Comparative Study on Variation of Quality of Life of Patients of Preemptive Kidney Transplantation and Nonpreemptive Kidney Transplantation.

BACKGROUND: There have been few studies that have reported the influence of kidney transplantation on the quality of life (QOL) of patients of preemptive kidney transplantation (PKT) and nonpreemptive kidney transplantation (NPKT). MATERIAL AND METHODS: Fifty patients of PKT and 49 patients of NPKT were employed as study subjects. A questionnaire survey using Short Form 36 and Kidney Disease QOL on patients' physical and psychological QOL was performed for these patients prior to transplantation and 1 month, 3 months, and 1 year after transplantation. RESULTS: The analysis of results has revealed that transplantation clearly has improved the physical and psychological QOL in patients with end-stage renal disease. For the items regarding physical burdens incurred by the transplantation, patient QOL deteriorated on a single occasion 1 month after the transplantation while it was improved 1 year after the transplantation. For the items regarding psychological burdens, the mental condition of the patients was improved overall without deterioration over time. Concerning the "Effect of Kidney Disease" and "Burden of Kidney Disease," QOL was significantly better in PKT than NPKT at baseline before transplantation, although the significant difference gradually decreased 1 month and 3 months after the transplantation and disappeared after 1 year. CONCLUSION: Transplantation certainly improved the QOL of patients with end-stage renal disease. Before transplantation, PKT was clearly better than NPKT in the QOL items associated with "Burden of Kidney Disease." This indicated that patients of PKT have improved QOL compared to patients of NPKT, and that the overall awareness of kidney disease is decreased. A postoperative gap in mental and bodies was observed especially in PKT, however, could be overcome by nursing interventions.

Causes of Ineligibility for Recipients in Living Kidney Transplantation.

BACKGROUND: Even if a living donor candidate exists, there are some cases that do not result in kidney transplantation (KTx) due to problems on the recipient side. The aim of this study was to clarify causes of ineligibility for KTx in these cases, so as to make RTx more applicable for patients. METHODS: We targeted 470 patients with end-stage renal disease who applied for the primary kidney KTx from 2010 to 2012. Then we selected those who were not applicable for KTx and investigated recipient causes of ineligibility for KTx or not receiving KTx. RESULTS: The average age of recipients was 47.6 ± 12.9 (7-82) years. A majority of the 470 patients were male (n = 305, 64.9%). Two hundred ninety-seven patients intended to receive a living donor KTx and the others hoped for a deceased donor KTx. Of the 297 patients, 207 (70.0%) underwent KTx and 9 (1.9%) were being prepared for KTx at the time of the survey. Eighty-three patients (27.9%) did not receive a living KTx, with 59 of these due to recipient-related problems and 30 due to donor-related problems. We further classified the reasons for these 59 recipients not undergoing KTx as follows: (1) unclear reasons (35.6%); (2) insufficient intention to receive transplant (13.6%); (3) heart disease (10.2%); (4) malignancy (8.5%); (5) immunologic risks (5.1%); (6) death during the waiting period (5.1%); (7) cerebrovascular events (5.1%); (8) cardiovascular problems (5.1%); (9) psychiatric disorders (3.4%); and (10) infections (3.4%). CONCLUSION: Nearly 50% of the reasons for ineligibility as a recipient were related to their intention to receive KTx, with 94.9% of the nontransplanted cases due to nonimmunologic reasons. Thanks to the recent advances in immunosuppressive therapy, there were only 3 patients who could not undergo KTx due to immunologic risks. Based on these results, transplant surgeons should not only emphasize physical evaluation but should also pay careful attention to the recipient's intention to receive KTx.

Influence of Long-term Dialysis on the Outcome of Kidney Transplantation: A Single-Center Study.

