Recoverability of Diabetic Nephropathy of Donor Kidney After Kidney Transplantation.

Some kidney donors have diabetes, and little of their natural course of diabetic nephropathy (DN) is known. The aim of this study was to analyze the changes in pathologic lesions in the diabetic donor kidney after KT by performing protocol biopsy two weeks and one year after KT. This retrospective study included 103 patients who underwent KT, with kidneys from donors with a history of diabetes mellitus (DM). Among them, data of 34 patients who underwent biopsy two weeks and one year after KT were reviewed. Biopsy specimens were reviewed using light microscopy and electron microscopy. Glomerular basement membrane (GBM) thickness at 2 weeks and 1 year was compared. Biopsy showed that DN occurred in 29 of the 34 patients. Only trivial histological changes were observed in 22 patients (64.7%), including 5 patients who did not show DN. At one year after transplantation, there was no change in the DN histologic class in 26 patients (76.5%), and there was no statistically significant difference in the change in GBM thickness. This pattern was observed regardless of the recipient's DM or glycemic control. With this understanding, clinicians can use kidneys from DM donors with more comfort, thereby reducing the kidney discard rate.

State-of-the-art Medical Therapy Versus Roux-en-Y Gastric Bypass Alone for Treatment of Early Diabetic Kidney Disease.

OBJECTIVE: Type 2 diabetic kidney disease (DKD) is the most common global cause of kidney disease and failure. Obesity is a major risk factor for DKD due to its causal relationship with diabetes, hypertension, and other factors promoting kidney disease. We therefore investigated whether metabolic surgery such as Roux-en-Y gastric bypass is more effective than state-of-the-art medical therapy (i.e., renin-angiotensin-aldosterone system, sodium-glucose co-transporter 2 inhibitors, and glucagon-like peptide-1 receptor agonists) in treating DKD. DESIGN AND METHODS: In a post hoc analysis of the Microvascular Outcomes after Metabolic Surgery trial, we compared the likelihood of regression of microalbuminuria as the primary endpoint and other renal and metabolic secondary endpoints in a population of patients with obesity, type 2 diabetes, microalbuminuria, and early chronic kidney disease followed for 24 months. Nine patients underwent Roux-en-Y gastric bypass, and 24 patients were on state-of-the-art medical therapy. RESULTS: The gastric bypass arm had a significantly higher rate of regression of microalbuminuria (P < .001), borderline significant reduction in mean urine albumin-to-creatinine ratio (P = .055), and much greater weight loss (P = .001). There were no statistically significant differences between arms in estimated glomerular filtration rate, risk of developing estimated glomerular filtration rate <60 mL/min/1.73 m2 over 5 years, mean hemoglobin A1c, systolic blood pressure, low-density lipoprotein cholesterol, or the American Diabetes Association triple endpoint. CONCLUSION: We found that metabolic surgery offers more kidney protection than state-of-the-art triple therapy for DKD at 24 months. Prospective studies in this area are necessary to better define the benefits and risks of medical versus surgical treatment of DKD.

Hypoxia preconditioning increases the ability of healthy but not diabetic rat-derived adipose stromal/stem cells (ASC) to improve histological lesions of streptozotocin-induced diabetic nephropathy.

