Safety and Efficacy of Vadadustat for Anemia in Patients Undergoing Dialysis.

BACKGROUND: Vadadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, a class of compounds that stimulate endogenous erythropoietin production. METHODS: We conducted two randomized, open-label, noninferiority phase 3 trials to evaluate the safety and efficacy of vadadustat, as compared with darbepoetin alfa, in patients with anemia and incident or prevalent dialysis-dependent chronic kidney disease (DD-CKD). The primary safety end point, assessed in a time-to-event analysis, was the first occurrence of a major adverse cardiovascular event (MACE, a composite of death from any cause, a nonfatal myocardial infarction, or a nonfatal stroke), pooled across the trials (noninferiority margin, 1.25). A key secondary safety end point was the first occurrence of a MACE plus hospitalization for either heart failure or a thromboembolic event. The primary and key secondary efficacy end points were the mean change in hemoglobin from baseline to weeks 24 to 36 and from baseline to weeks 40 to 52, respectively, in each trial (noninferiority margin, -0.75 g per deciliter). RESULTS: A total of 3923 patients were randomly assigned in a 1:1 ratio to receive vadadustat or darbepoetin alfa: 369 in the incident DD-CKD trial and 3554 in the prevalent DD-CKD trial. In the pooled analysis, a first MACE occurred in 355 patients (18.2%) in the vadadustat group and in 377 patients (19.3%) in the darbepoetin alfa group (hazard ratio, 0.96; 95% confidence interval [CI], 0.83 to 1.11). The mean differences between the groups in the change in hemoglobin concentration were -0.31 g per deciliter (95% CI, -0.53 to -0.10) at weeks 24 to 36 and -0.07 g per deciliter (95% CI, -0.34 to 0.19) at weeks 40 to 52 in the incident DD-CKD trial and -0.17 g per deciliter (95% CI, -0.23 to -0.10) and -0.18 g per deciliter (95% CI, -0.25 to -0.12), respectively, in the prevalent DD-CKD trial. The incidence of serious adverse events in the vadadustat group was 49.7% in the incident DD-CKD trial and 55.0% in the prevalent DD-CKD trial, and the incidences in the darbepoetin alfa group were 56.5% and 58.3%, respectively. CONCLUSIONS: Among patients with anemia and CKD who were undergoing dialysis, vadadustat was noninferior to darbepoetin alfa with respect to cardiovascular safety and correction and maintenance of hemoglobin concentrations. (Funded by Akebia Therapeutics and Otsuka Pharmaceutical; INNO2VATE ClinicalTrials.gov numbers, NCT02865850 and NCT02892149.).

Vadadustat in Patients with Anemia and Non-Dialysis-Dependent CKD.

BACKGROUND: Vadadustat is an oral hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor, a class of drugs that stabilize HIF and stimulate erythropoietin and red-cell production. METHODS: In two phase 3, randomized, open-label, active-controlled, noninferiority trials, we compared vadadustat with the erythropoiesis-stimulating agent (ESA) darbepoetin alfa in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD) not previously treated with an ESA who had a hemoglobin concentration of less than 10 g per deciliter and in patients with ESA-treated NDD-CKD and a hemoglobin concentration of 8 to 11 g per deciliter (in the United States) or 9 to 12 g per deciliter (in other countries). The primary safety end point, assessed in a time-to-event analysis, was the first major adverse cardiovascular event (MACE; a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke), pooled across the two trials. Secondary safety end points included expanded MACE (MACE plus hospitalization for either heart failure or a thromboembolic event). The primary and key secondary efficacy end points in each trial were the mean change in hemoglobin concentration from baseline during two evaluation periods: weeks 24 through 36 and weeks 40 through 52. RESULTS: A total of 1751 patients with ESA-untreated NDD-CKD and 1725 with ESA-treated NDD-CKD underwent randomization in the two trials. In the pooled analysis, in which 1739 patients received vadadustat and 1732 received darbepoetin alfa, the hazard ratio for MACE was 1.17 (95% confidence interval [CI], 1.01 to 1.36), which did not meet the prespecified noninferiority margin of 1.25. The mean between-group differences in the change in the hemoglobin concentration at weeks 24 through 36 were 0.05 g per deciliter (95% CI, -0.04 to 0.15) in the trial involving ESA-untreated patients and -0.01 g per deciliter (95% CI, -0.09 to 0.07) in the trial involving ESA-treated patients, which met the prespecified noninferiority margin of -0.75 g per deciliter. CONCLUSIONS: Vadadustat, as compared with darbepoetin alfa, met the prespecified noninferiority criterion for hematologic efficacy but not the prespecified noninferiority criterion for cardiovascular safety in patients with NDD-CKD. (Funded by Akebia Therapeutics and Otsuka Pharmaceutical; PRO2TECT ClinicalTrials.gov numbers, NCT02648347 and NCT02680574.).

