Thiazide diuretics arrest the progression of nephrocalcinosis in children with X-linked hypophosphatemia.

OBJECTIVE: X-linked hypophosphatemia (XLH) is characterized clinically by rickets, hypophosphatemia, and hyperphosphaturia. Conventional treatment of XLH with oral phosphate and vitamin D is associated with increased urinary calcium excretion and nephrocalcinosis. Thiazide diuretics decrease urinary calcium excretion. The objective of this study was to determine the effect of thiazide diuretics on the clinical and radiologic course of nephrocalcinosis in children with XLH. METHODS: The effect of hydrochlorothiazide (HCTZ) on clinical and radiologic progression of nephrocalcinosis was evaluated in 11 children with XLH. All patients had been treated previously with vitamin D and oral phosphate and had radiologic evidence of nephrocalcinosis. The average age of the patients at the start of HCTZ was 6.6 +/- 1.0 years. The effect of oral HCTZ at 0.8 +/- 0.1 mg/kg body weight per day given for 3.3 +/- 0.6 years on the progression of nephrocalcinosis and urinary calcium excretion was evaluated. RESULTS: There was no change in serum phosphorous, calcium, potassium, and chloride after HCTZ therapy. HCTZ therapy increased serum bicarbonate and decreased urinary calcium excretion. The grade of nephrocalcinosis increased from 0.4 +/- 0.2 to 1.5 +/- 0.3 in the 2.3 +/- 0.3 years before initiation of HCTZ therapy, whereas the degree of nephrocalcinosis was stable after 3.3 +/- 0.6 years of HCTZ therapy (1.5 +/- 0.3 vs 3.0 +/- 0.3). CONCLUSION: HCTZ decreased urinary calcium excretion but did not result in the resolution of nephrocalcinosis. However, when compared with the control period, HCTZ prevented the progression of nephrocalcinosis in children with XLH.

Role of glucocorticoids in the maturation of the rat renal Na+/H+ antiporter (NHE3).

BACKGROUND: Neonates have a lower Na+/H+ antiporter activity on the apical membrane of proximal tubule than that of adults. The maturational increase in Na+/H+ antiporter activity occurs at the time when there is a rise in serum glucocorticoid levels in rats. The purpose of the present study was to examine whether glucocorticoids are responsible for the postnatal increase in Na+/H+ antiporter activity. METHODS: Nine-day-old Sprague-Dawley rats were compared with rats studied at 30 days of age who had either a sham operation or adrenalectomy (ADX) at nine days of age and with rats that had an adrenalectomy and physiologic corticosterone replacement (ADX-Cort) to determine whether glucocorticoid deficiency prevented the maturational increase in Na+/H+ antiporter activity. Na+/H+ antiporter activity was measured in proximal convoluted tubules perfused in vitro by the change in cell pH (pHi) following luminal sodium removal. NHE3 mRNA abundance was measured using Northern blot analysis, and NHE3 protein abundance was measured by immunoblot. RESULTS: Na+/H+ antiporter activity was 93.8 +/- 17.7, 157.0 +/- 18.0, 356.7 +/- 29.9, and 402.5 +/- 14.5 pmol/mm. min in nine-day-old, ADX, ADX-Cort, and sham control groups, respectively. The ADX-Cort and sham control were higher than the 9-day-old and the 30-day-old ADX group (P < 0.05). Brush-border membrane NHE3 protein abundance in the nine-day-old and ADX groups were sixfold less than ADX-Cort and sham control groups (P < 0.001). Nine-day-old neonates had fivefold less renal cortical NHE3 mRNA than the ADX, ADX-Cort, and sham-operated control groups (P < 0.01). CONCLUSIONS: These data demonstrate that glucocorticoids play a role in the postnatal maturation of the proximal tubule Na+/H+ antiporter activity and brush-border membrane NHE3 protein abundance. Glucocorticoid deficiency does not completely prevent the maturational increase in Na+/H+ antiporter activity and does not affect NHE3 mRNA abundance.

