Borgnino Lc

Lipid Abnormalities in Insulin-dependent Diabetic Patients with Albuminuria

The relationship between serum lipid, lipoprotein, and apolipoprotein levels and abnormalities of renal function has been investigated in 112 insulin-dependent (type I) diabetic patients. They were subdivided into three matched groups according to the amount of albuminuria: group A (albuminuria < 20 μg/min), group B (albuminuria between 20 and 150 μg/min; Albustix negative), and group C (albuminuria > 150 μg/min; Albustix positive). Twenty-one nondiabetic subjects with albuminuria above 150 μg/min but without nephrotic syndrome and/or renal failure and 77 healthy subjects were also studied. Mean total and LDL cholesterol, triglycerides, and apo B were higher, while HDL cholesterol and HDL/LDLcholesterol ratio were lower in group C than in groups A and B; the apo A/apo B ratio was lower in group C than in group A. Differences in apo B and in apo A/apo B ratio were found between groups A and B. No correlation between lipid parameters and amount of albuminuria was observed. Significant differences in lipid concentrations were also found in diabetic patients when compared with nondiabetic subjects with albuminuria and with healthy subjects. The present study confirmed previous reports of lipid disorders in insulin-dependent (type I) diabetes; however, the most important observation was the finding of albuminuria-related differences in lipid parameters in diabetic patients without renal failure. We think that the greater lipid abnormalities observed in diabetic patients with larger amounts of albuminuria might be the consequence both of impairment of glomerular permeability and of the diabetic state.

Renal Transplantation in Patients with Microscopic Polyarteritis and Antimyeloperoxidase Antibodies: Report of Three Cases

This paper reports on 3 patients on renal dialysis for crescentic glomerulonephritis associated with microscopic polyarteritis (MPA) and antineutrophil cytoplasmic autoantibodies specific for myeloperoxidase (MPO-ANCAs). They successfully underwent renal transplantation from a cadaver donor 6-63 months after the onset of the disease, despite the persistence of antibodies at high titer. A triple immunosuppressive regimen including steroids, cyclosporin and azathioprine was used. One patient underwent transplantectomy for surgical complications 3 months later, while the serum creatinine was 2.0 mg/dl (178 mu mol/l): the remainder have a well-functioning graft after 21 and 38 months, no clinical sign of disease recurrence, and a MPO titer within the normal range. We conclude that MPA patients can undergo renal transplantation even if ANCAs persist at a high titer in the circulation.

Plasma exchange treatment in rapidly progressive glomerulonephritis associated with anti-neutrophil cytoplasmic autoantibodies.

This study reports on 12 patients with acute renal failure due to biopsy-proven rapidly progressive glomerulonephritis and signs of systemic disease in whom antineutrophil cytoplasmic autoantibodies (ANCA) were detected by indirect immunofluorescence (IIF) on alcohol-fixed neutrophils and assessed in serial determinations by ELISA. The diagnosis was: Wegeners granulomatosis in nine patients who showed a diffuse cytoplasmic pattern at IIF (c-ANCA), and microscopic polyarteritis in three where a perinuclear pattern (pANCA) was seen. All patients underwent a course of plasma exchange - PE - (3-10 sessions per patient) associated with steroids and cyclophosphamide. The ANCA titer dropped steeply during PE in all cases and was followed by disappearance of systemic symptoms and renal function improvement within four weeks. After a follow-up period of 50 ± 31.2 months all patients were alive without signs of disease activity; ten had stable renal function, with serum creatinine 1.8 ± 0.7 mg/dl; two had entered regular dialysis treatment after 44 and 82 months. Our results suggest that the rapid removal of ANCA by means of PE can help control disease activity and reduce the risk of death or end-stage renal disease.

Combined treatment in Wegener's granulomatosis with crescentic glomerulonephritis--clinical course and long-term outcome.

This study reports on 9 patients suffering from Wegeners granulomatosis (WG) with crescentic GN and severe systemic manifestations. On admission the mean serum creatinine was 10.9 ± 5.1 mg/dl (4-20 mg/dl); 8 patients were oliguric and required dialysis treatment. Renal biopsy showed crescents in all cases, involving 66 to 100% of glomeruli. Patients were treated with a protocol including: a plasmaexchange (PE) course; methyl-prednisolone; cyclophosphamide; and an antithrombotic agent (defibrotide). Clinical picture and renal function progressively improved in all patients within the first 4 weeks of treatment. After 1 month serum creatinine was 2.7 ± 0.8 mg/dl and dialysis was no longer needed in any patient. Five relapses occurred in 3 patients 12-26 months after the onset of the disease, while they were still receiving immunosuppressive treatment. At follow-up (22 to 112 months: mean 71) all patients were alive with no clinical signs of disease activity. One patient was on regular dialysis while the others had a serum creatinine of 1.2-2.8 mg/dl (mean 1.9). Our results confirm that crescentic GN associated with WG can be successfully treated even when associated with severe clinical picture and suggest that PE can contribute to control the disease without increasing immunosuppression.

Validity of flow cytometry for cross-match evaluation in clinical renal transplantation.

