Serum Creatinine Concentrations In Patients Research Articles

Interference of metamizole in the measurement of serum creatinine concentration

Abstract Objectives There is little literature on the interference of metamizole in measurement creatinine concentration by the enzymatic method. Some studies have postulated that the dipyrone molecule is responsible for interfering in the last reaction of the enzymatic method sequence, due to its similarity with the 4-aminophenazone molecule. The aim of this study is to examine the interference of the presence of metamizole in the measurement of serum creatinine concentration by the enzymatic method. Methods An interference study of the measurement of creatinine concentration was carried out with two measurement procedures (enzymatic and Jaffe), by adding different concentrations of metamizole to pool from 30 serum samples of patients. Results The interference study indicates that the results of serum creatinine concentrations in patients, as measured by the enzymatic method, decrease with the addition of increasing concentrations of metamizole. Conclusions There is interference with metamizole in the measurement of serum creatinine concentration by the enzymatic method that it is have not seen in the Jaffe method.

Impact of solute carrier transporter gene polymorphisms on serum creatinine concentrations in healthy volunteers.

In this study, we investigated the impact of single nucleotide polymorphisms in solute carrier (SLC) transporters, that is, SLC22A7 c.1586 + 206A > G, SLC22A2 c.808G > T, SLC22A3 c.1233G > A, SLC47A1 c.922-158G > A, and SLC47A2 c.-130G > A, on serum creatinine (SCr) concentrations. This cross-sectional study included residents who participated as volunteers in a health promotion study. Lifestyle data, blood chemical analysis data, and SLC gene polymorphism information were collected from each participant. Univariate analyses were carried out to determine differences between groups and correlations in SCr. Stepwise multiple regression analysis was performed to confirm the independence of factors that were significantly different in the univariate analyses. In multiple regression analyses, muscle mass, serum cystatin C concentrations, body fat percentage, serum albumin concentrations, and SLC47A2 c.-130G/G had the highest contribution to SCr concentrations, in that order (standardized regression coefficients=.505, .332, -.234, .123, and .084, respectively). The final model explained 72.2% of the variability in SCr concentrations. The SLC47A2 c.-130G > A polymorphism may affect creatinine dynamics in the proximal tubules. Further studies are needed to determine the effects of SLC transporter gene polymorphisms on SCr concentrations in patients with various diseases in real-world clinical settings.

Does acute normovolemic hemodilution affect intraoperative value of serum-creatinine concentration in patients undergoing cardiac surgery

Does acute normovolemic hemodilution affect intraoperative value of serum-creatinine concentration in patients undergoing cardiac surgery

Microalbuminuria in primary aldosteronism

Background. Primary aldosteronism (PA) is an adrenal disorder which is characterized by the overproduction of the mineralocorticoid hormones by the adrenal glands when not as a result of excessive renin secretion. Different studies report the prevalence of PA in from 7 to 15 % patients with hypertension. Nowadays PA is considered to be the most frequent cause of secondary hypertension taking up to 30% of it. The importance of case detection of PA among hypertensive patients is not a matter of controversy presently. It has been demonstrated recently that patients with PA are more prone to cardiovascular events and target organ damage than essential hypertensive patients.Aim: to establish renal dysfunction in PA.Methods. We evaluated 192 low-renin hypertensive patients and 30 normotensive subjects. The mean age of the hypertensives was 47,5±3,4 years. The control group was 51,8±4,2 years old. PA was established in 57 patients, all the others were classified as low-renin essential hypertensives (LREH). Both groups were similar with respect to age (44,7±4,2 in PA, 48,3±3,9 in LREH), sex (female 63% of PA and 67% of LREH) and blood pressure (158±16/96±8 mm Hg in PA, 164±21/99±13 mm Hg in LREH). There were slight differences in BMI (31,4±4,3 in PA and 28,7±3,5 in LREH, p<0,05). PA and LREH patients significantly differed with respect to prevalence of diabetes mellitus (26,3% in PA and 9,6% in LREH, p<0,01) and duration of hypertension (7±5 years in PA and 13±4 in LREH, p<0,05).Results. We observed an increase in urinary protein excretion in both group. But in group of patients with PA it was higher than in LREH (0,14±0,06 vs. 0,05±0,03 g/24 h, p<0,05). In addition, patients with PA had higher serum creatinine concentrations (101,7±13,2 vs. 83,4±9,1 mkmol/l, p<0,05). Subgroup analyses of normoglycemic subjects showed that PA patients still had a higher creatinine concentration (84,3±11,8 vs. 81,9±10,5 mkmol/l) but the difference was no longer statistically significant. Although, microalbuminuria was significantly higher in non-diabetic PA patients (0,12±0,04 vs. 0,05±0,07 g/24 h, p<0,05). Diabetic subjects in both groups did not differ significantly with respect to microalbuminuria.Conclusions. Cross-sectional Primary Aldosteronism Prevalence in Italy (PAPY) study showed an increased prevalence of microalbuminuria in PA. The data from German Conn’s Registry showed a significant increase of serum creatinine concentrations in patients with PA but they did not observe any significant differences in protein excretion. In our study the differences in creatinine concentration were diabetes-dependent. Although, we suppose an increase of microalbuminuria in patients with PA to be aldosterone-dependent. However, this hypothesis should be confirmed in wider populations.

