Pradeep Arora

Preoperative use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers is associated with increased risk for acute kidney injury after cardiovascular surgery.

BACKGROUND AND OBJECTIVES Acute kidney injury (AKI) occurs commonly after cardiac surgery. Most patients who undergo cardiac surgery receive long-term treatment with angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB). The aim of this study was to determine whether long-term use of ACEI/ARB is associated with an increased incidence of AKI after cardiac surgery. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This was a retrospective cohort study of 1358 adult patients who underwent cardiac surgery between January 1, 2001, and December 31, 2005, in two tertiary care hospitals in Buffalo, NY. The incidence of AKI was determined after cardiac surgery. Clinical data were collected using a standardized form that included comorbid condition, use of ACEI/ARB, and intraoperative and postoperative complications. RESULTS Overall, 40.2% of patients developed AKI. Preoperative variables that were significantly associated with development of AKI included increasing age; nonwhite race; combined valve surgery and coronary artery bypass grafting compared with coronary artery bypass grafting alone; American Society of Anesthesiologists (ASA) Risk Score category 4/5 compared with 2 to 3; presence of diabetes, congestive heart failure, or neurologic disease at baseline; use of ACEI/ARB; and emergency surgery. Intra- and postoperative factors that were associated with postoperative AKI were hypotension during surgery, use of vasopressors, and postoperative hypotension. Multiple regression logistic model confirmed an independent and significant association of AKI and preoperative use of ACEI/ARB. This was confirmed using a bivariate-probit and propensity score model that adjusts for confounding by indication of use and selection bias. CONCLUSIONS Preoperative use of ACEI/ARB is associated with a 27.6% higher risk for AKI postoperatively. Stopping ACEI or ARB before cardiac surgery may reduce the incidence of AKI.

CKD in MYH9-related disorders.

MYH9-related disorders are rare causes of chronic kidney disease (CKD) presenting as chronic glomerulonephritis and derive from mutations of the MYH9 gene, which encodes for the nonmuscle myosin heavy chain IIA. These disorders are autosomal dominant and include May-Hegglin anomaly and Sebastian, Fechtner, and Epstein syndromes. Diagnosis of these disorders is made first in early childhood because of the characteristic peripheral-blood smear findings of thrombocytopenia, giant platelets, and variably detected basophilic cytoplasmic inclusion bodies in leukocytes. CKD typically develops later in adulthood and may progress to end-stage renal disease. MYH9-related disorders may be associated with deafness and cataract; hence, Alport syndrome becomes important in the differential diagnosis. However, the autosomal dominance pattern of inheritance and characteristic peripheral-blood smear findings in the former help differentiate the two conditions. New evidence suggests that MYH9 gene alterations also are associated with a greater risk of focal segmental glomerulosclerosis and hypertensive nephrosclerosis in African Americans. The purpose of this review is to focus on the known, but rarely recognized association of MYH9-related disorders with CKD and highlight the recent discoveries related to the MYH9 gene that may explain the reason for a high CKD burden in African Americans.

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.

Chronic Renal Failure in India

A prospective study of all new cases of chronic renal failure (CRF) including inservice referrals was done at our hospital over a period of 1 year from May 1994 to April 1995. The diagnosis of CRF was based on clinical, laboratory, and radiological features. Kidney biopsies were done when indicated. The patients were subdivided into various etiologic groups of primary renal disease according to standard criteria. There were a total of 835 cases of CRF with a median age of 43 years (range 10 days to 90 years); 67.8% of them were men. Glomerulonephritis (28.6%), diabetic nephropathy (23.2%), and interstitial nephritis (16.5%) were the most common causes of CRF, followed by obstructive nephropathy (6.4%), benign nephrosclerosis (4.1%), and polycystic kidney disease (2%). However, in patients more than 40 years of age, diabetic nephropathy was the most common cause (36.8%). The cause of CRF was unknown in 16.2% of the cases. One hundred twenty-one patients (14.5%) had an acute deterioration of their underlying renal dysfunction at presentation. This was most commonly due to accelerated hypertension (26.1%), infection (22.4%), volume depletion (20.1%), and drugs (14.9%). Anti-inflammatory drugs were the most common drugs responsible for the acute decline in renal function. One year after their initial presentation, of the 512 patients (61.3%) with end stage renal disease, 12.5% had died, 17% had received a kidney allograft, 12.7% were on some form of maintenance dialysis, and 295 patients were lost to follow-up. Of the 323 patients with less severe illness, 7 died, 209 were on outpatient treatment, and 107 patients were lost to follow-up. We conclude that the pattern of CRF in India does not differ greatly from that in the developed countries. However, it carries a poorer prognosis due to late referral and limited availability and affordability of renal replacement therapy in India.

