Elevated Creatinine Concentration Research Articles

The Informative Value of N-Terminal Pro-type B Natriuretic Peptide in Cardiac Surgical Patients with Hypercreatininemia

Objective: to study the informative value of a dramatic increase in the preoperative blood level of the inactive moiety of the precursor of N-terminal pro-type B natriuretic peptide (NT-proBNP) in cardiac surgical patients with hypercreatininemia. Subjects and materials. Twenty-one patients with a preoperative NT-proBNP level of 1000 pg/ml or more, who underwent myocardial revascularization under extracorporeal circulation (ECC), were examined. The patients were divided into groups with normal (up to 120 ^mol/l) (Group 1; n=11) and elevated (Group 2; n=10) creatinine concentrations. The values of circulation were processed after skin incision and at the end of surgery. The clinical features of a perioperative period were analyzed. Results. Creatininemia was 103±3.3 and 183±12.9 ^mol/l in Groups 1 and 2, respectively (p 0.05). There were no intergroup differences in intraoperative circulatory parameters. The intensity of sympatomimetic therapy after ECC was equal in the identified patient groups and there were either no differences (p>0.05) in the frequency of intra-aortic balloon counterpulsation (18.2 and 10.0%), the length of mechanical ventilation (15±1.5 and 18.7±2.3 hours) and intensive care unit stay (1.8±0.5 and 2.0±0.7 days) in survivors, and inpatient mortality (23.7 and 20.0%) that proved to be substantially higher than the EuroSCORE-predicted one. Regression analysis showed that in the entire group of operated patients, the level of NT-proBNP turned out to be a more significant predictor of inpatient mortality (p=0.012) than EuroSCORE-predicted one (p = 0.04). The similar regularity was characteristic for patients with hypercreatininemia. In the patients with hypercholesterolemia, the EuroSCORE-predicted mortality completely lost its significance (p=0.61) in predicting actual mortality rates. In this group, NT-proBNP showed a predicting trend. Conclusion. The blood NT-proBNP concentration of 1000 pg/ml or more preserves its significance as a high operative risk factor in the presence of myocardial revascularization under ECC in patients with the blood creatinine level of 140—270 ^mol/l. Key words: N-terminal pro-type B natriuretic peptide (NT-proBNP), myocardial revascularization, extracorporeal circulation, hypercreatininemia.

Traumatic urothorax in a dog: a case report

Pleural effusion caused by post-traumatic extravasation of urine from the abdominal cavity to the pleural cavity (urothorax) is an uncommon complication following traumatic injury. To the authors' knowledge, this is the first report of a case of traumatic urothorax in a dog presented with pleural and abdominal urine effusion. Combined urothorax and uroabdomen should be included in the differential-diagnosis list for dogs with recent trauma and a bicavitary effusion. The diagnosis can be confirmed by elevated creatinine concentrations in both effusates, compared to its serum concentration.

The Effects of a Probiotic on Blood Urea Nitrogen and Creatinine Concentrations in Large Felids

Chronic kidney disease is a common finding in older captive exotic felids. The purpose of this study was to evaluate the effectiveness of a probiotic to reduce blood urea nitrogen and creatinine in large felids. Fifteen adult, large felids (6 tigers [Panthera tigris], 5 lions [Panthera leo], 3 cougars [Puma concolor], and 1 leopard [Panthera pardus]) were administered a probiotic twice daily after a baseline complete blood cell count and plasma chemistry panel was obtained. Plasma chemistry values were rechecked at 2 mo (n = 14) and 6 mo (n = 9). There was no significant change in blood urea nitrogen over time; however, there was a significant change in creatinine over time (P = 0.04). Creatinine concentration decreased significantly between 2 and 6 mo (P = 0.02), and a decrease was seen between 0 and 6 mo, but this change was not significant (P = 0.05). There was no significant difference noted for creatinine concentration between 0 and 2 mo (P = 0.35). This probiotic may be helpful in large felids with elevated creatinine concentrations because of chronic kidney disease; however, further studies are warranted.

