Form Of Acute Renal Failure Research Articles

Urinary subclasses of glutathione-s-transferase (α и Ï€) as an indicator of early damages in human kidney tubular cells

The aim of this work was to obtained information about the possibility of differentiating (with a- and TE-GST) between cellular damage at different levels of the tubular system in specific forms of acute renal failure (ARF) - ischemic vs. obstruction. The study focused specifically on differencing between acute allograft rejection and cyclosporineA induced nephrotoxicity. PATIENTS AND METHODS. Twenty two patients, hospitalized at the Department of Nephrology, Clinical centre-Skopje, suffering from ARF with the average age 48.1±5.6 years were studied. Forty five recipients with renal allograft were followed daily from the time of transplantation until discharge from hospital and then twice weekly for a total 3 months. Urine sample were obtained from patients with ARF as an ischemic tubular necrosis and acute obstructive renal insufficiency and patients with renal transplantation. The concentration of a- and TE-GST in urine were measured following the method of quantitative EIA (Biotrin Int.LTD). The serum samples from transplanted patient were measured for creatinine and CystatinC. RESULTS. Significant differences of p-GST values between ischemic ARF and acute renal obstruction were observed, while they were insignificant for the values of a-GST. There were no significant differences for a-GST values of all three samples in both groups with ARF. In the cases of acute rejection after transplantation, the release of a-GST into the urine is limited, while that of the TE-GST isoenzyme is extensive. In contrast to the case of acute rejection, in the early stages of CsA induced nephrotoxicity a significant amount of a-GSTs excreted into the urine, but no significant elevation of urinary TE-GST is seen. Scripta Scientifica Medica 2011;43(2): 107-111

Nitric Oxide Supplementation in Postischemic Acute Renal Failure: Normotension Versus Hypertension

Nitric oxide (NO) has been suggested to play a pivotal role in ischemic acute renal failure (ARF) but there are controversies about its role in hypertensive and non hypertensive ischemic kidney. Multiple strategies including administration of exogenous NO donors have been shown to protect the kidney against toxic or ischemic injury, suggesting endothelial dysfunction as impaired NO generation due to ischemia. However, in postischemic kidney, NO derived from inducible nitric oxide synthase (iNOS) has been considered to enhance the tissue damage while iNOS inhibition decreased the tubular damage. It is well known decrease in basal production of NO in essential hypertension and that long lasting hypertension damages medium size and small-size blood vessels, therefore predisposes nephroangiosclerosis patients to ARF. Many studies have shown that long term stimulation of NO release in normotension improves renal haemodymnamics and kidney function in ischemic form of ARF. On the other hand, there are studies that have shown that NO synthesis stimulation has no effect or even worsens tubular damage in postischemic hypertensive kidney. Therefore, it seems likely that NO supplementation plays different role in postischemic renal damage development, beneficial in well preserved normotensive kidney and limited in postischemic hypertensive kidney due to disturbed tubuloglomerular response, vasoreactivity and kidney vascular structure.

Acute Cortical Renal Necrosis: A Rare Form of Acute Renal Failure

Acute Cortical Renal Necrosis: A Rare Form of Acute Renal Failure

Contrast nephropathy: can we see the whole picture

Renal protection has remained a highly topical subject for years. The focus of any prophylactic strategy remains adequate hydration. It has become clear that the liberal hydration policy practised for years by most anaesthetists has been based on flawed logic and has been, to a large extent, inappropriate and even harmful to patients.1 We see an increased usage of invasive radiology techniques for both diagnostic and therapeutic procedures. The radiocontrast media used in these procedures may cause a reversible form of acute renal failure.

