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.

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.

Patient and Care Partner Burden in CKD Patients With and Without Anemia: A US-Based Survey.

Rationale & Objective: Chronic kidney disease (CKD) has a far-reaching impact on both patients and care partners, which can be further compounded by frequent complications such as anemia. This study assessed the burden experienced by patients with CKD and the care partners of patients with CKD, with and without anemia. Study Design: Online survey. Setting & Participants: Adult patients with CKD and the care partners of adult patients with CKD living in the United States were recruited through the American Association of Kidney Patients and a third-party online panel (January 9, 2020-March 12, 2020). Outcomes: Patient and care partner characteristics, care received or provided; health-related quality of life, and work productivity. Analytical Approach: Descriptive statistics were reported separately based on the presence or absence of anemia. Results: In total, 410 patients (anemia: n=190, no anemia: n=220) and 258 care partners (anemia: n=110, no anemia: n=148) completed the survey. Most patients reported receiving paid or unpaid care because of their health condition (anemia: 58.9%, no anemia: 50.9%), with an overall average of 14.2 and 11.3 h/wk among the anemia and no anemia patients, respectively. The care partners also reported providing numerous hours of care (anemia: 33.6 h/wk, no anemia: 38.0 h/wk), especially care partners living with their care recipient (anemia: 52.6 h/wk, no anemia: 42.8 h/wk). Among the patients, those with anemia reported a numerically lower average health-related quality of life (Functional Assessment of Cancer Therapy-Anemia score, anemia: 110.1; no anemia: 121.6). Most care partners reported a severe or very severe burden (Burden Scale for Family Caregivers-Short Version score≥15, anemia: 69.1%; no anemia: 58.8%). The work productivity impairment was substantial among employed patients (anemia: 44.9%, no anemia: 35.4%) and employed care partners (anemia: 47.9%, no anemia: 40.7%). Limitations: The survey results may have been subject to selection and recall biases; moreover, the observational nature of the study does not allow for causal inferences. Conclusions: Patients with CKD and the care partners of patients with CKD experience a considerable burden, especially when anemia is present.

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.

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.).

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.

Serum vitamin D and sex hormones levels in men and women: The Multi-Ethnic Study of Atherosclerosis (MESA).

INTRODUCTION: 25-hydroxyvitamin D [25(OH)D] deficiency has been associated with low testosterone levels in men, but there are conflicting reports of its associations with sex hormones in women. Less is known about whether these associations are independent of adiposity and lifestyle factors, and whether they differ by race/ethnicity. AIM: To examine associations of 25(OH)D concentrations with sex hormone levels. METHODS: Cross-sectional analysis of 3017 men and 2929 women in a multi-ethnic cohort. MAIN OUTCOME MEASURES: Testosterone, estradiol, dehydroepiandrosterone (DHEA), sex hormone binding globulin (SHBG), and free testosterone. RESULTS: The mean (SD) levels of 25(OH)D in men and women were 25.7(10.4) and 26.1(12.0)ng/ml, respectively. In men, after adjusting for demographic and lifestyle variables, a 10ng/ml [25nmol/L] decrease in 25(OH)D was associated with an average difference of -0.70nmol/L (95%CI -1.36, -0.05) in SHBG and 0.02 percent (0.01, 0.04) in free testosterone, but was not associated with low total testosterone level (<10.41nmol/L). In women, a 10ng/ml decrease in 25(OH)D levels was associated with an average difference of -0.01nmol/L (-0.01, -0.00) for estradiol, -8.29nmol/L (-10.13, -6.45) for SHBG, 0.06 percent (0.04, 0.07) for free testosterone, and 0.40nmol/L (0.19, 0.62) for DHEA. There was no significant interaction by race/ethnicity. CONCLUSIONS: Lower 25(OH)D concentrations were associated with lower SHBG levels and higher free testosterone levels in both men and women, and lower estradiol and higher DHEA levels in women, independent of adiposity and lifestyle. We observed no significant association of 25(OH)D with total testosterone in men. Future studies are needed to determine whether vitamin D supplementation influences sex hormone levels.

