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Beaudrey T, Bedo D, Weschler C, Caillard S, Florens N. From Risk Assessment to Management: Cardiovascular Complications in Pre- and Post-Kidney Transplant Recipients: A Narrative Review. Diagnostics (Basel) 2025; 15:802. [PMID: 40218153 PMCID: PMC11988545 DOI: 10.3390/diagnostics15070802] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2025] [Revised: 03/17/2025] [Accepted: 03/21/2025] [Indexed: 04/14/2025] Open
Abstract
Kidney transplantation remains the best treatment for chronic kidney failure, offering better outcomes and quality of life compared with dialysis. Cardiovascular disease (CVD) is a major cause of morbidity and mortality in kidney transplant recipients and is associated with decreased patient survival and worse graft outcomes. Post-transplant CVD results from a complex interaction between traditional cardiovascular risk factors, such as hypertension and diabetes, and risk factors specific to kidney transplant recipients including chronic kidney disease, immunosuppressive drugs, or vascular access. An accurate assessment of cardiovascular risk is now needed to optimize the management of cardiovascular comorbidities through the detection of risk factors and the screening of hidden pretransplant coronary artery disease. Promising new strategies are emerging, such as GLP-1 receptor agonists and SGLT2 inhibitors, with a high potential to mitigate cardiovascular complications, although further research is needed to determine their role in kidney transplant recipients. Despite this progress, a significant gap remains in understanding the optimal management of post-transplant CVD, especially coronary artery disease, stroke, and peripheral artery disease. Addressing these challenges is essential to improve the short- and long-term outcomes in kidney transplant recipients. This narrative review aims to provide a comprehensive overview of cardiovascular risk assessment and post-transplant CVD management.
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Affiliation(s)
- Thomas Beaudrey
- Nephrology Department, Hôpitaux Universitaires de Strasbourg, 67000 Strasbourg, France; (T.B.); (D.B.); (C.W.); (S.C.)
- Inserm UMR_S 1109 Immuno-Rhumatology Laboratory, Translational Medicine Federation of Strasbourg (FMTS), FHU Target, Faculté de Médecine, Université de Strasbourg, 67000 Strasbourg, France
| | - Dimitri Bedo
- Nephrology Department, Hôpitaux Universitaires de Strasbourg, 67000 Strasbourg, France; (T.B.); (D.B.); (C.W.); (S.C.)
- Inserm UMR_S 1109 Immuno-Rhumatology Laboratory, Translational Medicine Federation of Strasbourg (FMTS), FHU Target, Faculté de Médecine, Université de Strasbourg, 67000 Strasbourg, France
| | - Célia Weschler
- Nephrology Department, Hôpitaux Universitaires de Strasbourg, 67000 Strasbourg, France; (T.B.); (D.B.); (C.W.); (S.C.)
| | - Sophie Caillard
- Nephrology Department, Hôpitaux Universitaires de Strasbourg, 67000 Strasbourg, France; (T.B.); (D.B.); (C.W.); (S.C.)
- Inserm UMR_S 1109 Immuno-Rhumatology Laboratory, Translational Medicine Federation of Strasbourg (FMTS), FHU Target, Faculté de Médecine, Université de Strasbourg, 67000 Strasbourg, France
| | - Nans Florens
- Nephrology Department, Hôpitaux Universitaires de Strasbourg, 67000 Strasbourg, France; (T.B.); (D.B.); (C.W.); (S.C.)
- Inserm UMR_S 1109 Immuno-Rhumatology Laboratory, Translational Medicine Federation of Strasbourg (FMTS), FHU Target, Faculté de Médecine, Université de Strasbourg, 67000 Strasbourg, France
- INI-CRCT (Cardiovascular and Renal Trialists), F-CRIN Network, 67000 Strasbourg, France
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Lee JH, Myung J, Gang S, Ryu HJ, Yi NJ, Yang J. Clinical characteristics and outcomes of kidney transplantation in autosomal dominant polycystic kidney disease patients. J Nephrol 2024:10.1007/s40620-024-02101-8. [PMID: 39495478 DOI: 10.1007/s40620-024-02101-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2024] [Accepted: 09/01/2024] [Indexed: 11/05/2024]
Abstract
BACKGROUND Kidney transplantation (KT) is the best kidney replacement treatment for autosomal dominant polycystic kidney disease (ADPKD). We aimed to investigate the clinical characteristics and outcomes of KT in ADPKD patients compared to those in non-ADPKD patients. METHODS We retrospectively analyzed KT recipients in two Korean transplantation centers from 2005 to 2020. Propensity score-matching and Cox regression analysis were used to assess the clinical outcomes of ADPKD compared to non-ADPKD and identify prognostic factors influencing outcomes in ADPKD. RESULTS Among a total of 4452 KT patients, 189 (4.2%) were ADPKD patients. Median age at transplantation was 53.0 and 47.0 in ADPKD and non-ADPKD patients, respectively. In both groups, living-donor KT was more common than deceased-donor KT. The ADPKD group had a 4.09-fold higher risk of post-transplant diabetes mellitus and a 1.65-fold higher risk of post-transplant infection compared to the non-ADPKD group; however, subjects with ADPKD had similar risk of rejection, graft failure, and mortality. In the ADPKD group, kidney volume decreased after KT, irrespective of kidney volume status (Mayo classification), while the size of hepatic cysts increased. Neither kidney volume nor nephrectomy of native kidneys were associated with risk of infection, graft failure, or mortality in the ADPKD group. CONCLUSIONS ADPKD patients have a higher risk of post-transplant diabetes mellitus and infection than non-ADPKD patients, with no significant impact of kidney volume or nephrectomy on post-transplant outcomes.
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Affiliation(s)
- Jin Hyeog Lee
- Division of Nephrology, Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Republic of Korea
- Division of Nephrology, Department of Internal Medicine, College of Medicine, International Saint Mary's Hospital, Catholic Kwandong University, Incheon, Republic of Korea
| | - Jiyeon Myung
- Division of Nephrology, Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Republic of Korea
| | - Sujin Gang
- Department of Surgery, Seoul National University Hospital, Seoul, Republic of Korea
| | - Hyun Jin Ryu
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Nam Joon Yi
- Department of Surgery, Seoul National University Hospital, Seoul, Republic of Korea
| | - Jaeseok Yang
- Division of Nephrology, Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Republic of Korea.
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Shin J, Jo EA, Woo HY, Cho A, Ko M, Kim S, Han A, Ha J, Min S. Perioperative glucose monitoring with continuous glucose monitors identifies risk factors for post-transplant diabetes mellitus in kidney transplant recipients. Sci Rep 2024; 14:21240. [PMID: 39261619 PMCID: PMC11390710 DOI: 10.1038/s41598-024-72025-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2024] [Accepted: 09/03/2024] [Indexed: 09/13/2024] Open
Abstract
Post-transplantation diabetes mellitus (PTDM) negatively affects graft and patient survival after kidney transplantation (KT). This prospective study used continuous glucose monitoring (CGM) to evaluate perioperative blood glucose dynamics, identify PTDM risk factors, and compare predictive accuracy with capillary blood glucose monitoring (CBGM) in 60 non-diabetic living-donor KT recipients. Patients underwent 2-week pre- and postoperative CGM, including routine CBGM during their in-hospital stays. PTDM-related risk factors and glucose profiles were analyzed with postoperative CGM and CBG. PTDM developed in 14 (23.3%) patients and was associated with older age, male sex, higher baseline HbA1c, high-density lipoprotein cholesterol, and 3-month cumulative tacrolimus exposure levels. Male sex and postoperative time above the range (TAR) of 180 mg/dL by CGM were PTDM-related risk factors in the multivariate analysis. For predictive power, the CGM model with postoperative glucose profiles exhibited higher accuracy compared with the CBGM model (areas under the curves of 0.916, and 0.865, respectively). Therefore, we found that male patients with a higher postoperative TAR of 180 mg/dL have an increased risk of PTDM. Postoperative CGM provides detailed glucose dynamics and demonstrates superior predictive potential for PTDM than CBGM.
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Affiliation(s)
- Jiyoung Shin
- Division of Transplantation and Vascular Surgery, Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Eun-Ah Jo
- Department of Surgery, Chung-Ang University Hospital, Seoul, Republic of Korea
| | - Hye Yong Woo
- Division of Transplantation and Vascular Surgery, Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Ara Cho
- Division of Transplantation and Vascular Surgery, Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Myeonghyeon Ko
- Division of Transplantation and Vascular Surgery, Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Sangwan Kim
- Institute of Health Policy and Management, Seoul National University Medical Research Center, Seoul, Republic of Korea
| | - Ahram Han
- Division of Transplantation and Vascular Surgery, Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jongwon Ha
- Division of Transplantation and Vascular Surgery, Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Sangil Min
- Division of Transplantation and Vascular Surgery, Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea.
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Hasbal NB, Copur S, Peltek IB, Mutlu A, Atalay HO, Kesgin YE, Karakaya AD, Siriopol D, Koçak B, Kanbay M. Pancreatic steatosis is an independent risk factor for post-transplant diabetes mellitus in kidney transplant patients. Clin Transplant 2024; 38:e15204. [PMID: 38041471 DOI: 10.1111/ctr.15204] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2023] [Revised: 11/13/2023] [Accepted: 11/20/2023] [Indexed: 12/03/2023]
Abstract
BACKGROUND AND AIM Post-transplant diabetes mellitus (PTDM) is associated with an increased risk of post-transplant cardiovascular diseases, and several risk factors of PTDM have been shown in the literature. Yet, the relationship between hepatic and pancreatic steatosis with post-transplant diabetes mellitus remains vague. We aimed to evaluate pancreatic steatosis, a novel component of metabolic syndrome, and hepatic steatosis association with post-transplant diabetes mellitus in a single-center retrospective cohort study conducted on kidney transplant recipients. METHOD We have performed a single-center retrospective cohort study involving all kidney transplant recipients. We have utilized pretransplant Fibrosis-4, nonalcoholic fatty liver disease fibrosis score, and abdominal computed tomography for the assessment of visceral steatosis status. RESULTS We have included 373 kidney transplant recipients with a mean follow-up period of 32 months in our final analysis. Post-transplant diabetes mellitus risk is associated with older age (p < .001), higher body-mass index (p < .001), nonalcoholic fatty liver disease-fibrosis score (p = .002), hepatic (p < .001) or pancreatic (p < .001) steatosis on imaging and higher pre-transplant serum triglyceride (p = .003) and glucose levels (p = .001) after multivariate analysis. CONCLUSION Our study illustrates that recipients' pancreatic steatosis is an independent predictive factor for post-transplant diabetes mellitus including in kidney transplant patients.
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Affiliation(s)
- Nuri Baris Hasbal
- Division of Nephrology, Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Sidar Copur
- Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Ibrahim B Peltek
- Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Ali Mutlu
- Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Hande Ozen Atalay
- Department of Radiology, Koc University School of Medicine, Istanbul, Turkey
| | - Yavuz E Kesgin
- Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Afak Durur Karakaya
- Department of Radiology, Koc University School of Medicine, Istanbul, Turkey
| | - Dimitrie Siriopol
- Department of Nephrology, "Saint John the New" County Hospital, "Stefan cel Mare" University of Suceava, Suceava, Romania
| | - Burak Koçak
- Munci Kalayoglu Organ Transplantation Center, Koc University Hospital, Istanbul, Turkey
| | - Mehmet Kanbay
- Division of Nephrology, Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
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Chen LC, Chu YC, Lu T, Lin HYH, Chan TC. Cardiometabolic comorbidities in autosomal dominant polycystic kidney disease: a 16-year retrospective cohort study. BMC Nephrol 2023; 24:333. [PMID: 37946153 PMCID: PMC10637020 DOI: 10.1186/s12882-023-03382-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Accepted: 10/30/2023] [Indexed: 11/12/2023] Open
Abstract
BACKGROUND Autosomal-dominant polycystic kidney disease (ADPKD) is the most prevalent hereditary kidney disease and the fourth leading cause of end-stage renal disease (ESRD) requiring renal replacement therapy (RRT). Nevertheless, there is a paucity of epidemiological research examining the risk factors and survival on RRT for ADPKD. Thus, we aimed to investigate the cumulative effects of cardiometabolic comorbidities, including hypertension (HTN), type 2 diabetes mellitus (DM), and dyslipidemia (DLP) to clinical outcomes in ADPKD. METHODS We identified 6,142 patients with ADPKD aged ≥ 20 years from 2000 to 2015 using a nationwide population-based database. HTN, DM, and DLP diagnoses before or at the time of ADPKD diagnosis and different combinations of the three diagnoses were used as the predictors for the outcomes. Survival analyses were used to estimate the adjusted mortality risk from cardiometabolic comorbidities and the risk for renal survival. RESULTS Patients with ADPKD who developed ESRD had the higher all-cause mortality (HR, 5.14; [95% CI: 3.88-6.80]). Patients with all three of the diseases had a significantly higher risk of entering ESRD (HR:4.15, [95% CI:3.27-5.27]), followed by those with HTN and DM (HR:3.62, [95% CI:2.82-4.65]), HTN and DLP (HR:3.54, [95% CI:2.91-4.31]), and HTN alone (HR:3.10, [95% CI:2.62-3.66]) compared with those without any three cardiometabolic comorbidities. CONCLUSIONS Our study discovered the cumulative effect of HTN, DM, and DLP on the risk of developing ESRD, which reinforces the urgency of proactive prevention of cardiometabolic comorbidities to improve renal outcomes and overall survival in ADPKD patients.
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Affiliation(s)
- Li-Chi Chen
- Research Center for Humanities and Social Sciences, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei, 115, Taiwan
- Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA
| | - Yi-Chi Chu
- Research Center for Humanities and Social Sciences, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei, 115, Taiwan
| | - Tzongshi Lu
- Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Hugo Y-H Lin
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, No.68, Jhonghua 3rd Road, Cianjin, Kaohsiung, 807, Taiwan.
- Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
- Department of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
| | - Ta-Chien Chan
- Research Center for Humanities and Social Sciences, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei, 115, Taiwan.
- Institute of Public Health, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
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Mitsuke A, Ohbo T, Arima J, Osako Y, Sakaguchi T, Matsushita R, Yoshino H, Tatarano S, Yamada Y, Sasaki H, Tanabe T, Fukuzawa N, Tanaka H, Nishio Y, Hideki E, Harada H. Low dose tacrolimus exposure and early steroid withdrawal with strict body weight control can improve post kidney transplant glucose tolerance in Japanese patients. PLoS One 2023; 18:e0287059. [PMID: 37819994 PMCID: PMC10566682 DOI: 10.1371/journal.pone.0287059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Accepted: 05/26/2023] [Indexed: 10/13/2023] Open
Abstract
The development of diabetes mellitus (DM) after living donor kidney transplantation (KT) is a risk factor for worsening transplant kidney function, cardiac disease, and cerebrovascular disease, which may affect prognosis after KT. At our institution, all patients' glucose tolerance is evaluated perioperatively by oral glucose tolerance tests (OGTTs) at pre-KT, and 3, 6, and 12 month (mo.) after KT. We analyzed the insulinogenic index (ISI) and homeostasis model assessment beta cell (HOMA-β) based on the immunoreactive insulin (IRI) levels to determine how glucose tolerance changed after KT in 214 patients who had not been diagnosed with DM before KT. In addition, we analyzed the body mass index (BMI) which may also influence glucose tolerance after KT. The concentration of tacrolimus (TAC) in blood was also measured as the area under the curve (AUC) to examine its effects at each sampling point. The preoperative-OGTTs showed that DM was newly diagnosed in 22 of 214 patients (10.3%) who had not been given a diagnosis of DM by the pre-KT fasting blood sugar (FBS) tests. The glucose tolerance was improved in 15 of 22 DM patients at 12 mo. after KT. ISI and IRI deteriorated only at 3 mo. after KT but improved over time. There was a trend of an inverse correlation between HOMA-β and TAC-AUC. We also found inverse correlations between IRI and an increase in BMI from 3 to 12 mo. after KT. Early corticosteroid withdrawal or the steroid minimization protocol with tacrolimus to maintain a low level of diabetogenic tacrolimus and BMI decrease after KT used by our hospital individualizes lifestyle interventions for each patient might contribute to an improvement in post-KT glucose tolerance.
