PubMed Health⌕ Search

Biomedical subjects

K M Gaudio

Publications and source records attributed to K M Gaudio.

32 records · Page 2Linked to original sources

Postischemic ATP-MgCl2 provides precursors for resynthesis of cellular ATP in rats.

Postischemic administration of ATP-MgCl2 is known to enhance recovery of renal function and accelerate the restitution of cellular ATP levels. To differentiate between a direct and indirect effect of the exogenous nucleotide, rats were subjected to 45 min of bilateral renal ischemia and were infused with either ATP-MgCl2, AMP-MgCl2, or normal saline. The immediate recovery of the cellular ATP was similar in all three groups of animals, whereas the subsequent recovery was accelerated by the infusion of either nucleotide. Since ATP-MgCl2 and AMP-MgCl2 produced similar results, this study provides evidence that exogenous ATP may act by providing precursors for the resynthesis of the cellular adenine nucleotide pool rather than being a direct source of energy.

Adenosine Triphosphate↗

Postischemic hemodynamics and recovery of renal adenosine triphosphate.

Renal vasoconstriction is an important pathophysiological component of an ischemic acute renal injury. The postischemic infusion of ATP-MgCl2 enhances recovery of glomerular and tubular function, accelerates regeneration of sublethally injured tubular cells, and augments resynthesis of cellular nucleotides. Since both ATP and MgCl2 are vasoactive compounds, postischemic enhancement of renal blood flow (RBF) by a pharmacological agent, dopamine, was examined to study the possible contribution of vasodilation. At 2 h, the infusion of dopamine resulted in RBF (1.70 +/- 0.09 ml X min-1 X 100 g body wt-1 X kidney-1) and inulin clearance (CIn, 400 +/- 44 microliter X min-1 X 100 g body wt-1) similar to rats treated with ATP-MgCl2 (1.73 +/- 0.27 RBF, 404 +/- 38 CIn) and significantly (P less than 0.01) greater than saline-treated rats (0.80 +/- 0.04 RBF, 78 +/- 19 CIn; P less than 0.01). However, by 24 h CIn in dopamine animals had not continued to improve (460 +/- 25 microliter X min-1 X 100 g body wt-1) and was similar to normal saline rats (388 +/- 40). In contrast, CIn in ATP-MgCl2 animals showed sustained recovery (676 +/- 28 microliter X min-1 X 100 g body wt-1, P less than 0.01). These differences resulted from improved integrity of tubular epithelium as reflected by decreased cell swelling and necrosis. Moreover, the recovery of renal ATP levels, as assessed by 31P nuclear magnetic resonance, in animals given saline (63 +/- 3%) or dopamine (66 +/- 5%) was slow and incomplete by 120 min after ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

Progression of orthostatic proteinuria to focal and segmental glomerulosclerosis.

Focal glomerulosclerosis, with the nephrotic syndrome and progressive renal insufficiency, developed in a 15-year-old boy who presented initially 1 year earlier with orthostatic proteinuria. Although generally considered to be a benign disorder, this case suggests that on rare occasions, serious glomerular diseases may develop in patients with orthostatic proteinuria or that significant glomerular disease may occasionally present with postural proteinuria.

Adolescent↗

Beneficial effect of thyroxin on recovery from toxic acute renal failure.

To determine the effect of thyroxin (T4) on the recovery from toxic acute renal failure, rats were injected, subcutaneously, with K-dichromate (15 mg/kg) and at the peak of the renal injury, each animal was given either T4 (4 micrograms/100 g body weight, i.p.) or normal saline (NS). The T4-treated rats had significantly better CIn (669 +/- 35 microliter/min/100 g body weight), improved FENa (0.49 +/- 0.05%) and increased UOsm (835 +/- 50 mOsm/kg) as compared to animals given only NS (CIn 422 +/- 27; FENa 1.02 +/- 0.12; and UOsm 613 +/- 23). A similar dose of T4 given to non-injured control rats had no effect on renal function. The beneficial effect of T4 on dichromate injected rats was sustained and lead to more prompt recovery of glomerular function. To eliminate any hemodynamic effects of T4, an isolated perfused kidney preparation was utilized, and kidneys from dichromate injected rats treated with T4 had significantly better CIn, urine flow and FENa compared to rats given NS. Cellular morphology was better preserved in T4-treated animals. These data indicate that treatment with T4 results in enhanced recovery from an acute toxic renal insult and that this beneficial effect is unlikely to be related to nonspecific systemic effects of the hormone.

