Showing papers in "Nephrology Dialysis Transplantation in 1999"

Acute renal failure following cardiac surgery.

Abstract: went valve surgery, none of these variables were significantly associated with the development of ARF or Background. Acute renal failure requiring dialysis (ARF-D) occurs in 1‐5% of patients following cardiac ARF-D in this group of patients. Conclusion. The development of ARF or ARF-D is surgery, and remains a cause of major morbidity and mortality. While some preoperative risk factors have associated with a high mortality following CABG surgery. We have identified perioperative variables, been characterized, the influence of preoperative and intraoperative factors on the occurrence of ARF fol- which may be useful in stratifying risk for the development of ARF. lowing cardiac surgery is less well understood. Methods. Preoperative and intraoperative data on Key words: cardiac surgery; haemodialysis; renal failure 2843 consecutive adult patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) from February 1, 1995 to February 1, 1997 were recorded and entered into a computerized database. Two defini- Introduction tions of renal failure were employed: (i) ARF defined as a rise in serum creatinine (Cr) of 1 mg/dl above Acute renal failure (ARF ) remains a frequent and baseline; and (ii) ARF-D defined as the development serious complication of cardiac surgery. The incidence of ARF for which some form of dialytic therapy was of ARF following cardiac surgery has been reported required. The association between preoperative and to vary between 1 and 30% [1‐6 ]. When renal failure intraoperative variables and the development of ARF develops following cardiac surgery and is severe and was assessed by multivariate logistic regression. associated with the need for haemodialysis support, it Results. A total of 2672 of the 2844 patients underwent is associated with increased mortality, hospital stay isolated coronary artery bypass grafting (CABG) sur- and cost. Despite steady improvements in the results gery, the remaining 172 underwent valve surgery with of cardiac surgery, there has been a trend in operating or without bypass grafting. Of the CABG patients on higher risk patients, which inevitably leads to 7.9% developed ARF and 0.7% developed ARF-D. increased morbidity and mortality. The aetiology of The mortality for patients who developed ARF was renal insuYciency following cardiac surgery is poorly 14% (OR 15, P=0.0001) compared with 1% among understood, but it is believed that ischaemic injury of those who did not develop ARF. The mortality for the kidney, resulting from inadequate perfusion, is a CABG patients who developed ARF-D was 28% (OR major factor, although renal injury by exotoxins (e.g. 20, P=0.0001) compared with 1.8% among those who antibiotics, anaesthetic agents, contrast media, diurdid not require dialysis. Variables that were signific- etics) and endotoxins (e.g. myoglobin) may also be antly associated with the development of ARF by involved [7]. multivariate analysis included: increased age, elevated This study was undertaken to evaluate the prevalpreoperative serum Cr, duration of CPB, presence of ence, in-hospital mortality rate and the main risk a carotid artery bruit, presence of diabetes, reduced factors for the development of ARF. In an eVort to cardiac ejection fraction and increased body weight. address this issue, we prospectively studied a cohort Variables independently associated with ARF-D of 2844 patients who underwent cardiac surgery at our included serum Cr, duration of CPB, carotid artery institution over the last 2 years. bruit and presence of diabetes. The utility of these models for predicting the development of ARF and ARF-D was confirmed by bootstrapping techniques. Patients and methods Because of the small number of patients who under

European best practice guidelines for the management of anaemia in patients with chronic renal failure.

Abstract: Best practice guidelines recommend management strategies and attempt to set standards for optimal patient care. The momentum towards formulating guidelines comes not only from health care professionals, but also from health care management organizations, who need some way of measuring the quality of the services they purchase. The European Best Practice Guidelines for the Management of Anaemia in Patients with Chronic Renal Failure have been drawn up by a Working Party including representatives of the European Renal Association/European Dialysis and Transplantation Association (ERA-EDTA) and the national nephrology societies of a cross-section of European countries. The guidelines draw on the National Kidney Foundation-Dialysis Outcomes Quality Initiative (NKF-DOQI) Clinical Best Practice Guidelines for the Treatment of Anemia in Chronic Renal Failure, but reflect European clinical practice and experience. They include additional publications, and new analysis and interpretation of the evidence base. Topics covered in the European guidelines include diagnosis of the anaemia of chronic renal failure, indications for starting treatment with epoetin, recommended minimum target haemoglobin concentrations, epoetin dosage and route of administration, assessing and optimizing iron stores, causes and management of epoetin resistance, and possible adverse effects of epoetin treatment. The guidelines are not intended to be prescriptive but rather to provide clinical guidance based on the best available evidence. The evidence supporting each guideline is graded, so that physicians may judge its reliability.

Long-term effects of sevelamer hydrochloride on the calcium x phosphate product and lipid profile of haemodialysis patients.

Abstract: Background. Short-term studies have suggested that sevelamer hydrochloride, a non-aluminium- and non-calcium-containing hydrogel, is an effective phosphate binder in haemodialysis patients, and may produce favourable changes in the lipid profile. Methods. To determine the long-term effectiveness of sevelamer hydrochloride, we performed an open-label clinical trial in 192 adult patients with end-stage renal disease on haemodialysis. Drug-related changes in the concentrations of serum phosphorus, calcium, calcium × phosphate product, parathyroid hormone, and low- and high-density lipoprotein cholesterol concentrations were the major outcomes of interest. Results. Treatment with sevelamer was associated with a mean change in serum phosphorus of -0.71±0.77 mmol/l, serum calcium of 0.08±0.22 mmol/l, and calcium × phosphate product of -1.46±1.78 mmol/l (P<0.0001 for all comparisons). There were no significant overall treatment-related changes in parathyroid hormone. Serum levels of LDL cholesterol decreased by 0.81±0.75 mmol/l (mean -30%, P<0.0001) and HDL cholesterol increased by a mean of 0.15±0.29 mmol/l (mean +18%, P<0.0001). Drug-related adverse events were infrequent and most were of mild intensity. Conclusion. Sevelamer is a safe and effective phosphate binder that leads to significant improvements in the calcium × phosphate product and lipid profile of haemodialysis patients.

Serum C-reactive protein (CRP) and risk of death in chronic dialysis patients

Abstract: Background. The prognosis of chronic dialysis patients is poor, in part due to the high incidence of cardiovascular disease. Malnutrition, such as hypoalbuminaemia, has been shown to be a predictor of death in this group of patients, while serum C-reactive protein (CRP) is a predictor of myocardial infarction and sudden death. Thus, the aim of the present study was to determine of the relationship between CRP and serum albumin concentration, and the value of baseline CRP data in the prediction of death. Methods. In one of the dialysis units in Okinawa, Japan, baseline CRP data was available (n=163, 95 men and 68 women) in January 1991. These patients were divided into two groups according to their baseline CRP levels, with group 1 consisting of CRP<10 mg/l (n=128) and group 2 of CRP≥10 mg/l (n=35), and then followed up until the end of 1997. Survival curves were calculated using the Kaplan-Meier method. The statistical significance of the relationship between CRP levels and the risk of death was evaluated by multiple logistic analysis with covariables such as age, sex, diabetes mellitus, serum albumin, and blood pressure. Results. The mean (SD) level of serum albumin was 38 (3) g/l in group 1 and 36 (3) g/l in group 2 (P<0.00001). The 5-year survival rate was significantly poorer in group 2 (44.4%) than in group 1 (82.5%) (P<0.0001). Furthermore, the risk of death was significantly higher in group 2 (relative risk 3.48 (95% confidence interval 1.76-6.89), P<0.0003) by multivariate Cox proportional hazard analysis. Conclusions. CRP is a significant predictor of death in chronic dialysis patients, independent of serum albumin and other possible confounders. Dialysis patients with high CRP levels should be carefully evaluated and monitored regardless of serum albumin concentrations in the normal range.

