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)

The actions of L-channel calcium antagonists on the kidney are the result of direct and indirect effects. The direct effects are characterized by vasodilation, especially when the renal vascular resistance was enhanced beforehand. The increase in glomerular filtration rate is small and transient in most of the clinical trials with chronic administration. An important direct effect of calcium channel antagonists on renal function is the increase of sodium and water excretion by a tubular action that occurs in the absence of hemodynamic changes. The mechanism of the tubular effects of calcium channel antagonists is not understood at present. An indirect effect of calcium channel antagonists on the kidney is the inhibition of the aldosterone secretion by the adrenals. A sodium and water loss due to inhibition of tubular reabsorption leads to an increase in renin activity and aldosterone concentration in the plasma as seen typically with diuretics. The dissociation of renin- and aldosterone increase by calcium channel antagonists is a new finding and contributes favorably to the anti-hypertensive efficacy of calcium channel antagonists. In experimental acute renal failure mainly diltiazem and verapamil improved recovery of kidney function. In kidney transplantation, diltiazem reduced posttransplant acute tubular necrosis and improved primary graft function. It remains to be seen whether other calcium channel antagonists have a similar beneficial therapeutic effect in pathological states of renal function.
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PMID:Renal actions of calcium channel antagonists. 207 37

Koolen, M.I. et al. (1984) measured urinary kallikrein (UKal) in renal transplant recipients using 2 methods, S-2266 amidolytic assay and radioimmunoassay, and reported that the values by the former method showed an increase in amount at the time of acute rejection episode (ARE) despite of no variation in those by the latter. To clear the discrepancy, 24 hours excretion of UKal was measured by the amidolytic assay using Pro-Phe-Arg-MCA under 2 conditions, with and without soybean trypsin inhibitor (STI), in 10 living related kidney recipients (LR), their donors (LD), and 8 cadaver kidney recipients (CR), Furthermore, gel filtration chromatography (Sephacryl S-200) was performed in some recipients and LD to confirm whether the amidolytic activity (ALA) indicates exclusively UKal or not. The results were as follows. In LD, there were no statistical differences in ALA between not only before and after uninephrectomy but also with and without STI. On the post-operative course, some recipients showed a tendency of decrease in ALA with STI, and some kept a constant level. There occasionally appeared a difference between ALA with and without STI just after the transplantation, and at the time of ARE, acute tubular necrosis (ATN) or urinary tract infection (UTI). There was no fixed characteristic variation in ALA, both with and without STI, at the time of ARE. ALA with STI was lower in LR than in LD, and the lowest in CR, From the second week of transplantation and afterward, ALA with STI showed a positive correlation not with creatinine clearance but with urinary aldosterone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Urinary kallikrein-like activity in renal transplant recipients]. 235 63

The physical properties and chemical composition of urine are highly variable and are determined in large measure by the quantity and the type of food consumed. The specific gravity is the ratio of the density to that of water, and it is dependent on the number and weight of solute particles and on the temperature of the sample. The weight of solute particles is constituted mainly of urea (73%), chloride (5.4%), sodium (5.1%), potassium (2.4%), phosphate (2.0%), uric acid (1.7%), and sulfate (1.3%). Nevertheless, urine osmolality depends only on the number of solute particles. The renal production of maximally concentrated urine and formation of dilute urine may be reduced to two basic elements: (1) generation and maintenance of a renal medullary solute concentration hypertonic to plasma and (2) a mechanism for osmotic equilibration between the inner medulla and the collecting duct fluid. The interaction of the renal medullary countercurrent system, circulating levels of antidiuretic hormone, and thirst regulates water metabolism. Renin, aldosterone, prostaglandins, and kinins also play a role. Clinical estimation of the concentrating and diluting capacity can be performed by relatively simple provocative tests. However, urinary specific gravity after taking no fluids for 12 h overnight should be 1.025 or more, so that the second urine in the morning is a useful sample for screening purposes. Many preservation procedures affect specific gravity measurements. The concentration of solids (or water) in urine can be measured by weighing, hydrometer, refractometry, surface tension, osmolality, a reagent strip, or oscillations of a capillary tube. These measurements are interrelated, not identical. Urinary density measurement is useful to assess the disorders of water balance and to discriminate between prerenal azotemia and acute tubular necrosis. The water balance regulates the serum sodium concentration, therefore disorders are revealed by hypo- and hypernatremia. The disturbances are due to renal and nonrenal diseases, mainly liver, cardiovascular, intestinal, endocrine, and iatrogenic. Fluid management is an important topic of intensive care medicine. Moreover, the usefulness of specific gravity measurement of urine lies in interpreting other findings of urinalysis, both chemical and microscopical.
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PMID:Relative density of urine: methods and clinical significance. 307 30