Acute Kidney Injury↗

Accelerated cellular recovery after an ischemic renal injury.

To determine the mode of action of the beneficial effect of adenosine triphosphate (ATP)-MgCl2, recovery of microinjected inulin, proximal tubular pressure (PTP), and cellular damage as quantitated by histomorphometric analysis of necrosis and swelling were evaluated at 2, 6, and 24 hours after 45 minutes of renal ischemia in rats treated with either normal saline or ATP-MgCl2. At 2 hours both groups of rats demonstrated increased permeability to inulin, elevated PTP, and severe ischemic damage and necrosis. By 6 hours ATP-MgCl2 rats had less tubular back leak of inulin, PTP was modestly reduced, and ultrastructural studies demonstrated improved cellular morphologic features with evidence of early regenerative changes. The saline rats had progressive ischemic cellular damage. At 24 hours ATP-MgCl2 rats had reestablished tubular integrity, PtP had fallen, and ischemic alterations were improved, with only focal evidence of necrosis. Saline-treated rats still had a back leak of inulin, elevated PTP, and progressive ischemic injury. This study demonstrates that 1) cellular damage continues to occur for 6 hours after renal ischemia; 2) ATP-MgCl2 enhances recovery of tubular integrity and cellular morphologic features. The salutary effect of ATP-MgCl2 appears related to the preservation of sublethally injured cells and acceleration of the process of restoration and repair of damaged cells.

Adenosine Triphosphate↗

Serum hemolytic factor D values in children with steroid-responsive idiopathic nephrotic syndrome.

Serum hemolytic factor D activity, an important component of the ACP, was measured in patients with SR-INS. The mean serum factor D hemolytic activity of patients with SR-INS in relapse was significantly reduced compared to the mean of the control group. Twenty-one of 27 SR-INS patients in relapse (78%) had reduced serum factor D activity. In contrast, the mean serum factor D hemolytic activity of SR-INS patients in remission was not significantly different from that in the control group. Factor D hemolytic activity was also reduced in other types of renal disease with the nephrotic syndrome. Serum factor D values were highly correlated with the serum albumin concentration. Although hemolytic factor D activity could not be detected in the urine, the low molecular weight and the significant correlation with serum albumin concentration suggest that urinary loss is responsible for the low serum levels of factor D. Deficient serum values of factor D may contribute to the increased susceptibility of SR-INS patients in relapse to bacterial infections with organisms which activate the ACP.

Adolescent↗

Accelerated recovery of single nephron function by the postischemic infusion of ATP-MgCl2.

This study was designed to investigate the effects of ATP-MgCl2 when infused immediately 8 or 24 hr after 45 min of bilateral renal artery ischemia and to determine if an initial improvement in clearance of inulin (CIn) would be sustained throughout the course of recovery. In addition, the influence of ATP-MgCl2 on the pattern of recovery of whole kidney and single nephron function was assessed by determining the impact of this agent on proximal tubular pressure and transepithelial backleak. The postischemic administration of ATP-MgCl2 resulted in significantly enhanced recovery of CIn irrespective of the time of the infusion after the initial insult. This beneficial effect was sustained in that the ATP-MgCl2-treated rats had significantly better CIn 1, 3 and 7 days after the injury when compared to normal saline-treated animals. Moreover, single nephron inulin clearance (SNCIn) was better preserved than whole kidney CIn in both groups of animals and in the ATP-MgCl2-treated animals SNCIn was similar to control values even 1 day after the injury. The enhanced recovery of single nephron function in the ATP-MgCl2-treated animals resulted from reduced proximal tubular pressure and diminished backleak of tubular fluid. Animals given ATP-MgCl2 had better preservation of cellular morphology. Horseradish peroxidase was excluded from most epithelial cells and the interstitium in a manner similar to that seen in control animals while saline-treated rats demonstrated backleak of this tracer compound. Based on these studies, it appears that the beneficial effect of ATP-MgCl2 occurs because of the preservation of sublethally injured cells by augmentation of the process of recovery.

