Urinary excretion of metabolizable acid in response to non-metabolizable acid ingestion.
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Biomedical subjects
Publications and source records attributed to G Mioni.
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The aim of this work was to study the effect of early administration of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II type-I receptors blockers (ARB) on renal function and proteinuria in renal transplant recipients with good, stable renal function and mild proteinuria. Twenty four patients started ACEI/ARB therapy within 14 months after surgery (RAS-). Before (T0) and every month for 2 years after the initiation of ACEI/ARB we evaluated creatinine clearance (CrCl), proteinuria/day (UP), UP/CrCl (FUP), arterial blood pressure, and serum lipid levels. Twenty-eight patients who never received ACEI/ARB (RAS+) were studied in the same fashion. In the RAS+ CrCl was reduced after 2 years compared with T0 (64.5 +/- 2.6 vs 75.0 +/- 3.2 mL/min, P < .003); UP and FUP were both significantly increased (666 +/- 65 vs 132 +/- 20 mg/day 8.8 +/- 1.2 vs 2.6 +/- 0.6 mg/mL x 10(3); P < .001 and .002) compared with T0. Moreover, UP (P < .04), FUP (P < .03), and the percentage reduction of CrCl (11.4% +/- 5% vs 4.6% +/- 1.8%; P < .05) were greater in RAS+ than RAS- subjects at 2 years of the study. The values of other parameters did not show significant differences between the two groups. In conclusion, this study suggested that ACEI/ARB have renoprotective effects, when used in patients with good stable renal function and mild proteinuria. These drugs may play a role to prevent chronic allograft nephropathy.
Twenty renal transplant recipients (RTx) with a normal ultrasound pattern of renal artery who began angiotensin-converting enzyme inhibitor (ACEI) therapy within 14 months after surgery (ACEI(+)) were studied retrospectively to evaluate endogenous creatinine clearance/1.73 m(2) body surface area (CrCl), proteinuria (UP), UP/CrCl (FUP), mean arterial pressure (MBP), total cholesterol, LDL, HDL, and triglycerides. Before (T(0)) and every month for 2 years after initiation of ACEI. Twenty-four RTx who never received ACEI (ACEI(-)) were studied in the same fashion. No differences in the parameters were noted at T(0); all RTx had CrCl >60 mL/min, Up less than 0.5 g/d, and stable renal function for 3 months before the study. In the ACEI cohort CrCl was reduced after 2 years compared with T(0) (65.6 +/- 2.8 vs 76 +/- 3.2 mL/min, P <.004), UP and FUP were both increased (660 +/- 60 vs 130 +/- 20 mg/d, 8.9 +/- 1.3 vs 2.8 +/- 0.6 mg/mL x 10(3); P <.001 and.002, respectively). UP >0.5 g/d was present in three cases. After 2 years the ACEI(+) group showed a decrease in CrCl (68.2 +/- 3.1 vs 73 +/- 2.2 mL/min) and the increase in UP (181 +/- 21 vs 139 +/- 18 mg/d) and in FUP (3.1 +/- 0.7 vs 2.6 +/- 0.9 mg/mL x 10(3)), which were not significantly different from the values at T(0). No cases showed UP >0.5 g/d. Moreover UP (P <.04), FUP (P <.03) and the percent reduction of CrCl (11.2 +/- 2.5% vs 4.6 +/- 1.8%, P <.05) were greater among ACEI(-) than ACEI(+) patients at 2 years. ACEI(-) patients showed correlation between the percent reduction of CrCl and UP (r =.51, P <.04). The values of MBP and lipids did not reveal any significant difference between the two groups. In conclusion, this study suggests that ACEI have a renoprotective effect, when used early, and may also prevent chronic allograft nephropathy.
