Protocol biopsy of kidney allograft enables early detection of BK virus nephropathy to preserve kidney allograft function.

BACKGROUND: The Banff Working Group has updated the histological classification of BK virus nephropathy (BKVN), highlighting the importance of early detection. However, an early detection strategy for BKVN using biopsy has not yet been established. Our investigation aimed to assess the efficacy of protocol biopsy for the diagnosis of BKVN. METHODS: We performed a retrospective cohort study of 314 patients who had undergone kidney transplantation between 2006 and 2021. Kidney allograft biopsies were performed as part of a protocol biopsy at 3 months and 1 year post-transplantation. Following the diagnosis of BKVN, the immunosuppressant dose was reduced. RESULTS: Twelve patients (3.8%) were diagnosed with BKVN by biopsy. Most diagnoses are established during the early stages of BKVN (polyomavirus nephropathy class 1 in six, class 2 in five, and class 3 in one). Following the reduction in immunosuppressant dose, kidney allograft function did not deteriorate in any patients. Additionally, test for BK virus DNA in the blood was negative. All but one patient demonstrated histological resolution of BKVN, and the other had a very slight positivity for the simian virus 40 large T antigen. The median follow-up time after BKVN diagnosis was 6 years. One patient developed de novo donor-specific antibody and subclinical acute antibody-mediated rejection that was successfully cured. CONCLUSIONS: Our analysis indicates that protocol biopsy may enable the early detection of BKVN, resulting in the preservation of kidney function.

Neutralizing antibody responses and cellular responses against SARS-CoV-2 Omicron subvariants after mRNA SARS-CoV-2 vaccination in kidney transplant recipients.

Although the mRNA SARS-CoV-2 vaccine has improved the mortality rate in the general population, its efficacy against rapidly mutating virus strains, especially in kidney transplant recipients, remains unclear. We examined the anti-SARS-CoV-2 spike protein IgG antibody and neutralizing antibody titers and cellular immunity against B.1.1, BA.1, and BA.5 antigens in 73 uninfected kidney recipients and 16 uninfected healthy controls who received three doses of an mRNA SARS-CoV-2 vaccine. The IgG antibody titers were significantly lower in recipients than in healthy controls. Similarly, neutralizing antibody titers against three viral variants were significantly lower in recipients. When the virus was mutated, the neutralizing antibody titers decreased significantly in both groups. In cellular immunity analysis, the number of spike-specific CD8 + non-naïve T cells against three variants significantly decreased in recipients. Conversely, the frequency of spike-specific Th2 CD4 + T-cells in recipients was higher than that in healthy controls. Nineteen recipients and six healthy controls also received a bivalent omicron-containing booster vaccine, leading to increase IgG and neutralizing antibody titers in both groups. After that, eleven recipients and five healthy controls received XBB.1.5 monovalent vaccines, increasing the neutralizing antibody titers against not only XBB.1.5, but also EG.5.1 and BA.2.86 antigens in kidney recipients. Although kidney recipients did not gain sufficient immunity against Omicron BA.5 with the third dose of vaccine, humoral response against mutant SARS-CoV-2 lineages significantly increased after bivalent Omicron-containing booster vaccine and the XBB.1.5 monovalent vaccine. Therefore, it is important for kidney recipients to continue to administer updated vaccines.

Longitudinal mortality risks and kidney functional outcomes in Japanese living kidney donors.

