Mehran Score Research Articles

Kidney diseases beyond nephrology: intensive care

Sodium bicarbonate has been used for several years for its presumed nephroprotective effects in several settings. In particular, its role in cardiac surgery-associated acute kidney injury (CSA-AKI) has been explored. CSA-AKI is a particular type of cardio-renal syndrome for which no clear understanding of pathogenesis exists and no proven effective prophylaxis or treatment has as yet been established [1]. Previous studies have reported injury to red cells and release of free haemoglobin during cardiopulmonary bypass (CPB) [2]. Besides complete red blood cell fragmentation (induced by CPB, valvular prosthesis, transfusion reactions or genetic defects predisposing to reduced erythrocyte membrane stability), there can also be sublethal red cell damage, resulting in altered rheological properties. Increased levels of free red blood cell constituents, together with an exhaustion of their scavengers, transferrin and haptoglobin, result in a variety of serious clinical consequences, such as increased systemic vascular resistance, altered coagulation prof ile, platelet dysfunction, renal tubular damage and increased mortality. Such injury raises concerns that CSA-AKI may be a form of renal sideropathy and that free or inappropriately liganded iron-related toxicity may play a role [3]. Free iron has the potential to catalyse the formation of super-oxide radical and hydrogen peroxide yielding hydroxyl radical. It is known that an acid environment typical of tubular urine enhances the formation of reactive hydroxyl radicals. Finally, tubular obstruction may allow greater time for endocytotic uptake of free haemoglobin into proximal tubular cells, which is associated with proximal tubular cell necrosis. Oxidative stress has been shown to play a key role in the development of toxic and ischaemic AKI. Interestingly, urinary alkalinization with sodium bicarbonate might protect from the pathophysiological mechanisms causing CSA-AKI. A recent double-blind randomized controlled trial showed that bicarbonate might attenuate CSA-AKI, potentially directly affecting iron-related toxicity, as indicated by a smaller increase in urinary biomarker neutrophil gelatinaseassociated lipocalin (NGAL) [4]. At neutral or alkaline pH, free ferric ions precipitate as insoluble ferric hydroxide, which is excreted as inert complex in the urine. More alkaline urine reduces the generation of injurious hydroxyl radicals and lipid peroxidation. Bicarbonate directly scavenges hydroxyl ions and, as a not well-adsorbable anion compared with chloride, causes more rapid volume excretion and thereby reduces the contact time between injurious radicals and renal tubules. Peak plasma creatinine increases were typical by the third post-operative day regardless of the study group. Furthermore, exposure to sodium bicarbonateattenuated renal oxidative stress as reflected by lower urinary NGAL levels and urinary NGAL/creatinine ratios. As expected, exposure to sodium bicarbonate infusion was associated with a higher plasma pH, higher plasma bicarbonate and urinary alkalinization. Fewer patients in the sodium bicarbonate group (16 of 50) developed a post-operative increase in serum creatinine compared with control (26 of 50) (P = 0.043). The increase in plasma creatinine, plasma urea, urinary NGAL, and urinary NGAL/urinary creatinine ratio was less in patients receiving sodium bicarbonate. As the authors acknowledge, bicarbonate apparently preventedonly mild renal dysfunction which may have limited effects on clinical outcome. Furthermore, the potential clinical risks of systemic alkalinization, e.g. oxyhaemoglobin dissociation curve shifts resulting in higher oxygen–haemoglobin affinity with possible relative tissue hypoxaemia, have not been fully evaluated in this pilot trial. The effects of bicarbonate on higher risk cardiac surgery patients remain to be evaluated. These results suggest finally a novel utility of urinary NGAL measurements not as diagnostic biomarker but as monitor of the efficacy of therapy for AKI. Sodium bicarbonate has also been used for nephroprotection in contrast-induced acute kidney injury (CI-AKI). The benefit of CI-AKI prophylaxis has mainly been shown for patients with reduced glomerular filtration rate (GFR) (<50 mL/min/1.73 m), heart failure or diabetes, and/or patients with high risk scores (Thakar score [5] or Mehran score [6]). In this light, intensive care unit (ICU) patients undergoing angiography should always be considered as high-risk patients. The International Consensus Conference in Intensive Care Medicine recently considered the

Statins for prevention of contrast‐induced nephropathy in patients undergoing non‐emergent percutaneous coronary intervention

