Characteristics of Anemia and Iron Deficiency After Kidney Transplant

BackgroundNumerous studies have shown that iron deficiency is common in patients with end-stage renal disease. However, change of iron deficiency after kidney transplant (KT) is not fully understood. This study was undertaken to examine sequential changes of iron level after KT.MethodsA total of 1080 KT recipients enrolled in a multicenter observational cohort study between July 2012 and August 2018. A total of 786 patients with transferrin saturation and ferritin level at pretransplant and 1 year after KT were reviewed. Iron deficiency was defined as ferritin <200 ng/mL and total saturation of transferrin (TSAT) < 20%. Anemia was defined as hemoglobin (Hb) < 13 g/dL (male) or <12 g/dL (female).ResultsHemoglobin at 1 year after KT was higher than Hb at KT (13.64 [SD, 1.87] g/dL vs 10.53 [SD, 1.63] g/dL; P < .001). The TSAT decreased from baseline at 1 year after KT (33.89% [SD, 18.73%] vs 29.09% [SD, 14.54%]; P < .001), and ferritin level decreased from baseline at 1 year (190.63 [SD, 217.43] ng/mL vs 141.39 [194.25] ng/mL; P < .001). In patients with anemia at pretransplant, the group with anemia at 1 year after KT (persistent group) and the group without anemia at 1 year after KT (improved group) were compared. The persistent group showed higher pretransplant TSAT, lower 1-year TSAT, and lower estimated glomerular filtration rate at 1 year after KT than the improved group. In multivariate analysis, low ferritin at KT, low TSAT at 1 year, and high ferritin at 1 year were the risk factors for low Hb level at 1 year after adjusting multiple variables.ConclusionAnemia improved within 1 year after KT, although patients with iron deficiency increased. While ferritin reflected the inflammatory status, low TSAT at 1 year after KT was a risk factor for anemia at 1 year after KT.     

Risk Factors of the Development of Diabetes Mellitus After Kidney Transplantation

BackgroundThe occurrence of diabetes mellitus is common after kidney transplantation (posttransplant diabetes mellitus [PTDM]) and enhances the cardiovascular risk and risk for kidney graft loss. The incidence of PTDM is about 5% to 40%. This study aimed to examine the potential risk factors that determine the occurrence of PTDM.MethodsThis study retrospectively included 298 patients from transplantation unit of Evangelismos who underwent kidney transplantation during a 10-year period (January 1, 2009, to January 1, 2019). Kidney transplant recipients with diabetes mellitus prior to transplantation or those with follow-up of <6 months were rejected from the study. In total, the study included 274 recipients with a mean age of 50 ± 18 years. The mean time of monitoring was 63 ± 18 months. The PTDM diagnosis was based on the 2018 criteria of the American Diabetes Association.ResultsOf 274 kidney transplant recipients, PTDM developed in 38 (13.8%) patients over a period of 11 ± 9 months after transplantation. Given that immunosuppressive therapy was identical in most patients, statistical analysis did not correlate the incidence of diabetes with treatment. However, there was a correlation for the occurrence of PTDM between the presence of hypomagnesemia and increased uric acid levels. Finally, there was a negative correlation between the age of the recipient and the time of PTDM onset.ConclusionHypomagnesemia and hyperuricemia increased the risk of PTDM in these patients. Given the association between hypomagnesemia and the development of diabetes mellitus after kidney transplantation, prospective studies are needed to identify the causes of PTDM and to develop prevention strategies.     

Incidence and Risk Factors of Posttransplantation Diabetes Mellitus in Living Donor Kidney Transplantation: A Single-Center Retrospective Study in China

Background

Posttransplantation diabetes mellitus (PTDM) is a frequent metabolic complication following solid organ transplantation and was proven to be associated with adverse outcome. This study aimed to identify the incidence and risk factors of PTDM under the background of relative-living renal transplantation in China.

Incidence and Importance of De Novo Diabetes Mellitus After Heart Transplantation

Introduction

Diabetes mellitus is one of the main metabolic complications after heart transplantation. The aims of our study were to determine the incidence and factors that determine the appearance of posttransplantation diabetes mellitus (PTDM) and its prognostic value.