Impact of Finerenone-Induced Albuminuria Reduction on Chronic Kidney Disease Outcomes in Type 2 Diabetes : A Mediation Analysis.

BACKGROUND: In patients with chronic kidney disease (CKD) and type 2 diabetes (T2D), finerenone, a nonsteroidal mineralocorticoid receptor antagonist, reduces cardiovascular and kidney failure outcomes. Finerenone also lowers the urine albumin-to-creatinine ratio (UACR). Whether finerenone-induced change in UACR mediates cardiovascular and kidney failure outcomes is unknown. OBJECTIVE: To quantify the proportion of kidney and cardiovascular risk reductions seen over a 4-year period mediated by a change in kidney injury, as measured by the change in log UACR between baseline and month 4. DESIGN: Post hoc mediation analysis using pooled data from 2 phase 3, double-blind trials of finerenone. (ClinicalTrials.gov: NCT02540993 and NCT02545049). SETTING: Several clinical sites in 48 countries. PATIENTS: 12 512 patients with CKD and T2D. INTERVENTION: Finerenone and placebo (1:1). MEASUREMENTS: Separate mediation analyses were done for the composite kidney (kidney failure, sustained ≥57% decrease in estimated glomerular filtration rate from baseline [approximately a doubling of serum creatinine], or kidney disease death) and cardiovascular (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) outcomes. RESULTS: At baseline, median UACR was 514 mg/g. A 30% or greater reduction in UACR was seen in 3338 (53.2%) patients in the finerenone group and 1684 (27.0%) patients in the placebo group. Reduction in UACR (analyzed as a continuous variable) mediated 84% and 37% of the treatment effect on the kidney and cardiovascular outcomes, respectively. When change in UACR was analyzed as a binary variable (that is, whether the guideline-recommended 30% reduction threshold was met), the proportions mediated for each outcome were 64% and 26%, respectively. LIMITATION: The current findings are not readily extendable to other drugs. CONCLUSION: In patients with CKD and T2D, early albuminuria reduction accounted for a large proportion of the treatment effect against CKD progression and a modest proportion of the effect against cardiovascular outcomes. PRIMARY FUNDING SOURCE: Bayer AG.

The association between dual RAAS inhibition and risk of acute kidney injury and hyperkalemia in patients with diabetic kidney disease: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Dual renin-angiotensin-aldosterone system (RAAS) blockade involves dual therapy with a combination of angiotensin-converting enzyme inhibitors (ACEis), angiotensin-receptor blockers (ARBs), direct renin inhibitors (DRIs), or mineralocorticoid receptor antagonists (MRAs). It is hypothesized that dual RAAS blockade would result in a more complete inhibition of the RAAS cascade. However, large clinical trials on dual RAAS inhibition have shown increased risk of acute kidney injury (AKI) and hyperkalemia without additional benefit on mortality, cardiovascular events, or chronic kidney disease (CKD) progression compared to RAAS inhibitor monotherapy in patients with diabetic kidney disease (DKD). The development of newer, more selective non-steroidal MRAs as cardiorenal protective therapies has created a new opportunity for dual RAAS inhibition. We conducted a systematic review and meta-analysis of the risks of AKI and hyperkalemia with dual RAAS blockade in patients with DKD. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: This is a systematic review and meta-analysis of the randomized controlled trials (RCT) published from 1 January 2006 to 30 May 2022. The study population included adult patients with DKD receiving dual RAAS blockade. A total of 31 RCTs and 33 048 patients were included in the systematic review. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using random effects. RESULTS: There were 208 AKI events in 2690 patients on ACEi + ARB versus 170 in 4264 patients with ACEi or ARB monotherapy (pooled RR 1.48, 95% CI: 1.23-1.39). There were 304 hyperkalemia events in 2818 patients on ACEi + ARB versus 208 in 4396 patients with ACEi or ARB monotherapy (pooled RR 1.97, 95% CI: 1.32-2.94). A non-steroidal MRA + ACEi or ARB showed no increase in the risk of AKI (pooled RR 0.97, 95% CI: 0.81-1.16) compared to ACEi or ARB monotherapy but had a 2-fold higher risk of hyperkalemia with 953 events in 7837 patients in dual therapy versus 454 events in 6895 patients in monotherapy (pooled RR 2.05, 95% CI: 1.84-2.28). A steroidal MRA + ACEi or ARB had a 5-fold higher risk of hyperkalemia with 28 events in 245 at risk in dual therapy versus five events in 248 at risk in monotherapy (pooled RR 5.42 95% CI: 2.15-13.67). CONCLUSION: Dual therapy with RAASi is associated with an increased risk of AKI and hyperkalemia compared to RAASi monotherapy. Conversely, dual therapy with RAAS inhibitors and non-steroidal MRAs have no additional risk of AKI but a similar risk of hyperkalemia, which is lower than dual therapy with RAAS inhibitors and steroidal MRAs.

