The plasma levels of homocysteine are elevated in moderate renal insufficiency but do not predict the rate of progression.

BACKGROUND: Chronic renal failure is characterized by specific alterations of the lipoprotein metabolism. It is also characterized by elevated plasma levels of total homocysteine (tHcy). Hyperhomocysteinemia has been shown to be a risk factor for atherosclerosis in both the general population and in patients with end-stage renal disease. AIM: To analyze whether elevated tHcy levels also may contribute to a higher rate of progression of renal insufficiency in patients with moderately advanced renal failure. METHODS: To investigate whether tHcy concentrations are associated with an accelerated rate of progression of renal insufficiency, we have correlated baseline plasma concentrations of tHcy with the progressive decline of renal function in an observational study of human chronic renal disease. RESULTS: Sixty-three nondiabetic patients (49 men, 14 women) were studied as part of an observational study of patients with moderately advanced renal insufficiency. The average follow-up time of the patient population was 3.0 years, and the mean rate of decline in glomerular filtration rate ((51)Cr- EDTA clearance) was -3.2 +/- (SD) 3.9 ml/min x 1.73 m(2) body surface area. The mean plasma concentration of tHcy at the beginning of the study was 28.3 +/- 12.0 micromol/l. Plasma tHcy concentrations correlated significantly with the glomerular filtration rate (r = -0. 32, p < 0.01). However, there was no association between the initial plasma level of tHcy and the rate of progression as assessed by linear regression analysis (r = 0.02; NS). In contrast, increased levels of apolipoprotein B, low-density lipoprotein cholesterol, and proteinuria were all significantly associated with a more rapid decline in renal function. CONCLUSIONS: Patients with moderately advanced chronic renal insufficiency have elevated plasma levels of homocysteine. The tHcy plasma levels increase in parallel with the degree of reduction in renal function. However, the hyperhomocysteinemia is not prospectively associated with a higher rate of progression of the renal functional impairment. Hence, there is no indication that elevated homocysteine levels play a contributing role for an accelerated glomerulosclerotic process.     

Stimulation of erythropoietin in renal insufficiency by hypobaric hypoxia.

Patients with renal anaemia show inadequate levels of immunoreactive erythropoietin (Epo) related to the degree of anaemia. The purpose of our study is to compare the degree of stimulation of Epo by means of hypobaric hypoxia in normal controls and patients with renal anaemia. Baseline Epo concentrations were found to be 11.1 +/- 2.0 U/l in 10 healthy volunteers and 11.4 +/- 4.6 U/l in six patients with renal anaemia. After exposure to hypobaric hypoxia equivalent to 4560 m above sea level for a duration of 3.5 h, we observed a significant increase in serum Epo in healthy volunteers to 22.8 +/- 9.1 U/l (P < 0.005), while there was no increase in patients with renal anaemia: 12.3 +/- 5.2 U/l (P < 0.2). Our results show that in patients with renal anaemia serum Epo concentrations are comparable to those of normal controls, but inadequate in view of the concomitant degree of anaemia. Stimulation by acute hypobaric hypoxia was not possible in patients with renal insufficiency as opposed to normal controls. From these data it can be concluded that either Epo production is working at maximum capacity under baseline conditions, or an additional hybobaric stimulus is not able to influence a disturbed set point of the oxygen sensor regulating Epo synthesis.     

Enhanced external counterpulsation: a new technique to augment renal function in liver cirrhosis.

