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Biomedical subjects

M Andreucci

Publications and source records attributed to M Andreucci.

At least 19 recordsLinked to original sources
PubMed2001

Polycystin-1 interacts with intermediate filaments.

Polycystin-1, the protein defective in a majority of patients with autosomal dominant polycystic kidney disease, is a ubiquitously expressed multi-span transmembrane protein of unknown function. Subcellular localization studies found this protein to be a component of various cell junctional complexes and to be associated with the cytoskeleton, but the specificity and nature of such associations are not known. To identify proteins that interact with the polycystin-1 C-tail (P1CT), this segment was used as bait in a yeast two-hybrid screening of a kidney epithelial cell library. The intermediate filament (IF) protein vimentin was identified as a strong polycystin-1-interacting partner. Cytokeratins K8 and K18 and desmin were also found to interact with P1CT. These interactions were mediated by coiled-coil motifs in polycystin-1 and IF proteins. Vimentin, cytokeratins K8 and K18, and desmin also bound directly to P1CT in GST pull-down and in in vitro filament assembly assays. Two observations confirmed these interactions in vivo: (i) a cell membrane-anchored form of recombinant P1CT decorated the IF network and was found to associate with the cytoskeleton in detergent-solubilized cells and (ii) endogenous polycystin-1 distributed with IF at desmosomal junctions. Polycystin-1 may utilize this association for structural, storage, or signaling functions.

Amino Acid Sequence↗
PubMed2001

Renal hemodynamic response to maximal vasodilating stimulus in healthy older subjects.

BACKGROUND: It is still unclear whether age per se is associated with preservation of renal functional reserve, that is, of the increase in glomerular filtration rate (GFR) induced by appropriate vasodilating stimulus. METHODS: To gain insights into this issue, we evaluated the renal response to a maximal vasodilating stimulus, represented by the combined infusion of mixed amino acid solution (AA) and dopamine at renal dose (D), in 10 young subjects (median age of 30 years, range of 19 to 32) and in 11 subjects of older age (median age of 67 years, range of 65 to 76). Two further age-matched groups of young (N = 15) and older (N = 11) living kidney donors underwent renal needle biopsy immediately before nephrectomy to perform semiquantitative scoring (0 to 3) of arteriosclerosis in intrarenal arteries. All of the study subjects were nonsmokers with healthy status proven by extensive diagnostic evaluation excluding any risk factor of renal dysfunction. RESULTS: Basal renal plasma flow (RPF) and GFR were proportionally lower in older subjects (RPF, 361 +/- 29 vs. 618 +/- 34 mL/min/1.73 m(2), P < 0.001; GFR, 79 +/- 4 vs. 127 +/- 5.8 mL/min/1.73 m(2), P < 0.001). After AA + D, a significant increase of RPF and GFR was observed in both groups, but the older subjects exhibited a smaller percentage increment (RPF, 25.5 +/- 4.8 vs. 42.4 +/- 5.8, P < 0.05; GFR, 19.6 +/- 5.7 vs. + 33.8 +/- 6.4, P < 0.05). Furthermore, the maximal vasodilating stimulus was not able to restore renal hemodynamics in older subjects to the level measured in young controls at baseline. Renal vascular resistances were higher (P < 0.05) in the older subjects both at baseline (0.19 +/- 0.02 vs. 0.09 +/- 0.004 mm Hg/mL/min) and after AA + D (0.14 +/- 0.01 vs. 0.06 +/- 0.004). Light microscopy examination detected the presence of a greater degree of arteriosclerosis at the level of interlobular and arcuate arteries (0.89 +/- 0.15 vs. 0.45 +/- 0.08) and interstitial fibrosis/tubular atrophy (1.18 +/- 0.13 vs. 0.53 +/- 0.13) in older than in young subjects. CONCLUSIONS: Therefore, aging has adverse effects on renal function despite the absence of any risk factor for renal disease, including chronic smoking: (1) GFR and RPF are lower, and (2) the renal response to maximal vasodilating stimulus is impaired. These aging-related alterations of renal hemodynamics are possibly due to organic lesions in renal vasculature.

