[Microalbuminuria and urinary albumin excretion: French guidelines]. / Microalbuminurie et excrétion urinaire d'albumine: recommandations pour la pratique clinique.

UNLABELLED: Measurement of urinary albumin excretion (UAE) may be done on a morning urinary sample or on a 24 hour-urine sample. Values defining microalbuminuria are: - 24-hour urine sample: 30-300 mg/24 hours - Morning urine sample: 20-200 mg/mL or 30-300 mg/g creatinine or 2.5-25 mg/mmol creatinine (men) or 3.5-35 mg/mol (women). - Timed urine sample: 20-200 mug/min. The optimal use of semi-quantitative urine test-strip is not clearly defined. It is generally believed that microalbuminuria reflects a generalized impairment of the endothelium; however, no definite proof has been shown in humans. In diabetic subjects, microalbuminuria is a marker of increased risk of cardiovascular (CV) and renal morbidity and mortality in type 1 and type 2 diabetic subjects. The increase in UAE during follow-up is also a marker of CV and renal risk in type 1 and type 2 diabetic subjects; its decrease during follow-up is associated with lower risks. In non-diabetic subjects, microalbuminuria is a marker of increased risk for diabetes mellitus, deterioration of the renal function, CV morbidity and all-cause mortality. It is a marker of increased risk for the development of hypertension in normotensive subjects, and is associated with unfavorable outcome in patients with cancer and lymphoma. Persistence or elevation of UAE overtime is associated with deleterious outcome in some hypertensive subjects. Measurement of UAE may be recommended in hypertensive subjects with 1 or 2 CV risk factors in whom CV risk remains difficult to assess, and in those with refractory hypertension: microalbuminuria indicates a high CV risk and must lead to strict control of arterial pressure. Studies focused on microalbuminuria in non-diabetic, non-hypertensive subjects are limited; most of them suggest that microalbuminuria predicts CV complications and deleterious outcome as it is in diabetic or hypertensive subjects. Subjects with a history of CV or cerebrovascular disease have an even greater CV risk if microalbuminuria is present than if it is not; however, in all cases, therapeutic intervention must be aggressive regardless of whether microalbuminuria is present or not. It is not recommended to measure UAE in non-diabetic non-hypertensive subjects in the absence of history of renal disease. Monitoring of renal function (UAE, serum creatinine and estimation of GFR) is annually recommended in all subjects with microalbuminuria. MANAGEMENT: in patients with microalbuminuria, weight reduction, sodium restriction (< 6 g/day), smoking cessation, strict glucose control in diabetic subjects, strict arterial pressure control are necessary; in diabetic subjects: use of maximal doses of ACEI or ARB are recommended; ACEI/ARB and thiazides have synergistic actions on arterial pressure and reduction of UAE; in non-diabetic subjects, any of the five classes of anti-hypertensive medications (ACEI, ARB, thiazides, calcium channel blockers or beta-blockers) can be used.

Microalbuminuria and urinary albumin excretion: French clinical practice guidelines.

Urinary albumin excretion (UAE) may be assayed on a morning urinary sample or a 24 h-urine sample. Values defining microalbuminuria are: 1) 24-h urine sample: 30-300 mg/24 h; 2) morning urine sample: 20-200 mg/ml or 30-300 mg/g creatinine or 2.5-25 mg/mmol creatinine (men) or 3.5-35 mg/mmol (women); 3) timed urine sample: 20-200 mug/min. The optimal use of semi-quantitative urine test-strip is not clearly defined. It is generally believed that microalbuminuria reflects a generalized impairment of the endothelium; however, no definite proof has been obtained in humans. IN DIABETIC SUBJECTS: Microalbuminuria is a marker of increased risk of cardiovascular (CV) and renal morbidity and mortality in type 1 and type 2 diabetic subjects. The increase in UAE during follow-up is associated with greater CV and renal risks in type 1 and type 2 diabetic subjects; its decrease during follow-up is associated with lower risks. IN NON-DIABETIC SUBJECTS: Microalbuminuria is a marker of increased risk for diabetes mellitus, deterioration of renal function, CV morbidity and all-cause mortality. It is a marker of increased risk for the development of hypertension in normotensive subjects, and is associated with unfavorable outcome in patients with cancer and lymphoma. Persistence of elevated UAE during follow-up is associated with poor outcome in some hypertensive subjects. Measurement of UAE may be recommended in hypertensive medium-risk subjects with 1 or 2 CV risk factors in whom CV risk remains difficult to assess, and in those with refractory hypertension: microalbuminuria indicates a high CV risk and must lead to strict control of arterial pressure. Studies focused on microalbuminuria in non-diabetic non-hypertensive subjects are limited; most of them suggest that microalbuminuria predicts CV complications and deleterious outcome. Subjects with a history of CV or cerebrovascular disease have an even greater CV risk if microalbuminuria is present than if it is not; however, in all cases, therapeutic intervention must be aggressive regardless of whether microalbuminuria is present or not. It is not recommended to measure UAE in non-diabetic non-hypertensive subjects in the absence of history of renal disease. Monitoring of renal function (UAE, serum creatinine and estimation of GFR) is recommended annually in all subjects with microalbuminuria. MANAGEMENT: In patients with microalbuminuria, weight reduction, sodium restriction (<6 g per day), smoking cessation, strict glucose control in diabetic subjects, strict arterial pressure control are necessary; in diabetic subjects: use of maximal doses of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) are recommended; ACEI/ARB and thiazides have synergistic actions on arterial pressure and reduction of UAE; in non-diabetic subjects, any of the five classes of anti-hypertensive medications (ACEI, ARB, thiazides, calcium channel blockers or beta-blockers) can be used.

