A Machine Learning Algorithm Avoids Unnecessary Paracentesis for Exclusion of SBP in Cirrhosis in Resource-limited Settings.

BACKGROUND & AIMS: Despite the poor prognosis associated with missed or delayed spontaneous bacterial peritonitis (SBP) diagnosis, <15% get timely paracentesis, which persists despite guidelines/education in the United States. Measures to exclude SBP non-invasively where timely paracentesis cannot be performed could streamline this burden. METHODS: Using Veterans Health Administration Corporate Data Warehouse (VHA-CDW) we included patients with cirrhosis between 2009 and 2019 who underwent timely paracentesis and collected relevant clinical information (demographics, cirrhosis severity, medications, vitals, and comorbidities). XGBoost-models were trained on 75% of the primary cohort, with 25% reserved for testing. The final model was further validated in 2 cohorts: Validation cohort #1: In VHA-CDW, those without prior SBP who received 2nd early paracentesis, and Validation cohort #2: Prospective data from 276 non-electively admitted University hospital patients. RESULTS: Negative predictive values (NPVs) at 5%,10%, and 15% probability cutoffs were examined. Primary cohort: n = 9643 (mean age, 63.1 ± 8.7 years; 97.2% men; SBP, 15.0%) received first early paracentesis. Testing-set NPVs for SBP were 96.5%, 93.0%, and 91.6% at the 5%, 10%, and 15% probability thresholds, respectively. In Validation cohort #1: n = 2844 (mean age, 63.14 ± 8.37 years; 97.1% male; SBP, 9.7%) with NPVs were 98.8%, 95.3%, and 94.5%. In Validation cohort #2: n = 276 (mean age, 56.08 ± 9.09; 59.6% male; SBP, 7.6%) with NPVs were 100%, 98.9%, and 98.0% The final machine learning model showed the greatest net benefit on decision-curve analyses. CONCLUSIONS: A machine learning model generated using routinely collected variables excluded SBP with high NPV. Applying this model could ease the need to provide paracentesis in resource-limited settings by excluding those unlikely to have SBP.

A Possible Reversible Cause of Cognitive Impairment: Undiagnosed Cirrhosis and Potential Hepatic Encephalopathy in Patients with Dementia.

BACKGROUND: Dementia and hepatic encephalopathy (HE) have symptom overlap and are challenging to differentiate. The presence of undiagnosed cirrhosis may lead to missed opportunities to treat HE, which was found in a Veterans database. This needs validation in a non-Veteran cohort. METHODS: A retrospective cohort study was conducted between 2009 and 2019 using national non-Veteran patient data from the multi-center TriNetX database. Participants included 68,807 patients with a dementia diagnosis at ≥2 visits, no prior diagnosis of cirrhosis, and with sufficient laboratory test results to calculate the Fibrosis-4 (FIB-4) index, which indicates liver disease. Prevalences of high FIB-4 scores (>2.67 and >3.25) were measured within the cohort, and associations between high FIB-4 and comorbidities/demographics were examined. RESULTS: Within the cohort (44.7% male, 78.0% white, mean age 72.73 years (±11.09)), 7.6% (n = 5815) had a FIB-4 index >3.25 and 12.8% (n=8683) had FIB-4 >2.67. In multivariable logistic regression models, FIB-4 > 3.25 was associated with male gender (OR: 1.42 [1.33-1.51]), congestive heart failure (OR:1.73 [1.59-1.87]), viral hepatitis (OR: 2.23 [1.84-2.68]), alcohol use disorder (OR: 1.39 [1.22-1.58]), and chronic kidney disease (OR: 1.38 [1.28-1.48]), and inversely associated with white race (OR: 0.76 [0.71-0.82]) and diabetes (OR: 0.82 [0.77-0.88]). Similar findings were associated with the FIB-4 > 2.67 threshold. CONCLUSION: The findings of this national cohort suggest that the FIB-4 index could be utilized to screen for potential undiagnosed cirrhosis in patients with dementia and that hepatic encephalopathy that might be misdiagnosed as dementia or cause worsening of cognitive function in patients with dementia.

Optimal Oral Iron Therapy for Iron Deficiency Anemia Among US Veterans.

