Novel factors potentially initiating acute antibody-mediated rejection in pig kidney xenografts despite an efficient immunosuppressive regimen.

Antibody-mediated rejection (AMR) is a common cause of graft failure after pig-to-nonhuman primate organ transplantation, even when the graft is from a pig with multiple genetic modifications. The specific factors that initiate AMR are often uncertain. We report two cases of pig kidney transplantation into immunosuppressed baboons in which we identify novel factors associated with the initiation of AMR. In the first, membranous nephropathy was the initiating factor that was then associated with the apparent loss of the therapeutic anti-CD154 monoclonal antibody in the urine when severe proteinuria was present. This observation suggests that proteinuria may be associated with the loss of any therapeutic monoclonal antibody, for example, anti-CD154 or eculizumab, in the urine, resulting in xenograft rejection. In the second case, the sequence of events and histopathology tentatively suggested that pyelonephritis may have initiated acute-onset AMR. The association of a urinary infection with graft rejection has been well-documented in ABO-incompatible kidney allotransplantation based on the expression of an antigen on the invading microorganism shared with the kidney graft, generating an immune response to the graft. To our knowledge, these potential initiating factors of AMR in pig xenografts have not been highlighted previously.

Oral Function and the Oral Microbiome in the Elderly in the Kyotango Area.

INTRODUCTION: Prevention of tooth loss contributes to an extended life expectancy, namely longevity. Aging-related oral hypofunction, including tooth loss, markedly increases the risks of functional disorder and mortality. Dysbiosis of the oral microbiome has recently been associated with various diseases, such as liver cirrhosis, pancreatic cancer, colorectal cancer, and inflammatory bowel disease. Therefore, the relationship between the oral microbiome and systemic health has been attracting increasing attention. In the present study, we examined oral function and the oral microbiome in the elderly in a world-leading longevity area. MATERIALS AND METHODS: An oral examination, chewing ability/tongue-lip motor function/saliva tests, and a metagenomic analysis with a 16S rRNA gene-targeting next-generation sequencer were conducted on 78 subjects aged ≥80 years. Twenty-six healthy individuals aged between 20 and 39 years were also investigated as controls. The data obtained were statistically analyzed. The protocol of the present study was approved by the Ethics Review Board of our university (ERB-C-885). RESULTS: Chewing ability, tongue-lip motor function, and saliva volume were normal in elderly subjects with a current tooth number ≥20, but were significantly lower in those with a current tooth number <20. The oral microbiome in elderly subjects with a current tooth number ≥20 and young controls differed from that in elderly subjects with a current tooth number <20. CONCLUSION: Tooth number ≥20 in elderly subjects in the longevity area contributed to the maintenance of both oral function and the diversity of the oral microbiome.

De novo membranous nephropathy in a pig-to-baboon kidney xenograft: A new xenograft glomerulopathy.

De novo membranous nephropathy (dnMN) is an uncommon immune complex-mediated late complication of human kidney allografts that causes proteinuria. We report here the first case of dnMN in a pig-to-baboon kidney xenograft. The donor was a double knockout (GGTA1 and ß4GalNT1) genetically engineered pig with a knockout of the growth hormone receptor and addition of 6 human transgenes (hCD46, hCD55, hTBM, hEPCR, hHO1, and hCD47). The recipient developed proteinuria at 42 days posttransplant, which progressively rose to the nephrotic-range at 106 days, associated with an increase in serum antidonor IgG. Kidney biopsies showed antibody-mediated rejection (AMR) with C4d and thrombotic microangiopathy that eventually led to graft failure at 120 days. In addition to AMR, the xenograft had diffuse, global granular deposition of C4d and IgG along the glomerular basement membrane on days 111 and 120. Electron microscopy showed extensive amorphous subepithelial electron-dense deposits with intervening spikes along the glomerular basement membrane. These findings, in analogy to human renal allografts, are interpreted as dnMN in the xenograft superimposed on AMR. The target was not identified but is hypothesized to be a pig xenoantigen expressed on podocytes. Whether dnMN will be a significant problem in other longer-term xenokidneys remains to be determined.

