Medical evaluation of living kidney donors with nephrolithiasis: a survey of practices in the United States.

BACKGROUND: A scarcity of organs has driven the transplant community to broaden selection criteria for both living and deceased donors. Living donor transplants offer better patient and allograft survival when compared with deceased donor transplants. Many transplant centers now allow complex living donors such as those with nephrolithiasis to undergo nephrectomy. METHODS: We conducted a survey of medical and surgical directors of kidney transplant programs in the United States to shed light on current practices pertaining to medical evaluation of living kidney donors with nephrolithiasis. 353 surveys were e-mailed to medical directors and surgical directors of transplant programs after contacts were obtained from UNOS. RESULTS: 49 completed surveys were returned (13.9%). 77.7% (38/49) of survey participants said their centers will consider living kidney donor candidates with a history of symptomatic kidney stones, 69.4% (34/49) said their centers will consider candidates who are incidentally found to have kidney stones and 10.2% (5/49) said their centers decline all potential donors with nephrolithiasis. CONCLUSIONS: Several programs are still reluctant to allow potential donors with nephrolithiasis to donate. There is an unmet need to develop evidence-based guidelines to optimize outcomes in this population of kidney donors with nephrolithiasis and their recipients.

When the living and the deceased cannot agree on organ donation: a survey of US organ procurement organizations (OPOs).

The legal concept of first person authorization (FPA) is based on the principle that a decision by a person with decision-making capacity should be respected even after he or she dies. Although the transplant community largely supports this concept, its implementation has not been universal. We conducted a web-based survey of all 58 Organ Procurement Organization (OPO)executive directors in the United States to assess OPOs' procurement policies and practices in the context of family objections. All 58 respondents(100%) responded to our survey. All OPOs except one have an online donor registration website. Most OPOs(89%) (51 of 57 respondents) estimated that the frequency of family objecting to organ donation in cases of registered donors was <10%. No OPOs reported the frequency to be higher than 25%. Only 50% (27 of 54) of the OPOs have a written policy on handling family objections. Approximately 80% of the OPOs reported honoring FPA. However, in the past 5 years, 20 OPOs (35%) have not yet participated in organ procurement from a registered deceased donor over family objection. Further research to identify the barriers and possible solutions to implementing FPA is warranted.

Abolition of Holter monitor-detected silent myocardial ischemia after percutaneous transluminal coronary angioplasty.

Twenty-four hour Holter ambulatory electrocardiographic recordings were obtained before and after successful coronary angioplasty in 36 patients. Twenty-five patients had one vessel, 10 had two vessel and 1 had three vessel coronary artery disease. Holter monitor-detected myocardial ischemia, defined as ST segment depression or elevation greater than or equal to 1 mm, was present in 10 patients (28%). These 10 patients had a total of 39 ischemic episodes of 3 to 144 minutes' duration, with a total cumulative duration of 398 minutes. None of the 10 had Holter monitor-detected ischemia after successful angioplasty (p less than 0.01). Treadmill exercise duration increased by 29% after coronary angioplasty (p less than 0.01), and peak exercise heart rate-systolic blood pressure product increased by 27% (p less than 0.01). Thus, Holter monitor-detected myocardial ischemia is a relatively uncommon finding in patients with predominant single vessel coronary artery disease undergoing coronary angioplasty. When such ischemia is present, it is eliminated by successful coronary angioplasty.

Prognostic significance of silent myocardial ischemia in patients with unstable angina.

