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Background: Infusion therapy is one of the most frequently prescribed medications in hospitalized patients. Currently used crystalloid solutes have a variable composition and may therefore influence acid-base status, intracellular and extracellular water content and plasma electrolyte compositions and have a major impact on organ function and outcome. The aim of our study was to investigate whether use of acetate-based balanced crystalloids leads to better hemodynamic stability compared to 0.9% saline., Methods: We performed a sub-analysis of a prospective, randomized, controlled trial comparing effects of 0.9% saline or an acetate-buffered, balanced crystalloid during the perioperative period in patients with end-stage renal disease undergoing cadaveric renal transplantation. Need for catecholamine therapy and blood pressure were the primary measures., Results: A total of 150 patients were included in the study of which 76 were randomized to 0.9% saline while 74 received an acetate-buffered balanced crystalloid. Noradrenaline for cardiocirculatory support during surgery was significantly more often administered in the normal saline group, given earlier and with a higher cumulative dose compared to patients receiving an acetate-buffered balanced crystalloid (30% versus 15%, p = 0.027; 68 ± 45 µg/kg versus 75 ± 60 µg/kg, p = 0.0055 and 0.000492 µg/kg body weight/min, ±0.002311 versus 0.000107 µg/kg/min, ±0.00039, p = 0.04, respectively). Mean minimum arterial blood pressure was significantly lower in patients randomized to 0.9% saline than in patients receiving the balanced infusion solution (57.2 [SD 8.7] versus 60.3 [SD 10.2] mm Hg, p = 0.024)., Conclusion: The use of an acetate-buffered, balanced infusion solution results in reduced need for use of catecholamines and cumulative catecholamine dose for hemodynamic support and in less occurrence of arterial hypotension in the perioperative period. Further research in the field is strongly encouraged.

Background: Recent studies have shown a decline in glomerular filtration rate and increased renal vasoconstriction after administration of normal saline when compared with IV solutions with less chloride. In this study, we investigated the impact of normal saline versus a chloride-reduced, acetate-buffered crystalloid on the incidence of hyperkalemia during cadaveric renal transplantation. The incidence of metabolic acidosis and kidney function were secondary aims., Methods: In this prospective randomized controlled trial, 150 patients received normal saline or an acetate-buffered balanced crystalloid during and after cadaveric renal transplantation. Venous blood gases were obtained at the start of anesthesia and every 30 minutes until discharge from the postoperative surveillance unit. Serum creatinine and 24-hour urine output were obtained on postoperative days 1, 3, and 7., Results: Patients received a similar amount of fluid (median: 2625mL [interquartile range: 2000 to 3100] vs 2500 mL [2000 to 3050], P = 0.83). Hyperkalemia, defined as serum potassium >5.9 mmol/L, occurred in 13 patients (17%) in the saline and 15 (21%) in the balanced group (P = 0.56; difference between proportions -0.037 [-16.5% to 8.9%]). Minimum base excess was lower in the saline group compared with the balanced regimen (-4.5 mmol/L [-6 to -2.4] vs -2.6 mmol/L [-4 to -1], P < 0.001) and maximum chloride was significantly higher in the saline group (109 mmol/L [107 to 111] vs 107 mmol/L [105 to 109], P < 0.001). No difference in creatinine or urine output was seen postoperatively. Significantly more patients needed catecholamines in the saline group (30% vs 15%, P = 0.03)., Conclusions: The incidence of hyperkalemia differed by less than 17% between groups. Use of balanced crystalloid resulted in less hyperchloremia and metabolic acidosis. Significantly more patients in the saline group required administration of catecholamines for circulatory support.

No effective interventions to reduce risk for new-onset diabetes after transplantation (NODAT), a condition associated with postoperative hyperglycemia and reduced patient and graft survival, have been established. In this 1-year, proof-of-concept clinical trial, we randomly assigned 50 renal transplant recipients to immediate-postoperative isophane insulin for evening blood glucose ≥140 mg/dl (treatment group) or short-acting insulin and/or oral antidiabetic agents for blood glucose ≥180-250 mg/dl (standard-of-care control group). We included only patients without a history of diabetes who received tacrolimus. By the third postoperative evening, all patients in the treatment group had blood glucose ≥140 mg/dl and were subsequently treated with basal insulin; during the first 3 weeks after transplantation, the mean ± SD daily insulin dosage was 17±11 IU/d. Among controls, 23 (92%) of 25 had blood glucose ≥200 mg/dl and 18 (72%) of 25 received standard-of-care antihyperglycemic treatment. Asymptomatic hypoglycemia occurred five times in the treatment group and once in the control group. Throughout follow-up, the treatment group had 73% lower odds of NODAT (odds ratio, 0.27) than the control group, and hemoglobin A1c was on average 0.38% lower in the treatment group than the control group. Twelve months after transplantation, all patients in the treatment group were insulin-independent, whereas 7 (28%) of 25 controls required antidiabetic agents. The groups did not differ for insulin sensitivity, but the treatment group showed better β-cell function throughout the 1-year follow-up. In conclusion, this study suggests regimens that include basal insulin significantly reduce the odds for NODAT after renal transplantation, presumably via insulin-mediated protection of β cells.

