Elevation of Trimethylamine-N-Oxide in Chronic Kidney Disease: Contribution of Decreased Glomerular Filtration Rate.

Gut microbiota-dependent Trimethylamine-N-oxide (TMAO) has been reported to be strongly linked to renal function and to increased cardiovascular events in the general population and in Chronic Kidney Disease (CKD) patients. Considering the lack of data assessing renal handling of TMAO, we conducted this study to explore renal excretion and mechanisms of accumulation of TMAO during CKD. We prospectively measured glomerular filtration rate (mGFR) with gold standard methods and plasma concentrations of trimethylamine (TMA), TMAO, choline, betaine, and carnitine by LC-MS/MS in 124 controls, CKD, and hemodialysis (HD) patients. Renal clearance of each metabolite was assessed in a sub-group of 32 patients. Plasma TMAO was inversely correlated with mGFR (r2 = 0.388, p < 0.001), confirming elevation of TMAO plasma levels in CKD. TMAO clearances were not significantly different from mGFR, with a mean ± SD TMAO fractional excretion of 105% ± 32%. This suggests a complete renal excretion of TMAO by glomerular filtration with a negligible participation of tubular secretion or reabsorption, during all stages of CKD. Moreover, TMAO was effectively removed within 4 h of hemodiafiltration, showing a higher fractional reduction value than that of urea (84.9% ± 6.5% vs. 79.2% ± 5.7%, p = 0.04). This study reports a strong correlation between plasma TMAO levels and mGFR, in CKD, that can be mainly related to a decrease in TMAO glomerular filtration. Clearance data did not support a significant role for tubular secretion in TMAO renal elimination.

[When and how we start the treatment in patients with ocular hypertension or in glaucoma suspects?]. / Când si cum initiem tratamentul la hipertensivul ocular si suspectul de glaucom?

The therapeutic decision should be a collaboration between us the doctor and the patient. Patients have different tolerance and education levels, ranging from the highly cautious to the careless one. Treatment initiation in glaucoma is based on intraocular pressure levels, age, race, life expectancy, family history, progression risk, associated pathology. The therapeutic effort is aiming to maintain both quality of life and sight, through sustainable costs. Now we have the proof that intraocular pressure is just another risk factor among many others, lowering-pressure treatment being able to reduce the individual risk of progression. Still, only the high-risk ocular hypertension will be treated, considering other risk factors. There is a fine line between early glaucoma and ocular hypertension, the therapeutic decision and monitoring algorithm varying with the individual risk of progression.