Functional and morphological changes in kidneys from marginal donors.

Despite the increased number of cadaver donors and overall organ transplantations, we have observed a dramatic increase in the waiting list. We evaluated transplantations performed using marginal (n = 63) and "ideal" or optimal donors (n = 86). Donor and recipient functional and histopathological data were studied at 1 and 5 years after transplantation. Among the marginal donor group, we investigated whether the age or pre-existent hypertension in the donor showed a strong impact on the functional deterioration of the grafts. Twenty-three graftectomies were performed in marginal, and 39 in ideal recipients (P = .002). Evaluating graft function, at 5 years, we observed the serum creatinine level (P = .0001) and the estimated glomerular filtration rate (P = .003) are significantly different between the two groups. At this time there was a significant difference in the serum creatinine level of patients who were older than the age of 55 years compared with those who showed hypertension (P = .0003). Evaluating morphological changes in the kidneys, acute rejection episodes (P = .0004) and interstitial fibrosis/tubular atrophy (P = .002) were significantly greater among the marginal versus the ideal groups. At 1 year after kidney transplantation, despite no significant difference regarding renal function, they were significant in the histology of marginal versus ideal donor kidneys.

Mental representations of the new organ and posttransplant patients' anxiety as related to kidney function.

Transplant patients' representations of their illness, body, and emotional state significantly influence their recovery. In this study, our primary aim was to examine the possible connections between emotional factors, body and illness representations, and renal function after 58 kidney transplantations. To measure mental representations of transplanted kidneys, we developed a projective drawing test. Other assessment instruments were the Beck Depression Inventory, Spielberger's State and Trait Anxiety Scale, and an in-house questionnaire. We also measured conventional kidney function markers, such as serum creatinine and urea levels. Analysis of our results revealed that patients with higher anxiety levels drew significantly larger kidneys in their projective drawing tests, and displayed significantly higher 10-day creatinine and urea level leading us to consider interrelations of an organ's intrapsychic integration and kidney function. If the graft is not integrated mentally in the body image, the representations of the "foreign body" can be associated with such psycho-neuro-immunologic processes of anxiety, which eventually may lead to adverse physiological effects on kidney function.

Post-transplant diabetes mellitus - risk factors and effects on the function and morphology of the allograft.

The incidence of post-transplant diabetes mellitus and its effects on the kidney allograft function and morphology were assessed. Patients were divided into three groups according to their glucose metabolism. Risk factors for diabetes were first assessed, and then changes in renal function were checked. Morphological changes in the allografts were examined by protocol biopsies. The overall incidence of diabetes was 16%. The development of diabetes was influenced significantly by the body mass index, the body weight and the age of the recipient. The incidence of diabetes was 8.6% in patients on cyclosporine A therapy and 28.8% in those on tacrolimus (p < 0.05). As to the morphology of the kidney, a significantly higher proportion of the biopsies showed severe interstitial fibrosis/tubular atrophy (p = 0.0004) and subclinical acute rejection ( p = 0.001) in the diabetic group compared to the normal one. This clinical study has revealed that the adverse effect of diabetes on the allograft can be detected with protocol biopsy before the manifestation of a functional deterioration.

Treatment of subclinical injuries detected by protocol biopsy improves the long-term kidney allograft function: a single center prospective randomized clinical trial.

BACKGROUND: The long-term benefit of early treatment of subclinical disorders detected in kidney allografts by protocol biopsy is controversial. We collected 145 protocol biopsies from 113 recipients for comparison with 51 control patients in a single-center, prospective, randomized trial. METHODS: Ultrasound-guided biopsies were performed in recipients with stable renal function. Samples were taken at 3 (n=66) and/or 12 months (n=79) after transplantation. The biopsies were evaluated according to the Banff scheme, and patients were treated based on the diagnosis. Changes in glomerular filtration rate (GFR) were compared with 51 patients who were randomized as a control group. RESULTS: The findings on 38 samples (29%) were considered to be normal. Based on the pathology findings, such as subclinical acute rejection (n=23), calcineurin inhibitor toxicity (n=28), chronic rejection (n=6), and other specific pathologies (n=23), including polyoma virus nephropathy (n=2), induced treatment among 82 recipients (57%). Significantly better graft function was observed at 3-year follow-up among the biopsy group, compared with controls: GFR = 46.0 ± 13.8 vs 35 ± 15 mL/min (P=.002). The 5-year graft survival was significantly higher in the biopsy (81%) than in the control (55.6%) group (P=.0012). CONCLUSION: Early detection and treatment of subclinical pathologies improved graft function and long-term survival. Protocol biopsies were a valuable tool for posttransplantation management.