BACKGROUND: Mesenchymal stromal cells (MSC) have demonstrated ability to improve diabetic nephropathy (DN) in experimental models, as well as by improving kidney endogenous progenitor cells proliferation and differentiation. Many studies have demonstrated the effect of hypoxia on MSC improving their functionality but the potential enhancement of the nephroprotective properties of MSC cultured under low oxygen concentration has been explored in few studies, none of them in the context of DN. On the other hand, diabetes is associated with abnormalities in MSCs functionality. These findings related to the hypoxia preconditioning ability to enhance adipose-tissue derived-MSC (ASC) performance have led us to wonder if hypoxia could increase the known beneficial effect of normal ASC in DN and if it could correct the expected inability of diabetic rat-derived ASC to exert this effect in vivo. To answer these questions, in the present study we have used ASC from healthy and diabetic-induced rats, cultured under standard conditions or hypoxia preconditioned, in a DN rat model induced by streptozotocin (STZ). METHODS: Diabetes was induced in Wistar-rats by 60 mg/kg streptozotocin (STZ) intraperitoneal injection. Fifteen days thereafter, five diabetic-induced rats and five healthy, previously injected with saline, were sacrificed and used as ASC donors . Both healthy and diabetic rat-derived ASC (cASC and dASC, respectively) were cultured under standard conditions (21%O2)(N) or were subjected to a 48 h conditioning period in hypoxia (3%O2)(H). Thus, four types of cells were generated depending on their origin (healthy or diabetic-induced rats) and the culture conditions(N or H):cASC-N, cASC-H, dASC-N and dASC-H. DN experimental study were carried out fifteen days after STZ induction of diabetes in fifty-two healthy rats. DN-induced-animals were randomly assigned to be injected with 200 µL saline as placebo or with 3 × 106 cASC-N, cASC-H, dASC-N or dASC-H, according to the study group. Serum glucose, urea and creatinine, and urine albumin levels were measured at 2-weeks intervals until day+ 45 after ND-induction.Animals were sacrificed and kidneys extracted for histopathological and transmission electron microcopy analysis RESULTS: None of the four study groups that received cell treatment showed significant changes in serum glucose, urea and creatinine levels, urine albumin concentration and body weight compared to placebo ND-induced group. Interestingly, only the group that received cASC-H showed a reduction in glucose and creatinine levels although it did not reach statistical significance.All DN-induced groups treated with ASC reduced significantly renal lesions such as mesangial expansion, mesangiolysis, microaneurysms and acute tubular necrosis compared to ND-induced placebo group (p ≤ 0.05). Renal injuries such as clear tubular cell changes, thickening of tubular basement membrane, tubular cysts and interstitial fibrosis significantly showed reduction in ND-induced rats treated with cASC-H regarding to their received cASCN (p ≤ 0.05). Non statistical differences were observed in the improvement capacity of cASC and dASC culture under standard condition.However, hypoxia preconditioning reduces the presence of tubular cysts (p ≤ 0.01). CONCLUSIONS: Hypoxia preconditioning enhances the ability of healthy rat-derived ASC to improve kidney injury in a rat model of DN. Moreover, diabetic-derived ASC exhibits a similar ability to healthy ASC which is clearly more than expected, but it is not significantly modified by hypoxia preconditioning.

Treatment with crocin suppresses diabetic nephropathy progression via modulating TGF-ß1 and oxidative stress in an experimental model of pinealectomized diabetic rats.

One of the most common complications of diabetes is diabetic nephropathy (DN). Uncontrolled hyperglycemia leads to histopathologic alterations in the kidney that prevent normal renal function. This study aimed to explore the effects of crocin treatment via virtue of its numerous beneficial properties in streptozotocin-induced pinealectomized diabetic rats. The pinealectomy procedure was conducted on the first day of the study. On the 30th day following pinealectomy, streptozotocin (STZ) (50 mg/kg) was administered intraperitoneally in Wistar rats for induction of diabetes. Diabetes was confirmed on the 3rd day following STZ administration by determining the glucose levels. Daily crocin treatment intraperitoneally for 15 days (50 mg/kg) ameliorated impaired renal oxidant/antioxidant balance, reduced TGF-ß1 immuno-staining around tubules, and promoted improvement of renal architecture. Moreover, crocin administration improved altered renal function parameters, including serum Cr and BUN, and also increased creatinine clearance. In conclusion, the protective effects of crocin on diabetic nephropathy might be associated with its powerful antioxidant properties, its ability to improve tissue antioxidant status, and its ability to prevent inflammatory pathways.

A Strategy to Simultaneously Cure Type 1 Diabetes and Diabetic Nephropathy by Transplant of Composite Islet-Kidney Grafts.

In recent years islet cell transplant has proven itself to be a viable clinical option for a select group of diabetic patients. Graft loss after transplant however continues to hinder the long-term success of the procedure. Transplanting the islets as a pre-vascularized composite islet-kidney graft has emerged as a relevant solution. Much groundbreaking research has been done utilizing this model in conjunction with strategies aimed towards islet cell survival and prolongation of function in the host. Transplanting the islet cells as a prevascularized graft under the capsule of the donor kidney as a composite islet-kidney graft has been shown to provide long term durable blood glucose control in large animal studies by limiting graft apoptosis as well as providing a physical barrier against the host immune response. While promising, this technique is limited by long term immunosuppression requirements of the host with its well-known adverse sequelae. Research into tolerance inducing strategies of the host to the allogeneic and xenogeneic islet-kidney graft has shown much promise in the avoidance of long-term immunosuppression. In addition, utilizing xenogeneic tissue grafts could provide a near-limitless supply of organs. The islet-kidney model could provide a durable and long-term cure for diabetes. Here we summarize the most recent data, as well as groundbreaking strategies to avoid long term immunosuppression and promote graft acceptance.

