Umbilical artery histomorphometry: a link between the intrauterine environment and kidney development.

Prematurity is a risk factor for hypertension, vascular stiffness, nephron deficit and adult onset cardiorenal disease. The vascular tree and kidneys share morphogenic drivers that promote maturation in utero before 36 weeks of gestation. Vascular elastin accrual terminates after birth leaving collagen to promote vascular stiffness. Our objective was to determine if the histomorphometry of the umbilical artery, an extension of the aorta, parallels nephron mass across gestational age groups. From a cohort of 54 newborns, 32 umbilical cord specimens were adequate for evaluation. The umbilical cord was sectioned, stained with trichrome, and digitalized. Muscular and collagenous areas of the umbilical artery were measured in pixels using the Image J 1.48q software. Total kidney volume was measured by ultrasound and factored by body surface area (TKV/BSA). The umbilical artery total area was significantly greater in term v. preterm infants (9.3±1.3 v. 7.0±2.0 mm2; P<0.05) and increased with gestational age; while the percent muscular and collagen areas were independent of gestational age (R 2=0.04; P=ns). Percent muscular area correlated positively with TKV/BSA (r=0.53; P=0.002); while an increase in collagen correlated inversely with kidney mass (r=-0.53; P=0.002). In conclusion, an enhanced % muscular area and presumed vascular elasticity was associated with increased renal mass in all infants. Umbilical artery histomorphometry provides a link between the intrauterine environment, vascular and kidney development.

Identification of poor responders to erythropoietin among children undergoing hemodialysis.

OBJECTIVES: To identify the factors determining a high recombinant human erythropoietin (rHuEPO) dose requirement and associated side effects in children undergoing hemodialysis. STUDY DESIGN: We retrospectively analyzed the clinical data of 23 children (aged 5-20 years) undergoing long-term hemodialysis. All subjects received intravenous rHuEPO to maintain hemoglobin levels > or = 10 g/dL and had iron supplement. Subjects were divided into 2 groups: those receiving high-dose rHuEPO (> or = 450 U/kg/wk) and those receiving an average dose (< 450 U/kg/wk). We compared the specific variables between both groups by using Mann-Whitney, Fisher exact, and linear regression tests; a P value < .05 was considered significant. RESULTS: Four of 23 subjects (17%) received high-dose rHuEPO despite iron repletion. These subjects were small and young and had frequent bacterial infections, high ferritin levels, and severe hyperparathyroidism. Two patients with human immunodeficiency virus infection required high-dose rHuEPO. The main adverse effect of high-dose rHuEPO was an increase in the heparin requirement during hemodialysis. CONCLUSIONS: Age, body weight, inflammatory status, and severity of hyperparathyroidism should be taken into account when adjusting rHuEPO dose for children undergoing hemodialysis. Furthermore, we suggest that high rHuEPO doses are related to an increase in the heparin requirement in these children.

ACE inhibition scintigraphy in the management of hypertension in children.

Angiotensin converting enzyme (ACE) inhibition scintirenography was performed to help establish the diagnosis and plan treatment of renovascular hypertension (RVH) in 57 hypertensive pediatric patients, 33 infants and 24 children older than 1 year. In 16 of 33 hypertensive infants, ACE inhibition scintirenography established the diagnosis of RVH from renal ischemia (due to aortic or renal arterial thrombi). Two scintigraphic criteria were used for the diagnosis of RVH: criterion I, ischemic and damaged kidney (a non-functioning kidney on or off ACE inhibition) and criterion II, ischemic but not damaged kidney (ACE inhibition induced deterioration of function of the kidney). When criterion I was present and the contralateral kidney was normal, ACE inhibitors could be used for treatment of hypertension without deterioration of renal function; kidneys satisfying criterion I eventually involuted or manifested growth arrest and frequently caused persistent RVH, even after resolution of the thrombus, requiring nephrectomy. When criterion II was present bilaterally, or it was associated with criterion I contralaterally, the use of antihypertensive drugs other than ACE inhibitors was necessary in order to prevent renal insufficiency or failure from ACE inhibitors. However, kidneys with criterion II showed normal growth and, following retraction or dissolution of the aortic thrombus, hypertension resolved. In 2 of 24 hypertensive children older than 1 year, the test was diagnostic of branch renal artery stenosis; RVH was cured by selective angioplasty. ACE inhibition scintirenography is useful in the evaluation and planning of treatment in children with hypertension and may predict the outcome of therapy and ultimate renal function.

