The main challenge with cytomegalovirus (CMV) prophylaxis in IgG donor-positive/recipient-negative (D+/R–) kidney transplant recipients is late-onset CMV disease. We evaluated a novel protocol for ...the prevention of late-onset CMV infection and disease in D+/R− organ recipients.
Our prospective, observational, cohort study included 100 adult kidney transplant recipients. Prophylaxis with low-dose valganciclovir (450 mg/d, 3 times a week for 6 months) was administered to D+/R− recipients. Risk factors for CMV infection and disease were identified. Renal function and the outcomes of CMV infection and disease were compared between D+/R− (n = 15) and recipient-positive (R+; n = 81) organ recipients.
D+/R− recipients showed significant independent risk factors with high hazard ratios for CMV infection (2.04) and disease (10.3). The proportion of CMV infection in D+/R− and R+ recipients was 80% and 46% (P = .023), and that of CMV disease was 33% and 6.2% (P = .008), repectively. D+/R− recipients developed CMV infection and disease within 6 months after transplantation. However, both CMV infection- and disease-free survival rates beyond 1 year post-transplantation defined as late-onset were stable in D+/R− recipients. Moreover, serum creatinine levels at 1 year post-transplantation were comparable between D+/R− and R+ recipients (1.45 ± 0.71 vs 1.16 ± 0.35 mg/dL, P = .26).
Our novel protocol prevented late-onset CMV infection and disease beyond 1 year post-transplantation in D+/R− recipients.
•The main challenge with CMV prophylaxis for D+/R− recipients is late onset.•We aimed to acquire CMV IgG in D+/R− recipients for preventing late onset.•Valganciclovir with reduced dosage and frequency of dosing was administered.•Low-dose valganciclovir 3 times a week can effectively prevent late onset.•Our protocol may improve long-term outcomes in D+/R− kidney transplant recipients.
Abstract Background 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. Methods 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. Results 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. Conclusion 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.
Background
Urinary tract infection caused by human adenovirus (HAdV) after renal transplantation (RT) results in graft loss because of concomitant nephropathy and acute rejection and may result in ...death because of systemic dissemination.
Methods
We assessed the time period between RT and disease onset, symptoms, treatment details, disease duration, renal graft function, outcomes, and complications.
Results
HAdV infection of the urinary tract occurred in 8 of 170 renal transplant recipients. Symptoms were macrohematuria in all 8 patients, dysuria in 7, and fever in 5. The median period from RT to disease onset was 367 (range, 7–1763) days, and the median disease duration was 15 (range, 8–42) days. The mean serum creatinine (sCr) level prior to onset was 1.35 ± 0.48 mg/dL and the mean maximum sCr level during disease was 2.34 ± 1.95 mg/dL. These values were increased by ≥25% in 5 patients. The mean sCr levels when symptoms resolved was 1.54 ± 0.67 mg/dL, and no significant difference was seen before, during, or after disease onset (P = 0.069). Two patients were diagnosed with HAdV viremia and 1 with acute tubulointerstitial nephritis revealed on biopsy. In addition to a reduction in immunosuppressant dosage, 2 patients received gammaglobulins and 5 received ganciclovir.
Conclusion
Symptoms of all patients were alleviated, although some patients developed nephritis or viremia. Hence, the possibility of exacerbation should always be considered. Adequate follow‐up observation should be conducted, and diligent and aggressive therapeutic intervention is required to prevent the condition from worsening.
The effectiveness of everolimus (EVR) for ABO-incompatible (ABOi) kidney transplantation is unknown. We evaluated outcomes of conversion from steroid to EVR in ABOi kidney transplant recipients.
We ...performed a retrospective observational cohort study of 33 de novo consecutive adult ABOi living donor kidney transplant recipients. Desensitization was performed using 0 to 4 sessions of plasmapheresis and 1 to 2 doses of 100 mg rituximab according to the anti-A/B antibody titer. ABOi recipients were administered a combination of tacrolimus, mycophenolate mofetil, and methylprednisolone. Diabetic patients were converted from methylprednisolone to EVR at 1 to 15 months post-transplantation to prevent diabetes progression. Graft outcomes, hemoglobin A1c (HbA1c) levels, and cytomegalovirus infection rates were compared between the EVR (n = 11) and steroid (n = 22) groups.