Adult↗
PubMed2001

Coadministration of losartan and enalapril exerts additive antiproteinuric effect in IgA nephropathy.

Angiotensin-converting enzyme (ACE) inhibitors and AT1-receptor antagonists (ARAs) are widely administered to reduce urinary protein loss and slow the progression of proteinuric nephropathy to end-stage renal failure. Our group recently observed that the combination of ACE inhibitors and ARAs may have an additive antiproteinuric effect, which may occur because ACE inhibitors do not completely reduce angiotensin II (Ang II) production. Ang II is also produced by chymase. Thus, combination therapy better antagonizes the effects of Ang II. The purpose of this study is to ascertain whether the additive antiproteinuric effect of ACE inhibitors plus ARAs is dose dependent and related to the drug-induced reduction in systemic blood pressure. Therefore, enalapril (E; 10 mg/d) and losartan (LOS; 50 mg/d) were randomly administered alone and then in association; initial dosages were doubled when drugs were administered alone and in association. To determine the influence of the drug-dependent effect on reducing blood pressure and the reduction in urinary proteinuria, both ambulatory and office blood pressures were recorded. E and LOS administered alone reduced proteinuria by the same extent; no further reduction was observed when E and LOS alone were administered at a doubled dose. When E and LOS were coadministered, proteinuria decreased by a greater extent compared with E and LOS alone; an additional reduction in proteinuria was observed when combined therapy doses were doubled. The reduction in proteinuria was not correlated with clinical through blood pressure; however, reductions in diastolic and mean ambulatory blood pressures significantly correlated with the decrease in proteinuria, as well as with creatinine clearance. In conclusion, this study shows that combination therapy with E and LOS has an additive dose-dependent antiproteinuric effect that is likely induced by the drug-related reduction in systemic blood pressure. In normotensive proteinuric patients, it is likely that even a small reduction in systemic blood pressure may affect intraglomerular hemodynamics by a great extent because efferent arteriole regulation is hampered more completely by the coadministration of ACE inhibitors and ARAs.

Adult↗
PubMed2001

Sodium retention in preascitic stage of cirrhosis.

Renal Na+ handling abnormalities have been shown in preascitic cirrhosis. To investigate the underlying pathophysiology, the effects of different sodium intakes on Na(+) balance and renal hemodynamics were assessed at 100 mEq Na+/day (low-sodium diet [LSD]) and after 6 days of 250 mEq Na+/day (high-sodium diet [HSD]). Eight asymptomatic patients with cirrhosis (Pugh-Child A class) (PAC) and 10 healthy controls (CON) were studied. At HSD, although CON readjusted Na+ excretion within the fourth day, PAC did not reach the new balance and developed a final greater Na+ retention (+437 mEq in PAC v +228 mEq in CON, P<.001). In PAC, fractional Na+ excretion (FENa) was significantly lower than in CON at LSD (P<.05), and, after HSD, increased in both groups (P<.05). In PAC, renal vascular resistances (RVR) at LSD resulted lower than in CON (P<.05) and failed to decrease after HSD. As a consequence, after HSD, glomerular filtration rate and renal plasma flow failed to increase in PAC. PRA and plasma aldosterone were significantly lower in PAC, than in CON at LSD (P<.05), and decreased in both groups after HSD (P<.05). Proximal Na+ reabsorption (RProx) [as indicated by fractional free water clearance measured in a state of maximal water diuresis] at LSD was lower in PAC than in CON (P<.05) and decreased in both groups after HSD (P<.05). In summary, early stages of cirrhosis are characterized by: (1) a reduction of RVR, probably associated with splanchnic vasodilation; (2) a Na+ retention already at LSD, as indicated by the lower FENa observed in PAC, that produces extracellular volume (ECV) expansion, with a consequent RProx and renin-angiotensin-aldosterone axis (RAS) suppression; (3) a greater Na+ retention after HSD, associated with an abnormal adaptation of renal hemodynamic, a greater ECV expansion and a consequent Rprox and RAS suppression. These data show the presence of early renal hemodynamic dysfunction in PAC. Our findings also show in this phase of the disease a preserved adaptation of RProx and RAS, thus suggesting that the observed tubular Na+ reabsorption derangement is probably related to abnormal ANP behavior.

