LONG-TERM MONITORING OF RENAL FUNCTION IN POLY-TRAUMATIZED INTENSIVE CARE PATIENTS

Introduction: For the long-term monitoring of kidney function, polytraumatized patients were examined and routine as well as specialized parameters were compared. Materials and methods: 30 patients of the Surgical Intensive Care Unit (ICU) were examined daily over the entire period they stayed in the ICU. The patients were retrospectively classified as either survivors or deceased patients. Group 1 consisted of 20 patients who resided in the ICU for 11–15 (Median 14) days before they could be transferred to a normal hospital unit. Group 2 consisted of 10 patients who had passed away after 13–18 (Median 16) days in the ICU. In addition to the routine parameters diuresis, serum creatinine and serum urea, specialized parameters for kidney function including the excretion rates of α1-microglobulin (α1-MG), N-Acetyl-β-d-glucosaminidase (NAG), angiotensinase A (ATA) and immunoglobulin G (IgG) were determined. Results: Similar biometric data were shown by all patients at admission into the ICU, but differences did exist regarding the Revised Trauma Score, Injury Severity Score and the APACHE-II-Score. In the period between the 5th and 8th day of intensive treatment almost all patients showed pathological excretion rates of tubular and glomerular parameters whereby no increased frequency of unusual events could be determined at these time-points. Conclusion: During treatment in the ICU, all examined patients showed at times pathological excretion rates of specialized kidney function parameters. Such transient damage was only apparent in a few of the patients when the standard parameters serum creatinine and serum urea were employed. In 90% of the surviving patients the kidney parameters had normalized until the time they were transferred, indicating that such parameters reflected the general state of health of these patients.     

Long-term monitoring of renal function in poly-traumatized intensive care patients

INTRODUCTION: For the long-term monitoring of kidney function, polytraumatized patients were examined and routine as well as specialized parameters were compared. MATERIALS AND METHODS: 30 patients of the Surgical Intensive Care Unit (ICU) were examined daily over the entire period they stayed in the ICU. The patients were retrospectively classified as either survivors or deceased patients. Group 1 consisted of 20 patients who resided in the ICU for 11-15 (Median 14) days before they could be transferred to a normal hospital unit. Group 2 consisted of 10 patients who had passed away after 13-18 (Median 16) days in the ICU. In addition to the routine parameters diuresis, serum creatinine and serum urea, specialized parameters for kidney function including the excretion rates of alpha1-microglobulin (alpha1-MG), N-Acetyl-beta-D-glucosaminidase (NAG), angiotensinase A (ATA) and immunoglobulin G (IgG) were determined. RESULTS: Similar biometric data were shown by all patients at admission into the ICU, but differences did exist regarding the Revised Trauma Score, Injury Severity Score and the APACHE-II-Score. In the period between the 5th and 8th day of intensive treatment almost all patients showed pathological excretion rates of tubular and glomerular parameters whereby no increased frequency of unusual events could be determined at these time-points. CONCLUSION: During treatment in the ICU, all examined patients showed at times pathological excretion rates of specialized kidney function parameters. Such transient damage was only apparent in a few of the patients when the standard parameters serum creatinine and serum urea were employed. In 90% of the surviving patients the kidney parameters had normalized until the time they were transferred, indicating that such parameters reflected the general state of health of these patients.     

Akutes Nierenversagen Noninvasive Frühdiagnostik des akuten Nierenversagens bei operativen Intensiv-patienten*