OBJECTIVES: Previous studies suggested that living kidney donors do not have a higher risk of death or kidney failure than the general population. However, living kidney donor risk is controversial. Furthermore, only a few studies have evaluated long-term kidney function after kidney donation. METHODS: This study evaluated Japanese kidney donor' long-term outcomes, including mortality and kidney function. From 1965 to 2015, 230 donors (76 males, 154 females, and a median age of 54) were enrolled in this study. The median observation period was 11.0 (range, 0.3-41.0) years. RESULTS: In total, 215 donors were still alive, and 15 had died. Causes of death included malignancies, cardiovascular disease, pneumonia, suicide, gastrointestinal bleeding, and kidney failure. Actual donor survival rates at 10, 20, and 30 years were 95.3%, 90.7%, and 80.9%, respectively. These values were comparable to age- and gender-matched expected survival. Long-term kidney function after donation was evaluated in 211 donors with serum creatinine data. Two donors developed kidney failure 24 and 26 years post-donation, respectively. The percentage of donors whose estimated glomerular filtration rate (eGFR) remained ≥45 mL/min/1.73 m2 at 10, 20, and 30 years after donation were 84.2%, 73.0%, and 63.9%, respectively. Survival rates of donors with eGFR <45 mL/min/1.73 m2 were comparable to those in persons with eGFR >45 mL/min/1.73 m2. CONCLUSION: Our findings revealed that kidney donors did not have a higher long-term risk of death than the general population. Although some donors showed decreased kidney function after donation, kidney function did not impact their survival.

Prophylactic bilateral nephrectomy and preemptive kidney transplantation for Denys-Drash syndrome prior to development of kidney failure.

BACKGROUND  : Nephropathy in Denys-Drash syndrome (DDS) develops within a few months of birth, often progressing to kidney failure. Wilms tumors also develop at an early age with a high rate of incidence. When a patient does not have Wilms tumor but develops kidney failure, prophylactic bilateral nephrectomy, and kidney transplantation (KTX) is an optimal approach owing to the high risk of Wilms tumor development. In the case presented here, prophylactic bilateral nephrectomy and KTX were performed in a patient who had not developed Wilms tumor or kidney failure. However, the treatment option is controversial as it involves the removal of a tumor-free kidney and performing KTX in the absence of kidney failure. CASE DIAGNOSIS/TREATMENT: We present the case of a 7-year-old boy, born at 38 weeks gestation. Examinations at the age of 1 year revealed severe proteinuria and abnormal internal and external genitalia. Genetic testing identified a missense mutation in exon 9 of the WT1 gene, leading to the diagnosis of DDS. At the age of 6 years, he had not yet developed Wilms tumor and had grown to a size that allowed him to safely undergo a KTX. His kidney function was slowly deteriorating (chronic kidney disease (CKD) stage 3), but he had not yet developed kidney failure. Two treatment options were considered for this patient: observation until the development of kidney failure or prophylactic bilateral nephrectomy with KTX to avoid Wilms tumor development. After a detailed explanation of options to the patient and family, they decided to proceed with prophylactic bilateral nephrectomy and KTX. At the latest follow-up 4 months after KTX, the patient's kidney functioned well without proteinuria. CONCLUSION: We performed prophylactic bilateral nephrectomy with KTX on a DDS patient who had not developed kidney failure or Wilms tumor by the age of 7 years. Although the risk of development of Wilms tumor in such a patient is unclear, this treatment may be an optimal approach for patients who are physically able to undergo KTX, considering the potentially lethal nature of Wilms tumor in CKD patients.

Design and testing of a humanized porcine donor for xenotransplantation.

Recent human decedent model studies1,2 and compassionate xenograft use3 have explored the promise of porcine organs for human transplantation. To proceed to human studies, a clinically ready porcine donor must be engineered and its xenograft successfully tested in nonhuman primates. Here we describe the design, creation and long-term life-supporting function of kidney grafts from a genetically engineered porcine donor transplanted into a cynomolgus monkey model. The porcine donor was engineered to carry 69 genomic edits, eliminating glycan antigens, overexpressing human transgenes and inactivating porcine endogenous retroviruses. In vitro functional analyses showed that the edited kidney endothelial cells modulated inflammation to an extent that was indistinguishable from that of human endothelial cells, suggesting that these edited cells acquired a high level of human immune compatibility. When transplanted into cynomolgus monkeys, the kidneys with three glycan antigen knockouts alone experienced poor graft survival, whereas those with glycan antigen knockouts and human transgene expression demonstrated significantly longer survival time, suggesting the benefit of human transgene expression in vivo. These results show that preclinical studies of renal xenotransplantation could be successfully conducted in nonhuman primates and bring us closer to clinical trials of genetically engineered porcine renal grafts.