A modified quantitative subjective global assessment of nutrition for dialysis patients.

Abstract: Background. Malnutrition, a predictor of increased mortality in dialysis patients, can be estimated using the subjective global assessment (SGA), a semiquantitative scale with three severity levels. This semiquantitative feature restricts the SGA's reliability and precision. Methods. Using the components of the conventional SGA, we developed a fully quantitative scoring system (the dialysis malnutrition score) consisting of seven variables: weight change, dietary intake, gastrointestinal symptoms, functional capacity, comorbidity, subcutaneous fat and signs of muscle wasting. Each component was assigned a score from 1 (normal) to 5 (very severe). The sum of all seven components in this malnutrition score lies between 7 (normal) and 35 (severely malnourished). To evaluate nutritional status in chronic dialysis patients, anthropometric measurements including mid-arm circumference (MAC), triceps skin-fold thickness, calculated mid-arm muscle circumference (MAMC), body mass index (BMI, ratio of weight to square of height) and laboratory parameters were used. Forty-one patients (20 men and 21 women) were randomly selected from a pool of 120 haemodialysis patients. Patients were aged between 26 and 81 years (mean±SD, 57±12 years) and had undergone haemodialysis for between 7 months and 12 years (mean±SD, 3.0±2.1 years). Results. The malnutrition score of each patient was assessed by a dietitian within 5-20 min (12.0±3.5 min) with no knowledge of anthropometric findings. Pearson correlation coefficients between the malnutrition score and biceps skin-fold (r=-0.32) MAC (r= -0.55), MAMC (r= -0.66), BMI (r=-0.35), total iron-binding capacity (TIBC, r=-0.77), the serum albumin concentration (r=-0.36) and total protein (r= -0.33) were all significant, whereas the conventional SGA had significant correlation only with TIBC (r= -0.35) and MAMC (r= -0.37). Malnutrition score showed a significant correlation with age (r= +0.34) and years dialysed (r=+0.28). Multiple regression analysis showed a significant correlation between the malnutrition score and the combination of the MAMC, BMI, serum albumin concentration and TIBC (r=0.81, P<0.001). There was no correlation between the malnutrition score and sex, urea reduction ratio, protein catabolic rate, and the absolute lymphocyte count. Conclusions. We conclude that our invented malnutrition score, which can be performed in minutes, reliably assesses the nutritional status of haemodialysis patients. We suggest that our malnutrition score may be superior to the SGA. More comparative and longitudinal studies are needed to confirm the validity of this scoring system in nutritional evaluation of dialysis patients.

Accumulation of advanced glycation end products in the peritoneal vasculature of continuous ambulatory peritoneal dialysis patients with low ultra-filtration.

Abstract: Advanced glycation end products (AGEs) are formed Methods Peritoneal biopsy specimens from 14 CAPD by a non-enzymatic reaction between reduced sugar patients with low ultra-filtration (n=9) and high ultra- and protein, known as the Maillard reaction [1,2] filtration (n=5) capacity were immunohistochemically AGEs accumulate on serum proteins and various tissue investigated using a monoclonal antibody against AGEs proteins in patients with diabetes mellitus (DM ), sug(6D12) The severity of peritoneal fibrosis, microvascu- gesting that they play a role in the pathogenesis of lar sclerosis and intensity of AGE accumulation were diabetic complications [3‐6 ] Recently, several reports semi-quantitatively evaluated Peritoneal ultra-filtration have disclosed AGE accumulation in sera and tissues capacity was evaluated by calculating daily ultra- of chronic renal failure (CRF ) patients, irrespective of filtration volume per body weight ( UFV/BW ) and D/D 0 the presence or absence of DM [7‐10] In CRF (glucose) of the peritoneal equilibration test patients, AGEs are formed due to high oxidative stress Results In all patients with low ultra-filtration, AGE associated with the uraemic state [11] The high conaccumulated in the peritoneal fibrous tissue and micro- centration of glucose in the peritoneal dialysate of vascular walls Remarkably, AGE accumulated more continuous ambulatory peritoneal dialysis (CAPD) intensely in hyalinized fibrosis of small venular media patients has been shown to facilitate AGE formation Extent of AGE accumulation in peritoneal interstitium in the peritoneal membrane [9,12] and vascular walls correlated with the progression We recently described the marked peritoneal vascular of interstitial fibrosis (r=0727, P=00088) and vas- changes in CAPD patients with ultra-filtration failure, cular sclerosis (r=0915, P=0001) UFV/BW was in- ie severe fibrosis and hyalinization of the media of versely correlated to interstitial fibrosis (r=‐0660, small venules [13] The present study was designed to P=00174), microvascular sclerosis (r=‐0671, evaluate the contribution of AGE in the development P=00155) and microvascular AGE accumulation of peritoneal lesions associated with ultra-filtration (r=‐0678, P=00145) failure Semi-quantitative analysis disclosed that the Conclusions In CAPD patients, AGE formation in severity of peritoneal changes were positively correlated the peritoneum correlates with the development of with the grade of AGE accumulation Furthermore, severe interstitial fibrosis and microvascular sclerosis, which is associated clinically with impaired peritoneal an inverse relationship between peritoneal ultraultra-filtration filtration capacity represented by daily ultra-filtration volume per body weight ( UFV/BW ) and histological changes was also observed In addition, the pathogen

Healthcare systems and end-stage renal disease (ESRD) therapies—an international review: costs and reimbursement/funding of ESRD therapies

Abstract: Background. In healthcare economics, the cost factor plays a leading role, particularly for chronic diseases such as end-stage renal disease because of the growing number of patients. Objectives. An international comparison was made of the costs and reimbursement/funding of a selection of key dialysis modalities—centre haemodialysis (CHD), limited care haemodialysis (LCHD), home haemodialysis (home HD), continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis (APD)—in various industrial countries. The focus was on treatment costs plus erythropoietin medication and reimbursement of transportatio n costs. Results. Reimbursement/funding of dialysis is different from country to country, with some healthcare systemspecific commonalities: in 'public' systems, the funding is based more on global budgets, whereas in mixed public and private countries it is based mainly on reimbursement rates per treatment. Only in the 'private system' of the US is there one DRG (diagnostic-related group)-type rate for dialysis. By comparing the costs (in public countries) or reimbursement s (in mixed countries) of treatment modalities within each country, we could see similar curves: the costs were the highest for public CHD, followed by private CHD. They were lower on LCHD and the lowest for home HD and CAPD, which were at nearly the same level. The cost level for APD was almost the same as that of LCHD. The reimbursements followed the cost pattern. Some countries introduced increases for CAPD and APD with the intention of increasing the share of home care. The costs and reimbursement patterns in the majority of countries (except the US and Japan) were very similar and therefore did not explain the different distribution of modalities in these countries. One explanation could be, however, the difference in microeconomics, CHD being a treatment with high fixed

Nutritional status of haemodialysis patients: a French national cooperative study. French Study Group for Nutrition in Dialysis.

