... membro nella famiglia, o ritardata fino alla comparsa di complicazioni d'organo come ins... more ... membro nella famiglia, o ritardata fino alla comparsa di complicazioni d'organo come insufficienza renale cronica, ipertrofia ven-tricolare sinistra e ... La risposta corretta alle domande sarà disponibile sul sito internet www.sin-italy.org/gin e in questo numero del giornale cartaceo ...
Cyclosporine A (CyA) is probably the most important advance in the immunosuppressive management o... more Cyclosporine A (CyA) is probably the most important advance in the immunosuppressive management of transplants, reducing the incidence of acute rejections without relevant incidence of haematologic and infective complications as observed with “traditional” therapy. This encouraged to evaluate the effectiveness of Cy in the treatment of several immunological diseases. In Nephrology, Cy has been mostly experimented -besides in renal tranplants- in the treatment of nephrotic syndrome secondary to different forms of glomerular diseases, with conflicting results. However, in the last few years many authors have pointed out that Cy can acutely impair renal function by inducing renal vasoconscriction or by reducing Kf (1–4) or both. Since systemic and renal haemodynamics is often impaired in nephrotic patients (NP), the detrimental effect of Cy on GFR could be magnificated in these patients, with dangerous clinical consequences (5).
Extensive studies in humans and in laboratory animals on acute cyclosporine A (CsA) nephrotoxicit... more Extensive studies in humans and in laboratory animals on acute cyclosporine A (CsA) nephrotoxicity have demonstrated that the decrease of GFR induced by CsA is due to a direct, although reversible impairment of renal hemodynamics ([1], [2]). Up to now, however, the pathogenesis of CsA-induced chronic nephrotoxicity has not been completely elucidated, although both hemodynamic and toxic mechanisms are suspected to be involved ([3], [4]). The present study was performed to test the renal hemodynamic effects of short-term therapy with low oral doses of CsA in humans with previously confirmed normal renal function and receiving CsA to treat psoriasis.
First discovered by Berger (1–2), primary IgA nephropathy has been recognized as a distinct glome... more First discovered by Berger (1–2), primary IgA nephropathy has been recognized as a distinct glomerulonephritis and defined as a disease with prominent mesangial IgA deposits in the absence of clinical signs of associated disease.
Experimental studies in rats have demonstrated that CyA causes tubular necrosis only when given a... more Experimental studies in rats have demonstrated that CyA causes tubular necrosis only when given at very high dosage. At a dosage of 20 mg/kg b.w./day proximal tubular changes are subtle and can be detected only by electron microscopy after a week of treatment (1). Some authors have suggested a direct toxic effect of the drug on proximal tubular cells. But the lack of early histopathologic lesions during CyA therapy (2), the increase of fractional proximal tubular reabsorption after acute or short-term administration of the drug (3–6) and the reversibility of renal dysfunction upon discontinuation of CyA (7,8) have supported the hypothesis that acute renal function impairment by CyA is due to reversible changes in renal hemodynamics, a form of “prerenal” failure.
Lupus nephritis is the most important cause of death in patients with systemic lupus erythematous... more Lupus nephritis is the most important cause of death in patients with systemic lupus erythematous (1–4). For this reason, an early biologic and clinic evaluation could be of great prognostic rilevance.
Pregnancy can be a dangerous trigger for patients with paroxysmal nocturnal hemoglobinuria (PNH),... more Pregnancy can be a dangerous trigger for patients with paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), or hemolysis, elevated liver enzymes and low platelet (HELLP) syndrome. Due to the possibility of several serious complications, pregnancy is somewhat discouraged in the presence of the above diseases. Eculizumab is a humanized antibody that may dramatically change the clinical course of PNH, aHUS and HELLP syndrome. However, data on the safety of eculizumab in pregnancy are scarce. In this narrative overview, we summarize current evidence on the use of eculizumab during pregnancy in women with PNH, aHUS and HELLP syndrome. Eculizumab is not present in breast milk, and the levels observed in umbilical cord blood samples are not sufficient to affect the concentrations of complement in newborns. Therefore, eculizumab may be regarded as safe in pregnancy. Nonetheless, given that data on eculizumab in pregnancy are limited, it is not possible to co...
