Brian M. Murray

Decreased pressor reactivity to angiotensin II in cirrhotic rats. Evidence for a post-receptor defect in angiotensin action.

We used a model of cirrhosis in the rat, produced by inhalation of carbon tetrachloride for 6 weeks, to investigate the mechanism of resistance to the pressor effects of angiotensin II. The pressor response to angiotensin II was significantly lower in conscious cirrhotic animals than in controls. On the other hand, cirrhotic animals had normal pressor responses to norepinephrine, indicating that a generalized defect in vascular reactivity does not cause the decreased pressor response to angiotensin II. Enhanced baroreceptor activity was not the cause of the decreased pressor response to angiotensin II, since baroreflex control of heart rate after angiotensin II was similar in cirrhotics and controls. Pretreatment with either the converting enzyme inhibitor captopril to reduce circulating angiotensin II or the prostaglandin synthesis inhibitor meclofenamate failed to normalize the response to angiotensin II. Thus, neither prior occupancy of receptors with endogenous angiotensin II nor the production of vasodilatory prostaglandins was responsible for the decreased angiotensin II response. Studies of angiotensin II binding by mesenteric artery smooth muscle particles showed that, in cirrhotic animals, receptor affinity for angiotensin II, was significantly lower than in controls (kd: cirrhosis 1.11 +/- 0.09 nM, control 0.94 +/- 0.13 nM; P less than 0.02), whereas receptor number was significantly increased (cirrhosis 315 +/- 42 fmol/mg protein, control 277 +/- 43 fmol/mg protein, P less than 0.01). However, total binding of AII by vascular receptors from cirrhotics was no different than in controls, since the decrease in affinity negated the increase in receptor number.(ABSTRACT TRUNCATED AT 250 WORDS)

Improving Chronic Kidney Disease Care in Primary Care Practices: An Upstate New York Practice-based Research Network (UNYNET) Study

Background: With the prevalence of chronic kidney disease (CKD) in the United States rising from 10% to 13%, implementation of the evidence-based Kidney Disease Outcomes Quality Initiative guidelines, which were developed for the delay of progression of CKD, is of increasing importance in primary care offices. Previous studies have shown limited knowledge and uptake of Kidney Disease Outcomes Quality Initiative guidelines by primary care physicians. CKD and its complications are still largely under-diagnosed and under-treated. A multifaceted quality improvement study was undertaken to test if these guidelines could be implemented to improve CKD care in underserved practices. Methods: Using a combination of practice enhancement assistants, computer decision-making support, and academic detailing, we sought to increase physician awareness and care of CKD in 2 inner-city practices. Using these 3 modalities, a rapid-cycle quality improvement process was implemented. Results: One hundred eighty-one patients met the inclusion criteria of having a glomerular filtration rate <60. This represented a 100% sample of patients with CKD at baseline. Recognition of CKD improved significantly from 30 (21%) to 114 (79%) (P < .001). Diagnosis of anemia also increased significantly from 26 (33%) to 53 (67%) (P < .001). Angiotensin-converting enzyme inhibitor and aspirin use did not change significantly (P = .31 and P = .233, respectively). Changes in medications that did show significance were metformin use, which decreased 50% from 12 to 6 patients (P < .001), and nonsteroidal anti-inflammatory drug use, which decreased 41% from 23 to 14 patients (P < .001). Mean glomerular riltration rate increased significantly from 45.75 to 47.34 (P < .001). Discussion: Recognition and treatment of CKD and its complications can be markedly improved in primary care offices using a combination of practice enhancement assistants, computer decision-making support, and academic detailing. A significant rise in glomerular riltration rate, although small, was a surprising and encouraging result. Larger studies in a more geographically spread region are needed to confirm these preliminary results.

Non-Traumatic Rhabdomyolysis Complicating Antihistamine Overdose

Antihistamines are common over the counter medications which are frequently involved in overdoses. The usual clinical course is dominated by the anticholinergic affects of these agents; it includes significant autonomic and central nervous system effects and direct cardiac toxicity (1). We report a case of a suicide attempt in a young adult male where ingestion of the antihistamines diphenhydramine and doxylamine was complicated by non-traumatic rhabdomyolysis and acute renal failure.