Differential associations of rheumatoid arthritis and periodontitis or tooth loss: A cross-sectional study.

AIM: To study the association between periodontitis, tooth loss, and rheumatoid arthritis (RA) by using a large national dataset. MATERIALS AND METHODS: An observational cross-sectional study was performed using the National Health and Nutrition Examination Survey cycles (2009-2014). RA status was detected using a questionnaire. Periodontal status was assigned on the basis of the clinical attachment level and periodontal pocket depth. Dentition status was assessed by the number of permanent teeth observed. We examined the association between RA as exposure and moderate/severe periodontitis and non-functional dentition as outcomes. We progressively adjusted our models for different sets of potential confounders. RESULTS: Moderate/severe periodontitis was more prevalent in participants reporting RA (53% vs. 41.5%, p = .0003). Non-functional dentition was more prevalent in participants with RA (41% vs. 15.5%, p = .0001). The fully adjusted model showed that participants with RA had higher odds of having non-functional dentition (odds ratio 1.8, 95% confidence interval [CI] 1.3-2.3, p = .0001) but no association with moderate/severe periodontitis (prevalence ratio 1.01, 95% CI 0.9-1.1, p = .9). CONCLUSION: RA was associated with a higher likelihood of having non-functional dentition but did not show any association with periodontitis after adjusting for the risk factors to control their confounding effect.

Psoriasis and oral health in adult United States population: a cross-sectional study.

OBJECTIVES: To detect the association between psoriasis as an exposure and oral health conditions as outcomes represented by periodontal and dentition status. This was addressed by analysis of a large number of adults in the United States. METHODS: By using The National Health and Nutrition Examination Survey datasets from 2009 to 2014, we performed a cross-sectional analysis of 11,726 participants included in our study population. For participants aged ≥ 30 years, the psoriasis status was assessed from the medical questionnaire. We used data from periodontal and oral examinations to assess the oral conditions of our participants. We examined the association between psoriasis as exposure and moderate/severe periodontitis and non-functional dentition as outcomes. RESULTS: The weighted prevalence of psoriasis was 3%, 44% for moderate/severe periodontitis, and 20.5% for non-functional dentition. The fully adjusted model showed no significant association between psoriasis and moderate/severe periodontitis (Prevalence Ratio 1.02, 95% CI 0.9-1.2, p = 0.8). There was no statistically significant association between psoriasis and non-functional dentition except in the fully adjusted model it became statistically significant (Prevalence Ratio 0.8, 95% CI 0.7-0.9, p = 0.04). CONCLUSION: Our results showed no association between psoriasis and periodontal or dentition status except in a fully adjusted model for non-functional dentition.

Erythropoietic effects of vadadustat in patients with anemia associated with chronic kidney disease.