Clinical and molecular correlation defines activity of physiological pathways in life-sustaining kidney xenotransplantation.

Porcine kidney xenotransplantation is accelerating towards clinical translation. However, despite the demonstrated ability of porcine kidneys to remove metabolic waste products, questions remain about their ability to faithfully recapitulate renal endocrine functions after transplantation. Here we analyze xenograft growth and function of two kidney dependent endocrine pathways in seventeen cynomolgus macaques after kidney xenotransplantation from gene edited Yucatan minipigs. Xenograft growth, the renin-angiotensinogen aldosterone-system, and the calcium-vitamin D-parathyroid hormone axis are assessed using clinical chemistries data, renin activity and beta-C-terminal-telopeptide assays, kidney graft RNA-sequencing and serial ultrasonography. We demonstrate that xenografts transplanted from minipigs show only modest growth and do not substantially contribute to recipient RAAS pathway activity. However, parathyroid hormone-independent hypercalcemia and hypophosphatemia are observed, suggesting a need for close monitoring and timely intervention during human testing. Further study of these phenotypes is warranted in designing prospective clinical trials.

Analysis of T-cell alloantigen response via a direct pathway in kidney transplant recipients with donor-specific antibodies.

Donor-specific antibodies (DSAs) are the main cause of graft loss over time. The direct pathway of alloantigen recognition is important in the pathogenesis of acute rejection. Recent studies have suggested that the direct pathway also contributes to the pathogenesis of chronic injury. Nevertheless, there are no reports on T-cell alloantigen response via the direct pathway in kidney recipients with DSAs. We analyzed the T-cell alloantigen response via the direct pathway in kidney recipients with DSAs (DSA+) or without DSAs (DSA-). A mixed lymphocyte reaction assay was implemented to assess the direct pathway response. DSA+ patients showed significantly higher CD8+ and CD4+ T cell responses to donor cells than DSA- patients. Furthermore, proliferating CD4+ T cells showed a marked increase in Th1 and Th17 responses in DSA+ patients than in DSA- patients. In a comparison between anti-donor and third-party responses, the anti-donor CD8+ and CD4+ T cell response was significantly lower than the anti-third-party response. In contrast, the donor-specific hyporesponsiveness was absent in DSA+ patients. Our study demonstrated that DSA+ recipients have a greater potential for developing immune responses against the donor tissues via the direct alloantigen recognition pathway. These data contribute to an understanding of DSAs pathogenicity during kidney transplantation.

Use of Mixed Lymphocyte Reaction Assay to Evaluate Immune Tolerance before Kidney Transplantation with an Immunosuppression-Free Protocol following Hematopoietic Stem Cell Transplantation from the Same Donor.

Several cases of kidney transplantation after hematopoietic stem cell transplantation (HSCT) from the same donor for end-stage renal disease have been reported. In those cases, immunosuppressive drugs were discontinued since immune tolerance was supposed to be induced. Theoretically, the recipient's immune system recognizes the kidney allograft as its own tissue with the same human leukocyte antigen (HLA) profile, and the kidney allograft will not be rejected, even without the use of immunosuppressive agents. However, almost all recipients receive immunosuppressants in the early stages after kidney transplantation owing to concerns of acute rejection. Here, we report a successful case of post-HSCT kidney transplantation without the use of immunosuppressive drugs, in which a mixed lymphocyte reaction (MLR) assay was used to evaluate immune tolerance before kidney transplantation. The patient was a 25-year-old woman. Five years prior, she developed acute myeloid leukemia and underwent HLA-half-matched peripheral blood stem cell transplantation. Thereafter, she was in remission of the acute myeloid leukemia, but 1 year later, she developed renal graft-versus-host disease. Subsequently, the patient's renal function gradually deteriorated to end-stage renal failure, and she underwent kidney transplantation with the previous stem cell donor: her mother. HLA typing of donor and recipient showed a complete chimerism in the peripheral blood. The pretransplantation complement-dependent cytotoxic crossmatch and flow cytometric T-cell crossmatch results were both negative, and HLA antibody measurements were all negative. The MLR assay revealed no T-lymphocyte reaction to the donor; therefore, immunosuppressants were not used. Two years after transplantation, the patient's serum creatinine concentration was around 0.8 mg/dL (down from 4 mg/dL before transplantation). No abnormalities were observed in a renal biopsy performed after 3 months. Our study, along with others, indicates that immune tolerance to a donor develops in post-HSCT kidney transplantation from the same donor.