Materials and methods

We performed a retrospective study of all heart transplant recipients in our hospital from January 1993 to December 2005, including 116 patients with prolonged monitoring with 59-month median follow-up. We divided the patients into two groups, according to whether they had de novo diabetes (group 1) or no diabetes (group 2).

Results

Patients with PTDM were significantly older, with a median difference (MD) of 5.4 years (95% confidence interval [CI], 1.53-9.28) and a greater body mass index (MD, 3.37 kg/m²; 95% CI, 1.68-5.06). Moreover, a greater percentage of patients in group 1 had ischemia compared to other etiologies. However, no significant differences were observed regarding other cardiovascular risk factors. PTDM was associated with a greater incidence of posttransplant hypertension (51.6% in group 1 vs 48.4% in group 2, P = .08) and posttransplant renal failure (59.5% in group 1 vs 40.5% in group 2, P = .001). However, no differences were observed in overall survival.

Conclusions

Age, overweight, and ischemic origin of cardiopathy were the main risk factors for the development of PTDM in our population. Although no differences were observed in survival rates, PTDM was associated with a greater incidence of hypertension and renal insufficiency, which may have long-term influences on patient survival.     

Incidence and Risk Factors of Persistent Hyperparathyroidism After Kidney Transplantation

Persistent hyperparathyroidism after kidney transplantation is related to graft function, but pre-transplantation risk factors of persistent hyperparathyroidism have not been evaluated in detail. We enrolled 86 patients who had undergone kidney transplantation between 2008 and 2014. Nine patients showed persistent hyperparathyroidism characterized by the following: 1) serum parathyroid hormone levels >65 pg/mL and serum calcium levels >10.5 mg/dL at 1 year after kidney transplantation; 2) parathyroidectomy after kidney transplantation; and 3) reintroduction of cinacalcet after kidney transplantation. Compared with other patients, these 9 patients had significantly longer duration of dialysis therapy (186 ± 74 mo vs 57 ± 78 mo) and more frequent treatment with cinacalcet during dialysis (89% vs 12%). Multivariate analysis showed that dialysis vintage, calcium phosphate products, and cinacalcet use before kidney transplantation were independent risk factors of persistent hyperparathyroidism after kidney transplantation. A receiver operating characteristic curve showed 72 months as the cutoff value of dialysis vintage and 55 as the cutoff value of calcium phosphate products. In conclusion, dialysis vintage >6 years, calcium phosphate products >55 (mg/dL)², and cinacalcet use before kidney transplantation are strong predictors of persistent hyperparathyroidism. High-risk patients should be evaluated for parathyroid enlargement, and parathyroidectomy must be considered before kidney transplantation.     

Diabetes Mellitus as Predictor of Patient and Graft Survival After Kidney Transplantation

Background

In this study, we used a single-center database to examine the risks of renal transplantation in patients with diabetes mellitus (DM). We aimed to compare 1-year outcomes of survival and morbidity after renal transplantation among recipients with and without DM.

Methods

We reviewed retrospectively 1211 adult patients who underwent renal transplantation from January 2001 to December 2010. The patients were divided into 2 groups: Those with (33%) and those without (67%) pretransplant diabetes. Unpaired Student's t tests and χ² tests were used to compare outcomes between diabetic and nondiabetic renal transplant recipients. We analyzed survival, renal function, development of proteinuria, rejection, and infection (requiring hospitalization).

Results

Patients with diabetes were older, had a greater body mass index (mean, 29.5 vs 25.3 kg/m²; P < .05), and had lower creatinine clearance (44.2 ± 11.4 vs 56.0 ± 18.2; P = .01). Forty-one patients died in hospital (3.4%; P = nonsignificant). Furthermore, survival rates were similar between these 2 groups. However, we found a trend toward decreased survival for those with DM at 1 year (80.4% vs 88.7%; P = .20). Mean follow-up time was 3.2 years. Infection rate within 6 months was greater among those with DM (19% vs 5%; odds ratio, 6.25). Freedom from rejection at 3 years was similar (75.2% vs 76.8%; P = .57). Multivariate analysis showed increased baseline creatinine level as a significant risk factor for survival. Body mass index >30 kg/m² was a significant risk factor for survival among patients with DM.