Patients with chronic kidney disease (CKD) develop anemia largely because of inappropriately low erythropoietin (EPO) production and insufficient iron available to erythroid precursors. In four phase 3, randomized, open-label, clinical trials in dialysis-dependent and non-dialysis-dependent patients with CKD and anemia, the hypoxia-inducible factor prolyl hydroxylase inhibitor, vadadustat, was noninferior to the erythropoiesis-stimulating agent, darbepoetin alfa, in increasing and maintaining target hemoglobin concentrations. In these trials, vadadustat increased the concentrations of serum EPO, the numbers of circulating erythrocytes, and the numbers of circulating reticulocytes. Achieved hemoglobin concentrations were similar in patients treated with either vadadustat or darbepoetin alfa, but compared with patients receiving darbepoetin alfa, those receiving vadadustat had erythrocytes with increased mean corpuscular volume and mean corpuscular hemoglobin, while the red cell distribution width was decreased. Increased serum transferrin concentrations, as measured by total iron-binding capacity, combined with stable serum iron concentrations, resulted in decreased transferrin saturation in patients randomized to vadadustat compared with patients randomized to darbepoetin alfa. The decreases in transferrin saturation were associated with relatively greater declines in serum hepcidin and ferritin in patients receiving vadadustat compared with those receiving darbepoetin alfa. These results for serum transferrin saturation, hepcidin, ferritin, and erythrocyte indices were consistent with improved iron availability in the patients receiving vadadustat. Thus, overall, vadadustat had beneficial effects on three aspects of erythropoiesis in patients with anemia associated with CKD: increased endogenous EPO production, improved iron availability to erythroid cells, and increased reticulocytes in the circulation.

Cardiovascular safety and efficacy of vadadustat for the treatment of anemia in non-dialysis-dependent CKD: Design and baseline characteristics.

Current clinical practice guidelines for anemia management in non-dialysis-dependent chronic kidney disease (NDD-CKD) recommend the use of erythropoiesis-stimulating agents (ESAs) as standard of care. Vadadustat, an investigational oral hypoxia-inducible factor prolyl-hydroxylase inhibitor, stimulates endogenous erythropoietin production. The PRO2TECT program comprises 2 global, Phase 3, randomized, open-label, active-controlled, sponsor-blind clinical trials to evaluate safety and efficacy of vadadustat vs darbepoetin alfa in adult patients with anemia associated with NDD-CKD. Patients recruited into the ESA-untreated NDD-CKD trial (N = 1751) had hemoglobin <10 g/dL and had not received an ESA within 8 weeks prior to inclusion in the study. Patients recruited into the ESA-treated NDD-CKD trial (N = 1725) had hemoglobin between 8 and 11 g/dL (US) or 9 and 12 g/dL (non-US) and were actively treated with an ESA for anemia associated with CKD. Trial periods in both trials include (1) correction/conversion (weeks 0-23); (2) maintenance (weeks 24-52); (3) long-term treatment (week 53 to end of treatment); and (4) safety follow-up (end-of-treatment to 4 weeks later). The primary safety endpoint is time to first adjudicated major adverse cardiovascular event, defined as all-cause mortality, nonfatal myocardial infarction, or nonfatal stroke, pooled across both trials. The primary efficacy endpoint in each trial is change in hemoglobin from baseline to primary evaluation period (weeks 24-36), comparing vadadustat vs darbepoetin alfa treatment groups. Demographics and baseline characteristics are similar among patients in both trials and broadly representative of the NDD-CKD population. These trials will help to evaluate the safety and efficacy of vadadustat for management of anemia associated with NDD-CKD.

Ferric Citrate Dosing in Iron Deficiency Anemia in Nondialysis-Dependent Chronic Kidney Disease.

INTRODUCTION: Ferric citrate (FC) is indicated as an oral iron replacement for iron deficiency anemia in adult patients with chronic kidney disease (CKD) not on dialysis. The recommended starting dose is one 1-g tablet three times daily (TID). This study investigated long-term efficacy and safety of different FC dosing regimens for treating anemia in nondialysis-dependent CKD (NDD-CKD). METHODS: In this phase 4, randomized, open-label, multicenter study, patients with anemia with NDD-CKD (estimated glomerular filtration rate, ≥20 mL/min and <60 mL/min) were randomized 1:1 to one FC tablet (1-g equivalent to 210 mg ferric iron) TID (3 g/day) or 2 tablets twice daily (BID; 4 g/day). At week 12, dosage was increased to 2 tablets TID (6 g/day) or 3 tablets BID (6 g/day) in patients whose hemoglobin (Hb) levels increased <0.5 g/dL or were <10 g/dL. Primary endpoint was mean change in Hb from baseline to week 24. RESULTS: Of 484 patients screened, 206 were randomized and 205 received FC. Mean (standard deviation) changes from baseline in Hb at week 24 were 0.77 (0.84) g/dL with FC TID 3 g/day and 0.70 (0.98) g/dL with FC BID 4 g/day. DISCUSSION/CONCLUSIONS: FC administered BID and TID for 48 weeks was safe and effective for treating anemia in this population, supporting potentially increased dosing flexibility.

