The triglyceride to HDL-cholesterol ratio and chronic graft failure in renal transplantation

BACKGROUND: Transplant vasculopathy (TV) is a major contributing factor to chronic graft failure in renal transplant recipients (RTR). TV lesions resemble atherosclerosis in several ways, and it is plausible to believe that some risk factors influence both atherosclerotic plaque formation and formation of TV. OBJECTIVE: The objective of this prospective longitudinal study was to determine if dyslipidemia reflected by the triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C) ratio is prospectively associated with death censored chronic graft failure in RTR. METHOD: 454 prospectively included RTR with a functioning graft for at least one year, were followed for a median of 7 years. RTR were matched based on propensity scores to avoid potential confounding and subsequently the association of the TG/HDL-C ratio with the endpoint chronic graft failure, defined as return to dialysis or re-transplantation, was investigated. RESULTS: Linear regression analysis showed that concentration of insulin, male gender, BMI and number of antihypertensives predict the TG/HDL-C ratio. Cox regression showed that the TG/HDL-C ratio is associated with chronic graft failure (HR = 1.43, 95%CI = 1.12-1.84, p = 0.005) in competing risk analysis for mortality. Interaction testing indicated that the relationship of the TG/HDL-C ratio with graft failure is stronger in subjects with a higher insulin concentration. CONCLUSION: Our results demonstrate that the TG/HDL-C ratio has the potential to act as a predictive clinical biomarker. Furthermore, there is a need for closer attention to lipid management in RTR in clinical practice with a focus on triglyceride metabolism. (c) 2021 National Lipid Association. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Statin Use Is Prospectively Associated With New-Onset Diabetes After Transplantation in Renal Transplant Recipients

OBJECTIVE New-onset diabetes after transplantation (NODAT) is frequent and worsens graft and patient outcomes in renal transplant recipients (RTRs). In the general population, statins are diabetogenic. This study investigated whether statins also increase NODAT risk in RTRs. RESEARCH DESIGN AND METHODS From a prospective longitudinal study of 606 RTRs (functioning allograft >1year,single academic center, follow-up: median 9.6 [range, 6.6–10.2] years), 95 patients using statins were age-and sex-matched to RTRs not on statins (all diabetes-free at inclusion). RESULTS NODAT incidence was 7.2% (73.3% of these on statins). In Kaplan-Meier (log-rank test, P 5 0.017) and Cox regression analyses (HR 3.86 [95% CI 1.21–12.27]; P 5 0.022), statins were prospectively associated with incident NODAT, even independent of several relevant confounders including immunosuppressive medication and biomarkers of glucose homeostasis. CONCLUSIONS This study demonstrates that statin use is prospectively associated with the development of NODAT in RTRs independent of other recognized risk factors

Sodium status and kidney involvement during COVID-19 infection

The angiotensin-converting enzyme 2 receptor (ACE2) is expressed in epithelial cells of many tissues including the kidney, and has been identified to interact with human pathogenic coronaviruses, including SARS-CoV-2. Although diffuse alveolar damage and acute respiratory failure are the main features of COVID-19 infection, two recent studies demonstrate that kidney impairment in hospitalized COVID-19 patients is common, and that kidney involvement is associated with high risk of in-hospital death. Interestingly, studies in rats have demonstrated that high dietary sodium intake results in down-regulation of the ACE2 expression in kidney tissue. We hypothesize that low sodium status makes kidney involvement during the course of COVID-19 infection more likely due to upregulation of membrane bound ACE2 in the kidneys. We propose that sodium intake and status should be monitored carefully during severe COVID-19 infections, and that low sodium intake be corrected early in its course, despite a potential conflict regarding common dietary recommendations to restrict dietary sodium intake in patients with hypertension, diabetes, and kidney disease.</p

Whole-body arginine dimethylation is associated with all-cause mortality in adult renal transplant recipients

