[Construction of a risk prediction model for diabetes after kidney transplantation based on genome-wide association study].

Objective: To explore the clinical risk factors and susceptibility genes of diabetes after kidney transplantation (PTDM) and construct a risk prediction model for PTDM. Methods: The data of kidney transplant recipients who underwent follow-up in the Affiliated Lihuili Hospital, Ningbo University and Sir Run Run Shaw Hospital, Zhejiang University School of Medicine from January 2001 to December 2022 were retrospectively analyzed. The recipients were divided into PTDM group and Non-PTDM group according to whether they were complicated with PTDM. The differences in clinical indicators between the two groups were compared, the risk factors affecting the incidence of PTDM were determined, and susceptibility genes of PTDM were screened by genome-wide association study (GWAS). PTDM risk prediction models based only on clinical indicators (Model 1) and clinical indicators combined with susceptibility genes (Model 2) were established respectively, and the predictive performance of the two prediction models was compared. Finally, the Nomogram of the optimal model was drawn, and the discrimination, calibration and clinical applicability of the model were evaluated. Results: A total of 113 kidney transplant recipients (70 males and 43 females) were included, with an average age of (46.2±10.8) years. There were 51 cases in PTDM group and 62 cases in Non-PTDM group. The related factors screened by GWAS and logistic regression analysis included family history of diabetes (OR=88.912, 95%CI: 5.827-1 356.601, P=0.001), preoperative triglyceride (TG) (OR=1.888, 95 %CI: 1.150-3.098, P=0.012), uric acid (UA) (OR=1.011, 95%CI: 1.000-1.022, P=0.045) and rs802707 (OR=10.046, 95%CI: 1.462-69.042, P=0.019). The area under the curve (AUC) of the receiver operating characteristics analysis (ROC) predicted by Model 1 for PTDM was 0.891 (95%CI: 0.811-0.972), with the sensitivity of 0.889 and the specificity of 0.742. The AUC of ROC curve predicted by Model 2 for PTDM was 0.930 (95%CI: 0.864-0.995), with the sensitivity of 0.885 and the specificity of 0.900. Conclusions: Family history of diabetes, preoperative TG and UA, and rs802707 are significantly associated with the occurrence of PTDM. In addition, the combination of susceptibility genes could improve the predictive ability of clinical indicators for the risk of PTDM.

[Clinical analysis of two brothers with Imerslund-Gräsbeck syndrome].

The clinical data of two children with Imerslund-Gräsbeck syndrome (IGS) who were admitted to the First Affiliated Hospital of Zhengzhou University in August 2019 was analyzed retrospectively. The two cases were siblings, aged 8 years and 8 months and 6 years and 2 months, respectively. These two boys had megaloblastic anemia, low level of vitamin B12, hyperhomocysteinemia, accompanied by proteinuria and renal tubular injury, while they showed normal folate level and renal function. Blood tandem mass spectrometry and urine organic acid analysis suggested methylmalonic acidemia (MMA). The initial diagnosis was MMA with homocysteinemia. No known pathogenic gene mutation related to MMA was found by gene sequencing. Compound heterozygous variants of amnionless (AMN) gene were detected: c.43+5G>A and c.C717G. The corrected diagnosis was IGS. Both brothers were treated with long-term intramuscular injection of vitamin B12. After follow-up for one year, these two cases had no clinical symptoms, and their blood indicators remained normal, but proteinuria and renal tubular injury persisted. Blood tandem mass spectrometry and urine organic acid analysis alone may easily lead to misdiagnosis, but combined with genetic testing can improve the accuracy of diagnosis of IGS. Lifelong parenteral vitamin B12 replacement therapy can effectively reverse the clinical and biochemical results, but is uncertain in alleviating albuminuria and renal tubule injury. It's necessary to monitor the renal function regularly.