Arginine vasopressin (AVP)-stimulated cAMP generation is decreased in the immature collecting duct (CD). This is the result of prostaglandin antagonism, most likely via the inhibitory guanine ...nucleotide-binding protein (Gi). The EP3-subtype prostaglandin E2 (PGE2) receptor, which is coupled to Gi, could mediate this effect. We studied the developmental expression of EP3 receptor in the rabbit kidney. Higher levels of EP3 mRNA were observed in the immature kidney using three different assays: 1) reverse transcription-polymerase chain reaction (RT-PCR) with internal standard, 2) competitive PCR, and 3) ribonuclease protection assay. The highest levels were observed at 2 wk of age. RT-PCR from isolated nephron segments detected EP3 mRNA in the medullary thick ascending limb, cortical CD (CCD), and inner medullary CD (IMCD) of adult and immature kidneys. We conclude that 1) renal expression of EP3 mRNA is increased in immature kidneys and 2) EP3 mRNA is localized in the distal nephron. This suggests that EP3 receptor may play a role in the regulation of distal tubular transport during development.
Immature animals have limited ability to concentrate the urine. This is in part the result of end-organ resistance to arginine vasopressin (AVP). To characterize this response, we measured water ...absorption in microperfused cortical collecting ducts (iCCD) and outer medullary CD (iOMCD) derived from 2- to 12-day-old rabbits. The roles of adenosine 3',5'-cyclic monophosphate (cAMP) and prostaglandins were investigated. Baseline osmotic water permeability (L(p), 10(-7) cm/atm per s) in the iCCD (20.3+/-2.4) and iOMCD (19.7+/-5.6) was not different from mature CCD (mCCD) (14.6+/-3.1). After AVP, L(p) in the iCCD (46.7+/-10.0) was significantly lower than in the mCCD (114.3+/-21.8). Neither stimulation with cAMP (85.6+/-51.3) nor inhibition of endogenous prostaglandin production with indomethacin (57.6+/-29.8) abolished the blunted response to AVP in the iCCD. We conclude that AVP-stimulated water transport in the iCCD is impaired. The disruption in AVP response is, at least in part, localized distal to cAMP, and is not mediated by prostaglandins.
A retrospective cohort study was conducted by the Southwest Pediatric Nephrology Study Group (SPNSG) to address whether a longer initial course of corticosteroids in patients with idiopathic ...nephrotic syndrome (INS) provides superior protection against relapse without increased adverse effects. In order to be included in the evaluation, patients with INS must have responded to an initial steroid course, either standard or long regimen as defined here, and completed at least 1 year of follow-up. The standard regimen consisted of prednisone 2.0±0.3 mg/kg per day or 60±10 mg/m2 per day for 28±4 days, followed by alternate-day prednisone for 4-12 weeks. The long regimen consisted of daily prednisone 2.0±0.3 mg/kg per day or 60±10 mg/m2 per day for 42±6 days, followed by alternate-day prednisone for 6-14 weeks. The primary outcome measure was relapse of NS within 12 months of discontinuing the initial course of prednisone. There were 151 children who met the criteria for the study; 82 received the standard regimen and 69 the long regimen. The two groups did not differ in age, race, blood pressure, serum albumin, or serum cholesterol prior to the initial steroid course. The cumulative prednisone dose was 49% higher in the long regimen group than in the standard regimen group. Relapse within 12 months was reported in 72.5% of patients who received the long regimen versus 84.1% of those who received the standard regimen. The odds ratio for relapse within 12 months was 0.496 (95% confidence interval 0.22, 1.088), long versus standard regimen. This did not reach statistical significance (χ2=3.058, P=0.08). The odds ratio of experiencing at least one side effect was 3.76, long relative to standard regimen (n=133, P<0.001). Our data suggest that prolongation of the steroid treatment for the initial episode of steroid-sensitive NS may have a beneficial effect, but at the cost of increased side effects. However, definitive conclusions are limited by the retrospective design of the study and the number of patients. This may have caused failure to achieve statistical significance on the basis of a type II error. PUBLICATION ABSTRACT
It has been generally accepted that primary distal renal tubular acidosis (DRTA) is the result of a defect in proton secretion in the distal nephron (secretory defect). We report an infant with DRTA, ...evidenced by spontaneous hyperchloremic metabolic acidosis with low urinary ammonium excretion rate and inability to decrease urine pH during acidosis, who nevertheless exhibited an intact ability to increase urinary carbon dioxide partial pressure (pCO
2) during maximal urine alkalinization and normal ability to acidify the urine after furosemide, suggestive of a gradient-type defect DRTA. This patient had never been exposed to amphotericin B. To our knowledge, this is the first fully documented report of primary DRTA that can be attributed to gradient defect.
