Vascular nephropathy

 

Introduction:

Vascular nephropathy with acute renal failure have four main types:

Acute necrotizing angiitis with or without associated glomerular involvement;

– hemolytic and uremic syndrome, primary or secondary;

– cholesterol emboli;

– renal arterial thromboses.

They represent a small but significant proportion of acute renal failure (ARI). Between 1986 and 1992, out of 616 patients hospitalized for ARI in Nephrology A at Tenon Hospital, 420 had organic IRA and 63 of these cases, or 15%, were due to vascular nephropathy. The physiopathological mechanisms, therapeutic modalities and prognosis vary according to the different types of vascular nephropathy, which are therefore considered here separately.

Acute renal failure of necrotizing vasculitis:

Necrotizing vasculitis consists of classic macaroscopic periarteritis nodosa (PAN), or Kussmaul and Maier disease, microscopic polyangiitis, Wegener’s syndrome, granulomatous allergic vasculitis or Churg and Strauss syndrome.Lupus erythematous hypersensitivity cases, rheumatoid purpura, essential mixed cryoglobulinemia, and Osler endocarditis, where glomerular damage is predominant, are not considered here.

These angiitis occur rather between 50 and 70 years but can appear at any age. They are more common among white and male subjects. The annual incidence is estimated at one to two cases per 100,000 inhabitants in Europe and North America.

ANATOMOPATHOLOGY:

Renal lesions of necrotizing angiitis are characteristic. In macroscopic PAN, there is involvement of the interlobular arteries and glomerular arterioles with an intraparietal and perivascular inflammatory infiltrate made of mononuclear and polymorphonuclear cells. Essential fact, there is necrosis of the vascular wall, with destruction of the elastic blade visible on sections after Weigert staining. The lesions are irregular, segmental and of different age on the same section.

They evolve towards cicatricial fibrosis with thickening of the wall and reduction of the vascular lumen. Downstream of arterial and arteriolar lesions, the glomeruli are ischemic, retracted into the urinary chamber of the glomerulus. The immunofluorescence examination does not find deposits of immunoglobulin or complement but shows the presence of fibrin within the necrosis lesions. In some macroscopic PANs and especially in microscopic polyangiitis, the lesions involve glomerular capillaries and associate foci of partial glomerular necrosis with complete disappearance of the glomerular basement membrane on silver staining and extracapillary cellular proliferation, consisting of glomerular epithelial cells but also monocytes / macrophages, T cells and fibroblasts. A periglomerular influx of these inflammatory cells can be observed, as well as ruptures of the Bowman capsule. There is no endocapillary proliferation. The severity of renal damage can be estimated by the percentage of damaged glomeruli and the degree of extension of the extracapillary crescent. In immunofluorescence, these glomerular necrotizing lesions are characterized by the absence of significant deposits of immunoglobulins and complement in the glomeruli. Fibrin deposits are visible in glomerular necrosis and extracapillary proliferation.

Very similar lesions can be observed during Wegener’s syndrome, which differs however in the formation of epithelioid granulomas without caseous necrosis. These granulomas are very characteristic when they are found in the interstitium of the kidney. Their interpretation is more delicate when they are located near or around an injured glomerulus, because the periglomerular influx of inflammatory cells is also common in PAN.

The degree of glomerular sclerosis will determine the prognosis, the cellular croissants being of more favorable prognosis than the fibrocellular or fibrous croissants.

CLINICAL SIGNS:

ARI macroscopic PAN usually occurs in a noisy context of significant deterioration of general condition, with weight loss, inflammatory syndrome, multiple extrarenal signs such as necrotic purpura, subcutaneous nicks, asymmetric or asymmetric sensitivomotor polyneuropathy, arthralgia and arthritis. Severe hypertension (hypertension) is associated with renal impairment, often greater than or equal to 180/120 mmHg. The lesions on the fundus (haemorrhages, exudates, dysoric nodules) are frequent. The oligoanuria settles quickly. Proteinuria is scarce and urinary sediment without any particularity. In microscopic polyangiitis and Wegener’s syndrome, renal failure is rapidly progressive, settling in a few days. HTA is common, usually mild. Abundant proteinuria of glomerular origin may be noted, associated with microscopic hematuria. The extrarenal signs are less severe than in the macroscopic PAN but there is often a fever, an inflammatory syndrome, arthralgia, an elevated purpura, testifying to a process not limited to the kidney. In Wegener’s syndrome, extra-renal signs are common, including otorhinolaryngological (ENT) and pulmonary involvement. Although rare, the IRA has also been reported during Churg and Strauss syndrome, where non-allergic asthma, eosinophilia and pulmonary infiltrates are in the foreground.

