Giuseppina Pettinato

Effect of fluvastatin on proteinuria in patients with immunoglobulin A nephropathy

3‐Hydroxy‐3‐methylglutaryl coenzyme A (HMG‐CoA) reductase inhibitors are established drugs for the treatment of hypercholesterolemia, but several studies have shown that benefits obtained with these drugs are not causally related only to regression of cholesterol lowering. Moreover, in experimental models of progressive renal disease, statins have reduced the extent of glomerulosclerosis. This study evaluated the antiproteinuric effect of a daily dose of 40 mg fluvastatin for 6 months in moderately proteinuric patients with immunoglobulin A nephropathy, stable renal function, and no indicators of poor long‐term prognosis. The effects of therapy were evaluated on the basis of 24‐hour proteinuria (total proteinuria and albuminuria), albuminemia, creatinine clearance, cholesterol, and triglyceride values. Renal function remained stable in all patients. A significant decrease in proteinuria was observed after 6 months of therapy and persisted for all the observations. An increase in serum albumin was observed after 6 months of therapy. This study suggests that there is an antiproteinuric effect of HMG‐CoA reductase inhibitors in moderately proteinuric patients with immunoglobulin A nephropathy. (Clin Pharmacol Ther 2000;67:427‐31.)

Renal Failure from Mitochondrial Cytopathies

Mitochondrial cytopathies are metabolic diseases, expressing mutations in nuclear DNA, punctiform mutations or depletions in mitochondrial DNA. These genetic lesions alter mitochondrial oxidative phosphorylation, with a reduction in energy produced for cell activity. Renal disease may be the first sign of mitochondrial cytopathy, or it may appear together with neurological and neuromuscular signs. Fanconis syndrome, a benign sign of renal tubulopathy, is particularly frequent in newborns with mitochondrial cytopathy, whereas tubulointerstitial nephropathy, which affects infants and adults, is more serious because it develops into terminal uremia. Findings of hyperlactatemia and reduced enzymatic activity on the respiratory chain in tissue biopsies are of diagnostic significance in mitochondrial cytopathy. A breakthrough is being made in our understanding of genetic alterations in mitochondrial DNA, and with future therapy, the kidney, a target organ, may be safeguarded.

Sclerostin levels in uremic patients: a link between bone and vascular disease.

Abstract Sclerostin is a marker of low-turnover bone disease in end stage renal disease patients. The aim of this study was to evaluate serum sclerostin in uremic patients, analyzing its behavior during a single hemodialysis session. Twenty-one adult patients on intermittent hemodialysis treatment were enrolled. Acetate Free Bio-filtration (AFB) was the technique employed. Uremic patients were characterized by higher levels of serum sclerostin when compared with values observed in healthy subjects. Sclerostin assessed in pre-dialysis samples was 1.4 ± 1.02 ng/mL, whereas, in post dialysis samples, a reduction of sclerostin values was observed (0.8 ± 0.6 ng/mL; p: 0.008). Sclerostin correlated with parameters of dialysis adequacy, such as creatinine levels and Kt/V values, and it was significantly associated with atherosclerotic disease. Receiver operating characteristics analysis revealed a good diagnostic profile in identifying atherosclerotic disease. Sclerostin, a full dialyzable substance during AFB dialysis, is closely associated with atherosclerotic disease. Its reduction obtained through AFB could represent a defensive mechanism, improving vascular disease and renal osteodystrophy.

From chronic kidney disease to transplantation: The roles of obestatin

BACKGROUND Kidney transplantation is the therapy of choice in most cases of end stage renal disease. The purpose of the present study was to evaluate serum obestatin levels in kidney transplant recipients (Tx), compare levels in patients with renal failure (CKD) with those in healthy subjects (HS), and to assess the role of this hormone in energetic metabolism. PATIENTS AND METHODS A total of 95 subjects were studied: 40 were Tx; 35 had CKD and 20 were HS. Inclusion criteria were age>18years and good allograft function. Patients with an inflammatory disease or a diagnosis of cancer were excluded from the study. RESULTS Obestatin levels in Tx patients were significantly lower than in HS (3.5 [3-4.8] versus 11 [8.56-28.60] ng/mL; p<0.0001) and patients with CKD (3.5 [3-4.8] versus 4.7 [3, 5-6, 1] ng/mL; p=0.008). At univariate analysis, a direct correlation was found between obestatin and calcemia (p: 0.0001; r: 0.51), phosphoremia (p: 0.0005; r: 0, 46), calcium-phosphate product (p<0.0001; r:0.53), and parathormone (p: 0.01; r: 0.32), whereas significant inverse correlations were evidenced for BMI (p<0.0001; r: -0.52). At multivariate analysis, significance was maintained for the correlation between obestatin and phosphoremia (β=0.47; p=0.008), for the calcium-phosphate product (β=0.55; p=0.0005) and for BMI (β=-0.53; p=0.01). CONCLUSION Obestatin, present in lower levels in Tx patients than in CKD patients and HS, plays a role in energy metabolism, affecting BMI and the metabolism of calcium-phosphorus.

Effects of lisinopril administration on blood bcl‐2 concentrations in patients with immunoglobulin A nephropathy

We evaluated blood concentrations of bcl‐2, a proto‐oncogene that can inhibit apoptotic phenomena, in a group of patients with immunoglobulin A (IgA) nephropathy. Concentrations of bcl‐2 were higher in patients with proteinuria than in those without proteinuria. A 6‐month course of 5 mg/day lisinopril given to subjects with proteinuria significantly reduced blood bcl‐2 concentrations and caused a reduction in proteinuria. Therefore increased blood bcl‐2 concentrations may be considered an index of risk in subjects with IgA nephropathy, and the positive effects of angiotensin‐converting enzyme inhibitors on proteinuria in patients with IgA nephropathy may be attributed, at least in part, to their effect on the mechanisms that regulate apoptosis. This is of fundamental importance in resolving glomerular hypercellularity in the course of glomerulonephritis.

Delayed graft function and chronic allograft nephropathy: diagnostic and prognostic role of neutrophil gelatinase-associated lipocalin

Abstract Context: Available markers are not reliable parameters to early detect kidney injury in transplanted patients. Objective: Examine neutrophil gelatinase associated lipocalin (NGAL) in early detection of delayed graft function (DGF) and as a long-term predictor of graft outcome. Patients and methods: NGAL was evaluated in 124 transplanted patients. Results: Urinary NGAL levels were associated to a 10% (HR: 1.10; 95% CI: 1.04–1.25; p < 0.001) and 15% (HR: 1.15; 95% CI: 1.09–1.26; p < 0.001) increased risk of DGF and allograft nephropathy progression, respectively. Conclusion: NGAL reflects the entity of renal impairment in transplanted patients, representing a biomarker and an independent risk factor for DGF and chronic allograft nephropathy progression.