Effects of an oral protein load on glomerular filtration rate in patients with solitary kidneys.
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Biomedical subjects
Publications and source records attributed to L Oldrizzi.
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A clinical study was performed in 2 groups of patients with solitary kidneys, followed for 11-146 months. Group 1 had 9 patients (7 males and 2 females, aged between 23 and 68 years) with unilateral renal agenesis. Group 2 had 13 patients (9 females and 4 males, aged between 27 and 70 years) who underwent unilateral nephrectomy for the following reasons: hydronephrosis secondary to ureteropelvic junction stenosis, 7 patients; renal trauma, 4 patients; benign neoplasia, 2 patients. During the follow up, urinary protein excretion of more than 300 mg/day was observed in 9 patients, 3 in group 1 and 6 in group 2. Eleven patients, 8 in group 1 and 3 in group 2, were hypertensive (diastolic blood pressure higher than 95 mm Hg). Hyperuricemia was observed in 14 patients, 10 in group 1 and 4 in group 2. Seven patients, 4 in group 1 and 3 in group 2, had a significant deterioration of renal function. Neither proteinuria nor renal failure were observed before at least 10 years had elapsed since the anatomic condition of solitary kidney had been established. A surgical renal biopsy was performed in 1 patient with unilateral renal agenesis and showed focal glomerular sclerosis. This study adds support to the view that the reduction of 50% of the renal tissue may be a risky situation in humans as well as in animals.
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Nine patients intolerant to acetate hemodialysis were treated with biofiltration. This consisted in a 4-h acetate hemodialysis during which an additional 2 liters of ultrafiltrate were replaced by a bicarbonate solution (100 mEq/l). Hypotensive episodes disappeared and six out of nine patients were symptom-free during the session. Compared to standard hemodialysis, arterial blood bicarbonate and pO2 did not drop during biofiltration. The anion gap did not change during standard hemodialysis, but was significantly reduced during biofiltration (24.5 +/- 2.9 vs 19.9 +/- 1.4 mEq/l). In our conditions clinical results were positive with biofiltration. On the basis of anion gap changes and preliminary results of plasma acetate determinations, it is suggested that a better cellular metabolism of acetate may be induced by bicarbonate infusion.
It has been shown that renal hemodynamic changes following the decrease in cardiac output (CO) after therapy with beta-blockers may affect glomerular filtration rate (GFR), therefore limiting the effectiveness of these drugs; obviously more serious effects might be expected in nephropathic patients with previously reduced renal function. Recent clinical studies have demonstrated that nadolol, a non-cardioselective beta-blocker, preserves the renal blood flow (RBF) and the GFR. In this study, the drug was administered alone (80 mg once daily) for 2 months to 9 male renal parenchymal hypertensive patients with normal or moderately reduced renal function. Systemic and renal hemodynamics, plasma volume (PV), plasma renin activity (PRA) and urinary aldosterone excretion (UA) were evaluated before and after treatment. As blood pressure (BP) fell so did the cardiac index (4.27 +/- 1.05 l/min/m2 to 3.14 +/- 0.48 p less than 0.01), while the peripheral resistance index (TPRI) rose slightly (2257 +/- 658 to 2459 +/- 498 p = NS). No change in PV, RBF, GFR and renal vascular resistance was observed. An increasing trend in PRA (0.81 +/- 0.56 to 1.27 +/- 0.95 ng/ml/h) and no change in UA were observed. Our data show that nadolol was both well tolerated and effective in lowering BP, that it caused systemic hemodynamic alterations similar to those described for other beta-blockers, and preserved RBF and GFR also in renal hypertensive patients with reduced non-azotemic renal function.
Nine patients with intolerance to acetate hemodialysis were treated with biofiltration. It consisted of a 4 hour acetate hemodialysis during which an additional 2 liters of ultrafiltrate was replaced by a bicarbonate solution (100 mEq/l). Hypotensive episodes disappeared and six out of nine patients were symptomless during the session. Compared to standard hemodialysis, arterial blood bicarbonate and pO2 did not drop during biofiltration. Serum acetate levels, which were abnormally high in patients during standard hemodialysis, were reduced during biofiltration to the levels of a control group of acetate tolerant patients. Our data show that positive clinical results are obtained with biofiltration and suggest that they can be due to a better cellular metabolism of acetate induced by the bicarbonate infusion.