Antibody-mediated rejection in xenotransplantation: Can it be prevented or reversed?

Antibody-mediated rejection (AMR) is the commonest cause of failure of a pig graft after transplantation into an immunosuppressed nonhuman primate (NHP). The incidence of AMR compared to acute cellular rejection is much higher in xenotransplantation (46% vs. 7%) than in allotransplantation (3% vs. 63%) in NHPs. Although AMR in an allograft can often be reversed, to our knowledge there is no report of its successful reversal in a pig xenograft. As there is less experience in preventing or reversing AMR in models of xenotransplantation, the results of studies in patients with allografts provide more information. These include (i) depletion or neutralization of serum anti-donor antibodies, (ii) inhibition of complement activation, (iii) therapies targeting B or plasma cells, and (iv) anti-inflammatory therapy. Depletion or neutralization of anti-pig antibody, for example, by plasmapheresis, is effective in depleting antibodies, but they recover within days. IgG-degrading enzymes do not deplete IgM. Despite the expression of human complement-regulatory proteins on the pig graft, inhibition of systemic complement activation may be necessary, particularly if AMR is to be reversed. Potential therapies include (i) inhibition of complement activation (e.g., by IVIg, C1 INH, or an anti-C5 antibody), but some complement inhibitors are not effective in NHPs, for example, eculizumab. Possible B cell-targeted therapies include (i) B cell depletion, (ii) plasma cell depletion, (iii) modulation of B cell activation, and (iv) enhancing the generation of regulatory B and/or T cells. Among anti-inflammatory agents, anti-IL6R mAb and TNF blockers are increasingly being tested in xenotransplantation models, but with no definitive evidence that they reverse AMR. Increasing attention should be directed toward testing combinations of the above therapies. We suggest that treatment with a systemic complement inhibitor is likely to be most effective, possibly combined with anti-inflammatory agents (if these are not already being administered). Ultimately, it may require further genetic engineering of the organ-source pig to resolve the problem entirely, for example, knockout or knockdown of SLA, and/or expression of PD-L1, HLA E, and/or HLA-G.

Dupilumab in a patient with severe asthma and glucocorticoid hypersensitivity: a case report.

Recently, several biologics have been approved for the treatment of severe asthma. Dupilumab, a biologic used to treat severe asthma, is a monoclonal antibody targeting interleukin-4 and interleukin-13. In the present case, inhaled corticosteroid-induced glucocorticoid hypersensitivity was suspected, and the administration of omalizumab and mepolizumab had no beneficial effects. Subsequently, we switched to dupilumab therapy, which produced better effectiveness. Therefore, when a biologic agent proves ineffective, changing to another suitable biologic agent should be considered.

EML4-ALK Gene Mutation Detected with New NGS Lung Cancer Panel CDx Using Sputum Cytology in a Case of Advanced NSCLC.

The detection of driver gene mutations has become essential for lung cancer; however, insufficient sample sizes make gene panel tests difficult to use. We previously reported that the lung cancer compact panel TM (LCCP) could detect EGFR and MET gene mutations with sputum cytology. To date, the detection of gene mutation using RNA from sputum samples is considered practically difficult. We report a case in which the EML4-ALK fusion gene was successfully detected from a sputum sample using the LCCP that was just released in Japan as a new next-generation sequencing lung cancer panel, CDx.

The case for the therapeutic use of mechanistic/mammalian target of rapamycin (mTOR) inhibitors in xenotransplantation.

The mechanistic/mammalian target of rapamycin (mTOR) is one of the systems that are necessary to maintain cell homeostasis, such as survival, proliferation, and differentiation. mTOR inhibitors (mTOR-Is) are utilized as immunosuppressants and anti-cancer drugs. In organ allotransplantation, current regimens infrequently include an mTOR-I, which are positioned more commonly as alternative immunosuppressants. In clinical allotransplantation, long-term efficacy has been established, but there is a significant incidence of adverse events, for example, inhibition of wound healing, buccal ulceration, anemia, hyperglycemia, dyslipidemia, and thrombocytopenia, some of which are dose-dependent. mTOR-Is have properties that may be especially beneficial in xenotransplantation. These include suppression of T cell proliferation, increases in the number of T regulatory cells, inhibition of pig graft growth, and anti-inflammatory, anti-viral, and anti-cancer effects. We here review the potential benefits and risks of mTOR-Is in xenotransplantation and suggest that the benefits exceed the adverse effects.

