Cognitive functioning in children on dialysis and post-transplantation.

We studied 124 children, 62 patient-subjects who had end-stage renal disease (ESRD) and 62 sibling-controls who closely matched the patient-subjects in terms of their ethnicity and their socioeconomic status, to discern whether children with ESRD would perform less well than their siblings on standardized achievement and intelligence quotient (IQ) tests, and to determine whether ethnicity would influence such results. The subjects were recruited from nine pediatric transplant and dialysis centers across the United States. Thirty-one subjects were white (Euro-American), 17 were African-American, and 14 were categorized as 'other'. The average age of the patient-subjects was 13.7 +/- 0.44 yr; and of the sibling-controls 13.7 +/- 0.38 yr. Most patients (61%) and siblings (84%) were in regular school classes, and most (87% and 92%, respectively) attended school full-time. The average IQ percentile rank for the patients was significantly lower than their siblings (31 +/- 4 vs. 44 +/- 5, respectively, with normal = 50). Patients tended to score lower on achievement tests compared with their siblings (spelling: 88.7 +/- 4 vs. 94.6 +/- 2; arithmetic: 88.5 +/- 2 vs. 94.0 +/- 2; reading: 91.9 +/- 2 vs. 100 +/- 3, respectively). Patients scores on achievement tests were influenced by age at diagnosis and by the mother/caregiver's lower achievement. Also, increased time on dialysis predicted lower scores on achievement tests. Neither dialysis/transplant status nor ethnicity significantly affected outcome. Our data suggest that ESRD, but not ethnicity or dialysis/transplant status, is a risk factor for lower IQ and academic achievement, especially in younger children, in children who spend more time living with ESRD, and in children whose mother's/caregiver's have lower educational levels.

Lovastatin preserves renal function in experimental diabetes.

Although hyperlipidemia has been associated with the progression of glomerulosclerosis, little attention has been directed toward the use of lipid-lowering agents in altering diabetic nephropathy. We tested the hypothesis that lovastatin and the combination of lovastatin and enalapril would preserve renal function in streptozotocin-induced diabetic Wistar rats. Five groups of animals were studied: group 1, nondiabetic (n = 10); group 2, diabetic, insulin only (n = 12); group 3, lovastatin, (15 mg/kg/day, n = 13); group 4, enalapril, (50 mg/L drinking water, n = 10) and group 5, lovastatin plus enalapril, (n = 14). After 8 weeks of treatment, glomerular filtration rate (GFR, insulin clearance) was measured in anesthetized animals. The diabetic group was characterized by a GFR of 0.18 +/- 0.03 ml/min/g of kidney weight (gKW), a blood glucose level of 441 +/- 36 mg/dL, plasma cholesterol and triglyceride levels of 64 +/- 6.0 and 103 +/- 26.0 mg/dL. Lovastatin preserved GFR, 0.52 +/- 0.06 ml/min/gKW compared with the diabetic control subjects (P < 0.05). Enalapril also maintained GFR (0.42 +/- 0.06 ml/min/gKW, P < 0.05). In the lovastatin plus enalapril group, GFR (0.62 +/- 0.05 ml/min/gKW) was greater than in the enalapril group (P < 0.05), but was not different from the lovastatin group. Plasma lipid levels were not altered in any of the groups. Assessment of the kidneys by histology after treatment showed that the mesangial matrix injury score was better in the lovastatin, enalapril, and lovastatin plus enalapril groups compared with the diabetic group (P < 0.05). Lovastatin, enalapril, and lovastatin plus enalapril abrogated the decline in GFR and glomerular injury in diabetic rats. Lovastatin's direct renal protective effect seems to be independent of its lipid-lowering properties.

Delta9 tetrahydrocannabinol and cannabidiol alter cytokine production by human immune cells.

Marijuana, a widely abused drug in the US, and its derivatives (cannabinoids) have been used in AIDS and cancer patients for treatment of intractable nausea and cachexia. Yet, objective investigations of the effect of cannabinoids on the human immune system are few. We investigated the effect of delta9 tetrahydrocannabinol (THC) and cannabidiol (CBD) on cytokine production in vitro by human leukemic T, B, eosinophilic and CD8+ NK cell lines as models. THC decreased constitutive production of IL-8, MIP-1alpha, MIP-1beta, and RANTES and phorbol ester stimulated production of TNF-alpha, GM-CSF and IFN-gamma by NK cells. It inhibited MIP-1beta in HTLV-1 positive B-cells but tripled IL-8, MIP-1alpha and MIP-1beta in B-cells and MIP-1beta in eosinophilic cells but doubled IL-8. Both cannabinoids strongly inhibited IL-10 production by HUT-78 T-cells. Results indicate that THC and nonpsychotropic CBD have complex lineage and derivative specific effects on cytokines consistent with previous animal studies. These effects while of potential benefits in some inflammatory/autoimmune diseases may worsen HIV infection, tumorigenesis and allergic inflammation in the lung.

