Time-dependent variations in urine output after renal transplantation

INTRODUCTION: Diuresis begins soon after renal transplantation. Although controversial, early post kidney transplant urine volume may correlate with favorable short- and long-term allograft survival. The aim of the present study was to examine the potential changes in urine volume within the first 6 months after renal transplantation. METHODS: In a prospective study, the first month serum creatinine level and daily urine volume were measured at 24 and 48 hours, and at 1 month after renal transplantation in patients with stable kidney function without the evidence of allograft rejection (n = 54). Fifteen patients were also followed for their urine output at least 6 months post kidney transplantation. Data are expressed in mean values +/- SD. Statistical analysis was performed by SPSS version 13.0 using ANOVA. Correlation between continuous variables was performed using the Pearson test. The P value was set at .05. RESULTS: The mean age of the renal allograft recipients was 35.5 +/- 12.1 years with a male to female ratio of approximately 1.3. The mean first month serum creatinine was 1.26 +/- 0.4 mg/dL. The mean urine outputs were 10.06 +/- 5.89, 5.45 +/- 3.05, and 3.44 +/- 1.25 L at 24 and 48 hours and 1 month post renal transplantation. Those patients who were followed for 6 months post transplant (n=15) were observed to have a mean urine volume of 3.20 +/- 1.24 L at the end of this period. This trend showed that urine volume steadily decreased from 24 and 48 hours to 1 month after renal transplantation (P<.05). However, urine volumes were rather comparable at one month and 6 months after transplantation (P>.05). A positive correlation was found between the first-month serum creatinine and the urine volume at one month (r=0.302 and P=.035). CONCLUSION: Although urine volume showed considerable variation early after renal transplantation, it stabilized by 1 month after transplantation, which was also positively correlated with the first-month serum creatinine. Moreover, we concluded that in stable patients, the final urine output was related to early graft function.     

Dexmedetomidine infusion is associated with enhanced renal function after thoracic surgery

STUDY OBJECTIVE: To test the hypothesis that dexmedetomidine, a selective alpha-2 agonist, enhances urine flow rate and perioperative renal function, a post hoc analysis was conducted on a recently completed study of dexmedetomidine used as an adjunct to epidural analgesia after thoracotomy. DESIGN: Post hoc analysis of a randomized, placebo-controlled, double-blind clinical trial. SETTING: Tertiary-care university medical center. PATIENTS: 28 patients undergoing elective thoracotomy. INTERVENTIONS: Patients were prospectively randomized to receive a supplemental 24-hour intravenous infusion of either dexmedetomidine (0.4 microg kg(-1) h(-1), n = 14) or saline placebo (equivalent infusion rate, n = 14). MEASUREMENTS: Available renal parameters including urine output, calculated creatinine clearance (cCl(Cr)), daily serum creatinine level (S(Cr)), and the fractional change in S(Cr) level (DeltaS(Cr)%, [peak postoperative S(Cr) - baseline S(Cr)] / baseline S(Cr)) x 100) were recorded. MAIN RESULTS: Values are expressed as means +/- SD. There were no significant differences in baseline values between the groups. The dexmedetomidine group had significantly greater cumulative urine output at postoperative hour 4 (473 +/- 35 vs 290 +/- 122 mL, P = 0.001) and 12 (1033 +/- 240 vs 822 +/- 234 mL, P = 0.02), although only 14% of the group received diuretic agents, compared with 43% in the control group. The dexmedetomidine group had significantly better preserved perioperative renal function compared with the control group, as assessed by DeltaS(Cr)% (0.04% decrease vs 21% increase, P = 0.0007) and cCl(Cr) (75.3 +/- 13.2 vs 62.5 +/- 15.5 mL/min, P = 0.02). CONCLUSION: Dexmedetomidine infusion administered as a supplement to epidural analgesia induced diuresis in postthoracotomy patients with normal preoperative renal function and undergoing fluid restriction. Although this finding may represent simple reversal of a tubular antidiuresis, the lower DeltaS(Cr)% and preservation of cCl(Cr) suggest a beneficial effect on glomerular filtration compared with controls.     

The effect of pneumoperitoneum on kidney function in laparoscopic donor nephrectomy

Between June 1999 and November 2001 a prospective study was conducted to evaluate the effects of pneumoperitoneum during laparoscopic donor nephrectomy on kidney function using two different pressure settings (15 and 10 mm Hg). The effects were evaluated in both the donor's remaining kidney and the procured kidney in the recipient. There was no statistical significant difference in donors and recipients in regard to age, gender, and body mass index. In the two donor groups there was no difference in operative time (2.77 +/- 0.51 vs 2.70 +/- 0.52 hours; P = 0.579), intraoperative fluid (16.53 +/- 4.72 vs 19.54 +/- 7.04, P = 0.056), and urine output (1.81 +/- 0.53 vs 1.75 +/- 0.96 mL/kg/hour, P = 0.782) respectively. Donors' preoperative and first-day postoperative serum creatinine concentrations also did not differ for the groups (preoperative 0.87 +/- 0.21 vs 0.88 +/- 0.17 mg/dL; and postoperative 1.44 +/- 0.32 vs 1.38 +/- 0.29 mg dL, respectively; P = 0.696). Recipients' preoperative and postoperative serum creatinine concentrations on days 1, 2, 3, 7, 14, and 30 differed over time (P < 0.001) but not between groups (P = 0.541). We conclude that procurement of kidneys under either 10 or 15 mm Hg abdominal pressure gives equally good intraoperative and postoperative results.     