Abstract: Background. Despite the severity and the prognosis value of undernutrition in haemodialysed patients, no large study is available as yet in Europe. Hence, this French National Cooperative Study aimed to determine the prevalence of undernutrition and its relationship to dialysis efficacy. Methods. Nutritional status was determined in 7123 patients (i.e. one-third of the French haemodialysis population) using body mass index (BMI), predialysis haemoglobin, albumin, pre-albumin, cholesterol, and also normalized protein catabolic rate (nPCR) and lean body mass (LBM) calculated from pre- and postdialysis urea and creatinine. Dialysis treatment was estimated from weekly dialysis time and KtV determination. Results. Dialysis time was 12.4±2.7 h/week and KtV 1.36±0.36. BMI was below 20 kg/m 2 in 24% and the observed/expected LBM ratio below 90% in 62%. Albumin, pre-albumin and nPCR were below the high-risk thresholds of 35 g/l, 300 mg/l and lg/kg/day in 20%, 36% and 35% of patients, respectively. Pre-albumin was the most representative nutritional parameter. Albumin, pre-albumin and LBM correlated with nPCR. A dialysis time above 12 h/week was associated with higher BMI, albumin, pre-albumin and LBM. LBM was higher in patients with a KtV value > 1.1. Conclusion. This study showed life-threatening undernutrition in 20-36% of the studied population, according to nutritional parameters. Protein intake (estimated by nPCR) and dialysis efficacy (estimated by dialysis time and KtV) appeared to be major determinants of nutritional status in this population.

Physical symptoms and quality of life in patients on chronic dialysis: results of The Netherlands Cooperative Study on Adequacy of Dialysis (NECOSAD)

Abstract: Background So far, little attention has been paid to the value of dialysis adequacy for patients' quality of life (QL). Therefore we studied the impact of demographic, clinical, and dialysis characteristics on physical symptoms and perceived QL. Methods The study population consisted of 120 incident chronic haemodialysis (HD) and 106 peritoneal dialysis (PD) patients, starting dialysis treatment in 13 Dutch centres. Data were collected 3 months after the start of dialysis. Nine physical symptoms were assessed with a self-administered questionnaire. Patient's self-assessment of QL was measured with the 36-item MOS Short Form (SF-36). Results The most common symptoms in HD and PD were fatigue (respectively 82 and 87%) and itching (73 and 68%). In HD only a medium to high comorbidity--age risk index was associated with greater symptom burden. In PD also a lower percentage lean body mass, a lower rGFR, and past episodes of underhydration were associated with greater symptom burden. The explained variance by these variables was only 12% in HD and 21% in PD. However, greater symptom burden explained a substantial additional amount of impaired physical and mental QL on top of demographics and clinical status. Dialysis variables were associated neither with symptoms nor with QL. Conclusion Symptom burden can be explained to a limited extent by demographic and clinical variables and not by dialysis characteristics. Addition of symptom burden to the other variables makes it possible to explain one-third of perceived QL. This underlines the importance of symptom reduction in order to improve patient's QL.

Fluid state and blood pressure control in patients treated with long and short haemodialysis.

Abstract: than the median ECVn in the SH group, without any diVerence in body mass index, but they were nevertheBackground. Patients treated at the haemodialysis (HD) centre in Tassin, France have been reported to less normotensive. The fall in BV was greater in SN than in TN patients, presumably due to a higher have superior survival and blood pressure (BP) control. This control has been ascribed to maintenance of an ultrafiltration rate in SN patients. However, SH patients had a smaller change in BV than SN patients, adequate fluid state, antihypertensive drugs being required in <5% of the patients, although it could not presumably because their state of overhydration facilitated refilling of BV from the interstitial fluid. be excluded that a high dose of HD regarding removal of uraemic toxins might also have been of value. Conclusions. Normotension can be achieved independently of the duration and dose ( Kt/V urea) of HD, if Methods. The aim of the study was to assess the fluid state and BP in normotensive patients on long HD the control of post-dialysis ECV is adequate. However, this is more diYcult to achieve with short than with (8 h) in Tassin (group TN ) using bioimpedance to measure extracellular volume ( ECV ), ultrasound for more prolonged HD during which the ultrafiltration rate is lower, BV changes are smaller and intradialysis determining the inferior vena cava diameter (IVCD), and ‘on-line’ monitoring of the change in blood volume symptoms less frequent. The results in the subgroup of patients with high ECVn at Tassin suggest that (BV ), and to compare them with normotensive (group SN ) and hypertensive (group SH ) patients on short normotension may also be achieved in patients with fluid overload provided that the dialysis time is long HD (3‐5 h) at centres in Sweden. ECV was normalized ( ECVn) by arbitrarily setting the median ECV (in % enough to ensure more eYcient removal of one or more vasoactive factors that cause or contribute to

Cardiovascular morbidity and risk factors in renal transplant patients.

Abstract: for 55% of their total mortality [1]. The cardiovascular Background. Cardiovascular disease is now the major mortality is, however, significantly higher in the cause of death in renal transplant patients. This study Northern than in the Southern parts of Europe [2]. aimed to assess the prevalence of cardiovascular disease Thus, cardiovascular mortality rates in renal transplant in stable renal transplant patients as compared with patients in Norway are particularly high, and up to 10 the general background population, and to assess risk times higher than found in Southern Europe [3]. factors for cardiovascular disease in this patient group. Whereas in European renal transplant patients at large, Methods. A cross-sectional multicentre study compris- cardiovascular disease accounts for 36% of the total ing 406 stable renal transplant patients (age 47±16 late mortality [3], ischaemic heart disease alone causes years, 60% males, 71% taking cyclosporin A) were as much as 53% of deaths in these patients in assessed clinically and biochemically 48 months Scandinavia [4]. (median) after transplantation and compared with the Only a few studies have compared mortality in general population. Multivariate analysis was used to patients on renal replacement therapy in general with assess the relation between cardiovascular disease and that of the background population [3‐5], and to our risk factors. knowledge none has assessed the cardiovascular morResults. Hypertension was present in 55% of males bidity specifically in renal transplant patients in the and 34% of females (P<0.001), in 51% with cyclospo- cyclosporin era. rin A and in 33% without (P<0.001). Ischaemic heart Thus, the aims of this study were first to assess the disease (i.e. angina pectoris and/or previous myocardial prevalence of cardiovascular disease in renal transplant infarction) was present in 14% (males: 18%, females: patients using a predominantly cyclosporin A based 10%, P<0.05) and in 24% of diabetics vs 12% of non- immunosuppressive regimen as compared with the diabetics (P<0.01). Cerebro- and peripheral vascular general background population, and second to evaluate disease was found in 3% and 4%, respectively. Odds the relation between cardiovascular disease and risk ratio for angina pectoris (patients vs general popula- factors in the patients. tion) was: in age group 40‐49 years (males/females), 12/16; 50‐59 years, 6/4; 60‐69 years, 3/4. Ischaemic heart disease was, besides age and gender, independ- Subjects and methods ently associated with total cholesterol (P<0.01), and peripheral vascular disease to systolic blood pressure The present study extends a recent analysis on hyperlipidae(P<0.01). mia in renal transplant patients in Norway [6 ]. In all, 406 Conclusions. Cardiovascular disease is highly prevalent stable renal transplant patients completed registration in in renal transplant patients, and is independently asso- 1991 at 18 centres of nephrology covering all regions of ciated with age, gender, total cholesterol and systolic Norway. The study patients represented 43% of the total blood pressure. national renal transplant population at the time, and had a similar age and gender distribution. Each patient was assessed

Health-related quality of life in dialysis patients. A report from an Italian study using the SF-36 Health Survey. DIA-QOL Group.

