Nephroprotection

NephroprotectionGeneralities:

Chronic kidney disease as well as chronic renal failure have recently been defined in American recommendations (K / DOQI), more recently adopted by the French National Agency for Accreditation and Evaluation in Health (ANAES, 2002) in France.

Schematically, chronic renal diseases are defined by the presence, for more than 3 months, of biological, morphological or histological renal abnormalities and / or renal insufficiency.

Chronic renal failure is divided into five stages, based on glomerular filtration estimated from the calculated clearance (according to the Cockcroft formula in France, according to the simplified formula of the United States’ Modification of Diet in Renal Diseases [MDRD]). -United).

This classification distinguishes five degrees of severity according to the calculated clearance values:

Renal failure is termed terminal for a clearance of less than 15 ml / min (stage 5);

– renal failure is called severe for a calculated clearance of 15 to 30 ml / min (stage 4);

Chronic renal failure is said to be moderate for a calculated clearance of between 30 and 60 ml / min (stage 3);

– Chronic kidney failure is called beginner for calculated clearances between 60 and 90 ml / min, in combination with known kidney disease (stage 2);

– chronic renal failure is considered absent for calculated clearances above 90 ml / min, but in this case, the presence of renal abnormalities defines chronic nephropathy without renal failure (stage 1).

This classification is conceptually important because it makes it possible to homogenize the epidemiological description of renal diseases and intervention trials, and finally because it gives primacy to the estimation of glomerular filtration by the calculated clearance, rather than plasma creatinine alone, as in the past.

Overall, the objectives of the management of patients with chronic renal failure are three:

– avoid dialysis or increase the life without dialysis by slowing the progression of kidney disease;

– maintain a good general state until the start of extrarenal treatment, especially when a kidney transplant is planned;

– prevent the complications of chronic renal failure and in particular cardiovascular morbidity / mortality.

The first two objectives are apparently conflicting and emphasize the importance of starting extra-renal cleansing at the best time, as it is currently defined by a calculated clearance of less than 10 ml / min and / or the occurrence of irreversible complications. defined by the recommendations of ANAES 2002.

Most, if not all, renal diseases are progressive, although the rate of change is extremely variable from one nephropathy to another and, for the same nephropathy, from one individual to another. Slowing down progression is one of the major challenges of nephrology in the 21st century. Curbing this progression can be achieved in two complementary and non-exclusive ways:

– ensuring the etiological diagnosis and optimizing specific treatments for nephropathies (eg corticosteroids and immunosuppressors of lupus nephropathy);

– by setting up a non-specific nephroprotective treatment.

It is this last point that will be the subject of this review (excluding the cases of the child and the renal transplant). This article will be written whenever possible on the basis of “evidence-based medicine” and will be followed by practical recommendations adapted themselves from the recommendations of learned societies, where these recommendations exist.

Risk Factors for Renal Disease Progression:

Many risk factors for kidney disease progression have been identified, some of which are modifiable.

The analysis of all these factors is beyond the scope of this review; only the modifiable risk factors that may be the subject of a therapeutic impact will be addressed: arterial hypertension and proteinuria.

ARTERIAL HYPERTENSION:

Hypertension is present in the majority of patients with chronic renal failure. Data from the initial MDRD cohort showed that hypertension was present in 65 to 75% of patients with glomerular filtration of 60 to 80 ml / min. Hypertension is a reversible risk factor for progression of kidney disease.

PROTEINURY:

The degree of proteinuria is one of the most important predictors of kidney disease progression, as is the response to antiproteinuric therapy, in virtually all chronic kidney disease studies. The relationship between the risk of progression and the level of proteinuria is globally “dose-dependent”. The degree of proteinuria is also a predictor of the response to treatment. For example, in the MDRD study, the patients who best responded to the sharp drop in blood pressure at 92 mmHg mean arterial pressure were those who excreted more than 3 g / 24 h of proteinuria.

