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We investigated the prevalence and potential predictors of Doppler echocardiographic evidence of diastolic function in untreated hypertensive children. Doppler and M-mode echocardiographic values from 42 children (mean age 13, range 5-17 years) from a pediatric hypertension clinic were retrospectively reviewed and compared to data from 39 age and gender matched normotensive children in a control group. Compared to the participants in the control group, hypertensive patients had increased mean body mass index (29 v 19 kg/M2, P < .0001), peak mitral A velocity (57 v 42 cm/sec, P < .0001), isovolumic relaxation time (65 v 42 msec, P < .0001, resting heart rate (90 v 74 bpm, P < .0001), mitral E deceleration time (150 v 137 msec, P = .006), indexed left ventricular mass index (32 v 26 g/M2.7, P < .0001), relative left ventricular wall thickness (0.32 v 0.29, P = .02), and decreased ratio of peak mitral E velocity/peak mitral A velocity (1.7 v 2.1, P = .0001). Mean age, height, mitral E velocity, mitral A deceleration time, fractional shortening, and indexed left ventricular diastolic dimension were similar in patients and control group children. In the hypertensive patients, multivariate analysis demonstrated that heart rate (P = .0008) and systolic blood pressure (P = .03) were significant predictors of peak A velocity. In addition, heart rate (P = .0003), body mass index (P = .04), and indexed left ventricular diastolic dimension (P = .04) predicted the ratio of peak E/peak A velocity. None of the measures of diastolic function correlated with left ventricular mass index or relative wall thickness. Furthermore, none of the analyzed variables predicted isovolumic relaxation time or mitral E deceleration time. We conclude that untreated hypertensive children have Doppler indices suggestive of impaired left ventricular relaxation. Resting heart rate was the strongest predictor of abnormal diastolic indices.

We report a 15-year-old girl who developed a ureteral perforation soon after living-related donor renal transplantation. Her presentation was unusual in that a symptomatic pleural effusion accumulated as an extension of the perinephric urine collection. Recognition and surgical correction of the ureteral pathology led to resolution of respiratory symptomatology and full recovery of renal function.

We report the case of a patient with infantile nephropathic cystinosis who required renal transplantation at age 30 months. Exhaustive evaluation did not identify a cause of progressive renal failure other than cystinosis. The patient's genetic lesion was allelic with those of other patients with cystinosis; fusion of this patient's fibroblasts with fibroblasts from another patient with infantile nephropathic cystinosis did not demonstrate complementation of the biochemical defect.

Since the advent of US, nearly every malformation of the urinary tract has been diagnosed in utero. Physiologic dilatation of the renal pelvis occurs and can be misdiagnosed as hydronephrosis, so the normal gestational development of the urinary tract, and its visualization by ultrasound, should be understood. Gestational diagnosis is important for family counseling, collaboration of the perinatal team, and for determining both the future evaluation needs and the possibility of intervention. Those infants at high risk, as well as others who have specific signs and symptoms of possible urinary tract disease, deserve prompt and careful postnatal imaging studies. Ultrasonograms may be combined with other imaging modalities in specific circumstances to provide accurate diagnoses and some functional information.

Prior to 1975 patients with systemic lupus erythematosus were generally not considered candidates for renal transplantation because of concern that immune complex deposition would rapidly destroy the allograft. However, recent evidence suggests that good patient and graft survival rates can be achieved comparable to other renal diseases. Between September 23, 1963 and July 31, 1990, 1070 renal transplants were performed at Washington University Medical Center (WUMC). During this period, 14 patients with SLE (12 female and 2 male) received 16 renal transplants (7 living-related donor [LRD], 1 living-unrelated donor [LURD], and 8 cadaver [CAD]). The mean age at the time of the first transplant was 32.5 +/- 10.3 years. The duration of disease prior to transplant was 88.0 +/- 45.9 months and the duration of hemodialysis prior to transplant was 36.0 +/- 33.7 months. Of these patients, 7/14 (50%) had negative and 3/14 (21%) positive SLE serology pre- and post-transplant, 3/14 (21%) had negative serology pretransplant that became positive posttransplant, and 1/14 (2%) was positive pretransplant and became seronegative posttransplant. Patient survival was 92.8% (13/14), and of the 16 kidneys transplanted 62.5% (10/16) are still functioning with a mean follow-up period of 43.7 +/- 45 months. The current mean serum creatinine was 1.4 +/- 0.26 mg/dl. One noncompliant patient developed recurrent lupus nephritis bringing the total number of cases reported in the literature to seven. The present study demonstrates that patients with SLE can be transplanted with excellent patient and graft survival and function and a low rate of recurrent lupus nephritis. From a review of the literature, there appears to be an association between positive SLE serology pre- and posttransplant and recurrent lupus nephritis.

