Acute renal insufficiency


Acute renal failure (ARF) represents 20% of the ARI etiologies. Its incidence is increasing because of the emergence of new potentially nephrotoxic molecules and the multiplication of drug prescriptions. This incidence is, however, certainly underestimated in view of the apparently silent nature of the symptomatology. Medication ARIs are classically considered to be better prognoses than ARIs of other origin. This notion must be nuanced in the hospitalized patient. Medication ARI, especially if it occurs with other visceral failures, is associated with excess mortality with an increased risk of death by 5.5 in some studies.

It is also burdened with a high morbidity: need for acute dialysis in 20 to 60% of cases, persistence of residual chronic renal failure (creatinine > 200 μmol / l) in 15% of patients. Finally, it is necessary to underline the deleterious role of the occurrence of a medicinal IRA on the evolution of a pre-existing nephropathy.

The drug IRA is more frequently described in the elderly, the renal transplant recipient or the single functional kidney and in some general diseases such as diffuse atheromatous disease, diabetes or myeloma. Most drug-induced ARIs involve renal hypoperfusion and exposure to therapy altering renal vasoregulation. It is most often tubulopathy.

The pathophysiology of renal impairment of drug origin is not univocal. The renal toxicity is particularly favored by the drug combinations and the nonadaptation of the dosages according to the glomerular filtration.

The importance of the dose administered, the mode and rate of administration and the interval between two administrations must be emphasized.

The medicinal IRA is in the vast majority of cases paucisymptomatic. It is most often preserved diuresis.

It is frequently diagnosed with delay, in the face of a rise in serum creatinine whose dosage is carried out “systematically”. In very rare cases, it results in more noisy symptomatology: hypersensitivity vasculitis, thrombotic microangiopathy, obstacle to the flow of urine, acute intravascular hemolysis, nephrotic syndrome …

Etiologies of acute renal insufficiency:


Aminoglycosides are classically the drugs most frequently involved; they would be responsible for about 25% of acute renal failure. They are poorly bound to proteins and are eliminated by glomerular filtration without metabolism. They are concentrated in proximal tubular cells, into which they enter endocytosis, and are stored in lysosomes as myeloid bodies. This intracellular accumulation induces necrosis of the tubular cell. The time of exposure of the tubular cell to the aminoglycoside is a determinant of toxicity and argues for the use of a single dose with spacing of reinjections.Renal failure usually occurs after several days of treatment (7 to 10 on average) and is sometimes seen after it has stopped.

Nephrotoxicity is multifactorial. It involves hypovolemia, which increases proximal reabsorption, therapeutic overdose with, in particular, the lack of adaptation of doses to renal function, reinjection too early, while the residual level is still high, prolonged duration of treatment, drug combinations, locoregional infection, sepsis, which combines hypovolemia, vascular redistribution and endotoxinemia. It should also be mentioned the administration to certain patients with a conventional contraindication such as hepatorenal syndrome.

The symptomatology of the IRA is most often of progressive installation, with preserved diuresis, within the framework of a proximal or even distal tubulopathy. Aminoglycosides should be discontinued as far as possible, except for absolute microbiological necessity and impossibility of substitution by another therapeutic class.

Symptomatic treatment requires the correction of any hypovolemia. In case of major overdose, dialysis is a means of purification of aminoglycosides. The IRA typically progresses to healing within 4 to 6 weeks, sometimes with incomplete recovery.

Prevention includes several measures: limitation of the prescription of aminoglycosides to the situations where their administration is recommended, non-use of diuretics (risk of hypovolemia), adaptation of the dosages, short-term use, administration in single daily dose, in the cases difficult (renal insufficiency, elderly subjects …), guided feedback on the results of residual serum levels. Respect for these practices contributes to improving the tolerance of aminoglycosides on risky sites.


The use of PCI intravenous or intra-arterial is constantly increasing in diagnostic and interventional radiology and thus exposes to an increasing risk of ARI to PCI. The incidence of hypoosmolar PCI-induced nephropathy is less than 2% in the general population; it is around 5.5% in chronic renal failure (CRF) and 12 to 50% in diabetic patients with renal insufficiency.

The risk factors for ARI at PCI are dehydration, diabetes, pre-existing renal insufficiency (attention to the elderly), the dose administered and the repetition of injections. In case of monoclonal gammopathy, the risk of intratubular precipitation of light chains does not seem to increase in the absence of dehydration, hypercalcemia or previous renal insufficiency.

The use of iso-osmolar PCI would reduce the risk of ARI. The main mechanisms involved in nephrotoxicity are medullary ischemia related to intrarenal vasoconstriction induced by endothelin or adenosine and direct tubular toxicity of PCI increased by ischemia.

The IRA occurs within 3 days after PCI injection and peaks on the fifth day. It is an acute tubular necrosis.

Most often, it is conservative diuresis, transient and regresses rapidly. The occurrence of an ARI after arteriography should always suggest in principle the possibility of cholesterol embolism disease.

Prevention of ARI to IBOs is based on several key points.

The prescription of an examination involving the intravascular injection of PCI must take into account the cost, risk and benefit to the patient compared to other medical imaging examinations.