In addition, the benefit of slowing progression depends directly on the reduction of proteinuria under intervention and more particularly the residual proteinuria under treatment (Ramipril Efficacy in Nephropathies [REIN], Reduction of Endpoint in Diabetic Nephropathy with the Angiotensin Antagonist Losartan [RENAAL]). This also illustrates the causal relationship between proteinuria and progression.

Strategies to slow progression:

ANTIHYPERTENESS TREATMENT:

Numerous studies and meta-analyzes have shown the benefit of reducing blood pressure on renal progression (accounting for 50% of the variance in the decrease in glomerular filtration). This discussion is quite academic because hypertensive patients with renal insufficiency, who are for the most part at high cardiovascular risk, must benefit from antihypertensive treatment anyway. The two really important questions in the clinic are:

– what is the optimal blood pressure target to slow progression?

– do certain classes of antihypertensive drugs have specific effects on progression?

The optimal level of blood pressure control in patients with renal impairment has been examined in several settings. In type 1 diabetics with nephropathy, the lowest arterial pressures are associated with the slowest glomerular filtration rates of decline, with no observed threshold effects.

In a post-hoc analysis of the RENAAL trial, the risk of end-stage renal disease increases proportionally with initial systolic blood pressure (starting from a threshold of 130 mmHg), with the initial pulse pressure (above a threshold of 60 mmHg), with systolic and diastolic and pulsed arterial pressures being studied. In this study, losartan reduces the risk of end-stage renal disease by approximately 30%, but there is an interaction between the effect of treatment and the level of blood pressure achieved during the study. The magnitude of the benefit of losartan is even greater in patients with blood pressure under study lower than both 140 and 90 mmHg (-40% reduction in the risk of end-stage renal failure) but, conversely , decreases when the systolic blood pressure is greater than 140 mmHg (risk reduction – 20%) and even disappears in patients with a diastolic blood pressure higher than 90 mmHg. This illustrates that the therapeutic goal is both blocking angiotensin 2 and achieving a blood pressure level of at least 130/80 mmHg as the risk of progression increases beyond this threshold.

In the MDRD study, nondiabetic patients were randomized to different levels of food restriction and randomized to two levels of mean arterial pressure: 107 versus 92 mmHg. A decrease in the rate of progression was observed in proteinuric patients with the lowest blood pressure level. In addition, there was a significant correlation between the level of blood pressure achieved and the rate of decrease in glomerular filtration rate, particularly in patients with more than 1 g of proteinuria per day.

In contrast to these observations, Afro-American Study of Kidney Diseases (AASK) studied two different blood pressure targets (usual target: mean blood pressure 102-107, versus intensive target: mean arterial pressure  92 mmHg) on ​​the progression of nephrosclerosis hypertension in black-American subjects. There was no difference in the rate of loss of renal function between the two blood pressure target values. Proteinuria in these patients was generally lower than that of the patients enrolled in the MDRD study, which could account for different results.

The meta-analysis of Jafar et al. studied individual data from 1860 non-diabetic patients, data from 11 randomized controlled trials comparing antihypertensive therapy with angiotensin-converting enzyme (ACE) inhibitors versus placebo or non-IEC non-blocker antihypertensive therapy. angiotensin 2 (ARA2) for an average of 2.2 years. In this meta-analysis, systolic (but not diastolic) blood pressure during treatment and proteinuria during treatment are strongly associated with the risk of progression (doubling of plasma creatinine and / or end-stage renal failure). In patients with proteinuria greater than 1 g / day, the risk of progression is minimal for a systolic blood pressure of 110-120 mmHg and increases rapidly ( Å ~ 4 to 5) if the systolic blood pressure is greater than 130 mmHg and this regardless of the type of antihypertensive treatment (IEC or non-IEC). The effect of systolic blood pressure level is poor in patients with proteinuria <1 g / day. In contrast, regardless of the level of proteinuria or the type of antihypertensive therapy (with or without ACE inhibitors), the risk of progression increases when the systolic blood pressure is below 110 mmHg, probably due to deterioration of renal perfusion. (curve in J).