Neuronal activation in the CNS during different forms of acute renal failure in rats

The effect of experimentally induced acute renal failure (ARF) on neuronal cell activation was investigated by immunohistochemistry for Fos and Fra-2 in the rat brain. ARF in rats was induced by bilateral nephrectomy (BNX), bilateral ureter ligature (BUL) and uranyl acetate injection with proper controls (sham-operation or saline injections, respectively). To follow the effect of the development of ARF, rats were killed 30 and 60 min, and 3, 12, 24 and 72 h after surgery, or 3 h to 12 days after uranyl acetate injections. In the BUL and BNX rats, urea and creatinine rose markedly in the plasma within 72 h, while in the uranyl acetate—injected rats the highest levels were observed on the 7th day, followed by a marked decline. At each time-point of the three different, experimentally induced ARF, the presence of Fos- and/or Fra-2-immunoreactive neurons was determined in 120 different brain areas and nuclei. In general, the 73 of 120 brain areas that showed time and intensity dependent activation in response to ARF can be classified into four groups: 1) biogenic amine (noradrenaline, adrenaline, histamine and 5-HT) expressing cell groups in the lower brainstem, 2) “stress-sensitive” forebrain areas, with regard to certain hypothalamic, limbic and cortical areas, 3) neuronal cell groups that participate in the central regulation of body and brain water and electrolyte homeostasis, including the circumventricular organs, and 4) central autonomic cell groups, especially visceral sensory cell groups in the brain, which are in primary, secondary or tertiary connections with renal afferents. Data presented here indicate that a wide variety of neurons in several regulatory mechanisms is affected by ARF-induced peripheral and central alterations.

Acute Renal Failure in Children

1. Dilys A. Whyte, MD* 2. Richard N. Fine, MD* 1. *State University of New York at Stony Brook, NY After completing this article, readers should be able to: 1. Define acute renal failure (ARF). 2. Differentiate the three forms of ARF. 3. Initiate treatment, including stabilization, of a patient who has ARF. 4. Discuss the various medications necessary for treating a patient who has ARF. Acute renal failure (ARF) is defined as an acute decline in renal function characterized by an increase in blood urea nitrogen (BUN) and serum creatinine values, often accompanied by hyperkalemia, metabolic acidosis, and hypertension. Significant morbidity and mortality can accompany ARF. Patients who have ARF recover their renal function either partially or completely or they develop end-stage renal disease. They also may develop associated multiorgan disease. ARF is divided into three forms: prerenal failure (most common), intrinsic renal failure, and postrenal failure. Treatment ranges from conservative medical management to dialysis or renal transplantation, depending on the severity of kidney disease and degree of renal function recovery. Worldwide, most cases of ARF in children are due to hemolytic-uremic syndrome or volume depletion. ### Causes Prerenal failure refers to hypoperfusion of the kidneys. There are a variety of causes for such hypoperfusion, the most common of which is hypovolemia due to gastrointestinal (GI) diseases, congenital heart disease, and sepsis (Table 1). | Extracellular Fluid Volume Deficits | || | | | Cardiac Dysfunction | | | Table 1. Causes of Prerenal Acute Renal Failure ### Pathophysiology Prerenal ARF …

Pathophysiology of septic acute kidney injury: What do we really know?

Septic acute kidney injury accounts for close to 50% of all cases of acute kidney injury in the intensive care unit and, in its various forms, affects between 15% and 20% of intensive care unit patients. However, there is little we really know about its pathophysiology. Although hemodynamic factors might play a role in the loss of glomerular filtration rate, they may not act through the induction of renal ischemia. Septic acute renal failure may, at least in patients with a hyperdynamic circulation, represent a unique form of acute renal failure: hyperemic acute renal failure. Measurements of renal blood flow in septic humans are now needed to resolve this pivotal pathophysiological question. Whatever may happen to renal blood flow during septic acute kidney injury in humans, the evidence available suggests that urinalysis fails to provide useful diagnostic or prognostic information in this setting. In addition, nonhemodynamic mechanisms of cell injury are likely to be at work. These mechanisms are likely due to a combination of immunologic, toxic, and inflammatory factors that may affect the microvasculature and the tubular cells. Among these mechanisms, apoptosis may turn out to be important. It is possible that, as evidence accumulates, the paradigms currently used to explain acute renal failure in sepsis will shift from ischemia and vasoconstriction to hyperemia and vasodilation and from acute tubular necrosis to acute tubular apoptosis or simply tubular cell dysfunction or exfoliation. If this were to happen, our therapeutic approaches would also be profoundly altered.

