Pharmacokinetics of ganciclovir in renal transplant children

Three cytomegalovirus (CMV)-seronegative children received renal transplants from CMV-seropositive donors and developed clinical symptoms of CMV infection between days 20 and 34 post transplantation. Ganciclovir (DHPG) was administered in a 1-h infusion, and the doses and dose intervals were adapted to the degree of renal insufficiency, according to the manufacturer's recommendations for adults. Individual pharmacokinetic parameters of DHPG were determined and were markedly altered. Plasma clearances were 0.4, 1.1 and 2.2 ml/min per kg and were related to individual creatinine clearances (20, 45 and 60 ml/min per 1.73 m²); the corresponding elimination half-lives were 23.7, 9.9 and 3.9 h. In two patients, the doses had to be further reduced in order to maintain plasma levels within the recommended values for peak and trough plasma concentrations. Therefore, monitoring of DHPG appears essential in adjusting dosage for optimal efficacy and minimal toxicity.     

更昔洛韦预防肾移植术后巨细胞病毒感染的前瞻性随机对照研究

目的研究更昔洛韦对肾移植术后巨细胞病毒(CMV)感染的预防作用。方法选取2004年行首次肾移植的55例患者,所有患者术后均常规应用环孢素A+霉酚酸酯+激素的免疫抑制方案。将患者随机分为2组,A组27例,从肾移植术后第2周起静脉滴注更昔洛韦5mg.kg-1.d-1,共30d,预防CMV感染;B组28例,没有针对CMV感染进行预防性用药。所有患者肾移植术后均随访6个月,检测其血清中CMV-IgG、CMV-IgM及CMV-DNA的表达,统计肾移植术后6个月时CMV感染率、CMV病的患病率、CMV感染时间、CMV病临床缓解时间、急性排斥反应发生率以及药物不良反应等项目。结果A、B两组患者的CMV感染率分别为37%和25%,CMV患病率分别为22.2%和14.3%,两组相比,差异无统计学意义。A组术后发现CMV感染时间较B组明显延迟(P<0.05),且发生CMV病后的临床缓解时间较B组显著缩短(P<0.05)。A、B两组急性排斥反应发生率分别为11.1%和21.4%,两组比较,差异无统计学意义。1例患者应用更昔洛韦后发生白细胞数减少,经集落刺激因子治疗后恢复。结论肾移植术后静脉滴注更昔洛韦对降低CMV感染率及发病率无明显作用,但可明显延迟肾移植术后CMV感染的发生时间,并显著缩短CMV发病后的临床症状缓解时间。提示肾移植术后CMV感染的预防性用药可能需要更长的时间。     

Pharmacokinetics of ganciclovir in pediatric renal transplant recipients

Ganciclovir (GCV) is effective in preventing and treating cytomegalovirus (CMV) infection in solid organ transplant recipients. The aims of the present study were to determine the pharmacokinetics of GCV administered intravenously (IV) and orally (p.o.) as pre-emptive anti-CMV therapy in pediatric renal transplant recipients and to monitor trough levels and side-effects during pre-emptive therapy. Eleven pediatric renal transplant recipients (aged 11.0±3.9 years) were included. The diagnosis of CMV infection, based on two positive pp-65 CMV blood antigen tests at 1 week apart, was made at 39±12 days post renal transplantation. They received IV GCV at a dose of 5.0±0.3 mg/kg per 12 h for 15 days, followed by GCV p.o. at a dose of 46.7±8.2 mg/kg per 12 h for 3 months. Pharmacokinetics (PK) were studied at steady state and GCV plasma concentrations were measured by high-performance liquid chromatography. After IV GCV administration, PK parameters were: C₀=0.84±0.66 g/ml; C_max=11.77±2.82 g/ml; AUC_{0–12 h}=42.29±17.57 g/ml per hour; Cl=0.13±0.05 l/h per kg. After p.o. GCV administration, PK parameters were: C₀=1.08±0.68 g/ml; C_max=2.70±1.07 g/ml; AUC_{0–12 h}=18.97±9.36 g/ml per hour; Cl/F=2.97±1.42 l/h per kg. Bioavailability (F) was 4.9±1.2%. Pre-dose concentrations (C₀) measured under p.o. GCV (n=51) were 1.29±0.80 g/ml (8 C₀ values were below 0.5 µg/ml). Pp-65 CMV blood antigen tests became negative after 16±11 days of treatment. GCV was well tolerated. Because of the limited bioavailability, the recommended high doses of p.o. GCV (50 mg/kg per 12 h) were administered and were associated with trough levels over 0.5 µg/ml. In 1 patient who received an erroneously low dosage p.o., CMV resistance to GCV appeared, requiring foscarnet.     