The 12th Annual Report of the North American Pediatric Renal Transplant Cooperative Study: renal transplantation from 1987 through 1998.

The North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) presents an annual report for all transplants registered from January 1987 onwards. In this report we reviewed 6,534 renal transplants recorded for 5,958 patients who had entered the study by January 1999, and attempted to identify changes in practice patterns that had led to improved graft survival. There has been a steady decline in cadaver source transplants nationally and our accrual for 1996 and 1997 reflected this trend. There has also been a decrease in the number of infants and young children receiving a transplant in recent years. From a peak of 23.3% in the 1987-91 cohort, the current report shows that children under 6 yr of age now account for only 20.4% of all transplants. Changing disease patterns and rates of progression of disease have decreased the percentage of Caucasian children in the transplant registry, from 68.5% in the first 5 yr to 62.9% in the most recent cohort. Changing practice patterns have markedly reduced the use of cadaver donor (CD) kidneys (recovered from donors younger than 10 yr of age) from 35% in 1991 to 22% in the current report. Acute rejection patterns are identical for CD and living donor (LD) grafts for the first 2 weeks post-transplant. The comparative percentages on days 30 and 45 are 36% and 44% for CD, and 26% and 32% for LD recipients respectively. By the end of the first year post-transplant, 45% of LD and 60% CD recipients have had an acute rejection. There has been a marked improvement in our ability to reverse the initial episode of rejection; in 1987, 52% were completely reversed in LD recipients, and in 1997 61% were reversed. Rejection percentages continued to be lower in patients maintained on cyclosporin A (CsA) doses of > 6.4 mg/kg. One-, 3-, and 5-yr graft survival probabilities were 91%, 85%, and 80%, respectively, for LD recipients, and 83%, 73%, and 65% for CD recipients. Comparative 1- and 3-yr figures from 1987 to 1991 were 88% and 81% for LD and 74% and 63% for CD recipients. When short-term graft survival (1 yr) results were compared, a significant improvement was demonstrated from 71.7% in 1987/88 to 92.6% in 1998/1999 for CD transplants. Hence, changing practice patterns have gradually brought the short-term graft survival of CD transplants very close to that of LD transplants. The continuing decrease in the incidence of acute rejections in more recent years should translate into a further delay in the onset of chronic rejection, thus improving graft longevity.

Thoracocentesis helps diagnose diaphragmatic defects in peritoneal dialysis patients.

Hydrothorax is an infrequent complication of peritoneal dialysis. Hydrothorax is often secondary to diaphragmatic defects. Available diagnostic tools are usually insensitive and false-negative results are common. We describe a modification to the standard isotopic peritoneogram that proved effective when other tests yielded false-negative results. We conclude that thoracocentesis prior to the standard isotopic peritoneogram facilitates the diagnosis of diaphragmatic defects.

The prevalence of osteopenia in pediatric renal allograft recipients varies with the method of analysis.

BACKGROUND: Pediatric renal allograft recipients often suffer from osteopenia and the potential for increased fractures. Although modern densitometers are widely available, their use in children is complicated by lack of optimal interpretive criteria. METHODS: We reviewed dual energy X-ray absorptiometry (DEXA) studies in 33 patients with functional renal allografts 4.4 +/- 3.6 years after transplantation. We interpreted our data using three previously described methods of assigning bone mineral density (BMD) Z scores. RESULTS: BMD was directly related to age, height, weight, body surface area, and pubertal status (p < 0.001). Using gender-mixed reference data matched by chronological age, the mean BMD Z score was -0.9 +/- 1.3 vs. 0.4 +/- 1.4 when matched by height-age (p < 0.001). Height-age adjustment particularly increased the BMD Z score of pubertal adolescents. In a subset of 22 patients, gender-matched reference data led to different results from the gender-mixed reference population (mean BMD Z score 0.0 +/- 1.7 vs. -0.8 +/- 1.4, p < 0.001). CONCLUSIONS: The perceived prevalence of osteopenia among pediatric kidney transplant recipients differs using analysis based on chronological age, height-age, or gender-matched reference data. Further studies are necessary to determine the clinical significance of measured bone density in this population.

