Hospitalizations for bacterial endocarditis after renal transplantation in the United States.

PURPOSE: The national rate of and risk factors for bacterial endocarditis in renal transplant recipients has not been reported. METHODS: Retrospective registry study of 33,479 renal transplant recipients in the United States Renal Data System (USRDS) between 1 July 1994 and 30 June 1997. Hospitalizations for a primary diagnosis of bacterial endocarditis (ICD-9 codes 421.x) within three years after renal transplant were assessed. RESULTS: Renal transplant recipients had an unadjusted incidence ratio for endocarditis of 7.84 (95% confidence interval 4.72-13.25) in 1996. In multivariate analysis, a history of hospitalization for valvular heart disease (adjusted odds ratio (AOR), 25.81, 95% confidence interval 11.28-59.07), graft loss (AOR, 2.81, 95% CI 1.34-5.09), and increased duration of dialysis prior to transplantation were independently associated with hospitalizations for bacterial endocarditis after transplantation. Hospitalization for endocarditis was associated with increased patient mortality in Cox Regression analysis, hazard ratio 4.79, 95% CI 2.97-6.76. CONCLUSIONS: The overall incidence of bacterial endocarditis was much greater in renal transplant recipients than in the general population, although it is still relatively infrequent. Independent risk factors for bacterial endocarditis in the renal transplant recipients were identified, the most significant of which was valvular heart disease. Endocarditis substantially impacts renal transplant recipient survival.     

Acute Coronary Syndromes after Renal Transplantation in Patients with End-Stage Renal Disease Resulting from Diabetes

Coronary heart disease is the leading cause of death in both diabetes mellitus and end-stage renal disease. Although renal transplantation is known to reduce mortality in end-stage renal disease, its effect on the incidence of acute coronary syndromes is unknown. Using data from the United States Renal Data System, we studied 11,369 patients with end-stage renal disease due to diabetes enrolled on the renal and renal-pancreas transplant waiting list from 1 July 1994 to 30 June 1997. Cox nonproportional hazards regression models were used to calculate the adjusted, time-dependent relative risk for the most recent hospitalization for acute coronary syndromes (including acute myocardial infarction, unstable angina, or other acute coronary syndromes, ICD9 Code 410.x or 411.x) for a given patient in the study period. Demographics and comorbidities were controlled by using data from the medical evidence form (HCFA 2728). After renal transplantation, patients had an incidence of acute coronary syndromes of 0.79% per patient year, compared to 1.67% per patient year prior to transplantation. In comparison to maintenance dialysis, renal transplantation was independently associated with a lower risk for acute coronary syndromes (hazard ratio 0.38, 95% confidence interval, 0.30-0.49). Patients with end-stage renal disease due to diabetes on the renal transplant waiting list were much less likely to be hospitalized for acute coronary syndromes after renal transplantation. The reasons for this decreased risk should be the subject of further study.     

Role of substrates in the maintenance of contractility of the rabbit urinary bladder.

Recent studies have shown that muscarinic stimulation causes an increase in the breakdown of glucose and glycogen leading to an increase in lactate and CO2 production and a decrease in the ratio of NADH/NAD. Similar studies using palmitate as substrate showed that bethanechol did not change the rate of palmitate oxidation. Using both isolated strips of rabbit bladder dome, and the rabbit in vitro whole-bladder model, the present study compares the ability of glucose, pyruvate, palmitate, succinate and malate to support contraction and correlates the results with the intracellular concentration of high-energy phosphates. The results can be summarized as follows. In the absence of substrate, the peak response of muscle strips to field stimulation (32 Hz, 80 V, 1 ms) decreased progressively with time to 85% of the initial response at 60 min and 72% at 160 min. In contrast, the plateau phase of the response decreased to 45 and 23% of the initial response at 60 and 160 min, respectively. When glucose was present in the incubation medium, the peak and plateau tensions were 86 and 73% of the initial values at 160 min. Similar experiments with pyruvate as substrate showed that at 160 min both peak and plateau were elevated above initial values (peak = 119%; plateau = 123%). In the presence of palmitate, succinate or malate, the peak and plateau tensions decreased with time at a similar rate as in the absence of substrate. The reduction in tissue content of pre-formed high energy phosphates was similar for zero substrate and when palmitate, succinate or malate were present in the bath.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparative studies on intracellular calcium and nadh fluorescence of the rabbit corpus cavernosum

