Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022672 (acute tubular necrosis)
 2,175 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to study the mechanism of dystrophic calcification, an anoxic incubation of rat renal cortex in a tissue culture medium was performed in vitro. Calcium and phosphate in the medium were adjusted to 1.6 and 1.2 mM/1 respectively. Calcification occurred in apposition to the inner surface of membranous cellular degradation products and associated with the flocculent densities within the degenerate organelles. The chemical nature of the flocculent density was not determined. In view of the known affinity of calcium for acidic phospholipids, particularly phosphatidyl serine (PS), which lines the inner surface of the plasma membrane, calcification along the inner surface of membrane was thought to be related to the presence of PS. Accumulation of calcium in mitochondria, which is presumably dependent upon residual substrate for energy production, appeared to cause calcification as well. Amorphous calcium phosphate in the form of spheroids, and possibly fine fibrils and granules, also appeared to play a role in calcification by their transformation into apatite. The seemingly simple phenomenon of tissue calcification is complex. Nephrocalcinosis in vitro is remarkably similar to the calcification in acute tubular necrosis in vivo, and is a convenient model with which to study the mechanism of calcification. It is concluded that the cellular degradation products are the initial loci of calcification and have a likely role in urolithiasis.
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PMID:Nephrocalcinosis in vitro. 664 38

In this study, the ability of low molecular dextrans to prevent morphologically detectable acute tubular necrosis during cold storage was evaluated. Rat kidneys were flushed with a sodium phosphate buffer (pH 7.2) containing different concentrations of dextran 10 (m.w. of 10,000 or less) and stored at 0-2 degrees C for up to 5 days (samples taken at 24-hr intervals). It was found that solutions containing 20% or more of dextran 10 provided significantly improved morphological preservation of kidney nephrons when compared with currently popular kidney cold storage preservation solutions (i.e. University of Wisconsin and Euro-Collins solutions). Adding smaller amounts (i.e., 15%) of dextran 10 to a cold storage solution already containing another effective osmotic agent (i.e., sucrose) also resulted in superior morphological preservation, indicating a beneficial additive effect of using more than one osmotic agent. Dextran 40 (m.w. 40,000) did not provide as good morphological preservation as did a similar concentration of dextran 10. It is concluded that the use of the proper kind and proper amount of low molecular weight dextrans in preservation solutions can significantly reduce the morphologically detectable acute tubular necrosis during cold storage.
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PMID:An evaluation of the ability of dextrans to reduce acute tubular necrosis during cold storage preservation. 751 87

As acute tubular necrosis (ATN) is still an important cause for postoperative malfunction of renal grafts, it would be useful to have a method predicting such a complication. We investigated the possibility to predict ATN by measuring the ratio of phosphomonoesters (PME, largely consisting of adenosine monophosphate) and inorganic phosphate (Pi) in the renal tissue, using 31P magnetic resonance spectroscopy (MRS) during the cold ischemia period. Assuming that this ratio reflects the tissue high-energy phosphate status, we studied five kidneys from living related donors (LRD), 28 kidneys from heart beating donors (HBD) and nine kidneys from non-heart beating donors (non-HBD). All kidneys were preserved with a phosphate free solution. We found an inverse relation between the time of 31P MRS and the PME/Pi ratio, suggesting a graded decay of tissue high energy phosphates during cold ischemia. The PME/Pi ratio was highest in grafts from LRD (2.65 +/- 0.50, no ATN), intermediate in grafts from HBD (1.65 +/- 0.41, 21% ATN) and lowest in those derived from non-HBD (1.05 +/- 0.47, 56% ATN). The differences in PME/Pi ratio between the groups was statistically significant (P < 0.01). Moreover, the ratio was significantly lower in grafts developing ATN (1.73 +/- 0.41 vs. 1.35 +/- 0.29 in the HBD group, 1.41 +/- 0.24 vs. 0.76 +/- 0.36 in the non-HBD group, P < 0.05). These observations point to a general relation between the pre-transplant kidney PME/Pi ratio and the development of ATN. However, the predictive value of a low PME/Pi ratio was too low (36%) to reliably predict development of ATN in individual cases.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pre-transplantation assessment of renal viability with 31P magnetic resonance spectroscopy. 770 29