United States ED Visits by Adult Women for Nonfatal Intimate Partner Strangulation, 2006 to 2014: Prevalence and Associated Characteristics.

INTRODUCTION: Nonfatal intimate partner strangulation poses significant acute and long-term morbidity risks and also heightens women's risk for future femicide. The lifetime prevalence of nonfatal intimate partner strangulation has been estimated to be approximately 10%, or 11 million women, in the general United States population. Given the potential for significant health risks and serious consequences of strangulation, this study adds to the limited literature by estimating prevalence and describing the associated characteristics of strangulation-related visits among United States ED visits by adult women after intimate partner violence. METHODS: Prevalence estimation as well as simple and multivariable logistic regression analyses were completed using data from the Nationwide Emergency Department Sample spanning the years 2006 to 2014. RESULTS: The prevalence of strangulation codes was estimated at 1.2% of all intimate partner violence visits. Adjusting for visits, hospital characteristics, and visit year, higher odds of strangulation were noted in younger women, metropolitan hospitals, level I/II trauma centers, and non-Northeast regions. Increases in strangulation events among intimate partner violence-related visits in recent years were also observed. DISCUSSION: A relatively low prevalence may reflect an underestimate of true nonfatal intimate partner strangulation visits owing to coding or a very low rate of ED visits for this issue. Higher odds of strangulation among intimate partner violence visits by women in more recent years may be due to increased recognition and documentation by frontline clinicians and coding teams. Continued research is needed to further inform clinical, postcare, and social policy efforts.

Vadadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, for treatment of anemia of chronic kidney disease: two randomized Phase 2 trials in Japanese patients.

BACKGROUND: Vadadustat is an investigational, oral hypoxia-inducible factor prolyl hydroxylase inhibitor in development in Japan for the treatment of chronic kidney disease (CKD)-induced anemia. METHODS: Two Phase 2, multicenter, double-blind, placebo-controlled studies randomized Japanese patients with nondialysis-dependent (NDD, n = 51) or dialysis-dependent (DD, n = 60) CKD-induced anemia to once-daily vadadustat (150, 300 or 600 mg) or placebo. A 6-week, fixed-dose primary efficacy period was followed by a 10-week vadadustat dose adjustment/maintenance period. The primary endpoint was the mean change in hemoglobin (Hb) level from pretreatment to Week 6. RESULTS: Statistically significant (P < 0.01) dose-dependent increases in mean Hb values were observed at Week 6 in all vadadustat groups versus placebo [placebo and vadadustat 150, 300 and 600 mg: -0.47, 0.43, 1.13 and 1.62 (NDD-CKD) and -1.48, -0.28, 0.08 and 0.41 (DD-CKD), respectively]. By Week 16, 91% (NDD-CKD) and 71% (DD-CKD) of vadadustat-treated participants achieved target Hb levels (10.0-12.0 g/dL) and significant dose-dependent changes in iron utilization and mobilization biomarkers were observed with vadadustat. During the primary efficacy period, the incidence of treatment-emergent adverse events (AEs) with placebo and vadadustat 150, 300 and 600 mg was 36, 33, 58 and 54% (NDD-CKD) and 40, 53, 73 and 40% (DD-CKD), respectively. The most common AEs during the primary efficacy period were nausea and hypertension (NDD-CKD) and diarrhea, nasopharyngitis and shunt stenosis (DD-CKD). Of 23 serious AEs in 18 patients, 1 was deemed related (hepatic function abnormal); no deaths were reported. CONCLUSIONS: The efficacy and safety results from these studies support the development of vadadustat for the treatment of anemia in patients with CKD.

Occupational risk factors for chronic kidney disease in Andhra Pradesh: 'Uddanam Nephropathy'.