Early initiation of sodium-glucose linked transporter inhibitors (SGLT-2i) and associated metabolic and electrolyte outcomes in diabetic kidney transplant recipients.

There is a paucity of data on the use of SGLT2 inhibitors on outcomes in kidney transplant recipients. There may be concern in initiating these agents, especially within the first year post-transplant when renal function is more labile and immunosuppression more intense, due to a presumed high risk of urinary infections and acute kidney injury. This is a retrospective study on 50 kidney transplant recipients, half of whom were started on therapy within the first year of transplant. Over a follow-up period of 6 months, overall patients had a statistically significant improvement in weight by -2.95 kg [SD 3.54, P = <.0001 (CI: 3.53, 1.50)] as well as hypomagnesemia 0.13 [SD 1.73, P = .0004 (CI: 0.06, 0.20)]. Overall insulin usage declined by -3.7 units [SD 22.8, P = .17]. 14% of patients had at least one urinary tract infection although this rate is not different (~20%) than that reported historically in this high-risk population.

Islet Transplantation Reverses Podocyte Injury in Diabetic Nephropathy or Induced by High Glucose via Inhibiting RhoA/ROCK/NF-κB Signaling Pathway.

OBJECTIVE: Abnormal signaling pathways play a crucial role in the mechanisms of podocyte injury in diabetic nephropathy. They also affect the recovery of podocytes after islet transplantation (IT). However, the specific signaling abnormalities that affect the therapeutic effect of IT on podocytes remains unclear. The purpose of this study was to assess whether the RhoA/ROCK/NF-κB signaling pathway is related to podocyte restoration after IT. METHODS: A mouse model of diabetic nephropathy was established in vivo using streptozotocin. The mice were then subsequently reared for 4 weeks after islet transplantation to determine the effect of IT. Islet cells, CCG-1423 (RhoA Inhibitor), and fasudil (ROCK inhibitor) were then cocultured with podocytes in vitro to assess their protective effects on podocyte injury induced by high glucose (HG). Protein expression levels of RhoA, ROCK1, synaptopodin, IL-6, and MCP-1 in kidney tissues were then measured using immunohistochemistry and Western blotting techniques. RESULTS: Islet transplantation reduced the expression levels of RhoA/ROCK1 and that of related inflammatory factors such as IL-6 and MCP-1 in the kidney podocytes of diabetic nephropathy. In the same line, islet cells reduced the expression of RhoA, ROCK1, and pp65 in immortalized podocytes under high glucose (35.0 mmol/L glucose) conditions. CONCLUSIONS: Islet transplantation can reverse podocyte injury in diabetes nephropathy by inhibiting the RhoA/ROCK1 signaling pathway. Islet cells have a strong protective effect on podocytes treated with high glucose (35.0 mmol/L glucose). Discovery of signaling pathways affecting podocyte recovery is helpful for individualized efficacy evaluation and targeted therapy of islet transplantation patients.

Transplantation of Apoptosis-Resistant Endothelial Progenitor Cells Improves Renal Function in Diabetic Kidney Disease.