Effect of dipyridamole on serum and urinary phosphate in X-linked hypophosphatemia.

X-linked hypophosphatemia (XLH) is characterized clinically by rickets, hypophosphatemia and hyperphosphaturia. Conventional treatment of XLH with oral phosphate and vitamin D is associated with hypercalcuria and nephrocalcinosis. Recently, intravenous and oral dipyridamole has been reported to decrease fractional excretion of phosphate in adults with idiopathic hyperphosphaturia. Our objective was to determine whether oral dipyridamole therapy reduces urinary phosphate excretion and increases serum phosphate concentration in children with XLH. A prospective study was performed in six children with XLH. The average age of the patients at the start of the study was 12.5+/-1.0 years. The effects of 12 weeks of oral dipyridamole therapy, at 4.4+/-0.4 mg/kg body weight per day, on serum phosphorous, parathyroid hormone (PTH), 1,25 (OH)2 vitamin D, osteocalcin, tubular maximum for phosphate reabsorption (TmP/GFR), urinary calcium excretion, and cyclic adenosine 3',5'-monophosphate (cAMP) excretion, were compared to baseline levels. Our results show that there was no change in serum phosphorous concentration or TmP/GFR after 12 weeks of dipyridamole therapy. Dipyridamole therapy also had no effect on serum PTH, serum 1,25 (OH)2 vitamin D, alkaline phosphatase, osteocalcin levels, urinary calcium or cAMP excretion. We therefore concluded that in children with XLH, a 12-week course of dipyridamole had no effect on serum phosphorous or its urinary excretion. Dipyridamole therapy is unlikely to improve the bone disease in children with XLH.

Nutritional rickets still afflict children in north Texas.

Nutritional rickets is uncommon in North America, particularly in regions where sunlight is plentiful. Recent epidemics in North America occurred in dark-skinned toddlers with poor nutrition who had insufficient exposure to sunlight and whose parents were members of ethnic, social, and socioeconomic groups with predisposing practices. Nine children (8 toddlers and 1 infant) were referred to the Bone Metabolic Clinic at Texas Scottish Rite Hospital for suspected rickets between October 1997 and October 1998. The diagnosis of nutritional rickets was based on clinical, biochemical, and radiological evidence. All children were dark-skinned: 8 were African Americans and 1 was of Hispanic parentage. All children were breast-fed with minimal intake of dairy products; none received vitamin supplementation. All children were followed up by health care professionals. Two patients were children of upper-middle class parents. Birth order was not a contributing factor in the development of nutritional rickets. Radiological and biochemical rachitic changes remitted within 3 months of vitamin D therapy combined with dietary modification. Primary care providers should consider vitamin D supplementation in all infants with increased skin pigmentation and especially in those who are primarily breast-fed. Nutritional rickets can develop in dark-skinned infants of any social or ethnic background. Residing in a geographical area with abundant sunlight is not a guarantee against the development of nutritional rickets in dark-skinned children.

Long-term clinical and pathological effects of cyclosporin in children with nephrosis.