Renal stone disease in children.

Renal stone disease has been regarded as an uncommon problem in children compared to adults. However, increased awareness of this problem in children may lead to early intervention preventing long-term consequences on the kidney and the urinary tract. This article reviews the epidemiology, pathogenesis, and the most common etiologies of renal stones in children. The clinical features and diagnostic and therapeutic modalities for the specific etiologies are also outlined. Using these guidelines may be helpful not only in the treatment but also in the prevention of renal stones.

Renal manifestations of tuberous sclerosis complex.

Patients with tuberous sclerosis complex (TSC) are at increased risk of renal disease, predominantly angiomyolipomas and renal cysts. We retrospectively reviewed clinical data of 71 patients diagnosed with TSC. Progression of renal lesions was noted. TSC patients with renal lesions were compared with TSC patients without renal disease. Fifteen of 38 patients had renal abnormalities by imaging at presentation. Six of 9 with initially normal kidneys subsequently developed new lesions. Although not of statistical significance, there was a trend toward increased retinal hamartomas, cardiac rhabdomyomas, and skin lesions in those patients who also had renal abnormalities. Renal disease should be considered and sought in all patients with TSC, both at initial presentation and subsequently, since renal disease is a very significant cause of morbidity and mortality.

Prevention of insulin-dependent diabetes mellitus: an overview of three trials.

Genetic, immune, and metabolic testing can reveal a person's risk of developing insulin-dependent diabetes mellitus (IDDM), and three large clinical trials are planned or underway to see if interventions can prevent IDDM in persons at risk. Researchers in diabetes prevention trials are screening first- and second-degree relatives of probands with IDDM for islet-cell antibodies. In the Cow's Milk Avoidance Trial, infant siblings of probands with IDDM will be randomized to receive either a baby formula containing a non-antigenic protein hydrolyzate or a standard cow's milk-based formula. The Diabetes Prevention Trial-Type I is randomly assigning subjects at high risk (more than a 50% probability of developing IDDM) to either receive insulin injections or undergo observation alone; subjects at intermediate risk (25% to 50%) will receive either oral insulin or placebo. In the European Nicotinamide Diabetes Intervention Trial, subjects receive either nicotinamide or placebo. If any of these trials show that IDDM can be prevented, then large-scale screening of children for IDDM risk factors may prove beneficial.

Cytokines in human milk.

Breast feeding improves the health of children. The greatest significance is to host defense, prevention of autoimmunity, and development of the digestive system; however, the underlying mechanisms for these effects are not well understood. Based on recent evidence that cytokines might be important in these processes, we have used ELISA to quantitate the cytokines in human colostrum, transitional, and mature milk from mothers delivering preterm or at term. We also used reverse transcription PCR to test breast milk cells for the production of cytokine mRNA. No significant (< 10 pg/ml) GM-CSF, SCF, LIF, MIP-1 alpha, IL-2, IL-4, IL-11, IL-12, IL-13, IL-15, sIL-2R, or IFN-gamma was detected. And, in contrast to earlier studies using bioassays or RIA, no significant IL-1 beta, TNF-alpha, or IL-6 was present; nor was IL-10, which had been tested using less specific antibodies. We did confirm the presence of high levels of M-CSF, which remained high throughout lactation. Human milk contained latent, but not free, TGF-beta 1, and especially TGF-beta 2, both of which may be activated by gastric acid pH. High levels of IL-1RA were detected, and like activated TGF-beta, may protect against autoimmunity. Chemokines, particularly GRO-alpha and MCP-1, but also RANTES and IL-8, were present and could protect against infection. Maternal cells in breast milk expressed mRNA for MCP-1 (20/20), IL-8 (14/20), TGF-beta 1 (14/16), TGF-beta 2 (4/6), M-CSF (9/12), IL-6 (6/12) and IL-1 beta (7/12), and may be a source of these cytokines. mRNA for IL-2, IL-10, IFN-gamma, TNF-alpha was not detected and only weak expression was found for RANTES (1/18). There was considerable variability between individual women, and women delivering preterm had lower levels of several cytokines in colostrum than women delivering at term. Yet, cytokine levels remained high months to years into lactation, providing immunological benefit to the breastfed infant/child.

Safety and cost effectiveness of pediatric percutaneous renal biopsy.

Because of the rising cost of health care, more patients are undergoing procedures as outpatients rather than inpatients. The purpose of this study was to compare safety and cost of outpatient versus inpatient, overnight stay, for children undergoing percutaneous renal biopsy. Charts of all such patients between January 1989 through January 1995 were reviewed for the following: age of patient, native versus allograft biopsy and preparation costs (in 1995 U.S. dollars), and complications. Of the 75 biopsies reviewed, 58 were native and 17 allograft with 35 (47%) of the biopsies being outpatient and 40 (53%) inpatient. There were four complications (11.4%) in 2 patients for the outpatient group and seven complications (17.5%) in 6 patients in the inpatient group (X2 = 0.1003, P = 0.75). The median cost for an outpatient biopsy was U.S. $1,968 while an inpatient biopsy was U.S. $3,178. We conclude that outpatient percutaneous renal biopsy in children is as safe as inpatient and more economic, with a saving of greater than U.S. $1,000 per biopsy.