AIM: We investigated clinical outcomes of patients in Japan with a history of long-term dialysis treatment. METHODS: We conducted 1171 kidney transplantations between 2000 and 2015. Sixty of the patients had undergone dialysis therapy for >20 years before the transplantation. We compared graft and patient survivals between the recipients with >20 years of dialysis (long dialysis group [LGD]) and those with <20 years (control group [CG]) in a case-control study, in which sex and age of both donors and recipients, ABO compatibility, and calendar year of transplantation were matched. RESULTS: Average age of LDG was 52.8 ± 8.9 years, and that of CG was 54.2 ± 12.6 (P > .05). Durations of dialysis were 25.4 ± 1.57 vs 5.8 ± 5.8 years, respectively (P < .05). The graft survival rates were 91.6%, 89.9%, and 81.8% at 3, 5, and 10 years in LDG vs 90.71%, 84.8%, and 78.3% in CG, respectively (P > .05). The patient survival rates were 96.6%, 93.2%, and 88.6% in LDG vs 94.5%, 91.0%, and 83.9%, respectively (P > .05). There was no significant difference in mean estimated glomerular filtration rates for post-transplant 10 years between them. CONCLUSION: LDG showed satisfying clinical outcomes comparable to those of CG both in graft and patient survivals and renal function.

Long-Term Outcomes in Kidney Transplantation From Expanded-Criteria Donors After Circulatory Death.

The number of recipients waiting for a transplant is increasing. In Japan, there is more frequent use of organs from expanded-criteria donors (ECDs) after circulatory death. We retrospectively analyzed long-term outcomes of kidney transplantation (KT) from expanded-criteria donation after circulatory death (DCD). From 1995 to 2013, 97 cases of KT from DCD donors were performed in our department. Death-censored graft survival rates of ECD kidneys (n = 50) versus standard-criteria deceased-donor (SCD) kidneys (n = 47) for 1, 5, and 10 years after transplantation were 84.0% vs 97.9%, 74.8% vs 95.6%, and 70.2% vs 81.8%, respectively. No significant difference was found between the 2 groups (P = .102). Kidneys from donors with a history of hypertension (HTN) and cerebrovascular events (CVE) and contribution from older donors had significantly lower 10-year graft survival rates (P values of .010, .036, and .050, respectively). Cox proportional hazard regression analyses showed donor age to be significantly associated with long-term graft survival independently from other factors. These results suggest that ECD kidneys remain an acceptable alternative to dialysis under certain conditions. Increased donor age was a significant risk factor determining long-term graft function. Moreover, comorbidities of HTN and CVE could become significant risk factors, especially in older donors.

Negative impact of underlying non-insulin-dependent diabetes mellitus nephropathy on long-term allograft survival in kidney transplantation: a 10-year analysis from a single center.

INTRODUCTION: We analyzed the relationship between underlying nephropathy and long-term outcomes in kidney transplant recipients. METHODS: We retrospectively analyzed data from 678 patients who underwent kidney transplantation (KTx) between 1998 and 2011. Recipients with 13 major nephropathies were evaluated for graft and patient survival, and causes of graft loss. RESULTS: The best 10-year graft survival rates (100%) were in the patients with autosomal-dominant polycystic kidney disease, preeclampsia, Alport syndrome, and purpura nephritis. The worst rate (50.8%) was in patients with non-insulin-dependent diabetes mellitus nephropathy (NIDDMN; P = .039). Causes of graft-loss in the NIDDM patients included chronic rejection (6 cases), acute rejection (3 cases), infection (2 cases), and cardiovascular event (2 cases). Significant risk factors for graft loss were donor age (P < .01) and NIDDMN (P < .01). CONCLUSION: Underlying NIDDMN before KTx was a significant risk factor for long-term graft function. Immunologic factors and nonimmunologic factors influenced the long-term outcomes in patients with underlying NIDDMN.

Efficacy and safety of febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase for the treatment of hyperuricemia in kidney transplant recipients.

BACKGROUND: Febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase, is a potential alternative to allopurinol for patients with hyperuricemia. In this study, we evaluated the efficacy and safety of febuxostat for the management of hyperuricemia in renal transplant recipients. PATIENTS AND METHODS: Between June 2012 and January 2013, a total of 22 renal transplant recipients (56 ± 10 years old) with hyperuricemia were enrolled in this study. All patients underwent de novo kidney transplantation, except for 1 patient, who received a second kidney transplant. Ten patients receiving allopurinol and 3 patients receiving benzbromarone were converted to febuxostat at doses of 10-20 mg/d. In the remaining 9 patients, who did not have a history of other urate-lowering medications, febuxostat was initiated at a dose of 10 mg/d. RESULTS: Uric acid levels after initiation of febuxostat were significantly lower than before treatment (5.7 ± 0.7 mg/mL vs 8.0 ± 0.8 mg/mL; P < .001). At last follow-up visit, 16 of the 22 patients (73%) achieved uric acid levels of ≤ 6.0 mg/dL, despite the low dosage of febuxostat. All patients were maintained on febuxostat without serious adverse events, except for 1 patient, who discontinued febuxostat because of numbness in the arms. CONCLUSIONS: Low-dose febuxostat is a promising alternative to allopurinol or benzbromarone for the treatment of hyperuricemia in kidney transplant recipients. The long-term urate-lowering efficacy and safety of febuxostat with regard to renal function in kidney transplant recipients with hyperuricemia requires further investigation.