The treatment of acute interstitial nephritis: More data at last

Acute interstitial nephritis (AIN) is an uncommon form of acute renal failure that is usually medication related. Although the clinical features and renal histopathology are well recognized, therapy beyond discontinuing the offending drug has been a challenge. The use of corticosteroids, although supported by numerous small retrospective studies and anecdotal case reports, has been controversial. The study by González et al., although it has limitations, provides solid support for the early use of corticosteroids in the treatment of drug-related AIN.

Old age and kidneys

Age-related changes in renal morphology and function cannot be regarded physiological. The number of glomeruli falls, sclerotic glomeruli and aglomerular arterioles develop. Besides tubular atrophy interstitial fibrosis is often seen, and the age-related vascular changes strongly affect the kidneys. Renal blood flow and GFR decrease, without concomitant changes in se-creatinine. Disorders of tubular transport manifest mainly in salt- and water-excretion and lead to hyposthenuria. The pathogenesis of these age-related changes is not fully understood. Nevertheless, such changes impair the excretory functions and the pharmacokinetics of drugs. In real chronic renal failure other functions (erythropoietin production, vitamin-D, Ca and P metabolism) are also impaired. Due to more frequent occurrence of systemic diseases (diabetes, hypertension, etc.) in the elderly, real chronic renal failure is also more common, and various forms of acute renal failure develop more easily.

Rolle des L-Arginin/NO-Stoffwechselweges im akuten Nierenversagen

Role of the L-arginine/NO-pathway in acute renal failure ■ Summary Regulation of renal hemodynamics – in particular intraglomerluar hemodynamics -is closely related to the L-arginine/ NO-pathway. Almost all forms of acute renal failure (ARF) are characterized by a reduction in renal plasma flow (RPF) and increased renal vascular resistance. NO, metabolized from L-arginine, is capable of improving renal function due to its vasorelaxing properties in almost all models of ARF, whereas unselective inhibition of nitric oxide synthase (NOS) generally exerts contrary effects. Increased tubular generation of oxygen radicals in the early course of ischemic ARF indicates increased oxidative stress. Simultaneously regulatory changes in expression of iNOS (inducible NOS) and eNOS (endothelial NOS) are observed. Apart from the positive functional effects with L-arginine supplementation a remarkable reduction in the formation of oxygen radicals and reduced overexpression of iNOS are observed. This is important, because in ischemic ARF increased expression of iNOS is accompanied by increased formation of oxygen radicals and peroxynitrite. Both substances are highly reactive and exert many cytotoxic effects. eNOS-derived NO probably plays such an important role in maintaining and improving renal and intraglomerular hemodynamics that negative effects from iNOS-derived NO are overcome. The roles of NOS are different for different types of NOS and also depend on the time course of ARF. Future management strategies should focus on the interplay between antioxidants and NO regulators and the correlation of reactive oxygen species and NO.

Levosimendan protects against experimental endotoxemic acute renal failure

Endotoxemia induces a hemodynamic form of acute renal failure (ARF; renal vasoconstriction +/- reduced glomerular ultrafiltration coefficient, K(f); minimal/no histological damage). We tested whether levosimendan (LS), an ATP-sensitive K+ (K(ATP)) channel opener with cardiac ionotropic and possible anti-inflammatory properties, might have utility in combating this form of ARF. CD-1 mice were injected with LPS +/- LS. LS effects on LPS-induced systemic inflammation (plasma TNF-alpha/MCP-1; cardiorenal mRNAs), plasma NO levels, and azotemia were assessed. Because K(ATP) channel opening has been reported to mediate hypoxic tubular injury, possible adverse LS effects on ischemic ARF and ATP depletion injury were sought. Effects of diazoxide (another K(ATP) channel agonist) and glibenclamide (a channel antagonist) on hypoxic tubular injury also were assessed. Finally, the ability of LS to alter rat mesangial cell (MC) contraction in response to ANG II (elevated in sepsis) was tested. LS conferred almost complete protection against LPS-induced ARF, without any apparent reduction in the LPS-induced inflammatory response. Neither LS nor diazoxide altered ATP depletion-mediated tubule injury (in vivo or in vitro). Conversely, glibenclamide induced a marked and direct cytotoxic effect. LS completely blocked ANG II-induced MC contraction, an action likely to increase K(f). We concluded that 1) LS can confer marked protection against LPS-induced ARF; 2) this likely stems from vasoactive properties, rather than reductions in LPS-induced inflammation; and 3) K(ATP) channel agonists (but not antagonists) appear to be devoid of toxic proximal tubular cell effects. This suggests that LS, and other K(ATP) channel agonists, have a margin of safety if employed in situations (sepsis syndrome, heart failure) in which severe renal vasoconstriction might lead to ischemic ARF.