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Acid generation and elimination processes were compared with total base (bicarbonate plus metabolizable anions) turnover in 18 anuric patients undergoing post-dilutional haemofiltration. The study was conducted during the second haemodialysis session of the week by means of a whole-body base balance technique. The results showed that the mean rates of base loss and base gain during dialysis did not differ (i.e. the dialysis base balance approximated to zero). The concurrent mean rate of intestinal base absorption was 66+/-26 mmol/2 days, as calculated from the whole-body balance of the various inorganic cation and anion differences in a metabolic steady state. This level of intestinal base absorption would be capable of neutralizing the 59+/-21 mmol of H(+) ions/2 days that is contributed by sulphuric acid, which is the most important endogenous acid produced in anuric patients. In spite of the fact that intestinal base supply was adequate to neutralize endogenous acid production completely, our patients presented with pre-dialysis non-carbonic acidosis. The depression of plasma bicarbonate levels could not, however, be explained by increased concentrations of the anion gap and organic acids, which were within normal limits both before and after dialysis. We suggest as an alternative hypothesis that this pre-dialysis acidosis may represent an isotonic dilution acidosis that is induced by the ingestion of base-free tap water in order for plasma tonicity to be protected from the accumulation of impermeant dietary solutes, which takes place during the interdialysis period in anuric patients.
BACKGROUND: Increased arachidonic acid content in red blood cell membranes of stone formers (SF) has recently been reported and is hypothesized as representing the underlying causal factor for both hyperoxaluria and hypercalciuria. We performed the present study to see whether we could confirm this finding and to test whether any relationship exists between the fatty acid composition of red blood cell membranes and the main metabolic factors involved in stone formation. METHODS: In 21 SF and 40 healthy controls subjects the fatty acid composition of red blood cell membranes was assessed. In addition, the following parameters were evaluated in SF: daily and fasting urinary calcium excretion, fractional intestinal calcium absorption, 1,25-dihydroxy-vitamin D, intact parathyroid hormone, hydroxyproline in fasting urine, daily urinary excretion of oxalate, citrate, urate, electrolytes, urea, sulphate, relative supersaturation for calcium oxalate monohydrate. RESULTS: The red blood cell membrane of SF had a lower content of arachidonic acid, linoleic acid, and docosahexaenoic acid than that of control subjects. Arachidonic acid content was not correlated with any of the parameters studied. However, when patients were grouped according to the degree of oxalate excretion, hyperoxaluric SF had a higher arachidonic acid content and arachidonic/linoleic acid ratio than SF with normal oxalate excretion. CONCLUSIONS: Our results do not confirm the finding of an increased arachidonic acid content of red blood cell membrane in SF. On the contrary, reduced arachidonic acid levels were found in our patients. However, hyperoxaluric SF had a relatively higher arachidonic acid content than SF with normal urinary oxalate excretion.
SUBJECTS AND METHODS: Eleven patients with postrenal transplant erythrocytosis were treated with angiotensin-converting enzyme inhibitors for 18 months. RESULTS: Indices of red blood cell production and destruction, renal function and kalemia were followed-up during the treatment. Angiotensin-converting enzyme inhibitors (ACEi) led to a progressive and significant fall in hemoglobin and hematocrit compared to the basal values at every time interval considered with a maximum reduction at 12th month for hemoglobin ( 17.04 +/- 0.21 vs. 15.10 +/- 0.42 g/dl, p < 0.0001) and at the 6th month for hematocrit (53.74 +/- 0.56 vs. 45.7 +/- 1.19 %, p < 0.0001). Serum erythropoietin levels were reduced significantly after the first month of therapy (13.56 +/- 2.7 vs. 7.48 +/- 1.6 mUI/dl, p < 0.05) after which no further variations were recorded. In the course of ACEi therapy, there was an inverse correlation between percentage reduction in erythropoietin values and those of hemoglobin emerged (r = 0.24, p < 0.05) and hematocrit (r = 0.39, p < 0.01). Indices of red blood destruction including haptoglobin, bilirubin and lactic dehydrogenase, were unaffected by ACE inhibitors treatment, as was creatininemia and kalemia. Treatment was well tolerated by all patients who completed the study without major adverse side-effects. No patient required phlebotomy and no thromboembolic event occurred during angiotensin-converting enzyme therapy. CONCLUSIONS: Our results suggest that angiotensin-converting enzyme inhibitors are a safe and effective long-term therapy of postrenal transplant erythrocytosis. These agents decrease the erythropoietin synthesis but this effect is not the sole mechanism by which angiotensin-converting enzyme inhibitors act in postrenal renal transplant erythrocytosis.