Conclusion

We found an increased risk of serious infections in patients with DM, particularly within the first 6 months. However, our data suggest that diabetes is not associated with worse 1-year survival or higher morbidity in renal transplant patients, as long as good blood glucose control is maintained.     

Unplanned Readmission Within 1 Year After Heart Transplantation in Taiwan

Introduction

Survival in patients with refractory heart failure greatly improves after heart transplantation (HTx).

Objective

To evaluate the rate of unplanned readmission within the first year post-HTx and the causes of such readmission.

Patients and Methods

From January 2005 to June 2008, the 112 patients who underwent HTx were regularly followed up at our hospital. A protocol biopsy was performed every week during the first month, then every 3 months during the first year. Any unplanned readmission was discussed in detail in a transplantation meeting. Data were collected from review of medical records.

Results

The rate of unplanned readmission was 19.3% in 2005, 21.5% in 2006, 22.2% in 2007, and 20.3% in 2008. Infection was the primary cause leading to unplanned readmission in 2005 (51.5%), 2006 (42.9%), and 2008 (30.7%). Rejection was the primary cause leading to readmission in 2007 (40%). Other causes included fluid retention, pericardial effusion, anemia, and systemic diseases.

Conclusion

To reduce unplanned readmissions and to promote quality of life and long-term survival, health professionals must meticulously monitor the adverse effects of treatments including immunosuppression agents and concomitantly used medications.     

Clinical Consequences of Diabetes Mellitus in Patients After Kidney Transplantation: A Paired Kidney Analysis

Background

Diabetes mellitus (DM) has been acknowledged as the most common disorder leading to end-stage renal failure in adults. Diabetic patients show higher survival rates after kidney transplantation (KTx) compared with dialysis therapy. The aim of the study was to evaluate follow-up after KTx in patients with DM as a reason of end-stage renal disease (ESRD), or with long-lasting diabetes before transplantation, compared with patients without DM.

Incidence of and Risk Factors for Posttransplant Diabetes Mellitus after Pancreas Transplantation

Posttransplant diabetes mellitus (PTDM) after pancreas transplantation (PTX) has not been extensively examined. This single center, retrospective analysis of 674 recipients from 1994 to 2005 examines the incidence of and risk factors for PTDM after PTX. PTDM was defined by fasting plasma glucose level ≥126 mg/dL, confirmed on a subsequent measurement or treatment with insulin or oral hypoglycemic agent for ≥30 days. The incidence of PTDM was 14%, 17% and 25% at 3, 5 and 10 years after PTX, respectively and was higher (p = 0.01) in solitary pancreas (PAN) versus simultaneous kidney pancreas (SPK) recipients (mean follow‐up 6.5 years). In multivariate analysis, factors associated with PTDM were: older donor age (hazard ratio [HR] 1.04, 95% confidence interval [CI] 1.03–1.06, p < 0.001), higher recipient body mass index (HR 1.07,CI 1.01–1.13, p = 0.01), donor positive/recipient negative CMV status (HR 1.65,CI 1.03–2.6, p = 0.04), posttransplant weight gain (HR 4.7,CI 1.95–11.1, p < 0.001), pancreas rejection (HR 1.94.CI 1.3–2.9, p < 0.001) and 6 month fasting glucose (HR 1.01,CI 1.01–1.02, p < 0.001), hemoglobin A₁c, (HR 1.12,CI 1.05–1.22, p = 0.002) and triglyceride to high‐density lipoprotein (TG/HDL) ratio (HR 0.94,CI 0.91–0.96, p < 0.001). This study delineates the incidence and identifies risk factors for PTDM after PTX.     

Prevalence and Treatment of New-Onset Diabetes Mellitus After Liver Transplantation in Korean Children: A Single-Center Study

The aim of this study was to investigate the prevalence, clinical characteristics, and management of new-onset diabetes mellitus (NODM) in Korean children with liver transplantation (LT). We retrospectively analyzed the medical records of 200 pediatric patients (5 months to 17 years old) who underwent LT at Asan Medical Center between January 1994 and December 2010; 26 pediatric patients who died at the maximal follow-up after LT or who were lost to follow-up were excluded from the study. Among these 174 children, NODM after LT developed in 18. The median interval time at the presentation of NODM after LT was 15 days (range, 1 day to 16.0 years), whereas the median patient age of NODM diagnosis was 10 years (range, 1.1 to 17.0 years). Insulin treatment with reduction in tacrolimus dosage, steroid tapering, and conversion from tacrolimus to cyclosporine with or without mycophenolate mofetil is highly effective in NODM after LT. In conclusion, careful diabetes mellitus monitoring and modification of immunosuppressive regimen should be required in pediatric patients after LT.     