Abstract: Background Interest in measuring health-related quality of life (HRQoL) has increased together with an awareness that such humanistic outcomes require valid and reliable measures. In the last decade short, simple and multidimensional generic and disease-specific questionnaires have been developed. Among the several generic questionnaires available, the Short Form 36 Items Health Survey (SF-36) was translated and validated in several languages, and applied to different settings and diseases. Methods Within the framework of a larger, prospective, multicentre study (DIA-QOL project) the SF-36 was administered to 304 patients to test its characteristics in terms of patient acceptability, and psychometric and clinical validity. Standard psychometric techniques were used to evaluate its validity in terms of convergence, divergence and internal consistency reliability (Cronbach's alpha). Correlations between clinical variables and HRQoL scores were performed to test the questionnaire's capability to capture differences across patients groups. Results Overall, the findings show that, in this sample, the SF-36's performance was very good. Acceptability was satisfactory, with a response rate higher than 80%. All the questionnaire scales met the psychometric standards suggested in terms of grouping and scaling assumptions. The internal reliability coefficients actually replicate the satisfactory findings reported previously for the original SF-36. In terms of the ability of the questionnaire scales to discriminate between groups expected to differ in a given health concept in relation to clinical variables, the results were also good. On average, females reported lower scores, the impact of ageing was more evident for physical scales. Diabetic patients score significantly worse on the physical function scale and patients with mental health problems score significantly lower on the mental health scale. No significant association was found with the index KtV, haemoglobin levels, body mass index, parathyroid hormone and type of dialysis. A strong association was indeed found between SF-36 scales measuring physical health concepts and the serum albumin level. This association held after adjusting for the confounding effect of age. Comparison of the health profile of the present sample with others from the US and UK and from a representative sample of the Italian general population highlights the potential of such questionnaire in dialysis setting. Conclusions The SF-36 questionnaire is easy to use in Italian dialysis patients and SF-36 scores are related to important clinical aspects. This approach can help in caring for dialysis patients and can be useful in outcome assessment programmes.

Increased renal resistive index in patients with essential hypertension: a marker of target organ damage.

Abstract: Conclusions. Increased RI is associated with early signs of TOD in EH and could be a marker of intrarenal Background. Increased renal resistance detected by ultrasound ( US) Doppler has been reported in severe atherosclerosis. essential hypertension ( EH ) and recently was shown to correlate with the degree of renal impairment in Key words: atherosclerosis; essential hypertension; michypertensive patients with chronic renal failure. roalbuminuria; renal vascular resistance; target organ However, the pathophysiological significance of this damage finding is still controversial. Methods. In a group of 211 untreated patients with EH, we evaluated renal resistive index (RI ) by US Doppler of interlobar arteries and early signs of target Introduction organ damage ( TOD). Albuminuria was measured as the albumin to creatinine ratio (ACR) in three non- Ultrasound ( US) Doppler of renal vasculature is a consecutive first morning urine samples. Left ventricu- reliable, non-invasive evaluation technique whose clinlar mass was evaluated by M-B mode echocardiogra- ical application has increased steadily in recent years. phy, and carotid wall thickness (IMT ) by high In fact its usefulness varies from the diagnosis of renal resolution US scan. artery stenosis and renovascular disease [1,2] to the Results. RI was positively correlated with age (r= assessment of intrarenal haemodynamics in several 0.25, P=0.003) and systolic blood pressure (SBP) (r= diVerent pathological conditions such as essential 0.2, P=0.02) and with signs of early TOD, namely hypertension [3], acute [4] and chronic renal failure ACR (r=0.22, P=0.01) and IMT (r=0.17, P<0.05), [5,6 ], and graft rejection [7‐9]. and inversely correlated with renal volume (r=’0.22, Several parameters can be calculated during the P=0.01) and diastolic blood pressure (r=’0.23, P= cardiac cycle on the basis of the shape of Doppler 0.006). Multiple linear regression analysis demon- waves at various sites of the renal vasculature both strated that age, gender, ACR and SBP independently extra- and intra-parenchymally. These parameters are influence RI and together account for ~20% of its independent of the angle and the position of the variations (F=8.153, P<0.0001). When clinical data exploring probe, allowing for accurate and reproduwere analysed according to the degree of RI, the cible measurements of downstream vascular impedpatients in the top quartile were found to be older ance. In particular, increased resistive (RI ) and (P<0.05) and with higher SBP (P<0.05) as well as pulsatility (PI ) indexes measured at the level of the early signs of TOD, namely increased ACR (P<0.002) interlobar arteries recently have been associated with and IMT (P<0.005 by ANOVA), despite similar body the severity and duration of essential hypertension [10] mass index, uric acid, fasting blood glucose, lipid and with worse renal function in renal parenchymal profile and duration of hypertension. Furthermore, disease [5], although the pathophysiological significpatients with higher RI showed a significantly higher ance of these findings deserves further investigation. prevalence of microalbuminuria (13 vs 12 vs 3 vs 33% The present study was initiated to investigate the x2=11.72, P=0.008) and left ventricular hypertrophy relationship between US Doppler RI of the intrarenal (40 vs 43 vs 32 vs 60%, x2=9.25, P<0.05). vasculature and early target organ damage such as left ventricular hypertrophy (LVH ), microalbuminuria and

Prevention of radiocontrast-media-induced nephropathy in patients with pre-existing renal insufficiency by hydration in combination with the adenosine antagonist theophylline.

Abstract: BACKGROUND Radiographic contrast media (CM) application causes a decline in renal function, especially in patients with pre-existing renal dysfunction. In addition to hydration, several vasodilating substances have been evaluated for their ability to prevent renal damage after CM application. In a prospective, double-blind, placebo-controlled study we investigated the effect of the oral administration of theophylline, an adenosine receptor antagonist, on changes in renal haemodynamics and tubular injury induced by CM in well-hydrated patients with mild-to-moderate renal insufficiency. METHODS We studied 80 patients with pre-existing chronic renal insufficiency (creatinine > 1.5 mg/dl) who received more than 100 ml iopromide. Hydration (either oral or intravenous) started at least 24 h before and lasted until 24 h after CM application. In addition, patients were randomly assigned to receive either theophylline (810 mg daily) or placebo. Serum creatinine and creatinine clearance were measured before and for 3 days after CM application. Urine was collected to measure N-acetyl-beta-glucosaminidase (NAG) enzymuria for the same period. Sixty-four patients completed the entire study protocol (theophylline, n = 35 and placebo, n = 29). RESULTS During the study period serum creatinine concentration and creatinine clearance did not change significantly in either group. Acute renal failure (increase of serum creatinine of at least 0.5 mg/dl) could be observed in two patients from the theophylline group (5.7%) and one from the placebo group (3.4%). The increase in NAG excretion reached statistical significance (P < 0.05) in the placebo group on days 2 and 3 after CM application. CONCLUSIONS Our results indicate a role for adenosine in CM-induced tubulotoxicity. However, the glomerular filtration rate is preserved by hydration alone in these patients. The application of theophylline did not bring an additional benefit. The use of adenosine antagonists may be beneficial in patients where sufficient hydration may be impossible or in patients with a concomitant decrease in renal blood flow (e.g. congestive heart failure).