Acid generation and elimination processes compared to titratable non-metabolizable base (NaOH equivalents, NB) turnover in end-stage renal disease patients are examined in the light of the Law of electroneutrality. The application over 2 days of the whole-body NB balance technique to 18 patients undergoing continuous ambulatory peritoneal dialysis is evaluated. The results show that the mean rate of NB loss with peritoneal effluent (as bicarbonate and organic acid anions) exceeded the mean rate of NB gain with the dialysis fluid (as salts of lactic acid) by 24 (27), m (SD), mmol per 2 days. In spite of this, the bicarbonate and pH of the plasma remained stable and within normal limits. The concurrent mean rate of the intestinal NB absorption was about 61 (27) mmol per 2 days, as calculated from the whole body balances of the several electrolytes in the metabolic steady-state. This intestinal absorption was more than sufficient to restore the body base consumed in neutralizing endogenous acid generation: 37 (14), 2H2SO4 mmol per 2 days, the remaining NB being eliminated as bicarbonate and organic acid anions. The ample spectrum of plasma acid-base (A B) values appears to some extent influenced by patient-related factors, such as the rate of drinking water intake and the set point deviation for organic acid turnover.
BACKGROUND: The persistence of secondary hyperparathyroidism after renal transplantation is frequent and often complicated by overt hypercalcemia. Recent investigations have shown an effect of the different vitamin D receptor (VDR) genotypes on parathyroid hormone (PTH) secretion in both primary and secondary hyperparathyroidism. The aims of this study were (i) to assess whether persistent secondary hyperparathyroidism after renal transplantation is characterized by any change in calcium-controlled PTH secretion, and (ii) whether different VDR allelic distributions might play any role on this setting. METHODS: Eighty-one cadaveric renal transplantation recipients, followed-up for at least 12 months, were checked for PTH, other primary metabolic and clinical variables, and VDR B/b alleles (BsmI). In 22 of these the following parameters were evaluated: (a) kinetics parameters of the Ca-PTH relation curve; (b) vertebral mineral density; (c) calcitriol serum levels; (d) PTH-related peptide serum levels; and (e) urinary hydroxyproline. RESULTS: According to the stabilised PTH levels (reached by the third month), the patients were divided in two groups: group A (N = 40, PTH < 80 pg/ml) and group B (N = 41, PTH > 80 pg/ml). Group B differed from group A in that patients had higher PTH levels at the time of transplantation, were older in age, and spent more time on dialysis. Group B had increased maximal and minimal PTH levels, and higher set-point levels than Group A. The patients with the BB pattern of VDR genotype were characterized by the lowest PTH levels both at time of transplantation and after stabilization, and lower set point values than patients with Bb and bb patterns. CONCLUSIONS: Our study suggests that (i) the severity of pre-existing secondary hyperparathyroidism is the main factor determining its persistence after renal transplantation, (ii) persistent secondary hyperparathyroidism is characterized by an autonomous pattern of PTH secretion, (iii) the VDR BB genotype seems to be related to lower PTH levels.