Acute renal failure is a common and severe complication in ICU. Renal laboratory examinations like creatinine and urea are late signs of renal dysfunction: Most of the functional abilities are reduced and there is no time for therapeutical interventions. The aim of this study was to find some earlier sensitive parameters of renal dysfunction and the order of appearance, the cause of acute renal failure and the value of the measured parameters. Methods: After agreement of the local ethic committe, 21 patients of the ICU were investigated. They were devided into two groups: 1st (n=14) with no signs of renal dysfunction and were regarded as control group and 2nd (n=7) were examined until the beginning of acute renal failure. For five days the glomerular filtration rate, proteinuria (immunglobulin G, Tamm-Horsfall protein, α-1- and β-2 microglobulin, lysozyme), the brush border enzymes angiotensinase A and the lysosomal enzyme N-acetyl-β-d-glucosaminidase were daily measured and compared with clinical standards like the excretion of albumin, the clearances of creatinine and urea and the fractional excretion of sodium. Results: Both groups were comparable with respect to drug therapy, APACHE-II-score (with the exception of the last day before ARF), and infusion therapy. There were differences in tubular functions between the 2 groups. Patients developing renal insufficiency showed an increased excretion of a-1-microglobulin, and decreased excretions of Tamm-Horsfall-protein, angiotensinase A as well as a low renal blood flow. Significant differences were also detectable in glomerular functions (glomerular filtration rate), albumin, and immunoglobulin G. Discussion: Only a short time intervall (1 to 2 days) between tubular and glomerular damage were detectable in patients with renal insufficiency. Renal failure must be due to circulatory problems because of the nearly simultaneous increase of tubular and glomerular parameters after RPF decreased. The parameters α1-microglobulin, angiotensinase A and Tamm-Horsfall-protein gave early indications for the acute renal failure. They showed satisfactory sensitivity and specifity, but the positive predictive value was poor.     

Evolution and predictive power of serum cystatin C in acute renal failure

AIMS: The serum concentration of cystatin C has recently been proposed as a better indicator of glomerular filtration rate (GFR) than plasma creatinine. Little is known about cystatin C in critical illness. We assessed serum cystatin C as a marker of renal function in acute renal failure (ARF) and its power in predicting survival of ARF patients. MATERIAL: 202 consecutive adult patients admitted into the intensive care unit (ICU) during a period of 9 months. METHOD: Serum cystatin C, plasma creatinine and plasma urea were measured on admission, daily during the first 3 days, and 5-7 times a week during the rest of the ICU stay. The patients with and without ARF were compared by the Mann-Whitney U-test. The correlation between different variables was calculated by Spearman's correlation. Forward stepwise multiple regression analysis was performed to test independent predictors of mortality. The positive predictive value of serum cystatin C and plasma creatinine for ARF and mortality was calculated by ROC analysis. RESULTS: ARF occurred in 54 patients (27%). Serum cystatin C showed excellent positive predictive value for ARF in critical illness by ROC analysis. In acute renal dysfunction, abnormal values of serum cystatin C and plasma creatinine appeared equally quickly (median 3 days). The diagnosis of ARF, the day 1 Apache II score and admission plasma creatinine appeared as independent predictors of hospital mortality. ROC analysis showed only weak predictive power for serum cystatin C and plasma creatinine regarding hospital mortality. CONCLUSIONS: Serum cystatin C was as good as plasma creatinine in detecting ARF in intensive care patients. Neither marker was clinically useful in predicting mortality.     

Effect of Fenoldopam Mesylate in Critically Ill Patients at Risk for Acute Renal Failure is Dose Dependent

Background: Acute renal failure (ARF) is common and difficult to prevent, especially in intensive care unit (ICU) patients with cancer. Therapeutic trials with various agents have generally been ineffective in preventing ARF. We describe the effects of two different doses of the dopamine DA-1 receptor agonist fenoldopam mesylate on renal function in a series of critically ill cancer patients at risk of developing ARF. Methods: We performed a retrospective chart review of 100 consecutive patients who received fenoldopam mesylate for at least 72 h in the medical and surgical ICUs of The University of Texas M. D. Anderson Cancer Center who were at risk of developing ARF. Eighteen patients received low-dose fenoldopam mesylate (≤ 0.05 µg/kg/min). The remaining 82 patients received high-dose fenoldopam mesylate (0.07–0.1 µg/kg/min). Data were collected relating to drug dosage, patient demographics, severity of illness, and indices of renal function. Results: Patients were moderately ill, with a mean APACHE II score of 18 ± 6 at initiation of fenoldopam infusion. Eighty-five percent of patients had at least two risk factors for the development of ARF, and 20% had four. For the group overall, the incidence of ARF was 13%, and the hospital mortality rate was 37%. When compared with the low-dose group, patients who received high-dose fenoldopam had a significantly shorter ICU length of stay despite a significantly higher APACHE II score (p = 0.01). The high-dose group also had a highly significant decrease in serum creatinine levels at 72 h (p = 0.005). Conclusions: These data support the hypothesis that fenoldopam mesylate may provide a degree of dose-dependent renal protection in cancer patients with early acute renal failure.     

