Susana Arrigain

A Clinical Score to Predict Acute Renal Failure after Cardiac Surgery

The risk of mortality associated with acute renal failure (ARF) after open-heart surgery continues to be distressingly high. Accurate prediction of ARF provides an opportunity to develop strategies for early diagnosis and treatment. The aim of this study was to develop a clinical score to predict postoperative ARF by incorporating the effect of all of its major risk factors. A total of 33,217 patients underwent open-heart surgery at the Cleveland Clinic Foundation (1993 to 2002). The primary outcome was ARF that required dialysis. The scoring model was developed in a randomly selected test set (n = 15,838) and was validated on the remaining patients. Its predictive accuracy was compared by area under the receiver operating characteristic curve. The score ranges between 0 and 17 points. The ARF frequency at each score level in the validation set fell within the 95% confidence intervals (CI) of the corresponding frequency in the test set. Four risk categories of increasing severity (scores 0 to 2, 3 to 5, 6 to 8, and 9 to 13) were formed arbitrarily. The frequency of ARF across these categories in the test set ranged between 0.5 and 22.1%. The score was also valid in predicting ARF across all risk categories. The area under the receiver operating characteristic curve for the score in the test set was 0.81 (95% CI 0.78 to 0.83) and was similar to that in the validation set (0.82; 95% CI 0.80 to 0.85; P = 0.39). In conclusion, a score is valid and accurate in predicting ARF after open-heart surgery; along with increasing its clinical utility, the score can help in planning future clinical trials of ARF.

Loop Ileostomy Closure After Restorative Proctocolectomy: Outcome in 1,504 Patients

PURPOSERoutine use of a temporary loop ileostomy for diversion after restorative proctocolectomy is controversial because of reported morbidity associated with its creation and closure. This study intended to review our experience with loop ileostomy closure after restorative proctocolectomy and determine the complication rates. In addition, complication rates between handsewn and stapled closures were compared.METHODSOur Department Pelvic Pouch Database was queried and charts reviewed for all patients who had ileostomy closure after restorative proctocolectomy from August 1983 to March 2002.RESULTSA total of 1,504 patients underwent ileostomy closure after restorative proctocolectomy during a 19-year period. The median length of hospitalization was three (range, 1–40) days and the overall complication rate was 11.4 percent. Complications included small-bowel obstruction (6.4 percent), wound infection (1.5 percent), abdominal septic complications (1 percent), and enterocutaneous fistulas (0.6 percent). Handsewn closure was performed in 1,278 patients (85 percent) and stapled closure in 226 (15 percent). No significant differences in complication rates and length of hospitalization were found between handsewn and stapled closure techniques.CONCLUSIONSOur results demonstrated that ileostomy closure after restorative proctocolectomy can be achieved with a low morbidity and a short hospitalization stay. In addition, we found that complication rates and length of hospitalization were similar between handsewn and stapled closures.

Demographic and clinical characteristics associated with glomerular filtration rates in living kidney donors.

Due to the shortage of organs, living donor acceptance criteria are becoming less stringent. An accurate determination of the glomerular filtration rate (GFR) is critical in the evaluation of living kidney donors and a value exceeding 80 ml/min per 1.73 m(2) is usually considered suitable. To improve strategies for kidney donor screening, an understanding of factors that affect GFR is needed. Here we studied the relationships between donor GFR measured by (125)I-iothalamate clearances (mGFR) and age, gender, race, and decade of care in living kidney donors evaluated at the Cleveland Clinic from 1972 to 2005. We report the normal reference ranges for 1057 prospective donors (56% female, 11% African American). Females had slightly higher mGFR than males after adjustment for body surface area, but there were no differences due to race. The lower limit of normal for donors (5th percentile) was less than 80 ml/min per 1.73 m(2) for females over age 45 and for males over age 40. We found a significant doubling in the rate of GFR decline in donors over age 45 as compared to younger donors. The age of the donors and body mass index increased over time, but their mGFR, adjusted for body surface area, significantly declined by 1.49+/-0.61 ml/min per 1.73 m(2) per decade of testing. Our study shows that age and gender are important factors determining normal GFR in living kidney donors.

The risk of developing coronary artery disease or congestive heart failure, and overall mortality, in type 2 diabetic patients receiving rosiglitazone, pioglitazone, metformin, or sulfonylureas: a retrospective analysis

Oral anti-diabetic agents have been associated with adverse cardiovascular events in type 2 diabetes (DM2). We investigated the risk of coronary artery disease (CAD), congestive heart failure (CHF), and mortality using multivariable Cox models in a retrospective cohort of 20,450 DM2 patients from our electronic health record (EHR). We observed no differences in CAD risk among the agents. Metformin was associated with a reduced risk of CHF (HR 0.76, 95% CI 0.64–0.91) and mortality (HR 0.54, 95% CI 0.46–0.64) when compared to sulfonylurea. Pioglitazone was also associated with a lower risk of mortality when compared to sulfonylurea (HR 0.59, 95% CI 0.43–0.81). No other significant differences were found between the oral agents. In conclusions, our results did not identify an increased CAD risk with rosiglitazone in clinical practice. However, the results do reinforce a possible increased risk of adverse events in DM2 patients prescribed sulfonylureas.