BACKGROUND: Advanced liver cirrhosis is characterized by cardiovascular changes, such as low arterial blood pressure, peripheral vasodilation and renal vasoconstriction. As a consequence, renal hypoperfusion, impaired diuresis and natriuresis and eventual hepatorenal syndrome may ensue. Previous studies using head-out water immersion to increase central blood volume have demonstrated the functional nature of the renal abnormalities. Enhanced external counterpulsation (EECP) is a new non-invasive cardiac assist device to augment diastolic blood pressure by electrocardiogram-triggered diastolic inflation and deflation of cuffs wrapped around the lower extremities. We investigated whether EECP would improve renal dysfunction of liver cirrhosis. METHODS: Twelve healthy controls and 19 patients with liver cirrhosis were observed during 2 h of baseline followed by 2 h of EECP. The following parameters of renal and cardiovascular function were measured: renal plasma flow by para-aminohippurate clearance, glomerular filtration rate (GFR) by inulin clearance, urine flow rate, urinary excretion rates of sodium and chloride, mean arterial blood pressure (MAP), renal vascular resistance (RVR) and plasma concentrations of renin, atrial natriuretic peptide (ANP), endothelin-1, antidiuretic hormone, epinephrine and N-epinephrine. RESULTS: EECP was well tolerated by healthy controls and cirrhotic patients alike. EECP increased MAP (cirrhotic patients: from 74+/-18 to 88+/-20 mmHg, P<0.01; controls: from 89+/-8 to 94+/-5 mmHg, P = NS) and ANP (cirrhotic patients: from 23+/-18 to 30+/-20 ng/l, P<0.05; controls: from 11+/-4 to 16+/-5 ng/l, P<0.01). The plasma renin concentration decreased (cirrhotic patients: from 98+/-98 to 58+/-57 ng/l, P<0.01; controls: from 4.6+/-1.6 to 3.4+/-1.1 ng/l, P<0.01). This was associated with improvement of the urinary flow rate (cirrhotic patients: from 3.6+/-1.8 to 4.6+/-0.7 ml/min, P<0.05; controls: from 1.8+/-1.5 to 2.8+/-1.9 ml/min, P<0.05), as well as of the sodium and chloride excretion rates in both groups. However, in contrast to healthy controls, GFR and renal plasma flow in cirrhotic patients failed to rise significantly. Renal vascular resistance fell numerically in healthy controls (68+/-5 vs 55+/-4 mmHg . min/l; P = NS). In contrast, RVR showed a significant increase by approximately 20% in cirrhosis (67+/-4 vs 80+/-8 mmHg . min/l; P<0.05). Endothelin-1 levels fell in controls (0.38+/-0.42 vs 0.31+/-0.35; P<0.05), whereas they remained statistically unchanged in cirrhotic patients. Epinephrine, N-epinephrine and vasopressin were not altered by EECP in either group. CONCLUSIONS: EECP is an effective procedure to augment renal excretory function in healthy volunteers as well as in patients with cirrhosis. In healthy volunteers, GFR and renal plasma flow increased during EECP. In contrast, these parameters remained unchanged in the patients and their renal vascular resistance increased during EECP. Therefore, EECP improves diuresis, but does not influence the vasoconstrictive dysregulation of the kidneys in liver cirrhosis.     

Trace elements and lipid peroxidation abnormalities in patients with chronic renal failure

Plasma selenium (Se), zinc (Zn) and copper (Cu) levels and antioxidant metalloenzymes, glutathione peroxidase (GPX) and superoxide dismutase (SOD), were studied in 17 patients on maintenance hemodialysis (HD) (group I), 14 uremic patients (group II) and 14 healthy subjects (group III). Plasma Se levels and erythrocyte GPX were significantly lower in the HD group (for Se: 0.69 +/- 0.12 vs. 1.05 +/- 0.13 mumol/l in controls; for erythrocyte GPX: 34.4 +/- 6.4 vs. 49.2 +/- 9 IU/g hemoglobin in controls) and a significant correlation was found between the two parameters (r = 0.66, p less than 0.005). There was also a correlation between decreased plasma Zn and erythrocyte SOD activity (r = 0.58, p less than 0.02) and between decreased plasma Cu and erythrocyte SOD (r = 0.60, p less than 0.02). Plasma malondialdehyde levels were augmented in HD patients (5.08 +/- 0.26 vs. 2.55 +/- 0.15 mumol/l in controls and 2.79 +/- 0.40 mumol/l in the uremic group). The catalase activity was increased in HD patients (202 +/- 24 vs. 140 +/- 40 IU/mg hemoglobin in group III). A defective antioxidant activity may thus contribute to increased peroxidative damage to cells in the course of dialysis.     