Importance: Optimal oral iron supplementation strategy is unclear in patients with iron deficiency anemia (IDA) who have either normal kidney function (NKF) or chronic kidney disease (CKD). Objective: To investigate the association of different oral iron supplementation strategies with the change in hemoglobin and iron indices among patients with IDA with either NKF or CKD. Design, Setting, and Participants: This retrospective cohort study was conducted between 2009 and 2019 at nationwide Veterans Health Administration facilities. Eligible participants included veterans with IDA (defined as hemoglobin <12 g/dL and either iron saturation <20% or ferritin <50 ng/mL) who received their first outpatient prescription of oral iron. Patients were further divided into those with NKF (estimated glomerular filtration rate >60 mL/min/1.73 m2) and CKD (estimated glomerular filtration rate ≥15 mL/min/1.73 m2 and <60 mL/min/1.73 m2). Data analysis was conducted from February to October 2023. Exposures: Patients were classified into 3 groups based on their oral iron dosing schedule: daily (once a day), multiple doses per day (MDD; ≥2 times per day), or alternate-day dose (ADD). Main Outcomes and Measures: The primary outcomes were change of hemoglobin, ferritin, total iron binding capacity (TIBC), and iron saturation (ISAT), which were calculated with linear mixed-effects models. Results: A total of 71 677 veterans with IDA (63 202 male [88.2%] and 8475 female [11.8%]; mean [SD] age, 68.47 [13.09] years), including 47 201 with NKF and 24 476 with CKD, were identifed. In patients with NKF in the daily group, hemoglobin increased from baseline (estimated per-30-day difference [SE], 0.27 [0.00] g/dL; P < .001). In comparison with the daily group, hemoglobin increased more in the MDD group (estimated per-30-day difference [SE], 0.08 [0.03] g/dL; P < .001), but no difference was noted in the ADD group (estimated per-30-day difference [SE], -0.01 [0.01] g/dL; P = .38). Ferritin, ISAT, and TIBC results were similar, except TIBC showed less change in the ADD group compared with the daily group. Patients with CKD showed similar trends but smaller magnitudes in changes. Among patients with NKF, the adjusted mean increase in hemoglobin was 1.03 g/dL (95% CI, 1.01-1.06 g/dL) for those in the daily group, 1.38 g/dL (95% CI, 1.36-1.40 g/dL) for those in the MDD group, and 0.93 g/dL (95% CI, 0.84-1.02 g/dL) for those in the ADD group at 90 days. Among patients with CKD, the adjusted mean increase in hemoglobin was 0.71 g/dL (95% CI, 0.68-0.73 g/dL) for those in the daily group, 0.99 g/dL (95% CI, 0.97-1.01 g/dL) for those in the MDD group, and 0.62 g/dL (95% CI, 0.52-0.73 g/dL) for those in the ADD group at 90 days. Conclusions and Relevance: In this retrospective cohort study of veterans with IDA, there was no significant difference in the improvement of hemoglobin and iron indices between daily and ADD groups, but quickest improvement was observed in the MDD group. These findings suggest that the choice of oral iron therapy should depend on the rapidity of response desired and patient preference due to adverse effects.

Undiagnosed Cirrhosis and Hepatic Encephalopathy in a National Cohort of Veterans With Dementia.