Mean postoperative duration was 814 and 727 days in the EVR and steroid groups, respectively (P = .65). Between the 2 groups, graft survival rate (100% vs 95.5%, P > .99), acute rejection rate (9.1% vs 18.2%, P = .64), and serum creatinine levels (1.46 mg/dL vs 1.68 mg/dL, P = .66) were comparable. Although HbA1c levels were elevated in the steroid group (5.47%, 5.87%; P = .003), no significant deterioration was observed in the EVR group without additional insulin administration (6.10%, 6.47%; P = .21). Cytomegalovirus infection rate was significantly lower in the EVR group than in the steroid group (18.2% vs 63.6%, P = .026).
Conversion from steroid to EVR in ABOi kidney transplant recipients maintained excellent graft outcomes and avoided diabetes progression and cytomegalovirus infection.
•We aimed to improve complications in ABO-incompatible kidney transplant recipients.•We evaluated outcomes of a new protocol using conversion from steroid to everolimus.•Steroid withdrawal using everolimus could avoid diabetes progression.•Steroid withdrawal using everolimus could suppress CMV infection.•Everolimus administration may contribute to improved patient and graft outcomes.
Desensitization for ABO-incompatible (ABOi) kidney transplantation mainly comprises removal of antibodies with the use of apheresis and suppression of antibody (Ab) production with the use of ...rituximab. This study aimed to estimate the outcomes of ABOi kidney transplantation with the use of an Ab removal–free protocol to avoid complications associated with apheresis.
A total of 32 de novo consecutive adults who underwent ABOi living-donor kidney transplantation were retrospectively evaluated. Our protocol for ABOi recipients was stratified and fixed according to the anti-A/B Ab titer at baseline before desensitization. Desensitization was performed before transplantation with 0–4 sessions of plasmapheresis or double-filtration plasmapheresis and 1–2 administrations of rituximab at 100 mg/body. Graft outcomes, anti-A/B Ab titer, and plasma fibrinogen level were compared between the Ab removal (n = 21) and Ab removal–free (n = 11) groups.
Between the Ab removal and Ab removal–free groups, the graft loss rate (4.8% vs 0.0%; P = 1.0), acute rejection rate (19.0% vs 0.0%; P = .14), and serum creatinine level (1.74 vs 1.40 mg/dL, P = .53) were similar. The anti-A/B Ab titer was maintained at a low level until postoperative month 12 in both groups. The plasma fibrinogen level on the operation day was significantly lower in the Ab removal group than in the Ab removal–free group (163.4 vs 250.2 mg/dL; P < .001).
Desensitization with the use of an antibody removal–free protocol for ABOi kidney transplant recipients with a low anti-A/B Ab titer can maintain excellent graft outcomes and avoid postoperative bleeding risk.
•We estimated outcomes of ABO-incompatible kidney transplantation without apheresis.•ABO-incompatible recipients with low titer received an antibody removal–free protocol.•Antibody removal–free protocol can achieve excellent graft outcomes.•Antibody removal–free protocol can help to avoid postoperative bleeding risk.•Antibody removal–free protocol can reduce the use of blood products.
Adverse events due to conventional immunosuppressive therapy decrease both graft and patient survival. We aimed to establish a new protocol using everolimus (EVR) to safely minimize conventional ...immunosuppressants in maintenance kidney transplant recipients.
A total of 86 consecutive kidney transplant recipients with no complications were maintained with triple-drug combination therapy (conventional group). In case of complications, the administration of very low-dose tacrolimus (C0: 5.0 to <3.0 ng/mL), reduced mycophenolate mofetil (1000–1500 to 500–1000 mg), and EVR (C0: 3.0–5.0 ng/mL) and methylprednisolone withdrawal (2–4 to 0 mg) were simultaneously conducted (EVR group). Graft survival and acute rejection rate were compared between groups. Within the EVR group, the dose of conventional immunosuppressants was compared between pre- and post-EVR administration. Renal function was evaluated 1 year post-EVR administration.
All grafts survived in the conventional (n = 50) and EVR (n = 36) groups, and biopsy-proven acute rejection rate exhibited no significant difference between these groups (12% vs 17%; P = .55). Furthermore, no acute rejection occurred post-EVR administration. In the EVR group, all immunosuppressants significantly decreased post-EVR administration compared with those pre-EVR administration (P < .01), and serum creatinine significantly improved at postoperative year 1 (P = .031).
EVR administration enables very low-dose tacrolimus administration, helps reduce mycophenolate mofetil and steroid withdrawal, and ameliorates renal function in maintenance kidney transplant recipients experiencing complications associated with conventional immunosuppressive therapy.
