Metabolic syndrome in pediatric renal transplant recipients: comparing early discontinuation of steroids vs. steroid group.

Steroids have played a valuable role in transplantation as a treatment option. The purpose of this study is to assess the prevalence of MS in pediatric RT patients receiving SG or early SWG; SG discontinued five days after transplantation. We retrospectively reviewed 58 pediatric RT patients between 2000 and 2007. MS criterion was defined as the presence of any three of five criteria: (i) BMI >97th percentile, (ii) hypertension (SBP/DBP > 95th percentile or on medications); (iii) triglycerides > 95thpercentile, (iv) HDL cholesterol < 5th percentile, (v) fasting glucose > 100 mg/dL. Twenty-five patients (43%) received SG and 33 patients (57%) received SWG. The prevalence of MS in SG was 68% compared to 15% in SWG. At six months and one yr after transplantation, mean serum glucose, total cholesterol, and triglycerides were significantly lower in the SWG. The prevalence of hypertension was significantly lower in the SWG, and patients in the SWG received significantly less lipid-lowering and anti-hypertensive medications than SG. Mean BMI percentile was significantly higher in SG one yr after transplantation but not after six months, although always significantly higher in patients with MS (p < 0.05). From this study, we conclude that for pediatric RT patients, cardiovascular risk factors are significantly lower in SG withdrawal groups.

The effect of indomethacin on systemic and renal hemodynamics in neonatal piglets during experimental endotoxemia.

Systemic and renal hemodynamics are affected by prostaglandin production during endotoxemia. To study indomethacin effects on endotoxinemia in a neonatal piglet model, sixteen 7-10 day old piglets were anesthetized, ventilated, and catheterized. Mean arterial pressure (MAP), heart rate (HR), and urine output were continuously monitored. Endotoxin (0.06 mcg/kg) was injected after baseline measurements. We studied two groups with either endotoxinemia alone (n = 7) or an additional indomethacin infusion (0.2 mg/kg per h, n = 9). HR, MAP, renal blood flow (RBF), systemic and renal vascular resistance (SVR, RVR), cardiac index (CI), and glomerular filtration rate (GFR), were obtained at baseline, at 1, 2 and 3 h. We observed a drop in CI and an increase in SVR and HR within 3 h of endotoxinemia, while MAP remained unchanged. These effects were prevented by indomethacin. RVR was not altered significantly. Endotoxinemia triggered a drop of RBF in both control (P < 0.01) and intervention group (P < 0.05). In the intervention group, drop of GFR, urine volume, and paraaminohippuric acid clearance were apparent signs of nephrotoxicity (P < 0.01, <0.05, and <0.01). In conclusion, indomethacin maintains hemodynamic parameters during endotoxinemia at the expense of nephrotoxicity. We speculate that indomethacin counteracts the renoprotective effect of prostaglandins.

Early effects of lipopolysaccharide on cytokine release, hemodynamic and renal function in newborn piglets.

BACKGROUND: Gram-negative sepsis in newborns is associated with high mortality and morbidity. Lipopolysaccharide (LPS) and cytokines released upon exposure to gram-negative sepsis are well known to be involved in the pathophysiology. OBJECTIVE: In this report we investigate cytokine release, hemodynamic, and renal function induced by LPS in a newborn animal model with the intention to further examine early changes in gram-negative sepsis. METHODS: Five 7- to 10-day-old domestic piglets were anesthetized and catheters placed in the jugular veins, left ventricle, and femoral artery. Urine output was monitored via suprapubic cystostomy. Mean arterial pressure, heart rate, and arterial blood gases were continuously monitored. Thirty minutes after line placement and obtaining baseline values, 0.06 mug/kg LPS were administered intravenously. One, 2, and 3 h later samples were taken to monitor tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, endothelin, and nitric oxide (NO)/nitrate via ELISA. In addition, blood flow was assessed by the microsphere method. RESULTS: Our data show an initial surge of TNF-alpha and IL-1beta at 1 h after exposure to LPS. NO/nitrate, endothelin, and hemodynamic as well as metabolic changes became apparent mostly 3 h after exposure, by which time TNF-alpha and IL-1beta fell back to baseline. CONCLUSIONS: Our sepsis model suggests a brief initial TNF-alpha and IL-1beta surge following LPS challenge; however, their effects become apparent by the time the levels are already subsiding. The emergence of vasoactive substances, NO and endothelin, precedes the first substantial clinical symptoms.