A certain number of so-called primitive necrotizing extracapillary glomerulonephritis, without abundant immunofluorescence immunoglobulin deposits, most certainly correspond to microscopic polyangiitis limited to the kidney.

They also result in rapidly progressive renal failure with hypertension, proteinuria and hematuria. It is not uncommon to observe an alteration of the general state, a fever or arthralgia, suggesting in fact an extrarenal subclinical diffusion of the lesions. More than 80% of patients have polynuclear anti-cytoplasmic antibodies, confirming their similarity, if not similarity to microscopic polyangiitis and Wegener’s syndrome.

BIOLOGICAL SIGNS:

Inflammatory syndrome, leukocytosis greater than 10 000 / mm 3 , and eosinophilia greater than 400 / mm 3 are frequently observed. The search for circulating immune complexes and hypocomplementemia is inconsistently positive.

Polynuclear anti-cytoplasmic antibodies are found in more than 80% of cases of necrotizing and extracapillary pauci-immune glomerulonephritis. These autoantibodies, originally described in eight patients with necrotizing glomerulonephritis by Davies in 1982, were observed in Wegener’s syndrome by Van der Woude et al in 1985. Their diagnostic interest was then shown, as well as their parallel variation with disease. It is now established that more than 90% of Wegener’s syndromes have c-anti-neutrophil cytoplasmic antibodies (ANCA), usually antiproteinase 3 (anti-PR3) specificity, and more rarely pANCA, antimyeloperoxidase (antiMPO).

Conversely, only 30% of patients with macroscopic PAN have ANCAs usually of the anti-MPO type. Microscopic polyangiitis and extracapillary ascending primary glomerulonephritis have ANCA in 75 to 85% of cases, anti-MPO type or, more rarely, anti-PR3. Anti-MPO antibodies are found in about 70% of cases of Churg and Strauss syndrome.

The mechanism by which ANCA is pathogenic is not certain. In vitro studies show that a viral infection causes neutrophil expression of the usually intracytoplasmic antigens, which are not recognized by ANCAs, on their surface.ANCAs thus interact with their antigens, causing neutrophilic release of free radicals derived from oxygen and proteases that are toxic to endothelial cells. This effect is increased in the presence of tumor necrosis factor (TNF) – a .In addition, ANCAs are found by double immunostaining on renal fibrinoid lesions in rapidly progressive glomerulonephritis (GNRP), accounting for a potential direct effect of these antibodies on endothelial cells.

Viral hepatitis B, but also hepatitis C or HIV should be systematically used, especially in macroscopic PAN. Vasculitis associated with viral diseases will indeed benefit from antiviral treatments often alone, to heal vasculitis.

RADIOLOGICAL SIGNS:

Renal angiography is indicated when necrotizing vasculitis is suspected in order to search for aneurysms or microaneurysms that are of great diagnostic value. These are rounded dilations in the arterial vessel path, 1 to 5 mm in diameter, sometimes larger, up to 1 cm. They can also enlarge the width of the vessel, which normally shrinks, and stay opacified longer than normal vascular lumen. They are sometimes still visible at nephrographic time. They can be associated with images of segmental infarction and intrarenal and perirenal hematomas. Their presence contraindicated renal biopsy. Such microaneurysms can also be observed on the branches of the superior mesenteric artery, or the hepatic artery.

The chest x-ray is usually normal in PAN, but infiltrates with intra-alveolar hemorrhages are possible. In Wegener’s syndrome, pulmonary, nodular infiltrates sometimes excavated are characteristic. In Churg and Strauss syndrome, bilateral interstitial or alveolar-interstitial syndrome is common.

TREATMENT:

Symptomatic treatment of ARIs includes the correction of hydroelectrolytic disorders and nitrogen retention by hemodialysis. Fluid retention, which is common, requires the use of ultrafiltration when renal impairment is severe and insufficient diuresis. Blood pressure should be normalized by the use of intravenous or oral antihypertensives.Angiotensin converting enzyme inhibitors and calcium channel blockers are often effective in this context.