Increased Prevalence of Reduced Estimated Glomerular Filtration Rate in Chronic Hepatitis C Patients

To investigate the prevalence and severity of reduced estimated glomerular filtration rate (eGFR) in patients with chronic hepatitis C (CHC). Medical record review of 831 consecutive CHC patients seen in our clinic between July 2000 and August 2003; eGFR was estimated using the abbreviated Modification of Diet in Renal Disease (aMDRD) equation. The stage of kidney disease was determined based on eGFR expressed in milliliters per minute per 1.73 m(2): stage 1 (signs of kidney damage but normal or elevated (eGFR >or= 90), stage 2 (eGFR 60-89), stage 3 (30-59), stage 4 (eGFR 15-29), stage 5 (eGFR < 15 or dialysis-dependent). A total of 522 patients had available data with using the aMDRD equation, 51% had abnormal eGFR (stage 1, 4.6%; stage 2, 36.4%; stage 3 or 4, 6.1%; stage 5, 3.8%). Of 190 patients with stage 2 kidney disease, 189 patients (99.5%) had normal serum creatinine and only one patient (0.5%) had elevated creatinine concentrations (>1.4 mg/dl). Of the 32 patients with stage 3 or 4 disease, 20 (62.5%) had a normal serum creatinine concentration. Of 349 patients without diseases known to cause renal insufficiency, 38% had stage 2-4 renal disease. In a subset of these patients, 95/522 (18%) the measured creatinine clearance showed good correlation with their aMDRD (R = 0.47, (p < 0.0001). In CHC patients, a normal serum creatinine concentration does not assure normal kidney function. Estimation of eGFR with the aMDRD equation is a more accurate method of identifying patients with chronic kidney disease and reduced eGFR. Therefore, CHC patients should be screened more rigorously for chronic kidney disease because of the high prevalence of reduced eGFR. Lastly, in all CHC patients, the aMDRD eGFR should be used in each encounter with these patients when assessing their renal function irrespective of their serum creatinine.

Treatment of Deep Vein Thrombosis in the Pelvis and Leg: Severe Renal Insufficiency

The molecular-weight-dependent risk of accumulation of low-molecular-weight heparins (LMWH) in the setting of renal failure is widely accepted. Unfortunately, the attribution of diagram 2 was omitted (from the work of S. Alban). Fondaparinux is discussed in the article as if it were comparable to enoxaparin; one must realize, however, that the cited study by Buller et al. (1) excluded patients with an elevated creatinine concentration – yet it is precisely these patients who so often present for treatment, among others, in everyday practice. A look at the information for physicians with regard to fondaparinux reveals that even moderate degree of renal insufficiency led to hemorrhagic complications in 6.6% of patients, while severe renal insufficiency did so in 14.5%. The figures for enoxaparin are similar; this clearly indicates that low molecular weight, renal function, and hemorrhagic tendency are closely associated with one another. Fondaparinux is absolutely contraindicated in patients with severe renal insufficiency. For enoxaparin, an adjustment of the dose is recommended, yet treating physicians often will not even know whether renal insufficiency is present, let alone how severe it is. Protamine is available as an antidote for low-molecular-weight heparins, but no such antidote is available for fondaparinux. In view of these facts, I think it is rather bold to call fondaparinux a good to heparins. At most, one can say that it might be an alternative if there is reason why low-molecular-weight heparins cannot or should not be given.

Effects of Aprotinin Dosage on Renal Function

The nonspecific serine protease inhibitor aprotinin is widely used in cardiac surgery to limit bleeding. Recently, concerns about the safety of this drug were raised, especially regarding impaired renal outcome. This event rate was supposed to be dose dependent. In this observational study, the authors analyzed prospectively collected data of a single-center cardiac-anesthetic database. Adult patients treated with various dosages of aprotinin were evaluated. Logistic regression analysis identified independent predictors of renal outcome. The primary endpoint was a composite of novel postoperative renal failure requiring hemodialysis, an increased postoperative creatinine plasma concentration of 2 mg/dl or greater, or a difference between maximal postoperative and preoperative plasma creatinine of 0.7 mg/dl or greater. The study analyzed 8,548 patients. Multiple logistic regression (c index = 0.861) did not show a significant association between aprotinin dosage and renal outcome, as did the bootstrap procedure (odds ratio, 0.98; confidence interval, 0.90-1.07). The most relevant predictor was a preoperatively elevated creatinine concentration (odds ratio, 11.4; confidence interval, 9.05-14.3). Patients with postoperative renal impairment or failure were at higher preoperative risk and/or underwent more complex procedures. In subgroups of patients with preoperatively impaired renal function (creatinine > or =1.5 mg/dl) (n = 1,075), complex procedures (n = 1,920), or insulin-dependent diabetes (n = 650) or patients undergoing isolated myocardial revascularization (n = 4,901), no association between aprotinin dosage and adverse renal outcome was observed. In the current analysis, aprotinin dosage was not associated with increased adverse renal outcome. In regard to renal outcome, this analysis did not demonstrate an essential detrimental influence of aprotinin dosage on renal function.