Natriuretic and renoprotective effect of chronic oral neutral endopeptidase inhibition in acute renal failure

Neutral endopeptidase (NEP: EC 3.4.24.11) is involved in the degradation of peptides such as atrial natriuretic peptide, angiotensin II (AngII), and endothelin-1 (ET-1). In this study we propose that NEP inhibition provides protection in glycerol-induced acute renal failure (ARF). Renal vascular responses were evaluated in ARF rats where ARF was induced by injecting 50% glycerol in candoxatril, a NEP inhibitor (30 mg/kg, orally; for 3 weeks) pretreated rats. AngII and U46619 (a TxA₂ mimetic) vasoconstriction was increased (2- to 4-fold) in ARF while ET-1 vasoconstriction was surprisingly reduced (23 ± 3%; p < 0.05). In ARF, candoxatril paradoxically enhanced ET-1 response (60 ± 20%; p < 0.05) but reduced AngII vasoconstriction (51 ± 11%; p < 0.05) without affecting U46619 response. However, candoxatril treatment was without effect on plasma ET-1 and TxB₂ levels in ARF. Candoxatril reduced plasma AngII by 34 ± 4% (p < 0.05) in ARF which was ～3.5-fold higher compared to control. Candoxatril doubled the nitrite excretion in control but was without effect on proteinuria or nitrite excretion in ARF. Candoxatril enhanced Na⁺ and creatinine excretion in ARF by 73 ± 9% and 33 ± 2%, respectively. These results suggest that NEP inhibition may confer protection in glycerol-induced ARF by stimulating renal function but without a consistent effect on renal production and renal vascular responses to endogenous vasoconstrictors.     

Torsemide Versus Furosemide After Continuous Renal Replacement Therapy Due to Acute Renal Failure in Cardiac Surgery Patients

Acute renal failure (ARF) usually develops in 5% to 30% of patients undergoing heart surgery and is associated with a more complicated clinical evolution course and with an excessive mortality of up to 80%. The objective of this study was to verify the frequency of ARF in postoperative coronary artery bypass surgery with and without cardiopulmonary bypass, by the evaluation of renal function markers' performance [ plasma creatinine, plasma urea, urinalysis, fractional excretion of sodium, creatinine clearance and Alpha‐glutathione S‐transferase (α‐GST)], besides to verify possible relations between clinical variables involved in postoperative heart surgery and the occurrence of renal insufficiency.     

Does urinalysis predict acute renal failure after heart surgery?

Acute renal failure (ARF) usually develops in 5% to 30% of patients undergoing heart surgery and is associated with a more complicated clinical evolution course and with an excessive mortality of up to 80%. The objective of this study was to verify the frequency of ARF in postoperative coronary artery bypass surgery with and without cardiopulmonary bypass, by the evaluation of renal function markers' performance [plasma creatinine, plasma urea, urinalysis, fractional excretion of sodium, creatinine clearance and Alpha-glutathione S-transferase (alpha-GST)], besides to verify possible relations between clinical variables involved in postoperative heart surgery and the occurrence of renal insufficiency.     

Renal failure in the ICU: comparison of the impact of acute renal failure and end-stage renal disease on ICU outcomes

