[Show abstract][Hide abstract] ABSTRACT: Introduction and Aims: Renal allograft recipients with thrombophilia are at higher risk for early allograft loss, microvascular occlusion and acute
rejection with major consequences for allograft survival. The aim of the present study was to evaluate the prevalence of prothrombotic
risk factors in patients awaiting renal transplantation and its contribution to patient and transplant outcomes.
Methods: All patients with a history of a thromboembolic event, early or recurrent vascular access thrombosis, family history of thrombosis,
or multiple miscarriages underwent laboratory screening for thrombophilia.
Results: Since the introduction of the screening for hypercoagulable risk factors, 156 candidates for renal transplantation underwent
laboratory evaluation. Eighty-eight patients (56%) exhibited at least one prothrombotic laboratory parameter, besides of isolated
hyperhomocysteinemia, which confirmed a thrombophilic state. Lupus anticoagulant, anticardiolipin and beta-2-glycoprotein
was present in 30%, 18% and 13%, and antithrombin III, protein C and protein S deficiencies in 11%, 8% and 10%, respectively.
Factor V Leiden mutation was present in only one patient and prothrombin gene G20210 mutation was not found. Among the 156
patients, 30 underwent renal transplantation and were followed for a median of 199 days (range, 9 – 418). All patients were
on triple immunosuppressive regimen compromising mycophenolate, tacrolimus and prednisone. Thrombophilia was identified in
16 (53%). Seventeen (57%) received perioperative anticoagulation with unfractionated heparin (9 patients with thrombophilia
and 8 without laboratory confirmed thrombophilia). Five (30%) of these patients developed perinephric hematomas. Three patients
with thrombophilia developed thrombotic complications (2 upper limbs deep-vein thrombosis and 1 allograft artery thrombosis)
and 1 patient without thrombophilia developed allograft vein thrombosis, p=0.35. Nine patients developed acute rejection (5 in the group with thrombophilia and 4 in the group without thrombophilia,
p=0.87). Mean glomerular filtration rate was similar between thrombophilic and non-thrombophilic patients in the last follow-up
(54±27 vs. 47±22 mL/min/1.73m², p=0.35). One graft loss and 1 patient death were observed in each group.
Conclusions: Prothrombotic risk factors, especially antiphospholipid antibodies, are highly prevalent in patients awaiting renal transplantation
with a clinical or familial history suggestive of thrombophilia, including early and recurrent vascular access failure. Despite
pre-transplant screening and perioperative treatment and/or monitoring, thrombotic and bleeding complications are still frequent
[Show abstract][Hide abstract] ABSTRACT: Klotho, a single-pass transmembrane protein primarily expressed in the kidneys, parathyroid glands, and choroid plexus of the brain, has a short cytoplasmic tail and a long extracellular domain, which can be cleaved and released as a soluble form. However, information regarding the origins and kinetics of soluble serum Klotho remains poorly understood. We evaluated serial changes in serum Klotho levels among living donors before and after retroperitoneoscopic nephrectomy as well as in their renal transplant recipients.
The levels of soluble Klotho in serum obtained from 10 living donors and their renal transplant recipients were determined using a sandwich enzyme-linked immunosorbent assay system.
Serum soluble Klotho was detectable in all subjects. The baseline serum Klotho concentrations in the living donors ranged from 726.4 to 1417.1 pg/mL (median, 909.8 pg/mL; interquartile ranges [IR], 754.8-1132.4), whereas that in the concomitant renal transplant recipients ranged from 397.5 to 1047.2 pg/mL (median, 613.0 pg/mL; IR, 445.9-750.8; P = .003). The levels of soluble serum Klotho measured 5 days after retroperitoneoscopic nephrectomy (median, 619.0 pg/mL; IR, 544.6-688.5; P = .001) were significantly lower than the baseline values. Among the renal transplant recipients, no significant changes in serum Klotho levels were observed during the observation period.
Our data regarding soluble serum Klotho levels obtained from living donors support the idea that the kidneys are a major source of soluble serum Klotho in human subjects without a deterioration of renal function. In recipients, concomitant acute kidney injuries and immunosuppressive protocols might modulate the release of soluble Klotho from the grafts into the circulation.