Currently, all learned societies (Kidney / Dialysis Outcomes Quality Initiative [K / DOQI], 2004; Joint National Committee report version 7 [JNC7], 2003 European Society of Hypertension – European Society of Cardiology [ESHESC], 2003; British Hypertension Society BHS, 2004, ANAES, 2004) recommend that blood pressure be lowered to below 130/80 mmHg in patients with renal impairment, or even lower if clinically well supported.

“Ultra-low” values ​​(up to a systolic blood pressure of 110-120 mmHg) are probably desirable (subject to good clinical tolerance), especially in patients with diabetic nephropathy (type 1 or type 2) and in non-diabetic patients with proteinuria greater than 1 g / day. The definitive validation of these ultra-low arterial pressures should, however, be based on additional specific studies.

ANTIPROTEINURIC TREATMENT: PLACE OF BLOCKERS OF THE RENIN-ANGIOTENSIN SYSTEM

In recent years, both clinical and experimental data have demonstrated that inhibition of the renineangiotensin system (either by ACE inhibitors or by ARBs) has a protective effect in addition to and beyond the effects of these treatments. blood pressure reduction. The benefits of blocking the renin-angiotensin system have now been demonstrated both in populations of subjects with diabetic and non-diabetic nephropathy. These studies have been analyzed in detail elsewhere and will therefore only be mentioned here.

Main studies:

In the context of diabetic nephropathy, the main interventions were made with captopril versus placebo during type 1 diabetes nephropathy and with losartan versus placebo (RENAAL) and irbesartan versus placebo versus amlodipine (Irbesartan Diabetic Nephropathy Trial [ IDNT]) in nephropathy of type 2 diabetes.

In the context of non-diabetic nephropathies, the main studies are Angiotensin-Converting-Enzyme Inhibition in Progressive Renal Insufficiency (AIPRI) (Benazepril versus placebo), REIN (ramipril versus placebo), AASK (bifactorial plan studying two levels of blood pressure target: pressure mean arterial 102-107 versus > 92 mmHg and three classes of antihypertensive drugs, ramipril versus metoprolol versus amlodipine). These and other smaller studies were meta-analyzed from individual data.

In the meta-analysis of Jafar et al. already cited, the IEC treatment is unequivocally more effective in reducing proteinuria, the risk of end-stage renal failure and the combined doubling of plasma creatinine + incidence of end-stage renal failure.

The renoprotective effect of ACE inhibitors is greater in patients with proteinuria that is abundant and greater than would be expected from isolated reduction in blood pressure or proteinuria.

These observations are consistent with experimental studies that have demonstrated the ability of ACE inhibitors to decrease intraglomerular pressure and the production of profibrotic cytokines and renal interstitial fibrosis lesions.

Compared with other antihypertensive drugs, the blockage of the renin-angiotensin system slows the progression rate by an average of 30 to 40%. Patients with the highest proteinuria benefit more from these forms of treatment, but the benefit in reducing the risk of end-stage renal failure can be demonstrated from a proteinuria level above 0.5 g / d.Below this value of proteinuria, the effect is probable but not demonstrated. The additional beneficial effect of blocking the renin-angiotensin system is mainly related to its ability to reduce proteinuria beyond the expected effect of blood pressure reduction, but the antiproteinuric benefit is synergistic with blood pressure reduction as shown in Figure 1. RENAAL study and suggests the study MDRD and especially the meta-analysis of Jafar. These studies have thus shifted the concept of antihypertensive intervention to a concept of antiproteinuric intervention, regardless of the blood pressure level.

In summary, these trials clearly demonstrate the specific renoprotective effect of ACEI and ARB2 to slow the progression of kidney disease. These agents should therefore be considered as the drugs of choice in patients with kidney disease (JNC7, ESH 2003, BHS 2004, KDOQI 2004, ANAES 2004).