Long-Term Results in Recipients of Late Conversion to a Calcineurin Inhibitor-Free Regimen with Everolimus After Kidney Transplantation.

BACKGROUND: Conversion to a calcineurin inhibitor (CNI)-free regimen in cases of CNI nephrotoxicity (CNIT) is a strategy to improve the long-term outcomes of kidney transplantation. However, the long-term results of late conversion to a CNI-free regimen using everolimus (EVR) remain uncertain. METHODS: Nine kidney transplant recipients with biopsy-confirmed CNIT were enrolled. The median time of CNIT diagnosis was 9.0 years. All recipients underwent a conversion from CNI to EVR. We evaluated the clinical outcomes, development of donor-specific antibody (DSA), the incidence of rejection, alternative arteriolar hyalinosis (aah) scores, renal function changes, and T cell responses by mixed lymphocyte reaction (MLR) assay after conversion. RESULTS: The median follow-up after conversion was 5.4 years. Currently, 7 of 9 recipients have received a CNI-free regimen for 1.6 to 9.5 years. In the other 2 recipients, one experienced graft loss due to CNIT 3.8 years after conversion, and the other had to resume CNI due to acute T cell-mediated rejection (ATMR) a year after conversion. None of the recipients developed DSA. No rejection was observed in the kidney allograft histology except for the ATMR case. Moreover, improvement in aah scores was noted in one patient. Furthermore, serum creatinine levels were stable in recipients without proteinuria before the EVR add-on. In the MLR analysis, low responses against donors were observed in stable patients. CONCLUSIONS: Late conversion to an EVR-based regimen without CNI may be a promising therapeutic strategy against CNIT, particularly for recipients without proteinuria before the EVR add-on.

TNX-1500, a crystallizable fragment-modified anti-CD154 antibody, prolongs nonhuman primate renal allograft survival.

The blockade of the CD154-CD40 pathway with anti-CD154 monoclonal antibody has been a promising immunomodulatory approach to prevent allograft rejection. However, clinical trials of immunoglobulin G1 antibodies targeting this pathway revealed thrombogenic properties, which were subsequently shown to be mediated by crystallizable fragment (Fc)-gamma receptor IIa-dependent platelet activation. To prevent thromboembolic complications, an immunoglobulin G4 anti-CD154 monoclonal antibody, TNX-1500, which retains the fragment antigen binding region of ruplizumab (humanized 5c8, BG9588), was modified by protein engineering to decrease Fc binding to Fc-gamma receptor IIa while retaining certain other effector functions and pharmacokinetics comparable with natural antibodies. Here, we report that TNX-1500 treatment is not associated with platelet activation in vitro and consistently inhibits kidney allograft rejection in vivo without clinical or histologic evidence of prothrombotic phenomena. We conclude that TNX-1500 retains efficacy similar to that of 5c8 to prevent kidney allograft rejection while avoiding previously identified pathway-associated thromboembolic complications.

Selective Bcl-2 inhibition promotes hematopoietic chimerism and allograft tolerance without myelosuppression in nonhuman primates.

