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Acute renal failure in the medical intensive care unit: predisposing, complicating factors and outcome.

The factors predisposing to and complicating acute renal failure (ARF) in the medical intensive care unit (ICU), and their relative influence on outcome during ARF are unclear. We retrospectively evaluated the relative importance of age, prior chronic disease (including chronic renal failure), sepsis and organ system failure, for development and outcome of ARF in the medical ICU. Of 487 consecutively admitted patients, 78 (16%) had ARF, in 63% treated with renal replacement therapy. Mortality was 63%. Independently from each other, advancing age, prior chronic disease, and cardiovascular and pulmonary failure directly related to the development of ARF, while neurological failure related inversely. Sepsis only contributed to ARF prediction from these variables if cardiopulmonary failure was excluded. Advancing age, cardiovascular failure before and after onset of ARF, pulmonary failure before ARF and use of renal replacement therapy were the major independent factors directly related to ARF mortality, while prior chronic renal failure related inversely and sepsis did not contribute. Hence, the outcome of ARF in a medical ICU is largely dependent on factors predisposing to ARF, even though the severity and complications of ARF may partly contribute. Our results may help in deciding on the prevention and therapy of ARF in a medical ICU.

Acute Kidney Injury↗

Noninvasive positive pressure ventilation via face mask. First-line intervention in patients with acute hypercapnic and hypoxemic respiratory failure.

OBJECTIVES: We have previously reported our experience with noninvasive positive pressure ventilation (NPPV) via face mask in a small group of selected patients with acute respiratory failure (ARF). NPPV was frequently effective (70% success rate) in correcting gas exchange abnormalities and in avoiding endotracheal intubation (ETI); NPPV also had a low rate of complications. We have evaluated the clinical application of NPPV as first-line intervention in patients with hypercapnic and short-term hypoxemic ARF. A dedicated respiratory therapist conducted an educational program with physicians-in-training rotating through the medical ICUs of a university medical center and supervised implementation of a simplified management protocol. Over 24 months, 164 patients with heterogeneous forms of ARF received NPPV. We report on the effectiveness of NPPV in correcting gas exchange abnormalities, in avoiding ETI, and associated complications, in different conditions precipitating ARF. PATIENT POPULATION: One hundred fifty-eight patients completed the study. Forty-one had hypoxemic ARF, 52 had hypercapnic ARF, 22 had hypercapnic acute respiratory insufficiency (ARI), 17 had other forms of ARF, and 26 with advanced illness had ARF and refused intubation. Twenty-five percent of the patients developed ARF after extubation. INTERVENTION: Mechanical ventilation was delivered via a face mask. Initial ventilatory settings were continuous positive airway pressure (CPAP) mode, 5 cm H2O, with pressure support ventilation of 10 to 20 cm H2O titrated to achieve a respiratory rate less than 25 breaths/min and an exhaled tidal volume of 7 mL/kg or more. Ventilator settings were adjusted following arterial blood gases (ABG) results. RESULTS: The mean duration of NPPV was 25 +/- 24 h. When the 26 patients with advanced illness are excluded, NPPV was effective in improving or correcting gas exchange abnormalities in 105 patients (80%) and avoiding ETI in 86 (65%). Failure to improve ABG values was the reason for ETI in 20 of 46 (43%). The overall average predicted and actual mortality were 32% and 16%, respectively. Survival was 93% in non-intubated patients and 79% in intubated patients. NPPV was effective in lessening dyspnea throughout treatment in all but seven patients. Complications developed in 24 patients (16%). In patients with hypercapnic ARF, nonresponders had a higher PaCO2 at entrance (91.5 +/- 4.2 vs 80 +/- 1.5; p < 0.01). In patients with hypercapnic ARF and ARI, arterial blood gases response (pH and PaCO2) within 2 h of NPPV predicted success (p < 0.0001). None of the entrance parameters predicted need for ETI. CONCLUSIONS: We conclude that application of NPPV in clinical practice is an effective and safe alternative to ETI in many hemodynamically stable patients with hypercapnic ARF and in those with hypoxemic ARF in whom the clinical condition can be readily reversed in 48 to 72 h. An educational and supervision program is essential to successfully implement this form of therapy.

Acute Disease↗

Morbidity and mortality of open lung biopsy in children.

