Plasma Concentrations of Trimethylamine-N-Oxide, Choline, and Betaine in Patients With Moderate to Advanced Chronic Kidney Disease and Their Relation to Cardiovascular and Renal Outcomes.

OBJECTIVES: Trimethylamine N-oxide (TMAO) is a gut bacteria-mediated liver metabolite of dietary betaine, choline, and carnitine, which is excreted by glomerular filtration. We studied whether TMAO is excreted by cardiovascular disease (CVD) in patients with chronic kidney disease (CKD). METHODS: Among 478 patients with CKD stage G2 (n = 104), G3a (n = 163), G3b (n = 123), and G4 (n = 88), we studied the association between fasting plasma concentrations of TMAO, choline, or betaine at baseline and kidney function, prevalent CVD, and future renal outcomes during a mean follow-up of 5.1 years. RESULTS: Decreased glomerular filtration rate was associated with higher plasma concentrations of TMAO, choline, and betaine. Baseline concentrations of TMAO were higher in participants with preexisting CVD compared to those without CVD (8.4 [10.1] vs. 7.8 [8.0] µmol/L; P = .047), but the difference was not significant after adjusting for confounders. During the follow-up, 147 participants experienced CVD or died, and 144 reached the predefined renal endpoint. In the adjusted regression analyses, TMAO or choline concentrations in the upper three quartiles (vs. the lowest quartile) were not associated with any of the study's clinical endpoints. In contrast, the adjusted hazard ratio of plasma betaine in the highest quartile versus the lowest quartile was 2.14 (1.32, 3.47) for the CVD endpoint and 1.64 (1.00, 2.67) for the renal endpoint. CONCLUSIONS: Elevated plasma TMAO concentrations were explained by impaired kidney function. Elevated plasma concentrations of betaine, but not those of TMAO or choline, constituted a risk factor for adverse outcomes. TMAO might not be an appropriate target to reduce CVD or renal outcomes in patients with preexisting CKD.

ELOVL2-methylation and renal and cardiovascular event in patients with chronic kidney disease.

BACKGROUND: Methylation of the Elongation Of Very Long Chain Fatty Acids-Like 2 (ELOVL2) gene promoter may predict premature ageing and cardiovascular risk. METHODS: We studied the cross-sectional associations between blood ELOVL2-methylation and cardiovascular risk factors in 350 patients with chronic kidney disease (CKD) stage G2-G4 aged between 22 and 90 years. In a follow-up study for a mean of 3.9 years, we investigated the association between baseline ELOVL2-methylation and renal or cardiovascular events including death. RESULTS: ELOVL2-methylation at seven CpG cites increased with age (the correlation coefficients between 0.67 and 0.87, p < 0.001). The ELOVL2-CpGs methylation was lower in patients with CKD stage G2 versus those in stage G3a, G3b and G4, but the differences were explained by age. ELOVL2-CpGs methylation showed no correlations with cardiovascular risk factors after adjusting for age. During the follow-up, 64 patients showed deterioration in renal function or died and 77 showed cardiovascular events or died. The hazard ratio and 95% confidence intervals for renal or cardiovascular events according to baseline ELOVL2-CpGs methylation were not significant after adjustment for covariates. CONCLUSIONS: ELOVL2-hypermethylation showed a strong association with age, but was not independently associated with cardiovascular risk factors or with future renal or cardiovascular events in patients with CKD. ELOVL2 gene methylation is not likely to be itself a cause for ageing or illnesses, but it could be rather influenced by other upstream processes that deserve investigation.

[Cardiovascular treatment in chronic kidney disease]. / Kardiovaskuläre Therapie bei chronischer Nierenerkrankung.

Patients with combined cardiac and renal diseases are particularly challenging in the routine clinical practice due to the substantial risk profile for increased morbidity and mortality. As cardiorenal patients have often been underrepresented in randomized, controlled interventional trials, guideline recommendations regarding the choice of treatment are often weaker for these individuals than for cardiovascular patients without chronic kidney disease. Furthermore, there are limitations in the approval of certain medications depending on the kidney function. This review addresses some considerations in crucial treatment areas for patients with cardiovascular diseases, whose treatment is significantly influenced by concomitant chronic kidney disease.

Anticoagulation, atrial fibrillation, and chronic kidney disease-whose side are you on?

Whether to initiate oral anticoagulant therapy in advanced chronic kidney disease patients with atrial fibrillation remains debatable. Although randomized trial data are lacking, observational studies yield controversial results. Keskar and colleagues analyzed data from a Canadian health care system and found that in elderly chronic kidney disease patients with atrial fibrillation, oral anticoagulant therapy did not prevent ischemic strokes, induced hemorrhages, but prolonged life. These paradoxical findings emphasize the dire need for an adequately powered randomized trial.

Percutaneous interventional thrombectomy of an endovascular AV-fistula, a case report.

