Association between malnutrition-inflammation score and risk of subsequent self-reported bone fractures in prevalent kidney transplant recipients.

Chronic inflammation and protein energy wasting (PEW) syndrome are common in kidney transplant recipients (KTR). The presence of inflammation and PEW syndrome can directly affect bone resorption and bone formation, leading to bone loss and fractures. We showed PEW is independently associated with new clinically detected bone fractures in prevalent KTR. INTRODUCTION: Kidney transplant recipients (KTR) have a 4-fold higher risk of fracture compared to the general population. Chronic inflammation and PEW syndrome are common in KTR and are associated with poor outcomes. We hypothesized that the Malnutrition-Inflammation Score (MIS), a validated measure of PEW, is associated with higher risk of bone fractures in KTR. METHODS: This prospective cohort study included 839 prevalent KTR from a Central European academic center. MIS, a semiquantitative instrument of PEW, was calculated at the study entry. Self-reported history of fractures was recorded during the 2-year follow-up period. The association between MIS and bone fractures was examined in logistic regression analyses with adjustment for age, gender, eGFR, smoking habits, history of pre-transplant bone fractures, and acute rejection. RESULTS: Mean age was 51 ± 13 years, and 56% of patients were males with median (interquartile range) transplant vintage 69 (38-112) months, estimated glomerular filtration rate 55 ± 21 ml/min/1.73 m2, and calculated MIS 3 (2-4) at enrollment. Fifty-five (7%) patients experienced self-reported bone fractures during the 2-year follow-up period. Higher MIS score showed linear association with increased risk of fracture. Each one-point higher MIS was associated with 23% higher risk of bone fractures (odds ratio (OR) and 95% CI 1.23, 1.12-1.34), which remained significant after multivariable adjustments (OR 1.17, 95% CI 1.06-1.29). CONCLUSION: The MIS is independently associated with new clinically detected bone fractures in prevalent KTR.

Mutation scanning of the p53 tumor suppressor gene in renal and liver transplant patients in Hungary.

INTRODUCTION: The increased incidence of malignancies among transplanted patients is well known. Abnormal function of the p53 tumor suppressor gene has been reported in more than half of all tumors. The aim of our study was to detect point mutations of p53 gene in transplanted patients because the presence of mutations may be a predictive factor for tumor development. An earlier diagnosis can help to develop new strategies for immunosuppressive therapies. METHODS: Three point mutations were chosen based on the literature: exon5-codon175, exon7-codon248, exon8-codon273. Genomic DNA from the plasma of 60 liver, 362 renal transplants, and 45 nontransplanted patients with different tumors and 20 suspected healthy patients were analyzed with a real-time PCR method using the Roche LightCycler. The mutations were evaluated by melting curve analysis. RESULTS: We elaborated a special protocol for scanning the above mentioned p53 point mutations, which were proved by sequencing as well. Among 487 patients, 486 showed a wild-type genotype. The only patient carrying a mutation at codon 273 (heterozygous) was a liver transplant patient, who developed pancreas carcinoma and had already died. CONCLUSION: Our data suggest that mutations of the targeted codons in leukocyte DNA seem to be rare, but a mutation could be lethal. The evaluated three point mutations of p53 gene were not predictive for tumor development.

Prediction of early renal graft function by the measurement of donor urinary glutathione S-transferases.

BACKGROUND: We have investigated the possibility of urinary alpha- and pi class glutathione S-transferases (GST-a; GST-pi) serving as a valuable parameter to predict early graft function after transplantation. METHOD: Urinary GST concentrations of 61 donors (DON) and recipients (REC) were analyzed at preoperative, intraoperative, and postoperative periods. We grouped recipients according to the early postoperative graft recovery days. RESULTS: The donor graft function, represented by the donor urinary GST concentration (GST-pi:17,1+/-12 microg/l mmol creatinine (crea); GST-a:14,3+/-10 microg/mmol crea), sustained a loss in comparison to the healthy controls (GST-a; pi< or =1 microg/mmol crea). According to statistical analysis, the donor GST-pi level showed a strong correlation with graft recovery days-pi (r = 0.84; P<0.001). The early graft function cannot be predicted by means of cold ischemia time (22.8+/-3.4 hr), nor handling time (42.4+/-11.1 min), nor even the intraoperative enzyme concentrations. The GST-pi cut off level (12.55 microg/mmol crea) might predict the possible posttransplant graft dysfunction. The discriminative analysis showed that using only DON GST-pi alone could discriminate well between the groups among all grafts in 68%. CONCLUSION: Prognosis is poorer if the donor GST-pi concentration is above 12.55 microg/mmol crea. On the basis of the determination of GST-pi concentration in the donor urine, we can predict graft viability before the surgical procedure with a reliability of 68%.