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

Blockade of the CD40/CD154 T cell costimulation pathway is a promising approach to supplement or replace current clinical immunosuppression in solid organ transplantation. We evaluated the tolerability and activity of a novel humanized anti-CD154 monoclonal antibody, TNX-1500 (TNX), in a nonhuman primate heterotopic cardiac allogeneic (allo) transplant model. TNX-1500 contains a rupluzimab fragment antigen-binding region and an immunoglobin G4 crystallizable fragment region engineered to reduce binding to the crystallizable fragment gamma receptor IIa and associated risks of thrombosis. Recipients were treated for 6 months with standard-dose TNX (sTNX) monotherapy, low-dose TNX monotherapy (loTNX), or loTNX with mycophenolate mofetil (MMF) (loTNX + MMF). Results were compared with historical data using chimeric humanized 5c8 monotherapy dosed as for loTNX but discontinued at 3 months. Median survival time was similar for humanized 5c8 and both loTNX groups, but significantly longer with sTNX (>265 days) than with loTNX (99 days) or loTNX + MMF (88 days) (P < 0.05 for both comparisons against sTNX). Standard-dose TNX prevented antidonor alloantibody elaboration, inhibited chronic rejection, and was associated with a significantly reduced effector T cells/regulatory T cells ratio relative to loTNX with MMF. No thrombotic complications were observed. This study demonstrated that TNX was well tolerated, prolongs allograft survival, and prevents alloantibody production and cardiac allograft vasculopathy in a stringent preclinical nonhuman primate heart allotransplant model.

Efficacy of combined transbronchial lung cryobiopsy and conventional forceps biopsy for lung malignancies: a prospective cohort study.

There are few prospective reports of transbronchial lung cryobiopsy (TBLC) for malignant tumors in combination with forceps biopsy. We investigated the clinical parameters in which TBLC is superior to forceps biopsy. This is a prospective cohort study to analyse the efficacy of TBLC for suspected malignancy. TBLC was performed after brushing cytology and forceps biopsy, and the diagnostic yield for TBLC, brushing cytology, and forceps biopsy were examined. Adverse events were defined as those requiring additional procedures. Next-generation sequencing (NGS) analysis was performed in each case of non-small cell lung cancer. Of the 100 patients, malignancy was confirmed in 94 cases. The diagnostic yield for TBLC/forceps biopsy/brushing cytology was 86/81/82% respectively, while the diagnostic yield for all procedures combined was 94%. There was no significant difference in the diagnostic yield between TBLC and forceps biopsy. When comparing the biopsy site, the diagnostic yield for TBLC at the lower lobe was significantly higher than forceps biopsy (P < 0.01). Endobronchial ultrasonography imaging using a guide-sheath did not significantly differ in the diagnostic yield of TBLC. The success rate of NGS for TBLC specimens was 100% (26 cases). Adverse events included two cases of severe bleeding. TBLC of peripheral lesions may improve the diagnostic yield when combined with forceps biopsy and brushing cytology. The diagnostic yield of TBLC was higher at the lower lobes. Furthermore, TBLC provided sufficient specimen quality for NGS.

Preliminary Results of NGS Gene Panel Test Using NSCLC Sputum Cytology and Therapeutic Effect Using Corresponding Molecular-Targeted Drugs.

