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Biomedical subjects

G Tydén

Publications and source records attributed to G Tydén.

At least 19 recordsLinked to original sources
PubMed2006

Pharmacodynamics of rituximab in kidney allotransplantation.

The anti-CD20 antibody rituximab has recently gained interest as a B-cell depleting agent in renal transplantation. However, little is known about the pharmacodynamics of rituximab in renal transplant recipients. We have therefore studied the effect of single-dose rituximab in combination with conventional triple immunosuppressive therapy on the B-cell population in peripheral blood as well as in tissues. A total of 49 renal transplant recipients received single-dose rituximab, as induction therapy (n = 36) or as anti-rejection therapy (n = 13). We counted B cells in peripheral blood and performed immunohistochemical staining on lymph nodes and kidney transplant tissue samples to assess the prevalence of B cells. In all but 6 patients (88%) complete depletion of B cells in peripheral blood was achieved. In adults, 15 months after treatment the CD19+ and CD20+ cell counts were still below 5 cells/muL in the majority of patients (78%). The immunohistochemical staining showed a complete elimination of B cells in kidney tissue and a reduction of B cells in lymph nodes. In conclusion, single-dose rituximab in kidney transplant recipients evokes a long-term elimination of B cells in peripheral blood as well as within the kidney transplant. The effect seems to extend beyond the expected 3-12 months observed in lymphoma patients.

Adult↗
PubMed2006

Introduction of hand-assisted retroperitoneoscopic living donor nephrectomy at Karolinska University Hospital Huddinge.

Living donor kidney transplantation accounts for about 50% of the total number of renal transplantations at our center. From 1999 through 2005, 75 out of 220 living donor nephrectomies were performed with a laparoscopic technique (LLDN). In June 2005, we introduced the technique of hand-assisted retroperitoneoscopic nephrectomy (HARS) for living donors. Since the introduction until the end of 2005, 11 out of 18 living donor nephrectomies (LDN) were performed with HARS. Reduced operation time was observed for the HARS group (mean, 166 minutes) compared with the LLDN (mean, 244 minutes). Two grafts showed delayed function, one in the LLND group and one in the HARS group. No major perioperative or postoperative complications were observed in the HARS group, whereas one patient who underwent LLDN developed severe pancreatitis. So far in our hands HARS is a fast and safe procedure with results comparable with open LDN. Compared to LLDN, we experienced reduced operation time together with the advantage of retroperitoneal access.

Adult↗
PubMed2005

ABO-incompatible kidney transplantation and rituximab.

We have designed a protocol for ABO-incompatible kidney transplantations based on antigen-specific immunoadsorption rather than plasmapheresis to remove anti-A or anti-B antibodies and with a Prograf/Cellcept/prednisolone protocol using rituximab rather than splenectomy to prevent rebound antibodies. Twelve patients have successfully received transplants with this protocol. The ABO-antibodies were readily removed by the antigen-specific immunoadsorption and maintained at a low-level posttransplantation. There were no side effects. All patients have normal renal transplant function with a follow-up of 1 to 34 months.

ABO Blood-Group System↗
PubMed2005

Refractory acute renal allograft rejection successfully treated with photopheresis.