OBJECTIVE: In patients with diffuse pulmonary infiltrates, when empiric therapy or less-invasive diagnostic procedures fail, physicians frequently resort to open lung biopsy (OLB) to provide a definite diagnosis and to help redirect therapeutic treatment. OLB is still widely regarded as a safe diagnostic procedure, even in the critically ill child. The objective of this study is to evaluate the accuracy of this view with regard to children with acute respiratory failure (ARF) and, for this purpose, compares the mortality and morbidity of such patients with those without ARF. DESIGN: Retrospective chart review. SETTING: University hospital. PATIENTS: Forty-two patients (mean age, 6.6 years) underwent 47 OLBs for undiagnosed diffuse pulmonary infiltrates between July 1984 and December 1994. Twenty-six patients (55%) were in ARF. Fifteen of these patients were intubated and receiving mechanical ventilatory support before the OLB procedure. RESULTS: The overall incidence of serious complications associated with the OLB procedure was 51%. Of the patients with ARF, 17 (65%) had at least one major complication compared with 3 (14%) of the patients without ARF. Pleural air complications (62% of the total) occurred only in patients with ARF: pneumothoraces and/or prolonged air leaks developed in 10 (38%) after their OLBs; 9 of these patients died, and 7 had pneumothorax complicating their chest tube removal, which required replacement chest tubes. All patients with ARF preoperatively required prolonged ventilatory support after the OLB procedure, whereas 90% of the patients without ARF could be extubated within 24 hours. Overall, 10 patients (24%) died after the OLB procedure. All deaths occurred in patients with ARF. Both ARF preoperatively and the presence of postoperative complications were significantly associated with decreased survival. CONCLUSIONS: The morbidity and mortality rates of children with ARF undergoing OLB for diffuse pulmonary infiltrates differ considerably from those of children without ARF. For children with ARF, OLB is associated with the risk of prolonged ventilatory support, recurrent pneumothoraces, and air leaks. These complications may be attributable to such patients' having diseased lungs with poor healing. Moreover, these complications may, in turn, contribute to the patients' poor outcomes.

Acute Disease↗

Validity of International Classification of Diseases, Ninth Revision, Clinical Modification Codes for Acute Renal Failure.

Administrative and claims databases may be useful for the study of acute renal failure (ARF) and ARF that requires dialysis (ARF-D), but the validity of the corresponding diagnosis and procedure codes is unknown. The performance characteristics of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes for ARF were assessed against serum creatinine-based definitions of ARF in 97,705 adult discharges from three Boston hospitals in 2004. For ARF-D, ICD-9-CM codes were compared with review of medical records in 150 patients with ARF-D and 150 control patients. As compared with a diagnostic standard of a 100% change in serum creatinine, ICD-9-CM codes for ARF had a sensitivity of 35.4%, specificity of 97.7%, positive predictive value of 47.9%, and negative predictive value of 96.1%. As compared with review of medical records, ICD-9-CM codes for ARF-D had positive predictive value of 94.0% and negative predictive value of 90.0%. It is concluded that administrative databases may be a powerful tool for the study of ARF, although the low sensitivity of ARF codes is an important caveat. The excellent performance characteristics of ICD-9-CM codes for ARF-D suggest that administrative data sets may be particularly well suited for research endeavors that involve patients with ARF-D.

Acute Kidney Injury↗

Impaired atrial natriuretic factor systemic clearance contributes to its higher levels in uremia.

