Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serum calcitriol and the free calcitriol index together with factors considered to regulate calcitriol production were measured in eleven patients with moderate chronic renal failure (MCRF) and eleven age- and sex-matched normal subjects. Although the serum dialysable calcium levels were similar in the two groups, there was depression of calcitriol levels and an elevation of PTH and nephrogenous cyclic AMP (NcAMP) levels in the MCRF patients. Furthermore, plasma phosphate levels were higher and the renal phosphate threshold was depressed in this patient group. When all subjects were grouped together calcitriol was positively correlated with GFR. When calcitriol levels were factored for GFR, to permit an assessment of calcitriol production per unit functioning renal mass, there was no significant difference between normal and MCRF subjects. To determine whether reserve for calcitriol production existed, six of the MCRF patients and six of the age- and sex-matched normal subjects received a low calcium diet for one week supplemented by cellulose phosphate to bind calcium within the gut. In both groups there was a significant rise in calcitriol, although the absolute levels were much lower in the MCRF patients than the normal subjects. These results suggest that calcitriol deficiency is a major feature of MCRF despite marked hyperparathyroidism. The rise in calcitriol levels in MCRF suggests persistent reserve secretory capacity in this condition. Therefore, the low serum calcitriol concentration may be due not only to structural renal damage, but also to suppression of calcitriol formation perhaps due to altered renal phosphate handling.
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PMID:Calcitriol deficiency with retained synthetic reserve in chronic renal failure. 283 40

The effects of intravenous acetylsalicylic acid (1.0 g bolus) on renal function and prostaglandin synthesis were evaluated in a prospective, controlled study in eight patients in an intensive care unit. Four of these patients had congestive heart failure. Administration of acetylsalicylic acid caused significant antidiuresis (-56%), antinatriuresis (-82%), renin suppression (-26%) and decreased GFR (-41%). All of these changes were completely reversible within 1-2 hours and tended to be more pronounced in the patients with congestive heart failure. Urinary excretion of prostaglandin E2 was depressed profoundly (-93%) and did not return to more than 45% of control 6 h after the administration of acetylsalicylic acid. We conclude that intravenous acetylsalicylic acid affects kidney function in a manner similar to other prostaglandin synthesis inhibitors. Its effects are, however, short-lived. The inhibition of urinary PGE2 excretion outlasts GFR depression, antidiuresis, antinatriuresis and renin suppression by several hours.
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PMID:Effects of intravenous aspirin on prostaglandin synthesis and kidney function in intensive care patients. 311 Jun 70

Ferrioxamine methanesulfonate (S-FDF) is a new magnetic resonance (MR) contrast agent developed to improve magnetic resonance imaging of the abdomen and pelvis. This stable complex of deferoxamine methanesulfonate and iron is excreted in the urine by glomerular filtration modified by active renal tubular resorption. This study examines the acute systemic and renal hemodynamic responses to this agent after intravenous administration either as an infusion of 25 mg/kg over 5 minutes or as a rapid bolus at a dose of 50 mg/kg. In eight anesthetized dogs, renal plasma flow (RPF) was measured with an electromagnetic flowmeter, and GFR was determined by the renal extraction of technetium-99m-DTPA. Mean arterial pressure (MAP), pulse rate, and a lead II ECG were assessed. At a dose of 25 mg/kg over 5 minutes, MAP decreased significantly (control 146.0 +/- 6.5 mm Hg vs. 107 +/- 18 mm Hg at 2 minutes; P less than .05). In two of the eight animals, the MAP dropped below 60 mm Hg. Significant decreases in GFR and RPF also were noted. All four of the animals receiving the rapid injection of S-FDF experienced profound hypotension (MAP less than 50 mm Hg). The drop in heart rate from 152 +/- 11.6 bpm to 121 +/- 4.9 bpm was associated with a marked depression of the ST wave in the lead II ECG. Further animal studies are needed to assess the mechanism of toxicity and a potential synergism of action with pentobarbital anesthesia.
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PMID:Effects of the magnetic resonance contrast medium ferrioxamine methanesulfonate on systemic and renal hemodynamics in the anesthetized dog. 318 16

We measured nephrogenous cyclic adenosine monophosphate (NcAMP) excretion, an in vivo bioassay for endogenous parathyroid hormone (PTH) secretion, and renal phosphate threshold (TmP/GFR) in 33 renal allograft recipients with stable renal function (creatinine clearance greater than or equal to 60 ml/min/1.73 m2 body surface area, 6 months or more post-transplant) and in 9 kidney donors. Sixteen patients had normal parathyroid function, 8 had hypercalcemic hyperparathyroidism and 9 had normocalcemic hyperparathyroidism; the latter were apparently resistant to the hypercalcemic actions of endogenous PTH, but the cause for this was not apparent. In all four subject groups, TmP/GFR was significantly and similarly lower (by 0.8-1.0 mg/dl) than predicted by multiple regression on age, sex, corrected plasma calcium and NcAMP (determined in 306 subjects spanning a wide range of parathyroid function) indicating a major PTH-independent mechanism for reducing phosphate reabsorption in the presence of a single kidney. In all four groups the contribution of this mechanism to the observed depression of TmP/GFR was substantially greater than the contribution of increased PTH secretion. In all groups, but more so in the recipients than in the donors, fasting urinary phosphate excretion/GFR was increased, so that fasting plasma phosphate, although reduced, did not accurately reflect the severity of the defect in phosphate reabsorption. We conclude that the dominant mechanism for the adaptive decrease in renal tubular phosphate transport in response to nephron reduction does not require the participation of PTH and is manifest in the presence of fasting hypophosphatemia.
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PMID:Reduced phosphate reabsorption unrelated to parathyroid hormone after renal transplantation: implications for the pathogenesis of hyperparathyroidism in chronic renal failure. 354 37