Adenosine Triphosphate↗

Steroid-dependent nephrotic syndrome in children: histopathology and relapses after cyclophosphamide treatment.

Children with steroid-dependent frequently relapsing nephrotic syndrome are generally assumed to have a minimal change in histology and therefore to respond favorably to treatment with cyclophosphamide. The clinical course of 38 children with steroid-sensitive frequently relapsing nephrotic syndrome was analyzed. Biopsy samples were obtained from these children several years (mean 6 years) after the onset of their disease but before they were treated with cyclophosphamide. Three histologic types of lesions were found: minimal change lesion, 18 patients (47%); focal and segmental glomerulosclerosis, 11 patients (29%); and mesangial proliferation, 9 patients (24%). Each patient then received cyclophosphamide (2mg/kg of body wt per day) for 12 weeks, and each responded with a complete remission, which lasted 1.5 +/- 0.2 years. During 6 years of followup after cyclophosphamide, 17 patients experienced one or more relapses, but 21 patients remained in sustained remission. The incidence of relapse after cyclophosphamide was significantly greater (P less than 0.01) in the patients with focal and segmental glomerulosclerosis (8/11, 73%) and mesangial proliferation (5/9, 56%), as compared with children with minimal change lesion (4/18, 22%). These data indicate that children with frequently relapsing steroid-dependent nephrotic syndrome (1) will not all develop minimal-change lesions within several years; in fact, approximately half will have either focal and segmental glomerulosclerosis or mesangial proliferation; and (2) after cyclophosphamide treatment, the incidence of relapse will be related to the histopathologic type of lesion present at the time of treatment with cyclophosphamide.

Adolescent↗

Enhanced recovery from acute renal failure by the postischemic infusin of adenine nucleotides and magnesium chloride in rats.

Although a number of manipulations prior to or during the initiation phase of an acute renal injury will modify the degree of functional impairment, agents administered after the acute insult usually have been ineffective. In the present study, adenine nucleotides (AMP, ADP, or ATP) combined with magnesium chloride were infused after an ischemic renal injury. Twenty-four hours later: (1) rats that received no infusion or one of the components of the mixture alone had reduced CIn (355 +/- 40 microliter/min/100 g of body wt vs. 977 +/- 40 control value), decreased RBF (3550 +/- 205 microliter/min/100 g of body wt vs. 5095 +/- 171 control value), elevated FENa (0.65 +/- 0.10% vs. 0.17 +/- 0.04 control value), and diminished UOsm (862 +/- 110 mOsm/kg vs. 1425 +/- 132 control value); (2) rats given dopamine or phenoxybenzamine maintained low CIn (365 +/- 50) despite improved RBF (4678 +/- 222); (3) rats infused with either AMP, ADP, or ATP combined with magnesium chloride had markedly improved CIn (594 +/- 44, P < 0.01), increased RBF (4269 +/- 223, P < 0.01); normalized FENa (0.18 +/- 0.07%, P < 0.01), and improved UOsm (1201 +/- 106 mOsm/kg, P < 0.05). In animals given no infusion or only magnesium chloride, ultrastructural studies demonstrated focal cellular necrosis and marked generalized tubular cell and mitochondrial swelling, whereas rats infused with ATP and magnesium chloride had fewer ultrastructural changes with better preservation of cellular morphology. Rats treated with ATP and magnesium chloride had improved CIn despite ischemic periods of 30, 45, and 60- min; and the degree of improvement was directly related to the quantity of ATP and magnesium chloride administered. The cellular content of exogenously administered ATP was 2.5 times greater in previously ischemic kidneys than in nonischemic kidneys. The data indicate that adenine nucleotides combined with magnesium chloride when infused after the initiation of acute renal failure significantly improve both CIn and tubular function and suggest that these agents effectively enhance recovery following an ischemc renal insult.