The incidence of ARF in pediatric population varies according to the definition of the syndrome. If the diagnosis is based on a decrease of glomerular filtration rate (GFR), possibly accompanied by a decrease of urinary output and the sudden change of renal function indexes, then the number of patients which can be considered affected by ARF in hospital practice is high, as it comprises all the cases with functional impairment of renal function. The availability of tables with normal values of serum creatinine for different gender and age and the knowledge of the minimal urine output compatible with the normality allows a precise diagnosis of ARF. The differential diagnosis of ARF must take into account prerenal, renal and postrenal causes. Prerenal and renal ARF may be sometimes difficult to differentiate. Indexes such as sodium fractional excretion, utilizing urinary to plasma ratios of sodium and creatinine, can be helpful: values less than 1 indicate prerenal ARF, more than 2 renal ARF. The management of ARF is dependent on the causes of ARF. Prerenal ARF is normally treated by measures of volume expansion and/or removal of the underlying cause. Renal ARF requires an accurate control of water and electrolyte balance and of nutritional status and the prevention or treatment of numerous complications, which may worsen the course of the syndrome. Indications to dialysis must be evaluated every day and an assessment of nutritional status performed. All the factors which may cause hypercatabolism, such as infections, hemorrhage, low calorie intake, must be recognized and treated. This approach allows a better control of serum urea, potassium, phosphate and acidosis. Nutrition must be implemented and an adequate protein and calorie intake must be obtained, through spontaneous oral route and, whenever required, enteral and parenteral nutrition. In conclusion, patients with mild-degree, mostly of prerenal origin, ARF represent a common finding in hospital practice. Identification and prompt treatment of the underlying cause is the best prevention of acute tubular necrosis. Patients with ARF of renal origin require, in particular, daily nutritional assessment and dietary treatment to delay the onset of dialysis.
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PMID:[Management of acute renal failure in hospital practice]. 928 Sep 5

The purpose of this study was to investigate the function of transplant kidneys in situ, and to detect pathologic changes, using volume-selective phosphorous NMR spectroscopy (31P MRS). Localized 31P MR spectra were obtained from 37 patients using a whole-body MR scanner with a combination of surface coils, adiabatic excitation pulses, and a modified image-selected in vivo spectroscopy (ISIS) sequence. Seventeen patients with pathologic changes after renal transplant were compared with a control group of 20 patients with no evidence of transplant dysfunction. The transplant kidneys with rejection reaction showed higher ratios of inorganic phosphate (P2i) to adenosine triphosphate-alpha (ATP-alpha) than the normal control group (.4 +/- .16 compared with .22 +/- .11, P = .01) and reduced pH. The spectra of transplant kidneys with tubular necrosis had lower phosphomonoester (PME)/phosphodiester (PDE) ratios than the control group (.65 +/- .35 compared with .96 +/- .5, P = .04). The pathologies of rejection and tubular necrosis could be differentiated from each other by pH (6.93 +/- .1 in rejection versus 7.14 +/- .19 in tubular necrosis, P = .04). Preliminary results indicate that localized image-guided 31P MR spectroscopy of transplant kidneys in situ can detect rejection reactions and acute tubular necrosis noninvasively, providing an incentive for further research.
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PMID:Localized 31P MR spectroscopy of the transplanted human kidney in situ shows altered metabolism in rejection and acute tubular necrosis. 930 12