Theophylline Improves Early Allograft Function in Rat Kidney Transplantation

Several previous studies have demonstrated a beneficial effect of the adenosine receptor (AdoR) antagonist theophylline in different forms of acute renal failure in laboratory animals and in humans. Therefore, we wanted to test whether theophylline can also improve impaired allograft function following ischemia reperfusion injury in experimental kidney transplantation (KT). Orthotopic transplantation of the left kidney was performed from Fisher 344 into Lewis rats. All transplanted rats received daily cyclosporine (5 mg/kg). The effect of theophylline treatment (10 mg/kg) on graft function was compared with appropriate controls on day 5 after KT by assessment of glomerular filtration rate (GFR) (inulin clearance). On day 5, GFR of allografts in control rats was 0.23 +/- 0.05 ml/min/g kidney weight (n = 10) compared with 0.50 +/- 0.09 ml/min/g in rats receiving theophylline (n = 9, p < 0.01), representing a 2-fold increase in GFR. Renal AdoR A(1) mRNA content was significantly increased in both KT groups compared with their respective control groups, whereas mRNA of AdoR A(2a), A(2b), and A(3) were found to be unchanged. Theophylline did not affect significantly interstitial infiltration of the graft by monocytes/macrophages and T-cells. Likewise, serum cytokines [interleukin (IL)-2, IL-6, IL-10, tumor necrosis factor-alpha] and erythropoietin plasma levels were not different among the allograft groups. The present study demonstrates that theophylline remarkably improved early renal allograft function in rats undergoing KT without influencing cytokine serum patterns or tissue inflammation. Since theophylline is a commonly used medication in humans, clinical studies in patients undergoing KT are warranted.

Wnt-4 and Ets-1 signaling pathways for regeneration after acute renal failure

Ischemic acute renal failure (ARF) is the most common form of ARF in the adult population. The molecular mechanisms of tubular regeneration after ischemic renal injury remain largely unknown. An understanding of the mechanisms that lead to renal cell proliferation and regeneration will be necessary for the exploration of novel therapeutic strategies for the treatment of ARF. It has been suggested that regeneration processes may recapitulate developmental processes in order to restore organ or tissue function. The adult tubular epithelial cells have a potent ability of regenerate after cellular damage. We examined functional role of two developmental genes, Wnt-4 and Ets-1, in renal tubular regeneration in ARF. The Wnt-β-catenin pathway plays key roles in embryogenesis. Wnt-4 is known to be expressed in the mesonephric duct in the embryonic development. To clarify the significance of the Wnt-4-β-catenin pathway in ARF, we used a rat ARF model in vivo and LLC-PK1 cells as an in vitro model. After clamping left rat renal artery for 1 hour, we examined whole kidney homogenate and total RNA extracted at 3, 6, 12, 24, 48, and 72 hours after reperfusion by Western blot analysis and real-time reverse transcription-polymerase chain reaction (RT-PCR). Wnt-4 mRNA and protein expression were strongly increased at 3 to 12 hours and 6 to 24 hours after ischemia, respectively. In immunohistologic examination, Wnt-4 was expressed in the proximal tubules and coexpressed with aquaporin 1 and proliferating cell nuclear antigen (PCNA). Cyclin D1 and cyclin A were expressed at 12 to 48 hours after reperfusion. Furthermore, overexpression of Wnt-4 and β-catenin promoted the cell cycle and increased the promoter activity and protein expression of cyclin D1 and cyclin A in LLC-PK1 cells. These data suggest that the Wnt-4-β-catenin pathway plays a key role in the cell cycle progression of renal tubules in ARF. The Ets family of transcription factors is defined by a conserved DNA-binding Ets domain that forms a winged helix-turn-helix structure motif. The Ets family is involved in a diverse array of biologic functions, including cellular growth, migration, and differentiation. To clarify the significance of Ets-1 in ARF, we used a rat ARF model in vivo and LLC-PK1 cells as an in vitro model. Ets-1 mRNA and protein expression were strongly increased at 3 to 12 hours and 6 to 24 hours after the ischemia, respectively. In the immunohistologic examination, Ets-1 was expressed in the proximal tubules and coexpressed with PCNA. Furthermore, overexpression of Ets-1 promoted the cell cycle and increased the promoter activity and protein expression of cyclin D1 in LLC-PK1 cells. Ets-1 promoter activity increased between 3 hours and 6 hours in hypoxia, and hypoxia also induced changes in the Ets-1 protein level in LLC-PK1 cells. Taken together, these data suggest that Ets-1 plays a key role in the cell cycle progression of renal tubules in ARF. Our data suggest that Wnt-4-β-catenin and Ets-1 pathways regulate the transcription of cyclin D1 and control the regeneration of renal tubules in ARF. These developmental genes may play key roles in dedifferentiation and regeneration of the renal tubular cells after ARF.

