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PubMed1985

Tubular ultrastructure in acute renal failure in man: epithelial necrosis and regeneration.

It is not clear whether tubular cell necrosis is present or not in acute renal failure (ARF) of ischaemic type ("acute tubular necrosis"). In order to get quantitative data, using precisely defined criteria for tubular cell necrosis, 25 renal biopsies from 24 patients with ARF (11 obtained in the active phase, 14 in the early recovery period) were compared with 12 control biopsies. In all 1959 proximal cells and 1603 distal cells were analysed by electron microscopy. Cellular disintegration was very rare in all groups. Shrinkage necrosis (apoptosis) was not present in the proximal tubules of the controls and was rare in ARF (1.6-2.1%). In the distal tubules of controls 2.7% of all cells showed shrinkage necrosis. The incidence in ARF was not significantly increased. "Non-replacement sites" in distal tubules (probably loci where cells have recently been desquamated) were significantly increased in number (5.2%) in the active phase in ARF compared to controls and recovery. The relative number of regenerating cells was not increased. These data show that there is no widespread necrosis of tubular cells in ARF. The increased incidence in distal tubules of focal, denuded areas of the basement membrane in the active phase of ARF indicates a slightly increased desquamation of cells and/or a failure to cover such sites by adjacent cells. This process is not restricted to the brief induction phase of ARF but continues during the whole active phase.

Acute Kidney Injury↗
PubMed1987

Acute renal failure in neonates: incidence, etiology and outcome.

Acute renal failure (ARF) occurs in as many as 8% of neonates admitted to neonatal intensive care units. Most often, ARF is recognized because of oliguria (urinary flow rate less than 1 ml/kg per hour) although nonoliguric neonatal ARF is being detected with increasing frequency. Among urinary indices utilized to differentiate oliguric neonatal ARF from prerenal oliguria, a fractional excretion of sodium greater than 3% or a renal failure index (RFI) greater than 3 are helpful in confirming ARF. Such indices must be viewed with caution in very premature infants who may have a physiologically high sodium excretion rate and in neonates with the nonoliguric form of ARF. The mortality of oliguric neonatal renal failure may be as high as 60% in medical ARF and even higher in neonates with congenital heart disease, or with anomalies of the genitourinary system. In contrast, nonoliguric renal failure in neonates has an excellent prognosis. Long-term abnormalities in glomerular filtration rate and in renal tubular function are common in survivors of neonatal ARF.

Acute Kidney Injury↗
PubMed2006

Transpyloric enteral nutrition in the critically ill child with renal failure.

OBJECTIVE: To study the efficacy and tolerance of transpyloric enteral nutrition (TEN) in the critically ill child with acute renal failure (ARF). DESIGN: Prospective observational study. SETTING: Paediatric intensive care unit. PATIENTS: Critically ill children with ARF who received TEN were included in the study. They were compared with the remaining 473 critically ill children receiving TEN in this period. Tolerance of nutrition and gastrointestinal complications were assessed. INTERVENTION: Transpyloric enteral nutrition. MEASUREMENTS AND RESULTS: Fifty-three critically ill children with ARF aged between 3 days and 17 years received TEN. Children with ARF more frequently received parenteral nutrition before TEN (56.6%) than the other patients (17.5%). The incidence of shock, hepatic alterations and mortality was significantly higher in patients with ARF than in the remaining children. In children with ARF the mean duration of the TEN was 16.5-27.3 days and the maximum caloric intake was 77-26.7 kcal/kg/day. Thirteen patients (24.5%) presented gastrointestinal complications, 9 (17%) abdominal distension and/or excessive gastric residue, 5 (9.4%) diarrhoea, 1 necrotising enterocolitis and 1 duodenal perforation. The frequency of gastrointestinal complications was significantly higher in children with ARF. TEN was definitive suspended in five patients due to gastrointestinal complications. Four of these patients were treated with continuous renal replacement therapy. Thirty percent of patients died during TEN. In only one patient was the death related to complications of the nutrition. CONCLUSIONS: Critically ill children with ARF tolerate TEN, although the incidence of gastrointestinal complications is higher than in other critically ill children.

Acute Kidney Injury↗
PubMed2006

Renal failure in septic shock: predictive value of Doppler-based renal arterial resistive index.

