Homocysteine and chronic kidney disease: an ongoing narrative

Excerpt

Chronic kidney disease (CKD) patients are a growing population worldwide, affected by a high cardiovascular risk. The cause of this increase is certainly multifactorial; one of the possible culprits that have been invoked may lie in the marked derangement in the complex sulfur metabolism peculiar to these patients, leading to altered levels of several compounds in this pathway (Fig. 1). Homocysteine is probably the most studied among these; however, despite the huge amount of evidence that homocysteine, and/or one of its precursors/metabolites, is toxic [1, 2], the negative interventional trials brought the scientific community to consider it as the epitome of something that does not come through [3]. It is possibile that the negative results of the trials in CKD patients, conducted by the way in countries where folate fortification is mandatory, can be ascribed to the presence in the intervention of cianocobalamin [4]. Vitamin B₁₂ is necessary for correct homocysteine remethylation, but cianocobalamin in CKD can accumulate and be detrimental. Another reason could be related to the possible adverse effects of high-dose folic acid, for example due to the presence of circulating UnMetabolized Folic Acid [UMFA, 5]. Slowly, however, new evidence is arising. In the China Stroke Prevention Primary Prevention Trial (CSPPT), it has been shown that low-dose folic acid (0.8 mg/day) is able to reduce the incidence of primary stroke in hypertensive patients [6]. In addition, a pre-specified CSPPT substudy demonstrates that low-dose folic acid is effective in slowing down the progression of CKD. Patients with moderate CKD (eGFR between 30–60 ml/min) benefit the most. The common methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism influences homocysteine levels and the renal outcome response [7]. Thus, if data are confirmed also in other populations, low-dose folic acid could constitute another tool to contrast CKD progression in our still scarce therapeutic armamentarium.

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