Long-term impact of hypertension on renal allografts.

OBJECTIVE: We assessed the impact of hypertension on renal transplant function and survival in the past decade after introduction of mycophenolate mofetil and rituximab. METHODS: We examined the 184 patients who underwent renal transplantation from March 1982 to September 1999 and presented at our outpatient clinic from 2001 to 2011. They were divided into group 1 with mean systolic blood pressure (mSBP) >130 mm Hg and Group 2 with mSBP <130 mm Hg. We compared mean serum creatinine (sCr) levels for 9 years and 12-year actuarial graft survival rates. Risk factors for graft survival were assessed by Cox regression analysis. RESULTS: There were 75 group 1 and 109 group 2 recipients. The mean sCr level of group 1 was 1.59 ± 0.12 mg/dL and that of group 2 1.54 ± 0.10 mg/dL (P < .0001). Of note was that mean sCr levels of group 1 started to increase about 3 years after transplantation. Although 5-year graft survival rates of both groups were 100%, 9- and 12-year rates among group 1 were 97.3% and 90.5%, respectively, whereas among group 2 they were 99.1% and 98.1%, respectively (P = .0195). Cox univariate and multivariate analyses showed mean SBP to be the only significant risk factor for graft survival (P < .05). CONCLUSIONS: We concluded that the hypertensive group showed deteriorating renal function from around 3 years after transplantation that lowered graft survival afterward, resulting in a clear distinction from the nonhypertensive group at around 10 years after transplantation. Mean SBP was a significant risk factor for graft survival. Hypertension may be a surrogate for a poor renal graft prognosis in the long run.

Renal transplantation in patients with human T-cell lymphotropic virus type 1.

BACKGROUND: Renal transplantation (RTx) in carriers of human T-cell lymphotropic virus type 1 (HTLV-1) has a risk of developing overt leukemia upon immunosuppression. Although there have been a few reports of such cases, it is unclear HTLV-1 carrier if patients on the modern immunosuppressants would develop HTLV-1-associated myelopathy or adult T-cell leukemia lymphoma. METHODS: We retrospectively reviewed the clinical outcomes of RTx in nine HTLV-1 carriers to assess a risk of developing leukemia from 2002 to 2011 using immunosuppression with a calcineurin inhibitor, mycophenolate mofetil (MMF), and steroid. The anti-CD25 monoclonal antibody basiliximab was used for induction. In two cases of ABO-incompatible RTx, the rituximab was also administered before RTx. RESULTS: The ratio of male to female subjects was 2 to 7 with an overall mean recipient age of 54.3 ± 8.1 years. We prescribed cyclosporine (n = 5) or tacrolimus (n = 4). There was only one graft loss due to the death caused by aspiration pneumonia with a functioning graft. No one developed overt leukemia with combined treatment with MMF, basiliximab and rituximab. CONCLUSION: We concluded that RTx in HTLV-1 carriers could be performed using a modern immunosuppressive regimen, without the risk of developing leukemia.

Early humoral-mediated graft injuries in ABO-incompatible kidney transplantation in human beings.