Risk factors for reduced bone density in haemodialysis patients

Abstract: Background. Renal osteodystrophy may result in considerable morbidity for patients with end-stage renal disease. Secondary hyperparathyroidism, adynamic bone disease and osteomalacia, the main bony problems in chronic renal failure, may all be responsible for a reduction in bone mineral density (BMD). This can result in an increased fracture risk. By virtue of their age, post-menopausal status (in women), sedentary life-style and treatment (including previous corticosteroids), haemodialysis patients may be expected also to be at risk for developing osteoporosis, but little is known about the relative importance of these factors. Methods. We report a prospective study examining the prevalence of reduced bone mineral density (BMD) and its association with a wide range of factors, in a heterogenous group of 88 chronic haemodialysis patients. Femoral neck and lumbar BMD were measured by dual-energy X-ray absorptiometry (DXA). Stepwise multiple linear regression analysis was used to identify risk factors associated with low bone mass. Results. Forty three patients (48.9%) had reduced BMD, and in 17 (19.3%) BMD was below the fracture threshold as defined on DXA measurements by the World Health Organization (WHO). The BMD had significant negative associations with age, serum parathyroid hormone (PTH) levels, current gastric acid suppression therapy, female gender, age at menarche and history of previous fracture. Positive associations were found with weight, haemoglobin concentration, average serum phosphate, weekly heparin dose, oral calcium supplementation and history of parathyroidectomy. Conclusions. We have confirmed the importance of PTH-related bone disease in affecting BMD in haemodialysis patients, but have found that some other factors, which are known to be risk factors for osteoporosis, are also important.

Enhanced oxidative stress in haemodialysis patients receiving intravenous iron therapy

Abstract: Background. Iron balance is critical for adequate erythropoiesis and there remains much debate concerning the optimal timing and dosage of iron therapy for haemodialysis patients receiving recombinant human erythropoietin therapy. Methods. In this study, we examined the influence of baseline ferritin level and intravenous infusion of 100 mg ferric saccharate on the oxidative status of the patients on maintenance haemodialysis. The levels of antioxidant enzymes and lipid peroxides were determined in erythrocytes and plasma of 50 uraemic patients on haemodialysis. These patients were divided into groups 1, 2, and 3, based on their baseline serum ferritin levels of 601 μg/l, respectively. Results. We found that the mean superoxide dismutase (SOD) activities in the erythrocytes were similar in the three groups of patients and did not differ from those of the age-matched controls. On the other hand, all the haemodialysis patients showed significantly higher plasma SOD activity as compared to controls. After intravenous iron infusion, group 3 patients showed the largest decrease in plasma SOD activity. The plasma glutathione peroxidase (GSHPx) activities of the patients in all three groups and the erythrocyte GSHPx activities of the patients in the groups 2 and 3 were lower than those of the healthy controls. In all three groups of patients, no difference in GSHPx activity was found before and after intravenous iron infusion. On the other hand, we found that the average baseline levels of plasma lipid peroxides of all three groups of patients were significantly higher than that of the controls. The patients in group 3 with the highest serum ferritin levels showed the highest levels of plasma lipid peroxides. More importantly, we found that after iron infusion, the patients in all three groups, particularly those in group 3, showed significantly elevated levels of plasma lipid peroxides. Conclusion. We demonstrated that increased oxidative stress in the blood circulation of the uraemic patients on haemodialysis is exacerbated by the elevated baseline serum ferritin levels and intravenous iron infusion. The resultant oxidative damage may contribute to the increased incidence of atherosclerosis in the patients with end-stage renal disease on long-term haemodialysis.

Impaired cellular immune function in patients with end-stage renal failure

Abstract: 3. Zimmet P. The epidemiology of diabetes mellitus and associated diabetes mellitus conferred by obesity and central adiposity in different ethnic groups. A comparative analysis of Asians disorders. In Alberti KGMM, Krall LP eds. The Diabetes Indians, Mexicans, Americans and Whites. Diabetes Res Clin Annual/6, Elsevier Science Publishers, Amsterdam, 1991: 1–19 Pract 1997; 36: 121–125 4. Viswanathan M, McCarthy MI, Snehalatha C, Hitman GA, 9. Roderick PJ, Raleigh VS, Hallam L, Mallick NP. The need and Ramachandran A. Familial aggregation of Type 2 diabetes demand for renal replacement therapy among ethnic minorities mellitus in South India, absence of excess maternal transmission. in England. J Epidemiol Comm Health 1996; 50: 334–339 Diabet Med 1996; 13: 232–237 10. Mani MK. Patterns of renal disease in indigenous populations 5. Viswanathan M, Mohan V, Snehalatha C, Ramachandran A. in India. Nephrology 1998; 4: S4–S7 High prevalence of Type 2 diabetes among the offspring of 11. Viswanathan V, Snehalatha C, Shina K, Lalitha S, conjugal Type 2 diabetic parents in India. Diabetologia 1985; Ramachandran A. Familial aggregation of diabetic kidney dis28: 907–910 ease in Type 2 diabetes in South India. Diabetes Res Clin Pract 6. Ramachandran A, Snehalatha C, Latha E, Vijay Viswanathan, 1999; 43: 167–171 Viswanathan M. Rising prevalence of NIDDM in an urban 12. Viswanathan V, Snehalatha C, Ramachandran A, population in India. Diabetologia 1997; 40: 232–237 Viswanathan M. Proteinuria in NIDDM in South India: analysis 7. Mohan V, Ramachandran A, Snehalatha C et al. High prevalof predictive factors. Diabetes Res Clin Pract 1995; 28: 41–46 ence of Maturity onset Diabetes of the young (MODY ) among 13. Viswanathan V, Snehalatha C, Terin Mathai, Muthu Jayaraman, Indians. Diabetes Care 1985; 8: 371–374 Ramachandran A. Cardiovascular morbidity in proteinuric 8. Ramachandran A, Snehalatha C, Vijay Viswanathan, South Indian NIDDM patients. Diabetes Res Clin Pract 1998; 39: 63–67 Viswanathan M, Haffner SM. Risk of Non-insulin dependent

Outcome and complications of temporary haemodialysis catheters.

Abstract: Background. The use of temporary haemodialysis catheters is often complicated by mechanical or infectious complications. Risk factors for these complications and optimal management to reduce their incidence are largely unknown. Methods. We conducted a prospective study of 105 haemodialysis catheters (79 subclavian, 26 jugular) inserted in 52 patients in order to identify patient outcomes and to analyse the effect of patient and catheter factors on the incidence of infectious complications by multivariate analysis. Results. Fifty-nine per cent of catheters were removed for a suspected complication. Catheter-related bacteraemia (CRB) was diagnosed in 17 catheters (16%), giving a bacteraemia rate of 6.5 episodes per 1000 catheter days. Subgroup analysis revealed a higher risk of CRB with the use of the internal jugular compared with the subclavian site (hazard ratio 3.97, P=0.02). Age, diabetes or catheter exchange over a guidewire did not alter the risk of CRB. The cumulative risk of developing CRB increased in a linear fashion as the period of catheterization increased. Exit-site infection was the cause for removal in eight catheters (8%). Although the number of exit-site infections was small, the risk of exit-site infection was increased in diabetic patients (hazard ratio 10, P=0.03) and the jugular position (hazard ratio 6.5, P=0.01) but not by age or catheter exchange over a guidewire. Staphylococcus aureus and coagulase-negative staphylococcus accounted for all proven episodes of CRB. Exit-site infection was associated with a mixture of Gram-positive and Gram-negative organisms. Conclusions. Temporary haemodialysis catheters have a high failure rate associated with a significant rate of complications. Use of the internal jugular site is associated with a significantly higher risk of infectious complications and methods to reduce this risk should be considered if this site is used.