Endogenous digitalis-like factors in hypertension and chronic renal insufficiency

Endogenous digitalis-like factors have been implicated in the adaptations that accompany renal insufficiency and in the pathogenesis of hypertension. We recently described several fractions of normal human plasma that inhibit NaK-ATPase and exhibit apparent digoxin-like immunoreactivity. To determine if hypertension and/or renal insufficiency affect plasma levels of these factors, we examined four patient groups: normotensive controls; hypertensive subjects with normal renal function; hypertensives with moderate renal insufficiency; and chronic dialysis patients. Plasma levels of digoxin-like immunoreactivity and NaK-ATPase inhibitory activity were significantly increased in hypertensive patients with mild renal failure (7.6 +/- 1.1 ouabain equivalents, mean +/- SEM, N = 21 vs 4.1 +/- 1.1 in normotensive controls, N = 20, P less than 0.05). NaK-ATPase inhibitory activity tended to be higher in patients with primary hypertension and normal renal function (5.5 +/- 0.7 ouabain equivalents, P less than 0.07); in dialysis patients, it was not different from controls. There was no correlation between NaK-ATPase inhibitory activity and blood pressure in any group. There was a significant rise in plasma NaK-ATPase inhibitory activity during dialysis (+ 1.8 +/- 0.7 ouabain equivalents, N = 22, P less than 0.03). As we have found that NaK-ATPase inhibitory activity in the plasma of normal humans can be separated into three distinct fractions, EI1, EI2, and EI3, we analyzed the plasma of 10 dialysis patients further. The increase in NaK-ATPase inhibitory activity could be attributed to fractions EI1 and EI3. These results suggest that plasma NaK-ATPase inhibitors increase with chronic renal insufficiency, but not hypertension alone. Although hemodialysis may acutely raise plasma levels, long-term dialysis returns them to the normal range.     

Low dialysance of asymmetric dimethylarginine (ADMA)--in vivo and in vitro evidence of significant protein binding

BACKGROUND: Increased blood levels of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) predict cardiovascular mortality in patients with end-stage renal disease. Despite its low molecular weight, available information on the impact of hemodialysis (HD) on ADMA plasma levels is controversial. METHODS: We assessed plasma concentrations, dialyzer clearance and total amount of ADMA removed in 30 patients with end-stage renal disease during regular HD. In addition, plasma ADMA levels were assessed in 10 patients with acute renal failure treated with extended HD. RESULTS: Regular HD decreased plasma creatinine (from 774 +/- 42 to 312 +/- 17 micromol/l) and urea (from 24.5 +/- 1.5 to 8.4 +/- 0.5 mmol/l) concentrations significantly (both p < 0.001), whereas plasma ADMA remained unchanged (4.35 +/- 0.19 vs. 4.76 +/- 0.24 micromol/l). ADMA clearance was 92 +/- 6 ml/min, and the total amount removed in the spent dialysate was 37 +/- 4 micromol. The clearances of creatinine (161 +/- 3 ml/min) and of urea (173 +/- 3 ml/min) were significantly higher. Furthermore, even during extended HD, plasma ADMA concentrations did not decrease significantly (1.73 +/- 0.22 vs. 1.63 +/- 0.18 micromol/l). CONCLUSION: In conclusion, dialysance of ADMA is markedly lower than expected from its molecular weight because of significant protein binding of the substance. Since markedly increased ADMA blood concentrations have been linked to cardiovascular complications due to atherosclerosis in patients with ESRD, new strategies should be evaluated to remove this putative uremic toxin.     

