Biocompatible membranes do not promote graft recovery following cadaveric renal transplantation.

BACKGROUND: Controversy surrounds the role of biocompatible membrane dialyzers in treatment of acute renal failure. Studies that have shown a benefit have involved critically ill patients where renal recovery and patient mortality are influenced by other comorbid disease. The aim of the present work is to clarify this issue in a more homogeneous population of patients with acute renal failure following cadaveric renal transplantation. METHODS: All patients with delayed graft function between January 1996 and February 1998 were randomized to receive either a biocompatible (BCM, polysulfone) membrane or bioincompatible (BICM, cuprophane) membrane for dialysis until onset of graft function. RESULTS: Forty-one patients were randomized, 23 to receive BCM and 18 BICM. Five patients (2 BCM, 3 BICM; p = NS) with primary non-function of graft were excluded from analysis, leaving 36 cases of acute tubular necrosis (ATN). Patient and donor characteristics were similar in both groups. The BCM group had significantly longer periods of dialysis dependency compared to the BICM group (14 vs 10 days; p = 0.03). There was a tendency towards higher serum creatinine levels in the short term in the BCM group (318 vs 164 micromol/l at 1 month (p = 0.1), 190 vs 169 micromol/l at latest visit (p = 0.07)) and a greater number of acute rejection episodes in the BCM group (3.7 vs 1.7 episodes per 100 days of dialysis dependency, p = 0.1). With an intention-to-treat analysis of all 41 patients originally randomized, there was no significant difference in time to graft recovery between the 2 groups (p = 0.18). CONCLUSIONS: In the setting of ARF posttransplantation, we have found no evidence to support the use of biocompatible membranes for dialysis. Rather, our study provides argument against a large benefit for the use of BCM in the recovery of ARF, as suggested by earlier studies.

The impact of late acute rejection after cadaveric kidney transplantation.

BACKGROUND: Acute graft rejection (AR) following renal transplantation results in reduced graft survival. However, there is uncertainty regarding the definition, aetiology and long-term graft and patient outcome of AR occurring late in the post-transplant period. AIM: To determine if rejection episodes can be classified by time from transplantation by their impact on graft survival into early acute rejection (EAR) and late acute rejection (LAR). MATERIALS AND METHODS: 687 consecutive adult renal transplant recipients who received their first cadaveric renal transplant at a single centre. All received cyclosporine (CyA)-based immunosuppression, from 1984 to 1996, with a median follow-up of 6.9 yr. Details were abstracted from clinical records, with emphasis on age, sex, co-morbid conditions, HLA matching, rejection episodes, patient and graft survival. ANALYSIS: Patients were classified by the presence and time to AR from the date of transplantation. Using those patients who had no AR (NAR) as a baseline, we determined the relative risk of graft failure by time to rejection. The characteristics of patients who had no rejection, EAR and LAR were compared. RESULTS: Compared with NAR, the risk of graft failure was higher for those patients who suffered a rejection episode. A much higher risk of graft failure was seen when the first rejection episode occurred after 90 d. Thus, a period of 90 d was taken to separate EAR and LAR (relative risk of 3.06 and 5.27 compared with NAR as baseline, p<0.001). Seventy-eight patients (11.4%) had LAR, 271 (39.4%) had EAR and 338 (49.2%) had NAR. The mean age for each of these groups differed (LAR 39.6 yr, EAR 40.8 yr compared with NAR 44 yr, p<0.003). The 5-yr graft survival for those who had LAR was 45% and 10-yr survival was 28%. HLA mismatches were more frequent in those with EAR vs. NAR (zero mismatches in HLA-A: 36 vs. 24%, HLA-B: 35 vs. 23% and HLA-DR: 63 vs. 41%, p<0.003). There was no difference in mismatching frequency between NAR and LAR. CONCLUSIONS: AR had a deleterious impact on graft survival, particularly if occurring after 90 d. AR episodes should therefore be divided into early and late phases. In view of the very poor graft survival associated with LAR, it is important to gain further insight into the main aetiological factors. Those such as suboptimal CyA blood levels and non-compliance with medication should be further investigated with the aim of developing more effective immunosuppressive regimens in order to reduce the incidence of LAR.