INTRODUCTION: Membranous nephropathy (MN) is known to affect frequently in elderly patients. Sinc... more INTRODUCTION: Membranous nephropathy (MN) is known to affect frequently in elderly patients. Since the duration of MN treatment is likely to be prolonged, it is desirable that the treatment duration would be shortened by the concomitant use of immunosuppressant and prednisolone (PSL). Here, we examined clinical and histological parameters related to the rapid response to the therapy by the retrospective analysis. METHODS: Biopsy-proven 82 cases with MN, hospitalized between April 2009 and December 2017, were enrolled in this study. All cases were divided into three groups, 1st (high responder), 2nd (middle responder) and 3rd (low responder) quantiles, based on the proteinuria-reduction ratio at a month after the beginning of therapy including sole administration of PSL and concomitant use of immunosuppressants such as Cyclosporin or Mizoribine. Cases in 1st and 3rd quantile were comparatively studied. All biopsy specimens were stained by anti-phospholipase A2 receptor (PLA2R) and thrombospondin type 1 domain containing 7A (THSD7A) antibodies by standard protocol. RESULTS: Age of 1st (n=23) and 3rd (n=24) quantile groups were 66.762.16 vs 66.663.11, showing no difference. Estimated glomerular filtration rate (eGFR) and baseline urine protein-to-Cr ratio (PCR) in 1st quantile group were significantly higher than those in 3rd quantile group; eGFR: 72.762.78 vs 59.764.64 ml/min (p = 0.018), baseline PCR: 8.3961.37 vs 5.0961.11 (p = 0.039). There was no difference in intensity of immunofluorescent staining of IgG, A, M, C3 between 1st and 3rd quantile groups. We also studied the difference in immunofluorescent intensity of PLA2R, THSD7A and IgG subclass, however, we could not find out significant difference in the both groups. CONCLUSIONS: Obtained results showed that higher eGFR and baseline PCR might be related to the rapid therapeutical response. Contrary to our expectation, staining intensity of PLA2R, THSD7A and IgG subclass might not be related the rapid response to the therapy.
It is well known that posture affects natriuresis in cirrhosis and heart failure. This study eval... more 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.
The possibility that the renal hemodynamic abnormalities associated with ciclosporin (CS) adminis... more The possibility that the renal hemodynamic abnormalities associated with ciclosporin (CS) administration are enhanced in nephrotic patients (NP), leading to severe impairment of renal function and/or to modifications in proteinuria, has not hitherto been tested. Ten NP and 8 healthy subjects (NC) were examined before and after oral CS administration (10 mg/kg body weight in NP and 12 mg/kg body weight in NC: a lower dosage was adopted in NP because of edema overestimating the actual body weight) under water diuresis by standard renal clearance methods. Basal blood volume was lower in NP. Blood CS levels were not significantly different in the two groups. Basal glomerular filtration rate (GFR) was similar in NP and NC, while renal plasma flow (RPF) was lower in NP. After CS, both GFR and RPF significantly decreased in the two groups, but the percent decrease in inulin clearance was greater in NP. Filtration fraction increased only in NC. Basal renal vascular resistances were greater in NP, and significantly increased after CS in both groups. Basal fractional sodium excretion (FENa) was lower in NP: after CS FENa decreased only in NC. Neither plasma renin activity, nor plasma aldosterone changed after CS. When urinary protein excretion (UP) was corrected by GFR, no change was observed after CS; by contrast, selectivity of proteinuria (as assessed by the CIgG/CTransferrin ratio) markedly increased. Our data indicate that CS induces a greater fall in the GFR in hypovolemic NP than in healthy subjects, probably because in the former GFR becomes extremely plasma flow dependent.(ABSTRACT TRUNCATED AT 250 WORDS)
