Therese Mangold

INFLUENCES ON RENAL FUNCTION IN CHRONIC SPINAL CORD INJURED PATIENTS

PURPOSE The optimal method of bladder management in the spinal cord injured population remains controversial. We determined the significance of bladder management and other factors on renal function in this population. MATERIALS AND METHODS We retrospectively reviewed the medical records and upper tract imaging studies of 308 patients with a mean followup of 18.7 years since injury. Renal function was assessed by serum creatinine, creatinine clearance and proteinuria measurement, and by upper tract abnormalities on renal ultrasound and nuclear medicine renal scan. Independent variables evaluated for an influence on renal function included patient age, interval since injury, injury level and completeness, vesicoureteral reflux, history of diabetes mellitus and bladder management method. RESULTS Mean serum creatinine plus or minus standard deviation in patients on chronic Foley catheterization, clean intermittent catheterization and spontaneous voiding was 1.08 +/- 0.99, 0.84 +/- 0.23 and 0.97 +/- 0.45 mg./dl. (analysis of variance p = 0.05, Students t test p = 0.10), and mean creatinine clearance was 91.1 +/- 46.5, 113.4 +/- 39.8 and 115 +/- 49 ml. per minute, respectively (analysis of variance and Students t test p <0.01), respectively. Proteinuria was present in 19 patients (6.2%) in the Foley catheterization, 3 (1%) in the clean intermittent catheterization and 4 (1.3%) in the spontaneous voiding group (chi-square test p <0.01), while there were upper tract abnormalities in 56 (18.2%), 20 (6.5%) and 24 (7.8%) patients, respectively (chi-square test p <0.01). Multiple regression analyses revealed no significant predictors of serum creatinine, although older patient age and Foley catheterization significantly predicted low creatinine clearance. Additional logistic regression analyses showed that Foley catheterization was associated with proteinuria and vesicoureteral reflux was associated with upper tract abnormalities. CONCLUSIONS While renal function may be preserved by all forms of bladder management, chronic indwelling catheters may contribute to renal deterioration.

Severe hypernatremia correction rate and mortality in hospitalized patients.

Introduction:Hypernatremia is a common problem in hospitalized patients and is associated with high morbidity and mortality. This study was designed to evaluate whether physicians follow the recommended guidelines for the rate of correction of hypernatremia of ≤0.5 mEq/L/hr and to evaluate the effect of the rate of correction of severe hypernatremia on the mortality of hospitalized patients. Methods:A retrospective chart review of 131 consecutively hospitalized patients with severe hypernatremia (serum sodium ≥155 mEq/L) was performed. Primary outcomes were 30-day patient mortality and 72-hour hypernatremia correction. The first 24-hour serum sodium (Na+) correction rate was tested as a categorical variable; slow rate (<0.25 mEq/L/hr) and fast rate (≥0.25 mEq/L/hr). Results:The mean admission serum Na+ level was 159 ± 3 mEq/L. Ninety percent of patients received the recommended <0.5 mEq/L/hr serum Na+ correction rate; however, hypernatremia was corrected only in 27% of patients after 72 hours of treatment. Thirty-day patient mortality rate was 37%. In multivariable analysis, do not resuscitate status [hazards ratio (HR), 3.85; P < 0.0001], slower correction rate of hypernatremia (HR, 2.63; P = 0.02) and high heart rate (>100 beats/min; HR, 1.99; P = 0.03) were the independent predictors of 30-day mortality. Conclusion:In patients with severe hypernatremia, the rate of correction of hypernatremia was slow and resulted in inadequate correction in majority of the patients. Both slow rate of hypernatremia correction during the first 24 hours and do not resuscitate status were found to be significant predictors of 30-day patient mortality.

Bacteremia In The Chronic Spinal Cord Injury Population: Risk Factors For Mortality