Silent myocardial ischemia is common in unstable angina, but its prognostic significance is unknown. Fifty-two (42 with subsequent angiography) of 81 patients prospectively evaluated for unstable angina had ambulatory electrocardiographic (Holter) recordings analyzed by compact analog technique after they had received medical treatment (3 of the 52 had unanalyzable recordings and were excluded). From 1,103 hours of recordings, 298 ischemic episodes were identified, only 9% associated with angina. By Ridit analysis a significant correlation was found between the cumulative duration of transient myocardial ischemia and the number of diseased coronary vessels and indexes of proximal stenosis. During a 3 to 6 month follow-up period, there was one death and one patient was lost to follow-up among 20 patients without transient ischemia; in the group of 11 patients with a cumulative duration of transient ischemia less than 60 minutes/24 h, 7 were alive and well, 2 required coronary bypass surgery, 1 had coronary angioplasty for recurrence of angina and 1 was lost to follow-up. In the group of 18 patients with ischemia duration greater than 60 minutes/24 h, only 1 developed a stable angina pattern; 12 required coronary surgery (n = 11) or angioplasty (n = 1) and 5 developed myocardial infarction (2 died, 2 needed surgery for postinfarction angina and 1 recovered). A favorable clinical outcome occurred in only 6% of patients in the group with ischemia duration greater than 60 minutes/24 h; this rate was significantly lower (p less than 0.001) than that (70%) for the group with ischemia duration less than 60 minutes/24 h or that (95%) for the group without ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Severity of silent myocardial ischemia on ambulatory electrocardiographic monitoring in patients with stable angina pectoris: relation to prognostic determinants during exercise stress testing and coronary angiography.

The relation of silent ischemia in patients with stable angina to known predictors of severity of coronary disease on exercise stress testing and coronary angiography is poorly defined. This issue was therefore examined with use of Holter electrocardiographic (ECG) recordings, treadmill exercise tests and angiographic indexes in 102 patients (not taking antianginal therapy) and the results were compared with Holter and treadmill findings in 42 volunteers. A total of 159 ischemic episodes (90% silent) were identified during 2,503 h on Holter recording in 97 patients (mean duration per episode 22.7 +/- 147 min; range 1 to 234). Holter recordings had a 92% specificity and an 80% positive predictive value, but a sensitivity of only 37% and a negative predictive value of 27% for coronary disease. Sixty-three patients (Group I) had no ischemia on Holter recording, 22 (Group II) had a cumulative duration of 1 to 60 min/24 h and in 12 (Group III) ischemia exceeded 60 min/24 h. There was no significant correlation between cumulative ischemia duration on Holter recording and exercise duration or time to ST segment depression on treadmill exercise. In general, the greater the number of coronary vessels involved and the higher the proximal coronary artery stenosis score, the greater the likelihood of ischemia and the longer the cumulative ischemia duration on Holter recording. Irrespective of the severity of coronary disease, in about 25% of Holter recordings in each angiographic category there were no ischemic episodes.(ABSTRACT TRUNCATED AT 250 WORDS)

Atypical echocardiographic and angiographic presentation of a postoperative pseudoaneurysm of the left ventricle after repair of a true aneurysm.

Subsequent to the repair of a true aneurysm from the posteromedial-basal aspect of the left ventricle, a 58 year old man developed a draining wound at the site of the sternotomy. Two-dimensional echocardiography revealed recurrence of the aneurysm at the site of the previous aneurysm repair. This aneurysm had a wide neck and looked similar in appearance to the previous true aneurysm. However, at surgery the patient was found to have a ventricular pseudoaneurysm with a cardiocutaneous fistula.

Tacrolimus therapy for refractory acute renal allograft rejection: definition of the histologic response by protocol biopsies.