[Show abstract][Hide abstract] ABSTRACT: Purpose: Atherosclerotic plaques progress in a highly individual manner. Plaque eccentricity has been associated with a rupture-prone phenotype and adverse coronary events in humans. Endothelial shear stress (ESS) critically determines plaque growth and low ESS leads to high-risk lesions. However, the factors responsible for rapid disease progression with increasing plaque eccentricity have not been studied. We investigated in vivo the effect of local hemodynamic and plaque characteristics on progressive luminal narrowing with increasing plaque eccentricity in humans.
Methods: Three-dimensional coronary artery reconstruction using angiographic and intravascular ultrasound data was performed in 374 patients at baseline (BL) and 6-10 months later (FU) to assess plaque natural history as part of the PREDICTION Trial. A total of 874 coronary arteries were divided into consecutive 3-mm segments. We identified 408 BL discrete luminal narrowings with a throat in the middle surrounded by gradual narrowing proximal and distal to the throat. Local BL ESS was assessed by computational fluid dynamics. The eccentricity index (EI) at BL and FU was computed as the ratio of max to min plaque thickness at the throat. Mixed-effects logistic regression was used to investigate the effect of BL variables on the combined endpoint of substantial worsening of luminal narrowing (decrease in lumen area >1.8 mm2 or >20%) with an increase in plaque EI.
Results: Lumen worsening with an increase in plaque EI was evident in 73 luminal narrowings (18%). Independent predictors of worsening lumen narrowing with plaque EI increase were low BL ESS (<1 Pa) distal to the throat (odds ratio [OR] =2.2 [95% CI: 1.3-3.7]; p=0.003) and large BL plaque burden (>51%) at the throat (OR=1.7 [95% CI: 1.0-2.8]; p=0.051). The incidence of worsening lumen narrowing with increasing plaque eccentricity was 30% in the presence of both predictors versus 15% in luminal narrowings without this combination of characteristics (OR=2.4 [95% CI: 1.4-4.3]; p=0.002).
Conclusions: Low local ESS independently predicts areas with rapidly progressive luminal narrowing and increasing plaque eccentricity. Coronary regions manifesting an abrupt anatomic change, i.e., at highest risk to cause an adverse event, can be identified early by assessment of ESS and plaque burden.
[Show abstract][Hide abstract] ABSTRACT: According to the Japanese renal transplant registry in 2009, there were 1123 living kidney transplantations (LKT), including 35% from spouses (husband/wife). Up to the present in Japan, biologically living unrelated donors (LURD) are most frequently spouses. This study summarized our experience with LURD, especially spousal, kidney transplantation.
We performed 112 cases of LKT between April 2003 and March 2011, including 44 (39%) from spouses and two from other LURD. The other 66 cases received kidneys from living related donors (LRD). We divided the patients into two groups: 44 patients (group 1) received kidneys from spouses (LURD) and 66 (group 2) from LRD. During the induction phase, tacrolimus or cyclosporine, mycophenolate mofetil, and methylprednisolone were prescribed for immunosuppression. Basiliximab was administered on postoperative days 0 and 4. In ABO-incompatible LKT, plasmapheresis was performed to remove anti-AB antibodies prior to LKT; splenectomy or rituximab administration, at the time of or before LKT.
Among group 1, one patient died with a functioning graft and one lost her graft. Among group 2, one patient died with a functioning graft and one lost his graft. The incidences of an acute rejection episode were 31.8% and 24.2% in groups 1 and 2, respectively. There were three cases of antibody-mediated rejection in group 1. No patient experienced a lethal infectious complication.
Our results demonstrated that spousal LKT (LURD) was equivalent to LKT from LRD. In response to the shortage of deceased donors, LKT between married couples and from ABO-incompatible donors will spread in Japan.
[Show abstract][Hide abstract] ABSTRACT: The number of kidney transplantations (KTx) among patients on long-term hemodialysis (HD) is increasing due to the donor shortage in Japan. We investigated the outcomes of KTx among long-term (more than 15 years) patients on HD.
We performed 103 KTx between April 2003 and April 2010 including seven patients (one living and six deceased donor grafts), who had been treated with HD for more than 15 years (group 1) compared with 96 patients (94 living and two deceased donor grafts) treated for less than 15 years (group 2) before KTx. We examined the differences in patient and graft survivals and complication rates between the groups.