These symptomatic measures alone are insufficient and the improvement in the prognosis of necrotizing vasculitis that was once catastrophic with a mortality of more than 80% at 1 year is linked to the use of powerful immunosuppressive treatments and in particular the combination of corticosteroids (1 to 2 mg / kg / day for 6-8 weeks) -cyclophosphamide (50-100 mg / day or 700 mg / m2 infusion each month). This combination improves kidney function in 70 to 85% of patients and complete remission in 60% of cases. Cyclophosphamide used as a bolus appears to be as effective as the daily remission treatment, causing fewer side effects but seems complicated by more relapses.Methylprednisolone emboli are used, especially in emergency, when the patient presents with a typical table of necrotizing vasculitis and rapidly progressive renal failure. Several studies have shown a beneficial effect of these treatments on the evolution of renal function.

Plasma exchanges have been shown to be effective in pulmonary involvement of Goodpasture’s syndrome and in renal impairment of macroscopic Hbs + PAN. On the other hand, they have not been recommended for PKU-immune GNRP and Churg and Strauss syndrome, although a beneficial effect has been reported in several limited series.Indeed, a recent prospective multicentre study of 39 patients with GNRP compared immunosuppression alone with plasmapheresis-associated immunosuppression. This study does not find, in this indication, improvement or survival or renal prognosis in the group of patients receiving plasmapheresis.

New immunosuppressants with more specific actions on lymphocyte response or some cytokines are also being studied.

The complications of all these immunosuppressants are numerous. Cyclophosphamide causes leukopenia, urothelial lesions with hemorrhagic cystitis, even carcinomatous transformation and infertility, so that the indications must be weighed rigorously. We always use prophylaxis with cotrimoxazole, especially since this drug may have a specific action on vasculitis.

A relay after remission with azathioprine or mycophenolate mofetil can also reduce complications with, apparently, effective prevention of recurrence. The duration of maintenance treatment is not formally established. It is at least 1 year and can be monitored according to clinical signs and circulating antibody levels.

ACUTE RENAL FAILURE OF THROMBOTIC MICROANGIOPATHY:

Thrombotic microangiopathies (MAT) are characterized by the occurrence of microthromboses of arterioles and capillaries in different organs. Their clinical expression is variable according to the organs affected and two clinical syndromes have been described: thrombotic thrombocytopenic purpura (TTP) in adults where the neurological involvement is predominant, which corresponds to the initial description of Moschcowitz in 1924 and the hemolytic syndrome and uremic (HUS) of the child, where renal damage is in the foreground, which corresponds to the description of Gasser in 1955. These two clinical syndromes are associated with intravascular mechanical hemolysis and thrombotic microangiopathy lesions consisting of Platelet aggregates, swelling and proliferation of endothelial cells without inflammatory infiltrates, and accumulation of hyaline material between the endothelium and the small vessel media. These two syndromes seem to represent different clinical expressions but often very close to an identical lesion process, thrombotic microangiopathy. In recent years the understanding of the pathophysiology of these two syndromes has made it possible to better distinguish them.

Anatomopathology:

Renal biopsy (PBR) during HUS with IRA is of diagnostic and prognostic value. Thrombocytopenia often prevents this procedure from being carried out percutaneously, but the transjugular renal biopsy technique now makes it possible to obtain good kidney fragments in these patients. The lesions can affect glomeruli, pre-glomerular arterioles and intrarenal arteries.

Typical glomerular lesions involve swelling of endothelial cells and enlargement of the subendothelial space that reduces the diameter of glomerular capillaries. Thrombi obstruct these capillaries. They are composed of agglutinated and degranulated platelets and polymerized fibrin.

The subendothelial clear deposits could correspond to plasma proteins accumulating at this level because of the increased permeability of the endothelial barrier. They could also represent platelet thrombi extensions from the injured capillary lumen. Rarely, mesangial expansion, inflammatory necrosis, or extracapillary proliferation are observed. In immunofluorescence, immunoglobulin G (IgG), IgM and complement deposits are very inconsistently present.

Arteriolar and arterial lesions are irregular and consist of thromboses made of platelet aggregates and fibrin, associated with intimal cell proliferation. Unlike necrotizing vasculitis, there is no inflammatory reaction in and around the vessel wall. This arteriolar obstruction results in ischemic retraction of the glomeruli downstream. At most cortical necrosis is possible. Similar microcirculatory lesions have been demonstrated in other organs. Arterial lesions have a less favorable prognosis, and more or less severe renal failure may persist after the initial episode. Other lesions, glomerular or vascular chronic, preexisting, can be discovered at the time of the HUS and are specific to each etiology.The existence of an acute tubular necrosis on the biopsy, however, has a favorable prognosis.