Acute Kidney Injury↗

Renal perfusion and intratubular pressure during ureteral occlusion in the rat.

To define the interrelationship between changes in total renal blood flow (TRBF) and proximal tubular hydrostatic pressure (PTP), rats were studied 2, 3, 4, 6, 12, 18, and 24 h after bilateral ureteral occlusion (BUO). In control animals, a peak rise in both TRBF (3.52 +/- 0.26 ml . min-1 . 100 g body wt-1 . kidney-1) and PTP (28.6 +/- 1.3 mmHg) occurred 3 h after BUO. At each subsequent time interval, both TRBF and PTP fell, so that by 24 h after BUO, TRBF was 1.53 +/- 0.34 and PTP was 16.5 +/- 0.6, while in sham-operated rats the values were 2.52 +/- 0.22 ml . min-1 . g body wt-1 . kidney-1 and 12.8 +/- 0.2 mmHg, respectively. In animals treated with indomethacin (10 mg/kg) at the time of BUO, the alterations in both TRBF and PTP were completely ameliorated. At 3 h, TRBF was 1.8 +/- 0.32 ml . min-1 . 100 g body wt-1 . kidney-1 and PTP was 15.3 +/- 1.0 mmHg. TRBF and PTP remained essentially unchanged at each subsequent time period. These data indicate that 1) alterations in TRBF and PTP follow a similar and parallel pattern during BUO; 2) the pattern of changes in TRBF and PTP can be eliminated by treatment with indomethacin; and 3) renal hemodynamics appear to be the dominant factor in producing these changes during the first 12 h after BUO, whereas a sustained increase in tubular hydrostatic pressure may play a primary role in decreasing TRBF 12-24 h after ureteral occlusion.

Animals↗

Disorders of urine volume in the critically ill child.

This article will provide a pathophysiologic basis for the assessment of critically ill children who have developed disorders of urine volume. The anatomical and pathophysiologic causes of oliguria and polyuria are considered. The physiologic basis for the use of urinary sodium and osmolarity as a guide to the assessment of patients with disorders of urine volume are discussed in detail. In addition, guidelines for the management of children with acute renal failure, with particular emphasis on the consideration for nutritional support of these patients, is discussed as a part of the comprehensive approach to this problem. This article emphasizes an understanding of the pathophysiology of salt and water excretion by the kidney as a foundation to the diagnosis and management of patients with oliguria and polyuria.

Acute Kidney Injury↗

Altered renovascular resistance after spontaneous recovery from hemolytic uremic syndrome.

Twenty-three patients were evaluated from 1-15 (mean 6) years after recovering from an episode of diarrhea-associated associated childhood hemolytic uremic syndrome (DA-HUS). All patients had received only conservative treatment; none had been given experimental, anti-coagulant, or immunological therapies. Follow-up studies included morphologic and duplex Doppler sonograms. Doppler sonography was used to determine the resistive index, a measure of renovascular resistance. Histories and physical examinations revealed no abnormalities. Results of laboratory studies, which included calculated glomerular filtration rates, were all within normal limits, except for one patient with minor urinary abnormalities. Renal sonograms showed no significant abnormalities of kidney length or parenchymal appearance. However, Doppler sonographic examinations revealed that the DA-HUS patients demonstrated less of a decrease in renovascular resistance with age than did the control group (p < 0.0002). After recovery, patients treated exclusively with conservative management during an acute episode of DA-HUS appeared to have an excellent long-term prognosis. Comparison of our results with those from other studies in which investigational therapies have been used during the acute phase of DA-HUS suggests that latent toxicities which cause long term sequelae may not have been appreciated previously. The clinical significance of the altered renal vascular resistance remains to be delineated.

Acute Disease↗