iloprost and Acute-Kidney-Injury

Iloprost, a prostacyclin analogue, has been effective in preventing renal dysfunction among transplant patients. We hypothesized that iloprost is protective against renal dysfunction in different settings, in which similar underlying mechanisms of nephrotoxicity occur. We conducted a literature review, and discuss the application of iloprost in reducing acute renal insufficiency and the pathophysiological mechanisms of contrast-induced nephropathy (CIN). One proposed mechanism of CIN is prolonged renal arterial vasoconstriction, causing renal hypoperfusion, ischemia, and release of free radicals. Iloprost is an analogue of the vasodilatory prostaglandin PGI2 . It has demonstrated cytoprotective properties in the renal transplant population by inhibiting lysosomal degradation and release of free radicals, allowing membrane stabilization. Two good-quality studies reported on iloprost and CIN. Five studies reported protective effects of iloprost in renal transplantation and 1 in coronary artery bypass grafting. Iloprost was found to be renoprotective in patients with baseline renal insufficiency who underwent coronary angiography for CIN (risk ratio [RR] = 0.32, 95% confidence interval [CI]: 0.16-0.67) and increases the weighted mean difference improvement in creatinine clearance (RR = 4.56, 95% CI: 1.82-7.30). CIN is associated with major adverse cardiac events. Preventing CIN is important for patient safety and reducing disease burden. Iloprost may reduce CIN by up to 68%. The same mechanisms of iloprost that inhibit graft dysfunction in the acute post-renal transplant and cardiopulmonary bypass setting may also contribute to preventing CIN. Large randomized controlled trials are necessary to determine the clinical efficacy of iloprost in the angiography setting.

Topics: Acute Kidney Injury; Contrast Media; Coronary Angiography; Humans; Iloprost; Vasodilator Agents

The aim of this pilot study was to compare the effect of heparin anticoagulation with and without iloprost administration during continuous renal replacement therapy (CRRT) in critically ill patients.. In a prospective, randomized, controlled pilot study at an intensive care unit at a university hospital, 20 patients requiring CRRT were investigated. Patients were allocated into two groups: group 1, the heparin group; and group 2, the heparin plus 1 ng/kg/min iloprost. In both groups, activated partial thromboplastin time (aPTT) was adjusted to 40-50 sec. Observation time was a maximum of 7 days.. Median filter run time was significantly prolonged by iloprost administration to a median of 14 h (13-26 h) compared to 10 h (4-12 h) in the heparin group (p = 0.004). A decrease in platelet count was attenuated by iloprost administration (p = 0.012). There were no bleeding complications in either group. Hemofiltration efficiency did not differ significantly between the groups.. Additional administration of iloprost prolonged the filter run time of continuous veno-venous hemofiltration (CVVH) in this setting and attenuated the fall in platelet count during CRRT.

Topics: Acute Kidney Injury; Aged; Aged, 80 and over; Analysis of Variance; Anticoagulants; Biomarkers; Blood Coagulation; Drug Therapy, Combination; Female; Hemofiltration; Heparin; Humans; Iloprost; Infusions, Intravenous; Male; Middle Aged; Partial Thromboplastin Time; Pilot Projects; Platelet Activation; Platelet Aggregation Inhibitors; Platelet Count; Prospective Studies; Treatment Outcome

To test the hypothesis that calcium antagonists decrease the incidence and severity of delayed graft function, we conducted three separate, prospective, randomized trials. In these trials, we investigated the effects of diltiazem and those of the prostacyclin analogue iloprost. In the first study, 22 control patients and 20 diltiazem patients received grafts perfused with either vehicle or diltiazem 20 mg/liter in the Euro-Collins solution. Subsequently, the diltiazem subjects were given the drug as a bolus of 0.28 mg/kg, followed by a continuous infusion of 0.002 mg/min/kg for the following two days. Thereafter, diltiazem 60 mg was given to the treated subjects orally for up to four years. In the second study, 11 control subjects and 10 diltiazem subjects received the same postoperative regimen, but all grafts were harvested without addition of diltiazem to the perfusion solution. In the third protocol, four groups were studied as follows: 19 control subjects who received no specific treatment, 16 subjects who received diltiazem, 16 subjects who were given iloprost, and 14 subjects who received both iloprost and diltiazem. The donor kidney of treated patients was perfused with either diltiazem, iloprost, or both drugs. Primary graft function occurred more commonly in the groups receiving diltiazem. Further, in the first study the number of hemodialyses per patient was reduced in those patients with delayed graft function. Fewer rejection episodes occurred in patients receiving diltiazem. Plasma levels of soluble interleukin-2 receptors decreased significantly during diltiazem treatment. Moreover, renal biopsies showed less severe signs of Cyclosporin A (CsA) nephrotoxicity in diltiazem-treated patients compared to controls, even though these patients also exhibited higher CsA trough levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Kidney Injury; Adult; Creatinine; Cyclosporine; Diltiazem; Graft Rejection; Humans; Iloprost; Kidney Transplantation; Middle Aged; Prospective Studies