Plasma levels of advanced glycation end products in children with renal disease

In adults, advanced glycation end products (AGEs) rise slowly in tissues and circulation during aging, and accumulate at an accelerated rate both in diabetes and chronic renal insufficiency (CRI). We aimed to investigate the pattern of AGE accumulation in children/adolescents with CRI and on renal replacement therapy by dialysis and transplantation. Concentrations of fluorescent AGEs, carboxymethyllysine (CML) and lipofuscin-like substance (LFLS, a marker of lipid peroxidation) were followed. Data were obtained from 11 CRI patients on conservative treatment (age 12.6±1.7 years, serum creatinine: 205.7±17.5 μmol/l), ten patients on renal replacement therapy with dialysis (13.6±1.7 years, 698.2±48.9 μmol/l) and nine patients after kidney transplantation (15.9±1.1 years, 115.9±12.0 μmol/l) and comparison made with the data from 28 healthy controls (11.8±8.2 years, 44.1±8.2 μmol/l). In controls, an age-dependent rise of fluorescent AGE and CML levels was observed. In the CRI group, fluorescent AGEs [0.38±0.03×10⁵ arbitrary units (AU)] and CML (369±26 ng/ml) concentrations were doubled compared with controls (0.16±0.03×10⁵ AU and 189±42 ng/ml, respectively) and even higher levels were revealed in dialyzed patients (0.80±0.05×10⁵ AU; 650±94 ng/ml). Successful kidney transplantation significantly reduced but did not normalize fluorescent AGE levels (0.39±0.03 ×10⁵ AU), while the decline in CML levels (550±47 ng/ml) was insignificant. Plasma LFLS was elevated in CRI (19.6± 1.7 AU) and was even higher in dialyzed children (32.0±5.3 AU) compared with healthy controls (7.1± 1.4 AU). Kidney transplantation did not normalize LFLS levels (20.3±5.3 AU), pointing to persistently enhanced lipid peroxidation. Our study provides the first data on enhanced fluorescent AGEs and CML levels in children/adolescents with CRI and on dialysis. Successful renal transplantation decreased but did not normalize AGE levels, probably because of still-impaired renal function with enhanced oxidative stress, as well as the influence of immunosuppressive therapy. Received: 13 July 2000 / Revised: 8 June 2001 / Accepted: 12 July 2001     

A study of xanthopterin in chronic renal failure.

Xanthopterin, a metabolic end product of the nonconjugated pterins dihydrobiopterin and tetrahydrobiopterin, is present in many organs and is known to inhibit the proliferation and growth of conconavalin-stimulated lymphocytes. We have developed a simple fluorometric method to measure xanthopterin in the blood and have validated the method by high pressure liquid chromatography (HPLC). Serum levels were 14 +/- 7 nmol/l in normal subjects and 141 +/- 51 nmol/l in hemodialysis patients (p < 0.02). Intermediate levels from patients with renal insufficiency not on dialysis correlated with serum creatinine levels (p < 0.001). Xanthopterin (MW 179) was cleared by hemodialysis at a slightly lower rate than creatinine. It is bound to protein, but the binding, 90 +/- 5% in normal subjects, is decreased in uremia to 60 +/- 15%, p < 0.01. Red cell levels of xanthopterin were five times higher than those of plasma in normal subjects (69 +/- 15 vs. 14 +/- 7 nmol/l, p < 0.001), but uremic patients had lower levels in red cells than in plasma (101 +/- 24 vs. 141 +/- 51 nmol/l, p < 0.05). Slight or moderate hemolysis induced by mechanical stress increased plasma xanthopterin levels by 35%, the effect being more pronounced when hemolysis was severe. We conclude that xanthopterin is increased and its binding to protein is decreased in chronic renal failure. The altered ratio of red cell/plasma xanthopterin levels may reflect an abnormality of the red cell membrane in uremia. We are conducting further studies to amplify our preliminary findings that xanthopterin inhibits cellular growth in vitro.     

Isolation, characterization, and evaluation of metallothionein in renal transplant patients

The plasma metallothionein concentration was studied in renal transplant patients. These patients are submitted to an attack of free radicals catalyzed by metals such as copper, zinc, cadmium, and others. The function of metallothionein is to bind toxic metals inhibiting the attack of free radicals and oxidative stress that patients receiving renal transplants are submitted to. This is the reason for studying this protein in this work. The metalloprotein was separated from the plasma by thermoprecipitation and molecular exclusion chromatography with Sephadex G-75 followed by anionic-ionic exchange chromatographic purification with a CINa gradient. Identification was done by SDS electrophoresis in acrylamide gel with markers and commercial protein. Finally, determinations were made by atomic absorption, silver saturation method. In this work, determinations were made in the plasma of 11 patients before and 48 h and 1 and 2 weeks after renal transplantation. The same study was carried out in parallel in a control group of 11 blood donors. The results obtained show the existence in the plasma of metallothionein, with lower concentrations in patients than in controls (19 +/- 1.2 mg vs. 12 +/- 1.2 mg). The levels were lowest in the patient group analyzed 48 h after having received the transplant (6.34 mg) and had recovered slightly one and two weeks later.     