去甲肾上腺素对原位肝移植术患者肾功能的影响

目的 探讨去甲肾上腺素对原位肝移植术患者肾功能的影响.方法 择期行原位肝移植术的晚期肝硬化患者40例,年龄40～60岁,体重53～78 kg,ASAⅢ级或Ⅳ级,随机分为2组(n=20):去甲肾上腺素组(N组)术中静脉输注去甲肾上腺素,初始输注速率为0.01～0.02 μg·kg-1 min-1;多巴胺组(D组)术中静脉输注多巴胺,初始输注速率为1～2 μg·kg-1·min-1.调整无肝前期、无肝期和新肝期去甲肾上腺素输注速率分别为0.01～0.05、0.03～0.25和0.02～0.40 μg·kg-1·min-1;多巴胺输注速率分别为1～5、3～30和1～10 μg·kg-1·min-1,以维持无肝期平均动脉压(MAP)60～80 mm Hg,其他时期MAP 60～100mm Hg.分别于切皮前、切皮后1 h、无肝期30min、新肝期1 h及4 h时记录、心输出量、体循环血管阻力,计算心指数及体循环血管阻力指数,于上述各时点抽取中心静脉血,并留取尿液,测定各项肾功能指标,术后1周内测定肾功能指标.结果 两组间各时点血液动力学指标比较差异无统计学意义(P＞0.05),血清胱抑素C(Cys C)、血清β2-微球蛋白(β2-MG)、血清肌酐(Cr)及血清肌酐清除率(CCr)均在正常范围内,组间及组内比较差异均无统计学意义(P＞0.05).D组于切皮后1 h时尿β2-MG高于N组(P＜0.05).两组无肝期尿量、术中总尿量、术中呋塞米用量及术后24 h尿量比较差异无统计学意义(P＞0.05).两组术后1周内各时点血清β2-MG、Cr及CCr均在正常范围内.结论 原位肝移植术中静脉输注去甲肾上腺素对患者肾功能无不利影响.     

Renal blood flow in experimental septic acute renal failure

Reduced renal blood flow (RBF) is considered central to the pathogenesis of septic acute renal failure (ARF). However, no controlled experimental studies have continuously assessed RBF during the development of severe septic ARF. We conducted a sequential animal study in seven female Merino sheep. Flow probes were implanted around the pulmonary and left renal arteries. Two weeks later, systemic hemodynamics and RBF were monitored continuously during a 48-h control period and, after a week, during a 48-h period of hyperdynamic sepsis induced by continuous Escherichia coli infusion. Infusion of E. coli induced hyperdynamic sepsis with significantly increased cardiac output (3.8+/-0.4 vs 9.8+/-1.1 l/min; P<0.05), decreased mean arterial pressure (89.2+/-3.2 vs 64.3+/-5.3 mm Hg; P<0.05), and increased total peripheral conductance (42.8+/-3.5 in controls vs 153.7+/-24.7 ml/min/mm Hg in septic animals; P<0.05). Hyperdynamic sepsis was associated with marked renal vasodilatation (renal conductance: 3.0+/-0.7 vs 11.4+/-3.4 ml/min/mm Hg; P<0.05) and a marked increase in RBF (262.3+/-47.7 vs 757.4+/-250.1 ml/min; P<0.05). Serum creatinine increased over 48 h (73+/-18 vs 305+/- micromol/l; P<0.05) whereas creatinine clearance decreased (95.5+/-25.9 vs 20.1+/-19.3 ml/min; P<0.05). After 24 h, urine output decreased from 1.4 to 0.3 ml/kg/h (P<0.05). Infusion of E. coli induced hyperdynamic sepsis and ARF. Septic ARF in this setting was associated with a marked increase in RBF and with renal vasodilatation.     

