Renal Hypoperfusion Research Articles

Anti-LG3 Antibodies Aggravate Renal Ischemia-Reperfusion Injury and Long-Term Renal Allograft Dysfunction.

Pretransplant autoantibodies to LG3 and angiotensin II type 1 receptors (AT1R) are associated with acute rejection in kidney transplant recipients, whereas antivimentin autoantibodies participate in heart transplant rejection. Ischemia-reperfusion injury (IRI) can modify self-antigenic targets. We hypothesized that ischemia-reperfusion creates permissive conditions for autoantibodies to interact with their antigenic targets and leads to enhanced renal damage and dysfunction. In 172 kidney transplant recipients, we found that pretransplant anti-LG3 antibodies were associated with an increased risk of delayed graft function (DGF). Pretransplant anti-LG3 antibodies are inversely associated with graft function at 1 year after transplantation in patients who experienced DGF, independent of rejection. Pretransplant anti-AT1R and antivimentin were not associated with DGF or its functional outcome. In a model of renal IRI in mice, passive transfer of anti-LG3 IgG led to enhanced dysfunction and microvascular injury compared with passive transfer with control IgG. Passive transfer of anti-LG3 antibodies also favored intrarenal microvascular complement activation, microvascular rarefaction and fibrosis after IRI. Our results suggest that anti-LG3 antibodies are novel aggravating factors for renal IRI. These results provide novel insights into the pathways that modulate the severity of renal injury at the time of transplantation and their impact on long-term outcomes.

Hepatorenal syndrome: a nurse's guide to identification, management and advocacy

Hepatorenal syndrome (HRS) is a serious complication of end-stage liver disease (ESLD) that dramatically increases the patient's mortality risk while waiting for a liver transplant. HRS is the result of portal hypertension and splanchnic arterial vasodilation with subsequent intense renal vasoconstriction and hypoperfusion. The key to managing HRS while waiting for a liver transplant is to differentiate this diagnosis from other forms of acute kidney injury (AKI), such as prerenal azotaemia (PRA) and acute tubular necrosis (ATN). Although there has been previous research guiding physicians to manage HRS, there is a lack of published material to help guide liver-transplant (LT) nurses. The purpose of this evidence-based paper is to bridge this gap in the literature and provide a guide for LT nurses treating HRS through a detailed literature review exploring the aetiology, pathophysiology, diagnosis and management of HRS.

Lower Blood Pressure-Induced Renal Hypoperfusion Promotes Cisplatin-Induced Nephrotoxicity

Background and Aims: Cisplatin-induced nephrotoxicity primarily occurs in the proximal tubules, and tubular injuries reduce glomerular filtration rates. Lower blood pressure causes renal hypoperfusion, which promotes ischemic acute kidney injury (AKI). Our study examined the relationship between lower blood pressure-induced renal hypoperfusion and cisplatin-induced nephrotoxicity. Methods: The relationship between cisplatin use and hypoalbuminemia is not clear. This study consisted of Japanese patients who received cisplatin as the first-line chemotherapy at Fujita Health University Hospital from April 2006 to December 2012. Hypoalbuminemia was defined as serum albumin levels ≤3.5 mg/dl. Results: Patients who experienced lower blood pressure during chemotherapy were included in the lower blood pressure group (n = 229), and those who did not were included in the normal blood pressure group (n = 743). Total cisplatin dose in the normal blood pressure and lower blood pressure groups was 58.9 ± 23.8 and 55.0 ± 20.4 mg/m², respectively. The rate of severe nephrotoxicity was higher and overall survival was shorter in the lower blood pressure group than in the normal blood pressure group. In a multivariable analysis, lower blood pressure significantly correlated with hypoalbuminemia. Conclusions: To prevent ischemic AKI, nutrition and cachexia controlling are important parts of cancer treatment.

Postischemic microvasculopathy and endothelial progenitor cell-based therapy in ischemic AKI: update and perspectives.