To define the role of medullary damage and the influence of solute load and blood pressure (BP) i... more To define the role of medullary damage and the influence of solute load and blood pressure (BP) in impairing urinary concentration, patients with chronic glomerulonephritis were investigated by histological and functional studies. In 59 biopsy specimens, the degree of medullary fibrosis was correlated inversely with urinary specific gravity and was significantly greater in hypertensive than in normotensive subjects. The following clearance studies were carried out in patients with a GFR of 15 to 40 ml/min in maximal antidiuresis: (1) Eight patients were studied while receiving a high sodium and protein diet and then after 1 week of low sodium, low protein diet; (2) ten patients were loaded with hypertonic saline (3%) to increase urine volume up to 25 to 30% of GFR; (3) the concentrating ability was compared in 15 normotensives and 15 hypertensives with comparable GFR; (4) the concentrating ability was studied in nine hypertensive patients before and after drug-induced normalization of BP. In (1) no change occurred in maximal urine osmolality (UOsm) even if fractional sodium excretion and filtered load of urea were reduced. In (2), values of UOsm fell below those of plasma osmolality. In (3), UOsm and negative free-water generation were lower in hypertensive than in normotensive subjects. In (4), normalization of BP was not associated with any change in UOsm. These results indicate that osmotic diuresis does not play a critical role in reducing urinary concentration. This defect is better accounted for by an intrinsic medullary damage, enhanced in hypertensive patients, which may impair the permeability of collecting ducts to water.
It is well known that posture affects natriuresis in cirrhosis and heart failure. This study eval... more 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.
suppression up to the maximal degree does not improve the Maximal suppression of renin-angiotensi... more suppression up to the maximal degree does not improve the Maximal suppression of renin-angiotensin system in nonprolifantiproteinuric response and is coupled with a decrement of erative glomerulonephritis.
... membro nella famiglia, o ritardata fino alla comparsa di complicazioni d'organo come ins... more ... membro nella famiglia, o ritardata fino alla comparsa di complicazioni d'organo come insufficienza renale cronica, ipertrofia ven-tricolare sinistra e ... La risposta corretta alle domande sarà disponibile sul sito internet www.sin-italy.org/gin e in questo numero del giornale cartaceo ...
Cyclosporine A (CyA) is probably the most important advance in the immunosuppressive management o... more Cyclosporine A (CyA) is probably the most important advance in the immunosuppressive management of transplants, reducing the incidence of acute rejections without relevant incidence of haematologic and infective complications as observed with “traditional” therapy. This encouraged to evaluate the effectiveness of Cy in the treatment of several immunological diseases. In Nephrology, Cy has been mostly experimented -besides in renal tranplants- in the treatment of nephrotic syndrome secondary to different forms of glomerular diseases, with conflicting results. However, in the last few years many authors have pointed out that Cy can acutely impair renal function by inducing renal vasoconscriction or by reducing Kf (1–4) or both. Since systemic and renal haemodynamics is often impaired in nephrotic patients (NP), the detrimental effect of Cy on GFR could be magnificated in these patients, with dangerous clinical consequences (5).
Extensive studies in humans and in laboratory animals on acute cyclosporine A (CsA) nephrotoxicit... more Extensive studies in humans and in laboratory animals on acute cyclosporine A (CsA) nephrotoxicity have demonstrated that the decrease of GFR induced by CsA is due to a direct, although reversible impairment of renal hemodynamics ([1], [2]). Up to now, however, the pathogenesis of CsA-induced chronic nephrotoxicity has not been completely elucidated, although both hemodynamic and toxic mechanisms are suspected to be involved ([3], [4]). The present study was performed to test the renal hemodynamic effects of short-term therapy with low oral doses of CsA in humans with previously confirmed normal renal function and receiving CsA to treat psoriasis.