Divergent effects of low versus high dose anti-TGF-beta antibody in puromycin aminonucleoside nephropathy in rats

BACKGROUND: Transforming growth factor-beta (TGF-beta) modulates immune/inflammatory cells, promotes extracellular matrix (ECM) accumulation, and is increased in fibrotic organs. Here we report the effects of administering a puromycin aminonucleoside nephropathy (PAN)-specific TGF-beta neutralizing antibody on glomerulosclerosis in vivo. METHODS: Adult male Sprague-Dawley rats underwent uninephrectomy (Nx) followed by intraperitoneal PAN at weeks 2, 6, 7 and 8. Rats were treated with either high (5 mg/kg body weight) (N= 9) or low (0.5 mg/kg body weight) (N= 7) dose TGF-beta antibody intraperitoneally three times weekly until sacrifice at week 10. A PAN untreated control group (N= 7) was dosed with an isotype specific, null antibody. The nephrectomy samples were studied as normal kidney control (NL) (N= 5). Rats undergoing left kidney Nx (N= 5) only were also included as age-matched control. Renal function and morphology were assessed, and molecular studies performed. RESULTS: Systolic blood pressure was increased in parallel over time in all groups (at 10 weeks, control 137 +/- 10 mm Hg; high 129 +/- 4 mm Hg; low 137 +/- 3 mm Hg) (P= NS). Both TGF-beta antibody treatments decreased renal cortex mRNA expressions similarly for TGF-beta1, TGF-beta2, and collagen III (TGF-beta1, control 0.36 +/- 0.02 mm Hg; high 0.19 +/- 0.01 mm Hg; low 0.19 +/- 0.02 mm Hg; P < 0.01 low and high vs. control; TGF-beta2, control 0.38 +/- 0.03 mm Hg; high 0.19 +/- 0.02 mm Hg; low 0.20 +/- 0.03 mm Hg; P < 0.01 low and high vs. control; and collagen III, control 0.33 +/- 0.01 mm Hg; high 0.14 +/- 0.01 mm Hg; low 0.19 +/- 0.01 mm Hg; P < 0.01 low and high vs. control; P < 0.05 low vs. high, data expressed as mRNA normalized density units vs. 18S RNA). However, only low dose TGF-beta antibody improved renal function and sclerosis measured by serum creatinine and creatinine clearance (serum creatinine, control 2.3 +/- 0.5 mg/dL; high 2.5 +/- 0.5 mg/dL; low 0.8 +/- 0.1 mg/dL; P < 0.05 low vs. control and high; creatinine clearance, control 0.44 +/- 0.11 mL/min; high 0.70 +/- 0.26 mL/min; low 1.34 +/- 0.30 mL/min; P < 0.05 low vs. control, P= NS vs. high). In parallel, sclerosis index (0 to 4+ scale) was improved in low dose (control 2.67 +/- 0.27; high 2.37 +/- 0.30; low 1.78 +/- 0.24; P < 0.05 low vs. control). This improved function and structure was linked to decreased glomerular infiltrating macrophages (0 to 4+ score, control 2.3 +/- 0.2; high 1.8 +/- 0.4; low 0.8 +/- 0.1; P < 0.01 low vs. control; P < 0.05 low vs. high; P= NS high vs. control). Further, plasminogen activator inhibitor-1 (PAI-1) mRNA expression in renal cortex was attenuated after low dose TGF-beta antibody treatment compared to control and high dose group (PAI-1/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA ratio, NL 0.18 +/- 0.003; control 0.45 +/- 0.03; high 0.40 +/- 0.04; low 0.23 +/- 0.01; P < 0.05 low vs. control and high). Matrix metalloproteinase-9 (MMP-9) activity was maintained at higher levels in kidneys of the low dose TGF-beta antibody-treated group. CONCLUSION: These results show an in vivo dose-response with an agent that blocks the biologic activity of TGF-beta. Higher dose of TGF-beta antibody was without beneficial effect, suggesting that TGF-beta-mediated effects on PAI-1 and macrophage influx are bimodal and closely regulated. Given that both antibody doses reduced the expression of TGF-beta isoforms and collagen III production, but only low dose ameliorated histologic sclerosis, it appears that pharmacologic effects of anti-TGF-beta antibody on matrix synthesis and degradation are not equivalent.     

Role of dietary salt intake in posttransplant hypertension with tacrolimus-based immunosuppression

Dietary salt is an important contributor to hypertension in the general population. While its role in cyclosporine-induced hypertension is minimal, its role in tacrolimus-based immunosuppression has not been defined. We measured the 24-hour urine sodium excretion as an estimate of intake in a group of stable renal transplant recipients on tacrolimus (N = 143) who had serum creatinine fluctuations <20% during the preceding 3 months. Average clinic-measured blood pressure (BP) from before and after the 24-hour urine collection was computed. Patients with recent changes in antihypertensive medications were excluded. Average systolic BP was 126 +/- 14 and diastolic BP 76 +/- 7 mm Hg. Urine sodium was 162.6 +/- 70 mmol/d (range 50 to 351), and the sodium/creatinine ratio was 15.4 +/- 6.4. There was no correlation between urine sodium excretion and either systolic or diastolic BP (R = 0.07 and R = 0.05, P = NS) or the sodium/creatinine and systolic/diastolic BP (R = 0.13, R = 0.11, P = NS). By multiple linear regression only weight and urine protein were independently associated with both systolic BP (P < .0001 for each) and diastolic BP (P < .05 for each). In conclusion, there is no appreciable influence of dietary salt intake on BP under tacrolimus-based immunosuppression. Restricting dietary salt intake in these patients cannot be recommended at the current time.     