Erectile function (erection and detumescence) involves the complex interaction of direct neuronal stimulation of corporal smooth muscle, neurohumoral release of specific endothelial contractile and relaxant factors, and secondary modulation by a variety of putative neuropeptides and vasoactive modulators. Using surface spectrofluorometry, we have correlated spontaneous contractile activity and the contractile response to field and pharmacological agents with intracellular calcium and NADH metabolism. The results demonstrate that the corpus cavernosal tissue has very unusual properties. Spontaneous contractile activity is correlated with a phasic increase in intracellular calcium. However, spontaneous contractile activity is most often correlated with a bi-phasic effect on the ratio of NADH/NAD. At the start of the spontaneous contraction, there is a sharp phasic increase in NADH/NAD; peak contractile force occurs simultaneous with a phasic decrease in this ratio showing that at peak force generation, there is a decrease in the level of intracellular energy. Phenylephrine stimulation results in an increase in intracellular calcium in proportion to the increase in tension; however, phenylephrine stimulation at low concentrations results in a net increase in the NADH/NAD ratio whereas high concentrations of phenylephrine result in a net decrease in the NADH/NAD ratio. In general, field stimulation results in a decrease in tension at low frequencies, a biphasic response at midfrequencies, and a contraction at high frequencies. These contractile responses are directly related to alterations in the intracellular concentration of calcium. That is, a decrease in tension is preceded by a decrease in intracellular calcium while an increase in tension is preceded by an increase in intracellular free calcium. Field stimulation results in a rapid and phasic alteration in the NADH/NAD ratio; however, the NADH/NAD response can be either an increase, decrease, or biphasic response. There does not appear to be a consistent relationship between the contractile/relaxant response to field stimulation and altered NADH/NAD ratio. Finally, ATP, bethanechol, and nitroprusside induce a decrease in the basal tension of the corpus cavernosal strips which corresponds with a decrease in the NADH/NAD ratio. However, whereas nitroprusside relaxation is correlated with a decreased intracellular calcium level, both ATP and bethanechol stimulate an increase in intracellular free calcium. These studies indicate that the response of the corpus cavernosal tissue to both field stimulation and pharmacological agents is complex and may involve both direct and indirect actions of a variety of cellular mediators on the corporal smooth muscle. © 1994 Wiley-Liss, Inc.     

Hospitalizations for bacterial septicemia after renal transplantation in the united states

BACKGROUND: It is common belief in the transplant community that rates of septicemia in transplant recipients have declined, but this has not been studied in a national population. METHODS: Therefore, 33,479 renal transplant recipients in the United States Renal Data System from July 1, 1994 to June 30, 1997 were analyzed in a retrospective registry study of the incidence, associated factors, and mortality of hospitalizations with a primary discharge diagnosis of septicemia (ICD9 Code 038.x). RESULTS: Renal transplant recipients had an adjusted incidence ratio of hospitalizations for septicemia of 41.52 (95% CI 35.45-48.96) compared to the general population. Hospitalizations for septicemia were most commonly associated with urinary tract infection as a secondary diagnosis (30.6%). In multivariate analysis, diabetes and urologic disease, female gender, delayed graft function, rejection, and pre-transplant dialysis, but not induction antibody therapy, were associated with hospitalizations for septicemia. Recipients hospitalized for septicemia had a mean patient survival of 9.03 years (95% CI 7.42-10.63) compared to 15.73 years (95% CI 14.77-16.69) for all other recipients. CONCLUSIONS: Even in the modern era, renal transplant recipients remain at high risk for hospitalizations for septicemia, which are associated with substantially decreased patient survival. Newly identified risks in this population were female recipients and pre-transplant dialysis.     

Lipid signaling changes in smooth muscle remodeling associated with partial urinary bladder outlet obstruction

AIMS: Hypertrophy of the urinary bladder smooth muscle (detrusor) is associated with partial bladder outlet obstruction (PBOO). Hypertrophied detrusor smooth muscle (DSM) reveals altered contractile characteristics. In this study, we analyzed the lipid-dependent signaling system that includes phospholipase A2 in PBOO-induced DSM remodeling and hypertrophy to determine whether the release of arachidonic acid (AA) from phospholipid is altered in the detrusor. METHODS: Partial bladder outlet obstruction (PBOO) was produced by partial ligation of the urethra in New Zealand white rabbits. Two weeks after the surgery, the bladder function was studied by keeping the rabbits in metabolic cages for 24 hr. Bladders were removed from rabbits that had bladder dysfunction (increased urinary frequency and decreased void volume) and the DSM separated from mucosa and serosa. The isolated smooth muscle was incubated with [3H] AA to equilibrate the cytoplasmic AA. The level of AA release was compared with the level obtained with 2-week sham-operated rabbits. RESULTS: The rate of AA release was high in DSM from bladders with PBOO-induced hypertrophy. Carbachol stimulated AA release in control DSM but DSM from obstructed rabbits revealed no further increase from the elevated basal AA release. The half-maximal concentration of carbachol that was required to stimulate AA release from control samples of detrusor was 35 microM. CONCLUSIONS: The increased levels of AA release that are observed in this tissue after PBOO indicate the activation of phospholipase A2. The finding that carbachol could induce contraction, but not an increase in AA, indicates that the carbachol-induced contraction in the obstructed bladders is independent of lipid signaling pathways that involve AA. It is possible that the increased rate of arachidonic acid release from obstructed bladders correlates with the enhanced rates of prostaglandin production reported by other investigators from the same tissue.     

