Quantitative EEG findings in patients with chronic renal failure.

OBJECTIVE: Chronic renal failure frequently causes uremic encephalopathy with impairment of various cognitive functions, but the pathophysiology of uremic syndrome is complex and poorly understood. In this study, we wished to establish a reliable tool and monitor system to evaluate the central nervous system dysfunction of patients with uremic encephalopathy. METHODS: A group of 31 patients with chronic renal failure was assessed with online real time brain mapping using the CATEEM technology to detect deviations and abnormal EEG patterns. Quantitative EEG data were compared with those of an age-matched healthy control group and correlated to laboratory markers and various dosages of erythropoietin. RESULTS: Electrical power was most prominent in delta, theta and alpha frequencies in the temporal and central brain areas (electrode positions T5, T6, C3 and C4). Explorative statistical comparison of the two data sets with respect to these brain areas revealed that the increases in electrical power in delta, theta and alpha frequency bands were different from healthy people with p-values of p<0.003 (delta), p<0.0003 (theta), p<0.01 (alpha 1) and p<0.01 (alpha 2). In addition, high levels of hemoglobin were significantly correlated with higher theta activity. CONCLUSION: We detected distinct EEG deviations from normality in patients with chronic renal failure. Online real time brain mapping using the CATEEM technology provides a unique possibility to monitor mental impairment and serves as a control for therapeutical intervention.

Effect of a silver device in preventing catheter-related infections in peritoneal dialysis patients: silver ring prophylaxis at the catheter exit study.

Catheter-related infections remain a significant cause of method failure in chronic peritoneal dialysis (PD) therapy. Given the increasing antibiotic resistance, such nonpharmacological strategies as local silver devices attract more interest. To establish whether a silver ring device (designed by Grosse-Siestrup in 1992) mounted onto the PD catheter and placed at the exit site at skin level is effective in preventing exit-site and other catheter-related infections, a prospective 12-month, multicenter, controlled study stratified by diabetes status was conducted. The study subjects were assessed by an extensive structured inventory, including a broad spectrum of control variables, such as age, body mass index (BMI), Staphylococcus aureus carrier status, catheter features, mode and quality of PD therapy, comorbidity, and psychosocial rehabilitation. Ten experienced German outpatient dialysis centers (seven adult, three pediatric) participated in the trial. All eligible patients (n=195) from the study area without catheter-related infections during the ascertainment period were included (incidental subjects undergoing PD therapy for at least 3 months). The main outcome measures were the occurrence of first exit-site infections (primary study end point), sinus tract/tunnel infection, and peritonitis. Ninety-seven patients were assigned to the silver ring and 98 patients to the control group. Baseline characteristics of age, sex, proportion of pediatric and incidental patients, S aureus carrier status, and other variables were similar in both groups. The incidence of infections in the silver ring group versus the control group was as follows: 23 of 97 versus 16 of 98 patients had exit-site infections, 12 of 97 versus 12 of 98 patients had sinus tract/tunnel infections, 16 of 97 versus 18 of 98 patients had peritonitis, respectively. Kaplan-Meier analysis for the probability of an infection-free interval showed no statistical difference (log-rank test) between the two groups. Displacement of the silver ring contributed to study termination in 6% of the study group patients, including two patients with catheter loss. Univariate analysis and multiple logistic regression identified younger age (<50 years), low serum albumin level (<35 g/L), number of previously placed PD catheters, short cuff-exit distance (<2 cm), and S aureus nasal carriage as risk factors for the development of exit-site infections. In conclusion, our study does not show any benefit of the silver ring in preventing catheter-related infections in PD patients. Thus, prevention of infection-related method failure in PD still has to rely on conventional antibiotic treatment strategies and less so on alternative methods.

Increased reduction of dimethylarginines and lowered interdialytic blood pressure by the use of biocompatible membranes.