Laparoscopic live donor nephrectomy: the four year Johns Hopkins University experience

Abstract: [1]. In the US, there is a growing disparity between The advantages of the laparoscopic live donor operathe organ supply and demand. This has resulted in tion arise from the ability to utilize small incisions and prolonged waiting times on the cadaveric renal transto place them at sites remote from the location of the plant waiting list [2]. Commensurate with the increased kidney, therefore avoiding a debilitating large flank waiting times has been an increase in the number of incision. Thus, a 5 cm lower midline or Pfannenstiel deaths of patients awaiting transplantation. Live incision suffices to deliver the kidney. The operation kidney donors have remained an under-utilized source can be performed by either a transperitoneal or of transplantable organs. retroperitoneal approach. We prefer the transperitoneal Live donor renal transplantation offers several approach because it affords more laparoscopic working advantages over cadaveric transplantation. First, the space. It also allows the kidney to be removed easily long waiting times are eliminated. Second, there is a from the abdomen through a relatively low pain, lower incidence of delayed function. Third, both midline incision. A pneumoperitoneum of 15 mmHg is patient and graft survival rates are significantly better created using CO2. Other centres have reported using with live donor transplantation [3]. Thus, not only are abdominal wall lifters. Dissection of vascular structures more organs made available, the need for repeat transis facilitated by the magnification achieved via the plantation is reduced. Also, live donor renal translaparoscope. The renal vasculature is divided using an plantation is more cost effective than cadaveric donor endo-GIA stapler. This device lays down two rows of transplantation [4]. However, despite these advantstaples and cuts between them simultaneously. On the ages, there exist significant disincentives to live kidney right side, use of this stapler results in loss of donation. 1.0–1.5 cm of vein, leaving the recipient surgeon with The long hospitalization and recuperation time assoa short thin vein to contend with. Therefore, the donor ciated with open nephrectomy via a flank approach operation is modified slightly for right kidneys. can pose significant financial and logistical problems However, because of technical considerations, we in terms of time out of work, lost income, job security prefer to utilize the left kidney, even if multiple left and inability to care for dependant children. Also, a renal arteries are present. The exception to this is if number of individuals express concerns about fear of there is a clear advantage to the donor by leaving the pain and the cosmetic results of major abdominal left kidney in situ. surgery. Thus, by reducing these disincentives, we

Donor age and delayed graft function as predictors of renal allograft survival in rejection-free patients.

Abstract: (DGF ), and it is commonly defined as the need for Background. Transplant recipients of kidneys harvested dialysis during the first week after transplantation. In from old donors have a high incidence of delayed graft kidney cadaveric transplantation, DGF usually ranges function (DGF ) and a poor graft outcome. This result between 10 and 50%, makes the management of is partly explained by the increased incidence of acute patients more complex, the diagnosis of rejection more rejection in patients suVering from DGF. However, the diYcult, prolongs hospital stay, increases the financial long-term impact of donor age and DGF in rejection cost of transplantation, and reduces graft survival rates free renal transplants is not well established. The aim [1,2]. During recent years it has been shown that DGF of the present work is to evaluate the impact of donor associated with acute rejection implies a poor longage and DGF on long-term outcome in renal transplants term graft outcome [3,4]. However, the influence of with or without acute rejection. DGF on long-term graft survival in rejection-free Patients. We review all cadaveric kidney transplants patients has not been well established. While some performed in our centre between April 1984 and authors support that DGF only has a negative impact December 1995 treated with a cyclosporin-based on long-term graft survival in patients who presented immunosuppression. acute rejection [4], others maintain that the negative Results. Five hundred and ninety-five patients were eVect of DGF is mediated through mechanisms not included. The overall incidence of DGF was 29.1%, involving acute rejection [5]. and this event was associated with an increased donor The persistent shortage of donors has stimulated age and cold ischaemia time. Univariate and multivari- diVerent strategies in order to increase the donor pool. ate analysis showed that graft loss was associated with For example, aged or non-heart-beating donors are acute rejection (relative risk (RR) 2.24, 95% confidence frequently considered for cadaveric kidney transplantainterval (CI ) 1.62‐3.01); DGF (RR 1.83, 95% CI tion. However, advanced donor age is clearly associ1.32‐2.54); donors >50 years (RR 1.65, 95% CI ated with an increased risk of DGF and a rather poor 1.13‐2.38); and retransplantation (RR 1.52, 95% CI graft outcome [6 ]. 1.01‐2.31). In rejection-free patients there were two The aim of the present retrospective study is to independent predictors of graft failure: donor >50 determine the eVect of donor age and post-transplant years (RR 2.40, 95% CI 1.45‐4.01); and DGF (RR DGF on allograft outcome in patients with or without 2.42, 95% CI 1.53‐3.84). acute rejection. Since we evaluate long-term results, Conclusions. Regardless of the presence of acute rejec- subgroups with immediate graft loss after transplantation, delayed graft function amplifies the detrimental tion have been eliminated from the study. eVect of advanced donor age on long-term graft outcome. Subjects and methods

The molecular biology of erythropoietin.

Abstract: Erythropoietin (Epo) controls the proliferation, differentiation and survival of the erythroid progenitors. Epo exerts its effects by binding to a cell surface receptor. The Epo receptor includes a p66 chain, which is dimerized upon Epo activation, and two accessory proteins, which have been defined by cross-linking. Epo binding induces stimulation of the Jak2 tyrosine kinase. Jak2 activation leads to the tyrosine phosphorylation of several proteins, including the Epo receptor itself. Different intracellular pathways are activated: Ras/MAP kinase, phosphatidylinositol 3-kinase and STAT transcription factors. However, the exact mechanisms by which the proliferation and/or differentiation of erythroid cells are regulated after Epo stimulation are not known. Target disruption of both Epo and Epo receptors showed that Epo is not involved in the commitment of the erythroid lineage; it seems to act mainly as a survival factor. Epo is synthesized largely by the kidney and the liver, and sequences required for tissue-specific expression have been localized in the Epo gene. A 3' enhancer is responsible for hypoxia-inducible Epo gene expression. Hypoxia-induced factor-1 (HIF-1) protein binds to this enhancer. In addition to anaemia of renal failure, the indication for treatment with epoetin has been extended to the anaemia of chronic diseases.

Dialysis in neonates with inborn errors of metabolism.