UNLABELLED: Protocol biopsies were performed to define the histologic response to tacrolimus therapy in patients with refractory acute renal allograft rejection. Renal allograft biopsies were performed at defined intervals after initiation of tacrolimus therapy. Protocol biopsies were performed before tacrolimus therapy (within 48 hr of initiation of therapy) and after 1 week of therapy. If the 1-week biopsy did not show rejection reversal, repeat protocol biopsies were obtained at 1- to 2-week intervals, until histologic reversal was observed. Additional biopsies were obtained at 4 weeks and at 8-12 weeks after initiation of tacrolimus therapy. Indicated biopsies were also performed to evaluate increases in serum creatinine. A total of 92 biopsies were performed in 23 patients (average 4.0 biopsies/ patient). Biopsies were performed in each patient immediately before starting tacrolimus therapy (23 biopsies), and 69 biopsies (3.0 biopsies/patient) were performed during tacrolimus therapy. Rejection diagnosis was based on strict Banff criteria. Pretacrolimus biopsies demonstrated mild acute rejection in 64% of patients and moderate acute rejection in 36%. One week after initiation of tacrolimus therapy, protocol biopsies revealed the following: no rejection (60%), improvement (13%), no change (20%), and worsening rejection (7%). Histologic changes at 1 week did not correlate with changes in renal function, as 63% of patients that showed histologic improvement or reversal during the first 2 weeks of therapy did not show improvement in serum creatinine. A lack of histologic improvement (or worsening) at 1 week was demonstrated in a significant proportion of patients (27%); increased tacrolimus dosing provided rejection reversal or improvement in 1-2 weeks in each of these patients. Recurrent rejection was diagnosed on eight biopsies in seven patients, however six episodes were diagnosed by protocol biopsies alone (i.e., in the absence of an elevation in serum creatinine). Delayed improvement in renal function, despite histologic reversal, was likely due to physiologic effects of tacrolimus (i.e., afferent arteriolar vasoconstriction), as histologic evidence of tacrolimus toxicity was not observed during the first 2 weeks of therapy. Histologic evidence of tacrolimus nephrotoxicity (nodular arteriolar hyalinosis) was found in 21% (15 of 69) of biopsies in 39% of patients (9 of 23) at a median time of 60 days (range 12-150 days). Tacrolimus dose and blood levels (by IMx assay) did not correlate with development of clinically silent or clinically evident nephrotoxicity. IN CONCLUSION: 1) protocol biopsies provide information that allows individualization of tacrolimus rejection therapy, 2) histologic resolution of rejection often precedes biochemical improvement, 3) histologic evidence of tacrolimus nephrotoxicity is seldom observed in the first 2 weeks of therapy, and 4) clinically silent recurrent rejection and clinically silent tacrolimus nephrotoxicity are observed with significant frequency during tacrolimus therapy for refractory renal allograft rejection.

Long-term outcome of kidney-pancreas transplant recipients with good graft function at one year.

To assess the long-term outcome of kidney/pancreas transplantation, patients were identified who had good graft function at one year posttransplant and a minimum of 3 years' follow-up. Fifty recipients from 1987-92 met these criteria. Records were reviewed for graft survival, graft function, readmissions, and medical complications. Psychosocial adjustment and quality of life were assessed using the SCL-90-R and SIP surveys, respectively. Patient, kidney, and pancreas survivals were 94%, 86%, and 85% at five years (Kaplan-Meier), with a mean follow-up of 4.3 years. The 3 deaths were due to 2 sudden arrests at home (presumed to be cardiac events) and 1 episode of sepsis. Other graft losses were due to rejection, except for one case of sepsis. The remaining patients are normoglycemic (glucose 92 +/- 23 mg/dl) and have a creatinine of 1.8 +/- 0.6 mg/dl. Mortality after the first year was 0.9%/year. Estimated kidney and pancreas half-lives were 15 +/- 2 and 23 +/- 7 years, respectively. Hospitalization, acute rejection, graft pancreatitis, dehydration, and severe infections all decreased dramatically after the first year. While CMV was the most common infection in the first year, foot infections predominated thereafter. Retinal hemorrhage was infrequent. Sudden death (presumably cardiac) was the chief cause of mortality, while peripheral vascular disease resulted in several amputations. Fractures were common, suggesting the need for increased attention to bone demineralization. Psychosocial and quality of life evaluations were within normal limits. In conclusion, most complications specifically related to transplantation occur in the first year, but underlying disease renders these patients susceptible to a variety of cardiovascular, bone, and other disorders.

Use of calcium antagonists in ventricular dysfunction.