The rate of progression of early renal failure was evaluated in three groups of adult patients with renal disease of diverse etiology on dietary protein and phosphorus restriction (about 0.6 g/kg of protein, 700 mg of phosphorus) and in a control group of 22 patients with the same renal disease, retrospectively studied, on a free diet. Group 1 had 33 patients with chronic glomerulonephritis (CG), initial serum creatinine (Scr) of 1.4 to 4.3 mg/dl (mean, 2.20), followed for 5 to 94 months (mean, 44). Group 2 had 17 patients with polycystic kidney disease (PKD), Scr 1.3 to 4.7 mg/dl (mean, 2.40), followed for 8 to 81 months (mean, 42). Group 3 had 28 patients with primary chronic pyelonephritis (CP), Scr of 1.5 to 4.5 mg/dl (mean, 2.57), followed for 9 to 92 months (mean, 41). The control group had 22 patients (11 with CG, five with PKD, and six with CP), with Scr 1.7 to 4.1 mg/dl, followed for 6 to 72 months (mean, 24). In the regression analysis between reciprocal creatinine and time, the slopes were -0.0017, -0.0025, and -0.00016 dl/mg/month in the three patient groups on a protein-restricted diet, respectively. The difference between both groups 1 and 2 and group 3 was statistically significant (P less than 0.05). The slopes in patients on a free diet were significantly greater than those found in patients on a protein-restricted diet. The actuarial survival probability at 72 months, assuming as "renal death" a Scr of 10 mg/dl, was 45% in patients with CG, 44% in those with PKD, and 67% in those with CP on a protein-restricted diet.(ABSTRACT TRUNCATED AT 250 WORDS)
32 polycystic kidney disease (PKD) patients, 16 with normal 16 with variably decreased renal function, were studied; 12 were normotensive, 20 were hypertensive. Mean arterial pressure (MAP) was 90 +/- 8 mm Hg in the normotensive group and 117 +/- 17 in hypertensive patients; plasma renin activity (PRA) was similar. The glomerular filtration rate (GFR) was lower, but not significantly, in the hypertensive group and plasma volume (PV) was higher in hypertensive patients (normotensive 40.25 +/- 3.47 ml/kg body weight; hypertensive 46.30 +/- 3.54). No correlation was found between MAP, and PRA or GFR but MAP correlated with PV. Cardiac output was higher in hypertensive patients (normotensive 3.48 +/- 0.70 l/min/m2; hypertensive 3.89 +/- 1.47), also total peripheral resistance was higher in the hypertensive group (normotensive 2,035 +/- 503 dyn/s/cm-5/m2; hypertensive 2,577 +/- 808). Cardiac output and PV showed a high degree of correlation, but no correlation was seen between total peripheral resistance and PV, or PRA. The hypertensive patients were divided into two groups: one with hypertension of less than 2 years duration and one with more than 2 years but with similar GFR, PRA, PV and hemodynamic pattern. Our data indicate that hypertension in PKD is volume-dependent; that the increase in PV was not related to the loss of GFR, and that the role of the renin-angiotensin system in maintaining the hypertensive state is not well defined. Hemodynamically hypertension is characterized by high cardiac output and total peripheral resistance independent of the duration of hypertension.
The frequency of renal tubular acidosis was evaluated in 28 adult patients with recurrent calcium nephrolithiasis (19 with 'renal' hypercalciuria, 9 with normocalciuria and no metabolic abnormality) and no evidence of obstruction or infection of the urinary tract. Eight patients with hypercalciuria (42%) had a defective renal reabsorption of bicarbonate, based on a fractional excretion of bicarbonate higher than 7% and a TmHCO3/GFR lower than 2.2 mEq/dl; 2 of them had an associated distal defect of acidification, as judged by a U-B pCO2 lower than 18 mm Hg in maximally alkaline urine. One patient with hypercalciuria had distal tubular acidosis, based on a urine pH higher than 5.3 during acidosis. Only 1 patient with normocalciuria had associated proximal and distal acidification defects. The remaining 8 patients displayed a normal renal acidifying capacity. The bicarbonate wastage was independent of serum PTH levels, vitamin D status and hypercalciuria and was associated with a defective tubular reabsorption of phosphate, increased random urinary pH and more active nephrolithiasis, with a prevalence of mixed calcium oxalate and phosphate stones. Our study shows a high incidence of defective tubular reabsorption of bicarbonate in patients with calcium nephrolithiasis and 'renal' hypercalciuria and suggests that the proximal acidification defect plays a pathogenetic role in promoting calcium nephrolithiasis.