Renal Failure Secondary to Acute Tubular Necrosis: Epidemiology, Diagnosis, and Management

Acute tubular necrosis (ATN) is a form of acute renal failure (ARF) that is common in hospitalized patients. In critical care units, it accounts for about 76% of cases of ARF. Despite the introduction of hemodialysis > 30 years ago, the mortality rates from ATN in hospitalized and ICU patients are about 37.1% and 78.6%, respectively. The purpose of this review is to discuss briefly the cause, diagnosis, and epidemiology of ARF, and to review in depth the clinical trials performed to date that have examined the influence of growth factors, hormones, antioxidants, diuretics, and dialysis. In particular, the role of the dialysis modality, dialyzer characteristics, and dosing strategies are discussed.

Urinary interleukin-18 is a marker of human acute tubular necrosis

Background: Interleukin-18 (IL-18) is a mediator of ischemic acute tubular necrosis (ATN) in mice. Methods: IL-18 was measured in human urine to determine whether it might serve as a marker of ATN. Seventy-two patients, including healthy controls, patients with different forms of acute renal failure, and patients with other renal diseases, were studied. Results: Patients with ATN had significantly greater median urinary IL-18 concentrations than those with all other conditions: patients with ATN, 644 pg/mg creatinine (mean, 814 ± 151 [SE] pg/mg creatinine; P <0.0001) versus healthy controls, 16 pg/mg creatinine (mean, 23 ± 9 pg/mg creatinine); patients with prerenal azotemia, 63 pg/mg creatinine (mean, 155 ± 68 pg/mg creatinine); patients with urinary tract infection, 63 pg/mg creatinine (mean, 149 ± 110 pg/mg creatinine); those with chronic renal insufficiency, 12 pg/mg creatinine (mean, 84 ± 45 pg/mg creatinine); and patients with nephrotic syndrome, 34 pg/mg creatinine (mean, 67 ± 47 pg/mg creatinine). Median urinary IL-18 concentrations measured in the first 24 hours after kidney transplantation were 924 pg/mg creatinine (mean, 1,199 ± 187 pg/mg creatinine) in patients who received a cadaveric kidney that developed delayed graft function compared with 171 pg/mg creatinine (mean, 367 ± 102 pg/mg creatinine) in patients who received a cadaveric kidney with prompt graft function and 73 pg/mg creatinine (mean, 176 ± 107 pg/mg creatinine) in patients who received a kidney with prompt graft function from a living donor (P <0.002). In kidney transplant recipients, lower urinary IL-18 levels were associated with a steeper decline in serum creatinine concentrations postoperative days 0 to 4 (P = 0.009). Conclusion: IL-18 levels are elevated in urine in patients with ATN and delayed graft function compared with other renal diseases. Urinary IL-18 may serve as a marker for proximal tubular injury in ATN. The clinical application of this test may be substantial because it is reliable, inexpensive, and easy to perform.