Historical Cohort With Diabetes Mellitus After Kidney Transplantation and Associated Factors of Its Development in Adult Patients of a Transplantation Reference Center in the State of Ceará, Brazil

Post-transplantation diabetes mellitus (PTDM) is an important complication related to kidney transplantation (KT), and its occurrence is associated with increased morbidity and mortality. Nevertheless, KT is considered to be the most effective treatment option that offers better quality of life for patients with end-stage kidney disease. This study aimed to describe the occurrence of PTDM and the risk factors associated with its development in kidney transplant patients of a transplantation reference center in the State of Ceará (Brazil). This historical cohort study, based on medical records data, included adult patients undergoing KT from January 2006 to December 2010 in a public tertiary hospital. Multivariate analysis was performed with the use of a logistic regression model, with PTDM presence as dependent variable and the possible risk factors under study as independent variables. Throughout the evaluated period, 430 KTs were performed; 92 patients were excluded. Diabetes mellitus was already present in 9.2% of patients before KT. Hyperglycemia during the 1st month after transplantation occurred in 34.5% of recipients, and the occurrence of PTDM to the end of study was 19.9%. Factors associated with PTDM development were: fasting plasma glucose 1 month after KT (P < .001; odds ratio [OR] 1.05), deceased-donor KT (P = .015; OR 3.53), impaired fasting glucose before transplantation (P = .014; OR 4.10), and acute rejection occurrence (P = .003; OR 6.43). High PTDM occurrence was found, in accordance with the literature. Identification of factors associated with PTDM development, as well as its early diagnosis, could result in long-term improvement in patient and graft survivals.     

Early Pulse Pressure and Low-Grade Proteinuria as Independent Long-Term Risk Factors for New-Onset Diabetes Mellitus After Kidney Transplantation

Risk factors for new-onset diabetes after transplantation (NODAT) need to be assessed in large cohorts.
We retrospectively evaluated the impact of early (3 and 6 months after transplantation) proteinuria, urinary albumin excretion (UAE) and arterial pressure on NODAT in 828 Causasian renal transplant recipients (median follow-up: 5.3 years; 5832 patient-years).
The 10- and 20-year incidence of NODAT was 15.0% and 22.0%, respectively. Low-grade (<1 g/day) (HR: 2.04 [1.25–3.33], p = 0.0042) and very low-grade (<0.3 g/day) (HR: 2.21 [1.32–3.70], p = 0.0025) proteinuria were independent risk factors for NODAT. There was a dose-dependent relationship across UAE categories (increasing risk from normoalbuminuria to macroalbuminuria) with NODAT. Tacrolimus, sirolimus and beta-blockers (HR: 1.86 [1.07–3.22], p = 0.0277) were significantly associated with NODAT even after multiple adjustments, but not diuretics, angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers. Systolic arterial pressure (HR per 10 mmHg: 1.16 [1.03–1.29], p = 0.0126) and pulse pressure (HR: 1.26 [1.12–1.43], p = 0.0002) were associated with NODAT. Only pulse pressure remained significant after adjustments. Patients at highest risks had early proteinuria and pulse pressure >60 mmHg.
Early low-grade proteinuria and pulse pressure (in addition to beta-blockers) constitute independent risk factors for NODAT; they may be markers of the metabolic syndrome and/or vascular damage in renal transplant recipients.     