Acute rejection episodes (ARE) occurred in 2 (29%) group 1 and 22 (22%) group 2 subjects. Urinary tract infections were diagnosed in 1 (14%) group 1 versus 8 (8%) group 2 cases. The incidence of perioperative complications, such as delayed graft function, cytomegalovirus infection, and surgical complications was higher among group 1. The serum creatinine at 1 year after KTx was the same (1.3 mg/dL). The patient/graft survivals were 100%/100% at 1 and 3 years in group 1 versus 100%/100% at 1 and 99%/98% at 3 years in group 2.
The outcomes of KTx among long-term dialysis patients were similar to those in short-term dialysis patients.
[Show abstract][Hide abstract] ABSTRACT: A 62-year-old man on continuous ambulatory peritoneal dialysis was transferred to our hospital with recurrent abdominal pain and a cloudy peritoneal effluent. Three weeks before the transfer, his symptoms were successfully treated with broad-spectrum antibiotics. However, their effectiveness was lost for his recurrent symptoms. Fungal peritonitis was diagnosed because of an increased white blood cell count in the peritoneal fluid on admission and isolation of Candida albicans from a peritoneal fluid culture. Intravenous fos-fluconazole was immediately started, although it was ineffective for his deteriorating symptoms. The concomitant isolation of Candida albicans in a stool culture suggested that fungal peritonitis had an enteric origin. An emergency laparotomy revealed multiple diverticulosis and sigmoid colon diverticulitis. A surgical drainage was performed in addition to peritoneal catheter removal. Postoperatively, the patient's symptoms improved rapidly and there were no signs of recurrence with continuous administration of fos-fluconazole. Surgical drainage accelerated the recovery from fungal peritonitis. This patient is the first case showing the usefulness of stool culture in the diagnosis of fungal peritonitis secondary to prior bacterial peritonitis. This case also demonstrated the importance of laparotomy to confirm the enteric origin of the fungus, and the efficacy of early surgical drainage for the treatment.
[Show abstract][Hide abstract] ABSTRACT: Recent studies suggest that the overall survival and risk of end-stage renal disease among renal transplant donors are similar to those of the general population, but few studies focused on elderly donors. Among 88 donors who underwent retroperitoneoscopic live donor nephrectomies; 20 (22.7%) were elderly, namely, older than 65 years. Perioperative characteristics, such as sex, donor kidney side (left or right), body mass index, operative time, blood loss, and complication rate were not significantly different among groups classified by age: young (<50), middle (50-65), or elderly (>65). One month after kidney donation, the serum, creatinine values in the young, middle, and elderly groups increased to 1.05 ± 0.25, 0.96 ± 0.24, and 1.06 ± 0.15 mg/dL (P = .103) and the estimated glomerular filtration rate (eGFR) decrease to 63 ± 10, 63 ± 14, 56 ± 8 mL/min/1.73 m(2), respectively (P = .037). At three months and at three years after donation these parameters showed the same degree of improvement in all groups. Percentage of eGFR (% eGFR) of its pre-donation value in the young and middle groups improved up to 21% and up to 9%, respectively, until four years after donation, whereas that of the elderly group remained unchanged below 1%. In conclusion residual renal function after retroperitoneoscopic kidney donation in elderly donors was stable and acceptable during mid-term observation. Our retroperitoneoscopic approach was safe.
[Show abstract][Hide abstract] ABSTRACT: Hand-assisted laparoscopic live donor nephrectomy has been widely applied, because it enables safe dissection of the renal vessels, reducing warm ischemia time (WIT) during rapid extraction of the kidney. In the method described in the current series, the hand-port device was placed after the kidney was mostly mobilized using a pure retroperitoneoscopic procedure. After placement of the hand port, the ureter was completely dissected by an open procedure. Finally, the renal vessels were dissected and transected under the hand-assisted retroperitoneoscopic procedure, and the kidney removed through the hand port. We performed 66 retroperitoneoscopic live donor nephrectomies, including 14 right-sided and 52 left-sided procedures, with this original method of hand assistance. The mean operative time, WIT, blood loss, and renal vein length were 246 +/- 43 minutes, 209 +/- 124 seconds, 202 +/- 180 mL, and 17.4 +/- 6.4 mm, respectively. Comparison of the operative data between the initial 30 cases and the recent 36 cases using the established method showed significant differences in blood loss and WIT that approached statistical significance. No delayed graft function was observed in the current series. The technical and functional outcomes were acceptable. The site and timing of hand assistance minimize the disadvantage of a small working space during the retroperitoneoscopic procedure, making surgery easier and safer.