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Affiliation(s)
- Akihiko Mitsuke
- Department of Urology, Graduate of School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
- Department of Kidney Transplant Surgery, Sapporo City General Hospital, Hokkaido, Japan
| | - Takahiko Ohbo
- Department of Diabetes and Endocrine Medicine, Graduate of School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
| | - Junya Arima
- Department of Urology, Graduate of School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
| | - Yoichi Osako
- Department of Urology, Graduate of School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
| | - Takashi Sakaguchi
- Department of Urology, Graduate of School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
| | - Ryosuke Matsushita
- Department of Urology, Graduate of School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
| | - Hirofumi Yoshino
- Department of Urology, Graduate of School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
| | - Shuichi Tatarano
- Department of Urology, Graduate of School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
| | - Yasutoshi Yamada
- Department of Urology, Graduate of School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
| | - Hajime Sasaki
- Department of Kidney Transplant Surgery, Sapporo City General Hospital, Hokkaido, Japan
| | - Tatsu Tanabe
- Department of Kidney Transplant Surgery, Sapporo City General Hospital, Hokkaido, Japan
| | - Nobuyuki Fukuzawa
- Department of Kidney Transplant Surgery, Sapporo City General Hospital, Hokkaido, Japan
| | - Hiroshi Tanaka
- Department of Kidney Transplant Surgery, Sapporo City General Hospital, Hokkaido, Japan
| | - Yoshihiko Nishio
- Department of Diabetes and Endocrine Medicine, Graduate of School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
| | - Enokida Hideki
- Department of Urology, Graduate of School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
| | - Hiroshi Harada
- Department of Kidney Transplant Surgery, Sapporo City General Hospital, Hokkaido, Japan
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Bang JB, Oh CK, Kim YS, Kim SH, Yu HC, Kim CD, Ju MK, So BJ, Lee SH, Han SY, Jung CW, Kim JK, Ahn HJ, Lee SH, Jeon JY. Changes in glucose metabolism among recipients with diabetes 1 year after kidney transplant: a multicenter 1-year prospective study. Front Endocrinol (Lausanne) 2023; 14:1197475. [PMID: 37424863 PMCID: PMC10325682 DOI: 10.3389/fendo.2023.1197475] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Accepted: 05/30/2023] [Indexed: 07/11/2023] Open
Abstract
Background Diabetes mellitus is a common and crucial metabolic complication in kidney transplantation. It is necessary to analyze the course of glucose metabolism in patients who already have diabetes after receiving a transplant. In this study, we investigated the changes in glucose metabolism after transplantation, and a detailed analysis was performed on some patients whose glycemic status improved. Methods The multicenter prospective cohort study was conducted between 1 April 2016 and 31 September 2018. Adult patients (aged 20 to 65 years) who received kidney allografts from living or deceased donors were included. Seventy-four subjects with pre-transplant diabetes were followed up for 1 year after kidney transplantation. Diabetes remission was defined as the results of the oral glucose tolerance test performed one year after transplantation and the presence or absence of diabetes medications. After 1-year post-transplant, 74 recipients were divided into the persistent diabetes group (n = 58) and the remission group (n = 16). Multivariable logistic regression was performed to identify clinical factors associated with diabetes remission. Results Of 74 recipients, 16 (21.6%) showed diabetes remission after 1-year post-transplant. The homeostatic model assessment for insulin resistance numerically increased in both groups throughout the first year after transplantation and significantly increased in the persistent diabetes group. The insulinogenic index (IGI30) value significantly increased only in the remission group, and the IGI30 value remained low in the persistent diabetes group. In univariate analysis, younger age, newly diagnosed diabetes before transplantation, low baseline hemoglobin A1c, and high baseline IGI30 were significantly associated with remission of diabetes. After multivariate analysis, only newly diagnosed diabetes before transplantation and IGI30 at baseline were associated with remission of diabetes (34.00 [1.192-969.84], P = 0.039, and 17.625 [1.412-220.001], P = 0.026, respectively). Conclusion In conclusion, some kidney recipients with pre-transplant diabetes have diabetes remission 1 year after transplantation. Our prospective study revealed that preserved insulin secretory function and newly diagnosed diabetes at the time of kidney transplantation were favorable factors for which glucose metabolism did not worsen or improve 1 year after kidney transplantation.
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Affiliation(s)
- Jun Bae Bang
- Department of Surgery, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Chang-Kwon Oh
- Department of Surgery, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Yu Seun Kim
- Department of Transplantation Surgery and Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Sung Hoon Kim
- Department of Surgery, Yonsei University Wonju College of Medicine, Wonju Severance Christian Hospital, Wonju, Republic of Korea
| | - Hee Chul Yu
- Department of Surgery, Jeonbuk National University College of Medicine, Jeonju, Republic of Korea
| | - Chan-Duck Kim
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Man Ki Ju
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Byung Jun So
- Department of Surgery, Wonkwang University Hospital, Iksan, Republic of Korea
| | - Sang Ho Lee
- Department of Internal Medicine, College of Medicine, Kyung Hee University, Seoul, Republic of Korea
| | - Sang Youb Han
- Department of Internal Medicine, Inje University Ilsan Paik Hospital, Goyang, Republic of Korea
| | - Cheol Woong Jung
- Department of Surgery, Korea University College of Medicine, Seoul, Republic of Korea
| | - Joong Kyung Kim
- Department of Internal Medicine, Bong Seng Memorial Hospital, Busan, Republic of Korea
| | - Hyung Joon Ahn
- Department of Surgery, Kyung Hee University School of Medicine, Seoul, Republic of Korea
| | - Su Hyung Lee
- Department of Surgery, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Ja Young Jeon
- Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, Republic of Korea
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González Delgado A, Hernández AF, Marrero D, Maside AF, Barroso GH, Carreño EP, Acosta Sørensen C, Rodríguez-Rodríguez AE, Collantes T, Anabel R, Álvarez CR, Rivero A, Jiménez Sosa A, Macia M, Terán García E, Álvarez González A, González Rinne A, Rodríguez A, Redondo EDB, Rodríguez Adanero C, Hernández D, Torres Ramírez A, Porrini E. Inflammation on the Waiting List Is a Risk Factor for New-Onset Prediabetes and Post-Transplant Diabetes Mellitus: A Prospective Study. Nephron Clin Pract 2023; 147:560-571. [PMID: 37276852 DOI: 10.1159/000531334] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Accepted: 05/13/2023] [Indexed: 06/07/2023] Open
Abstract
INTRODUCTION Inflammation is a risk factor for diabetes in the general population. The role of inflammation in prediabetes or post-transplant diabetes mellitus (PTDM) is not clear. We evaluated the association between inflammatory markers in patients on the waiting list for renal transplantation and the onset of prediabetes and PTDM 12 months after transplantation. METHODS This is a post hoc analysis of a prospective study that included nondiabetic patients on the waiting list for kidney transplantation who underwent an oral glucose tolerance test (OGTT) and were followed up to 12 months after transplantation. At this time, those patients without PTDM underwent another OGTT. At pre-transplantation, five cytokines: TNFα, IL6, IL1β, CRP, MCP1 were determined. The association between inflammation and prediabetes/PTDM was evaluated using multiple regression models. RESULTS 110 patients on the waiting list were enrolled: 74 had normal glucose metabolism and 36 had prediabetes or occult diabetes. At 12 months, 53 patients had normal glucose metabolism, 25 prediabetes, and 32 PTDM. In multiple regression analysis, pre-transplant inflammation was not a risk factor for prediabetes or PTDM. This was attributed to the high interrelation between obesity, prediabetes, and inflammation: about 75% of the cases had these conditions. In a sub-analysis, we analyzed only patients without prediabetes and occult diabetes on the waiting list and found that TNFα levels and BMI at pre-transplantation were independently associated with the onset of prediabetes or PTDM 1 year after transplantation. CONCLUSIONS Pre-transplant inflammation and BMI are risk factors for prediabetes and PTDM in patients without glucose metabolism alterations.
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Affiliation(s)
| | | | - Domingo Marrero
- Nephrology Unit, Hospital Universitario de Canarias, Tenerife, Spain
| | - Andrés Franco Maside
- Central Laboratory, Immunology Unit, Hospital Universitario de Canarias (HUC), Tenerife, Spain
| | | | | | | | | | - Tatiana Collantes
- Hospital Clínico de la Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Rodríguez Anabel
- Nephrology Service, Hospital Universitario NS de La Candelaria, Tenerife, Spain
| | | | - Antonio Rivero
- Nephrology Service, Hospital Universitario NS de La Candelaria, Tenerife, Spain
| | | | - Manuel Macia
- Nephrology Service, Hospital Universitario NS de La Candelaria, Tenerife, Spain
| | | | | | | | - Aurelio Rodríguez
- Nephrology Unit, Hospital Universitario de Canarias, Tenerife, Spain
| | | | | | - Domingo Hernández
- Nephrology Service, Hospital Regional Universitario de Málaga, Universidad de Málaga, IBIMA, Málaga, Spain
| | - Armando Torres Ramírez
- Nephrology Unit, Hospital Universitario de Canarias, Tenerife, Spain
- Instituto de Tecnologías Biomédicas (ITB), Universidad de La Laguna, Tenerife, Spain
| | - Esteban Porrini
- Nephrology Unit, Hospital Universitario de Canarias, Tenerife, Spain
- Instituto de Tecnologías Biomédicas (ITB), Universidad de La Laguna, Tenerife, Spain
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Xiaojie N, Bicheng C, Yongling L, Tingting H, Yi Z, Chen Z. Metabolic-Related Index to Predict Post-Transplantation Diabetes Mellitus After Kidney Transplantation. Horm Metab Res 2023; 55:343-354. [PMID: 37130537 DOI: 10.1055/a-2053-2688] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/04/2023]
Abstract
Metabolic-related markers are novel tools for assessing insulin resistance. Early identification of post-transplantation diabetes mellitus (PTDM) before hyperglycemia can be helpful to attenuate the rapid development of diabetic complications. This article aims to explore the convenient and inexpensive values of metabolic-related markers, including TyG, TyG-BMI, TG/HDL-C, and non-HDL-C/HDL-C for predicting PTDM. The data of 191 kidney transplant recipients in our center were collected retrospectively. The association between TyG, TyG-BMI, TG/HDL-C, non-HDL-C/HDL-C and the risk of PTDM was examined by the area under the curve and logistic regression analyses. During 6 months follow-up, 12.04% of KT recipients developed PTDM, and significantly higher values of TyG-BMI, TyG, and non-HDL-C/HDL-C was found in patients with PTDM than in nondiabetic patients, especially among the recipients taking tacrolimus, regardless of gender. The incidence of PTDM increased along with the values of TyG or TyG-BMI. After adjusting for multiple potential factors, recipients with the highest trisector of TyG or TyG-BMI still had a higher risk of PTDM morbidity. In conclusion, TyG, TyG-BMI, TG/HDL-C and non-HDL-C/HDL-C can be used as cost-effective and promising monitors to identify individuals at high risk of PTDM, and TyG-BMI was the best alternative marker among the four markers.
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Affiliation(s)
- Ni Xiaojie
- Department of Urology (Renal Transplantation), Wenzhou Medical University First Affiliated Hospital, Wenzhou, China
| | - Chen Bicheng
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, Wenzhou Medical University First Affiliated Hospital, Wenzhou, China
| | - Li Yongling
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, Wenzhou Medical University First Affiliated Hospital, Wenzhou, China
| | - Huang Tingting
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, Wenzhou Medical University First Affiliated Hospital, Wenzhou, China
| | - Zhou Yi
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, Wenzhou Medical University First Affiliated Hospital, Wenzhou, China
| | - Zimiao Chen
- Department of Endocrine and Metabolic Diseases, Wenzhou Medical University First Affiliated Hospital, Wenzhou, China
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10
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Fariña-Hernández A, Marrero-Miranda D, Perez-Carreño E, De Vera-Gonzalez A, González A, Acosta-Sorensen C, Rodríguez-Rodríguez AE, Collantes T, García MDP, Rodríguez-Muñoz AI, Rodriguez-Alvarez C, Rivero A, Macía M, Teran E, Sanchez-Dorta NV, Perez-Tamajón L, Alvarez-González A, González-Rinne A, Rodríguez-Hernández A, De Bonis-Redondo E, Rodriguez-Adanero C, Hernández D, Porrini E, Torres A. Pretransplant evaluation and the risk of glucose metabolic alterations after renal transplantation: a prospective study. Nephrol Dial Transplant 2023; 38:778-786. [PMID: 36083994 DOI: 10.1093/ndt/gfac256] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Post-transplant prediabetes (PreDM) and diabetes (PTDM) are common and have an impact on cardiovascular events. We sought to investigate the pathogenesis and best approach for prediction. METHODS We prospectively studied 115 waitlisted patients from a single center without manifest diabetes. An oral glucose tolerance test (OGTT) was performed yearly until transplantation and 12 months later. Insulin secretion, insulin sensitivity (IS) and disposition index (DI) were derived from the OGTT. RESULTS PreDM and PTDM were observed in 27% and 28.6% of patients, respectively. Pretransplant age, body mass index (BMI), 120 min glucose, IS, DI, and prediabetes or undiagnosed diabetes were significantly associated with these alterations. In multivariate analysis, pretransplant age [odds ratio (OR) 1.5; 95% confidence interval (CI) 1.04-2.1], BMI (OR 1.16; 95% CI 1.04-1.3) and cumulative steroids (OR 1.5; 95% CI 1.02-2.2) were predictors of PreDM or PTDM. Receiver operating characteristic curve analysis showed that pretransplant BMI and 120 min glucose had the highest area under the curve (0.72; 95% CI 0.62-0.8; and 0.69; 95% CI 0.59-0.79, respectively). The highest discrimination cut-off for BMI (≥28.5 kg/m2) and 120 min glucose (≥123.5 mg/dL) yielded a similar number needed to diagnose (2.5). CONCLUSIONS PreDM or PTDM develops in waitlisted patients with an ineffective insulin secretion and BMI shows a similar diagnostic capacity to OGTT. Pretransplant interventions may reduce post-transplant glucose alterations.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | - Antonio Rivero
- Nephrology Service, Hospital Universitario NS de La Candelaria, Tenerife, Spain
| | - Manuel Macía
- Nephrology Service, Hospital Universitario NS de La Candelaria, Tenerife, Spain
| | - Elena Teran
- Nephrology Service, Hospital Universitario de Canarias, Tenerife, Spain
| | | | | | | | | | | | | | | | - Domingo Hernández
- Nephrology Service, Hospital Regional Universitario de Málaga, Universidad de Málaga, IBIMA
| | - Esteban Porrini
- Instituto de Tecnologías Biomédicas (ITB), Universidad de La Laguna, Tenerife, Spain
| | - Armando Torres
- Nephrology Service, Hospital Universitario de Canarias, Tenerife, Spain.,Instituto de Tecnologías Biomédicas (ITB), Universidad de La Laguna, Tenerife, Spain
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11
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Alfieri C, Favi E, Campioli E, Cicero E, Molinari P, Campise M, Gandolfo MT, Regalia A, Cresseri D, Messa P, Castellano G. Prevalence and Risk Factors of Abnormal Glucose Metabolism and New-Onset Diabetes Mellitus after Kidney Transplantation: A Single-Center Retrospective Observational Cohort Study. MEDICINA (KAUNAS, LITHUANIA) 2022; 58:1608. [PMID: 36363565 PMCID: PMC9694737 DOI: 10.3390/medicina58111608] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 10/22/2022] [Accepted: 11/03/2022] [Indexed: 11/09/2022]
Abstract
Background and objectives: New-onset diabetes after transplantation (NODAT) represents a primary cause of morbidity and allograft loss. We assessed prevalence and risk factors for NODAT in a population of Italian kidney transplant (KT) recipients. Methods: Data from 522 KT performed between January 2004 and December 2014 were analyzed. Participants underwent clinical examination; blood and urine laboratory tests were obtained at baseline, one, six, and 12-month of follow-up to detect glucose homeostasis abnormalities and associated metabolic disorders. An oral glucose tolerance test (OGTT) was performed at six months in 303 subjects. Results: Most patients were Caucasian (82.4%) with a mean age of 48 ± 12 years. The prevalence of abnormal glucose metabolism (AGM) and NODAT was 12.6% and 10.7%, respectively. Comparing characteristics of patients with normal glucose metabolism (NGM) to those with NODAT, we found a significant difference in living donation (16.6% vs. 6.1%; p = 0.03) and age at transplant (46 ± 12 vs. 56 ± 9 years; p = 0.0001). Also, we observed that patients developing NODAT had received higher cumulative steroid doses (1-month: 1165 ± 593 mg vs. 904 ± 427 mg; p = 0.002; 6-month:2194 ± 1159 mg vs. 1940 ± 744 mg; p = 0.002). The NODAT group showed inferior allograft function compared to patients with NGM (1-year eGFR: 50.1 ± 16.5 vs. 57 ± 20 mL/min/1.73 m2; p = 0.02). NODAT patients were more likely to exhibit elevated systolic blood pressure and higher total cholesterol and triglyceride levels than controls. Conclusions: The prevalence of NODAT in our cohort was relatively high. Patient age and early post-transplant events such as steroid abuse are associated with NODAT development.
