe CI (SCI) under 20 points). MoCA subscale analysis revealed that the mean score for visuospatial/executive domain and attention were the lowest with 5.41±1.1 /8max and 2.93±1.75/6 max, and scores for orientation were the highest 5.92±0.57/6 max. At baseline, higher levels of each inflammatory marker were associated with poorer age-adjusted performance. In analyses adjusted for baseline cognition, demographics, comorbid conditions, and kidney function, participants in the highest tertile of hs-CRP, the highest tertile of fibrinogen, and the highest tertile of ferritin had an increased risk of impairment in attention compared to participants in the lowest tertile of each marker (p=0.043, p=0.047, p=0.029, respectively. The high level of ferritin was evaluated as a risk of impairment visuospatial/executive ability, and no relationship of inflammatory markers was observed with impairment of orientation p=0.01. hs-CRP and ferritin and low albumin level were independently associated with longitudinal global cognitive function (p=0.04, p=0.02, p=0.49 respectively). Conclusion In CKD patients, we have a relatively high risk for cognitive impairment. Our results extend the findings from prior studies by showing that inflammatory markers used in routine practice contribute and are independently associated with longitudinal changes in some domains of cognitive function in patients with CKD going in parallel with the inflammatory mechanisms that have been implicated in the pathogenesis of vascular and Alzheimer’s dementia.

110 Pain Medication Prescription Patterns and the American Burn Association 2020 Guidelines on the Management of Acute Pain in the Adult Burn Patient

Abstract Introduction In September 2020, the American Burn Association released new pain guidelines following a rigorous literature review and input from experts. These guidelines were last updated 14 years ago and represent a multitude of changes including increased importance for non-opioid pain medication use and non-pharmacologic adjuncts given the current opioid crisis. Specifically, the main recommendations were to use opioid medication sparingly and always with adjuncts; acetaminophen utilized in all patients; NSAID use depending on baseline comorbidities and kidney function; neuropathic pain therapy for those with such pain/refractory to standard therapy; and ketamine for procedural sedation/adjunct for opioid consumption. Further, nonpharmacologic treatments include cognitive-behavioural therapy (‘CBT’), hypnosis, and virtual reality should be considered. The objective of this study is to describe current pain medication prescription habits at one ABA-verified centre and how well they are in compliance with these new guidelines. Methods We conducted phase one of a quality improvement retrospective study of 514 patients admitted to an ABA-verified centre over a two-year period. Data included demographics and pain medication use which was compared against the new ABA American Burn Association 2020 Guidelines on the Management of Acute Pain in the Adult Burn Patient. Pain medication contraindications were defined using UpToDate Drug Information. Statistical analysis was descriptive in nature. Results 422 patients were admitted for acute burns. 65.9% were male with an average age of 46.4 (st dev 17.6,range 15–96). Flame burns were most common(n=209,49.5%) with average TBSA of 11.9%(st dev 16.5,range 0–98%) and 54 inhalation injuries(12.8%) covering an average length of stay of 15.6 days in the burn centre (st dev 16.8,range 1–146 days). A total of 3549 pain medications were prescribed: 1792 opioid(50.5%) and 1757 non-opioid(49.5%). Of those admitted, 93.8% were prescribed opioids, 72.5% NSAIDs, 87.2% acetaminophen, 74.4% nerve pain medications, and 25.3% ketamine. Opioids were not prescribed in 26 patients(6.2%) and only prescribed in 29 patients(6.9%). Regarding adjuncts, 4(0.94%) had documented contraindications to NSAIDs and 3(0.71%) to acetaminophen. No referrals were completed for CBT. Virtual reality and hypnosis are not available at this centre. Conclusions This work represents the first known study examining compliance to the new pain guidelines in an ABA-verified burn centre. There is significant room for improvement for the use of adjuncts specifically NSAIDs and acetaminophen as both were under prescribed. In addition, nonpharmacologic treatments are largely not available or not used and may be an untapped resource for better pain control.

Abstract MP07: The Association of Optimism, Chronic Kidney Disease and Rapid Kidney Function Decline Among African Americans in the Jackson Heart Study