Pathophysiology:

It is still poorly known. Two phenomena appear to play an important role: intravascular platelet aggregation and the alteration of endothelial cell properties from antiplatelet platelet, antithrombotic and profibrinolytic activity to pro-aggregating, prothrombotic and antifibrinolytic activity. Different agents responsible for toxic, infectious or immunological thrombotic microangiopathy can actually cause endothelial damage. Deficiency of local fibrinolytic activity in affected microvessels has been demonstrated, probably related to an excess of plasminogen activator inhibitor (PAI-1).

In indirect immunofluorescence, we found evidence of PAI-1 within fibrin in thrombotic microangiopathy lesions in children and adults.

However, the event cascade between endothelial injury and microthrombosis is not always clear and seems different in HUS and PTT. In all cases, endothelial cell damage induces platelet aggregates, resulting in microthromboses.Hemolytic anemia is secondary to the fragmentation of erythrocytes on these microthromboses.

In some cases of so-called idiopathic or familial HUS, and even in some postinfectious HUS, a constitutional deficiency or acquired factor H or an abnormal H factor were found. Factor H is the most important regulator of the alternative complement pathway. Its deficit therefore leads to hyperactivation of the complement. The H-factor anomaly, combined with other viral or circulating factors, probably explains the predisposition to HUS in some patients or families.

In the PTT, on the other hand, there is no abnormality of the factor H, but a constitutional or acquired deficit of the activity of the protease of the vWF. The complexes of high molecular weight, so-called ultralarges complexes von Willebrand factor contained in the endothelial cells are released into the circulation where they cause platelet aggregation, and especially in the capillaries where shear stress is important. In the acute phase of PTT, these ultralarges complexes are found in the blood of patients. It should be noted that in cases of familial PTT, these ultralarges complexes persist after the acute episode, suggesting that another cofactor would be required for PTT expression.

The hypothesis of a circulating factor triggering HUS is supported by the experience of renal transplantation. Indeed, in many cases of kidney transplants, recurrences occur. They are less common in biphrectomized patients suggesting that native kidneys release a toxic factor that, by interfering with vWF or H-factor protease abnormalities, would trigger HUS.

Epidemic HUS associated with diarrhea are due to certain strains of pathogenic enterobacteria (Escherichia coli, Shigella dysenteriae, mainly Salmonella typhi) suggesting a role for bacterial enterotoxins. In 1977, Konowalchuk et al isolated a toxin secreted by a strain of E. coli. coli responsible for hemorrhagic diarrhea and HUS in children. This toxin has a cytotoxic effect on Vero cells, cells of the African green monkey kidney, and is called Verotoxin. Recently, it has been shown that the toxin crosses the digestive mucosa and is transported by the polynuclear cells to a specific receptor on the endothelial cells. Internalization in the endothelial cell then leads to blockage of protein synthesis and cell death.

The endothelial lesion could also be of autoimmune origin, since cytotoxic endothelial cell antibodies have been detected in some cases of HUS.

Clinical signs:

This is a rare disease whose annual incidence in adults has been estimated at about 0.1 per 100,000. The most common symptoms include: asthenia, mental disorders, purpura, hemorrhage, abdominal pain, fever. More rarely, jaundice, myalgia, arthralgia are noted. Central neurological disorders range from simple headache with confusion to motor deficits, aphasia, visual disturbances, seizures and coma. Renal involvement, prominent in HUS and very common during PTT, is characterized by microscopic hematuria, more rarely macroscopic and proteinuria. ARI, often oligoanuric, is usually associated with severe hypertension and complicates 10 to 20% of adult thrombotic microangiopathies. The examination of the fundus can find papilled edema, retinal hemorrhages and vitreous. Retinal detachment is possible. More rarely are arrhythmias or

heart failure, acute respiratory failure related to intra-alveolar haemorrhage, diabetes due to pancreatic involvement, or rhabdomyolysis due to muscle involvement.

Biological signs:

Haemolytic anemia of the microangiopathic type is characteristic. It is a haemolytic anemia of mechanical type due to the fragmentation of red blood cells on microaggregates obstructing the small vessels, resulting in the formation of fragmented red blood cells or schizocytes. At the same time, reticulocytosis is increased, as is the level of serum lactic dehydrogenase (LDH), hemoglobinemia,

hemoglobinuria, unconjugated bilirubin. Serum haptoglobin is decreased. The Coombs test is negative.