Acute kidney injury (AKI) dramatically increases mortality of hospitalized patients. Incidences have been increased in recent years. The most frequent cause is transient renal hypoperfusion or ischemia which induces significant tubular cell dysfunction/damage. In addition, two further events take place: interstitial inflammation and microvasculopathy (MV). The latter evolves within minutes to hours postischemia and may result in permanent deterioration of the peritubular capillary network, ultimately increasing the risk for chronic kidney disease (CKD) in the long term. In recent years, our understanding of the molecular/cellular processes responsible for acute and sustained microvasculopathy has increasingly been expanded. The methodical approaches for visualizing impaired peritubular blood flow and increased vascular permeability have been optimized, even allowing the depiction of tissue abnormalities in a three-dimensional manner. In addition, endothelial dysfunction, a hallmark of MV, has increasingly been recognized as an inductor of both vascular malfunction and interstitial inflammation. In this regard, so-called regulated necrosis of the endothelium could potentially play a role in postischemic inflammation. Endothelial progenitor cells (EPCs), represented by at least two major subpopulations, have been shown to promote vascular repair in experimental AKI, not only in the short but also in the long term. The discussion about the true biology of the cells continues. It has been proposed that early EPCs are most likely myelomonocytic in nature, and thus they may simply be termed proangiogenic cells (PACs). Nevertheless, they reliably protect certain types of tissues/organs from ischemia-induced damage, mostly by modulating the perivascular microenvironment in an indirect manner. The aim of the present review is to summarize the current knowledge on postischemic MV and EPC-mediated renal repair.

Metformin: An Old Taboo yet a New Friend for Targeted Glucose Control in Critically Ill Patients

Glucose management in critically ill adults and children has always been controversial. A few recent studies mention that the use of any drug other than insulin for glucose control in intensive care unit is not recommended anymore1. Increased levels of counter-regulatory hormones and insulin resistance at organ levels contribute immensely to the emergence of hyperglycemia in these patients. Consequently, in some patients higher doses of insulin are required for the maintenance of normoglycemia and in such scenarios incidence of hypoglycemia becomes a real concern. Moreover, insulin therapy might lead to hypokalaemia and hypomagnesaemia which in turns promote insulin resistance and higher blood glucose level (BGL). All these events make insulin administration unavoidable; thereby, beginning a vicious cycle with adverse outcomes. One of therapeutic options in this scenario is using insulin sensitizing agents as an adjunct therapy for glycemic control in critically ill patients. Different studies have shown that metformin, similar to insulin, is of anti-inflammatory and antioxidant properties, improves lipid profile, decreases nursing workload and lowers the incidence of adverse effects related to high-dose insulin therapy without being associated with the increased risk of lactic acidosis or hypoglycemia2-4. Panahi et al., in their study, showed that metformin therapy in hyperglycemic critically ill patients resulted in similar outcomes with insulin thersapy5. Also, there are some studies reporting that metformin limits ischemia reperfusion injury, modulates inflammation; it consequently contributes to the survival benefits probably through increasing adenosine receptor stimulation6-8. In sepsis, there is a biphasic inflammatory response; Systemic Inflammatory Response Syndrome (SIRS), as an initial hyperinflammatory phase, and Counterregulatory anti-inflammatory response syndrome as a later hypoactive phase. Therefore, anti-inflammatory drugs like metformin may be associated with the best results only if added prior to the initial hyperinflammatory response and might have detrimental effects if added during hypoactive phase9,10. Timing of metformin administration may be an important factor contributing to its effect in critically ill patients. Finally, in patients with refractoriness to insulin who require high doses of insulin, metformin could be used as a safe adjunct therapy to reach targeted glucose levels. Metformin plus insulin appears to lower the incidence of insulin resistance, insulin requirements while maintaining blood glucose level control, and consequently the incidence of adverse effects related to high-dose insulin therapy, particularly hypoglycaemia. Declined nursing workload is also considered a major benefit. However, two important items should be noted: first, timing of drug administration and second, characteristics of the patients like renal function, hypoperfusion status and monitoring of drug complications.

Preclinical Evaluation of the Phosphodiesterase‐4 Inhibitor, Rolipram, in an Infant Model of Sepsis‐Induced Cardiorenal Syndrome

