Search

Background: Acute kidney injury (AKI) requiring renal replacement therapy (RRT) is associated with high in-hospital morbidity and mortality in critically ill patients. Long-term outcomes have received little attention., Methods: The aim of this study was to characterize AKI-chronic kidney disease (CKD) nexus in critically ill patients with AKI (RIFLE class F). We performed a single-centre prospective observational study of 425 consecutive critically ill patients with AKI requiring RRT. None of these patients had pre-existing kidney disease. Primary outcomes were vital status and renal function at hospital discharge and at 5 and 10 years of follow-up., Results: The overall in-hospital mortality of the study cohort was 47%, the mortality rates at 1, 5 and 10 years were 65, 75 and 80%, respectively. At hospital discharge, recovery of renal function was complete in 56% of survivors. None of these patients developed CKD during follow-up. Ninety percent of the 100 survivors with partial recovery of renal function had ongoing CKD during long-term follow-up. CKD progressed to end-stage renal disease (ESRD) in 12 patients (3% of the cohort or 5% of survivors). The patients with post-AKICKD had a higher prevalence of hypertension, a higher rate of fatal cardiac diseases and a higher all-cause death rate., Conclusion: Long-term survival of critically ill patients with AKI requiring RRT is poor and determined by the development of de novo CKD. There is a need for close follow-up of patients surviving AKI to prevent progressive CKD and to reduce associated lethal cardiac events.

Background: Current research priorities in critical care medicine are focusing on long-term outcomes of survivors of critical illness. Severe acute kidney injury (AKI) is a common occurrence in intensive care. However, few studies have followed up these patients beyond 12 months after hospital discharge., Methods: Of a cohort of 425 patients, 226 survivors with severe AKI necessitating renal replacement therapy (RRT) were followed up for 60 months after hospital discharge. None of these patients had pre-existing kidney disease. Vital status and renal function were documented annually for 5 years., Results: None of the discharged or transferred patients was dependent on RRT; 57% had complete recovery and 43% had partial recovery of renal function. During the first year after hospital discharge, 18% of survivors died, during the second year 4% and during the third to fifth year 2% per year. At 5 years, 25% of the cohort were still alive. Further improvement in renal function (eGFR) was noted in 26 patients within the first year only. Deterioration of renal function occurred in eight patients. At 5 years, renal function was normal in 86% of the remaining survivors, it was impaired in 9% and 5% of the patients alive needed dialysis again. The proportional Cox regression analysis model showed that pre-existing extrarenal comorbidity, surgery and partial recovery of renal function were independent determinants of long-term survival., Conclusions: This prospective observational study indicates that severe AKI is not only a determinant of excess in-hospital case fatalities of critically ill patients, but it also carries significant implications for long-term mortality.

Background: Data on the incidence of end-stage renal disease (ESRD) resulting from irreversible acute tubular necrosis (ATN) are controversial. This prospective cohort study was designed to assess the need for short- and long-term dialysis in critically ill patients with severe ATN and to define risk factors for lack of renal recovery., Methods: 433 consecutive patients with clinically diagnosed severe ATN necessitating renal replacement therapy were enrolled. Eight patients were excluded because renal biopsy revealed another cause of acute renal failure. None of the remaining 425 patients had pre-existing chronic renal insufficiency. Primary outcome criteria were recovery of renal function at discharge and ESRD status at 1 year follow-up., Results: The overall in-hospital mortality of the cohort was 47%. At discharge, 57% of the 226 surviving patients had normal renal function, 33% had mild to moderate renal failure (serum creatinine: 1.3-3 mg/dl) and 10% had severe renal failure (serum creatinine: 3-6 mg/dl). Multivariate analysis showed that neither patient characteristics (age, gender, comorbid conditions), severity of illness (APACHE III, number of failed organs) nor mode and duration of renal replacement therapy were related to recovery of renal function. After 1 year, 76 of the surviving patients had died and in one patient chronic renal failure had progressed to ESRD., Conclusions: If critically ill patients with normal renal function prior to the renal insults survive the precipitating cause of ATN, the overwhelming majority will recover sufficient renal function.