Nutritional intake in children with renal insufficiency: a report of the growth failure in children with renal diseases study.

OBJECTIVE: This study was designed to assess sequentially the nutrient intake in children with chronic renal insufficiency and its relationship to body size, the level of renal failure, and growth velocity. METHODS: The nutrient intake from 401 4-day food records obtained from 120 children with renal insufficiency over a 6-month observation period was analyzed. The height and weight were measured at the beginning and end of the observation period. The glomerular filtration rate was estimated from the height and serum creatinine. RESULTS: The mean caloric intake in these children was 80 +/- 23% (mean +/- SD) of the Recommended Dietary Allowance (RDA) for age. Fifty-six percent of the food records obtained from these children revealed a caloric intake that was less than 80% of the RDA. Caloric intake expressed as the %RDA for age decreased with increasing age. However, the mean caloric intake when factored by body weight was in the normal range. There was no correlation between caloric intake and height velocity. The mean protein intake in these children was 153 +/- 53% of the RDA. Further, 45% of the food records indicated a protein intake greater than 150% of the RDA. There was no relationship between the degree of renal insufficiency and caloric or protein intake. Calcium, vitamin, and zinc intakes were also low. CONCLUSIONS: Children with chronic renal failure consume less calories than their age matched peers, but the majority of these children appear to ingest adequate amounts for their body mass. This reduction in caloric intake occurs early in renal insufficiency. They also ingest inadequate amounts of calcium, zinc, vitamin B6, and folate.

Validity of random urines to quantitate proteinuria in children with human immunodeficiency virus nephropathy.

Accurate assessment of proteinuria in pediatric patients infected with the human immunodeficiency virus (HIV) is limited by constraints imposed by timed urine collections and low creatinine excretion in very ill patients with low muscle mass. We therefore sought to validate the use of random urine specimens to quantitate total protein and creatinine excretion in a population of 236 HIV-positive children. A mathematical derivation for estimating urine volume (V) was constructed. The accuracy of the final calculation [V = 832 (kL/Ucr)BSA] (where k = constant, L body length, UCr urine creatinine and BSA body surface area) was tested by regression analysis comparing the calculated and measured volume of 31 urines from ambulatory HIV-negative patients. The correlation coefficient was highly significant (r = 0.77, P < or = 0.0001). The relationship was also applied to 23 timed urine specimens from HIV-positive patients with similar significance (r = 0.87, P < 0.0001). A regression analysis of measured proteinuria against the urine protein: creatinine ratio (Upr/Ucr) in these same urines from the HIV-positive patients yielded a significant relationship both in the linear (r = 0.95, y = 0.4x) and the logarithmic regression (r = 0.97, y = x + 0.4). These data support the use of random Upr/Ucr ratios to estimate daily proteinuria in HIV-infected pediatric patients despite low creatinine excretion rates. The previously accepted values continue to apply, with Upr/Ucr < or = 2.0 considered normal and > 2.0 representative of nephrotic proteinuria.

A prospective, double-blind study of growth failure in children with chronic renal insufficiency and the effectiveness of treatment with calcitriol versus dihydrotachysterol. The Growth Failure in Children with Renal Diseases Investigators.

Because controlled trials in adults have shown accelerated deterioration of renal function in a small number of patients receiving calcitriol for renal osteodystrophy, we initiated a prospective, randomized, double-blind study of the use of calcitriol versus dihydrotachysterol in children with chronic renal insufficiency. We studied children aged 1 1/2 through 10 years, with a calculated glomerular filtration rate between 20 and 75 ml/min per 1.73 m2, and with elevated serum parathyroid hormone concentrations. Ninety-four patients completed a mean of 8.0 months of control observations and were randomly assigned to a treatment period; 82 completed the treatment period of at least 6 months while receiving a calcitriol dosage (mean +/- SD) of 17.1 +/- 5.9 ng/kg per day or a dihydrotachysterol dosage of 13.8 +/- 3.3 micrograms/kg per day. With treatment the height z scores for both calcitriol- and dihydrotachysterol-treated groups showed no differences between the two groups. In relation to cumulative dose, there was a significant decrease in glomerular filtration rate for both calcitriol and dihydrotachysterol; for calcitriol the rate of decline was significantly steeper (p = 0.0026). The treatment groups did not differ significantly with respect to the incidence of hypercalcemia (serum calcium concentration > 2.7 mmol/L (> 11 mg/dl)). We conclude that careful follow-up of renal function is mandatory during the use of either calcitriol or dihydrotachysterol because both agents were associated with significant declines in renal function. There was no significant difference between calcitriol and dihydrotachysterol in promoting linear growth or causing hypercalcemia in children with chronic renal insufficiency. Dihydrotachysterol, the less costly agent, can be used with equal efficacy.