The clinical course of eight children with minimal change disease (MCNS) who were treated with cyclosporin (CYA) was retrospectively reviewed (group A). Five children had frequently relapsing (FRNS) and three had steroid-resistant (SRNS) primary nephrotic syndrome (PNS). The mean age (+/-SEM) of the patients at the time of initiation of CYA therapy was 8.01+/-1.30 years. Twelve follow-up renal biopsies, obtained from patients in group A, were compared with baseline 3.36+/-0.76 years after the initiation of CYA. Follow-up renal biopsies from group A were compared with another cohort of eight children with PNS who did not receive CYA (group B, controls). In this later group four children had FRNS and four had SRNS, and all had MCNS on the initial renal biopsy. In group B, the time between the initiation of CYA and the last renal biopsy was 4.07+/-0.82 years. All 36 baseline and follow-up renal biopsies, from group A and B, were retrospectively reviewed by the same pathologist who was blinded to the clinical course and therapy. CYA decreased the number of relapses in patients from group A from 5.20+/-1.02 to 1.14+/-0.63 episodes per year (P<0.05). All patients with SRNS went into remission after initiation of CYA. Estimated creatinine clearance before CYA therapy was unchanged at the end of the observation period, 133+/-10 vs. 131+/-8 ml/min per 1.73m2, respectively. One child developed reversible acute renal failure while on CYA therapy. Attempts to wean three patients off CYA after 3.89+/-0.87 years of CYA therapy were unsuccessful. Mild but increasing tubular atrophy and interstitial fibrosis was observed in serial biopsies of 75% of the patients in group A compared with 25% of the patients in group B, all of whom had MCNS on initial biopsy. In addition, the percentage of renal cortex showing interstitial fibrosis and tubular atrophy in biopsies from group A patients was slightly greater than that of the group B patients (P<0.05). Hence, CYA therapy in children with MCNS is associated with mild renal interstitial fibrosis and tubular atrophy similar to that noted in a minority of the patients with primary MCNS who were not treated with CYA. However, the mild chronic interstitial damage is more frequent and extensive in MCNS patients treated with CYA, suggesting drug-related interstitial alteration. Despite its efficacy and minimal nephrotoxicity in most patients with MCNS, CYA therapy carries the potential for significant morbidity.

Mycophenolate mofetil--is it worth the cost? The in-favor opinion.

Since its introduction, mycophenolate mofetil (MMF) has rapidly gained acceptance among renal transplant physicians. Three large multicenter studies have shown that MMF decreased the incidence of acute rejection episodes by 50%. While clinical data supporting the long-term benefits of MMF are not available, there is some experimental evidence which demonstrates that MMF may play a role in the prevention of chronic allograft rejection. Furthermore, MM F is a potent immunosuppressive agent, which could result in a reduction of the dose of cyclosporin A (CsA) required and subsequently reduce its associated toxicity. Despite the fact that MMF is six to seven times more expensive than azathioprine (AZA), its introduction into maintenance immunosuppressive protocols may not increase renal transplant charges during the first year after renal transplant as its cost can be offset by the reduced number of acute rejection episodes (ARE). The long-term societal impact of MMF will need to be evaluated as the data related to graft and patient survival, as well as chronic rejection, become available.

Renal Na/H exchanger NHE-3 and Na-PO4 cotransporter NaPi-2 protein expression in glucocorticoid excess and deficient states.

Administration of pharmacologic doses of glucocorticoid in vivo increases renal proximal tubule apical membrane Na/H exchange and decreases Na/PO4 cotransport activity (1). Current data suggest that the NHE-3 and NaPi-2 proteins mediate significant fractions of proximal tubule apical membrane Na/H exchange and Na/PO4 cotransport, respectively. This study examines whether glucocorticoid excess or deficiency affects NHE-3 and NaPi-2 protein abundance and the intrarenal distribution of these transporters. Protein abundance of NHE-3 and NaPi-2 in control rats was compared to rats rendered glucocorticoid-deficient by bilateral adrenalectomy, and to rats receiving pharmacologic doses of dexamethasone using immunoblots and immunohistochemistry. Adrenalectomy had modest effects on NHE-3 protein abundance, but dexamethasone administration to either adrenalectomized or sham-operated rats significantly increased NHE-3 protein abundance in both the proximal tubule and thick ascending limb, but not the thin descending limb. Adrenalectomy increased NaPi-2 protein abundance in the proximal tubule, whereas dexamethasone administration dramatically suppressed NaPi-2 protein on the apical membrane in both adrenalectomized and sham-operated animals. No significant reciprocal increase in subapical NaPi-2 staining was seen in the dexamethasone-treated rats. The present study shows that glucocorticoids regulate proximal tubule apical membrane Na/H exchange and NaPi cotransport by changes in protein abundance of NHE-3 and NaPi-2, respectively.

Glomerular filtration rate in children following renal transplantation.

