Colorectal complications of end-stage renal failure and renal transplantation: a review.

AIM: End-stage renal failure (ESRF) and renal transplant recipients are thought to be associated with an increased risk of colorectal complications. METHOD: A review of the literature was performed to assess the prevalence and outcome in both benign and malignant colorectal disease. RESULTS: No prospective randomized studies assessing colorectal complications in ESRF or renal transplant were identified. Case series and case reports have described the incidence and management of benign colorectal complications. Complications included diverticulitis,infective colitis, colonic bleeding and colonic perforation. There was insufficient evidence to associated iverticular disease with adult polycystic kidney disease.Three population-based studies have shown up to a twofold increased incidence of colonic cancer but not rectal cancer for renal transplant recipients. Bowel cancer screening (as per the general population) by faecal occult blood testing appears justified for renal transplant patients; however, evidence suggests that consideration of starting screening at a younger age may be worthwhile because of an increased risk of developing colonic cancer.Two population-based studies have shown a threefold and 10-fold increased incidence of anal cancer for renal transplant recipients. A single case­control study demonstrated significant increased prevalence of anal human papilloma virus (HPV) and intraepithelial neoplasia (AIN)in patients with established renal transplants. CONCLUSIONS: Despite the lack of high-level evidence,ESRF and renal transplantation were associated with colorectal complications that could result in major morbidity and mortality. Bowel cancer screening in this patient group appears justified. The effectiveness of screening for HPV, AIN and anal cancer in renal transplant recipients remains unclear.

Importance of minimizing HLA-DR mismatch and cold preservation time in cadaveric renal transplantation.

Univariate and multivariate analyses have been performed on donor an d recipient variables to determine possible effects on the outcome of 516 primary cadaveric renal transplants performed in our single center from 1989 until 1993. The overall actuarial patient survival at 1 year and 5 years was 94.4% and 87.4%, respectively; the 1 year and 5 year graft survival rates were 88.3% and 77.8%, respectively. A total of 95 grafts were lost; death with function (35%) and chronic rejection (22%) were the major causes. Three variables (HLA-DR mismatch, delayed graft function, and prolonged cold ischemia time) had a significant detrimental effect on both short- and long-term graft survival. Zero HLA-DR mismatched grafts showed significantly enhanced survival over those with 1 HLA-DR mismatch both at 1 year (92.8% vs. 84.5%) and at 5 years (88.3% vs. 73.9%) only if cold ischemia time was less than 26 hours (P=0.0009). Occurrence of delayed graft function significantly lowered graft survival at both 1 year and 5 years (P=0.002), and the incidence was significantly associated with prolonged cold ischemia time (P<0.0001). HLA-A or HLA-B matching, percentage panel reactive antibodies (PRA), and anastomosis time showed no independent effect on long-term survival. The small number of 2 HLA-DR mismatched grafts (n=6) precluded separate analysis of this group. Acute rejection accounted for 12% of losses but had no statistically significant effect on graft survival, even though an increased frequency of rejection episodes was significantly associated with HLA-DR mismatch (P<0.0001). These results would suggest that significant survival benefits may be achieved by prospective HLA matching if cold ischemia times are limited. The efficiency of organ sharing must he improved to make optimal use of a limited resource.

Late perfusion. A simple remedy for renal allograft primary nonfunction.

Primary nonfunction in renal allografts makes the diagnosis of allograft dysfunction more difficult and may effect long-term graft survival. The prevention of primary nonfunction by a reperfusion technique has been assessed in a prospective analysis of 145 consecutive renal transplants performed in a single center. All kidneys were retrieved using an in situ perfusion method, and all but 13 recipients received a standardized immunosuppressive protocol with cyclosporine. The first 106 transplants were performed without the benefit of any additional perfusion, and the incidence of primary nonfunction was 57.5% in these patients. The last 39 kidneys received additional perfusion with kidney perfusion fluid immediately prior to implantation (late perfusion). In the latter group, the incidence of primary nonfunction was 30.8% (P = 0.007). Using logistic regression analysis, only three factors were found to be associated with primary nonfunction: immunosuppression with cyclosporine (P = 0.01), a second warm ischemia time of greater than 35 min (P = 0.002), and late perfusion (P = 0.003). In this study, the use of late perfusion alone has reduced the incidence of primary nonfunction by almost one half. The technique is simple, safe, inexpensive, and effective. Its routine use is now advocated in all renal transplants.

Anti-CD45 monoclonal antibody perfusion of human renal allografts prior to transplantation. A safety and immunohistological study. CD45 Study Group.