Calcium antagonists are now widely used in a variety of cardiocirculatory disorders, many of which are associated with varying levels of depressed myocardial function. Thus, the hemodynamic effects of calcium antagonists in patients with normal as well as depressed ventricular function are clinically relevant. None of the 3 agents verapamil, nifedipine or diltiazem exerts significant negative inotropic effects in patients with relatively normal myocardial function, although increases in left ventricular end-diastolic pressure may occur with verapamil and possibly diltiazem. In a setting in which ischemia, hypertension or arrhythmias contribute to cardiac failure, all 3 agents may ameliorate myocardial decompensation if they reverse the precipitating causes. In patients with depressed myocardial function, the effects of diltiazem are not known; verapamil may depress myocardial function, especially if the ventricular filling pressure is increased. Nifedipine generally has little depressant action in this setting and usually improves cardiac function, especially if the sympathetic reflexes are intact. However, hemodynamic deterioration after nifedipine administration has been reported. Thus, the available data do not support the use of calcium antagonists as afterload-reducing agents in heart failure and suggest caution in the use of these agents in patients with impaired ventricular performance.

Effects of flecainide on ventricular function: clinical and experimental correlations.

Flecainide has unusual electrophysiologic properties and a high potency for the suppression of ventricular tachyarrhythmias. Little is known about its inotropic and hemodynamic actions. In isolated rabbit papillary muscle, it produced a concentration-dependent depression of contractile force, the threshold concentration being 1.0 micrograms/ml. In patients undergoing coronary angiography for ischemic heart disease and given 1 (n = 11) and 2 mg/kg (n = 11) of flecainide acetate i.v., there was no change in heart rate or mean arterial pressure. The vehicle in which i.v. flecainide was suspended had no significant effects in 6 patients in whom it was tested. Both doses produced comparable hemodynamic effects irrespective of the level of the left ventricular ejection fraction. The mean right atrial pressure increased by 12% (p less than 0.05) after 1 mg/kg and by 15% (p less than 0.01) after 2 mg/kg of the drug. The corresponding increases in mean wedge pressure were 44% (p less than 0.05) and 33% (p less than 0.05), in mean pulmonary artery pressure 27% (p less than 0.01) and 28% (p less than 0.05), in systemic vascular resistance 10% (p less than 0.05) and 9% (not significant [NS]) and in pulmonary vascular resistance 6% (NS) and 49% (p less than 0.05). Significant decreases in cardiac index (8 and 12%, p less than 0.05), stroke volume index (11 and 15%, p less than 0.01) and stroke work index (12%, p less than 0.05, and 21%, p less than 0.01) as well as in left ventricular ejection fraction (15 and 16%, p less than 0.01) were also induced by the 2 doses of flecainide.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodynamic and metabolic effects of diltiazem during coronary sinus pacing with particular reference to left ventricular ejection fraction.

To determine the systemic and coronary hemodynamic effects of diltiazem at rest and during pacing, 14 patients with stable angina pectoris undergoing coronary angiography were studied before and after 0.165 mg/kg (n = 7) and 0.25 mg/kg (n = 7) of intravenously administered diltiazem. Hemodynamic variables, metabolic measurements and left ventricular (LV) ejection fraction (EF) were obtained at rest and during coronary sinus (CS) pacing before and during diltiazem administration. Lactate production during control pacing turned into extraction after diltiazem (p less than 0.05). At rest, systemic resistance was reduced by 21% (p greater than 0.01) and mean arterial pressure by 12% (p less than 0.01); cardiac index increased from 2.4 +/- 0.4 to 2.6 +/- 0.4 liters/min/m2 (p less than 0.01), with no significant change in heart rate. The mean pulmonary artery pressure increased from 17 +/- 2 to 19 +/- 3 mm Hg (p less than 0.01), but other hemodynamic variables were not affected. Diltiazem given during pacing reduced the mean aortic pressure (from 112 +/- 15 to 104 +/- 15 mm Hg, p less than 0.05), but other hemodynamic variables were not affected significantly. LVEF decreased 16%, from 0.63 +/- 0.9 to 0.53 +/- 0.8 with CS pacing (p less than 0.01); when the pacing was performed after diltiazem administration the 8% decrease in LVEF from 0.64 +/- 0.09 to 0.59 +/- 13 was less marked (p less than 0.01). Diltiazem had no significant effect on LVEF at rest. The overall data suggest that the ischemic manifestations of CS pacing are attenuated by diltiazem in doses of the drug that exert no significant depressant effect on LV function in patients with coronary artery disease.