Background Diabetic kidney disease is associated with glomerulosclerosis and poor renal perfusion. Increased capillary formation and improved perfusion may help to halt or reverse the injury. Transplanting apoptosis-resistant p53-silenced endothelial progenitor cells (p53sh-EPCs) may help improve vascularization and renal perfusion and could be more beneficial than another stem cell such as the mouse mesenchymal stromal cell (mMSC). Methods and Results Hyperglycemia and proteinuria were confirmed at 8 to 10 weeks in streptozotocin-induced type1 diabetic C57Bl/6 mice, followed by transplantation of 0.3 million p53sh-EPCs, Null-EPCs (control), or mMSC under each kidney capsule. Urine was collected weekly for creatinine and protein levels. Blood pressure was measured by direct arterial cannulation and renal perfusion was measured by renal ultrasound. The kidneys were harvested for histology and mRNA expression. Reduction of protein/creatinine (AUC) was observed in p53sh-EPC-transplanted mice more than null-EPC (1.8-fold, P=0.03) or null-mMSC (1.6-fold, P=0.04, n=4) transplanted mice. Markers for angiogenesis, such as endothelial nitric oxide synthase (1.7-fold, P=0.06), were upregulated post p53sh-EPC transplantation compared with null EPC. However, vascular endothelial growth factor-A expression was reduced (7-fold, P=0.0004) in mMSC-transplanted mice, compared with p53sh-EPC-transplanted mice. Isolectin-B4 staining of kidney section showed improvement of glomerular sclerosis when p53sh-EPC was transplanted, compared with null-EPC or mMSC. In addition, mean and peak renal blood velocity (1.3-fold, P=0.01, 1.4-fold, P=0.001, respectively) were increased in p53sh-EPC-transplanted mice, relative to null-EPC transplanted mice. Conclusions Apoptosis-resistant p53sh EPC transplantation could be beneficial in the treatment of diabetic kidney disease by decreasing proteinuria, and improving renal perfusion and glomerular architecture.

Early changes in renal resistive index and mortality in diabetic and nondiabetic kidney transplant recipients: a cohort study.

BACKGROUND: Renal resistive index (RI) predicts mortality in renal transplant recipients (RTR). However, its predictive value may be different according to the time of measurement. We analysed RI changes between 1 month and 3 months after transplantation and its predictive value for death with a functioning graft (DWFG). METHODS: We conducted a retrospective study in 1685 RTR between 1985 and 2017. The long-term predictive value of changes in RI value from 1 month to 3 months was assessed in diabetic and non-diabetic RTR. RESULTS: Best survival was observed in RTR with RI < 0.70 both at 1 and 3 months, and the worst survival was found in RTR with RI ≥ 0.70 both at 1 and 3 months (HR = 3.77, [2.71-5.24], p < 0.001). The risk of DWFG was intermediate when RI was < 0.70 at 1 month and ≥ 0.70 at 3 months (HR = 2.15 [1.29-3.60], p = 0.003) and when RI was ≥0.70 at 1 month and < 0.70 at 3 months (HR = 1.90 [1.20-3.03], p = 0.006). In diabetic RTR, RI was significantly associated with an increased risk of death only in those with RI < 0.70 at 1 month and ≥ 0.70 at 3 months (HR = 4.69 [1.07-20.52], p = 0.040). RI considered as a continuous variable at 1 and 3 months was significantly associated with the risk of DWFG in nondiabetic but not in diabetic RTR. CONCLUSION: RI changes overtime and this impacts differently diabetic and nondiabetic RTR. RI short-term changes have a strong prognosis value and refines the risk of DWFG associated with RI.

COVID-19 in pancreas transplant recipients.

Coronavirus disease 2019 (COVID-19) has become a pandemic since first being described in January 2020. Clinical manifestations in non-transplant patients range from asymptomatic infection to severe pneumonia with acute respiratory distress syndrome, multiorgan system failure, and death. Limited reports in kidney transplant recipients suggest similar characteristics in that population. We report here the first case series of COVID-19 infection occurring in pancreas transplant recipients.

Diabetic nephropathy alters circulating long noncoding RNA levels that normalize following simultaneous pancreas-kidney transplantation.

Simultaneous pancreas-kidney transplantation (SPKT) replaces kidney function and restores endogenous insulin secretion in patients with diabetic nephropathy (DN). Here, we aimed to identify circulating long noncoding RNAs (lncRNAs) that are associated with DN and vascular injury in the context of SPKT. Based on a pilot study and a literature-based selection of vascular injury-related lncRNAs, we assessed 9 candidate lncRNAs in plasma samples of patients with diabetes mellitus with a kidney function >35 mL/min/1.73 m2 (DM; n = 12), DN (n = 14), SPKT (n = 35), healthy controls (n = 15), and renal transplant recipients (KTx; n = 13). DN patients were also studied longitudinally before and 1, 6, and 12 months after SPKT. Of 9 selected lncRNAs, we found MALAT1, LIPCAR, and LNC-EPHA6 to be higher in DN compared with healthy controls. SPKT caused MALAT1, LIPCAR, and LNC-EPHA6 to normalize to levels of healthy controls, which was confirmed in the longitudinal study. In addition, we observed a strong association between MALAT1, LNC-EPHA6, and LIPCAR and vascular injury marker soluble thrombomodulin and a subset of angiogenic microRNAs (miR-27a, miR-130b, miR-152, and miR-340). We conclude that specific circulating lncRNAs associate with DN-related vascular injury and normalize after SPKT, suggesting that lncRNAs may provide a promising novel monitoring strategy for vascular integrity in the context of SPKT.