Obesity, Adiponectin and Inflammation as Predictors of New-Onset Diabetes Mellitus After Kidney Transplantation

The high incidence of new-onset diabetes mellitus after transplantation (NODAT) suggests the need to find new factors to explain the pathogenesis. Our objectives were (1) to confirm that low levels of pre-transplant adiponectin are an independent risk factor for the development of NODAT in a larger transplanted population; (2) to analyze whether adiponectin is a better predictor of NODAT than other inflammatory markers (C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and pregnancy-associated plasma protein A (PAPP-A)) and (3) to assess the relationship between obesity, inflammatory markers and NODAT. One hundred ninety-nine non-diabetic patients (128 men; age: 53 +/- 11 years; body mass index (BMI) 24.98 +/- 3.76 kg/m2) were included. Pre-transplant plasma glucose, insulin, adiponectin, CRP, TNF-alpha, IL-6 and PAPP-A were measured. Forty-five patients developed NODAT. Patients with NODAT had a greater BMI (p = 0.005). Adiponectin was lower (p < 0.001) and CRP higher (p = 0.032) in patients with NODAT. Multivariate logistic regression and Cox analysis showed that the calcineurin inhibitor used, pre-transplant BMI and adiponectin were predictors of NODAT. ROC analysis showed that an adiponectin concentration of 11.4 microg/mL had a significant negative prediction for NODAT risk (sensitivity: 81% and specificity: 70%). Of the inflammatory markers studied, adiponectin proved to be an independent predictor of NODAT.     

Prognostic Significance of 1‐Year Serum Albumin Levels Within the Normal Range After Kidney Transplantation

Hypoalbuminemia is associated with poor outcomes in kidney transplantation (KT). However, what level is optimal in serum albumin is not clear for the long‐term prognosis. To determine whether the long‐term outcomes are different even between the normal ranges of serum albumin after KT, we analyzed data from 404 renal allograft recipients whose 1‐year post‐transplant serum albumin levels were within the normal limits (3.5–5.5 g/dL). During a follow‐up of 122 ± 56 months, 97 graft losses, 20 patient deaths, and 50 cardiovascular (CV) events occurred. Based on 1‐year serum albumin levels, the patients were divided into high normal (≥4.6 g/dL, n = 209) and low normal (<4.6 g/dL, n = 195) groups. Kaplan–Meier analyses revealed that the low normal group had poorer allograft survival (P = 0.01), patient survival (P < 0.001), and CV event‐free survival (P < 0.001) than the high normal group. Cox regression analysis confirmed that 1‐year serum albumin was inversely associated with the risk of graft loss (hazard ratio [HR] 0.414, 95% confidence interval [CI] 0.200–0.856), patient death (HR 0.097, 95% CI 0.019–0.484), and CV events (HR 0.228, 95% CI 0.074–0.702). In conclusion, a relatively low 1‐year post‐transplant serum albumin level within the normal limits (<4.6 g/dL) significantly predicts poor long‐term outcomes.     

Pilot Study: Association of Traditional and Genetic Risk Factors and New-Onset Diabetes Mellitus Following Kidney Transplantation

Introduction

New-onset diabetes mellitus, which occurs after kidney transplant and type 2 diabetes mellitus (T2DM), shares common risk factors and antecedents in impaired insulin secretion and action. Several genetic polymorphisms have been shown to be associated with T2DM. We hypothesized that transplant recipients who carry risk alleles for T2DM are “tipped over” to develop diabetes mellitus in the posttransplant milieu.

Methods

We investigated the association of genetic and traditional risk factors present before transplantation and the development of new-onset diabetes mellitus after kidney transplantation (NODAT). Markers in 8 known T2DM-linked genes were genotyped using either the iPLEX assay or allelic discrimination (AD)-PCR in the study cohort testing for association with NODAT. We used univariate and multivariate logistic regression models for the association of pretransplant nongenetic and genetic variables with the development of NODAT.

Results

The study cohort included 91 kidney transplant recipients with at least 1 year posttransplant follow-up, including 22 who developed NODAT. We observed that increased age, family history of T2DM, pretransplant obesity, and triglyceridemia were associated with NODAT development. In addition, we observed positive trends, although statistically not significant, for association between T2DM-associated genes and NODAT.

Conclusions

These findings demonstrated an increased NODAT risk among patient with a positive family history for T2DM, which, in conjunction with the observed positive predictive trends of known T2DM-associated genetic polymorphisms with NODAT, was suggestive of a genetic predisposition to NODAT.