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Biomedical subjects

Diego H Aviles

Publications and source records attributed to Diego H Aviles.

9 recordsLinked to original sources

Treatment of primary and secondary hypertension in children.

The incidence of pediatric hypertension (HTN) is increasing, mainly due to an increase in primary (essential) HTN, or PH. There are only a limited number of studies assessing the characteristics and treatment efficacy of PH versus secondary HTN (SH). We conducted a retrospective analysis of 158 pediatric patients (mean age: 10.8 years; sex ratio: 51.1% female, 48.9% male) with HTN of whom 34.4% had PH and 65.6% had SH. The vast majority were either African-American or Caucasian. Among all patients, therapy induced a significant decrease in systolic blood pressure (SBP) and diastolic BP (DBP) (both p<0.0001). SBP (p<0.0001) and DBP (p=0.002) declined significantly in PH patients. PH and SH patients with a body mass index (BMI) >95th percentile (%) had a significantly higher post-therapy SBP (both p<0.05) than those with a BMI <95th%. SBP declined similarly in PH patients treated with calcium-channel blockers (CCB) and angiotensin-converting enzyme inhibitors (ACEI). DBP declined only in PH patients treated with ACEI. SBP and DBP (both p<0.0001) declined significantly in SH patients. Post-therapy BP was similar in SH patients treated with either CCB or ACEI. Post-therapy SBP and DBP were significantly lower in SH patients than in PH patients; moreover, therapy induced a greater decline in SBP and DBP in the SH patients. Compared to PH patients, SH patients were twofold more likely to achieve a SBP less than the 95th% after therapy. We conclude that (1) significant lowering of BP with either CCB or ACEI is achievable in most children with HTN, and (2) SH patients respond better to therapy than those with PH.

Adolescent↗

Effect of age, ethnicity, and glucocorticoid use on tacrolimus pharmacokinetics in pediatric renal transplant patients.

Tacrolimus has become an effective alternative to cyclosporine as a component of primary immunosuppression in pediatric renal transplant patients, but the information on the pharmacokinetic characteristics of tacrolimus in young patients is still limited. The primary objective of this study was to determine the effect of patient age, ethnicity, and concurrent steroid administration on tacrolimus pharmacokinetics in pediatric renal transplant patients. The study population consisted of 30 pediatric patients, age 1.5-18.6 yr, who received a kidney transplant between July 1999 and February 2004. After twice daily dosing was stabilized based on clinical judgment, at least 5 days postoperatively, tacrolimus levels were drawn prior to, and 1, 2, 4, 8, and 12 h after the morning dose. The mean dose of tacrolimus was 0.12 mg/kg/dose. Mean trough level was 11.9 +/- 5.0 ng/mL. Mean area under the curve (AUC) was 192 +/- 84 with a range of 78-360 h x (ng/mL). The correlation between trough level and AUC was only fair (r = 0.74); later time points correlated better with AUC, and an excellent correlation (r = 0.96) was obtained between the mean of trough and 2-h level (C(2)) and AUC. There was a negative correlation between age and dose per body weight (r = -0.68). African-American patients had marginally lower drug exposure with similar dosing. Three age groups (<5, 5-12, and >12 yr) were compared with respect to dosing and AUC. Despite similar AUC in all three groups, the mean dose per kg required to achieve the AUC was 2.7- and 1.9-fold higher in the <5 and 5-12-yr groups, respectively, compared with the >12-yr group. Nine of the 30 patients were on a totally steroid-free regimen. Their tacrolimus dose and trough levels were similar to those of steroid-exposed patients, but their mean AUC was 41% higher. Our results show an inverse correlation between age and required tacrolimus dose, wide interindividual variation, and greater exposure with steroid-free regimen despite no change in trough level.

Black or African American↗

Results of one-year follow-up of steroid-free immunosuppression in pediatric renal transplant patients.

Renal transplantation in children has traditionally required immunosuppression with multiple medications including glucocorticoids. Data collected over almost 30 yr suggest that although glucocorticoids are efficacious as part of a regimen to minimize the incidence of acute rejection episodes, their use is associated with increased risk for post-transplant hypertension, hyperlipidemia, and reduced growth rates. We desired to reduce these complications and thus used an immunosuppressive protocol including daclizumab, tacrolimus, and mycophenolate mofetil and study the efficacy of this protocol in a population with a high percentage of African-American recipients. No patient received glucocorticoids at any time post-transplant. Our results show that at 1 yr post-transplant, glomerular filtration rate, serum glucose, calcium and phosphorous metabolism, serum magnesium, and serum lipids were similar in patients receiving steroid-free and those receiving steroid-based immunosuppression. The incidence of acute rejection was similar in the two groups. Hematocrit and white blood count levels were lower 1 month after transplant in the steroid-free patients but these levels increased within several months. Systolic blood pressure was similar in the two groups, although this was achieved, in part, in the patients who received steroids by the administration of medications to lower blood pressure. Finally, tacrolimus levels were similar in the two groups, but patients receiving steroids required higher doses of tacrolimus at several time points studied during the first post-transplant year. Taken together, our data suggests that at one-year follow-up, steroid-free immunosuppression is safe, and efficacious in pediatric renal transplant recipients.

Anemia↗

High incidence of initial and late steroid resistance in childhood nephrotic syndrome.