The long-term effects of cyclosporine on renal function were evaluated in eleven liver transplant recipients over a 6-26-month follow-up period. Renal hemodynamic function (glomerular filtration rate [GFR], effective renal plasma flow [ERPF]) fell 60% postoperatively, subsequently improved, and stabilized at 45-60% of normal despite continued drug administration. Tubular sodium transport studies during water diuresis suggested that the proximal tubule is a major site of cyclosporine nephrotoxicity. In contrast to the acute effects of cyclosporine on renal function, the fraction of glomerular filtrate reabsorbed in the proximal tubule was less in the patient group while the fractional excretion of sodium, potassium, and phosphate was increased. When the fraction of filtered sodium reabsorbed in the diluting segment was examined as a function of sodium delivery, functional impairment occurred in the diluting segment as well. Eight renal biopsies performed in six patients 4-29 months posttransplantation showed only mild to moderate changes, predominantly vascular, which correlated poorly with corresponding renal function. These data showed that long-term cyclosporine administration produced early and persistent depression of both hemodynamic and tubular function. A functional rather than structural mechanism appears to be more significant during this period of observation.
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PMID:Long-term effects of cyclosporine on renal function in liver transplant recipients. 355 55

Experiments were performed on 26 rats to evaluate the effect of furosemide and muzolimine in an experimental model of acute renal failure (ARF). After control clearance measurements from both the left and the right kidney, an acute hydronephrosis was produced on the left side only, to completely interrupt urine flow rate. At the 17th minute of stop-flow, placebo (4 animals), furosemide (4 mg i.v. in 5 animals) or muzolimine (1.2 mg i.v. in 5 rats) were injected and three minutes later the renal arteries were clamped bilaterally for 20 minutes. The arterial clamps and the left hydronephrosis were removed at the 20th minute of ischemia and then 5 consecutive clearance periods were performed from either side to assess recovery from post-ischemic ARF. There was no difference in the entity of GFR depression and speed of recovery of either kidney between placebo, muzolimine and furosemide. The left, post-hydronephrotic kidney consistently exhibited a post-ischemic renal function more depressed than that measured in the contralateral side, although the speed of recovery was the same. The ATP content of the renal tissue was significantly larger in the right kidney compared to the contralateral side in the group receiving furosemide. In the animals treated with muzolimine ATP was significantly depressed in both kidneys. In the post-ischemic period the urinary Na excretion and the fractional water excretion rose significantly with either diuretic compared to placebo. However, this did not influence the recovery in GFR.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prevention of acute renal failure by diuretics. 400 97

In the present study 1 h of total occlusion of the left renal artery in conscious rats was chosen as experimental model of ischemic acute renal failure (ARF), while the contralateral kidney was left intact. Chronic high dietary sodium intake, acute isotonic saline infusion, or administration of saralasin did not protect from ARF. Furosemide, mannitol, and verapamil converted oliguric into non-oliguric ARF in 100%, 75%, and 60% of the animals, resp. Protection from oliguria and preservation of GFR inversely correlated with the depression of cortical ATP-concentration (control: 1.32 +/- 0.07 mumoles/g wet weight) 6 h after ischemia by 16%, 41%, and 58% in mannitol- and verapamil- treated rats and in untreated rats, resp. At this time, Na-K-ATPase enzyme activities in renal cortex and papilla were unaffected, while enzyme activity in outer medulla was suppressed from 15.4 +/- 1.4 to 9.4 +/- 1.0 mumoles Pi/mg protein h in all groups of animals. The results suggest that in this model of ARF renal ischemia not only affects cellular energy supply in renal cortex but also causes severe structural and functional impairment in the outer medulla, probably leading to tubular obstruction and depression of glomerular function. Pharmacological protection from ischemic oliguric ARF cannot be achieved by prior induction of high urine flow rates alone but depends on the degree of metabolic and functional reserve of the injured tubular epithelium.
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PMID:Renal functional and metabolic studies on the role of preventive measures in experimental acute ischemic renal failure. 641