Endotoxemia and the effects of dopamine on renal functions of neonatal piglets.

In this study, we observed the effects of moderate and high doses of dopamine on the renal functions of neonatal piglets during endotoxic shock. We found that fluid therapy alone was better at maintaining cardiac index and preventing elevation of systemic vascular resistance, than dopamine at 10 and at 20 microg/kg/min. Furthermore, urine output and glomerular filtration rate were reduced by dopamine. Following endotoxin administration dopamine decreased SVR and maintained a CI better than fluid alone. However, in spite of a better CI, greater deterioration in renal functions occurred in the dopamine groups as compared to the fluid group.

Effects of tezosentan, a dual endothelin receptor antagonist, on the cardiovascular and renal systems of neonatal piglets during endotoxic shock.

BACKGROUND/PURPOSE: Endothelin is a potent mediator of the cardiovascular and renal systems. Studies have found that endothelin has an important role in regulating cardiac function and renal perfusion in neonates who are suffering from endotoxic shock. The authors believe that blockade of the endothelin response during endotoxemia will have a beneficial effect on neonatal cardiac and renal functions. In this study the authors have examined the effects of tezosentan, a dual endothelin-receptor antagonist, on the cardiovascular and renal systems of neonatal piglets during endotoxemia. METHODS: Thirteen piglets were subjected to endotoxic shock and divided into a fluid-therapy group that received 0.9% normal saline and a group that received tezosentan (1 mg/kg/h). Mean arterial pressure (MAP), heart rate (HR), and glomerular filtration rate (GFR) were plotted at baseline, 1, 2, and 3 hours. Cardiac index (CI), renal blood flow (RBF), systemic vascular resistance (SVR), and renal vascular resistance (RVR) were obtained at baseline, 1, and 3 hours after baseline. RESULTS: (P <.05 for 3 hours versus baseline and tezosentan versus fluid). Although fluid therapy in endotoxemia had no significant effect on MAP and RVR, it significantly increased HR (139 plus minus 17 to 246 plus minus 17 beats/min) and SVR (0.08 plus minus 0.05 to 0.33 plus minus 0.09 mm Hg/mL/min) and decreased CI (407 plus minus 208 to 98 plus minus 13 mL/min/kg), RBF (1.84 plus minus 0.38 to 0.97 plus minus 0.34 mL/min/kg kidney), and GFR (0.20 plus minus 0.05 to 0.11 plus minus 0.04 mL/min/kg) at 3 hours. The use of tezosentan also significantly increased HR (130 plus minus 14 to 220 plus minus 31 beats/min), but unlike in the fluid therapy group, there was a significant fall in MAP (77 plus minus 10 to 54 plus minus 9 mm Hg) and RVR (1.92 plus minus 0.44 to 1.77 plus minus 0.64 mm Hg/mL/min) and a less severe decrease in CI (482 plus minus 188 to 176 plus minus 67 mL/min/kg) at 3 hours. SVR, RBF, and GFR were maintained. CONCLUSIONS: Endotoxic shock affected cardiac and renal functions in both treatment groups. Fluid therapy alone could not prevent a statistically significant fall in CI, RBF, and GFR or prevent the increase in HR and SVR. Endothelin antagonism with tezosentan resulted in a statistically significant fall in MAP and RVR from baseline, not seen in the fluid-therapy group. CI and RBF were significantly higher, and MAP, SVR, and RVR were significantly lower when compared with the fluid-therapy group at 3 hours. GFR also was maintained at baseline with tezosentan. During endotoxemia, endothelin antagonism maintained renal and cardiac functions better than with fluid therapy alone.