[Evaluation of plasmatic homocysteine determination by gas chromatography-mass spectrometry]. / Evaluation d'un transfert de méthode : dosage de l'homocystéine plasmatique par chromatographie en phase gazeuse couplée à la spectrométrie de masse.

Total plasma homocysteine emerged in the past few years as an independent risk factor for cardiovascular diseases. This test is now currently prescribed for the diagnosis of unexplained thrombosis in young adults or recurrent thrombosis in patients with arteriopathy. This sulphured amino-acid is an important intermediate in transsulfuration and remethylation pathways of methionine metabolism. Within the context of a collaboration between Monastir and Grenoble Universities and because a gas chromatograph mass spectrometer (GC-MS) instrument was available in Monastir, we proposed to transpose a GC-MS method previously developed in Grenoble's hospital for this parameter and to validate it by comparison with the liquid chromatography tandem mass spectrometry (LC-MS-MS) method, used at present. Analytical performances were good: detection limit 0.4 micromol/L and linear range up to 4 mg/L (29.6 micromol/L), and between-run and within-run precision with coefficients of variation < 5% and < 8 %, respectively. The comparison with LC-MS-MS method showed a good correlation (y = 0.9874 x -0.208; r(2) = 0.84). Mean difference from LC-MS-MS was -0.4 micromol/L. Plasma concentrations of homocysteine (mean + SD) determined among Tunisian adults, 29 men, 27 women, of the same age were respectively: 11.6 +/- 2.4 micromol/L and 10.1 +/- 2.7 micromol/L, p = 0.025. This method is now currently used to evaluate tHcy concentration in patients with risk factors for cardiovascular disease.

Phenotypic and genotypic risk factors for cardiovascular events in an incident dialysis cohort.

Cardiovascular disease (CVD) remains the major cause of death in patients with end-stage renal disease (ESRD). Traditional risk factors do not explain the high prevalence of CVD in this population, and other non-traditional cardiovascular (CV) risk markers have now been described. Therefore, the potential relationship between CVD and phenotypic and genotypic risk markers was investigated prospectively in incident dialysis patients cohort. The 279 patients (244 on hemodialysis, 35 on peritoneal dialysis) within the Diamant Alpin Dialysis Cohort Study were investigated. Phenotypic and genotypic parameters were determined at dialysis initiation, patients monitored over a 2-year period, and CV events (morbidity and mortality) recorded. Globally, 82 CV events occurred and 26 patients (9.3%) died from CVD, whereas 28 (10%) died from non-CV causes. Previous CV events were strongly predictive of CV events occurrence, whatever patients had had one (hazard ratio (HR) 2, 95% confidence intervals (CI) 1.1-3.5) or more (HR 3.9, 95% CI 2.1-7.1) CV accidents before starting dialysis. Both lipoprotein(a) (HR 1.67, 95% CI 1-2.5) and total plasma homocysteine at cutoff 30 micromol/l (HR 1.7, 95% CI 1.1-2.8) were independent predictors of CV events outcome. In the subgroup of patients with homocysteine < 30 micromol/l, methylenetetrahydrofolate reductase (MTHFR) TT was the sole biological parameter predictive of CV event outcome (HR 2.5, 95% CI 1.1-10, P = 0.03). ESRD patients who enter chronic dialysis with a previous CV event, high total homocysteinemia levels, or MTHFR 677TT genotype must be considered at high risk of incident CV events.