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Affiliation(s)
- Carlo Alfieri
- Nephrology, Dialysis and Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, 20122 Milan, Italy
| | - Evaldo Favi
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, 20122 Milan, Italy
- Kidney Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
| | - Edoardo Campioli
- Nephrology, Dialysis and Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
| | - Elisa Cicero
- Nephrology, Dialysis and Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
| | - Paolo Molinari
- Nephrology, Dialysis and Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
| | - Mariarosaria Campise
- Nephrology, Dialysis and Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
| | | | - Anna Regalia
- Nephrology, Dialysis and Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
| | - Donata Cresseri
- Nephrology, Dialysis and Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
| | - Piergiorgio Messa
- Nephrology, Dialysis and Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
| | - Giuseppe Castellano
- Nephrology, Dialysis and Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, 20122 Milan, Italy
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12
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Sitagliptin Versus Placebo to Reduce the Incidence and Severity of Posttransplant Diabetes Mellitus After Kidney Transplantation-A Single-center, Randomized, Double-blind Controlled Trial. Transplantation 2022; 107:1180-1187. [PMID: 36279020 PMCID: PMC10125117 DOI: 10.1097/tp.0000000000004373] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
BACKGROUND Postkidney transplant diabetes mellitus (PTDM) affects cardiovascular, allograft, and recipient health. We tested whether early intervention with sitagliptin for hyperglycemia (blood glucose >200 mg/dL) within the first week of transplant and discontinued at 3 mo could prevent development of PTDM in patients without preexisting diabetes. METHODS The primary efficacy objective was to improve 2-h oral glucose tolerance test (OGTT) by > 20 mg/dL at 3 mo posttransplant. The secondary efficacy objective was to prevent new onset PTDM, defined as a normal OGTT at 3 mo. RESULTS Sixty-one patients consented, and 50 patients were analyzed. The 3-mo 2-h OGTT (end of treatment) was 141.00 ± 62.44 mg/dL in the sitagliptin arm and 165.22 ± 72.03 mg/dL ( P = 0.218) in the placebo arm. The 6-mo 2-h OGTT (end of follow-up) was 174.38 ± 77.93 mg/dL in the sitagliptin arm and 171.86 ± 83.69 ng/dL ( P = 0.918) in the placebo arm. Mean intrapatient difference between 3- and 6-mo 2-h OGTT in the 3-mo period off study drug was 27.56 + 52.74 mg/dL in the sitagliptin arm and -0.14 + 45.80 mg/dL in the placebo arm ( P = 0.0692). At 3 mo, 61.54% of sitagliptin and 43.48% of placebo patients had a normal 2-h OGTT ( P = 0.2062), with the absolute risk reduction 18.06%. There were no differences in HbA1c at 3 or 6 mo between sitagliptin and placebo groups. Participants tolerated sitagliptin well. CONCLUSION Although this study did not show a significant difference between groups, it can inform future studies in the use of sitagliptin in the very early posttransplant period.
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13
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Dachy A, Decuypere JP, Vennekens R, Jouret F, Mekahli D. Is autosomal dominant polycystic kidney disease an early sweet disease? Pediatr Nephrol 2022; 37:1945-1955. [PMID: 34988697 DOI: 10.1007/s00467-021-05406-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Revised: 12/09/2021] [Accepted: 12/10/2021] [Indexed: 10/19/2022]
Abstract
The clinical course of autosomal dominant polycystic kidney disease (ADPKD) starts in childhood. Evidence of the beneficial impact of early nephron-protective strategies and lifestyle modifications on ADPKD prognosis is accumulating. Recent studies have described the association of overweight and obesity with rapid disease progression in adults with ADPKD. Moreover, defective glucose metabolism and metabolic reprogramming have been reported in distinct ADPKD models highlighting these pathways as potential therapeutic targets in ADPKD. Several "metabolic" approaches are currently under evaluation in adults, including ketogenic diet, food restriction, and metformin therapy. No data are available on the impact of these approaches in childhood thus far. Yet, according to World Health Organization (WHO), we are currently facing a childhood obesity crisis with an increased prevalence of overweight/obesity in the pediatric population associated with a cardio-metabolic risk profile. The present review summarizes the knowledge about the role of glucose metabolism in the pathophysiology of ADPKD and underscores the possible harm of overweight and obesity in ADPKD especially in terms of long-term cardiovascular outcomes and renal prognosis.
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Affiliation(s)
- Angélique Dachy
- PKD Research Group, GPURE, Department of Development and Regeneration, KU Leuven, Leuven, Belgium.,Department of Pediatrics, ULiège Academic Hospital, Liège, Belgium.,Laboratory of Translational Research in Nephrology (LTRN), GIGA Cardiovascular Sciences, ULiège, Liège, Belgium
| | - Jean-Paul Decuypere
- PKD Research Group, GPURE, Department of Development and Regeneration, KU Leuven, Leuven, Belgium
| | - Rudi Vennekens
- Laboratory of Ion Channel Research, Department of Cellular and Molecular Medicine, VIB Center for Brain and Disease Research, KU Leuven, Leuven, Belgium
| | - François Jouret
- Laboratory of Translational Research in Nephrology (LTRN), GIGA Cardiovascular Sciences, ULiège, Liège, Belgium.,Division of Nephrology, Department of Internal Medicine, ULiège Academic Hospital, Liège, Belgium
| | - Djalila Mekahli
- PKD Research Group, GPURE, Department of Development and Regeneration, KU Leuven, Leuven, Belgium. .,Department of Pediatric Nephrology, University Hospitals Leuven, Herestraat 49, B-3000, Leuven, Belgium.
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14
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Vinson AJ, Thanamayooran A, Kiberd BA, West K, Siddiqi FS, Gunaratnam L, Tennankore KK. The Association of Pre-Transplant C-Peptide Level with the Development of Post-Transplant Diabetes: A Cohort Study. KIDNEY360 2022; 3:1738-1745. [PMID: 36514718 PMCID: PMC9717663 DOI: 10.34067/kid.0003742022] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Accepted: 06/28/2022] [Indexed: 01/12/2023]
Abstract
Background Post-transplant diabetes mellitus (PTDM) is an important complication after kidney transplantation that results in reduced patient and allograft survival. Although there are established risk factors for PTDM, whether pretransplant C-peptide levels associate with PTDM is unknown. Therefore, in this study, we aimed to examine the association of pretransplant C-peptide levels with PTDM. Methods This was a cohort study of nondiabetic adult patients who underwent kidney transplant in Nova Scotia, Canada, between January 1, 2016, and March 31, 2021, with fasting C-peptide levels measured before transplant. Multivariable logistic regression was used to determine the association of pretransplant C-peptide (dichotomized around the median) with PTDM at 1 year post transplant. Given the known association between pretransplant obesity and PTDM, we repeated our primary analysis in a cohort restricted to a BMI of 20-35 kg/m2. Results The median C-peptide value was 3251 (Q1 2480, Q3 4724); pretransplant C-peptide level was dichotomized at 3000 pmol/L. PTDM occurred in 25 (19%) individuals. Thirty percent of patients in the high and only 2% of patients in the low C-peptide groups developed PTDM (P<0.001). A C-peptide level ≥3000 pmol/L was strongly associated with PTDM in multivariable analysis (OR=18.9, 95% CI, 2.06 to 174.2). In a restricted cohort with a BMI of 20-35 kg/m2, an elevated pretransplant C-peptide remained independently associated with the risk of PTDM (OR=15.7, 95% CI, 1.64 to 150.3). C-peptide was the only factor independently associated with PTDM in this restricted BMI cohort. Conclusions A pretransplant C-peptide level ≥3000 pmol/L was associated with a nearly 20-fold increased odds of PTDM at 1 year post kidney transplantation. Identifying patients with high pretransplant C-peptide levels may therefore help identify those at risk for PTDM who may benefit from focused preventative and therapeutic interventions and support.
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Affiliation(s)
- Amanda J. Vinson
- Division of Nephrology, Department of Medicine, Dalhousie University, Halifax, Canada
| | - Aran Thanamayooran
- Division of Nephrology, Department of Medicine, Dalhousie University, Halifax, Canada
| | - Bryce A. Kiberd
- Division of Nephrology, Department of Medicine, Dalhousie University, Halifax, Canada
| | - Kenneth West
- Division of Nephrology, Department of Medicine, Dalhousie University, Halifax, Canada
| | - Ferhan S. Siddiqi
- Division of Endocrinology and Metabolism, Department of Medicine, Dalhousie University, Halifax, Canada
| | - Lakshman Gunaratnam
- Multiorgan Transplant Program, London Health Sciences Centre, London, Canada,Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, Canada
| | - Karthik K. Tennankore
- Division of Nephrology, Department of Medicine, Dalhousie University, Halifax, Canada
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15
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Singer J, Aouad LJ, Wyburn K, Gracey DM, Ying T, Chadban SJ. The Utility of Pre- and Post-Transplant Oral Glucose Tolerance Tests: Identifying Kidney Transplant Recipients With or at Risk of New Onset Diabetes After Transplant. Transpl Int 2022; 35:10078. [PMID: 35368638 PMCID: PMC8967957 DOI: 10.3389/ti.2022.10078] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Accepted: 02/24/2022] [Indexed: 11/13/2022]
Abstract
Background: New onset diabetes after transplant (NODAT) is common in kidney transplant recipients (KTRs). Identifying patients at risk prior to transplant may enable strategies to mitigate NODAT, with a pre-transplant oral glucose tolerance test (OGTT) suggested by the KDIGO 2020 Guidelines for this purpose. Methods: We investigated the utility of pre- and post-transplant OGTTs to stratify risk and diagnose NODAT in a retrospective, single-centre cohort study of all non-diabetic KTRs transplanted between 2003 and 2018. Results: We identified 597 KTRs who performed a pre-transplant OGTT, of which 441 had their post-transplant glycaemic status determined by a clinical diagnosis of NODAT or OGTT. Pre-transplant dysglycaemia was identified in 28% of KTRs and was associated with increasing age (p < 0.001), BMI (p = 0.03), and peritoneal dialysis (p < 0.001). Post-transplant dysglycaemia was common with NODAT and impaired glucose tolerance (IGT) occurring in 143 (32%) and 121 (27%) patients, respectively. Pre-transplant IGT was strongly associated with NODAT development (OR 3.8, p < 0.001). Conclusion: A pre-transplant OGTT identified candidates at increased risk of post-transplant dysglycaemia and NODAT, as diagnosed by an OGTT. Robust prospective trials are needed to determine whether various interventions can reduce post-transplant risk for candidates with an abnormal pre-transplant OGTT.
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Affiliation(s)
- Julian Singer
- Department of Renal Medicine, Kidney Centre, Level 2 Professor Marie Bashir Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia.,Kidney Node, Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia.,Central Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
| | - Leyla J Aouad
- Department of Renal Medicine, Kidney Centre, Level 2 Professor Marie Bashir Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia.,Kidney Node, Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia.,Central Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
| | - Kate Wyburn
- Department of Renal Medicine, Kidney Centre, Level 2 Professor Marie Bashir Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia.,Kidney Node, Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia.,Central Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
| | - David M Gracey
- Department of Renal Medicine, Kidney Centre, Level 2 Professor Marie Bashir Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia.,Kidney Node, Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia.,Central Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
| | - Tracey Ying
- Department of Renal Medicine, Kidney Centre, Level 2 Professor Marie Bashir Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia.,Kidney Node, Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia.,Central Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
| | - Steven J Chadban
- Department of Renal Medicine, Kidney Centre, Level 2 Professor Marie Bashir Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia.,Kidney Node, Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia.,Central Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
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16
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Immunosuppressive drugs and associated complications in abdominal organ transplantation. Curr Opin Crit Care 2022; 28:208-215. [PMID: 35142726 DOI: 10.1097/mcc.0000000000000927] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE OF REVIEW Intensive care management of patients who have undergone organ transplantation of liver, small bowel, pancreas, and/or kidney requires a basic knowledge of immunosuppression principles and the management of immunosuppressive medications. This review highlights the core principles of immunosuppression management in abdominal organ transplantation with a focus on complications arising from immunosuppressive drugs, both in the immediate postoperative period and in long-term usage. RECENT FINDINGS The general principles of management of immunosuppression in the abdominal organ transplant population have remained largely unchanged. Improvements in drug monitoring coupled with improvements in knowledge of pathways involved in allograft rejection have further refined immunosuppressive therapy. Infectious and central nervous system complications remain prevalent and are common complications of immunosuppressive drug therapy. SUMMARY For the intensive care professional who cares for abdominal organ transplant recipients, a foundational knowledge of the core principles of immunosuppression management is essential. In addition, an understanding of the common immunosuppressive drug regimens and the complications associated with these regimens is required for optimal management, risk assessment, and outcomes.
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17
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Ben-David E, Hull R, Banerjee D. Diabetes mellitus in dialysis and renal transplantation. Ther Adv Endocrinol Metab 2021; 12:20420188211048663. [PMID: 34631007 PMCID: PMC8495524 DOI: 10.1177/20420188211048663] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Accepted: 08/29/2021] [Indexed: 12/31/2022] Open
Abstract
Diabetes mellitus is the commonest cause of end-stage kidney failure worldwide and is a proven and significant risk factor for the development of cardiovascular disease. Renal impairment has a significant impact on the physiology of glucose homeostasis as it reduces tissue sensitivity to insulin and reduces insulin clearance. Renal replacement therapy itself affects glucose control: peritoneal dialysis may induce hyperglycaemia due to glucose-rich dialysate and haemodialysis often causes hypoglycaemia due to the relatively low concentration of glucose in the dialysate. Autonomic neuropathy which is common in chronic kidney disease (CKD) and diabetes increases the risk for asymptomatic hypoglycaemia. Pharmacological options for improving glycaemic control are limited due to alterations to drug metabolism. Impaired glucose tolerance and diabetes are also common in the post-kidney-transplant setting and increase the risk of graft failure and mortality. This review seeks to summarise the literature and tackle the intricacies of glycaemic management in patients with CKD who are either on maintenance haemodialysis or have received a kidney transplant. It outlines changes to glycaemic targets, monitoring of glycaemic control, the use of oral hypoglycaemic agents, the management of severe hyperglycaemia in dialysis and kidney transplantation patients.