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1. Dietary calcium restriction, an efficient practice in reducing urinary calcium excretion, has been reported to induce either an increase or no change in oxalate excretion, questioning its use in hypercalciuric stone-forming patients. In addition, calcium restriction has been previously demonstrated to induce other urinary changes which might influence the relative supersaturation of calcium oxalate. So the overall effect of calcium deprivation on the relative supersaturation of calcium oxalate is unpredictable. 2. The aim of the study was to evaluate the effect of dietary calcium restriction on the relative supersaturation of calcium oxalate in the urine of stone-forming patients utilizing a computer methodology which takes into account the main soluble complex species of oxalate. 3. We studied 34 stone-forming patients on both a free-choice diet, whose Ca and oxalate content (24 and 1.2 mmol respectively) was assessed by dietary inquiry, and after 30 days on a prescribed low-calcium and normal oxalate diet (11 and 1.1 mmol respectively). Under both conditions, the excretion of the main urinary parameters related to dietary composition, electrolytes, oxalate and daily citrate urinary excretion, were measured. The relative supersaturation of calcium oxalate was calculated by means of an iterative computer method which takes into account the main soluble complex species on which the solubility of calcium oxalate is dependent. In addition, intact parathyroid hormone and 1,25-dihydroxyvitamin D blood levels were also evaluated. In 13 of the patients intestinal calcium absorption was evaluated during both a free- and a low-calcium diet, utilizing kinetics methodology. 4. The low-calcium diet induced, together with an expected reduction of calcium excretion, a marked increase in oxalate urinary output. This finding was independent of the presence or otherwise of hypercalciuria and of the serum levels of parathyroid hormone and vitamin D. Intestinal calcium absorption was also stimulated by calcium deprivation and its levels were well correlated with oxalate excretion. Minor changes in magnesium and citrate excretion were also observed. The overall effect on the relative supersaturation of calcium oxalate consisted in a substantial increase in this parameter during the low-calcium diet. 5. In conclusion, our data reinforce the concept that dietary calcium restriction has potentially deleterious effects on lithogenesis, by increasing the relative supersaturation of calcium oxalate.
BACKGROUND: Although the methodology for calculating the PTH secretory parameters is well established, a consensus on a common methodology for calculation of the set point value has not yet been achieved. This is probably one of the major reasons for the conflicting results obtained for this secretory parameter. The aim of the present study was to analyse the influence of the different methods of calculation on the values of set point obtained in clinical nephrology practice. METHODS: We analysed 68 PTH-calcium sigmoidal curves, obtained by infusion of 37 mg/kg Na2-EDTA i.v. in 2 h and 8 mg/kg Ca gluconate based on the calcium element i.v. in 2 h on two separate days. The set point was calculated according to three different methods: method A, the originally described method, based on the classical four-parameter model, which considers the set point as the calcium concentration corresponding to the PTH value intermediate between the maximal and minimal values (the midrange value method); method B (set point = calcium concentration corresponding to 50% of maximal PTH), and method C (set point = calcium concentration corresponding to 50% inhibition of basal PTH value). The three different sets of set point values were entered into the formula of the sigmoidal curve to test the best fitting of the PTH experimentally observed values. RESULTS: The set point values calculated with the classical midrange value method were lower than the corresponding values calculated by the other two methods; method C gave the highest values. Furthermore the best fitting of the experimentally observed PTH levels was obtained by method A the worst by method C, while method B gave intermediate results. The difference between method A and method B was analysed in order to see if this difference is constant over the whole range of PTH secretory conditions and calcium concentrations. The higher the basal serum calcium concentrations and the lower the suppressibility of PTH, the greater was the overestimation of set point values by method B compared to the midrange value method. CONCLUSIONS: Method A, the midrange value method, gives the set point values closest to the original concept of the four parameter model. Although method B (50% of maximal PTH) is well correlated with the original method, it overestimates the set point values and most importantly, this overestimation is not constant, but largely affected by calcium concentration and by the secretory conditions of parathyroid glands.