INTRODUCTION: Acute humoral rejection is the most important risk factor for early graft loss in ABO-incompatible (ABO-i) renal transplantation (RTx) and is present from the early period after RTx. However, the characteristics of early humoral-mediated graft injury are pathologically uncertain. OBJECTIVE: To analyze tissue from 10 protocol graft biopsies performed in 10 patients within 30 days post-RTx to clarify the pathologic features of early humoral-mediated graft injuries in ABO-i RTx. METHODS: Pathologic findings were examined using light and electron microscopy and immunofluorescence studies for C4d. Protocol biopsies were performed within 30 days after RTx in the absence of an episode of dysfunction (creatinine concentration 1.21-1.81 mg/dL). RESULTS: The immunofluorescence study demonstrated C4d deposition in peritubular and glomerular capillaries. Acute glomerulitis with infiltration of mononuclear cells and neutrophils was observed in 3 patients. Furthermore, glomerulitis was accompanied by endothelial cell injuries, widening of subendothelial spaces with a double-contoured glomerular basement membrane, and mesangiolysis. CONCLUSION: In ABO-i RTx, early humoral-mediated graft injuries were observed in approximately 30% of patients despite normal graft function. They were characterized by C4d deposition and glomerular capillary injury. These findings suggest that renal glomeruli are the first site of graft injury by anti-A or anti-B blood type antibody with complement activation in ABO-i RTx.

Persistent glomerular hematuria in living kidney donors confers a risk of progressive kidney disease in donors after heminephrectomy.

Although glomerular hematuria is likely a sign of chronic kidney disease that will develop into overt nephropathy after donation, it remains unclear whether prospective donors with hematuria should be excluded. We reviewed the medical records of 242 donors who donated at our institution from 2001 to 2007 and surveyed the prevalence of hematuria pre- and postdonation. We then investigated the association of hematuria with proteinuria postdonation and trends in glomerular filtration rate. Before donation, 8.3% of 242 donors presented with persistent hematuria, a finding that was significantly associated with dysmorphic hematuria before donation. Most cases of predonation persistent hematuria persisted after donation, and the overall prevalence increased to 15.3%. During a median follow-up period of 2.3 years after donation, 8.3% developed persistent proteinuria, with incidence being significantly higher in donors having persistent hematuria with dysmorphic red blood cells (d-RBC) both before and after donation. Postdonation persistent hematuria with d-RBC was also associated with a progressive decline in renal function. These results indicate that persistent glomerular hematuria is strongly associated with a higher incidence of postdonation progressive kidney disease. Potential donors with persistent glomerular hematuria should be excluded, while those with isolated hematuria need to be evaluated with heightened caution.

How do living kidney donors develop end-stage renal disease?

The clinical course and risk factors for developing end-stage renal disease (ESRD) after heminephrectomy in living kidney donors have scarcely been investigated. We reviewed medical records and identified eight case donors who developed chronic kidney disease (CKD) stage 5 or ESRD, and subsequently investigated the association between postoperative clinical courses and changes in renal function. To conduct a case-control study, we also selected a control group comprising 24 donors who had maintained stable renal function and were matched for age, sex and follow-up time since donation. Except for one donor who developed ESRD caused by a traffic accident, none of the donors developed progressive renal dysfunction immediately after donation. Their renal functions remained stable for a long period of time, but started to decline after developing new comorbidities, especially risk factors known as progression factors (proteinuria or hypertension) or accelerating factors (cardiovascular [CV] event or infection) of CKD. As compared with the control donors, incidence of postoperative persistent proteinuria, acute CV event, severe infection and hospitalization due to accelerating factors of CKD were significantly higher in the case donors. These results suggest the importance of long-term (more than 10 years) follow-up of donors with special attention on the risk factors of CKD.

Hand-assisted laparoscopic splenectomy in ABO-incompatible kidney transplant recipients.

OBJECTIVE: We perform living-related ABO-incompatible kidney transplantations to alleviate the organ shortage in our country. Splenectomy has been performed routinely in these recipients, although its clinical significance remains controversial. In this study, we have reported our experience with a hand-assisted laparoscopic splenectomy (HALS) technique. METHODS: Between April 2000 and December 2006, 50 patients (23 males) underwent ABO-incompatible kidney transplantation with HALS. The mean age and weight of the recipients were 44 +/- 13 years and 56 +/- 12 kg, respectively. All patients underwent preoperative plasmapheresis to reduce isoagglutinin (A and/or B antibody). In 6/50 patients, a hand-assisted device was placed through a peritoneal window in the right lower abdominal skin incision for kidney engraftment. In the remaining 44 patients, a 6-cm upper midline or periumbilical midline incision was made for the hand-assisted device in the lateral position. RESULTS: An ABO-incompatible procedure was completed successfully in all cases. The average HALS time was 118 +/- 42 minutes, with an average pneumoperitoneum time of 79 +/- 40 minutes and average blood loss of 48 +/- 81 g. There were two conversions to open splenectomy because of intraoperative bleeding and suspected pneumothorax. Two other cases required relaparotomy because of hematoma and perforation of the ileum. Successfully operations were achieved through the previous periumbilical incision. CONCLUSIONS: Although meticulous, rigorous surgical technique is essential, HALS is safe and feasible for recipients of ABO-incompatible grafts with tissue weakness and a bleeding tendency because of renal failure and preoperative plasmapheresis.

