In the August 15, 1996, issue of Transplantation (1996; 62(3): 421), Lufft et al. (1) reported a retrospective analysis of the overall incidence, clinical course, and conditions contributing to the manifestation of Pneumocystis carinii pneumonia (PCP) after renal transplantation. They observed a marked increase in the incidence of PCP at their center between December 1993 and June 1994, coinciding with their participation in an international, multicenter, comparative trial assessing the efficacy and safety of tacrolimus (FK506) therapy. They concluded that tacrolimus appeared to be an important risk factor for the development of PCP as a result of its high immunosuppressive potential, and implied that tacrolimus was associated with a higher incidence of infectious complications; however, there are no data available to substantiate this. No significant difference was evident between tacrolimus- and cyclosporine-treated patients in the results that Lufft et al. presented (tacrolimus: 4/28 [14.3%], cyclosporine: 3/38 [7.9%]; P=0.668). During the international, multicenter trial mentioned above, PCP was diagnosed at a relative low frequency compared with the literature (2%, 6/303, for tacrolimus patients compared with 0%, 0/145, for cyclosporine patients; P=NS). Interestingly, the six patients with PCP came from two institutions. Four of these patients were from Medizinische Hochschule Hannover, Hannover, Germany. The two additional cases also came from a single institution. These results are strongly indicative of a center-specific effect. Furthermore, in the multicenter study, it was observed in both treatment arms that increasing age was correlated with increasing morbidity. In line with these results, an age effect was evident in the article by Lufft et al. (1). Seven of the 10 patients diagnosed with PCP in Hannover between January 1986 and June 1994 were over the age of 55 years. The basic immunosuppressive regimen in all patients consisted of triple therapy. It may be more appropriate, therefore, to decrease total immunosuppressive load, i.e., to avoid triple therapy in patients >55 years rather than recommend routine prophylaxis against PCP. Johannes P. van Hooff1 Department of Nephrology; University Hospital Maastricht; 6202 AZ Maastricht, The Netherlands

BACKGROUND:It has been hypothesized that correction of metabolic acidosis might improve the nutritional state of acidotic haemodialysis (HD) patients partly because of a reduced oxidation of branched-chain amino acids (BCAA).AIM:We investigated whether bicarbonate (Bic) supplementation in acidotic HD patients results in increased plasma levels of BCAA.METHODS:In a longitudinal study (run-in period, 2 months; study period, 6 months), the effect of Bic supplementation on plasma levels of BCAA was studied in 12 acidotic HD patients (7 men, 5 women, mean age 54 +/- 18 years) with a predialysis bicarbonate (Bic) concentration smaller or equal to 22 mmol/l. Bic was supplemented by increasing Bic concentration of the dialysate and by oral Bic supplementation.RESULTS:Predialysis Bic increased significantly during the study period (18.7 +/- 2.7 vs. 23.1 +/- 11.5 mmol/l). There was no change in nutritional parameters. However, plasma levels of the BCAA valine, leucine, and isoleucine increased significantly.CONCLUSIONS:In haemodialysis patients with metabolic acidosis, Bic supplementation over a 6-months period resulted in an increase in plasma levels of BCAA. Further study is needed to elucidate the mechanisms behind, and the clinical importance of the observed changes in plasma BCAA levels.

The aim of combined pancreas-kidney transplantation (PKT) in type I diabetic patients with end-stage nephropathy is to restore both functions, Quality of life (QoL) is supposed to improve as a result of this combined transplantation. The objectives of this study are to evaluate QoL before and after PKT and to compare the results with patients in whom the pancreas graft failed soon after the transplantation (PKT-P), The trial is a prospective controlled multicenter study, The control group consists of patients before transplantation and patients who received a PKT in whom the pancreas rejected or thrombosed soon after the transplantation (PKT-P), A standardized home-based interview is done during dialysis, and repeated 5, 12, and 18 months after transplantation in both groups by the same interviewer. The interview consisted of disease-specific questions (RSCL), general questionnaires (NHP I and II, ABS), the Visual Analogue Scale, a specific questionnaire (Anxiety), and evaluative questions about social support and transplantation. Patients in whom the PKT is successful (n = 17) improve significantly or show a strong tendency toward improvement on many aspects of quality of life. Patients in whom the pancreas failed (n = 5) still demonstrate improvement, although this is not statistically significant in most cases, Intergroup comparison shows that PKT patients are less anxious, suffer of less itching, have better average daily living conditions, have no diet restrictions, and have and a better global quality of life.