OBJECTIVE: Because acute renal failure (ARF) is frequent in septic shock, an early marker of ARF could impact on management of such patients. High renal arterial resistive index (RI) is associated with parenchymatous renal failure. We assessed whether Doppler-measured RI on day 1 (D1) of septic shock can predict ARF. DESIGN: Prospective descriptive clinical study. SETTING: A 20-bed medical intensive care unit in a university hospital. PATIENTS: All patients with septic shock, excluding those with chronic renal failure (serum creatinine >120 micromol/l). MEASUREMENTS AND RESULTS: RI was determined during the first 24 h (D1) following vasopressor introduction, concomitant with recording of: age, SAPS II, mean arterial pressure, arterial lactate, catecholamine (dose and type), urine output and serum creatinine. ARF was diagnosed according to the RIFLE classification. RI measurement was possible for 35 of 37 included patients. On day 5 (D5), 17 patients were without ARF (RIFLE-0 or R) and 18 patients were classified as having ARF (RIFLE-I or F). On D1, RI was higher in these latter 18 patients (0.77+/-0.08 vs. 0.68+/-0.08, p<0.001). They also had higher SAPS II and arterial lactate concentration. RI >0.74 on D1 had a positive likelihood ratio of 3.3 (95% CI 1.1-35) for developing ARF on D5. RI correlated inversely with mean arterial pressure (rho=-0.48, p=0.006) but not with catecholamine type or dose or with lactate concentration. CONCLUSION: Doppler-based determination of RI on D1 in septic shock patients may help identify those who will develop ARF.

Acute Kidney Injury↗
PubMed1999

Acute neuromuscular respiratory failure after ICU discharge. Report of five patients.

OBJECTIVE: To describe a syndrome of acute neuromuscular respiratory failure (NM-ARF) caused by ICU-acquired acute myopathy and neuropathy. DESIGN: Case series. SETTING: General Regional University Hospital in Brescia, Italy. PATIENTS: Five adult patients with NM-ARF after prolonged ICU stay and successful weaning from the ventilator and ICU discharge. INTERVENTIONS: None. MEASUREMENTS: Clinical signs of NM-ARF, electroneurography and electromyography (ENMG) of peripheral nerves and muscles, and functional assessment of respiratory muscles. RESULTS: NM-ARF was diagnosed at the time of (one case), or 1-3 days after, ICU discharge. Limb weakness alarmed the physicians, while the signs of the NM-ARF were initially undetected. In the first observed case the acute respiratory failure was near fatal, and necessitated ICU readmission, while in the other cases 2 weeks of aggressive chest physiotherapy permitted resolution of the respiratory failure. History, clinical course and ENMG indicated the diagnosis of critical illness myopathy and neuropathy (CRIMYNE). Three patients recovered fully, while two had persisting evidence of axonal polyneuropathy several months after the onset. CONCLUSIONS: Critically ill patients with prolonged ICU stay, sepsis and MOF are at great risk of developing CRIMYNE, which in turn may be responsible for NM-ARF. This latter complication may arise after resolution of the respiratory and cardiac dysfunctions and successful weaning from the ventilator. As NM-ARF may cause unplanned ICU readmission or even unexpected death, strict clinical surveillance and monitoring of respiratory muscle function is recommended after discharge to the general ward of patients with proven NM-ARF. Early intensive chest physiotherapy can resolve the condition.

Adult↗
PubMed2002

Interleukin genetic variants and the risk of renal failure in infants with infection.

Systemic infection is a major risk factor for the development of neonatal acute renal failure (ARF). We investigated whether genetic polymorphisms of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and IL-10 genes leading to a more intense inflammatory response might predispose very low birth weight (VLBW) infants to the development of ARF in severe infection. The medical records of 92 VLBW newborns (birth weight under 1,500 g) with systemic infection were analyzed. ARF developed in 38 infants during the 1st postnatal week, while 54 neonates exhibited normal renal function. The variants of TNF-alpha, IL-1beta, IL-6, and IL-10 genes were determined from dried blood samples with polymerase chain reaction and restriction fragment length polymorphism methods. The allele frequencies did not differ in ARF and in non-ARF babies, while the (TNF-alpha /IL-6) AG/GC or AG/CC haplotypes were more often present in ARF (26% vs. 6%, P<0.01). The single presence of TNF-alpha, IL-1beta, IL-6, and IL-10 variants does not influence the development of ARF, but the constellation of TNF-alpha and IL-6 genetic variants is associated with ARF. We hypothesize that the simultaneous presence of these polymorphisms might lead to an enhanced inflammatory response in the kidneys in babies with infection.