Sinusoidal Occlusion Syndrome Following Exposure to Gemtuzumab: Unsuccessful Treatment with Defibrotide

Purpose: Sinusoidal occlusion syndrome (SOS) is a rare, life-threatening disorder characterized by abdominal distention, weight gain, tender hepatomegaly, ascites, and elevated aspartate aminotransferase (AST) and creatinine (Cr) concentrations. Ultrasonography (US) demonstrates patent portal and hepatic venous circulations. SOS arises most commonly in the setting of bone marrow transplantation (BMT). Gemtuzumab, an anti-CD33 monoclonal antibody, is a new agent for the management of relapsed acute myeloid leukemia (AML). Abnormal liver tests occur in 1/3 of gemtuzumab-treated patients, but only 1–2% have documented SOS. A 24 year-old man, diagnosed with AML 13 months after receiving chemotherapy for a mediastinal germ cell malignancy failed to respond to initial protocol chemotherapy with amonafide, cytarabine and mitoxantrone. Salvage chemotherapy with gemtuzumab was initiated in standard dose and schedule. Five days after first exposure to gemtuzumab the patient began gaining weight, and by day 9 his weight gain was 4 kg. His abdomen was distended and uncomfortable, and he required oxygen for dyspnea. Laboratory studies were as follows: AST 6733 IU/L (normal range [NR]: 10–60), alkaline phosphatase 162 IU/L (NR: 30–135), prothrombin time 17.7 s (NR: 11.1–13), total bilirubin 1.9 mg% (NR: 0.2–1.2) and Cr 5.9 mg% (NR: 0.4–1.4). US scan confirmed the presence of splenomegaly and ascites; the hepatic and portal vein branches were patent. However, the direction of flow in the latter was reversed. Both the vena cava and hepatic artery were patent. Relevant acute viral, metabolic and immune forms of liver disease were excluded on the basis of appropriate serologic studies. Given the symptom complex, compassionate approval was sought for use of the non FDA-approved drug, defibrotide. However, despite this intervention, continuous veno-veno hemodialysis, and further antimicrobial therapy, the patient developed acute liver failure and died 26 days after first gemtuzumab exposure. This man's clinical, laboratory and US findings met diagnostic criteria for SOS. While experience with SOS in the BMT setting is well recorded, other etiologies are rarely recorded. This patient's clinical course was virtually diagnostic of gemtuzumab-induced SOS. Although use of defibrotide has been reported to improve 1/3 of patients having SOS in the BMT setting, experience among patients with SOS after gemtuzumab therapy is very limited.

Creatinine Elevation Associated with Nitromethane Exposure: A Marker of Potential Methanol Toxicity

Nitromethane, methanol, and oil are the common components of radio-controlled (R/C) vehicle fuels. Nitromethane can cause a false elevation of serum creatinine concentration as measured by the widely used Jaffe colorimetric method. We gathered data from our poison control system and from previously published case reports to see if a correlation exists between serum methanol concentrations and spuriously elevated serum creatinine concentrations after human exposures to R/C fuel. The California Poison Control System (CPCS) computerized database was queried for all cases of human exposure to R/C vehicle fuel reported between December 1, 2002 and December 1, 2004. Serum creatinine and methanol concentrations were recorded when available, as was the method used to determine serum creatinine. A MEDLINE search was used to obtain previously published cases of human nitromethane exposure associated with falsely elevated creatinine concentrations. During the 2-year period, serum creatinine concentrations were recorded in 7 of 26 R/C fuel exposures (all ingestions), and 6 of these were abnormal (range of 1.9–11.5 mg/dL). In this series, the higher the serum creatinine concentration measured by Jaffe method, the higher the serum methanol concentration. The MEDLINE search yielded data from six previously published case reports on this topic. The data from these case reports seem to follow the trend seen in our case series. These data suggest that a spuriously elevated serum creatinine (by Jaffe method) may have value as an early surrogate marker of methanol poisoning in those who ingest R/C fuel. Also, the degree to which the serum creatinine is elevated may indicate the severity of methanol poisoning.

