Machine learning for morbid glomerular hypertrophy.

A practical research method integrating data-driven machine learning with conventional model-driven statistics is sought after in medicine. Although glomerular hypertrophy (or a large renal corpuscle) on renal biopsy has pathophysiological implications, it is often misdiagnosed as adaptive/compensatory hypertrophy. Using a generative machine learning method, we aimed to explore the factors associated with a maximal glomerular diameter of ≥ 242.3 µm. Using the frequency-of-usage variable ranking in generative models, we defined the machine learning scores with symbolic regression via genetic programming (SR via GP). We compared important variables selected by SR with those selected by a point-biserial correlation coefficient using multivariable logistic and linear regressions to validate discriminatory ability, goodness-of-fit, and collinearity. Body mass index, complement component C3, serum total protein, arteriolosclerosis, C-reactive protein, and the Oxford E1 score were ranked among the top 10 variables with high machine learning scores using SR via GP, while the estimated glomerular filtration rate was ranked 46 among the 60 variables. In multivariable analyses, the R2 value was higher (0.61 vs. 0.45), and the corrected Akaike Information Criterion value was lower (402.7 vs. 417.2) with variables selected with SR than those selected with point-biserial r. There were two variables with variance inflation factors higher than 5 in those using point-biserial r and none in SR. Data-driven machine learning models may be useful in identifying significant and insignificant correlated factors. Our method may be generalized to other medical research due to the procedural simplicity of using top-ranked variables selected by machine learning.

Correcting anemia and native vitamin D supplementation in kidney transplant recipients: a multicenter, 2 × 2 factorial, open-label, randomized clinical trial.

Anemia and vitamin D deficiency are associated with allograft failure, and hence, are potential therapeutic targets among kidney transplant recipients (KTRs). We conducted a multicenter, two-by-two factorial, open-label, randomized clinical trial to examine the effects of anemia correction and vitamin D supplementation on 2-year change in eGFR among KTRs (CANDLE-KIT). We enrolled 153 patients with anemia and >1-year history of transplantation across 23 facilities in Japan, and randomly assigned them to either a high or low hemoglobin target (>12.5 vs. <10.5 g/dl) and to either cholecalciferol 1000 IU/day or control. This trial was terminated early based on the planned interim intention-to-treat analyses (α = 0.034). Among 125 patients who completed the study, 2-year decline in eGFR was smaller in the high vs. low hemoglobin group (i.e., -1.6 ± 4.5 vs. -4.0 ± 6.9 ml/min/1.73 m2 ; P = 0.021), but did not differ between the cholecalciferol and control groups. These findings were supported by the fully adjusted mixed effects model evaluating the rate of eGFR decline among all 153 participants. There were no significant between-group differences in all-cause death or the renal composite outcome in either arm. In conclusion, aggressive anemia correction showed a potential to preserve allograft kidney function.

Preoperative assessment system for hand-assisted laparoscopic donor nephrectomy by discriminant analysis.

We developed a preoperative assessment system to predict surgical workload in hand-assisted laparoscopic donor nephrectomy (HALDNx) using the normal-based linear discriminant rule (NLDR). A total of 128 cases of left HALDNx performed by a single operator were used as training data. Surgical workload was measured by operative time. The optimized model had 9 explanatory variables: age, total protein, total cholesterol, number of renal arteries (numberRA), 4 variables of perinephric fat (PNF), and thickness of subcutaneous fat. This model was validated using cross-validation and the .632 estimator to estimate discrimination rates with future test data. PNF and numberRA were the predominant factors affecting workload followed by the computed tomography value of PNF, body weight, and male sex. The estimated accuracy of the prediction system was 94.6%. The complication rate was 9.38% and did not correlate with surgical workload. We also made our program available online for constructing assessment functions from other cohort data. In conclusion, the surgical workload of HALDNx could be predicted with PNF and numberRA as the dominant risk factors.

Single fixed low-dose rituximab as induction therapy suppresses de novo donor-specific anti-HLA antibody production in ABO compatible living kidney transplant recipients.