Effects of immunosuppressants on the progression of hepatitis C in hepatitis C virus-positive renal transplantation and the usefulness of interferon therapy.

OBJECTIVE: The purpose of this study was to analyze the effects of immunosuppressants on hepatitis C virus (HCV) replication to establish optimal immunosuppressive therapy in HCV-positive renal transplantation. MATERIALS AND METHODS: Cyclosporine (CsA), tacrolimus (Tac), mycophenolate acid (MPA), the active metabolite of mycophenolate mofetil (MMF), and methylprednisolone (MP) were administered to HCV replicon cells alone or in combination with interferon (IFN). HCV RNA was quantitatively determined. Of our 2064 recipients of renal transplantations between 1980 and 2005, 153 were HCV-positive. We analyzed changes in hepatic function and the efficacy of IFN therapy in these patients. RESULTS: Only CsA strongly inhibited the growth of HCV RNA (13.1% at 1.0 microg/mL). MPA enhanced the inhibition of the growth of HCV RNA in the presence of IFN. Tac and MP reduced, rather than enhanced, the efficacy of IFN. Progression to chronic hepatitis occurred in a significantly smaller number of patients in the CsA than the Tac group (6 vs 19; P = .04). Serum alanine aminotransferase (ALT) levels were comparable pretransplantation and posttransplantation in the CsA group (24.8 +/- 20.5 vs 28.9 +/- 28.3 IU/L, respectively, while a significant elevation was noted in the Tac group (22.2 +/- 21.5 vs 32.6 +/- 30.8 IU/L, respectively; P = .024). Two of 4 patients who underwent combination therapy with IFN and ribavirin during treatment with CsA and MMF obtained an HCV-negative status for over 24 weeks. CONCLUSIONS: CsA effectively prevents the progression of chronic hepatitis in HCV-positive renal transplant patients. A greater response rate can be expected by concurrent administration of CsA and MMF under IFN therapy.

Successful third kidney transplantation with intensive immunosuppression in a highly sensitized recipient.

HLA sensitization associated with previous kidney transplantation is a major drawback to retransplantation. Recently we successfully performed a third graft using intensive immunosuppression for a highly sensitized recipient. The patient was a 31-year-old man who had previously undergone a living donor graft from his father at our institute in 1999. His kidney graft function had deteriorated due to chronic allograft nephropathy, returning to hemodialysis therapy in 2005. He received a second graft from a deceased donor in another country on August 14, 2006. It rejected on postoperative day 3 possibly due to acute accelerated rejection. He was offered a third kidney from his brother. Panel-reactive antibody (PRA) tested before the third procedure revealed positive class I (88%) and class II (96%) PRAs. Mycophenolate mofetil (MMF) was started 3 weeks before the third transplantation, and preoperative plasmapheresis performed thrice. He underwent the living donor graft on March 9, 2007. Immunosuppression consisted of tacrolimus, MMF, methylprednisolone, and basiliximab. Immediately afterward there was a sudden decrease in allograft blood flow and urine output, implying hyperacute rejection. Following treatment with plasmapheresis and a single dose of rituximab (200 mg), the kidney allograft function recovered, although the PRA at 3 weeks was still positive. Six months posttransplantation, he is well with a creatinine of 0.9 mg/dL. Our protocol may reduce the risk for graft loss in a highly sensitized transplant recipient.

Glomerular expression of plasmalemmal vesicle-associated protein-1 in patients with transplant glomerulopathy.