Increase in overall mortality risk in patients with type 2 diabetes receiving glipizide, glyburide or glimepiride monotherapy versus metformin: A retrospective analysis

Aims: It remains uncertain if differences in mortality risk exist among the sulfonylureas, especially in patients with documented coronary artery disease (CAD). The purpose of this study was to assess the overall mortality risk of the individual sulfonylureas versus metformin in a large cohort of patients with type 2 diabetes.

Serum Bicarbonate and Mortality in Stage 3 and Stage 4 Chronic Kidney Disease

BACKGROUND AND OBJECTIVES The incidence and prevalence of metabolic acidosis increase with declining kidney function. We studied the associations of both low and high serum bicarbonate levels with all-cause mortality among stage 3 and 4 chronic kidney disease (CKD) patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We examined factors associated with low (<23 mmol/L) and high (>32 mmol/L) serum bicarbonate levels using logistic regression models and associations between bicarbonate and all-cause mortality using Cox-proportional hazard models, Kaplan-Meier survival curves, and time-dependent analysis. RESULTS Out of 41,749 patients, 13.9% (n = 5796) had low and 1.6% (n = 652) had high serum bicarbonate levels. After adjusting for relevant covariates, there was a significant association between low serum bicarbonate and all-cause mortality (hazard ratio [HR] 1.23, 95% CI 1.16, 1.31). This association was not statistically significant among patients with stage 4 CKD and diabetes. The time-dependent analysis demonstrated a significant mortality risk associated with a decline from normal to low bicarbonate level (HR 1.59, 95% CI 1.49, 1.69). High serum bicarbonate levels were associated with death irrespective of the level of kidney function (HR 1.74, 95% CI 1.52, 2.00). When serum bicarbonate was examined as a continuous variable, a J-shaped relationship was noted between serum bicarbonate and mortality. CONCLUSIONS Low serum bicarbonate levels are associated with increased mortality among stage 3 CKD patients and patients without diabetes. High serum bicarbonate levels are associated with mortality in both stage 3 and stage 4 CKD patients.

Development and Validation of an Electronic Health Record–Based Chronic Kidney Disease Registry

BACKGROUND AND OBJECTIVES Chronic kidney disease (CKD) is increasing, and outcomes-related research from diverse health care settings is needed to target appropriate efforts and interventions. We developed an electronic health record (EHR)-based CKD registry at the Cleveland Clinic and validated comorbid conditions. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Patients who had at least one face-to-face outpatient encounter with a Cleveland Clinic health care provider and (1) had two estimated GFR values <60 ml/min per 1.73 m(2) >90 days apart as of January 1, 2005 and/or (2) were patients with International Classification of Diseases-9 (ICD-9) diagnosis codes for kidney disease were included. RESULTS Our registry includes 57,276 patients (53,399 patients met estimated GFR criteria and 3877 patients met ICD-9 diagnosis code criteria) as of March 2010. Mean age was 69.5 ± 13.4 years, with 55% women and 12% African Americans. Medicare is the primary insurer for more than one half of the study cohort. The κ statistics to assess the extent of agreement between the administrative dataset extracted from the EHR and actual EHR chart review showed substantial agreement (>0.80) for all conditions except for coronary artery disease and hypertension, which had moderate agreement (<0.60). CONCLUSIONS Development of an EHR-based CKD registry is feasible in a large health system, and the comorbid conditions included in the registry are reliable. In addition to conducting research studies, such a registry could help to improve the quality of care delivered to CKD patients and complement the ongoing nationwide efforts to develop a CKD surveillance project.