Most studies evaluating renal function post-renal transplantation in children have used serum creatinine (S(Cr)) or estimates of its clearance (C(SCH)). When renal function is impaired both S(Cr) and the C(SCH) overestimate glomerular filtration rate (GFR), especially during cyclosporine therapy. This study measured GFR in 64 children (age range: 4-19 years) with stable renal function who received renal allografts at the Childrens Medical Center of Dallas, 31 from live related donors (LRD) and 33 from cadaveric donors (CAD). 125I-iothalamate clearance (C(IO)) was used as the reference standard for measuring GFR. Data from 100 C(IO) studies, were analyzed and results reported as mean +/- S.E.M. C(IO) performed during the first year after renal transplantation in 23 children who received allografts from LRD was 72.4+/-5.5 ml/min per 1.73 m2 compared to 50.4+/-7.4 ml/min per 1.73 m2 in 18 children who received allografts from CAD (p<0.05). Beyond the first year post-renal transplantation there was no difference in C(IO) between LRD and CAD allografts. When S(Cr) was compared to C(IO), the relationship was nonlinear. C(IO) was also compared to the simultaneous estimation of creatinine clearance by C(SCH). The overestimation of GFR by C(SCH) was inversely proportional to the level of renal function. When renal function was normal or mildly reduced (C(IO) > 50 ml/min per 1.73 m2), C(SCH) closely approximated C(IO). When renal function was moderately to severely curtailed (C(IO) < or = 50 ml/min per 1.73 m2), C(SCH) overestimated C(IO) by 43.6+/-5.6%. The study concludes that in children with renal transplant: 1) C(IO) is higher in allografts from LRD compared to CAD kidneys only in the first 12 months following renal transplantation; 2) S(Cr) is a poor predictor of C(IO); and 3) C(SCH) consistently overestimates GFR children following renal transplantation unless renal function is normal or only mildly decreased.

The effect of recombinant human growth hormone in children with X-linked hypophosphatemia.

BACKGROUND: X-linked hypophosphatemia (XLH) is characterized clinically by rickets and growth retardation. Conventional treatment of XLH with oral phosphate and vitamin D fails to normalize linear growth. Objective. To determine the benefit and the potential side effects of recombinant human growth hormone (rhGH) therapy in patients with XLH. DESIGN AND METHODS: A randomized, double-blind, crossover study was performed throughout a 24-month period in five children with XLH, each patient serving as his own control. The effect of 12 months of rhGH therapy on height, mineral metabolism, glucose and lipid metabolism, hemoglobin, thyroid and parathyroid function, serum 1,25-(OH)2 vitamin D, osteocalcin, growth hormone, urinary calcium, phosphate, nephrocalcinosis, renal function, and bone density was compared with the effects of 12 months of placebo administration on the same parameters. RESULTS: The average age (mean +/- SEM) of the patients at the start of the study was 5.6 +/- 1.4 years. Growth hormone therapy improved the height standard deviation score (z-score) from a baseline of -2.66 +/- 0.21 to -2.02 +/- 0.25 and to -1.46 +/- 0.28, after 3 and 12 months, respectively. At the start of the control period the height z-score was -2.27 +/- 0.30 compared with -2.22 +/- 0.16 after 12 months of placebo administration. The growth velocity standard deviation score was -1. 90 +/- 0.40 during the 12 months of placebo administration and +4.04 +/- 1.50 during the 12 months of rhGH therapy. An increase in serum phosphate from 0.88 +/- 0.07 mmol/L to 1.17 +/- 0.14 mmol/L and tubular maximum for phosphate reabsorption (TmP/GFR) from 2.12 +/- 0. 15 to 3.41 +/- 0.25 mg/dL, was observed after 3 months of rhGH therapy. However, both serum phosphate and TmP/GFR were unchanged from baseline after 6, 9, and 12 months of rhGH therapy. Neither serum phosphate nor TmP/GFR changed from baseline during the placebo administration. Insulin-like growth factor 1 (IGF-1) increased from 114 +/- 25 to 354 +/- 51 ng/mL after 12 months of rhGH therapy. Despite the increase in IGF-1 after rhGH therapy, the value did not exceed normal serum concentration. IGF-1 did not change from baseline after 12 months of placebo administration. Neither therapy with rhGH nor with placebo had an effect on glucose and lipid metabolism, hemoglobin, thyroid and parathyroid function, serum 1, 25-(OH)2 vitamin D, alkaline phosphatase, osteocalcin, urinary calcium excretion, the grade of nephrocalcinosis, glomerular filtration rate, or urinary albumin excretion. Twelve months of rhGH therapy increased bone mass and width but not density. Twelve months of placebo administration had no effect on bone mass, width, or density. CONCLUSION: Patients with XLH have an improvement in linear growth and a transient increase in serum phosphate attributable to a transient decrease in urinary phosphate excretion when treated with rhGH.