To evaluate the interaction between plasma levels and the systemic uptake of atrial natriuretic factor (ANF) with thyroid hormone levels during acute renal failure (ARF), seven groups of rats were analyzed: Group 1, Controls (C); Group 2, ARF; Group 3, filtering kidney with uremia; Group 4, ARF with thyroxine (T4) supplement (ARF + T4); Group 5, thyroidectomy (Tx); Group 6, ARF on Tx rats (Tx + ARF); Group 7, Tx + ARF supplemented with T4 (Tx + ARF + T4). Plasma creatinine (Cr), urea, T4, blood volume, and ANF were measured; ANF half-life (ANF t1/2; expressed in seconds) was calculated. Rats with ARF developed uremia (Cr, 377 +/- 58 versus 41 +/- 5 mumol/L), significant reduction in T4 (40 +/- 4 versus 89.2 +/- 6 nmol/L). elevation of ANF (287.7 +/- 35 versus 60.9 +/- 8 fmol/mL), and lengthening of ANF t1/2 (69.7 +/- 8 versus 37.2 +/- 6 s) compared with C (P less than 0.01). T4 supplements to ARF rats resulted in a lesser degree of uremia (Cr, 283 +/- 27; P less than 0.05) and normalization of ANF t1/2 (31.4 +/- 5); however, ANF levels remained higher than C (100.4 +/- 11.4 versus 60.9 +/- 8; P less than 0.01). Tx by itself did not change either parameter. The filtering kidney with uremia group developed mild uremia (Cr, 199 +/- 8), T4 fell (58 +/- 8), ANF levels rose (83.4 +/- 5.4), and ANF t1/2 was prolonged (54.5 +/- 12). Tx before ARF doubled the ANF level and lengthened ANF t1/2 similarly than in ARF. T4 addition (Tx + ARF + T4) normalized ANF t1/2 (29.8 +/- 3) in spite of a persistently high ANF (145.7 +/- 21). Blood volume did not change in any group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Acute oliguric renal failure in hypoxic neonates born at full term].

INTRODUCTION: Acute renal failure (ARF) is a frequent clinical condition in neonatal intensive care units (NICU). The leading cause of neonatal ARF is perinatal asphyxia (PS). The aim of this study was to examine the relationship between the degree of PS and the severity of ARF in term neonates. METHODS: A prospective survey of 31 term neonates with Ps and but without congenital malformations or sepsis was performed in NICU of the regional Hospital of Gynaecology and Obstetrics in Belgrade (average number of deliveries about 6000 per year). ARF was diagnosed in the first 7 days of life when plasma creatinine was above 133 mumol/L for at least 48 hours while maternal renal function was normal. The degree of PS was determined according to Apgar score (AS) at 1 min. The severe PS was defined as AS < 3 and moderate PS as AS 4-6. RESULTS: Twenty neonates (64%) had oliguric ARF with urine output of 0.37 +/- 0.16 ml/kg/h while the others had nonoliguric ARF with urine output of 2.4 +/- 0.7 ml/kg/h. Most of neonates with oliguric ARF (65%) had severe perinatal asphyxia while in those with nonoliguric ARF moderate perinatal asphyxia predominated (73%). DISCUSSION: During hypoxic-ischaemic events many organs are injured, and the most vulnerable ones are kidneys and central nervous system. Our results showed a strong connection between perinatal asphyxia and A, which was in accordance with the results of other studies. Neonates with severe perinatal asphyxia had serious impairment of renal function, which was confirmed with strong correlation between Apgar score and plasma creatinine. In neonates with oliguric ARF, but not in those with nonliguric ARF, the highly positive linear correlations were found between AS and urinary output (r = 0.77; p < 0.01), plasma creatinine (r = 0.78; p < 0.01), fractional excretion of sodium (r = 0.76; p < 0.01), and index of renal failure (r = 0.80; p < 0.01). Only in oliguric neonates with severe perinatal asphyxia (31%) the outcome was fatal. CONCLUSION: We conclude that in tgerm neonates with severe perinatal asphyxia oliguric ARF was the predominant type of ARF. There is a good prediction of the severity of oliguric ARF according to the degree of perinatal asphyxia determined by Apgar score at 1 min.

Acute Kidney Injury↗

Acute renal failure in patients with severe civilian trauma.

We reviewed our experience with patients suffering from civilian trauma to identify risk factors for the development of acute renal failure (ARF) and ARF outcome. Of the 437 patients consecutively admitted to a surgical intensive care unit (SICU), 206 had a SICU stay of at least 1 day and ARF developed in 30 of these patients. All ARF patients had additional organ system failure (OSF). Pre-existing chronic disease (including chronic renal failure), malnutrition, injury severity score (ISS), number of organs injured, sepsis, and all OSFs before the onset of ARF were factors predisposing to ARF. Mortality was 40%. Chronic disease, malnutrition, ISS, failure of cardiovascular, pulmonary, hepatic, and neurological systems (either before and after ARF) were significantly associated with mortality. When OSFs were considered in their temporal relationships to ARF, only cardiovascular and pulmonary failure before, and gastrointestinal failure after, the onset of ARF were related to mortality. An increasing number of OSFs increased mortality, both before and after the development of ARF. However, the number of OSFs before was significantly greater than after ARF. Sepsis was not associated with increased mortality. Thus, the outcome of ARF patients with critical trauma seems to be dependent on factors predisposing to ARF. Our results suggest that more attention must be paid to prevention of these precipitating conditions.