Background: The burden of chronic kidney disease (CKD) and incidence of end-stage renal disease are greater among African Americans than other racial and ethnic groups. A number of studies have attributed the higher prevalence of CKD to traditional risk factors and lower socioeconomic status. However, few studies have examined the association of kidney disease with dispositional optimism, the expectation that positive things will happen. Hypothesis: We hypothesize that there would be an inverse association between optimism and CKD and RKFD. Objective: To examine the association of optimism with CKD at baseline (2000-2004) and rapid kidney function decline (RKFD) between exams 1 and 3 (2000-2013) among African Americans. Methods: We examined 5292 African American participants from the Jackson Heart Study. Optimism was measured using the 6-item Life Orientation Test-Revised (LOT-R) scale and was categorized into tertiles. CKD at baseline was defined as the presence of albuminuria or reduced glomerular filtration rate (eGFR) &lt;60 ml/min/1.73m 2 , or report of dialysis at baseline examination. RKFD was defined as a decline &gt; 4 ml/min/1.73m 2 / year between exams 1 and 3. The associations between optimism and kidney outcomes were tested using multivariable logistic regression to obtain odds ratios (OR) and 95% confidence intervals (CI), adjusting for age, sex, education, income, waist circumference, alcohol intake, physical activity, smoking, diabetes, and hypertension. Results: After exclusion of missing CKD status, there were 682/3422 (19.9%) cases of CKD at exam 1 and 303/3706 (8.2%) who had RKFD at exam 3. Participants with CKD and RKFD were less optimistic ( p &lt;0.05) and were more likely to be older, less educated, have a higher waist circumference, a higher diabetes prevalence. After full adjustment, high (vs. low) optimism was associated with a 32% lower odds of CKD (OR 0.68, 95% CI 0.53-0.85). After 7.21 median years of follow up, high (vs. low) baseline optimism was associated with a 33% lower odds of RKFD after full adjustment (OR 0.67 95% CI 0.48-0.95). Conclusions: Higher optimism was associated with a lower odds of CKD and a lower odds of RKFD over a period of 7 years in this sample of African Americans.

Remedial Effects of Vitamins C and E on Atazanavir/Ritonavir-Induced Alterations in Biomarkers of Renal Function and Oxidative Stress of Male Albino Rats

Background: Atazanavir/ritonavir (ATV/r) combination is used for the management of human immunodeficiency virus and could be associated with renal toxicity characterized by oxidative stress. Objective : This study evaluated the effects of pretreatments with vitamins C and E on ATV/r- induced serum levels of creatinine, urea, uric acid, total protein, albumin and kidney levels of malondialdehyde, catalase, superoxide dismutase, glutathione and glutathione peroxidase in male albino rats. Effects of treatments with vitamins C and E on baseline levels of the above parameters were also evaluated. Methods : Fifty four (54) male albino rats used for this study were divided into 9 groups, A – I of 5 animals each. Animals in group A (placebo control) and group B (solvent control) were treated orally with water and arachis oil respectively for 30 days. Animals in groups C- F were treated with vitamin C (20mg/kg), vitamin E (20mg/kg), a combination of vitamin E+C and ATV/r (90/30mg/kg) for 30 days respectively. Animals in groups G – I were pretreated with vitamin C, vitamin E and vitamin C+E before treatment with ATV/r for 30 days respectively. Results: Baseline serum creatinine, urea, uric acid and kidney MDA levels were significantly ( p >0.05) decreased while kidney SOD, CAT, GSH, and GPX levels were increased in vitamins C and E treated animals when compared to the control. In contrast, ATV/r treatment significantly ( p >0.05) increased serum creatinine, urea, uric acid and kidney MDA levels while serum total protein, albumin, kidney SOD, CAT, GSH, and GPX levels were decreased when compared to the control. However, ATV/r –induced changes in all evaluated parameters were mitigated in vitamins C and E pretreated animals with more mitigation observed in animals pretreated with combined doses of vitamin C and E. Conclusion : Observations in this study could be attributed to the oxidative effect of ATV/r and the anti-oxidative effects of vitamins C and E.

Aortic stiffness and change in glomerular filtration rate and albuminuria in older people.

Aortic stiffness increases with age and increases pulsatile stress in the microcirculation. Abnormalities in kidney microvascular structure and function may contribute to development or progression of chronic kidney disease in older people. We performed a longitudinal analysis of 629 community-dwelling elderly Icelandic adults from the Age, Gene/Environment Susceptibility-Reykjavik Study with two visits over a mean follow-up of 5.3 years. We evaluated the associations of carotid-femoral pulse wave velocity (CFPWV), carotid pulse pressure (CPP) and augmentation index (AI), with the change in estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) assessed as annual change and dichotomized as large changes. Models were adjusted for age, sex, height, heart rate, traditional cardiovascular disease risk factors and baseline kidney measures. When eGFR was analyzed as a continuous variable, higher baseline CFPWV and CPP, but not AI, were significantly associated with a larger annual decline in eGFR in models adjusted for age, sex, height, heart rate and baseline eGFR, but not after additional adjustment for the mean arterial pressure. When eGFR was analyzed as a categorical variable, higher CFPWV was significantly associated with a decrease in eGFR of ≥3 mL/min/1.73 m 2 /year [odds ratio (OR) 1.53, 95% confidence interval (CI) 1.11-2.13] and higher AI was associated with 30% eGFR decline during follow-up (OR 1.44 and 95% CI 1.03-2.00) in fully adjusted models. None of the tonometry measures was associated with change in UACR. Abnormalities in vascular health may play a role in large declines in eGFR beyond the traditional cardiovascular disease risks in this older Icelandic cohort.