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Measurement of urinary albumin excretion (UAE) may be done on a morning urinary sample or on a 24 hours-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 microg/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.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.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 one or two 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.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 antihypertensive medications (ACEI, ARB, thiazides, calcium channel blockers or betablockers) can be used.

Clinical and therapeutic characteristics of chronic dialysis patients vary widely at national and/or regional levels. Their increased cardiovascular (CV) mortality is not explained by traditional cardiovascular disease (CVD) risk factors only. Therefore, this study aimed to investigate and compare the characteristics of patients starting dialysis in a homogeneous Alpin region and possibly to identify new biological parameters (phenotypes or genotypes), which eould be responsible for the increased CVD seen in end-stage renal disease (ESRD) patients.A cohort of 279 non-selected consecutive patients entering a dialysis program was prospectively investigated in eight centers of three adjacent regions in France, Italy and Switzerland. In addition to the usual demographic, clinical and biological data, we analyzed at study entry the blood levels of homocysteine, lipoprotein(a) (Lp(a)) and antioxidized low density lipoprotein (LDL) antibodies, vitamin B12 status, Lp(a) and haptoglobin phenotypes, methylenetetrahydrofolate reductase (MTHFR), angiotensin-converting enzyme (ACE), allele epsilon E4 of apolipoprotein (ApoE4) and plasminogen activator inhibitor-1 (PAI-1) genetic polymorphism.At entry, 90.3% of patients were hypertensive, 30% had type 2 diabetes mellitus and 17.6% were current smokers; 42% of patients had already experienced at least one CV event: peripheral artery disease (26% of the cohort), coronary artery disease (22%) or ischemic cerebro-vascular disease (16%). Forty-two patients had hador =2 CV events or documented atherosclerotic localizations. Anemia was not optimally treated: mean hemoglobin (Hb) was at 97.7 g/L and, while overall 62% of patients received erythropoietin (EPO) prior to dialysis, large national differences were observed. Compared to the reference population, ESRD patients exhibited increased homocysteinemia, Lp(a) levels and ApoE4 allele prevalence. Conversely, the distribution of Lp(a) phenotype, MTHFR TT, ACE DD and PAI-1 4G/4G was equivalent to that of the reference population. In addition, none of the analyzed phenotypical or genotypical parameters, except for the haptoglobin 2.2 phenotype, could be associated with the existence of a previous adverse CV event.(1) The clinical characteristics of the ESRD patients entering dialysis in our region were comparable to the currently observed dialysis populations in most European countries with the deleterious role of advancing age, diabetes, previous CVD, smoking and hypertension evident (2). Except for anemia therapy, there were no regional or national differences observed at dialysis start. (3) An analysis of the phenotypic and genotypic CV risk factors demonstrated differences with the reference population only for hyperhomocysteinemia, Lp(a) and ApoE4 allele prevalence, with no notable differences among the participating centers.

In the early days of hemodialysis efforts to treat and rehabilitate uremic diabetics were largely unsuccessful [1] until dialysis procedures and volume control had become more effective. Although diabetics have a poorer outcome than non-diabetics, survival has improved progressively, e.g. in the US adjusted first year mortality decreasing from 46% in 1982 to 30% in 1992 [2], although long-term survival is still very unsatisfactory, e.g. at 5 years 45% in type I and 10% in type II diabetics according to a recent German multicenter study [3]. Nevertheless it is no longer justified to deny admission to renal replacement therapy to the diabetic patient [4].

In the early days of haemodialysis, efforts to treat and rehabilitate uremic diabetics were largely unsuccessful [1] until dialysis procedures and volume control had become more effective. Although diabetics have a poorer outcome than non-diabetics, survival on dialysis has improved to such an extent that today virtually no restrictions for admission to renal replacement therapy for these patients are justified. Consequently, diabetic nephropathy (assuming that in most cases renal failure is due to diabetic nephropathy) accounts for a large proportion of the dialysis population second only to glomerulonephritis and in some centers (as in Heidelberg) even exceeding glomerulonephritis [3].