Increase in Endogenous Glucose Production With SGLT2 Inhibition Is Unchanged by Renal Denervation and Correlates Strongly With the Increase in Urinary Glucose Excretion.

OBJECTIVE: Sodium-glucose cotransporter 2 (SGLT2) inhibition causes an increase in endogenous glucose production (EGP). However, the mechanisms are unclear. We studied the effect of SGLT2 inhibitors on EGP in subjects with type 2 diabetes (T2D) and without diabetes (non-DM) in kidney transplant recipients with renal denervation. RESEARCH DESIGN AND METHODS: Fourteen subjects who received a renal transplant (six with T2D [A1C 7.2 ± 0.1%] and eight non-DM [A1C 5.6 ± 0.1%) underwent measurement of EGP with [3-3H]glucose infusion following dapagliflozin (DAPA) 10 mg or placebo. Plasma glucose, insulin, C-peptide, glucagon, and titrated glucose-specific activity were measured. RESULTS: Following placebo in T2D, fasting plasma glucose (FPG) (143 ± 14 to 124 ± 10 mg/dL; P = 0.02) and fasting plasma insulin (12 ± 2 to 10 ± 1.1 µU/mL; P < 0.05) decreased; plasma glucagon was unchanged, and EGP declined. After DAPA in T2D, FPG (143 ± 15 to 112 ± 9 mg/dL; P = 0.01) and fasting plasma insulin (14 ± 3 to 11 ± 2 µU/mL; P = 0.02) decreased, and plasma glucagon increased (all P < 0.05 vs. placebo). EGP was unchanged from baseline (2.21 ± 0.19 vs. 1.96 ± 0.14 mg/kg/min) in T2D (P < 0.001 vs. placebo). In non-DM following DAPA, FPG and fasting plasma insulin decreased, and plasma glucagon was unchanged. EGP was unchanged from baseline (1.85 ± 0.10 to 1.78 ± 0.10 mg/kg/min) after DAPA, whereas EGP declined significantly with placebo. When the increase in EGP production following DAPA versus placebo was plotted against the difference in urinary glucose excretion (UGE) for all patients, a strong correlation (r = 0.824; P < 0.001) was observed. CONCLUSIONS: Renal denervation in patients who received a kidney transplant failed to block the DAPA-mediated stimulation of EGP in both individuals with T2D and non-DM subjects. The DAPA-stimulated rise in EGP is strongly related to the increase in UGE, blunting the decline in FPG.

Hypoglycemia Following Pancreas Transplant: A Diagnostic Challenge in the Immediate Posttransplant Setting.

Few studies have described glucose metabolism in the immediate posttransplant period. Here, we report a 37-year-old female patient who had transient hypoglycemia after combined pancreas and kidney transplant for poorly controlled type 1 diabetes and renal failure. Although the patient's blood sugar decreased from 420 to less than 120 mg/dL and the kidney demonstrated graft function immediately posttransplant, at 19 hours after transplant, the patient's blood glucose decreased to below the normal range at a nadir of 59 mg/dL. When treated with intravenous dextrose, her blood glucose levels increased over 7 hours to 119 mg/dL but then again declined, appearing to follow a circadian rhythm, with hypoglycemia shown during early morning hours and then improving during the afternoon. This prompted treatment with a continuous infusion of 5% dextrose on day 2, resulting in blood sugar levels returning to normal by day 4 and discharge on day 6. She has since remained euglycemic. The differential diagnosis of hypoglycemia immediately after kidney-pancreas transplant is wide. Indeed, after we excluded ischemia-reperfusion injury, impaired renal clearance, insulin-associated antibodies, and lack of pancreatic innervation, we believe that cause was most likely due to impairment of early glucose counterregulatory responses or delayed alpha cell function.