Renal nerves contribute to the genesis of at least four disease processes. 1. Excess renal nerve activity contributes significantly to salt and water retention by patients with congestive circulatory failure. 2. Circumstantial evidence suggests that dopamine production may be deficient in a group of patients with idiopathic edema. Aldosterone secretion is high in this group and it has been shown that dopamine exerts a tonic inhibitory effect on angiotensin-stimulated aldosterone secretion. 3. Excess renal nerve activity probably plays a crucial role in the transition from hypotension and pre-renal failure to ischemic acute tubular necrosis. 4. Without doubt hyperactivity of renal nerves causes systemic hypertension in a variety of animal disease models. There is also good reason to believe that this occurs in some forms of human hypertension. The effects of the sympathetic nervous system on renal vascular resistance, renin release, tubular electrolyte reabsorption and aldosterone secretion are discussed in the context of these four diseases.
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PMID:Nervous disorders of renal function. 688 67

Hypokalemia in leptospirosis acute renal failure (ARF) was studied in nine patients with severe leptospirosis ARF and five patients with moderate leptospirosis ARF and compared with five patients with severe acute tubular necrosis (ATN) and eight healthy individuals. Urinary volumes of both the severe and moderate leptospirosis groups were higher than those of the severe ATN group. Leptospirosis groups had serum potassium levels lower than those found in the healthy and severe ATN groups. Serum sodium levels were lower in the severe leptospirosis group than in the moderate leptospirosis, the severe ATN, and the healthy groups. There was a positive correlation between the fractional excretion of sodium and potassium in the severe leptospirosis group as well as between serum creatinine and potassium levels in the pooled leptospirosis groups. Urinary pH in the severe and moderate leptospirosis groups was lower than in the severe ATN group. Aldosterone levels were higher in the severe leptospirosis group than in the healthy individuals. Cortisol levels were higher in the leptospirosis groups than in the healthy subjects. These results strongly suggest that hypokalemia in leptospirosis ARF is due to renal potassium wasting potentialized by aldosterone and cortisol, requiring that special attention is given to potassium replacement as well as to volume repletion in the treatment of leptospirosis ARF.
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PMID:Peculiar electrolytic and hormonal abnormalities in acute renal failure due to leptospirosis. 865 60

Acute tubular necrosis (ATN) is associated with hyperkalemia. We have shown that the medulla is the main site of impaired sodium (Na+)/potassium (K+) pump activity in ATN. CHIF, a gene that evokes K+ conductance in oocytes, is regulated in the colon by aldosterone and in the kidney by K+ intake. It is assumed that CHIF has a role in K+ homeostasis. To characterize the impaired K+ handling in ATN, the effect of impaired renal function on CHIF mRNA expression in the kidney and colon was studied. Three groups of rats with glycerol-induced ATN were studied: (1) control group, (2) moderate-ATN group, and (3) severe-ATN group. Serum creatinine levels in the control group were 45+/-2.1 micromol/L; in the moderate-ATN group, 224.8+/-16.9 micromol/L; and in the severe-ATN group, 376.5+/-15.9 micromol/L. In the group with severe ATN, significant hyperkalemia (P < 0.001 v control group) was noted. The expression of CHIF mRNA in relative units (percentage of control) in the moderate-ATN group, in the medulla, papilla, and colon, was 16.3%+/-5.6% (P < 0.001), 94.2%+/-9.3% (P=not significant ), and 165.9%+/-11.1% (P < 0.001); and in the severe-ATN group was 11.1%+/-6.4% (P < 0.001), 73.7%+/-4% (P < 0.001), and 310.8%+/-27.3% (P < 0.001), respectively. These results show that (1) in both moderate and severe ATN, CHIF mRNA is dramatically reduced in the medulla, (2) in severe ATN, CHIF mRNA expression decreases in the papilla, and (3) CHIF mRNA is upregulated in direct relationship to the severity of ATN and to the levels of aldosterone in the colon. These results suggest that the hyperkalemia that occurs in severe ATN stems at least in part from the downregulation of CHIF mRNA in the kidney medulla and papilla. The compensatory increase in colonic CHIF mRNA is not sufficient to maintain normal serum K+ levels.
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PMID:Role of down-regulated CHIF mRNA in the pathophysiology of hyperkalemia of acute tubular necrosis. 977 21

