Todd H. Driver

Low Serum Bicarbonate and Kidney Function Decline: The Multi-Ethnic Study of Atherosclerosis (MESA)

BACKGROUND Among populations with established chronic kidney disease (CKD), metabolic acidosis is associated with more rapid progression of kidney disease. The association of serum bicarbonate concentrations with early declines in kidney function is less clear. STUDY DESIGN Retrospective cohort study. SETTING & PARTICIPANTS 5,810 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) with a baseline estimated glomerular filtration rate (eGFR) > 60mL/min/1.73 m(2) using the CKD-EPI (CKD Epidemiology Collaboration) creatinine-cystatin C equation. PREDICTORS Serum bicarbonate concentrations. OUTCOMES Rapid kidney function decline (eGFR decline > 5% per year) and incident reduced eGFR (eGFR < 60mL/min/1.73 m(2) with minimum rate of eGFR loss of 1 mL/min/1.73 m(2) per year). RESULTS Average bicarbonate concentration was 23.2 ± 1.8mEq/L. 1,730 (33%) participants had rapid kidney function decline, and 487 had incident reduced eGFR during follow-up. Each 1-SD lower baseline bicarbonate concentration was associated with 12% higher adjusted odds of rapid kidney function decline (95% CI, 6%-20%) and higher risk of incident reduced eGFR (adjusted incidence rate ratio, 1.11; 95% CI, 1.03-1.20) in models adjusting for demographics, baseline eGFR, albuminuria, and CKD risk factors. The OR for the associations of bicarbonate level < 21 mEq/L relative to 23-24 mEq/L was 1.35 (95% CI, 1.05-1.73) for rapid kidney function decline, and the incidence rate ratio was 1.16 (95% CI, 0.83-1.62) for incident reduced eGFR. LIMITATIONS Cause of metabolic acidosis cannot be determined in this study. CONCLUSIONS Lower serum bicarbonate concentrations are associated independently with rapid kidney function decline independent of eGFR or albuminuria in community-living persons with baseline eGFR > 60 mL/min/1.73 m(2). If confirmed, our findings suggest that metabolic acidosis may indicate either early kidney disease that is not captured by eGFR or albuminuria or may have a causal role in the development of eGFR < 60 mL/min/1.73 m(2).

Serum Bicarbonate Concentrations and Kidney Disease Progression in Community-Living Elders: The Health, Aging, and Body Composition (Health ABC) Study

BACKGROUND In populations with prevalent chronic kidney disease (CKD), lower serum bicarbonate levels are associated with more rapid CKD progression, but whether lower bicarbonate levels also are associated with risk of incident estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m(2) and CKD progression among community-living persons with predominantly preserved kidney function is unknown. STUDY DESIGN Longitudinal observational cohort study. SETTING & PARTICIPANTS Well-functioning community-living elders aged 70-79 years at inception. PREDICTOR Serum bicarbonate level measured at the time of collection by arterialized venous blood sample using an arterial blood gas analyzer. OUTCOMES Change in eGFR over 7 years, and new eGFR < 60 mL/min/1.73 m(2) with a rate of loss of at least 1 mL/min/1.73 m(2) per year. MEASUREMENTS Linear and logistic regressions were used to evaluate associations of baseline serum bicarbonate level with change in eGFR and incident eGFR < 60 mL/min/1.73 m(2). RESULTS At baseline, mean eGFR was 84 ± 16 (SD)mL/min/1.73 m(2), and serum bicarbonate level was 25.2 ± 1.9 mmol/L. Compared with participants with higher bicarbonate concentrations (23.0-28.0 mmol/L), those with bicarbonate concentrations < 23 mmol/L (n = 85 [8%]) lost eGFR0.55 (95% CI, 0.13-0.97) mL/min/1.73 m(2) per year faster in models adjusted for demographics, CKD risk factors, baseline eGFR, and urine albumin-creatinine ratio. Among the 989 (92%) participants with baseline eGFRs > 60 mL/min/1.73 m(2), 252 (25%) developed incident eGFRs < 60 mL/min/1.73 m(2) at follow-up. Adjusting for the same covariates, participants with bicarbonate concentrations < 23 mmol/L had nearly 2-fold greater odds of incident eGFRs < 60 mL/min/1.73 m(2) (OR, 1.72; 95% CI, 0.97-3.07) compared with those with higher bicarbonate concentrations. LIMITATIONS Only 2 measurements of kidney function separated by 7 years and loss to follow-up due to intervening mortality in this elderly population. CONCLUSIONS Lower serum bicarbonate concentrations are associated independently with decline in eGFR and incident eGFR < 60 mL/min/1.73 m(2) in community-living older persons. If confirmed, serum bicarbonate levels may give insight into kidney tubule health in persons with preserved eGFRs and suggest a possible new target for intervention to prevent CKD development.