Importance: Dementia and hepatic encephalopathy (HE) are challenging to distinguish clinically. Undiagnosed cirrhosis in a patient with dementia can lead to missed opportunities to treat HE. Objective: To examine the prevalence and risk factors of undiagnosed cirrhosis and therefore possible HE in veterans with dementia. Design, Setting, and Participants: A retrospective cohort study was conducted between 2009 and 2019 using data from the Veterans Health Administration (VHA) and 2 separate validation cohorts from the Richmond Veterans Affairs Medical Center. Data analysis was conducted from May 20 to October 15, 2023. Participants included 177 422 US veterans with a diagnosis of dementia at 2 or more clinic visits, no prior diagnosis of cirrhosis, and with sufficient laboratory test results to calculate the Fibrosis-4 (FIB-4) score. Exposures: Demographic and clinical characteristics. Main Outcomes and Measures: An FIB-4 score (>2.67 suggestive of advanced fibrosis and >3.25 suggestive of cirrhosis), capped at age 65 years even for those above this cutoff who were included in the analysis. Results: Among 177 422 veterans (97.1% men; 80.7% White; mean (SD) age, 78.35 [10.97] years) 5.3% (n = 9373) had an FIB-4 score greater than 3.25 and 10.3% (n = 18 390) had an FIB-4 score greater than 2.67. In multivariable logistic regression models, FIB-4 greater than 3.25 was associated with older age (odds ratio [OR], 1.07; 95% CI, 1.06-1.09), male gender (OR, 1.43; 95% CI, 1.26-1.61), congestive heart failure (OR, 1.48; 95% CI, 1.43-1.54), viral hepatitis (OR, 1.79; 95% CI, 1.66-1.91), Alcohol Use Disorders Identification Test score (OR, 1.56; 95% CI, 1.44-1.68), and chronic kidney disease (OR, 1.11; 95% CI, 1.04-1.17), and inversely associated with White race (OR, 0.79; 95% CI, 0.73-0.85), diabetes (OR, 0.78; 95% CI, 0.73-0.84), hyperlipidemia (OR, 0.84; 95% CI, 0.79-0.89), stroke (OR, 0.85; 95% CI, 0.79-0.91), tobacco use disorder (OR, 0.78; 95% CI, 0.70-0.87), and rural residence (OR, 0.92; 95% CI, 0.87-0.97). Similar findings were associated with the FIB-4 greater than 2.67 threshold. These codes were associated with cirrhosis on local validation. A local validation cohort of patients with dementia showed a similar percentage of high FIB-4 scores (4.4%-11.2%). Conclusions and Relevance: The findings of this cohort study suggest that clinicians encountering patients with dementia should be encouraged to screen for cirrhosis using the FIB-4 score to uncover reversible factors associated with cognitive impairment, such as HE, to enhance outcomes.

Early paracentesis is associated with better prognosis compared with late or no-paracentesis in hospitalized veterans with cirrhosis and ascites.

Guidelines recommend that all hospitalized patients with cirrhosis and ascites receive an early (<24 h from admission) paracentesis. However, national data are not available regarding compliance with and the consequences of this quality metric. We used the national Veterans Administration Corporate Data Warehouse and validated International Classification of Disease codes to evaluate the rate and subsequent outcomes of early, late, and no paracentesis for patients with cirrhosis and ascites during their first inpatient admission between 2016 and 2019. Of 10,237 patients admitted with a diagnosis of cirrhosis with ascites, 14.3% received an early paracentesis, 7.3% received a late paracentesis, and 78.4% never received a paracentesis. In multivariable modeling, compared with an early paracentesis: both late paracentesis and no-paracentesis were significantly associated with increased odds of acute kidney injury (AKI) development [OR: 2.16 (95% CI, 1.59-2.94) and 1.34 (1.09-1.66), respectively]; intensive care unit (ICU) transfer [OR: 2.43 (1.71-3.47) and 2.01 (1.53-2.69), respectively] and inpatient death [OR: 1.54 (1.03-2.29) and 1.42 (1.05-1.93), respectively]. Nationally, only 14.3% of admitted veterans with cirrhosis and ascites received the American Association for the Study of Liver Diseases (AASLD) guideline-recommended diagnostic paracentesis within 24 hours of admission. Failure to complete early paracentesis was associated with higher odds of AKI, ICU transfer, and inpatient mortality. Universal and site-specific barriers to this quality metric should be evaluated and addressed to improve patient outcomes.

Primary prophylaxis for spontaneous bacterial peritonitis is linked to antibiotic resistance in the Veterans Health Administration.