Oxidative stress and ischaemia are suggested as possible mechanisms of contrast-induced nephropathy (CIN). Statins may offer renoprotection in both acute and chronic kidney diseases because of their antioxidant and anti-inflammatory properties. We investigated whether use of statins before non-emergent percutaneous coronary intervention (PCI) reduces the incidence of CIN. We retrospectively evaluated 540 consecutive adult patients who underwent non-emergent PCI over a 3 year period at a tertiary care centre. CIN was defined as 25% or 44 mmol/L increase from baseline creatinine at 48-72 h. In addition, we classified patients based on Mehran score for risk of development of CIN and analysed the effect of statins. Three-hundred and fifty-three patients met inclusion criteria. Two-hundred and thirty-nine patients were taking statins before PCI and 114 were not. Baseline characteristics were similar for both groups. CIN occurred in 75 patients (21.2%). There was a higher incidence of CIN in patients on statins as compared with patients not on statins (24.7% vs 14%; 95% CI: 1.09-3.67; P = 0.02). However, propensity-based adjustment for receipt of statins revealed no significant differences in CIN between both groups (OR: 1.6; 95% CI: 0.87-3.22; P = 0.12). Multivariate logistic regression revealed Mehran score to be independently predictive of CIN. None of the patients who developed CIN required dialysis. Statin use before non-emergent PCI is not associated with reduction in CIN. Further randomized controlled trials based on proper risk adjustment for development of CIN are needed.

Safety and Performance of Targeted Renal Therapy: The Be-RITe! Registry

To evaluate the safety and patterns of use of targeted renal therapy (TRT) with the Benephit system. TRT, the delivery of therapeutic agents directly to the kidneys by renal arterial infusion, has the advantage of providing a higher local effective dose with potentially greater renal effects, while limiting systemic adverse effects due to renal first-pass elimination. The Benephit System Renal Infusion Therapy (Be-RITe!) Multicenter Registry was a post-market registry following patients treated using the Benephit systems for TRT. The registry enrolled 501 patients (332 men; mean age 72.2+/-9.5 years) at high risk for contrast-induced nephropathy (CIN) during coronary or peripheral angiography/intervention or cardiovascular surgery. The Mehran score was used to compare the actual to predicted incidence of CIN within 48 hours post procedure. Bilateral renal artery cannulation was successful in 94.2%, with a mean cannulation time of 2.0 minutes. Either fenoldopam mesylate, sodium bicarbonate, alprostadil, or B-type natriuretic peptide (BNP) was infused for 184+/-212 minutes. Mean creatinine levels did not change significantly (baseline, 24, and 48 hours post procedure: 1.95, 1.99, and 1.98 mg/dL, respectively; p = NS). In 285 patients who received TRT with fenoldopam and were followed for at least 48 hours, the incidence of CIN was 71% lower than predicted (8.1% actual CIN versus 28.0% predicted; p<0.0001). Only 4 (1.4%) patients required dialysis (versus the 2.6% predicted rate, p = NS). The Benephit system and TRT during coronary and endovascular procedures in patients at high risk for renal failure is simple to use and safe. With the infusion of intrarenal fenoldopam, the incidence of CIN was significantly lower than predicted by risk score calculations.

Frequency and predictors of contrast-induced nephropathy after angioplasty for chronic total occlusions

Background The incidence and predictors of contrast-induced nephropathy (CIN) after percutaneous coronary intervention (PCI) of chronic total occlusions (CTO) have not been specifically reported. Methods This retrospective analysis included all consecutive patients referred for PCI of CTO between April 2003 and March 2008, with baseline and 24 h postprocedural available creatinine levels. CIN was defined as 24 h postprocedural increase of baseline creatinine levels ≥ 0.5 mg/dl (CIN 05) or ≥ 25% (CIN 25). Severe renal dysfunction (SRD) was defined as acute renal failure requiring dialysis, or an increase in baseline creatinine levels ≥ 2.0 mg/dl (SRD 2) or ≥ 50% (SRD%). Patients were classified into risk categories for CIN, according to the validated Mehran risk score. Results A total of 227 patients were included, mean age of 64 ± 10 years, the majority being at low risk for CIN (55% with ≤ 5 points in the Mehran score). CIN 25 occurred in 6.16% (14/227) patients and CIN 05 in 0.88% (2/227). The incidence of SRD 2 or SDR% was 0% (0/227) and 0.9% (2/227), respectively, with no patient requiring dialysis. Patients who developed CIN 25 received a higher contrast volume than those who did not (312 ml (210–400) vs 260 ml (200–345), p = 0.14), but the difference was not statistically significant. Conclusions In this consecutive cohort of patients, the incidence of CIN following PCI for CTO was low despite the administration of moderate to large volumes of contrast media. Attempts at revascularization of CTO should not be discouraged or be prematurely interrupted because of the fear of CIN.