To test the hypothesis that calcium antagonists decrease the incidence and severity of delayed graft function, we conducted three separate, prospective, randomized trials. In these trials, we investigated the effects of diltiazem and those of the prostacycline analogue iloprost. In the first study, 22 control patients and 20 diltiazem patients received grafts perfused with either vehicle or diltiazem 20 mg/L in the Euro-Collins solution. Subsequently, the diltiazem subjects were given the drug as a bolus of 0.28 mg/kg, followed by a continuous infusion of 0.002 mg/min/kg for the following 2 days. Thereafter, diltiazem 60 mg was given to the treated subjects orally for up to 4 years. In the second study, 11 control subjects and 10 diltiazem subjects received the same postoperative regimen, but all grafts were harvested without addition of diltiazem to the perfusion solution. In the third protocol, four groups were studied as follows: 19 control subjects who received no specific treatment, 16 subjects who received diltiazem, 16 subjects who were given iloprost, and 14 subjects who received both iliprost and diltiazem. The donor kidney of treated patients was perfused with either diltiazem, iloprost, or both drugs. Primary graft function occurred more commonly in the groups receiving diltiazem. Further, in the first study the number of hemodialyses per patient was reduced in those patients with delayed graft function. Fewer rejection episodes occurred in patients receiving diltiazem. Plasma levels of soluble interleukin-2 receptors decreased significantly during diltiazem treatment. Moreover, renal biopsies showed less severe signs of cyclosporin-A (CyA) nephrotoxicity in diltiazem-treated patients compared to controls, even though these patients also exhibited higher CyA trough levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Kidney Injury; Adult; Cyclosporine; Diltiazem; Follow-Up Studies; Graft Survival; Humans; Iloprost; Immunosuppression Therapy; Kidney Transplantation; Middle Aged; Organ Preservation; Prospective Studies

Topics: Acute Kidney Injury; Adult; Diltiazem; Drug Therapy, Combination; Epoprostenol; Glomerular Filtration Rate; Graft Survival; Humans; Iloprost; Kidney Transplantation; Middle Aged; Prospective Studies; Renal Circulation

To investigate that exogenous prostacyclin would counterbalance an endotoxemia-induced intrarenal vasoconstriction and would therefore have beneficial effects on kidney function.. Prospective, randomized, controlled study.. University medical center research laboratory.. Eighteen male Wistar rats.. In anesthetized and ventilated animals, arterial blood pressure (mean arterial blood pressure [MAP]) and renal blood flow (RBF) were recorded. Renal microvascular Po2 (muPo2) and renal venous Po2 were continuously measured by phosphorescence lifetime technique. All animals received a 30-minute infusion of lipopolysaccharide (LPS) (2.5 mg/kg) to induce endotoxemia. One group of rats was not resuscitated. A second group received fluid resuscitation 90 minutes after stop of LPS infusion. In a third group of rats, the prostacyclin analogue iloprost (100 ng/kg/min) was continuously infused in addition to fluid resuscitation. Furthermore, in all the animals, plasma NOx levels, renal inducible nitric-oxide synthase (iNOS) messenger RNA (mRNA) expression, and creatinine clearance were determined.. During LPS infusion, MAP and RBF progressively dropped to 50% of baseline at 120 minutes. After an initial increase in MAP and RBF, start of fluid resuscitation with iloprost resulted in the stabilization of both parameters. All animals became anuric during endotoxemia. Only in animals receiving iloprost was creatinine clearance totally restored at the end of the experiment. Iloprost had no significant effects on average muPo2, but prevented the occurrence of cortical microcirculatory hypoxic areas. NOx levels and iNOS mRNA expression were significantly increased in all animals receiving LPS after 5 hours. There was no difference in NOx concentration between the different groups. In animals receiving iloprost, iNOS mRNA expression was significantly suppressed in the inner medulla.. Iloprost significantly restored kidney function of endotoxemic rats to baseline values. This beneficial effect of iloprost on renal function might be addressed to an improvement in intrarenal oxygenation.

Topics: Acute Kidney Injury; Animals; Endotoxemia; Iloprost; Kidney; Male; Oxygen; Rats; Rats, Wistar; Recovery of Function; Vasodilator Agents

Topics: Acute Kidney Injury; Contrast Media; Humans; Iloprost; Prostaglandins, Synthetic; Protective Agents

The decision for an anticoagulant for renal replacement therapy (RRT) in patients with acute renal failure and heparin-induced thrombocytopenia (HIT) has to be made carefully. Based on results from the literature argatroban is favoured in patients without hepatic dysfunction, referring to its short halftime and easy feasable monitoring. In the case of coexsisting hepatic disorder, danaparoid provides a safe alternative therapy. However, long halftime and the difficult elimination of the substance are unfavourable. Lepirudin represents another possible anticoagulant therapy. Bleeding complications and monitoring of the ecarin clotting time imposes limitations. Experiences with bivalirudin, fondaparinux and prostaglandines are limited and future trials will have to determine the significance of their application in RRT in HIT patients. Furthermore it has to be proven whether the combination of alternative anticoagulants with citrate prolongates circuit halftime of CVVH.