Lovastatin has direct renal hemodynamic effects in a rodent model.

PURPOSE: Lovastatin, an HMG-CoA reductase inhibitor, has been shown to preserve renal function in models of chronic renal failure. We determined the effect of lovastatin on renal function and hemodynamics in normal nonpathologic kidneys in a rodent model. MATERIALS AND METHODS: Renal function was measured in anesthetized (Inactin) control rats (n = 13) and lovastatin-treated rats (15 mg./kg./day, 3 weeks, orally, n = 17). Renal blood flow was measured with an ultrasonic flowprobe, and glomerular filtration rate was measured by inulin clearance. The effect of lovastatin on pre- and postglomerular vessel diameters was also observed in a hydronephrotic kidney preparation by videomicroscopy. RESULTS: Lovastatin significantly increased (p < 0.05) renal blood flow and glomerular filtration rate by 17% (3.4 +/- 0.2 ml./min./gram kidney weight (gKW) versus 2.9 +/- 0.2 ml./min./gKW) and 49% (0.67 +/- 0.04 ml./min./gKW versus 0.45 +/- 0.06 ml./min./gKW). The increase in renal blood flow was mediated by preglomerular vasodilation (expressed as percent increase from baseline diameter, n = 20), 25% in the interlobular artery and 20% in the afferent arteriole (p < 0.05). CONCLUSIONS: In addition to its known lipid-lowering properties, lovastatin has a direct renal hemodynamic effect, increasing renal blood flow and glomerular filtration rate in normal nonpathologic kidneys. Lovastatin's selective preglomerular vasodilation may account for the observed increase in renal blood flow and glomerular filtration rate. Accordingly, this additional hemodynamic effect may be useful in preserving renal function in models of chronic renal failure.

Post-transplant renal artery stenosis: impact of therapy on long-term kidney function and blood pressure control.

PURPOSE: We assessed the long-term outcome of different treatment methods for transplant renal artery stenosis. MATERIALS AND METHODS: Outcome data for 23 patients with transplant renal artery stenosis treated during a 16-year period were reviewed and analyzed. RESULTS: There was a higher incidence of renal artery stenosis in cadaveric donor kidneys compared to living donor kidneys (2% versus 0.3%, p < 0.02), and in cadaveric kidneys from pediatric donors less than 5 years old compared to those from adults (13.2% versus 1.3%, p < 0.01). Six patients underwent primary medical treatment for renal artery stenosis, with a successful outcome in 4 (mean followup plus or minus standard error 57 +/- 22 months) and failure in 2. Of the patients 16 were treated with percutaneous transluminal angioplasty, including 12 who were cured or improved with respect to hypertension (followup 44.7 +/- 7.6 months). Five patients underwent surgical revascularization for renal artery stenosis with postoperative improvement of hypertension (followup 18.8 +/- 11.6 months). Overall, 21 of 23 patients (91%) were treated successfully for transplant renal artery stenosis with cure or improvement of associated hypertension. Posttreatment renal function was stable or improved in 18 patients, while renal function deteriorated due to parenchymal disease in 3. CONCLUSIONS: Most patients with transplant renal artery stenosis can be treated successfully. Percutaneous transluminal angioplasty is the initial interventive treatment of choice for high grade renal artery stenosis. Surgical revascularization is indicated if percutaneous transluminal angioplasty cannot be done or is unsuccessful.

Research in pediatric residency programs.

BACKGROUND AND OBJECTIVES: We have required residents in pediatrics at the Cleveland Clinic Foundation to give research presentations since 1989; this article reviews our experience with this program. Additionally, we sought to determine how many other accredited pediatric programs in the United States also require this. METHODS: Retrospective review of the Cleveland Clinic program; descriptive statistics of other United States residency programs, obtained by questionnaire. RESULTS: Pediatric residents at the Cleveland Clinic have given 108 research presentations since 1989, and have developed 33 (30.5%) of them into manuscripts or abstracts. We mailed questionnaires to 215 pediatric residency program directors and received responses from 177 (82%). Of these, 48 (27%) indicated their programs had a research requirement; residents could present their findings in departmental meetings or submit an abstract or manuscript to a professional society or journal. Respondents cited several barriers to research: residents are too busy, there are too few faculty members to mentor them, financial resources are limited, and there is no residency review committee requirement. CONCLUSIONS: Even though only approximately one fourth of the pediatric residency programs in the United States require research, we feel it is worthwhile experience. Despite barriers, residents can and do perform research and publish their findings.