Renal dysplasia and agenesis as isolated findings are usually considered sporadic, noninherited abnormalities. We report three kindreds with familial renal adysplasia. Two or more children were affected in each of the families and at least one member--whether proband, sibling, or parent--had a clinically silent anomaly. Normal kidneys in the parents did not preclude the occurrence of renal adysplasia in more than one child. The empiric risks for offspring and first-degree relatives were 50% and 25%, respectively, suggesting a strong genetic factor such as a major dominant gene with variable expression. Because the disease appears to be genetic in some cases of renal adysplasia, careful screening of the proband's family, subsequent children, and pregnancies is important for the purpose of accurate genetic counseling.

Pre-emptive (primary) renal transplantation is occurring with greater frequency as pediatric transplant centers attempt to initiate renal replacement therapy at a time best designed to optimize growth and development in children. Psychosocial benefits of performing pre-emptive transplant are highlighted by an intervention before the child has symptoms of uremia and, thus, develops a self-image as a "sick patient with end-stage renal disease", avoidance of dependence on machine technology, avoidance of a change in parenting that may occur with fears about dialysis, and maintenance of an orientation toward future goals. In addition, the child will likely have less loss of school time and less disturbance in previously established social patterns. Difficulties that may be enhanced in pre-emptive transplantation arise from potentially decreased involvement of the child and family in the medical (transplant) care system prior to transplantation. The two major issues of concern are: (1) optimal education regarding patient (family) responsibility toward quality care of the graft recipient; (2) the accurate assessment of coping skills coupled with the development of optimum psychosocial support from the health care workers and community support services. The provision of a good educational and supportive program is time consuming and financially draining. We must develop creative approaches to these areas in order to enhance each child's opportunity for family and community interaction, as well as physical well-being.

Idiopathic nephrotic syndrome has been postulated to have an immunopathogenic basis. To determine whether steroid-sensitive nephrotic syndrome is associated with greater than expected frequencies of specific extended haplotypes of the major histocompatibility complex, we studied genetic markers (Class I, II, III HLA alleles and glyoxalase I) in 173 subjects in 42 families of patients with nephrotic syndrome of childhood. The single allele, DQW2, was found in 72% of steroid sensitive patients compared with only 35% of the controls (P = 0.003). In half of 32 steroid sensitive, but not 10 steroid resistant, patients, one or both of two specific extended haplotypes (alleles that segregate together) were identified. The first, [HLA-A1, B8, DR3, DRW52, SCO1], occurred in 11 of 64 haplotypes, or 17%, compared to 5% of controls (P = 0.017). The other, [HLA-B44, DR7, DRW53, FC31], occurred in 10 of 64 haplotypes, 16% compared to 3.8% of controls (P = 0.014). Five patients had both haplotypes. Patients with these specific extended haplotypes had a greater frequency of relapses than did those with other haplotypes. These data provide additional support for the hypothesis that steroid-sensitive nephrotic syndrome has an immunogenetic basis.

Computed tomography of the head in 15 children with end-stage renal disease revealed cerebral cortical atrophy in eight and ventricular enlargement in an additional two. These changes were not necessarily associated with any clinical signs or symptoms. Although high doses of steroids may have been responsible for some of the lesions, alternate etiologies are required to explain the abnormality in others cases. The mean length of time the patients received chronic hemodialysis was twice as long in patients with atrophy as in those with normal scans. However, possible causative factor/s related to dialysis could not be identified. The high incidence of cerebral atrophy is cause for concern and indicates the need for further study of this phenomenon.

Extracts of rat atria are potent stimulators of sodium and urine excretion, and relax vascular and intestinal smooth muscle preparations. The structures of six biologically active peptides obtained from atrial extracts are reported here. Ion exchange chromatography of a low molecular weight fraction obtained by gel filtration of atrial extracts produced two natriuretic fractions: the first induced relaxation of intestinal smooth muscle strips only, whereas the second also relaxed vascular strips as well. From the first fraction four pure biologically active peptides obtained by reverse phase HPLC have been sequenced: the 21 amino acid peptide, designated atriopeptin I, and three homologs (des- ser1 -, des- ser1 -ser2-, and des- ser21 - atriopeptin I). From the second fraction two pure biologically active peptides were obtained, which had C-terminal extensions of atriopeptin I: atriopeptins II (23 amino acid residues) and III (24 residues), having respectively phe-arg and phe-arg-tyr C-termini. These results suggest that this family of six peptides, sharing the same 17 membered ring formed by an internal cystine disulfide, is derived from a common high molecular weight precursor.