The effect of flow cytometry crossmatches on clinical outcome was studied retrospectively in two groups of immunologically well-documented patients who had received transplants with a negative complement-dependent cytotoxicity crossmatch. The first group consisted of 114 consecutive renal allograft recipients, and the second group consisted of 76 immunologically at-risk recipients. Flow cytometry crossmatches were performed with current and historic sera. In group 1, positive flow cytometry (FC) crossmatches were shown in 15/114 (13%) recipients. Rejection occurred in 8/15 (53%) FC-positive versus 41/99 (41%) FC-negative recipients. The 1-year graft survival rate was 80% for FC-positive patients and 87% for FC-negative patients. Sixty-seven patients were nonsensitized patients; 4 of them had a positive FC crossmatch but no rejection episodes, graft loss, or patient loss. Of 47 retransplanted and/or sensitized recipients, 11 had a positive FC crossmatch. Rejection treatment was needed in 8/11 (73%) FC-positive patients compared with 19/36 (53%) FC-negative patients. Their 1-year graft survival rates were 73% and 81%. None of these differences reached statistical significance. Group 2 consisted of 76 at-risk recipients; 37 were retransplant patients and 39 were sensitized first-transplant patients. Twenty-one (28%) patients showed a positive FC crossmatch. Rejection episodes did not differ between the FC-positive (48%) and FC-negative patients (46%). There was no difference in 1-year graft survival rate (76% vs. 80%) or in 1-year patient survival rate (100% vs. 95%). We conclude that FC crossmatches in our patient group are not superior to the classical complement-dependent cytotoxicity crossmatches with regard to clinical outcome. On the contrary, transplantation with a mandatory negative FC crossmatch would have excluded 28% of the recipients from transplantation, who in fact are doing well.

Although as yet no major breakthroughs have occurred to improve long-term survival of haemodialysis patients with impaired cardiovascular function, it is possible to reduce morbidity by intra-dialytic hypotension in these patients by the use of relatively simple manoeuvres. In our experience, this can be achieved using the following approach (Table 1). First, the decline in plasma volume can be reduced by adequate estimation of the optimal dry weight by objective methods, such as echography of the inferior caval vein or bioimpedance measurements. Furthermore, the ultrafiltration rate during haemodialysis should be moderate and should be limited to a maximum value, which has to be defined empirically for each individual patient. Especially in patients with excess inter-dialytic weight gain, isolated ultrafiltration should be used when the required amount of fluid cannot be removed during haemodialysis. The use of low-sodium dialysate should be avoided. Probably it is best to use a physiological sodium concentration of the dialysate because a greater sodium concentration may result in increased thirst and intra-dialytic weight gain. Sodium profiling should be based on further studies concerning plasma volume changes during haemodialysis in different patient groups. Because of the deleterious impact of acetate on vascular reactivity, it should never be used in patients prone to hypotensive periods. Vascular reactivity can also be impaired by the use of vasoactive medication prior to haemodialysis treatment. Therefore, in patients prone to hypotensive periods, vasoactive medication should be withheld the morning before haemodialysis, if possible. Also, one should be very cautious with the use of low-calcium dialysate in patients with frequent hypotensive periods, and ideally it should be avoided. If the use of these manoeuvres fails to control intra-dialytic hypotension, one should consider the use of cold dialysate. Switching to haemofiltration or to continuous treatment modes such as CAPD are other options. Future studies should address haemodynamics during other treatment modes, such as haemodiafiltration or acetate-free biofiltration.