Correlation of continuous-wave Doppler assessment of chronic aortic regurgitation with hemodynamics and angiography.

Fifteen patients with chronic aortic regurgitation (AR) were studied by cardiac catheterization and continuous-wave (CW) Doppler echocardiography. The slope of the AR CW Doppler signal was higher in patients with severe AR (5.7 +/- 2.1 m/s2) than in those with moderate (2.5 +/- 1.3 m/s2) or mild (1.8 +/- 0.7 m/s2) AR (p less than 0.05). The slopes in patients with mild (less than or equal to 18 mm Hg), moderate (19 to 24 mm Hg) and severe (greater than 24 mm Hg) elevation of left ventricular end-diastolic pressure were significantly different (1.9 +/- 0.6, 3.3 +/- 1.2 and 7.1 +/- 0.4 m/s2, respectively, p less than 0.05). Patients with severe AR had shorter pressure half-times than those with mild AR (283 +/- 141 vs 820 +/- 393 ms, p less than 0.05). There was a significant correlation between the slope and left ventricular end-diastolic pressure (r = 0.80, p less than 0.001) and a weaker inverse correlation between pressure half-time and left ventricular end-diastolic pressure (r = -0.59, p less than 0.05). The end-diastolic pressure gradient estimated from CW Doppler using a simplified Bernoulli equation correlated poorly with the catheter measured gradient (r = 0.59, p less than 0.02). The slope of the CW Doppler signal is a better predictor of severity than pressure half-time and is affected by left ventricular end-diastolic pressure in addition to angiographic severity of AR.

Circadian variation in occurrence of transient overt and silent myocardial ischemia in chronic stable angina and comparison with Prinzmetal angina in men.

Circadian periodicity was examined in 68 patients with chronic stable angina and in 9 patients with Prinzmetal angina. The frequency and duration of transient ischemic episodes were determined from analysis of 1 or more 24-hour Holter recordings by the compact analog technique. Ninety percent of the episodes in both syndromes were silent; 80% of the episodes of Prinzmetal angina were associated with ST-segment elevation and all episodes of chronic stable angina had ST-segment depression. Ischemic episodes were shorter (3 +/- 2 vs 18 +/- 23 minutes, p less than 0.0005) but more frequent (21 +/- 18 vs 6 +/- 4 per 24 hours, p less than 0.0001) in patients with Prinzmetal angina than in those with chronic stable angina. In patients with chronic stable angina, both silent and painful episodes had a peak occurrence in the morning and early afternoon hours (between 8 AM and 3 PM); the fewest episodes were between 1 AM and 5 AM. This distribution was not random by chi-square test (p less than 0.001). Cosinor analysis of ischemic episodes periodicity showed the acrophase at 1 PM, which was not different from that (3 PM) of the circadian rhythmicity for heart rate. In case of Prinzmetal angina, the acrophase of heart rate changes was at 5 PM, but a clear periodicity in the distribution of the ischemic episodes was not found. These differences in the circadian periodicity may reflect differences in the mechanism of ischemia in chronic stable angina and in Prinzmetal angina and are likely to be of therapeutic significance.

Hemodynamic and electrocardiographic correlates of symptomatic and silent myocardial ischemia: pathophysiologic and therapeutic implications.

