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    "textoCompleto" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">To the Editor&#58;</span></p><p class="elsevierStylePara">In his letter to <span class="elsevierStyleItalic">Nefrolog&#237;a</span> published in this issue&#44;<span class="elsevierStyleSup">1</span> J&#46; Serra Tarragon makes a series of very interesting questions regarding clinical practice based on our original article&#44; &#8220;About the discrepancies between consensus documents&#44; clinical practice guidelines&#44; and legal regulations for the treatment of type 2 diabetes&#8221;&#44;<span class="elsevierStyleSup">2</span> which we agree still need some clarification&#46;</p><p class="elsevierStylePara">Firstly&#44; he makes allusions to the antiquated classification of chronic kidney disease &#40;CKD&#41; as mild&#44; moderate&#44; and severe&#44; instead of the more modern KDOQI<span class="elsevierStyleSup">3</span> and KDIGO<span class="elsevierStyleSup">4</span> system of stages 1-5&#46; We must keep in mind that both classification systems &#40;KDOQI and KDIGO&#41; were published relatively recently&#46; The older of the two &#40;KDOQI&#41; only dates back to 2002&#44; and many drug summary of characteristics have yet to be adapted to this new system&#46;</p><p class="elsevierStylePara">However&#44; in Table 1 and Figure 1 of our article&#44;<span class="elsevierStyleSup">2</span> we discuss the administration of oral anti-diabetic drugs &#40;OAD&#41; using the current KDOQI staging system&#46; Even in Figure 3&#44; in which we evaluate the appropriateness of using dipeptidyl peptidase-4 inhibitors &#40;iDPP-4&#41; for treating patients with renal failure &#40;RF&#41; and liver failure&#44; while we do discuss this issue in terms of mild&#44; moderate&#44; or severe RF&#44; we used the creatinine clearance cut-off value of &#60;30ml&#47;min&#47;1&#46;73m<span class="elsevierStyleSup">2</span>&#44; which corresponds to stage 4 CKD in the current classification system&#46;</p><p class="elsevierStylePara">Traditionally&#44; the Cockcroft-Gault formula &#40;C-G&#41; was used for adjusting medication prescriptions for patients with RF&#46; The adjustment tables published for this purpose were elaborated prior to the publication of the KDOQI guidelines&#44; which established the 1-5 stage system&#46; As such&#44; these tables corresponded to the categories of mild&#44; moderate&#44; and severe&#46; With the objective of analysing which is the most appropriate model for adjusting medication doses&#44; Stevens et al&#46;<span class="elsevierStyleSup">5</span> examined 5504 patients from several studies to compare the MDRD and C-G formulas&#44; incorporating parameters such as ideal weight and standardised creatinine values to perform a pharmacokinetic simulation&#46; The MDRD equation was shown to be better aligned with renal function than the C-G formula&#44; suggesting that the MDRD formula can and should be used for pharmacokinetic studies&#44; as well as in medication adjustment tables&#46; Although it is difficult to prompt an update to the technical data sheets for all medications that require adjustments based on renal function&#44; we can at least hope that all new drugs that appear on the market follow the more updated recommendations from the KDOQI and KDIGO guidelines&#46;</p><p class="elsevierStylePara">The next question refers to the contraindication against the prescription of acarbose in patients with stage 4-5 CKD&#44; in light of the fact that this medication is not eliminated by the kidneys&#46; Indeed&#44; acarbose&#44; as opposed to other &#945;-glucosidase inhibitors such as miglitol&#44; is practically not absorbed by the body&#44; and less than 2&#37; of ingested molecules are eliminated through the urine in the form of active metabolites&#44; for which this drug does not accumulate in cases of RF&#46; To respond to the question posed by Dr&#46; Serra&#44; the contraindication against prescribing acarbose in patients with stage 4-5 CKD is based on two reasons&#58; the first is the lack of studies performed among patients with RF using this drug&#44; as mentioned by other authors&#44;<span class="elsevierStyleSup">6</span> but the primary reason is that the drug technical data sheet<span class="elsevierStyleSup">7</span> states that patients with a creatinine clearance rate &#60;25ml&#47;min&#47;1&#46;73m<span