BACKGROUND: Acute renal failure (ARF) is associated with a persistent high mortality in critically ill patients in intensive care units (ICUs). Most studies to date have focused on patients with established, intrinsic ARF or relatively severe ARF due to multiple factors. None have examined outcomes of dialysis-dependent chronic renal failure [end-stage renal disease (ESRD)] patients in the ICU. We examined the incidence and outcomes of ARF in the ICU using a standard definition and compared these to outcomes of ICU patients with either ESRD or no renal failure. We sought to determine the impact of renal dysfunction and/or loss of organ function on outcome. METHODS: We prospectively scored 1530 admissions to eight ICUs over a 10-month period for illness severity at ICU admission using the Acute Physiological and Chronic Health Evaluation (APACHE III) evaluation tool. Patients were defined as having ARF based on the definition of Hou et al (Am J Med 74:243-248,1983) designed to detect significant measurable declines in renal function based on serum creatinine. ESRD patients were identified as being chronically dialysis-dependent prior to ICU admission and the remainder had no renal failure. Clinical characteristics at ICU admission and ICU and hospital outcomes were compared between the three groups. RESULTS: We identified 254 cases of ARF, 57 cases of ESRD and 1219 cases of no renal failure for an incidence of ARF of 17%. Roughly half the ARF patients had ARF at ICU admission and the remainder developed ARF during their ICU stay. Only 11% of ARF patients required dialysis support. ARF patients had significantly higher acute illness severity scores than those with no renal failure, whereas patients with ESRD had intermediate severity scores. ICU mortality was 23% for patients with ARF, 11% for those with ESRD, and 5% for those with no renal failure. There was no difference in outcome between patients who had ARF at ICU admission and those who developed ARF in the ICU. Patients with ARF severe enough to require dialysis had a mortality of 57%. APACHE III predicted outcome very well in patients with no renal failure and patients with ARF at the time of scoring but underpredicted mortality in those who developed ARF after ICU admission and overestimated mortality in patients with ESRD. CONCLUSIONS: ARF is common in ICU patients and has a persistent negative impact on outcomes, although the majority of ARF is not severe enough to require dialysis support. The mortality of patients with ARF from all causes is almost exactly similar to that noted using the same criteria two decades ago. More profound ARF requiring dialysis continues to have an even greater mortality. Nevertheless, acute declines in renal function are associated with a mortality that is not well explained simply by loss of organ function. The majority of ARF patients who did not require dialysis still had a considerably higher mortality than the ESRD patients, all of whom required dialysis; while ARF patients who did require dialysis had a much higher morality than ESRD patients. APACHE III performs well and captures the mortality of patients with ARF at the time of scoring. Development of ARF after scoring has a profound effect on standardized mortality. We were unable to identify a unique mortality associated with ARF, but the presence of measurable renal insufficiency continues to be a sensitive marker for poor outcome.     

Acute renal failure after isolated CABG surgery: six years of experience

BACKGROUND: A prospective observational study was carried out in a Cardiosurgical Intensive Care Unit (ICU) in order to evaluate the incidence of Acute Renal Failure (ARF) after coronary artery bypass graft surgery and identify its predictors. The effects of ARF on outcome were also investigated. METHODS: The study enrolled 3,013 consecutive patients undergoing coronary artery bypass graft surgery. Baseline variables including age, sex, preoperative renal failure, left-ventricular dysfunction, emergency surgery, neurological adverse events, patient history of chronic obstructive pulmonary disease and diabetes mellitus were collected. Intraoperative variables were: type of surgery (on- or off-pump), intra-aortic balloon pump placement, and cardiopulmonary bypass duration. The measured postoperative variables were: low cardiac output syndrome, hemorrhage, transfusion of blood products, and surgical revision. RESULTS: Preoperative renal dysfunction (creatinine >1.4 mg/dL), blood transfusion, low-output syndrome, emergency surgery, low ejection fraction and age were independently associated with ARF. The median (interquartile range) ICU stay was 5.5 (range 4-11.5) days in patients who did and 1 (range 1-2) day in those who did not develop ARF (P<0.001). The median (interquartile range) hospital length of stay was 10 (range 8-21) days in patients who did and 5 (range 4-7) days in those who did not develop ARF (P<0.001). CONCLUSION: Preoperative renal dysfunction, blood transfusion, low-output syndrome, emergency surgery, low ejection fraction and age were independently associated with ARF. Length of ICU and hospital stay were reduced in patients not developing ARF.     