Hypertension contributes to cardiac and cerebrovascular complications in HD patients. Endogenous inhibitors of nitric oxide synthase accumulate in renal failure and may interfere with the regulation of vascular tone. We investigated the elimination of asymmetric dimethylarginine (ADMA) by using biocompatible Polyamide Strade mark membranes in low-flux (Polyflux 6L) or high-flux (Polyflux 14S) hemodialysis or hemodiafiltration (HDF) compared with hemodialysis with cellulosic membranes. Removal rates for ADMA, symmetric dimethylarginine (SDMA), and beta2-microglobulin significantly increased in HDF. The plasma total amino acid concentration and the arginine/ADMA ratio increased, and the mean 24-hour blood pressure decreased during the study. In a second study, we investigated whether plasma amino acids and interdialytic blood pressure are influenced by the use of a biocompatible membrane and HDF. Seventeen end-stage renal disease patients were treated for six weeks with hemodialysis using cellulosic membranes, six weeks with low-flux hemodialysis using Polyflux 6L, and six weeks with HDF using Polyflux 14S. Only in the diabetic patients were the hemoglobin concentration (from 10.6 +/- 1.5 to 11.9 +/- 0.6 mg/dL) and hematocrit (from 33.6 +/- 1.9 to 36.2 +/- 1.5%) increased significantly, whereas the mean 24-hour systolic blood pressure decreased (from 154 +/- 22 to 129 +/- 18 mm Hg). No significant changes were observed in nondiabetic patients. We conclude that primarily diabetic patients seem to benefit from the use of biocompatible membranes--most in HDF--after a period of six weeks. The regulation of nitric oxide pathways by ADMA removal and changed ADMA/arginine ratio might be contributing factors. Further prospective studies are required to show whether the long-term application of HDF or other changes of dialysis treatment modalities may help to improve well-being, morbidity, and mortality in hemodialysis patients.

The analgesic problem in the Federal Republic of Germany: analgesic consumption, frequency of analgesic nephropathy and regional differences.

The recent withdrawal of phenacetin from the pharmaceutical market in the FRG has stimulated the discussion of the extent of analgesic abuse and analgesic nephropathy (AN). Data from wholesale statistics, given here, revealed in the FRG population a high yearly per-capita consumption of analgesics (18.2 g), mostly used in mixed compounds. According to standardized data, the FRG ranks first among the north European countries. We suggest that the prevalence data given from the EDTA-registry (4.6% of the endstage renal population) underestimates the real extent of AN. AN in the FRG shows a north-to-south decline and is most prevalent in northern areas and West Berlin. It is assumed that the analgesic dilemma in the FRG is identical to the dilemma in Switzerland and Belgium.

Characteristics and clinical course of hemodialysis patients with analgesic-associated nephropathy.

The knowledge of some characteristic findings on the personality of patients with analgesic-associated nephropathy (AAN) may facilitate diagnosis of the disease at an early stage. We therefore investigated the 144 patients at our hemodialysis center and compared the AAN patients (33%) with those having other kidney diseases (controls). Patients with AAN were older (60 +/- 10 vs 52 +/- 15 years, p less than 0.001) and predominantly women. Acetaminophen and metamizol metabolites were detected more frequently in blood from the AAN patients than in that from the controls (25% vs 3%, p = 0.002). More AAN patients were smokers, and they more frequently complained of vague symptoms (pain, sensitivity to changes in weather, insomnia) and also more frequently requested prescriptions for analgesics, hypnotics, laxatives, stomachics and antipruritics. Because they were older, AAN patients had fewer occupational and financial problems. The compliance of the AAN patients was significantly better with respect to important dialysis parameters such as weight gain between dialysis treatments (3.6 +/- 1.3 vs 4.0 +/- 1.3% body weight, p less than 0.05) and diastolic blood pressure (81 +/- 12 vs 86 +/- 12 mmHg, p = 0.025). Despite an older age and higher morbidity, the cumulative 17-year survival rate of the AAN patients did not differ from that of the controls. We conclude that AAN patients have characteristic personality traits. Their better compliance, adjustment to the hemodialysis situation and social conditions are responsible for their good survival on hemodialysis.

Membrane plasma exchange in Goodpasture's syndrome.