As more molecular-targeted drugs for advanced non-small cell lung cancer are brought to market, batch tests for the identification of gene mutations are needed at initial diagnosis. However, since current gene panel tests require a sufficient amount of tissue sample, there are many instances where panel tests cannot be performed. Therefore, we have developed a highly sensitive next generation sequencing (NGS) panel test to facilitate cytological specimens. Herein, we describe three cases positive for epidermal growth factor receptor (EGFR) exon 19 deletion, MET exon 14 skipping, and KRAS G12A using NGS analysis from sputum. In each case, genetic information was consistent with companion diagnostic analysis obtained from tissue samples collected under bronchoscopy. In cases of EGFR and MET mutations, the corresponding tyrosine kinase inhibitors were highly effective. This is the first report to demonstrate that a novel panel test could detect gene mutations in sputum samples in clinical practice and compare the gene allele ratio with the sample directly collected from the lesion.

Two-year outcomes of low-exposure extended-release tacrolimus and mycophenolate mofetil regimen in de novo kidney transplantation: A multi-center randomized controlled trial.

BACKGROUND: Once-daily extended-release tacrolimus (TACER) is commonly administered following kidney transplantation (KTx); however, its optimal dosage remains unknown. METHODS: In this multi-center, randomized controlled trial, 62 living donor KTx recipients were assigned to either standard-exposure (SE; n = 32) or low-exposure (LE; n = 30) TACER (Graceptor®, Astellas Pharm Inc.) groups. All patients received basiliximab and mycophenolate mofetil (MMF). The primary outcomes were acute rejection, graft/patient survival, and the secondary outcomes were incidence of cytomegalovirus infection, and de novo donor-specific antibodies (dnDSA) production. RESULTS: The tacrolimus trough level and estimated area under the blood concentration-time curve (eAUC) were significantly higher in SE than in LE (SE vs. LE; 1 year: 5.0 ± 0.9 ng/ml and 206.9 ± 26.8 ng h/ml vs. 3.4 ± 1.0 ng/ml and 153.9 ± 26.4 ng h/ml; 2 years: 4.8 ± 1.0 ng/ml and 204.9 ± 30.1 ng h/ml vs. 3.8 ± 0.9 ng/ml and 164.4 ± 27.0 ng h/ml). In contrast, the dosage and eAUC of MMF did not differ between groups. Two-year graft and patient survival rates were 100% in both groups, and acute rejection rates were 0% and 10% in the SE and LE, respectively (p = 0.11). The mean estimated glomerular filtration rates did not differ between the groups. Cytomegalovirus infection was slightly lower in the LE (SE: 12.5% and LE: 6.7%, p = 0.37). In the LE, four cases of dnDSA were noted within 2 years of transplantation; no case was observed in the SE (p = 0.034). CONCLUSIONS: Although the LE TACER regimen showed similar rates of acute rejection, as well as graft and patient survival compared with SE after KTx, LE was significantly more associated with dnDSA. Further investigation of its long-term effect on graft survival is warranted. (University Hospital Medical Information Network Clinical Trials Registry ID: UMIN000033089).

A Prospective Comparative Study of Mastication Predominance and Masticatory Performance in Kennedy Class I Patients.

Mastication predominance in Kennedy class I (KC I) patients has not been well defined. This study aimed to investigate mastication predominance and masticatory performance in KC I patients, including the significance of remaining posterior teeth and removable partial-denture (RPD) treatment. KC I patients who had differences in the number of posterior teeth between left and right sides (D+) and KC I patients who had no differences (D-) were enrolled. Healthy dentate (HD) subjects were also registered as a positive control. Mastication predominance, defined by mastication predominance index (MPI; range 0-100%) calculated from electromyogram activities during voluntary chewing, and masticatory performance were evaluated at pre- and post-RPD treatment. Pre-MPI in KC I D+ was significantly higher than in HD. RPD treatment could significantly improve MPI and masticatory performance in both KC I groups. However, there were significant differences in masticatory performance between each KC I group and HD, regardless of RPD treatment. It was considered that the mastication predominance in KC I patients was affected by the difference in the number of remaining posterior teeth. RPD treatment could improve mastication predominance and masticatory performance in KC I patients, although the latter was not similar to HD group.

Long-term impact of baseline serum uric acid levels on living kidney donors: a retrospective study.