This study was conducted to evaluate de novo donor-specific anti-human leukocyte antigen (HLA) antibody (dnDSA) production leading to antibody-mediated rejection (ABMR) after rituximab induction in non-sensitized ABO-compatible living kidney transplantation (ABO-CLKTx). During 2008-2015, 318 ABO-CLKTx were performed at the Department of Surgery III at Tokyo Women's Medical University Hospital. To reduce confounding factors, we adopted a propensity score analysis, which was applied with adjustment for age, gender, duration of pretransplant dialysis, HLA mismatch count, preformed DSA, non-insulin-dependent diabetes mellitus, immunosuppressive treatment, and estimated glomerular filtration rate (eGFR) on postoperative day 7. Using a propensity score matching model (1:1, 115 pairs), we analyzed the long-term outcomes of 230 ABO-CLKTx recipients retrospectively. Recipients were classified into a rituximab-treated (RTX-KTx, N = 115) group and a control group not treated with rituximab (C-KTx, N = 115). During five years, adverse events, survival rates for grafts and patients, and incidence of biopsy-proven acute rejection (BPAR) and dnDSA production for the two groups were monitored and compared. All recipients in the RTX-KTx group received rituximab induction on preoperative day 4 at a single fixed low dose of 100 mg; the CD19+ B cells were eliminated completely before surgery. Of those recipients, 13 (11.3%) developed BPAR; 1 (0.8%) experienced graft loss. By contrast, of C-KTx group recipients, 25 (21.7%) developed BPAR; 3 (2.6%) experienced graft loss. The RTX-KTx group exhibited a significantly lower incidence of BPAR (P = .041) and dnDSA production (13.9% in the RTX-KTx group vs. 26.9% in the C-RTx group, P = .005). Furthermore, lower incidence of CMV infection was detected in the RTX-KTx group than in the C-KTx group (13.9% in the RTX-KTx group vs. 27.0% in the C-KTx group, P = .014). No significant difference was found between groups for several other factors: renal function (P = .384), graft and patient survival (P = .458 and P = .119, respectively), and the respective incidences of BK virus infection (P = .722) and leukopenia (P = .207). During five-year follow-up, single fixed low-dose rituximab therapy is sufficient for ensuring safety, reducing rejection, and suppressing dnDSA production for immunological low-risk non-sensitized ABO-CLKTx.

Single Graft Utilization From Donors With Severe Acute Kidney Injury After Circulatory Death.

Chronic shortages of organs for transplantation have led to the use of marginal kidneys from donors after circulatory death with acute kidney injury (AKI), but the utilization of kidneys with severe AKI is not well established. We retrospectively analyzed eight kidney transplantation (KTx) cases from donation after circulatory death (DCD) with terminal creatinine (t-Cr) concentrations higher than 10.0 mg/dL and/or oliguria for more than 5 days (AKI network criteria: stage III). Although all patients showed delayed graft function, no cases of primary nonfunction (PNF) were found. Five patients maintained stable renal function for approximately 15.5, 10, 10, 5, and 0.5 years after KTx. Only 1 patient showed biopsy-proven acute rejection. Also, 2 patients developed graft failure: one attributable to chronic antibody mediated rejection at 11.3 years after KTx, and one attributable to recurrence of IgA nephropathy at 4.6 years after KTx. Kidneys with AKI stage III yielded great outcomes without the risk of primary nonfunction and rejection. Although the AKI kidneys were associated with delayed graft function, these results suggest that even the most severe kidneys with AKI stage III from DCD donors can be considered a valid alternative for recipients on a waiting list for KTx.

Longterm renal allograft survival after sequential liver-kidney transplantation from a single living donor.

Combined liver-kidney transplantation (CLKT) is well established as a definitive therapy with the potential to provide complete recovery for certain liver-kidney diseases, although the results might be contingent on the cause of transplantation. The purposes of the present study were to review the longterm outcome of renal allografts in CLKT patients from single living donors and to investigate the beneficial factors, compared with solitary renal transplantation. Thirteen patients underwent sequential liver transplantation (LT) and kidney transplantation (KT) from single living donors. The indications for KT were oxaluria (n = 7), autosomal recessive polycystic disease (n = 3), and others (n = 3). The same immunosuppressive regimen used after LT was also used after KT. KT was performed between 1.7 and 47.0 months after the LT. The overall patient survival rate was 92.3% at 10 years. In 12 of the 13 surviving patients, the renal allografts were found to be functioning in 11 patients after a mean follow-up period of 103.6 months. The death-censored renal allograft survival rate at 10 years was 100%, which was better than that of KT alone (84.9%) in Japan. Immunological protection conferred by the preceding liver allograft may have contributed to the longterm outcomes of the renal allografts. In addition, the donation of double organs from a single living and related donor may have a favorable impact on the graft survival rate. In the future, investigations of factors affecting the longterm outcome of renal allografts, including details of the involvement of de novo donor-specific antibody, will be needed. Liver Transplantation 23 315-323 2017 AASLD.