The thrombocytopenia is constant, sometimes very deep (less than 10 000 platelets / mm 3 ), linked to a significant peripheral consumption not compensated by the increase of medullary production as evidenced by the increase of the megakaryocytes on the marrow smear.

There is no evidence of disseminated intravascular coagulation. Quick and activated partial thromboplast times are normal. The levels of fibrinogen and other coagulation factors are normal in more than 90% of cases. There is, however, a slight increase in fibrin degradation products (PDF) in blood and urine, indicating minimal activation of fibrinolysis. A decrease in platelet aggregation in vitro has been shown to be related to preactivation of platelets in vivo.

A decrease in serum complement (CH50, C3 and C4) has been observed in some patients, this is uncommon but has an unfavorable prognosis.

Treatment:

The symptomatic treatment has considerably contributed to the improvement of the prognosis of HUS with ARI.

Potent vasodilators, particularly ACE inhibitors and / or angiotensin II receptor antagonists, with or without hydralazine, calcium channel blockers or beta-blockers are most often used to control hypertension. and decrease renal ischemia and the mechanical component of hemolysis. It is an essential component of symptomatic treatment with a strict blood pressure goal not exceeding 120 mmHg systolic. The correction of hydroelectrolytic disorders by hemodialysis, with or without ultrafiltration, makes it possible to prevent the metabolic and volume complications of the IRA, whatever the cause.

The etiological treatments that have been tested are numerous and of inconsistent efficiency. If possible, it is necessary to identify the responsible factor and to treat it. However, for postinfectious HUS, secondary to Escherichia coli O157: H7, antibiotic treatment does not improve or even worsen the prognosis of the disease. Only fosfomycin, given in the first two days of diarrhea due to Escherichia coli 0157: H7, could reduce the incidence of HUS in children.

The use of fresh plasma infusion (20 to 30 mL / kg / day) or plasma exchange has in many cases been successful in correcting the haemolysis and thrombocytopenia of HUS and PTT in adults. In PTT, these infusions have proven effective with a dose-related effect. George, on a series of 169 patients, carried out daily or even twice daily exchanges, obtaining a survival rate of 85%. The use of plasma exchange is necessary in case of volume overload and / or antibodies directed against the vWF protease. In the HUS, no study has shown the value of PFCs or plasma exchange, even if the retrospective study of Dundas suggests it. Plasma infusions seem logical in case of deficiency of factor H. In the other cases, the majority of the adult teams use the PFC, even the plasma exchanges by analogy with the treatment of the PTT. In contrast, in typical child HUS, neither plasma exchange nor fresh frozen plasma infusions are recommended.

Corticosteroid therapy, 0.5 to 1 mg / kg / day of prednisone, may have a beneficial effect in approximately 30% of adult patients with PTT. It appears essential in patients with autoimmune disease such as systemic lupus erythematosus, or in patients with autoantibody inhibiting vWF protease.

It must be discussed on a case by case basis according to the etiology.

Platelet antiaggregants, 50 to 100 mg / day of acetylsalicylic acid and / or 150 to 450 mg / day of dipyridamole, have also been proposed but their efficacy has not been demonstrated. They are less and less used.

Exceptionally, vincristine and splenectomy are also used, sometimes successfully, in forms refractory to conventional treatments.

Particular etiological circumstances:

They are numerous and varied in the adult. In a recent series, of 55 cases of adult HUS admitted to our service, all confirmed by renal biopsy, the etiologies found can be classified into two major groups: the so-called primitive HUS, that is to say on anteriorly healthy kidney (72.7%) and secondary complicating underlying nephropathy (27.2%).

Postinfectious or idiopathic forms:

The incidence of post-Escherichia coli O157: H7 HUS is particularly important in children. This postinfectious form exists nevertheless in the adult and even in the elderly and justifies the systematic search for the toxin in the stool of all the patients presenting a HUS. The ACB allows to recognize the forms with predominant arteriolar involvement, of worse prognosis than the forms with exclusive or predominant glomerular damage. Hemodialysis and antihypertensive symptomatic treatment and fresh plasma etiopathogenic treatment in adults have upset the prognosis of these once catastrophic forms.