Prospective study on renal outcome of IgA nephropathy superimposed on diabetic glomerulosclerosis in type 2 diabetic patients.

BACKGROUND AND METHODS: In order to examine the clinical outcome of IgA nephropathy (IgAN) superimposed on diabetic glomerulosclerosis in type 2 patients we studied 36 Chinese patients (26 men, 10 women), who were recruited for renal biopsy when they had proteinuria of more than 1 g/day. Twenty-seven had isolated diabetic glomerulosclerosis and nine had IgAN superimposed on diabetic glomerulosclerosis (combined). Renal function was assessed by serial serum creatinine, 24-h urine protein and creatinine measurements. Patient survival rate, incidence of end-stage renal disease (ESRD), blood pressure, and glycaemic control status were determined. RESULTS: The age at the time of renal biopsy was younger for the combined group when compared with the diabetic glomerulosclerosis group (44+/-3.6 vs 58+/-2.1 years, P=0.006). The duration of diabetes was, however, similar for the two groups (8.0+/-2.3 vs 6.7+/-1.2 years, P=NS). After a mean follow-up of 31.6+/-15.3 months, 15 patients (one in the combined group and 14 in the diabetic glomerulosclerosis group) developed ESRD. Nine patients (all in the diabetic glomerulosclerosis group) died during follow-up. With similar glycaemic and blood pressure control, the two groups had comparable rate of decline of creatinine clearance (CrCl) (-0.73+/-0.26 vs -0.73+/- 0.18 ml/min/1.73 m(2)/month, P=NS), final serum creatinine (363+/-134 vs 426+/-52 micromol/l, P=NS) and proteinuria levels (4.3+/-0.9 vs 4.4+/-0.6 g/day, P=NS), as well as CrCl (44.1+/-19.0 vs 33.4+/-6.9 ml/min/ 1.73 m(2), P=NS). CONCLUSION: It is concluded that the superimposed IgAN does not significantly alter the medium-term clinical outcome of patients with diabetic glomerulosclerosis.     

Does adult liver transplantation without venovenous bypass result in renal failure?

Thirty-eight adult orthotopic liver transplant recipients were studied to compare renal hemodynamics and renal function with (17 patients) and without (21 patients) venovenous bypass. Bypass was used when mean arterial blood pressure decreased by greater than 30% or cardiac index decreased by greater than 50%, or both, during a 5-min trial of clamping of the suprahepatic and infrahepatic vena cava and portal vein. Intraoperative measurements were performed 2 h after induction of anesthesia, 10 min before the end of the anhepatic phase, and 2 h after cava unclamping. During the anhepatic stage, renal perfusion pressure decreased significantly in the group with no bypass (79 +/- 20 vs 60 +/- 17 mm Hg, P less than 0.05) (mean +/- SD), whereas it remained unchanged in the group with bypass (77 +/- 14 vs 74 +/- 16 mm Hg, NS); urinary output was not modified in the bypass group, whereas it decreased significantly in the group with no bypass compared with the dissection phase (0.7 +/- 0.6 vs 1.7 +/- 2.0 mL.kg-1.h-1, P less than 0.05). However, during the postreperfusion phase, urinary output was similar in both groups and was more when compared with the dissection phase (P less than 0.05). Serum creatinine level was increased in both groups on the third postoperative day, but no difference occurred between the groups (bypass group 107 +/- 49 mmol/L; nonbypass group 126 +/- 95 mmol/L). No patient required dialysis in either group in the postoperative period. This study suggests that in patients without preoperative renal failure and who tolerate the trial of clamping well, venovenous bypass is not required to maintain postoperative renal function after liver transplantation.     

连续性肾脏替代疗法治疗难治性急性左心衰竭患者的预后危险因素分析

目的通过分析因难治性急性左心衰竭而行连续性肾脏替代疗法(continuous replacement therapy,CRRT)患者的资料,寻找患者预后的影响因素。方法通过佛山市第一人民医院的病历系统及血液透析系统,筛选2012年1月1日至2019年1月1日因难治性急性左心衰竭而行CRRT治疗的所有患者,将所有的患者按照最终治疗结果分为生存组及死亡组。通过分析患者的年龄、性别、心脏原发病、使用血管活性药情况、治疗起始平均动脉压、治疗前尿量、血红蛋白、血清肌酐、血白蛋白、C反应蛋白、脑钠肽、左心室射血分数及CRRT治疗时长等资料,寻找患者预后的影响因素。结果共130例患者被纳入本研究,其中生存组96例,死亡组34例,病死率为26.15%。生存组男性所占比例高于死亡组(71.88%比50.00%,χ2=5.366,P=0.021),起始平均动脉压、治疗前尿量、血清肌酐显著高于死亡组(t=4.677,P<0.001;Z=3.904,P<0.001;Z=2.866,P=0.004),血红蛋白低于死亡组(Z=-2.587,P=0.011),治疗时长短于死亡组(Z=-3.447,P=0.001)。多因素Logistic回归分析结果显示,女性(OR=2.950,95%CI 1.102~7.898,P=0.031)及较高水平血红蛋白(OR=1.024,95%CI 1.004~1.045,P=0.019)是CRRT治疗难治性急性左心衰竭患者死亡的危险因素,而较高水平治疗前平均动脉压(OR=0.959,95%CI 0.930~0.989,P=0.008)和治疗前尿量(OR=0.998,95%CI 0.997~0.999,P=0.004)是患者预后的保护因素。结论即使采用CRRT治疗难治性急性左心衰竭,其病死率仍较高,女性及血红蛋白水平升高是患者预后的危险因素,而治疗前较高水平尿量和治疗前平均动脉压是患者预后的保护因素。     