Krankenhausletalität der akuten Ösophagus-/Fundusvarizenblutung: Eine Analyse des Aufnahmeblutzuckers und weiterer Faktoren bei 99 Patienten

The analysis of risk factors in acute variceal bleeding may help to optimize patient management. The influence of hyperglycemia, which has been demonstrated for different diseases in the intensive care unit, has not been investigated for acute variceal bleeding. We reviewed a consecutive series of 99 patients with acute variceal bleeding treated in our clinic between 1996 and 2005. Possible risk factors leading to death during the hospital stay were analysed. The in-hospital mortality was increased in patients with a raised Child-Pugh index of cirrhosis, active bleeding during emergency endoscopy and an elevated creatinine concentration. The baseline blood glucose value was of no prognostic value. Even in the current management of variceal bleeding the Child-Pugh index for cirrhosis as well as and active bleeding during emergency endoscopy remain decisive factors in the short-term prognosis. In contrast to other diseases occurring in the intensive care unit, hyperglycemia or insulin resistance plays no significant role.

A randomized controlled trial comparing hydration therapy to additional hemodialysis or N-acetylcysteine for the prevention of contrast medium-induced nephropathy

Contrast medium-induced nephropathy (CIN) is a serious complication with increasing frequency and an unfavorable prognosis. Previous analyses of surrogate parameters have suggested beneficial effects of hemodialysis that are assessed in this randomized clinical trial. We performed a prospective single-center trial in 424 consecutive patients with serum creatinine concentrations between 1.3- 3.5 mg/dl who underwent elective coronary angiography. Patients were randomized to one of three treatment strategies with all patients receiving pre- and postprocedural hydration: One group received no additional therapy, patients in the second group were hemodialyzed once, and the third group received oral N-acetylcysteine. The frequency of CIN (defined as an increase in serum creatinine>or=0.5 mg/dl) from 48 to 72 h after catheterization was 6.1% in the hydration-only group, 15.9% with hemodialysis treatment, and 5.3% in the N-ACC group (intention-to-treat analysis; P=0.008). There were no differences between the treatment groups with regard to increased (>or=0.5 mg/dl) serum creatinine concentrations after 30-60 days (4.8%, 5.1%, and 3.1%, respectively; P=0.700). Analyses of long-term follow-up (range 63 to 1316 days) by Cox regressions models of the study groups found quite similar survival rates (P=0.500). In contrast to other (retrospective) studies, long-term survival of patients with vs those without CIN within 72 h was not different, but patients who still had elevated creatinine concentrations at 30-60 days suffered from a markedly higher 2-year mortality (46% vs 17%, P=0.002). In conclusion, hemodialysis in addition to hydration therapy for the prevention of CIN provided no evidence for any outcome benefit but evidence for probable harm. Increased creatinine concentrations at 30-60 days, but not within 72 h, were associated with markedly reduced long-term survival.