Abstract: associated with a lethal outcome. Simulation studies showed that the eYcacy of neonatal CVVHD is limited Methods. We report our experience with continuous venovenous haemodialysis (CVVHD) in six neonates with hyperammonaemic coma due to urea-cycle disorders or propionic acidaemia and in one child with Introduction leucine accumulation due to maple-syrup urine disease (MSUD), in comparison with five patients managed Inherited dysfunctions of amino and organic acid by peritoneal dialysis (PD) (2 hyperammonaemia, metabolism usually become manifest in the early neo- 3 MSUD). Application of a new extracorporeal device natal period by neurological abnormalities such as specifically designed for use in small children permitted irritability, somnolence, and eventually coma (1-3). In the establishment of stable blood circuits utilizing urea-cycle defects or in organic acidaemias, these small-sized catheters, and the tight control of balanced symptoms are mainly due to excessive hyperammonae- dialysate flows over wide flow ranges. mia, which may cause irreversible neuronal damage Results. Plasma ammonia or leucine levels were (4,5). In disorders of branched-chain amino acid reduced by 50% within 7.1±4.1 h by CVVHD and (BCAA) metabolism such as maple-syrup urine disease within 17.9±12.4 h by PD (P<0.05). Also, total (MSUD), prolonged accumulation of leucine and/or dialysis time was shorter with CVVHD (25±21 h) its metabolites (2-ketoisocaproic acid) may lead to than with PD (73±35 h, P<0.02). A comparison of severe permanent neurotoxicity (6 ). the CVVHD results with published literature confirmed During the past two decades, the prognosis of these superior metabolite removal compared to PD, and previously lethal disorders has been considerably suggested comparable eYcacy as achieved with improved by the introduction of several therapeutic continuous haemofiltration techniques. Apart from principles. Primarily, the generation of toxic meta- accidental pericardial tamponade during catheter inser- bolites can be suppressed by high calorie supply indu- tion in one case, no major complications were noted cing a state of anabolism and reduced proteolysis. In with CVVHD. In three of the five PD patients, dialysis hyperammonaemic disorders such as urea-cycle defects, was compromised by mechanical complications. None lacking physiological or alternative pathway substrates of the MSUD patients but four children with urea- can be infused to reduce ammonia concentrations. In cycle disorders died, two during the acute period and MSUD, a diet with reduced BCAA contents can be two later during the first year of life, with signs of instituted. Finally and most importantly, the accumula- severe mental delay. Of the eight children presenting tion of neurotoxic metabolites can be rapidly reversed with hyperammonaemic coma, the four with the most by dialytic removal. rapid dialytic ammonia removal rate (50% reduction Historically, PD was shown to be of superior eYcacy in <7 h) survived with no or moderate mental retard- in urea-cycle disorders compared to the previously ation, whereas slower toxin removal was always used exchange transfusions and pharmacological treat-

N-acetylcysteine attenuates cyclosporin-induced nephrotoxicity in rats.

Abstract: Background. Cyclosporin(CsA) has played an important role in the improvement of solid-organ transplant patients and graft survival. However, nephrotoxicity due to CsA remains an important clinical challenge. The renal toxicity of CsA is attributed to reduced renal blood flow which leads to hypoxia-reoxygenation injury accompanied by excessive generation of oxygen-derived free radicals (ODFR). N-acetyl-L-cysteine (NAC) is a highly potent antioxidant that has been shown to reduce ODFR injury. In this study an attempt was made to assess the effect of NAC on CsA-induced lipid peroxidation and nephrotoxicity.

Increased plasma malondialdehyde levels in glomerular disease as determined by a fully validated HPLC method.

Abstract: BACKGROUND Reactive oxygen species and particularly free radical induced lipid peroxidative tissue damage have been implicated in the pathogenesis of various renal diseases. Lipid peroxidation is assessed indirectly by the measurement of secondary products, such as malondialdehyde (MDA), using the widely employed thiobarbituric acid reactive substances (TBARS) method. However, this method lacks sensitivity and specificity. We have therefore developed and validated an HPLC (high-performance liquid chromatography) method for measurement of MDA and applied this to a variety of plasma samples in renal patients. METHODS The optimized method involves antioxidant treatment of the plasma sample, followed by a protein precipitation step using trichloroacetic acid, acid hydrolysis and formation of an MDA thiobarbituric acid complex. The MDA-(TBA)2 adduct is separated from other interfering compounds by C18 reverse-phase HPLC techniques, with visible detection at 532 nm. RESULTS The assay was linear over the ranges 0.25-1.0 microM MDA and the detection limit was 0.06 microM MDA. Within-run precision was <4.5% and between-run precision was <10.0%. MDA plasma concentrations (mean+/-SD) were higher in ESRF diabetic patients (0.32 +/- 0.14 microM, n=20), non-diabetic ESRF patients (0.32 +/- 0.09 microM, n=20), and CRF patients (0.14 +/- 0.06 microM, n=40) compared to healthy controls (0.11 +/- 0.03 microM, n=40), (P < 0.001, P < 0.001 and P = 0.008). Levels were similar in healthy controls with normal renal function and transplanted patients (0.12 +/- 0.03 microM MDA, n=40), (P=NS). No correlation was observed between MDA and creatinine levels (r2 = 0.05, n=80), which suggests that MDA does not correlate with the degree of renal impairment. We matched CRF patients with glomerular and non-glomerular causes of renal failure for creatinine levels and found that MDA levels were higher in patients with glomerulonephritis (0.16 +/- 0.06 microM) than in those with CRF from non-glomerular causes (0.12 +/- 0.04 microM, P = 0.002). CONCLUSIONS We have introduced a reliable and sensitive HPLC technique to enhance the specificity of MDA-(TBA)2 measurement, with a significant improvement in HPLC column life. Using this method, picomole quantities of MDA can be detected in plasma. We have shown that MDA levels are significantly raised in patients with CRF due to glomerulonephritis, regardless of serum creatinine, which suggests that there is oxidative injury independent of any possible MDA retention due to renal impairment.

Pregnancy in women receiving renal dialysis or transplantation in Japan: a nationwide survey.

Abstract: Background Since a report on the first successful pregnancy of a woman on long-term haemodialysis in Japan in 1977, there has been a growing number of case reports on successful pregnancy in patients on dialysis. We undertook a nationwide survey on pregnancy in women on renal replacement therapy in 1996. Methods A preliminary questionaire was sent to 2504 dialysis units and 143 renal transplant units in Japan. For each reported pregnancy, a more detailed questionaire was sent to collect nephrological, obstetric and neonatal information. Results There were 172 pregnancies (0.44%) reported in 38889 women on dialysis, with 90 successful pregnancies (0.23%), and 194 pregnancies reported in 852 female renal transplant recipients. Detailed pregnancy information was collected from 74 women on dialysis and 194 renal transplant recipients. Of the 74 pregnancies in the women on dialysis, 36 (48.6%) resulted in surviving infants, nine (12.2%) in neonatal death, nine (12.2%) spontaneous abortions and 14 (18.9% elective abortions were reported. The outcome of six pregnancies (8.1%) was unknown. Of 194 pregnancies in renal transplant recipients, 159 (82.0%) resulted in surviving infants, two (1.4%) in neonatal death and 28 (14.4%) in spontaneous or elective abortion. In five cases the pregnancy outcome was not reported. No congenital anomalies were reported, except two infants with mental retardation and one with epilepsy. Conclusion The current survey revealed that the rate of successful pregnancy in women on dialysis has improved. More than half of the pregnancies resulted in infant survival. But, premature birth is a major problem for the children of women on dialysis and there is a higher rate of neonatal death. There are significant differences in gestational age, birth weight, frequency and severity of prematurity and rates of neonatal death between pregnancies of women undergoing dialysis and those who are renal transplant recipients.

Change from conventional haemodiafiltration to on-line haemodiafiltration.

