Improving the residual risk of renal and cardiovascular outcomes in diabetic kidney disease: A review of pathophysiology, mechanisms, and evidence from recent trials.

Based on global estimates, almost 10% of adults have diabetes, of whom 40% are estimated to also have chronic kidney disease (CKD). Almost 2 decades ago, treatments targeting the renin-angiotensin system (RAS) were shown to slow the progression of kidney disease. More recently, studies have reported the additive benefits of antihyperglycaemic sodium-glucose co-transporter-2 inhibitors in combination with RAS inhibitors on both CKD progression and cardiovascular outcomes. However, these recent data also showed that patients continue to progress to kidney failure or die from kidney- or cardiovascular-related causes. Therefore, new agents are needed to address this continuing risk. Overactivation of the mineralocorticoid (MR) receptor contributes to kidney inflammation and fibrosis, suggesting that it is an appropriate treatment target in patients with diabetes and CKD. Novel, selective non-steroidal MR antagonists are being studied in these patients, and the results of two large recently completed clinical trials have shown that one such treatment, finerenone, significantly reduces CKD progression and cardiovascular events compared with standard of care. This review summarizes the pathogenic mechanisms of CKD in type 2 diabetes and examines the potential benefit of novel disease-modifying agents that target inflammatory and fibrotic factors in these patients.

Can billing codes accurately identify rapidly progressing stage 3 and stage 4 chronic kidney disease patients: a diagnostic test study.

BACKGROUND: The International Classification of Diseases (ICD) coding system is the industry standard tool for billing, disease classification, and epidemiology purposes. However, ICD codes are often not assigned or incorrectly given, particularly among Chronic Kidney disease (CKD) patients. Our study evaluated the diagnostic accuracy of CKD-staging ICD codes among CKD patients from a large insurer database in identifying individuals rapidly progressing towards end-stage renal disease (ESRD). PATIENTS AND METHODS: Serial observations including outpatient serum creatinine measurements collected from 2007 through 2014 of 216,529 patients were examined. The progression of CKD using a serum creatinine based longitudinal mixed-model was contrasted with that documented by CKD-staging ICD codes. Rapid progressors, defined as those with yearly estimated glomerular filtration rate (eGFR) loss greater than 4 ml/min/1.73m2) were identified. The diagnosis of CKD using eGFR was also compared to diagnosis using a set of CKD related ICD codes. RESULTS: Of 10,927 clinically identified CKD patients qualifying for inclusion in the progression analysis, 323 were clinically identified as rapid progressors. CKD-staging ICD codes identified 83 of these, for a sensitivity of 25.7% with positive predictive value (PPV) of 13.74%, and specificity 95.09% with negative predictive value (NPV) of 97.68%. Of 28,762 laboratory-confirmed CKD patients, 9249 had a qualifying ICD code, for a sensitivity of 16% with PPV of 63.10%; Of 187,767 patients with laboratory-confirmed absence of CKD, 182,359 also did not have a qualifying ICD code, for a specificity of 97.12% with NPV of 90.33%. CONCLUSION: This study depicts the novel finding that ICD-codes display poor capacity to identify rapidly progressing CKD patients when compared to gold standard eGFR measures, and further demonstrates the limitations of coding in CKD diagnosis. This analysis further defines the limitations of ICD codes in addressing diagnosis of disease severity or disease progression for clinical or epidemiological purposes.

Preoperative serum potassium predicts the clinical outcome after non-cardiac surgery.

BACKGROUND: Potassium disorders have been linked to adverse outcomes in various medical conditions. However, the association of preoperative serum potassium with postoperative outcome is not well established. We aimed to examine the association between preoperative potassium with a 30-day mortality and adverse cardiovascular event (MACE). METHODS: We conducted a cohort study using a prospectively collected database of patients, undergoing surgical procedures from 1998 to 2013 in the VA Western New York Healthcare System, which are reported to the Veterans Affairs Surgical Quality Improvement Program (VASQIP). The patients were categorized into three groups based on their documented preoperative potassium concentrations. Hypokalemia was defined as serum potassium concentration <4 mmol/L and hyperkalemia was defined as serum potassium concentrations >5.5 mmol/L. The values within the range of 4.0-5.5 mmol/L were considered as normokalemia and used as the control group. Statistical analyses included Chi-square test, analysis of variance and multivariate logistic regression to estimate the risk of MACE within 30 days of surgery. RESULTS: Study included 5959 veterans who underwent surgery between 1998 and 2013. The patients in the hyperkalemics group had lower kidney function compared to the other two groups. The frequency of MACE was 13.6% in hypokalemics and 21.9% in hyperkalemics that were both significantly higher than 4.9% in controls. In multivariate logistic regression the hazard risk (HR) ratios of MACE were (2.17, 95% CI 1.75-2.70) for hypokalemics and (3.23, 95% CI 2.10-4.95) for hyperkalemics when compared to normokalemic controls. CONCLUSIONS: Preoperative hypokalemia and hyperkalemia are both independent predictors of MACE within 30 days.