Assessment of access blood flow after preemptive angioplasty

In an effort to prolong the life of synthetic grafts used for hemodialysis access, current recommendations suggest regular monitoring of vascular access by means of measurements of access blood flows (ABFs) and/or pressures and prompt referral for prophylactic angiography with angioplasty when appropriate. Previous data suggested that angioplasty transiently reduces venous pressure, but repeated angioplasty is often required. Few data exist on the effect of angioplasty on ABF, especially the durability of the response. In this study, we report our experience with 49 consecutive angioplasties of 32 synthetic polytetrafluoroethylene grafts in which ABF was measured serially preangiography and postangiography using the Transonic hemodialysis monitor (Transonic Inc, Ithaca, NY). The primary indication for angiography was a low graft ABF rate (<600 mL/min). Although the most common site for stenosis was the venous anastomosis, the majority of grafts had multiple lesions requiring angioplasty. Mean ABF rate increased from 596 +/- 41 to 922 +/- 48 mL/min postangiography, an increase of almost twofold. This level of blood flow was maintained for the first month, but thereafter ABF began to decrease, reaching 672 +/- 70 mL/min at 3 months and 658 +/- 93 mL/min at 6 months. Two patients were lost to follow-up (one patient died, one patient received a transplant) and 2 grafts were electively ligated. The remaining 28 grafts were followed up for at least 6 months. Four grafts clotted within 3 months of angioplasty and were lost. Nine additional grafts required a second intervention (surgical revision, 2 grafts; repeated angioplasty, 7 grafts) within 6 months, either for a poor initial response to angioplasty or recurrent stenosis. Two of these 9 grafts subsequently clotted and were lost. In all, 22 of the 28 grafts remained patent at 6 months postangioplasty, and 15 grafts were maintaining an ABF greater than 600 mL/min without reintervention at 6 months. In summary, this study indicates that preemptive angioplasty of graft stenoses results in an initial doubling of ABF, but the effect is temporary, with the average ABF decreasing to baseline values by 3 months. Approximately half the grafts required reintervention for either thrombosis or recurrent low flow. However, sustained responses with ABF maintained at greater than 600 mL/min were achieved in the other half.

Late cytomegalovirus infection after oral ganciclovir prophylaxis in renal transplant recipients

Abstract: The purpose of this study was to retrospectively review our experience with a consecutive group of 41 renal transplant recipients (R) who received a kidney from a cytomegalovirus (CMV) seropositive donor (D+) and had 3 months of prophylaxis with oral ganciclovir. Patients were prospectively monitored clinically and with determinations of CMV antigenemia for at least 6 months. Patients were followed for a mean period of 247±16 days. CMV antigenemia developed in 51% of patients (53% D+R−, 47% D+R+) after the transplant, but in no case was antigenemia seen during the period of oral ganciclovir therapy. Antigenemia developed at a median of 167 days post transplant (range 99–522 days) and peak antigen counts ranged from <1–3940, and tended to be higher in D+R− recipients. Infection was symptomatic in 67% of the antigenemic patients and symptoms tended to be more marked in the D+/R− than in the D+/R+ group. All symptomatic patients were treated with intravenous ganciclovir (21 days) followed by 9 weeks of oral ganciclovir and responded with resolution of symptoms and antigenemia. No evidence of tissue‐invasive disease was seen. Recurrence of antigenemia was observed exclusively in the D+R− group, occurred with less severe manifestations of CMV infection, and invariably responded to retreatment with ganciclovir. Our results suggest that oral ganciclovir prophylaxis is effective in preventing CMV infection during the 3‐month period of prophylaxis, that a 3‐month period of prophylaxis appears to be sufficient for D+R+ recipients, but a longer period of oral ganciclovir prophylaxis may be needed in D+R− recipients. Clinicians caring for renal transplant recipients should be vigilant to the possibility of late CMV infection, especially in D+R− recipients.

Effect of Erythropoiesis-Stimulating Agents on Healthcare Utilization, Costs, and Outcomes in Chronic Kidney Disease

Background: Anemia commonly complicates chronic kidney disease (CKD). Treating anemia of CKD with erythropoiesis-stimulating agents (ESAs) may attenuate cardiovascular and renal sequelae, reducing morbidity, morality, and healthcare costs. Objective: To compare clinical outcomes, healthcare utilization, and costs in ESA-treated and untreated patients with anemia of CKD who are not on dialysis. Methods: This retrospective claims analysis considered more than 13 million US health plan members for outpatient, inpatient, emergency department, and prescription experience. Eligible patients were aged 15 years or ordor with 2 or more ICD-9 diagnoses of CKD or 1 or more CKD diagnosis and 1 or more claims for ESA within 12 months. The first CKD diagnosis within the study period (January 1, 2000-December 31, 2003) defined the index date. Anemia was ascertained by ICD-9 codes or ESA claims on or after the CKD index date. Patients were censored for dialysis, transplant, inpatient death, disenrollment, or study end. Utilization and costs per patient per month were compared between ESA and non-ESA patients. Generalized linear modeling identified predictors of total and anemia-related costs. Results: Of 26,244 patients with CKD, 8188 (31.2%) had anemia; of those, only 14.6% (n = 1197) received ESAs. ESA recipients had lower total monthly healthcare costs than did untreated anemic patients (

Access flow after angioplasty predicts subsequent arteriovenous graft survival

3876 vs

Ganciclovir pharmacokinetics and cytokine dynamics in renal transplant recipients with cytomegalovirus infection

4758; p = 0.0061). Lower monthly inpatient and emergency department costs in treated versus untreated anemic patients (

Why do grafts clot despite access blood flow surveillance

2507 vs

Effect of steroid-free low concentration calcineurin inhibitor maintenance immunosuppression regimen on renal allograft histopathology and function

3849 and