[Screening of patients waiting for kidney transplantation]. / A veseátültetésre váró betegek kivizsgálása.

The authors summarise the indications and contraindications of kidney transplantation according to their our experiences. They report the changes of the number of kidney transplantation in Hungary, the distribution of the kidney diseases and they also report the risk factors, which can influence the results of the kidney transplantation.

[Haemodialysed, hemiparetic patient operated on for aortic aneurysm followed by successful renal transplantation]. / Vascularis encephalopathiában szenvedó krónikus hemodializált betegen végzett aortaaneurysma-mútétet követó vesetranszplantáció.

The authors present the case of a 58 years old male patient. According to his preceding record in 1991 he suffered speech disturbance and left-side hemiparesis due to multiplex vascular lesions. A fresh cerebral ictus caused a right side hemiparesis mainly in the upper limb in 1993 and sensomotororic aphasia has also been developed. In 1995 the patient was begun acute haemodialysis treatment due to his gravis uremic state, then his dialysis was continued 3 times 4 hours weekly. In 1997 the then 56 years old inveterate right-sided hemiparetic patient, treated with chronic haemodialysis requested to be put on the transplantation waiting list. The first thing that had to be done in case of this high-risk patient was the resection of the abdominal aortic aneurysm (38 mm x 67 mm x 115 mm in size) noticed at the ultrasound examination which was carried out in January 1997. The continuity of the vessel was secured by graft-interposition where the arteria mesenterica was also implanted. Following the successful operation, the patient was qualified for the transplantation list and in the February of 1998 a successful kidney-transplantation was carried out. Following the temporary, post-transplantation difficulties (post-operative 5th day acute rejection well-reacting to 3 steroid-shots; the two re-operations due to partial necrosis in the uretero-ureteralis anastomosis and successfully overcoming the Pseudomonas aeruginosa uroinfection) the patient is currently doing well and has no complaint.

Anemia is associated with mortality in kidney-transplanted patients--a prospective cohort study.

Although anemia is a known risk factor of mortality in several patient populations, no prospective study to date has demonstrated association between anemia and mortality in kidney-transplanted patients. In our prospective cohort study (TransQol-HU Study), we tested the hypothesis that anemia is associated with mortality and graft failure (return to dialysis) in transplanted patients. Data from 938 transplanted patients, followed at a single outpatient transplant center, were analyzed. Sociodemographic parameters, laboratory data, medical history and information on comorbidity were collected at baseline. Data on 4-year outcome (graft failure, mortality or combination of both) were collected prospectively from the patients' charts. Both mortality and graft failure rate during the 4-year follow-up was significantly higher in patients who were anemic at baseline (for anemic vs nonanemic patients, respectively: mortality 18% vs. 10%; p < 0.001; graft failure 17% vs 6%; p < 0.001). In multivariate Cox proportional hazard models the presence of anemia significantly predicted mortality (HR = 1.690; 95% CI: 1.115-2.560) and also graft failure (HR = 2.465; 95% CI: 1.485-4.090) after adjustment for several covariables. Anemia, which is a treatable complication, is significantly and independently associated with mortality and graft failure in kidney-transplanted patients.

Comparing cytomegalovirus prophylaxis in renal transplantation: single center experience.

BACKGROUND: Cytomegalovirus (CMV) presents a serious threat to CMV-seronegative recipients (R-), who have received an organ from a seropositive donor (D+). OBJECTIVES: We compared the effectiveness of three different prophylactic protocols in CMV D+/R- patients and reviewed data on patients who received no prophylaxis. PATIENTS AND METHODS: We reviewed 1137 kidney transplantations from 1995 to 2004. Of these, 147 recipients were CMV negative (D+/R-); 125 patients received CMV prophylaxis. Group I received CMV hyperimmune gammaglobulin only, group II received CMV hyperimmune gammaglobulin plus oral ganciclovir, and group III received prophylaxis with oral ganciclovir only. RESULTS: In group I, CMV infection was observed in 31 of 53 patients (59%), and CMV disease was diagnosed in 9 (17%) during the prophylaxis. In the first year post transplant, a total of 41 of 53 patients (77.5%) had primary CMV infection. In group II, CMV infection occurred in 7 of 30 patients (23%), and CMV disease was diagnosed in only 2 (7%) during prophylaxis. In the first year post transplant, a total of 9 of 30 patients (30%) had primary CMV infection. In group III, 9 of 42 patients (21%) developed CMV infection during prophylaxis, and CMV disease was not observed. In the first year post transplant, a total of 13 of 42 patients (30%) had primary CMV infection. In contrast, all 22 CMV D+/R- patients without prophylaxis developed CMV infection (100%); CMV disease was diagnosed in 10 (45%), and 1 patient died. CONCLUSIONS: Prophylaxis with hyperimmune gammaglobulin and/or oral ganciclovir significantly reduces CMV infection and disease. Prophylaxis with ganciclovir was significantly more effective than hyperimmune gammaglobulin monoprophylaxis, and more cost effective than combined prophylaxis.