Background: While folic acid deficiency causes macrocytic anaemia in non-renal patients, the relevance of altered folate metabolism in anaemia of end-stage renal disease and its response to rHu-EPO is less clear., Methods: Ten haemodialysis patients with macrocytic anaemia due to dietary folic acid deficiency were compared to 10 matched (age, duration of dialysis, degree of anaemia) patients with normocytic normochromic anaemia. Nineteen patients received erythropoietin-alpha intravenously thrice weekly. The study design was a prospective crossover (ABA) comparison of the effects of intravenously administered high doses of folic acid on haemoglobin levels and EPO doses, with 6 months active supplementation (B) and two periods of 6 months duration each without folic acid supplementation (A)., Results: The two patient groups did not differ at recruitment. Red blood cell folate levels were normal in patients with normocytic anaemia, but they were subnormal in all patients with macrocytic anaemia. Compared to the first period without folic acid supplementation, patients with macrocytic anaemia had significantly higher haemoglobin levels despite lower EPO doses after 6 months high-dose folic acid, and red cells had become normocytic. The removal of folic acid supplementation resulted in re-occurrence of macrocytosis and in a significantly lower response to rHu-EPO. In contrast, high-dose folic acid supplementation had no effect on response to rHu-EPO in patients with normocytic anaemia., Conclusions: Folic acid deficiency may occur in elderly haemodialysis patients with poor dietary folate intake without regular oral supplementation and may cause hyporesponsiveness to rHu-EPO. Macrocytosis is a simple and cheap indicator for folate deficiency in end-stage renal disease patients on maintenance dialysis.

Background: Residual renal function is beneficial for adequacy of haemodialysis, quality of life and mortality in dialysis patients. Our prospective randomised investigation aimed to analyse the effects of the microbiological quality of dialysis fluid on the course of residual renal function after initiation of haemodialysis., Methods: Thirty patients starting haemodialysis were randomly assigned to ultrapure or conventional dialysate. During the 24-month study period, creatinine clearance, CRP and IL-6 levels, hydration status, number of hypotensive episodes and blood pressure recordings were assessed every 6 months., Results: Residual renal function declined in both groups during the study period, although there were no statistically significant differences in demographic (age, gender), renal (cause of end-stage renal disease, residual renal function, hypertension, ACE inhibitors) and treatment characteristics (Kt/V urea) at recruitment. The use of mildly contaminated (up to 300 CFU/ml) dialysate resulted in higher CRP and IL-6 levels and more pronounced loss of residual renal function. Multiple regression analysis showed that the microbiological quality of the dialysate is an independent determinant of the loss of residual renal function., Conclusions: Ultrapure dialysis fluid combined with high-flux synthetic membranes are effective components of renal replacement therapy to slow the loss of residual renal function in haemodialysis patients. These improvements of haemodialysis are desirable, but add to treatment costs.

Background: The study was designed to investigate the safety and feasibility of gadopentetate dimeglumine, a gadolinium-based contrast medium, as an alternative angiographic contrast agent in patients with impaired renal function and high risk for iodinated contrast-induced nephropathy., Methods: Gadopentetate dimeglumine was used as the radiographic contrast agent in 32 diagnostic or interventional angiographic procedures in 29 patients (59% diabetics) with severe renal insufficiency (average serum creatinine of 3.6+/-1.4 mg/dl). The average dose of gadopentetate dimeglumine was 0.34+/-0.06 mmol/kg body weight. Gadopentetate dimeglumine was used either alone (n=20) or in conjunction with carbon dioxide (n=12)., Results: Thirty-two angiographic procedures (24 diagnostic angiographies and 8 interventional procedures) were performed in 29 patients. For diagnostic purposes, eleven selective renal arteriographies, six angiographies of the iliac arteries and lower extremities, and seven venous angiographies of the upper extremity and central veins were performed. Interventional procedures consisted of two percutaneous transluminal renal angioplasties with stenting, four percutaneous peripheral vascular interventions, and two balloon angioplasties of a dialysis fistula. None of the patients, except one, had evidence of post-procedure contrast material-induced renal failure (increase in serum creatinine >0.5 mg/dl within 72 h) or other complications. This patient had a clinically important increase in serum creatinine level after percutaneous transluminal renal angioplasty and stenting, probably due to cholesterol embolism. Gadopentetate dimeglumine had sufficient radiographic density to allow adequate diagnostic visualization with digital subtraction equipment in all cases., Conclusions: Gadopentetate dimeglumine is an alternative and safe radiographic contrast agent for angiography and interventional procedures in patients with severe pre-existing renal impairment. In this population with high risk for contrast-induced acute renal failure, it is obviously less nephrotoxic than iodinated contrast media.