Prevalence of Hyperparathyroidism, Mineral and Bone Disorders in Children with Advanced Chronic Kidney Disease.

OBJECTIVE: To identify the prevalence and risk factors for secondary hyperparathyroidism in children with advanced stages of chronic kidney disease (CKD). METHODS: A retrospective cross-sectional observational study of clinical and laboratory data of pediatric patients with CKD stage 3, 4 was conducted from 2005 through 2013 at a single center in the Kingdom of Saudi Arabia. RESULTS: One hundred nineteen children (60.5 % boys) with mean age of 10.1 ± 5.1 y were included in the study. The mean eGFR (estimated Glomerular Filtration Rate) was 18.3 ± 15.4 ml/min/1.73m(2) and the mean intact parathyroid hormone (iPTH) level was 62.2 ± 89.4 pmol/L. Patients with a high iPTH had lower eGFR than those who were euparathyroid (16 ± 13.4 vs. 29.7 ± 19 ml/min/1.73m(2), respectively; p = 0.006), had lower calcium levels (2.2 ± 0.3 vs. 2.4 ± 0.3 mmol/L; p = 0.03) and a lower bicarbonate level (21.2 ± 4.2 vs. 23.3 ± 3.2 mmol/L; p = 0.04). Three children with hyperparthyrodism (4.9 %) had fractures, 16 (26.2 %) had bone deformities compared to 5 in the euoparathyroid group (p = 0.012). Parathyroid hormone negatively correlated with the patient's eGFR (r = -0.55), serum calcium (r = -0.43), and positively correlated with serum phosphate (r = 0.38). CONCLUSIONS: The single most important predictor of hyperparathyroidism in children in the present sample was eGFR.

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.

Renal impairment in children with posterior urethral valves.

BACKGROUND: Posterior urethral valves (PUV) are a common cause of end-stage renal failure in childhood. Our aim was to describe a cohort of patients with PUV and to investigate the predictors of renal impairment. METHODS: We performed a retrospective chart review of children with PUV who were followed at King Abdulaziz University hospital between 2002 and 2011. RESULTS: The cohort comprised 68 boys. There was a significant difference in the duration of follow-up (p = 0.024), nadir serum creatinine (p < 0.001), and last known serum creatinine level (p = 0.001) between the patients with and without renal impairment. The duration of follow-up appeared to be a significant predictor for serum creatinine doubling (p = 0.003; odds ratio, 1.8). There was no difference in the age of presentation, age at the time of the study, and first or last serum creatinine between children who initially had vesicostomy and children who had ablation. CONCLUSIONS: Ablation of PUV or vesicostomy did not influence kidney function in our study cohort. Children with a normal nadir serum creatinine who presented early had a better outcome.

Chronic kidney disease in the Arab world: a call for action.

Chronic kidney disease (CKD) is an emerging non-communicable disease worldwide. The Arab countries have a high prevalence of CKD risk factors, e.g. diabetes, obesity and hypertension. Unfortunately, the magnitude of CKD in the Arab world has not been studied well. This review presents the current data on CKD in the Arab world and proposes a call for action to address this rising epidemic.

Modulation of platelet activation in chronic kidney disease patients on erythropoiesis-stimulating agents.

BACKGROUND: Clinical trials demonstrate either no benefit or increased risk of cardiovascular events and mortality in patients with chronic kidney disease (CKD) targeted for higher hemoglobin levels, who are treated with erythropoiesis-stimulating agents (ESAs). The mechanism underlying this observation remains unexplained. METHODS AND RESULTS: We assessed platelet activation by measuring soluble P-selectin (sPsel), CD40 ligand (CD40L), and circulating microparticles (CMP) in patients with CKD. Higher hemoglobin levels were associated with increased Psel levels in patients on ESAs but not in ESA-naïve anemic and nonanemic patients. Psel positively correlated with CMP and CD40L in both anemic and nonanemic patients. Multivariate linear regression analysis revealed an association between increased Psel levels and hemoglobin concentration in patients receiving ESAs. CONCLUSIONS: Anemic CKD patients on ESAs demonstrate increased levels of markers of platelet activation. These observations suggest a potentially complex interplay between platelet activation, impaired kidney function, and treatment of CKD anemia with ESAs.