•Everolimus minimizes conventional immunosuppressants in kidney transplant recipients.•Everolimus improves renal function in kidney transplant recipients with complications.•Everolimus administration may contribute to improved patient and graft survival.
Abstract Objectives To evaluate the selection criteria for kidney laterality and the usefulness of pretransplant intervention in living donor nephrectomy. Methods We compared conventional and revised ...criteria. The conventional criteria were that left kidneys were chosen in preference and provided the kidney with the fewest structural abnormalities and lowest functional decline and that most renal arteries remained in the donor. From April 2013, we allowed the use of left kidneys with double renal arteries. Patient characteristics and surgical outcomes were retrospectively compared between right and left retroperitoneoscopic living donor nephrectomies. Results We compared data for 30 right kidney and 222 left kidney nephrectomies. Right kidneys were selected because of multiple renal arteries (n = 18), structural abnormalities (n = 10) of the left kidney, or functional decline (n = 2) of the right kidney. Right retroperitoneoscopic nephrectomies were associated with significantly longer operating times (267 minutes vs 241 minutes), larger blood losses (240 g vs 55 g), and higher open conversion rates (10% vs 0.9%). Pretransplant intervention was necessary for structural abnormalities in right kidneys, but the amended selection criteria resulted in fewer right nephrectomies. Pretransplant intervention was still necessary by ex vivo arterial anastomosis for multiple left renal arteries, which increased the total ischemia time (94 minutes vs 64 minutes); however, post-transplantation renal function was not significantly different. Conclusions Pretransplant intervention was beneficial both for repairing structural abnormalities and for reducing the difficulties of retroperitoneoscopic living donor nephrectomy.
Abstract Background Klotho is a single-pass transmembrane protein predominantly expressed in the kidneys. The soluble form of klotho has been shown to participate in various pathophysiological ...activities. However, information regarding the kinetics of soluble klotho remains limited. We herein assessed serial changes in the amounts of 24-hour urinary excreted soluble klotho among renal transplant recipients and concomitant living donors before and after transplantation. Methods A total of 15 recipients and donors were included in the current study, and the amounts of urinary soluble klotho were quantified using a sandwich enzyme-linked immunosorbent assay. Results Urine samples were available in 6 of the 15 recipients prior to the procedure. The amounts of urinary klotho in these 6 recipients and overall living donors at the baseline were 58.6 ng/day (IR: 29.3–142) and 698.8 ng/day (IR: 62.3–1619.5), respectively. Those in the recipients on postoperative day 2 (median 522.3 ng/day; IR 337.1–1168.5, P < .05) and day 5 (median 723.2 ng/day; IR 254.7–1238.6, P < .05) were significantly higher than the baseline values. Among the living donors, only a transient increase was observed in the amounts of urinary klotho on postoperative day 2. Conclusion The current data regarding the urinary soluble klotho in recipients support the hypothesis that the kidney is a major source of urinary soluble klotho among the numerous components of the urinary tract. In living donors, the complex nature of events associated with acute reductions in the renal mass may modulate the release of soluble klotho from the kidneys into the urine.
Abstract Introduction In Japan, ABO-incompatible (ABO-IC) living kidney transplantation (LKT) has been performed among more than 2000 patients between 1989 and 2010 seeking to compensate for the ...shortage of donor organs. In addition, many patients lack a genetically living related donor (LRD); therefore, volunteer spouses (unrelated, LURD) have been considered since about 1990. Patients and methods We performed 112 LKT between April 2003 and March 2011, including 44 (39%) spousal and two other LURD. The other 66 cases received LRD kidneys. We divided patients into two groups: 44 patients (group 1) received a kidney from a spouse (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. For ABO-IC LKT, plasmapheresis was performed to remove anti-AB antibodies prior to LKT. Splenectomy was performed at the time of or before LKT. Since March 2010, rituximab administration was performed before transplantation instead of splenectomy. Results Death-censored graft survival rates were 97.7% in group 1 and 98.5% in group 2, respectively. The incidences of acute rejection episodes 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. Conclusions Our results demonstrated that spousal LKT (LURD) was equivalent to LRD. In response to the shortage of deceased donors and genetically LRD, LKT between married couples or from ABO-IC donors will spread in Japan.
Abstract Introduction 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. Patients and methods 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. Results 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. Conclusions 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.