The Incidence and Risk Factors of Acute Kidney Injury After Coronary Artery Bypass Graft Surgery

Background: Acute Kidney Injury (AKI) is a prevalent and important complication of cardiac surgery, which is associated with significant morbidity and mortality. Identification of risk factors associated with AKI will help it’s prevent. Objectives: The objective of the present investigation was to identify risk factors for acute kidney injury in patients who underwent coronary artery bypass graft (CABG) surgery at a tertiary care center for cardiovascular patients in Iran. Patients and Methods: From March 2014 to April 2015, 490 consecutive patients who underwent On-pump CABG at Rajaie cardiovascular medical and research center were assessed. Baseline variables and perioperative data were collected and their association with the development of AKI was evaluated. Results: Patients’ mean age was of 67.9 (SD = 12.5) years. From these patients 353 (72%) were male and 137 (28%) were female. Six deaths (1.3%) occurred among patients. Thirteen patients (2%) had AKI. The baseline serum creatinine concentrations in patients with AKI were significantly higher than other patients (P = 0.04). Volume of transfused red blood cells and hemoglobin value were different, associated with AKI (P 0.05). Mean arterial pressure (MAP) was not different in patients with AKI (P = 0.85). The mean pump time in patients with AKI was significantly higher than the other patients (P = 0.02). Postoperative Left ventricle ejection fraction (LVEF) in patients who developed AKI was significantly reduced compared with patients without AKI (P = 0.01). The in-hospital mortality of patients who developed AKI was 7.69% compared with 1.04% among those who did not (P = 0. 01). Conclusions: Acute kidney injury is the important postoperative organ dysfunction in patients who underwent CABG and preoperative elevated serum creatinine concentration, cardiopulmonary bypass time > 120 minutes, intraoperative anemia and blood transfusion were serious risk factors associated with AKI.

Foods With Added Fiber Lower Serum Creatinine Levels in Patients With Chronic Kidney Disease

To determine the effect of foods with added fiber on blood urea nitrogen (BUN) and serum creatinine concentrations in patients with chronic kidney disease (CKD). Participants were enrolled in a 6-week single-blind crossover study. Free living with partial dietary intervention. Thirteen CKD patients with Modification of Diet in Renal Disease formula-based estimated glomerular filtration rate (eGFR) ≤50 mL/minute/1.73 m(2) at the time of screening (5 men, 8 women; mean age, 67.0 ± 14.8 years) completed the study. Patients consumed control foods (cereal, cookies, and bars) providing 1.6 g/day fiber daily for 2 weeks, followed by similar foods providing 23 g/day fiber daily for 4 weeks, incorporated into their usual diets. The main outcome of the study was the determination of the impact of foods with added fiber on BUN and serum creatinine levels. Consuming foods with added fiber resulted in a 10.6% decrease in mean BUN concentration (13.8 ± 2.0 to 12.1 ± 1.8 mmol/L or 38.5 ± 5.6 to 34.0 ± 5.1 mg/dL; P < .05). Serum creatinine level decreased from a baseline value of 216 ± 26 to 201 ± 23 mmol/L (2.44 ± 0.30 to 2.27 ± 0.26 mg/dL; P < .05) after 2 weeks of fiber-containing food consumption, and remained significantly lower at 195 ± 23 mmol/L (2.21 ± 0.26 mg/dL) after 4 weeks of the intervention (P < .05). Calculated eGFR increased from a baseline value of 29.6 ± 3.5 to 31.4 ± 3.8 mL/minute/1.73 m(2) at the end of 2 weeks, and remained higher at 32.5 ± 3.6 mL/minute/1.73 m(2) after 4 weeks of fiber intervention (P < .05). We conclude that increasing fiber intake in CKD patients through the consumption of foods with added fiber may reduce serum creatinine levels and improve eGFR. Additional studies are warranted to confirm these findings and to determine whether the changes are due to direct effects on kidney function.