Various desensitization protocols were shown to enable successful living donor kidney transplantation across a positive complement-dependent cytotoxicity crossmatch (CDCXM). Positive crossmatch transplantation, however, is less well established for deceased donor transplantation. We report a cohort of 68 deceased donor renal allograft recipients who, on the basis of broad sensitization (lymphocytotoxic panel reactivity ≥40%), were subjected to a protocol of peritransplant immunoadsorption (IA). Treatment consisted of a single session of immediate pretransplant IA (protein A) followed by posttransplant IA and antilymphocyte antibody therapy. Twenty-one patients had a positive CDCXM, which could be rendered negative by pretransplant apheresis. Solid phase HLA antibody detection revealed preformed donor-specific antibodies (DSA) in all 21 CDCXM-positive and in 30 CDCXM-negative recipients. At 5 years, overall graft survival, death-censored graft survival and patient survival were 63%, 76% and 87%, respectively, without any differences between CDCXM-positive, CDCXM-negative/DSA-positive and CDCXM-negative/DSA-negative recipients. Furthermore, groups did not differ regarding rates of antibody-mediated rejection (24% vs. 30% vs. 24%, p = 0.84), cellular rejection (14% vs. 23% vs. 18%, p = 0.7) or allograft function (median 5-year serum creatinine: 1.3 vs. 1.8 vs. 1.7 mg/dL, p = 0.62). Our results suggest that peritransplant IA is an effective strategy for rapid desensitization in deceased donor transplantation., (© 2010 The Authors Journal compilation © 2010 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Antibody-mediated rejection (AMR) frequently causes refractory graft dysfunction. This randomized controlled trial was designed to evaluate whether immunoadsorption (IA) is effective in the treatment of severe C4d-positive AMR. Ten out of 756 kidney allograft recipients were included. Patients were randomly assigned to IA with protein A (N = 5) or no such treatment (N = 5) with the option of IA rescue after 3 weeks. Enrolled recipients were subjected to tacrolimus conversion and, if indicated, 'anti-cellular' treatment. All IA-treated patients responded to treatment. One death unrelated to IA occurred after successful reversal of rejection. Four control subjects remained dialysis-dependent. With the exception of one patient who developed graft necrosis, non-responders were subjected to rescue IA, however, without success. Because of a high graft loss rate in the control group the study was terminated after a first interim analysis. Even though limited by small patient numbers, this trial suggests efficiency of IA in reversing severe AMR.

Background: Kidney transplant recipients with a current positive complement-dependent cytotoxicity crossmatch (CDCXM) are at high risk for hyperacute rejection and graft loss. Immunoadsorption (IA) represents an efficient strategy to remove donor-specific alloantibodies. In this analysis, we evaluated effectiveness of peritransplant IA as an anti-humoral strategy to overcome a current positive CDCXM in presensitized renal allograft recipients., Methods: Between 1999 and 2003, 40 high risk cadaveric kidney allograft recipients (median CDC panel reactive antibody [PRA] level, 77%; number of retransplants, n = 38) were subjected to peritransplant IA with protein A (one pretransplant IA session followed by a course of repeat posttransplant IA sessions) in addition to preemptive antilymphocyte antibody therapy., Results: In nine of these patients, a current positive CDCXM was rendered negative by a single pretransplant IA session. Thirty-one recipients had a negative CDCXM already before pretransplant IA. No difference in graft survival was found between CDCXM-positive and CDCXM-negative recipients (3-year graft survival, 78% vs. 71%, P = 0.6). Comparable rates of immunological graft loss at 3 years were observed (11% vs. 13%, P = 0.8). Patient groups did not significantly differ with respect to median serum creatinine at 1 year (1.23 mg/dL [CDCXM-positive] vs. 1.57 mg/dl [CDCXM-negative], P = 0.07) and at the end of follow-up (median 32 months; 1.19 mg/dL vs. 1.63 mg/dL, P = 0.06). Moreover, patient groups showed similar rates of biopsy-proven cellular rejection (11% vs. 20%) or C4d-positive graft dysfunction (33% vs. 32%)., Conclusion: Our results demonstrate that peritransplant IA enables successful cadaveric kidney transplantation in the context of a positive CDCXM.