Epidemiology of chronic kidney disease in the Kingdom of Saudi Arabia (SEEK-Saudi investigators) - a pilot study.

There are no available data about the prevalence of chronic kidney disease (CKD) and its risk factors in the general population of the kingdom of Saudi Arabia. To estimate the prevalence of CKD and its associated risk factors in the Saudi population, we conducted a pilot community-based screening program in commercial centers in Riyadh, Saudi Arabia. Candidates were interviewed and blood and urine samples were collected. Participants were categorized to their CKD stage according to their estimated Modification of Diet in Renal Disease (MDRD3)-based, the new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and the presence of albuminuria. The sample comprised 491 (49.9% were males) adult Saudi nationals. The mean age was 37.4 ± 11.3 years. The over-all prevalence of CKD was 5.7% and 5.3% using the MDRD-3 and CKD-EPI glomerular filtration equations, respectively. Gender, age, smoking status, body mass index, hypertension and diabetes mel-litus were not significant predictors of CKD in our cohort. However, CKD was significantly higher in the older age groups, higher serum glucose, waist/hip ratio and blood pressure. Only 7.1% of the CKD patients were aware of their CKD status, while 32.1% were told that they had protein or blood in their urine and 10.7% had known kidney stones in the past. We conclude that prevalence of CKD in the young Saudi population is around 5.7%. Our pilot study demonstrated the feasibility of screening for CKD. Screening of high-risk individuals is likely to be the most cost-effective strategy to detect CKD patients.

Kidney pathological changes in metabolic syndrome: a cross-sectional study.

BACKGROUND: The worldwide prevalence of metabolic syndrome is increasing and has been associated with chronic kidney disease. Kidney pathological findings in patients with metabolic syndrome have not been well described, as was explored in this study. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: We retrospectively screened clinical information for 146 patients who underwent elective nephrectomy for renal cell carcinoma between January 2005 and March 2007 at Brigham and Women's Hospital, Boston, MA. Twelve patients with metabolic syndrome were identified. Twelve age- and sex-matched patients who did not have any of the criteria for metabolic syndrome were used as controls. PREDICTOR: Presence of metabolic syndrome defined by using Adult Treatment Panel III criteria. OUTCOMES: Histological characteristics in each group, decrease in kidney function at 1-year follow-up. MEASUREMENTS: Two pathologists blinded to the clinical diagnosis independently evaluated nephrectomy specimens using Banff criteria to objectively assess histological characteristics. RESULTS: Baseline characteristics were similar between the 2 groups. On histopathologic examination, patients with metabolic syndrome compared with controls had a greater prevalence of tubular atrophy (P = 0.006), interstitial fibrosis (P = 0.001), and arterial sclerosis (P = 0.001), suggesting microvascular disease. Patients with metabolic syndrome had greater global (P = 0.04) and segmental glomerulosclerosis (P = 0.05). Glomerular volume and cross-sectional surface area were not different. The combined end point of tubular atrophy greater than 5%, interstitial fibrosis greater than 5%, and presence of arterial sclerosis was more prevalent in patients with metabolic syndrome (P = 0.003; odds ratio, 33; confidence interval, 2.9 to 374.3) than controls. After 1 year, estimated glomerular filtration rate was significantly lower in patients with metabolic syndrome compared with controls (P = 0.03). LIMITATIONS: Small sample size, retrospective design. CONCLUSIONS: We report a high prevalence of microvascular disease in patients with metabolic syndrome. There was a steeper decrease in kidney function over time in patients with metabolic syndrome, suggesting limited renal reserve. Aggressive screening and management may be warranted in patients with metabolic syndrome to protect kidney function.