Oliguria as predictive biomarker of acute kidney injury in critically ill patients.

IntroductionDuring critical illness, oliguria is often used as a biomarker of acute kidney injury (AKI). However, its relationship with the subsequent development of AKI has not been prospectively evaluated.MethodsWe documented urine output and daily serum creatinine concentration in patients admitted for more than 24 hours in seven intensive care units (ICUs) from six countries over a period of two to four weeks. Oliguria was defined by a urine output < 0.5 ml/kg/hr. Data were collected until the occurrence of creatinine-defined AKI (AKI-Cr), designated by RIFLE-Injury class or greater using creatinine criteria (RIFLE-I[Cr]), or until ICU discharge. Episodes of oliguria were classified by longest duration of consecutive oliguria during each day were correlated with new AKI-Cr the next day, examining cut-offs for oliguria of greater than 1,2,3,4,5,6, or 12 hr duration,ResultsWe studied 239 patients during 723 days. Overall, 32 patients had AKI on ICU admission, while in 23, AKI-Cr developed in ICU. Oliguria of greater than one hour was significantly associated with AKI-Cr the next day. On receiver-operator characteristic area under the curve (ROCAUC) analysis, oliguria showed fair predictive ability for AKI-Cr (ROCAUC = 0.75; CI:0.64-0.85). The presence of 4 hrs or more oliguria provided the best discrimination (sensitivity 52% (0.31-0.73%), specificity 86% (0.84-0.89%), positive likelihood ratio 3.8 (2.2-5.6), P < 0.0001) with negative predictive value of 98% (0.97-0.99). Oliguria preceding AKI-Cr was more likely to be associated with lower blood pressure, higher heart rate and use of vasopressors or inotropes and was more likely to prompt clinical intervention. However, only 30 of 487 individual episodes of oliguria preceded the new occurrence of AKI-Cr the next day.ConclusionsOliguria was significantly associated with the occurrence of new AKI-Cr, however oliguria occurred frequently compared to the small number of patients (~10%) developing AKI-Cr in the ICU, so that most episodes of oliguria were not followed by renal injury. Consequently, the occurrence of short periods (1-6 hr) of oliguria lacked utility in discriminating patients with incipient AKI-Cr (positive likelihood ratios of 2-4, with > 10 considered indicative of a useful screening test). However, oliguria accompanied by hemodynamic compromise or increasing vasopressor dose may represent a clinically useful trigger for other early biomarkers of renal injury.

Impact of serum acetaminophen concentration on changes in serum potassium, creatinine and urea concentrations among patients with acetaminophen overdose