We report two cases with Goodpasture's syndrome successfully treated by membrane plasma exchange. In both patients, pulmonary infiltrations and hemoptysis had already resolved after the first pulse methylprednisolone dose (1000 mg IV). Following plasma exchange, renal function did not further deteriorate in one patient and returned to normal in the other patient. From the clinical course of our patients and a review of the literature, we conclude that membrane plasma exchange is effective in preventing deterioration of renal function in Goodpasture's syndrome. Analysis of the literature shows that patients who respond to plasma exchange have significantly fewer crescents and lower plasma creatinine, while non-responders are more often oliguric or anuric and require dialysis at the time of plasma exchange.

Outcome of patients with ventricular assist devices and acute renal failure requiring renal replacement therapy.

The significance of acute renal failure (ARF) for patients treated with a ventricular assist device (VAD) is uncertain. There is little information on the outcome of patients who require renal replacement therapy during treatment with a VAD. A retrospective review was undertaken to evaluate the impact of renal failure requiring renal replacement therapy on such patients. Studied were 227 patients who were supplied with a VAD at the German Heart Institute Berlin. Fifty-five patients required renal replacement therapy during treatment with a VAD. These were compared with patients not needing renal replacement therapy (ARF and non-ARF groups). Significant differences for the end points of survival, heart transplantation, and discharge from hospital were observed in patients with ARF (p < 0.01). Survival was then analyzed according to indications for treatment with a VAD (bridge to transplantation or cardiac recovery after cardiotomy, transplantation, myocardial infarction, myocarditis, and endocarditis). Survival for bridge-to-transplantation patients was clearly influenced in a negative way by ARF (p < 0.01). For cardiac recovery patients, only a small difference in survival was observed (p = 0.05). We conclude that ARF is a negative predictor for bridge-to-transplantation patients. For cardiac recovery patients the impact of ARF on survival is marginally significant.

Vancomycin dosing in haemodialysis patients and Bayesian estimate of individual pharmacokinetic parameters.

A dose reduction of vancomycin to 1000 mg once a week usually is recommended for haemodialysis patients. Our modified dosing schedule consists of a loading dose of 1000 mg and a maintenance dose of 500 mg administered 3 times a week after haemodialysis. Different vancomycin regimens were retrospectively evaluated by therapeutic drug monitoring and bayesian parameter estimates in 39 dialysis patients. The mean (+/- SD) trough level in 7 patients receiving only the conventional dosage regimen was significantly lower than in 17 patients strictly treated by the modified schedule (7 +/- 4 versus 17 +/- 8 mg/L; p = 0.001). The corresponding peaks were low in both groups and no different (23 +/- 10 versus 27 +/- 12 mg/L). The one week average vancomycin clearance was significantly lower in the conventional dosage group compared to the modified dosage group (6 +/- 3 versus 10 +/- 3 ml/min; p = 0.001). High-flux dialysers were not used in the conventional dosage group but for 30 percent of the procedures in the modified dosage group, where the vancomycin one week average elimination half-life was 66 hours (+/- 18) and the volume of distribution 50 litres (+/- 5). As compared to the bayesian programme, NONMEM calculated comparable pharmacokinetic parameters but could be applied only in 5 cases with a sufficient number of concentration measurements. Ototoxicity occurred in 1 patient, whereas vancomycin treatment was judged as ineffective against infection in 5 of the 39 patients. Their troughs were below 15 mg/L.(ABSTRACT TRUNCATED AT 250 WORDS)

[Chronic use of analgesics]. / Daten zum chronischen Schmerzmittelgebrauch.

Quantitative aspects of longterm analgesic intake are presented, based on a case-control-study on the relation between regular analgesic intake and endstage renal failure in the area of West Berlin (1984-86). Lifetime analgesic consumption of more than 1000 persons were investigated. A total of 285 longterm analgesic users (185 cases = 35.8%; 100 controls = 19.3%) were detected. An odd ratio of 2.44 (95% CI: 1.77-3.39) was computed. Regular analgesic intake was defined as an intake of at least 15 analgesic doses per month continuously over a period of at least 12 months. 90% of the regular users preferred mixed analgesics compounds, in most cases with the psychotropic additive caffeine.