[Percutaneous compression plate for pertrochanteric fixation of hip fractures: surgical technique and first results]. / Ostéosynthèse des fractures du massif trochantérien par plaque de compression percutanée: Technique chirurgicale et premiers résultats.

We have used a minimally invasive technique for fixation of trochanteric fractures since 2003. We use the percuntaneous compression plate described by Gotfried. We describe here the osteosynthsis technique and our special approach which limits operative time. This technique avoids wide opening of the aponeurosis of the tensor fascia lata, major detachment, and section of the vastus lateralis. The plate is inserted via a 2-cm incision over the greater trochanter. Head and shaft screws are inserted via a second incision measuring 3 to 4 cm. Perfect reduction before plate insertion is the key to success. The results of our first twenty cases have demonstrated an uneventful postoperative period and a short operative time of 25 minutes on average. Peri-operative bleeding has been very limited. Radiographic healing was obtained in three months. Weight bearing was possible immediately after fixation in five cases and was delayed in fifteen. There were two early displacements which were analyzed.

[Severe angular deformity of the humerus: unilateral external fixation for correction and bone lengthening]. / Allongement et correction d'une déformation angulaire sévère de l'humérus par fixateur externe mono-latéral.

We report the case of a 10-year-old child who presented a severely deformed upper limb due to post-traumatic partial proximal epiphysiodesis of the humerus. The goal of treatment was to correct the severe angular deformity, prevent recurrence, and lengthen the humerus 6 cm. We used the De Bastiani callotasis method with osteotomy of the humeral shaft and unilateral external fixation (Orthofix LRS). The bony deformations were corrected progressively. Angular correction induced a geometric lengthening sufficient to match the length of the healthy limb. Lengthening index was 22.7 days/cm. The functional and esthetic results were remarkable. Complementary epiphysiodesis of the proximal physis successfully prevented recurrent deformation.

[Extensor tendon rupture after dorsal surgery of the rheumatoid wrist: analysis of nine reviewed cases]. / Les ruptures des tendons extenseurs aprés chirurgie dorsale du poignet rhumatoïde: analyse de 9 cas revus.

We led a retrospective study to determine the causes of the tendon ruptures post-operating in the surgery of the wrist rheumatoid dorsal and to estimate the clinical result. At follow-up, we measured the extension lag and the rolling-up of fingers by the distance palm-pulps. Nine patients were so revised in the average of 40 months, average age was of 50.7 years. The tendon ruptures arose in 3 months in 67% of the cases. Seven times, a procedure on the distal radio-ulnar joint had been necessary (5 Sauvé-Kapandji and 2 Darrach). Thirty tendons had been concerned in this study, that is 3.3 tendons on average (1-5). Two main causes were found: attrition on the stub ulnaire and great intra-tendinous synovitis (per operating observation). At the revision, the lag extension means was 23 degrees (0-40). Rolling-up of the long fingers was complete 4 times on 7. The best results were observed after tendinous grafting or index proprius transfer with a lateral suture. Tendinous adhesions had arisen 6 times and persisted still at 3 patients. Our study underlines the interest to stabilize the stub ulnaire to prevent the post-operating ruptures and proposes a transfer or a graft in front of tendons very weakened by the synovitis.

Proteinuria and the expression of the podocyte slit diaphragm protein, nephrin, in diabetic nephropathy: effects of angiotensin converting enzyme inhibition.

AIMS/HYPOTHESIS: Proteinuria, reflecting increased glomerular permeability to macromolecules is a characteristic feature of diabetic nephropathy. Nephrin, a 1241-residue transmembrane protein is a key component of the podocyte slit pore membrane and a major contributor of the glomerular filtration barrier. We investigated the expression of nephrin in human kidney tissue from patients with diabetic nephropathy to elucidate its relationship with proteinuria and the effects of anti-proteinuric therapy with angiotensin converting enzyme inhibition. METHODS: Renal biopsies were examined from 14 patients with Type II (non-insulin-dependent) diabetes mellitus and proteinuria who had been randomised to receive treatment with the ACE inhibitor, perindopril (4 mg/day) or placebo for the preceding 2 years. These specimens were compared with control human tissue sections, obtained from areas of normal renal cortex following nephrectomy for malignancy. Proteinuria was measured, specimens were examined histologically for injury and the expression of nephrin messenger RNA was assessed by quantitative in situ hybridisation. RESULTS: Glomeruli from placebo-treated patients with diabetic nephropathy, showed a 62% reduction in nephrin expression compared with control subjects (p=0.0003). In contrast, nephrin RNA in glomeruli from perindopril treated patients was similar to that in the non-diabetic control group. In both placebo and perindopril treated patients, a close inverse correlation was noted between the magnitude of nephrin gene expression and the degree of proteinuria (placebo: r=0.86, p=0.013, perindopril: r=0.91, p=0.004). CONCLUSION/INTERPRETATION: Modulation in nephrin expression is related to the extent of proteinuria in diabetic nephropathy. These changes define, at a molecular level alterations in the glomerulus that occur in relation to proteinuria in diabetes and the effects of anti-proteinuric treatment with ACE inhibition.