Intravenous ganciclovir prophylaxis for cytomegalovirus in heart, heart-lung, and lung transplant recipients

Cytomegalovirus (CMV) disease has had a significant clinical impact on the heart, heart-lung and lung transplant recipients in our centre. CMV disease has been so severe with CMV antibody-negative heart-lung transplant patients receiving organs from CMV antibody-positive donors (CMV-mismatched patients) that in 1986 we adopted the policy of not transplanting CMV-positive organs into CMV-negative heart-lung or lung recipients. In December 1992, we instituted a policy of providing intravenous ganciclovir (5 mg/kg twice a day for 28 days) during the immediate postoperative period for CMV-mismatched heart recipients and CMV antibody-positive heart-lung and lung patients, who have been the patients at greatest risk of severe CMV disease in our centre. A placebo group was not employed because of ethical considerations, ganciclovir having been shown to be effective for the treatment of CMV infections among transplant patients. Compared with a historical control group of patients receiving no prophylaxis, prophylactic ganciclovir reduced the incidence of CMV infection (39 % vs 91 %, P = 0.0006) and CMV disease (17 % vs 74 %, P = 0.0004) among CMV antibody-positive heart-lung recipients. Prophylactic ganciclovir did not significantly reduce the incidence of CMV infection or disease among heart or isolated lung recipients. Ganciclovir was well tolerated, with few adverse reactions. In the case of heart-lung transplant patients, one month of intravenous prophylactic ganciclovir significantly reduced the incidence of both CMV infection and disease when compared with patients who received no prophylaxis. With the lung transplant and heart transplant patients, there were no significant differences between the prophylaxis and nonprophylaxis groups, although there was a consistent trend towards less infection and disease in the prophylaxis groups. Received: 14 April 1998 Received after revision: 24 September 1998 Accepted: 18 December 1998     

Treatment of cytomegalovirus pneumonitis with ganciclovir in renal transplantation

Ganciclovir, also called DHPG, was administered intravenously to eight renal transplant recipients with life-threatening cytomegalovirus (CMV) pneumonitis. One patient died of pulmonary failure; a favorable clinical response was observed in the seven others. In one patient, CMV pneumonitis recurred but responded well to a second course of the drug. At no time was the immunosuppressive regimen completely stopped in the seven surviving patients. Six of them maintained a good renal function 1–11 months after treatment with ganciclovir. No toxic effect was detected during therapy. We conclude that ganciclovir appears to be a promising and effective treatment for CMV pneumonitis after renal transplantation.     

Treatment of cytomegalovirus pneumonitis with ganciclovir in renal transplantation

Abstract. Ganciclovir, also called DHPG, was administered intravenously to eight renal transplant recipients with life-threatening cytomegalovirus (CMV) pneumonitis. One patient died of pulmonary failure; a favorable clinical response was observed in the seven others. In one patient, CMV pneumonitis recurred but responded well to a second course of the drug. At no time was the immunosuppressive regimen completely stopped in the seven surviving patients. Six of them maintained a good renal function 1–11 months after treatment with ganciclovir. No toxic effect was detected during therapy. We conclude that ganciclovir appears to be a promising and effective treatment for CMV pneumonitis after renal transplantation.     