Acetaminophen overdose may be accompanied by electrolyte disturbances. The basis for electrolyte change appears to be due to increased fractional urinary electrolyte excretion. This study investigated the impact of serum acetaminophen concentration on changes in serum potassium, creatinine and urea concentrations in patients with acetaminophen overdose. This was a retrospective cohort study which included patients admitted to the emergency department and hospital within 24 h of acetaminophen ingestion. The study was conducted over a period of 5 years from 1 January 2004 to 31 December 2008. Data are presented as mean ± SD and as medians (interquartile range) and groups were compared using independent two-tailed Student t-test. Statistical Package for Social Sciences (SPSS) 15 was used for data analysis. Two hundred and eighty-three patients were studied (44 males and 239 females), mean age 23 ± 7.5 years. Patients who had a serum acetaminophen concentration above a 'possible toxicity' treatment line were associated with an elevation in serum creatinine concentration (p=0.044) and a reduction in the serum potassium concentration (p<0.001) but were not associated with a reduction in serum urea concentration (p>0.99). During the study period, 63.3% (179 patients) had serum potassium concentrations less than the normal concentration (3.5 mmol/l) and 31.4% (89 patients) had serum urea concentrations less than the normal concentration (2.5 mmol/l). The serum creatinine concentration in all patients was within the normal range. Acetaminophen appears to cause a concentration-dependent reduction of potassium concentrations and an elevation of creatinine concentrations of short duration (<24 h) after overdose.

Clinical and laboratory findings in patients with leptospirosis at a tertiary teaching hospital in Jamaica

correspondence: Donovan McGrowder Department of Pathology, Faculty of Medical sciences, The University of the West indies, Mona campus, Kingston 7, Jamaica, West indies Tel +876 927 1410 Fax +876 977 1811 email dmcgrowd@yahoo.com Background: Leptospirosis is a zoonotic disease that is endemic in most Caribbean countries. This study examined the clinical presentations and laboratory findings in serologically confirmed cases of leptospirosis. Patients and methods: The medical records of all hospitalized patients with presumptive and confirmed leptospirosis between June 2005 and May 2006 at the University Hospital of the West Indies were retrospectively reviewed. Results: There were five serologically confirmed cases of leptospirosis. The mean age of patients with leptospirosis was 57.33 ± 8.21 years (range 41–67 years); all were men exposed to contaminated water or soil, and most cases were diagnosed in November. The most common symptoms were fever, myalgia, nausea, vomiting, headache, abdominal pain, and arthralgia. Increase in the mean serum creatinine concentration in patients with leptospirosis (439.40 ± 129.18 μmol/L) was significant when compared with that in the controls (87.86 ± 4.72 μmol/L; P = 0.005). Four of the five patients with leptospirosis showed evidence of hematuria. All patients with leptospirosis showed evidence of hyperbilirubinemia, which was mostly direct hyperbilirubinemia. The mean concentration of total bilirubin was 291.40 ± 52.33 μmol/L in patients with leptospirosis when compared with 9.83 ± 1.28 μmol/L in controls (P , 0.001). Thrombocytopenia (platelet count ,150,000 cells/mm) was observed in 80% of the patients with leptospirosis. Conclusion: The study indicates the variable clinical manifestations of leptospirosis and emphasizes the importance of continued vigilance of physicians and primary health care workers in increasing the awareness of the seasonal distribution and the need for early diagnosis of leptospirosis.

Estimation of Glomerular Filtration Rate by Using Serum Cystatin C and Serum Creatinine Concentrations in Patients with Human Immunodeficiency Virus

To compare the predictive performance of four equations for estimating glomerular filtration rate (GFR) relative to the gold standard measurement, iothalamate clearance, in patients with human immunodeficiency virus (HIV) who have various degrees of kidney function. Prospective, cross-sectional analysis. General clinical research center. Twenty-two adult (mean age 51 yrs) HIV-positive patients with various degrees of stable kidney function and with lean body mass considered normal for a well-nourished person. Patients were administered a single dose of intravenous iothalamate 456 mg as a rapid infusion over 3 minutes, 1 hour after an oral fluid load of 600 ml of caffeine-free, sugar-free liquids. Serial blood and urine samples were obtained for determination of measured GFR. Estimated GFR values were calculated by using four equations: the Cockcroft-Gault equation, the simplified Modification of Diet in Renal Disease Study (MDRD) equation, an equation that incorporates serum creatinine and cystatin C concentrations, and an equation incorporating only serum cystatin C concentration. The predictive performance of the equations was determined by comparing the bias, accuracy, and precision of the estimates with the measured values. Body composition was determined by dual-energy x-ray absorptiometry. The four predictive equations underestimated the measured GFR obtained by the iothalamate method, but the differences were not statistically significant. The MDRD equation and the equation that included both serum cystatin C and creatinine concentrations, as well as age, sex, and race, provided the least bias, most precision, and best accuracy in estimating the measured GFR. The MDRD equation and the equation that included both serum cystatin C and creatinine concentrations appear to provide accurate, precise, and relatively unbiased estimates of GFR in patients with HIV. Larger studies are needed that include patients with muscle wasting and lipodystrophy in order to validate these preliminary observations and the effects of body composition on the predictability of GFR with use of these equations.