Total body water (TBW), extracellular water (ECW), exchangeable potassium pool (EKP), and alkali-soluble nitrogen in skeletal muscle tissue (N) were determined in 9 CAPD patients on treatment from 5 to 14 months (mean 8.6 months). The parameters were reevaluated in 6 of these patients 5 to 13 months later (mean 8.6 months). The mean value of TBW was normal and directly correlated to body weight (BW), but TBW was abnormally distributed between extracellular and intracellular space. ECW volume was significantly lower than the predicted value (12.1 +/- 1.4 versus 16.8 +/- 1.9 l) and out of proportion to TBW (34.8 +/- 3.9% versus 47.8 +/- 1.5%). The calculated intracellular water, therefore, appeared clearly hyperexpanded. The mean value of EKP was slightly reduced, but in three patients there was a 25% reduction. N content was low in 5 out of 9 patients. When the parameters were re-evaluated BW and TBW were unchanged in two subjects. A third patient showed a simultaneous increase in both BW (12.7%) and TBW (19%). TBW variations (+19%, -23%, -24%) without changes in BW were seen in three patients. The mean value of EKP was unchanged, but there was a 25% reduction in one patient. N content improved in two and worsened in one of the three patients in whom it was determined. The data suggest that cell overhydration was the distinctive feature in our CAPD patients, and that the evolution of the nutritional status was variable, since the patients could remain stable, gain or loose body fat, and probably change their lean body mass.
Total body water (TBW) and extracellular water (ECW) were determined in 9 CAPD patients on treatment from 5 to 14 months (mean 8.6 months). The mean value of TBW was normal and directly correlated to body weight, but TBW was abnormally distributed between extracellular and intracellular space. ECW volume was significantly lower than the predicted value (12.1 +/- 1.4 l versus 16.8 +/- 1.9 l) and out of proportion to TBW (34.8 +/- 3.9% versus 47.8 +/- 1.5%). The calculated ICW, therefore, appeared clearly hyperexpanded. The data suggest that cell overhydration was the distinctive feature in our CAPD patients.
A diet containing about 40 kcal/kg, 0.6 g/kg of protein, 700 mg of phosphorus, and 1,000 to 1,500 mg of calcium (orally supplemented) was prescribed to three groups of patients with chronic renal failure for 6 to 76 months. The mean serum creatinine values were 2.18 mg/dl in group 1 (25 patients), 4.24 mg/dl in group 2 (20 patients), and 6.10 mg/dl in group 3 (8 patients). An additional group of 30 patients (group 4) who had followed no specific dietary treatment for 3 to 72 months was taken as control. The plots of reciprocal serum creatinine against time gave slopes of -0.0008, -0.0010, and -0.0041 in the three groups of patients on the protein-restricted diet, and a slope of -0.020 in the patients on the free diet. The differences between the slopes in patients in groups 1, 2, and 3 versus that in patients in group 4 are statistically significant (analysis of variance and F ratio: P less than 0.01). During the follow-up period a decline in reciprocal serum creatinine greater than the mean values in the whole group was observed in 37.5% of patients in group 3, in 20% of those in group 2, and in only 12% of those in group 1. Thus, the degree of functional renal deterioration is critical in modulating the effects of dietary protein and phosphorus restriction. Several nonimmunologic factors, including hypertension, infection, electrolyte abnormalities, and low-calorie intake, appeared to play an important role in influencing the rate of progression of renal failure in patients on dietary protein restriction.
Three groups of patients with chronic renal failure were studied. Group 1 comprised 25 patients with a mean serum creatinine of 2.18 mg/dl and a mean arterial pressure of 117 mm Hg. Group 2 had 20 patients with a mean serum creatinine of 4.24 mg/dl and a mean arterial pressure of 119 mm Hg. All these patients were kept for 18 to 76 months on a diet containing about 40 kcal/kg, 0.6 g/kg of protein, 700 mg of phosphorus, and 1,000 to 1,500 mg of calcium (orally supplemented). Group 3 comprised 30 patients with a mean serum creatinine of 2.28 mg/dl and a mean arterial pressure of 116 mm Hg. They had followed no specific dietary regimen for 3 to 72 months, and their dietary calorie, protein, phosphorus, and calcium intakes averaged 35 kcal/kg, 70 g, 900 mg, and 800 mg, respectively. The plots of reciprocal creatinine against time gave slopes of -0.0008 and -0.0010 in patients in groups 1 and 2, and a slope of -0.020 in group 3 patients. The slopes of both groups 1 and 2 were statistically different (analysis of variance and "F" test, P less than 0.01) from that of group 3. No evidence of progressive protein and phosphorus depletion was observed in groups 1 and 2 patients. We conclude that a moderate dietary restriction of protein and phosphorus is an acceptable and effective regimen for delaying progression of functional deterioration in early renal failure.