Abstract Background: Individuals with spinal cord injury (SCI) have a lifelong increased risk of systemic infection, which may be associated with episodes of life-threatening bacteremia. Information concerning specific organisms causing bacteremia, the sites of primary infection, and clinical predictors for mortality are necessary to provide optimal treatment. Methods: A retrospective review of positive blood cultures collected over a 3 2-month period in chronic SCI patients treated at the Veterans Affairs Medical Center SCI Unit. Results: One hundred and twenty-three episodes of bacteremia occurred in 63 patients during 83 hospitalizations; 30 patients had multiple episodes of bacteremia. There were 1 ,644 admissions during this period, yielding an incidence of bacteremia of 7 .5% (5.8% after excluding positive cultures that were believed to be caused by contaminants). The patients (31 with paraplegia and 32 with quadriplegia) had a mean age of 59 ± 2 years, and a mean duration of injury of 23 ± 2 years. Bladder management technique consisted of indwelling bladder catheter (n = 53), ileal conduit (n = 6), intermittent catheterization (n = 2), and spontaneous voiding (n = 2). Episodes of bacteremia were nosocomial in 89 out of 123 episodes. Multiple debilitating factors were present, including pressure ulcers in 3 6 out of 63 patients, chronic ventilator dependency in 5 out of 63 patients, recent surgical procedures in 17 out of 63 patients, unde rlying malignancy in 5 out of 63 patients, and evidence of malnutrition in 2 9 out of 63 patients (serum albumin concentration < 2.5 g/dl). Early mortality rate (death within 30 days of bacteremia) occurred in 8 out of 63 patients (13 %) and late mortality (> 1 month following a bacteremic episode) occurred in 1 0 additional participants, such that total mortality was 1 8 out of 63 (2 9%). The sources of bacteremia were urinary tract infection (n = 3 9), presumed contaminant (n = 28), decubitus ulcers (n = 21 ), intravascular catheter (n = 1 9), pneumonia (n = 5), and other (n = 11 ). Gram-negative rods accounted for 2 6 out of 3 9 episodes of bacteremia from a urinary source. Methicillin-resistant Staphylococcus au reus, methicillin-sensitiveS au reus, and coagulase-negative staphylococci were the predominant organi sms when intravascular catheters or pressure ulce rs were the source of bacteremia. Conclusion: In this population, bacteremia predominantly was caused by hospital-associated organisms, and occurred mainly in malnourished patients who required hospitalization for major unde rlying debilitating conditions, particularly pressure ulcers. Chronic indwelling bladder cathet e rs and chronic vascular catheter usage also were highly prevalent in patients with bacteremic episodes. Hypoalbuminemia was the strongest independent predictor for mortality.

INDUCIBLE NITRIC OXIDE SYNTHASE IN THE BLADDER OF SPINAL CORD INJURED PATIENTS WITH A CHRONIC INDWELLING URINARY CATHETER

PURPOSE Spinal cord injured patients are at increased risk for bladder carcinoma. Nitric oxide production in areas of chronic inflammation may provide a stimulus for carcinogenesis by serving as a source of nitrosating agents that generate potentially carcinogenic nitrosamines from secondary amines normally present in urine. MATERIALS AND METHODS To determine whether inducible nitric oxide synthase is expressed as a catalyst for sustained nitric oxide production by cellular elements in chronically inflamed bladder mucosa immunohistochemical studies were performed on mucosal biopsies obtained from 37 adults with spinal cord injury. All participants had required a chronic indwelling urethral or suprapubic catheter for greater than 8 years. RESULTS Histopathological studies revealed active inflammatory infiltrates in all 37 biopsy specimens, squamous metaplasia in 20, epithelial dysplasia in 3 and carcinoma in 1. Inducible nitric oxide synthase was detected in inflammatory cells localized to the lamina propria. Inducible nitric oxide synthase positive cells were identified as macrophages using monoclonal antibodies to macrophage antigen. There was no inducible nitric oxide synthase expression in the urothelial cell layers. Immunostaining for inducible nitric oxide synthase was not detected in bladder mucosal biopsy specimens obtained from cadaveric organ donors. CONCLUSIONS Inducible nitric oxide synthase is expressed in inflammatory macrophages in areas of chronic inflammation in the bladder mucosa of spinal cord injured patients with a chronic indwelling bladder catheter. The expression of inducible nitric oxide synthase may potentially lead to the sustained production of nitric oxide and its oxidative products, the nitrosation of urinary amines and the formation of potentially carcinogenic nitrosamines in the bladder.