The categories of patients who benefit the most from these interventions blocking the renin-angiotensin system are:

– Certainly, patients with renal impairment defined by a calculated clearance of between 30 and 60 ml / min and this especially as there is proteinuria;

– this benefit can be extended to patients with nephropathy defined by proteinuria and a calculated clearance greater than 60 ml / min (stages 1 and 2). Although the benefit has not been formally demonstrated in this category of patients (as it would require much longer studies to demonstrate an effect on the end-stage renal failure endpoint), this benefit is reasonably extrapolable given the same favorable effect on patients. intermediate criteria such as proteinuria. It must also be emphasized that the impact of such treatment applied at these early stages is much stronger in both individual and collective terms since the total number of years of dialysis avoided is much greater;

– the benefit is likely in patients with chronic renal failure defined by a clearance calculated between 15 and 30 ml / min (some studies, like REIN, included patients up to 20 ml / min). However, blockage of the renin-angiotensin system in these patients should be used with extreme caution because of the greater initial risk of worsening renal function which, in this case, may cause some patients to switch to dialysis more rapidly. .

Combined blockade of the renin-angiotensin system:

ACE inhibitors and ARBs differ in the mechanisms by which they inhibit angiotensin 2. Treatment with ACE inhibitor + ARA2 blocks the effect of angiotensin 2 by decreasing its synthesis and antagonizing its effect on the AT1 receptor.These two classes of drugs are individually effective in experimental and clinical studies to reduce proteinuria and the progression of renal failure. Experimental studies have suggested that such a combination may have an additional effect on the progression of renal impairment compared to that of each drug alone.

COOPERATE, a randomized, double-blind study designed to test the efficacy and safety of combined treatment with ACE inhibitor (trandalopril) and ARA2 (losartan) compared monotherapy with each of these drugs in 263 patients with renal disease of non-diabetic origin (glomerular filtration calculated at 70 ml / min). Patients were followed for a median duration of 2.9 years. With combination therapy, 11% of patients achieved the combined doubling of plasma creatinine + end stage renal failure, compared to 23% of patients treated with trandolapril alone and 23% of patients treated with losartan alone. There was no difference in blood pressure between the groups. The combined treatment was responsible for a marked antiproteinuric effect, compared with each of the monotherapies. Overall, both monotherapies and combination therapy were well tolerated. A higher incidence of hyperkalemia and cough was observed with trandolapril and combination therapy compared with losartan.

Other trials with combination therapies were conducted but included smaller numbers, shorter duration of follow-up, and judgmental criteria based on decreased proteinuria or blood pressure.

These studies, performed in diabetic and non-diabetic nephropathies, suggest a beneficial effect of combination therapy with acceptable tolerance. None of these studies, however, can definitively establish whether the additional benefit observed is obtained because of a synergistic IEC-ARA2 action or by a more intense and prolonged blockade of the renineangiotensin system (double dose).

OPTIMIZATION OF BLOCKING OF THE RENIN-ANGIOTENSIN SYSTEM:

What blockers of the renin-angiotensin system to use and how to proceed?

Based on the available trials, ARA2 should be favored in type 2 diabetic nephropathy and ACE in all other cases (type 1 diabetes nephropathy and non-diabetic nephropathy) (ANAES 2004, KQOQI 2004). The class effect has never been formally studied. However, it is likely, given the consistency of the positive results and the magnitude of benefit in the different studies that used drugs of the same class. Until proven otherwise, it is better to favor molecules that have demonstrated efficacy in controlled trials, ie ramipril, enalapril, benazepril, captopril or trandolapril for ACE inhibitors, and losartan or irbesartan for ARBs. In all cases, it is important to remember that the benefit depends on the dose used which is generally high in all these intervention trials (eg ramipril 10 mg / d and losartan 100 mg / d). Using lower doses than trials reduces the expected benefit amplitude pro rata, as shown by the DIABHYCAR and ATLAS studies.