Acute Kidney Injury↗

[Management of acute renal failure in hospital practice].

The incidence of ARF in pediatric population varies according to the definition of the syndrome. If the diagnosis is based on a decrease of glomerular filtration rate (GFR), possibly accompanied by a decrease of urinary output and the sudden change of renal function indexes, then the number of patients which can be considered affected by ARF in hospital practice is high, as it comprises all the cases with functional impairment of renal function. The availability of tables with normal values of serum creatinine for different gender and age and the knowledge of the minimal urine output compatible with the normality allows a precise diagnosis of ARF. The differential diagnosis of ARF must take into account prerenal, renal and postrenal causes. Prerenal and renal ARF may be sometimes difficult to differentiate. Indexes such as sodium fractional excretion, utilizing urinary to plasma ratios of sodium and creatinine, can be helpful: values less than 1 indicate prerenal ARF, more than 2 renal ARF. The management of ARF is dependent on the causes of ARF. Prerenal ARF is normally treated by measures of volume expansion and/or removal of the underlying cause. Renal ARF requires an accurate control of water and electrolyte balance and of nutritional status and the prevention or treatment of numerous complications, which may worsen the course of the syndrome. Indications to dialysis must be evaluated every day and an assessment of nutritional status performed. All the factors which may cause hypercatabolism, such as infections, hemorrhage, low calorie intake, must be recognized and treated. This approach allows a better control of serum urea, potassium, phosphate and acidosis. Nutrition must be implemented and an adequate protein and calorie intake must be obtained, through spontaneous oral route and, whenever required, enteral and parenteral nutrition. In conclusion, patients with mild-degree, mostly of prerenal origin, ARF represent a common finding in hospital practice. Identification and prompt treatment of the underlying cause is the best prevention of acute tubular necrosis. Patients with ARF of renal origin require, in particular, daily nutritional assessment and dietary treatment to delay the onset of dialysis.

Acute Kidney Injury↗

Acute renal failure after cadaveric related liver transplantation.

Acute renal failure (ARF) is a frequent medical complication after liver transplantation (LT). We analyzed cadaveric related liver transplant recipients who had developed ARF early in the postoperative course. Between January 1982 and August 2003, a total of 67 patients underwent cadaveric related LT. Their mean age was 28.64 years at LT. The 67 recipients had the following indications: biliary atresia (n = 17), Wilson's disease (n = 15), hepatitis B-related liver cirrhosis (n = 14), hepatitis C-related liver cirrhosis (n = 4), primary biliary cirrhosis (n = 4), hepatitis B-related liver cirrhosis with hepatoma (n = 3), hepatitis C-related liver cirrhosis with hepatoma (n = 2), Budd-Chiari syndrome (n = 2), neonatal hepatitis (n = 1), choledochus cyst (n = 1), autoimmune cirrhosis (n = 1), neuroendocrine tumor (n = 1), and hemangioendothelioma (n = 1). Forty-nine patients received cyclosporine (CsA), azathioprine, and steroids and 18, a combination with tacrolimus (FK506). Eight (11.94%) patients developed ARF at a mean time of 17.25 days after LT. The mean peak serum creatinine was 2.24 mg%. Four of these patients had a diagnosis of hepatitis B-related liver cirrhosis; two, hepatitis C-related liver cirrhosis; one, primary biliary cirrhosis; and one, hepatitis B-related liver cirrhosis with hepatoma. The ARF etiology was multifactorial for the majority of patients. Eight ARF patients had a history of liver cirrhosis, which may be a risk factor for intraoperative ARF. ARF treatment included fluid replacement, decreased or altered immunosuppressive agents, avoiding exposure to nephrotoxic drugs, and adjusting antibiotic dosages. The majority of patients returned to normal renal function at 1 to 3 weeks after the diagnosis of ARF. No patient required dialysis and/or experienced a mortality. We conclude that the incidence of ARF is relatively low and with good outcomes. ARF etiology was multifactorial for the majority of patients, but eight patients had a history of liver cirrhosis, which may be a risk factor for intraoperative ARF. We suggest that in the early postoperative period of LT cases diagnosis and treatment of ARF are important.