Early graft function and patient survival following cadaveric renal transplantation.

BACKGROUND: The influence of events that occur early following renal transplantation such as delayed graft function (DGF) and acute rejection on long-term graft survival has been widely reported, but its association with patient survival has received less attention. METHODS: We studied 589 patients who received their first cadaveric transplants between 1984 and 1993, all of whom received cyclosporine-based immunosuppression and who had a median follow-up of seven years. The following factors were identified, and both univariate and multivariate analyses were used to determine their association with long-term patient and graft survival: age, sex, duration of pretransplant dialysis, primary renal disease, immediate graft function (IGF), DGF, primary nonfunction (PNF), acute rejection, and serum creatinine at 3, 6, and 12 months. RESULTS: Patients with PNF had a poorer survival than those with DGF and IGF (P = 0.01), but there was no difference in survival between DGF and IGF (P = 0.54). Good graft function (serum creatinine of less than 200 mumol/liter) at three months was predictive of better long-term patient survival (P = 0.03). Other factors associated with poor patient outcome were older age, diabetes, adult polycystic kidney disease, male gender, and acute rejection. Cardiovascular disease was the most common cause of death (51.8%). Good graft function at three months (P < 0.001) and an absence of rejection episodes (P = 0.01) were associated with better graft survival. CONCLUSION: Patients with poor levels of early graft function (but not DGF) and those with either acute rejection episodes or early graft loss are at an increased risk of early death. These high-risk groups should be targeted for interventional studies in an attempt to improve patient survival.

Long-term outcome of a prospective randomized trial of conversion from cyclosporine to azathioprine treatment one year after renal transplantation.

BACKGROUND: Since the introduction of cyclosporine (CsA), 1-year renal allograft survival has improved, but concern persists about the long-term adverse effects of CsA, especially with respect to renal function and blood pressure. This randomized controlled trial was set up to establish whether withdrawal of CsA would alter long-term outcome. METHODS: Adult patients who, at 1 year after renal transplantation, had a stable serum creatinine of less than 300 micromol/L and who had not had acute rejection within the last 6 months were eligible for entry. Patients were randomized either to continue on CsA (n=114) or to stop CsA and start azathioprine (Aza, n=102). All patients remained on prednisolone. Median follow-up was 93 months after transplantation (range: 52-133 months). RESULTS: There was no significant difference in actuarial 10-year patient or graft survival (Kaplan-Meier), despite an increased incidence of acute rejection within the first few months after conversion. Median serum creatinine was lower in the Aza group (Aza: 119 micromol/L; CsA. 153 micromol/L at 5 years after randomization, P=0.0002). The requirement for antihypertensive treatment was also reduced after conversion to Aza; 75% of patients required antihypertensive treatment at the start of the study, decreasing to 55% from 1 year after randomization in the Aza group and increasing to >80% in the CsA group (55% (Aza) and 84% (CsA) at 5 years after randomization, P<0.005). CONCLUSIONS: Conversion from CsA to Aza at 1 year after renal transplantation results in improvement in both blood pressure control and renal allograft function, and is not associated with significant adverse effects on long-term patient or graft survival.

Pre-operative echocardiographic abnormalities and adverse outcome following renal transplantation.

BACKGROUND: Premature cardiovascular disease is now the leading cause of death in renal transplant recipients. Although patients with progressive renal disease have many of the conventional risk factors for cardiovascular disease these do not have the same predictive power as they do in the general population. Echocardiographic abnormalities, notably left ventricular hypertrophy, have been shown to be associated with adverse outcome in patients on dialysis. METHODS: The echocardiograms were studied from 141 patients who were examined on the eve of renal transplantation between 1988 and 1990 to try to identify factors predicting outcome. Thirty-four patients have since died, 22 of cardiovascular disease. Ninety-three of the survivors and 27 of the dead patients had echocardiographic traces suitable for analysis. RESULTS: Left ventricular mass index was increased in those patients who died (median 167 vs 134 g/m2; P=0.03), as were end-systolic (4.3 vs 3.4 cm; P<0.01) and end-diastolic (5.8 vs 5.2 cm; P<0.01) diameters. Systolic function was also more severely impaired (fractional shortening, 27 vs 33%; P<0.01). Apart from age, only systolic function and end systolic diameter were independent predictors of outcome in multivariate analysis. CONCLUSIONS: This pattern of echocardiographic abnormality is similar to that reported in long-term dialysis populations, despite the adverse effects on survival. Moreover, despite potential benefits of transplantation on cardiac function, left ventricular hypertrophy, ventricular dilatation and systolic dysfunction were all associated with adverse outcome following transplantation. We conclude that echocardiography identifies markers for premature death following transplantation and provides targets for therapeutic intervention.

