No abstract

Since the introduction of amphotericin B as an antifungal agent, the morbidity and mortality of pediatric patients with mycotic infections have increased, primarily because of the increased immunocompromised patients. Despite the fact that deoxycholate amphotericin B was once the primary drug used for mycotic infections, its administration to children older than neonates is currently controversial because of its nephrotoxic effects. Three lipid-associated formulations have been developed and have reportedly shown similar efficacy and fewer nephrotoxic effects in adults than conventional amphotericin B, but the conclusions from comparative studies in children evaluating the nephrotoxicity risks of the 4 agents are controversial. Nevertheless, guidelines favor liposomal or lipid complex amphotericin B when polyene antifungal therapy is recommended in this age group. However, high acquisition costs often preclude their prescription in economically poor regions. Thus, physicians must consider all of these factors when determining the most cost-effective polyene antifungal treatment for their pediatric patients. This is particularly pertinent in developing countries where resources are scarce. Adjuvant sodium supplementation has been reported to be effective in protecting kidney function in extremely low birth weight infants prescribed deoxycholate amphotericin B. Further pharmacokinetic and pharmacodynamic studies of the drug in children could also provide information for rational dosing regimens designed to decrease nephrotoxicity. Conventional amphotericin B, with appropriate kidney protective measures, still plays a role in the treatment of empiric invasive mycotic infections in most pediatric patients. Liposomal and lipid complex amphotericin B should be reserved for those receiving long-term nephrotoxic agents or with altered renal function or disease. Antifungal susceptibility, renal compromise and the clinical status of the patient should determine treatment for culture-proven infections. Under the current cost limitations, undertaking and evaluating low-cost, kidney-sparing, deoxycholate amphotericin B treatments for children should be a primary concern.

In young ADPKD patients, normal levels of UACR suggest that renal interstitium is comparable to that in healthy subjects and indicate an absence of subtle atherosclerotic changes in the carotid arteries. Likewise, early renal and vascular changes may be present at UACR below the levels defined as microalbuminuria.

Sodium transport correlates with varying Na+-K+-ATPase activity rates along the nephron. Whether differences in Na+-K+-ATPase regulation by protein kinase C-dependent phosphorylation are also present has not been tested. We measured the degree of Na+-K+-ATPase alpha1 subunit phosphorylation by the binding of McK-1 antibody to dephosphorylated Ser-23 and Na+-K+-ATPase activity in medullary thick ascending limb of Henle (mTAL) and proximal tubules (PCT). The degree of Na+-K+-ATPase phosphorylation at Ser-23 was lower in mTAL than in PCT (DU 13.43+/-1.99 versus 2.3+/-0.20, respectively, P<0.01) while Na+-K+-ATPase activity was higher in mTAL (3,402+/-83 vs 711+/-158 pmol/mm tubule per hour in PCT, P<0.01). PKC inhibitor RO-318220 10(-6) M decreased phosphorylation in PCT to 125+/-10% ( P<0.05). In mTAL, RO-318220 did not modify the phosphorylation degree or the activity of Na+-K+-ATPase. Both calcineurin inhibitor FK-506 10(-6) M and phorbol 12-myristate 13-acetate (PMA) 10(-6) M increased the degree of Na+-K+-ATPase phosphorylation ( P<0.05) and inhibited Na+-K+-ATPase activity to 657+/-152 and 1,448+/-347 pmol/mm tubule per hour, respectively, in mTAL ( P<0.01). Increase in [Na+]i to 30, 50 and 70 mM resulted in no changes in Na+-K+-ATPase phosphorylation degree or activity in mTAL. Conversely, in PCT increments in [Na+]i were paralleled by decreased phosphorylation (from 120+/-7 to 160+/-15% of controls, P<0.05) and increased Na+-K+-ATPase activity (from 850+/-139 to 1,874+/-203 pmol/mm tubule per hour, P<0.01). Dopamine (DA) 10(-6) M decreased both Na+-K+-ATPase dephosphorylation to 41.85+/-9.58% ( P<0.05) and Na+-K+-ATPase activity to 2,405+/-176 pmol/mm tubule per hour in mTAL ( P<0.01). RO-318220 reversed DA effects. Data suggest that regulation of the degree of Na+-K+-ATPase alpha1 subunit phosphorylation at Ser-23 and enzyme activity have different mechanisms in mTAL than in PCT, and may help us to understand the physiological heterogeneity of both segments.