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 chronic kidney disease in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis.

BACKGROUND: The incidence and prevalence of chronic kidney disease (CKD) continue to rise worldwide. Increasing age, diabetes, hypertension, and cigarette smoking are well-recognized risk factors for CKD. Chronic obstructive pulmonary disease (COPD) is characterized by chronic airway inflammation leading to airway obstruction and parenchymal lung destruction. Due to some of the common pathogenic mechanisms, COPD has been associated with increased prevalence of CKD. METHODS: Systematic review of medical literature reporting the incidence and prevalence of CKD in patients with COPD using the Cochrane Collaboration Methodology, and conduct meta-analysis to study the cumulative effect of the eligible studies. We searched Medline via Ovid, PubMed, EMBASE and ISI Web of Science databases from 1950 through May, 2016. We included prospective and retrospective observational studies that reported the prevalence of CKD in patients with COPD. RESULTS: Our search resulted in 19 eligible studies of which 9 have been included in the meta-analysis. The definition of CKD was uniform across all the studies included in analysis. COPD was found to be associated with CKD in the included epidemiological studies conducted in many countries. Our meta-analysis showed that COPD was found to be associated with a significantly increased prevalence of CKD (Odds Ratio [OR] = 2.20; 95% Confidence Interval [CI] 1.83, 2.65). STUDY LIMITATIONS: Studies included are observational studies. However, given the nature of our research question there is no possibility to perform a randomized control trial. CONCLUSIONS: Patients with COPD have increased odds of developing CKD. Future research should investigate the pathophysiological mechanism behind this association, which may lead to better outcomes.

Positive Predictive Value of a Single Assessment of Estimated GFR in the Diagnosis of Chronic Kidney Disease.

OBJECTIVES: The positive predictive value (PPV) of a single assessment of estimated glomerular filtration rate (eGFR) in the diagnosis of chronic kidney disease (CKD) is not known. Our objective was to determine the PPV of a single assessment of eGFR among adults with at least one eGFR <60 mL/min in their lifetime, using the Distributed Area Research and Therapeutics Network CKD natural history dataset. METHODS: In all, 47,104 adults who were cared for by 113 practices in the United States were included. Proportions of patients in eGFR categories at baseline were calculated using the following categories: <15 mL/min, 15 to 29.99 mL/min, 30 to 44.99 mL/min, and 45 to 59.99 mL/min. Comparisons were then made between the baseline and the endpoint to identify patients who had a follow-up eGFR that remained at <60 mL/min. The proportions of patients in each eGFR category were compared baseline to endpoint using cross-tabulations. To test the proposed cutpoint, the proportions of patients who had an eGFR that remained at <60 mL/min were measured, using the cutpoints that included the highest cumulative proportion of patients. The sensitivity and specificity of that cutpoint were calculated. RESULTS: A cutpoint of <45 mL/min was identified, yielding a PPV of 93% with a sensitivity of 28% and a specificity of 94%. CONCLUSIONS: A valid cutpoint to screen for CKD was identified. This cutpoint may prove important to early screening for CKD while reducing the burden on the healthcare system and patients suspected of having CKD.

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.

The role of perioperative transfusion on long-term survival of veterans undergoing surgery.