INTRODUCTION: Acute rejection episodes still occur in spite of modern immunosuppressive protocols. We present seven patients with biopsy-proven acute rejections after kidney transplantation refractory to repeated pulses of high-dose steroids and antithymocyte globulin (ATG) or OKT-3, but responsive to photopheresis therapy. METHODS: Photopheresis is a nontoxic immunomodulatory, apheresis-based treatment with no general immunosuppressive action. Rather, it suppresses specific pathogenic T-cell clones. During photopheresis mononuclear leukocytes are collected from the patient using centrifugation technique, treated with a photosensitizing agent, irradiated, and subsequently retransfused. RESULTS: All patients tolerated the treatment well, with no notable side effects. At the 12-month follow-up the median creatinine had decreased to 161 mumol/L compared to 282 mumol/L at the start of photopheresis and at the last follow-up 12 to 43 months after transplantation all patients still had functioning grafts. In five of the seven cases there had been a significant improvement in renal function, whereas in two of the patients the renal function remained stable but without a decrease in creatinine. CONCLUSIONS: It is our experience that the prognosis for renal allografts with acute rejection unresponsive to conventional antirejection treatment (ie, repeated pulses of methylprednisolone and ATG or OKT-3) is very poor. Therefore, we conclude that the photopheresis treatment contributed to the favorable outcome in this small group of patients. We are presently designing a prospective randomized study to further evaluate the effect of photopheresis after renal transplantation.

Acute Disease↗
PubMed2001

No evidence of accelerated loss of kidney function in living kidney donors: results from a cross-sectional follow-up.

BACKGROUND: There is a lack of kidneys available for kidney transplantation, and living donors are increasingly used. It is important to examine the possible long-term adverse affect on the renal function and blood pressure of the donors. METHODS: We have made a comprehensive follow-up of all living kidney donors at our center from 1964 to 1995. Of 402 donors still alive, we were able to get information about serum creatinine, urinary proteins, and blood cells in urine using reagent strips, and blood pressure from 87%. The glomerular filtration rate (GFR) was estimated using a formula and was measured with Iohexol clearance in 43 of the donors. Individual data on GFR and the prevalence of hypertension were compared with the age- and gender-expected values. RESULTS: The mean age of the examined donors was 61 years (SD:13) at follow-up, and the time since donation was 12 years (SD:8). The average estimated GFR was 72% (SD:18) of the age-predicted value. The ratio of the estimated to the predicted GFR showed no correlation to the time since donation, indicating that there is no accelerated loss of renal function after donation. GFR below 30 ml/min was found in five donors. No donor died in uremia or had dialysis treatment before death. However, three donors developed renal disease, and one was in dialysis treatment. In two of these cases, hereditary factors were possibly involved. Hypertension was present in 38% of the donors but the age-adjusted prevalence of hypertension among donors was not higher than in the general population. Significant proteinuria (> or =1.0 g/L) was found in 3% and slight proteinuria (<1.0 g/L) in 9% of the donors. Proteinuria was associated with hypertension and a lower GFR. CONCLUSIONS: On average, the remaining renal function of kidney donors did not deteriorate more rapidly than what may be expected from ageing. However one-third of the female and half of the male donors developed hypertension and, approximately, 10% displayed proteinuria. Nevertheless, our study supports the continued use of living kidney donors if strict criteria are used for acceptance.

Adult↗
PubMed2001

The use of pretransplant erythropoietin to normalize hemoglobin levels has no deleterious effects on renal transplantation outcome.

BACKGROUND: The aim of this study was to establish the outcome of renal transplantation in patients given pretransplant erythropoietin (EPO) treatment targeted at reaching a normal hemoglobin concentration (Hb), compared to those given EPO-treatment aimed at maintaining subnormal Hb. METHODS: A total of 416 patients from Scandinavian countries and with renal anaemia were enrolled to examine the effects of increasing Hb from a subnormal level (90-120 g/liter) to a normal level (135-160 g/liter) by EPO treatment. Half of the patients were randomized to have their Hb increased, with the other half randomized to maintain a subnormal Hb. Thirty-two patients from the normal Hb group and 24 patients from the subnormal group received a renal graft during the study period. The outcomes of these transplantations were examined prospectively for 6 months. RESULTS: Preoperative Hb levels were 143+/-17 and 121+/-14 g/liter in the two groups, respectively (P<0.0001). The Hb remained higher in the normal Hb group during the first 2 weeks after transplantation. The percentage of patients requiring postoperative blood transfusions in the normal Hb group was 16%, compared with 50% in the subnormal group (P<0.01). No statistically significant difference in the proportion of functioning grafts or in the serum creatinine levels could be detected. No correlation between EPO treatment and creatinine levels after transplantation was found. The frequency of adverse events was similar in the two groups. CONCLUSIONS: EPO treatment aimed at reaching a normal Hb in renal transplant recipients reduces the postoperative requirement for blood transfusions and has no deleterious effects on kidney graft function.