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Affiliation(s)
- Eyal Ben-David
- Renal and Transplantation Unit, St George's University Hospitals NHS Foundation Trust, London, UK
| | - Richard Hull
- Renal and Transplantation Unit, St George's University Hospitals NHS Foundation Trust, London, UK
| | - Debasish Banerjee
- Renal and Transplantation Unit, St George's University Hospitals NHS Foundation Trust, Room G2.113, Second Floor, Grosvenor Wing, Blackshaw Road, Tooting, London SW17 0QT, UK
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18
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Tong L, Li W, Zhang Y, Zhou F, Zhao Y, Zhao L, Liu J, Song Z, Yu M, Zhou C, Yu A. Tacrolimus inhibits insulin release and promotes apoptosis of Min6 cells through the inhibition of the PI3K/Akt/mTOR pathway. Mol Med Rep 2021; 24:658. [PMID: 34278483 DOI: 10.3892/mmr.2021.12297] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Accepted: 06/06/2021] [Indexed: 11/06/2022] Open
Abstract
As a calcineurin inhibitor, tacrolimus is commonly used as a first‑line immunosuppressant in organ transplant recipients. Post‑transplantation diabetes mellitus (PTDM) is a common complication following kidney transplantation and is associated with immunosuppressant drugs, such as tacrolimus. PTDM caused by tacrolimus may be related to its influence on insulin secretion and insulin resistance. However, the specific mechanism has not been fully elucidated. The aim of the present study was to investigate whether the PI3K/Akt/mTOR signaling pathway served an important role in the pathogenesis of PTDM induced by tacrolimus. In the present study, the Cell Counting Kit‑8 assay was used to measure the effect of tacrolimus on the viability of Min6 mouse insulinoma cells. The effects of tacrolimus on the insulin secretion and the activity of caspase‑3 of Min6 cells stimulated by glucose exposure were measured by ELISA. Superoxide dismutase (SOD) and malondialdehyde (MDA) levels were measured using WST‑8 and thiobarbituric acid assays, respectively. The effects of tacrolimus on the mRNA expression levels of PI3K, Akt and mTOR were detected by reverse transcription‑quantitative PCR (RT‑qPCR), whereas the protein expression levels of PI3K, Akt, mTOR, phosphorylated (p)‑AKT and p‑mTOR in Min6 cells were assessed using western blotting. The present data indicated that, compared with the control group, 5, 25 and 50 ng/ml tacrolimus treatment could inhibit the insulin secretion of Min6 cells stimulated by glucose solution, and 50 ng/ml tacrolimus could notably decrease the stimulation index (P<0.05). Moreover, 50 ng/ml tacrolimus markedly increased the activity of caspase‑3 by 175.1% (P<0.05), it also decreased the SOD activity (P<0.01) and increased MDA levels (P<0.05). The RT‑qPCR results demonstrated that the mRNA expression levels of PI3K, Akt and mTOR were downregulated by 25 and 50 ng/ml tacrolimus (P<0.01). Furthermore, the western blotting results suggested that tacrolimus had no significant effects on the expression levels of total PI3K, Akt and mTOR proteins (P>0.05), but 25 and 50 ng/ml tacrolimus could significantly inhibit the expression levels of p‑Akt and p‑mTOR (P<0.01). In conclusion, tacrolimus decreased the activity and insulin secretion of pancreatic β cells and induced the apoptosis of islet β cells by inhibiting the mRNA expression levels of PI3K, Akt and mTOR and reducing the phosphorylation of Akt and mTOR proteins in the PI3K/Akt/mTOR signaling pathway, which may ultimately lead to the occurrence of diabetes mellitus, and may be considered as one of the specific mechanisms of PTDM caused by tacrolimus.
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Affiliation(s)
- Ling Tong
- Department of Clinical Pharmacy, General Hospital of Central Theater Command, Wuhan, Hubei 430000, P.R. China
| | - Weiliang Li
- Department of Clinical Pharmacy, General Hospital of Central Theater Command, Wuhan, Hubei 430000, P.R. China
| | - Ying Zhang
- Department of Clinical Pharmacy, General Hospital of Central Theater Command, Wuhan, Hubei 430000, P.R. China
| | - Fan Zhou
- Department of Clinical Pharmacy, General Hospital of Central Theater Command, Wuhan, Hubei 430000, P.R. China
| | - Yan Zhao
- Department of Clinical Pharmacy, General Hospital of Central Theater Command, Wuhan, Hubei 430000, P.R. China
| | - Linlin Zhao
- Department of Clinical Pharmacy, General Hospital of Central Theater Command, Wuhan, Hubei 430000, P.R. China
| | - Jing Liu
- Department of Clinical Pharmacy, General Hospital of Central Theater Command, Wuhan, Hubei 430000, P.R. China
| | - Zhirui Song
- Department of Clinical Pharmacy, General Hospital of Central Theater Command, Wuhan, Hubei 430000, P.R. China
| | - Mengchen Yu
- Department of Clinical Pharmacy, General Hospital of Central Theater Command, Wuhan, Hubei 430000, P.R. China
| | - Chengrui Zhou
- Department of Clinical Pharmacy, General Hospital of Central Theater Command, Wuhan, Hubei 430000, P.R. China
| | - Airong Yu
- Department of Clinical Pharmacy, General Hospital of Central Theater Command, Wuhan, Hubei 430000, P.R. China
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Morelli MC, Rendina M, La Manna G, Alessandria C, Pasulo L, Lenci I, Bhoori S, Messa P, Biancone L, Gesualdo L, Russo FP, Petta S, Burra P. Position paper on liver and kidney diseases from the Italian Association for the Study of Liver (AISF), in collaboration with the Italian Society of Nephrology (SIN). Dig Liver Dis 2021; 53 Suppl 2:S49-S86. [PMID: 34074490 DOI: 10.1016/j.dld.2021.03.035] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Revised: 03/31/2021] [Accepted: 03/31/2021] [Indexed: 02/07/2023]
Abstract
Liver and kidney are strictly connected in a reciprocal manner, in both the physiological and pathological condition. The Italian Association for the Study of Liver, in collaboration with the Italian Society of Nephrology, with this position paper aims to provide an up-to-date overview on the principal relationships between these two important organs. A panel of well-recognized international expert hepatologists and nephrologists identified five relevant topics: 1) The diagnosis of kidney damage in patients with chronic liver disease; 2) Acute kidney injury in liver cirrhosis; 3) Association between chronic liver disease and chronic kidney disease; 4) Kidney damage according to different etiology of liver disease; 5) Polycystic kidney and liver disease. The discussion process started with a review of the literature relating to each of the five major topics and clinical questions and related statements were subsequently formulated. The quality of evidence and strength of recommendations were graded according to the GRADE system. The statements presented here highlight the importance of strong collaboration between hepatologists and nephrologists for the management of critically ill patients, such as those with combined liver and kidney impairment.
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Affiliation(s)
- Maria Cristina Morelli
- Internal Medicine Unit for the treatment of Severe Organ Failure, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico di S.Orsola, Bologna, Italy, Via Albertoni 15, 40138, Bologna, Italy
| | - Maria Rendina
- Gastroenterology Unit, Department of Emergency and Organ Transplantation, University of Bari, Policlinic Hospital, Piazza G. Cesare 11, 70124, Bari, Italy
| | - Gaetano La Manna
- Department of Experimental Diagnostic and Specialty Medicine (DIMES), Nephrology, Dialysis and Renal Transplant Unit, St. Orsola Hospital, University of Bologna, Via Massarenti 9, 40138, Bologna, Italy
| | - Carlo Alessandria
- Division of Gastroenterology and Hepatology, Città della Salute e della Scienza Hospital, University of Torino, Corso Bramante 88, 10126, Torino, Italy
| | - Luisa Pasulo
- Gastroenterology and Transplant Hepatology, "Papa Giovanni XXIII" Hospital, Piazza OMS 1, 24127, Bergamo, Italy
| | - Ilaria Lenci
- Department of Internal Medicine, Hepatology Unit, Tor Vergata University, Rome Viale Oxford 81, 00133, Rome, Italy
| | - Sherrie Bhoori
- Hepatology and Hepato-Pancreatic-Biliary Surgery and Liver Transplantation, Fondazione IRCCS, Istituto Nazionale Tumori, Via Giacomo Venezian, 1, 20133, Milan, Italy
| | - Piergiorgio Messa
- Unit of Nephrology, Università degli Studi di Milano, Via Commenda 15, 20122, Milano, Italy; Nephrology, Dialysis and Renal Transplant Unit-Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, Via Commenda 15, 20122 Milano, Italy
| | - Luigi Biancone
- Division of Nephrology Dialysis and Transplantation, Department of Medical Sciences, Città Della Salute e della Scienza Hospital, University of Turin, Corso Bramante, 88-10126, Turin, Italy
| | - Loreto Gesualdo
- Nephrology Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation, Università degli Studi di Bari "Aldo Moro", Piazza G. Cesare 11, 70124, Bari, Italy
| | - Francesco Paolo Russo
- Multivisceral Transplant Unit, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padua, Via Giustiniani 2, 35128, Padua, Italy
| | - Salvatore Petta
- Section of Gastroenterology and Hepatology, PROMISE, University of Palermo, Piazza delle Cliniche, 2 90127, Palermo, Italy
| | - Patrizia Burra
- Multivisceral Transplant Unit, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padua, Via Giustiniani 2, 35128, Padua, Italy.
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20
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Topaloğlu Ö, Cengiz M, Cengiz A, Evren B, Yoloğlu S, Yılmaz S, Şahin İ. New-onset diabetes mellitus after liver transplantation in the patients with acute liver failure. Int J Diabetes Dev Ctries 2021. [DOI: 10.1007/s13410-021-00922-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/22/2022] Open
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21
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Acosta-Gualandri A, Blydt-Hansen T, Islam N, Amed S. Risk Factors for Developing Posttransplant Diabetes After Pediatric Kidney Transplant in a Canadian Tertiary Care Children's Hospital Between 1995 and 2016. Can J Diabetes 2021; 45:481-489. [PMID: 34176612 DOI: 10.1016/j.jcjd.2021.05.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2020] [Revised: 04/07/2021] [Accepted: 05/10/2021] [Indexed: 11/16/2022]
Abstract
BACKGROUND Posttransplant diabetes mellitus (PTDM) is a serious complication in kidney transplant recipients (KTRs) due to its negative impact on graft and patient survival. Although reported in 3% to 20% of pediatric KTRs, it has not been as well characterized in adults. In this study we describe incidence and risk factors associated with development of PTDM in pediatric KTRs. METHODS This work is a retrospective cohort study of nondiabetic pediatric patients, aged 6 months to 19 years, who underwent a first kidney transplant during 1995 to 2016. We estimated the cumulative incidence rate and used multivariable logistic regression to identify the diabetogenic risk factors for PTDM. RESULTS A total of 142 KTRs were included in this study. The cumulative incidence of PTDM was 31% and 14.1% in the first and second year posttransplant, respectively. Significant risk factors for PTDM in the first year after transplant included: dysglycemia in the first 8 to 30 days posttransplant (adjusted odds ratio [aOR], 3.02; 95% confidence interval [CI], 1.21 to 7.53; p=0.018) and use of sirolimus in the first 30 days posttransplant (aOR, 5.33; 95% CI, 1.16 to 24.35; p=0.031). No significant association was found with typical diabetogenic factors. CONCLUSIONS The incidence of PTDM is high among pediatric KTRs. Independent risk factors associated with PTDM included meeting the criteria for dysglycemia or diabetes and sirolimus use in the first month posttransplant. Typical diabetogenic risk factors for type 2 diabetes were not associated with increased risk. This study provides valuable information for posttransplant medical care and future research.
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Affiliation(s)
- Alejandra Acosta-Gualandri
- Division of Endocrinology, Department of Pediatrics, British Columbia Children's Hospital and the University of British Columbia, Vancouver, British Columbia, Canada
| | - Tom Blydt-Hansen
- Division of Nephrology, Department of Pediatrics, British Columbia Children's Hospital and the University of British Columbia, Vancouver, British Columbia, Canada
| | - Nazrul Islam
- Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
| | - Shazhan Amed
- Division of Endocrinology, Department of Pediatrics, British Columbia Children's Hospital and the University of British Columbia, Vancouver, British Columbia, Canada.
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22
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Rodríguez-Rodríguez AE, Porrini E, Hornum M, Donate-Correa J, Morales-Febles R, Khemlani Ramchand S, Molina Lima MX, Torres A. Post-Transplant Diabetes Mellitus and Prediabetes in Renal Transplant Recipients: An Update. Nephron Clin Pract 2021; 145:317-329. [PMID: 33902027 DOI: 10.1159/000514288] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Accepted: 01/04/2021] [Indexed: 11/19/2022] Open
Abstract
Post-transplant diabetes mellitus (PTDM) is a frequent and relevant complication after renal transplantation: it affects 20-30% of renal transplant recipients and increases the risk for cardiovascular and infectious events. Thus, understanding pathogenesis of PTDM would help limiting its consequences. In this review, we analyse novel aspects of PTDM, based on studies of the last decade, such as the clinical evolution of PTDM, early and late, the reversibility rate, diagnostic criteria, risk factors, including pre-transplant metabolic syndrome and insulin resistance (IR) and the interaction between these factors and immunosuppressive medications. Also, we discuss novel pathogenic factors, in particular the role of β-cell function in an environment of IR and common pathways between pre-existing cell damage and tacrolimus-induced toxicity. The relevant role of prediabetes in the pathogenesis of PTDM and cardiovascular disease is also addressed. Finally, current evidence on PTDM treatment is discussed.
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Affiliation(s)
| | - Esteban Porrini
- Research Unit, Hospital Universitario de Canarias, Universidad de la Laguna, Tenerife, Spain
- Faculty of Medicine, Universidad de la Laguna, Tenerife, Spain
- Instituto de Tecnologías Biomédicas (ITB), Faculty of Medicine, Universidad de la Laguna, Tenerife, Spain
| | - Mads Hornum
- Department of Nephrology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Javier Donate-Correa
- Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Tenerife, Spain
| | | | | | | | - Armando Torres
- Faculty of Medicine, Universidad de la Laguna, Tenerife, Spain
- Instituto de Tecnologías Biomédicas (ITB), Faculty of Medicine, Universidad de la Laguna, Tenerife, Spain
- Servicio de Nefrología, Hospital Universitario de Canarias, Tenerife, Spain
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23
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Choudhary NS, Saraf N, Saigal S, Soin AS. Long-term Management of the Adult Liver Transplantation Recipients. J Clin Exp Hepatol 2021; 11:239-253. [PMID: 33746450 PMCID: PMC7953009 DOI: 10.1016/j.jceh.2020.06.010] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Accepted: 06/14/2020] [Indexed: 12/12/2022] Open
Abstract
The survival of liver transplantation (LT) recipients has been improved remarkably in short-term. The major causes of mortality in long-term include nonimmunological causes such as cardiovascular, de novo malignancy, chronic kidney disease, and recurrence of primary disease. Rejection-related mortality is rare in the long-term after LT. We discuss nonrejection causes of long-term morbidity/mortality, risk factors, and management strategies in LT recipients. In addition, we discuss osteoporosis, contraception, and pregnancy in LT recipients.