Aldosterone↗
PubMed2001

Edema and acute renal failure.

Acute renal failure (ARF) with overhydration and edematous state may follow Acute endocapillary proliferative glomerulonephritis and extracapillary glomerulonephritis, because of reduction of the glomerular capillary area available for filtration. But ARF may also be observed in edematous patients with minimal change nephrotic syndrome; it may require dialysis until recovery and is attributable to some of the following factors: (1) ischemic renal injury, (2) hypovolemia, (3) interstitial edema with tubular collapse, (4) redistribution of renal blood flow (RBF) from cortical to juxtaglomerular nephrons, (5) decrease of capillary filtration coefficient (Kf), (6) use of nonsteroidal antiinflammatory drugs. Congestive heart failure also leads to prerenal azotemia and edema formation secondary to salt retention. Multiple organ dysfunction syndrome (MODS) is frequently associated with ARF; but edema occurs even without ARF in septic patients with severe inflammatory response syndrome (SIRS). ARF may follow severe burns; burned patients are frequently edematous because of a rapid leak of fluid from the vascular bed into the wound; edema in undamaged areas occurs in the 'flow phase', because of a fall of oncotic pressure because of massive loss of plasma proteins into the wound. Edema must be treated with diuretics or by dialysis.

Acute Kidney Injury↗
PubMed2000

Current indications for renal biopsy: a questionnaire-based survey.

Indications for renal biopsy are still ill defined. We recently sent a detailed questionnaire to 360 nephrologists in different areas of the world with the aim of providing information on this critical issue by evaluating the replies. The questionnaire was organized in four sections that included questions on renal biopsy indications in patients with normal renal function, renal insufficiency, and a transplanted kidney. In addition, the questions included methods applied to each renal biopsy procedure and to specimen processing. We received 166 replies; North Europe (50 replies), South Europe (47 replies), North America (31 replies), Australia and New Zealand (24 replies), and other countries (14 replies). In patients with normal renal function, primary indications for renal biopsy were microhematuria associated with proteinuria, particularly greater than 1 g/d of protein. In chronic renal insufficiency, kidney dimension was the major parameter considered before renal biopsy, whereas the presence of diabetes or serological abnormalities was not considered critical. In the course of acute renal failure (ARF) of unknown origin, 20% of the respondents would perform renal biopsy in the early stages, 26% after 1 week of nonrecovery, and 40% after 4 weeks. In a transplanted kidney, the majority of nephrologists would perform a renal biopsy in the case of graft failure after surgery, ARF after initial good function, slow progressive deterioration of renal function, and onset of nephrotic proteinuria. The last section provided comprehensive information on the technical aspects of renal biopsy. This survey represents the first attempt to provide a reliable consensus that can be used in developing guidelines on the use of kidney biopsy.

Acute Kidney Injury↗
PubMed2000

Role of different dialysis membranes in the release of interleukin-6-soluble receptor in uremic patients.