Acute Kidney Injury↗
PubMed2003

Fluid overload and acute renal failure in pediatric stem cell transplant patients.

Acute renal failure (ARF) with fluid overload (FO) occurs often in stem cell transplant (SCT) recipients. We have previously demonstrated that an increased percentage of FO prior to the initiation of continuous renal replacement therapy (CRRT) is associated with mortality in children with ARF. Based on these data, we devised a protocol for the prevention of FO in SCT patients with ARF. SCT patients with ARF and 5% FO were started on furosemide and low-dose dopamine. To allow for nutrition, medication, and blood product administration, RRT was initiated for patients with > or =10% FO. There were 272 patients who received allogeneic SCT from 1999 to 2002. Of these, medical records of 26 SCT patients with a first episode of oliguric ARF were reviewed. The mean patient age was 13+/-5 years (range 2-23.5 years). Mean days to ARF after SCT were 28+/-29 days (range 2-90 days). Of the 26 patients, 11 (42%) survived an initial ARF episode. All 11 survivors either maintained <10% FO during their course or re-attained <10% FO with RRT treatment. Of the 15 non-survivors, 6 had <10% FO at the time of death. Of 14 patients who received RRT, 4 (29%) survived. Mechanical ventilation and pediatric risk of mortality score > or =10 at the time of admission to the intensive care unit were associated with lower survival ( P<0.05). The use of one or more pressors, the presence of graft-versus-host disease, and septic shock were not correlated with survival. Our data demonstrate that maintenance of euvolemia ( <10% FO) is critical but not sufficient for survival in SCT patients with ARF, as all non-euvolemic patients died. We suggest that aggressive use of diuretics and early initiation of RRT to prevent worsening of FO may improve the survival of SCT patients.

Acute Kidney Injury↗
PubMed2005

Acute renal failure in Nigerian children: Port Harcourt experience.

Acute renal failure (ARF) is a significant cause of morbidity and mortality in children. It may be pre-renal, intrinsic, or post-renal (obstructive) in aetiology. ARF was investigated in children in the south-southern part of Nigeria to determine the prevalence, aetiology, management and outcome of ARF. A retrospective review of data from all children from birth to 16 years of age admitted into the Department of Paediatrics, University of Port Harcourt Teaching Hospital (UPTH), with the diagnosis of ARF over an 18 year period (January 1985 to December 2003) was performed. Information was obtained about the age, sex, clinical features, blood pressure, laboratory and radiological investigations, aetiology, and treatment received including dialysis. Information on the outcome, factors influencing outcome, and possible causes of death were reviewed. There were 211 patients, 138 (65.4%) males and 73 (34.6%) females (M:F, 1.9:1), with a hospital prevalence of 11.7 cases/year. The patients were aged 5 days to 16 years (mean 5.6+/-4.7 years). Oliguria was the most common clinical presentation in 184 (87.2%) patients. Hypertension was seen in only 39 (18.5%) patients. The causes were age-related. The neonates had ARF from severe birth asphyxia 27 (35.5%), septicaemia 17 (22.4%), with tetanus 4 (5.3%) and congenital malformations 11 (14.5%). Sixty-one (28.9%) and 29 (13.7%) patients had ARF from gastroenteritis and malaria respectively. The patients with leukaemia were all more than 10 years old and had acute lymphoblastic leukaemia. Two patients (1.9%) had Burkitts lymphoma involving the abdomen and 3 patients had HIVAN. 112 (53%) patients had anaemia with a mean haematocrit of 20.25+/-6.9%. Dialysis was indicated in 108 patients, but only 24 patients (22.2%) had peritoneal dialysis (PD), because of financial constraints and lack of dialysis equipment. Mortality rate was 40.5%. The causes of death were uraemia 60 (70.6%), overwhelming infection 5 (5.9%), and recurrent anaemia 20 (23.5%). Hypertension (X2 15.7, P<0.001) and lack of dialysis (X2 7.96, P<0.01) significantly affected outcome. Other factors associated with demise were delayed presentation (58.8%), use of herbal treatment (35%), and unaffordability of treatment (40%). ARF is a significant cause of mortality in Nigerian children. The patients are not adequately managed because of poverty and lack of facilities for dialysis. The causes of ARF in our environment are preventable, and should be expected.