OBJECTIVE: To examine the influence of perioperative blood transfusions on perioperative outcomes and late survival. BACKGROUND: Perioperative blood transfusion has been reported to have a negative impact on perioperative morbidity but its long-term effect on survival is unknown. The purpose of this study was to evaluate the effects of perioperative transfusion on perioperative outcomes and survival. METHODS: We studied 12,345 surgical procedures from Veteran Administration Surgical Quality Improvement Program database from July 1998 through 2010. Patients with transfusion were compared with a severity-matched control group. We performed the Fisher exact test for comparison of categorical values and Wilcoxon rank sum test for continuous values. Multivariate regression was used to eliminate other confounding factors. The predictive value of multivariate risk model was tested with receiver-operator curves. Patients were matched using an optimal 1:1 digit-matching algorithm. All analyses were performed with NCSS-2007 version 1-12. P < 0.05 was considered statistically significant. RESULTS: The 848 patients who received perioperative transfusions had higher unadjusted rates of mortality and decreased long-term survival. The odds ratio (OR) for 10 years mortality in transfused group was 2.92 and after adjusting for preoperative risk factors decreased to 1.40 (P < 0.01). However, after data were filtered for any perioperative complications, such an association was seen before, OR = 2.05 (P = 0.006), and was lost after propensity matching, OR = 1.19 (P = 0.35). CONCLUSIONS: After filtering out perioperative complications and adjusting for preoperative morbidity, our final analysis did not reveal an increased long-term mortality. We conclude that transfusion may reduce long-term survival through its effects on perioperative complications.

The effect of acute kidney injury after revascularization on the development of chronic kidney disease and mortality in patients with chronic limb ischemia.

OBJECTIVE: This study examined the effect of perioperative acute kidney injury (AKI) on long-term kidney dysfunction and death after lower extremity revascularization. Perioperative AKI is commonly seen in the form of mild rises of serum creatinine after major cardiovascular surgeries. Its effect on long-term survival and development of chronic kidney disease (CKD) is well established in cardiac surgery patients. However, there are no data on the effect of AKI on long-term outcomes after revascularization for lower limb ischemia. METHODS: We retrospectively reviewed the patients with peripheral arterial occlusive diseases who underwent endovascular or surgical revascularization of the lower extremities from 2001 through 2010. All demographic and clinical information have been maintained prospectively by the surgeon and followed up by the research team. Perioperative AKI was defined as rises of ≥0.3 mg/dL in serum creatinine from the values measured preoperatively. The primary end points were development of CKD (estimated glomerular filtration rate <60 mL/min) and all-cause mortality. Univariate and multivariate analyses were performed to examine relevant associations. RESULTS: Within the study period, 717 patients underwent 875 procedures. Mean follow-up was 42 ± 14 months. AKI developed in 86 patients after the index procedure. Overall prevalence of CKD diagnosed postoperatively was 14.9%. Overall mortality reported within the follow-up period was 55.9%. Perioperative AKI was a significant predictor of CKD (area under the curve, 0.84 ± 0.13) and all cause mortality (area under the curve, 0.82 ± 0.12). CONCLUSIONS: Perioperative AKI is associated with an increased occurrence of CKD and a higher mortality rate after revascularization procedures of the lower extremities.

The effect of adding functional classification to ASA status for predicting 30-day mortality.

BACKGROUND: The functional capacity to perform the activities of daily living is identified as an independent predictor of perioperative mortality but is not formally incorporated in the American Society of Anesthesiologists (ASA) classification. Our primary objective was to assess whether functional capacity is an independent predictor of 30-day and long-term mortality in a general population and, if so, to define how it may formally be incorporated into the routine preoperative ASA classification assessment. METHODS: This retrospective, observational cohort study was conducted using 1998 to 2009 data extracted from the Veterans Affairs Surgical Quality Improvement Program of Western New York, a perioperative prospectively maintained database. Mortality follow-up was performed for all records in 2013. This population-based sample included all patients undergoing any noncardiac surgery (n = 12,324). Each patient's ASA class (assigned preoperatively) was appended with subclasses A or B, with A representing patients who were functionally independent and B representing partially or fully dependent patients. The primary outcome was all-cause mortality during the follow-up period. Secondary outcomes included 30-day postoperative complications and mortality. Multivariate logistic regression was used to identify independent risk factors for mortality. RESULTS: The likelihood for mortality was significantly lower for A patients than B patients within each ASA class. The odds ratios for mortality for group A patients significantly favored survival over group B within each ASA class (0.14, 0.29, and 0.50, for ASA class II, III, and IV, respectively, each P < 0.0001). The odds ratio for mortality of IIB over IIIA patients was 1.92 (95% confidence interval [CI], 1.19-3.11; P = 0.01); 1.29 (95% CI, 1.04-1.60; P = 0.03) for IIIB over IVA patients; and 2.03 (95% CI, 0.99-4.12, P=0.11) for IVB over ASA V patients, despite each higher class carrying a greater disease burden, by definition. The area under the curve the receiver operator characteristic curve was 0.811 ± 0.010 for traditional ASA classification in predicting death within 30 days, which improved 4.7% to 0.848 ± 0.008 using the modified ASA classification, P < 0.00001. CONCLUSIONS: Functional capacity was an independent predictor of mortality within each ASA class, indicating that it should be considered for incorporation into the routine preoperative evaluation. Functional dependence may be an indication for increasing a patient's ASA class by 1 class-point to better reflect his or her perioperative risk, but prospective validation of these findings is recommended, as this is a preliminary study.