Diagnostic value of cystatin C for predicting acute kidney injury in patients with liver cirrhosis

Background/AimsThe present study aimed to determine the role of cystatin C as a prognostic factor for acute kidney injury and survival in cirrhotic patients.MethodsThe study investigated 53 liver cirrhosis patients. The renal function was evaluated by serum creatinine, serum and urine cystatin C, and 24-hour creatinine clearance on admission. Acute kidney injury was defined as a serum creatinine level exceeding the normal range (>1.2 mg/dl) and an increase of at least 50% from the baseline value. Multivariate analysis, receiver operating characteristic curve, and survival analysis were used to investigate prognostic factors for acute kidney injury and survival.ResultsNine of the 53 cirrhotic patients (17.0%) developed acute kidney injury within 3 months. Both serum creatinine and cystatin C were predictive factors for acute kidney injury in univariate analysis, with a diagnostic accuracy of 0.735 (95% confidence interval (CI), 0.525-0.945; p=0.028) for serum cystatin C and 0.698 (95% CI, 0.495-0.901, p=0.063) for creatinine. In multivariate analysis, only serum cystatin C was an independent risk factor for acute kidney injury. The sensitivity and specificity of a serum cystatin C level of >1.23 mg/L to acute kidney injury were 66% and 86%, respectively. Serum cystatin C was positively correlated with the Model for End-Stage Liver Disease (MELD) and MELD-Na scores (r=0.346 and p=0.011, and r=0.427 and p=0.001, respectively). Comparison of the survival rates over the observation period revealed that a serum cystatin C level of >1.23 mg/L was a useful marker for short-term mortality (p<0.001).ConclusionsThe accuracy in predicting acute kidney injury and short-term mortality was higher for a serum cystatin C level of >1.23 mg/L than for the serum creatinine concentration in patients with cirrhosis.

The Issue of Renal Safety of Zoledronic Acid from a Nephrologist's Point of View

The Oncologist 2005;10:306–308 www.TheOncologist.com Administration of bisphosphonates for cancer bone metastases, especially by the i.v. route, carries a certain, wellestablished risk of deterioration of renal function [1–9]. Although toxic acute tubular necrosis and collapsing focal segmental glomerulosclerosis have been implicated in the mechanism of renal toxicity [10–12], the pathogenesis is still poorly understood. In patients who have pre-existing chronic kidney disease (CKD) or other risk factors for the deterioration of renal function, for example, multiple myeloma, diabetes mellitus, hypertension, or advanced age, the administration of bisphosphonates is to be carried out with caution to avoid its deleterious effect on kidney function [13, 14]. Renal function monitoring guidelines have been introduced to reduce the incidence of this serious, potentially life-threatening, adverse event, and serum creatinine level measurement has been proposed as the primary parameter to assess renal risk and to provide guidance to avoid renal toxicity when zoledronic acid is administered [15]. However, excessive changes in glomerular filtration rate (GFR)—the most important parameter in assessing kidney function—correspond to only small changes in plasma creatinine concentration when patients have near normal to mildly/moderately impaired renal function [16, 17], making plasma creatinine a poor indicator of the corresponding GFR in the earlier stages of CKD. GFR must decline to approximately half the normal level before the serum creatinine concentration rises above the upper limit of normal [18]. Moreover, the plasma creatinine level underestimates renal impairment in those with reduced muscle mass, including women, children, the elderly, and the malnourished [19], many of whom have underlying malignant diseases. Therefore, serum creatinine level is not the optimal tool for establishing administration guidelines for patients treated with zoledronic acid (Zometa®; Novartis Pharmaceuticals Corporation, East Hanover, NJ, http://www.pharma.us.novartis.com), which is known to cause deterioration of renal function—defined as a ≥0.5 mg/dl increase in serum creatinine concentration in patients with normal baseline levels or a ≥1.0 mg/dl elevation in serum creatinine in patients with abnormal baseline levels (≥1.4 mg/dl)—in about 10% of patients receiving this treatment for their cancer-induced bone disease during the course of their treatment [3, 15]. Creatinine clearance and GFR predicted by the CockcroftGault formula or by the equation from the MDRD study [18, 20, 21] would offer a more reliable approach to indicate renal function impairment and to determine and monitor the stage of CKD during the overall course of zoledronic acid therapy. What is extremely worrisome is the fact that among the U.S. adult population at large there are an estimated 5.7 million people with GFRs of 60–89 ml/min per 1.73 m2, a second group of 7.4 million people with GFRs of 30–59 ml/min per 1.73 m2, and another 300,000 people with GFRs of 15–29 ml/min per 1.73 m2, many of whom have normal serum creatinine levels and are not even aware of their CKD [22]. Overall, these three groups account for 2.8%, 3.7%, and 0.13% of the U.S. adult population, respectively, The Oncologist Letter to the Editor