Prior to 2002, the incidence of acute renal failure (ARF) varied as there was no standard definition. To better understand its incidence and etiology and to develop treatment and prevention strategies, while moving research forward, the Acute Dialysis Quality Initiative workgroup developed the RIFLE (risk, injury, failure, loss, end-stage kidney disease) classification. After continued data suggesting that even small increases in serum creatinine lead to worse outcomes, the Acute Kidney Injury Network (AKIN) modified the RIFLE criteria and used the term acute kidney injury (AKI) instead of ARF. These classification and staging systems provide the clinician and researcher a starting point for refining the understanding and treatment of AKI. An important initial step in evaluating AKI is determining the likely location of injury, generally classified as prerenal, renal, or postrenal. There is no single biomarker or test that definitively defines the mechanism of the injury. Identifying the insult(s) requires a thorough assessment of the patient and their medical and medication histories. Prerenal injuries arise primarily due to renal hypoperfusion. This may be the result of systemic or focal conditions or secondary to the effects of drugs such as nonsteroidal anti-inflammatory drugs, calcineurin inhibitors (CIs), and modulators of the renin-angiotensin-aldosterone system. Renal, or intrinsic, injury is an overarching term that represents complex conditions leading to considerable damage to a component of the intrinsic renal system (renal tubules, glomerulus, vascular structures, inter-stitium, or renal tubule obstruction). Acute tubular necrosis and acute interstitial nephritis are the more common types of intrinsic renal injury. Each type of injury has several drugs that are implicated as a possible cause, with antiinfectives being the most common. Postrenal injuries that result from obstruction block the flow of urine, leading to hydronephrosis and subsequent damage to the renal parenchyma. Drugs associated with tubular obstruction include acyclovir, methotrexate, and several antiretrovirals. Renal recovery from drug-induced AKI begins once the offending agent has been removed, if clinically possible, and is complete in most cases. It is uncommon that renal replacement therapy will be needed while recovery occurs. Pharmacists can play a pivotal role in identifying possible causes of drug-induced AKI and limit their toxic effect by identifying those most likely to cause or contribute to injury. Dose adjustment is critical during changes in renal function, and the pharmacist can ensure that optimal therapy is provided during this critical time.
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PMID:The role of medications and their management in acute kidney injury. 2935 17

Kidney transplant patients (KTPs), and particularly those with advanced chronic kidney rejection, may be affected by opportunistic infections, metabolic alterations and vascular and oncologic diseases that promote clinical conditions that require a variety of treatments, the combinations of which may predispose them to hyponatremia. Salt and water imbalance can induce abnormalities in volemia and/or serum sodium depending on the nature of this alteration (increase or decrease), its absolute magnitude (mild or severe) and its relative magnitude (body sodium:water ratio). Hyponatremia appears when the body sodium:water ratio is reduced due to an increase in body water or a reduction in body sodium. Additionally, hyponatremia is classified as normotonic, hypertonic and hypotonic and while hypotonic hyponatremia is classified in hyponatremia with normal, high or low extracellular fluid. The main causes of hyponatremia in KTPs are hypotonic hyponatremia secondary to water and salt contraction with oral hydration (gastroenteritis, sepsis), free water retention (severe renal failure, syndrome of inappropriate antidiuretic hormone release, hypothyroidism), chronic hypokalemia (rapamycin, malnutrition), sodium loss (tubular dysfunction secondary to nephrocalcinosis, acute tubular necrosis, tubulitis/rejection, interstitial nephritis, adrenal insufficiency, aldosterone resistance, pancreatic drainage, kidney-pancreas transplant) and hyponatremia induced by medication (opioids, cyclophosphamide, psychoactive, potent diuretics and calcineurinic inhibitors). In conclusion, KTPs are predisposed to develop hyponatremia since they are exposed to immunologic, infectious, pharmacologic and oncologic disorders, the combinations of which alter their salt and water homeostatic capacity.
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PMID:Hyponatremia in kidney transplant patients: its pathophysiologic mechanisms. 3009 23

The coronavirus 2019 (COVID-19) pandemic has caused a huge impact on health and economic issues. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes cellular damage by entry mediated by the angiotensin-converting enzyme 2 of the host cells and its conjugation with spike proteins of SARS-CoV-2. Beyond airway infection and acute respiratory distress syndrome, acute kidney injury is common in SARS-CoV-2-associated infection, and acute kidney injury (AKI) is predictive to multiorgan dysfunction in SARS-CoV-2 infection. Beyond the cytokine storm and hemodynamic instability, SARS-CoV-2 might directly induce kidney injury and cause histopathologic characteristics, including acute tubular necrosis, podocytopathy and microangiopathy. The expression of apparatus mediating SARS-CoV-2 entry, including angiotensin-converting enzyme 2, transmembrane protease serine 2 (TMPRSS2) and a disintegrin and metalloprotease 17 (ADAM17), within the renal tubular cells is highly associated with acute kidney injury mediated by SARS-CoV-2. Both entry from the luminal and basolateral sides of the renal tubular cells are the possible routes for COVID-19, and the microthrombi associated with severe sepsis and the dysregulated renin-angiotensin-aldosterone system worsen further renal injury in SARS-CoV-2-associated AKI. In the podocytes of the glomerulus, injured podocyte expressed CD147, which mediated the entry of SARS-CoV-2 and worsen further foot process effacement, which would worsen proteinuria, and the chronic hazard induced by SARS-CoV-2-mediated kidney injury is still unknown. Therefore, the aim of the review is to summarize current evidence on SARS-CoV-2-associated AKI and the possible pathogenesis directly by SARS-CoV-2.
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PMID:Novel Evidence of Acute Kidney Injury in COVID-19. 3315 16