Spontaneous bacterial peritonitis (SBP) is a major cause of mortality. Although SBP primary prophylaxis (SBPPr) with fluoroquinolones and trimethoprim-sulfamethoxazole (TMP-SMX) is often used, resistance could reduce its benefit. AIM: Analyze peritoneal fluid resistance patterns in patients with a first SBP episode with/without SBPPr using the Veterans Health Administration corporate data warehouse and to evaluate national antibiograms. Corporate data warehouse data were extracted using validated International Classification of Disease-9/10 codes, culture, resistance data, and outcomes of 7553 patients who developed their first inpatient SBP between 2009 and 2019 and compared between those with/without SBPPr. Escherichia coli ( E. coli ) and Klebsiella pneumoniae ( K. pneumoniae ) sensitivity to ciprofloxacin and TMP-SMX was calculated using 2021 Veterans Health Administration antibiogram data from all states. The most common isolates were E. coli , K. pneumoniae , and Staphylococcus species. Veterans taking ciprofloxacin SBBPr had higher fluoroquinolone resistance (34% vs 14% no SBPPr, p <0.0001); those taking TMP-SMX had higher TMP-SMX resistance (40% vs 14%, p <0.0001). SBPPr patients showed higher culture positivity, greater length of stay, higher second SBP, and higher probability of liver transplant rates versus no SBPPr. Multivariable models showed SBBPr to be the only variable associated with gram-negative resistance, and SBPPr was associated with a trend toward longer length of stay. E. coli ciprofloxacin sensitivity rates were 50%-87% and 43%-92% for TMP-SMX. K. pneumoniae ciprofloxacin sensitivity was 76%-100% and 72%-100% for TMP-SMX. CONCLUSION: Among patients who developed their first SBP episode, there was a higher prevalence of antibiotic resistance in those on SBPPr, with a high rate of fluoroquinolone resistance across the Veterans Health Administration sites.

Development of New Mental and Physical Health Sequelae among US Veterans after COVID-19.

Background:COVID-19 sequelae among veterans need evaluation. Design: Propensity-score-matched retrospective cohort study. Participants: A total 778,738 veterans, who were tested for COVID-19 at VA facilities between 20 February 2020−27 March 2021. Main Outcomes: Development of new physical and mental health conditions (incidence) during the follow-up period of 7 days to 3 months after the diagnosis of COVID-19. Results: Out of 778,738 veterans, 149,205 (19.2%) were inpatients and 629,533 (80.8%) were outpatients. 123,757 (15.9%) diagnosed with COVID-19. Mean age was 61 ± 15.4, mostly men (89%) who were White (68%) and non-Hispanic (88%). In hospitalized patients, COVID-19 is associated with significantly higher incidences of physical conditions (venous thromboembolism (5.8% vs. 2.9%, p < 0.001), pulmonary circulation disorder (5.1% vs. 2.9%, p < 0.001), chronic lung disease (8.4% vs. 4.3%, p < 0.001), acute kidney injury (16.4% vs. 9.3%, p < 0.001), chronic kidney disease (6.5% vs. 4.8%, p < 0.001), cardiac arrhythmia (15.2% vs. 10.9%, p < 0.001), complicated hypertension (12% vs. 8.5%, p < 0.001), coagulopathy (6.1% vs. 2.6%, p < 0.001), fluid/electrolyte disorders (24.4% vs. 12.6%, p < 0.001) and neurological disorders (7.1% vs. 3.8%, p < 0.001)) and mental health conditions (depressive episode (6.6% vs. 4.3%, p < 0.001), adjustment disorder (2.5% vs. 1.7%, p < 0.001), insomnia (4.9% vs. 3.2%, p < 0.001) and dementia (3.0% vs. 1.9%, p < 0.001)) compared to propensity-matched hospitalized COVID-19 negative patients. In outpatient settings, COVID-19 diagnosis is associated with smaller increase in the incidences of the physical sequelae. Conclusions: In this propensity-score-matched analysis of US veterans, COVID-19 survivors, especially those who were hospitalized, developed new physical and mental health sequelae at a significantly higher rate than those without COVID-19.

Angiotensin-Converting Enzyme Inhibitors and Contrast-Associated Acute Kidney Injury After Coronary Angiography and Intervention.

Contrast-associated acute kidney injury has multiple definitions, but is generally described as worsening renal function after administration of iodinated contrast media. It is associated with high in-hospital mortality and poor long-term survival. Furthermore, patients undergoing coronary angiography commonly have comorbidities such as hypertension or congestive heart failure, which are often treated with renin-angiotensin-aldosterone system-blocking agents such as angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. Trials assessing the effects of these renin-angiotensin-aldosterone system-blocking agents on the subsequent development of contrast-associated acute kidney injury have shown conflicting data, suggesting both beneficial and harmful effects. Therefore, there are no clear guidelines on whether clinicians should discontinue renin-angiotensin-aldosterone system-blocking agents peri-procedurally. In this article, we review the data from trials assessing the effects of peri-procedural renin-angiotensin system-blocking agent use in patients undergoing coronary and peripheral angiography and intervention. Future studies will likely focus on the extent of damage or potential benefit of these agents on renal function, cardiac function, as well as morbidity and mortality. Currently, there is insufficient evidence to recommend discontinuation of angiotensin-converting enzyme inhibitors prior to coronary angiography.