Increased calcitonin (CT) levels have been reported in chronic renal failure, even before the uraemic phase and in the absence of hypercalcaemia. Furthermore, a sigmoidal CT-calcium relationship was recently observed in rats and haemodialysed patients. We carried out the present investigation in order to assess: (a) whether the sigmoidal CT-calcium relationship is also evident in renal patients with a variable degree of renal failure and in normal subjects; (b) whether the four secretory parameters already described for the PTH-calcium relation curve might be described for CT too; (c) whether any change in some, if any, of these secretory parameters could be found at a variable degree of renal insufficiency. We studied 33 renal patients (RP), with a variable degree of renal failure (creatinine clearance ranging from 16 to 164 ml/min), and 10 normal subjects (C). All RP and C were submitted to a basal evaluation including the assessment of (1) basal concentrations of 1,25(OH)2 vitamin D, 25(OH) vitamin D, monomeric CT, intact PTH; (2) GFR by Cr51EDTA clearance. On the 2 subsequent days, a hypocalcaemic test (Na2-EDTA about 37 mg/kg of body-weight/2 h) and a hypercalcaemic test (Ca gluconate giving 8 mg/kg body-weight/2 h of Ca element) were carried out for the assessment of both CT and PTH secretory parameters. According to GFR values, the RP were divided into three groups: group RP1 (GFR > 70 ml/min per 1.73 m2; n = 10), group RP2 (GFR between 30 and 70 ml/min per 1.73 m2; n = 15), group RP3 (GFR < 30 ml/min per 1.73 m2; n = 8). In most, but not all, RP and C a sigmoidal CT-calcium relationship was evident, opposite in direction to the PTH-calcium relation curve. In these RP and C the four secretory parameters, characteristic for the PTH-calcium secretion curve, were calculated for CT too. When pooled RP and C were considered, both minimal (9.0 +/- 6.4 pg/ml) and maximal CT levels (71.8 +/- 56.2 pg/ml) significantly differed from basal levels (24.3 +/- 18 pg/ml; P < 0.001). The CT set point (CT SP) and sensitivity (CT SENS) values were significantly higher and lower than the corresponding PTH secretory parameters (CT SP 1.39 +/- 0.08 mmol/l, PTH SP 1.23 +/- 0.05 mmol/l, P < 0.001) (CT SENS 243 +/- 67%/mmol, PTH SENS 598 +/- 329%, P < 0.001). However, the CT SP values were strictly correlated with PTH SP values (r = 0.78, P < 0.001). When CT secretory parameters were considered separately in the RP groups, increased levels of basal (36.1 +/- 28.6 pg/ml), minimal (17.9 +/- 10.4), and maximal (139.9 +/- 39.7) CT levels were found in the RP3 group, when compared with both the other RP groups and C. No significant difference was found as regards the CT SP and CT SENS values between RP and CT. These results suggest that (1) CT secretion is homeostatically controlled by calcium changes in the same range of the PTH-calcium system; (2) a sigmoidal CT-calcium relationship is demonstrable in most (but not all) RP and C; in these subjects it is possible to calculate the CT secretory parameters as for PTH; (3) the increase in CT levels in the course of chronic renal failure is quite similar to the already known increase of PTH, and is characterized by the increase of basal, minimal and maximal CT values, suggesting that an increased secretion of CT by the thyroid C-cells (rather than CT retention due to a decrease in renal function), is responsible for these findings.
Secondary hyperparathyroidism (SHP) is a well documented finding even in the early stages of chronic renal failure (CRF). A sigmoidal relationship, fitting a four parameter model, links PTH secretion rate and calcium concentration changes. To our knowledge, PTH secretory parameters have only been studied in uremic patients who are in dialysis treatment. As a result of these studies, a possible role for derangement in setpoint values (that is, the serum calcium concentration corresponding to the mid-range value on the sigmoidal curve) has been suggested in the pathogenesis of SHP in CRF. Our study was undertaken to gain insight into the calcium-PTH relationship curve in the first course of CRF and to assess whether a change in any of the secretory parameters is related to the beginning of SHP. We studied 27 male renal patients with a variable degree of renal function (creatinine clearance 12 to 164 ml/min) and 9 control subjects. In all patients and controls the following parameters were evaluated: (1) basal 1,25(OH)2 vitamin D, 25(OH)vitamin D, calcitonin (CT), intact PTH; (2) GFR by Cr51EDTA clearance; (3) the sigmoidal PTH-ionized calcium relation curve, by means of a hypocalcemic stimulating test (Na2-EDTA 37 mg/kg body weight/2 hr) and a hypercalcemic test (Ca gluconate giving 8 mg/kg of body weight/2 hr of Ca element), performed on two consecutive days.(ABSTRACT TRUNCATED AT 250 WORDS)
We describe a case, seemingly sporadic, in which ocular and acral malformations were associated with an interstitial nephropathy; we made a diagnosis of acro-renal-ocular syndrome. There was no stasis, reflux, or urinary tract infection in our patient. We believe that interstitial nephritis in acro-renal-ocular syndrome may not always be pyelonephritis, as previously reported.