Acute Kidney Injury↗
PubMed2006

Pediatric acute kidney injury: it's time for real progress.

Mortality and morbidity from acute renal failure has not improved in pediatric or adult patients over the past 40 years. This lack of improvement stems from varied definitions for acute renal failure (ARF), changes in ARF epidemiology, and the reliance on changes in serum creatinine for ARF diagnosis. Significant research has occurred in the past 5 years to standardize ARF definitions, recognize ARF earlier, discover urinary biomarkers of early renal insult, and more optimally manage patients with ARF. As a result, changes in nomenclature from ARF to acute kidney injury and earlier institution of renal replacement therapy may lead to improvements in patient outcome. The aim of this editorial is to provide a description of the state of the art in pediatric ARF diagnosis and management by highlighting recent significant clinical and research progress.

Acute Kidney Injury↗
PubMed2001

Variance of ACE and AT1 receptor gene does not influence the risk of neonatal acute renal failure.

High neonatal activity of the renin-angiotensin system (RAS) is crucial for the maintenance of glomerular filtration of the newborn. The aim of the present study was to investigate whether genetic polymorphisms leading to lower angiotensin converting enzyme activity (ACE) or impaired functionality of angiotensin II (AII) type 1 receptor (AT1R) might predispose very low birth weight newborns (VLBWs) to the development of acute renal failure (ARF). The medical records of 110 VLBW infants were analyzed. ARF developed in 42 of them during the first postnatal week, while 68 neonates exhibited normal renal function. The ACE I/D polymorphism and the A1166C variants of AT1R were determined from dried blood samples. The frequency of the ACE I allele did not differ in ARF and non-ARF groups (0.307 and 0.284); the frequency of the AT1R C1166 variant was also the same in ARF and non-ARF groups (0.250 and 0.227). Although low activity of RAS has been implicated in the development of neonatal ARF and data indicated that the functionality of RAS is influenced by the I/D variants of the ACE gene and the A1166C variant of the AT1R gene, we could not demonstrate any effect of these polymorphisms on the development of ARF in VLBW infants.

Acute Kidney Injury↗
PubMed2006

Factors affecting the outcome of acute renal failure among the elderly population in India: a hospital based study.

The spectrum of acute renal failure (ARF) in the elderly population and the factors predicting poor outcome in these patients are not well defined in literature. Identification of risk factors and poor prognostic markers in these patients can help in planning strategies to prevent ARF and to prioritise the utilization of sparse and expensive therapeutic modalities, especially in a developing country like ours. We retrospectively analyzed data of 454 elderly patients (age >or=60 years), detected having ARF in a tertiary care super-speciality hospital in North India, from April 2000 to March 2004. The mean age of this population was 66.4 years with 70.5% being male. 64% patients had more than one precipitating factors for ARF, with volume depletion being the most common precipitating factor (33% cases). Infection/sepsis (21.6%) and drugs (11.5%) were other important precipitating factors. 31.8% were recorded as having oliguric ARF (urine output <400 ml/day) and 33.5% required renal replacement therapy (RRT). Acute peritoneal dialysis was the most frequent form of RRT given (62.5%). Mortality was 41.2% (187 cases), of whom 56 (29.8%) died inspite of recovery from ARF. Among the survivors, 103 patients (22.7%) had complete renal recovery, 141 (31.1%) had partial renal recovery, while 23 (8.6%), remained dialysis dependent. The factors which were found to be associated with increased mortality were; age >or=70 years, presence of previous chronic illness, ARF precipitated by cardiac failure and infection, need for RRT, oliguria and increasing numbers of failed organs. To conclude, ARF among elderly is a common problem in nephrology practice at our institute and is responsible for 48.9% of nephrology admissions/consultations among elderly patients. Majority of these patients are prone to multiple renal insults. Underlying chronic illness, presence of cardiac failure and sepsis, oliguria, need for RRT and increasing number of organ failure is associated with poor outcome.

Acute Kidney Injury↗
PubMed1982

Acute respiratory failure in scoliosis or kyphosis: prolonged survival and treatment.