[How does one explain the very good performance of Spanish nephrology]. / Comment expliquer les très bonnes performances de la néphrologie espagnole actuelle?

Spain is a highly performing country in nephrology with 2000 kidney grafts a year (50 pmp); 42% of end stage renal disease patients have a functioning kidney graft (338 pmp); the highest level worldwide of organ donors (33.9 pmp) and very few living donors and finally one of the lowest level in Europe of "late referral to nephrologists" (18%). Amongst various explanations emerge the fact that the number of nephrologist is high in this 40 millions inhabitants country (more than one thousand) when they are less than the thousand for 60 millions inhabitants in France.

Does ACE inhibition slow progression of glomerulopathy in patients with Type 2 diabetes mellitus?

AIMS: To examine the effect of ACE inhibition on glomerular structure in Type 2 diabetic patients with nephropathy. METHODS: Twenty-two patients were randomized to receive either perindopril (PE) or placebo (PO) and biopsied at baseline and after 2 years. Nineteen patients completed the study and data on interstitial changes, examined by light microscopy, have already been published. Only 11 patients (five PE, six PO) had sufficient tissue at baseline and follow-up to provide material for detailed electron microscopic examination. RESULTS: At baseline, mean +/- sd age (PE vs. PO) was 48 +/- 12 vs. 45 +/- 7 years; creatinine clearance 116 +/- 24 vs. 128 +/- 68 ml/min; median (range) proteinuria 0.7 (0.1-1.0) vs. 0.5 (0.07-3.9) g/24 h (P = NS for all). This cohort of 11 patients showed the same interstitial changes as the whole group. Between-group analysis showed that the change in interstitial volume fraction was significantly greater in the PO compared with PE group (0.10 +/- 0.07 vs. -0.001 +/- 0.04, P = 0.020). There were no significant changes in proteinuria or glomerular structural parameters (mesangial volume fraction PO 0.40 +/- 0.17 to 0.42 +/- 0.21; PE 0.29 +/- 0.08 to 0.28 +/- 0.14) in either treatment group. CONCLUSIONS: Interstitial changes appear to be more sensitive to ACE inhibition than glomerulopathy. Larger patient groups and longer treatment periods are necessary in order to detect any possible impact of ACE inhibition on the glomerular changes in Type 2 diabetes mellitus.

Role of ACE inhibitors in patients with diabetes mellitus.

The adjective 'epidemic' is now attributed to the rapidly growing number of patients with diabetes mellitus, mainly type 2. and the specific complications linked to this disorder. Provided they are recognised early enough, these different complications can be treated; in some patients the evolutive course of these complications can be slowed or even stopped. Furthermore, some recent observations suggest that specific tissular lesions may be prevented or even reversed. Although glycaemic control is essential, other therapeutic measures that must also be taken include those to control blood pressure and to lower lipid levels. Of the agents available to control the complications of diabetes mellitus, cardiovascular drugs, and particularly ACE inhibitors, have a pre-eminent place. Experimental and epidemiological data suggest that activation of the renin-angiotensin-aldosterone system plays an important role in increasing in the micro- and macrovascular complications in patients with diabetes mellitus. Not only are ACE inhibitors potent antihypertensive agents but there is a growing body of data indicating that also they have a specific 'organ-protective' effect. For the same degree of blood pressure control, compared with other antihypertensive agents, ACE inhibitors demonstrate function and tissue protection of considered organs. ACE inhibitors have been reported to improve kidney, heart, and to a lesser extent, eye and peripheral nerve function of patients with diabetes mellitus. These favourable effects are the result of inhibition of both haemodynamic and tissular effects of angiotensin II. Finally, there are a growing number of arguments favouring the use of ACE inhibitors very early in patients with diabetes mellitus.