[Analgesics and laxatives as risk factors for cancer in the efferent urinary tract--results of the Berlin Urothelial Carcinoma Study]. / Analgetika und Laxantien als Risikofaktoren für Krebs der ableitenden Harnwege--Ergebnisse der Berliner Urothelkarzinom-Studie (BUS).

A retrospective case-control study (1990-1995), the Berlin Urothelial Cancer Study (BUS), examined analgesics and laxatives as risks for the induction of urothelial cancer in renal pelvis, ureter and bladder. Especially for renal pelvis cancer could observe substance and dose specific risk of compound analgesics. The analgesic substances Phenacetin, Paracetamol, Acetylsalicylic acid (ASA) and Pyrazolones were assessed. Besides a risk of contact laxatives (chemical or anthranoide ingredients) for urothelial cancer was found, not yet described. The highest risk shows the anthranoide plant Senna. Thus this study confirms the risk of specific analgesic ingredients and found an evidence for a new risk of contact laxatives. As both, analgesics and contact laxatives, are typical OTC--("Over the counter") products, a severe controlling is demanded and for laxatives further studies are needed.

De novo membrano-proliferative glomerulonephritis in a renal allograft.

De novo glomerulonephritis (GN) in the graft is an uncommon complication of renal transplantation. We report a case of de novo membrano-proliferative GN which occurred in a second cadaver allograft in a 42-year-old woman, who developed severe hypertension, nephrotic syndrome, and progressive renal failure. Our material and a review of the literature suggest an incidence of de novo GN of about 0.5-2%. In contrast to most of the cases described by other authors, the membrano-proliferative type of de novo GN in renal allografts seems to be very rare.

[Analgesic consumption in the Federal Republic of Germany. The extent and the risk groups]. / Analgetika-Verbrauch in der Bundesrepublik Deutschland. Ausmass und Risikogruppen.

An analysis of still unpublished sales statistics shows that during 1976-1983 the annual sales of all analgesic package units remained relatively stable (about 115 million units per year), while the consumption of large packings mostly preferred by analgesic abusers increased from 8.13 to 11.28 million (units of 100 tablets). The annual per capita consumption of analgesic substances (1983) was 18.2 g. Among these, drugs containing salicylate and phenazone headed the list, whereas phenacetin consumption is increasingly on the downgrade (0.87 g per capita). 95% of all analgesics are used outside of the clinics. Furthermore, 80% of them are purchased on the prescription-free market. High consumption of analgesics can be assumed in 5% of the normal population. Analgesic abuse is more prevalent in women, especially in some industrial areas.

Urothelial cancer at different tumour sites: role of smoking and habitual intake of analgesics and laxatives. Results of the Berlin Urothelial Cancer Study.

BACKGROUND: In Germany about 20000 new cases of urothelial cancer (UC) and about 7500 deaths from bladder cancer alone occur each year. Among the manifold risk factors, little research has been done on the role of smoking and the habitual intake of analgesics and laxatives-practices that are common in parts of the German population. The aim of this study is to define the proportion of risk derived from these preventable habits for the development of UC at its different sites. Subjects and methods. A case-control study in the area of the former West Berlin was performed from 1990 to 1995 including all newly diagnosed incident cases of UC from the eight hospitals of the study area. Study subjects and population-based controls individually matched by age (+/-2 years) and sex were evaluated by a standardized face-to-face interview about the lifelong exposure to cigarette smoking, analgesics, and laxatives. Adjusted risk analysis was carried out for the main exposure variables in relation to the different sites of UC in the bladder, ureter, and renal pelvis. RESULTS: Six hundred and forty-seven cases of UC (571 bladder, 25 ureter, and 51 renal pelvis) and an identical number of controls were included in the analysis (response rate in cases, 84.6%; in controls, 70.2%). Smoking increased the risk of bladder cancer (BC) by an odds ratio (OR) of 3.22 (95% confidence interval (CI) 2.29-4.52), that of ureter (URC) or renal pelvis cancer (RPC) together by OR 6.20 (95% CI 2.04-18.81), and that of RPC alone by OR 5.91 (95% CI 1.47-23.66). Ex-smoking was associated with an increased risk for BC (OR 1.55, 95% CI 1.10-2.19). Intake of more than 1 kg of phenacetin in analgesic mixtures was associated with an OR of 5.28 for RPC (intake of > or = 1 kg paracetamol, OR 3.27; > or = 1 kg pyrazolones, 1.12) and 0.75 for BC (not significant). Laxatives significantly increased the risk of BC (OR 2.14, 95% CI 1.26-3.63) and RPC/URC (OR 9.62, 95% CI 1. 01-91.24) in both sexes. CONCLUSION: Habitual risks from smoking and intake of laxatives significantly contribute to the development of UC, especially of the renal pelvis and ureter cancer. Intake of at least 1 kg of analgesic substances (anilides, pyrazolones) as calculated from this study base is associated with increased but not significant risks for RPC. These data underline that restrictive and educational measurements focusing on common habits would have a strong impact on preventing UC in Germany.