Clinical features and burden of new onset diabetic foot ulcers post simultaneous pancreas kidney transplantation and kidney only transplantation.

BACKGROUND: Patients with diabetes and kidney disease are at risk of diabetes-related foot ulcers (DFU). Whether this risk is modified post simultaneous pancreas-kidney (SPK) or kidney only (KO) transplant is unknown. METHODS: We evaluated the incidence of new onset DFU post SPK and KO transplant in 235 patients with diabetic kidney disease and diabetic neuropathy. In total 90 (51% male) SPK patients and 145 KO (66% male, 26% Type 1 DM) were evaluated in a single centre retrospective study. Median (range) follow up was 6 (3 to 13) years for both cohorts. RESULTS: We observed that 16 (17%) of SPK and 22 (15%) KO patients respectively developed a DFU during follow up. In both cohorts a history of peripheral arterial disease [37.5% vs. 4%] and pre-transplant history of DFU were associated with post transplant DFU (p ≪ 0.05). In KO cohort, patients who developed a DFU were more likely to have T1DM than T2DM (29% vs. 10%), p ≪ 0.05. There was no impact of DFU on SPK transplant failure. In contrast patients with DFU post KO transplant had more than five fold increased hazard ratio (HR) of transplant failure as compared to those without DFU independent of other risk factors [HR 5.19 95% CI (2.05 to 13.18) p = 0.001]. CONCLUSION: Nearly 1 in 7 patients develop a new onset DFU post KO or SPK transplantation and DFU also significantly increases risk of failure of the transplanted kidney. Our results highlight the need for greater awareness of regular foot examination, DFU prevention and risk evaluation in post-transplant patients. RESEARCH IN CONTEXT: Evidence before this study Patients with diabetes and kidney disease are at enhanced risk of diabetic foot ulcers (DFU). Whether this risk is modified post successful kidney only (KO) or simultaneous pancreas and kidney (SPK) transplantation is unknown. Small case series and studies with short term follow up report varied rates of incidence and are from historical cohorts before the use of modern anti-transplant medications and treatments. Short term studies also suggest that post SPK the resultant normoglycaemia may reverse some features and risk markers of DFU. There are no long term studies on the incidence and impact of diabetic foot ulcers in patients with diabetic kidney disease post SPK or KO transplantation. Added value of this study We report the long term follow up results on DFU incidence, clinical features and related impact on transplant viability in 235 patients with diabetic kidney disease and neuropathy post successful SPK and KO transplant at a single centre. We observed that nearly 1 in 7 patients developed a DFU during follow up and that in patients who received KO transplant onset of DFU was associated with more than 5 fold increase of transplant failure. Implications of all the available evidence Our results highlight the need for greater awareness of regular foot examination, DFU prevention and risk evaluation in post-transplant patients. Despite normoglycaemia post SPK there is a residual burden and risk of DFU. Our work establishes a clinical rationale for further research to explore putative mechanisms that could explain the association between DFU and renal transplant dysfunction.

Management of Diabetes Mellitus in Normal Renal Function, Renal Dysfunction and Renal Transplant Recipients, Focusing on Glucagon-Like Peptide-1 Agonist: A Review Based upon Current Evidence.

Diabetes Mellitus (DM) is a leading cause of both Cardiovascular Disease (CVD) and End-stage Renal Disease (ESRD). After 2008, there has been much evidence presented, and recently the guidelines for sugar control have changed to focus on being more disease orientated. GLP-1 Receptor Agonists (GLP-1R) and sodium glucose cotransporter-2 inhibitors are suggested as the first line towards fighting all DM, CVD and ESRD. However, the benefits of GLP-1R in organ transplantation recipients remain very limited. No clinical trials have been designed for this particular population. GLP-1R, a gastrointestinal hormone of the incretin family, possesses antidiabetic, antihypertensive, anti-inflammatory, anti-apoptotic and immunomodulatory actions. There are few drug-drug interactions, with delayed gastric emptying being the major concern. The trough level of tacrolimus may not be significant but should still be closely monitored. There are some reasons which support GLP-1R in recipients seeking glycemic control. Post-transplant DM is due to an impaired ß-cell function and glucose-induced glucagon suppression during hyperglycemia, which can be reversed by GLP-1R. GLP-1R infusion tends to relieve immunosuppressant related toxicity. Until now, in some cases, glycemic control and body weight reduction can be anticipated with GLP-1R. Additional renal benefits have also been reported. Side effects of hypoglycemia and gastrointestinal discomfort were rarely reported. In conclusion, GLP-1R could be implemented for recipients while closely monitoring their tacrolimus levels and any potential side effects. Any added benefits, in addition to sugar level control, still require more well-designed studies to prove their existence.