Dosage titration should be performed until the target is achieved (systolic blood pressure 110-130 mmHg and diastolic blood pressure < 80 mmHg and proteinuria < 0.5 g / d).

This titration must be carried out up to the maximum authorized doses for the chosen molecule until these targets are obtained, but may be limited by clinical or biological tolerance.

In case of specific intolerance to ACE (disabling cough and especially angioneurotic edema), ACE can be replaced by ARBs. In all cases, conventional contraindications to ACE inhibitors and ARBs should be respected (allergy, pregnancy and renal artery stenosis). In patients at high risk for renal artery stenosis, such as patients with type 2 diabetes or a posteriori in patients with severe hypertension resistant to triple therapy, it should be systematically sought.

A reduction in sodium intake to 5 to 8 g / 24 hours should be systematically associated with these drugs, given the significant potentiation expected on the antihypertensive response on the one hand and antiproteinuric on the other hand.

The effectiveness of the treatment is judged by the blood pressure reduction, which can be estimated after 4 to 6 weeks of treatment, and by the proteinuric response, which is significant after 2 to 3 months of treatment but probably only after 6 months.

In initially normotensive patients, lowering of blood pressure is usual, especially for orthostatism, and should be respected if clinical tolerance is satisfactory. If not, dose adjustment may be necessary.

Patients with chronic kidney disease are at high risk of complications from pharmacological treatments and should be monitored more frequently, more rigorously than patients without these renal complications. Biological monitoring with at least creatinine, calculated clearance and serum potassium should be routinely performed 10 to 15 days after initiation of treatment and after each dose change.

The increase in dosage should be gradual and especially as the renal function is initially impaired.

The increase in plasma creatinine or the decrease in clearance calculated immediately after the initiation of treatment is usual and represents a criterion of efficacy, this initial reduction in clearance being correlated with the reduction of proteinuria in the short term and with slower growth in the longer term. The increase in plasma creatinine or the reduction in clearance should not exceed 30% over 4 months after initiation of treatment. In this case, it is necessary to seek a favorable factor (anti-inflammatory treatment, dehydration or too aggressive diuretic treatment) and to stop transiently or to reduce the dosage of the treatment with blockers of the renin-angiotensin system. Such aggravation does not constitute a definitive contraindication to this type of treatment but encourages it to be resumed more gradually (more gradual titration and possibly lower maximum dosage).

In this situation, a stenosis of the renal artery is usually sought if it has not been previously, especially in older subjects, vascular or diabetic. The diagnostic and therapeutic cost-effectiveness of such an approach is however low in this specific context.

Hyperkalemia is the most serious complication of these blocking treatments of the renin-angiotensin system.

Hyperkalemia is all the more frequent and severe because of the following factors:

– renal failure more marked;

– nephropathy of diabetic origin;

– coprescription of drugs blocking the synthesis of aldosterone or its action (nonsteroidal anti-inflammatory drugs, COXIB, amiloride, spironolactone, eplerenone, heparins, anticalcineurins …);

– high doses of ACE seem to be more often responsible for hyperkalemia than high doses of ARB2, but this point is not definitively established.

The occurrence of hyperkalemia does not constitute a definitive contraindication to the blockers of the renin-angiotensin system but encourages us to be doubly vigilant in the use of these drugs and to implement appropriate dietary and therapeutic measures to limit serum potassium below 5.0 mmol / l. It is then necessary to look for a food excess in potassium (high kaliuresis) and to correct the hyperkalemia by increasing the elimination of the potassium, either by the renal route (diuretic), or by the digestive way (ion exchange resin: polystyrene sulfonate, Kayexalate t ).The use of long-term fludrocortisone is not advisable because of the significant risks of sodium retention and arterial hypertension, or even heart failure.

