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Biomedical subjects

Mark M Mitsnefes

Publications and source records attributed to Mark M Mitsnefes.

27 records · Page 2Linked to original sources
PubMed2004

Impaired left ventricular diastolic function in children with chronic renal failure.

BACKGROUND: Diastolic dysfunction is frequent in adults with renal failure. However, in children with mild-to-moderate chronic renal insufficiency (CRI), it has not been evaluated. We compared diastolic function and assessed risk factors associated with diastolic dysfunction in children with CRI with those on dialysis. METHODS: Thirty-three children with CRI, 17 on chronic dialysis, and 33 control patients, had echocardiography performed. Early diastole was assessed using indices of left ventricular (LV) relaxation derived from transmitral and tissue Doppler, and reported as the peak E/A wave ratio, and septal mitral annular velocities (Em). Late diastole was determined using an index of LV compliance (E/Em ratio). Left atrial (LA) dimension was also determined. RESULTS: Children with CRI had worse diastolic function (lower Em, and higher E/Em ratio than control patients, P < 0.001). Dialysis patients had worse diastolic function (lower E/A ratio and Em, and higher E/Em ratio, P < 0.001) than CRI children. LA dimension was higher in renal patients when compared with control patients (P < 0.001). In children on dialysis, LV relaxation (Em) was significantly related to left ventricular mass (LVM) index (r=-0.58, P= 0.04), and LV compliance (E/Em) was significantly associated with LA index (r= 0.67, P= 0.01), LVM index (r= 0.75, P < 0.01), hemoglobin level (r=-0.65, P= 0.02), serum phosphorus (r= 0.56, P= 0.05), and calcium-phosphorus ion product (r= 0.59, P= 0.04). CONCLUSION: Our results indicate that diastolic dysfunction is already present in children with mild-to-moderate CRI. Worse diastolic function in dialysis patients might be related to LV hypertrophy. The results suggest that children with advanced renal failure and diastolic dysfunction may be at risk for ultimate worsening of cardiac function over time.

Adolescent↗
PubMed2003

Activation of mitochondrial apoptotic pathways in human renal allografts after ischemiareperfusion injury.

BACKGROUND: Ischemia-reperfusion injury in cadaveric (CAD) kidney allografts is associated with tubular cell injury, delayed graft function, and an increased incidence of acute and chronic rejection. We tested the hypothesis that activation of specific apoptotic pathways represents a mechanism for tubular cell death after CAD kidney transplantation. METHODS: Serial tissue sections from paraffin-embedded needle biopsy specimens obtained at approximately 1 hr of reperfusion after transplantation of 13 CAD and 12 living-related donor (LRD) renal allografts were examined by using the terminal deoxynucleotide transferase-mediated dUTP nick-end labeling assay to detect apoptosis and by immunohistochemistry for expression of key pro-apoptotic molecules (Bax, Bak, tumor necrosis factor receptor [TNFR]-1, Fas, and cytochrome c). RESULTS: Apoptosis was detected primarily in tubular cells, with a mean+/-standard deviation of 6.8+/-2.2 apoptotic cells per 100 cells examined in CAD renal allografts compared with 1.8+/-2.7 cells per 100 in LRD (P<0.001) renal allografts. There was a significant correlation between apoptosis rate and cold ischemia time in CAD (r=0.86, P<0.001) renal allografts. Bax was expressed in 100% of CAD versus 17% of LRD renal allografts (P<0.001), Bak in 92% of CAD versus 17% of LRD renal allografts (P<0.001), and TNFR-1 in 100% of CAD versus 58% of LRD renal allografts (P<0.05). Fas was expressed in only a small number of samples (23% of CAD and 17% of LRD renal allografts, P=not significant). Bax and Bak were expressed predominantly in apoptotic cells. Cytochrome c was detected as a mitochondrial pattern in LRD renal allografts, but in a diffuse cytosolic distribution in CAD renal allografts. CONCLUSIONS: Ischemia-reperfusion injury in CAD kidney transplants is associated with a duration-dependent increase in tubular cell apoptosis, mediated at least in part by activation of mitochondrial pathways.

Biopsy, Needle↗
PubMed2003

Left ventricular mass and systolic performance in pediatric patients with chronic renal failure.