Effect of Metformin-Containing Antidiabetic Regimens on All-cause Mortality in Veterans With Type 2 Diabetes Mellitus

Objective:There are conflicting reports concerning metformin use and mortality rates in patients with type 2 diabetes (T2DM). The aim of this study was to examine the relationship between metformin use and all-cause mortality in veterans with T2DM. Research design and methods:An observational cohort study involving 2206 patients with T2DM was performed using computerized database from the Veterans Affairs Medical Center, Memphis, TN. All-cause mortality was compared among cohorts of metformin and nonmetformin users. Univariate and multivariate Cox regression models were used to estimate hazard ratios (HR) for all-cause mortality after adjusting for age, race, baseline estimated glomerular filtration rate, glycosylated hemoglobin, use of insulin, use of ACE inhibitors or angiotensin II receptor blockers or statins. Results:The average length of follow-up in metformin and nonmetformin users was 62 ± 17 and 61 ± 18 months, respectively. The mean age was 63 ± 11 years. Crude mortality rates were similar in both groups: 266 (22%) metformin users and 253 (25.3%) nonmetformin users died. There was a trend for improved survival with metformin use (unadjusted HR 0.85, P = 0.07). After multivariate adjustment, metformin users had significantly decreased HR for time to all-cause mortality compared with nonmetformin users (adjusted HR 0.77, P < 0.01). Insulin use was an independent predictor of worsened survival in both univariate and multivariate analyses. In subgroup analysis of patients exposed to insulin, all-cause mortality remained decreased in metformin users (adjusted HR 0.62, P < 0.04). Conclusion:Treatment of T2DM with regimens containing metformin alone or in combination with other hypoglycemic agents was associated with reduced all-cause mortality compared with regimens without metformin.

Risk factors for development of proteinuria in chronic spinal cord injury

A retrospective, case-control study was performed to investigate the risk factors that may contribute to the development of proteinuria in patients with chronic spinal cord injury (SCI). During an 18-month period, 31 subjects with a 24-hour protein excretion of 1.0 g or greater were identified. Three control subjects with SCIs with a 24-hour urinary protein excretion of less than 1.0 g during the same time period were randomly selected for each study subject with proteinuria. Clinical data, including level and duration of injury, age, presence of indwelling bladder catheter, number of decubitus ulcer procedures, serum albumin and creatinine concentrations, hematocrit, creatinine clearance, and the presence of hypertension and diabetes mellitus, were obtained from medical records. Subjects with proteinuria had other evidence of renal dysfunction with greater serum creatinine concentrations and reduced creatinine clearances, serum albumin concentrations, and hematocrits. Proteinuric subjects were older, had a longer duration of injury, had undergone a greater number of decubitus ulcer procedures, and were more likely to have hypertension and indwelling bladder catheters. The independent predictors for the development of proteinuria using logistic stepwise multiple linear regression analysis were the use of chronic indwelling bladder catheters, number of decubitis ulcer procedures, presence of hypertension, and older age. These data suggest that inflammatory complications associated with complications of chronic SCI, rather than SCI per se, contribute to the development of proteinuria. SCI patients with proteinuria have more impaired renal function and increased mortality compared with SCI patients without proteinuria.

Effect of Timed Semirecumbency and Furosemide Dosing on Urinary Sodium Excretion in Patients with Compensated Heart Failure

Purpose:The management of chronic cardiac failure, a salt-sensitive state, frequently includes administration of a loop diuretic to enhance urinary Na+ excretion. We hypothesized that a period of timed semirecumbency (vis-à-vis upright posture) would enhance the natriuresis that accompanies oral furosemide dosing in patients with compensated cardiac failure. Methods:Four ambulatory patients with compensated chronic cardiac failure (NYHA Class III) of ischemic and nonischemic origin and systolic dysfunction (ejection fraction <35%), who were receiving a stable regimen of oral furosemide and angiotensin-converting enzyme inhibitor, were enrolled into the study. In the institutions Clinical Research Center, we monitored and compared urine flow rate (mL/min) and Na+ excretion rate (mEq/hr) in each patient in response to two different protocols. Protocol 1 consisted of an initial 90-minute period of bedrest followed by the patients oral furosemide dose and 180 minutes of upright activity and a subsequent 90-minute period of bedrest. Protocol 2 was similar, with the exception that furosemide dosing was given after upright activity and immediately prior to the second period of bedrest. Results:With each patient serving as his or her own control, both urine flow rate and urinary Na+ excretion rate were markedly increased when furosemide was given prior to bedrest as compared to its dosing prior to upright activity. Conclusions:In patients with compensated chronic cardiac failure, the natriuresis that accompanies oral furosemide dosing is enhanced when given just prior to a period of timed semirecumbency. This approach represents a more optimal use of this loop diuretic in patients with compensated heart failure.

Differences and similarities between patients with and without end-stage renal disease, with regard to location of intracardiac calcification.