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Key Words
- AIH, autoimmune hepatitis
- BMI, body mass index
- CKD, chronic kidney disease
- CNI, calcineurin inhibitors
- CVD, cardiovascular disease
- DDLT, deceased donor liver transplantation
- DM, diabetes mellitus
- DNM, de novo malignancy
- HCV, hepatitis C virus
- HR, hazard ratio
- IUCD, Intrauterine contraceptive devices
- LDLT, living donor liver transplantation
- LT, liver transplantation
- MDRD, Modification of Diet in Renal Disease
- MMF, mycophenolate
- MS, metabolic syndrome
- NAFLD, nonalcoholic fatty liver disease
- NASH, nonalcoholic steatohepatitis
- OR, odds ratio
- PBC, primary biliary cholangitis
- PSC, primary sclerosing cholangitis
- PTDM, posttransplantation diabetes mellitus
- PTMS, posttransplantation metabolic syndrome
- SVR, sustained virological response
- cardiovascular disease
- de novo malignancy
- eGFR, estimated glomerular filtration rate
- mTORi, Mammalian target of rapamycin inhibitors
- osteoporosis
- pregnancy
- recurrence
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Affiliation(s)
- Narendra S. Choudhary
- Institute of Liver Transplantation and Regenerative Medicine, Medanta The Medicity, Gurgaon, Delhi (NCR), India
| | - Neeraj Saraf
- Institute of Liver Transplantation and Regenerative Medicine, Medanta The Medicity, Gurgaon, Delhi (NCR), India
| | - Sanjiv Saigal
- Institute of Liver Transplantation and Regenerative Medicine, Medanta The Medicity, Gurgaon, Delhi (NCR), India
| | - Arvinder S. Soin
- Institute of Liver Transplantation and Regenerative Medicine, Medanta The Medicity, Gurgaon, Delhi (NCR), India
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Bang JB, Oh CK, Kim YS, Kim SH, Yu HC, Kim CD, Ju MK, So BJ, Lee SH, Han SY, Jung CW, Kim JK, Lee SH, Jeon JY. Insulin Secretion and Insulin Resistance Trajectories over 1 Year after Kidney Transplantation: A Multicenter Prospective Cohort Study. Endocrinol Metab (Seoul) 2020; 35:820-829. [PMID: 33202516 PMCID: PMC7803593 DOI: 10.3803/enm.2020.743] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Accepted: 09/22/2020] [Indexed: 01/02/2023] Open
Abstract
BACKGROUND We investigated the changing patterns of insulin secretion and resistance and risk factors contributing to the development of post-transplant diabetes mellitus (PTDM) in kidney recipients under tacrolimus-based immunosuppression regimen during 1 year after transplantation. METHODS This was a multicenter prospective cohort study. Of the 168 subjects enrolled in this study, we analyzed a total 87 kidney transplant recipients without diabetes which was assessed by oral glucose tolerance test before transplantation. We evaluated the incidence of PTDM and followed up the index of insulin secretion (insulinogenic index [IGI]) and resistance (homeostatic model assessment for insulin resistance [HOMA-IR]) at 3, 6, 9 months, and 1 year after transplantation by oral glucose tolerance test and diabetes treatment. We also assessed the risk factors for incident PTDM. RESULTS PTDM developed in 23 of 87 subjects (26.4%) during 1 year after transplantation. More than half of total PTDM (56.5%) occurred in the first 3 months after transplantation. During 1 year after transplantation, insulin resistance (HOMA-IR) was increased in both PTDM and no PTDM group. In no PTDM group, the increase in insulin secretory function to overcome insulin resistance was also observed. However, PTDM group showed no increase in insulin secretion function (IGI). Old age, status of prediabetes and episode of acute rejection were significantly associated with the development of PTDM. CONCLUSION In tacrolimus-based immunosuppressive drugs regimen, impaired insulin secretory function for reduced insulin sensitivity contributed to the development of PTDM than insulin resistance during 1 year after transplantation.
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Affiliation(s)
- Jun Bae Bang
- Department of Surgery, Ajou University School of Medicine, Suwon, Seoul, Korea
| | - Chang-Kwon Oh
- Department of Surgery, Ajou University School of Medicine, Suwon, Seoul, Korea
| | - Yu Seun Kim
- Department of Transplantation Surgery and Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Korea
| | - Sung Hoon Kim
- Department of Surgery, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Seoul, Korea
| | - Hee Chul Yu
- Department of Surgery, Jeonbuk National University Medical School, Jeonju, Seoul, Korea
| | - Chan-Duck Kim
- Department of Internal Medicine, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Seoul, Korea
| | - Man Ki Ju
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Byung Jun So
- Department of Surgery, Wonkwang University Hospital, Iksan, Seoul, Korea
| | - Sang Ho Lee
- Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Korea
| | - Sang Youb Han
- Department of Internal Medicine, Inje University Ilsan Paik Hospital, Goyang, Seoul, Korea
| | - Cheol Woong Jung
- Department of Surgery, Korea University College of Medicine, Seoul, Korea
| | - Joong Kyung Kim
- Department of Internal Medicine, Bong Seng Memorial Hospital, Busan, Korea
| | - Su Hyung Lee
- Department of Surgery, Ajou University School of Medicine, Suwon, Seoul, Korea
- Su Hyung Lee, Department of Surgery, Ajou University School of Medicine, 164 World cup-ro, Yeongtong-gu, Suwon 16499, Korea, Tel: +82-31-219-5760, Fax: +82-31-219-4438, E-mail:
| | - Ja Young Jeon
- Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, Korea
- Corresponding authors: Ja Young Jeon, Department of Endocrinology and Metabolism, Ajou University School of Medicine, 164 World cup-ro, Yeongtong-gu, Suwon 16499, Korea, Tel: +82-31-219-7459, Fax: +82-31-219-4497, E-mail:
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25
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Van Laecke S, Van Biesen W. Novel non-cystic features of polycystic kidney disease: having new eyes or seeking new landscapes. Clin Kidney J 2020; 14:746-755. [PMID: 33777359 PMCID: PMC7986322 DOI: 10.1093/ckj/sfaa138] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2020] [Indexed: 01/08/2023] Open
Abstract
For decades, researchers have been trying to decipher the complex pathophysiology of autosomal dominant polycystic kidney disease (ADPKD). So far these efforts have led to clinical trials with different candidate treatments, with tolvaptan being the only molecule that has gained approval for this indication. As end-stage kidney disease due to ADPKD has a substantial impact on health expenditures worldwide, it is likely that new drugs targeting kidney function will be developed. On the other hand, recent clinical observations and experimental data, including PKD knockout models in various cell types, have revealed unexpected involvement of many other organs and cell systems of variable severity. These novel non-cystic features, some of which, such as lymphopenia and an increased risk to develop infections, should be validated or further explored and might open new avenues for better risk stratification and a more tailored approach. New insights into the aberrant pathways involved with abnormal expression of PKD gene products polycystin-1 and -2 could, for instance, lead to a more directed approach towards early-onset endothelial dysfunction and subsequent cardiovascular disease. Furthermore, a better understanding of cellular pathways in PKD that can explain the propensity to develop certain types of cancer can guide post-transplant immunosuppressive and prophylactic strategies. In the following review article we will systematically discuss recently discovered non-cystic features of PKD and not well-established characteristics. Overall, this knowledge could enable us to improve the outcome of PKD patients apart from ongoing efforts to slow down cyst growth and attenuate kidney function decline.
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Affiliation(s)
- Steven Van Laecke
- Renal Division, Department of Internal Medicine, Ghent University Hospital, Ghent, Belgium
| | - Wim Van Biesen
- Renal Division, Department of Internal Medicine, Ghent University Hospital, Ghent, Belgium
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26
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Autosomal Dominant Polycystic Kidney Disease Is a Risk Factor for Posttransplantation Diabetes Mellitus: An Updated Systematic Review and Meta-analysis. Transplant Direct 2020; 6:e553. [PMID: 32548247 PMCID: PMC7213605 DOI: 10.1097/txd.0000000000000989] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2020] [Accepted: 01/29/2020] [Indexed: 12/12/2022] Open
Abstract
Supplemental Digital Content is available in the text. Autosomal dominant polycystic kidney disease (ADPKD) is linked with risk for posttransplantation diabetes mellitus (PTDM), but this association has methodologic limitations like diagnostic criteria. The aim of this study was to use contemporary diagnostic criteria for PTDM and explore any risk association for kidney transplant recipients with ADPKD.
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27
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Chadban SJ, Ahn C, Axelrod DA, Foster BJ, Kasiske BL, Kher V, Kumar D, Oberbauer R, Pascual J, Pilmore HL, Rodrigue JR, Segev DL, Sheerin NS, Tinckam KJ, Wong G, Knoll GA. KDIGO Clinical Practice Guideline on the Evaluation and Management of Candidates for Kidney Transplantation. Transplantation 2020; 104:S11-S103. [PMID: 32301874 DOI: 10.1097/tp.0000000000003136] [Citation(s) in RCA: 345] [Impact Index Per Article: 69.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
The 2020 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline on the Evaluation and Management of Candidates for Kidney Transplantation is intended to assist health care professionals worldwide who evaluate and manage potential candidates for deceased or living donor kidney transplantation. This guideline addresses general candidacy issues such as access to transplantation, patient demographic and health status factors, and immunological and psychosocial assessment. The roles of various risk factors and comorbid conditions governing an individual's suitability for transplantation such as adherence, tobacco use, diabetes, obesity, perioperative issues, causes of kidney failure, infections, malignancy, pulmonary disease, cardiac and peripheral arterial disease, neurologic disease, gastrointestinal and liver disease, hematologic disease, and bone and mineral disorder are also addressed. This guideline provides recommendations for evaluation of individual aspects of a candidate's profile such that each risk factor and comorbidity are considered separately. The goal is to assist the clinical team to assimilate all data relevant to an individual, consider this within their local health context, and make an overall judgment on candidacy for transplantation. The guideline development process followed the Grades of Recommendation Assessment, Development, and Evaluation (GRADE) approach. Guideline recommendations are primarily based on systematic reviews of relevant studies and our assessment of the quality of that evidence, and the strengths of recommendations are provided. Limitations of the evidence are discussed with differences from previous guidelines noted and suggestions for future research are also provided.
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Affiliation(s)
- Steven J Chadban
- Royal Prince Alfred Hospital and Charles Perkins Centre, University of Sydney, Sydney, Australia
| | - Curie Ahn
- Seoul National University, Seoul, South Korea
| | | | - Bethany J Foster
- The Montreal Children's Hospital, McGill University Health Centre, Montreal, Canada
| | | | - Vijah Kher
- Medanta Kidney and Urology Institute, Haryana, India
| | - Deepali Kumar
- University Health Network, University of Toronto, Toronto, Canada
| | | | | | | | | | - Dorry L Segev
- Johns Hopkins University School of Medicine, Baltimore, MD
| | | | | | | | - Gregory A Knoll
- The Ottawa Hospital and Ottawa Hospital Research Institute, Ottawa, Canada
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28
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Abstract
Solid organ transplantation (SOT) is an established therapeutic option for chronic disease resulting from end-stage organ dysfunction. Long-term use of immunosuppression is associated with post-transplantation diabetes mellitus (PTDM), placing patients at increased risk of infections, cardiovascular disease and mortality. The incidence rates for PTDM have varied from 10 to 40% between different studies. Diagnostic criteria have evolved over the years, as a greater understating of PTDM has been reached. There are differences in pathophysiology and clinical course of type 2 diabetes and PTDM. Hence, managing this condition can be a challenge for a diabetes physician, as there are several factors to consider when tailoring therapy for post-transplant patients to achieve better glycaemic as well as long-term transplant outcomes. This article is a detailed review of PTDM, examining the pathogenesis, diagnostic criteria and management in light of the current evidence. The therapeutic options are discussed in the context of their safety and potential drug-drug interactions with immunosuppressive agents.
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Affiliation(s)
| | - Kathryn Biddle
- St George's University Hospitals NHS Foundation Trust, London, UK
| | | | - Shazli Azmi
- Manchester University NHS Foundation Trust, Manchester, UK
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29
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Porrini E, Díaz JM, Moreso F, Lauzurrica R, Ibernon M, Torres IS, Ruiz RB, Rodríguez Rodríguez AE, Mallén PD, Bayés-Genís B, Gainza FJ, Osorio JM, Osuna A, Domínguez R, Ruiz JC, Sosa AJ, Rinne AG, Miranda DM, Macías M, Torres A. Prediabetes is a risk factor for cardiovascular disease following renal transplantation. Kidney Int 2019; 96:1374-1380. [PMID: 31611066 DOI: 10.1016/j.kint.2019.06.026] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2019] [Revised: 06/04/2019] [Accepted: 06/27/2019] [Indexed: 12/14/2022]
Abstract
Prediabetes and post-transplant diabetes mellitus affect about 20-30% of renal transplant patients. The latter is a risk factor for cardiovascular disease. However, no clear evidence linking prediabetes and cardiovascular disease is available. To study this we analyzed the impact of prediabetes on cardiovascular disease in 603 renal transplant patients followed with repeated oral glucose tests for up to five years and a long term survival evaluation. Prediabetes and post-transplant diabetes mellitus were defined at 12 months after transplantation to avoid their high reversibility rate before this period. 73 cardiovascular events were observed. The incidence of events was significantly higher in patients with either prediabetes, (17%; 0.023 person/year) or post-transplant diabetes mellitus (20%; 0.028 person/year) than in normal individuals, (7%; 0.0095 person/year). The incidence of events was comparable between prediabetes and post-transplant diabetes mellitus. Prediabetes at 12 months was a risk factor for cardiovascular events in univariate and multivariate Cox survival analyses (hazard ratio 2.24, 95% confidence interval 1.11-4.52). Prediabetes at three months and hemoglobin A1c at 12 months were not significantly associated with cardiovascular disease. Thus, prediabetes is a risk factor for cardiovascular disease in renal transplantation, a population at high risk for cardiovascular events. Since prediabetes is potentially a reversible condition, there is an opportunity to prevent cardiovascular disease in this population.
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Affiliation(s)
- Esteban Porrini
- Instituto de Tecnologías Biomédicas, University of La Laguna, Tenerife, Spain.
| | | | | | | | | | | | | | | | | | | | | | - José Manuel Osorio
- Nephrology Section, Hospital Nuestra Señora Virgen de las Nieves, Granada, Spain
| | - Antonio Osuna
- Nephrology Section, Hospital Nuestra Señora Virgen de las Nieves, Granada, Spain
| | - Rosa Domínguez
- Nephrology Unit, Hospital Marqués de Valdecilla, Santander, Spain
| | - Juan Carlos Ruiz
- Nephrology Unit, Hospital Marqués de Valdecilla, Santander, Spain
| | | | | | | | - Manuel Macías
- Nephrology Unit, Hospital Universitario Nuestra Señora de la Candelaria, Tenerife, Spain
| | - Armando Torres
- Instituto de Tecnologías Biomédicas, University of La Laguna, Tenerife, Spain; Nephrology Unit, Hospital Universitario de Canarias, La Laguna, Spain
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30
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Alnasrallah B, Goh TL, Chan LW, Manley P, Pilmore H. Transplantation and diabetes (Transdiab): a pilot randomised controlled trial of metformin in impaired glucose tolerance after kidney transplantation. BMC Nephrol 2019; 20:147. [PMID: 31035960 PMCID: PMC6489311 DOI: 10.1186/s12882-019-1321-2] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2018] [Accepted: 03/31/2019] [Indexed: 01/02/2023] Open
Abstract
BACKGROUND Post transplantation diabetes mellitus (PTDM) is a common and serious complication after renal transplantation with significant morbidity and mortality. Metformin has proven benefits in the general population and might be advantageous in the prevention and management of PTDM. METHODS Transplantation and Diabetes (Transdiab) is a single-centre, unblinded, pilot randomised controlled trial assessing the feasibility, tolerability and efficacy of metformin after renal transplantation in patients with impaired glucose tolerance (IGT). Participants had an oral glucose tolerance test (OGTT) in the 4-12 weeks post-transplantation; those with IGT were randomised to standard care or standard care and metformin 500 mg twice daily and followed up for 12 months. RESULTS Seventy eight patients had an OGTT over 24 months, 25 of them had IGT, of those, 19 patients were randomised, giving a feasibility of recruitment of 24.4%. Ten patients were randomised to metformin and 9 patients to standard care. Tolerability and efficacy was similar between the 2 groups with no serious adverse events. There was no difference in secondary outcomes relating to the metabolic profile. CONCLUSIONS The use of metformin post renal transplantation appeared feasible and safe. Larger randomised controlled trials (RCTs) are needed to establish and confirm the efficacy and safety of metformin post renal transplantation. TRIAL REGISTRATION Australian New Zealand Clinical Trials Registry ACTRN12614001171606 . Date of registration 7/11/2014.