BACKGROUND:It is well known that vascular reactivity is impaired during combined ultrafiltration-haemodialysis as compared to isolated ultrafiltration and haemofiltration, which might be related to differences in plasma osmolality. Therefore vascular reactivity was studied during combined ultrafiltration-haemodialysis in relation to sodium-related differences in plasma osmolality/tonicity.METHODS:With each patient serving as his or her own control, nine stable dialysis patients (23-71 years) were studied during 2 h of combined ultrafiltration-haemodialysis (bicarbonate; UF rate 1.0 l/h)) at two different dialysate sodium concentrations: 134 and 144 mmol/l. Before dialysis as well as every 20 min during dialysis, blood pressure (Dinamap), heart rate (ECG), and forearm vascular resistance and venous tone (strain-gauge plethysmography) were measured. Relative blood volume was monitored continuously by an optical reflection method (Haemoguard 2000), while before and after dialysis blood was obtained for the estimation of plasma prostaglandin E2.RESULTS:High-sodium dialysis resulted in a significantly higher post-dialysis plasma sodium concentration (139. 9 vs 135.0 mmol/l; P<0.01) while the decrease in relative blood volume was significantly smaller as compared to low-sodium dialysis (-8.4 vs -18.4%; P<0.01). There were no significant differences in the different haemodynamic parameters between the two treatment modalities. Both high- and low-sodium dialysis were associated with a significant increase in forearm vascular resistance while venous tone remained unchanged. Although there was no significant difference in plasma PGE2 between the two treatment modalities, PGE2 increased significantly only during low-sodium dialysis. We found no relationship between changes in PGE2 and vascular reactivity.CONCLUSIONS:We conclude that vascular reactivity during combined ultrafiltration-haemodialysis is not directly influenced by sodium-related changes in plasma tonicity. Although not directly studied, the reported improved haemodynamic stability with high-sodium dialysis is probably only mediated through a better preservation of plasma volume. Finally, an increase in plasma PGE2 as observed during low-sodium dialysis does not lead to a decrease in vascular tone.

Because of the decreased venous compliance in hypertensive dialysis patients, it was investigated whether their venous system exhibited structural abnormalities. Venous samples were taken during transplantation from the common and external iliac vein in 12 hypertensive and 6 normotensive uremic patients and from the distal inferior caval vein and the common iliac vein in 7 kidney donors and 5 autopsy patients without history of cardiovascular disease. The thickness of the venous media was significantly increased in hypertensive uremic patients as compared to controls, but did not differ between normotensive patients and controls. The quantity of medial collagen did not differ among the various groups. The smooth muscle content of the media was increased in 5 uremic patients (2 normotensive and 3 hypertensive patients), whereas almost no smooth muscle was observed in the media of controls. Intimal thickening was observed neither in uremic patients nor in controls. In conclusion: increased medial thickness in hypertensive dialysis patients could be an explanation for the decreased venous compliance previously found in these patients.

BACKGROUND The present study was performed to assess the role of the extracorporeal blood temperature in the disparate cardiovascular response between isolated ultrafiltration and combined ultrafiltration-haemodialysis. METHODS In twelve stable dialysis patients (21-77 years), blood pressure and heart rate (Finapres) as well as forearm vascular resistance and venous tone (strain-gauge plethysmography) were measured during 1-h isolated ultrafiltration and 1-h combined ultrafiltration-haemodialysis (bicarbonate, sodium 141 mmol/l) at a fixed ultrafiltration rate of 0.91 l/h. The sequence of both treatment modalities was randomly defined within each patient. Serving as his or her own control, each patient was studied at two different dialysate temperatures: 37.5 and 35.0 degrees C. RESULTS At a dialysate temperature of 35.0 degrees C extracorporeal blood cooling during combined ultrafiltration-haemodialysis was comparable to isolated ultrafiltration. The cardiovascular response in isolated ultrafiltration was characterized by a significant increase in both forearm vascular resistance and venous tone, while heart rate even decreased. As a result, blood pressure remained unchanged or even increased. In contrast, during combined ultrafiltration-haemodialysis at a dialysate temperature of 37.5 degrees C the increase in forearm vascular resistance was only small and insignificant, while venous tone decreased significantly. Heart rate tended to increase. Combined ultrafiltration-haemodialysis at a dialysate temperature of 35.0 degrees C was also associated with a small increase in forearm vascular resistance. However, venous tone remained stable while heart rate decreased. At both dialysate temperatures, blood pressure was well maintained. CONCLUSIONS We conclude that differences in cardiovascular reactivity between isolated ultrafiltration and combined ultrafiltration-haemodialysis are only partially explained by differences in the extracorporeal blood temperature. In addition, especially venous reactivity is improved by lowering the dialysate temperature.