Emerich Ullmann (1861-1937) is the acknowledged pioneer of kidney transplantation. In 1902 he performed experiments with auto-, allo-, and xenotransplantations in dogs and sheep. In the same year he unsuccessfully tried to perform a human kidney grafting by transplanting a pig kidney to a woman with end-stage renal disease. Ullmann also conducted many experiments with other organ and tissue transplantations. In fact he should be regarded as the father of intestinal transplantation. Furthermore, he systematically investigated skin, testicles, ovary and bone transplantation. Moreover, he recorded clinical transplantations and in 1914 wrote a booklet (which in abridged form was published in English) summarizing knowledge on the organ and tissue transplantations of his time. Ullmann was an extremely innovative surgeon, he introduced various new surgical techniques. Last but not least, he was a broadly educated and literary man and an internationally renowned art expert and art collector.

Background: Re-transplanted kidney allograft recipients with high levels of panel reactive antibodies (PRA) are at increased risk of early immunologic graft loss. In these patients, prophylactic peri-operative antibody depletion by immunoadsorption (IA) could prevent humoral graft injury and thus, in combination with anti-cellular rejection therapy, improve graft survival., Methods: Twenty re-transplanted and broadly immunized cadaver kidney recipients (median PRA reactivity 87%, range 55-100%) were treated with IA (protein A) immediately before transplantation and during the early post-transplantation period (median number of IA sessions 11, range 1-24). Patients received additional prophylactic anti-lymphocyte antibody therapy. Nineteen patients had a negative pre-transplant cross-match. In one patient, a positive cross-match was rendered negative by the pre-transplant IA session., Results: One-year graft survival was 80% and patient survival 95%. Median (range) serum creatinine in functioning grafts was 1.6 (0.8-2.7) mg/dl at discharge and 1.5 (1.0-5.8) mg/dl at 1 year. Two grafts were lost due to acute vascular rejection, whereby one rejection occurred after withdrawal of immunosuppression due to septicaemia. One patient had acute cellular rejection, which was reversed by a second course of anti-lymphocyte antibody therapy. Thrombotic microangiopathy and surgical complications were the causes for one graft loss each. Retrospective immunohistochemistry revealed peritubular C4d staining, a presumed marker for humoral alloreactivity, in 12 out of 15 biopsies., Conclusions: These results suggest that prophylactic peri-operative IA and anti-lymphocyte antibody therapy might be an effective therapeutic strategy for the prevention of early graft failure in sensitized re-transplant recipients.

Between 1880 and 1930 there was a rapid surge in experiments with tissue transplantation, initially mainly of endocrine tissues (thyroid, parathyroid, testicles, ovary, adrenals etc.) with the aim of replacing endocrine function. Emerich Ullmann (1861-1937), who was born in Pecs, Hungary and worked his whole life as a surgeon in Vienna was the first to perform transplantations of solid organs in the modern sense of medicine. During 1899 and 1900 he conducted several experiments with intestinal transplantation and must be regarded as the father of intestinal transplantation--a hitherto unknown fact. He then moved to kidney transplantation and on March 7, 1902 he demonstrated a dog with a functioning kidney graft anastomized to the collar vessels with urine dripping off the ureter sutured to the skin of the neck in the lecture hall of the Society of Physicians in Vienna. Ullmann was the first to perform kidney auto-, homo- and heterotransplantations and in 1902 also tried--unsuccessfully--to perform the first human kidney transplantation using a pig kidney which he anastomized into the cubital region of a women with end stage renal disease. Ullmann also performed tissue transplantations (skin, testicles, ovaries) and made other scientific discoveries and described several novel surgical techniques. Finally, in 1914 he wrote the first monograph on the state of the art of transplantation medicine, a booklet on "Tissue and Organ Transplantation" summarizing the surprisingly extensive experience in transplantation medicine of his time. With the obvious immunologic barriers to transplantation, the first "technical surgical period" of transplantation came to an end around the times of Ullmann's death and clinical transplantation was not to be revived before effective means of immunosuppression became available in the 1950s.