BACKGROUND: Interleukin-6 (IL-6) exerts its actions through a cell-surface receptor system that consists of two transmembrane subunits: the IL-6 binding glycoprotein gp 80 (IL-6R) and the signal-transducing component (gp 130). Soluble forms of the IL-6R (sIL-6R) are generated by shedding of the membrane-associated proteins. The sIL-6R binds the ligand IL-6 with comparable affinity as the membrane-associated IL-6R and enhances the actions of IL-6. METHODS: Our aim was to evaluate the role of both uremia and different dialysis membranes on peripheral blood mononuclear cell (PBMC) release (either in absence or in presence of mitogen stimulation) and plasma levels of sIL-6R. Ten patients chronically dialyzed with cuprophan membranes (CU), eight patients on regular dialysis treatment with polymethylmethacrylate (PMMA) membranes, 11 uremic nondialyzed patients (UR), and 12 healthy subjects (CON) were included in the study. RESULTS: PBMCs harvested from CU spontaneously released significantly (P < 0.01) greater amounts of sIL-6R (881.8 +/- 80.1 pg/mL), as compared with CON (267.5 +/- 26.5 pg/mL), UR (258.4 +/- 38.1 pg/mL), and PMMA (288.4 +/- 24.6 pg/mL). Under mitogenic stimulation, the sIL-6R release was significantly (P < 0.01) increased in all groups. The greater PBMC production of sIL-6R in CU was followed by significantly (P < 0.01) higher levels of circulating soluble receptors (48.7 +/- 2.5 ng/mL, 60%), as compared with CON (30.5 +/- 1.9 ng/mL). UR also showed high circulating levels of sIL-6R (53.3 +/- 5.9 ng/mL), probably secondary to an impaired urinary excretion. Circulating levels of sIL-6R in PMMA were comparable to CON (30.3 +/- 3.3 ng/mL). Either the absence of monocyte activation or the adsorption of sIL-6R on the hydrophobic PMMA surface could explain this finding. CONCLUSIONS: These results suggest an important role for poor dialysis biocompatibility of CU on the release of sIL-6R, which increases sIL-6R plasma levels, thereby enhancing the inflammatory effects of IL-6.

Adult↗
PubMed2000

Effect of posture on sodium excretion and diuretic efficacy in nephrotic patients.

It is well known that posture affects natriuresis in cirrhosis and heart failure. This study evaluates the role of posture on spontaneous urinary salt excretion (U(Na)V) and diuretic-induced natriuresis in nephrotic patients with mild renal impairment. U(Na)V and plasma concentrations of the main hormones involved in sodium regulation were evaluated at baseline (Baseline) and after furosemide administration (20 mg intravenously at 8:00 AM [Diuretic]) in seven nephrotic patients with mild renal impairment (creatinine clearance, 68.5 +/- 7.6 mL/min) in either the supine or upright position for 6 hours (from 8:00 AM to 2:00 PM). At baseline, U(Na)V was greater in the supine than upright position (sodium, 51.8 +/- 6.2 versus 38.3 +/- 6.1 mEq/d; P: < 0.01). Similarly, furosemide was more effective in increasing U(Na)V in the supine (sodium, 51.8 +/- 6.2 to 87.4 +/- 9.1 mEq/d; P: < 0.005) than upright position (sodium, 38.3 +/- 6.1 to 59.0 +/- 6.8 mEq/d; P: = not significant). Consequently, body weight decreased in the supine but not the upright position (-0.73 +/- 0.15 versus -0.17 +/- 0.22 kg; P: < 0. 05). Peripheral renin activity (PRA) and plasma aldosterone (Aldo) concentrations were greater in the upright than supine position at both Baseline and Diuretic. A similar pattern was observed for hematocrit, used as an index of plasma volume. In addition, a positive correlation was detected between hematocrit and PRA (r = 0.89; P: < 0.001) in the upright position. Postural changes did not influence plasma concentrations of atrial natriuretic peptide. These data indicate that in nephrotic patients with mild impairment of glomerular filtration rate, the upright position causes a reduction in plasma volume; this hypovolemia activates the renin-Aldo system responsible for sodium retention in unstimulated conditions and a blunted natriuretic response to furosemide.

Aldosterone↗
PubMed2000

Serine-threonine protein kinase Akt does not mediate ischemic tolerance after global ischemia in the gerbil.

The protein kinase Akt/PKB has been implicated in antiapoptosis and neuronal survival. The authors now show that Akt is phosphorylated in the hippocampus during the early reperfusion period after 3.5 minutes bilateral carotid artery occlusion (BCAO) in the gerbil. Repeated sublethal ischemia induces ischemic tolerance, which is known as ischemic preconditioning. Ischemic preconditioning does not affect the amount of Akt protein, but rather decreases the phosphorylation of Akt at Ser-473 after 10 minutes reperfusion after 3.5 minutes BCAO. These results suggest that although Akt may play a role in neuronal survival after ischemia, it may not play a role in ischemic tolerance by preconditioning.