Effect of renal-artery stenting on progression of renovascular renal failure.

BACKGROUND: Placement of renal-artery stents has a high technical success rate in atherosclerotic renovascular disease, but little is known about the clinical benefits of the procedure. We monitored renal function serially before and after stent insertion in patients with renovascular renal failure. METHODS: Renal function was assessed before and after stent placement by means of serial serum creatinine values in 32 patients with atherosclerotic renal-artery stenosis. The effect on the progression of renal failure was analysed in 23 patients by comparison of the reciprocal slopes of serum creatinine versus time plots before and after stent placement. FINDINGS: 33 transluminal stents were placed in 32 patients with atherosclerotic renovascular disease. Immediate patency was achieved in all cases: the angiographic restenosis rate at 6 months was 12% (n = 24). One patient died after a procedure-related haemorrhage. Median diastolic blood pressure was significantly lower after stenting than before (95 [IQR 86-103] vs 87 [81-90] mm Hg; p > 0.01) but the requirement for antihypertensive drugs was unchanged. Renal function improved or stabilised in 22 (69%) of the 32 patients. Progression of renal failure was significantly slowed after the procedure; the mean (SE) of the slopes of reciprocal serum creatinine values was -4.34 (0.85) L mumol-1 day-1 before stent placement, and -0.55 (1.0) L mumol-1 day-1 after stent placement (p < 0.01, two-sample t test). INTERPRETATION: Renal-stent placement in selected patients slows the progression of renovascular renal failure and may delay the need for renal replacement therapy.

The need for renal replacement therapy in Scotland.

Each year 80-100 people per million of the population develop end stage renal failure and are medically suitable for renal replacement therapy. This need has been met in Scotland in each of the last three years. With current knowledge there is no prospect of measures to prevent renal disease affecting this number in the foreseeable future. The number of patients on renal replacement therapy in Scotland will increase over the next 15 years to approximately 160% of the current number. The mean age of patient on replacement therapy will increase progressively over the next 15 years. The increase in numbers will be in patients receiving 'in centre' haemodialysis and in those with functioning renal transplants. To meet this increase an approximately 3-4 increase in the current 'in centre' haemodialysis facilities will be required. Additional haemodialysis centres should be established to reduce the time spent by patients travelling for treatment and to avoid centres becoming 'impersonal' by becoming too large. Moves to increase the transplantation rate should be encouraged as transplantation offers the best quality of life for patients. Research should be directed towards improving long term graft survival.

Ranitidine reduces phosphate binding in dialysis patients receiving calcium carbonate.

BACKGROUND: In a previous controlled study we showed that ranitidine significantly reduced the phosphate binding of aluminium hydroxide in patients with renal failure, probably increasing intragastric pH. METHODS: In this study we have investigated the effect of ranitidine on the phosphate binding of calcium carbonate in fifteen dialysis patients. Ranitidine 300 mg or a placebo tablet was taken before breakfast for two 4-week periods in a double-blind crossover trial with no washout period. The mean daily dose of calcium carbonate was 2 g and neither the dose nor the patient's diet was changed during the study period. Blood was taken at 2-weekly intervals for serum phosphate, calcium, albumin, and alkaline phosphatase measurements, and at the end of each treatment period for parathyroid hormone (PTH) level. RESULTS: Serum phosphate concentrations were significantly higher during the ranitidine than the placebo phase, 1. 78 (+/-0.43 SD) versus 1.59 (+/-0.49 SD) mmol/l (P<0.001). Serum calcium, albumin, PTH, and alkaline phosphatase concentrations did not differ between the two treatment periods. CONCLUSION: This study shows that ranitidine has a significant adverse effect on the phosphate binding of calcium carbonate in patients with renal failure.