Many viruses (enterovirus, human immunodeficiency virus [HIV]) and in particular cytomegalovirus in the transplanted patient are involved in triggering thrombotic microangiopathy. Causality is often difficult to establish, particularly in transplant patients for whom recurrence of initial nephropathy, acute vascular rejection, and medication may also be suspected.

However, in some cases, the simultaneous occurrence of HUS and a documented viral syndrome in a patient whose medications have not been modified for several months may allow HUS to be linked to the viral pathology.

Hemolytic uremic syndrome and scleroderma:

Acute renal failure of scleroderma is rare, but known.

It can occur, depending on the series, in 10 to 40% of scleroderma patients. It manifests itself as a hemolytic uremic syndrome, most often with malignant hypertension. Scleroderma, of the acrosclerosis type, is usually known at the onset of renal failure, but this can be revealing in 5 to 10% of cases. An increase in visceral signs, an alteration of the general state, an inflammatory syndrome can precede the “vasculorenal crisis”. Nonsteroidal anti-inflammatory drugs or corticosteroids have been implicated as a triggering factor. HTA, when present, may exceed 200/120 mmHg.However, despite severe kidney damage and an authentic HUS, some patients are not hypertensive. The fundus lesions are constant with dysoric nodules and / or retinal detachment, uncorrelated with the level of arterial pressure.Renal biopsy shows predominantly vascular lesions, mostly affecting the interlobular arteries, which is characterized by proliferative endarteritis or fibrous circumferential vascular lumen. The endarter is infiltrated by a mucoid material, rather characteristic of scleroderma or by fibrinoid material. Cortical and corticomedullary segmental necrosis is possible, also detectable by renal angiography. Later, nephroangiosclerosis lesions due to malignant hypertension can be superadded, mainly affecting pre- and post-glomerular arterioles with proliferative endarteritis and fibrinoid necrosis.

The prognosis of ARI during scleroderma, once catastrophic, remains pejorative, mortality can reach 50% in first year, by stroke, heart failure or cachexia. It has improved since the use of angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists. Hemodialysis and transplantation can be performed. Late recovery of renal function is observed after several weeks or months of hemodialysis, correction of blood pressure allowing slow regression of endarteritis and fibrinoid necrosis lesions.

Malignant nephroangiosclerosis:

It manifests as malignant hypertension with diastolic blood pressure greater than 130 mmHg, and major visceral repercussions. It can occur spontaneously but follows most often to an old HTA not or poorly controlled, regardless of the etiology.

Renal involvement is marked by acute or rapidly progressive renal failure, which may become oligoanuric. Most often, however, patients report a polyuropolydipsic phase preceding their hospitalization, associated with asthenia and weight loss. Cachexia states can be installed quickly. Proteinuria is minimal. There is no hematuria. Visual disturbances and fundal lesions are usual: haemorrhages, exudates, papilledema.

Hypertensive encephalopathy is sometimes in the foreground with headache, confusion, somnolence, coma, general convulsions or cerebromeningeal hemorrhage. Left ventricular failure, related to the significant increase in peripheral vascular resistance, can lead to pulmonary edema.

Biologically, a haemolytic anemia of microangiopathic type is frequent; thrombocytopenia is absent or poorly marked.An increase in muscle enzymes (creatine phosphokinase [CPK], aldolase) may indicate muscle ischemia due to extreme peripheral vasoconstriction. Plasma renin is constantly extremely high. Plasma volume, which can be measured by isotopic dilution of 125 I- labeled albumin or dilution of Evans blue, is often decreased because of HTA-induced polyuria.

After control of hypertension and haemostasis disorders, an ACB can be performed. It shows lesions characteristic of major proliferative endarteritis affecting the interlobular arteries and especially the pre- and postglobular arterioles. The exuberant proliferation of smooth muscle cells in the intimal position results in the formation of classic “onion bulb” lesions, which can also be found in HUS and scleroderma.

More typically, necrosis of smooth muscle cells and fibrin infiltrates in the vascular wall can be observed, constituting fibrinoid necrosis lesions. Fibrinoid necrosis of the afferent arteriole, possibly extended to the glomerulus, is very characteristic of malignant nephroangiosclerosis and is not observed in other vascular nephropathy. Hyperplasia of the juxtaglomerular apparatus and an increase in the number of cells containing renin were observed.

²The pathogenesis of malignant HTA during malignant nephroangiosclerosis involves, above all, significant secretion of renin and intrarenal and systemic angiotensin II generation.