The perfusion of kidneys with anti-CD45 monoclonal antibodies prior to transplantation offers a means of targeting passenger antigen-presenting cells with the aim of reducing the subsequent incidence of rejection episodes. A safety study was performed in humans of such pretreatment in 40 unsensitized recipients of first cadaveric renal grafts, who were followed for 3 months after transplantation. A 50-ml solution containing 2 mg of each of the rat anti-CD45 mAbs YTH 24.5 and YTH 54.12 was injected into the allograft renal artery ex vivo and just before transplantation while the renal vein was kept clamped. No patients died, but 4 grafts were lost. Two were lost due to primary nonfunction, 1 was lost because of late renal artery thrombosis, and 1 was lost to rejection. There were no cases of renal vein thrombosis and 1 trivial renal artery stenosis, and only 2 patients produced human anti-rat antibodies. Between 63.5% and 100% (median 96.4%) of CD45+ cells in the postperfusion biopsies were coated with anti-CD45 as determined by double-immunolabeling. The number of patients experiencing rejection episodes was inversely associated with this "antibody uptake": 75% of the low uptake group (< 95%) had at least 1 rejection episode, compared with 22% of the high uptake group (> or = 95%) (P = 0.001). The complement components C3 and C5b-9 colocalized with perfused anti-CD45 in 32/33 (97.0%) and 11/33 (33.3%) of the biopsy specimens, respectively. We conclude that: (1) this technique appears free of adverse effects, (2) high antibody uptake within the kidney is associated with a lower incidence of rejection, and (3) the antibodies used fix and activate complement in vivo.

Small intestinal infarction: a fatal complication of systemic oxalosis.

Primary hyperoxaluria is a rare genetic disorder characterised by calcium oxalate nephrolithiasis and nephrocalcinosis leading to renal failure, often with extra-renal oxalate deposition (systemic oxalosis). Although ischaemic complications of crystal deposition in vessel walls are well recognised clinically, these usually take the form of peripheral limb or cutaneous ischaemia. This paper documents the first reported case of fatal intestinal infarction in a 49 year old woman with systemic oxalosis and advocates its consideration in the differential diagnosis of an acute abdomen in such patients.

Plasma oxalate concentration and secondary oxalosis in patients with chronic renal failure.

To examine the association between hyperoxalaemia and secondary oxalosis, measurement of plasma oxalate concentration was combined with a search for tissue deposition of calcium oxalate crystals in patients with chronic renal disease. Two groups of patients were studied. In the first, samples of the inferior epigastric artery were taken from 35 patients at the time of renal transplantation. In the second, sections taken at necropsy from 23 patients with chronic renal failure in whom plasma oxalate had been measured before death were examined. Though plasma oxalate concentrations ranged between 6 and 116 mumol/l (four to 78 times greater than the upper limit of the reference range), no extrarenal deposits of oxalate were found in either study. Renal deposition of oxalate was associated with a plasma oxalate concentration of greater than 20 mumol/l. This study gives no support to the suggestion that hyperoxalaemia of the degree seen in patients with the type of chronic renal failure that is not due to primary hyperoxaluria confers an appreciable risk of extrarenal oxalosis.

Gastric hyalinization presenting in life and mimicking gastric cancer.

Gastric hyalinization is an unusual abnormality that has in the past been regarded by some authorities as a postmortem artifact. We describe a 69-year-old patient who presented with symptoms due to the condition, and who was treated by surgical resection of the diseased stomach. To our knowledge, no other case presenting in life has been identified in the literature, which we reviewed in the light of the present case. The cause of the condition remains unknown.

Azathioprine-induced pure red cell aplasia: case report and review.

The major adverse effect of azathioprine is its myelotoxicity, with leukocytes being affected more commonly than the other bone marrow elements. Although megaloblastic change is frequent, reportedly seen in 16% to 82% of bone marrow aspirates, long-term use of azathioprine rarely causes severe anemia. We report a case of refractory pure red cell aplasia resulting from long-term use of azathioprine in a renal transplant recipient and examine the possible underlying mechanisms. There was no response to dose reduction or to erythropoietin administration. However, there was immediate recovery after complete drug withdrawal. A review of the literature revealed that only ten cases of azathioprine-induced red cell aplasia have so far been described, all in transplant recipients.

Surgical aspects of chronic peritoneal dialysis in the neonate and infant under 1 year of age.