Variables Associated with Outcome in Dogs Undergoing Extrahepatic Biliary Surgery: 60 Cases (1988–2002)

To report clinical findings and define clinical variables associated with outcome in dogs undergoing extrahepatic biliary surgery. Retrospective study. Sixty dogs that had extrahepatic biliary tract surgery. Primary diagnoses included necrotizing cholecystitis (36 dogs, 60%), pancreatitis (12 dogs, 20%), neoplasia (5 dogs, 8%), trauma (4 dogs, 7%), and gallbladder rupture from cholelithiasis without necrotizing cholecystitis (3 dogs, 5%). Bile peritonitis occurred in 19 (53%) dogs with necrotizing cholecystitis, 4 dogs with trauma, and 3 dogs with cholelithiasis without evidence of necrotizing cholecystitis. Cholecystectomy (37 dogs, 62%) and cholecystoduodenostomy (14 dogs, 23%) were the 2 most commonly performed procedures. Median hospitalization for survivors was 5 days (range, 1-15 days). There were 43 surviving dogs (72%) and 17 nonsurvivors (28%, 4 died, 13 euthanatized). Presence of septic bile peritonitis (P=.038), elevation in serum creatinine concentration (P=.003), prolonged partial thromboplastin times (PTTs; P=.003), and lower postoperative mean arterial pressures (P=.0001) were significantly associated with mortality. Extrahepatic biliary surgery is associated with high mortality and a relatively long hospitalization time for survivors. Cholecystectomy and cholecystoduodenostomy were the most common surgical procedures to treat the 4 major biliary problems (necrotizing cholecystitis, pancreatitis, neoplasia, and trauma) observed in this cohort of dogs. The relatively high mortality rate likely reflects the underlying diseases and their effects on the animal (septic bile peritonitis, higher serum creatinine, prolonged PTT, and lower postoperative mean arterial pressure) rather than complications of surgery. Septic bile peritonitis, preoperative elevated creatinine concentration, and immediate postoperative hypotension in dogs undergoing extrahepatic biliary tract surgery are associated with a poor clinical outcome. Adequate supportive care and monitoring in the perioperative period is critical to improve survival of dogs with extrahepatic biliary disease.

Patterns of bleeding after endoscopic sphincterotomy, the subsequent risk of bleeding, and the role of epinephrine injection.

The patterns of bleeding following endoscopic sphincterotomy (ES) and their predictive value for subsequent bleeding are poorly understood. Similarly, the efficacy and side effects of epinephrine (E) injection for persistent bleeding have not been well studied. Over a 44-month period, all patients undergoing ES were prospectively assessed and followed-up. The character of bleeding (pulsatile, oozing, trickle, none) was recorded immediately, 5 minutes following ES and at the completion of the procedure. Patients with persistent bleeding at the time the procedure was completed (5 minutes or greater) received E injection(s) (1:10,000 concentrations) into the bleeding point with a sclerotherapy needle. ES was performed in all patients with a single electrosurgical generator Valleylab (Force 1B) using pure cutting current. 506 patients (68% females, mean age 54 years) who underwent 550 ES were studied. Bleeding patterns immediately following ES were: 6% pulsatile, 42% oozing, 27% trickle, and 24% none. E (median 0.5 cc; range 0.5-4 cc total) was injected during 79 procedures (14%); none of these patients had complications nor delayed bleeding. For all patients, delayed bleeding occurred in 8 (1.6%, 95% CI 0.57-0.0269); of these 8 delayed bleeders, 1 had no bleeding after ES, and only 1 had any bleeding at 5 minutes. The only variable associated with bleeding after ES was abnormal labs (thrombocytopenia, elevated creatinine concentration, hypoprothrombinemia). The pattern of bleeding following ES may not predict the risk of late bleeding. Abnormal labs are associated with visible bleeding. Epinephrine injection is safe and appears to provide effective hemostasis.

Opportunities for improving the care of patients with chronic renal insufficiency: current practice patterns.