Renal Potassium Excretion: Comparison between Chronic Renal Disease Patients and Old People

Senescence and chronic renal failure bring about a progressive glomerular filtration reduction. Moreover, a reduction in glomerular filtration usually modifies the potassium renal excretion. In the present study, we compared the renal potassium handling between old and chronic renal disease populations. Materials and Methods: Fifty-five volunteers were studied, 43 of them were healthy old persons and 12 were predialysis chronic renal disease patients. Exclusion criteria were: presence of altered plasma potassium (Kp), diabetes mellitus, obstructive uropathy, drugs that could alter plasma potassium levels. All volunteers were on a diet with a potassium content around 50 mmol/day (3-day dietary register). We measured potassium, creatinine, urea in plasma and 24 hours urine. We also measured creatinine clearance (CrCl) and fractional excretion of potassium (FEK), and we studied the relationship between these parameters. Statistical analysis was made using Student’s test. Results: Slopes of the correlation curves between CrCl and FEK. Conclusion: The relationship between creatinine clearance and fractional excretion of potassium in old and chronic renal disease groups were different with the excretion of potassium being lower in the elderly.     

Mortality Risk Factors and Validation of Severity Scoring Systems in Critically Ill Patients with Acute Renal Failure

Background. Risk stratification and prediction of outcome in acute renal failure patients in the intensive care unit are important determinants for improvement of patient care and design of clinical trials. Methods. In order to identify mortality risks factors and validate general and specific predictive models for acute renal failure (ARF) patients in the intensive care unit (ICU), 324 patients were prospectively evaluated. Multivariate analysis by logistic regression was utilized for identification of mortality risk factors. Discrimination and calibration were used to evaluate the performance of the following models at referral to nephrologist and at initiation of renal replacement therapy: APACHE II, SAPS II, LODS, and ATN-ISI. Organ failure was assessed by SOFA and OSF. Results. The hospital mortality rate was 85%. The identified mortality risk factors were: age ≥ 65 yr, BUN ≥ 70 mg/dL, ARF of septic origin, and previous hypertension. Serum creatinine ≥ 3.5 mg/dL, systolic blood pressure ≥ 100 mm Hg, and normal consciousness were associated with mortality risk reduction. Performance of all prognostic models was disappointing with unsatisfactory calibration and underestimation of mortality on the day of referral to the nephrologist and at initiation of renal replacement therapy. Conclusions. Cross-validation of prognostic models for ARF resulted in poor performance of all studied scores. Therefore, a specific model is still warranted for the design of clinical trials, comparison of studies, and for prediction of outcome in ARF patients, especially in the ICU.     

Soluble intercellular adhesion molecule-1 (sICAM-1) after kidney transplantation: the origin and role of urinary sICAM-1?

BACKGROUND: Intercellular adhesion molecule-1 (ICAM-1) binds to leukocyte adhesion receptors LFA-1 and MAC-1, and mediates leukocyte adhesion to target structures. During acute rejection there is increased expression of ICAM-1 in vascular and tubulointestial cells, and consequently accumulation of inflammatory leukocytes. Soluble ICAM-1 (sICAM-1) is released from ICAM-1 expressing cells and excreted into the surrounding fluid. Increased serum sICAM-1 levels are found in patients with acute rejections of various allografts, and high urinary levels in steroid resistant acute kidney allograft rejection. METHODS: Urinary excretion of sICAM-1 was measured by EIA in 136 kidney allograft recipients during the first 1-6 post transplant weeks: 30 patients developed acute rejection, and 106 patients had stable graft function. The molecular weight, binding to hyaluronan, and the origin of urinary sICAM-1 were studied. RESULTS: We show that urinary sICAM-1 circulates as a monomer with a molecular weight between 50 and 100 kD. It binds to immobilized, but not to circulating hyaluronan. About one week after transplantation the mean sICAM-1/creatinine ratio (306 ng/mmol) in transplanted patients was higher than in the healthy controls (167 ng/mmol, P<0.01), and remained basically unchanged during the follow-up in patients with stable graft function, whereas it increased in patients developing rejection, being about 2.5-fold above the initial level a few days before rejection (P<0.01). Urinary sICAM-1 did not correlate with the urinary albumin, whereas in patients developing rejection it correlated with urinary IL-2R (r=0.5146, P<0.001), a marker of lymphocyte activation. In the urinary sediment of rejecting patients ICAM-1 was demonstrated in the tubular epithelial cells, and in the macrophages. CONCLUSIONS: Increased urinary excretion of sICAM-1 was demonstrated in kidney transplanted patients a few days before acute rejection. It seems to originate from activated macrophages and/or from the tubular epithelial cells. The fact that urinary sICAM-1 is not bound to hyaluronan or to leukocytes suggests that it is not able to compete with membrane-bound ICAM-1 for these bindings, but may do so for the binding of activated macrophages.     