Animals↗
PubMed1999

Additive antiproteinuric effect of converting enzyme inhibitor and losartan in normotensive patients with IgA nephropathy.

We tested the hypothesis that the combination of converting enzyme inhibitor (CEI) with losartan (LOS) produces a more profound antiproteinuric effect than either drug alone in normotensive patients with immunoglobulin A (IgA) nephropathy. Eight normotensive (mean blood pressure, 88.9 +/- 2.1 mm Hg) patients with biopsy-proven IgA nephropathy, nonnephrotic proteinuria (protein, 1 to 3 g/d), and normal or slightly reduced creatinine clearance (range, 69 to 119 mL/min) were studied. Clinical evaluations and laboratory tests were performed (1) before CEI treatment (basal) and after (2) CEI alone (CEI, 12 weeks); (3) the combination of CEI and LOS, the latter at a dosage of 50 mg/d (CEI + LOS, 4 weeks); (4) LOS alone (LOS; 50 mg/d; 12 weeks); (5) the combination of LOS and CEI (LOS + CEI, 4 weeks, at the same dosage as CEI + LOS); and (6) a doubled dose of either CEI alone or LOS alone for 4 weeks. CEI and LOS as monotherapy significantly reduced proteinuria by 38% and 30%, respectively. No further reduction of proteinuria was achieved by doubling the dose of CEI or LOS. Both combinations induced a more remarkable reduction of proteinuria (73%; P < 0.05 v other periods) than either drug administered alone. The antiproteinuric effect of CEI or LOS and the more remarkable effect achieved with both combinations was not dependent on the reduction of blood pressure and/or creatinine clearance. In conclusion, this study provides first-time evidence that the combination of CEI and LOS in normotensive patients with IgA nephropathy produces a more profound decrease in proteinuria than either drug. This additive antiproteinuric effect is not dependent on changes in systemic blood pressure and creatinine clearance. Nevertheless, a larger controlled study is required to confirm this novel observation.

Adult↗
PubMed1999

Randomized, double-blind, placebo-controlled study of arginine supplementation in chronic renal failure.

BACKGROUND: Supplementation with L-arginine (ARG) strikingly ameliorates proteinuria and glomerulosclerosis in remnant rats by overcoming nitric oxide (NO) deficiency. Whether or not the same holds true in humans is unknown. This study aimed at evaluating the effects of ARG on the NO system and renal function in proteinuric patients with moderate chronic renal failure (CRF). METHODS: We measured plasma arginine, urinary and plasma NO3 (an index of NO synthesis), and urinary cGMP (an intracellular mediator of NO), as well as proteinuria and renal functional reserve (RFR) in CRF patients orally treated for six months with either ARG (0.2 g/kg body wt/day, CRF-A group) or the control vehicle (CRF-C). Normal subjects (NOR) were also included for basal comparisons. RESULTS: In CRF patients at baseline, plasma arginine was within the normal range; similarly, the urinary excretion of NO3 was comparable to the NOR value (CRF, 0. 440 +/- 0.02; NOR, 0.537 +/- 0.08 micromol/min, P = NS). The plasma NO3 levels were higher than in NOR (CRF, 74 +/- 6; NOR, 27 +/- 2 micromol/liter, P < 0.001), and consequently the renal clearance of NO3 resulted as being reduced. During the six months of treatment, although a remarkable steadiness of ARG and NO3 levels was detected in the CRF-C group, the CRF-A group was characterized by a marked and immediate increase of plasma ARG. This was associated, however, with a delayed increment in urinary and plasma NO3 levels and no change in urinary cGMP. In CRF-A, as in CRF-C, blood pressure, proteinuria, glomerular filtration rate, and renal plasma flow did not vary. Likewise, RFR, which was reduced at baseline in CRF, did not improve after ARG. CONCLUSIONS: In moderate CRF, the tonic release of NO is constant and, likely, not impaired, and ARG supplementation does not lead to an enhancement of NO activity, thus resulting in no renal effect.