Acute Cardiac Tamponade in a 58-Year-Old Male with Poststreptococcal Glomerulonephritis.

Pericarditis in conjunction with nephritis is an uncommon clinical scenario with a broad differential diagnosis. We present the case of a 58-year-old male who developed nephritis and pericardial effusion with tamponade physiology. In the following, we discuss the differential diagnosis for concomitant nephritis and pericarditis and discuss the work-up performed on our patient. We also review the epidemiology of postinfectious glomerulonephritis in adults and describe previous cases of Streptococcus pyogenes pericarditis in the literature.

Proton pump inhibitors are associated with increased risk of development of chronic kidney disease.

BACKGROUND: Acute interstitial nephritis secondary to proton pump inhibitors (PPIs) frequently goes undiagnosed due to its subacute clinical presentation, which may later present as chronic kidney disease (CKD). We investigated the association of PPI use with the development of CKD and death. METHODS: Two separate retrospective case-control study designs were employed with a prospective logistic regression analysis of data to evaluate the association of development of CKD and death with PPI use. The population included 99,269 patients who were seen in primary care VISN2 clinics from 4/2001 until 4/2008. For evaluation of the CKD outcome, 22,807 with preexisting CKD at the first observation in Veterans Affairs Health Care Upstate New York (VISN2) network data system were excluded. Data obtained included use of PPI (Yes/No), demographics, laboratory data, pre-PPI comorbidity variables. RESULTS: A total of 19,311/76,462 patients developed CKD. Of those who developed CKD 24.4 % were on PPI. Patients receiving PPI were less likely to have vascular disease, COPD, cancer and diabetes. Of the total of 99,269 patients analyzed for mortality outcome, 11,758 died. A prospective logistic analysis of case-control data showed higher odds for development of CKD (OR 1.10 95 % CI 1.05-1.16) and mortality (OR 1.76, 95 % CI 1.67-1.84) among patients taking PPIs versus those not on PPIs. CONCLUSIONS: Use of proton pump inhibitors is associated with increased risk of development of CKD and death. With the large number of patients being treated with proton pump inhibitors, healthcare providers need to be better educated about the potential side effects of these medications.

Prevalence of various comorbidities among veterans with chronic kidney disease and its comparison with other datasets.

Chronic kidney disease (CKD) has a complicated interrelationship with various comorbidities. The purpose of this study was to describe the prevalence of various comorbidities among veterans with CKD and compare it with other datasets like Kidney Early Evaluation Program (KEEP), National Health and Nutrition Examination Survey (NHANES) and Medicare. Patients who had at least one outpatient visit in year 2007 (1 January 2007 to 31 December 2007) were included in the study (n = 75,787). Glomerular filtration rate (eGFR) was estimated by the Modification of Diet in Renal Disease (MDRD) study equation. CKD prevalence was calculated based on one or two serum creatinine values at least 3 months apart. Demographic data were obtained including age, gender, race, weight, height and body mass index (BMI). The prevalence of various comorbidities was also collected based on ICD 9 codes from the problem list. The prevalence of CKD among veterans was 47.3%, much higher than estimated in the US population. Patients with CKD were more likely to have any vascular disease (36.89% vs. 14.87%), diabetes (34.18% vs. 17.83%), hypertension (86.65% vs. 57.56%), and cancer (18.69% vs. 9.23%). Irrespective of age, the prevalence of vascular disease was much higher among veterans with CKD. The prevalence of coronary artery disease, peripheral vascular disease, and cancer was much higher among elderly veterans with CKD as compared to other datasets. CKD is a growing endemic associated with a high frequency of concomitant chronic illnesses. Public health resources should be applied for early recognition and risk modification of CKD.

Renin-Angiotensin-Aldosterone System Blockers in Elderly Adults with Chronic Kidney Disease without Diabetes Mellitus or Proteinuria.