Effect of N-Acetylcysteine on Serum Creatinine Concentration in Patients with Chronic Renal Insufficiency Who Are Undergoing Coronary Angiography

Background: Prior studies have produced conflicting results on whether N-acetylcysteine (NAC) reduces the incidence of contrast-induced nephropathy (CIN) in patients undergoing coronary angiography (CA). The dosing regimens of NAC in these studies seemed impractical for everyday clinical practice. Objective:We studied the effect of NAC, with a novel dosing strategy, on serum creatinine concentration (SCr), and the incidence of CIN, in patients who were undergoing CA and/or percutaneous coronary intervention (PCI). Methods: Twenty-five subjects with baseline renal insufficiency who were undergoing CA and/or PCI were randomized to either NAC or placebo.The treatment schedule was 800 mg of NAC 12 h prior to angiography, 600 mg of NAC 2 h prior to angiography, and 600 mg of NAC 6 h after angiography or matching placebo. All subjects were hydrated with 1 ml/kg of 0.45% saline and received non-ionic contrast for angiography. The primary endpoint was change in SCr and the secondary endpoint was the incidence of CIN as defined by an increase of 0.5 mg/dl or 25% in SCr at 48 h. Results:The average SCr at enrollment was 1.7 mg/dl and average dye exposure was 171 ml. The average change in SCr in the NAC and placebo groups was 0.14 and 0.06 mg/dl, respectively (p = 0.60). The incidence of CIN was 18 and 14% in the NAC and placebo groups, respectively (p = 1.0). Conclusion: In this small study, there was no significant difference in the change inSCr nor the incidence of CIN in patients with baseline renal insufficiency undergoing CA and/or PCI who were treated with NAC or placebo.

Norepinephrine for hypotensive vasodilatation after cardiac surgery: impact on renal function.

Norepinephrine use in patients after cardiac surgery is controversial because of the fear that norepinephrine might decrease kidney function through regional vasoconstriction. Accordingly, we studied the renal effects of norepinephrine use for hypotensive vasodilatation after cardiac surgery. Retrospective controlled study in the cardiothoracic ICU of tertiary hospital. PATIENTS. 100 cardiac surgery patients with post-operative hypotensive vasodilatation and 100 control cardiac surgery patients. Treatment of hypotension (MAP<70 mmHg) with continuous norepinephrine infusion. We collected data on demographic and surgical characteristics, haemodynamics, serum creatinine and mortality. Just after surgery the norepinephrine group had a significantly higher mean central venous pressure, lower mean arterial pressure, and lower systemic vascular resistance index with a similarly elevated mean cardiac index. Despite norepinephrine administration at a mean peak dose of 7.3+/-6.4 micro g/min the mean post-operative change in creatinine was not different between two groups on days 0, 2 or 4 after surgery. Norepinephrine does not increase post-operative serum creatinine concentrations in patients with hypotensive vasodilatation after cardiac surgery. Concerns related to its potential adverse effects on the kidney function in this setting appear unjustified.

Non-heart-beating donors: renewed source of organs for renal transplantation during the twenty-first century.