This paper reports a 2-year experience of more than 5,000 cross-match tests for renal transplantation. Tests were performed by means of both standard light microscopy and an innovatory method based on flow cytometry, an up-to-date investigative technique for computerized analysis of individual cell characteristics. Flow cytometry allowed a better detection of weak positive reactions (false-negative cross-matches) than light microscopy, thus reducing the risk of selecting candidates with donor presensitization. Transplant clinical outcome supported the value of this original and advanced technological method.

Kidney Function After Improved Metabolic Control in Newly Diagnosed Diabetes and in Diabetic Patients with Nephropathy

To evaluate the effect of improved metabolic control on kidney function, urinary excretion rate of β-2- microglobulin, lysozyme, and γ-glutamyltransferase were evaluated in nine poorly controlled, newly diagnosed diabetic patients before and during treatment. In six poorly controlled insulin-dependent nephropathic diabetic patients, besides the parameters cited above, urinary albumin excretion rate and IgG/transferrin clearance ratio were further investigated to estimate the permeability and the selectivity of glomerular barrier during conventional treatment and after improvement of the metabolic control by a glucose-controlled insulin infusion system (GCIIS). The improved glycemic control resulted in a significant reduction of urinary β-2-microglobulin and lysozyme excretion in all diabetic patients. Significant decreases of urinary albumin excretion and of IgG/transferrin clearance ratio (indicating a more selective proteinuria) during strict metabolic control were also observed in nephropathic diabetic patients. The reduction of urinary β-2-microglobulin and lysozyme excretion indicates that a tubular reabsorptive dysfunction, reversible with the amelioration of glycemic control, can be observed in poorly controlled, newly diagnosed and in insulin-dependent nephropathic diabetic patients during conventional treatment. In the latter patients, the permeability and the selectivity properties of glomerular barrier also improved during GCIIS.

A screening test for microalbuminuria in type 1 (insulin-dependent) diabetes

In this study we evaluated the acceptability of using the first morning urine albumin concentration (FMAC) and the first morning urine albumin/creatinine (FMA/C) ratio as an indirect estimation of timed albumin excretion in order to screen for microalbuminuria in a large diabetic population. Urinary albumin excretion rate (AER) was determined in samples from 4-h urine collection in 99 type 1 diabetic patients aged 30 +/- 10 years with a mean duration of diabetes of 15 +/- 8 years. The results of timed albumin excretion were successively compared with single-void first morning samples. On the basis of AER, 46 patients were normoalbuminuric (AER less than 20 micrograms/min), 28 microalbuminuric (AER 20-200 micrograms/min), and 25 proteinuric (AER greater than 200 micrograms/min). The relationship of 4-h AER to FMAC and FMA/C ratio was highly significant (r = 0.96 and r = 0.98 respectively). High sensitivity and specificity were found when cut-offs of 20 micrograms/ml and 2.5 mg/mmol were selected for albumin concentration and albumin/creatinine ratio respectively to discriminate between normal and elevated albuminuria. It is concluded that the measurements of albumin concentration and albumin/creatinine ratio in first morning urine samples are highly representative of 4-h timed albumin excretion. Because of their sensitivity, specificity and simplicity to perform, the tests proposed might be used in routine diabetic care and as a screening test for microalbuminuria in type 1 (insulin-dependent) diabetic patients. The not negligible day-to-day variability in albumin excretion confirms the need of several measurements to establish the presence of abnormal levels of albuminuria above all in patients with borderline values and/or clinically unstable metabolic control.

Fibroblast proliferation over dialysis membrane: an experimental model for "tissue" biocompatibility evaluation.

The present study reports on a biological model based on fibroblast proliferation applied to 3 different types of flat-plate dialysis membrane, in order to ascertain whether the artificial materials currently used in hemodialysis cause in vitro cellular proliferation. The study plan we followed involved plate membrane isolation from non-used dialyzers and used dialyzers, observed through scanning electron microscopy (SEM) both before and after testing with human fibroblasts by means of cell culture. Fibroblast growth was assessed by phase contrast light microscopy examination and cytometric DNA content evaluation. Our investigations proved that the artificial materials we considered interact with fibroblast cultures. Noticeable proliferative response was observed both after contact with unused material and on mediation by the protein layer absorbed on the membrane surface at the end of dialysis sessions. In this last case fibroblast proliferative activity appeared higher than that observed with unused membranes, showing that the soluble molecules entrapped in the protein layer appeared able to exert a biological activity even in in vitro tests

Application of flow cytometry in clinical renal transplantation

Flow cytometry (FC) may be considered as a fundamental technique in studying cell biology and pathology. It combines the quantitative character of biochemical methods with the multiparametric capacities of microscope analysis in a high-precision process for rapid analysis of individual cell characteristics. Three original FC techniques routinely applied in the field of renal transplantation are reported in the present study. They concern the donor-recipient cross-match test, the morphological analysis of urinary sediment and the modulation of the density of various membrane antigens on the lymphocyte surface. A common factor underlies all these methods: they aim to provide the physician with a reliable diagnostic tool in clinical renal transplantation.