First discovered by Berger (1–2), primary IgA nephropathy has been recognized as a distinct glome... more First discovered by Berger (1–2), primary IgA nephropathy has been recognized as a distinct glomerulonephritis and defined as a disease with prominent mesangial IgA deposits in the absence of clinical signs of associated disease.
Experimental studies in rats have demonstrated that CyA causes tubular necrosis only when given a... more Experimental studies in rats have demonstrated that CyA causes tubular necrosis only when given at very high dosage. At a dosage of 20 mg/kg b.w./day proximal tubular changes are subtle and can be detected only by electron microscopy after a week of treatment (1). Some authors have suggested a direct toxic effect of the drug on proximal tubular cells. But the lack of early histopathologic lesions during CyA therapy (2), the increase of fractional proximal tubular reabsorption after acute or short-term administration of the drug (3–6) and the reversibility of renal dysfunction upon discontinuation of CyA (7,8) have supported the hypothesis that acute renal function impairment by CyA is due to reversible changes in renal hemodynamics, a form of “prerenal” failure.
Lupus nephritis is the most important cause of death in patients with systemic lupus erythematous... more Lupus nephritis is the most important cause of death in patients with systemic lupus erythematous (1–4). For this reason, an early biologic and clinic evaluation could be of great prognostic rilevance.
Pregnancy can be a dangerous trigger for patients with paroxysmal nocturnal hemoglobinuria (PNH),... more Pregnancy can be a dangerous trigger for patients with paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), or hemolysis, elevated liver enzymes and low platelet (HELLP) syndrome. Due to the possibility of several serious complications, pregnancy is somewhat discouraged in the presence of the above diseases. Eculizumab is a humanized antibody that may dramatically change the clinical course of PNH, aHUS and HELLP syndrome. However, data on the safety of eculizumab in pregnancy are scarce. In this narrative overview, we summarize current evidence on the use of eculizumab during pregnancy in women with PNH, aHUS and HELLP syndrome. Eculizumab is not present in breast milk, and the levels observed in umbilical cord blood samples are not sufficient to affect the concentrations of complement in newborns. Therefore, eculizumab may be regarded as safe in pregnancy. Nonetheless, given that data on eculizumab in pregnancy are limited, it is not possible to co...
INTRODUCTION: Membranous nephropathy (MN) is known to affect frequently in elderly patients. Sinc... more INTRODUCTION: Membranous nephropathy (MN) is known to affect frequently in elderly patients. Since the duration of MN treatment is likely to be prolonged, it is desirable that the treatment duration would be shortened by the concomitant use of immunosuppressant and prednisolone (PSL). Here, we examined clinical and histological parameters related to the rapid response to the therapy by the retrospective analysis. METHODS: Biopsy-proven 82 cases with MN, hospitalized between April 2009 and December 2017, were enrolled in this study. All cases were divided into three groups, 1st (high responder), 2nd (middle responder) and 3rd (low responder) quantiles, based on the proteinuria-reduction ratio at a month after the beginning of therapy including sole administration of PSL and concomitant use of immunosuppressants such as Cyclosporin or Mizoribine. Cases in 1st and 3rd quantile were comparatively studied. All biopsy specimens were stained by anti-phospholipase A2 receptor (PLA2R) and thrombospondin type 1 domain containing 7A (THSD7A) antibodies by standard protocol. RESULTS: Age of 1st (n=23) and 3rd (n=24) quantile groups were 66.762.16 vs 66.663.11, showing no difference. Estimated glomerular filtration rate (eGFR) and baseline urine protein-to-Cr ratio (PCR) in 1st quantile group were significantly higher than those in 3rd quantile group; eGFR: 72.762.78 vs 59.764.64 ml/min (p = 0.018), baseline PCR: 8.3961.37 vs 5.0961.11 (p = 0.039). There was no difference in intensity of immunofluorescent staining of IgG, A, M, C3 between 1st and 3rd quantile groups. We also studied the difference in immunofluorescent intensity of PLA2R, THSD7A and IgG subclass, however, we could not find out significant difference in the both groups. CONCLUSIONS: Obtained results showed that higher eGFR and baseline PCR might be related to the rapid therapeutical response. Contrary to our expectation, staining intensity of PLA2R, THSD7A and IgG subclass might not be related the rapid response to the therapy.