Proliferative endarteritis and fibrinoid necrosis reduce vascular lumen and result in glomerular ischemia that causes renin secretion. This secretion of renin increases vasoconstriction and hypertension, increasing proliferative endarteritis, and therefore renal ischemia, which in turn stimulates renin secretion. A vicious circle of autoaggravation sets in, resulting in the malignant HTA with IRA.

The lesions of proliferative endarteritis may be secondary to poorly controlled old hypertension, but they may also appear in young subjects with no particular history. This primary nephroangiosclerosis is similar to the vascular lesions observed in the spontaneously hypertensive rat (SHR), whose arterial and glomerular lesions appear and progress despite the control of hypertension. It could be a primary disease of the endothelial cell or smooth arterial muscle cell.

In addition to hemodialysis, which is used to correct hydroelectrolytic disorders, the treatment of ARF during malignant hypertension is mainly based on antihypertensive therapy.

The ACE inhibitors alone or in combination with other vasodilators, particularly the angiotensin II receptor antagonists, are also remarkably effective here and have completely replaced the previously required biphrectomy. Normalization of blood pressure is usually accompanied initially by worsening renal failure, or even a reduction in diuresis. However, it is essential to prevent the installation of new arteriolar lesions. This short-term worsening does not prevent a long-term improvement in kidney function within a few weeks or months. This delay could correspond to the time required for the regression of proliferative endarteritis. During this period, iterative hemodialysis and antihypertensive therapy should be strictly maintained. The other etiopathogenic treatments (corticosteroids, frozen fresh plasma) have not been evaluated in this circumstance and do not seem justified to us.

Hemolytic uremic syndrome and pregnancy:

The HUS of pregnancy usually occurs during the third trimester of pregnancy and poses diagnostic problems with some forms of preeclampsia and Haemolysis, Elevated Liver Low Platelet Count (HELLP) enzymes where HTA, proteinuria, microangiopathic hemolytic anemia, thrombocytopenia, and insufficiency renal can be observed. Signs of disseminated intravascular coagulation (DIC) that are absent in HUS are usually present in preeclampsia. In the absence of treatment, a fetal mortality of about 80% has been reported. Conversely, the infusion of fresh plasma has made it possible to control HUS, prolong pregnancy and considerably improve the fetal and maternal prognosis.

HUS can also appear in the postpartum after normal delivery and a symptom free interval of a few weeks to a few months. This postpartum HUS is often more severe than that during pregnancy, with frequent progression to end-stage renal failure.

Thrombotic microangiopathies of cancers and after chemotherapy:

Evidence of thrombotic microangiopathy (TMA) has been observed in acute promyelocytic leukemias, prostate cancers, gastric and pancreatic carcinomas. Signs of CIVD are often associated and lesions may be related to tumor emboli.

MAT may be related to the disease itself or its treatment. MAT after chemotherapy was observed mainly in patients treated with mitomycin C and more recently gemcitabine. Other drug substances (cisplatin, bleomycin, vinblastine or vindesine) have also been implicated. The cessation of chemotherapy and plasma exchanges most often make it possible to effectively treat these HUS. The evolution is especially that of the cancerous disease.

Other medical causes:

Numerous drugs have also been implicated in cases of HUS in healthy kidneys: among others FK506 (1 to 5% of patients), ciclosporin A, interferon- a , clopidogrel and quinine. All tables can be observed from simple histological findings to multiorgan failure.

The mechanism is often not explained, but one can sometimes, as after taking a quinine, find in the patient’s serum different autoantibodies, in particular against the glycoproteins of the platelet membrane GpIIbIIIa, but also against the erythrocytes, the leucocytes and endothelial cells.

Acute renal failure of atheromatous origin:

ACUTE RENAL FAILURE BY CHOLESTEROL CRYSTAL EMBOLISM:

Although renal failure due to emboli of cholesterol crystals in the renal circulation has been described since 1945, its frequency has long been underestimated as autopsy series have shown. For example, a Dutch study found an autopsy incidence of 0.3 to 0.4%, compared with an estimated incidence of 0.6 / 100 000.

Pathology and physiopathology:

Lesions due to cholesterol emboli are characteristic.