Acute Kidney Injury↗

Acute renal failure in severely burned patients.

Acute renal failure (ARF) is a well known complication of severe burns and is an important factor leading to an increase in mortality. In order to analyze possible pathogenetic and prognostic factors associated with ARF in burned patients we reviewed in a retrospective study the files of 328 patients with burns > 10% body surface area (BSA), admitted to our burn unit between 01.01.94 and 01.05.98. We found 48 patients with acute renal failure corresponding with an incidence of 14.6%. Patients with ARF had a mean burned surface area of 48% (13-95) and an abbreviated burn severity index score (ABSI) of 9.8 (4-15). Thirty eight (79%) of these patients had an inhalation injury diagnosed. Renal insufficiency was divided in a late and an early form depending on its time of onset and we found 15 (31%) patients with ARF occurring within the first 5 days of the hospital stay and 33 (69%) patients with ARF developing >5 days following the thermal injury. The incidence of myoglobinuria and hypotension during the resuscitation phase was significantly higher in the group with early ARF, whereas patients with late ARF presented sepsis more frequently than patients with early occurring renal failure. Accordingly, potential nephrotoxic antibiotics were administered more often in patients with late ARF. Patients with ARF were treated by continuous arteriovenous hemofiltration (CAVH) for a mean period of 10.5 days (1-47) and CAVH was associated with a complication rate of 10%. Most of the complications were associated with the vascular access in the femoral artery. The mortality rate in patients with ARF was 85% and death was due to multiple organ failure in 83% of the cases. Only burned BSA and inhalation injury proved to be significantly correlated with the development of ARF, whereas age, third degree burn or electric injury were not significantly different between the two groups. Neither age, TBSA, day of onset of ARF nor duration of the renal replacement therapy proved to be significantly different comparing survivors with non-survivors, and thus predictive for the survival rate.

Acute Kidney Injury↗

Increased endothelin 1 expression in adult-onset minimal change nephropathy with acute renal failure.

BACKGROUND: Acute renal failure (ARF) occurs in some adult patients with minimal change nephropathy (MCN). To investigate clinical and pathological factors associated with developing ARF, we compared clinical features and kidney pathological characteristics of endothelin 1 (ET-1) expression in patients with adult-onset MCN with and without ARF. METHODS: The patient population consisted of 53 patients consecutively diagnosed with adult-onset MCN during a 10-year period. Based on creatinine clearance, 25 patients were assigned to the ARF group and 28 patients were assigned to the non-ARF group. RESULTS: Clinical data show that the ARF group had a higher blood pressure, higher serum cholesterol level, and lower serum albumin level than the non-ARF group. Pathological data showed more severe foot-process effacement, interstitial edema, and flattened tubular epithelium in the same group. Greater ET-1 expression was detected in vessels, tubules, and glomeruli of the ARF compared with non-ARF group. The ARF group experienced a lower steroid response rate. However, there was no significant difference in stability of remission to steroid treatment in patients who achieved a remission. CONCLUSION: ARF associated with enhanced kidney ET-1 expression is a reversible complication of MCN that occurs frequently in patients with apparently expanded extracellular fluid. Presumptively, ARF may develop as an amplification of the underlying pathogenesis of MCN involved in enhanced ET-1 expression, which may be superimposed by a transient episode of circulatory insufficiency during diuretic treatment.

Acute Kidney Injury↗

Acute renal failure after cardiac surgery for carcinoid heart disease: incidence, risk factors, and prognosis.