Arginine residues in proteins can be singly or doubly methylated post-translationally. Proteolysis of arginine-methylated proteins provides monomethyl arginine, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA). ADMA and SDMA are considered cardiovascular risk factors, with the underlying mechanisms being not yet fully understood. SDMA lacks appreciable metabolism and is almost completely eliminated by the kidney, whereas ADMA is extensively metabolized to dimethylamine (DMA), with a minor ADMA fraction of about 10% being excreted unchanged in the urine. Urinary DMA and ADMA are useful measures of whole-body asymmetric arginine-dimethylation, while urinary SDMA serves as a whole-body measure of symmetric arginine-dimethylation. In renal transplant recipients (RTR), we previously found that higher plasma ADMA concentrations and lower urinary ADMA and SDMA concentrations were associated with a higher risk of all-cause mortality. Yet, in this RTR collective, no data were available for urinary DMA. For the present study, we additionally measured the excretion rate of DMA in 24-h collected urine samples of the RTR and of healthy kidney donors in the cohort, with the aim to quantitate whole-body asymmetric (ADMA, DMA) and symmetric (SDMA) arginine-dimethylation. We found that lower DMA excretion rates were associated with higher all-cause mortality, yet not with cardiovascular mortality. In the healthy donors, kidney donation was associated with considerable decreases in ADMA (by - 39%, P < 0.0001) and SDMA (by - 21%, P < 0.0001) excretion rates, yet there was no significant change in DMA (by - 9%, P = 0.226) excretion rate. Our results suggest that protein-arginine dimethylation is altered in RTR compared to healthy kidney donors and that it is pronouncedly shifted from symmetric to asymmetric arginine-dimethylation, with whole-body protein-arginine dimethylation being almost unaffected

Sodium-Glucose Cotransporter 2 Inhibitors and Kidney Outcomes:True Renoprotection, Loss of Muscle Mass or Both?

Inhibitors of sodium-glucose cotransporter 2 (SGLT2) have emerged as practice-changing treatments for patients with type 2 diabetes, reducing both the risk of cardiovascular events and kidney events. However, regarding the latter, caution is warranted, as these kidney endpoints are defined using glomerular filtration rate estimations based on creatinine, the non-enzymatic product of creatine residing in muscles. Creatinine-based estimations of the glomerular filtration rate are only valid if the treatment has no effect on changes in muscle mass over time. Yet, circumstantial evidence suggests that treatment with SGLT2 inhibitors does result in a loss of muscle mass, rendering serum creatinine-based kidney endpoints invalid. Currently, it cannot be excluded that the described renoprotective effect of SGLT2 inhibitors is in part or in whole the consequence of a loss of muscle mass. Post-hoc analyses of existing trials or new trials based on kidney function markers independent of muscle mass can provide more definitive answers on the proposed renoprotective effects of SGLT2 inhibitors

Personalized Nutrition in Patients with Type 2 Diabetes and Chronic Kidney Disease:The Two-Edged Sword of Dietary Protein Intake

In type 2 diabetes (T2D), there is a general and strong focus on carbohydrate restriction. However, this may have unwarranted consequences for those with concomitant chronic kidney disease (CKD) since decreasing intake of carbohydrates implies a higher proportion of dietary protein, which is of critical debate in patients with CKD due to its ambiguous implications in maintaining either kidney function or nutritional status. We evaluated adherence to the protein recommendations, taking into account the nutritional status of patients with T2D with or without CKD. Patients were divided in three groups according to their estimated Glomerular Filtration Rate (eGFR): mild to no CKD (eGFR > 60 mL/min/1.73 m(2)), moderate CKD (eGFR 30–60 mL/min/1.73 m(2)), or advanced CKD (eGFR 1.3 g/kg/day, and 60% of the patients with advanced CKD consumed > 1.0 g/kg/day. In addition, patients with moderate- or advanced CKD tend to have a lower muscle mass, normalized by height, compared to patients with mild to no CKD (p < 0.001), while body mass index was not significantly different between patients with or without CKD (p = 0.44). We found that although dietary protein restriction has not been indicated in either of the CKD stages, approximately 10% had a dietary protein intake < 0.8 g/kg/day, with accompanying risks of malnourishment and sarcopenia. Our main advice is to maintain a dietary protein intake of at least 0.8 g/kg/day in order to prevent patients from becoming malnourished and sarcopenic