Hematopoietic stem cell transplantation (HSCT) has many potential applications beyond current standard indications, including treatment of autoimmune disease, gene therapy, and transplant tolerance induction. However, severe myelosuppression and other toxicities after myeloablative conditioning regimens have hampered wider clinical use. To achieve donor hematopoietic stem cell (HSC) engraftment, it appears essential to establish niches for the donor HSCs by depleting the host HSCs. To date, this has been achievable only by nonselective treatments such as irradiation or chemotherapeutic drugs. An approach that is capable of more selectively depleting host HSCs is needed to widen the clinical application of HSCT. Here, we show in a clinically relevant nonhuman primate model that selective inhibition of B cell lymphoma 2 (Bcl-2) promoted hematopoietic chimerism and renal allograft tolerance after partial deletion of HSCs and effective peripheral lymphocyte deletion while preserving myeloid cells and regulatory T cells. Although Bcl-2 inhibition alone was insufficient to induce hematopoietic chimerism, the addition of a Bcl-2 inhibitor resulted in promotion of hematopoietic chimerism and renal allograft tolerance despite using only half of the dose of total body irradiation previously required. Selective inhibition of Bcl-2 is therefore a promising approach to induce hematopoietic chimerism without myelosuppression and has the potential to render HSCT more feasible for a variety of clinical indications.

A multicenter, phase II study of full-dose THP-COP therapy for elderly patients with newly diagnosed, advanced-stage, aggressive non-Hodgkin lymphoma.

The cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) regimen, containing doxorubicin (DXR), which is a key drug for aggressive non-Hodgkin lymphoma (NHL), is a standard chemotherapeutic regimen; however, its administration in elderly patients is often intolerable. Pirarubicin (tetrahydropyranyl adriamycin [THP]) is an anthracycline developed in Japan. We have conducted a phase II trial of a full-dose THP-COP (modified CHOP regimen with DXR replaced by THP) regimen for elderly patients with newly diagnosed, advanced-stage, aggressive NHL. Patients aged 70-79 years old with previously untreated NHL according to the Working Formulation (D through H and J), disease stage I with a bulky mass or stage II-IV, and performance status of 0-1 were eligible. The THP-COP regimen, which consisted of 750-mg/m2 cyclophosphamide, 50-mg/m2 THP, 1.4-mg/m2 vincristine (capped at 2.0 mg) on day 1, and 100-mg prednisolone daily on days 1 to 5, was delivered every 3 weeks for 6 cycles. The primary endpoint was complete response (CR) rate. Twenty-nine patients were enrolled in the study. The CR rate was 65.5% (95% confidence interval, 45.7-82.1%). The 3-year failure-free and overall survival rates were 54.1% and 53.9%, respectively. The most frequent observed grade 3 or 4 toxicity was neutropenia, which occurred in 80% of the patients. Grade 3 cardiac dysfunction was observed in one patient. The full-dose THP-COP regimen exhibited similar efficacy and safety, and a tendency for less cardiac toxicity, when compared with the standard CHOP regimen in elderly Japanese patients with newly diagnosed, advanced-stage, aggressive NHL.

Clinical trials for renal allograft tolerance induction through combined hematopoietic stem cell transplantation: A narrative review.

During the last four decades, development of effective immunosuppressants has significantly improved short-term results of organ transplantation. However, long-term results have not been satisfactory due to chronic rejection or complications caused by immunosuppressive drugs. Therefore, induction of immunological tolerance of the transplanted organ is considered essential to improve the long-term results. Despite numerous tolerance strategies that have been successful in murine models, inducing hematopoietic chimerism through donor hematopoietic stem cell transplantation is the only method that reproducibly induces kidney allograft tolerance in nonhuman primates or humans. Combining kidney and hematopoietic stem cell transplantation to achieve allograft tolerance has now been attempted with different chimerism strategies. This review summarizes the status of current clinical trials on the induction of allograft tolerance. We also summarize recent studies to extend the chimerism approach to deceased donor transplant recipients.

Vesicoureteral reflux treatment following kidney transplantation potentially prevents graft function deterioration and allows long-term graft survival.