BACKGROUND: Children with chronic renal disease have a high prevalence of left ventricular hypertrophy (LVH), which is thought to be adaptive to improve contractility and lower wall stress in the face of increased afterload and preload. The aim of this study was to determine the association between LV mass, LV performance, and LV contractility in children with chronic renal insufficiency (CRI) and children undergoing chronic dialysis. METHODS AND RESULTS: Twenty-five children with CRI, 12 undergoing chronic dialysis, and 24 controls had echocardiographic evaluation during rest and peak exercise. LV performance was assessed by calculation of shortening fraction and heart rate-corrected velocity of circumferential fiber shortening (VCF). Contractility (VCF difference) was determined based on the relation between VCF and end-systolic wall stress. Contractile reserve was assessed by the difference between contractility at rest and peak exercise. The dialysis group had higher LVM index than the group with CRI (42.9+/-10.3 versus 29.9+/-9.4 g/m(2.7), P<0.001). Both groups had higher LVM index compared with controls (22.2+/-6.1 g/m(2.7), P<0.001). At rest, the CRI and dialysis groups had significantly higher VCF(c) (P<0.001) and VCF difference (P<0.05) and significantly lower wall stress (P<0.01) compared with the control group. Dialysis patients had significantly lower contractile reserve compared with the control group (P<0.03). CONCLUSIONS: These results indicate that children with CRI and undergoing chronic dialysis have increased LVM, LV performance, and contractility at rest. However, dialysis patients have diminished contractile reserve during exercise, which might be an indicator for the development of more severe systolic dysfunction over time.

Adolescent↗
PubMed2003

Early posttransplantation hypertension and poor long-term renal allograft survival in pediatric patients.

OBJECTIVE: To evaluate the effect of early hypertension on long-term allograft survival in children with kidney transplantation. STUDY DESIGN: Data from a total of 159 patients (mean age, 12.8+/-4.8 years) who underwent kidney transplantation between 1978 and 1998 and whose allograft was functioning for at least 1 year were analyzed retrospectively. Patients were divided according to the presence of hypertension within the first year after transplantation. Primary outcome was time of allograft failure (death, return to dialysis, or retransplantation). RESULTS: Kaplan-Meier analysis showed that systolic (P<.0001) and diastolic (P=.016) hypertension was associated with overall worse allograft survival. Children with systolic hypertension had a significantly higher graft failure rate regardless of the type of donor, cause of kidney failure, presence or absence of acute rejection, and allograft function at 1 year after transplantation. The multivariate Cox regression model proved that systolic hypertension was a significant and independent risk factor for poor graft survival (hazard ratio [HR], 1.79; P<.0001). Other predictors included allograft function at 1 year after transplantation (HR, 0.97; P<.0001), acquired cause of end-stage kidney disease (HR, 1.96; P=.01) and age <6 years (HR, 2.61; P=.045). CONCLUSIONS: Early posttransplantation systolic hypertension strongly and independently predicts poor long-term graft survival in pediatric patients.

Acute Disease↗
PubMed2003

Ambulatory blood pressure monitoring in pediatric renal transplantation.

Over last two decades ABPM has evolved from a research device to an established and valuable clinical tool for BP evaluation. More than 10 yrs ago ABPM was introduced to pediatrics and since that time, its importance has been increasing in the management of hypertension in children and adolescents. This review summarizes the information gathered from the studies of ABPM in adult and pediatric patients with renal transplants. We will review the importance of hypertension in this patient subset, discuss the advantage of ABPM over CBP and focus on specific abnormalities and clinical significance of ABPM in renal transplant recipients.

Blood Pressure Monitoring, Ambulatory↗
PubMed2002

Office and ambulatory blood pressure elevation in children with chronic renal failure.

Hypertension is a frequent complication in patients with chronic renal insufficiency (CRI) and is associated with target organ damage, including left ventricular hypertrophy (LVH). To better assess hypertension in pediatric patients with CRI, we performed 24-h ambulatory blood pressure monitoring (ABPM) and evaluated the relationship between ABPM parameters and LVH in 29 children, mean age 12.4+/-3.8 years. There was no significant difference in the frequency of hypertension comparing casual systolic blood pressure (SBP) (21%) with the mean 24-h (21%) or daytime mean SBP (21%). However, diastolic hypertension was detected more frequently using ABPM: 24% for 24-h diastolic blood pressure (DBP), 14% for daytime DBP, and 7% for casual DBP. Nighttime systolic hypertension as well as diastolic hypertension was detected in 12 (41%) children. Seventeen (59%) patients had attenuated dipping for SBP and 9 (31%) had abnormal DBP dipping. Lower SBP dipping was associated with lower glomerular filtration rate (r=0.44, P<0.05). LVH was found in 6 (21%) patients. LVM index was significantly correlated with 24-h SBP (r=0.43, P<0.05). Multiple regression analysis confirmed that higher 24-h SBP was the only independent predictor for increased LVM index (P=0.001). No significant relationship was found between LVM index and office blood pressure. These results confirm a high prevalence of blood pressure abnormalities using ABPM criteria in children with CRI and suggest that ABP may better predict end-organ damage in these patients than casual BP.