Background: Malnutrition and chronic systemic inflammatory response syndrome not only coexist in uraemia, but may also have a bi-directional cause-and-effect relationship. To evaluate the role of dialysate-related cytokine induction in inflammatory response and nutritional status, we conducted a prospective comparison of two dialysis fluids differing in their microbiological quality., Methods: Forty-eight early haemodialysis patients were assigned to either treatment with conventional (potentially microbiologically contaminated) or on-line produced ultrapure dialysis fluid. Study parameters were bacterial growth, markers of systemic inflammation (C-reactive protein (CRP) and interleukin 6), and parameters of nutritional status (estimated dry weight, upper mid-arm muscle circumference, serum albumin concentration, insulin-like growth factor 1, leptin, and protein catabolic rate). Patients were followed for 12 months., Results: There were no statistically significant differences in demographic and treatment characteristics, degree of bacterial contamination of the dialysate, markers of systemic inflammation, or parameters of nutritional status among the two treatment groups at recruitment. Changing from conventional to ultrapure dialysis fluid reduced significantly the levels of IL-6 (19+/-3 pg/ml to 13+/-3 pg/ml) and CRP (1.0+/- 0.4 mg/dl to 0.5+/-0.2 mg/dl), and resulted in significant increases in estimated dry body weight, mid-arm muscle circumference, serum albumin concentration, levels of the humoral factors, and in protein catabolic rate after 12 months. Continuous use of conventional dialysis fluid (median 40-60 c.f.u./ml) was not associated with significant alterations in markers of inflammation (IL-6 21+/-4 pg/ml vs 24+/-6 pg/ml, CRP 0.9+/-0.3 mg/dl vs 1.1+/-0.4 mg/dl) or of nutritional status at any time of the study. All differences in systemic inflammation and nutritional parameters observed during the study period (from recruitment to month 12) were significant between the two patient groups., Conclusions: Cytokine induction by microbiologically contaminated dialysis fluid has a negative impact on nutritional parameters of early haemodialysis patients. The microbiological quality of the dialysis fluid represents an independent determinant of the nutritional status in addition to known factors, such as dose of dialysis and biocompatibility of the dialyser membrane. Ultrapure dialysis fluid adds to the cost of the dialytic treatment, but may improve the nutritional status in long-term haemodialysis patients.

Background: Chronic inflammatory disorders or infections represent a major cause of hyporesponsiveness to recombinant human erythropoietin (rHuEpo). To test the hypothesis that dialysate-related cytokine induction alters the response to rHuEpo, we conducted a prospective study with matched pairs of chronic haemodialysis patients. We compared the effect of two dialysis fluids, differing in their microbiological quality, on the rHuEpo therapy., Methods: Thirty male patients with end-stage renal disease maintained on regular haemodialysis were assigned either to a group treated with conventional (potentially microbiologically contaminated) dialysate (group I) or to a group treated with online-produced ultrapure dialysate (group II). Randomization was stratified according to the maintenance dose of rHuEpo necessary to maintain a target haemoglobin level of 10-10.5 g/dl. Patients were followed for 12 months. Kt/V was calculated by the formula of Daugirdas. Haemoglobin levels were measured weekly and serum ferritin concentrations were determined at 6-week intervals. C-reactive protein (CRP) and interleukin-6 (IL-6) was measured by an ELISA at the start of the study and after 3, 6 and 12 months., Results: In group I, continuous use of bicarbonate dialysate did not change the rHuEpo dosage given to achieve the target haemoglobin level and was associated with elevated surrogate markers (CRP, IL-6) of cytokine-induced inflammation. The switch from conventional to online-produced ultrapure dialysate in group II resulted in a lower bacterial contamination with a significant decrease of CRP and IL-6 blood levels. It was accompanied by a significant and sustained reduction of the rHuEpo dosage, which was required to correct the anaemia. Using multiple regression analysis, IL-6 levels are shown to have a strong predictive value for rHuEpo dosage in both groups., Conclusions: Our data demonstrate that dialysate-related factors such as low bacterial contamination can induce the activation of monocytes, resulting in elevated serum levels of IL-6. Dialysate-related cytokine induction might diminish erythropoiesis. The use of pyrogen free ultrapure dialysate resulted in a better response to rHuEpo. Not only would it save money, but it would also help to maintain an optimal haemoglobin level without further increase in rHuEpo dosage.