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Affiliation(s)
- Basil Alnasrallah
- Department of Nephrology, Auckland City Hospital, Auckland, 1023, New Zealand.
| | - Tze Liang Goh
- Department of Nephrology, Auckland City Hospital, Auckland, 1023, New Zealand
| | - Lai Wan Chan
- Department of Nephrology, Auckland City Hospital, Auckland, 1023, New Zealand
| | - Paul Manley
- Department of Nephrology, Auckland City Hospital, Auckland, 1023, New Zealand
| | - Helen Pilmore
- Department of Nephrology, Auckland City Hospital, Auckland, 1023, New Zealand.,Department of Medicine, University of Auckland, Auckland, New Zealand
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Ussif AM, Åsberg A, Halden TAS, Nordheim E, Hartmann A, Jenssen T. Validation of diagnostic utility of fasting plasma glucose and HbA1c in stable renal transplant recipients one year after transplantation. BMC Nephrol 2019; 20:12. [PMID: 30630438 PMCID: PMC6327477 DOI: 10.1186/s12882-018-1171-3] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2018] [Accepted: 12/03/2018] [Indexed: 01/29/2023] Open
Abstract
Background The use of HbA1c ≥6.5% for diagnosis of diabetes has been challenged for post-transplantation diabetes mellitus (PTDM) also known as new onset diabetes after transplantation (NODAT) due to a low sensitivity early after renal transplantation. PTDM diagnosed with an oral glucose tolerance test (OGTT) is highly predictable for long-term patient mortality. HbA1c was introduced for diagnosis based on the risk of developing diabetic retinopathy. The utility of HbA1c measures versus glucose criteria has not been widely assessed in stable transplant patients but still HbA1c is widely used in this population. The aim of the present analyses was to validate the utility of fasting plasma glucose (FPG) together with HbA1c in diagnosing PTDM in stable renal transplant recipients (RTRs). Methods OGTT’s were performed one year after transplantation in 494 consecutive RTRs without diabetes. FPG and HbA1c were obtained the same day, before starting the OGTT. Validation was performed using C-statistics and logistic regression analyses. Results PTDM was diagnosed in 51 patients (10.3%) by glucose criteria, 38 (74%) patients were diagnosed by FPG ≥7.0 mmol/L [126.1 mg/dl], and 13 (26%) only by 2-h plasma glucose. Six of the latter had HbA1c ≥6.5%. Only seven patients out of the 51 (13.7%) PTDM patients remained undiagnosed when HbA1c ≥6.5% was used together with FPG, and five of these regressed to normal after a median follow-up of 14 months. ROC curves including FPG and HbA1c versus OGTT derived criteria revealed an AUC of 0.858. Conclusions Combining standard diagnostic FPG and HbA1c criteria captured almost all patients with persistent PTDM in stable RTRs. The combined use of the criteria appears to be an applicable diagnostic strategy for PTDM without the need of an OGTT one year post-transplant. Trial registration Retrospectively registered.
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Affiliation(s)
- Amin M Ussif
- Department of Transplantation Medicine, Oslo University Hospital, Rikshospitalet, P.O.Box 4950, 0424, Oslo, Nydalen, Norway.
| | - Anders Åsberg
- Department of Transplantation Medicine, Oslo University Hospital, Rikshospitalet, P.O.Box 4950, 0424, Oslo, Nydalen, Norway.,Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway.,The Norwegian Renal Registry, Oslo University Hospital, Rikshospitalet, Oslo, Norway
| | - Thea Anine Strøm Halden
- Department of Transplantation Medicine, Oslo University Hospital, Rikshospitalet, P.O.Box 4950, 0424, Oslo, Nydalen, Norway
| | - Espen Nordheim
- Department of Transplantation Medicine, Oslo University Hospital, Rikshospitalet, P.O.Box 4950, 0424, Oslo, Nydalen, Norway.,Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Anders Hartmann
- Department of Transplantation Medicine, Oslo University Hospital, Rikshospitalet, P.O.Box 4950, 0424, Oslo, Nydalen, Norway.,Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Trond Jenssen
- Department of Transplantation Medicine, Oslo University Hospital, Rikshospitalet, P.O.Box 4950, 0424, Oslo, Nydalen, Norway.,Metabolic and Renal Research Group, Faculty of Health Sciences UiT, The Arctic University of Norway, Tromsø, Norway
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32
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Yang B, Wang Q, Wang R, Xu T. Clinical Manifestation, Management and Prognosis of Acute Myocardial Infarction in Autosomal Dominant Polycystic Kidney Disease. Kidney Blood Press Res 2018; 43:1806-1812. [PMID: 30504716 DOI: 10.1159/000495638] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2018] [Accepted: 11/21/2018] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND/AIMS Cardiovascular complications are the most common cause of death in individuals with autosomal dominant polycystic kidney disease (ADPKD), yet there is no substantial data concerning the clinical characteristics of acute myocardial infarction (AMI) in this population. This study thus aimed to investigate AMI in persons with ADPKD. METHODS A retrospective analysis of ADPKD patients admitted to our hospital over a 13 year period was conducted. Age and gender-matched control patients without ADPKD were also selected at a ratio of 1: 10. RESULTS A total of 52 ADPKD and 520 non-ADPKD patients were enrolled in the present study, with those in the former group exhibiting significantly poorer kidney function. The distribution of AMI types differed significantly between these two groups. The incidence of ST-segment elevation myocardial infarction (STEMI) was higher (75.0%) and the incidence of non-ST segment elevation myocardial infarction (NSTEMI) was lower (25.0%) in the ADPKD group. At the onset of AMI, sudden cardiac death (SCD) was more common in ADPKD patients (11.5% vs. 4.6%). In terms of risk factors, the occurrence of hypertension was greater in ADPKD patients (78.8% vs. 39.6%). With regard to subsequent management, ADPKD patients had a higher prevalence of triple-branch coronary lesions (21.1% vs. 11.2%), undergoing more coronary artery bypass grafting (CABG) (7.7% vs. 5.4%) and fewer percutaneous coronary interventions (PCI) (73.1% vs. 84.6%). Overall, ADPKD patients had higher rates of mortality (13.5% vs. 6.2%). CONCLUSION ADPKD patients with AMI suffer from more severe conditions and difficult therapies, resulting in a poorer prognosis.
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Affiliation(s)
- Bo Yang
- Department of Urology, Peking University People's Hospital, Beijing, China
| | - Qi Wang
- Department of Urology, Peking University People's Hospital, Beijing, China
| | - Rui Wang
- Department of Urology, Peking University People's Hospital, Beijing, China
| | - Tao Xu
- Department of Urology, Peking University People's Hospital, Beijing, China,
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Torres A, Hernández D, Moreso F, Serón D, Burgos MD, Pallardó LM, Kanter J, Díaz Corte C, Rodríguez M, Diaz JM, Silva I, Valdes F, Fernández-Rivera C, Osuna A, Gracia Guindo MC, Gómez Alamillo C, Ruiz JC, Marrero Miranda D, Pérez-Tamajón L, Rodríguez A, González-Rinne A, Alvarez A, Perez-Carreño E, de la Vega Prieto MJ, Henriquez F, Gallego R, Salido E, Porrini E. Randomized Controlled Trial Assessing the Impact of Tacrolimus Versus Cyclosporine on the Incidence of Posttransplant Diabetes Mellitus. Kidney Int Rep 2018; 3:1304-1315. [PMID: 30450457 PMCID: PMC6224662 DOI: 10.1016/j.ekir.2018.07.009] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Revised: 06/08/2018] [Accepted: 07/02/2018] [Indexed: 12/16/2022] Open
Abstract
INTRODUCTION Despite the high incidence of posttransplant diabetes mellitus (PTDM) among high-risk recipients, no studies have investigated its prevention by immunosuppression optimization. METHODS We conducted an open-label, multicenter, randomized trial testing whether a tacrolimus-based immunosuppression and rapid steroid withdrawal (SW) within 1 week (Tac-SW) or cyclosporine A (CsA) with steroid minimization (SM) (CsA-SM), decreased the incidence of PTDM compared with tacrolimus with SM (Tac-SM). All arms received basiliximab and mycophenolate mofetil. High risk was defined by age >60 or >45 years plus metabolic criteria based on body mass index, triglycerides, and high-density lipoprotein-cholesterol levels. The primary endpoint was the incidence of PTDM after 12 months. RESULTS The study comprised 128 de novo renal transplant recipients without pretransplant diabetes (Tac-SW: 44, Tac-SM: 42, CsA-SM: 42). The 1-year incidence of PTDM in each arm was 37.8% for Tac-SW, 25.7% for Tac-SM, and 9.7% for CsA-SM (relative risk [RR] Tac-SW vs. CsA-SM 3.9 [1.2-12.4; P = 0.01]; RR Tac-SM vs. CsA-SM 2.7 [0.8-8.9; P = 0.1]). Antidiabetic therapy was required less commonly in the CsA-SM arm (P = 0.06); however, acute rejection rate was higher in CsA-SM arm (Tac-SW 11.4%, Tac-SM 4.8%, and CsA-SM 21.4% of patients; cumulative incidence P = 0.04). Graft and patient survival, and graft function were similar among arms. CONCLUSION In high-risk patients, tacrolimus-based immunosuppression with SM provides the best balance between PTDM and acute rejection incidence.
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Affiliation(s)
- Armando Torres
- Hospital Universitario de Canarias, Instituto de Tecnologías Biomédicas (ITB)-Universidad de La Laguna, Tenerife, Spain
| | - Domingo Hernández
- Hospital Regional Universitario de Málaga, Universidad de Málaga, IBIMA, Málaga, Spain
| | - Francesc Moreso
- Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Daniel Serón
- Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - María Dolores Burgos
- Hospital Regional Universitario de Málaga, Universidad de Málaga, IBIMA, Málaga, Spain
| | | | - Julia Kanter
- Hospital Universitario Dr Peset, Valencia, Spain
| | | | | | | | | | - Francisco Valdes
- Complexo Hospitalario Universitario Juan Canalejo, A Coruña, Spain
| | | | - Antonio Osuna
- Hospital Universitario Virgen de las Nieves, Granada, Spain
| | | | | | - Juan C. Ruiz
- Hospital Universitario Marqués de Valdecilla, Santander, Spain
| | - Domingo Marrero Miranda
- Hospital Universitario de Canarias, Instituto de Tecnologías Biomédicas (ITB)-Universidad de La Laguna, Tenerife, Spain
| | - Lourdes Pérez-Tamajón
- Hospital Universitario de Canarias, Instituto de Tecnologías Biomédicas (ITB)-Universidad de La Laguna, Tenerife, Spain
| | - Aurelio Rodríguez
- Hospital Universitario de Canarias, Instituto de Tecnologías Biomédicas (ITB)-Universidad de La Laguna, Tenerife, Spain
| | - Ana González-Rinne
- Hospital Universitario de Canarias, Instituto de Tecnologías Biomédicas (ITB)-Universidad de La Laguna, Tenerife, Spain
| | - Alejandra Alvarez
- Hospital Universitario de Canarias, Instituto de Tecnologías Biomédicas (ITB)-Universidad de La Laguna, Tenerife, Spain
| | - Estefanía Perez-Carreño
- Hospital Universitario de Canarias, Instituto de Tecnologías Biomédicas (ITB)-Universidad de La Laguna, Tenerife, Spain
| | - María José de la Vega Prieto
- Hospital Universitario de Canarias, Instituto de Tecnologías Biomédicas (ITB)-Universidad de La Laguna, Tenerife, Spain
| | - Fernando Henriquez
- Hospital Universitario de Gran Canaria Dr Negrín, Las Palmas de GC, Spain
| | - Roberto Gallego
- Hospital Universitario de Gran Canaria Dr Negrín, Las Palmas de GC, Spain
| | - Eduardo Salido
- Hospital Universitario de Canarias, Instituto de Tecnologías Biomédicas (ITB)-Universidad de La Laguna, Tenerife, Spain
| | - Esteban Porrini
- Hospital Universitario de Canarias, Instituto de Tecnologías Biomédicas (ITB)-Universidad de La Laguna, Tenerife, Spain
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Kumar S, Sanyal D, Das P, Bhattacharjee K, Rungta R. An observational Prospective Study to Evaluate the Preoperative Risk Factors of New-onset Diabetes Mellitus after Renal Transplantation in a Tertiary Care Centre in Eastern India. Indian J Endocrinol Metab 2018; 22:610-615. [PMID: 30294568 PMCID: PMC6166566 DOI: 10.4103/ijem.ijem_121_18] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVES This study aimed to determine the pre-transplant risk factors as independent predictors on the new-onset of diabetes mellitus after renal transplants (NODATs). MATERIALS AND METHODS A single-centred prospective real-world observational study of 100 subjects who underwent renal transplantation over a period of 2 years. All known patients with diabetes were excluded from the study. NODAT was defined according to the American Diabetes Association definition. In addition to pre-transplant workup 2 days prior to transplant, post-transplant follow-up done on weekly basis for 1st month, every 15th day from 1st month to 3rd month, monthly from 3rd month to 12th month. Each transplant patient followed up for 1 year post-transplant or for 6 months post-development of NODAT, whichever was later. All the pre-transplant variables namely body mass index (BMI), family history of diabetes mellitus (DM), HbA1c, fasting insulin level, fasting c-peptide level, serology for hepatitis B, C, serum magnesium level and pre-operative insulin ressistance were further compared between NODAT and non-NODAT groups at the end of the study to assess their strength of associations. RESULTS Among the 100 subjects included in the study, 24 developed NODAT. Risk factors namely age, family history of DM, BMI, hepatitis B and C infection, total cholesterol, triglyceride level, pre-operative HbA1c, pre-operative insulin resistance and pre-diabetes were significantly higher, whereas beta-cell function, ABO compatibility and magnesium levels being significantly lower in NODAT cohort. CONCLUSION The incidence of NODAT is quite high (24%). Risk of development of NODAT was related to traditional as well as novel risk factors. Key aspects lies in identifying patients at risk of developing NODAT, using traditional risk factors for early diagnosis and introducing interventions on modifiable risk factors for prevention and timely intervention.
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Affiliation(s)
- Santosh Kumar
- Department of Nephrology, Rabindranath Tagore International Institute of Cardiac Sciences, EM Bypass, Kolkata, West Bengal, India
| | - Debmalya Sanyal
- Department of Endocrinology, KPC Medical College, Jadavpur, Kolkata, West Bengal, India
| | - Pratik Das
- Department of Nephrology, Rabindranath Tagore International Institute of Cardiac Sciences, EM Bypass, Kolkata, West Bengal, India
| | | | - Rohit Rungta
- Department of Nephrology, Rabindranath Tagore International Institute of Cardiac Sciences, EM Bypass, Kolkata, West Bengal, India
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Conte C, Secchi A. Post-transplantation diabetes in kidney transplant recipients: an update on management and prevention. Acta Diabetol 2018; 55:763-779. [PMID: 29619563 DOI: 10.1007/s00592-018-1137-8] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2018] [Accepted: 03/26/2018] [Indexed: 12/14/2022]
Abstract
Post-transplantation diabetes mellitus (PTDM) may severely impact both short- and long-term outcomes of kidney transplant recipients in terms of graft and patient survival. However, PTDM often goes undiagnosed is underestimated or poorly managed. A diagnosis of PTDM should be delayed until the patient is on stable maintenance doses of immunosuppressive drugs, with stable kidney graft function and in the absence of acute infections. Risk factors for PTDM should be assessed during the pre-transplant evaluation period, in order to reduce the likelihood of developing diabetes. The oral glucose tolerance test is considered as the gold standard for diagnosing PTDM, whereas HbA1c is not reliable during the first months after transplantation. Glycaemic targets should be individualised, and comorbidities such as dyslipidaemia and hypertension should be treated with drugs that have the least possible impact on glucose metabolism, at doses that do not interact with immunosuppressants. While insulin is the preferred agent for treating inpatient hyperglycaemia in the immediate post-transplantation period, little evidence is available to guide therapeutic choices in the management of PTDM. Metformin and incretins may offer some advantage over other glucose-lowering agents, particularly with respect to risk of hypoglycaemia and weight gain. Tailoring immunosuppressive regimens may be of help, although maintenance of good kidney function should be prioritised over prevention/treatment of PTDM. The aim of this narrative review is to provide an overview of the available evidence on management and prevention of PTDM, with a focus on the available therapeutic options.