BACKGROUND: Cardiac surgery for carcinoid heart disease may be associated with acute renal failure (ARF) and multiorgan dysfunction postoperatively. This study was performed to determine the incidence, risk factors, and prognosis of ARF after cardiac surgery for carcinoid heart disease. METHODS: This is a case-control study of 86 consecutive patients who underwent cardiac surgery for carcinoid heart disease. ARF is defined as hemodialysis requirement or serum creatinine level 50% greater than baseline, resulting in an estimated creatinine clearance less than 40 mL/min (0.67 mL/s). Preoperative, operative, and postoperative characteristics were examined and compared between groups to determine risk factors and prognosis of ARF. RESULTS: ARF occurred in 22% of cases (19 of 86 patients). Preoperative characteristics and type of procedure did not differ between groups. Operative variables associated with ARF by means of univariate analysis included longer surgical and bypass times, intra-aortic balloon pump use, and perioperative epinephrine requirement. Postoperatively, ARF was associated with epinephrine use, prolonged mechanical ventilation, prolonged intensive care unit admission, and higher Acute Physiology and Chronic Health Evaluation II scores. Perioperative mortality in the ARF group was 47% versus 4.5% in the control group (odds ratio, 36.1; 95% confidence interval, 8.0 to 261.8). CONCLUSION: ARF developed in a relatively high proportion of this cohort, but traditional preoperative risks failed to predict post-cardiac surgery ARF. Variables closely related to perioperative hemodynamic compromise were associated with ARF. ARF portends a particularly poor prognosis in this cohort that is explained largely by multiorgan failure syndrome.

APACHE↗

Phosphoinositide-dependent activation of the ADP-ribosylation factor GTPase-activating protein ASAP1. Evidence for the pleckstrin homology domain functioning as an allosteric site.

The ADP-ribosylation factor (Arf) family of GTP-binding proteins are regulators of membrane traffic and the actin cytoskeleton. Both negative and positive regulators of Arf, the centaurin beta family of Arf GTPase-activating proteins (GAPs) and Arf guanine nucleotide exchange factors, contain pleckstrin homology (PH) domains and are activated by phosphoinositides. To understand how the activities are coordinated, we have examined the role of phosphoinositide binding for Arf GAP function using ASAP1/centaurin beta4 as a model. In contrast to Arf exchange factors, phosphatidylinositol 4, 5-bisphosphate (PtdIns-4,5-P(2)) specifically activated Arf GAP. D3 phosphorylated phosphoinositides were less effective. Activation involved PtdIns-4,5-P(2) binding to the PH domain; however, in contrast to the Arf exchange factors and contrary to predictions based on the current paradigm for PH domains as independently functioning recruitment signals, we found the following: (i) the PH domain was dispensable for targeting to PDGF-induced ruffles; (ii) activation and recruitment could be uncoupled; (iii) the PH domain was necessary for activity even in the absence of phospholipids; and (iv) the Arf GAP domain influenced localization and lipid binding of the PH domain. Furthermore, PtdIns-4,5-P(2) binding to the PH domain caused a conformational change in the Arf GAP domain detected by limited proteolysis. Thus, these data demonstrate that PH domains can function as allosteric sites. In addition, differences from the published properties of the Arf exchange factors suggest a model in which feedforward and feedback loops involving lipid metabolites coordinate GTP binding and hydrolysis by Arf.

ADP-Ribosylation Factors↗

Acute renal failure in pregnancy in a developing country: twenty years of experience.

UNLABELLED: Acute renal failure (ARF) has become a rare complication of pregnancy in developed countries. The aim of this study was to describe changing trends in pregnancy-related acute renal failure (PR-ARF) in two successive periods; 1982-1991 and 1992-2002. From July 1982 to December 2002, 190 cases of PR-ARF were observed in Eastern India (11.6% of total number of ARF needing dialysis). Obstetrical complications were causative factors for ARF in 15% (65/426) and 10% (125/1201) of patients in the two periods, respectively. The incidence of PR-ARF fell from 15% in 1982-1991 to 10% in 1992-2002, with respect to the total number of acute renal failure cases. Post-abortal ARF showed a declining trend, 9% in the 1980s to 7% in the 2000s, of the total number of ARF cases. Preeclampsia-eclampsia was the cause of obstetrical ARF in 23% (1982-1991) and 14.4% (1992-2002) of cases in these two periods. The percentage of total ARF due to eclampsia declined from 3.5% during the period 1982-1991 to 1.4% in 1992-2002. Puerperal sepsis contributed to 0.8% of total ARF in recent years, compared to 2.4% in the earlier period. The incidence of cortical necrosis decreased significantly (p < 0.001) from 17% in 1982-1991 to 2.4% in the 2000s. The maternal mortality reduced to 6.4% in 1992-2002 from initial high mortality of 20% in the period of 1982-1991. CONCLUSION: PR-ARF which remained high in the initial period has decreased in recent years. This is associated with a declining trend in

Abortion, Induced↗

Functional genomic analysis of the ADP-ribosylation factor family of GTPases: phylogeny among diverse eukaryotes and function in C. elegans.