Mammalian atria possess bioactive peptides that are natriuretic-diuretic and potent relaxants of vascular and nonvascular smooth muscle. Characterization of the biological activity of rat atrial extracts indicates two major peaks, having apparent molecular weight of 20,000-30,000 (atriopeptigen) and less than 10,000 (atriopeptins). The amino acid sequence of atriopeptins I, II and III have been determined, and it has been found that their structures are only slightly different. Atriopeptin I (twenty-one amino acid residues); ser-ser-cys-phe-gly-gly-arg-ile-asp-arg-ile-gly-ala-gln-ser-gly-leu-gly- cys- asn-ser) relaxes intestinal but not vascular smooth muscle strips, and is natriuretic. Atriopeptins II and III (23 and 24 residues; the 21-sequence of I with the addition of phe-arg or phe-arg-tyr at the C-terminus, respectively) relax intestinal and vascular smooth muscle strips and are potent natriuretics. Since atriopeptigen and the atriopeptins exhibit similar biological effects the possibility of a precursor-product relationship was tested. Mild proteolytic digestion (1IU/ml trypsin) of atriopeptigen activates this peptide and reduces its apparent molecular weight. Examination of whether the atria of Krebs perfused isolated hearts released the bioactive atrial peptides revealed the presence in the cardiac effluent of a trypsin-labile substance that was natriuretic-diuretic and a smooth muscle relaxant. To determine which form of the atrial peptide (e.g. atriopeptigen or atriopeptin) is released by the atria the cardiac effluents were concentrated and partially purified. The cardiac effluent contained a substance(s) similar to atriopeptin, but did not appear to possess the less-active high molecular weight peptide, atriopeptigen.(ABSTRACT TRUNCATED AT 250 WORDS)

Sprague-Dawley rats given bolus intravenous injections of vasoconstrictors, including 1-deamino-Arg8-vasopressin (dAVP), demonstrated remarkable increases in plasma immunoreactivity (APir) to atriopeptin (AP). These elevations were accompanied by increases in systemic blood pressure, right atrial pressure and urinary volume excretion. Fractionated plasma APir peaks obtained by stimulation with dAVP were identified as primarily AP 28, with a smaller amount of AP 24, suggesting that AP 28 is the predominant circulating atrial peptide. Rats with reduced renal mass have increased single-nephron glomerular filtration rates (GFR). Despite these increases, AP 24 stimulated a marked increase in total GFR and promoted a profound natriuresis and diuresis. Atriopeptin 24 may therefore have potential as a therapeutic tool in the management of volume overload in chronic renal failure.

The excretion of both endogenous organic (aryl) acids, such as benzoic acid, and exogenous ones, such as p-aminohippuric acid (PAH), penicillin, and furosemide, is reduced in the human neonate and other immature animals. The unique developmental pattern of aryl acid transport in immature rabbit kidney cortex slices is produced by the interrelationships of PAH uptake, efflux, and amount of intracellular binding protein, all of which reach mature levels at different ages.

Thirty-five patients, 29 with severe proliferative glomerulonephritis and six with either steroid resistant or steroid dependent nephrotic syndrome, were treated with high dose bolus infusions of methylprednisolone (pulses) followed by prednisone given orally in more conventional doses for 6 mo or longer. Twenty-one of the 29 patients with severe proliferative glomerulonephritis had sustained improvement in renal function after treatment. In addition, pulse treatments reduced proteinuria and urine sediment abnormalities in these patients. Those who did not respond had a long duration of disease before receiving pulse therapy. Five of six patients with the nephrotic syndrome had reduction in proteinuria and three of these patients entered prolonged remission after treatment. Few side effects occurred with pulse therapy. Our observations suggest that the use of steroid pulses may limit or prevent long-term major loss of renal function in many patients with severe proliferative glomerulonephritis. It may be effective also in treatment of some patients with steroid refractory or frequently relapsing nephrotic syndrome. This therapeutic approach deserves continuing evaluation.

Since adult polycystic kidney disease, an autosomal-dominant disease, results in renal failure in at least 50% of affected patients, its detection before childbearing age is desirable. To evaluate this capability and the preferred screening technique, 28 members of two generations of an affected kindred were studied. Sonograms, excretory urograms with nephrotomograms, and clinical laboratory evaluation were compared. Five of six studied members of the older generation had cysts demonstrated by both sonograms and excretory urograms with nephrotomograms. Eleven of 22 members of the younger generation were affected, the youngest being 5 years old. In this group, excretory urograms with nephrotomograms were a slightly more sensitive detector, especially in the younger patients. However, sonography provided sufficient sensitivity in the older child, and, because of its noninvasive nature, was the preferred screening technique. The clinical laboratory evaluation was of little diagnostic aid in children with adult-type polycystic disease.