Functional and histopathologic changes in renal transplant patients with new-onset diabetes and dyslipidemia.

BACKGROUND: The principal risk factors for cardiovascular mortality posttransplantation are hyperglycemia, hypertriglyceridemia, obesity, and smoking. METHODS: Among 115 patients, we assessed the risk factors for new-onset diabetes (NODM) and dyslipidemia (NODL), and their effects on the function and histopathologic changes in the allografts at 1 year posttransplantation. RESULTS: When evaluating the risk factors and the initial recipient data, we observed a significant difference in age when comparing normal vs NODM patients (P=.004), normal versus NODL patients (P=.002), and normal versus NODL + NODM patients (P=.0001). The difference in body mass index (BMI) was significant when comparing normal with NODM + NODL patients (P=.003). In regard to immunosuppressive therapy, NODM was significantly more frequent among/prescribed tacrolimus (tac; P=.005), whereas subjects who received cyclosporine (CsA) showed a significantly higher incidence of NODL (P=.001). The triglyceride levels were 3.02 ± 1.51 mmol/L among those on CsA versus 2.15 ± 1.57 mmol/L for (P=.004). The difference also proved to be significant for total cholesterol level: 5.43 ± 1.23 mmol/L versus 4.42 ± 1.31 mmol/L respectively (P=.001). In regard to allograft function a significant difference was noted at 1 year after transplantation between the NODM + NODL and the normal group in serum creatinine level (P=.02) as well as the estimated glomerular filtration rate (P=.004). Among diabetic patients, the serum creatinine level measured at posttransplant year 5 was significantly higher than that in 1 year (212.43 vs 147.00 µmol/L; P=.0003). When assessing morphologic changes in the kidney, we observed significantly more frequent interstitial fibrosis/tubular atrophy in all 3 groups compared with normal function patients. CONCLUSION: Our clinical study suggested that at 1 year after transplantation allograft function is already impaired in the presence of both medical conditions (NODM and NODL). However, in regard to morphology, a single condition (NODM or NODL) was sufficient to produce histologic changes in the kidney.

Peritubular capillary damage in acute humoral rejection: an ultrastructural study on human renal allografts.

The ultrastructural features of peritubular capillary (PC) damage was studied in 12 kidney allografts with acute humoral rejection (AHR). AHR manifested in diffuse linear PC staining for C4d, and histology consistent with Banff grade III in 7 recipients and Banff grade II in 5. Allografts with acute tubular necrosis served as controls. First biopsies (post-transplantation day 16.2 +/- 2.2): The intra-capillary exudate comprised monocytes (59%), polymorphonuclears (14%), lymphocytes (12%) and not otherwise specified mononuclears (15%). Three patterns of focal PC endothelial injury were observed: lysis, an increased rate of apoptosis and fragmentation. No correlation was found between the respective damage types and the inflammatory cell types or the Banff grades. Controls revealed endothelial swelling, detachment from basement membrane and fragmentation. Follow-up biopsies: Monocytes transformed into macrophages intra-luminally. The reparative changes comprised endothelial cytoplasmic protrusions, binucleated endothelial cells and capillary sprouts. Early transplant capillaropathy and transplant glomerulopathy were noted in 2 recipients. Literature data indicate that lysis is mediated by anti-HLA alloantibodies; apoptosis, demonstrated first in the present study, may be induced by non-HLA-type anti-endothelial antibodies. Fragmentation is caused by ischemia. Ongoing endothelial injury leads to transplant capillaropathy and transplant glomerulopathy, the characteristic lesions of chronic rejection.

The value of electron microscopy in the diagnosis of chronic renal allograft rejection.