Numerous hemodynamic, electrocardiographic, metabolic and radionuclide measurements in various subsets of patients with coronary artery disease (CAD) reveal that ischemia does not always occur on the basis of increases in myocardial oxygen consumption. Continuous hemodynamic monitoring indicates that most episodes of myocardial ischemia are not preceded by increases in such major determinants of oxygen consumption as heart rate or blood pressure, but that these usually increase in response to the development of ischemia. The development of pain during ischemia is a late feature and most episodes are silent. There are no significant differences in the hemodynamic characteristics of symptomatic versus asymptomatic episodes of myocardial ischemia in patients with angina at rest or between those associated with ST-segment depression and those with ST-segment elevation. Continuous Holter recordings analyzed by compact analog technique in hospitalized and ambulatory patients with ischemic heart disease indicate that in both unstable and chronic stable angina, over two-thirds of myocardial ischemic episodes are clinically silent. Symptomatic and silent episodes do not differ significantly with respect to duration. Most symptomatic and asymptomatic episodes are not triggered by increases in the determinants of oxygen demand. Such episodes may arise on the basis of a critical reduction in the lumen of the diseased coronary artery leading to a primary reduction in blood flow. Intermittent obstruction due to changes in coronary vasomobility or possibly formation of thrombi may be a common mechanism for the pathogenesis of myocardial ischemia in patients with a varying spectrum of coronary artery lesions. At present, the precise clinical and prognostic significance of silent ischemia in CAD is not completely defined.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects on hemodynamics and left ventricular ejection fraction of intravenous bepridil for impaired left ventricular function secondary to coronary artery disease.

To define the hemodynamic effects of bepridil in patients with depressed left ventricular (LV) function, 22 patients with an LV ejection fraction (EF) of 0.45 or less were studied before and after 2 mg/kg (n = 11) and 4 mg/kg (n = 11) of intravenous bepridil. Maximal hemodynamic effects were evident between 15 and 30 minutes after drug infusion. After 2 mg/kg, heart rate decreased 9% (p less than 0.01), cardiac index 17% (p less than 0.01), LV dP/dt max 16% (p less than 0.01), stroke work index 14% (p less than 0.01) and mean aortic pressure 8% (difference not significant). Right atrial pressure increased 8% (not significant), pulmonary arterial wedge pressure 24% (p less than 0.01) and systemic vascular resistance 17% (p less than 0.01). After administering 4 mg/kg of bepridil the changes in heart rate, cardiac index, right atrial pressure, LV dP/dt max, mean aortic pressure and systemic vascular resistance were almost identical to those after the smaller dose. The larger dose produced a 40% (p less than 0.01) increase in pulmonary arterial wedge pressure and a 22% decrease in stroke work index (p less than 0.01), but only the change in wedge pressure was significantly greater (p less than 0.01) than that produced by the lower dose. Radionuclide-determined LVEF decreased 6% (p less than 0.05), from 0.33 +/- 0.14 after 2 mg/kg and 11% (p less than 0.05) from 0.27 +/- 0.11 after 4 mg/kg of bepridil. The data indicate that bepridil exerts significant negative inotropic and chronotropic effects in patients with impaired LV function.

Characteristics and clinical significance of silent myocardial ischemia in unstable angina.

The frequency and duration of transient myocardial ischemia on Holter recordings, analyzed by the compact analog technique, were determined in 41 patients (all men, mean age 54) with unstable angina (33 with angiographic evidence). There were 781 episodes of ischemia: 392 (50%) with ST-segment depression, 242 (31%) with ST elevation, 45 (6%) with ST elevation and depression in different leads, 70 (9%) with pseudonormalization of T waves and 32 (4%) with T-wave augmentation. Ventricular arrhythmias were associated with 18% of the episodes. The mean duration of ischemic episodes was 14 minutes (range 30 seconds to almost 12 hours); most were less than 5 minutes. Only 154 (20%) of the 781 episodes of ischemia were associated with pain. Conversely, 77 episodes of chest pain were not associated with electrocardiographic changes. Analysis of the temporal sequence of heart rate during the development of ischemia (analyzed in 415 episodes) showed that in only 43 (10%) the heart rate at the beginning of ischemia was significantly (greater than 6 beats/min) higher than that at 5 minutes (baseline) before the onset of ischemia. At the peak of the ischemic abnormality, the mean heart rate increase was 10% and returned to baseline at the end of the ischemic episode. The data indicate that 80% of ischemic episodes in unstable angina are silent and over 90% are not triggered by increases in heart rate; apparently increased oxygen demand is an uncommon cause of ischemia in unstable angina. Although most of the episodes were short-lived, some were extremely protracted without the development of myocardial infarction. The findings are of therapeutic significance.