Limitations to body length/serum creatinine ratio as an estimate of glomerular filtration in children.

The ability of the Schwartz formula (CSCH) to estimate glomerular filtration rate (GFR) accurately was investigated in children with renal disease. 125Iodine-iothalamate clearance (CIO) was used as the reference standard for measuring GFR. Data from 176 CIO studies performed on 133 children (aged between 1 and 18 years) were compared with the simultaneous estimation of GFR by CSCH. The overestimation of GFR by CSCH was inversely proportional to the level of renal function. When CIO was > 90 ml/min per 1.73 m2, CSCH overestimated GFR by only 0.1% +/- 3%, but when CIO was < or = 15 ml/min per 1.73 m2, CSCH overestimated GFR by 164% +/- 42%. When renal function is normal or mildly reduced (GFR > 50 ml/min per 1.73 m2), CSCH overestimated CIO by only 10.3 +/- 3.0%, compared with 90.3 +/- 14.5% when renal function was moderately to severely curtailed (GFR < or = 50 ml/min per 1.73 m2). We conclude that CSCH is valid in predicting GFR only in children with normal renal function and mild insufficiency.

125Iodine-iothalamate clearance in children. A simple method to measure glomerular filtration.

Glomerular filtration rate (GFR) is the most widely used test to evaluate renal function. Several clearance markers have been used to measure GFR in adults. In children, however, a simple and reliable method to measure GFR is not available. Renal 125iodine (I)-iothalamate clearance, after a single subcutaneous injection, is a simple and accurate test to measure GFR in adults. The validity of unlabelled iothalamate, as a marker for measurement of GFR in children, was reported recently. Unfortunately, the unlabelled iothalamate assay is arduous. We report our experience with a single subcutaneous injection of 125I-iothalamate to measure GFR in normal children and those with renal disease. A weight-adjusted dosing regimen was adopted. This regimen resulted in sufficient above-background radioactivity in both blood and urine for reproducible measurement of GFR. Intra-test variability for GFR was not affected by the degree of renal insufficiency. The test was well tolerated with only 2 patients developing mild headache during the procedure. Our study showed that renal clearance of 125I-iothalamate is reproducible, simple, and practical in healthy children and those with mild and advanced renal disease.

Nephrocalcinosis is associated with renal tubular acidosis in children with X-linked hypophosphatemia.

BACKGROUND: X-linked hypophosphatemia is characterized clinically by rickets and growth retardation. Therapy of this disorder with phosphate and vitamin D often produces nephrocalcinosis. The long-term effects of nephrocalcinosis on renal function in patients with X-linked hypophosphatemia are unknown. The purpose of this study was to evaluate the prevalence of glomerular and tubular disorders in patients with X-linked hypophosphatemia who developed nephrocalcinosis. METHODS: The creatinine clearance and the prevalence of renal tubular acidosis were compared in 19 patients with X-linked hypophosphatemia and nephrocalcinosis with 15 patients with X-linked hypophosphatemia without nephrocalcinosis. RESULTS: Sixteen of the 19 patients (84%) with nephrocalcinosis had a hyperchloremic metabolic acidosis compared with one of the 13 patients without nephrocalcinosis (P < .01). The serum bicarbonate of patients with nephrocalcinosis was 20.0 +/- 0.7 as compared to 24.5 +/- 0.6 mmol/L in patients without nephrocalcinosis (P < .01). The urinary anion gap was positive in all patients with acidosis (+62.1 +/- 13.3 mmol/L). The creatinine clearance was 125 +/- 6 mL/min/1.73 m2 in patients with nephrocalcinosis and 124 +/- 7 mL/min/1.73 m2 in those without nephrocalcinosis. CONCLUSION: Therapy of X-linked hypophosphatemia is often associated with nephrocalcinosis. Nephrocalcinosis is associated with renal tubular acidosis in patients with X-linked hypophosphatemia.