Topics: Acute Kidney Injury; Anticoagulants; Arginine; Blood Coagulation Tests; Chondroitin Sulfates; Citrates; Critical Care; Dermatan Sulfate; Diagnostic Errors; Dose-Response Relationship, Drug; Epoprostenol; Fondaparinux; Hemofiltration; Heparin; Heparin, Low-Molecular-Weight; Heparitin Sulfate; Hirudins; Humans; Iloprost; Pipecolic Acids; Polysaccharides; Recombinant Proteins; Sodium Citrate; Sulfonamides; Thrombocytopenia; Thrombosis

Cholesterol embolism is a serious disease with a high morbidity and mortality rate. There is no clear evidence that any specific treatment helps this syndrome. We report a patient who developed acute renal failure due to cholesterol crystal embolism following percutaneous transluminal angioplasty of a renal artery. Treatment with iloprost for peripheral symptoms of cholesterol emboli resulted in rapid resolution of toe cyanosis, decrease in leg pain and a significant decrease in serum creatinine shortly after initiation of treatment. One month after initiation of iloprost therapy, skin signs of cholesterol emboli disappeared and leg pain diminished. Gradually reduction in serum creatinine level was also observed (from 390 to 160 micromol/L). Eighteen months after the arteriography, the patient had stable renal function with creatinine levels of 150-160 micromol/L, and he was asymptomatic.

Topics: Acute Kidney Injury; Angioplasty, Balloon; Embolism, Cholesterol; Follow-Up Studies; Humans; Iloprost; Male; Middle Aged; Renal Artery Obstruction; Vasodilator Agents

Topics: Acute Kidney Injury; Antiphospholipid Syndrome; Cardiomyopathies; Child; Hemolytic-Uremic Syndrome; Humans; Iloprost; Male; Peripheral Vascular Diseases; Peritoneal Dialysis, Continuous Ambulatory; Plasmapheresis; Skin

A 66-year-old woman presented with acute-onset rapid atrial fibrillation and right upper quadrant pain which had appeared 24 h prior to admission. The patient also manifested acute oliguric renal failure (serum creatinine 6.9 mg/dl). Selective renal angiography revealed total occlusion of the right renal artery with normal visualization of the left kidney vasculature. The patient was treated with intra-arterial urokinase and intravenous heparin, with no response. Intravenous administration of the prostacyclin analogue, iloprost, resulted in rapid resolution (within hours) of the oliguric acute renal failure, in spite of the continuing presence of a nonfunctioning right kidney. We conclude that the etiology of the acute renal insult in this patient is probably related to unilateral renal arterial embolization accompanied by arterial spasm of the unaffected kidney. The contralateral vasospasm can be reversed by iloprost, which then leads to a rapid recovery from acute renal failure. We are unaware of prior reports documenting the beneficial effect of iloprost in a clinical setting as described here.

Topics: Acute Kidney Injury; Aged; Atrial Fibrillation; Embolism; Female; Humans; Iloprost; Oliguria; Renal Artery Obstruction; Rheumatic Heart Disease; Vasodilator Agents

Tissue protective activities of Iloprost, a stable analogue of PGI2, and of UK 38485, an inhibitor of thromboxane synthetase, were investigated in rats, in which acute renal failure was elicited by the injection of glycerol. The effects of these compounds on PGE2- and LTC4-like activities in the kidney tissue were also studied. Glycerol injection caused acute kidney damage as evidenced by light microscopic examination and abundant hematuria. Glycerol injection also caused an increase in tissue PGE2- and LTC4-like activities. Although both metabolites were increased, the ratio of PGE2/LTC4 was found to be decreased when compared with the control value. Both Iloprost and UK 38485 partially prevented tissue damage due to glycerol and caused an increase in the ratio of PGE2/LTC4. The preventive effects of the drugs were more pronounced when both drugs were used in combination. The participation of arachidonic acid metabolites in the mechanism of the production of kidney damage due to glycerol and possible preventive effects of the compounds are discussed.

Topics: Acute Kidney Injury; Animals; Female; Glycerol; Iloprost; Imidazoles; Kidney Cortex; Kidney Tubules; Male; Rats; Reference Values; Thromboxane-A Synthase

Operative trauma, ischemia, release of catecholamines and thermal stimuli in consequence of harvesting, preservation and transplantation deteriorate the renal capillary circulation. By crossing of tolerance limits arises an irreversible transplant damage. The conditions of our examinations were placed in this field. By pre- and postischemic application of Iloprost was demonstrable an improvement of the ischemic tolerance of the kidney. Correction of renal hemodynamics, antiplatelet action and cytoprotection are the reasons of the protective influence of Iloprost in our opinion.

Topics: Acute Kidney Injury; Animals; Creatinine; Hemodynamics; Iloprost; Ischemia; Kidney; Kidney Transplantation; Rabbits; Swine