The purpose of this study was to examine proximal and distal tubular function in rats with nonoliguric, myohemoglobinuric acute renal failure (ARF). ARF was induced with glycerol (50%, 10 ml/kg of body wt, i.m.), and renal function was studied 24 hours after glycerol or saline (controls) injection. Glycerol injection caused a 50 to 90% depression in GFR and a significant rise in blood urea nitrogen concentration. Animals with ARF exhibited glycosuria with normal blood sugar levels and a striking depression in tubular glucose reabsorption per milliliter of GFR. The capacity to reabsorb (mEq/liter GFR) was intact at normal blood bicarbonate levels, but was markedly depressed when blood bicarbonate was raised. The tubular maximum for para-aminohippurate (PAH) secretion and the renal extraction fraction of PAH were strikingly depressed in rats with ARF. Distal acidification as assessed by the urine-to-blood gradient of PCO2 (UB PCO2) was normal both during maximal alkalinization of the urine with bicarbonate (urine pH, approximately 7.8) or during neural phosphate infusion (urine pH, approximately 7.0). Net acid excretion per milliliter GFR and minimal urine pH (less than 5.5) following 3 days of ammonium chloride ingestion was similar in control and ARF animals. Potassium excretion was intact in maximal urinary osmolality were significantly altered in animals with ARF. Cortical and outer medullary Na-K-ATPase specific activities were significantly depressed in ARF rats. This occurred as a consequence of enzyme loss and not secondary to alterations in enzyme kinetics of absolute tubular sodium reabsorption. Light and electron microscopy showed diffuse proximal tubular damage, whereas glomeruli and distal tubules were intact. These data demonstrate that glycerol injection produces a diffuse proximal tubular transport defect associated with histologic and enzymatic alterations.
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PMID:Renal tubular function in glycerol-induced acute renal failure. 678 13

The toxicity of aminoglycosides is related to their concentrative uptake by proximal tubular cells and their capacity to interact with critical intracellular targets. Concentrative uptake is mediated by adsorptive endocytosis across the apical membrane followed by sequestration within lysosomes. The fundamental mechanism underlying the toxicity of these organic polycations is their capacity to interact electrostatically with and disrupt the metabolism of anionic phospholipids, especially the phosphoinositides. Polyaspartic acid, a polyanionic peptide, protects against aminoglycoside nephrotoxicity by forming electrostatic complexes with these drugs and inhibiting their interaction with critical intracellular targets. The selective toxicity of beta-lactams towards renal proximal tubular cells is related to their concentrative uptake via the organic anion transport system. Lipid peroxidation appears to play a major role in the toxicity of cephaloridine. Depressed mitochondrial respiration secondary to acylation of the mitochondrial transporter for succinate has been implicated in the pathogenesis of toxicity caused by other cephalosporins and carbapenems. The predilection of the kidney for amphotericin B toxicity is unclear as little drug is excreted by the kidneys. Toxicity is manifested by increased renal vascular resistance, depression of RBF and GFR, and altered tubular function that reflects the capacity of this drug to interact with cholesterol-containing membranes and increase membrane permeability to ions including potassium, hydrogen, calcium, and magnesium.
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PMID:Antibiotic-related nephrotoxicity. 780 Feb 46

Postischemic filtration failure in experimental animals results primarily from depression of the transcapillary hydraulic pressure difference (delta P), a quantity that cannot be determined in humans. To circumvent this limitation we determined the GFR and each of its remaining determinants in transplanted kidneys. Findings in 12 allografts that exhibited subsequent normofiltration (group 1) were compared with those in 11 allografts that exhibited persistent hypofiltration (group 2). Determinations were made intraoperatively in the exposed graft after 1-3 h of reperfusion. GFR (6 +/- 2 vs 29 +/- 5 ml/min) and renal plasma flow by Doppler flow meter (140 +/- 30 vs 315 +/- 49 ml/min) were significantly lower in group 2 than group 1. Morphometric analysis of glomeruli obtained by biopsy and a structural hydrodynamic model of viscous flow revealed the glomerular ultrafiltration coefficient to be similar, averaging 3.5 +/- 0.6 and 3.1 +/- 0.2 ml/(min.mmHg) in group 2 vs 1, respectively. Corresponding values for plasma oncotic pressure were also similar, averaging 19 +/- 1 vs 21 +/- 1 mmHg. We next used a mathematical model of glomerular ultrafiltration and a sensitivity analysis to calculate the prevailing range for delta P from the foregoing measured quantities. This revealed delta P to vary from only 20-21 mmHg in group 2 vs 34-45 mmHg in group 1 (P < 0.001). Further morphometric analysis revealed the diameters of Bowman's space and tubular lumens, as well as the percentage of tubular cells that were necrotic or devoid of brush border, to be similar in the two groups. We thus conclude (a) that delta P depression is the predominant cause of hypofiltration in this form of postischemic injury; and (b) that afferent vasoconstriction rather than tubular obstruction is the proximate cause of the delta P depression.
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PMID:Mechanisms of filtration failure during postischemic injury of the human kidney. A study of the reperfused renal allograft. 786 Jul 66


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