The main causes of the late dysfunction of renal allografts are chronic rejection and chronic transplant nephropathy. Both are clinicopathologic entities, with a similar clinical presentation, but different histologic appearances. Chronic rejection is characterized by the presence of alloantigen-induced lesions (transplant arteriopathy and transplant glomerulopathy), and chronic transplant nephropathy by nonspecific sclerosing changes. The incidence of transplant arteriopathy and transplant glomerulopathy is relatively low. Electron microscopy (EM) may overcome the limitations in the histologic diagnosis of chronic rejection, because it verifies alloantigen-induced chronic microvasculopathy in the peritubular capillaries (transplant capillaropathy), and identifies transplant glomerulopathy more precisely than does light microscopy. To assess the value of EM in chronic rejection diagnosis, a retrospective search for transplant capillaropathy and transplant glomerulopathy was performed in a consecutive series of 91 biopsies performed > or = 6 months after implantation (median: 26 months, range 6-186) and the diagnoses were reclassified on the basis of the ultrastructural findings. The definitions used were: transplant capillaropathy: a peritubular capillary profile with seven or more circumferential basement membrane layers, or at least three profiles with five or six circumferential layers; ultrastructurally verified transplant glomerulopathy: thickening of the capillary wall in at least three loops in consequence of the widening of the subendothelial space by abnormal basement membrane material, and the formation of a new layer(s) of basal lamina; and chronic rejection: the presence of transplant capillaropathy and/or transplant glomerulopathy and/or transplant arteriopathy. Histologically, chronic transplant nephropathy, chronic rejection, chronic cyclosporine nephrotoxicity, glomerulonephritis, acute rejection, "suspicious" for acute rejection, and "others" were diagnosed in 37%, 34%, 21%, 19%, 57%, 30%, and 5% of the specimens, respectively. The results of EM increased the diagnosis of chronic rejection to 69% of the cases, and decreased chronic transplant nephropathy to 15%. The individual incidence of transplant capillaropathy and transplant glomerulopathy was 79% and 57%, respectively, and their cumulative incidence was 92%. Five biopsies exhibited merely transplant arteriopathy. A late dysfunction typically had more than one cause; the most frequent combination was chronic rejection and acute rejection. In conclusion, the EM search for transplant capillaropathy and transplant glomerulopathy doubled the frequency of the diagnosis of chronic rejection. Currently, the evaluation of renal allograft biopsies from recipients with a late dysfunction relies on standard light microscopy. Because light microscopy per se proved to be insensitive in the diagnosis of chronic rejection, incorporation of EM into the evaluation of late dysfunction biopsies is strongly recommended.

Ureter diverticulum of transplanted kidney. Case report.

OBJECTIVES: Authors present a case of successful surgical treatment of a ureter diverticulum observed 3 months after kidney transplantation. METHODS: The fluid collection was detected by ultrasound. Percutaneous drainage was performed, after that the excretion of 4 litres of fluid was observed during 12 hours. This finding clearly indicated the connection with the urinary system. This fact was proved and precisely localised by contrast filling of the lesion under fluoroscopic control. RESULTS: Resection of the ureter diverticulum was performed, and the patient recovered fully, there was no change observed in the graft function during the whole procedure. CONCLUSION: The ureter diverticulum is a rare complication after kidney transplantation: the present case is the only one observed among more then 600 kidney transplantations performed during 20 years in our centre.

Progress in the management and treatment of infected pancreatic necrosis.

Infected pancreatic necrosis and sepsis are the leading causes of mortality in necrotizing pancreatitis. A review has been undertaken of the results of the past two decades relating to different surgical treatments of infected pancreatic necrosis. During the period 1978-85, the surgical treatment of necrotizing pancreatitis and its complications in our department consisted of the 'conventional' therapy (resection of the involved pancreatic tissue, or necrosectomy and drainage) in 61 patients, with a mortality rate of 36% (22 patients died). Since 1986, we have performed necrosectomy and other surgical interventions combined with continuous widespread lavage in 142 patients with infected pancreatic necrosis. The overall mortality decreased significantly to 6.3% (9 patients died). This result was achieved by means of aggressive surgical treatment, continuous, prolonged washing and suction drainage and supportive therapy, including immunonutrition, modifying the cytokine production and adequate antibiotic and antifungal medication. This surgical strategy provides the possibility for recovery in cases of necrotizing pancreatitis with septic complications.

[Complex treatment of infected necrotizing pancreatitis]. / Inficiálódott nekrotizáló pancreatitis komplex kezelése.