[Show abstract][Hide abstract] ABSTRACT: According to the Japanese renal transplant registry 2005, 834 transplantations were performed using living donors. Among them 112 (13.4%) patients were transplanted from living donors before the initiation of maintenance dialysis. Preemptive kidney transplantation (PreKTx) has been associated with improved allograft and patient survival rates compared to non-PreKTx. This study was designed to summarize our experience with PreKTx.
From April 2003 to July 2007, 44 living kidney transplantations were performed at our institution. We divided these 44 patients into two groups: 5 (11.4%) patients (group 1; G1) who underwent PreKTx and the other 39 patients (group 2; G2) who received kidneys after the institution of maintenance dialysis. Living unrelated donors were mostly spouses. During the induction phase, tacrolimus or cyclosporine, mycophenolate mofetil, and methylprednisolone were used for immunosuppression. In ABO-incompatible cases, plasmapheresis was performed to remove anti-AB antibodies prior to transplantation and splenectomy at the time of or before transplantation.
Among G1, no patient died. Among G2, two patients died with functioning grafts, one due to a traumatic subdural hematoma and another due to malignant B cell lymphoma. Death-censored graft survival rates were 100% in both groups. The incidence of acute rejection was 20.0% and 20.5% in G1 and G2, respectively.
Our results demonstrated that PreKTx from a living donor was equivalent to the non-PreKTx. However, there were also potential benefits to PreKTx in the long-term outcome, including avoidance of morbidity associated with dialysis and access procedures, as well as reduced cost. In response to the shortage of deceased donors, PreKTx from living donors will spread in Japan.
[Show abstract][Hide abstract] ABSTRACT: According to the Japanese renal transplant registry 2005, 834 transplantations were performed using living donors. Among them 199 (23.9%) kidneys were donated from spouses (husband/wife) and 174 (20.9%) from ABO-incompatible donors. This study summarized our experience of ABO-incompatible and living unrelated, especially spousal kidney transplantation.
We performed 44 cases of living donor kidney transplantation (LKT) between April 2003 and July 2007, including 14 (31.8%) from spouses (unrelated donor) who were divided into two groups: six patients (group 1; G1) from ABO-incompatible donors and eight patients (group 2; G2) from ABO-compatible donors. During the induction phase, tacrolimus or cyclosporine, mycophenolate mofetil, and methylprednisolone were used for immunosuppression. Basiliximab was administered on postoperative days 0 and 4. In all G1 patients plasmapheresis was performed to remove anti-AB antibodies prior to LKT, and splenectomy performed at the time of or before LKT.
Among G1, no patient died. Among G2, one patient died with a functioning graft due to a traumatic subdural hematoma. Graft survival rate was 100% in both groups. The incidence of acute rejection was 33.3% and 25.0% in G1 and G2, respectively. No patient experienced a lethal infectious complication.
Our results demonstrated that transplantation from an ABO-incompatible spousal donor was equivalent to transplantation from an ABO-compatible spousal donor. In response to the shortage of deceased donors, LKT between married couples and from ABO-incompatible donors will spread in Japan.
[Show abstract][Hide abstract] ABSTRACT: We assessed the feasibility of retroperitoneoscopic hand-assisted live-donor nephrectomy according to the basic principle of transplantation in kidney selection, namely, leaving the better-functioning kidney in the donor.
Thirty consecutive live-donor nephrectomies, including 10 right-sided and 20 left-sided procedures, were evaluated. The surgery was started endoscopically using three ports, followed by hand assistance for dissecting the renal pedicles through the extended inner-port incision. A vascular Endostapler and polymer clips were used to transect the renal vessels.
Two right-sided cases required open conversion because of multiple renal vessels and uncontrollable bleeding. The median operative time, warm ischemia time (WIT), blood loss, and renal vein length were 244 minutes (upper and lower quartile 215 and 274 minutes), 186 seconds (134, 239 seconds), 175 mL (45, 305 mL), and 22 mm (19, 26 mm), respectively. The operative time and WIT were longer, and the renal vein was shorter, in the right-sided than in the left-sided procedures (P < 0.05), but no difference was found in the other perioperative data for the two sides. No delayed graft function was observed, and the kidney function 1 month postoperatively was acceptable in all donors and all recipients.