Longitudinal evaluation of peritoneal macrophage function and activation during CAPD: maturity, cytokine synthesis and arachidonic acid metabolism.

The release of cytokines and prostaglandins (PG) by peritoneal macrophages (PM luminal diameter of) may influence the cytokine network controlling peritoneal inflammation and in the long-term the function of the peritoneum as a dialysis membrane. In the present study, an evaluation of the long-term effects of peritoneal dialysis on the release of cytokines and prostaglandins, and the expression of surface markers of cellular maturation on blood and mononuclear cells has been performed in patients during their first year on CAPD. Spontaneous release of tumour necrosis factor alpha (TNF alpha) and interleukins 6 (IL-6) by PM luminal diameter of, after 4 or 24 hours in culture, increased significantly with time on CAPD, while there was a small but significant decrease in release of prostaglandin E2 (PGE2). Production of TNF alpha and IL-6 was enhanced following incubation of the cells with lipopolysaccharide (LPS), but the effect of LPS was proportionally greater on blood monocytes than on PM luminal diameter of. There was a significant increase in the concentrations of PGE2 and 6-keto-prostaglandin F1 alpha in overnight dwell peritoneal dialysis effluent with time on CAPD. The levels of TNF alpha and IL-6 in uninfected PDE were below the detection limit of the immunoassay over the whole time period studied. Expression of CD15, which correlates with immaturity, by PM luminal diameter of and blood monocytes increased with time on CAPD, while expression of CD11c, a marker of maturation, decreased on blood monocytes, but did not change significantly on PM luminal diameter of. There was also a slight increase in expression of transferrin receptor in both PM luminal diameter of and monocytes, but this did not reach statistical significance. These findings suggest that peritoneal macrophages and blood monocytes isolated from CAPD patients over a one year period become increasingly immature with time, and this is accompanied by a significant modulation of their ability to secrete inflammatory cytokines. Dysregulation of macrophage function may have important consequences with respect to inflammatory processes and the long-term function of the peritoneal membrane in CAPD patients.

Treatment of postrenal transplant erythrocytosis. Long-term efficacy and safety of angiotensin-converting enzyme inhibitors.

Fifty-two patients with postrenal transplant erythrocytosis were treated with an angiotensin-converting enzyme inhibitor (lisinopril or enalapril) for a median of 13 months (range 0-44). A significant fall in haemoglobin of 1.8 +/- 1.6 g dl-1 (range - 0.8 to 6.6) occurred over the first 3 months (p < 0.0001). The haemoglobin then remained stable for as long as 3 years. Both enalapril and lisinopril were equally effective. Therapy was withdrawn in 16 patients (31%) because of decline in renal function (6), anaemia (5), hypotension (3), hyperkalaemia (1) or erectile impotence (1) - complications which were all reversible. Angiotensin-converting enzyme inhibitors in low dose are a safe and effective long-term therapy for postrenal transplant erythrocytosis.

Nursing involvement in research: an academic pursuit or relevant to nursing practice?

It is said that nursing is 'informed by research'. We evaluated the effect a clinical research project had on the nursing procedure of a nonrotating, permanent continuous ambulatory peritoneal dialysis (CAPD) team involved primarily in patient care. A trial of the overnight solute clearance as a simple measure of the adequacy of CAPD was carried out and its effect on the following aspects of nursing practice was assessed: 1. Teamwork-Can research be successfully incorporated within the team's work structure in a clinical environment? 2. Nurse's role-Duties of the nurse involved in the research (selection of patients, organization of appointments, collection of samples, and calculation of results). 3. Nurse/patient relationship-Individual knowledge of patients' needs and communication skills employed (necessity for true informed consent). The experience showed us that the participation in research is not only possible, but also interesting from the nurses' viewpoint and of direct benefit to the patients.

Colour Doppler ultrasound in renal transplant artery stenosis: which Doppler index?