A randomized prospective controlled trial of oral ganciclovir versus oral valacyclovir for prophylaxis of cytomegalovirus disease after renal transplantation

Oral ganciclovir and valacyclovir reduce the incidence of cytomegalovirus (CMV) disease after renal transplantation (RTx). Our study was designed to compare the efficacy, costs, and safety of oral ganciclovir and valacyclovir in the prophylaxis of CMV disease over the first 6 months after RTx. A total of 38 patients was randomized to 3-month treatment with either oral ganciclovir (1 g t.i.d., n=14, GAN group) or oral valacyclovir (2 g q.i.d., n=12, VAL group). A third group (C, n=12) received no prophylaxis. The patients were monitored by CMV-nested PCR in whole blood. No differences were found between the groups in their demographic characteristics, immunosuppressive protocols, or donor and recipient CMV serology. Thirty-six out of 38 (94.7%) recipients were CMV-seropositive. Over the 6-month post-RTx period, there were 13 episodes of CMV disease in eight (66.7%) patients of the C group compared with none in the GAN and VAL groups ( P=0.0005, GAN vs C; P=0.001, VAL vs C). The incidence of CMV viremia was 30.8%, 50.0%, and 91.7% in the GAN, VAL, and C groups, respectively ( P=0.004, GAN vs C; P=0.07, VAL vs C; P=NS, GAN vs VAL). Treatment failure (death, graft loss, CMV disease, or withdrawal from study) occurred in 14.3%, 0% and 66.7% in the GAN, VAL, and C groups, respectively ( P=0.014, GAN vs C; P=0.001, VAL vs C; P=NS, GAN vs VAL). The average CMV-associated costs per patient (in 2001 euros) were 2,449+/-1,178, 2,485+/-581, and 4,259+/-4,616 in the GAN, VAL, and C groups, respectively. Ganciclovir and valacyclovir were well tolerated, with ganciclovir having had to be withdrawn shortly in one patient only because of thrombocytopenia. In conclusion, oral ganciclovir and valacyclovir are equally safe and effective in the prophylaxis of CMV disease after RTx. Both are cost-effective and help reduce CMV-associated costs by some 40% compared with patients without prophylaxis.     

Ganciclovir therapy of symptomatic cytomegalovirus infection in renal transplant recipients

We used ganciclovir to treat 11 renal transplant recipients with symptomatic cytomegalovirus infection (seven primary), including one severe, five mild and five moderate cases. Two patients exhibited a non-mechanically ventilated pneumonitis and two others a gastrointestinal involvement. Ganciclovir was used intravenously according to a schedule which took into account renal function, for a median time of 14 days. All patients survived. Cytomegalovirus infection was cured in all patients but two: in the first an early clinical relapse required a second successful ganciclovir course; in the other graftectomy was needed to control infection. Graft was lost in an additional cured patient. Ganciclovir was well tolerated, especially with regard to haematological status. At the current follow-up of at least one month after the end of ganciclovir therapy, no further clinical relapse was observed; however, in one clinically cured patient cytomegalovirus was isolated from blood one week after ganciclovir cessation. These encouraging preliminary data suggest that ganciclovir therapy should be started as soon as cytomegalovirus infection is suspected, especially in cytomegalovirus seronegative recipients receiving a seropositive graft.     

Prophylaxis of CMV disease by ganciclovir (DHPG) in seronegative recipients of renal allograft from seropositive donors

In an open-label randomized study of prophylactic treatment by ganciclovir, 23 seronegative recipients of kidney allograft from seropositive donors were randomized to receive from day 14 to day 28 after transplantation either no treatment (n = 11) or ganciclovir, 5 mg/kg twice daily (n = 12). Both groups were similar in age, immunosuppressive therapy, number of acute rejections and in steroid bolus. Seroconversion occurred in ten patients of the control group (91%) and in ten of the ganciclovir group (84%). CMV disease occurred in ten patients of the control group (91%) and in eight patients of the ganciclovir group (66%), three of whom had asymptomatic viraemia. The delay between transplantation and onset of CMV disease was significantly increased by ganciclovir prophylaxis (78.5 ± 7.7 vs 46.5 ± 7.5 days, P < 0.05). We conclude that in renal transplant recipients at risk of CMV disease, ganciclovir prophylaxis delays the onset of the disease and seems to decrease its incidence and its severity.     