In-vitro contractile response of the rabbit corpus cavernosa to field stimulation and autonomic agonists and antagonists: A qualitative study

Field stimulation of rabbit corporus cavernosum tissue strips can result in relaxation, contraction, or a biphasic response depending on the frequency and the power utilized. In this study we characterized the autonomic components of this response by exposing corporal tissue strips to a variety of autonomic agonists and antagonists including phentolamine, isoproterenol, methoxamine, propranolol, bethanechol, atropine, and ATP. Low frequency electrical field stimulation produced a bi-phasic response characterized by an initial relaxation followed by a contraction. High frequencies (≥ 32 Hz) produced contraction only. All responses were abolished by tetrodotoxin, indicating that both the contractile and relaxant responses to field stimulation are mediated by complex neural mechanisms. The initial relaxation response involves a combination of mediators which include musca-rinic cholinergic stimulation, purinergic, beta-adrenergic, and non-adrenergic, non-cholinergic (NANC) stimulation. The non-cholinergic contribution to corporal smooth muscle relaxation appeared to be approximately equal in significance to the cholinergically mediated relaxation. Beta adrenergic stimulation mediated a direct relaxation of the corporal smooth muscle. The contractile portion of the bi-phasic response was mediated by alpha-adrenergic stimulation. Additionally we have noted a rebound contraction following termination of field stimulation at all frequencies that is not affected by adrenergic or cholinergic blockade and may reflect the field-stimulated release of an endogenous smooth muscle contractile factor.     

Comparison of the contractile and metabolic effects of muscarinic stimulation with those of KCl

Urinary bladder emptying is mediated primarily by a coordinated contraction of the bladder body in response to parasympathetic stimulation and muscarinic receptor activation. In previous studies we presented evidence that the contractile response to bethanechol stimulation could be dissociated from the metabolic response through the use of diltiazem (calcium channel blockade). The conclusion from these studies was that muscarinic stimulation resulted in a significant increase in metabolic activity which was not directly associated with contraction. KCl stimulates contraction in isolated strips by directly depolarizing the membrane rather than from binding to specific membrane receptors. The current study directly compares the metabolic and contractile activity of bethanechol (muscarinic stimulation) with KCl (direct membrane depolarization). Isolated strips of rabbit urinary bladder body were monitored in vitro for changes in intracellular-free calcium, NADH/NAD ratio, and contraction. Intracellular-free calcium was monitored by preincubation of isolated bladder smooth muscle strips with FURA-2 AM and continuously measuring the fluorescence with an MB2 surface spectrofluorometer using excitation wavelengths of 340 and 380 nm, and an emission wavelength of 510 nm. The NADH/NAD ratio was monitored with the MB2 surface spectrophotometer using an excitation wavelength of 366 nm and an emission wavelength of 450 nm. Contraction was monitored using a isometric force transducer connected to a Grass model D polygraph. The results can be summarized as follows. (1) Both bethanechol and KCl stimulate a sharp decrease in the NADH/NAD ratio, a rapid increase in intracellular-free calcium, and a slower increase in contractile force.(ABSTRACT TRUNCATED AT 250 WORDS)     

Human immunodeficiency virus/acquired immunodeficiency syndrome-associated nephropathy at end-stage renal disease in the United States: patient characteristics and survival in the pre highly active antiretroviral therapy era.

BACKGROUND: The patient characteristics and course of HlV/AIDS-associated nephropathy (HIVAN) are presented for a national sample of end-stage renal disease (ESRD). METHODS: 375,152 patients in the United States Renal Data System were initiated on ESRD therapy between 1 January 1992 and 30 June 1997 and analyzed in an historical cohort study of HIVAN. RESULTS: Of the study population, 3653 (0.97%) had HIVAN. Among patients with HIVAN, 87.8% were African American. HIVAN had the strongest association with African American race compared to other causes of renal failure except sickle cell anemia in logistic regression analysis (odds ratio 12.20, 95% confidence interval (CI) 10.57-14.07). In a separate logistic regression analysis, HIVAN was associated with male gender, decreased age (39.32 +/- 8.51 vs. 60.97 +/- 16.43 years, p<0.01 by Student's t-test), weight, body mass index, hemoglobin, albumin, decreased rate of pre-dialysis erythropoietin use, increased creatinine, decreased hypertension and increased rate of no medical insurance. The geographic distribution of HIVAN was similar to the distribution of HIV cases nationally. Two-year all cause unadjusted survival was 36% for HIVAN vs. 64% for all other patients with ESRD. HIVAN was associated with decreased patient survival in Cox regression analysis (hazard ratio for mortality 5.74, 95% CI, 5.40-6.10). CONCLUSIONS: HIVAN had the strongest association with African American race of all causes of renal failure among patients on maintenance dialysis. HIVAN was associated with decreased patient survival after initiation of dialysis, which may be associated with poorer medical condition at initiation of dialysis.