Previous reports have shown a stimulatory effect of vasopressin (VP) on Na-K-ATPase and rBSC-1 expression and activity. Whether these VP-dependent mechanisms are operating in vivo in physiological conditions as well as in chronic renal failure (CRF) has been less well studied. We measured ATPase expression and activity and rBSC-1 expression in the outer medulla of controls and moderate CRF rats both before and under in vivo inhibition of VP by OPC-31260, a selective V 2-receptor antagonist. OPC-31260 decreased Na-K-ATPase activity from 11.2 Ϯ 1.5 to 3.7 Ϯ 0.8 in controls (P Ͻ 0.05) and from 19.0 Ϯ 0.8 to 2.9 Ϯ 0.5 mol P i ⅐ mg protein Ϫ1 ⅐ h Ϫ1 in moderate CRF rats (P Ͻ 0.05). CRF was associated with a significant increase in Na-K-ATPase activity (P Ͻ 0.05). Similarly, CRF was also associated with a significant increase in Na-K-ATPase expression to 164.4 Ϯ 21.5% compared with controls (P Ͻ 0.05), and OPC-31260 decreased Na-K-ATPase expression in both controls and CRF rats to 57.6 Ϯ 9.5 and 105.3 Ϯ 10.9%, respectively (P Ͻ 0.05). On the other hand, OPC-31260 decreased rBSC-I expression in both controls and CRF rats to 60.8 Ϯ 6.5 and 30.0 Ϯ 6.9%, respectively (P Ͻ 0.05), and was not influenced by CRF (95.7 Ϯ 5.2%). We conclude that 1) endogenous VP modulated Na-K-ATPase and rBSC-1 in both controls and CRF; and 2) CRF was associated with increased activity and expression of the Na-K-ATPase in the outer medulla, in contrast to the unaltered expression of the rBSC-1. The data suggest that endogenous VP could participate in the regulation of electrolyte transport at the level of the outer medulla.vasopressin; rbsc-1; sodium-potassium-adenosine 5Ј-triphosphatase; chronic renal failure THERE IS STRONG EVIDENCE that vasopressin (VP) stimulates Na-K-ATPase and Na ϩ -K ϩ -Cl Ϫ cotransporter in the kidney outer medulla and, more precisely, in the medullary thick ascending limb of Henle (mTAL) (15). However, the experimental designs so far have been mostly related to the administration of exogenous VP, to either intact animals or in vitro preparations. The question of whether the level of endogenous VP activity plays a homeostatic role at the kidney outer medulla has not yet been examined. The introduction of powerful VP inhibitors has made it possible to design experiments looking at that question. OPC-31260 is a nonpeptide V 2 -receptor inhibitor developed by Yamamura et al. (21), and its actions are limited to states where VP activity is present. This approach was recently used by Ohara et al. (18), who were able to show a VP-mediated upregulation of the aquaporin-2 water channel in pregnant rats by using OPC-31260.In addition, previous experiments from our laboratory and those of others have suggested that in chronic renal failure the remaining nephrons suffer diverse adaptive mechanisms. Thus Bertuccio et al. (1, 2) showed an increase in intracellular cAMP levels in microdissected mTAL segments in chronic renal failure (CRF) rats, which were unresponsive to VP in vitro, opposed to baseline lower levels and a dose-respon...

Chronic hyponatremia, unless associated with extracellular fluid volume expansion, is an infrequent electrolyte imbalance in pediatrics. We report an infant with chronic hyponatremia suggestive of a syndrome of inappropriate secretion of antidiuretic hormone (SIADH), in the absence of ADH secretion. A mutation was found in the same codon of the gene that results in a loss-of- function of arginine vasopressin receptor 2 (AVPR2) observed in congenital nephrogenic diabetes insipidus. In this case, a gain-of- function of AVPR 2 was found to be responsible for a SIADH-like state.

No abstract

Background: Malnutrition is widely prevalent in dialysis. Malnourished patients present depletion of somatic protein stores and a decrease in lean body mass (LBM) that can be measured by different techniques. Aims: (1) To assess the reliability of lean mass measurements obtained by creatinine kinetics (CrK) in a group of stable peritoneal dialysis (PD) patients, using dual-energy x-ray absorptiometry (DEXA) measurements as the reference method; (2) to establish the reproducibility of LBM estimated by CrK in individual patients analyzing repeated measurement in the short term, and (3) to correlate measurements of LBM with laboratory determinations that assess nutritional status. Methods: We performed a cross-sectional evaluation of LBM by DEXA and CrK in 39 PD patients. In 14 patients we performed repeated measurements of LBM by CrK in the short term. Results: No significant difference was found in mean lean mass values estimated by both methods: mean DEXA LBM was 41.7 kg, 36.1 ± 4.5 kg in females and 52.7 ± 6.4 kg in males and mean CrK LBM was 41.08 kg, 37.5 ± 6.1 kg in females and 48.1 ± 8.4 kg in males. A good correlation was found between both techniques (r = 0.71; p < 0.003). The mean difference between the two methods was 0.638 ± 6.95 kg (95% confidence limits: –12.98 and +14.26). A wide scatter of the differences between both methods was seen throughout the range of measurements of LBM. When LBM by CrK was repeatedly (2–3 times) measured in a period of 3–4 months in 14 patients, it had a coefficient of variation (CV) of 15.39% (range 2.89–42.88%), while body weight CV in the same period was 0.69% (range 0–1.9%). Conclusions: CrK is an unsatisfactory method for the assessment of LBM in PD patients.