An observational study of the quality of care for chronic kidney disease: a Buffalo and Albany, New York metropolitan area study.

BACKGROUND: The database of a major regional health insurer was employed to identify the number and frequency of covered patients with chronic kidney disease (CKD). We then examined the characteristics of their care as defined, in part, by the frequency of physician visits and specialty referral, the characteristics of laboratory testing and total costs as indices of the quality of care of the subject population. METHODS: This retrospective, cross-sectional study analyzed insurance claims, laboratory results and medication prescription data. Patients with two estimated glomerular filtration rate readings below 60 ml/min/1.73 m(2) (n = 20,388) were identified and classified by CKD stage. RESULTS: The prevalence of CKD stages 3a and above was 12 %. Vascular comorbidities were common with prevalence increasing steadily from stage 3a through stage 5. Only 55.6 % of stage 4 CKD patients had claims for nephrology visits within one year of their index date. Fifty-nine percent of patients had claims for renin-angiotensin system (RAS) blockers. Twenty-five percent of patients in stage 3a CKD filled a prescription for non-steroidal anti-inflammatory drugs. Fifty-two percent of patients who developed end-stage renal disease received their first dialysis treatment as inpatients. CONCLUSIONS: The pattern of medical practice observed highlights apparent deficiencies in the care of CKD patients including inappropriate medication use, delayed nephrology referral, and a lack of preparation for dialysis. This study shows the potential value of using large patient databases available through insurers to assess and likely improve regional CKD care.

Early versus late initiation of renal replacement therapy in critically ill patients with acute kidney injury after cardiac surgery: a systematic review and meta-analysis.

OBJECTIVE: To investigate the impact of early versus late renal replacement therapy (RRT) on mortality in patients with acute kidney injury (AKI) after cardiac surgery. DESIGN: Meta-analysis of 9 retrospective cohort studies and 2 randomized clinical trials extracted from the Medline engine from 1950 to 2013. SETTING: University medical school. PARTICIPANTS: 841 Patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 841 patients were studied. Pooled estimates of the odds ratio with 95% confidence interval using a random-effect model were conducted as well as the heterogeneity, publication bias, and sensitivity analysis. Primary outcome was 28-day mortality, and secondary outcome was the intensive care unit (ICU) length of stay. The 28-days mortality rate was lower in the early RRT group (OR = 0.29, 95% CI, 0.16-0.52, p<0.0001, NNT = 5). Heterogeneity was high (I2 = 56%), and publication bias was low. Secondary outcome suggested 3.9 (1.5-6.3) days shorter ICU stay in the early RRT group, p<0.0001, with extremely high heterogeneity (I(2) = 99%), and low publication bias. Specifically, studies before 2000 and studies with mortality less than 50% in the late RRT group reported significantly higher odds ratio and mean difference than overall value favoring early RRT. CONCLUSION: Early initiation of RRT for patients with AKI after cardiac surgery revealed lower 28-days mortality and shorter ICU length of stay. However, this was based on 11 studies of various qualities with very high heterogeneity of results. Defining treatment guidelines needs further research with a larger and better database.

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.

Acute Kidney Injury in Patients Undergoing Both Right and Left Heart Catheterization with Coronary Angiography Vs Right Heart Catheterization Only.

