Vincenzo Bellizzi

Salt Intake and Renal Outcome in Patients with Progressive Renal Disease

Experimental studies suggest that salt intake plays a critical role in the progressive glomerular filtration rate (GFR) loss of established renal disease; however, this issue has never been addressed in humans. To this aim, we have retrospectively analyzed the clinical data of patients with chronic renal failure (CRF), in whom a low-protein diet was prescribed, over a period of about 3 years. On the basis of the daily urinary sodium output, the patients were divided into two groups: a group of patients constantly ingesting >200 mEq NaCl/day (high sodium intake, HSD, n = 30) and a group in which salt intake was <100 mEq/day (low sodium intake, LSD, n = 27). Patients taking diuretics or ACE inhibitors were excluded. At baseline, the LSD group, as compared to the HSD group, was characterized by significantly lower creatinine clearance (24 ± 2 vs. 28 ± 2 ml/min) and higher proteinuria (2.9 ± 0.3 vs. 1.5 ± 0.2 g/day). Despite the presence of these risk factors for progression, and a similar control of blood pressure (the average of the mean arterial pressure during follow-up was 111 ± 2 mm Hg in LSD and 107 ± 2 mm Hg in HSD), the LSD patients showed a better renal outcome: in this group, as compared to HSD, the GFR decline was lower (0.25 ± 0.07 vs. 0.51 ± 0.09 ml/min/month, p < 0.05), and proteinuria did not change while it markedly increased in HSD. During follow-up, LSD patients also ingested a significantly lower amount of protein. This study therefore suggests that efficacious salt restriction in CRF patients improves the outcome of renal disease independent from its antihypertensive effects.

Early Impairment of Renal Hemodynamic Reserve in Patients With Asymptomatic Heart Failure Is Restored by Angiotensin II Antagonism

BACKGROUND The early/asymptomatic stages of heart failure (HF) are characterized by sodium retention secondary to derangement of sodium reabsorption at the proximal nephron level. Because this phenomenon is reversed by ACE inhibition, abnormalities of renal sodium handling may depend on intrarenal changes of angiotensin II (AII)/nitric oxide (NO) levels. Renal hemodynamic reserve (ie, the glomerular vasodilatory response to amino acid infusion) has been proposed as a reliable test to assess in vivo AII/NO balance. METHODS AND RESULTS In this study, the effects of 6 weeks of treatment with 5 mg/d of enalapril or with 50 mg/d of losartan on systemic hemodynamics and renal function were assessed, at baseline and after amino acid infusion (AA), in patients with mild HF (NYHA class I) and in healthy volunteers. Untreated HF patients showed a basal renal function comparable to that of healthy subjects. After AA, glomerular filtration rate and renal plasma flow significantly increased in healthy subjects (+29.0% and +30.4%, respectively), whereas no vasodilatory response was observed in HF. Although they did not affect basal renal hemodynamics, both enalapril and losartan restored a normal response to AA in HF patients. Blood pressure and heart rate were comparable in HF subjects and healthy subjects at baseline and were not modified by either treatment. Left ventricular ejection fraction was depressed in HF but did not change after either drug. Urinary excretions of cGMP and nitrate (indexes of NO activity in the kidney), comparable in healthy subjects and in HF patients, were unchanged by either enalapril or losartan and did not correlate with renal reserve. CONCLUSIONS (1) Renal functional reserve is absent in patients with early/asymptomatic HF and normal renal function and (2) both enalapril and losartan restore a normal vasodilatory response to AA in these patients without affecting basal systemic and renal hemodynamics. These data suggest a major role of AII in the development of early abnormalities in patients with HF.

Automated enzymatic determination of urinary nitrates in humans

Abstract Urinary nitrate determinations are used to evaluate the in vivo synthesis of nitric oxide, the major endothelial-derived relaxing factor. In the present study, the enzymatic method using the Aspergillus nitrate reductase was applied to an autoanalyzer to determine urinary nitrate in 17 healthy men. This method was fast and required a small amount of biologic sample (7 μL). Linearity of the assay was between 0.062 μmol/mL and 1.00 μmol/mL; accuracy, measured as percentage of nitrate recovered, ranged from 96% to 118%; between-day imprecision, assessed as coefficient of variation, ranged from 3.5% to 4.5%. The mean urinary nitrate concentration was 0.73 ± 0.29 μmol/mL (range, 0.26 to 1.26 μmol/mL). To carefully quantify nitrate production, urinary nitrate excretion rates were also measured. Rates averaged 0.71 ± 0.18 μmol/min (range, 0.44 to 0.98 μmol/min). Nitrate excretion rates were much less variable than nitrate concentrations. Nitrate excretion rates, but not concentrations, differed significantly in smokers (n = 7, 0.54 ± 0.08 μmol/min) and nonsmokers (n = 10, 0.85,± 0.11 μmol/min). In conclusion, (1) the nitrate reductase assay applied to an autoanalyzer is an accurate, fast, and convenient method for the determination of urinary nitrates in humans; (2) urinary nitrate excretion rate is less variable than nitrate concentration; and (3) cigarette smoking is associated with a diminished nitrate excretion rate. Further studies are needed to assess the nitric oxide generation rate in these subjects.

Fetal proteins and chronic treatment with low-dose erythropoietin.

The potential stimulating effect of erythropoietin on the production of fetal proteins (FPs) has not been explored in human subjects. Therefore, the plasma levels of fetal fibrinogen (FF), carcinoembriogenic antigen (CEA), alpha-fetoprotein (AFP), and fetal hemoglobin (HbF) were measured in 12 uremic hemodialyzed patients before the first administration and after 1, 2, and 3 months of low-dose erythropoietin (r-Hu-EPO; 45 U/kg body wt I.V., thrice weekly). Such a treatment efficaciously increased total hemoglobin (Hb). CEA and AFP increased from 5.8 +/- 1.1 ng/ml and 2.9 +/- 0.9 ng/ml to the final value of 43.2 +/- 3.9 ng/ml and 8.7 +/- 1.1 ng/ml, respectively, in the absence of detectable neoplastic diseases. The levels of FF did not change. HbF levels increased from <3% of Hb to the peak value of 48% at the end of the first month; subsequently, a progressive reduction in HbF was observed. Similar changes were detected in the reticulocyte count (RET). A striking correlation was found between HbF and RET (r = 0.8633, p < 0.0001), indicating that the increment in HbF was dependent on the erythroid activity. In conclusion, this study evidences broader than expected effects of erythropoietin on the synthesis of FP and suggests that (1) r-Hu-EPO markedly increases HbF in a condition of suppressed bone marrow activity, (2) the measurement of the cell proliferation markers CEA and AFP is unreliable during r-Hu-EPO therapy, and (3) the prothrombotic state associated with chronic r-Hu-EPO treatment in patients with uremia cannot be attributed to the presence of FF.

Relationship Between Physical Activity and Nutritional Status in Patients on Maintenance Hemodialysis

Gutman and coworkers have recently reported that only 60% of non-diabetic patients on maintenance hemodialysis are capable of physical activity beyond caring for themselves and even fewer are able to work outside home (1). Other common characteristics of dialysis patients which may directly affect rehabilitation are malnutrition and psychic depression.