Urinary kidney injury molecule 1 (KIM-1) and interleukin 18 (IL-18) as risk markers for heart failure in older adults: the Health, Aging, and Body Composition (Health ABC) Study.

BACKGROUND Kidney damage and reduced kidney function are potent risk factors for heart failure, but existing studies are limited to assessing albuminuria or estimated glomerular filtration rate (eGFR). We evaluated the associations of levels of urinary biomarkers of kidney tubular injury (interleukin 18 [IL-18] and kidney injury molecule 1 [KIM-1]) with future risk of heart failure. STUDY DESIGN Retrospective cohort study. SETTING & PARTICIPANTS 2,917 participants without heart failure in the Health, Aging, and Body Composition (Health ABC) cohort. PREDICTORS Ratios of urine KIM-1, IL-18, and albumin to creatinine (KIM-1:Cr, IL-18:Cr, and ACR, respectively). OUTCOMES Incident heart failure over a median follow-up of 12 years. RESULTS Median values of each marker at baseline were 812 (IQR, 497-1,235)pg/mg for KIM-1:Cr, 31 (IQR, 19-56)pg/mg for IL-18:Cr, and 8 (IQR, 5-19) mg/g for ACR. 596 persons developed heart failure during follow-up. The top quartile of KIM-1:Cr was associated with risk of incident heart failure after adjustment for baseline eGFR, heart failure risk factors, and ACR (HR, 1.32; 95% CI, 1.02-1.70) in adjusted multivariate proportional hazards models. The top quartile of IL-18:Cr also was associated with heart failure in a model adjusted for risk factors and eGFR (HR, 1.35; 95% CI, 1.05-1.73), but was attenuated by adjustment for ACR (HR, 1.15; 95% CI, 0.89-1.48). The top quartile of ACR had a stronger adjusted association with heart failure (HR, 1.96; 95% CI, 1.53-2.51). LIMITATIONS Generalizability to other populations is uncertain. CONCLUSIONS Higher urine KIM-1 concentrations were associated independently with incident heart failure risk, although the associations of higher ACR were of stronger magnitude.

Comparisons of creatinine and cystatin C for detection of kidney disease and prediction of all-cause mortality in HIV-infected women

Background:Cystatin C could improve chronic kidney disease (CKD) classification in HIV-infected women relative to serum creatinine. Design:Retrospective cohort analysis. Methods:Cystatin C and creatinine were measured from specimens taken and stored during the 1999–2000 examination among 908 HIV-infected participants in the Womens Interagency HIV study (WIHS). Mean follow-up was 10.2 years. Predictors of differential glomerular filtration rate (GFR) estimates were evaluated with multivariable linear regression. The associations of baseline categories (<60, 60–90, and >90 ml/min per 1.73 m2) of creatinine estimated GFR (eGFRcr), cystatin C eGFR (eGFRcys), and combined creatinine-cystatin C eGFR (eGFRcr-cys) with all-cause mortality were evaluated using multivariable Cox regression. The net reclassification index (NRI) was calculated to evaluate the effect of cystatin C on reclassification of CKD staging. Results:CKD risk factors were associated with lower eGFRcys and eGFRcr-cys values compared with eGFRcr. Relative to eGFR more than 90, the eGFR less than 60 category by eGFRcys (Adjusted hazard ratio: 2.56; 95% confidence interval: 1.63–4.02), eGFRcr-cys (3.11; 1.94–5.00), and eGFRcr (2.34; 1.44–3.79) was associated with increased mortality risk. However, the eGFR 60–90 category was associated with increased mortality risk for eGFRcys (1.80; 1.28–2.53) and eGFRcr-cys (1.91; 1.38–2.66) but not eGFRcr (1.20; 0.85–1.67). The overall NRI for mortality was 26% when reclassifying from eGFRcr to eGFRcys (P < 0.001) and was 20% when reclassifying from eGFRcr to eGFRcr-cys (P < 0.001). Conclusion:The addition of cystatin C may improve mortality risk prediction by stages of kidney function relative to creatinine. CKD risk factors are associated with an overestimate of GFR by serum creatinine relative to cystatin C.

Return to the Operating Room After Resident-Performed Cataract Surgery

Return to the Operating Room After Resident-Performed Cataract Surgery Cataract surgery is one of the most commonly performed operations during ophthalmology residency training, and its complications have been well described.1-3 While returns to the operating room within 30 days after routine surgery serve as a benchmark for surgical quality in other specialties such as neurosurgery and general surgery, reoperation after cataract surgery has not been investigated.4,5 The aim of this study was to examine the rate and indications for reoperation after resident-performed cataract surgery at 30 and 90 days.