Urinary excretion of aluminium after a successful transplant can reverse pre-transplant aluminium intoxication. We have evaluated the time course of urinary aluminium excretion and its correlation with several parameters of renal function and mineral metabolism in 49 patients (33 men and 16 women) with a wide range of pre-transplant serum aluminium concentrations, performing sequential determinations at pre-transplant time and at 7, 30, 60, and 90 post-transplant days. Mean serum aluminium at pre-transplant was 54.5+/-46.8 microg/l decreasing progressively to 28.7+/-24.4 microg/l at 90 days (P<0.0002), paralleling the decrease in serum creatinine. Urinary aluminium decreased from 63.0+/-77.9 to 52.4+/-55.9 microg/l at 90 days (P<0.0001). The maximum urinary aluminium/creatinine was 1.8+/-2.7 at 7 days and was associated with the greatest fractional excretion of sodium (4.7+/-5.1%), and the lowest tubular reabsorption of phosphate (55.7+/-25.1%). The fractional excretion of aluminium was also greatest at day 7 (1.1+/-0.9%) when serum creatinine was still elevated (3.6+/-2.3 mg/dl). At each period of time after transplantation fractional excretion of aluminium was similar in all patients despite disparate serum aluminium concentrations. Fractional excretion of aluminium was highest in those patients who developed post-Tx acute tubular necrosis (0.7+/-0.5 vs 1.5+/-1.0%, P=0.008). We found a direct positive correlation (r=0.43; P<0.002) between urinary aluminium and urinary phosphate. Basal levels and sequential changes in serum PTH, calcium, and phosphate did not correlated with fractional excretion of aluminium. These findings suggest: (i) urinary aluminium remains elevated during prolonged periods after transplant and is probably a marker of pre-transplant tissue aluminium accumulation; (ii) post-transplant fractional excretion of aluminium seems to correlated positively with other evidences of renal tubular dysfunction. Early post-transplant tubular malfunction could significantly enhance urinary aluminium elimination.
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PMID:Time course and functional correlates of post-transplant aluminium elimination. 956 31

The culture of renal tubular cells from genetically modified animals opens the opportunity of biochemical, cell biology and physiological studies under strictly controlled conditions. Either primary cultures or cell lines can be used. Through two examples of primary cultures of proximal tubular cells obtained from knock-out mice, important information about the function of proteins were obtained. Mice lacking vimentin, an intermediate filament normally reexpressed in tubular cells during regeneration and culture, have a normal tubular function under basal conditions. Proximal cells grown from these animals exhibit a defect in sodium-glucose cotransport activity, most likely related to alterations in the dimer/monomer ratio of the transporter in the apical membranes. These alterations may be important in terms of tubular function during the recovery phase following acute tubular necrosis. The situation is strikingly different with regard to mice lacking HNF-1, a transactivator involved in the transcription of multiple genes. These animals suffer from severe Fanconi syndrome related to decreased expression of proximal transporters including isoforms of sodium-glucose (SGLT2) and sodium-phosphate (NPT1) cotransporters. Whereas transport defects are observed in isolated tubules, they are no longer apparent in cultured proximal cells because the expression of these isoforms is suppressed under culture conditions. These observations illustrate the interest and limits of the in vitro models for studying renal function in transgenic animals.
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PMID:Renal tubular cells cultured from genetically modified animals. 1055 38

Ex vivo NMR spectroscopy was used to investigate pH in 67 human kidney transplants. (1)H and (31)P spectra were recorded at 1.5 T during regular hypothermic storage in histidine-tryptophane-alpha-ketoglutarate (HTK) solution. Estimations of cytosolic pH from chemical shift differences between inorganic phosphate and phosphodiesters and of extracellular pH from the varepsilon1 and delta2 protons of histidine were based upon systematic titration studies. The possibility to predict acute tubular necrosis (ATN) by measuring pH was compared to results obtained with peak area ratios of phosphomonoesters (PME) and Pi and of the gamma-phosphorus of nucleoside 5'-triphosphate (gamma-NTP) and Pi. Cytosolic pH was 6.86+/-0.10 in kidneys showing immediate post-transplant function and 6.84+/-0.10 in those with ATN. Time-dependent studies demonstrated a monoexponential pH decay (velocity constant: 0.14+/-0.07 h(-1)). Extracellular pH varied between 7.40 and 7.15. Grafts with immediate function showed higher PME/Pi (2.24+/-0.57 vs. 1.77+/-0.50, p<0.05) and gamma-NTP/Pi (0.33+/-0.16 vs. 0.16+/-0.08, p<0.001). Intra- and extracellular pH can be monitored non-invasively during hypothermic transplant storage. The pH gradient between both compartments provides quantitative information about the buffer capacity of the preservation medium. Acidification is not a primary cause of ATN during regular HTK storage. The total nucleotide pool is a determinant of the reversibility of ischemic injury.
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PMID:Tissue pH in human kidney transplants during hypothermic ischemia. 1093 Jul 84

