Ben H. Brouhard

Cognitive functioning in children on dialysis and post‐transplantation

Abstract: 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/caregivers 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 mothers/caregivers have lower educational levels.

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.

The association of idiopathic hypercalciuria and asymptomatic gross hematuria in children

Seven children with asymptomatic gross hematuria are described. Six had recurrent hematuria; one had a single episode. Occasional global glomerulosclerosis and/or mesangial electron dense deposits were present in the three patients in whom renal bipsy was performed; the changes were felt to be insufficient to account for the hematuria. None of the patients had urolithiasis or any significant urinary tract abnormality. One was an adopted child; a family history of urolithiasis was obtained in the other six. Idiopathic hypercalciuria was documented in six patients; the seventh subsequently passed a calcium oxalate calculus. One patient is 10 weeks of age at the time of this submission. Of the remainder, three patients received no specific therapy; renal calculi developed six months, six years, and eight years later. Three patients were treated with a thiazide diuretic soon after onset of hematuria and confirmation of idiopathic hypercalciuria; there was complete cessation of hematuria within five days with no recurrence as long as therapy was continued. We suggest that measurement of urinary calcium excretion as part of the initial evaluation of a child with gross hematuria may, in some cases, obviate invasive investigations and allow for effective therapy.

Cognitive functioning and school performance in children with renal failure

Although previous studies have documented neuropsychological deficits in children with end-stage renal disease, few have evaluated and compared the cognitive functioning and the school performance of children with renal failure. The current study evaluated the influence of chronic renal failure on cognitive functioning and school performance in children and adolescents with end-stage renal disease undergoing dialysis and after renal transplantation. Participants were given standardized IQ and achievement tests to assess cognitive functioning and ability. Academic performance was determined by evaluating grades for the semester in which the testing was performed; a grade point average (GPA) was calculated based on a 4.0-point scale. The 11 dialysis patients and 13 transplant patients were comparable in age, race, sex, and socioeconomic status. Overall IQ and subtest scores demonstrated no differences between the two groups. Performance on the Woodcock-Johnson achievement tests showed that the transplant patients did better on achievement tests of written language (P=0.04) and in school performance in English compared with dialysis patients (P<0.05). Furthermore the dialysis patients tended to be below age and grade level in all areas, whereas the transplant patients were achieving at or above these levels. There were significant differences in the age equivalent scores between the dialysis and transplant patients in the areas of mathematics and written language (P<0.05). However, when grades were evaluated there were no differences in overall GPA or in the mathematics GPA. Days absent were not different between the two groups. These data demonstrate that both groups of patients were of similar intellectual ability; the achievement of the dialysis patients was behind that of the transplant patients and this lag was not necessarily reflected in school grades. Patients with chronic renal failure should have cognitive and achievement testing on a regular basis, and areas of deficit should be addressed by the schools.

Bone mineral density of the lumbar vertebrae in children and adolescents with insulin-dependent diabetes mellitus

To test the hypothesis that bone mineral density (BMD) is lower in children with insulin-dependent diabetes mellitus (IDDM), we measured BMD of the lumbar vertebrae (L-2 to L-4) by dual-photon absorptiometry in 31 boys and 25 girls, mean age 12.3 years, with IDDM of varying clinical duration (range 0.1 to 14.8 years). Mean standard deviation scores (z scores) were determined for L-2-L-4 BMD, weight, height, weight percentile, and weight-adjusted L-2-L-4 BMD index (L-2-L-4 BMD/weight), with reference data from a previously described white, nondiabetic, age-matched control group (n = 221). Compared with nondiabetic control subjects, male patients with short-term IDDM and all female patients with IDDM did not have significantly different L-2-L-4 BMD, weight, weight percentile, height, or BMD index. Boys with IDDM longer than 1 year had significantly lower weight, weight percentile, and height than did age-matched control subjects. When L-2-L-4 BMD of boys with long-term diabetes was corrected for weight, the L-2-L-4 BMD index was significantly greater than that of control subjects, indicating that weight was disproportionately lower than BMD. There were no significant linear correlations between metabolic control and L-2-L-4 BMD. When L-2-L-4 BMD was adjusted for differences in body weight, spinal BMD values in children with IDDM were not lower than in control subjects. These findings indicate that in children with IDDM, as in previously studied nondiabetic youths, body weight and spinal BMD are highly correlated; although BMD is reduced in some children with diabetes, the reduction parallels reductions in growth, and may simply reflect a normal response of the skeleton to a lower weight-bearing load.