Acute respiratory failure (ARF) in adults with severe thoracic spinal deformity is said to be a preterminal event with a median survival of one year. Twenty patients with ARF (mean +/- S.D., arterial oxygen tension [PaO2] 35 +/- 7 mm Hg, arterial carbon dioxide tension [PaCO2] 63 +/- 9 mm Hg, pH 7.34 +/- 0.08) due to severe scoliosis or kyphosis (spinal curve 113 +/- 28 degrees ) were seen between 1965 and 1980. All 20 survived the initial episode of ARF and during the follow-up period (median, six years) experienced 2.4 additional episodes of ARF. The age at presentation was 52 years (mean, range 13 to 78), and the cause of spinal deformity was idiopathic (seven patients), poliomyelitis (seven), tuberculosis (five), and arthrogryposis multiplex congenita (one). ARF was treated with controlled low dose oxygen by Venturi mask and intensive general measures in 13 patients and by mechanical ventilation in seven. Of the latter seven patients, ventilatory failure was treated in two with a tank respirator and a cuirass, avoiding endotracheal intubation. Outpatient management was similar to conventional therapy for chronic obstructive pulmonary disease (COPD). Severe restrictive ventilatory impairment characterized the group after recovery from the first episode of ARF: vital capacity (VC) 906 +/- 362 ml (31 percent predicted) and FEV1 589 +/- 197 ml (23 percent). During follow-up, the VC decreased by 1.5 ml/year and the FEV1 by 13.9 ml/year. The PaO2 increased by 2.6 mm Hg/year and the PaCO2 increased by 1.7 mm Hg/year. Successful management of ARF due to severe scoliosis or kyphosis is possible in the great majority of patients, and long-term survival may be expected. Unlike COPD, pulmonary function following ARF in kyphosis or scoliosis deteriorates at a slower than expected rate and, in fact, may improve with treatment over many years.

Acute Disease↗
PubMed1995

Outcome of severe acute renal failure in patients with acquired immunodeficiency syndrome.

Among a spectrum of renal disorders encountered in patients infected with the human immunodeficiency virus (HIV), the lesion studied most often has been the glomerular disease known as HIV-associated nephropathy. Of the other coincidental renal perturbations reported, the most significant are a heterogenous group encompassing potentially reversible acute renal failure (ARF), primarily acute tubular necrosis. While HIV-associated nephropathy may frequently be seen in asymptomatic HIV-seropositive individuals, acute tubular necrosis almost always is encountered in patients with clinical acquired immunodeficiency syndrome (AIDS). We analyzed our decade's experience in the management of 146 HIV disease patients with ARF (132 AIDS patients and 14 HIV-seropositive patients) and compared it with a contemporaneous group of 306 non-HIV subjects with ARF. All patients evaluated for ARF between January 1984 and December 1993 by the Renal Division at Kings County Hospital Center, Brooklyn, NY, were reviewed. Only those patients with ARF who reached a serum creatinine concentration of 530 mumol/L or higher were included in the analysis. Ninety-one percent of 146 HIV disease patients with ARF were less than 50 years old compared with only 33% of the 306 non-HIV subjects (P < 0.001). Septicemia was directly or indirectly responsible for 75% of patients with ARF in the AIDS group and for 39% in the non-HIV subjects (P < 0.006). Urinary tract obstruction was the cause of ARF in 54 of 306 (17%) non-HIV patients compared with none in the HIV group (P < 0.00001).(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Associated Nephropathy↗
PubMed1995

Interventions in clinical acute renal failure: what are the data?