BACKGROUND: Recent studies have challenged the reported causal association between acute kidney injury and iodinated contrast administration, ascribing some cases to changes in renal function that are independent of contrast administration. METHODS: We studied 1779 consecutive patients undergoing right heart catheterization (RHC) at a Veterans Administration Medical Center. We compared the incidence of acute kidney injury and of nephropathy at 3 months in veterans undergoing right and left heart catheterization and coronary angiography (R&LHC) to the incidence of acute kidney injury and of nephropathy at 3 months in patients undergoing RHC only. RESULTS: The incidence of acute kidney injury at 3 days was 47 (9.7%) in the R&LHC group and 58 (9.6%) in the RHC group (P = .99). The incidence of nephropathy at 3 months was 115 (17%) in the L&RHC group and 141 (19.2%) in the RHC group (P = 0.31). In a propensity score-paired analysis of 782 patients and after adjustment for baseline characteristics, the odds ratio for acute kidney injury at 3 days among patients undergoing R&LHC was 1.25 (95% confidence interval, 0.65-2.42; P = .50), and the odds ratio for nephropathy at 3 months was 0.69 (95% confidence interval, 0.46-1.04; P = .08). CONCLUSION: The incidence of changes in creatinine consistent with acute kidney injury at 3 days and of nephropathy at 3 months was not significantly different in patients undergoing R&LHC compared with patients undergoing RHC only. This supports the thesis that not all changes in creatinine after procedures involving administration of contrast are caused by the contrast.

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.

Low levels of high-density lipoproteins are associated with acute kidney injury following revascularization for chronic limb ischemia.

OBJECTIVES: Perioperative acute kidney injury (AKI) is not uncommon, following revascularization. HDL has been shown to reduce organ injury in animal models. The aim of the study is to examine the association of HDL on AKI in patients undergoing revascularization for chronic limb ischemia. METHODS: All patients who underwent revascularization between June 2001 and December 2009 were analyzed. Patients on dialysis and with incomplete data were excluded. Patients were grouped for HDL < or ≥40 mg/dL. Univariate and multivariate analysis were used to identify factors associated with AKI. RESULTS: A total of 684 patients were included. Eighty-two (12.0%) patients developed postoperative AKI (15.7% in low HDL group vs. 6.3% in high HDL group, p < 0.001). The AKI group were more likely to be older (71.5 ± 10.1 vs. 68.0 ± 10.8, p = 0.01), ASA 4 class (26% vs. 14%, p < 0.001), to have albumin <3 g/dL (59% vs. 32%, p < 0.001), low HDL levels (79% vs. 58%, p < 0.001), DM (61% vs. 44%, p = 0.005), CAD (67% vs. 55%, p = 0.003), preoperative chronic kidney disease (CKD) stage III-IV (55% vs.39%, p < 0.001), to present with critical limb ischemia (82% vs. 63%, p = 0.001), and to be on ACEI (67% vs. 51%, p = 0.006). Multivariate logistic regression analysis showed low HDL (Odds Ratio (OR) 1.66 [1.23-2.24]) and serum albumin levels <3 g/dL (OR 1.66 [1.29-2.13], p < 0.001) were independently associated with increased odds for developing AKI. Propensity score analyses showed low HDL was independently associated with increased odds of AKI (OR 2.4 (1.4-4.2)). CONCLUSIONS: AKI following revascularization is not uncommon (12.0%), and lower concentrations of HDL and serum albumin are associated with increased odds of postoperative AKI. There was also a trend of higher prevalence of AKI among those with pre-existing CKD.

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.

Development of the nephrotic syndrome during treatment of Crohn's disease with adalimumab.

We report a patient with Crohn's disease who presented with renal insufficiency and the nephrotic syndrome after initiating therapy with adalimumab. Renal biopsy showed stages 2 to 3 membranous glomerulonephritis, and immunostaining showed glomerular deposition of immunoglobulin G and C3. The patient's serum creatinine decreased after discontinuation of adalimumab, and treatment with prednisone and mycophenolic acid reversed his proteinuria. The pathogenesis of glomerular disease induced by antitumor necrosis factor antibodies is uncertain, and the potential roles of the generation of autoantibodies, development of antiadalimumab antibodies, and the interaction of adalimumab with glomerular tumor necrosis factor are discussed.

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.