The immature kidney is characterized by resistance to arginine vasopressin (AVP). In the immature cortical collecting duct (iCCD), AVP-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) ...generation is decreased, but the mechanisms involved are not known. We examined cAMP production in isolated CCD from immature and mature rabbits. Cellular cAMP levels were measured by radioimmunoassay under basal conditions and after stimulation with hormone. Basal cAMP production in the iCCD was not different from that in the mature CCD (mCCD). In contrast, AVP- and forskolin-stimulated cAMP generation were severely decreased in the iCCD. Inhibition of endogenous prostaglandin production by indomethacin increased AVP-stimulated cAMP generation in the iCCD to levels that were not different from the mCCD. Inhibition of protein kinase C (PKC) by staurosporine and inhibition of Gi by pertussis toxin elicited a mature cAMP response in the iCCD. These data suggest that the defect in AVP-stimulated cAMP production in the iCCD is mediated by prostaglandins via 1) activation of Gi and 2) direct inhibition of the adenylyl cyclase catalytic subunit. In addition, PKC appears to play a significant role.
Neonatal presentation of Gordon syndrome Gereda, Jose E.; Bonilla-Felix, Melvin; Kalil, Bryan ...
The Journal of pediatrics,
10/1996, Letnik:
129, Številka:
4
Journal Article
Recenzirano
Gordon syndrome, the association of hypertension with hyperkalemic acidosis, has been described in older children and adults. We report an affected family in which two of the members had exhibited ...the metabolic manifestations of the disease since infancy. Both patients responded well to thiazides. To our knowledge, these are the youngest patients with documented cases of Gordon syndrome. (J P
EDIATR 1996;129:615-7)
Distal renal tubular acidosis is frequently associated with hypercalciuria. To further investigate the cause-and-effect relationships between the two conditions, we examined 20 children (5 to 18 ...years of age) with idiopathic hypercalciuria for evidence of renal tubular acidosis. Serum electrolytes and urine citrate levels were normal in all subjects. After a single dose of furosemide, 1 of the 20 subjects did not show a decrease in urine pH < 5.5, which suggests an acidification defect in the cortical collecting duct. Three other patients failed to show an increase in urine-minus-blood partial pressure of carbon dioxide > 20 mmHg after urine alkalinization with orally administered acetazolamide, a finding compatible with a rate-dependent distal renal tubular acidosis. These four subjects underwent acute acid loading with arginine hydrochloride. In all four subjects urine pH decreased < 5.5 but urinary ammonium excretion failed to increase normally; this supports the diagnosis of a defect in distal acidification. Four of six patients with nephrolithiasis had evidence of distal renal tubular acidosis, in contrast to none of the 14 patients without stones (p = 0.003). We conclude that distal acidification abilities seem to be intact in children with hypercalciuria in the absence of nephrolithiasis. We speculate that calcium precipitation may lead to tubular damage, including distal renal tubular acidosis.
Response of cortical collecting ducts from remnant kidneys to arginine vasopressin. Chronic renal failure is associated with impaired urine concentration. Previous studies have demonstrated that ...cortical collecting ducts (CCD) from uremic rabbits (with remnant kidneys) have an impaired response to arginine vasopressin (AVP). To determine whether this defect is an early, integral component of compensatory renal growth by the remnant kidney, we studied the response of CCD derived from rabbits one week after 75% nephrectomy. At one week, hypertrophy and adaptation in sodium transport are fully developed, but azotemia and interstitial fibrosis are absent. The animals with remnant kidneys failed to respond normally to water deprivation and dDAVP (maximum urine osmolality 738 ± 29.1 mOsm/kg compared to 1378 ± 207 in sham operated). However, in isolated, perfused CCD from remnant kidneys, AVP stimulated hydraulic water permeability to the same extent as in normal CCD or CCD from sham operated animals. AVP-induced cAMP generation per mm tubule length was significantly higher in the CCD from remnant kidneys (137.4 ± 14.5 fmol/mm) than in the control group (82.4 ± 11.9 fmol/mm), but not different when expressed per µ% protein. These studies demonstrate that one week after reduction in renal mass there is no defect in the response of CCD to AVP, suggesting that the mechanisms responsible for the hyposthenuria after loss of renal mass are not related to any intrinsic cellular changes that occur in CCD early during compensatory renal growth.
We report a 16-year-old male who developed nephrotic syndrome related to membranous glomerulopathy with clinical and serological evidence of systemic lupus erythematosus after treatment with ...griseofulvin. To our knowledge, this is the first case of griseofulvin-exacerbated lupus in which nephrotic syndrome has been observed.
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