Adolescent↗
PubMed2002

Body mass index and allograft function in pediatric renal transplantation.

Recent studies indicate that pre-transplant (Tx) obesity and increased body mass index (BMI) after renal Tx in adults are associated with decreased long-term renal allograft survival. This study examined whether obesity prior to renal Tx or the development of obesity within the 1st year after Tx in children is associated with worse allograft function at 1 year post Tx. This is a retrospective review of medical records from 76 pediatric renal allograft recipients between January 1994 and December 2000. Recipients had their renal allograft functioning at 1 year, and had a glomerular filtration rate (GFR) measured 1 year post Tx. Obesity was defined as body mass index (BMI)> or =95th percentile for age, sex, and race. Patients were divided into three groups: (1) children who had BMI> or =95th percentile at time of Tx, (2) children who had BMI<95th percentile at time of Tx but became obese at 1 year after Tx, and (3) children with BMI<95th percentile at time of Tx and 1 year later. The number of patients with BMI> or =95th percentile doubled at 1 year after Tx when compared with pre-Tx data: 10 (13%) versus 22 (29%), respectively. Fifteen (20%) patients developed obesity and 10 (13%) patients had BMI between the 85th and 95th percentile at 1 year post Tx. Children in group 1 had significantly lower mean GFR (46.1+/-15.0 ml/min per 1.73 m(2)) than children in group 2 (57.7+/-24.5 ml/min per 1.73 m(2), P<0.05) and group 3 (60.4+/-21.5 ml/min per 1.73 m(2), P<0.01). The difference remained significant after adjusting GFR to height: group 1 24.0+/-5.2 ml/min per m, group 2 31.5+/-11.2 ml/min per m, P<0.05, and group 3 32.2+/-10.6 ml/min per m, P<0.01. Children with pre-Tx obesity (group 1) had significantly higher indexed systolic blood pressure ( P<0.01) than children from other groups. We conclude that pre-Tx obesity is associated with decreased GFR in children at 1 year after Tx. The reason may be persistence or development of post-Tx hypertension in severely obese patients.

Adolescent↗
PubMedDate not supplied

Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery.

BACKGROUND: The scarcity of early biomarkers for acute renal failure has hindered our ability to launch preventive and therapeutic measures for this disorder in a timely manner. We tested the hypothesis that neutrophil gelatinase-associated lipocalin (NGAL) is an early biomarker for ischaemic renal injury after cardiopulmonary bypass. METHODS: We studied 71 children undergoing cardiopulmonary bypass. Serial urine and blood samples were analysed by western blots and ELISA for NGAL expression. The primary outcome measure was acute renal injury, defined as a 50% increase in serum creatinine from baseline. FINDINGS: 20 children (28%) developed acute renal injury, but diagnosis with serum creatinine was only possible 1-3 days after cardiopulmonary bypass. By contrast, urine concentrations of NGAL rose from a mean of 1.6 microg/L (SE 0.3) at baseline to 147 microg/L (23) 2 h after cardiopulmonary bypass, and the amount in serum increased from a mean of 3.2 microg/L (SE 0.5) at baseline to 61 microg/L (10) 2 h after the procedure. Univariate analysis showed a significant correlation between acute renal injury and the following: urine and serum concentrations of NGAL at 2 h, and cardiopulmonary bypass time. By multivariate analysis, the amount of NGAL in urine at 2 h after cardiopulmonary bypass was the most powerful independent predictor of acute renal injury. For concentration in urine of NGAL at 2 h, the area under the receiver-operating characteristic curve was 0.998, sensitivity was 1.00, and specificity was 0.98 for a cutoff value of 50 microg/L. INTERPRETATION: Concentrations in urine and serum of NGAL represent sensitive, specific, and highly predictive early biomarkers for acute renal injury after cardiac surgery.

Acute Kidney Injury↗