OBJECTIVES: The impact of vesicoureteral reflux post-kidney transplantation on graft survival remains unclear, and guidelines on appropriate vesicoureteral reflux management post-kidney transplantation are lacking. For this reason, we conducted a retrospective study on the impact of vesicoureteral reflux and its treatment on graft survival. METHODS: We evaluated 347 consecutive kidney transplantation recipients, who also underwent a ureteroneocystostomy, between 1996 and 2012. RESULTS: Vesicoureteral reflux was diagnosed in 55 cases (15.9%), with a median post-kidney transplantation duration of 50 months (range 0-172 months). Among these, 22 were monitored, 17 underwent transurethral collagen injections, and 16 received a ureteroneocystostomy. The 10-year graft survival rate was significantly lower in recipients with vesicoureteral reflux (68.9%) than in those without vesicoureteral reflux (84.4%) (P = 0.0165). Moreover, among the vesicoureteral reflux recipients, the 10-year graft survival rate was significantly higher in those whose vesicoureteral reflux was cured (80.1%) than in those whose vesicoureteral reflux persisted (53.6%) (P = 0.0062). Multivariate analysis showed that vesicoureteral reflux was significantly associated with both overall and death-censored graft loss (odds ratio 3.737 and 3.685; P = 0.0015 and P = 0.0052, respectively). Lastly, the incidence of interstitial fibrosis and tubular atrophy was higher in recipients with vesicoureteral reflux than in those without vesicoureteral reflux (P = 0.0009). CONCLUSIONS: Post-kidney transplantation vesicoureteral reflux has a negative impact on long-term graft survival, and that treatment prevents graft deterioration. From the perspective of maintaining long-term graft function in kidney recipients, vesicoureteral reflux may be one of the most important complications to be addressed.

Kidney transplantation from triple-knockout pigs expressing multiple human proteins in cynomolgus macaques.

Porcine cells devoid of three major carbohydrate xenoantigens, αGal, Neu5GC, and SDa (TKO) exhibit markedly reduced binding of human natural antibodies. Therefore, it is anticipated that TKO pigs will be better donors for human xenotransplantation. However, previous studies on TKO pigs using old world monkeys (OWMs) have been disappointing because of higher anti-TKO pig antibodies in OWMs than humans. Here, we show that long-term survival of renal xenografts from TKO pigs that express additional human transgenes (hTGs) can be achieved in cynomolgus monkeys. Kidney xenografts from TKO-hTG pigs were transplanted into eight cynomolgus recipients without pre-screening for low anti-pig antibody titers. Two recipients of TKO-hTG xenografts with low expression of human complement regulatory proteins (CRPs) (TKO-A) survived for 2 and 61 days, whereas six recipients of TKO-hTG xenografts with high CRP expression (TKO-B) survived for 15, 20, 71, 135, 265, and 316 days. Prolonged CD4+ T cell depletion and low anti-pig antibody titers, which were previously reported important for long-term survival of αGal knock-out (GTKO) xenografts, were not always required for long-term survival of TKO-hTG renal xenografts. This study indicates that OWMs such as cynomolgus monkeys can be used as a relevant model for clinical application of xenotransplantation using TKO pigs.

Phase I, multicenter, dose-escalation study of avadomide in adult Japanese patients with advanced malignancies.