It is well known that posture affects natriuresis in cirrhosis and heart failure. This study eval... more 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.
The possibility that the renal hemodynamic abnormalities associated with ciclosporin (CS) adminis... more The possibility that the renal hemodynamic abnormalities associated with ciclosporin (CS) administration are enhanced in nephrotic patients (NP), leading to severe impairment of renal function and/or to modifications in proteinuria, has not hitherto been tested. Ten NP and 8 healthy subjects (NC) were examined before and after oral CS administration (10 mg/kg body weight in NP and 12 mg/kg body weight in NC: a lower dosage was adopted in NP because of edema overestimating the actual body weight) under water diuresis by standard renal clearance methods. Basal blood volume was lower in NP. Blood CS levels were not significantly different in the two groups. Basal glomerular filtration rate (GFR) was similar in NP and NC, while renal plasma flow (RPF) was lower in NP. After CS, both GFR and RPF significantly decreased in the two groups, but the percent decrease in inulin clearance was greater in NP. Filtration fraction increased only in NC. Basal renal vascular resistances were greater in NP, and significantly increased after CS in both groups. Basal fractional sodium excretion (FENa) was lower in NP: after CS FENa decreased only in NC. Neither plasma renin activity, nor plasma aldosterone changed after CS. When urinary protein excretion (UP) was corrected by GFR, no change was observed after CS; by contrast, selectivity of proteinuria (as assessed by the CIgG/CTransferrin ratio) markedly increased. Our data indicate that CS induces a greater fall in the GFR in hypovolemic NP than in healthy subjects, probably because in the former GFR becomes extremely plasma flow dependent.(ABSTRACT TRUNCATED AT 250 WORDS)
To define the role of medullary damage and the influence of solute load and blood pressure (BP) i... more To define the role of medullary damage and the influence of solute load and blood pressure (BP) in impairing urinary concentration, patients with chronic glomerulonephritis were investigated by histological and functional studies. In 59 biopsy specimens, the degree of medullary fibrosis was correlated inversely with urinary specific gravity and was significantly greater in hypertensive than in normotensive subjects. The following clearance studies were carried out in patients with a GFR of 15 to 40 ml/min in maximal antidiuresis: (1) Eight patients were studied while receiving a high sodium and protein diet and then after 1 week of low sodium, low protein diet; (2) ten patients were loaded with hypertonic saline (3%) to increase urine volume up to 25 to 30% of GFR; (3) the concentrating ability was compared in 15 normotensives and 15 hypertensives with comparable GFR; (4) the concentrating ability was studied in nine hypertensive patients before and after drug-induced normalization of BP. In (1) no change occurred in maximal urine osmolality (UOsm) even if fractional sodium excretion and filtered load of urea were reduced. In (2), values of UOsm fell below those of plasma osmolality. In (3), UOsm and negative free-water generation were lower in hypertensive than in normotensive subjects. In (4), normalization of BP was not associated with any change in UOsm. These results indicate that osmotic diuresis does not play a critical role in reducing urinary concentration. This defect is better accounted for by an intrinsic medullary damage, enhanced in hypertensive patients, which may impair the permeability of collecting ducts to water.
It is well known that posture affects natriuresis in cirrhosis and heart failure. This study eval... more 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.
suppression up to the maximal degree does not improve the Maximal suppression of renin-angiotensi... more suppression up to the maximal degree does not improve the Maximal suppression of renin-angiotensin system in nonprolifantiproteinuric response and is coupled with a decrement of erative glomerulonephritis.
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