Growth of uremic infants on forced feeding regimens.

Infants born with congenital renal insufficiency generally grow poorly during the first years of life and incur a height deficit that is rarely regained. Actual energy and protein requirements have not been determined for these children. In 12 infants with creatinine clearances less than 70 ml/min per 1.73 m2, growth and nutrient intakes were monitored during the first 2 years of life. Forced feeding regimens after 3 months of age, including gastrostomy in 3 patients, were necessary to maintain energy intakes near 100% of the recommended dietary allowance (RDA). Protein intakes averaged in excess of 140% RDA. Linear growth did not correlate with either energy or protein intakes, suggesting that neither was a limiting factor to growth. Length velocity standard deviation score (LV-SDS) did not correlate with degree of renal insufficiency at any age, but average LV-SDS did relate significantly and inversely to C-terminal parathyroid hormone (PTH) levels. Growth parameters, including LV-SDS and weight velocity SDS (WV-SDS) were lowest at 6 months of age. Weight and length SDS followed with a maximum decline at 12 months of age. While weight for length SDS remained normal and WV-SDS showed recovery during the 2nd year, LV-SDS remained negative. Length SDS stabilized near--2 SDS. In summary, these data suggest that the major height deficit in infants with renal insufficiency is incurred during the first 6 months of life. Ponderal indices suggested that very early nutritional deficits may have been a primary contributor to subsequent height deficits.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical management of the pediatric renal-allograft recipient.

Management of the pediatric renal-transplant recipient requires careful pretransplant evaluation including psychosocial assessment and cautious donor/recipient selection. Early transplantation is preferable in infants less than 1 year of age if a suitable live-related donor is available. However, cadaveric-allograft transplantation is best reserved for patients older than 3 years with donors older than 5 years. Pre-emptive transplantation is suitable for approximately one fifth of the population. Medical preparation includes careful HLA-A, -B, and -DR loci matching, interferon treatment for positive hepatitis antigenemia, and acyclovir prophylaxis for a cytomegalovirus (CMV) antibody-negative patient to a seropositive donor. Postoperative management requires close monitoring of the patient's volume status with careful fluid replacement in the form of colloid and crystalloid. Immunosuppression involves multiple drug regimens that include corticosteroids, ciclosporin, azathioprine, antilymphocyte (or -thymocyte) globulin (ALG/ATG), monoclonal antibodies (OKT3), and a ciclosporin alternative: FK-506. Long-term complications dictate management and are divided into medical, surgical, immune, and infectious categories. These are predominated by treatment of acute and chronic rejection, hypertension, and CMV infection.

Linear growth and anthropometric and nutritional measurements in children with mild to moderate renal insufficiency: a report of the Growth Failure in Children with Renal Diseases Study.

