James W. Lohr

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.

Osmotic demyelination syndrome following correction of hyponatremia: Association with hypokalemia

The osmotic demyelination syndrome (ODS) is a neurologic complication associated with rapid correction of hyponatremia. A case is described in which the patient was found to have hypokalemia as well as hyponatremia prior to the development of ODS. The literature was reviewed for cases of ODS in which patients had hyponatremia (serum sodium < or = 126 mmol/L) at presentation followed by correction of the hyponatremia. Of the 74 cases in which serum sodium and serum potassium values were reported at the time of presentation, 66 patients (89%) had hypokalemia. In 20 of these cases, serial measurements of sodium and potassium were reported, and in no instance was the potassium level normalized prior to the time of most rapid correction of the serum sodium. Hypokalemia may predispose patients to develop osmotic demyelination following correction of hyponatremia. The etiology of this complication is unclear. In neurologically stable patients with severe hyponatremia, it may be beneficial to correct hypokalemia prior to correction of the serum sodium. This maneuver may further reduce the incidence of ODS.

Isovolumetric regulation of isolated S2 proximal tubules in anisotonic media.

Sudden alteration in medium osmolality causes an osmometric change in proximal tubule cell size followed by restoration of cell volume toward normal in hypotonic but not in hypertonic medium. We determined the capability of isolated nonperfused proximal tubules to prevent a change in cell volume in anisotonic media. The external osmolality was gradually changed over a range from 110 to 480 mosM. At 1.5 mosM/min, cell volume remained constant between 167 +/- 9 and 361 +/- 7 mosM, a phenomenon termed isovolumetric regulation (IVR). Cells lost intracellular solutes in hypotonic and gained intracellular solutes in hypertonic media. Raffinose or choline chloride substitution showed that osmolality, rather than NaCl, signalled cell volume maintenance in hyperosmotic media. Cooling (7-10 degrees C) blocked IVR. IVR was maintained when osmolality was lowered at a rate of 27, but not at 42 mosM/min. IVR was not observed when the rate of osmolality increase exceeded 3 mosM/min. We conclude that proximal tubule cells sensitively regulate intracellular volume in an osmolality range of pathophysiologic interest by mechanisms dependent on the rate of net water movement across basolateral membranes and the absolute intracellular content of critical solutes.

A Clinical Index to Predict Survival in Acute Renal Failure Patients Requiring Dialysis

Recent advances in technology have not substantially changed the relatively low survival rate associated with acute renal failure (ARF). Several clinical prognostic variables and multivariate models have been reported to predict survival in individual patients, but these are either cumbersome to use or restrictive in their application. A straightforward clinical index has been developed to predict survival in ARF based on data obtained for all patients receiving dialysis for ARF at the University of Kansas Medical Center from November 1979 through October 1985. During this period, 126 patients received dialysis for ARF, with an overall survival of 25% (32/126). There were no significant differences between survivors and nonsurvivors in age, gender, or indication for dialysis. Eleven variables were statistically related to survival, and were reduced to five when clinically similar variables were combined or eliminated. A clinical survival index was based on these five easily determined variables that were significantly related to survival: systolic blood pressure less than or equal to 110 mm Hg, assisted ventilation, congestive heart failure, proven or suspected sepsis, and gastrointestinal (GI) dysfunction (bleeding, ileus, obstruction, or recent abdominal surgery). Survival was directly related to the number of factors present: zero, 62% (8/13); one, 44% (8/18); two, 30% (10/33); three, 19% (5/26); four, 0% (0/20); and five, 6% (1/16). This straightforward index, derived from easily obtained clinical data, is useful for judging survival prognosis in patients with ARF severe enough to warrant treatment with dialysis.

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.

Safety of Regional Citrate Hemodialysis in Acute Renal Failure

Regional citrate anticoagulation is an alternative to heparin anticoagulation for hemodialysis of patients at increased risk of bleeding. We report the successful use of this technique in 326 dialyses in 49 high bleeding risk patients with acute renal failure. Systemic anticoagulation did not occur as a result of any dialysis procedure, and in no instance was bleeding observed. Dialysis was effective, as judged by removal of creatinine. The safety of this procedure is demonstrated by the lack of bleeding complications and the small incidence of electrolyte and acid-base abnormalities. In addition we document the absence of citrate intoxication by serial measurements of serum citrate levels. Regional citrate anticoagulation is a safe and effective method of performing hemodialysis in patients with acute renal failure at increased risk of bleeding.

Rituximab-based therapy for gemcitabine-induced hemolytic uremic syndrome in a patient with metastatic pancreatic adenocarcinoma: a case report.

PurposeThe purpose of this report is to describe the management and outcome of an unusual complication of a commonly used chemotherapeutic agent. Gemcitabine is a known risk factor for hemolytic uremic syndrome (HUS), which can often have a rapidly fatal clinical course despite intervention with steroids, plasmapheresis and hemodialysis.MethodsA retrospective report of the first case of gemcitabine-related HUS, in a patient with metastatic pancreatic adenocarcinoma, treated with a variety of standard therapies in addition to rituximab is presented. The hematologic response parameters and clinical outcomes to each of the therapies given are described.ResultsChemotherapy-induced HUS was aggressively treated with plasmapheresis, high-dose steroids, vincristine and rituximab. Platelet recovery and clinical improvement coincided with administration of rituximab. In addition, aggressive supportive measures to manage renal failure (hemodialysis) and labile hypertension, allowed this patient to have an extended survival as a result of successful therapy for this complication despite an underlying rapidly fatal malignancy.ConclusionThis case highlights the importance of timely application of aggressive measures even in patients with known diagnosis of a fatal malignancy as these interventions can prolong life and be of palliative benefit.

MYCOBACTERIUM MARINUM INFECTION IN A RENAL TRANSPLANT RECIPIENT

BACKGROUND Infections with atypical mycobacteria occur more frequently in patients with solid organ transplants than in the normal host. METHODS We report a case of cutaneous Mycobacterium marinum infection in a renal transplant recipient. The patient presented with nodules on the forearm after returning from a fishing trip and was treated for cellulitis without success. RESULTS Cultures of a biopsy of the lesion grew M. marinum. The patient was treated with ethambutol and ciprofloxacin with a good response; however, 9 months of treatment were required for complete resolution. CONCLUSION Immunosuppressive therapy for renal transplantation increases susceptibility to a variety of opportunistic infections. A patient who presents with nodules on the extremities should be questioned regarding contact with fish, aquatic environments, or fish tank water, in which case infection with M. marinum should be considered. The diagnosis and treatment of this infection in transplant recipients is discussed.

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.