A prospective study comparing colour Doppler ultrasound (US) with the 'gold standard' of intra-arterial digital subtraction angiography in the evaluation of renal transplant artery stenosis was performed. Both the intrarenal vessels and the transplant renal artery were examined by Doppler US. Diagnostic arteriography was performed only if, on Doppler, the peak systolic velocity in the transplant renal artery exceeded 1.5 ms-1. Of 109 patients, the transplant artery could not be visualized using colour Doppler US in three, and these were omitted from statistical analysis. Of the remaining 106 patients, 31 had a peak systolic velocity greater than 1.5 ms-1 in the transplant renal artery and were referred for DSA. Of the multiple renal Doppler indices recorded, the peak systolic velocity in the transplant artery was the best discriminating measurement for the detection of renal artery stenosis. A peak systolic velocity of > or = 2.5 ms-1 in the transplant renal artery had a sensitivity of 100% and a specificity of 95% for the detection of renal artery stenosis ( > 50% diameter reduction). Although a significant difference in Pulsatility Index, Resistive Index, Acceleration Index and Acceleration Time was recorded from the intrarenal vessels in the angiographically normal and stenosed groups with Doppler, these measurements were less useful as discriminating diagnostic tests. In conclusion, the peak systolic velocity in the transplant renal artery is the most sensitive Doppler criterion for renal artery stenosis and is sensitive and specific enough to be used as a screening test. The intrarenal acceleration time and index should not be used in isolation.

Polymorphisms in angiotensin-converting-enzyme gene and progression of IgA nephropathy.

We have investigated the influence of the functional insertion (I) and deletion (D) polymorphism in intron 16 of the gene for angiotensin-converting enzyme (ACE) in a retrospective study of 100 patients with IgA nephropathy. There was no difference in genotype frequency compared with normal subjects. However, patients homozygous for the D allele tended to present at an earlier age (medians: DD, 33; ID, 34; II, 42 years) and to require renal replacement therapy at a younger age (medians 37, 42, and 48 years, respectively). The rate of progression was significantly worse in patients homozygous for the D allele. The DD genotype is associated with increased severity of disease in patients with IgA nephropathy.

Long-term outcome of the use of OKT3 to treat steroid-resistant acute renal allograft rejection.

OKT3 was used to treat steroid-resistant acute renal allograft rejection in 30 of 496 adult patients transplanted over a 6-year period. Rejection was reversed (defined as a fall in serum creatinine by 50% or more within 30 days of treatment with OKT3) in 40% of cases. Successful reversal was significantly more likely when rejection occurred shortly after transplantation (t ratio -2.53; P = 0.019). The long-term outcome was disappointing; the actuarial graft survival at 1 year from the start of treatment with OKT3 was 42%, and no grafts have thus far survived longer than 3 years. Graft survival was shorter in older patients (coefficient/standard error 2.226; P < 0.05), and no other predictor of long-term outcome was identified. Patient survival at 3 years was 88%. Serious infection occurred in 33% of patients, with two deaths. Our experience suggests that treatment with OKT3 is unlikely to reverse acute renal allograft rejection in more than half of patients where rejection is resistant to steroids. Although long-term graft survival occurred in a few cases, the overall long-term outcome was disappointing, particularly in older patients. Finally, our analysis indicates the difficulty of predicting which patients will derive long-term benefit when OKT3 is used to treat steroid-resistant rejection.

Immunosuppression in sclerosing peritonitis.

Sclerosing peritonitis (ScP) is a rare but fatal complication of continuous ambulatory peritoneal dialysis (CAPD), presenting as small bowel obstruction. We have observed that only patients receiving a renal transplant survived more than a few months after the diagnosis of ScP. We now report prolonged survival of patients given immunosuppressive therapy with or without a functioning transplant. ScP was found at laparotomy in 17 Glasgow patients, 15 of whom had been exposed to chlorhexidine in alcohol. All patients discontinued CAPD after diagnosis. Within a year 12 died with recurrent bowel obstruction; none received immunosuppressive therapy. The remaining 5 patients received immunosuppressive therapy; 4 are alive between 1 and 9 years later, and one patient with widespread vascular disease died after 3 years with mesenteric ischemia. Four of the 5 received a renal transplant. One patient rejected his transplant; when immunosuppression was stopped he developed symptoms suggestive of recurrent ScP. Immunosuppressive therapy was restarted and he remains well 3 years later. The fifth patient, who did not receive a transplant, was immunosuppressed after ScP was diagnosed. She remains well 18 months later. Our experience suggests that immunosuppression is beneficial in ScP.