BACKGROUND: Conventional wisdom states that greater than 80% of children with nephrotic syndrome (NS) respond to steroid treatment, remain steroid-sensitive during subsequent relapses, and consequently have a favorable long-term prognosis. In contrast, steroid resistance is believed to be associated with a high risk of developing chronic renal failure. Recent reports suggest that the histologic pattern of NS in children may be changing, but whether the change is accompanied by a parallel change in steroid sensitivity is unknown. METHODS: Initial and subsequent steroid responsiveness was evaluated in all children aged 1 to 18 years who presented with newly diagnosed NS to the 2 pediatric nephrology referral centers in southeastern Louisiana between 1994 and 2003. NS was defined as presence of edema, heavy proteinuria, and serum albumin concentration below 2.5 g/dL. Steroid sensitivity (SS) was defined as total resolution of proteinuria and edema, and partial response to steroids (PR) was defined as loss of edema with continuing proteinuria. RESULTS: There were 210 new cases of NS. Forty-one patients (20%) had immune complex glomerulonephritis. Six patients were excluded because of incomplete data availability. Of the remaining 163 patients, 115 (71%) were SS and 23 (14%) achieved PR during the initial 4 weeks of treatment; 25 (15%) were steroid-resistant (SR). Follow-up data were available for 91 of the 115 initially SS patients; 19 subsequently became steroid-resistant. Thus, at least 45% of the patients with new-onset NS did not have typical childhood steroid-responsive NS. Initial steroid resistance was more likely in African American children and in children with older age at onset (11.5 vs. 4.6 years). Development of steroid resistance after initial SS was associated with shorter interval to the first relapse (2.2 vs. 5.4 months) and having the first relapse during the initial steroid treatment. CONCLUSION: Compared to previous reports, our results show a higher incidence of initial and subsequent steroid resistance, characteristics not consistent with typical minimal change NS with a benign prognosis. The results suggest that in the current era, NS in children may not be as benign as indicated by earlier studies.

Adolescent↗

Sudden blindness in a child with end-stage renal disease.

Continuous peritoneal dialysis (CPD) is the preferred modality for renal replacement therapy in children with end-stage renal disease. Anterior ischemic optic neuropathy (AION) is a rare complication in patients on CPD. AION is characterized by ischemic injury of the optic nerve caused by hypoperfusion of the posterior ciliary arteries. It presents with acute visual loss and disc swelling, without additional neurological findings. We report a 2-year-old child with end-stage renal disease on CPD who developed AION. He was dehydrated and received intravenous fluid on admission. Additional treatment included methylprednisolone and levodopa. On his 3rd admission day, his pupils became reactive to light and his vision showed improvement. The improvement in vision might be due to the early detection and aggressive treatment of hypotension. It is difficult to demonstrate whether steroids or levodopa played a role in the improvement of his vision. Prospective studies to evaluate the effectiveness of levodopa in the treatment of AION are warranted in this potentially devastating condition.

Anti-Inflammatory Agents↗

False-positive human immunodeficiency virus antibody test in a dialysis patient.

A patient developed end-stage renal disease secondary to p-anti-neutrophil cytoplasmic antibody (p-ANCA) positive rapidly progressive glomerulonephritis. He subsequently had human immunodeficiency virus (HIV)-1 antibody screening performed as part of a pre-transplant evaluation. The HIV-1 enzyme immunoassay (EIA) antibody test was repeatedly reactive. The HIV-1 western blot was indeterminate. The western blot pattern revealed "non-specific staining obscuring bands in that region." Another sample of serum was sent and the results were identical to the first result. An HIV-1 proviral qualitative polymerase chain reaction test was then performed several months later and no HIV-1 DNA was detected. One year later, an HIV-1 RNA test was negative. Thus, the positive antibody EIA test and the indeterminate western blot represent a false-positive result, most likely due to cross-reacting antigens in the patient's serum with various HIV antibodies. Throughout this period and thereafter, the patient has exhibited no symptoms of HIV infection.

Adolescent↗

Decreased expression of T-cell NF-kappaB p65 subunit in steroid-resistant nephrotic syndrome.

BACKGROUND: Although the etiology of childhood nephrotic syndrome is unclear, there is evidence to suggest an important role for T cells in the pathogenesis. Steroid resistance is considered a poor prognostic sign but the mechanism of the resistance is unknown. The study examined the potential role of T-cell nuclear transcription factors in the steroid resistance. METHODS: The expression of the nuclear transcription factors activating protein-1 (AP-1) and nuclear factor-kappaB (NF-kappaB) as well as that of lymphokines interleukin (IL)-2, IL-4, and interferon-gamma (IFN-gamma) were compared in T cells obtained from normal subjects, children with steroid-sensitive nephrotic syndrome (SSNS) and children with steroid-resistant nephrotic syndrome (SRNS) before any treatment was given. Changes in expression and binding of the nuclear transcription factors were studied with electrophoretic mobility shift assay (EMSA) and Western blot, whereas mRNA cytokine expression were evaluated by enzyme-linked immunosorbent assay (ELISA)-linked reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: A significant decrease of the p65 subunit protein of NF-kappaB but not in p50 was documented by both EMSA (N= 7) and Western blotting (N= 5) in five of five SRNS patients but not in control subjects or SSNS patients; there was a decrease in mRNA expression as shown by ELISA-linked RT-PCR. In contrast, there were no significant differences in AP-1 expression by EMSA. IL-2 mRNA level was higher in T cells from SRNS patients than in T cells from either SSNS or control subjects. IL-4 and IFN-gamma were equally decreased in both groups of patients. CONCLUSION: The results show differences in T cells between untreated SSNS and SRNS patients. The decrease of NF-kappaB p65 subunit and up-regulation of IL-2 are potential mechanism of glucocorticoid resistance in SRNS.

Adolescent↗