The growing demand of organs for renal transplantation makes it necessary to explore alternative routes for kidney donation. Non-heart-beating donors (NHBDs) are a valuable source of cadaveric organs and have been the subject of renewed interest in recent years. In addition to difficulties with legal and ethical acceptability, there are concerns regarding medical safety. The current NHBD program at St. George's Hospital in London was started in March 1995. A total of 41 kidneys from category I to III donors (according to the Maastricht classification) were retrieved from the Accident and Emergency Department and several intensive care units and were subsequently transplanted. Cold in situ perfusion was commenced via femoral access or rapid aortic cannulation in most donors. Of these transplanted kidneys, 35 started functioning within 4 weeks. The permanent nonfunction (PNF) rate was 14.6% (6/41) and the estimated 1-year graft survival 82.9% (34/41). The delayed graft function (DGF) rate (defined as recipients requiring posttransplant dialysis for 3 days or longer) was 80.0% (28/35). The median serum creatinine concentration in patients with a functioning graft at 1 year was 165 micromol/L. NHBD kidneys have contributed about 15% to the regional transplant activity over the last 6 years, even though not all potential NHBDs were used. It was possible to lower the PNF rate with strict donor selection criteria and more recently with pulsatile machine perfusion. NHBDs represent a valuable source for kidneys and can extend the donor pool. More experience is currently needed to continue to lower PNF rates reliably before promoting more widespread use of NHBDs for renal transplantation.

Complications of cirrhosis. II. Renal and circulatory dysfunction. Lights and shadows in an important clinical problem

The pathophysiology of circulatory and renal dysfunction in cirrhosis and the treatment of ascites and related conditions (hepatorenal syndrome and spontaneous bacterial peritonitis) have been research topics of major interest during the last two decades. However, many aspects of these problem remain unclear and will constitute major areas of investigation in the next millennium. The pathogenesis of sodium retention, the most prevalent renal function abnormality of cirrhosis, is only partially known. In approximately one third of patients with ascites, sodium retention occurs despite normal activity of the renin-aldosterone and sympathetic nervous systems and increased circulating plasma levels of natriuretic peptides and activity of the so-called natriuretic hormone. These patients present an impairment in circulatory function which, although less intense, is similar to that of patients with increased activity of the renin-aldosterone and sympathetic nervous systems, suggesting that antinatriuretic factors more sensitive to changes in circulatory function that these systems may be important in the pathogenesis of sodium retention in cirrhosis. The development of drugs that inhibit the tubular effect of antidiuretic hormone and increase renal water excretion without affecting urine solute excretion has opened a field of great interest for the management of water retention and dilutional hyponatremia in cirrhosis. Two families of drugs, the V2 vasopressin receptor antagonists and the kappa-opioid agonists, have been shown to improve free water clearance and correct dilutional hyponatremia in human and experimental cirrhosis with ascites. The first type of drugs blocks the tubular effect of antidiuretic hormone and the second inhibits antidiuretic hormone secretion by the neurohypophysis. On the other hand, two new treatments have also been proved to reverse hepatorenal syndrome in cirrhosis. The most interesting one is that based on the simultaneous administration of plasma volume expansion and vasoconstrictors. The second is transjugular intrahepatic portosystemic shunt. The long-term administration (1–3 weeks) of analogs of vasopressin (ornipressin or terlipressin) or other vasoconstrictors together with plasma volume expansion with albumin is associated with a dramatic improvement in circulatory function and normalization of serum creatinine concentration in patients with severe hepatorenal syndrome. Of interest is the observation that in many of these patients, hepatorenal syndrome does not recur following discontinuation of the treatment, thus raising important questions about the mechanism by which hepatorenal syndrome follows a progressive course in most untreated cases. The pathogenesis of circulatory dysfunction in cirrhosis and the role of local mechanisms in the development of the splanchnic arteriolar vasodilation associated with portal hypertension will continue as important topics in clinical and basic research in Hepatology. Of special interest is the study of the mechanism by which circulatory function further deteriorates following complications such as severe bacterial infection or therapeutic interventions such as therapeutic paracentesis, and the adverse consequences of the impairment in circulatory function on renal and hepatic hemodynamics. Finally, although major advances have been made concerning the treatment and secondary prophylaxis of spontaneous bacterial peritonitis in cirrhosis, many aspects of the pathogenesis of this infection remain unclear. The mechanism of bacterial translocation and of the colonization of bacteria in the ascitic fluid are particularly important to design adequate measures for primary prophylaxis of this severe bacterial infection.