Simple blood and urinary parameters measured at ICU admission may sign for AKI development in the early postoperative period: a retrospective,exploratory study

Recent studies have suggested that some blood physicochemical and urinary biochemical parameters have a standardized behavior during acute kidney injury (AKI) development. The changes in these parameters frequently begin to occur before significant rises in serum creatinine (sCr) and may help in identifying patients with more subtle decreases in glomerular filtration rate (GFR). Surgical patients have an increased risk of AKI but renal impairment is usually not evident at ICU admission. We hypothesized that the surgical patients who have AKI diagnosed in the early postoperative period have an impaired GFR since ICU admission, indirectly inferred by alterations in these blood physicochemical and urinary biochemical parameters even in the presence of a still normal sCr. We retrospectively evaluated 112 surgical patients who were categorized according to AKI development during the first 3 ICU days. Twenty-eight patients developed AKI, most of them in the first day (D1) after ICU admission (D0). AKI patients had, at D0, lower serum pH and albumin, higher C - reactive protein (CRP), lower urine sodium (NaU) and fractional excretion of urea (FEUr). Fractional excretion of potassium (FEK) was high in both groups at D0 but remained high in the subsequent days only in AKI patients. Very low CRP and high serum albumin, high NaU and FEUr values at ICU admission had a significant negative predictive value for AKI. We concluded that some easily assessed parameters in blood and urine may help to identify patients with indirect signs of increased inflammatory response and decreased GFR at ICU admission, which could help to predict the risk of postoperative AKI development.     

Antioxidant U74389G Improves Glycerol-Induced Acute Renal Failure without Affecting PPARγ Gene

Oxygen metabolites play an important role in the pathogenesis of myoglobinuric acute renal failure (ARF). Previously, we have reported a down regulation of peroxisome proliferator activated receptor γ (PPARγ) in glycerol-induced ARF, and the induction of PPARγ has been shown to provide renal protection. In this study, we determined the protective influence of U74389G, a hydroxyl radical scavenger in myoglobinuric ARF, and its association with PPARγ-mediated renal protection in the rat. Vascular responses to AII were determined in renal pre-glomerular vessels following the induction of ARF with glycerol (50%, v/v, i.m.). The extent of renal damage and function were assessed with or without pre-treatment with U74389G (10 mg/kg × 21 days). In ARF, AII vasoconstriction was enhanced (97%; p < 0.05), and AII production was doubled. U74389G reduced AII vasoconstriction and production by 42% (p < 0.05) and 40% (p < 0.05), respectively. U74389G reduced proteinuria (85%; p < 0.05), which was four times higher in ARF. Similarly, U74389G enhanced Na⁺ excretion twofold while reducing plasma creatinine (24%; p < 0.05) and BUN (31%; p < 0.05). U74389G attenuated free radical generation in ARF while nitrite excretion was unchanged. In renal pre-glomerular vessel, PPARγ expression, activity, and mRNA were significantly lower in ARF rats; this was unchanged with U74389G treatment. On the other hand, U74389G significantly reduced NFκB protein expression, which was elevated in ARF by 25% (p < 0.05). We suggest that antioxidant U74389G blunted renal injury and improved renal function in glycerol-induced ARF through the reduction of free radical production and/or inhibition of NFκB without affecting PPARγ.     