Multi‐organ failure is a frequent complication of infant sepsis. Sepsis‐induced cardiorenal syndrome (type 5), defined as development of acute cardiac dysfunction and acute kidney injury, is a frequent complication of infant sepsis that dramatically increases mortality. Septic shock in adults typically presents as a hyperdynamic state with high cardiac output and low systemic vascular resistance. However, most infants with septic shock show low cardiac output and high systemic vascular resistance (cold shock). To define the apparently unique pathogenic mechanisms contributing to renal and cardiac failure during septic shock in infants, and identify targeted therapies to reverse them, we developed a rat pup (17–19 days old) model of infant cardiorenal syndrome induced by cecal ligation and puncture (CLP), a model of infant sepsis that replicates the key cardio‐renal abnormalities. Rolipram is a phosphodiesterase‐4 inhibitor shown to reduce renal vascular resistance and improve microvascular perfusion in an adult mouse model of sepsis. The therapeutic potential of rolipram was evaluated using intravital video microscopy (IVVM) and echocardiography at specific time points following CLP in our rat pup model. A dose‐finding study was completed using IVVM at 6h following CLP that showed that a dose of 0.1 mg/kg, administered at the time of CLP, protected the pups from sepsis‐induced renal hypoperfusion. This dose was then used in further studies. At 18h following CLP, the single dose of rolipram administered at the time of CLP still prevented renal hypoperfusion and also prevented sepsis‐induced decline in stroke volume, left ventricular velocity, fractional shortening, ejection fraction, and most importantly, cardiac output as measured by echocardiography. Rolipram was also able to prevent the increase in blood urea nitrogen, which is used clinically to assess renal function. The protection by rolipram on perfusion and cardiac output indicate that rolipram may be therapeutically beneficial in infant cardiorenal syndrome.Support or Funding InformationCRS supported by T32 GM106999, F31DK104533, AHA PRE20450050; PRM supported by AHA 15GRNT2508025 and UAMS Medical Research Foundation.

Hepatic erythropoietin response in cirrhosis

Background Erythropoietin (EPO) is produced in the liver during fetal life, but after birth the production shifts to the kidneys. The liver maintains a production capacity of 10% of the total EPO-production, but can be up-regulated to 100%. Previous studies have demonstrated both elevated and reduced concentrations of EPO in cirrhosis. Increased EPO concentrations could be expected due to anemia, hypoxia, renal hypoperfusion, or EPO-mediated hepatoprotective mechanisms. In contrast, poor hepatic production capacity may cause reduced EPO concentrations in cirrhosis. In the present paper we aimed to study hepatic and renal venous concentrations of EPO in relation to the severity of the disease. Materials and methods We included 24 patients with alcoholic cirrhosis and eight age-matched healthy controls. All had a full catheterization performed with the determination of EPO concentrations in the hepatic, renal and femoral veins and artery. All patients were clinically, biochemically, and hemodynamically characterized. Results The median arterial EPO concentrations in the cirrhotic patients and controls were 7.1 mIU/mL (range 3.5–179) and 7.2 mIU/mL (range 3.8–15.3), respectively. In the patient group we found no significant correlations to stage of disease of hemodynamic derangement. Conclusion We found no significant differences in EPO concentrations across the liver, kidney, or peripheral circulation in the patient or control groups; and no significant correlations to clinical, biochemical, or hemodynamic characteristics. This suggests that hepatic EPO synthesis is not enhanced in cirrhosis, but larger scale studies are needed to clarify this question.

The Pathophysiological Hypothesis of Kidney Damage during Intra-Abdominal Hypertension.

The Pathophysiological Hypothesis of Kidney Damage during Intra-Abdominal Hypertension.

Prevenzione Della Nefropatia da Mezzo di Contrasto Iodato “La Flebo Intelligente”: una Valida Strategia Nella Prevenzione della Nefropatia da Mezzo di Contrasto

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Acute renal injury after partial hepatectomy.

Currently, partial hepatectomy is the treatment of choice for a wide variety of liver and biliary conditions. Among the possible complications of partial hepatectomy, acute kidney injury (AKI) should be considered as an important cause of increased morbidity and postoperative mortality. Difficulties in the data analysis related to postoperative AKI after liver resections are mainly due to the multiplicity of factors to be considered in the surgical patients, moreover, there is no consensus of the exact definition of AKI after liver resection in the literature, which hampers comparison and analysis of the scarce data published on the subject. Despite this multiplicity of risk factors for postoperative AKI after partial hepatectomy, there are main factors that clearly contribute to its occurrence. First factor relates to large blood losses with renal hypoperfusion during the operation, second factor relates to the occurrence of post-hepatectomy liver failure with consequent distributive circulatory changes and hepatorenal syndrome. Eventually, patients can have more than one factor contributing to post-operative AKI, and frequently these combinations of acute insults can be aggravated by sepsis or exposure to nephrotoxic drugs.