Trends of Nontraumatic Lower-Extremity Amputation in End-Stage Renal Disease and Diabetes: United States, 2000-2015.

OBJECTIVE: Nontraumatic lower-extremity amputation (NLEA) is a complication of end-stage renal disease (ESRD) and diabetes. Although recent data show that NLEA rates in the U.S. ESRD population are declining overall, trends in diabetes and diabetes subgroups remain unclear. RESEARCH DESIGN AND METHODS: We estimated annual rates of NLEA hospitalizations during 2000-2015 among >2 million adults (≥18 years) with ESRD from the U.S. Renal Data System. Age, sex, and race-adjusted NLEA rates were stratified by diabetes status, age, sex, race, and level of amputation (toe, foot, below the knee, and above the knee). Time trends were assessed using Joinpoint regression with annual percent changes (APC) reported. RESULTS: Among adults with diabetes, NLEA rates declined 43.8% between 2000 and 2013 (from 7.5 to 4.2 per 100 person-years; APC -4.9, P < 0.001) and then stabilized. Among adults without diabetes, rates of total NLEAs declined 25.5% between 2000 and 2013 (from 1.6 to 1.1; APC -3.0, P < 0.001) and then stabilized. These trends appear to be driven by a slowing or stagnation in declines of minor NLEAs (toe and foot) in more recent years, while major NLEAs (above the knee) continue to decline. CONCLUSIONS: Despite an initial period of decline, this analysis documents a stall in progress in NLEA trends in recent years in a high-risk population with both ESRD and diabetes. Increased attention to preventive foot care in the ESRD population should be considered, particularly for those with diabetes.

Reduced Cardio-Renal Function Accounts for Most of the In-Hospital Morbidity and Mortality Risk Among Patients With Type 2 Diabetes Undergoing Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction.

OBJECTIVE: ST-segment elevation myocardial infarction (STEMI) patients with type 2 diabetes mellitus (DM) have higher in-hospital mortality than those without. Since cardiac and renal functions are the main variables associated with outcome in STEMI, we hypothesized that this prognostic disparity may depend on a higher rate of cardiac and renal dysfunction in DM patients. RESEARCH DESIGN AND METHODS: We retrospectively analyzed 5,152 STEMI patients treated with primary angioplasty. Left ventricular ejection fraction (LVEF) and estimated glomerular filtration rate (eGFR) were evaluated at hospital admission. The primary end point was in-hospital mortality. A composite of in-hospital mortality, cardiogenic shock, and acute kidney injury was the secondary end point. RESULTS: There were 879 patients (17%) with DM. The incidence of LVEF ≤40% (30% vs. 22%), eGFR ≤60 mL/min/1.73 m2 (27% vs. 18%), or both (12% vs. 6%) was higher (P < 0.001 for all comparisons) in DM patients. In-hospital mortality was higher in DM patients than in non-DM patients (6.1% vs. 3.5%; P = 0.002), with an unadjusted odds ratio (OR) of 1.81 (95% CI 1.31-2.49; P < 0.001). However, DM was no longer associated with an increased mortality risk after adjustment for cardiac and renal function (OR 1.03, 95% CI 0.68-1.56; P = 0.89). A similar behavior was observed for the secondary end point, with an unadjusted OR for DM of 1.52 (95% CI 1.25-1.85; P < 0.001) and an OR after adjustment for cardiac and renal function of 1.07 (95% CI 0.85-1.36; P = 0.53). CONCLUSIONS: The study indicates that the increased in-hospital mortality and morbidity of DM patients with STEMI is mainly driven by their underlying cardio-renal dysfunction.