Stimulation of growth hormone secretion in children with X-linked hypophosphatemia.

X-linked hypophosphatemia is characterized by low serum phosphorus, relative vitamin D deficiency and rickets. Despite adequate metabolic control with oral phosphate and vitamin D therapy, patients with X-linked hypophosphatemia have short stature. Whether growth hormone (GH) deficiency plays a role in short stature in patients with X-linked hypophosphatemia is not known. The purpose of this report was to investigate the response of GH to sequential paired pharmacological stimulation in patients with X-linked hypophosphatemia. Basal GH was 3.8 +/- 0.7 ng/ml, insulin-like growth factor-I (IGF-I) was 225 +/- 38 ng/ml and IGF binding protein-3 was 3.0 +/- 0.2 mg/l in 16 children studied with X-linked hypophosphatemia. In response to L-dopa and arginine hydrochloride stimulation, serum GH rose to above 7 mg/ml in all patients. Thus, the short stature in patients with X-linked hypophosphatemia is not due to a GH/IGF-I secretory defect.

In vitro production of angiotensin II by isolated glomeruli.

The glomerulus has several components of the renin-angiotensin system (RAS). The purpose of this study was to evaluate the ability of glomeruli isolated from adult Wistar-Kyoto rats to produce angiotensin II (ANG II). When isolated glomeruli were incubated in Krebs buffer, the peak concentration of immunoreactive angiotensin (ANG) in the incubation medium, representing simultaneous production and degradation, occurred after 15 min of incubation (3.98 +/- 0.34 pg.mg protein-1.15 min-1, of which 18% was ANG II. When 125I-labeled ANG II was incubated with isolated glomeruli, the half-life of ANG II was 6.06 min. Hence, we estimated ANG II production at 3.77 +/- 0.21 pg.mg protein-1.15 min-1. When angiotensinogen-rich serum was added to the incubation medium, ANG concentration at 15 min increased by 500-fold (1,978 +/- 44 pg.mg protein-1.15 min-1, P < 0.001). ANG concentration in the glomerular incubate responded to perturbations known to alter systemic RAS. Enalaprilat, chymostatin, propranolol, and renin antiserum decreased ANG concentration in glomerular incubate, whereas salt depletion increased this (P < 0.05). We conclude that the rat glomerulus can generate ANG II independent of neural, hormonal, or vascular control.

Reversible idiopathic acute renal failure in children with primary nephrotic syndrome.

We describe the clinical features of four pediatric patients (20 months to 10 years of age) in whom reversible idiopathic acute renal failure (RIARF) developed during the course of primary nephrotic syndrome (PNS). All patients had severe PNS and were in relapse at the onset of RIARF. This complication of PNS was preceded by primary peritonitis in three of four patients. Renal biopsy done in the early phases of RIARF showed tubular epithelial changes similar to those observed in acute tubular ischemia. All patients required dialysis. Recovery of renal function followed fluid removal in three of four patients. The RIARF lasted from 12 days to 1 year and was followed by complete recovery of renal function in all patients. We conclude that (1) RIARF is a potential complication in children with severe PNS, (2) RIARF is associated with primary ischemic renal tubular injury, and (3) recognition of the reversibility of this complication of PNS could alter long-term plans for management of renal failure in these patients.