The Smart Drip-Feed: A Powerful Strategy to Prevent Contrast Induced Nephropathy

Contrast-induced nephropathy (CIN) frequently affects patients with chronic kidney disease and heart dysfunction, patients older than 65 years and patients with diabetes mellitus, multiple myeloma and sepsis. It is often related to the use of high doses of contrast medium. Vasodilators and antioxidant drugs may have positive effects on the prevention of this clinical condition. One of the most important strategies for the prevention of contrast induced nephropathy is an adequate hydration of the patient, with subsequent intravascular volume expansion, renin-angiotensin system suppression, reduced vasoconstriction and renal hypoperfusion. Anyway, an active diuresis is the most important condition for the prevention of CIN. A new system, called RenalGuard®, has been recently proposed to prevent acute kidney injury secondary to the administration of the contrast medium. In this review, we have analyzed the different strategies in the prevention of CIN and the use of RenalGuard® system.

Acute Kidney Injury Associated with Linagliptin.

Linagliptin is a dipeptidyl peptidase-IV (DPP-IV) inhibitor that is approved for the treatment of type 2 diabetes mellitus. About 5% of linagliptin is eliminated by the kidneys and no dose adjustment is recommended in kidney impairment. We report a first case of linagliptin-associated acute kidney injury (AKI) in a patient with preexisting chronic kidney disease (CKD). We hypothesize that AKI was due to renal hypoperfusion from linagliptin-induced natriuresis and intravascular volume contraction in the setting of concomitant lisinopril use, which is known to impair autoregulation and potentiate hypotension-induced AKI. It may be prudent to exert caution and closely monitor kidney function when initiating linagliptin in combination with ACE-inhibitors in CKD patients.

Prevention of Pediatric Acute Kidney Injury

The incidence of acute kidney injury (AKI) in critically ill pediatric patients has been reported as increasing to 25 %, depending on population characteristics. The etiology of AKI has changed over the last 10-20 years from primary renal disease to the renal conditions associated with systemic illness. The AKI in pediatric population is associated with increased mortality and morbidity, and prevention is needed to reduce the consequence of AKI. It is known that the most important risk factors for AKI in critically ill pediatric patients are clinical conditions to be associated with decreased renal blood flow, direct renal injury, and illness severity. Renal hypoperfusion leads to neurohormonal activation including renin-angiotensin-aldosterone system, sympathetic nervous system, antidiuretic hormone, and prostaglandins. Prolonged renal hypoperfusion can result in acute tubular necrosis. The direct renal injury can be predisposed under the condition of renal hypoperfusion, and appropriate treatment of volume depletion is important to prevent AKI. The preventable causes of AKI include contrast-induced nephropathy, hemodynamic instability, inappropriate mediation use, and multiple nephrotoxic insults. Given the evidence of preventable factors for AKI, several actions such as the use of protocol for prevention of contrast-induced nephropathy, appropriate treatment of volume depletion, vigorous treatment of sepsis, avoidance of combinations of nephrotoxic medications, and monitoring of levels of drugs should be recommended. Key words: Acute kidney injury; Biomarker; Children

High Dose Meclizine Prevents Renal Ischemia–Reperfusion Injury in Healthy Male Mice

High Dose Meclizine Prevents Renal Ischemia–Reperfusion Injury in Healthy Male Mice

Effects of acute and chronic hypohydration on kidney health and function.

The kidneys play a critical role in the homeostasis of body fluid tonicity and effective circulating volume. Renal homeostatic mechanisms are frequently challenged in acutely ill people. Fluid depletion causing hypovolemia may result in renal hypoperfusion that, if left untreated, may lead to acute kidney failure. Some populations, notably older people and neonates, are less tolerant of extremes in fluid loading and deprivation, similar to those with established chronic kidney disease. Risk of kidney injury during fluid depletion is increased by medications including diuretics, nonsteroidal antiinflammatory drugs, and renin-angiotensin system blockers. There is no consistent evidence indicating that lower-than-average fluid intake can cause chronic kidney disease, nor accelerate progression of established kidney disease. Increasing consumption of sugar-containing beverages is, however, a major concern for kidney health as a precursor of obesity and diabetes. There is no evidence that high dietary protein intake can cause chronic kidney disease, nor accelerate progression of established kidney disease. Idiosyncratic, adverse renal responses have been described with creatine supplements. There are only a few clinical conditions for which high fluid intake should be considered. These include recurrent kidney stones or urinary tract infections and, possibly, polycystic kidney disease.