BACKGROUND: CKD of unknown etiology (CKDu) has been reported in several countries including India. We previously showed a prevalence of CKD in India to be 17.2% and we found a CKD epidemic in Andhra Pradesh (AP) to be 46.8%. We conducted this study to further explore the unexplained CKD epidemic in AP. METHODS: We recruited 1201 adult participants through systematic random sampling from eight administrative divisions. Demographic, medical, and detailed occupational history was collected. Anthropometric measurements and blood pressure were taken and blood and urine samples were collected. Poisson regression model was used to identify potential predictors for CKD. RESULTS: We analyzed data for 1184 individuals with mean age of 44.6 ± 14.0 years, of whom 44% were male. Prevalence of CKD was 32.2%. Working as a farmer had 20% more prevalence of CKD compared to non-farmers in the fully adjusted model (PR 1.2, 95% CI 1.01-1.42). Age, alcohol consumption, and chewing tobacco were also independent predictors of CKD. Gender, hypertension, and diabetes were not associated with CKD. CONCLUSIONS: The prevalence of CKD in AP is 32.2%. Occupational exposure among farmers could play a potential role in this epidemic. Large longitudinal epidemiologic research studies are needed to trace the causes of this problem.

Outcome of acute kidney injury in pediatric patients admitted to the intensive care unit.

BACKGROUND: Acute kidney injury (AKI) is common in the pediatric intensive care unit (PICU). We aimed to describe the etiology, clinical features, and outcome of AKI in pediatric patients and to determine the predictors for initiation of renal replacement and mortality. METHODS: A retrospective chart review was performed of the medical records for all patients who were admitted to the PICU at King Abdulaziz University Hospital between January 1 and December 31, 2011. The pediatric-modified RIFLE criteria were used to classify AKI. RESULTS: We included 102 children with AKI, aged 4 - 60 months. Oliguria (61.5%, p < 0.0001) and hypervolemic signs (38.5%, p = 0.03) were more common among patients with RIFLE class failure. They also had the highest mortality (53.9%, p = 0.01). Oliguric patients were ~ 23 times more likely than their non-oliguric counterparts to be initiated on renal replacement therapy (RRT) (RR = 23.38, 95% CI: 3.07 - 178.16). Diuretic infusion was also a strong predictor for RRT initiation (RR = 10.00, 95% CI: 2.77 - 36.12). Hypervolemic patients were twice more likely to die during hospitalization in both unadjusted and adjusted models (RR = 2.06, 95% CI: 1.09 - 3.90, and aRR = 2.45, 95% CI: 1.09 - 5.51, respectively). Mechanical ventilation and RRT initiation were associated with higher likelihood of death (ARR = 13.23, 95% CI: 1.90 - 92.04, and ARR = 2.20, 95% CI: 1.18 - 4.12, respectively). Patients with RIFLE class Failure were about thrice more likely than patients with RIFLE class Risk to die in both the unadjusted (RR = 2.76, 95% CI: 1.35 - 5.65), and adjusted models (ARR = 2.88, 95% CI: 1.38 - 6.04). Children with AKI had longer PICU stay (0.0003) and higher mortality (< 0.0001) than the non-AKI group. CONCLUSION: Severe AKI predicted high mortality in critically ill children.

Burden and predictors of hypertension in India: results of SEEK (Screening and Early Evaluation of Kidney Disease) study.

BACKGROUND: Hypertension (HTN) is one of the major causes of cardiovascular morbidity and mortality. The objective of the study was to investigate the burden and predictors of HTN in India. METHODS: 6120 subjects participated in the Screening and Early Evaluation of Kidney disease (SEEK), a community-based screening program in 53 camps in 13 representative geographic locations in India. Of these, 5929 had recorded blood pressure (BP) measurements. Potential predictors of HTN were collected using a structured questionnaire for SEEK study. RESULTS: HTN was observed in 43.5% of our cohort. After adjusting for center variation (p < 0.0001), predictors of a higher prevalence of HTN were older age ≥ 40 years (p < 0.0001), BMI of ≥ 23 Kg/M2 (p < 0.0004), larger waist circumference (p < 0.0001), working in sedentary occupation (p < 0.0001), having diabetes mellitus (p < 0.0001), having proteinuria (p < 0.0016), and increased serum creatinine (p < 0.0001). High school/some college education (p = 0.0016), versus less than 9th grade education, was related with lower prevalence of HTN. Of note, proteinuria and CKD were observed in 19% and 23.5% of HTN subjects. About half (54%) of the hypertensive subjects were aware of their hypertension status. CONCLUSIONS: HTN was common in this cohort from India. Older age, BMI ≥ 23 Kg/M2, waist circumference, sedentary occupation, education less, diabetes mellitus, presence of proteinuria, and raised serum creatinine were significant predictors of hypertension. Our data suggest that HTN is a major public health problem in India with low awareness, and requires aggressive community-based screening and education to improve health.