There is increasing evidence for an important pathogenetic role of alloantibodies in acute renal allograft rejection. Acute humoral rejection (AHR) has been reported to be associated with a poor transplant survival. Although treatment modalities for cellular rejection are fairly well established, the optimal treatment for AHR remains undefined. Ten of 352 kidney allograft recipients transplanted at the authors' institution between November 1998 and September 2000 were diagnosed as having AHR, supported by severe graft dysfunction, C4d deposits in peritubular capillaries (PTC), and accumulation of granulocytes in PTC. AHR was diagnosed 18.9 +/- 17.5 d posttransplantation. All patients were subjected to immunoadsorption (IA) with protein A (median number of treatment sessions, 9; range, 3 to 17). Seven recipients with additional signs of cellular rejection (according to the Banff classification) received also antithymocyte globulin. In nine of ten patients, AHR was associated with an increase in panel reactive antibody reactivity. A pathogenetic role of alloantibodies was further supported by a positive posttransplant cytotoxic crossmatch in all tested recipients (n = 4). In nine of ten recipients, renal function recovered after initiation of anti-humoral therapy. One patient lost his graft shortly after initiation of specific therapy. Another recipient with partial reversal of AHR returned to dialysis 8 mo after transplantation. Mean serum creatinine in functioning grafts was 2.2 +/- 1.2 mg/dl after the last IA session (n = 9) and 1.5 +/- 0.5 mg/dl after a follow-up of 14.2 +/- 7.1 mo (n = 8). In conclusion, this study suggests that AHR, characterized by severe graft dysfunction, C4d staining, and peritubular granulocytes, can be effectively treated by timely IA. In the majority of patients, IA treatment can restore excellent graft function over a prolonged time period.

Excellent graft outcome has been reported for spousal-donor kidney transplantation. In husband-to-wife transplantation, however, a tendency toward inferior graft survival has been described for recipients who were previously pregnant. In our series of spousal-kidney transplantations (nine transplantations; three female recipients), actual graft survival is 100% (median observation time, 339 days). Five patients experienced early allograft rejection. In four transplant recipients, rejection was easily reversible by conventional antirejection therapy. In a multiparous recipient, however, mild interstitial allograft rejection associated with early graft dysfunction was resistant to anticellular treatment (antilymphocyte antibody, tacrolimus rescue therapy). The particular finding of polymorphonuclear neutrophils in peritubular capillaries and the finding of diffuse capillary deposits of the complement split product, C4d, in a posttransplantation biopsy specimen suggested a role of antibody-mediated graft injury. Retrospective flow cytometry cross-matching showed the presence of preformed immunoglobulin G (IgG) antibodies to HLA class I antigens that were not detectable by pretransplantation lymphocytotoxic cross-match testing or screening for panel reactive antibodies. After transplantation, however, complement-fixing antibodies, also presumably triggered by reexposure to spousal-donor HLA antigens, could be detected in the patient's serum. These findings suggested antibody-mediated allograft rejection and led to the initiation of immunoadsorption therapy (14 sessions) with staphylococcal protein A. Selective removal of recipient IgG resulted in complete reversal of graft dysfunction. Our findings suggest that in husband-to-wife transplantation, donor-specific antibodies, presumably triggered by previous pregnancies, might occasionally induce sustained allograft dysfunction. Thus, in this particular setting, a detailed immunologic and histopathologic work-up regarding antibody-mediated allograft dysfunction is warranted because immunoadsorption may be a highly effective treatment modality.

Serum folic acid levels were determined by radioimmunoassay in 26 chronic hemodialysis patients, in 52 renal transplant recipients and in 20 healthy controls. In the dialyzed patients, the mean serum folic acid level was 3.37 +/- 1.25 ng/ml and was significantly lower than that of the controls (6.1 +/- 1.38 ng/ml, P less than 0.001). In renal transplant recipients the mean folic acid concentration was 4.09 +/- 1.58 ng/ml and was also significantly decreased (P less than 0.001). 15 (29 per cent) out of 52 renal transplant patients showed serum folic acid concentrations lower than 3.0 ng/ml. Diminished serum folic acid levels were found not only in patients shortly after surgery but also in cases with excellent graft function up to 6 years after transplantation. The highest serum folic acid level was observed in one transplant patient who had taken no azathioprine for 24 months. Macrocytosis was found in 52 per cent of our renal transplant patients. There was no significant difference between the serum folic acid levels of renal transplant recipients with (n = 27) and without (n = 25) macrocytosis; however, serum creatinine levels were significantly lower in cases revealing macrocytosis. Relative folic acid deficiency does not seem to be responsible for macrocytosis after renal transplantation. Macrocytosis was observed only in patients with good graft function treated with azathioprine. Serum vitamin B12 levels were within the normal range in both dialyzed and renal transplant patients.