BACKGROUND: Preoperative characteristics of living kidney donors are commonly considered during donor selection and postoperative follow-up. However, the impact of preoperative uric acid (UA) levels is poorly documented. The aim of this study was to evaluate the association between preoperative serum UA levels and post-donation long-term events and renal function. METHODS: This was a single-center retrospective analysis of 183 living kidney donors. The donors were divided into high (≥5.5 mg/dl) and low (< 5.5 mg/dl) UA groups. We analyzed the relationship between preoperative UA levels and postoperative estimated glomerular filtration rate (eGFR), as well as adverse events (cardiovascular events and additional prescriptions for hypertension, gout, dyslipidemia, and diabetes mellitus), over 5 years after donation. RESULTS: In total, 44 donors experienced 52 adverse events over 5 years. The incidence of adverse events within 5 years was significantly higher in the high UA group than in the low UA group (50% vs. 24%, p = 0.003); this was true even after the exclusion of hyperuricemia-related events (p = 0.047). UA emerged as an independent risk factor for adverse events (p = 0.012). Donors with higher UA levels had lower eGFRs after donation, whereas body mass index, hemoglobin A1c, blood pressure, and low-density lipoprotein cholesterol did not have any impact on the eGFR. CONCLUSIONS: The findings suggest that preoperative UA levels should be considered during donor selection and postoperative follow-up.

HbA1c and Aortic Calcification Index as Noninvasive Predictors of Pre-Existing Histopathological Damages in Living Donor Kidney Transplantation.

We previously reported that allografts from living donors may have pre-existing histopathological damages, defined as the combination of interstitial fibrosis (ci), tubular atrophy (ct), and arteriolar hyalinosis (ah) scores of ≧1, according to the Banff classification. We examined preoperative characteristics to identify whether the degree of these damages was related to metabolic syndrome-related factors of donors. We conducted a single-center cross-sectional analysis including 183 living kidney donors. Donors were divided into two groups: chronic change (ci + ct ≧ 1 ∩ ah ≧ 1, n = 27) and control (n = 156). Preoperative characteristics, including age, sex, blood pressure, hemoglobin A1c (HbA1c), aortic calcification index (ACI), and psoas muscle index (PMI), were analyzed. Comparing the groups, the baseline estimated glomerular filtration rate was not significantly different; however, we observed a significant difference for ACI (p = 0.009). HbA1c (p = 0.016) and ACI (p = 0.006) were independent risk factors to predict pre-existing histopathological damages, whereas PMI was not. HbA1c correlated with ct scores (p = 0.035), and ACI correlated with ci (p = 0.005), ct (p = 0.021), and ah (p = 0.017). HbA1c and ACI may serve as preoperative markers for identifying pre-existing damages on the kidneys of living donors.

Optimizing Intraoperative Blood Pressure to Improve Outcomes in Living Donor Renal Transplantation.

BACKGROUND: Adequate renal perfusion at the time of unclamping is important because it has been known to affect outcomes in renal transplantation. Nevertheless, the ideal intraoperative systolic arterial pressure (SAP) has not been well defined. METHODS: We performed a retrospective analysis of 106 living donor renal transplants performed at our center from June 2010 to May 2019. We divided the cohort into 2 groups according to our center's goal SAP of ≥150 mm Hg: 57 patients had SAP ≥150 mm Hg and 49 patients had SAP <150 mm Hg. We analyzed pretransplant characteristics, intraoperative measurements, and postoperative laboratory values to validate our center's target SAP at the time of reperfusion. This study strictly complied with the Helsinki Congress and the Istanbul Declaration regarding donor sources. RESULTS: Patients with SAP ≥150 mm Hg had been on dialysis for a significantly shorter duration before transplant compared with those who had SAP <150 mm Hg. In the SAP ≥150 mm Hg group, urinary sodium excretion normalized earlier, and they had a significantly smaller stroke volume variation, higher cardiac output and cardiac index, earlier initial urination, and higher intraoperative urine output. There were no differences in intraoperative volume repletion, central venous pressure, or postoperative estimated glomerular filtration rate. CONCLUSION: Achieving SAP ≥150 mm Hg at the time of reperfusion may be associated with early stabilization of graft function. Nevertheless, our data suggested that recipients with a prolonged dialysis history are less likely to achieve SAP ≥150 mm Hg at the time of unclamping in living donor renal transplantation.