Dialysis access thrombosis is a common complication in the process of care. With the introduction of endovascular AV-fistulas [AVF]s the situation gained complexity with new potential thrombosis localizations. Several thrombectomy methods are available for recanalization of thrombosed AVFs ranging from invasive surgical methods to minimal invasive endovascular approaches. Early assessment, diagnosis and treatment is crucial for prolonging the life span of an AVF and preventing the need for placement of central venous catheters. To our best knowledge, we present the first case in which an obstructed antecubital communicating vein (aka perforating vein) of an endovascular created AVF was re-opened via interventional thrombectomy with the Rotarex® System (BD Interventional). The procedure was performed primarily under ultrasound guidance with fluoroscopic support. Our case report shows that this method, if done correctly and successfully, may prevent loss of the dialysis access. Additionally, we point towards the central role of ultrasound in this method.

[Volume Management in Chronic kidney disease]. / Volumenmanagement bei chronischen Nierenerkrankungen.

Understanding the (patho-)physiology of volume regulation and osmoregulation is fundamental to guide patient advice and therapy in chronic kidney disease (CKD). Volume regulation primarily impacts the amount of sodium in the body, and it mainly affects the extracellular space, while osmoregulation primarily impacts the amount of free water, and it affects both the intra- and extracellular space. The kidneys control water and sodium homeostasis both through their sensor (e. g. tubuloglomerular feedback) and regulator systems (e. g. sodium reabsorption). Many CKD patients are advised by non-nephrologists to a high fluid intake, although they often do not require a daily intake of more than 1.5 litres. Many CKD patients are hypervolemic, and sodium restriction is of key importance in patients' effort to utilize lifestyle changes as therapeutic means. Pharmacologically, (particularly loop) diuretics are the basis of therapy, increasing sodium excretion. Recent developments shift the focus towards classes of drugs ameliorating prognosis in CKD: sodium-glucose linked transporter 2 (SGLT2) inhibitors have proven beneficial in heart and renal failure - by sodium and fluid excretion, among others; additionally, a novel mineralocorticoid receptor antagonist (MRA), finerenone, was recently shown to improve prognosis in CKD.

[Antidiabetic SGLT-2 inhibitors prevent progression of chronic kidney disease]. / SGLT-2-Inhibitoren zur Progressionshemmung der chronischen Nierenerkrankung.

Several interventional trials that studied cardiovascular safety of antidiabetic drugs in patients with diabetes mellitus and elevated risk of cardiovascular disease suggested potential nephroprotective effects of SGLT-2 inhibitors. Subsequently, the CREDENCE study confirmed reduced progression of chronic kidney disease (CKD) towards dialysis-dependency in diabetic patients with mildly or moderately impaired glomerular filtration rate and high albuminuria. Next, the DAPA-CKD and EMPA-KIDNEY studies were initiated to test whether SGLT-2-inhibitors will also affect CKD progression in (a) non-diabetic CKD patients, (b) in CKD patients without albuminuria and/or (c) in patients with advanced CKD. The premature stop of DAPA-CKD was announced in March 2020 because of overwhelming nephroprotective effects of dapagliflozin. The final publication of DAPA-CKD is expected in late 2020. Parallelly, new treatment guidelines from the Kidney-Disease:-Improving-Global-Outcomes (KDIGO)-Initiative will recommend SGLT-2 inhibitors as standard treatment for CKD patients with diabetes mellitus, even though these drugs are not yet licensed for patients with moderately-to-severely reduced renal function.

[Pharmacologic treatment of heart failure with reduced ejection fraction in chronic kidney disease]. / Medikamentöse Therapie der Herzinsuffizienz mit reduzierter Ejektionsfraktion bei chronischer Nierenerkrankung.

Medical management of patients with co-existing Heart Failure with reduced Ejection Fraction (HFrEF) and chronic kidney disease (CKD) poses a significant challenge to treating physicians. On the one hand, the traditional therapeutic strategies such as betablockers, angiotensin converting enzyme inhibiotors, angiotensin receptor blockers and mineralocorticoid receptor antagonists have been evaluated in clinical trials that broadly excluded patients with significant CKD. On the other hand, inhibition of the renin angiotensin aldosterone system can lead to worsening of renal function and hyperkalemia potentially causing harm. Consequently, the cornerstones of heart failure treatment are often not adequately employed in HFrEF patients with CKD, a fact which is in itself a risk factor for worse outcomes in this patient population. Notably, it has been shown that these established pharmacologic strategies can be safely administered when carefully monitored. Iron treatment in anemia in CKD is well established and outcome trials in HFrEF are underway. New therapeutic strategies are under current investigation. Sodium glucose transporter 2 inhibitors show promising results in HFrEF and in CKD trials. In addition, Sacubitril/Valsartan significantly reduced events in HFrEF and might reduce renal events in HFpEF.