Successful Long-term Graft Survival of a Renal Transplantation Patient with Wiskott-Aldrich Syndrome.

Wiskott-Aldrich syndrome, a rare X-linked hereditary syndrome, is characterized by immunodeficiency, thrombocytopenia, and eczema. The underlying T-cell defect renders renal transplantation and immunosuppressive treatments uncertain. The present case exhibited the mild clinical manifestation, regarded as X-linked thrombocytopenia. He successfully underwent a living-donor ABO-compatible renal transplantation and splenectomy in 2002, and thereafter experiencing no severe rejection, serious infection, or malignancy for more than 10 years. Though IgA nephropathy was detected 8 months after transplantation, the patient's renal function and proteinuria were stable without any treatment. The present case showed a successful long-term graft survival and the importance of splenectomy added to renal transplantation.

Outcomes of Kidney Transplantation from Circulatory Death Donors With Increased Terminal Creatinine Levels in Serum.

BACKGROUND: To alleviate chronic renal graft shortages in Japan, donation after circulatory death (DCD) is an increasingly used organ resource. Organs from DCD donors with progressively increased terminal creatinine (t-Cr) levels are frequently used, but the effects of this condition on kidney transplantation (KTx) remain unclear. METHODS: Between 1996 and 2013, 99 KTx from DCD donors were conducted in our department. Recipients were grouped according to the t-Cr (in mg/dL) of donors: group 1, t-Cr less than < 1.5; group 2, 1.5 ≤ t-Cr < 3.0; and group 3, t-Cr ≥ 3.0. We analyzed the long-term outcomes of KTx from DCD donors retrospectively in terms of donors' terminal renal function. RESULTS: The respective mean donor t-Cr in groups 1, 2, and 3 were 0.73 ± 0.28, 2.02 ± 0.40, and 6.69 ± 3.68. The respective death-censored graft survival rates (%) in groups 1, 2, and 3 were 90.2, 96.2, and 86.7 at 1 year and 70.3, 86.2, and 73.4 at 10 years after transplantation. Group 1 exhibited lower incidence of delayed graft function than either group 2 or group 3 (80.5% vs 100% and 93.3%). Nevertheless, no significant difference was found between groups for several measures: Cr levels 1 month after KTx and lowest Cr levels throughout the observation period, prevalence of biopsy-proven acute rejection, and graft survival. Cox proportional hazard regression showed that donor age, cerebrovascular event, terminal urine output, and history of hypertension were significantly associated with graft survival. CONCLUSIONS: Results suggest that, under certain conditions, kidneys from DCD donors with progressively increased t-Cr can be used safely with promising long-term outcomes.

Nine-yr experience of 700 hand-assisted laparoscopic donor nephrectomies in Japan.

OBJECTIVE: We reviewed the introduction of a new, minimally invasive, live kidney donation program in our department. METHODS: The operating times of 700 consecutive hand-assisted laparoscopic donor nephrectomies (HALDN) conducted from February 2001 to April 2010 were examined. The risk factors for prolonging operating times were analyzed and major surgical barriers in HALDN investigated. RESULTS: All procedures were successfully performed without the requirement for conversion to open surgery or blood transfusion. The overall prevalence of perioperative complications was 3.0%, with no mortality, in this non-obese donor population with mean body mass index (BMI) as low as 23.2 ± 3.2 kg/m(2) . After the initial learning curve, a second learning plateau was detected until around case 300. Multivariate analyses showed that the significant risk factors were male sex, graft weight, number of renal arteries, right nephrectomy, and previous epigastric surgery (p < 0.05). HALDN provided direct handling of the surgical field, secure vascular control, safe manipulation of adhesive tissues, and served to maintain surgical safety. Mean values of the BMI of donors had a significant positive correlation with the prevalence of complications between large studies (p = 0.042). CONCLUSIONS: Laparoscopic donor nephrectomy was safely introduced and established in a single institution with the help of the hand-assistance method.