The crystals, at very acute angles, are found in the lumen of medium-sized arterioles, 150 to 200 μm in diameter. They are surrounded by amorphous material and associated with cell proliferation of the vascular wall which plays a major role in the obstruction of the vessels. They are birefringent in polarized light on unfixed sections. Fixation and staining of the sections cause the dissolution of cholesterol, so that the presence of crystals is indicated by crystal-shaped gaps in the obstructed vascular lumen. Vascular obstruction is irregular and healthy areas may be adjacent to ischemic areas characterized by glomerular sclerosis and tubule degeneration.

It appears that cholesterol crystals induce a foreign body reaction with macrophage influx, giant cell formation, endothelial cell injury, platelet activation and coagulation, leading to migration and proliferation of media cells in the body. the intima. There are sometimes rare phenomena of repealing.

Clinical signs:

Emboli of cholesterol crystals are found mainly in the atheromatous subject, over 60 years of age, with a history of lower extremity arteritis, stroke, or myocardial infarction.

The most common triggers are:

Surgery of the suprarenal aorta or atheromatous renal arteries;

Catheterization of the aorta during angiograms;

– anticoagulant treatment, with or without overdose.

Many cases appear without obvious triggers.

Renal involvement is characterized by the association of ARF and arterial hypertension on an atheromatous site, often already insufficient chronic renal and hypertensive. Scarce proteinuria and normal urine sediment provide little information.

At the same time, other territories than the kidney are affected such as cutaneous vessels or retinal vessels, but also the brain, the digestive tract or the pancreas causing various clinical manifestations, sometimes mimicking vasculitis.

Some biological abnormalities have been observed during cholesterol emboli such as eosinophilia, hypocomplementemia, and the presence of autoantibodies. They are fickle and unspecific.

Diagnostic certainty is provided by the renal biopsy, or the biopsy of other affected territories, cutaneous or muscular, and the fundus when it shows emboli of crystals in the retinal vessels.

Treatment:

In addition to symptomatic treatment, there is currently no effective treatment of ARI by emboli of cholesterol crystals: perfusion of dextran, vasodilators, corticosteroids, sympatholytics have proved ineffective. The treatment of hypertension should be strengthened but progressive, because the risk is to cause additional cerebral or renal ischemia. The use of angiotensin converting enzyme inhibitors should be careful also because atherosclerotic stenosis of the renal arteries is common in this field.

The most important is certainly to avoid recurrences. Statins would help stabilize atheroma plaques. Invasive examinations and anticoagulation should be prohibited in these patients.

The evolution is usually not very favorable: most often, it persists a chronic renal insufficiency, requiring or not the iterative hemodialysis, or more rarely the renal function improves progressively and incompletely. Cases secondary to aortic catheterization or anticoagulant therapy would have a more favorable prognosis than spontaneous cholesterol emboli.

Acute renal failure during atheromatous stenosis of the renal arteries:

Many cases of acute renal failure induced by angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists in patients with stenosed or simply atheromatous renal arteries without stenosis visible at angiography have been reported . The arrest of glomerular filtration is related to the suppression of intrarenal angiotensin II generation, vasorelaxation of the glomerular efferent arteriole and subsequent drop in filtration pressure.

Importantly, this ARI, which is all the more severe as there is hypovolemia or low cardiac output, is rapidly reversible upon discontinuation of the conversion enzyme inhibitor and rehydration therapy. The angio-MRI of the renal arteries can confirm the diagnosis in a non-invasive way. Renal angiography, despite the risk of cholesterol embolism that it involves in these patients, is then indicated to attempt an angioplasty or decide on a revascularization surgery.

Meyrier has reported a series of 32 atheromatous patients with renal failure. In 30 cases, renal angiography showed tight stenosis of the renal arteries (or the renal artery of a single functional kidney). The deterioration of renal function was triggered by the use of angiotensin I converting enzyme inhibitors in 16 cases. Very often, renal artery stenoses were associated with multiple stenoses of intrarenal vessels, inaccessible to treatment, and cholesterol emboli. All these lesions grouped together by these authors under the term atheromatous renal disease seems to be a frequent but underestimated cause of chronic renal failure of the atheromatous subject.

The sudden occlusion of an atheromatous renal artery on a single functional kidney can also be observed. It causes acute renal failure, often oligoanuric, with hypertension and pulmonary edema. Arteriography confirms arterial occlusion and sometimes shows a supply of peripheral blood supply through the perirenal arteries. This vascularization, which can be appreciated by renal scintigraphy, although weak, prevents complete necrosis of the kidney and explains the renal revascularization success observed a few days or even weeks after the renal artery occlusion.

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