Intravenous dipyridamole combined with isometric handgrip for near maximal acute increase in coronary flow in patients with coronary artery disease.

Twenty-four patients with coronary artery disease were studied during cardiac catheterization to determine the effects of sustained isometric handgrip exercise and intravenous dipyridamole and their combination on coronary and systemic hemodynamics and measured coronary luminal caliber. During 4 to 5 minutes of 25 percent maximal handgrip, blood pressure and heart rate increased 24 and 19 percent, respectively, coronary sinus flow increased to 1.7 x baseline value, and epicardial coronary arteries constricted to increase predicted flow resistance by 40 percent in 36 diseased arterial segments. After a 4 minute intravenous infusion of dipyridamole (0.56 mg/kg body weight), systemic pressure decreased 8 percent, heart rate increased 23 percent, coronary sinus flow increased to 2.4 x baseline value and coronary luminal caliber was unchanged. During isometric handgrip initiated 6 minutes after the infusion of dipyridamole, systemic pressure and heart rate increased to 14 and 31 percent, respectively, above control values, coronary sinus flow increased to 3.3 x baseline value (3.8 x baseline value in patients with normal anterior perfusion) and stenotic flow resistance increased by 36 percent. The response of coronary flow to the combined stresses was 68 percent greater than the response to dipyridamole alone (p less than 0.02); these flow levels exceed values previously reported for the human coronary circulation. Aminophylline plus nitroglycerin appears to assure patient safety.

Granulomatous tubulointerstitial nephritis in the renal allograft.

Granulomatous tubulointerstitial nephritis has rarely been described in renal allografts. Of 1,574 renal allograft tissue specimens obtained from 514 patients in the period 1993 to 1998, we report three cases (0.6%) with interstitial nephritis containing multiple noncaseating granulomas. Biopsy specimen 1 was obtained from a 44-year-old woman with a 6-day history of systemic Candida albicans infection and showed multiple granulomas containing budding yeasts. Biopsy specimen 2 was from a 33-year-old man who presented with miliary spread of Mycobacterium tuberculosis 12 days before the allograft biopsy. Biopsy specimen 3 was from a 23-year-old woman who presented with Escherichia coli urinary infection and bacteremia that was treated with antibiotics for 10 days before the biopsy. Granulomatous inflammation in reponse to infectious agents or drugs in immunosuppressed kidney transplant recipients can rarely give rise to allograft interstitial nephritis that is distinct from acute rejection. To our knowledge, there are no prior reports of granulomatous tubulointerstitial nephritis associated with C albicans and E coli infection or antibiotic therapy in human renal allografts.

Pregnancy in a nonimmunosuppressed transplant recipient.

A 30-year-old woman with a living related six-antigen-matched kidney allograft conceived 10 years posttransplantation. She had discontinued her immunosuppression medications 3 years previously. The allograft functioned well throughout gestation, which was complicated by preeclampsia, leading to induction at 35 weeks and delivery of a 2,175-g male.

Drug-induced acute interstitial nephritis in renal allografts: histopathologic features and clinical course in six patients.

Drug-induced acute interstitial nephritis is a common cause of dysfunction in native kidneys, but is rarely reported in renal allografts. This report describes six renal transplant recipients with acute renal allograft dysfunction or delayed allograft function in whom a renal transplant biopsy showed histopathologic features of drug-induced interstitial nephritis with no diagnostic evidence of acute rejection, cyclosporine or tacrolimus nephrotoxicity, or other lesion that could account for the graft dysfunction. In five of the six patients, interstitial nephritis occurred within 4 weeks of transplantation. All the patients were receiving trimethaprim-sulfamethoxazole and/or other drugs associated with interstitial nephritis. After discontinuation of these drugs and short-term corticosteroid treatment, all patients showed improvement in renal function, although the time course of this improvement varied considerably, with three patients showing a return to baseline serum creatinine level within 2 weeks and two patients showing a gradual improvement over 8 weeks. Four of the five patients followed up for more than 1 year (range, 14 to 33 months) after the episode of interstitial nephritis had good allograft function (serum creatinine level