During the control period of the Growth Failure in Children With Renal Diseases Study, investigators at 23 centers were able to observe and characterize growth and to make anthropometric and nutritional measurements in 82 children with mild to moderate renal insufficiency. As a multicenter, controlled clinical trial designed to study the relative efficacy of 1,25-dihydroxyvitamin D3 and dihydrotachysterol in the treatment of renal osteodystrophy, no prior vitamin D exposure and a creatinine clearance of 25 to 75 ml/min/1.73 m2 were criteria for entrance into the clinical trial. Ages ranged from 18 months to 11 years (mean 5.6 +/- 3.1 years), and distribution by age category was as follows: 38%, 1 to 3 years; 28%, 4 to 6 years; and 34%, 7 to 10 years. There was a 3:1 male/female ratio; 72% of the patients had congenital disease by the International Classification of Diseases (ninth revision). Mean creatinine clearance was 49.5 +/- 20 ml/min/1.73 m2. The C-terminal parathyroid hormone values (1121 +/- 1562 pg/ml) were well above 2 SD of the mean of a normal growing population of similar age. Parathyroid hormone values correlated with degree of renal insufficiency (r = -0.57) and with height by bone age but not with chronologic height or growth velocity. The bone age/height age ratio, a predictor of growth potential in normal children, was low for the entire series of patients (0.88 +/- 0.35) but failed to correlate with growth velocity and was negatively correlated with rising parathyroid hormone levels. Average values for height, weight, triceps skin fold, mid-arm muscle circumference, and body mass index were within 2 SD of the mean of the normal population, although measurements for the 1- to 3-year age group were significantly less than those of the older patients. Total energy intake averaged less than 86% of the recommended dietary allowances; total protein intake was more than 161% of the allowance. Nitrogen balance in 23 patients was positive and correlated most significantly with increasing energy intake (r = 0.6). Growth velocity, calculated from the interval gain during the month control period, averaged +0.3 SD, with the highest growth velocity z scores recorded for those with acquired disease. A growth velocity index, expressed as the slope of the regression between change in height SD and growth velocity z score, was used to describe the growth accomplished in the control period by age category.(ABSTRACT TRUNCATED AT 400 WORDS)

Use of a soft catheter for acute peritoneal dialysis in infants and children.

Acute peritoneal dialysis in 49 infants and children is described comparing the use of the conventional hard Trocath catheter and the soft catheter. The mean age of the patients was 3.6 years (range 1 day--17 years). Sixteen were treated using the hard Trocath catheter and 33 were treated using a soft catheter. Overall mortality for the total patient population was 43%. Twenty-three neonates were included in the series with an overall mortality of 61%. Significantly less mortality was observed in the 26 patients older than two months of age (31%). Major complications of the dialysis procedure included viscus perforation in three neonatal patients and subcutaneous extravasation of dialysate in two older patients. These major complications occurred only with the use of the Trocath. Two episodes of peritonitis occurred in two adolescent patients and were associated with an interruption of the sterile system. Peritonitis was not specifically related to the type of catheter used. We conclude that major complications associated with the use of the hard catheter for peritoneal dialysis in neonates precludes its continued use in this population. The alternative use of a soft catheter is recommended in neonates. Elective use of a soft catheter for acute peritoneal dialysis in older patients would also seem to be indicated.

Treatment of critical neonatal edema with hemo-ultrafiltration.

Three neonates with extreme edema associated with cardiovascular and renal insufficiency were treated with hemo-ultrafiltration for removal of critical edema fluid. In each patient peritoneal dialysis had not been effective in expedient fluid removal. Ultrafiltration was accomplished by occlusion of the proximal dialysate portal of a Travenol EX12-11, 0.8 m2 dialyzer and the application of vacuum suction to the distal portal. Blood flow ranged from 10-25 ml/min. The rate of ultrafiltration averaged 0.57 ml/kg/min resulting in losses of 4-16% of body weight. Episodes of hypotension were associated with too rapid ultrafiltration rate and not total volume removed. All patients tolerated the procedure. Two of the three patients demonstrated improvement in blood pressure, oxygenation and urine flow following the ultrafiltration. Ultrafiltration in the newborn may be a useful therapeutic procedure when conventional treatment fails.

Effects of amino acid additives during hemodialysis of children.

The intradialytic losses into the dialysate of free amino acids (AA) and alpha-amino nitrogen were determined during the dialysis of three children. Variations in plasma AA were determined pre- and postdialysis. The effect of these losses with the addition of an Abbott General Amino Acid Mixture to the dialysate in concentrations of 8.5, 17, and 34 mg/100 ml was studied. The major determinant of AA losses was the plasma concentration of the AA before beginning the dialysis treatment. Dialysance of individual AA varied inversely with their molecular weights. A zero flux of alpha-amino nitrogen occurred at a derived concentration of 22 mg/100 ml of the AA additive in the dialysate. Plasma concentrations of nonessential amino acids were little affected by the dialysate additive. In contrast, total essential amino acid nitrogen which fell during baseline dialyses showed significant improvement when the AA solution was added to the dialysate. This study suggests that the addition of AA to the dialysate bath may be effective in decreasing AA nitrogen losses during dialysis.