Reduced citrate in urine and increased fasting excretion of calcium are abnormalities frequently reported in stone forming (SF) patients. Increased dietary acid (or reduced alkali) introduction or absorption may be a potential cause of both these pathological findings. To test this hypothesis, we studied 64 SF patients (32 with fasting hypercalciuria (FH) and 32 without FH (NFH)). After a basal evaluation for nephrolithiasis, while on a 500 mg calcium diet, they were evaluated for: (1) daily intestinal alkali absorption (IAA), by urinary electrolyte excretion; (2) basal concentrations of PTH, calcitonin (CT) and 1,25(OH)2-VitD; (3) oral calcium load for evaluation of changes in calcium and hydroxyproline urinary excretions; (4) intestinal calcium absorption (18 patients), with double curve analysis (stable Sr as tracer); and (5) changes in citrate excretion after an alkali load (50 mEq of a mixture of calcium gluconate, lactate and carbonate) in 10 patients. The results demonstrated: (1) FH stone formers had reduced citrate excretion and lower mean IAA levels than NFH stone formers; (2) FH stone formers also had higher bone resorption levels with lower PTH and higher CT levels; (3) IAA levels were related to both citrate excretion and bone turnover indices; and (4) the increases in citrate excretion after oral alkali load were strictly related to basal IAA values (index of alkali absorption and/or generation after oral load), demonstrating that a different absorptive capacity of alkali rather than a different dietary content may underlie these metabolic abnormalities.
In order to assess the role, if any, of atrial natriuretic peptide (ANP) and hemodynamic changes in diuretic response to concentrated ascitic fluid reinfusion (CAFR) in cirrhotic patients, we studied 10 patients with liver cirrhosis before and after aspiration, concentration and intravenous reinfusion of their ascitic fluid. Basal ANP levels were higher than in normal subjects, but not related to the degree of water and sodium excretion. CAFR induced a variable degree of ANP changes and diuretic response, and these two parameters were strictly correlated to each other. No major changes of cardiac output and systemic vascular resistances were observed after CAFR. In conclusion, the apparent resistance to ANP diuretic action observed in basal condition in cirrhotic patients seems to revert after expanding blood volume by CAFR.
The authors investigated whether the reduction of arterial pressure, induced by the oral administration of clonidine (CLO), enalapril (EN), and nifedipine (NIF), has any effect on peritoneal transport rates. The study was performed in nine hypertensive patients undergoing continuous ambulatory peritoneal dialysis (CAPD). The patients were submitted to administration of CLO, EN, and NIF, each in randomized succession for two weeks, after withdrawal of any hypotensive therapy for eight days (washout period). The nine patients underwent a four-hour dwell exchange using a 2.27 g/dL glucose two-liter bag after washout and after each hypotensive period. The following parameters were analyzed: mean arterial pressure (MAP), performed in the sitting position; net ultrafiltration; effluent/initial dialysate glucose ratio (GL D/Do); peritoneal clearance of K, BUN, creatinine (Cr), phosphate, beta-2 microglobulin (beta 2), total proteins, and the ratio between beta 2 and Cr clearance. Moreover, residual renal Cr and beta 2 clearances were analyzed. The three drugs significantly reduced MAP at a similar rate. The peritoneal transport parameters after CLO were similar to the results in the washout period. On the contrary, after EN and NIF therapy, Cr and beta 2 clearances were significantly increased, and GL D/Do decreased in comparison to the washout period. The other peritoneal transport parameters after EN and NIF were similar to the washout period. Residual renal Cr and beta 2 clearances after the three drugs were similar to those in the washout. these data suggest that after two weeks of therapy with EN and NIF, glucose, Cr, and beta 2 peritoneal transports are influenced by these hypotensive drugs irrespective of the effect on the arterial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)