A variety of therapeutic approaches have been used both to prevent acute ischemic and nephrotoxic renal injury and to improve renal function and reduce mortality once acute renal failure (ARF) has developed. Unfortunately, there have been few rigorous assessments of the efficacy of these treatment interventions. The reasons for the lack of abundant critical data regarding treatment effects in ARF are several. First, ARF is a functional disorder. It has a spectrum of etiologies, occurs in a variety of clinical settings and varies in severity. Second, selected endpoints of treatment success vary and co-morbid factors frequently determine outcome. Third, it had been difficult to carry out prospective controlled studies in a disorder in which the mortality rate approaches 50%. In this review, an effort was made to analyze the available literature with a primary focus on controlled studies to determine significant prophylactic and treatment effects of various interventions in ARF. Three endpoints of therapy (change in renal function, change in course of azotemia, and change in mortality) were examined for pharmacologic agents. Changes in course of azotemia and mortality were assessed in evaluating different dialysis modes. Effect on nitrogen balance, change in course of azotemia, and change in mortality were used as endpoints to determine treatment effects of different nutritional regimens. When weight was given to prospective controlled studies, some insights emerged as to treatment interventions that are most likely to have beneficial effects in specific settings of ARF. Among pharmacologic agents, mannitol appears to have a positive prophylactic effect in kidney transplantation. There are no other significant beneficial effects of diuretics for prophylaxis or as treatment in early or established ARF. Of vasoactive agents, there is a relatively small amount of data suggesting that diltiazem may have a positive prophylactic effect in kidney transplantation, and dopamine possibly is beneficial early in the evolutionary phase of ARF. Atrial natriuretic peptide and calcium channel blockers may have beneficial effects in established disease. No other pharmacologic interventions are supported by substantial data. At best, the results are equivocal regarding the use of early and vigorous dialysis in ARF. However, there are recent impressive data indicating that the use of biocompatible membranes is efficacious in recovery and survival. There is no clear evidence that one form of nutritional therapy has advantages over others, but some level of amino acid supplementation in addition to basic energy replacement is supported by the overall data.

Acute Kidney Injury↗
PubMed1986

Proton MR study of different types of experimental acute renal failure in rats.

Kidney cortical and medullary spin-lattice (T1) and spin-spin (T2) relaxation times were measured in several types of experimental acute renal failure in rats with a Bruker PC "Multispec." Gentamicin ARF was obtained after one i.p. injection of 100mg Gentamicin/kg BW/day for 8 days. Glycerol ARF: 24 hours after one i.m. injection of 10 ml 50% Glycerol/kg BW. Obstruction ARF: 3 days after complete ureteral ligation. Renal tissue total water content, hydration fraction, fraction bound, blood urea and creatinine were measured at the end of the experiments. Shortened T1 and prolonged T2 were found in both cortex and medulla in the Glycerol ARF group. Gentamicin renal toxicity and the non-functioning kidney with ureteral obstruction are characterized by significant prolongation of T1 and T2 in cortex, while the medullary T1 and T2 were prolonged only in obstruction ARF. The highest T1 and T2 were found in the obstructed non-functioning kidney. The total water content decreased in the Glycerol ARF, increased in the obstruction and remain unchanged in Gentamicin ARF. The hydration fraction and the fraction bound changed significantly in the opposite direction with the total water content. Different profiles of renal cortical and medullary magnetic resonance properties found in several models of experimental ARF in rats indicate that MR properties may provide etiopathogenetic diagnostic possibilities.

Acute Kidney Injury↗
PubMed2005

p16INK4a and p14ARF methylation as a potential biomarker for human bladder cancer.

Promoter hypermethylation is one of the putative mechanisms underlying the inactivation of negative cell-cycle regulators. We examined whether the methylation status of p16(INK4a) and p14(ARF), genes located upstream of the RB and p53 pathway, is a useful biomarker for the staging, clinical outcome, and prognosis of human bladder cancer. Using methylation-specific PCR (MSP), we examined the methylation status of p16(INK4a) and p14(ARF) in 64 samples from 45 bladder cancer patients (34 males, 11 females). In 19 patients with recurrent bladder cancer, we examined paired tissue samples from their primary and recurrent tumors. The methylation status of representative samples was confirmed by bisulfite DNA sequencing analysis. The median follow-up duration was 34.3 months (range 27.0-100.1 months). The methylation rate for p16(INK4a) and p14(ARF) was 17.8% and 31.1%, respectively, in the 45 patients. The incidence of p16(INKa) and p14(ARF) methylation was significantly higher in patients with invasive (>or=pT2) than superficial bladder cancer (pT1) (p=0.006 and p=0.001, respectively). No MSP bands for p16(INK4a) and p14(ARF) were detected in the 8 patients with superficial, non-recurrent tumors. In 19 patients with tumor recurrence, the p16(INK4a) and p14(ARF) methylation status of the primary and recurrent tumors was similar. Of the 22 patients who had undergone cystectomy, 8 (36.4%) manifested p16(INKa) methylation; p16(INK4a) was not methylated in 23 patients without cystectomy (p=0.002). Kaplan-Meier analysis revealed that patients with p14(ARF) methylation had a significantly poorer prognosis than those without (p=0.029). This is the first study indicating that MSP analysis of p16(INK4a) and p14(ARF) genes is a useful biomarker for the pathological stage, clinical outcome, and prognosis of patients with bladder cancer.