Correlation between Viral Loads of Cytomegalovirus in Blood and Bronchoalveolar Lavage Specimens from Lung Transplant Recipients Determined by Histology and Immunohistochemistry

ABSTRACT Cytomegalovirus (CMV) is an important pathogen in lung transplant recipients. Early detection of CMV end-organ disease should help with treatment management. We determined the CMV viral load by hybrid capture in bronchoalveolar lavage (BAL) fluid samples from patients who had undergone lung transplantation. For 39 of these samples (from 25 patients), corresponding transbronchial biopsy samples were available for CMV immunohistochemistry (IHC). The CMV IHC results were interpreted and categorized as positive or negative, and the positive results were subcategorized as typical if cells with both significant nuclear enlargement or Cowdry A-type inclusions and positive staining were present or as atypical if definitive nuclear staining was seen but significant nuclear enlargement was not. Diagnostic CMV viral inclusions were reported in the anatomic diagnosis, based on hematoxylin-eosin staining alone, for three (8%) of the biopsy samples. CMV was detected by IHC in 13 (33%) samples (5 typical, 8 atypical). The median CMV viral load in BAL samples was 0 copies/ml for BAL samples from patients with IHC-negative biopsy samples; 47,678 copies/ml for BAL samples from patients with biopsy samples with positive, atypical staining; and 1,548,827 copies/ml for BAL samples from patients with biopsy samples with positive, typical staining (P < 0.001). Compared to routine pathology of biopsy samples, the use of IHC increased the diagnostic yield of CMV. Also, the CMV viral load in BAL fluid samples increased along with immunoreactivity from negative to positive, atypical staining to positive, typical staining. The CMV viral load determined with the end-organ sample, the BAL fluid sample, was higher than the corresponding viral load determined with blood. Both IHC and determination of the CMV viral load in BAL samples may be useful for the detection of individuals at risk for the development of fulminant invasive CMV disease.

The Risk of Overall Mortality in Patients with Type 2 Diabetes Receiving Glipizide, Glyburide, or Glimepiride Monotherapy: A Retrospective Analysis

OBJECTIVE Sulfonylureas have historically been analyzed as a medication class, which may be inappropriate given the differences in properties inherent to the individual sulfonylureas (hypoglycemic risk, sulfonylurea receptor selectivity, and effects on myocardial ischemic preconditioning). The purpose of this study was to assess the relationship of individual sulfonylureas and the risk of overall mortality in a large cohort of patients with type 2 diabetes. RESEARCH DESIGN AND METHODS A retrospective cohort study was conducted using an academic health center enterprise-wide electronic health record (EHR) system to identify 11,141 patients with type 2 diabetes (4,279 initiators of monotherapy with glyburide, 4,325 initiators of monotherapy with glipizide, and 2,537 initiators of monotherapy with glimepiride), ≥18 years of age with and without a history of coronary artery disease (CAD) and not on insulin or a noninsulin injectable at baseline. The patients were followed for mortality by documentation in the EHR and Social Security Death Index. Multivariable Cox models were used to compare cohorts. RESULTS No statistically significant difference in the risk of overall mortality was observed among these agents in the entire cohort, but we did find evidence of a trend toward an increased overall mortality risk with glyburide versus glimepiride (hazard ratio 1.36 [95% CI 0.96–1.91]) and glipizide versus glimepiride (1.39 [0.99–1.96]) in those with documented CAD. CONCLUSIONS Our results did not identify an increased mortality risk among the individual sulfonylureas but did suggest that glimepiride may be the preferred sulfonylurea in those with underlying CAD.

Evaluation of Creatinine-Based Estimates of Glomerular Filtration Rate in a Large Cohort of Living Kidney Donors

Background. Accurate determination of kidney function is critical in the evaluation of living kidney donors and higher donor glomerular filtration rate (GFR) is associated with better allograft outcomes. However, among transplant centers donor kidney function evaluation varies widely. Methods. The performance of creatinine clearance (CrCl), Modification of Diet in Renal Disease (MDRD), the re-expressed MDRD equations with standardized creatinine, and the Cockcroft-Gault (CG) formula as compared with 125I-iothalamate GFR (iGFR) was analyzed in 423 donors. All methods of GFR measurement were then evaluated for their association with graft function at 1 year. Results. The MDRD and re-expressed MDRD equations underestimated iGFR whereas CG showed minimal bias (median difference=−11.0, −16.3, and −0.5 mL/min/1.73 m2, respectively). CrCl overestimated iGFR (10 mL/min/1.73 m2). The MDRD, re-expressed MDRD, and CG formulas were more accurate (88%, 86%, and 88% of estimates within 30% of iGFR, respectively) than CrCl (80% within 30% of iGFR). Interestingly, low bias and high accuracy were achieved by averaging the MDRD estimation with the CrCl result; both methods available to the clinician in most transplant centers. We also showed that predonation GFR as measured by isotopic renal clearance or any of the creatinine-based estimation formulas may be associated with allograft function at 1 year, whereas the widely used CrCl was not. Conclusions. Variable performance was seen among different GFR estimations, with CrCl being the poorest. Recent recommendations to use the MDRD equation with standardized serum creatinine did not improve its performance. However, recognizing the limited availability of GFR laboratories, these methods are still clinically useful if used with caution and understanding their limitations.