Transplant glomerulopathy (TG) is a prominent feature of chronic rejection that is characterized by double contours of the glomerular capillaries (GC). In this report, we demonstrate that one of the histopathological features of TG is a phenotypic change of glomerular endothelial cells which is illustrated by increased caveolae formation. To verify the endothelial changes in this disease, we examined the expression of plasmalemmal vesicle-associated protein-1 (PV-1), a glycoprotein associated with plasmalemmal vesicles (caveolae), in the glomeruli of TG patients using pathologische anatomie Leiden-endothelium (PAL-E) antibody. Twenty-six cases of chronic allograft nephropathy (CAN) with TG were examined, compared with 16 cases of CAN without TG, type I MPGN (4 cases), and transplant glomerulitis (8 cases). Overall, 24 of 26 (92.3%), 4 of 16 (25%), 0 of 4, 0 of 8 cases were PAL-E-positive for GC, respectively. Further, the extent of glomerular PAL-E expression was positively correlated with both the grade of TG (rs= 0.72, p = 0.0003) and proteinuria (g/day) (rs= 0.51, p = 0.02). A correlation was not observed between glomerular PAL-E positivity and peritubular capillary C4d deposits (Yetes chi = 0.23, p = 0.89). In summary, the present study demonstrates expression of PV-1 in the GC of TG which is correlated with the grade of TG and proteinuria.

Thickening of the peritubular capillary basement membrane is a useful diagnostic marker of chronic rejection in renal allografts.

In kidney transplantation, the multilayering of the peritubular capillary basement membrane (MLPTC) in electron microscopy (EM) has been recognized as a feature of chronic rejection (CR). In this study, thickening of the peritubular capillary (PTC) basement membrane was evaluated by light microscopy (LM) to determine whether it corresponds to the MLPTC in EM and whether it can be used as a diagnostic marker of CR. Forty-eight patients with late renal allograft were divided into chronic allograft nephropathy (CAN) with CR (Group 1, n = 23), CAN without CR (Group 2, n = 19) and CAN-free (Group 3, n = 6). The thickening of the PTC basement membrane (ptcbm) was scored from grades 0 to 2 (ptcbm score), and the MLPTC thickness was measured in EM. Interobserver agreement on ptcbm scores was statistically significant (Kappa coefficient = 0.63). LM and EM lesions corresponded very well. The ptcbm score was highest in Group 1, and ptcbm2 corresponded closely with CR. Group 1 showed significantly thicker MLPTC than Groups 2 and 3. The results validated the usefulness of the ptcbm score and suggested that the thickening of the PTC basement membrane can be a novel diagnostic marker of CR.

Improved outcomes of renal transplantation from cardiac death donors: a 30-year single center experience.

Outcomes of renal transplantation from donation after cardiac death (DCD) donors over 30 years were analyzed. Between 1975 and 2004, 256 renal transplantations from DCD donors were performed. The recipients were divided into four groups according to a time period as follows: 1975-1979 (Group 1; n = 18), 1980-1989 (Group 2; n = 81), 1990-1999 (Group 3; n = 84) and 2000-2004 (Group 4; n = 73). Of the 256 transplanted kidneys from DCD donors, 38 (15%) functioned immediately after transplantation. The incidence of delayed graft function (DGF) was 72%. Warm ischemic time and total ischemic time were 7.4 +/- 9.4 min and 11.9 +/- 5.6 h, respectively. The overall graft survival rates at 1, 5 and 10 years were 80%, 72% and 53%, respectively. Graft survival rates in each group have continually improved over time (5-year graft survival; 23% vs. 64% vs. 74% vs. 91%, respectively). However, there was no significant difference in graft survival rates between the groups of patients who survived with a functioning graft for more than 1 year. A multivariate Cox regression analysis showed acute rejection and donor age to be independently associated with graft outcome. DCD donors are a valuable source of kidneys for transplantation with promising long-term outcomes.

A pathological analysis of lymphatic vessels in early renal allograft.

