The appearance of renal insufficiency during diabetes completely changes the prognosis and management of the disease. The priority for the nephrologist is to control the blood pressure and adjust the antidiabetic treatment.
The occurrence of kidney damage during diabetes profoundly modifies the prognosis and management of the disease due to the worsening of the cardiovascular prognosis that it induces. This will also induce changes in therapeutic objectives, for diabetes of course, but also for blood pressure and this is a major element of kidney protection. Finally, this will be accompanied by a privileged choice of antidiabetic molecules which have a protective effect for the kidney, but also restrictions on the use of other molecules which are contraindicated in the event of renal insufficiency.
Screening that can be improved
Screening for renal insufficiency is correctly done in diabetics and 80% of patients have an annual or biannual measurement of creatinine, which is not ideal, but which is not so bad either. On the other hand, what is not sufficiently done is the dosage of albuminuria, which is very important in determining the level of renal and cardiovascular risk.
Indeed, an albumin level greater than 30 milligrams in the urine indicates that there is kidney damage. This finding will lead to the prescription of anti-hypertensives blocking the renin-angiotensin system (angiotensin-converting enzyme inhibitor or angiotensin 2 receptor antagonists). This is to solve the problem of high blood pressure which is almost always associated and to prevent the worsening of kidney failure.
A cardiovascular risk factor
When kidney function is impaired, there will be an increased risk of coronary syndrome, atrial fibrillation, heart failure, sudden death and stroke. And the more renal function is impaired, the greater the risk, and therefore this will necessarily modify cardiovascular monitoring and the therapeutic strategy for cardiovascular protection. Finally, this will modify the strategy for the use of antidiabetics because not all drugs can be used in the event of impaired renal function.
Diabetics in general have more acute renal failure accidents than others and this excess risk can be multifactorial (medication, dehydration or infection) and from the moment the renal function is impaired, they even more. It is therefore necessary to intensify monitoring of the kidney and the heart, because the occurrence of acute renal failure also worsens the cardiovascular prognosis.
An event that changes the strategy
Impaired renal function in diabetes is a major cardiovascular risk factor. For nephrologists, as soon as a diabetic has microalbuminuria, it is absolutely necessary to control blood pressure as well as possible with treatment combining at least one blocker of the renin-angiotensin system (angiotensin-converting enzyme inhibitor or antagonist of angiotensin receptors 2). It is also necessary to ensure that the doses of these drugs are maximized and that blood pressure is well controlled, including at home, by implementing automated blood pressure monitoring measures.
In case of moderate impairment of renal function, the combination of a diuretic with one of these 2 antihypertensive blockers of the renin-angiotensin system is a very good combination because it is synergistic on renal protection. On the other hand, if there is no proteinuria, and we see more and more diabetics with renal insufficiency without proteinuria, the most suitable combination is that of a blocker of the renin system and a calcium channel blocker. Second point, from the moment the albuminuria is not normal, it will be necessary to have closer monitoring.
The antidiabetic revolution
From the point of view of antidiabetics, there have been considerable advances in terms of protection of the kidney, “nephroprotection”. SGLT2 inhibitors have thus been shown to provide considerable protection for the kidney. This class of drugs is not yet available in France but they will become essential. The same is true for some GLP1 analogues which provide major nephroprotection and, for some (dulaglutide, liraglutide), without the need for dose adjustment until an advanced stage of renal failure.
On the other hand, the deterioration of renal function poses problems of choice and adaptation of doses among the other drug classes: there are no dosage adjustments to be made for dulaglutide, liraglutide (agonists of GLP1) and DPPP-4 inhibitors, which can be used up to 15 milliliters per minute without dose adjustment. On the other hand, it is necessary to adapt the dose of metformin, but we can now continue to use it up to 30 milliliters per minute if it was already prescribed before the onset of the deterioration of renal function. SGLT2 inhibitors should not be used below 45 milliliters per minute. Sulfonylureas should not be used below 30 milliliters per minute.
The management of a diabetic who has kidney failure, and therefore a high cardiovascular risk, must primarily focus on controlling blood sugar and blood pressure. It is also necessary to ensure that blood pressure is well controlled at home. This is the most important point. It is also necessary to adjust the antidiabetic treatments according to the progression of the renal insufficiency but, the great progress of these last years, is the demonstration that certain antidiabetics have a protective effect for the kidney. Finally, if one is not sure that the deterioration of renal function is related to diabetes, it is absolutely necessary to seek the opinion of the nephrologist who will carry out the necessary examinations to affirm or invalidate this hypothesis.
Interview with Pr Jean-Michel Halimi, nephrologist at CHU Tours
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