Recently, we demonstrated a reduction in the compliance of the carotid, femoral and brachial arteries in sodium-sensitive subjects who had consumed a regular sodium intake of approximately 120 mmol per day, as compared to both sodium-resistant borderline hypertensive subjects and normotensive controls. Venous compliance was not different between the two borderline hypertensive groups and was only slightly lesser than in controls. Large artery compliance was studied using a non-invasive ultrasound vessel wall movement detector system, while venous compliance was determined by means of strain gauge plethysmography. The borderline hypertensive subjects were subsequently treated with enalapril 10 mg/day, felodipine 5 mg/day or placebo during six months. Despite similar reductions in blood pressure, enalapril induced a significant increase of the muscular femoral and brachial artery compliance, but not of the elastic carotid artery, while felodipine did not influence large artery compliance at all in the sodium-sensitive group. The effect of enalapril on muscular artery compliance was established through a dose-dependent increase in distension and not through a change in arterial diameter. Arterial compliance was not influenced by either of the drugs in the resistant group. Venous compliance was also not altered by the medication. In conclusion, femoral and brachial artery compliance in sodium-sensitive borderline hypertensive subjects, which was found to be lower than that of sodium-resistant subjects, improved with antihypertensive treatment with enalapril but not with felodipine, despite the similar reductions in blood pressure induced by both drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

The role of fluid overload in the pathogenesis of hypertension in hemodialysis patients is not clear. One problem is the lack of techniques to determine the fluid state. Recent new noninvasive techniques have become available which make it possible to accurately determine the dry weight in these patients. Therefore, we studied the influence of interdialytic weight gain on interdialytic blood pressure in 10 normotensive and 10 hypertensive hemodialysis patients without antihypertensive medication. The dry weight was determined with echography of the vena cava. The blood pressure was measured during 2-day and 3-day interdialytic periods using Spacelabs 90207 ambulatory blood pressure monitors. Mean systolic and diastolic blood pressures of the last day of the interdialytic period were compared with mean systolic and diastolic blood pressures of the 1st day of the interdialytic period. Although the interdialytic weight gain in the normotensive and hypertensive patients was greater during the 3-day than during the 2-day interdialytic period, the interdialytic systolic and diastolic blood pressure changes were not greater during the 3-day period. Also, the interdialytic blood pressure rise did not correlate significantly with weight gain, neither in the normotensive nor in hypertensive patients. No significant interdialytic blood pressure changes were found between the normotensive and the hypertensive patients. We conclude that fluid overload does not seem to play a major role in interdialytic blood pressure control in normotensive and hypertensive hemodialysis patients.

Transplantation is published monthly and is the most cited and influential journal in the field, with more than 25,000 citations per year. The journal celebrated its 50th year in 2016. Transplantation has been the trusted source for extensive and timely coverage of the most important advances in transplantation. The Editors and Editorial Board are an international group of research and clinical leaders that includes many pioneers of the field, representing a diverse range of areas of expertise. This capable editorial team provides thoughtful and thorough peer review, and delivers rapid, careful and insightful editorial evaluation of all manuscripts submitted to the journal.