Is the Living Donor Kidney Profile Index Valuable in Japanese Patients?

INTRODUCTION: The Living Kidney Donor Profile Index (LKDPI) was recently proposed in the United States to evaluate living donor quality. Japan has a largely different renal transplant circumstance, such as a high ABO incompatibility rate. The aim of this study was to validate the LKDPI among the Japanese population and adjust the score. METHODS: We performed a retrospective analysis of 133 living donors in renal transplant in our institution. We analyzed the clinical characteristics and outcomes, and created a modified LKDPI score considering the favorable ABO incompatible kidney transplant outcomes in Japan. RESULTS: Median (interquartile range [IQR]) donor age was 59 (51 to 65) and median (IQR) body mass index was 22.9 kg/m2 (20.9 to 25.2). ABO incompatibility rate was 28.5%. Median (IQR) donor estimated glomerular filtration rate (eGFR) (Chronic Kidney Disease Epidemiology Collaboration equation) was 108.7 mL/min/1.73 m2 (99.9 to 115.5). The 1-year graft survival rate was 98.5%, and the 3-year graft survival rate was 97%. The incidence of antibody mediated rejection was 5.2%. The median (IQR) LKDPI score was 30.2 (11.8 to 46.8). This was significantly higher than the previously reported score in the United States, which was 12.8 (-0.8 to 27.2). The modified LKDPI (mLKDPI) score was 23.2 (4.1 to 35.1). LKDPI and mLKDPI did not show a diagnostic value in graft survival; however, LKDPI and mLKDPI showed significant diagnostic value in eGFR at 1 year (area under the curve [AUC]=0.627, P = .017; and AUC=0.673, P = .01). CONCLUSION: Our outcomes had better survival even though with higher ABO incompatibility rate. According to original LKDPI, our donor pool is higher than the general US population. In this study, lower LKDPI tended to be associated with good allograft function, and mLKDPI has better diagnostic value than LKDPI. To compare internationally, an adjusted model for Japan might be necessary based on the outcomes of a large population.

Impact of Very Low-Dose Trimethoprim-Sulfamethoxazole on Serum Creatinine after Renal Transplantation: A Retrospective Study.

BACKGROUND: It is well known that high-dose trimethoprim, through its effect of inhibiting creatinine secretion, increases serum creatinine levels without changes in real glomerular filtration rate. However, there has been no report regarding the effect of very low-dose trimethoprim on serum creatinine levels after renal transplantation. METHODS: We retrospectively investigated 76 renal transplantation recipient outpatients who completed their course of initial prophylaxis at our institution. Twelve patients who experienced events that might affect their serum creatinine levels were excluded. Fifty-one patients who required readministration of trimethoprim-sulfamethoxazole to prevent a possible outbreak of pneumocystis jirovecii pneumonia and 13 patients who did not receive readministration (control) were analyzed. Dosage was 80 mg/400 mg (per tablet), administered as 3 tablets per week for 30.6 ± 13.5 days. This study strictly complied with the Helsinki Congress and the Istanbul. Declaration regarding donor source. RESULTS: All patients completed readministration without adverse events. Serum creatinine increased significantly in the readministration group (1.40 ± 0.64 mg/dL to 1.48 ± 0.70 mg/dL, P < .01) while not in the control group. The higher the initial serum creatinine level, the greater the increase of Δ serum creatinine (R = 0.59, P < .001). Sex, baseline urine protein level, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use, donor type, and time after renal transplantation did not affect Δ serum creatinine. Serum creatinine returned to baseline levels after cessation. CONCLUSIONS: Very low-dose trimethoprim-sulfamethoxazole prophylaxis significantly raised serum creatinine reversibly by 6% after renal transplantation.

Factors related to suboptimal recovery of renal function after living donor nephrectomy: a retrospective study.