Arterial elasticity measurement in renal transplant patients under anticalcineurin immunosuppression

INTRODUCTION: Calcineurin inhibitors may be associated with decreased arterial elasticity and increased vascular risk. We measured pulse wave velocity (PWV) in large or small arteries as an index of elasticity. The aim of our study was to determine aortic and radial arterial elasticity in 30 stable kidney transplant patients treated with calcineurin inhibitor immunosuppression. PATIENTS AND METHODS: In stable kidney transplant patients we determined the usual biochemical parameters as well as lipid profiles, 24-hour blood pressure (BP) monitoring (CBPM) using a chronobiological program (Garapa), and PWV with a HDI-PWV CR-2000 monitor. RESULTS: Sixteen patients received cyclosporine (CsA, G-1) and 14 tacrolimus (G-2) immunosuppression. There were no baseline differences regarding age (G-1: 56 +/- 12 years, G-2: 56 +/- 14 years), renal transplant follow-up (G-1: 7 +/- 3 years, G-2: 7.5 +/- 3 years), Systolic BP, pulse pressure or plasma creatinine (G-1: 163 +/- 35 umol/L, G-2: 173 +/- 26 umol/L). Patients in the G-1 showed higher diastolic BP (79 +/- 11 vs 74 +/- 8 mm Hg), greater proteinuria (1.26 +/- 0.4 vs 0.6 +/- 0.2 g/d, P < .05), total cholesterol (5.51 +/- 1.2 mmol/L) and low-density lipoprotein (3.08 +/- 0.3 vs 2.99 +/- 0.3 mmol/L, P = NS). Aortic arterial elasticity was decreased in G-1 patients (10.4 +/- 6 vs 14.3 +/- 2 mL/mm Hg x10, P < .05) as well as that in the radial artery (G-1: 5.52 +/- 1 vs 5.57 +/- 1.2 mL/mm Hg x100, P = NS). Almost 100% of the patients presented normal diurnal BP with high nocturnal BP in a nondipper pattern in both groups. CONCLUSION: Calcineurin immunosuppression may contribute to arterial stiffness in kidney transplant patients. No differences between CsA or tacrolimus were observed in our study. CBPM and PWV are useful tools to evaluate subclinical atherosclerosis in renal transplant patients.     

Mycophenolate mofetil may allow cyclosporine and steroid sparing in de novo heart transplant patients

BACKGROUND: Mycophenolate mofetil (MMF) provides superior prophylaxis against acute rejection when compared with azathioprine (AZA) in heart and renal transplantation. However, it remains unclear whether this results in improved survival or reduced morbidity after heart transplantation. METHOD: In a sequential study, 240 cardiac transplant patients were treated with either MMF (n=119) or AZA (n=121) both in combination with cyclosporine and corticosteroids after rabbit antithymocyte globulin induction. RESULTS: By protocol lower cyclosporine levels were targeted in the MMF group during the first year (e.g. 203+/-52 ng/mL MMF vs. 236+/-59 ng/mL AZA, P=0.0006 at 6 months). Patient survival at 1 year (82% MMF vs. 79% AZA, P=0.55) and at 3 years was similar in both groups. The cumulative probability of receiving antirejection treatment within 1 year was lower in the MMF group, as was biopsy-proven acute rejection with International Society of Heart and Lung Transplantation grade > or =3A (24% vs. 35%, P=0.03). The MMF group also had fewer episodes requiring cytolytic therapy (6% vs. 13%, P=0.04) and more patients had steroids withdrawn by 1 year (66% vs. 32%, P<0.001). Renal function was better in the MMF group with lower creatinine levels at 1 year (133+/-45 vs. 155+/-46 micromol/L, P=0.0004). Calculated creatinine clearance (Cockcroft and Gault formula) at 1 year was also better (MMF 74+/-32 mL/min vs. AZA 62+/-24 mL/min, P=0.004). CONCLUSION: Our results suggest that immunosuppression with MMF rather than AZA may allow lower cyclosporine levels, better renal function, and increased steroid weaning at 1 year while also achieving better control of acute rejection.     