Acyclovir plus CMV immunoglobulin prophylaxis and early therapy with ganciclovir are effective and safe in CMV high-risk renal transplant pediatric recipients

Abstract Cytomegalovirus (CMV) infection is still a major cause of morbidity in high-risk renal transplant recipients. In the present report, we have reviewed our records of renal transplant pediatric recipients (RTPR; mean age 14.1 ± 4.9 years) since 1991, when we started a policy of CMV prophylaxis constituting high-dose oral acyclovir plus CMV hyperimmune immunoglobulins (Hlg) followed by early i.v. ganciclovir therapy in high-risk patients (i.e., CMV donor +/ recipient -). Four patients received a kidney from a living relative (LR), 2 patients had one previous transplant, and 1 had a combined liver -kidney transplant. Thirty-three patients who were negative for CMV antibodies (ab) before transplantation received a kidney from CMV ab positive donors. The immunosuppressive regimen included cyclosporin A and steroids, with the addition of azathioprine in the 4 patients who received an LR kidney. Serial assessments for CMV antigenemia (pp 65) were routinely performed for 6 months after transplantation to define CMV infection. Among the 33 CMV seronegative recipients (R -) who received the graft from a CMV seropositive donor (D +), 18 (54.5 %) experienced CMV infection, whereas among the 28 CMV R +, who received a graft from a CMV D +, 11 (39.3 %) experienced CMV infection. With regard to CMV - related symptoms, only 2 patients suffered from a CMV syndrome (fever and leukopenia in 1 patient, fever and arthralgia in the other). In no case did the spectrum of CMV disease occur; only minor symptoms were present in 7 of the remaining CMV-infected patients (fever in 6 and leukopenia in 1). Rejection episodes and renal function did not differ between CMV-infected and non-CMV-infected patients. Our experiences support the use of prophylactic acyclovir plus CMV HIg followed by early therapy with i.v. ganciclovir to combat the risk of increased morbidity in high risk RTPR.     

Low-dose valaciclovir prophylaxis against cytomegalovirus disease in renal transplant recipients

High-dose valaciclovir at up to 8 g/day has been shown to be effective in prophylaxis against cytomegalovirus (CMV) disease in renal transplant recipients. We report our experience with low-dose valaciclovir prophylaxis of up to 3 g/day, adjusted to creatinine clearance. A group of patients at high risk of developing CMV disease who received prophylaxis were selected as the study group. This included all CMV-positive patients who received antilymphocyte therapy (R+, n=20) and all CMV-negative recipients of CMV-positive organs (D+R–, n=15). D+R– patients receiving antilymphocyte therapy were excluded, as most of the patients in the control group had received ganciclovir prophylaxis. A historical control group was used, which consisted of patients who did not receive prophylaxis. Low-dose valaciclovir prophylaxis resulted in a statistically significant decrease (8.5 vs 37%, P=0.004) in CMV disease in the study group at 6 months. On subgroup analysis the decrease was statistically significant only in the R+ group (5 vs 45%, P=0.003), not in the D+R– group (13.3 vs 26.6%, P=0.651). Low-dose valaciclovir prophylaxis seems to be adequate for R+ patients receiving antilymphocyte therapy. The role of low-dose valaciclovir prophylaxis needs to be assessed further in a prospective trial.     