ADP-ribosylation factor (Arf) and Arf-like (Arl) proteins are a family of highly conserved 21 kDa GTPases that emerged early in the evolution of eukaryotes. These proteins serve regulatory roles in vesicular traffic, lipid metabolism, microtubule dynamics, development, and likely other cellular processes. We found evidence for the presence of 6 Arf family members in the protist Giardia lamblia and 22 members in mammals. A phylogenetic analysis was performed to delineate the evolutionary relationships among Arf family members and to attempt to organize them by both their evolutionary origins and functions in cells and/or organisms. The approximately 100 protein sequences analyzed from animals, fungi, plants, and protists clustered into 11 groups, including Arfs, nine Arls, and Sar proteins. To begin functional analyses of the family in a metazoan model organism, we examined roles for all three C. elegans Arfs (Arf-1, Arf-3, and Arf-6) and three Arls (Arl-1, Arl-2, and Arl-3) by use of RNA-mediated interference (RNAi). Injection of double-stranded RNA (dsRNA) encoding Arf-1 or Arf-3 into N2 hermaphrodites produced embryonic lethality in their offspring and, later, sterility in the injected animals themselves. Injection of Arl-2 dsRNA resulted in a disorganized germline and sterility in early offspring, with later offspring exhibiting an early embryonic arrest. Thus, of the six Arf family members examined in C. elegans, at least three are required for embryogenesis. These data represent the first analysis of the role(s) of multiple members of this family in the development of a multicellular organism.

ADP-Ribosylation Factors↗

Retrospective analysis on Chinese patients diagnosed with acute renal failure hospitalized during the last decade (1994-2003).

OBJECTIVES: To investigate the epidemiology, diagnosis and prognosis of acute renal failure (ARF) in hospitalized Chinese during the last decade. METHODS: The diagnosis of patients with ARF in Peking University Third Hospital from January 1994 to December 2003 was reconfirmed and the data of epidemiology, etiology and prognosis were analyzed. RESULTS: Only 209 discharged cases were diagnosed with ARF and all were reconfirmed. Two peak occurrences were found at ages of 35-45 and 60-80 with a male predominance of approximately 59.7%. Patients diagnosed with ARF accounted for 1.19 per thousand of the admissions in the same period and increased significantly in the last 5 years (p = 0.038). The creatinine level at diagnosis was 345.8 +/- 122.6 micromol/l and had no significant change (p > 0.05). The percent of hospital-acquired ARF (HA-ARF) demonstrated a significant increase in 1999-2003 compared to 1994-1998 (p = 0.008). Intrarenal ARF accounted for 73.69% and was multifactorial, with drugs, infections and operations as leading causes. Renal biopsy was performed in 37.32% (78/209) with 53.84% (42/78) having acute interstitial nephritis. Maintenance dialysis was discontinued in 46.41% because their renal function completely or partially recovered. The overall mortality was 37.91% without improvement over time. The mortality was 6.25% for patients in nephrology department, but 65.51% in ICU (p < 0.001), and was 21.6% for patients in community-acquired ARF (CA-ARF), but 63.1% in HA-ARF (p < 0.001). CONCLUSIONS: During the past 10 years, the number of patients diagnosed with ARF has been rising in hospitalized Chinese. HA-ARF was the major source, and infections, drugs and operations were the leading causes. The diagnosis and prognosis of acute renal failure did not improve much in this population over the decade studied.

Acute Kidney Injury↗

Role of creatine phosphokinase in predicting acute renal failure in hypocalcemic exertional heat stroke.