Albuminuria: An Underappreciated Risk Factor for Cardiovascular Disease.

Albuminuria, an established biomarker of the progression of chronic kidney disease, is also recognized as a biomarker for the risk of cardiovascular disease. Elevated urinary albumin excretion indicates kidney damage and systemic vascular disease, including myocardial capillary disease and arterial stiffness. Albuminuria is associated with an increased risk of coronary artery disease, stroke, heart failure, arrhythmias, and microvascular disease. There are now several therapeutic agents that can lead to albuminuria lowering and a reduction in cardiovascular risk. However, screening for albuminuria is still low. Considering the importance of multidisciplinary management of patients with cardiovascular disease, it is crucial that health care professionals managing such patients are aware of the benefits of albuminuria surveillance and management.

Impact of Preoperative Weight Loss on 30-Day Complication Rate after Bariatric Surgery.

BACKGROUND: The aim of this study is to evaluate the impact of preoperative weight loss on surgical outcomes and operating room (OR) times after primary bariatric procedures, including laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (RYGB). STUDY DESIGN: A retrospective cohort study uses the 2021 MBSAQIP dataset. Preoperative total weight loss (TWL)% was calculated. Patients were then divided in to 4 groups: those with no weight loss, lost <0 to <5%, lost ≥5% to <10%, or lost ≥10% TWL preoperatively. These groups were then stratified into those with BMI less than 50 kg/m 2 and those with BMI 50 kg/m 2 or more and 30-day outcomes and OR times were compared. RESULTS: Analysis included 171,010 patients. For BMI less than 50 kg/m 2 , preoperative weight loss led to no consistent improvement in surgical outcomes. Although >0% to <5% TWL led to a decrease in intra- and postoperative occurrences after RYGB and a decrease in reoperation rates after LSG, these observations were not seen in those with higher degree of weight loss. In patients with BMI 50 kg/m 2 or more, preoperative weight loss showed a consistent improvement in reintervention rates after LSG, and readmission rates after RYGB. There was no improvement in other outcomes, however, irrespective of degree of preoperative weight loss. CONCLUSIONS: In patients undergoing primary bariatric surgery, preoperative weight loss does not lead to a consistent improvement in outcomes or OR times. In those with BMI 50 kg/m 2 or more, there may be improvement in select outcomes that is procedure-specific. Overall, these data do not support a uniform policy of preoperative weight loss, although selective use in some high-risk patients may be appropriate.

Association of Bioimpedance Parameters with Increases in Blood Pressure during Hemodialysis.

BACKGROUND: Intradialytic hypertension, defined as an increase in BP from pre- to post-hemodialysis (HD), affects 5%-15% of patients receiving maintenance HD and is associated with cardiovascular and all-cause mortality. Hypervolemia is believed to be a major etiological factor, yet the association of more objective biomarkers of volume status with intradialytic hypertension is not well described. METHODS: In a post hoc analysis of the Frequent Hemodialysis Network Daily Trial ( n =234), using data from baseline, 1-, 4-, and 12-month visits ( n =800), we used random-effects regression to assess the association of bioimpedance estimates of volume (vector length) with post-HD systolic BP (continuous) and any increase in systolic BP (categorical) from pre- to post-HD. We adjusted models for randomized group; age; sex; self-reported race; Quételet (body mass) index; vascular access; HD vintage; hypertension; history of heart failure; diabetes; residual kidney function (urea clearance); pre-HD systolic BP; ultrafiltration rate; serum-dialysate sodium gradient; and baseline values of hemoglobin, phosphate, and equilibrated Kt/V urea. RESULTS: The mean age of participants was 50±14 years, 39% were female, and 43% were Black. In adjusted models, shorter vector length (per 50 Ω/m) was associated with higher post-HD systolic BP (2.9 mm Hg; 95% confidence interval [CI], 1.6 to 4.3) and higher odds of intradialytic hypertension (odds ratio 1.66; 95% CI, 1.07 to 2.55). Similar patterns of association were noted with a more stringent definition of intradialytic hypertension (>10 mm Hg increase from pre- to post-HD systolic BP), where shorter vector length (per 50 Ω/m) was associated with a higher odds of intradialytic hypertension (odds ratio 2.17; 95% CI, 0.88 to 5.36). CONCLUSIONS: Shorter vector length, a bioimpedance-derived proxy of hypervolemia, was independently associated with higher post-HD systolic BP and risk of intradialytic hypertension.