Unrecognized renal damage in critically ill patients

INTRODUCTION: The objective of this study was to evaluate the percentage of unrecognized renal damage in patients with normal creatinine and urea in serum and normal creatinine clearance and to evaluate the usefulness of various proteins and enzymes as supplementary procedures for the investigation of renal function. MATERIAL AND METHODS: Forty critically ill male patients (APACHE II-score > 20, injury severity score > 15) were daily screened for a period of five days. In the 1st group there were 30 patients with normal creatinine and urea in serum and with normal creatinine clearances. In the second group there were ten patients with increased values of these parameters. The base-line condition of all patients and any changes in hemodynamic, nutrition and ventilation were noted. Clearances of inulin, para-aminohippuric acid, and creatinine were measured and the Cockcroft-Gault equation was calculated daily for a period of five days. Excretion of alpha-1-microglobulin. Tamm-Horsfall-protein, alanine aminopeptidase, angiotensinase A, albumin and immunoglobulin G were also measured daily. RESULTS: 21 Patients of group 1 and all patients of group 2 showed the expected correlation between the routine parameters of creatinine and urea in serum and the level of protein and enzyme excretion. Nine patients of group 1 (30%) showed normal glomerular filtration rates but pathological excretion fractions of all proteins and enzymes. CONCLUSIONS: Although all routine parameters of renal function (creatinine and urea in serum, creatinine clearance both by 24-h collection period and from the Cockcroft-Gault equation), and additionally inulin and para-aminohippuric acid clearance were measured, no references on tubular and glomerular damage were found in 30% of the investigated patients.     

Risk Factors of Acute Renal Failure After Orthotopic Liver Transplantation: Single-center Experience

Background

Acute renal failure (ARF) is one of the most significant complications of orthotopic liver transplantation (OLT), associated with increased mortality rate and the development of chronic renal dysfunction. The aim of the study was to determine the perioperative risk factors for ARF in patients without previous history of renal disease who are undergoing OLT.

Materials and methods

Forty-six patients who developed ARF after OLT performed in 1 transplant center were included in the study, and 52 consecutive patients without that complication served as a control group. Renal dysfunction was defined as a glomerular filtration rate <60 mL/min/1.73 m². The data concerning preoperative diseases, perioperative renal function, first-line immunosuppressive therapy, and blood transfusion requirement were retrospectively analyzed and compared among groups. Logistic regression modeling was used to determine risk factors for ARF.

Results

Patients who developed ARF were significantly older (mean age 53.3 vs 46.3 years, P = .057), had higher level of preoperative (0.79 vs 0.71 mg/dL, P = .0062) and intraoperative (0.85 vs 0.74 mg/dL, P = .0045) creatinine. The risk factors for ARF were intraoperative and 24-hour post-transplant creatinine level >0.9 mg/dL and high-dose tacrolimus-based immunosuppression. Transfusion of ≤6 units of red blood cells diminished the risk of ARF. Sex and preoperative diseases were not predictive to ARF in our regression models.

Conclusion

Careful operative technique with low blood loss and immunosuppressive therapy of low nephrotoxic potential should be recommended in older patients to diminish the risk of renal dysfunction after orthotopic liver transplantation. Patients with higher levels of perioperative creatinine should be considered to have first-line immunosuppression without calcineurin inhibitors or with low-dose immunosuppressants of known nephrotoxic potential.     

Serum and urinary insulin-like growth factor-1 and tumor necrosis factor in neonates with and without acute renal failure

Acute renal failure (ARF) in neonates may occur after renal ischemia. Growth factors participate in the tubular regeneration process. Insulin-like growth factor-1 (IGF-1) is produced in the kidney during the recovery phase of ARF. Tumor necrosis factor-alpha (TNFα) may play a role in renal apoptosis. We examined serum and urinary IGF-1 and TNFα in neonates with or without ARF after asphyxia, in order to assess their possible use as markers of renal damage and recovery. We studied 20 full-term asphyxiated neonates, 10 with ARF and 10 without ARF, and compared them with 13 normal newborns for 7 days after birth. Blood urea, creatinine, pH, base deficit, and serum and urine IGF-1 and TNFα were assessed. Neonates with ARF had more-severe acidosis than patients without ARF. All patients had lower serum IGF-1 values immediately after birth than control children. Serum IGF-1 remained low in the ARF patients. The initial urinary IGF-1 was higher in all patients compared with control newborns, and remained elevated for the rest of the study only in the ARF neonates. Serum and urinary TNFα concentrations were similar for all healthy and diseased neonates. Measurement of serum and urinary IGF-1 levels in ARF neonates might be of additional value for clinical assessment of ARF. Received: 31 January 2001 / Revised: 30 October 2001 / Accepted: 7 January 2002     