Renal function in patients with cadaveric kidney transplants treated with tacrolimus or cyclosporine

INTRODUCTION: Renal function predicts graft survival in kidney transplant patients. This study compared the 2-year evolution of renal function in patients treated with cyclosporine or tacrolimus in combination with mycophenolate mofetil (MMF) and prednisone. METHODS: We studied 1558 cadaveric renal transplant recipients from 14 Spanish hospitals between January 2000 and December 2002. Of these, 1168 were treated with tacrolimus and 390 with cyclosporine. The primary efficacy endpoint was long-term renal function. Renal function was measured by serum creatinine and glomerular filtration rate (GFR) by creatinine clearance calculated from the Cockcroft-Gault formula. This report summarizes the 2-year results. RESULTS: At 24 months the tacrolimus group showed significantly better serum creatinine (1.5 +/- 0.7 vs 1.8 +/- 0.8 mg/dL, P < .001) and GFR (60.5 +/- 20.9 mL/min vs 47.9 +/- 10.0, P < .001) than the cyclosporine group. Additionally, recipients with ideal graft donors (23.5 +/- 2.8 vs 24.0 +/- 2.9 years) had a better serum creatinine at 2 years (1.23 +/- 0.2 vs 1.5 +/- 0.4 mg/dL, P < .05). Multivariate analysis showed that tacrolimus was an independent factor associated with better renal function: odds ratio 1.6, 95% confidence interval (1.2 to 2.2), P < .001. CONCLUSIONS: Patients with a renal transplant treated with tacrolimus in combination with MMF and prednisone displayed better renal function at 2 years than those who received cyclosporine.     

Is pneumoperitoneum harmful during intra-abdominal hemorrhage in rats?

BACKGROUND: Laparoscopic surgical interventions are being used in trauma patients for diagnostic and therapeutic purposes, but there are limited studies on this subject. The effect of pneumoperitoneum during intra-abdominal hemorrhage has not been elucidated. The aim of this study was to investigate the hemodynamic, respiratory, and renal effects of pneumoperitoneum in the splenic injury/ hemorrhagic shock model in rats. MATERIAL AND METHODS: In this study, 80 anesthetized Wistar male rats (294.5 +/- 31.2 g) were randomized into 2 main groups: nontraumatized (group A) and traumatized (group B). After initial preparation and monitoring, each group was divided according to the degree of pneumoperitoneum. The nontraumatized subgroups were A1, sham-operated; A2, 4-8 mm Hg; A3, 9-13 mm Hg; and A4, 14-18 mm Hg. The traumatized subgroups were B1, splenic injury without pneumoperitoneum; B2, B3, and B4, splenic injury with pneumoperitoneum at 4-8 mm Hg, 9-13 mm Hg, and 14-18 mm Hg, respectively. Mean arterial pressure, heart rate, and respiratory rate were monitored continuously. Blood samples were obtained for hemoglobin, hematocrit, arterial blood gases, and biochemical analyses. Twenty-four hour urine output was collected. RESULTS: In group B4, pH, pCO2, and HCO3 levels were lower than in all other groups, while pCO2 and base deficit levels were significantly higher (P < 0.05). Both blood and urine analysis results showed that 24-hour urine output and the glomerular filtration rate of groups A4 and B4 were significantly lower (P < 0.05), while urinary osmolarity and fractional sodium excretion levels were significantly higher (P < 0.05). CONCLUSION: High-pressure pneumoperitoneum in splenically traumatized rats amplifies acidosis, decreases urine output, decreases glomerular filtration rate, and increases urinary osmolarity and fractional sodium excretion significantly.     

Short-term effect of atorvastatin in hypercholesterolaemic renal-transplant patients unresponsive to other statins.

BACKGROUND: Atherosclerosis associated with hyperlipidaemia is a major cause of morbidity and mortality after renal transplantation. Atorvastatin is a new HMG-CoA reductase inhibitor that has shown a favourable profile of lipid reduction when compared with other statins. The aim of the study was to assess the efficacy and safety of atorvastatin in hypercholesterolaemic renal transplant patients who had previously been on statins with little or no effect. METHODS: Atorvastatin, 10 mg/day, was administered to 10 renal transplant recipients with persistent hypercholesterolaemia (total cholesterol >240 mg/dl) for a period of 3 months. All of them had already been on statins for at least 3 months. RESULTS: Atorvastatin exerted a satisfactory lipid-lowering effect in seven of 10 patients. On average, serum total cholesterol (311+/-36.2 vs 253+/-48.8 mg/dl; P:<0.05) and serum LDL cholesterol (184+/-30.9 vs 136+/-22.9 mg/dl; P:<0.05) significantly decreased after atorvastatin therapy, whereas serum HDL cholesterol (86+/-14.6 vs 84+/-22.1 mg/dl) remained unchanged. In five subjects with a baseline serum triglyceride level above 150 mg/dl, a marked reduction in triglycerides was also observed (261+/-80.3 vs 193+/-53.3 mg/dl; P:<0.05). Lp(a) did not significantly change (13+/-16.3 vs 15+/-23.9 mg/dl, P:=NS). Serum creatinine, transaminases, creatinine phosphokinase (55+/-21.3 vs 56+/-29.4 IU/l) and fasting cyclosporin A levels were unaffected. The drug was generally well tolerated and neither myositis nor rhabdomyolysis was reported. CONCLUSION: Short-term therapy with the new HMG-CoA reductase inhibitor, atorvastatin, appears to be effective in lowering atherogenic lipids in renal transplant patients who had had little or no response to other statins.     