Tyrosine supplementation in chronic experimental uremia.

The occurrence of low tyrosine tissue levels in uremic subjects, possibly due to impaired phenylalanine hydroxylation, suggests that tyrosine may be an essential amino acid in uremia. Additional dietary tyrosine may thus re-dress the deficiency. This study examined growth and tyrosine/phenylalanine metabolism in uremic rats during tyrosine supplementation. Rats made uremic (U) by 7/8 nephrectomy were compared to pair-fed (CP) and ad libitum-fed (CA), sham-operated controls. Two sets of each group of rats were studied after 21 days on the respective diets: I = Purina Lab Chow; II = same + 3.5% tyrosine. Plasma tyrosine was below normal in U and CP-fed diet I. With diet II, the tyrosine:phenylalanine ratio in U was lower than both CA and CP. In rats fed diet II, the tyrosine:phenylalanine ratio became indistinguishable among the three groups. Growth parameters in U and CP were similar, regardless of the diet. Body weight gain, tibial length, muscle mass, and tissue protein did not improve in uremic animals supplemented with tyrosine. The specific activity of liver phenylalanine hydroxylase in U was not different from CA or CP. However, loss of cortical renal mass appeared to be the major determinant of decreased kidney phenylalanine hydroxylation in experimental uremia. This alteration is likely to be the greatest contributory factor to the alteration of plasma levels of tyrosine and phenylalanine. The data presented do not support a proposed essentiality of tyrosine in uremia.

The effect of energy and nitrogen intake upon urea production in children with uremia and undernutrition.

Children with severe uremia who had anorexia were observed in a clinical study center where dietary energy and nitrogen intake could be compared with urea nitrogen production (UNPr). The children received a supplement of dextrose and amino acids at night, ate a self-selected diet and were encouraged to use carbohydrate supplements. Energy intake varied from 22 to 110 kcal/kg/day and nitrogen intake from 105 to 323 mg/kg/day. UNPr was reciprocally related to energy intake. Nitrogen intake minus UNPr, an index of nitrogen balance, was positively related to energy intake. UNPr was not related to nitrogen intake. Nitrogen intake (NI) and NI-UNPr were correlated and the slope of the regression was 1.15. We inferred from the data that low energy intakes (less than 60 kcal/kg/day) were associated with catabolic losses of body protein. Intakes above that level were associated with a low and stable rate of UNPr. The level of energy and nitrogen intake within the range observed limited the rate of nitrogen retention. Once maintenance requirements for energy and nitrogen were satisfied, the efficiency with which nitrogen was used for net protein synthesis was very high.

Total parenteral nutrition in anuric children.

Six children who were anuric, intolerant of oral nutrition and depleted of body protein, were treated with total parenteral nutrition. Nitrogen utilization was studied during infusion of dextrose alone and dextrose with essential amino acids. An increase in non-protein (glucose) calories from 20 to 70 kcal/kg/day progressively reduced body protein catabolism; nitrogen balance became less negative. When essential amino nitrogen was added, net urea production decreased; protein nitrogen balance became positive. It is concluded that total parenteral nutrition with essential amino acids improves the nutritional status of severely ill, anuric children, and may influence recovery.

Plasma amino acid patterns during supplemental intravenous nutrition of low-birth-weight infants.

In 42 low-birth-weight infants (smaller than 1,200 gm), we have compared the effects of intravenous nutrition supplement versus conventional feedings on growth, morbidity, mortality, and plasma amino acid patterns. Despite similar total caloric intake in INS and control groups, weight gain was greater in the INS infants. The overall mortality rate did not differ in the two groups. Nonsurviving infants receiving INS lived longer (mean equal to 30 days) than nonsurviving CON infants (mean equal to 5 days). Complications were equally frequent in both groups except that hyperglycemia occurred more often in infants receiving INS. The plasma aminogram of the LBW infant is described and compared to those of the full-term infant and adult. Hypoaminoacidemia was present at birth in the LBW infants, concentrations of glutamine, alamine, glycine, histidine, and ornithine being significantly (P smaller than 0.05) below FT values. During INS, elevations of threonine, serine, and methionine above FT values occurred. Glutamine remained subnormal despite INS. Recommendations for an INS solution more suitable for use in LBW infants are presented.