It has been known for some time that mitral annulus calcification is common in end‐stage renal disease (ESRD) patients on long‐term dialysis, as well as in elderly patients without renal failure. However, a systematic comparison of cardiac calcification in these two types of patients has not yet been made. We examined two‐dimensional echocardiograms in 33 patients with ESRD (mean age 66 ± 10 years) and in 34 other patients with intracardiac calcification but no ESRD (mean age 69 ± 9 years), with particular attention to precise anatomic location of calcification. Age was not significantly different in the two groups. The incidences of posterior mitral annulus calcification and aortic valve calcification were not significantly different in the ESRD and non‐ESRD groups, though mitral annulus calcification tended to be larger in ESRD patients. Basal mitral leaflet calcification and papillary muscle calcification was much more common in the ESRD group. Calcification of intervalvar fibrosa and of tricuspid annulus were noted only in ESRD patients.

Predictors of mortality in end-stage renal disease patients with mitral annulus calcification.

Objective:Mitral annulus calcification (MAC) is an independent predictor of cardiovascular mortality in the general population. The purpose of the current historical cohort study is to assess risk factors for long-term mortality in end-stage renal disease (ESRD) patients with MAC (n = 30; age, 62 ± 2 yr), as compared to ESRD patients without MAC (n = 30; age, 63 ± 2 yr). Additional analysis compared ESRD patients with MAC to non-ESRD patients with MAC (n = 32; age, 66 ± 2 yr). Methods:The groups included age-matched male patients followed at a single center. Long-term survival was assessed by Kaplan-Meier analysis. Regular and stepwise Cox proportional hazards models were used to determine risk factors for mortality. Results:There was a similarly high prevalence of cardiovascular complications, including hypertension, coronary artery disease, left ventricular hypertrophy, atrial fibrillation, and congestive heart failure, in all three groups. Median survival time was significantly longer in non-ESRD patients (90 months), compared with the ESRD with MAC (45 months) and ESRD without MAC (45 months) patients (log-rank test; P < 0.001). With stepwise Cox proportional hazards model, including ESRD patients with MAC and ESRD patients without MAC, increased calcium × phosphate product, decreased serum creatinine concentration, and the presence of coronary artery disease and lower extremity amputations were independent predictors of mortality for patients with ESRD. With stepwise Cox proportional hazards model, including ESRD patients with MAC and non-ESRD patients with MAC, the presence of ESRD, atrial fibrillation, diabetes, aortic valve calcification, coronary artery disease, and tricuspid regurgitation were independent predictors of mortality. Conclusion:The mortality rate was high in ESRD patients, approximately 15% per year. After accounting for baseline cardiovascular disease and traditional risk factors, the presence of MAC did not confer additional risk for mortality.

Chronic Kidney Disease and Diabetes Mellitus Predict Resistance to Vitamin D Replacement Therapy

Background:25-Hydroxyvitamin D [25(OH)D] is a marker of nutritional status; however, chronic kidney disease (CKD) results in alterations in vitamin D metabolism, including the loss of vitamin D-binding proteins and alterations in CYP27B1 and CYP24 enzymes that metabolize 25(OH)D. This study was designed to determine the predictors of responsiveness to correction of vitamin D deficiency with oral vitamin D2 (ergocalciferol) in adults. Methods:A retrospective study of 183 veterans with 25(OH)D level <30 ng/mL, who were treated with 50,000 IU per week of vitamin D2, was performed. Logistic regression models were developed to determine the factors predicting the response to treatment, defined as either the change in serum 25(OH)D level/1000 IU of vitamin D2 or the number of vitamin D2 doses (50,000 IU per dose) administered. Results:The mean age of the patients was 63 ± 12 years. About 87% were men and 51% diabetic, and 29% had an estimated glomerular filtration rate of <60 mL/min/1.73 m2. The average number of vitamin D2 doses was 10.91 ± 5.95; the average increase in 25(OH)D level was 18 ± 10.80 ng/mL. 25(OH)D levels remained <30 ng/mL in 61 patients after treatment. A low estimated glomerular filtration rate and the presence of diabetes mellitus were significant independent predictors for inadequate response to vitamin D2 treatment in logistic regression models. Patients with CKD required greater amounts of vitamin D2 to achieve similar increases in 25(OH)D levels, versus non-CKD patients. Conclusions:The presence of CKD and diabetes mellitus is associated with resistance to correction of 25(OH)D deficiency with vitamin D2 therapy. The underlying mechanism needs to be evaluated in prospective studies.