Streptozotocin (STZ) is widely applied in animal models of insulin-dependent diabetes mellitus. Adverse effects of STZ mainly concern liver and kidney. In nonhuman primates a single 100-150 mg/kg dose invariably induces diabetes with only rare adverse effects. We report one animal with renal failure necessitating sacrifice. Body weight (age) might be a confounding factor, i.e. older animals might be more vulnerable to STZ-related toxicity. We therefore recommended to administer STZ on a mg/m2 basis and not on a mg/kg basis. In our islet transplantation program nonhuman primates with STZ-induced diabetes received transplants under chronic immunosuppression including calcineurin inhibitors (cyclosporine, tacrolimus), drugs in the rapamycin class affecting growth factor-induced cell proliferation, and the sphingosine 1-phosphate receptor antagonist FTY720. Four animals developed renal failure and had to be sacrificed, most likely caused by cyclosporine. Kidney histology was typical for cyclosporine toxicity including thrombotic microangiopathy in glomeruli and fibrinoid necrosis of arteries, and for STZ toxicity including acute tubular necrosis and accumulations of erythroid precursors. This adverse effect was observed at a pharmacologically active cyclosporine exposure. Additionally, six diabetic animals without major adverse effects during cyclosporine or tacrolimus treatment are presented. We conclude that cyclosporine facilitates renal dysfunction in animals with STZ-induced diabetes, presumably related to an increased vulnerability to a toxic insult after STZ administration.
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PMID:Cyclosporine toxicity in immunosuppressed streptozotocin-diabetic nonhuman primates. 1559 Jan 27

Glomerular and tubular function of transplanted kidneys were assessed in 46 children aged 15.7 +/- 4.6 yr, 4.2 +/- 2.8 yr after renal transplantation. There were 34 cadaveric, and 12 living-related donors. Twelve patients (26%) had acute episodes (acute tubular necrosis, rejection, or urinary tract infection) during follow-up. All patients were on triple immunosuppression. The mean serum creatinine was 1.5 +/- 0.6 mg/dL. Creatinine clearance (Ccreat) calculated from a 24-h urine collection was 48.0 +/- 19.7 mL/min/1.73 m(2), and that estimated from the Schwartz formula, 61.0 +/- 22.5 mL/min/1.73 m(2). A positive correlation was found between the calculated and estimated clearances. Mean urine concentrating ability was 487 +/- 184 mOsmol/kg, with a value lower than 400 mOsmol/kg in 35% of patients. There was a positive correlation between urine osmolality and estimated Ccreat. Metabolic acidosis (bicarbonate <22 mmol/L) was found in 41% of patients, with relatively alkaline urine and high chloride level. Fractional excretion (FE) of sodium was above 1% in 68% of patients (mean 1.66 +/- 1.06%), and FE(Mg) was above 3% (mean 10.9 +/- 5.2%) in 93% of patients. Tubular reabsorption of phosphate (TP)/glomerular filtration rate (GFR) was 3.2 +/- 0.8 mg/dL glomerular filtrate (GF). FE(K), FE(UA), and Ca/creatinine in urine were normal. There were no functional group differences between the cadaveric and living-related kidneys. Significant group differences were found in those with acute episodes and those with a normal course. Estimated Ccreat was 54 +/- 20 vs. 67 +/- 20 mL/min/1.73 m(2) in the acute episodes and the normal course groups, respectively. Also, the FE(NA), FE(UA), and FE(Mg) were higher in the acute episodes group -2.3 +/- 1.6, 10.6 +/- 4.4, and 14.8 +/- 6.5%, respectively, compared with the normal course group -1.4 +/- 0.6, 8.2 +/- 2.8, and 9.6 +/- 4.0%, respectively. There were no between-group differences in plasma bicarbonate, FE(K), TP/GFR, and urine osmolality. We believe that most, if not all tubular dysfunctions in the transplanted kidney are secondary to renal failure and interstitial damage from acute episodes and nephrotoxic drugs. These dysfunctions are similar to those in chronic renal failure, where interstitial fibrosis plays a role in kidney function deterioration.
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PMID:Tubular and glomerular function in children after renal transplantation. 1604 94


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