Background: Highly permeable biocompatible dialysis membranes may postpone the development of AB-amyloidosis, but the relative contribution of enhanced flux or reduced inflammation by highly biocompatible membranes and sterile dialysis fluid remains unknown., Methods: In this retrospective investigation, 89 patients with end-stage renal disease maintained on regular haemodialysis for at least 10 years and treated with one type of dialysis membrane exclusively were selected for analysis. They were divided into three groups: low-flux, bioincompatible cellulose (I), low-flux, intermediately biocompatible polysulphone or PMMA (II), or high-flux, highly biocompatible polysulphone or AN69 (III). In addition, the patients were analysed according to the microbiological quality of the dialysis fluid, which had been tested regularly and was classified either as standard or as intermittently contaminated. The clinical manifestations indicative of AB-amyloidosis, namely, carpal tunnel syndrome, arthropathy and bone cysts, were diagnosed after recruitment., Results: Clinical symptoms were most pronounced in group I, intermediate in group II, and lowest in group III. Patients treated with intermittently contaminated dialysis fluid showed a higher prevalence of AB-amyloidosis than patients with less contaminated dialysis fluid. Logistic regression analysis demonstrated that the flux characteristics of the dialyser and the microbiological quality of the dialysis fluid as well as the biocompatibility of the dialyser were independent determinants of AB-amyloidosis., Conclusion: It would be prudent clinical practice to employ high-flux biocompatible membranes in conjunction with ultrapure dialysis fluid for the treatment of end-stage renal disease patients who need to remain on long-term haemodialysis.

We compared peritoneal dialysis effluents from 18 CAPD patients who had not suffered from peritonitis during the last 6 months (group 1) with the effluents from five patients with acute peritonitis (group 2), measuring activation markers of coagulation and fibrinolysis. These markers included prothrombin fragment F1 + 2 (F1 + 2), thrombin-antithrombin III complex (TAT), fibrin monomer (FM), and fibrin degradation products (FbDP). In the dialysate of group 1 we found remarkably high levels of F1 + 2, TAT and FM concomitant with a high concentration of FbDP, indicating a high rate of intraperitoneal fibrin turnover. The balance between peritoneal generation and degradation of fibrin was disturbed in untreated patients of group 2, who had significantly higher levels of coagulation markers and a higher ratio between FM and FbDP. Seven days after treatment with intraperitoneal administration of antibiotics and heparin, F1 + 2, TAT, FM and FbDP decreased significantly. To evaluate the role of mesothelial cells (MC) in the high peritoneal fibrin turnover we investigated the expression of tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA), plasminogen activator inhibitor type-1 (PAI-1), and tissue factor in cultured human peritoneal MC under basal conditions and after exposure to tumour necrosis factor alpha (TNF alpha), interleukin-1 alpha (IL-1 alpha), or bacterial lipopolysaccharide (LPS). The exposure of MC to TNF alpha or to a lesser extent IL-1 alpha or LPS reduced their fibrinolytic activity by decreasing t-PA production and increasing PAI-1 synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

We investigated whether cGMP might be a suitable marker of ideal weight in chronic haemodialysis patients. In 20 patients on chronic haemodialysis (10 males, 10 females, mean age 55.5 +/- 7.4 years; mean interdialytic weight gain 2.4 +/- 1.1 kg) we determined plasma ANP and cGMP values before and after several haemodialysis treatments. ANP and cGMP before haemodialysis were markedly elevated (ANP 255 +/- 190 pg/ml; cGMP 28.6 +/- 16.2 pmol/ml). A significant decrease was found after haemodialysis (ANP 169 +/- 88 pg/ml; cGMP 13.5 +/- 7.4 pmol/ml). These values were still well above normal. There was a significant positive correlation between excessive body-weight delta P (difference between actual weight and estimated ideal weight), indicating fluid overload and ANP before (r = 0.57; P less than 0.001) and after haemodialysis (r = 0.47; P less than 0.001) as well as cGMP before (r = 0.42; P less than 0.01) and after haemodialysis (r = 0.85; P less than 0.0001). With cGMP and delta P after haemodialysis, the correlation appeared to be close enough for clinical application. All patients with a cGMP value of 18 pmol/ml or more after haemodialysis had an excessive body-weight of at least 0.5 kg. We conclude from these data that the plasma cGMP value determined immediately after haemodialysis is a sensitive marker for hyperhydration in patients with end-stage renal disease.