Adult↗
PubMed2000

Development of renal cell carcinoma in living donor kidney grafts.

BACKGROUND: Although development of malignancies after transplantation is well recognized, de novo development of cancer in renal transplants is a rare phenomenon. We describe two cases of de novo development of renal cell carcinoma in two living donor grafts. MATERIALS AND RESULTS: The recipients were 45 and 4 years, respectively, at transplantation and their fathers were donors. Because of failure to grow, they were both treated with human growth hormone. Over the years a number of cysts developed in the grafts and after 8 and 7 years the echogenecity of some of the cysts changed. Biopsy confirmed the diagnosis renal cell carcinoma 9 and 11 years after transplantation. The grafts were removed and the immunosuppressive therapy discontinued. The two fathers are well with normal function of the native kidney and no signs of cyst formation or cancer. CONCLUSION: Two cases of de novo development of cancer in living donor kidney transplants are described. Because a stimulatory effect of growth hormone on tumor genesis has been described, this treatment may have been of importance in the tumor development. The findings emphasize the importance of annual ultrasonographic surveillance of renal grafts, especially in the pediatric population.

Carcinoma, Renal Cell↗
PubMed2000

Daclizumab prevents acute rejection and improves patient survival post transplantation: 1 year pooled analysis.

Daclizumab is a genetically engineered human IgG1 monoclonal antibody specific for the alpha chain of the IL-2 receptor. A pooled analysis of two randomized, double-blind studies was performed on the efficacy and safety of daclizumab in renal transplantation, given in addition to standard immunosuppression. Patients receiving their first cadaveric renal allograft were randomized to receive 5 doses of daclizumab (n = 267) or placebo (n = 268), starting pre-operatively. Acute rejection at 1 year occurred less frequently with daclizumab (n = 74, 27.7 %) than with placebo (n = 116, 43.3%) (P = 0.0001). Fewer patients treated with daclizumab required anti-lymphocyte therapy for acute rejection (7.9 % vs. 15.3 %; P = 0.005). Mean cumulative doses of corticosteroids were lower with daclizumab (4133 mg) than with placebo (4562 mg). One year graft survival was 91.4 % with daclizumab, compared with 86.6 % on placebo (P = 0.065), with patient survival of 98.5 % and 95.1 % for daclizumab and placebo respectively (P = 0.022). Daclizumab was well tolerated. No increase in infectious episodes or lymphoproliferative disorders was observed with daclizumab. The incidence of cytomegalovirus infections was similar with daclizumab and placebo (15 % vs. 17.5 %). Therapy with daclizumab significantly reduces acute rejection in renal transplantation and improves patient survival without any increase in morbidity.

Adult↗
PubMed2000

Combined pancreas and kidney transplantation improves survival in patients with end-stage diabetic nephropathy.

The purpose of this study was to find out whether prolonged normoglycemia, as achieved by a successful pancreas transplantation, can improve survival in patients with insulin-dependent diabetes mellitus. A retrospective analysis of actual 10-yr patient survival rates was done for all renal graft recipients who were given transplants more than 10 yr ago but within the cyclosporin era (i.e. 1981-1988). The actual 10-yr patient survival rate in non-diabetic renal graft recipients was 72%, In recipients of pancreas and kidney grafts and with prolonged function of the pancreas graft, the survival rate was 60%, whereas in patients subjected to simultaneous pancreas and kidney transplantation, but where the pancreatic grafts failed within 2 yr, the survival rate was 33%. In diabetic recipients of kidney transplants alone, the survival rate was 37%. The patient survival rate was substantially higher in non-diabetic patients and patients with functioning pancreas grafts compared with diabetic patients with kidney transplants alone or with failed pancreas grafts. We speculate that the decrease in mortality was due to the beneficial effect of long-term normoglycemia on diabetic late complications.