Abstract: BACKGROUND On-line haemodiafiltration (HDF) is a technique which combines diffusion with elevated convection and uses pyrogen-free dialysate as a replacement fluid. The purpose of this study was to evaluate the difference between conventional HDF (1-3 l/h) and on-line HDF (6-12 l/h). METHODS The study included 37 patients, 25 males and 12 females. The mean age was 56.5 +/- 13 years and duration of dialysis was 62.7 +/- 49 months. Three patients dropped out for transplantation, three patients died and three failed to complete the study period. Initially all patients were on conventional HDF with high-flux membranes over the preceding 34 +/- 32 months. Treatment was performed with blood flow (QB) 402 +/- 41 ml/min, dialysis time (Td) 187 min, dialysate flow (QD) 654 +/- 126 ml/min and replacement fluid (Qi) 4.0 +/- 2 l/session. Patients were changed to on-line HDF with the same filtre and dialysis time, QD 679 +/- 38 ml/min (NS), QB 434 +/- 68 ml/min (P < 0.05) and post-dilutional replacement fluid 22.5 +/- 4.3 l/session (P < 0.001). We compared conventional HDF with on-line HDF over a period of 1 year. Dialysis adequacy was monitored according to standard clinical and biochemical criteria. Kinetic analysis of urea and beta2-micro-globulin (beta2m) was performed monthly. RESULTS Tolerance was excellent and no pyrogenic reactions were observed. Pre-dialysis sodium increased 2 mEq/l during on-line HDF. Plasma potassium, pre- and post-dialysis bicarbonate, uric acid, phosphate, calcium, iPTH, albumin, total proteins, cholesterol and triglycerides remained stable. The mean plasma beta2m reduction ratio increased from 56.1 +/- 8.7% in conventional HDF to 71.1 +/- 9.1% in on-line HDF (P < 0.001). The pre-dialysis plasma beta2m decreased from 27.4 +/- 8.1 to 24.2 +/- 6.5 mg/l (P < 0.01). Mean Kt/V (Daugirdas 2nd generation) was 1.35 +/- 0.21 in conventional HDF compared with 1.56 +/- 0.29 in on-line HDF (P < 0.01), Kt/Vr (Kt/V taking into consideration post-dialysis urea rebound) 1.12 +/- 0.17 vs 1.26 +/- 0.20 (P < 0.01), BUN time average concentration (TAC) 44.4 +/- 9 vs 40.6 +/- 10 mg/dl (P < 0.05) and protein catabolic rate (PCR) 1.13 +/- 0.22 vs 1.13 +/- 0.24 g/kg (NS). There was a significant increase in haemoglobin (10.66 +/- 1.1 vs 11.4 +/- 1.5) and haematocrit (32.2 +/- 2.9 vs 34.0 +/- 4.4%), P < 0.05, during the on-line HDF period, which allowed a decrease in the erythropoietin doses (3861 +/- 2446 vs 3232 +/- 2492 UI/week), (P < 0.05). Better blood pressure control (MAP 103.8 +/- 15 vs 97.8 +/- 11 mmHg, P < 0.01) and a lower percentage of patients requiring antihypertensive drugs were also observed. CONCLUSION The change from conventional HDF to on-line HDF results in increased convective removal and fluid replacement (18 l/session). During on-line HDF treatment, dialysis dose was increased for both small and large molecules with a decrease in uraemic toxicity level (TAC). On-line HDF provided a better correction of anaemia with lower dosages of erythropoietin. Finally, blood pressure was easily controlled.

The effect of exercise during haemodialysis on solute removal

Abstract: Background. Urea rebound results as urea re-equilibrates between intracellular and intravascular compartments post haemodialysis. The mechanism of the rebound is thought to be due to either a reduced diffusion rate or blood flow. It is hypothesized that low blood flow in the skeletal muscles might be responsible. We tested this by studying the effect of exercise during dialysis on the removal of urea, creatinine and potassium. Methods. Eleven patients (aged 32-78 years) on haemodialysis (4-58 months) were studied on paired dialysis sessions; one with exercise and the other as a control. Patients pedalled on a cycle for 5-20 min at submaximal workload followed by 10 min rest to achieve a total of 60 min exercise. Plasma concentrations of urea, creatinine and potassium were measured pre-, post- and 30-min post dialysis. The post-dialysis rebound (% rebound) and reduction ratios (RR) of the solutes and equilibrated (two-pool) urea Kt/V were calculated for comparison. Results. The rebound of all three solutes was reduced significantly following exercise. The rebound of urea decreased from 12.4 to 10.9% (median, P<0.01 Wilcoxon signed rank test), creatinine from 21.2 to 17.2% (P<0.001) and potassium from 62 to 44% (P<0.05). Kt/V and RR increased significantly as a result: Kt/V urea from 1.00 to 1.15 (P=0.001), RR urea from 0.63 to 0.68 (P<0.001); Kt/V creatinine from 0.71 to 0.84 (P<0.01); and RR creatinine from 0.51 to 0.57 (P<0.05). Conclusion. Exercise increased the efficiency of dialysis by reducing the rebound of solutes due to increased perfusion of the skeletal muscles.

Rapid and accurate assessment of glomerular filtration rate in patients with renal transplants using serum cystatin C

Abstract: Background. Assessment of renal function in patients with renal transplants is of great importance. Various studies have reported cystatin C as an easily and rapidly assessable marker that can be used for accurate information on renal function impairment. To date, no study is available to define the role of cystatin C in patients with renal transplants. Methods. Thirty steady-state patients (50% male/50% female) with status post-kidney transplantation were studied. To assess renal function, cystatin C, creatinine clearance, serum creatinine, β 2 -microglobulin (β 2 M), and [ 125 I]iothalamate clearance were determined. Correlations and non-parametric ROC curves for accuracy, using a cut-off glomerular filtration rate (GFR) of 60 ml/min, were obtained for the different markers allowing for calculations of positive predictive values (PPV), positive likelihood ratios (PLR), specificity and sensitivity, respectively. Further, to evaluate the usefulness of these markers for monitoring, intraindividual coefficients of variation (CVs) for cystatin C and creatinine measurements were compared in 85 renal transplant patients. Measurements consisted of at least six pairs of results, which were obtained at different time points during routine follow-up. Results. Cystatin C correlated best with GFR (r= 0.83), whereas serum creatinine (r=0.67), creatinine clearance (r=0.57) and β 2 M (r=0.58) all had lower correlation coefficients. The diagnostic accuracy of cystatin C was significantly better than serum creatinine (P=0.025), but did not differ significantly from creatinine clearance (P=0.76) and β 2 M (P=0.43). At a cut-off of 1.64 mg/l, cystatin C has a PPV of 93%, PLR of 6.4, specificity 89% and sensitivity 70%, respectively. For β 2 M, PPV 83%, PLR 1.7, specificity 67% and sensitivity 75% was seen at a cut-off of 3.57 mg/l. Accordingly, at a cut-off of 125 μmol/l for serum creatinine, a PPV 76%, PLR 1.4, specificity 44% and sensitivity 80% was revealed. Finally, at a cut-off of 66 ml/min/1.73 m 2 for creatinine clearance, the following characteristics were found: PPV 94%, PLR 7.7, specificity 89% and sensitivity 85%. The intraindividual variation of creatinine was significantly lower than that of cystatin C (P<0.001). With increasing concentrations, their ratios of CV tended towards a value of 1, demonstrating identical variability at low GFR. Conclusion. Together, our data show that in patients with renal transplants, cystatin C, in terms of PPV and PLR, has a similar diagnostic value as creatinine clearance. However, it is superior to serum determinations of creatinine and β 2 M. The intraindividual variation of cystatin C is greater than that of creatinine. This might be due to the better ability of cystatin C to reflect temporary changes especially in mildly impaired GFR, most critical for early detection of rejection and other function impairment. Thus, cystatin C allows for rapid and accurate assessment of renal function (GFR) in renal transplants and is clearly superior to the commonly used serum creatinine.