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Affiliation(s)
- Caterina Conte
- I.R.C.C.S. Ospedale San Raffaele, Via Olgettina 60, 20132, Milan, Italy.
| | - Antonio Secchi
- I.R.C.C.S. Ospedale San Raffaele, Via Olgettina 60, 20132, Milan, Italy
- Vita-Salute San Raffaele University, Via Olgettina 58, 20132, Milan, Italy
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Gomes V, Ferreira F, Guerra J, Bugalho MJ. New-onset diabetes after kidney transplantation: Incidence and associated factors. World J Diabetes 2018; 9:132-137. [PMID: 30079149 PMCID: PMC6068739 DOI: 10.4239/wjd.v9.i7.132] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2018] [Revised: 05/24/2018] [Accepted: 06/13/2018] [Indexed: 02/05/2023] Open
Abstract
AIM To determine the incidence and associated factors of new-onset diabetes after transplantation (NODAT) in a Portuguese central hospital.
METHODS This single-center retrospective study involved consecutive adult nondiabetic transplant recipients, who had undergone kidney transplantation between January 2012 and March 2016. NODAT was diagnosed according to the criteria of the American Diabetes Association. Data were collected from an institutional database of the Nephrology and Kidney Transplantation Department (Santa Maria Hospital, Lisbon, Portugal) and augmented with data of laboratorial parameters collected from the corresponding patient electronic medical records. Exclusion criteria were preexisting diabetes mellitus, missing information and follow-up period of less than 12 mo. Data on demographic and clinical characteristics as well as anthropometric and laboratorial parameters were also collected. Patients were divided into two groups: With and without NODAT - for statistical comparison.
RESULTS A total of 156 patients received kidney transplant during the study period, 125 of who were included in our analysis. NODAT was identified in 27.2% of the patients (n = 34; 53% female; mean age: 49.5 ± 10.8 years; median follow-up: 36.4 ± 2.5 mo). The incidence in the first year was 24.8%. The median time to diagnosis was 3.68 ± 5.7 mo after transplantation, and 76.5% of the patients developed NODAT in the first 3 mo. In the group that did not develop NODAT (n = 91), 47% were female, with mean age of 46.4 ± 13.5 years and median follow-up of 35.5 ± 1.6 mo. In the NODAT group, the pretransplant fasting plasma glucose (FPG) levels were significantly higher [101 (96.1-105.7) mg/dL vs 92 (91.4-95.8) mg/dL, P = 0.007] and pretransplant impaired fasting glucose (IFG) was significantly more frequent (51.5% vs 27.7%, P = 0.01). Higher pretransplant FPG levels and pretransplant IFG were found to be predictive risk factors for NODAT development [odds ratio (OR): 1.059, P = 0.003; OR: 2.772, P = 0.017, respectively].
CONCLUSION NODAT incidence was high in our renal transplant recipients, particularly in the first 3 mo posttransplant, and higher pretransplant FPG level and IFG were risk factors.
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Affiliation(s)
- Vânia Gomes
- Endocrinology, Diabetes and Metabolism Department, Santa Maria Hospital, Lisbon 1649-035, Portugal
| | - Florbela Ferreira
- Endocrinology, Diabetes and Metabolism Department, Santa Maria Hospital, Lisbon 1649-035, Portugal
| | - José Guerra
- Nephrology and Kidney Transplantation Department, Santa Maria Hospital, Lisbon 1649-035, Portugal
| | - Maria João Bugalho
- Endocrinology, Diabetes and Metabolism Department, Santa Maria Hospital, Lisbon 1649-035, Portugal
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Jankowska M, Qureshi AR, Barany P, Heimburger O, Stenvinkel P, Lindholm B. Do metabolic derangements in end-stage polycystic kidney disease differ versus other primary kidney diseases? Nephrology (Carlton) 2017; 23:31-36. [DOI: 10.1111/nep.12927] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2016] [Revised: 09/16/2016] [Accepted: 09/20/2016] [Indexed: 12/21/2022]
Affiliation(s)
- Magdalena Jankowska
- Division of Renal Medicine and Baxter Novum; Karolinska Institutet; Stockholm Sweden
- Department of Nephrology, Transplantology and Internal Medicine; Medical University of Gdansk; Poland
| | - Abdul Rashid Qureshi
- Division of Renal Medicine and Baxter Novum; Karolinska Institutet; Stockholm Sweden
| | - Peter Barany
- Division of Renal Medicine and Baxter Novum; Karolinska Institutet; Stockholm Sweden
| | - Olof Heimburger
- Division of Renal Medicine and Baxter Novum; Karolinska Institutet; Stockholm Sweden
| | - Peter Stenvinkel
- Division of Renal Medicine and Baxter Novum; Karolinska Institutet; Stockholm Sweden
| | - Bengt Lindholm
- Division of Renal Medicine and Baxter Novum; Karolinska Institutet; Stockholm Sweden
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Guthoff M, Wagner R, Weichbrodt K, Nadalin S, Königsrainer A, Häring HU, Fritsche A, Heyne N. Dynamics of Glucose Metabolism After Kidney Transplantation. Kidney Blood Press Res 2017; 42:598-607. [PMID: 28930756 DOI: 10.1159/000481375] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2016] [Accepted: 05/12/2017] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND/AIMS Posttransplantation diabetes mellitus (PTDM) impacts patient and allograft survival after kidney transplantation. Prediabetes, which is an independent risk factor for PTDM, is modifiable also in a post-transplant setting. Understanding the risks and dynamics of impaired glucose metabolism after transplantation is a key component for targeted intervention. METHODS A retrospective chart analysis of all adult non-diabetic renal allograft recipients (n=251, 2007-2014) was performed. Longitudinal follow-up included fasting plasma glucose and HbA1c, as well as data on allograft function and immunosuppression at consecutive time points (months 3-6 to >5 years post transplantation). RESULTS Throughout follow-up, median prevalence of prediabetes and PTDM was 53.3 [52.4-55.7]% and 15.4 [15.0-16.5]%, respectively. Continuously high fluxes between states of glucose metabolism, with individual patients' state deteriorating or improving over time, resulted in a high number of incident patients even long after transplantation. The greatest number of patients shifted between normal glucose tolerance and prediabetes, followed by those between prediabetes and PTDM. CONCLUSION Prediabetes and PTDM are highly prevalent after kidney transplantation and incidences remain relevant throughout follow-up. Patient fluxes into and out of the prediabetic state show that glucose metabolism is highly dynamic after transplantation. This provides a continuous opportunity for intervention in an aim to reduce diabetes-associated complications.
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Affiliation(s)
- Martina Guthoff
- Dept. of Endocrinology and Diabetology, Angiology, Nephrology and Clinical Chemistry, University of Tübingen, Tübingen, Germany.,Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany.,German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany
| | - Robert Wagner
- Dept. of Endocrinology and Diabetology, Angiology, Nephrology and Clinical Chemistry, University of Tübingen, Tübingen, Germany.,Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany.,German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany
| | - Karoline Weichbrodt
- Dept. of Endocrinology and Diabetology, Angiology, Nephrology and Clinical Chemistry, University of Tübingen, Tübingen, Germany
| | - Silvio Nadalin
- Dept. of General-, Visceral- and Transplant Surgery, University of Tübingen, Tübingen, Germany
| | - Alfred Königsrainer
- Dept. of General-, Visceral- and Transplant Surgery, University of Tübingen, Tübingen, Germany
| | - Hans-Ulrich Häring
- Dept. of Endocrinology and Diabetology, Angiology, Nephrology and Clinical Chemistry, University of Tübingen, Tübingen, Germany.,Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany.,German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany
| | - Andreas Fritsche
- Dept. of Endocrinology and Diabetology, Angiology, Nephrology and Clinical Chemistry, University of Tübingen, Tübingen, Germany.,Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany.,German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany
| | - Nils Heyne
- Dept. of Endocrinology and Diabetology, Angiology, Nephrology and Clinical Chemistry, University of Tübingen, Tübingen, Germany.,Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany.,German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany
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Diabetes Mellitus Following Renal Transplantation: Clinical and Pharmacological Considerations for the Elderly Patient. Drugs Aging 2017; 34:589-601. [PMID: 28718072 DOI: 10.1007/s40266-017-0478-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
Post-transplant diabetes mellitus occurs in 30-50% of cases during the first year post-renal transplantation. It is associated with increased morbidity, mortality and healthcare costs. Risk factors include age and specific immunosuppression regimens. At the same time, renal transplantation is increasingly indicated in elderly (aged >65 years) patients as this proportion of older patients in the prevalent dialysis population has increased. The immune system and β cells undergo senescence and this impacts on the risk for developing post-transplant diabetes and our ability to prevent such development. It may, however, be possible to identify patients at risk of developing post-transplant diabetes, enabling treatment protocols that prevent or reduce the impact of post-transplant diabetes. Much work remains to be completed in this area and is facilitated by the growing base of knowledge regarding the pathophysiology of post-transplant diabetes. Should post-transplant diabetes develop, there are a range of treatment options available. There is increasing interest in using newer agents, although their safety and efficacy in transplant recipients remains to be conclusively established.
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Schachtner T, Stein M, Reinke P. Diabetic kidney transplant recipients: Impaired infection control and increased alloreactivity. Clin Transplant 2017; 31. [DOI: 10.1111/ctr.12986] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/20/2017] [Indexed: 12/22/2022]
Affiliation(s)
- Thomas Schachtner
- Department of Nephrology and Internal Intensive Care; Campus Virchow Clinic; Charité University Medicine Berlin; Berlin Germany
- Berlin-Brandenburg Center of Regenerative Therapies (BCRT); Berlin Germany
- Berlin Institute of Health (BIH) - Charité and Max-Delbrück Center; Berlin Germany
| | - Maik Stein
- Berlin-Brandenburg Center of Regenerative Therapies (BCRT); Berlin Germany
| | - Petra Reinke
- Department of Nephrology and Internal Intensive Care; Campus Virchow Clinic; Charité University Medicine Berlin; Berlin Germany
- Berlin-Brandenburg Center of Regenerative Therapies (BCRT); Berlin Germany
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Magistroni R, Boletta A. Defective glycolysis and the use of 2-deoxy-D-glucose in polycystic kidney disease: from animal models to humans. J Nephrol 2017; 30:511-519. [PMID: 28390001 DOI: 10.1007/s40620-017-0395-9] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2017] [Accepted: 03/27/2017] [Indexed: 02/06/2023]
Abstract
Autosomal dominant polycystic kidney disease (ADPKD) is an inherited renal disease characterized by bilateral renal cyst formation. ADPKD is one of the most common rare disorders, accounting for ~10% of all patients with end-stage renal disease (ESRD). ADPKD is a chronic disorder in which the gradual expansion of cysts that form in a minority of nephrons eventually causes loss of renal function due to the compression and degeneration of the surrounding normal parenchyma. Numerous deranged pathways have been identified in the cyst-lining epithelia, prompting the design of potential therapies. Several of these potential treatments have proved effective in slowing down disease progression in pre-clinical animal studies, while only one has subsequently been proven to effectively slow down disease progression in patients, and it has recently been approved for therapy in Europe, Canada and Japan. Among the affected cellular functions and pathways, recent investigations have described metabolic derangement in ADPKD as a major trait offering additional opportunities for targeted therapies. In particular, increased aerobic glycolysis (the Warburg effect) has been described as a prominent feature of ADPKD kidneys and its inhibition using the glucose analogue 2-deoxy-D-glucose (2DG) proved effective in slowing down disease progression in preclinical models of the disease. At the same time, previous clinical experiences have been reported with 2DG, showing that this compound is well tolerated in humans with minimal and reversible side effects. In this work, we review the literature and speculate that 2DG could be a good candidate for a clinical trial in humans affected by ADPKD.
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Affiliation(s)
- Riccardo Magistroni
- Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Via Olgettina, 58, 20132, Milan, Italy
- Division of Nephrology and Hypertension, San Raffaele Hospital, Milan, Italy
- Division of Nephrology and Dialysis, AOU Policlinico di Modena, Università di Modena e Reggio Emilia, Modena, Italy
| | - Alessandra Boletta
- Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Via Olgettina, 58, 20132, Milan, Italy.
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A Prospective Study of Renal Transplant Recipients: A Fall in Insulin Secretion Underpins Dysglycemia After Renal Transplantation. Transplant Direct 2016; 2:e107. [PMID: 27826600 PMCID: PMC5096434 DOI: 10.1097/txd.0000000000000618] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2016] [Accepted: 07/25/2016] [Indexed: 02/06/2023] Open
Abstract
Background Dysglycemia (encompassing impaired glucose tolerance and diabetes mellitus) arising after renal transplantation is common and confers a significant cardiovascular mortality risk. Nonetheless, the pathophysiology of posttransplant dysglycemia is not well described. The aim of this study was to prospectively and comprehensively assess glucose handling in renal transplant recipients from before to 12 months after transplantation to determine the underpinning pathophysiology. Materials and Methods Intravenous and oral glucose tolerance testing was conducted before and at 3 and 12 months posttransplantation. An intravenous glucose tolerance test was also performed on day 7 posttransplantation. We followed up 16 transplant recipients for 3 months and 14 recipients for 12 months. Insulin secretion, resistance and a disposition index (DI (IV)), a measure of β cell responsiveness in the context of prevailing insulin resistance, were also determined. Results At 12 months, 50% of renal transplant recipients had dysglycemia. Dysglycemia was associated with a dramatic fall in DI (IV) and this loss in β cell function was evident as early as 3 months posttransplantation (23.5 pretransplant; 6.4 at 3 months and 12.2 at 12 months posttransplant). Differences in the β cell response to oral glucose challenge were evident pretransplant in those destined to develop dysglycemia posttransplant (2-hour blood glucose level 5.6 mmol/L versus 6.8 mmol/L; P < 0.01). Conclusions Dysglycemia after renal transplantation is common, and the loss of insulin secretion is a major contributor. Subclinical differences in glucose handling are evident pretransplant in those destined to develop dysglycemia potentially heralding a susceptible β cell which under the stressors associated with transplantation fails.