Lymphatic vessels are an essential part of the immunological response. Nevertheless, little is known about the pathology of renal transplant rejection. In part the reason may be not distinguishing peritubular capillaries from lymphatic vessels by periodic acid-Schiff (PAS) staining. This study examined the morphology of lymphatic vessels in early renal allografts using double staining with PAS and podoplanin. The 41 cases were divided into four categories: (I) acute antibody-mediated rejection, (II) acute cellular rejection, (III) peritubular capillaritis only, and (IV) controls. I through III had the evidence of peritubular capillaritis exceeding grade 1 on a biopsy obtained an average of 17.3 +/- 5.5 days after kidney transplantation. In addition, each lymphatic vessel density (LVD) and nodular lesion of lymphocytes (NL) were quantified as the number of each podoplanin-positive vascular profiles and NL per unit area of cortex measured Lumina Vision (Mitani). The average of the LVD was 73.0, 35.1, 37.1, and 8.1 per 10 mm2 for groups I to IV and the average of NL was 2.8, 5.5, 1.3, 0.9, respectively. There was a significant correlation between LVD and NL. NL showed a strong relation to the accumulation of lymphocytes in lymphatic vessels (AL); 22% of the AL scores were greater than the peritubular capillaritis grade. We found lymphatic vessels to be strongly associated with any kind of inflammatory process that occurred unexpectedly soon after kidney transplantation. In addition, to avoid misdiagnosis of peritubular capillaritis, NL in early renal allograft must especially be excluded.

Cyclosporine-sparing effect of basiliximab in renal transplant recipients with mycophenolate mofetil.

UNLABELLED: Basiliximab added to a maintenance regimen consisting of cyclosporine microemulsion and mycophenolate mofetil was studied for its effectiveness in allowing early steroid withdrawal in renal transplantation. Furthermore, the cyclosporine-sparing effects between groups with and without basiliximab induction therapy were compared. PATIENTS: Between September 2001 and June 2003, 90 patients underwent renal transplants with cyclosporine-based immunosuppression, namely, cyclosporine, mycophenolate mofetil, and methylprednisolone, (group 1; n = 25). During the latter half of the study basiliximab was administered during the induction phase (group 2; n = 65). In group 2, steroids were completely withdrawn on postoperative day 14 in 57 patients. RESULTS: The incidence of acute rejection was significantly higher among group 1 patients (P = .005). The incidence of steroid-resistant rejection in group 1 patients was significantly higher (P = .025). At each time point cyclosporine levels in group 1 patients were significantly higher (P < .01). The incidence of infection was comparable between the groups. Patient and graft survival rates in group 1 were 100% and 100%; in group 2, they were 99% and 99%, respectively. In group 2, steroids were discontinued in 57 patients with permanent withdrawal achieved in 32 patients (56%). CONCLUSION: The use of basiliximab, together with mycophenolate mofetil allowed for a significant reduction in the cyclosporine dose without increasing the risk of acute rejection. Although further follow-up is necessary to confirm the effect, this regimen may attenuate cyclosporine nephrotoxicity thereby affecting the long-term outcomes of renal transplantation.

Loss of peritubular capillaries in the development of chronic allograft nephropathy.

BACKGROUND: Chronic allograft nephropathy (CAN) remains the most important cause of late renal graft loss. In this study, we examined the role of peritubular capillary (PTC) injury in the development of CAN. METHODS: We studied renal biopsies (n = 79) obtained from grafts with CAN. PTC injury was examined morphologically by immunohistochemistry for CD34. These findings were correlated with interstitial fibrosis and graft dysfunction. Humoral immunity involved in CAN was studied by C4d staining. RESULTS: The CAN cases in the present study included chronic rejection (CR) (n = 14, 17.8%) and C4d-positive chronic humoral rejection (CHR; n = 6, 42.9% in CR cases). Irrespective of CR, CHR, or other CAN, the development of CAN was characterized by injury to and loss of identifiable PTCs, accompanied with the development of interstitial fibrosis. In CR and CHR cases, the loss of PTCs was prominent and seemed to progress within a relatively short period after transplantation. A decrease in the number of PTCs significantly correlated with the development of interstitial fibrosis (r = -0.75, P < .001) and impairment of graft function (r = -0.69, P < .001). CONCLUSIONS: Irrespective of whether CR, CHR, or other factors contribute to CAN, the processes involved in its development appear similar and are characterized by progressive injury and loss of PTCs, with the development of renal scarring. Immunohistochemistry for CD34 in human renal biopsies is a useful method for the detection of microvascular injury.