Kidney diseases beyond nephrology--intensive care

Sodium bicarbonate has been used for several years for its presumed nephroprotective effects in several settings. In particular, its role in cardiac surgery-associated acute kidney injury (CSA-AKI) has been explored. CSA-AKI is a particular type of cardio-renal syndrome for which no clear understanding of pathogenesis exists and no proven effective prophylaxis or treatment has as yet been established [1]. Previous studies have reported injury to red cells and release of free haemoglobin during cardiopulmonary bypass (CPB) [2]. Besides complete red blood cell fragmentation (induced by CPB, valvular prosthesis, transfusion reactions or genetic defects predisposing to reduced erythrocyte membrane stability), there can also be sublethal red cell damage, resulting in altered rheological properties. Increased levels of free red blood cell constituents, together with an exhaustion of their scavengers, transferrin and haptoglobin, result in a variety of serious clinical consequences, such as increased systemic vascular resistance, altered coagulation prof ile, platelet dysfunction, renal tubular damage and increased mortality. Such injury raises concerns that CSA-AKI may be a form of renal sideropathy and that free or inappropriately liganded iron-related toxicity may play a role [3]. Free iron has the potential to catalyse the formation of super-oxide radical and hydrogen peroxide yielding hydroxyl radical. It is known that an acid environment typical of tubular urine enhances the formation of reactive hydroxyl radicals. Finally, tubular obstruction may allow greater time for endocytotic uptake of free haemoglobin into proximal tubular cells, which is associated with proximal tubular cell necrosis. Oxidative stress has been shown to play a key role in the development of toxic and ischaemic AKI. Interestingly, urinary alkalinization with sodium bicarbonate might protect from the pathophysiological mechanisms causing CSA-AKI. A recent double-blind randomized controlled trial showed that bicarbonate might attenuate CSA-AKI, potentially directly affecting iron-related toxicity, as indicated by a smaller increase in urinary biomarker neutrophil gelatinaseassociated lipocalin (NGAL) [4]. At neutral or alkaline pH, free ferric ions precipitate as insoluble ferric hydroxide, which is excreted as inert complex in the urine. More alkaline urine reduces the generation of injurious hydroxyl radicals and lipid peroxidation. Bicarbonate directly scavenges hydroxyl ions and, as a not well-adsorbable anion compared with chloride, causes more rapid volume excretion and thereby reduces the contact time between injurious radicals and renal tubules. Peak plasma creatinine increases were typical by the third post-operative day regardless of the study group. Furthermore, exposure to sodium bicarbonateattenuated renal oxidative stress as reflected by lower urinary NGAL levels and urinary NGAL/creatinine ratios. As expected, exposure to sodium bicarbonate infusion was associated with a higher plasma pH, higher plasma bicarbonate and urinary alkalinization. Fewer patients in the sodium bicarbonate group (16 of 50) developed a post-operative increase in serum creatinine compared with control (26 of 50) (P = 0.043). The increase in plasma creatinine, plasma urea, urinary NGAL, and urinary NGAL/urinary creatinine ratio was less in patients receiving sodium bicarbonate. As the authors acknowledge, bicarbonate apparently preventedonly mild renal dysfunction which may have limited effects on clinical outcome. Furthermore, the potential clinical risks of systemic alkalinization, e.g. oxyhaemoglobin dissociation curve shifts resulting in higher oxygen–haemoglobin affinity with possible relative tissue hypoxaemia, have not been fully evaluated in this pilot trial. The effects of bicarbonate on higher risk cardiac surgery patients remain to be evaluated. These results suggest finally a novel utility of urinary NGAL measurements not as diagnostic biomarker but as monitor of the efficacy of therapy for AKI. Sodium bicarbonate has also been used for nephroprotection in contrast-induced acute kidney injury (CI-AKI). The benefit of CI-AKI prophylaxis has mainly been shown for patients with reduced glomerular filtration rate (GFR) (<50 mL/min/1.73 m), heart failure or diabetes, and/or patients with high risk scores (Thakar score [5] or Mehran score [6]). In this light, intensive care unit (ICU) patients undergoing angiography should always be considered as high-risk patients. The International Consensus Conference in Intensive Care Medicine recently considered the