Predictors of Matching in Ophthalmology Residency for International Medical Graduates

Interleukin-8 is an inflammatory cytokine that promotes angiogenesis and increases capillary leakage. The IL-8 rs4073 and VEGF rs699947 are promoter polymorphisms connected to transcriptional activity of the genes. The A allele in IL-8 rs4073 has been associated with higher levels of circulating and secreted IL-8, and a poorer response to bevacizumab in ovarian cancer. The C allele in VEGF rs699947 has been associated with higher VEGF production. In our patients, the C allele was associated with somewhat less CS gain. However, the A allele was more strongly associated with persisting macular fluid and more frequent reinjections. The reason for the possible dichotomous effect of this VEGF polymorphism on the anatomic and functional outcomes is unclear. Complement activity stimulates IL-8 production in endothelial and retinal pigment epithelial cells. The combination of a deficient regulation of alternative complement pathway and greater IL-8 production may lead to IL-8 stimulated angiogenesis and capillary leakage. The cumulative effect of the risk alleles suggests that IL-8 signaling may serve as a compensatory proangiogenic mechanism during anti-VEGF treatment. An explanation for the less producing VEGF genotype to require more injections could be that it maymake such potential compensatory mechanisms more active.

Acute Hepatitis C in an HIV-Infected patient: A Case Report and Review of Literature

ABSTRACTWith the decrease in transmission via transfusions and injection drug use, acute symptomatic hepatitis C is infrequently seen in developed countries. We report a case of a human immunodeficiency virus (HIV)–infected adult who presented with abdominal pain. His alanine aminotransferase was greater than sixty times the upper limit of normal without any evidence on examination of fulminant hepatic failure. His workup revealed an elevated hepatitis C viral level with a negative hepatitis C antibody. He was discharged once his liver function tests improved. As an outpatient, he had a recurrent bout of symptoms with an elevation of his alanine aminotransferase and hepatitis C viral levels that promoted anti-hepatitis C virus treatment. This case illustrates the importance of considering acute hepatitis C as a cause of acute hepatitis in HIV-infected men who have sex with men. While patients with acute symptomatic hepatitis C generally have a higher rate of spontaneous viral clearance compared to those with an insidious acute infection, most still progress to chronic hepatitis C infection, and patients with HIV coinfection carry a higher risk of progression to chronic disease.

Risk Factors for Return to the Operating Room after Resident-Performed Cataract Surgery

ABSTRACT Objective: Investigate risk factors for unplanned return to the operating room after resident-performed cataract surgery. Design: Retrospective case-control study. Setting: Institutional. Methods: Study population: All patients with reoperation within 90 days of resident-performed phacoemulsification were matched to four control eyes which had surgery within 30 days of the reoperation at the same institution. Observation Procedure: Billing codes were used to identify all patients who underwent resident-performed intended phacoemulsification with intraocular lens placement from January 2005 to December 2010. Main Outcome Measures: Investigated risk factors for reoperation included cataract characteristics and preexisting ocular co-morbidities, including diabetic retinopathy, retinal detachment history, glaucoma, corneal pathology, and uveitis. Additional preoperative risk factors studied included resident training year, history of tamsulosin use, phacodonesis, pupillary dilation, presence of pseudoexfoliation, myopia, history of trauma, visual acuity, and monocular status. Intraoperative variables were the use of iris expansion devices, use of capsular stain, attending type, incision type, use of sutures, vitreous loss, anesthesia type, and phacoemulsification technique. Results: There were 67 returns to the operating room (i.e., cases) over five years that were assigned to 268 control eyes. In preoperative multivariate analysis, phacoemulsification done by a first- or second-year resident (OR 3.2, 95% CI: 1.7–6.0, p < 0.001) was associated with an increased risk of reoperation. In postoperative multivariate analysis, only the use of the divide-and-conquer technique (OR 4.0, 95% CI:1.7–9.2, p = 0.001) was associated with an increased risk of reoperation. Conclusions: Phacoemulsification done by a junior resident or using the divide-and-conquer technique had the highest risk of reoperation.

Can healthcare go from good to great

Healthcares improvement efforts have focused on the point of care, targeting specific processes such as preventing central line infections, while paying relatively less attention to the larger issues of organizational structure and leadership. Interestingly, the business community has long recognized that poor management and structure can thwart improvement efforts. Perhaps the corporate worlds best-known study of these issues is found in the book Good to Great, which identifies top-performing corporations, compares them to carefully selected organizations that failed to achieve similar levels of performance, and gleans lessons from these analyses. In this article, we analyze the feasibility of carefully applying Good to Greats methods for analyzing organizational structure and leadership to healthcare. While a few studies in healthcare have come close to emulating Good to Greats methodology, none have matched its rigor. These shortcomings highlight key information and measurement gaps that must be addressed to facilitate unbiased, rigorous studies of the organizational and leadership predictors of institutional excellence in healthcare.