[The late referral of diabetic patients with kidney insufficiency to nephrologists has a high human and financial cost: interdisciplinary communication is urgently needed]. / Le recours tardif des diabétiques insuffisants rénaux aux néphrologues a un coût humain et financier très élevé

The "late referral to nephrologist" (LRN) phenomenon has been described recently, first in Europe and subsequently in every country where dialysis and transplantation are offered without restriction. Definition of LRN is based on an arbitrary date of referral which is three months before the first dialysis session. LRN patients suffer much more morbidities and consequently more hospitalizations, particularly in intensive care units. They have less access to home and self dialysis, to peritoneal dialysis and to renal transplantation than their "on time" referred counterparts. Even if mortality is more important in late referred patients, the additional cost of LRN phenomenon is substantial; it has been evaluated from 16 800 to 30 500 euros for the first year of treatment. Every kind of patients are concerned, including diabetics. Explanation of the LRN phenomenon is complex and needs a multidisciplinary approach.

Role of metalloproteases and inhibitors in the occurrence and progression of diabetic renal lesions.

Renal remodelling in hyperinsulinic/insulinopenic states is mediated by glucotoxicity, endothelial dysfunction and vascular and nephron collagen turnover. Hypertensive and renal links are renewed by renoprotective interventions of renin-angiotensin. Vasoactive peptide processing and vascular collagen deposition are under the tight control of two zinc metalloproteinase families that regulate vascular tone and trophicity: gluzincins (or vasopeptidases) are convertases of angiotensins, endothelins or atrial natriuretic factors; and metzincins or matrix metalloproteases (MMP, matrixins)] regulate vascular type IV collagen basement membrane proteolysis. Association of natural tissue inhibitors of MMPs, pharmacological inhibitors of vasopeptidases [either conventional (angiotensin-converting enzyme inhibitors) or innovative (omapatrilat)], together with synthetic MMP inhibitors, are currently screened to counteract vascular remodelling and renal scarring. Our studies focused on the 72 kDa (MMP-2) and 92 kDa (MMP-9) matrixin gelatinases and tissue inhibitors involved in basement membrane degradation and rebuilding. Three complementary settings were developed, allowing evaluations from basic to clinical stages. A leucocyte-endothelial transmigration model was designed for transcription and addressing of enzymes and inhibitors, in situ matrix degradation, and blockading by metalloprotease inhibitors (captopril). Insulin-resistant fructose-fed rats showed heavy proteinuria and glomerulosclerosis involving angiotensin II-dependent changes in renal gelatinases and inhibitors. Urinary gelatinolytic profiles from Type 2 diabetic patients with overt nephropathy were compared with those of normal first-degree relatives and age-matched healthy controls. Physiologically, MMP-9 was the primary urinary gelatinolytic enzyme. In Type 2 diabetic proteinuric patients, MMP-9 and MMP-2 releases were significantly increased in the absence of renin-angiotensin blockade, while first-degree relatives showed reduced gelatinase levels suggestive of a genetic control of renal matrix regulation prior to potential glycaemic dysregulation. These preliminary data suggest that local MMP/TIMP imbalance is involved in diabetic renal remodelling. Further studies are needed to define the redundancies and specificities of vasopeptidase and MMP inhibitors, differentiate the antihypertensive effect from target-organ protection, screen for innovative pharmacological compounds, and validate simple, efficient biological markers of renal fibrosis progression and the effect of anti-fibrotic therapeutic interventions.

[Heterogeneity of nephropathies in type 2 diabetes]. / Hétérogénéité de la néphropathie chez les diabétiques de type 2.

DIVERSE KIDNEY DISORDERS: Patients with type 2 diabetes mellitus who develop nephropathy can have various types of disorders capable of progressively destroying the kidneys. It is now clear that the same type of diffuse or nodular glomerulosclerosis develops irrespective of the type of diabetes, i.e. the pathophysiology of hyperglycemia. HETEROGENEITY: There is however a certain degree of heterogeneity in terms of clinical presentation, clinical course and response to treatment. Heterogeneity is due to age, the number of different accumulated risk factors and disease states, genetic factors that are in the process of being identified, and finally, lesions to the urologic apparatus, the arteries, and the renal parenchyma itself that are not directly caused by diabetes. PRACTICAL IMPACT: Mixed lesions, due to both diabetic and non-diabetic causes, may therefore exist in the same kidney. These different possibilities should be systematically considered in order to adopt an individualized investigative and therapeutic attitude for each new patient.