Zinc metabolism in patients on maintenance hemodialysis

Recent studies have focused attention on the possible role of zinc depletion in the pathogenesis of uremic symptoms such as dysgeusia and impotence. The present studies were undertaken to evaluate the prevalence of zinc deficiency and abnormalities of zinc metabolism in patients with end-stage renal disease. A total of 43 stable chronic hemodialysis patients were screened for evidence of zinc deficiency by measurement of fasting predialysis leukocyte and plasma zinc. The results were compared with those from 30 healthy volunteers. Seventeen of these 43 patients had 65Zn absorption measured, and in 9 the rate of disappearance of 65Zn from the body was also measured. The results were compared with those obtained in 20 healthy controls. The nutritional status of these 17 patients was estimated by global nutritional assessment and calculation of the Quetelet index while 9 of 17 had dietary zinc intake calculated from a diet history. The mean plasma zinc level was lower in the hemodialysis patients (11.7 +/- 2.3 mumol/l vs. 13.3 +/- 2.9 mumol/l in controls; p less than 0.05). The mean leukocyte zinc level was 0.81 +/- 0.27 mumol/g dry weight in dialysis patients and 0.81 +/- 0.22 mumol/g in controls (p greater than 0.2). The mean 65Zn absorption in the patients was 49 +/- 14% and in controls 53 +/- 12% (p greater than 0.2). Mean turnover of body 65Zn was 0.47 +/- 0.11%/day in patients and 0.43 +/- 0.18%/day in controls (p greater than 0.1). The mean 65Zn half-life was 154 +/- 29 days in patients and 187 +/- 75 days in controls (p greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Sympathetic nervous system overactivity in hypertensive patients with chronic renal failure--role of upright body position.

OBJECTIVE: The renal functional consequences of an activated sympathetic nervous system and plasma atrial natriuretic hormone (ANP) in various renal diseases are not well described. We hypothesize that norepinephrine (NE) and ANP have antagonizing effects on renal hemodynamics in diseased kidneys. MATERIAL AND METHODS: Plasma NE, ANP. glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and mean arterial pressure (MAP) were measured in the upright position in healthy controls (n = 9) and hypertensive patients with reduced GFR (n =11). The same parameters were compared between healthy controls (n = 6) and hypertensive patients with reduced GFR (n = 6) in upright and supine positions. RESULTS: Upright plasma NE and ANP were significantly elevated in the patients compared with the controls (4.4 +/- 0.4 vs 2.1 +/- 0.2 nmol/l (p < 0.001) and 1.3.5 +/- 2.1 vs 6.9 +/- 1.0 nmol/l (p < 0.01) respectively). With change from upright to supine position plasma NE decreased in the controls (2.2 +/- 0.3 vs 1.7 +/- 0.3 nmol/l) (p < 0.01) and patients (3.8 +/- 0.4 vs 2.6 +/- 0.4) (p < 0.01). Supine ANP increased in controls (5.5 +/- 1.0 vs 8.3 +/- 1.1) (p < 0.01) but not in patients (14.3 +/- 3.8 vs 16.1 +/- 3.8 nmol/l) (p > 0.10). Plasma NE correlated positively with MAP (p < 0.001) and negatively with GFR (p < 0.01) in the upright but not supine position. A positive correlation between NE and ANP was observed in upright (p < 0.001) but not in supine position. ANP correlated negatively with GFR in the upright (p < 0.01) but not supine position. No position dependent changes were seen in GFR and ERPF, but supine filtration fraction (FF) increased insignificantly in the patient group (0.23 +/- 0.02 vs 0.24 +/- 0.02) (p < 0.05). CONCLUSION: Hypertensive patients with reduced GFR have elevated levels of plasma NE and ANP in the upright body position. When the upright and supine positions are compared, plasma NE declines in the supine position in controls and hypertensive renal failure patients. and plasma ANP levels are elevated only in the upright position in hypertensive renal failure patients where the sympathetic nervous system is activated. A significant positive relationship between plasma NE and ANP was observed only in the upright position. The upright body position seems superior to recumbency in the characterization of these hormonal changes in hypertensive chronic renal failure patients.     

Effects of cholinergic muscarinic blockade on growth hormone responses to growth hormone-releasing hormone in uraemic patients.