Pancreatic necrosis associated with septic conditions is the leading cause of mortality in acute pancreatitis. Since 1986, 155 patients with infected pancreatic necrosis have been treated. The mean APACHE II score was 18.5 (range 11-32). In all cases, the infected pancreatic necrosis was combined with retroperitoneal abscesses. The surgical treatment was performed on average 18.5 days (range 8-25 days) after the onset of acute pancreatitis. The operative management consisted of wide-ranging necrosectomy in the total affected area, combined with widespread lavage and suction drainage. In 69 of the 155 cases (45%), some other surgical intervention (distal pancreatic resection, splenectomy, cholecystectomy, sphincteroplasty or colon resection) was also performed. Following surgery supportive therapy was applied in all patients, which also consisted orf immunonutrition (glutamine and arginine supplementation) and modification of cytokine production by petoxyfillin and dexamethasone from 1992. TNF and IL-6 serum levels were measured by ELISA and in vitro stimulation of leukocytes were induced by E. coli LPS. Following surgery, continuous lavage and suction drainage were applied for an average of 41.5 days (range 21-90 days), with an average of 9.5 (range 5-20) litres of saline per day. The bacteriologic findings revealed mainly enteral bacteria, but Candida infection was also frequently detected. The incidence of fungal infection was 20%. Thirty-two patients (21%) had to undergo reoperation. The cytokine production capacity (TNF and IL-6) was shown to correlate with the prognosis. As a consequence of pentoxifyllin and dexamethasone therapy, the TNF production generally dropped to the normal level. The overall hospital mortality was 6.4% (10 patients died). In our experience, infected pancreatic necrosis responds well to aggressive surgical treatment, continuous, long-standing lavage and suction drainage, together with supportive therapy consisting of immunonutrition and modification of cytokine production, combined with adequate antibiotic and antifungal medication.

[The role of ultrasonography and biopsy following kidney transplantation]. / Ultrahangvizsgálat és biopszia szerepe és helye vesetranszplantáció után.

Several complications can occur during both the early and late postoperative periods after kidney transplantation. The methods used to follow up 575 kidney transplanted patients, (transplantations performed between October 1979 and November 1997) in the early (within 6 weeks) and late postoperative periods have been assessed. The diagnostic value of core biopsies and ultrasound examinations, the prevalence of complications, and the applicability of the diagnostic tools in the evaluation of the graft status and viability were analyzed. In the early postoperative period, graft rupture occurred more frequently after biopsy than in the late period (7.4% vs 0.82%), this leading graft loss in 18 of 20 cases. The sonographically diagnosed morphologic and functional changes were also analyzed. Sonography proved a very accurate method for the detection of perirenal fluid collections and masses and severe vascular complications. The data demonstrated that biopsy is indicated in the early postoperative period when the result of sonography is doubtful. In the late postoperative period, biopsy should be performed in every case.

Surgical strategy and management of infected pancreatic necrosis.

Infected pancreatic necrosis and sepsis are the leading causes of death in patients with necrotizing pancreatitis. Between 1986 and 1993, 123 patients with infected pancreatic necrosis were treated; in all cases the infected necrosis extended to the retroperitoneal area. Surgical treatment was performed a mean of 18.5 days after the onset of acute pancreatitis. Operative management consisted of wide-ranging necrosectomy through all the affected area, combined with continuous widespread lavage and suction drainage applied for a mean of 39.5 days, with a median of 6.5 litres of normal saline per day. In 56 cases (46 per cent), another surgical intervention (distal pancreatic resection, splenectomy, cholecystectomy, sphincteroplasty or colonic resection) was also performed. Bacteriological findings revealed mainly enteric bacteria, but Candida infection was detected in 21 per cent of patients. The overall hospital mortality rate was 7 per cent (nine patients died). Infected pancreatic necrosis responds well to aggressive surgical treatment, continuous, long-standing lavage and suction drainage, together with supportive therapy combined with adequate antibiotic and antifungal medication.

[Management of septic complications od acute necrotizing pancreatitis]. / Az akut nekrotizáló pancreatitis szeptikus szövödményének kezeléséröl.

The authors present the case of a 47 year old male patient with acute necrotizing pancreatitis complicated with widespread mesenteric necrosis and abscess. The critically ill patient (APACHE score: 28.5) underwent on seven operations and required 50 days of intensive care. The authors analyse the conditions of successful treatment and emphasize the importance of new available therapeutic approaches and instruments.