OBJECTIVES: To compare the effect of renin-angiotensin-aldosterone system (RAAS) blockers with that of other antihypertensive agents on outcomes in a cohort of elderly veterans with incident chronic kidney disease (CKD) without diabetes mellitus or proteinuria. DESIGN: Retrospective cohort study. SETTING: Veterans Affairs (VA) Upstate New York Healthcare System. PARTICIPANTS: All participants were seen in primary care clinic in Veterans Integrated Service Network 2, which comprises five VA medical centers and 29 community-based outpatient clinics, from April 2001 to April 2008. Veterans with incident CKD who were taking antihypertensive medications and did not have proteinuria or diabetes mellitus on the date of onset of CKD were selected from this population. MEASUREMENTS: The outcome variables studied were progression of kidney disease (doubling of serum creatinine level or Stage 5 CKD (estimated glomerular filtration rate <15 mL/min per 1.73 m2 )), all-cause mortality, and combined outcome. RESULTS: Analysis included 2,474 participants, 47.9% of whom were taking RAAS blockers at baseline and the rest other antihypertensives. Time-varying Cox proportional hazards analyses did not reveal a statistically significant difference in primary combined outcome in participants taking RAAS blockers and those taking other antihypertensives (hazard ratio = 1.09, 95% confidence interval = 0.93-1.27). There was also no significant effect on individual outcomes (death or progression of kidney disease). CONCLUSION: Use of RAAS blockers was not associated with less hazard of combined and individual outcomes (doubling of serum creatinine, Stage 5 CKD, death) in elderly veterans with incident CKD without diabetes mellitus or proteinuria.

Safety and efficacy of milk and molasses enemas in the emergency department.

BACKGROUND: Increased scrutiny is occurring from regulatory agencies about the use of nonsterile enema preparations in the emergency department (ED) for constipation. This includes the "off-label" use of milk and molasses (M&M) enemas, as there are no reported data in the medical literature to determine safety and efficacy. OBJECTIVES: To evaluate the success and complication rates of administering M&M enemas in the ED. METHODS: This was a structured retrospective study at two EDs over 8 years. Primary success was defined as the patient having a bowel movement. Secondary measures of success included improved pain score by 2 or more points or lowering of a heart rate initially over 100 beats/min by 20 or more beats/min. Complications included: hemodynamic compromise, increased pain, electrolyte disturbances, bacteremia, bowel perforation, rectal pain or bleeding, cardiac dysrhythmias, anaphylaxis, electrolyte disturbances, dizziness or syncope, or hospital admission for issues surrounding enema. RESULTS: There were 2013 enemas given, of which 261 were M&M enemas; 214 were given alone. Success rates defined only as bowel evacuation for M&M enemas alone were 87.9% (188/214) and, when used after other treatment failures, were 82.4% (28/34) successful. Five additional patients improved with the secondary measures (90.2% success). There were 8/261 complications (3.1%), of which four had an increased heart rate, two had decreased blood pressure, one had an increased pain score, and one subsequently developed a fever. CONCLUSION: M&M enemas have a low complication rate when used in the ED.

Acute kidney injury and death associated with renin angiotensin system blockade in cardiothoracic surgery: a meta-analysis of observational studies.

BACKGROUND: Acute kidney injury (AKI) is a common complication after cardiovascular surgery. The use of renin angiotensin system (RAS) blockers preoperatively is controversial due to conflicting results of their effect on the incidence of postoperative AKI and mortality. STUDY DESIGN: Meta-analysis of prospective or retrospective observational studies (1950 to January 2013) using MEDLINE, EMBASE, the Cochrane Library, conferences, and ClinicalTrials.gov, without language restriction. SETTING & POPULATION: Patients undergoing cardiovascular surgery. SELECTION CRITERIA FOR STUDIES: Retrospective or prospective studies evaluating the effect of preoperative use of RAS blockers in the development of postoperative AKI and/or mortality in adult patients. INTERVENTION: Preoperative use of RAS blockers. RAS-blocker use was defined as long-term use of either angiotensin-converting enzyme inhibitors or angiotensin receptor blockers until the day of surgery. OUTCOMES: The primary outcome was the development of postoperative AKI; the secondary outcome was mortality. AKI was defined by different authors using different criteria. Death was ascertained in the hospital, at 30 days, or at 90 days in different studies. RESULTS: 29 studies were included (4 prospective and 25 retrospective); 23 of these involving 69,027 patients examined AKI, and 18 involving 54,418 patients studied mortality. Heterogeneity was found across studies regarding AKI (I2 = 82.5%), whereas studies were homogeneous regarding mortality (I2 = 20.5%). Preoperative RAS-blocker use was associated with increased odds for both postoperative AKI (OR, 1.17; 95% CI, 1.01-1.36; P = 0.04) and mortality (OR, 1.20; 95% CI, 1.06-1.35; P = 0.005). LIMITATIONS: Lack of randomized controlled trials, different definitions of AKI, different durations of follow-up used to analyze death outcome, and inability to exclude outcome reporting bias. CONCLUSIONS: In retrospective studies, preoperative use of RAS blockers was associated with increased odds of postoperative AKI and mortality in patients undergoing cardiovascular surgery. A large, multicenter, randomized, controlled trial should be performed to confirm these findings.