Recruits frequently develop hypocalcemia in exertional heat stroke (ExHS) with rhabdomyolysis and acute renal failure (ARF) from intensive training. It usually indicated severe skeletal muscle damage. However, the relative risk of ARF in ExHS patients complicated with hypocalcemia was unknown. The present study was undertaken to evaluate the value of peak serum creatine phosphokinase (CPK) level in predicting ARF in ExHS patients with hypocalcemia. Sixty-eight army recruits with ExHS were hospitalized at the Tri-Service General Hospital, Taiwan: 17 with ARF and hypocalcemia (group A); 7 with ARF but without hypocalcemia (group B); 20 without ARF but with hypocalcemia (group C); and 24 without ARF or hypocalcemia (group D). In the 24 patients with ARF (groups A and B) the serum phosphate and peak CPK levels were significantly higher than in patients without ARF (groups C and D; p < 0.001), serum calcium levels were also significantly lower in the former (p < 0.001). In the 37 patients with hypocalcemia (groups A and C), the peak serum CPK levels were significantly higher than in those without hypocalcemia (groups B and D; p < 0.001). There was a higher proportion of hypocalcemic patients with peak serum CPK levels greater than 10,000 U/l among ARF compared with patients without ARF (chi 2 = 12.48, p < 0.001). In 24 patients with ARF, there was a negative correlation between serum Ca and peak CPK levels (t = 3.37, r = -0.58, p < 0.01). However, a positive correlation was found between serum creatinine and peak serum CPK levels in 37 patients with hypocalcemia (t = 2.47, r = 0.39, p < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗

Renal handling of phosphorus in oliguric and nonoliguric mercury-induced acute renal failure in rats.

The renal handling of phosphorus was evaluated in rats with acute renal failure (ARF) induced by injection of mercuric chloride (HgCl(2)). Clearances of endogenous creatinine (Ccr) and of phosphorus (Cp) were measured in the following groups: 1. Intact animals (control); 2. Parathyroidectomized rats (PTX) with normal kidney function (PTX control); 3. Animals with mercury-induced acute renal failure (Hg-ARF); 4. PTX rats with Hg-ARF; 5. Rats with Hg-ARF maintained normophosphatemic with dietary phosphate restriction; 6. Animals with oliguric ARF following renal artery constriction; 7. Rats with unilateral Hg-ARF. In addition, radioinulin clearances were measured in 6 normal and in 14 azotemic animals and correlated with simultaneously recorded endogenous Ccr. Radioinulin clearance was also used as an estimate of GFR (glomerular filtration rate) in the animals of group 7. The Cp/GFR in the intact animals (group 1) was 0.25 +/-0.06 (mean +/-SD). PTX (group 2) caused a subsequent decrease in Cp/GFR to 0.11 +/-0.04 P < 0.0005. The ARF animals in group 3 were classified either as oliguric (U(vol) [urine volume] <2 ml/24 hr, Ccr 0.008 +/-0.005 ml/min) or nonoliguric (V(vol) >2 ml/24 hr, Ccr 0.136 +/-0.12). The Cp/GFR in the oliguric animals (0.16 +/-0.09) was lower than that in group 1, P < 0.0005, and failed to increase following administration of exogenous parathyroid hormone. The Cp/GFR in the oliguric animals in groups 5 and 7 was also lower than the clearance ratio in group 1, 0.030 +/-0.08 and 0.077 +/-0.006, respectively. In the nonoliguric ARF animals of group 3 the Cp/GFR (0.94 +/-0.29) was higher than that in group 1, P < 0.0005. In the nonoliguric ARF animals of group 4 the Cp/GFR 0.27 +/-0.08 did not differ from the clearance ratio in group 1, however it was higher than that in the PTX animals (group 2) P < 0.0005. Cp/GFR in the nonoliguric animals of group 5 was not different from that in the nonoliguric rats of group 3. In the animals with nonoliguric unilateral Hg-ARF Cp/GFR on the affected side 0.51 +/-0.16 was higher than that on the control (contralateral) side, 0.23 +/-0.07, P < 0.0005. These results indicate that the low Cp/GFR observed in the oliguric ARF animals was not related to the level of circulating parathyroid hormone nor to the presence or absence of azotemia but probably was due to a reduced renal cortical perfusion. The high Cp/GFR in the nonoliguric ARF animals could be explained by secondary hyperparathyroidism and impaired phosphorus reabsorption due to tubular injury.

Absorption↗