In order to gain insight into the role of IgG Fc receptors in essential mixed cryoglobulinaemia (EMC), we analyzed quantitatively the expression of such molecules on polymorphonuclear leukocytes (PMN) and assessed them, functionally, on PMN, tissue macrophages and circulating monocytes in 6 HLA-B8-, DR3-negative patients with EMC and glomerulonephritis. The Fc receptors expressed on PMN surface, as estimated by using AB 8.28 monoclonal antibody to PMN Fc receptor and 125I-labelled rabbit F(ab')2 fragments to mouse IgG as detecting system, were found to be quantitatively normal in EMC patients, whereas PMN Fc- receptor-mediated phagocytosis was reduced. Moreover, the patients were found to have prolonged macrophage clearance of IgG-sensitized autologous erythrocytes and reduced kinetics of ingestion of IgG-coated material by circulating monocytes. This impairment of Fc receptor function may play a remarkable role in the tissue localization of immune material in this disease.

Thirty human cryoglobulin precipitates obtained from 21 patients were fixed and examined by electron microscopy; following biochemical isolation and identification. This study showed that the fine structure of cryoprecipitates depends on the involved immunoglobulins and on their respective quantities. Monoclonal IgG kappa 1 or 3 cryoglobulins with antibody activity form crystalling precipitates of 22-nm diameter rods and annuli. When polyclonal, they form 6-nm-wide filaments. Mixed IgG and IgM cryoprecipitates appear as cylindric and annular bodies with an internal diameter of 12 nm and a total diameter of 62 nm. When IgM predominates over IgG, globular condensations with a diameter of 30 nm are seen. Mixtures in which the IgG is more abundant than the IgM include fingerprint-like periodic condensations.

The Fc-receptor function of the mononuclear phagocyte system was examined in 30 patients affected by multisystem diseases with glomerular involvement by measuring the immune clearance of IgG-sensitized autologous red blood cells in vivo and the immune phagocytosis of monocytes in vitro. Patients studied in the phase of clinically active renal disease showed a significantly reduced Fc-receptor function by both in vivo (p less than 0.001) and in vitro (p = 0.003) assays, as compared to those studied during an inactive phase. Though the nature of the defect remains uncertain, it appears to be related to the active phase of the renal disease as also confirmed by the analysis of individual cases studied longitudinally.

Comparative studies of renal biopsy specimens and in vitro cryoprecipitate were carried out in a patient with mixed immunoglobulin G (IgG)-immunoglobulin M (IgM) cryoglobullnemia associated with glomerulonephritis. The IgM isolated from the cryoprecipitate was an antibody with anti-IgG activity. Proliferative endocapillary glomerulonephritis was found in the kidney, with large amorphous deposits in the capillary walls. On immunofluorescent examination, these deposits contained IgG and C3. Ultrastructural studies of both cryoprecipitate and glomerular deposits revealed unusual structures designated as "cylindrical or annular bodies." The morphologic characteristics of these bodies were exactly the same in the kidney and in the cryoprecipitate. These findings suggest an identity between the glomerular deposits and the circulating cryoglobulin, supporting the hypothesis that the glomerulonephritis reported here is an immune-complex disease.

Nineteen patients with idiopathic membranous nephropathy were typed for HLA pattern and analyzed for the Fc receptor function of splenic macrophages by detecting in vivo the clearance of IgG-sensitized 51Cr-labelled autologous erythrocytes. Seven out of 19 patients were found to have a macrophage dysfunction. This defect was not related to any HLA-A, B, C, DR, DQ antigen tested nor to the levels of IgG-containing immune complexes, as detected by a Clq solid phase test, nor to the magnitude of proteinuria. Since HLA-B8 and HLA-DR3 antigens were significantly more frequent in patients than in the control group, the factors that may impair the macrophage system in individuals predisposed to this nephropathy are discussed.

The effect of mitomycin C (MMC) on the biosynthesis of prostacyclin was tested in culture of human umbilical cord vein endothelial cells. A 30% inhibition of the thrombin-stimulated prostacyclin synthesis by MMC was observed at concentrations of the same order as those found in MMC-treated patients (3 μg/ml as compared with the peak plasma concentration varying between 0.4 and 3.2 μg/ml (J. Den Hartigh et al. , Cancer Res 40 : 5017–5021,1983)). This inhibition was found for incubation times ranging from 15 to 30 min during which the cell viability was unaltered. Under these conditions it was found that the release of von Willebrand factor by the endothelial cell was unaffected. Since MMC toxicity in man is expressed by a chronic haemolytic and uraemic syndrome, the inhibitory capacity of MMC on prostacyclin synthesis favours the hypothesis that a deficiency in prostacyclin synthesis leads to the development of this syndrome in man.