Plasma levels of pancreatic secretory trypsin inhibitor in relation to amylase and lipase in patients with acute and chronic renal failure

Plasma levels of pancreatic secretory trypsin inhibitor (PSTI), lipase and amylase were measured in patients with chronic renal failure (CRF), patients undergoing regular hemodialysis treatment (RDT) or continuous ambulatory peritoneal dialysis (CAPD), patients with acute renal failure (ARF) and patients following successful cadaveric kidney transplantation. Plasma PSTI values were 9.2 +/- 0.8 ng/ml in controls (CO), 156.9 +/- 16.2 ng/ml in CRF patients, 257.6 +/- 22.3 ng/ml in RDT patients, 376.8 +/- 57.5 ng/ml in CAPD patients and 2,300 +/- 276.9 ng/ml in patients with posttraumatic ARF. RDT patients with malignant diseases displayed significantly higher PSTI values (1,014 +/- 148.7 ng/ml; p less than 0.01) than RDT patients without malignancy. Transplant patients with normal kidney function (creatinine 1.25 +/- 0.1 mg/dl) showed significantly lower PSTI values (16.7 +/- 2.1 ng/ml) than transplant patients with impaired renal function (creatinine 4.7 +/- 0.5 mg/dl; PSTI 72.8 +/- 11.8 ng/ml; p less than 0.01). Daily urinary excretion of PSTI increased from 26.7 +/- 3.1 micrograms (CO) to 551.8 +/- 54.8 micrograms in CRF patients. In CAPD patients, daily peritoneal loss of PSTI was 164.3 +/- 58.4 micrograms. Plasma PSTI values increased during hemodialysis with dialyzers made of cuprophan (317.0 +/- 32.6 vs. 422.0 +/- 46.2 ng/ml; p less than 0.05) and decreased with polysulfone dialyzers (226.6 +/- 19.9 vs. 86.6 +/- 18.1 ng/ml). There was no correlation between PSTI and urea, creatinine, lipase or amylase in each tested group. Our results document markedly elevated plasma PSTI values in all forms of renal insufficiency, suggesting extrapancreatic PSTI production and/or reduced renal elimination.     

Urinary biochemistry in experimental septic acute renal failure.

BACKGROUND: Several biochemical urine tests and derived indices are reported as useful in the diagnosis of acute renal failure (ARF) and its classification in prerenal (hypoperfusion) or intrarenal (acute tubular) necrosis. However, they have not been adequately studied in sepsis, the most frequent cause of ARF in ICU. METHODS: In 10 female Merino ewes, we implanted flow probes around the pulmonary and renal arteries to measure cardiac output and renal blood flow (RBF) continuously. Cardiovascular variables were monitored and urine samples collected during a 48 h control period and one week later during a 48 h period of hyperdynamic sepsis induced by an infusion of live Escherichia coli. RESULTS: Infusion of live E. coli induced systemic hyperdynamic sepsis with renal vasodilatation and increased RBF. Serum creatinine increased from 73.3 +/- 15.1 to 276.9 +/- 156.3 micromol/l (P < 0.05) and creatinine clearance decreased from 84.6 +/- 21.4 to 27.5 +/- 21.4 ml/min (P < 0.05). Urine sodium concentration (UNa) decreased significantly from 164.5 +/- 50.4 to 14.6 +/- 14.3 mmol/l, fractional excretion of sodium (FeNa) from 1.5 +/- 0.17 to 0.12 +/- 0.11%, fractional excretion of urea nitrogen (FeUn) from 62.7 +/- 9.5 to 11.5 +/- 15.4%, and urine osmolality from 724.8 +/- 277.1 mosmol/l to 329.0 +/- 52.1 mosmol/l. The u/p creatinine ratio did not change. CONCLUSION: Sustained Gram-negative sepsis induced a hyperdynamic state and hyperaemic ARF. Despite increased renal perfusion, UNa, FeNa and FeUn decreased significantly. Our findings suggest that, in sepsis, these urinary biochemical changes are not reliable markers of renal hypoperfusion.