Adolescent↗
PubMed1999

Effects of water hardness on urinary risk factors for kidney stones in patients with idiopathic nephrolithiasis.

Both amount and timing of dietary calcium intake influence the recurrence of renal calcium stones. We have evaluated whether the hardness of extra meal drinking water modifies the risk for calcium stones. The urinary levels of calcium, oxalate and citrate, i.e., the main urinary risk factors for calcium stones, were measured in 18 patients with idiopathic nephrolithiasis, maintained at fixed dietary intake of calcium (800 mg/day), after drinking for 1 week 2 liters per day, between meals, of tap water and at the end of 1 week of the same amount of bottled hard (Ca2+ 255 mg/l) or soft (Ca2+ 22 mg/l, Fiuggi water) water, in a double-blind randomized, crossover fashion. As compared with both tap and soft water, hard water was associated with a significant 50% increase of the urinary calcium concentration in the absence of changes of oxalate excretion; the calcium-citrate index revealed a significant threefold increase during ingestion of hard water as compared with respect to soft water (Fiuggi water), making the latter preferable even when compared with tap water. This study suggests that, in the preventive approach to calcium nephrolithiasis, the extra meal intake of soft water is preferable to hard water, since it is associated with a lower risk for recurrence of calcium stones.

Biomarkers↗
PubMed1999

Hemodialysis-related lymphomononuclear release of interleukin-12 in patients with end-stage renal disease.

Interleukin-12 (IL-12) is a cytokine produced by peripheral blood mononuclear cells (PBMC) that causes interferon-gamma (IFN-gamma) production and enhancement of cell-mediated cytotoxicity. To clarify the role of hemodialysis biocompatibility on IL-12 production and uremic immunodeficiency, we have studied the IL-12 and IFN-gamma release by PBMC harvested from 12 patients dialyzed with cuprophan membrane (CU), eight patients dialyzed with polymethylmethacrylate membrane (PMMA), and eight nondialyzed uremic patients (UR). Ten healthy subjects constituted the control group (CON). PBMC were cultured for 48 h with and without nonspecific mitogen stimulation. In unstimulated conditions, CU showed an IL-12 PBMC production higher than CON, UR, and PMMA (46.67 +/- 30.13 versus 2.56 +/- 1.38, 6.16 +/- 7.09, and 4.62 +/- 4.76 pg/ml, respectively; P < 0.01). IL-12 production was correlated with C3a concentration measured at the outlet of hemodialyzer after 15 min of dialysis (r = 0.69, P < 0.01). IL-12 release in CU remained unchanged under mitogen stimulation (44.34 +/- 23.86 pg/ml) and was lower than in CON, UR, and PMMA (66.0 +/- 12.41, 68.37 +/- 25.78, and 67.75 +/- 22.61 pg/ml, respectively; P < 0.05). IFN-gamma production was similar, in unstimulated conditions, in all groups. Under stimulation, IFN-gamma release was lower in CU (13.42 +/- 12.04 IU/ml) than in CON, UR, and PMMA (51.84 +/- 30.74, 32.16 +/- 13.86, and 32.16 +/- 13.86 IU/ml, respectively; P < 0.01). These results demonstrate that hemodialysis with CU induces monocyte activation with an enhanced release of IL-12. On the contrary, stimulated PBMC production of both IL-12 and IFN-gamma is lower in these patients than in CON, UR, and PMMA. The altered release of these cytokines could play a role in cell-mediated immunodeficiency of the uremic patients dialyzed with CU.

Adult↗
PubMed1998

Gross hematuria of uncommon origin: the nutcracker syndrome.