The MDRD equation underestimates the prevalence of CKD among blacks and overestimates the prevalence of CKD among whites compared to the CKD-EPI equation: a retrospective cohort study.

BACKGROUND: Black individuals are far more likely than white individuals to develop end stage renal disease (ESRD). However, earlier stages of chronic kidney disease (CKD) have been reported to be less prevalent among blacks. This disparity remains poorly understood. The objective of this study was to evaluate whether the lower prevalence of CKD among blacks in early stages of CKD might be due in part to an inability of the MDRD equation to accurately determine early stages of CKD in both the black and white population. METHODS: We conducted a retrospective cohort study of 97, 451 patients seen in primary care clinic in Veterans Integrated Service Network 2 (VISN 2) over a 7 year period to determine the prevalence of CKD using both the Modification of Diet in Renal Disease (MDRD) Study equation and the more recently developed CKD Epidemiology Collaboration (CKD-EPI) equation. Demographic data, comorbid conditions, prescription of medications, and laboratory data were recorded. Logistic regression and quantile regression models were used to compare the prevalence of estimated glomerular filtration rate (eGFR) categories between black and white individuals. RESULTS: The overall prevalence of CKD was lower when the CKD-EPI equation was used. Prevalence of CKD in whites was 53.2% by MDRD and 48.4% by CKD-EPI, versus 34.1% by MDRD and 34.5% by CKD-EPI in blacks. The cumulative logistic regression and quantile regression showed that when eGFR was calculated by the EPI method, blacks were as likely to present with an eGFR value less than 60 mL/min/1.73 m2 as whites. Using the CKD-EPI equation, blacks were more likely than white individuals to have stage 3b, 4 and 5 CKD. Using the MDRD method, the prevalence in blacks was only higher than in whites for stage 4 and 5 CKD. Similar results were obtained when the analysis was confined to patients over 65 years of age. CONCLUSIONS: The MDRD equation overestimates the prevalence of CKD among whites and underestimates the prevalence of CKD in blacks compared to the CKD-EPI equation.

Effect of steroid-free low concentration calcineurin inhibitor maintenance immunosuppression regimen on renal allograft histopathology and function.

BACKGROUND: The most common cause of late kidney transplant failure is insidiously progressive renal dysfunction associated with organ scarring and fibrosis. Advanced donor age, delayed graft function, calcineurin toxicity and repeated acute rejection episodes are risk factors for this pathophysiology. METHODS: We employed 3, 12 and 24 months surveillance renal biopsies, scored using the Chronic Allograft Damage Index (CADI), with periodic estimates of glomerular filtration rate (eGFR) to assess the effect of a steroid-free maintenance immunosuppression regimen on allograft histology and function. Ninety-one patients were induced with Alemtuzumab and then treated with mycophenolate sodium and low trough concentrations of tacrolimus. RESULTS: Fifty-six of 91 patients followed for 24 months showed no clinical rejection and in 16 more only minimal histological or borderline changes as defined by Banff criteria were observed. Histologically acute rejection was observed in 14 patients including two detected on surveillance biopsy. Five patients refused biopsies but showed stable eGFR for 24 months. Graft histopathology in the group with no rejection did not worsen. In contrast, nearly half the patients with acute rejection showed progression of CADI scores and a total of four grafts were lost over the 2 years. The 16 patients with borderline rejection changes exhibited stable glomerular filtration rate throughout, but 12.5% showed progression of CADI scores in the 12- to 24-month period. CONCLUSIONS: Following Alemtuzumab induction and in conjunction with low-dose tacrolimus and mycophenolate, continuous steroid therapy was not required to prevent progressive injury or preservation of graft function in patients without biopsy-proven acute rejection. Scored surveillance renal biopsies provide a useful tool to monitor transplanted kidneys.