BACKGROUND: Several alterations in growth hormone (GH) secretion have been reported in patients with chronic renal insufficiency. However, cholinergic modulation of somatotopic cell function has not been fully clarified in uraemic patients. To gain further insight into the disrupted mechanism of GH regulation in chronic renal failure, we investigated whether the blockade of cholinergic muscarinic receptor with pirenzepine could modify the response of GH to its physiological releasing hormone. METHODS: Eight uraemic male patients on peritoneal dialysis and six normal controls were studied. All subjects underwent two endocrine tests in random order. In one of them placebo was administered 60 min before the injection of GH-releasing hormone (GHRH, 100 microg, i.v. in bolus at 0 min). In another the muscarinic blocking agent pirenzepine, 100 mg p.o., was administered at that time. Blood samples for GH were collected at -60, 0, 15, 30, 45, 60 and 90 min. RESULTS: Baseline plasma GH concentrations were similar in patients and controls. GH responses to GHRH were characterized by great interindividual variability in uraemic patients with regard to the amount and the time to maximal peak. In the placebo plus GHRH test, the maximum GH concentrations in patients (14.0 +/- 3.2 microg/l) were similar to those reached by controls (18.0 +/- 3.1 microg/l), although GH secretion was more sustained in patients. The area under the secretory curve (AUC) of GH secretion in patients was also similar to that found in controls (14.4 +/- 2.9 vs 15.4 +/- 3.3 microg/h/l). When subjects were given pirenzepine before GHRH injection an abolishment of GHRH-induced GH release was observed in all controls and in all but one of the uraemic patients. The AUC of GH secretion was, therefore, significantly reduced both in uraemic patients (4.1 +/- 2.0 microg/h/l, P<0.05) and in control subjects (2.0 +/- 0.3 microg/h/l, P<0.05). CONCLUSION: These results suggest that GH secretion in uraemic patients is modulated, at least in part, by a cholinergic mechanism. The muscarinic blockade, possibly acting via an increase in somatostatin release, is able to inhibit GH release in response to direct pituitary stimulation with GHRH.     

High-dose calcium carbonate with stepwise reduction in dialysate calcium concentration: effective phosphate control and aluminium avoidance in haemodialysis patients

To reduce potentially toxic aluminium exposure, the phosphate binding agent aluminium hydroxide was replaced by high-dose oral calcium carbonate in 15 haemodialysis patients. Stepwise reduction in dialysate calcium concentration (from 1.75 to 1.35 mmol/l and then to 1.05 mmol/l) was made when necessitated by hypercalcaemia. After 6 months, the mean daily dose of calcium carbonate was 62 mmol (range 25-150 mmol). This dose maintained good control of plasma phosphate (baseline, 1.34 +/- 0.32 mmol/l (mean +/- SD); 12 weeks, 1.30 +/- 0.22 mmol/l; 24 weeks, 1.51 +/- 0.31 mmol/l). Calcium x phosphate product did not rise significantly (baseline, 3.41; 12 weeks, 3.44; 24 weeks, 4.02). Apart from a transient early increase, ionised calcium did not change significantly (baseline, 1.23 +/- 0.10 mmol/l; 12 weeks, 1.24 +/- 0.10 mmol/l). Intact (1-84) parathyroid hormone concentration decreased from 241 pg/ml to 116 pg/ml (median values, P less than 0.05) after 12 weeks. This simple and well-tolerated regimen almost completely eliminated oral aluminium exposure, effectively controlled plasma phosphate and calcium concentrations, and reduced hyperparathyroidism.     