Aged↗
PubMed2004

Cold visceral perfusion improves early survival in patients with acute renal failure after thoracoabdominal aortic aneurysm repair.

INTRODUCTION: Despite advances in organ protection during thoracoabdominal aortic aneurysm (TAAA) repair, acute renal failure (ARF) remains a significant clinical problem, associated with increased morbidity and mortality. We studied outcome of ARF after TAAA repair in patients who underwent either warm or cold visceral perfusion. METHOD: Between 1991 and 2001 657 TAAA repairs were performed, of which 359 (55%) had either warm or cold visceral perfusion. Twelve patients with renal failure who had undergone preoperative dialysis were excluded from the study. Of the remaining 347 patients, ARF developed in 81 (23%) after TAAA repair. Forty-four (54%) of the 81 patients with ARF received cold visceral perfusion, and 37 (46%) patients received warm visceral perfusion. ARF was defined as either an increase of 1 mg/dL in serum creatinine (SCr) concentration per day for 2 consecutive days or dialysis requirement. Patient records were reviewed through hospital discharge. RESULTS: Twenty six (32%) of the 81 patients in whom ARF developed died, 17 of 37 (46%) patients in the warm perfusion group versus 9 of 44 (21%) patients in the cold perfusion group (P <.02). Median onset of ARF was on postoperative day 1 in both groups. Twenty-six of 81 (32%) patients recovered renal function, 10 of 37 (27%) patients in the warm perfusion group versus 16 of 44 (36%) patients in the cold perfusion group. Preoperative SCr concentration was predictive of recovery of renal function (odds ratio, 4.5 per mg/dL increase; P <.03) in patients who received either warm or cold visceral perfusion. CONCLUSIONS: ARF after TAAA repair remains a significant clinical problem. Recovery of renal function occurred in approximately one third of patients. Preoperative SCr concentration was the only significant determinant of recovered renal function. While cold visceral perfusion did not alter renal recovery, it significantly reduced hospital mortality.

Acute Kidney Injury↗
PubMed2006

Role of PPAR-gamma on the pathogenesis and vascular changes in glycerol-induced acute renal failure.

Peroxisome proliferator activated receptor-gamma (PPAR-gamma), a nuclear transcription factor, modulates angiotensin II (AII) or thromboxane A(2) (TxA(2)) response in the vasculature via transcriptional regulation of their gene or receptor expression. Increased AII or TxA(2) vasoconstriction and deteriorating renal function observed in glycerol-induced acute renal failure (ARF) may be attributed to a down-regulated PPAR-gamma expression/activity probably via an increased free radical generation. In this study, we investigated the effect of PPAR-gamma induction in glycerol-induced ARF by examining renal vascular reactivity to AII and TxA(2) and by renal expression/activity of PPAR-gamma. Vascular responses to AII or U46619, a TxA(2) mimetic were determined in rat isolated perfused kidney following induction of ARF with glycerol (50%, v/v, i.m.). Extent of renal damage and function were assessed with or without pre-treatment with ciglitazone (9 nmol kg(-1) x 21 days), a PPAR-gamma inducer. In ARF, vasoconstriction was enhanced to AII (three-fold; p<0.05) and U46619 (82%; p<0.05). Ciglitazone reduced AII and U46619 vasoconstriction by 59+/-1% (p<0.05) and 56+/-1% (p<0.05), respectively. Ciglitazone reduced proteinuria (38+/-3%) which was two-fold higher in ARF. Similarly, ciglitazone enhanced Na(+) excretion by 1.5 times while reducing BUN by 49+/-6%. On the contrary, ciglitazone did not change plasma creatinine which was significantly higher in ARF rats. Ciglitazone reduced free radical generation by 30+/-3% while elevating nitrite excretion approximately 2-fold. PPAR-gamma expression and activity were significantly lower in ARF rats and ciglitazone enhanced PPAR-gamma protein expression and activity by 45+/-3% and 52+/-4%, respectively. Data from this study suggest that reduced PPAR-gamma expression and activity may be involved in the pathology of glycerol-induced ARF and induction of PPAR-gamma by ciglitazone confers protection through reduced AII and TxA(2) vasoconstriction and/or enhanced renal function via reducing free radical generation.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