Elevated serum activity of N-acetyl-beta-glucosaminidase in essential hypertension: diagnostic value and reversal to normal values after antihypertensive therapy

Previous studies have shown that urinary N-acetyl-beta-glucosaminidase (NAG) is elevated in patients with hypertension, even without renal disease. To elucidate the value of measuring NAG, both in urine and serum of hypertensive patients, we measured NAG activity in the serum, plasma, and 24-hour urine by the fluorimetric method in 84 patients with uncomplicated essential hypertension before and after 6 months of effective treatment. NAG activities of these hypertensive patients were compared with those of 102 healthy normotensive subjects and 97 patients with various renal diseases and controlled hypertension. Serum NAG activity was clearly greater in patients with essential hypertension (427 +/- 124 U/mL) than in normotensive subjects (380 +/- 109 U/mL) or patients with renal disorders (393 +/- 115 U/mL) (P less than or equal to 0.004). The greater was the diastolic pressure in the hypertensive group, the greater was serum NAG activity (r = +0.30, P = 0.004). Hypertensive patients with high serum NAG activity were further characterized by a more exaggerated increase in systolic pressure (34 +/- 16 v 25 +/- 15 mm Hg, P = 0.051) and total peripheral resistance (19% +/- 18% v 12% +/- 13%, P = 0.042) in response to the cold pressor test and by a greater increase in systolic pressure (56 +/- 15 v 45 +/- 13 mm Hg, P = 0.009) and diastolic pressure (11 +/- 7 v 6 +/- 9, P = 0.043) in response to bicycle exercise testing than the group with low serum NAG activity. In contrast, urinary NAG activity tended to be only slightly higher in patients with essential hypertension than in the normotensive control group (33 +/- 31 v 23 +/- 29 U/mg creatinine [cr], P = 0.062), whereas patients with renal diseases had clearly increased urinary NAG activity (87 +/- 105 U/mg cr) (P less than 0.001). Following effective antihypertensive therapy, serum NAG activity decreased in patients with essential hypertension to values of normotensive control subjects (from 427 +/- 124 U/mL to 386 +/- 106 U/mL, P less than 0.01). A significant decrease in serum NAG activity was observed in patients with both initially high as well as low pretreatment serum NAG activities (P less than 0.001 and P less than 0.02, respectively). Urinary NAG activity overall was unchanged by antihypertensive treatment. We conclude that in patients with mild essential hypertension, serum NAG activity was already elevated (whereas urinary NAG activity was not) and was normalized by effective antihypertensive treatment.(ABSTRACT TRUNCATED AT 400 WORDS)     

Urine macrophage migration inhibitory factor concentrations as a diagnostic tool in human renal allograft rejection.

BACKGROUND: Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that is a potent activator of macrophages and T cells. Previous studies have shown that local MIF production is increased in acute renal allograft rejection, suggesting that it may play an important role in the rejection process. AIMS: To determine if urine and serum MIF concentrations: (1) are increased in acute rejection, and (2) can be used as noninvasive tools to discriminate between acute rejection (AR) and cyclosporine nephrotoxicity (CyA toxicity). METHODS: In a prospective study of nine renal allograft patients (five acute rejection and four stable), serial urine MIF concentrations were measured by ELISA in the first 14 days after transplantation. In a retrospective study, MIF concentrations in urine and serum were measured in 24 patients who were biopsied for acute renal transplant dysfunction (11 AR, 13 CyA toxicity). Urine and serum MIF were also measured in 23 stable renal transplant patients and 10 normals. RESULTS: MIF was readily detected in the urine of normal healthy controls (106+/-61 pg/micromol creatinine). In the prospective study, the urinary MIF concentration was increased substantially on day 1 posttransplantation and subsequently fell in parallel with the serum creatinine. However, urine MIF increased before episodes of biopsy proven acute rejection. The retrospective study showed that urine MIF concentrations in patients with AR were increased 5-fold compared to normal controls (439+/-313 pg/micromol Cr; P<0.01). In contrast, urine MIF concentrations in CyA toxicity were not significantly different to normal controls (145+/-119 pg/micromol Cr; P=NS). A marked increase in MIF immunostaining was seen in biopsies of AR, but not in CyA toxicity. No significant differences were evident in serum MIF levels between normals and any transplant patient group. CONCLUSIONS: These results suggest that measurement of urine MIF concentration may be useful in monitoring renal transplant patients for acute rejection and as a discriminator from cyclosporine nephrotoxicity.     