Our technical devices, such as the site and timing of hand assistance and control of the renal vessels, seem feasible. Although we could not draw a conclusion about the safety of the right-sided procedure, this alternative procedure should be applicable for laparoscopic donor nephrectomy uninfluenced by the side of the donor kidney provided the surgical team has sufficient expertise.
Journal of Endourology 07/2007; 21(6):589-94. DOI:10.1089/end.2006.0326 · 1.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Several protocols allow the successful ABO incompatible living-related kidney transplantation (ABO-ILKT), yet no single method has emerged as the best. We have made several substantial changes to our ABO-ILKT protocol over the past decade and a half and have attempted to determine whether the changes in immunosuppressive agents have resulted in a better outcome. We used methylprednisolone (MP), cyclosporine (CsA), azathioprine (AZ), antilymphocyte globulin (ALG) and deoxyspergualine (DSG) in the 105 cases of ABO-ILKT (group 1) between 1989 and 1999, and MP, tacrolimus (FK506), mycophenolate mofetil (MMF) in the 117 cases of ABO-ILKT (group 2) between 2000 and 2004. We compared the patient and graft survival rates as well as the incidence rate of acute rejection in these two eras, when different regimens were used. There were significant differences in the 1- and 5-year graft survival rates between groups 1 and 2 (1-year: 78% in group 1 vs. 94% in group 2; 5-year: 73% in group 1 vs. 90% in group 2, p = 0.008). Also, a higher incidence rate of acute rejection was significantly observed in group 1 (50/105, 48%) than in group 2 (18/117, 15%) (p < 0.001). We conclude that the FK/MMF combination regimen provides excellent graft survival results in ABO-ILKT.
American Journal of Transplantation 05/2007; 7(4):825-31. DOI:10.1111/j.1600-6143.2006.01676.x · 5.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recently, it has been revealed that alloantigen-independent causes are important factors for late graft loss in kidney transplantation. We compared the results of living kidney transplantation from HLA-identical siblings with those from HLA-non-identical siblings to analyse the impact of alloantigen-independent factors on long-term graft survival.
Two hundred and sixty-six recipients who were grafted from their siblings between 1983 and 2002 were subdivided into those transplanted from HLA-identical donors (n=86) and those from HLA-non-identical donors (n=180).
The incidence of acute rejection was significantly lower in the HLA-identical group than in the HLA-non-identical group (9.3% vs 53.9%, respectively; P<0.0001). Graft survival was significantly higher in the HLA-identical group than in the HLA-non-identical group (91.3% vs 79.2% at 5 years, 80.3% vs 66.8% at 10 years and 59.1% vs 51.7% at 15 years, respectively; P=0.0372). Although acute rejection was not seen as a cause of graft loss in the HLA-identical group, death with functioning graft, recurrence of the original disease or chronic allograft nephropathy were observed as the major causes of graft loss in the late period of the HLA-identical group.
We concluded that alloantigen-independent causes constitute a crucial factor for graft loss in the late period of HLA-identical kidney transplantation.
International Journal of Urology 05/2006; 13(5):502-8. DOI:10.1111/j.1442-2042.2006.01350.x · 2.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Renal transplantation across the blood barrier is a unique model for investigating the humoral response to different carbohydrate antigens. However, in such a renal transplantation, the characteristics of B cells as well as of the antibodies produced by B cells are less well defined.
In the present study we investigated B cell subsets (i.e., the CD5(+) B-1 and CD5- B-2 subsets) by flow cytometric analysis, and their subclasses of antibody, by ELISA, in patients who had undergone renal transplantation across the blood barrier. The subjects consisted of five recipients with good function (group 1) and five recipients with graft loss (group 2) accompanied by antibody-titer elevation after ABO-incompatible renal transplantation.
The B-cell population analysis revealed that CD5(+) B-1 cells temporarily increased in all patients in both groups soon after transplantation, and that CD5- B-2 cells significantly increased 1 month after transplantation only in group 2. The antibody subclasses analysis showed mild elevation of immunoglobulin (Ig) G2 and IgM in group 1 as opposed to remarked elevation of IgG2, IgM and IgG1 in group 2.
The results of this study suggested that CD5(+) B-1 cell T-independent activation usually occurs soon after ABO-incompatible renal transplantation, but that CD5- B-2 cell T-dependent activation occurs only in patients who experience graft rejection.