class="elsevierStyleSup">2</span> produce Cmax values and areas under the curve that are 6 and 5 times greater&#44; respectively&#44; than in healthy volunteers with normal renal function&#44; which would indicate that a greater prevalence of secondary side effects would be expected in these patients&#46; This&#44; in addition to the possible interaction between acarbose and diuretics such as furosemide&#44; makes the use of this drug more unadvisable than contraindicated in patients with RF&#46;</p><p class="elsevierStylePara">As regards metformin&#44; the dilemma here lies in the discrepancies between clinical guidelines&#44; recommendations for clinical practice&#44; and the drug technical data sheet&#46; As long as this last element is not modified &#40;a task that falls to the health authorities&#41;&#44; it would be prudent to be cautious in using metformin in clinical practice&#46; Our recommendation&#44; especially in elderly patients&#44; those with important atheromatous disease&#44; and those receiving concomitant treatments with angiotensin-converting enzyme inhibitors&#44; angiotensin receptor blockers&#44; distal diuretics&#44; or non-steroidal anti-inflammatory drugs&#44; would be to closely monitor glycaemia&#44; haemogram results&#44; and renal function when estimated glomerular filtration rates &#40;GFR&#41; fall below 45ml&#47;min&#47;1&#46;73m<span class="elsevierStyleSup">2</span>&#44; and interruption of treatment when GFR falls below 30ml&#47;min&#47;1&#46;73m<span class="elsevierStyleSup">2</span>&#46;</p><p class="elsevierStylePara">As regards treatment with iDPP-4&#44; the differences derive from the variable level of metabolisation of this compound in the kidneys&#46; As such&#44; several clinical trials and studies in patients with diabetes mellitus and RF of varying severity recommend reducing or suspending the dose of iDPP-4 below a fixed glomerular filtration rate cut-off value due to the possibility of hypoglycaemia&#46; Linagliptin can be administered in any stage of CKD&#44; since this is the only iDPP-4 that can be eliminated through the bile&#44; with only a small percentage of molecules passing through the kidneys&#46; As described in the ACCORD&#44;<span class="elsevierStyleSup">8</span> ADVANCE&#44;<span class="elsevierStyleSup">9</span> and other studies&#44; strict control of HbA<span class="elsevierStyleInf">1c</span> in diabetic patients can produce increased morbidity and mortality rates&#44; which are accentuated in the presence of RF and high comorbidity&#46; On the other hand&#44; HbA<span class="elsevierStyleInf">1c</span> does not appear to be the most reliable biochemical marker for ensuring proper control of glycaemia in patients with RF&#46; Glycated albumin appears to be a more reliable option&#44; especially in patients with CKD in stage 3 or higher&#46;<span class="elsevierStyleSup">10</span> The inconveniences of this technique are its high cost and the relative scarcity of laboratory analyses using this parameter&#46;</p><p class="elsevierStylePara">Finally&#44; another important issue is the measures to be taken in the case of patients with diabetes and acute renal failure&#46; The 2011 updates to the KDIGO guidelines<span class="elsevierStyleSup">11</span> reported on the convenience of adapting the dosage of medications in patients with chronic vs&#46; acute RF&#46; In diabetic patients on treatment with OAD who suffer an episode of acute RF&#44; and especially in those cases that require renal replacement therapy with dialysis&#44; we suggest proceeding with great caution&#46; The patient should be administered rapid-acting insulin and basal insulin analogues&#44; with frequent monitoring and control of glycaemia in the context of the evolution of renal function parameters&#46; This management should be carried out with special emphasis in patients with oligoanuria&#44; since the dosage of insulin will have to be modified based on the recovery of diuresis in these patients&#46;</p><p class="elsevierStylePara">We hope this has contributed to clarifying some of the aforementioned controversial aspects of this issue&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Conflicts of interest</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">The authors state that they have no potential conflicts of interest related to the content of this article&#46;</p>"
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