肾移植术后口服伐昔洛韦预防巨细胞病毒性肺炎的观察

目的探讨口服伐昔洛韦（valaciclovir）预防肾移植术后巨细胞病毒（CMV）性肺炎的有效性和安全性。方法前瞻性研究121例肾移植的临床资料，其中供、受者血清CMV-IgG均为阳性（D＋R＋组）肾移植63例，供者血清CMV-IgG阳性、受者血清CMV-IgG阴性（D＋R-组）肾移植58例。上述两组受者随机再分为预防组和对照组，预防组口服伐昔洛韦，对照组不给予抗病毒药物。观察肾移植术后1年内CMV性肺炎的发生率。结果预防组的受者对口服伐昔洛韦有良好的耐受性。预防组CMV性肺炎发生率为8．06％，对照组为22．03％，两组比较，差异有统计学意义（P〈0．05）。结论对供者血清CMV-IgG阳性、受者血清CMV-IgG阴性或供、受者血清CMV-IgG均为阳性的肾移植，受者预防性口服伐昔洛韦可以安全有效地降低术后CMV性肺炎的发生率。     

肾移植术后巨细胞病毒感染的pp67 mRNA检测及其临床意义

目的　采用核酸基础序列扩增法 (NASBA)检测巨细胞病毒晚期mRNA基因编码的基质蛋白 pp67的表达 ,探讨pp67对肾移植术后HCMV活动性感染及指导抗病毒治疗上的作用。方法　择近期 5 0例肾移植患者进行 pp67检测并随访观察 ,与现用的CMV抗原血症法比较 ,了解pp67与HCMV活动性感染及CMV病的关系。 结果　 5 0例患者中共 5例出现CMV病 ,其CMV Ag与 pp67均呈阳性 ,pp67阳性组中CMV抗原指数显著高于pp67阴性组 ,CMV Ag与pp67平均出现阳性时间无差异 ,以pp67作为抗病毒治疗指标可以明显缩短用药时间 ,pp67比CMV Ag在抗病毒治疗后更早转阴。结论　pp67更准确地反映了肾移植术后HCMV的活动性 ,能更好的指导临床抗病毒用药。     

The effect of fluvastatin of hyperlipidemia in renal transplant recipients: A prospective,placebo- controlled study

Posttransplant hyperlipidemia is a common complication which may affect long term cardiovascular mortality. In this prospective, placebo-controlled study, 19 renal transplant recipients (11 male 8 female, mean age 31.2 ± 8.4 years) with good allograft function (serum creatinine <2 mg/dl) more than 6 months after transplantation were included. All the patients had hyperlipidemia (serum cholesterol >230 mg/dl and/or LDL-cholesterol >130 mg/dl) despite dietary interventions. The patients were treated with a triple immunosuppressive regimen. After a 8-week period of placebo plus diet regimen, the patients were put on fluvastatin plus diet for another 8 weeks. The patients were followed for its effect on lipid parameters and side effects. After convertion to fluvastatin, serum cholesterol (263.0 ± 31.6 vs 223.2 ± 31.6 mg/dl, p = 0.001), LDL-cholesterol (174.4 ± 28.3 vs 136.4 ± 28.5 mg/dl, p = 0.002), Apolipoprotein (Apo) A₁ (131.1 ± 16.9 vs 114.7 ± 18.4 mg/dl, p = 0.001) and Apo B (109.0 ± 29.8 vs 97.3 ± 31.5 mg/dl, p = 0.02) levels decreased significantly. Serum levels of triglycerides, VLDL-cholesterol and HDL-cholesterol levels did not vary under fluvastatin. Serum lipoprotein (a) levels were also unchanged during the whole study period (24.9 ± 19.4 vs 23.1 ± 19.8 mg/dl, p > 0.05). We concluded that fluvastatin effectively decreased atherogenic lipoproteins such as serum cholesterol, LDL-cholesterol, Apo B in posttransplant hyperlipidemia, however fluvastatin had no effect on another independent risk factor of atherogenesis, serum lipoprotein (a) levels. This revised version was published online in June 2006 with corrections to the Cover Date.     