Non-Hodgkin lymphoma (NHL) treated with chemoimmunotherapy has limited efficacy in some patients, resulting in relapsed or refractory disease. Avadomide (CC-122) is a novel cereblon-binding agent that exhibits antilymphoma and immune-modulation activities with a biological profile distinct from similar agents, such as lenalidomide. This phase I multicenter study evaluated avadomide in Japanese patients with advanced solid tumors or NHL. Fourteen patients with NHL and one with a solid tumor (esophageal carcinoma), were enrolled in four dose-escalation cohorts using a 3 + 3 design. Primary endpoints included safety, dose-limiting toxicities (DLT), maximum-tolerated dose and/or recommended phase II dose (RP2D), and pharmacokinetics. Secondary endpoints included overall response rate (ORR) and duration of response. One patient with NHL experienced DLT, which included face edema, pharyngeal edema, and tumor flare (all grade 1) that led to a dose reduction. Eleven patients had grade ≥3 treatment-emergent adverse events, most frequently decreased neutrophil count (33%) and decreased lymphocyte count (20%). The ORR in patients with NHL (n = 13) was 54%, including four complete and three partial responses. The best response for the solid tumor patient was progressive disease. Avadomide dose intensity was consistent across cohorts, and the 3-mg dose given five consecutive days/week was established as the RP2D. This phase I study identified a tolerable dose of avadomide, with an acceptable toxicity profile and clinically meaningful efficacy in Japanese patients with previously treated NHL.

The 31-nucleotide Y4-RNA fragment in plasma is a potential novel biomarker.

The 31- and 32-nt 5'-fragment of Y4-RNA (Y4RNAfr) exists abundantly in human peripheral blood plasma. Although physiological roles of the plasma Y4RNAfr are not well established, its potential utility as a diagnostic/prognostic marker for acute coronary syndrome was suggested. In this paper, to establish a normal range of the Y4RNAfr level in plasma, we measured plasma Y4RNAfr levels of 40 healthy persons using the method we have developed, and compared them with other blood test data. From the obtained data, we tentatively regarded <0.1 fmol/ng as normal for the Y4RNAfr level in peripheral blood plasma. And the white blood cell count (WBC) and the C-reactive protein (CRP) level showed moderate positive correlations with the Y4RNAfr level, suggesting that Y4RNAfr could be a potential novel inflammatory marker. We also measured the Y4RNAfr level in peripheral blood plasma from four multiple myeloma patients. The plasma Y4RNAfr level was abnormal in all four myeloma patients, and the levels for two patients were far beyond the normal level. The WBC for each patient was normal and the CRP levels for two patients were normal. These observations together suggest that a high level of Y4RNAfr in peripheral blood plasma and a normal WBC could be indicative of multiple myeloma.

A 2-mm Cutoff Value Is Reasonable and Feasible for Vascular Reconstruction in a Kidney Allograft With Multiple Arteries.

BACKGROUND: Multiple renal arteries are found in approximately 20% of living donor kidneys. We have been using an accessory artery cutoff diameter of 2 mm on preoperative computed tomography angiography to determine whether to sacrifice or reconstruct the artery. In this study, we assessed the validity and feasibility of this cutoff value. METHODS: Living related kidney recipients from 2005 to 2013 were enrolled in this retrospective study. The diameter of the accessory artery and adverse events were evaluated. The lost parenchymal volume (%) due to vascular obstruction or branch ligation was calculated by computed tomography volumetry. RESULTS: Among 128 kidney transplants, 30 donor kidneys had multiple arteries. Accessory arteries were reconstructed in 18 cases and intentionally ligated in 12 cases (mean diameter of accessory arteries, 3.10 [SD, 0.75] mm and 1.81 [SD, 0.28] mm, respectively). The mean estimated glomerular filtration rate at 1 or 12 months after transplant was not significantly different between the groups. Among reconstructed cases, 14 cases (77.8%) had good patency in the reconstructed arteries whereas the other 4 had vascular complications. The percentage of lost parenchymal volume due to ligation or occlusion of the reconstructed artery (calculated in 16 cases) was predictable with the following formula: lost volume (%) = 9.09 × diameter (mm) - 10.5 (P= .03, rs= 0.533 by Spearman rank correlation coefficient). This formula indicated that ligation of a 2-mm accessory artery leads to 7.68% loss of the renal parenchyma. CONCLUSIONS: Reconstruction using a cutoff diameter of 2 mm is worth attempting in terms of the success rate and graft function. Sacrifice of a 2-mm accessory artery leads to parenchymal loss of <8%.