Effect of growth hormone treatment on serum creatinine concentration in patients with cystinosis and chronic renal disease

Three patients with nephropathic cystinosis and chronic renal disease, treated since early childhood with orally administered cysteamine, had an accelerated rate of rise of serum creatinine values after receiving recombinant human growth hormone. During 18 to 24 months of growth hormone treatment, each patient had a twofold to fourfold increase in growth velocity. The slope of the plot of reciprocal serum creatinine values versus age for each patient after growth hormone treatment was significantly steeper than the pretreatment slope. Growth hormone treatment had no effect on the rate of change of the uncorrected 24-hour renal creatinine clearance. We conclude that these patients gained body size but failed to compensate for their increased creatinine production with an increase in glomerular filtration rate. The result was an accelerated rate of rise of their serum creatinine values, hastening renal transplantation in one patient and the anticipated need for transplantation in another.

Effect of growth hormone treatment on serum creatinine concentration in patients with cystinosis and chronic renal disease

Three patients with nephropathic cystinosis and chronic renal disease, treated since early childhood with orally administered cysteamine, had an accelerated rate of rise of serum creatinine values after receiving recombinant human growth hormone. During 18 to 24 months of growth hormone treatment, each patient had a twofold to fourfold increase in growth velocity. The slope of the plot of reciprocal serum creatinine values versus age for each patient after growth hormone treatment was significantly steeper than the pretreatment slope. Growth hormone treatment had no effect on the rate of change of the uncorrected 24-hour renal creatinine clearance. We conclude that these patients gained body size but failed to compensate for their increased creatinine production with an increase in glomerular filtration rate. The result was an accelerated rate of rise of their serum creatinine values, hastening renal transplantation in one patient and the anticipated need for transplantation in another.

Plasma Immunoreactive Endothelin, But Not Thrombomodulin, Is Increased in Patients with Essential Hypertension and Ischemic Heart Disease

To ascertain an involvement of vascular endothelial cells in cardiovascular disease, we have determined plasma levels of two endothelium-derived substances, endothelin (ET) and thrombomodulin (TM), in essential hypertension (EH) and ischemic heart disease. Plasma ET was determined by radioimmunoassay (RIA) after extraction. Plasma TM levels were determined by enzymunoimmunoassay. Plasma ET levels were significantly elevated in patients with EH involving target organ damage, vasospastic angina pectoris (VSA), and acute myocardial infarction (AMI), especially in those associated with cardiogenic shock. There was a weak but significant correlation between plasma ET levels and serum creatinine concentration in patients with EH. Plasma ET levels were elevated even before the coronary spasm in patients with VSA, whereas they did not show any further increase during the spasm. In contrast, plasma TM levels in patients with EH and VSA did not show a significant difference from that in normal subjects. These results suggest that ET plays an important role in the pathophysiology of EH and ischemic heart disease, and also that increases in plasma ET cannot be simply attributed to a leakage of the peptide from the injured endothelial cells.

Prediction of glomerular filtration rate from changes in serum creatinine

The glomerular filtration rate (GFR) was estimated from serum creatinine concentration in patients in whom the individual relation between GFR and serum creatinine had been previously determined. 51Cr-EDTA plasma clearance was used as reference method for GFR. The relation between 51Cr-EDTA clearance and estimated GFR was determined from 340 investigations in 197 adult patients with a variety of infectious and internal diseases. The imprecision of estimated GFR was 46% (1 CV) at 20 ml/min, 23% at 45 ml/min, 20% at 75 ml/min and 18% at 110 ml/min. This poor precision was probably due to the fact that many patients with acute infectious diseases, congestive heart failure, diabetes mellitus, etc., have an unstable renal function and therefore their creatinine distribution is not under steady state. This must always be considered when serum creatinine is used to estimate GFR.