The administration of gadolinium used in nuclear magnetic resonance and sometimes in conventional radiology is not free of risk of ARI. The patient should be informed of potential adverse effects related to the use of PCI. The injection of a small volume of iso-osmolar non-ionic PCI will be favored, being careful not to perform another examination with PCI injection in a close manner. It is necessary to perform a plasma creatinine test before the examination and 48 hours later to avoid ignoring the occurrence of an ARI to PCI. Non-essential nephrotoxic drugs, such as nonsteroidal anti-inflammatory drugs (NSAIDs), should be discontinued transiently. It also seems prudent to stop, if possible, diuretics within 24 hours before and after PCI injection. The benefit of dopamine preventive administration observed in the experimental models is not confirmed in humans. The efficacy of fenoldopam suggested in a recent uncontrolled study requires confirmation.

In chronic renal failure, furosemide and mannitol exacerbate the nephrotoxicity of IBD. Volume expansion reduces the nephrotoxicity of PCI in diabetic patients and in CKD; it seems preferable to perform it with isotonic solutes rather than with hypotonic solutes. Inhibition of A 2 adenosine receptors by theophylline would reduce the risk of ARI to PCI.Prophylactic administration of theophylline in coronary angiography prevents PCI nephrotoxicity in patients with diabetes and CKD. Prophylactic oral administration of N-acetylcysteine ​​(NAC) 600 mg every 12 hours on the day before and the day of examination in CKD, combined with hydration, would prevent PCI nephropathy following computed tomography with iodine injection or after coronary angiography. However, in these studies, the beneficial effect is usually achieved through an improvement in creatinine clearance in the treated group. In a recent work conducted in healthy volunteers, the administration of NAC improves the clearance of creatinine while it does not change the degree of glomerular filtration appreciated by the assay of cystatin C.

This suggests that NAC promotes tubular secretion of creatinine and this result challenges the data reported in the NAC positive studies.

The administration of an intermittent hemodialysis session after coronarography to patients with CKD does not prevent the occurrence of PCI nephropathy. In a recent randomized controlled trial in these patients, the efficacy of venous haemofiltration continued, started 6 hours before coronary angiography and continued 18 hours after the examination (blood flow: 200 ml / min, substitution rate = 1 l / h, ultrafiltration rate = 1 l / h), is superior to crystalloid injection (saline, 1 ml / kg / h) administered during the same period to prevent IRA at PCI. Hospital mortality and 1-year mortality are significantly reduced in the haemofiltration group. However, the high hospital mortality in the control group (14%), the lack of information on the date of occurrence of these deaths in relation to the examination, the absence of data concerning heparin therapy in the control group or concerning atherothrombotic complications in both groups make it difficult to interpret the results.


They are responsible for histological lesions of osmotic nephrosis that affect the entire tubule and can persist for up to 2 years, evoking a process of hoarding. However, their repercussions on renal function remain controversial after renal transplantation and in septic shock. In the renal transplant patient, retrospective studies show that HES used at conventional dosages do not impair graft function, even in the presence of histological lesions. However, a prospective study on a small group of patients showed an increase in serum creatinine on Day 10, and the use of renal replacement therapy in the HEA versus gelatin group, without any increase in mortality. Another prospective study during severe sepsis reports similar results; however, there is a higher incidence of renal dysfunction, hypovolemia, and nephrotoxic drugs at inclusion in the HEA group.


Given their frequent use, these drugs represent a major etiology of ARD drugs. Thus, in the month following the initiation of NSAID therapy, the risk of hospitalization for ARI is multiplied by 4. Patients with bilateral stenosis of the renal arteries, single stenosis on anatomical or functional single kidney, or a   Nephroangiosclerosis with renal arterial network reduction in distal are particularly exposed to this type of ARI.

Diuretics, ACE inhibitors, angiotensin 2 receptor antagonists, and NSAIDs result in an initially functional IRA by interfering with factors that modulate glomerular filtration such as the vasoconstrictor neurohormonal system and vasodilator prostaglandins. In absolute or relative hypovolemia, noradrenaline, the renineangiotensin-aldosterone system and the antidiuretic hormone (ADH) will contribute, by indirect hemodynamic mechanisms (vasoconstriction of the efferent arteriole) and by direct tubular mechanisms (water-soluble reabsorption ), maintenance of blood volume and glomerular filtration. This reaction is counterbalanced by the production of vasodilator prostaglandins on the afferent and efferent arterioles, the tubular effects of which lead to an increase in water-soluble excretion.

Volume contraction (digestive losses, osmotic diuresis, heat stroke …) is the determining factor in the occurrence of IRA reported during these treatments. Diuretics induce hypovolemia. ACE inhibitors and angiotensin 2 receptor blockers antagonize the action of angiotensin 2. NSAIDs decrease prostaglandin synthesis. The combination of these treatments increases the risk of ARI.


The mechanisms responsible for these nephropathies are multiple: hypersensitivity vasculitis, acute interstitial nephropathy …

Principles of treatment:

The treatment of the medicinal IRA consists in interrupting the nephrotoxic treatments, except in case of impossibility.Preventive treatment is the cornerstone of the treatment of the medicinal IRA. The prescription of potentially nephrotoxic treatments must take into account the benefit / risk ratio for the patient. Care should be taken to adjust dosages to renal function, to respect treatment times, to limit therapeutic combinations and to prevent hypovolemia.Symptomatic treatment is nonspecific. The administration of diuretics is not recommended. The use of extrarenal treatment may be necessary in the event of significant accumulation of nitrogenous wastes, severe metabolic disorders, or threatening water-overload.