There are between 2 and 13 million Americans with chronic kidney disease (CKD). Recent reports suggest that their treatment is currently suboptimal. To further investigate this issue, patterns of practice for the treatment of patients with CKD who were enrolled in a large health maintenance organization in New Mexico were analyzed. Among the >200,000 patients who were enrolled in the health maintenance organization between 1994 and 1997, a cohort of 1658 patients who exhibited at least two gender-specific, elevated creatinine concentrations (Cr), separated by at least 90 d, were identified. The proportions of patients with Cr values of <2.0, 2.0 to 2.9, 3.0 to 3.9, and > or =4.0 mg/dl were 73, 17, 3, and 7%, respectively. The majority of patients were treated by a primary care physician until Cr values reached 3.0 mg/dl, at which time a nephrologist was consulted. Care tended to be transferred to the nephrologist when the Cr reached 4.0 mg/dl. Only 7.4% of patients received erythropoietin (EPO). Use of EPO increased as Cr increased. EPO was unlikely to be prescribed unless the patient had visited a nephrologist. Fewer than one half of all patients with CKD and fewer than 20% of patients with CKD with Cr values of > or =4.0 mg/dl received an angiotensin-converting enzyme inhibitor (ACEI). Nephrologists were not more likely to prescribe ACEI than were primary care physicians. Diabetic patients were more likely to receive ACEI than were nondiabetic patients, but ACEI use was quite low even among diabetic patients with CKD. The average number of hospitalizations per patient-year increased as Cr increased and was more than twice as high for patients with Cr values of > or =4.0 mg/dl, compared with those with Cr values of <2.0 mg/dl. The reasons for hospitalization were more likely to be related to comorbidities than to CKD itself, however. There are many opportunities to improve the care of patients with CKD. Better adherence to practices known to be of clinical benefit for patients with CKD not only will improve patient outcomes but also may reduce the costs of care. Providers, policy-makers, and payers should view CKD as a major public health problem and initiate innovative programs to address this growing patient population.

Vitamin D deficiency among older women with and without disability

Vitamin D deficiency is associated with bone loss and bone fractures, and the identification of vulnerable populations is important to clinical practice and public health. The objectives of this study were to determine the prevalence of vitamin D deficiency and to examine associated risk factors for vitamin D deficiency in older women. We measured serum concentrations of 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1, 25(OH)(2)D], intact parathyroid hormone (PTH), osteocalcin, and ionized calcium in women aged >/=65 y who were participating in the Women's Health and Aging Study I, an observational study of women representing the approximately one-third most disabled women living in the community, and women aged 70-80 y who were participating in the Women's Health and Aging Study II, an observational study of women among the two-thirds least disabled women living in the community in Baltimore. The women were classified into 4 domains of physical disability. Among 371 women with 0 or 1 domain of disability and 682 women with >/=2 domains of disability, 6.2% and 12.6%, respectively, had vitamin D deficiency [serum concentrations of 25(OH)D < 25 nmol/L]. In univariate analyses, risk factors for vitamin D deficiency included increasing age, black race, low educational level, high body mass index, high triceps skinfold thickness, increasing level of disability, winter season, and elevated creatinine concentration. In multivariate models, black race had a strong association with vitamin D deficiency when other risk factors were adjusted for. Vitamin D deficiency, a preventable disorder, is a common and important public health problem for older disabled women living in the community; black women are at higher risk than are white women.

HIV-associated nephropathy is a late, not early, manifestation of HIV-1 infection

Human immunodeficiency virus-associated nephropathy (HIVAN) can be the initial presentation of HIV-1 infection. As a result, many have assumed that HIVAN can occur at any point in the infection. This issue has important implications for appropriate therapy and, perhaps, for pathogenesis. Since the development of new case definitions for acquired immunodeficiency syndrome (AIDS) and better tools to assess infection, the relationship of HIVAN to the time of AIDS infection has not been addressed. In this study, we reassessed the stage of infection at the time of HIVAN diagnosis in 10 patients, and we reviewed all previously published cases applying the new case definitions to assess stage of infection. HIVAN was confirmed by kidney biopsy in HIV seropositive patients with azotemia and/or proteinuria. CD4+ cell count and plasma HIV-1 RNA copy number were measured. We also reviewed all published cases of HIVAN to determine if AIDS-defining conditions, by current Centers for Disease Control definitions, were present in patients with biopsy-proven HIVAN. Twenty HIV-1 seropositive patients with proteinuria and an elevated creatinine concentration were biopsied. HIVAN was the single most common cause of renal disease. CD4+ cell count was below 200/mm3 in all patients with HIVAN, fulfilling Centers for Disease Control criteria for an AIDS-defining condition. HIV-1 plasma RNA was detectable in all patients with HIVAN. In reviewing previous reports, an AIDS-defining condition was present in virtually all patients with HIVAN. HIVAN develops late, not early, in the course of HIV-1 infection following the development of AIDS. This likely accounts for the poor prognosis noted in previous publications and has implications for pathogenesis. In addition, given the detectable viral RNA levels, highly active antiretroviral therapy is indicated in HIVAN. Highly active antiretroviral therapy may improve survival as well as alter the natural history of HIVAN.