Renal Manifestatións 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.

Effect of antihistamine-antiserotonin and ganglionic blocking agents upon increased capillary permeability following burn trauma.

: Tiny (0.2% TBS), partial thickness, non-contact radiant heat burns in guinea pigs resulted, within 3 hours, in significant edema formation and protein leakage at the site of the injury. Areas of skin distant to the burn also showed an increase in water content but no protein leakage. Pretreatment of the animals with either chlorisondamine hydrochloride or a mixture of methysergide and chlorpheniramine significantly decreased postburn edema formation and protein leakage. Liquid emulsion autoradiography revealed that leakage of protein occurs primarily in the areas of skin adjacent to the panniculus carnosus. The studies suggest that: the increase in vascular permeability that occurs as a consequence of burn injuries is humorally mediated; albumin leakage is limited to the injured tissues; and histamine, serotonin, and presumably catecholamines play significant roles in the development of this phenomenon.

Burn edema and protein leakage in the rat. I. Relationship to time of injury.

Abstract Studies to determine the relationship between increased vascular permeability (water content and protein leakage) and time postinjury were performed in rats. Three small, thermal burns were inflicted to the left of the spine. Animals were sacrificed at the following time intervals postinjury: 0.5, 1.5, 3, 6, 12, 18, 24, 36, and 48 hr. Radio-iodinated human serum albumin (131I-RISA), 200 μCi/kg body weight, was given iv 30 min prior to sacrifice. Segments of skin were obtained, weighed, counted (scintillation counting), dried (60° for 96 hr), and reweighed. Autoradiographic studies were also performed. Water content was maximal at 3 h postburn and was no longer demonstrable by 24 hr. Albumin leakage was maximal at 30 min and disappeared by 12 hr postinjury. In another set of experiments in which 131I-RISA was injected at the time of the burn, high tissue counts persisted for as long as 48 hr. These studies have shown that abnormal albumin extravasation occurs only during the first 6 to 12 hr postinjury. Once in the interstitium, however, albumin may remain trapped for up to 48 hr.

Immune deposits and mesangial hypercellularity in minimal change nephrotic syndrome: Clinical relevance

Occasional patients with nephrotic syndrome and minimal histologic change demonstrate glomerular deposition of small amounts of immunoglobulin and complement. Some consider this a disease distinct from MCNS. To investigate the clinical importance of immune deposits and mesangial hypercellularity in the initial biopsy, the clinical records, follow-up data, and renal biopsies of 68 patients (ages 6 months to 16 years) with MCNS by light microscopy were reviewed. Among 68 patients followed a mean of 6.2 years, eight of 25 patients with immune deposits on initial renal biopsy were steroid nonresponsive. Only one of 43 patients without immune deposits was steroid nonresponsive (P = 0.00005). Of 44 patients with normal mesangial cellularity, 31 experienced fewer than three relapses a year, whereas of 15 patients with mesangial hypercellularity, only six experienced fewer than three relapses a year (P = 0.035). The data suggest that immune deposits and increased mesangial cellularity in children with NS and minimal light microscopic change may predict the clinical course.

Urinary Excretion of N-Acetyl-Beta-D-Glucosaminidase in Children with Type I Diabetes Mellitus

N-acetyl-beta-D-glucosaminidase (NAG), a lysosomal enzyme, has been shown to be increased in the urine of patients with various glomerulonephritides, tubulointerestitial diseases, renal allograft rejection, toxic renal injury, and diabetes mellitus. Although it has been suggested that urinary NAG may reflect blood glucose control, no studies have correlated this with other measures of metabolic control. Thirty-four children from a diabetic summer camp were found to have urinary NAG to creatinine ratios significantly above those of normal controls of similar age (5.22 ± 1.19 versus 1.51 ± 0.17 U). Urinary NAG was found to positively correlate with an arbitrary control index (r =0.82; P < 0.05) and in seven patients with hemoglobin A1c (r =0.70; P < 0.001). In a closely followed group of 40 clinic patients, urinary NAG to creatinine ratio was again found to be significantly increased over normal controls (7.55 ± 0.70 versus 1.51 ± 0.17 U; P < 0.05). Again, urinary NAG was positively correlated with HbA1c (r =0.62; P < 0.001) and urinary albumin to creatinine ratio (r =0.47; P < 0.01). In neither group was there a correlation with UNAG:UCr and duration of disease. Thus, these data suggest that urinary NAG to creatinine ratio appears to be a reflection of blood sugar control.