Left renal vein hypertension, also called "nutcracker phenomenon" or "nutcracker syndrome," is a rare vascular abnormality responsible for gross hematuria. The phenomenon is attributable to the idiopathic decrease in the angle between the aorta and the superior mesenteric artery with consequent compression of the left renal vein. The entrapment of the left renal vein is not easily detectable by ordinary diagnostic procedures. We report two cases of gross hematuria (persistent in one patient and recurrent in the other) caused by "nutcracker phenomenon." In both cases, no remarkable findings were obtained from medical history, urinary red blood cells morphology, repeated urinalysis, pyelography, cystoscopy, or ureteroscopy. Left renal vein dilation in one case was found with a computed tomography (CT) scan performed on the venous tree of left kidney. The diagnosis of "nutcracker phenomenon" was confirmed by renal venography with measurement of pressure gradient between left renal vein and inferior vena cava in both cases. In one case, the diagnosis was complicated by the presence of Mycobacterium tuberculosis in urine. The "nutcracker phenomenon" is probably more common than thought. Early diagnosis is important to avoid unnecessary diagnostic procedures and complications such as the thrombosis of the left renal vein. Many procedures are available to correct the compression of the left renal vein entrapped between the aorta and the superior mesenteric artery: Gortex graft vein interposition, nephropexy, stenting, and kidney autotransplantation. After surgery, gross hematuria ceases in almost all patients.

Adult↗
PubMed1998

The impact of early normalization of haematocrit by erythropoietin on renal damage in the remnant kidney model.

BACKGROUND: Correction of anaemia in moderate to advanced renal failure is still a matter of debate because of postulated detrimental effects of erythropoietin on the progression of renal damage. METHODS: The renal effects of early normalization of haematocrit (Htc) by erythropoietin (rHuEpo) were investigated from the time of 5/6 nephrectomy up to 8 weeks post-intervention in three groups of remnant kidney model rats: untreated controls (CON), rats receiving 100 UI/kg body-wt of rHuEpo i.p. twice a week (EPO), and rats receiving rHuEpo in which periodic phlebotomies maintained Htc similar to the value of the control group (PHL). The latter group was included to evaluate the direct effects of rHuEpo on renal damage, i.e. independent from Htc correction. RESULTS: Two weeks after renal ablation (basal), Htc decreased in CON and PHL rats (from 49.3+/-1.4% to 43.2+/- 1.1, P < 0.05 and from 49.6+/-1.1 to 43.3+/-1.5%, P<0.05 respectively), while it remained consistently normal in EPO rats (48.9+/-1.2% to 48.9+/-1.50/%, P<0.05 vs other groups). Thereafter Htc did not change throughout the remaining period in all groups. At the end of the study, with respect to basal, resting blood pressure increased significantly by the same extent in CON (+ 13+/-2%) and EPO rats (+ 15+/-5%), while it remained constant in PHL rats. Notably, creatinine clearance significantly decreased in CON (-53+/-8% 8 vs basal) and EPO (-38+/-8% vs basal), while it did not change in PHL rats. Likewise the degree of proteinuria as well as renal morphologic alterations and glomerular hypertrophy/sclerosis was similar in CON and EPO rats, and was significantly more severe than in the phlebotomized group. The only difference detected between CON and EPO group was the greater mesangial hypercellularity in rHuEpo-treated rats. CONCLUSION: In uraemic rats, chronic treatment with rHuEpo aimed at normalization of Htc beginning the early stage of renal failure does not inevitably account for a rise in systemic blood pressure. In addition, neither erythropoietin per se nor the correction of haematocrit accelerates the progression of renal damage when blood pressure remains constant.

Animals↗
PubMed1997

Enhancement of nitric oxide synthesis by L-arginine supplementation in renal disease: is it good or bad?

L-Arginine is a important component of our diet characterized by multiple physiological and pharmacological actions. In the last decade, this amino acid has attracted major interest since it has been identified as the natural substrate of nitric oxide, and is now recognized to play a major role in the regulation of vascular tone. This review, while summarizing the knowledge of the renal actions of the L-arginine/nitric oxide pathway in health and renal disease, focuses on the potential therapeutic implications of the increase in nitric oxide synthesis attained by L-arginine supplementation.

Animals↗