Oxidative stress status in adults with nephrotic syndrome

BACKGROUND: Excessive generation of reactive oxygen species is one of the incriminated mechanisms in the pathogenesis of progressive renal injury. The role of oxidant stress in acute and chronic glomerular diseases has been investigated through experimental and clinical studies. SUBJECTS, MATERIALS AND METHODS: In the present study, oxidative stress status in adult nephrotic patients was studied by determining plasma selenium levels, erythrocyte and plasma glutathione peroxidase (GSH-Px) activities, erythrocyte superoxide dismutase (Cu-Zn-SOD) activity, erythrocyte and plasma levels of malondialdehyde (MDA). RESULTS: Twenty adult nephrotic syndrome patients included into the study had lower activities of erythrocyte (17.17 +/- 2.29 U/gHb) and plasma (153.76 +/- 20.12 U/l) GSH-Px activities when compared the controls ( 27.05 +/- 7.30 U/gHb and 308.89 +/- 55.04 U/l for erythrocyte and plasma GSH-Px activities, respectively). They also had lower erythrocyte Cu-Zn-SOD activity (1896.30 +/-94.31 U/gHb) than that of the controls (2506.17 +/- 461.08 U/gHb). Erythrocyte (483.40 +/- 37.45 nmol/gHb in patients vs 210.35 +/- 55.55 nmol/gHb in controls) and plasma (4.84 +/- 0.65 nmol/ml in patients vs 2.03 +/- 0.41 nmol/ml in controls) levels of MDA were higher in patients. Plasma selenium levels of the patients (48.0 +/- 7.28 ng/ml) were lower than that of the controls (69.25 +/-5.80 ng/ml). CONCLUSION: In conclusion, these results obtained in adult nephrotic syndrome patients support the previous data indicating an abnormality in antioxidative system of nephrotic patients.     

Decreased renal clearance of xanthine and hypoxanthine in a patient with renal hypouricemia: a new defect in renal handling of purines.

Renal handling of urate, xanthine and hypoxanthine was studied in a hypouricemic patient who had increased plasma concentrations of xanthine and hypoxanthine. The patient, a 50-year-old man, had been suffering from Parkinson's disease, while neither systemic disorders nor particular renal diseases known to affect plasma purine levels were found. His serum urate level was 58 +/- 6 mumol/l (healthy controls for males, 310 +/- 48 mumol/l, mean +/- SD) and the renal uric acid clearance was 3 times higher than that of the controls, establishing a diagnosis of renal hypouricemia. Xanthine and hypoxanthine concentrations in the plasma were elevated to 1.3 +/- 0.1 mumol/l (controls, 0.5 +/- 0.3) and 5.9 +/- 3.5 mumol/l (controls, 1.6 +/- 0.4), respectively. Both renal xanthine and hypoxanthine clearance was only half the value of the controls, indicating reduced urinary excretion of xanthine, and hypoxanthine appears to be responsible for their elevation in plasma. A probenecid loading test revealed no response of urinary urate excretion but normal responses of xanthine and hypoxanthine excretion. However, urinary excretion of urate, xanthine or hypoxanthine did not respond at all to pyrazinamide administration. These findings indicate that the patient had a defective renal handling of xanthine and hypoxanthine as well as urate.     

Can low-dosage aluminium hydroxide control the plasma phosphate without bone toxicity?

Sixteen patients treated exclusively by haemodialysis using reverse osmosis water treatment for up to 7 years (mean 49.3 +/- 17 months) were assessed for evidence of bone aluminium accumulation and toxicity. All patients were treated with aluminium hydroxide phosphate binders for the duration of dialysis but the dosage was restricted to a maximum of 2.85 g daily (mean daily dose 2.6 +/- 0.8 g). The mean plasma phosphate over the 12 months prior to the study was 1.68 +/- 0.42 mmol/l and in only three patients was adequate control of the plasma phosphate not achieved. No patient had evidence of fracturing bone disease. Bone aluminium staining was present in only two patients but was seen at the calcification front in only one of these. Three patients had histological evidence of osteomalacia, but in none was aluminium staining present. Mean bone aluminium was moderately high at 36.67 +/- 31 micrograms/g and in only three patients exceeded 40 micrograms/g. This study indicates that adequate control of the plasma phosphate can be achieved with low dosage of aluminium hydroxide, and in the medium term is not associated with evidence of bone aluminium toxicity.     

Plasma level of atrial natriuretic peptide in renal venous blood--marker of kidney ischemia?

In 12 patients with unilateral significant renal ischemia plasma levels of atrial natriuretic peptide (ANP) were estimated in renal vein blood of the ischemic (IK) and contralateral kidney (NK) and in arterial blood under supine and upright conditions. Plasma ANP levels in renal vein blood were compared with plasma renin activity (PRA) of the same blood samples. Plasma ANP levels in renal vein blood of the contralateral kidney (87 +/- 9 pg/ml) were significantly lower than in arterial blood (131 +/- 11 pg/ml) and renal vein blood of the ischemic kidney (139 +/- 16 pg/ml). In contrast plasma ANP concentrations in renal vein blood of the ischemic kidney were slightly or markedly higher than in arterial blood. A positive correlation was found between the ratio of plasma ANP in renal vein blood of the IK to that of the NK under supine condition and the respective ratio of PRA. Data presented in this paper suggest the presence of abnormal handling of ANP by an ischemic kidney and that plasma ANP levels in renal vein blood may be a marker of renal ischemia.     