Early mechanical function in the heterotopic heart transplant

The characteristics of left ventricular (LV) function in the nonimmunosuppressed heterotopic heart transplant (TX) with less than 3 hr of cold preservation, were studied in 12 awake chronically instrumented dogs prior to TX (control), 1-12 hr post TX (P1), 12-24 hr post TX (P2), and 24-48 hr post TX (P3). Micromanometers measured LV transmural pressure and ultrasonic transducers measured ventricular dimension in order to allow calculations of myocardial mechanical properties. Immediately after transplant (P1) there was significant (P less than 0.05) depression noted in both diastolic function and systolic function (peak LV pressure, 137 +/- 5 vs 80 +/- 10 mm Hg; dp/dtmax, 2642 +/- 170 vs 1038 +/- 98 mm Hg/sec; maximum velocity of minor axis shortening, 4.46 +/- 0.50 vs 2.41 +/- 0.56; and Emax, 6.5 +/- 1.2 vs 2.0 +/- 1.4 mm Hg/ml). However, the contractility reserve (studied in six dogs) as estimated by postextrasystolic potentiation ratio was maintained (1.41 +/- 0.07 vs 1.37 +/- 0.15), suggesting reversibility of the depressed function. Over the next 2 days the diastolic function and the systolic function (at P3: 109 +/- 6 mm Hg, 1842 +/- 450 mm Hg/sec, 5.54 +/- 0.77 cm/sec, and 4.5 +/- 1.3 mm Hg/ml, respectively) gradually improved toward control. Microscopic examination of the autopsied hearts did not show significant evidence of rejection. Thus, the early depression of function in the heart TX appeared to be the result of ischemia from preservation and surgical trauma.(ABSTRACT TRUNCATED AT 250 WORDS)     

Renal effects of amlodipine in normotensive renal transplant recipients.

Renal effects of amlodipine in normotensive renal transplant recipients. The use of cyclosporin A (CsA) has improved the success of renal transplantation, but is associated with hypertension and significant renal toxicity. Previous reports suggest that calcium channel blockers may be useful in opposing the adverse effects of CsA. We have evaluated the effects of amlodipine (5 mg, once daily for 8 weeks) on renal function in 27 normotensive renal transplant recipients with stable renal function, in a double-blind, placebo-controlled, multicentre, cross over study. Amlodipine significantly reduced serum creatinine concentration relative to placebo (mean+/-SD: 168+/-65 vs 177+/-66 micromol/l; P=0.002) and there was a strong trend towards an increase in effective renal plasma flow on amlodipine relative to placebo (238+/-92 vs 217+/-87 ml/min; P=0.055). Glomerular filtration rate and lithium clearance were unaffected. Trough CsA blood concentration was unaffected. Amlodipine was well tolerated, with a low incidence of adverse events, and did not affect blood pressure or heart rate. In conclusion, amlodipine reduced serum creatinine in normotensive renal transplant recipients after only 8 weeks treatment, and was well tolerated in concomitant administration with CsA.     

Findings of Doppler sonography do not correlate with serum lipoprotein and total homocysteine concentrations in renal transplant recipients

Atherosclerosis may be evaluated by structural or functional changes of the main arteries. We sought to investigate the probable associations of static and dynamic arterial changes with lipoprotein (a) and homocysteine levels, the two risk factors for atherosclerosis. Intima-media thickening and vasodilatory responses to nitroglycerine of the common carotid artery and the renal transplant artery were studied by color Doppler sonography in 75 renal transplant recipients and 30 controls. At 3, 5, and 10 minutes after 0.4 mg of sublingual nitroglycerine are measured resistive index and peak systolic velocity of the common carotid artery and renal transplant artery. Intima-media thickening in renal transplant recipients and controls were 0.86 +/- 0.34 mm and 0.74 +/- 0.14 mm (P = .05), respectively. Although intima-media thickness did not correlate with the duration of renal transplantation, it was significantly higher in older renal transplant recipients. Peak systolic velocity of common carotid artery was significantly decreased by nitroglycerine in the controls (81.8 +/- 16.7 m/s to 73.2 +/- 12.8 m/s, P = .03). This decrement was more obvious in renal transplant recipients, especially at 10 minutes (69.6 +/- 18.5 m/s vs 59.3 +/- 2 m/s, P = .01). These reductions did not correlate with intima-media thickening, latter of which also did not correlate with homocysteine concentrations, which were higher among renal transplant patients with creatinine more than 1.8 mg/dL. Basal resistive indices of the common carotid artery and renal transplant artery were higher among graft recipients with dysfunction than recipients with good function, (0.7 vs 0.59, P = .003). In conclusion, neither homocysteine nor lipoprotein(a) concentrations predict static and dynamic vascular properties.