Since 1982 eight patients under 1 year of age with end-stage renal failure have been treated by chronic peritoneal dialysis (CPD) following insertion of an abdominal Tenckhoff catheter. We routinely perform a partial omentectomy now, and in males undertake bilateral exploration of the groins at the time of catheter insertion, with herniotomy or ligation of the patent processus vaginalis as required. Up to January 1990, 19 straight double-cuff catheters had been inserted with a total follow-up of 244.5 patient months. The median age at the initial catheter insertion was 14.6 weeks (range, 2 days to 11 months) and the median weight was 3.89 kg (range, 2.2 to 5.5). Peritonitis was the most common complication, with 46 episodes, representing one episode of peritonitis per 5.3 patient months on dialysis. The frequency of peritonitis has decreased in the last 6 months since all patients have been dialysed by two caregivers. The present rate of peritonitis is 1 episode per 10 patient months on dialysis. One patient has died of septicemia secondary to associated congenital abnormalities, one patient has regained renal function, and two patients have been transplanted, one successfully. Five patients are currently dialysing via their abdominal Tenckhoff catheters and awaiting transplantation. We conclude that neonates and infants under 1 year of age can be treated satisfactorily by CPD to enable successful preparation for transplantation later in childhood.

Blood transfusion and surgery: the effect on growth of a syngeneic sarcoma.

The effects of blood transfusion, blood components, and surgical trauma on the growth of an experimental sarcoma have been examined. Recipient animals were inbred adult female WAB rats, which received allogeneic transfusions from inbred adult female PVG rats, syngeneic blood from inbred colony-mates, or saline infusions. Small volume transfusions (1-4 ml) of whole blood had no effect on tumour growth, but growth of the MC7 sarcoma was significantly enhanced following allogeneic transfusions of 5 ml whole blood, or when 4 ml was combined with sham laparotomy. Maximal enhancement of tumour growth occurred when 4 ml transfusions of allogeneic washed cells were given, but allogeneic plasma was also able, to a lesser degree, to enhance tumour growth. These data confirm that blood transfusion may enhance growth of the MC7 sarcoma, that the effect may be dose dependent, and synergistic with the immunosuppression of surgery. Many components of an allogeneic transfusion may be responsible for this effect.

Metabolic and inflammatory responses after laparoscopic and open inguinal hernia repair.

A prospective comparison of metabolic and inflammatory responses after laparoscopic and open inguinal hernia operations was undertaken. There were 10 patients in each group. Plasma levels of cortisol, growth hormone, prolactin, C-reactive protein (CRP) and interleukin-6 (IL-6) were measured preoperatively and at fixed intervals up to 120 h postoperatively. In vitro, endotoxin stimulated whole blood tumour necrosis factor alpha (TNF alpha) was measured in preoperative and 24 h postoperative blood samples. Changes in the plasma levels of cortisol, growth hormone and prolactin showed no statistically significant difference between the groups. No significant change in IL-6 levels were recorded in any group. Changes in CRP levels were significantly higher (P < 0.006) in open hernia patients. Endotoxin stimulated TNF alpha production was suppressed in both groups. The degree of suppression in open hernia patients was significantly higher (P < 0.005). This study has shown that both these operations produce similar stress responses. However, open hernia operation results in a higher acute phase response and induces a greater endotoxin tolerance.

The outcomes of living donor renal transplants with multiple renal arteries: a large cohort study with a mean follow-up period of 10 years.

BACKGROUND: Living donor kidney transplants with multiple arteries are presumed to be associated with an increased risk of complications. OBJECTIVES: The aim of the study was to compare the outcomes in living donor transplantation with the specific intention of comparing long-term outcomes in which the donor kidney had 1 or more renal arteries. The study was undertaken in 2 large transplant centers. METHODS: A retrospective analysis of 201 living donor kidney transplants with multiple arteries that were performed between January 1985 and December 2004 was undertaken. We recorded patient and graft survivals, urological and vascular complications. Kaplan-Meier survival estimates were calculated, and 2-tailed Student t-test was used to compare outcomes. P < .05 was considered statistically significant. RESULTS: Graft and patient survival at 1 year were 93% and 97% and at 5 years were 87% and 92%. The most common complications were vascular (8.9%), followed by urological (6%), acute tubular necrosis (5.5%), and posttransplant hypertension (4.0%). There was significantly higher incidence of acute tubular necrosis (ATN) in multiple-artery transplants. CONCLUSION: In this large cohort of patients studied, apart from a higher incidence of ATN and vascular complications, it appears that the number of renal arteries did not have any adverse impact on the outcomes. The findings from this study suggest that live donor kidneys with multiple renal arteries can be safely utilized for renal transplantation.