Detection of urinary polyamine by a new enzymatic differential assay. (III). Studies on urinary polyamines in patients with malignant genitourinary diseases

A new enzymatic method for isolation and determination of urinary polyamines was presented and basically studied in previous report 1 and 2 in comparison with existing techniques. Using the new method, urinary polyamines were isolated and determined in 56 patients with genitourinary cancer. Urinary polyamines were also determined in 63 controls consisting of 20 normal subjects, 25 patients with benign urological disease and 18 patients with BPH. The mean concentrations of Diamine, Spermidine, Spermine in 20 normal subjects were 16.6 +/- 5.8 mumoles/g Cr, 4.7 +/- 2.0 mumoles/g Cr and 0.99 +/- 0.51 mumoles/g Cr respectively. To emphasize the specificity to cancer, the level of positiveness was modified to a higher value than M+3SD. The positive values thus calculated were 40 mumoles/g Cr for Diamine, 15 mumoles/g Cr for Spermidine and 3 mumoles/g Cr for Spermine. The positive ratios of Diamine in patients with early cancer were 43% in renal cell cancer, 20% in pelvic and ureter cancer, 0% in bladder cancer and 20% in prostatic cancer. Those of Spermidine were 29% in renal cell cancer, 0% in pelvic and ureter cancer, 20% in bladder cancer and 40% in prostatic cancer. Those of Spermine were 29% in renal cell cancer, 20% in pelvic and ureter cancer, 20% in bladder cancer and 0% in prostatic cancer. In early diagnoses, Diamine indicated high positive ratios to renal cell cancer and Spermidine to prostatic cancer. Relatively high positive ratios were demonstrated, when any one of the isolated polyamines was found positive: namely, 57% in renal cell cancer, 20% in pelvic and ureter cancer, 30% in bladder cancer and 40% in prostatic cancer.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of two models of hypercalcemia on renal acid base metabolism

The effects of two models of chronic hypercalcemia on renal acid-base metabolism were studied in rats. In the first series of experiments, rats were rendered hyperparathyroid by the autologous grafting of 20 to 24 parathyroid glands into a single recipient. Hypercalcemia (5.48 +/- 0.03 mEq/liter in high PTH animals, 4.96 +/- 0.06 mEq/liter in pair-fed controls, P less than 0.001) occurred as did metabolic alkalosis (plasma total carbon dioxide 25.44 +/- 0.47 mEq/liter vs. 23.84 +/- 0.57 in controls, P less than 0.05). The rise in total carbon dioxide was in part a renal tubular effect since urine pH was lower (6.77 +/- 0.04 vs. 6.95 +/- 0.04, day 5, P less than 0.01) bicarbonaturia less (165 +/- 26 vs. 283 +/- 28 mumoles/24 hr, day 5, P less than 0.01) and titratable acid (TA) excretion increased (164 +/- 43.4 vs. 48.2 +/- 2.53 mEq/24 hr, day 5, P less than 0.01) in hyperparathyroid animals vs. pair-fed controls. To test the specific role of hypercalcemia versus PTH in this effect, normoparathyroid animals were treated with 1.25 (OH)2 vitamin D3 or SHAM injected, Urinary cAMP was reduced in these animals (0.030 +/- 0.004 mumoles/8 hr) compared to hyperparathyroid rats (0.055 +/- 0.01 mumoles/8 hr P less than 0.05) suggesting differences i PTH levels. Hypercalcemia occurred in 1,25(OH)2 vitamin D treated animals as did increased plasma total carbon dioxide and urinary TA while urinary bicarbonate excretion and urinary pH were reduced. Because hypercalcemia was associated with elevated total carbon dioxide in both models, it is proposed that chronic hypercalcemia stimulated renal acid excretion and in a sustained manner results in metabolic alkalosis, at least in part, on a renal basis.