Highly elevated levels of prostaglandin D synthase in the serum of patients with renal failure

Objectives. To investigate whether prostaglandin D (PGD) synthase levels differ in the serum of patients with or without renal dysfunction. PGD synthase or beta-trace protein is a major constituent (approximately 3% of total protein) of human cerebrospinal fluid (CSF). We previously reported that PGD synthase levels in serum are approximately 40- to 60-fold lower than those in CSF. Methods. We measured the PGD synthase concentration in various sera with a highly sensitive and specific immunofluorometric assay along with the serum creatinine level. Analysis for PGD synthase and creatinine was performed in 30 sera from non-renal failure subjects, in 7 sera from patients treated with continuous ambulatory peritoneal dialysis, and in 34 sera that were before and after hemodialysis samples from 17 patients with renal failure. Results. Elevated creatinine concentration was observed in patients with renal insufficiency, as expected (Mann-Whitney P < 0.0001; chi-square P < 0.0001). We found that serum PGD synthase concentration from patients with renal failure is significantly elevated compared with the serum PGD synthase concentration from non-renal failure subjects (Mann-Whitney P < 0.0001; chi-square P < 0.0001). Approximately a 35-fold increase of serum PGD synthase is observed for patients with renal failure compared with non-renal failure subjects. Serum PGD synthase concentration is not affected by hemodialysis in acute renal failure patients (Mann-Whitney P = 0.918), unlike serum creatinine levels, which were decreased significantly after hemodialysis (Mann-Whitney P = 0.0001). Conclusions. We conclude that renal impairment is highly associated with elevated serum PGD synthase levels. Measurement of PGD synthase in serum is a new biochemical marker of renal insufficiency.

Elderly patients receive less aggressive medical and invasive management of unstable angina: potential impact of practice guidelines.

The Agency for Health Care Policy and Research (AHCPR) released a practice guideline on the diagnosis and management of unstable angina in 1994. To examine practice variation across the age spectrum in the management of patients hospitalized with unstable angina 2 years before release of the AHCPR guideline. Retrospective cohort. Urban academic hospital. All nonreferral patients diagnosed as having unstable angina who were hospitalized directly from the emergency department to the intensive care or telemetry unit between October 1, 1991, and September 30, 1992. Percentage of eligible patients receiving medical treatment concordant with 8 important AHCPR guideline recommendations. Half of the 280 patients were older than 66 years; women were older than men on average (70 vs 64 years; P<.001). After excluding those with contraindications to therapy, patients in the oldest quartile (age, 75.20-93.37 years) were less likely than younger patients to receive aspirin (P<.009), beta-blockers (P<.04), and referral for cardiac catheterization (P<.001). Overall guideline concordance weighted for the number of eligible patients declined with increasing age (87.4%, 87.4%, 84.0%, and 74.9% for age quartiles 1 to 4, respectively; chi2, P<.001). Increasing age, the presence of congestive heart failure at presentation, a history of congestive heart failure, previous myocardial infarction, increasing comorbidity, and elevated creatinine concentration were associated with care that was less concordant with AHCPR guideline recommendations; only age and congestive heart failure at presentation remained significant in the multivariate analysis (odds ratios, 1.28 per decade [95% confidence interval, 1.02-1.61] and 3.16 [95% confidence interval, 1.57-6.36], respectively). Older patients were less likely to receive standard therapies for unstable angina before release of the 1994 AHCPR guideline. Patients presenting with congestive heart failure also received care that was more discordant with guideline recommendations. The AHCPR guideline allows identification of patients who receive nonstandard care and, if applied to those patients with the greatest likelihood to benefit, could lead to improved health care delivery.