Morbidity of patients with analgesic-associated nephropathy and end-stage renal failure.

In our haemodialysis centre patients (n = 144), we compared 48 aspects of morbidity in patients with analgesic-associated nephropathy (AAN) and patients with other kidney diseases to determine the presence of characteristic diagnostic features of AAN in addition to a history of habitual analgesic intake. The comparison between 48 AAN patients and the control patients revealed statistically significant differences (p less than 0.05) with regard to myocardial infarction (25% vs 7%), angina pectoris (63% vs 32%), atrial fibrillation (21% vs 4%), arteriosclerosis obliterans of the lower extremity (52% vs 33%), anaemia (mean haemoglobin, 8.38 vs 9.16 g/dl), renal osteodystrophy (67% vs 41%), carpal tunnel syndrome (23% vs 7%), peptic ulcers and erosive gastritis (54% vs 23%), colonic diverticula (15% vs 4%), and haemorrhoids (67% vs 28%). AAN patients therefore have significantly higher morbidity with a characteristic pattern than do patients with other renal diseases.

Patients' expectations from renal grafting and transplantation outcome.

Prevailing reports on psychological prediction of renal graft integration are rare, mostly based on case studies. Focusing on patients' expectations from the transplantation process before grafting, we investigate the influence of psychological data and statements on the final transplantation results. In the whole group (n = 83) the attitude toward transplantation was very optimistic. Comparing the features of patients with successful graft outcome (n = 23) and graft failure or patient's death (n = 10) the latter group shows: lower scale values of optimistic attitude toward transplantation outcome, higher level of fear concerning surgical treatment, less willingness to agree preoperatively to second transplantation in case of first graft failure. Psychological data indicate a greater tendency toward more submissive, rigid, and depressive behavior. It is assumed that the patient's attitude and expectation on grafting is a part of the conditions influencing the final transplantation result. Further studies should prove this concept.

[Characteristics of terminal analgesics-induced nephropathy]. / Merkmale der terminalen Analgetika-Nephropathie.

The diagnosis of analgesic-associated nephropathy (AAN) may be missed because of the patients denial or regular analgesic intake. We therefore performed a cross-sectional study of the 144 patients of our hemodialysis center to investigate differences between the 48 patients with AAN (33%) and patients with other kidney diseases who served as controls. The aim was to find other attributes of analgesic users relating to social history, habits and morbidity. Dialysis patients with AAN were significantly older (60 +/- 10 versus 52 +/- 15 years) and more frequently women (65% versus 37%) compared with controls; they often had a family history of analgesic abuse. Comparison with an age-matched control group of hemodialysis patients with other kidney diseases showed that AAN patients smoked, used hypnotics and laxatives, and required prescriptions significantly more frequently; they were less frequently willing to undergo renal transplantation. With regard to accompanying diseases, they suffered significantly more often than the age-matched controls from anemia, renal osteodystrophy, peptic ulcer disease, diverticulosis, hemorrhoids, atrial fibrillation, coronary heart disease, hyperlipidemia, carpal tunnel syndrome, and urinary tract infections. The characteristic pattern of habits, social history and accompanying diseases may facilitate the diagnosis of AAN even in cases where analgesic consumption is denied.