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Xue M, Lv C, Chen X, Liang J, Zhao C, Zhang Y, Huang X, Sun Q, Wang T, Gao J, Zhou J, Yu M, Fan J, Gao X. Donor liver steatosis: A risk factor for early new-onset diabetes after liver transplantation. J Diabetes Investig 2016; 8:181-187. [PMID: 27511316 PMCID: PMC5334314 DOI: 10.1111/jdi.12560] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2015] [Revised: 07/26/2016] [Accepted: 08/04/2016] [Indexed: 01/01/2023] Open
Abstract
AIMS/INTRODUCTION To investigate whether donor liver steatosis increases the incidence of new-onset diabetes after transplantation (NODAT) in liver transplant recipients. MATERIALS AND METHODS We retrospectively analyzed liver transplant recipients at Zhongshan Hospital, Shanghai, China, from April 2001 to December 2014. The final analysis involved 763 patients. The cumulative incidence of NODAT at 1, 3, 5 and 10 years after liver transplantation was investigated. Furthermore, according to the findings of donor liver biopsy before transplantation, patients were divided into steatotic and non-steatotic donor liver groups, and NODAT incidence was compared between these groups. Multivariate Cox regression was used to explore the risk factors for NODAT in the patients. RESULTS Of the 763 donors, 309 (40.5%) had liver steatosis. At the end of follow up, 130 (42.1%) patients in the steatotic donor liver group developed NODAT, an incidence that exceeded that in the non-steatotic donor liver group (P = 0.001). The cumulative incidence of NODAT among all patients at 1, 3, 5, and 10 years after transplantation was 33, 43, 50 and 56%, respectively. The cumulative incidences of NODAT at 1, 3, 5 and 10 years in the steatotic donor liver group were significantly higher than those in the non-steatotic donor liver group (P = 0.003). Multivariate Cox regression analyses showed that donor liver steatosis was an independent risk factor for NODAT among liver transplant recipients, after other potential risk factors were adjusted for (hazard ratio 1.774, 95% confidence interval: 1.025-3.073; P = 0.041). CONCLUSIONS Donor liver steatosis increases NODAT incidence among liver transplant recipients.
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Affiliation(s)
- Mengjuan Xue
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Chaoyang Lv
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xianying Chen
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China.,Department of Endocrinology and Metabolism, Hainan Provincial Nong Ken Hospital, Hainan, China
| | - Jing Liang
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Chenhe Zhao
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yao Zhang
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xiaowu Huang
- Department of Liver Surgery, Zhongshan Hospital, Fudan University, China
| | - Qiman Sun
- Department of Liver Surgery, Zhongshan Hospital, Fudan University, China
| | - Ting Wang
- Department of Liver Surgery, Zhongshan Hospital, Fudan University, China
| | - Jian Gao
- Center of Clinical Epidemiology and Evidence-based Medicine, Fudan University, Shanghai, China
| | - Jian Zhou
- Department of Liver Surgery, Zhongshan Hospital, Fudan University, China
| | - Mingxiang Yu
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jia Fan
- Department of Liver Surgery, Zhongshan Hospital, Fudan University, China
| | - Xin Gao
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
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Sinangil A, Celik V, Barlas S, Sakaci T, Koc Y, Basturk T, Akin EB, Ecder T. New-Onset Diabetes After Kidney Transplantation and Pretransplant Hypomagnesemia. Prog Transplant 2016; 26:55-61. [PMID: 27136250 DOI: 10.1177/1526924816633949] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
AIM Hypomagnesemia is a frequent finding in kidney transplant patients and plays a causal role in insulin resistance and diabetes. The aim of this study was to investigate whether the pretransplant magnesium (Mg) level is a risk factor for the development of new-onset diabetes after kidney transplantation (NODAT) and the presence of relationship between pretransplant hypomagnesemia and the development period of NODAT. METHODS Four hundred and nineteen nondiabetic renal transplant recipients were evaluated retrospectively. The patients were divided into NODAT and non-NODAT groups. The time of diagnosis of patients with NODAT was divided into 0 to 3, 3 to 6, 6 to 12 months, and after 12 months. Patients' characteristics and pretransplant Mg levels in NODAT were compared with non-NODAT, and it was investigated whether pretransplant hypomagnesemia was a risk factor for the development of NODAT. RESULTS Totally 70 (16.6%) patients (36 female [F], mean age 51.7 ± 8.2 years) were diagnosed with NODAT. Three hundred and forty-nine patients (115 F, mean age 43.2 ± 12.5 years) did not have NODAT. Pretransplant mean Mg level was 1.97 ± 0.40 mg/dL in patients with NODAT, while it was 2.5 ± 0.45 mg/dL in non-NODAT patients (P < .001). Serum Mg level was found to be similar in subgroups according to the development period of NODAT (P = .07). When patients were stratified according to quartiles of Mg level, the frequency of NODAT was significantly higher in patients in the lower quartile (Mg < 2.1 mg/dL; P < .001). Older age, high body mass index, and low pretransplant serum Mg levels were established as risk factors for developing NODAT. According to the quartile of Mg level, the risk of developing NODAT was highest in the lowest quartile. CONCLUSION Pretransplant hypomagnesemia is an independent risk factor of NODAT. Therefore, it is necessary to closely monitor the Mg levels in the posttransplant period.
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Affiliation(s)
- Ayse Sinangil
- Division of Nephrology, Department of Internal Medicine, Istanbul Bilim University, Istanbul, Turkey
| | - Vedat Celik
- Division of Nephrology, Department of Internal Medicine, Istanbul Bilim University, Istanbul, Turkey
| | - Soykan Barlas
- Renal Transplantation Unit, Istanbul Bilim University, Istanbul, Turkey
| | - Tamer Sakaci
- Clinical Nephrology, Sisli Hamidiye Etfal Research and Educational Hospital, Istanbul, Turkey
| | - Yener Koc
- Clinical Nephrology, Sisli Hamidiye Etfal Research and Educational Hospital, Istanbul, Turkey
| | - Taner Basturk
- Clinical Nephrology, Sisli Hamidiye Etfal Research and Educational Hospital, Istanbul, Turkey
| | - Emin Baris Akin
- Renal Transplantation Unit, Istanbul Bilim University, Istanbul, Turkey
| | - Tevfik Ecder
- Division of Nephrology, Department of Internal Medicine, Istanbul Bilim University, Istanbul, Turkey
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Cheungpasitporn W, Thongprayoon C, Vijayvargiya P, Anthanont P, Erickson SB. The Risk for New-Onset Diabetes Mellitus after Kidney Transplantation in Patients with Autosomal Dominant Polycystic Kidney Disease: A Systematic Review and Meta-Analysis. Can J Diabetes 2016; 40:521-528. [PMID: 27184299 DOI: 10.1016/j.jcjd.2016.03.001] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2015] [Revised: 02/09/2016] [Accepted: 03/01/2016] [Indexed: 12/12/2022]
Abstract
OBJECTIVES New-onset diabetes after kidney transplantation (NODAT) is associated with both renal allograft failure and increased rates of mortality. The objective of this meta-analysis was to evaluate the risk for NODAT in patients with autosomal dominant polycystic kidney disease (ADPKD). METHODS A literature search was performed using MEDLINE, EMBASE and Cochrane Database of Systematic Reviews from inception through July 2015. Studies that reported relative risks, odd ratios or hazard ratios comparing the risk for NODAT in patients with ADPKD were included. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using a random-effect, generic inverse variance method. RESULTS Included in the analysis were 12 cohort studies, which comprised 1379 patients with ADPKD of a total of 9849 patients who had undergone kidney transplants. The pooled RRs of NODAT in patients with ADPKD were 1.92 (95% CI, 1.36 to 2.70). When meta-analysis was limited only to studies with confounder-adjusted analysis, the pooled RRs for NODAT were 1.98 (95% CI, 1.33 to 2.94). However, the association between NODAT requiring insulin treatment was insignificant, with pooled RRs of 1.57 (95% CI, 0.75 to 3.27). CONCLUSIONS Our meta-analysis demonstrates a significant association between ADPKD and NODAT in recipients of kidney transplants. The findings of this study may impact clinical management and follow up for patients with ADPKD after kidney transplantation.
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Affiliation(s)
- Wisit Cheungpasitporn
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, United States.
| | - Charat Thongprayoon
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, United States
| | - Priya Vijayvargiya
- Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, United States
| | - Pimjai Anthanont
- Division of Endocrinology, Mayo Clinic, Rochester, Minnesota, United States; Faculty of Medicine, Thammasat University Hospital, Bangkok, Thailand
| | - Stephen B Erickson
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, United States
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Shivaswamy V, Boerner B, Larsen J. Post-Transplant Diabetes Mellitus: Causes, Treatment, and Impact on Outcomes. Endocr Rev 2016; 37:37-61. [PMID: 26650437 PMCID: PMC4740345 DOI: 10.1210/er.2015-1084] [Citation(s) in RCA: 215] [Impact Index Per Article: 23.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Post-transplant diabetes mellitus (PTDM) is a frequent consequence of solid organ transplantation. PTDM has been associated with greater mortality and increased infections in different transplant groups using different diagnostic criteria. An international consensus panel recommended a consistent set of guidelines in 2003 based on American Diabetes Association glucose criteria but did not exclude the immediate post-transplant hospitalization when many patients receive large doses of corticosteroids. Greater glucose monitoring during all hospitalizations has revealed significant glucose intolerance in the majority of recipients immediately after transplant. As a result, the international consensus panel reviewed its earlier guidelines and recommended delaying screening and diagnosis of PTDM until the recipient is on stable doses of immunosuppression after discharge from initial transplant hospitalization. The group cautioned that whereas hemoglobin A1C has been adopted as a diagnostic criterion by many, it is not reliable as the sole diabetes screening method during the first year after transplant. Risk factors for PTDM include many of the immunosuppressant medications themselves as well as those for type 2 diabetes. The provider managing diabetes and associated dyslipidemia and hypertension after transplant must be careful of the greater risk for drug-drug interactions and infections with immunosuppressant medications. Treatment goals and therapies must consider the greater risk for fluctuating and reduced kidney function, which can cause hypoglycemia. Research is actively focused on strategies to prevent PTDM, but until strategies are found, it is imperative that immunosuppression regimens are chosen based on their evidence to prolong graft survival, not to avoid PTDM.
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Affiliation(s)
- Vijay Shivaswamy
- Division of Diabetes, Endocrinology, and Metabolism (V.S., B.B., J.L.), Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198; and VA Nebraska-Western Iowa Health Care System (V.S.), Omaha, Nebraska 68105
| | - Brian Boerner
- Division of Diabetes, Endocrinology, and Metabolism (V.S., B.B., J.L.), Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198; and VA Nebraska-Western Iowa Health Care System (V.S.), Omaha, Nebraska 68105
| | - Jennifer Larsen
- Division of Diabetes, Endocrinology, and Metabolism (V.S., B.B., J.L.), Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198; and VA Nebraska-Western Iowa Health Care System (V.S.), Omaha, Nebraska 68105
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Porrini EL, Díaz JM, Moreso F, Delgado Mallén PI, Silva Torres I, Ibernon M, Bayés-Genís B, Benitez-Ruiz R, Lampreabe I, Lauzurrica R, Osorio JM, Osuna A, Domínguez-Rollán R, Ruiz JC, Jiménez-Sosa A, González-Rinne A, Marrero-Miranda D, Macía M, García J, Torres A. Clinical evolution of post-transplant diabetes mellitus. Nephrol Dial Transplant 2015; 31:495-505. [DOI: 10.1093/ndt/gfv368] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2015] [Accepted: 09/22/2015] [Indexed: 12/11/2022] Open
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Pimentel AL, Bauer AC, Camargo JL. Renal posttransplantation diabetes mellitus: An overview. Clin Chim Acta 2015; 450:327-32. [DOI: 10.1016/j.cca.2015.09.010] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2015] [Revised: 09/05/2015] [Accepted: 09/10/2015] [Indexed: 12/25/2022]
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Guthoff M, Vosseler D, Langanke J, Nadalin S, Königsrainer A, Häring HU, Fritsche A, Heyne N. Diabetes Mellitus and Prediabetes on Kidney Transplant Waiting List- Prevalence, Metabolic Phenotyping and Risk Stratification Approach. PLoS One 2015; 10:e0134971. [PMID: 26398489 PMCID: PMC4580460 DOI: 10.1371/journal.pone.0134971] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2015] [Accepted: 07/15/2015] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Despite a significant prognostic impact, little is known about disturbances in glucose metabolism among kidney transplant candidates. We assess the prevalence of diabetes mellitus (DM) and prediabetes on kidney transplant waiting list, its underlying pathophysiology and propose an approach for individual risk stratification. METHODS All patients on active kidney transplant waiting list of a large European university hospital transplant center were metabolically phenotyped. RESULTS Of 138 patients, 76 (55%) had disturbances in glucose metabolism. 22% of patients had known DM, 3% were newly diagnosed. 30% were detected to have prediabetes. Insulin sensitivity and-secretion indices allowed for identification of underlying pathophysiology and risk factors. Age independently affected insulin secretion, resulting in a relative risk for prediabetes of 2.95 (95%CI 1.38-4.83) with a cut-off at 48 years. Body mass index independently affected insulin sensitivity as a continuous variable. CONCLUSIONS The prevalence of DM or prediabetes on kidney transplant waiting list is as high as 55%, with more than one third of patients previously undiagnosed. Oral glucose tolerance test is mandatory to detect all patients at risk. Metabolic phenotyping allows for differentiation of underlying pathophysiology and provides a basis for early individual risk stratification and specific intervention to improve patient and allograft outcome.
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Affiliation(s)
- Martina Guthoff
- Dept. of Endocrinology and Diabetology, Angiology, Nephrology and Clinical Chemistry, University of Tübingen, Otfried-Müller-Str. 10, 72076, Tübingen, Germany
| | - Dorothea Vosseler
- Dept. of Endocrinology and Diabetology, Angiology, Nephrology and Clinical Chemistry, University of Tübingen, Otfried-Müller-Str. 10, 72076, Tübingen, Germany
| | - Julia Langanke
- Dept. of Endocrinology and Diabetology, Angiology, Nephrology and Clinical Chemistry, University of Tübingen, Otfried-Müller-Str. 10, 72076, Tübingen, Germany
| | - Silvio Nadalin
- Dept. of General-, Visceral- and Transplant Surgery, University of Tübingen, Hoppe-Seyler-Str. 3, 72076, Tübingen, Germany
| | - Alfred Königsrainer
- Dept. of General-, Visceral- and Transplant Surgery, University of Tübingen, Hoppe-Seyler-Str. 3, 72076, Tübingen, Germany
| | - Hans-Ulrich Häring
- Dept. of Endocrinology and Diabetology, Angiology, Nephrology and Clinical Chemistry, University of Tübingen, Otfried-Müller-Str. 10, 72076, Tübingen, Germany
| | - Andreas Fritsche
- Dept. of Endocrinology and Diabetology, Angiology, Nephrology and Clinical Chemistry, University of Tübingen, Otfried-Müller-Str. 10, 72076, Tübingen, Germany
| | - Nils Heyne
- Dept. of Endocrinology and Diabetology, Angiology, Nephrology and Clinical Chemistry, University of Tübingen, Otfried-Müller-Str. 10, 72076, Tübingen, Germany
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Langsford D, Dwyer K. Dysglycemia after renal transplantation: Definition, pathogenesis, outcomes and implications for management. World J Diabetes 2015; 6:1132-51. [PMID: 26322159 PMCID: PMC4549664 DOI: 10.4239/wjd.v6.i10.1132] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2014] [Revised: 07/06/2015] [Accepted: 08/16/2015] [Indexed: 02/05/2023] Open
Abstract
New-onset diabetes after transplantation (NODAT) is major complication following renal transplantation. It commonly develops within 3-6 mo post-transplantation. The development of NODAT is associated with significant increase in risk of major cardiovascular events and cardiovascular death. Other dysglycemic states, such as impaired glucose tolerance are also associated with increasing risk of cardiovascular events. The pathogenesis of these dysglycemic states is complex. Older recipient age is a consistent major risk factor and the impact of calcineurin inhibitors and glucocorticoids has been well described. Glucocorticoids likely cause insulin resistance and calcineurin inhibitors likely cause β-cell toxicity. The impact of transplantation in incretin hormones remains to be clarified. The oral glucose tolerance test remains the best diagnostic test but other tests may be validated as screening tests. Possibly, NODAT can be prevented by administering insulin early in patients identified as high risk for NODAT. Once NODAT has been diagnosed altering immunosuppression may be acceptable, but creates the difficulty of balancing immunological with metabolic risk. With regard to hypoglycemic use, metformin may be the best option. Further research is needed to better understand the pathogenesis, identify high risk patients and to improve management options given the significant increased risk of major cardiovascular events and death.
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