28 adult patients with radiological evidence of medullary sponge kidney (MSK) were studied. Hypercalcemia and increased serum parathyroid hormone (PTH) values were found in 10 patients (36%). In 7 of them, parathyroid surgery was performed: a single adenoma was found in 6 cases and multiple-gland hyperplasia in 1 case. After surgery, 3 patients had normalization of calcium metabolism; 4 patients had persistence of hypercalciuria with progressive increase in serum PTH values (and recurrence of the adenoma in 1 case). Of the remaining patients, 10 (36%) had definite or marginal hypercalciuria, resulting from renal calcium leak in 8 and from intestinal calcium hyperabsorption in 2 of them. In 8 patients (28%), no evidence of disordered calcium metabolism was found. The association of MSK and hyperparathyroidism is not a chance occurrence. MSK might be a renal anatomical complication of primary hyperparathyroidism, or it might be regarded as an anatomic substrate--or rather as a consequence--of prolonged hypercalciuria, regardless of its pathogenesis. The lack of disordered calcium metabolism in a considerable number of patients, however, shows that the enigma of MSK is still far from being solved.
The plasma levels of factor VIII related antigen (FVIIIRA), factor VIII coagulant activity (FVIIIC) and the ratio between them were evaluated in 57 patients with kidney disease of diverse etiology, and with either normal (49) or impaired (8) renal function. Renal biopsy specimens were obtained from 47 patients with normal renal function. No correlation was observed between the increased plasma values of FVIIIRA and FVIIIC and renal function, histologic findings, and the pattern of deposition of immunoglobulin and complement. In contrast, plasma levels of both components of factor VIII were positively correlated with the magnitude of proteinuria. In the authors' opinion, the determination of factor VIII components is of no value in establishing the diagnosis and prognosis of patients with kidney disease. The finding on immunofluorescence of simultaneous deposition of factor VIII and C3 in the arteriolar walls might suggest incipient atherosclerotic damage. The FVIIIRA/FVIIIC ratio was increased in 87% of the patients and particularly in those with membrano-proliferative glomerulonephritis and chronic renal failure; however, the clinical relevance of this finding remains to be elucidated. The significant correlation between the two components suggests that in renal disease a simultaneous aggregation of the two proteins in factor VIII takes place.
The treatment of systemic hypertension in chronic renal disease is now mostly based on the administration of drugs which are able to reduce proteinuria and to slow down the progressive functional deterioration. Angiotensin-converting-enzyme inhibitors (ACEI), which lower both proteinuria and blood pressure, have emerged as drugs of choice in proteinuric patients with either normal renal function or mild to moderate chronic renal failure. In non proteinuric nephropathies no controlled studies exist demonstrating the superiority of ACEI over other drugs. In these conditions calcium antagonists might also be used. The approach to patients with hypertension and renal disease should always take into consideration the quality of the results that are to be achieved. If the aim is to control blood pressure and to protect other organs at risk, then a variety of drugs can be used. If the aim is to reduce proteinuria and slow down progression, then ACEI, possibly associated with calcium antagonists, are the drugs of choice.
The effects of an oral protein load, consisting of 1.5 g/kg body weight as cooked red meat, on: serum creatinine (SCr); glomerular filtration rate (GFR) ([125I]iothalamate clearance); and "renal functional reserve" (test-baseline GFR) (RFR) were evaluated in two groups of patients with solitary kidneys (SK). Group 1 had 7 patients with SCr of 1.00 to 1.40 mg/dl. Group 2 had 7 patients with SCr of 1.40 to 3.00 mg/dl. SCr and GFR were recorded during the 4 hours preceding and the 4 hours following the protein load. SCr rose significantly in both groups after protein load (from 1.16 to 1.19 mg/dl in Group 1, from 1.65 to 1.80 mg/dl in Group 2). GFR changes were: from 114.8 to 195.5 ml/min, from 59.0 to 107.7 ml/min, respectively in the two groups. The RFR was smaller in SK patients with early renal failure (ERF) (Group 2), 48.70 ml/min, than in those with normal renal function (Group 1), 80.77 ml/min. However, despite the smallest RFR, SK patients with ERF had the highest percentage increase in their GFR. In conclusion, in SK patients a hemodynamic adaptation to protein intake is present at different levels of renal function, and further studies are necessary to establish whether protein intake should be monitored in these patients.