Provider Use of Preventive Strategies for Radiocontrast Nephropathy in High-Risk Patients

Background/Aims: Radiocontrast nephropathy (RCN) is a common and costly form of acute renal failure. Current preventative strategies include the use of intravenous (IV) fluids and the discontinuation of nephrotoxic medications at the time of radiocontrast administration. We sought to determine whether providers employ these strategies in high-risk patients to limit the development of RCN. Methods: High-risk patients undergoing procedures using radiocontrast media over a 12-month period were identified. Medical records were reviewed for all subjects who developed RCN and a randomly selected 25% of patients without RCN. Patients with a contraindication to IV volume expansion were excluded. Medical records of the remaining patients were reviewed to determine whether IV fluids were administered and whether NSAIDs or COX-2 inhibitors were prescribed at the time of contrast administration. Results: RCN developed in 8% of patients overall. Of 144 patients eligible for IV volume expansion, 16% failed to receive any IV fluids. When IV fluids were employed, their dose and timing of administration varied significantly by treating specialty and procedure. NSAIDs and COX-2 inhibitors were prescribed to 8% of patients. Conclusions: Commonly accepted strategies for the prevention of RCN are underutilized. Quality improvement efforts are needed to increase the use of these two simple prophylactic measures.

Effect of N‐Acetylcysteine on Antioxidant Status in Glycerol‐Induced Acute Renal Failure in Rats

Myoglobinuric acute renal failure has three pathogenic mechanisms: tubular obstruction, renal vasoconstriction, and oxidative stress. The latter is generated through the iron released from the group hemo of the myoglobin. Iron induces the formation of high‐activity oxygen free radicals that increase oxidative stress and provoke lipid peroxidation and cellular death. This oxidative stress can be measured in several ways, both total or partially with the total antioxidant status or the intermediate enzymes. On the other hand, N‐acetylcysteine is a demonstrated substance with antioxidant properties. The aim of the present work was to assess the effect of N‐acetylcysteine on the oxidative stress in the glycerol‐induced acute renal failure in rats model. We observed that the animals treated with N‐acetylcysteine showed an improvement in the antioxidant activity given by an increase in the total antioxidant status and glutathione reductase levels in serum. This improvement was greater when treatment was administered before the induction of rhabdomyolysis. Nevertheless, the observed increase in antioxidant status was only statistically significant for glutathione reductase but not for total antioxidant status. Our results support an important role for N‐acetylcysteine in the treatment of this form of acute renal failure, although we think that oxidative stress is not the main pathogenic mechanism of the tubular necrosis induced by rhabdomyolysis, tubular obstruction and renal vasoconstriction being still more important.

Contrast agent-associated nephrotoxicity

Radiocontrast media can lead to a reversible form of acute renal failure that begins soon after the contrast dye administration and generally is benign. Contrast media accounts for 10% of all causes of hospital-acquired acute renal failure and represents the third leading cause of in-hospital renal function deterioration after decreased renal perfusion and postoperative renal insufficiency. The in-hospital mortality rate in patients developing renal insufficiency is related directly to the magnitude increase of serum creatinine concentration. The mortality rate ranges from 3.8% with an increase in serum creatinine level of 0.5 to 0.9 mg/dL to 64% with an increase of greater than 3.0 mg/dL. The mechanism by which contrast-induced renal failure occurs is not well understood. Contrast agent-associated nephrotoxicity appears to be a result of direct contrast-induced renal tubular epithelial cell toxicity and renal medullary ischemia. Furthermore, a key mechanism seems to be alteration in renal dynamics, probably caused by imbalances between vasodilator and vasoconstrictor factors, including the activities of nitric oxide, prostaglandins, endothelin, and reactive oxygen species. The optimal strategy to prevent contrast-associated nephrotoxicity remains uncertain. At present, recommendations are as follows: (1) periprocedural hydration, (2) use of a low-osmolality contrast, and (3) limiting the amount of contrast agent. Recently, considerable interest has resulted from the preliminary positive data on the effectiveness of prophylactic administration of acetylcysteine and fenoldopam. The former may prevent the direct oxidative tissue damage, whereas the latter is a selective intrarenal vasodilator. Copyright 2003, Elsevier Science (USA). All rights reserved.