In case of failure to obtain the therapeutic target at maximum doses of blockers of the renin-angiotensin system as monotherapy, the best second-line strategy has not been much studied.

If the blood pressure target is not reached, most learned societies recommend the use of diuretic therapy (thiazide or loop diuretic according to renal function). The frequency and importance of water-soluble retention, sometimes clinically occult, is often underestimated in kidney disease. Third-line drugs include beta-blockers and / or calcium antagonists. Recall that dihydropyridines should not be used as monotherapy or first-line therapy in patients with renal proteinuria, because of the risk of its aggravation and potentially renal failure (AASK, REIN, IDNT).

If the antiproteinuric target (proteinuria < 0.5 g / 24 h) is not reached under maximal dose monotherapy blockers of the renin-angiotensin system, the attitude is less formally established. Given the importance of residual proteinuria as a progression factor and the results of COOPERATE, we recommend the addition of a blocker drug of the renin-angiotensin system of the class not previously used (ie an ARA2 in addition to an IEC or vice versa) with progressive titration according to the clinical and biological tolerance until obtaining the proteinuric target. The direct comparison of such an association with the introduction of a diuretic treatment, especially if the food intake is too important, has not been formally studied.

DIETARY INTERVENTIONS:

In addition to the moderately restricted sodium diet (between 5 and 8 g / 24 h) necessary and systematic to potentiate the antihypertensive and antiproteinuric effect of the blockers of the renin-angiotensin system, a restriction of the food protein intake has been proposed to slow down the progression of renal failure.

In animals, protein restriction reduces kidney damage and slows progression in almost all experimental models.However, in humans, the results of protein dietary restriction on renal disease progression are more controversial.

The main study conducted in this field (MDRD) has not demonstrated any beneficial effect of protein restriction.

Some methodological limitations of this study have been put forward to explain the negative results:

– high proportion of patients with polycystic kidney disease;

Impossibility of obtaining the protein restriction at the desired level, in particular in the very small group of proteins;

– fairly liberal use of IEC in more than 60% of patients in the study;

– relatively low monitoring time.

The post-hoc analysis of MDRD taking into account the level of protein restriction actually reached during the study (so-called “perprotocol” analysis) suggests a renoprotective effect, with a decrease in the rate of progression of 1.15 ml / min / year. for each decrease of 0.2 g / kg / day of protein intake. On the basis of this analysis, the delay to end-stage renal failure would be prolonged by approximately 40%. In these post-hoc analyzes, patients with polycystic kidney disease do not benefit from the protein restriction.

An important methodological point should be emphasized: the primary endpoint in MDRD was the declining slope of glomerular filtration and this was measured by a reference technique (clearance of iothalamate). The analysis of the same data with, as a criterion of judgment, the decay slope of the inverse of the plasma creatinine would have on the contrary suggested a benefit of the protein restriction. This is because the protein restriction is associated with a decrease in muscle mass and thus indirectly a reduction in creatinine production and plasma creatinine. Clearly, the indicator of measurement of progression is affected in itself by dietary intervention. This observation is fundamental because it probably invalidates all studies on protein restriction with the sole criterion of judgment the slope of the inverse of plasma creatinine.

Several meta-analyzes have been published, generally suggesting a benefit of the protein restriction on progression, especially the most recent one, taking renal death as a criterion for judgment. It should be noted that these meta-analyzes included, in addition to MDRD, many studies carried out before the use of IEC and with small staff. On the other hand, it has not been possible, from these rather heterogeneous studies, to establish an optimal level of protein restriction, so that the recommendations of K / DOQI 31 and ANAES 2004 are to restrict food protein intake at 0.75-0.8 g / kg / d, equivalent to that recommended by the World Health Organization (WHO) and the French Food Safety Agency (AFSSA) for the diet of normal subjects, but in any case, well below the protein intake prevalent in a conventional Western diet (about 1.3 g / kg / d).