Renal Outcome After Open Surgery and Fenestrated Endovascular Aneurysm Repair of Juxta-renal Aneurysms

function. 1 New onset of renal insufficiency was detected in 26.5% of the open surgery group and 8.5% of the endovascular group, which was persistent in 11.8% and 5.7%, respectively.Three per cent of the patients in each group required dialysis in the longer term.The rate of renal failure after open repair and after FEVAR in a recent systematic review were 13.9% and 11.4%, respectively, with no difference in the rate of permanent dialysis between the groups (2.8% and 1.9%, respectively). 2 In a propensity-matched comparison, the rates of perioperative renal insufficiency were 2.7% after open repair and 7.1% after FEVAR (p ¼ .1); the FEVAR group were initially considered to be high risk for open surgery. 3 Despite the transient nature of postoperative renal dysfunction, in most cases it remains a significant predictor of mortality in these patients. Serum creatinine is the most commonly reported marker of renal function, but estimated glomerular filtration rate (eGFR) can offer greater functional sensitivity. 4 Renal volume has been assessed in various urological studies as a predictor of graft function in living donor renal transplantation. It can be calculated from computed tomography (CT) data and has been shown in the context of endovascular aneurysm repair to be an early marker of renal dysfunction and to correlate well with eGFR. 5 Renal impairment in FEVAR is related to the nephrotoxicity of the contrast medium, micro- and macro-embolisation into the renal arteries during device manipulation in the aorta, and the inflammatory response associated with the procedure. Carbon dioxide has been used as a contrast medium in patients with renal failure, but it is associated with a high complication rate including right heart strain and fatal nonocclusive mesenteric ischaemia. 6 The repositionability of the Cook and Anaconda stent-grafts is intended to allow better alignment between the device and the renal artery ostia but it may also cause embolisation of athero-embolic material into the renal arteries. Other endovascular considerations include the design of the bridging stents, the amount of flaring of the proximal end, and the anatomy of the renal artery. Aortic cross-clamping during open surgical repair results in renal hypoperfusion and every additional 5 minutes of renal ischaemia time has been shown to double the risk of postoperative renal dysfunction. 7 Clamp placement above both renal arteries, and manipulation of the aorta and renal arteries results in embolisation of material and this effect is compounded by ischaemia-reperfusion injury. Division of the left renal vein increases the risk of renal dysfunction by six times. 7 Perfusion of the renal arteries with cold crystalloid solution may preserve renal function during thoracoabdominal aneurysm repair but is not widely used in juxtarenal aneurysm repair. Imaging surveillance is mandatory after FEVAR but repeated CT angiography exposes the patient to nephrotoxic iodinated contrast agent. Studies investigating the effect of different CT contrast agents on renal kinetics and renal oxygenation have shown that low osmolar compared with iso-osmolar contrast agents have a superior profile regarding rapid excretion, short-term renal exposure, and renal oxygenation. 8 Surveillance is currently changing from repeated CT angiography to immediate post-EVAR cone-beam CT in the hybrid room with ultrasound performed prior to hospital discharge. 9 CT angiograms are then performed at years 1 and 3 in the presence of good renal function with ultrasound performed annually. Ultrasound provides a hemodynamic evaluation of the bridging stents and target vessels, and the CT images are used to verify device integrity and positioning. Contrast-enhanced ultrasound has been shown to be as accurate as CT scan in detecting endoleaks and in assessing both target vessel patency and aortic diameter after fenestrated endovascular repair. 10 Future work should be directed towards investigation of potential biomarkers to predict risk, prognosis, and therapeutic response in patients with acute kidney injury. Renal impairment should be assessed with eGFR, which is a sensitive and reliable measure of renal function. Definite evidence of a difference between open surgical repair and FEVAR would require a randomised controlled trial and long term followup of 5e10 years.

Renal Artery Stenosis: Optimal Therapy and Indications for Revascularization.