Combination of Continuous Renal Replacement Therapies (CRRT) and Extracorporeal Membrane Oxygenation (ECMO) for Advanced Cardiac Patients

Background. The critically ill patients may require mechanical ventilation, cardiac mechanical support, and other types of critical support. Extracorporeal membrane oxygenation (ECMO) is a supportive therapy, which provides good cardiopulmonary and end-organ support. Continuous renal replacement therapies (CRRT) exhibit important advantages in terms of clinical tolerance and blood purification. This investigation aims to evaluate the acute renal failure in cardiac patients under ECMO, and assess the effect of combining these two technologies, ECMO and CRRT. Methods. Between 12 1998 and 06 2001, 10 adult cardiac patients were treated on ECMO. Five of them were treated with both ECMO and CRRT. The clinical outcomes were retrospectively analyzed. Results. Of the 10 patients studied, five were men and five were women. The mean age of survivors and non-survivors was 37.00 ± 14.54 years and 46.17 ± 7.41 years, respectively. The overall mortality rate was 60%. Survivors did not differ significantly from non-survivors in age or gender. The APACHE II scores on the first day of ECMO support between survival and non-survival were 19.00 ± 9.38 and 24.67 ± 3.50 (P value = 0.392) (Table ), which demonstrates no significant differences too. The cause of death in most patients was related to organ system failure during the 24 h immediately before ECMO started. Five patients with acute renal failure treated by CRRT were eventually died. The median and mean survival in this group on CRRT was 40.50 ± 18.07 h and 92.60 ± 60.50 h. Conclusion. We conclude that mortality rate for acute renal failure in cardiac patients under ECMO continues to be high. Our data suggest that acute renal failure is generally a part of multiorgan failure. This unique form of acute renal failure, causes generalized edema and fluid overload despite still low serum creatinine and azotemia, and deteriorates rapidly to death. From this study shows, advanced cardiac failure may need more aggressive and early initiation of ECMO support before acute renal failure develops. Acute renal failure in advanced heart failure under ECMO support means a grave sign, need aggressive heart transplantation therapy as soon as possible. Combination of CRRT and ECMO might serve an alternative therapy bridging the temporary replacement treatment and heart transplantation in advanced cardiac patients.

Kidney Injury Molecule-1 (KIM-1): A novel biomarker for human renal proximal tubule injury

Traditional blood and urine markers for the diagnosis of various renal diseases are insensitive and nonspecific. Kidney Injury Molecule-1 (KIM-1) is a type 1 transmembrane protein, with an immunoglobulin and mucin domain, whose expression is markedly up-regulated in the proximal tubule in the post-ischemic rat kidney. The ectodomain of KIM-1 is shed from cells. The current studies were carried out to evaluate whether KIM-1 is present in human acute renal failure and might serve as a urinary marker of acute renal tubular injury. Kidney tissue samples from six patients with biopsy-proven acute tubular necrosis (ATN) were evaluated by immunohistochemistry for expression of KIM-1. Urine samples were collected from an additional thirty-two patients with various acute and chronic renal diseases, as well as from eight normal controls. Urinary KIM-1 protein was detected by immunoassay and was quantified by ELISA. There was extensive expression of KIM-1 in proximal tubule cells in biopsies from 6 of 6 patients with confirmed ATN. The normalized urinary KIM-1 levels were significantly higher in patients with ischemic ATN (2.92 +/- 0.61; N = 7) compared to levels in patients with other forms of acute renal failure (0.63 +/- 0.17, P < 0.01; N = 16) or chronic renal disease (0.72 +/- 0.37, P < 0.01; N = 9). Adjusted for age, gender, length of time delay between the initial insult and sampling of the urine, a one-unit increase in normalized KIM-1 was associated with a greater than 12-fold (OR 12.4, 95% CI 1.2 to 119) risk for the presence of ATN. Concentrations of other urinary biomarkers, including total protein, gamma-glutamyltransferase, and alkaline phosphatase, did not correlate with clinical diagnostic groupings. A soluble form of human KIM-1 can be detected in the urine of patients with ATN and may serve as a useful biomarker for renal proximal tubule injury facilitating the early diagnosis of the disease and serving as a diagnostic discriminator.