In practice, when such restricted protein diets are applied, they must be in addition to optimized treatment blocking of the renin-angiotensin system and certainly not in its place. Indeed, the expected amplitude of the “protein restriction” effect on progression is only 10 to 20% of the effect provided by the IEC treatment.

These diets restricted in protein should be carried out under strict dietary supervision and reinforced so as to avoid severe undernutrition. The reduction in protein intake must be compensated by a sufficient energy intake, from 30 to 35 kcal / kg / day (except associated obesity). Dietary protein intake can be monitored from the measurement of urinary urinary excretion on a 24-hour urine collection. Protein intake in g / d is calculated as urinary urea in mmol / d divided by 5.5. In practice, these restricted protein diets are not very applicable to patients with a nephrotic syndrome or an abundant proteinuria because the interpretation of albuminemia becomes difficult and it is generally not possible to maintain an albumin level higher than 40 g / l. as recommended by K / DOQI.

In the stage of severe renal insufficiency (glomerular filtration < 15 ml / min), protein restriction limits the uremic syndrome, especially metabolic acidosis from catabolism of animal sulfur proteins, hyperhomocysteinemia from methionine, hyperphosphatemia whose main food sources are constantly associated with proteins, and finally probably the concentration of urea itself.

Despite these symptomatic benefits, diets should not reduce the indication of extrarenal treatment, since it must be based on the criteria defined above (ANAES 2002). The risk of severe undernutrition is important here, especially since a large number of patients spontaneously limit their dietary protein intake. A French study of 239 patients treated with a very restricted protein diet supplemented with ketoanalogues is relatively reassuring in showing that, subject to very precise nutritional monitoring, morbidity and mortality after dialysis initiation was not increased.

OTHER TYPES OF INTERVENTIONS:

Other interventions have been proposed to slow the progression of renal failure but can not be validated in the absence of randomized controlled trials.

Among the possible interventions, some indirect clinical experimental arguments suggest a benefit of correction of metabolic acidosis, hyperphosphatemia and, more generally, disorders of phosphocalcic metabolism and secondary hyperparathyroidism, and finally the correction of ‘anemia. All of these abnormalities are common during renal failure, but are usually considered as consequences or complications that require treatment to prevent or correct the general impact on the body. None of these measures, however, has so far proven to have a direct effect on progression.

Several retrospective studies in diabetic and non-diabetic patients have shown an association between the severity of hyperlipidemia and the rapid decline in renal function. A meta-analysis included 12 randomized prospective trials (including 11 with a statin) evaluating the effects of reducing hyperlipidemia on the progression of renal failure. This analysis concludes that there is a beneficial effect on the preservation of glomerular filtration and the reduction of proteinuria. A recent post hoc analysis of a subgroup of the CARE study in 3384 patients with glomerular filtration below 60 ml / min suggests a marginal beneficial effect of pravastatin on the progression of renal failure, possibly more marked in very proteinuric patients.

The Heart Prevention Study (HPS) confirmed the importance of simvastatin treatment in reducing the cardiovascular morbidity and mortality of patients selected for high cardiovascular risk, regardless of the initial values ​​of total or low-density cholesterol. lipoprotein (LDL) cholesterol.

The interest of this study was to include a subgroup of 1,329 patients with moderate renal impairment (plasma creatinine > 130 and < 200 μmol / l) and to confirm the benefit of statin therapy in this population. Given the high cardiovascular risk prevalent in patients with even moderate renal impairment, K / DOQI 2003 recommends that LDL-cholesterol levels of less than 1.00 g / l be achieved by dietary changes, and then failure after 3 months, statin therapy.

All these data therefore suggest the value of a more aggressive treatment of lipid abnormalities during renal diseases, preferably by combining diet and statin, and under strict surveillance of creatine phosphokinases, given the increased risk of rhabdomyolysis. in this population.

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Editor-in-chief of the Medical Actu website; general practitioner graduated from the Faculty of Medicine of Algiers in 2005 currently practicing as a liberal.

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