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.

Eculizumab therapy for gemcitabine induced hemolytic uremic syndrome: case series and concise review

The incidence of gemcitabine-induced hemolytic uremic syndrome (GiHUS) has been reported to be between 0.02% and 2.2% (1,2). A variety of therapies have been employed in the treatment of GiHUS with varying success. In some cases the discontinuation of drug will result in remission of HUS (3). The benefit of plasmapheresis in the treatment of atypical forms of HUS (aHUS) such as GiHUS has been questioned (4). Other treatment modalities have been used with varying rates of success including high dose corticosteroids, vincristine, and rituximab (3,5). Eculizumab is a monoclonal antibody directed against the complement protein C5 that has been recently approved for treatment of atypical HUS (3). We report four cases of GiHUS seen over 2-month period and successfully treated with eculizumab.

Mild acute kidney injury is associated with increased mortality after cardiac surgery in patients with eGFR < 60 mL/min/1.73 m2

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 m2 had fivefold higher mortality with rise of serum creatinine >0.3 mg/dL. Conclusions: Patients with baseline eGFR < 60 mL/min/1.73 m2 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 m2 did not increase mortality.

Visceral Leishmaniasis in a Renal Transplant Recipient: Diagnostic and Therapeutic Problems

Visceral leishmaniasis is infrequently reported in renal transplant recipients. A 40-year-old renal transplant recipient developed hepatosplenomegaly and pyrexia of unknown origin 5 months after transplantation. Visceral leishmaniasis was confirmed on bone marrow examination. The usual dose of antiparasitic therapy with stibogluconate sodium failed to eradicate Leishmania donovani. High-dose conventional therapy with stibogluconate sodium for an extended period of time was successful in the treatment of a relapse of leishmaniasis.

Preventable Risk Factors for Acute Kidney Injury in Patients Undergoing Cardiac Surgery

f s c t t ACUTE KIDNEY INJURY (AKI) develops in 5% to 42% of patients who undergo cardiac surgery depending on the efinition of AKI, and 1% to 4% of patients require dialysis.1-6 AKI requiring dialysis after cardiac surgery is associated with an increased incidence of infection, length of critical care unit stay, and long-term need for dialysis.7-9 Chertow et al10 have shown that AKI requiring dialysis is an independent risk factor for mortality after cardiac surgery. Recent studies have shown that even small increases in serum creatinine ( 0.3 mg/dL) postoperatively are associated with increased mortality.11-13 The presence of stage-3 chronic kidney disease (CKD) at baseline (serum creatinine 1.47 mg/dL or glomerular filtration rate [GFR] 60 mL/min/1.73 m2) has been associated ith an increased incidence of postoperative AKI, a longer ospital stay, increased hospital mortality, and a poorer ong-term outcome.14-16 CKD is now defined in stages acording to the estimated GFR derived from serum creatinine evels (Table 1).17 Given the significant morbidity and mortality risk associated with postoperative AKI, the prevention of renal dysfunction is of paramount importance. This has led to the formulation and validation of many clinical risk scores to predict post–cardiac surgery AKI requiring renal replacement therapy (RRT).18-21 Chertow et al18 were among the first to develop a preoperative enal risk stratification algorithm based on the Veterans Affairs oronary Artery Surgery Study experience.18 Subsequently, a umber of investigators derived and validated equations to stimate the risk of post–cardiac surgery AKI requiring RRT Table 2). Finally, Palomba et al22 designed the Acute Kidney Injury After Cardiac Surgery Score based on a cohort of patients who underwent elective surgery at a Brazilian center.22 The Palomba study predicted the risk for post–cardiac surgery AKI not requiring dialysis. Most of the factors used in the development of prediction equations are nonmodifiable. These include female sex, congestive heart failure, a low ejection fraction ( 35%), diabetes mellitus, CKD, chronic obstructive pulmonary disease, peripheral vascular disease, combined valve surgery, and emergency surgery.18-22 Preoperative assessment increases the awareness of risk for AKI and can be used when obtaining consent and in planning for the perioperative period. Most importantly, the identification of high-risk patients provides an opportunity to optimize preoperative care. There are both modifiable and nonmodifiable risk factors associated with the development of AKI in cardiac surgery. This review focuses on modifiable risk factors to prevent the occurrence of AKI. These have been classified as preoperative, intraoperative, and postoperative modifiable risk factors (Table

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.