Atrial function in heart transplant recipients operated with the bicaval technique

Objectives: In heart transplantation (HTx) with the bicaval technique the whole right atrium (RA) is donor tissue while the left atrium (LA) consists of both donor and recipient tissue. The aims of the study were to describe atrial function in comparison with healthy controls and to identify determinants of dysfunction. Design: Forty-three patients and 30 controls were retrospectively included. Echocardiography was performed within 24 h of right heart catheterization (RHC) (HTx recipients). Results: The peak longitudinal atrial systolic strain (?) described the atrial reservoir function. The LA and RA reservoir function were reduced versus controls (LA-? 18?±?8 versus 44?±?10%; RA-? 22?±?10 versus 69?±?17%, p?<?0.001). There were moderate relationships between atrial-? and ventricular filling pressure (r?=??0.64 for LA-?; r?=??0.57 for RA-?). In a multiple regression analysis the LA-? was determined by pulmonary capillary wedge pressure (PCWP) and LA minimum volume index (r?=??0.71) while RA-? was dependent on the right ventricular ? (r?=??0.77). Conclusions: Atrial reservoir function is markedly reduced in HTx recipients related to elevated PCWP and LA-enlargement in the LA and in the RA impaired longitudinal right ventricular function.     

Nocardiosis in renal transplant recipients in Kuwait

BACKGROUND.: Nocardiosis has emerged as an important bacterial disease amongrenal transplant recipients, leading to considerable morbidityand mortality. Apart from the increasing problem of resistancein pathogenic nocardiae, the spectrum of species causing diseasehas enlarged in recent years. There are no published reportson nocardiosis from Middle-East countries. METHODS.: A retrospective review of case records of 513 renal transplantrecipients between January 1989 and January 1995 was done inthe transplant unit of our hospital. Information was collectedon clinical details, type of donor, immunosuppressive therapy,prophylaxis, and outcome. Isolation of Nocardia species fromappropriate clinical specimens was the sole criterion for diagnosis. RESULTS.: Nocardiosis was diagnosed in six recipients with a disease incidenceof 1.2%. Four patients had received unrelated kidneys. Co-morbidconditions were diabetes mellitus (3), viral hepatitis (2) andneutropenia (1). Clinical manifestations included deep-seatedskin abscesses and pulmonary disease in three each. Cerebralabscess and meningitis were found in two patients with pulmonarydisease. Pathogens were Nocardia asteroides in four and N. otitidiscaviarum and N. farcinica in one each. In contrast to invitro susceptibility results, clinical response was differentin that five patients who received trimethoprim-sulphamethoxazole(TMP-SMX) alone (2) or in combination with cefuroxime (3) respondedwell. CONCLUSION.: The study stresses a high index of suspicion for nocardiosisin susceptible hosts who present with cutaneous abscess, pulmonaryinfiltrative lesions, and cerebral manifestations. TMP-SMX incombination with cefuroxime seems to be a highly effective therapy.It does not appear mandatory to reduce or discontinue immunosuppressivetherapy during treatment of nocardiosis.     

Prevention of cytomegalovirus infection in the pediatric renal transplant recipient

Cytomegalovirus (CMV) infection is the most important single infectious complication of organ transplantation, affecting more than 70% of transplant recipients. Its emergence as a major pathogen has coincided with the use of cytotoxic therapy. Manifestations of serious CMV disease include: pneumonia, hepatitis, gastrointestinal disease, leukopenia and chorioretinitis. CMV is associated with superinfection with opportinistic organisms, graft failure and increased mortality. Serious infection most frequently occurs with primary CMV infection in which latently infected cells from CMV-positive donors are given to seronegative recipients. Pediatric patients who have a lower pre-transplant rate of CMV seropositivity are at particularly high risk of developing serious CMV disease. Preventative efforts range from the ideal but impractical use of only CMV-negative donors (organ and blood products), to the use of CMV hyperimmune globulin and antiviral chemotherapy. Data support the use of prophylactic hyperimmune globulin and preliminary information supports the use of prophylactic high-dose acyclovir in renal transplant patients. Prophylactic gancyclovir alone or with hyperimmune globulin and pre-transplant vaccination with live-attenuated Towne strain CMV vaccine remain investigational.     