Adult↗
PubMed1999

Improved survival in patients with insulin-dependent diabetes mellitus and end-stage diabetic nephropathy 10 years after combined pancreas and kidney transplantation.

BACKGROUND: The purpose of pancreatic transplantation in insulin-dependent diabetic patients is to restore normoglycemia and thereby prevent the secondary complications of diabetes. However, uncertainty remains as to whether the mortality rate in diabetic patients can be affected by this procedure. METHOD: We followed 14 patients with insulin-dependent diabetes mellitus (IDDM) and end-stage diabetic nephropathy for 10 years after successful combined kidney and pancreas transplantation. Fifteen diabetic patients subjected to kidney transplantation alone have served as controls. The glycemic control has been studied annually for 10 years and diabetic polyneuropathy has been assessed in both groups after 2, 4, and 8 years. RESULTS: In recipients of pancreas-kidney grafts, metabolic control was maintained throughout the observation period, with values of glycated hemoglobin in the normal range. In contrast, glucose metabolism was impaired in the control group, with glycated hemoglobin values around 10%. Nerve conduction and parasympathetic autonomic dysfunction improved in both groups after 2 years; there was no difference between the groups. After 4 years, we found a significant difference between the study group and the control group, and after 8 years it had widened. At the 4-year evaluation, there was no difference in mortality between the groups. At 8 years, however, a significant difference was noted, which was further substantiated at 10 years with a 20% mortality rate in the pancreas-kidney group versus an 80% mortality in the kidney alone group. CONCLUSIONS: We found a substantial reduction in mortality in IDDM patients 10 years after successful combined pancreas and kidney transplantation. We speculate that the decrease in mortality was due to the beneficial effect of long-term normoglycemia on diabetic late complications and suggest therefore that combined pancreas and kidney transplantation, rather than kidney transplantation alone, should be offered to IDDM patients with end-stage diabetic nephropathy.

Adult↗
PubMed1999

High-dose acyclovir prophylaxis reduces cytomegalovirus disease in liver transplant patients.

Cytomegalovirus (CMV) is still a major pathogen in liver transplantation (LTX). The clinical efficacy of prophylactic high-dose acyclovir therapy (800 mg qid) was assessed for the prevention of CMV infection and disease in liver recipients. Fifty-five patients were enrolled in a prospective, randomised, double-blind and placebo-controlled trial; 28 on acyclovir vs. 27 on placebo. The therapy was given for 12 weeks. The patients were followed for 24 weeks. CMV infection was diagnosed in 60% (16 on acyclovir, 17 on placebo) and CMV disease developed in 38% (7 on acyclovir, 14 on placebo) of the patients. The total mortality was 27% (6 on acyclovir, 10 on placebo). Acyclovir delayed 32% of the CMV infections and prevented 59% of the CMV disease cases which occurred in the placebo cohort. The time to CMV disease was significantly prolonged in patients on acyclovir as compared to patients on placebo (P=0.013). Adverse events included neurotoxicity which occurred in 5 cases in the acyclovir, but none in the placebo arm, and nephrotoxicity which was detected in 6 patients in the acyclovir and 5 in the placebo arm, respectively. We conclude that acyclovir prophylaxis significantly reduced the incidence of CMV disease, and delayed the onset of CMV infection in liver transplant patients.

Acyclovir↗
PubMed1999

Tacrolimus whole blood concentrations correlate closely to side-effects in renal transplant recipients.