BACKGROUND: The renal function of the remaining kidney in living donors recovers up to 60~70% of pre-donation estimated-glomerular filtration rate (eGFR) by compensatory hypertrophy. However, the degree of this hypertrophy varies from donor to donor and the factors related to it are scarcely known. METHODS: We analyzed 103 living renal transplantations in our institution and divided them into two groups: compensatory hypertrophy group [optimal group, 1-year eGFR ≥60% of pre-donation, n = 63] and suboptimal compensatory hypertrophy group (suboptimal group, 1-year eGFR < 60% of pre-donation, n = 40). We retrospectively analyzed the factors related to suboptimal compensatory hypertrophy. RESULTS: Baseline eGFRs were the same in the two groups (optimal versus suboptimal: 82.0 ± 13.1 ml/min/1.73m2 versus 83.5 ± 14.8 ml/min/1.73m2, p = 0.588). Donor age (optimal versus suboptimal: 56.0 ± 10.4 years old versus 60.7 ± 8.7 years old, p = 0.018) and uric acid (optimal versus suboptimal: 4.8 ± 1.2 mg/dl versus 5.5 ± 1.3 mg/dl, p = 0.007) were significantly higher in the suboptimal group. The rate of pathological chronicity finding on 1-h biopsy (ah≧1 ∩ ct + ci≧1) was much higher in the suboptimal group (optimal versus suboptimal: 6.4% versus 25.0%, p = 0.007). After the multivariate analysis, the pathological chronicity finding [odds ratio (OR): 4.8, 95% confidence interval (CI): 1.3-17.8, p = 0.021] and uric acid (per 1.0 mg/dl, OR: 1.5, 95% CI: 1.1-2.2, p = 0.022) were found to be independent risk factors for suboptimal compensatory hypertrophy. CONCLUSION: Chronicity findings on baseline biopsy and higher uric acid were associated with insufficient recovery of the post-donated renal function.

Prediction model of compensation for contralateral kidney after living-donor donation.

BACKGROUND: Compensation of contralateral kidney function after living-donor kidney donation is well known, and many predictive factors have been proposed. However, no prediction model has been proposed. This study was performed to establish a tool with which to estimate the degree of compensation of the contralateral kidney after living-donor kidney donation. METHODS: We retrospectively analyzed 133 living donors for renal transplantation in our institution. We defined a favorable compensation as a post-donation estimated glomerular filtration rate (eGFR) at 1 year (calculated by the Chronic Kidney Disease Epidemiology Collaboration equation) of > 60% of the pre-donation eGFR. We analyzed the living donors' clinical characteristics and outcomes. RESULTS: The median (range) donor age was 59 (24-79) years, median (range) body mass index was 22.9 (16.8-32.7) kg/m2, and median (range) body surface area was 1.6 (1.3-2.0) m2. All donors were Japanese, and 73% of the donors were biologically related. The median (range) donor pre-donation eGFR was 108.7 (82-144) ml/min/1.73 m2, and the median (range) post-donation eGFR at 1 year was 86.9 (43-143) ml/min/1.73 m2. Eighty-six percent of donors had compensatory hypertrophy. In the univariate analysis, age, female sex, history of hypertension, body surface area, and pre-donation eGFR were significantly associated with hypertrophy (p < 0.05). In the multivariate analysis, age, female sex, history of hypertension, and ratio of the remnant kidney volume to body weight were significantly associated with hypertrophy (p < 0.05). Based on these results, we created a compensation prediction score (CPS). The median (range) CPS was 8.7 (1.1-17.4). Receiver operating characteristic analysis showed strong diagnostic accuracy for predicting favorable compensation (area under the curve, 0.958; 95% confidence interval, 0.925-0.991, p < 0.001). The optimal cut-off value of the CPS was 5.0 (sensitivity, 92.0%; specificity, 89.5%). The CPS had a strong positive correlation with the post-donation eGFR (R = 0.797, p < 0.001). CONCLUSION: The CPS might be useful tool with which to predict a favorable compensation of the contralateral kidney and remnant kidney function. If the CPS is low, careful management and follow-up might be necessary. Further investigations are needed to validate these findings in larger populations.