[Acute interstitial nephritis caused by drugs]. / Akute interstitielle Nephritis durch Medikamente.

Within 30 months the diagnosis of drug-induced acute interstitial nephritis was made in ten patients with acute onset of renal failure of clinically unknown cause. Allergenic substances were discovered to be antibiotics, pyrazol and indol derivatives, piromidic acid and chlorazanil. In contrast to the known course of methicillin nephritis the clinical signs were undramatic. Non-oliguric renal failure predominated, sometimes with leucocyturia, microhaematuria and moderate proteinuria. Intermittent haemodialysis was necessary in half the cases. Renal function developed favourably without further specific treatment, however, plasma creatinine did not return to normal levels in most cases. Percutaneous renal biopsy was the definitive diagnostic step. Indications for biopsy in cases of unclear acute renal failure should thus be handled liberally in order to prevent continued drug exposure with the danger of irreversible renal failure.

[Risk factors for urothelial carcinoma: drinking measures, smoking and other life style-related risk factors--results of the Berlin Urothelial Study (BUS)]. / Risikofaktoren für das Urothelkarzinom: Trinkmenge, Rauchen und andere lebensstilbezogene Risikofaktoren--Ergebnisse der Berliner Urothelstudie (BUS).

With the exception of smoking and several occupational exposures there is little knowledge about risk factors for urothelial cancer. A case control study in the area of former West Berlin was performed from 1990-1995 to investigate the role of several lifestyle risk factors, such as smoking, drinking behaviour and regular intake of analgesics and laxatives. The study includes 647 hospital-based incident cases with bladder cancer (n = 571), renal pelvis cancer (n = 51), and ureter cancer (n = 25), and 647 population-based controls which were matched individually by sex and age. Data analyses were carried out using standard methods for case control studies (conditional multiple logistic regression analysis). Odds ratios (OR) and 95% confidence intervals (CI) were applied as effect parameter. Statistically significantly increased odds ratios were observed for current smoking (OR: 3.46, 95% CI: 2.50-4.78), previous but now abandoned smoking (OR: 1.51, 95% CI: 1.09-2.81), and for regular intake of laxatives (OR: 2.52, 95% CI: 1.56-4.09). Furthermore, an increased risk for urothelial cancer was observed for daily consumption of three and more litres of cold drinks (OR: 2.65 95% CI: 1.12-6.24). The results underline that lifestyle factors other than smoking may contribute to a higher risk of urothelial cancer.

[The quality of the treatment of diabetics in kidney failure in Germany]. / Behandlungsqualität niereninsuffizienter Diabetiker in Deutschland.

BACKGROUND AND OBJECTIVE: In recent years there has been a rapid increase in the number of dialysis-dependent diabetics in Germany. Survival on dialysis is not satisfactory and damage acquired in the preterminal stage of renal failure is thought to play an important role. Late referral to a nephrologist and insufficient quality of medical management are thought to contribute importantly to poor outcome. This hypothesis was evaluated in the present study. PATIENTS AND METHOD: The data of all 173 diabetic patients (16 with type 1, 157 with type 2 diabetes, 90 men, 83 women, mean age 63.3 [31-95] years), who had been referred in 1996 for the first time to five renal units, were retrospectively assessed using a structured protocol. RESULTS: Patients were usually referred in advanced renal failure (median creatinine clearance 29 ml/min, range 1-216) with insufficient control of systolic (170 [120-260] mmHg) and diastolic blood pressure (90 [60-180] mmHg), insufficient antihypertensive therapy (without treatment 32 of 173 patients; median number of classes of antihypertensive agents used 2 [range 1-6]; ACE inhibitors 79 of 173 patients), high HbA1c (7.9 [4.9-15.7]%) and LDL cholesterol (176 [67-307] mg/dl). Immediate dialysis was required in 45 patients. CONCLUSION: The data document insufficient quality of treatment and late incorporation of a nephrologist into the medical team involved in the care of diabetic patients. Changes in the structure of diabetes care are necessary to improve treatment quality.