Eight patients with severe glomerulonephritis and an average inulin clearance of 21.7 ml/min/1.73 m2 body surface were treated with high-dosage intravenous methylprednisolone, 30 mg/kg given over a one-hour period on each of six alternate days. The mean inulin clearance rate doubled after this "pulse" therapy. In the six patients treated early in the course of their disease, GFR increased to a mean of 100.2 ml/min/1.73 m2 during the follow-up period extending for up to three years and was accompanied by clinical improvement. These observations suggest that "pulse" methylprednisolone may be beneficial in treating some patients with potentially life-threatening severe glomerulonephritis.

Mammalian atrial extracts possess natriuretic and diuretic activity. In experiments reported here it was found that atrial, but not ventricular, extract also causes relaxation of isolated vascular and nonvascular smooth muscle preparations. The smooth muscle relaxant activity of atrial extract was heat-stable and concentration-dependent and could be destroyed with protease. Rabbit aortic and chick rectum strips were used for the detection of atrial biological activity. The atrial activity was separated by column chromatography into two peaks having apparent molecular weights of 20,000 to 30,000 and less than 10,000. The atrial substance that copurified with the smooth muscle relaxant activity in both peaks caused natriuresis when injected into conscious rats. It appears that atria possess at least two peptides that elicit smooth muscle relaxation and natriuresis, suggesting an endogenous system of fluid volume regulation.

To determine the frequency of autosomal recessive and autosomal dominant polycystic kidney disease (PKD) in infants and to compare the rate of progression of these conditions, we conducted a retrospective survey of 48 patients who were seen with PKD before 1 year of age and who survived the first month of age. Seventeen patients had recessive PKD; six had dominant PKD. Eighteen patients had insufficient data to categorize the type of PKD with certainty. Seven patients were classified as "other"; three had glomerulocystic disease and the remainder had multiple malformation syndromes or tuberous sclerosis. Renal ultrasonography and excretory urography accurately detected 15 of 17 patients with recessive PKD, but only one patient with dominant PKD was correctly diagnosed by excretory urography. The majority of patients in all groups required antihypertensive therapy. The 17 children with recessive PKD have been followed up for 6.1 +/- 4.3 (SD) years. Eight patients are doing well. Two patients have died; five others have required treatment for renal failure. Only one patient has an estimated glomerular filtration rate within the normal range after 6 years of age. Long-term evaluation of most of the patients with dominant PKD is not yet available; however, by age 42 months one patient has required dialysis. To provide optimum genetic counseling and accurate diagnosis for patients with PKD, a combination of careful family evaluation, radiography, and liver or kidney biopsy is required. The outcome of patients who survive the neonatal period appears not to be so grim as previously feared, underscoring the importance of aggressive supportive care and the need for physician and family education.

Mammalian atrial extracts have been shown to contain bioactive peptides which exert natruiretic, diuretic, and smooth muscle relaxant effects. These extracts include several low molecular weight (less than 5,000 Mr) atrial peptides (atriopeptins) which exhibit identical sequences over a central core region which are derived from the high molecular weight peptide (atriopeptigen) precursor which has been purified and sequenced. In the current study we found that extracts of rabbit atria possess both high and low molecular weight bioactive atrial peptides, however, the coronary venous effluent obtained from the isolated perfused rabbit heart only contained the low molecular weight peptide. This trypsin labile activity causes a dose-dependent relaxation of rabbit aorta and chicken rectum assay strips. Separation of the bioactivity with gel filtration chromatography and reversed phase HPLC indicates the heart releases a single substance similar to atriopeptin III. There was no evidence that atriopeptigen was released from the isolated perfused rabbit heart. We suggest that atriopeptigen is proteolytically processed in the atria to an atriopeptin which is subsequently the released form of the atrial peptide.

A new procedure, plasma fibrinogen chromatography, has been utilized, together with other blood coagulation assays, to quantify fibrin formation in 43 children with acute poststreptococcal glomerulonephritis (AGN) from the time of hospitalization until recovery. During the prediuretic phase of AGN, significant evidence for substantial increase in fibrin formation (intravascular coagulation) included gross increase in plasma high molecular weight fibrinogen complexes (HMWFC), the development of either hypo- or hyperfibrinogenemia and gross depression of coagulation factor XIII concentration and of alpha2-macroglobulin concentration. During the diuretic phase of the disease, these abnormalities regressed and evidence of enhanced plasma fibrinolytic activity, documented by an increase in fibrinogen first derivative, was detected. Concomitantly, urinary excretion of fibrin(ogen) degradation products (FDP) underwent substantial increase. With disease recovery, which occurred in all children, urinary FDP excretion ceased and all coagulation findings normalized.