Atherosclerotic renal artery stenosis (ARAS) is associated with increased cardiovascular risk and overall mortality. Manifestations of ARAS include resistant or malignant hypertension, progressive deterioration of renal function, and cardiac dysfunction syndromes of flash pulmonary edema and angina. Diagnosis rests upon non-invasive studies such as duplex ultrasonography and is confirmed using invasive renal arteriography. Regardless of the severity of ARAS, management of this entity has been a topic of contentious debate. For over two decades, the use of percutaneous revascularization to treat ARAS has been studied with various clinical trials. Though case series seem to demonstrate favorable clinical response to revascularization, the overwhelming majority of randomized clinical trials have not mirrored a robust outcome. In these trials, poor correlation is noted between the reduction of stenosis and the improvement of renovascular hypertension and glomerular filtration rate, and decrease in cardiovascular outcomes and mortality. With dichotomizing results, the explanation for these discrepant findings has been attributed to improper trial design and inappropriate patient selection. An overview of the treatment options available will be provided, with a focus on the methodology and design of clinical trials investigating the efficacy of percutaneous revascularization. Emphasis is placed on appropriate patient selection criteria, which may necessitate the use of hemodynamic lesion assessment and clinical correlation based on individualized care. When clinical equipoise exists between optimal medical therapy and revascularization, the current paradigm supports ongoing medical therapy as the treatment of choice. However, renal artery stenting remains a viable therapeutic option for those who continue to have clinical syndromes consistent with renal hypoperfusion while adequately treated with optimal medical therapy. Despite observational studies suggesting clinical benefit for this specific patient population, there remains a paucity of randomized clinical trial data. Further trials targeting the patients who are inadequately treated with optimal medical therapy need to be undertaken to confirm the efficacy of revascularization.

Impact of an Early Decrease in Systolic Blood Pressure on The Risk of Contrast-Induced Nephropathy after Percutaneous Coronary Intervention

The early postprocedural period was thought to be the rush hour of contrast media excretion, causing rapid and prolonged renal hypoperfusion, which was the critical time window for contrast-induced nephropathy (CIN). 349 consecutive patients were enrolled into the study. The relation between an early postprocedural decrease in systolic blood pressure (SBP) and the risk of CIN was assessed using multivariate logistic regression. A postprocedural decrease in SBP was observed in 63% of patients and CIN developed in 28 (8.0%) patients. The CIN group had a lower postprocedural SBP (114.5±13.5 vs. 123.7±15.6mmHg, P=0.003) and a greater postprocedural decrease in SBP (16.2±19.1 vs. 5.9±18.7mmHg, P=0.005) than the no-CIN group. ROC analysis revealed that the optimum cutoff value for the SBP decrease in detecting CIN was >10mmHg (sensitivity 60.7%, specificity 59.5%, AUC=0.66). Multivariate logistic regression analysis found that a postprocedural decrease in SBP >10mmHg was a significant independent predictor of CIN (OR 2.368, 95%CI: 1.043-5.379, P=0.039), after adjustment for other risk factors. An early moderate postprocedural decrease in SBP may increase the risk of CIN in patients undergoing PCI.

Cardio Renal Syndromes 2015: Is there a Silver Lining to the Dark Clouds?

Kidneys have a pivotal role in maintaining our homeostasis. Kidneys and heart work in tandem to maintain volume homeostasis. Heart failure impacts renal function in many ways including renal hypo perfusion but also due to increased venous pressure along with stimulation of various neuro-humoral responses. Renal failure induces cardiac damage and dysfunction by causing volume overload, inflammation and cardiomyocyte fibrosis. Concomitant comorbidities like Hypertension and Diabetes also play important role resulting in Cardiorenal Syndrome (CRS). Acute Dialysis Quality Initiative, 2007 recognized the bidirectional nature and different manifestations of CRS in acute and chronic settings. Diuretics are the most common drugs to treat the most common symptoms of CRS i.e., peripheral edema and pulmonary congestion. Diuretics could nevertheless contribute to worsening renal function (WRF). Initially it was accepted that WRF during the course of treatment of acute decompensated heart failure (ADHF) uniformly resulted in worse prognosis. However, in view of a few recent studies, the significance of WRF early in response to treatment of ADHF is being debated. The optimal dose and method of delivery of diuretics is still undecided. Isolated ultrafiltration does not improve renal function in patients with CRS despite the early promise. A large, multicentre trial ruled out any survival benefits with Recombinant Brain Natriuretic Peptide (Nesiritide). Despite good physiological basis and early promise with smaller studies, many drugs like Dobutamine, Rolofylline and Tolvaptan failed to show survival benefit in larger studies. However, two recent studies involving Relaxin and Neprilysin have shown good survival advantage. There had been little progress in treatment of CRS until studies involving Relaxin and Neprilysin inhibitor combination with ARB were published. There may after all, be a glimmer of hope in the field of CRS bogged by multiple negative studies.

A Review of the Use of Iloprost, A Synthetic Prostacyclin, in the Prevention of Radiocontrast Nephropathy in Patients Undergoing Coronary Angiography and Intervention

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.