AIMS: To evaluate the relationship between tacrolimus whole blood concentrations and side-effects and rejections in 14 renal transplant recipients. METHODS: Tacrolimus was measured by MEIA in whole blood in samples collected repeatedly during the first year after transplantation. Retrospectively, tacrolimus trough concentrations on the days with adverse events (n=172) or rejection (n=28) were related to the total distribution of the concentration values (n=656). RESULTS: Side-effects (one or more) were noted in connection with 76% of tacrolimus concentrations above 30 ng ml-1, with 41% of concentrations within the interval of 20-30 ng ml-1, with 26% of the concentrations within the interval of 10-20 ng ml-1 and with only 5.3% on the concentrations lower than 10 ng ml-1. No relation to the tacrolimus concentration was seen for rejection episodes. CONCLUSIONS: We conclude that therapeutic drug monitoring may be helpful in the management of tacrolimus therapy and that tacrolimus whole blood trough concentrations (MEIA) should preferably be kept below 20 ng ml-1 to avoid side-effects, such as nephro-and neurotoxicity and infections. The lower limit of the therapeutic range has yet to be defined.

Adult↗
PubMed1999

Renal transplantation in patients with urinary diversion: a case-control study.

BACKGROUND: Renal transplantation in Sweden in patients with ileal conduits or continent reservoirs was investigated in order to compare the outcome with regard to graft and patient survival as compared to controls. METHODS: Patient data from the four transplantation centres in Sweden were collected on: treatment prior to transplantation, time needed for the operative procedure, and postoperative care and outcome in terms of renal function as well as graft and patient survival at 1 and 5 years. The pattern of urinary tract infection was also investigated. Each case with urinary diversion was matched with two non-diabetic controls. RESULTS: Ten male and 12 female cases were found who had received 27 grafts between 1982 and 1996. Five patients had a Kock reservoir and 17 had a Bricker conduit. The time needed for the transplant procedure was significantly longer in the case group. After matching the case group with 54 controls, we found that the renal function was similar in both groups. Graft and patient survival was similar in both groups, over 90% after 1 year. Graft survival was about 70% after 5 years. Postoperative surgical complications in the case group were only seen in a few cases. The pattern of bacteria causing urinary tract infection was slightly different among the patients with ileal conduits or continent reservoirs. CONCLUSION: Patients with ileal conduits or continent reservoirs have similar graft and patient survival rates as the general kidney transplant population. The presence of constant bacteriuria did not adversely affect survival. Prophylactic antibiotic treatment seems not to be warranted. There appears to be no indication for native nephrectomy, except in selected cases. The study did not show any advantage with regard to continent reservoirs vs ileal conduits.

Adolescent↗
PubMed1998

Hyperlipidemia in renal transplant recipients treated with sirolimus (rapamycin).

BACKGROUND: Sirolimus is an interesting immunosuppressive drug that does not seem to cause nephrotoxicity, neurotoxicity, or diabetogenicity, as commonly seen in patients treated with cyclosporine or tacrolimus. In this report, we describe a possible association between sirolimus and observed hyperlipidemia. METHODS: Serum levels of triglycerides and cholesterol were analyzed in 11 patients who participated in a pilot study evaluating the effect of oral sirolimus or placebo combined with cyclosporine and corticosteroids on the occurrence of acute renal transplant rejection. RESULTS: In four of nine patients given sirolimus, significantly increased serum triglyceride levels were seen, with peak levels occurring 2-4 months after transplantation and ranging between 11.7 and 42.0 mmol/L (reference value <2.2 mmol/L). In two patients given placebo, the serum triglyceride levels remained below 5.0 mmol/L. After reduction or discontinuation of sirolimus, the serum triglyceride levels decreased within 1-2 months and after 1-8 months levels had returned to their pretransplant values. A significant increase in serum cholesterol levels was seen in one of nine patients given sirolimus. CONCLUSION: It seems that long-term treatment with sirolimus in combination with cyclosporine and corticosteroids may increase the risk of hypertriglyceridemia.

Adrenal Cortex Hormones↗