Comparative analysis of kidneys retrieved from the same donor and transplanted into different recipients.

We have reviewed the outcome of kidney transplantations where both kidneys retrieved from the same donor were transplanted at our Department and the factors which might be decisive in the outcome. Between 1973 and 1996, 1325 kidney transplantations were performed at our Department. In 360 cases, both kidneys retrieved from the same donor were transplanted at our Department. We evaluated only first transplant cases who were treated with a combination of cyclosporin and prednisolon. After this selection, 248 pairs of kidneys were left for analysis. We divided them into three groups. The first comprised immediately functioning kidneys (135 pairs), the second, no immediate graft function in any of the recipients (29 pairs). The third group was mixed: the kidneys retrieved from the same donor were functioning in one recipient and not in the other, so this group was omitted from the analysis. We therefore analysed the donor factors of age, sex and cause of death. We found no significant difference between the groups relating to the cause of donor death. There was, however a significant difference in the age of donors: those kidneys functioning well in both recipients derived from a younger donor group (16-40 years), 18/58 versus 136/270, P < 0.01, chi 2 = 7.17. There were significantly fewer older donors (41-65 years) in the immediately functioning group than in the other, 38/58 versus 110/ 270, P < 0.001, chi 2 = 11.84. We investigated the number of HLA mismatches, ischaemic time, cytotoxicity index and the type and duration of pretransplantation dialysis. It appears from this analysis that the age of the donor is a significant factor in the short-term outcome of transplanted kidneys. Recipient factors as HLA match, ischaemic time and cytotoxicity index seems to be less important.

Evaluation of the state of health of living related kidney transplantation donors.

Renal transplantation is the optimal mode of therapy for patients with end-stage renal disease; the results are even better with living related donors. This procedure, therefore, favours the recipients, but what are the consequences for the donor? At our Department, between 1973 and 1996, 1325 kidney transplantations were performed, 78 from living, related donors (5.89%). We decided to follow up these patients and investigate the function of the remaining kidney and also their current general health status. Thirty donors (38.4%) were investigated. Of these, 25 of had normal blood pressure and 5 were hypertensive, needing antihypertensive treatment. The average age was higher in the hypertensive group (60.2/53.25 years). The time interval since transplantation was longer in the hypertensive group than in the normal one. We carried out a scintigraphy of the kidney with Tc-99mMAG-3. The mean value of the glomerular filtration rate calculated from the MAG clearance was 98.1 ml/min and this value is higher than half of the normal isotope clearance value, i.e. higher then the expected value for a single kidney. We conclude that no impairment of renal function is observed in the living, related kidney donors. In 16.66% a mild hypertension developed. With isotope investigation we found hypertrophy of the remaining kidney. Thus, after a correct preoperative assessment, unilateral nephrectomy has no long-term consequences in healthy donors.

Attitudes of donors towards organ transplantation in living related kidney transplantations.

The demand for transplantation exceeds the availability of cadaveric organs, which is why the importance of living, related kidney transplantation is increasing. In our study we wanted to evaluate the experiences of living related donors (LRD). Between 1973 and 1996, 1325 kidney transplantations were performed at our Department. Of these 1247 were from cadaver donors while 78 were from LRD. We contacted each living donor by post. We carried out a physical examination, laboratory tests, ultrasound and isotope investigations and they were interviewed and completed a questionnaire. Thirty previous kidney donors came to our Department who were all blood relatives of the recipients. In the recipient group, 16 still have a functioning kidney, the average time since transplantation being 8.92 years. The longest kidney survival time is 18 years. All the donors willingly donated their kidney, none was worried about their own health and their only concern was whether the kidney would function or not. Regarding general attitudes towards living related organ transplantation, all were in favour of blood relative donor transplantation and also husband/wife transplantation. Opinions regarding non-related transplantation were more mixed; 63.3% would have given their kidneys to a friend, only 46.6% to a stranger. Almost two-thirds (63.3%) of donors were not in favour of selling and buying organs but, controversially, they would have bought an organ had one been available. All agreed that the donation did not change their general health. In conclusion, the donors of living, related kidney transplantation all agreed that it was a good thing to donate; All confirmed they would go through the same procedure again in order to help. Apart from one person, who emphasised that he is agnostic, all belonged to a Christian religion.