Congenital cytomegalovirus infection after recurrent infection in a mother with a renal transplant

A woman with a renal transplant developed a systemic cytomegalovirus infection. She recovered and 3 years later she became pregnant. She had 3 days of fever in the first trimester. She delivered an infant severely affected with congenital cytomegalovirus infection. The incidence of symptomatic congenital cytomegalovirus infection in infants born to immunosuppressed mothers who develop reactivated cytomegalovirus during their pregnancy seems high. Received April 22, 1996; received in revised form September 3, 1996; accepted October 22, 1996     

人巨细胞病毒被膜磷蛋白pp65的检测及其在肾移植的临床应用

目的建立一种快速、简便诊断肾移植受者人巨细胞病毒（human cytomegalovirus,HCMV）活动性感染的方法。方法运用免疫组织化学的催化信号扩增法检测外周血白细胞中的人巨细胞病毒磷蛋白（phosphoprotein,pp65）,并与抗HCMV-IgM检测法、巨细胞病毒信使核糖核酸（pp67-mRNA）检测法作比较。结果检测53例肾移植受者中,HCMVpp65抗原阳性26例,IgM抗体阳性17例,pp67-mRNA检测阳性27例,pp65抗原阳性细胞指数为（71±45）个／2×10^5个白细胞（WBC）,而有症状的CMV病16例,抗原阳性细胞指数为（83±46）个／2×10^5个WBC。pp65的敏感性、特异性、阳性预测值与阴性预测值分别是100％、73．0％、61．5％和100％。结论该法敏感,简便,可作为肾移植术后HCMV病的早期诊断,并可指导抗病毒治疗。     

Impaired glucose oxidation and glucose-induced thermogenesis in renal transplant recipients.

BACKGROUND: Renal transplant recipients often show various metabolic abnormalities including reduced glucose tolerance, impaired insulin sensitivity and altered lipid metabolism. However, the acute effects of carbohydrate ingestion on substrate utilization and energy expenditure have not been fully elucidated. METHODS: We evaluated: (i) basal energy expenditure (EE) and substrate utilization, (ii) metabolic fate of an oral glucose load, and (iii) substrate-induced thermogenesis in: (a) 15 non-diabetic renal transplant recipients (Tx) (BMI 25+/-1) on triple immunosuppressive therapy, (b) 11 patients with primary glomerulonephritis (BMI 25+/-1) (Cort) receiving prednisone treatment, and (c) 12 healthy subjects (BMI 26+/-1) (N). Continuous indirect calorimetry was performed in the basal post-absorptive state for 60 min and continued for an additional 180 min following an oral glucose load (75 g). RESULTS: In the basal state, EE was similar in the three study groups. It averaged 14.6+/-0.7, 15.7+/-1.3, and 14.1+/-0.8 cal/kg/min in Tx, Cort, and N respectively. Glucose oxidation was higher in N (1.3+/- 0.2 mg/kg/min) than in Tx (0.7+/-0.2) and Cort (1.0+/-0.2) (P<0.05 in N vs. Tx and vs. Cort), whereas lipid oxidation was lower in N (0.6+/-0.1 mg/kg/min) than in Tx (0.9+/-0.1) and Cort (0.9+/-0.05) (P<0.03 in N vs. Tx and vs. Cort). After glucose ingestion, total carbohydrate oxidation averaged 21.2+/-2, 31.0+/-3, and 29.6+/-3 g, which represented 28+/-3, 41+/-3 and 39+/-2% of the total glucose load in Tx, Cort and N respectively (P<0.01 Tx vs Cort and N). The cumulative increase of EE (180 min) was 9.7+/-2, 13.2+/-3 and 13+/-3 kcal in Tx, Cort, and N respectively. CONCLUSIONS: The present data show that in non-diabetic renal transplant recipients basal EE is normal. However, basal lipid oxidation is higher and glucose oxidation is lower than in healthy subjects. In addition, the oxidative disposal of a glucose load and substrate-induced thermogenesis are impaired.