Mild acute kidney injury is associated with increased mortality after cardiac surgery in patients with eGFR < 60 mL/min/1.73 m(2).

BACKGROUND: A small increase in serum creatinine after cardiac surgery has been associated with increased mortality. However, it is unclear whether this association varies with baseline renal function. METHODS: We retrospectively reviewed data on 1359 patients who underwent cardiac surgery over a 4-year period in two tertiary care hospitals including demographic data, comorbid conditions, and intra- and postoperative complications using a standardized form. We followed patients for 90 days postoperatively and death rates and length of hospital stay were noted. RESULTS: The incidence of acute kidney injury (AKI) after cardiac surgery was 40.2%. Patients were grouped into terciles based on change in serum creatinine. Kaplan-Meier survival analysis and Cox regression analysis showed that the development of AKI with a small increase in serum creatinine of more than 0.3 mg/dL from baseline (tercile 3) was associated with a higher risk of mortality within 90 days and 7 days longer hospitalization following a cardiac surgery. Stratified analysis showed that only patients with baseline eGFR < 60 mL/min/1.73 m (2) had fivefold higher mortality with rise of serum creatinine >0.3 mg/dL. CONCLUSIONS: Patients with baseline eGFR < 60 mL/min/1.73 m(2) had increased risk of mortality after cardiac surgery with a small increase in serum creatinine whereas a similar increase in serum creatinine in those with eGFR ≥ 60 mL/min/1.73 m(2) did not increase mortality.

Transmetallation and gadolinium: do low iron stores prevent the development of nephrogenic systemic fibrosis in high-risk end-stage renal disease patients?

Nephrogenic systemic fibrosis (NSF) is a systemic disorder that occurs in patients with renal failure and manifests as a thickening of the skin and flexion contractures of the joints. The etiology may involve an exposure to a gadolinium (Gd)-based magnetic resonance contrast agent. It has been proposed that in hemodialysis (HD) patients, iron mobilization (decreased total iron-binding capacity, increased iron level, and transferrin oversaturation) causes a transmetallation reaction and the release of free Gd from its chelator with the deposition of both Gd and iron in the affected tissues leading to fibrosis. The objective of this study was to investigate whether the use of gadopentetate dimeglumine leads to iron mobilization and to the development of NSF in HD patients. A retrospective chart analysis of 236 HD patients was performed and patients who had received a Gd-containing contrast agent were selected for analysis of their iron studies before and after the Gd exposure. A total of 25 patients were identified as having had a magnetic resonance imaging study and all were administered gadopentetate dimeglumine and no patients had any signs or symptoms suggestive of NSF. Six patients had the appropriate iron studies, which showed no statistically significant difference in the serum iron, total iron-binding capacity, ferritin, or transferrin saturation before and after exposure to gadopentetate dimeglumine. Our data suggest that the use of gadopentetate dimeglumine in HD patients did not cause iron mobilization and transmetallation therefore may partially explain the lack of development of NSF seen in our patient population.

Dialysis disequilibrium syndrome: a narrative review.

Dialysis Disequilibrium Syndrome (DDS) is characterized by neurological symptoms caused by rapid removal of urea during hemodialysis. It develops primarily from an osmotic gradient that develops between the brain and the plasma as a result of rapid hemodialysis. This results in brain edema that manifests as neurological symptoms such as headache, nausea, vomiting, muscle cramps, tremors, disturbed consciousness, and convulsions. In severe cases, patients can die from advanced cerebral edema. Recent advancements in cell biology implicate the role of urea disequilibrium (with a smaller contribution from organic osmolytes) as the pathophysiological mechanism responsible for this syndrome. In this review, we discuss the pathogenesis, clinical features and prevention of DDS.