Serum Creatinine Concentration and Risk of Cardiovascular Disease

Elevated serum creatinine has been associated with increased mortality in hypertensive persons, the elderly, and patients with myocardial infarction or stroke in whom cardiovascular disease is the major cause of death. We have examined the relationship between serum creatinine concentration and the risk of major ischemic heart disease and stroke events and all-cause mortality in a general population of middle-aged men. We present a prospective study of middle-aged men (aged 40 to 59 years) drawn from 24 British towns who have been followed up for an average of 14.75 years. Data on serum creatinine were available for 7690 men in whom there were 287 major stroke events, 967 major ischemic heart disease events, and 1259 deaths from all causes during follow-up. The median serum creatinine concentration was 98 micromol/L (95% range, 76 to 129 micromol/L). Stroke risk was significantly increased at levels above 116 micromol/L (90th percentile) even after adjustment for a wide range of cardiovascular risk factors (relative risk [RR], 1.6; 95% CI, 1.1 to 2.1; > 116 micromol/L versus the rest). Risk of a major ischemic heart disease event was significantly increased at or above 130 micromol/L (97.5 percentile), but this was attenuated after adjustment (RR, 1.2; 95% CI, 0.8 to 1.7; > or = 130 micromol/L versus the rest). There was a weak but significant positive association between diastolic blood pressure and creatinine concentration. However, elevated creatinine concentration (> or = 116 micromol/L) was associated with a significant increase in stroke in both normotensive and hypertensive men. All-cause mortality and overall cardiovascular mortality were significantly increased only above the 97.5 percentile, and no significant association was seen with cancer or other noncardiovascular mortality. A high serum creatinine concentration within the normal range is a marker for increased risk of cerebrovascular disease in both normotensive and hypertensive subjects. These findings support the evidence indicating that subtle impairment of renal function is a factor for increased risk of stroke and suggest mechanisms in the pathogenesis of stroke that warrant further investigation.

Exposure to excessive parenteral Zn and/or cisplatin affects trace element metabolism and enzyme activities in reproductive tissues and kidney of male rats

Cisplatin (CDDP) is a platinum coordination compound with antineoplastic properties. Cisplatin chemotherapy is known to cause serious damage to the kidney tubules and to the germinal epithelium of the testis. Results of recent investigations suggest that pretreatment with parenteral Zn will prevent some of the damage in these tissues. The present study determined the effects of pretreatment with large doses of parenteral Zn on trace element metabolism and enzyme activity in CDDP-treated rats. Treating young male rats (200 g) with intraperitoneal injections of 90 mg Zn/kg body weight prior to CDDP treatment (3 mg/kg body weight for 3 days) did not inhibit kidney damage; confirmed by elevated area and creatinine concentrations in serum of CDDP-treated rats. Serum and testicular testosterone concentrations were significantly lower in CDDP-treated rats than controls, which suggests Leydig cell damage. Zn treatment did not, however, alleviate this effect. Although angiotensin-converting enzyme activity was significantly elevated in the kidney by Zn treatment, activities in the testis and epididymis were not affected. Contrary to the suggestions that high parenteral Zn treatment protects kidneys and testes from damage, this study shows no such positive effects. However, the study demonstrated that treating rats with high concentrations of Zn and/or CDDP caused numerous changes in tissue concentrations of zinc, copper, and iron and in the activities of Zn-dependent as well as non-Zn-dependent membrane-bound enzymes.

Management and follow-up of arterial thrombosis in the neonatal period

The management and follow-up of 12 patients with major aortic thrombus formation occurring in the neonatal period between 1982 and 1987 are reported. Umbilical arterial catheters were inserted in 8 of the 12 patients before thrombus formation. Two patients had congenital thrombi. Hypertension, oliguria, hematuria, and elevated blood creatinine concentration were found at the time of diagnosis of the thrombus; nine of the patients had a patent ductus arteriosus. Supportive care was instituted in seven patients who were hemodynamically stable. Five of the patients had congestive heart failure, shock, or both, and were treated with surgical thrombectomy. Thrombolytic therapy was not used in either group. The five surgically treated patients and six of seven medically treated patients survived. Ultrasound examination suggested resolution of the thrombus in all survivors in 6 to 30 days. Sequelae from thrombus formation were present in all patients at the time of discharge and included hypertension in 9 of the 11 survivors and decreased renal function in six of them. Follow-up at 1 to 3 years revealed normal blood pressure, good growth, and good renal function in 10 of the survivors.