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Biomedical subjects

G Coen

Publications and source records attributed to G Coen.

At least 19 recordsLinked to original sources

Diagnosis and outcome of renal function in patients with renal artery stenosis: which role have color Doppler sonography and magnetic resonance angiography?

AIM: Minimally invasive diagnostic techniques would be useful in the preoperative diagnosis of patients with hypertension and ischemic renal disease. The aim of our study was to compare color Doppler sonography (CDS), and magnetic resonance angiography (MRA) with the reference standard, digital subtraction angiography (DSA), in the diagnosis of renal artery stenosis. METHODS: Thirty-nine patients with arterial hypertension and monolateral or bilateral renal artery stenosis documented by CDS underwent renal artery MRA and then DSA during corrective percutaneous transluminal angioplasty. CDS and MRA scans were evaluated by 3 independent observers who studied 78 main renal arteries. Stenosis of 70% or more were regarded as significant. Sensitivity, specificity, positive and negative predictive values and two-sided 95% confidence intervals of CDS and MRA for the detection of significant renal artery stenosis were calculated. The statistical significance of the differences in sensitivities between CDS and MRA was assessed by means of the kappa test (< or =1). RESULTS: CDS and MRA, therefore, both achieved 97.6% sensitivity and 100% specificity for diagnosing stenoses at the origin of the renal artery; CDS yielded 100% sensitivity and 97.1% specificity and MRA 87.5% sensitivity and 98.6% specificity for diagnosing stenosis in the intermediate distal segments. CONCLUSIONS: Statistically significant differences between CDS and MRA in the diagnosis of renal artery stenosis have not been observed. However, according to our experience, CDS is the preferred technique because it also provides useful information about the development of kidney disease before correction.

Aged↗

Cardiac calcifications in hemodialysis patients assessed with spiral computed tomography.

AIM: Cardiac disease is a major cause of mortality in uremic patients. The aim of this paper was to evaluate cardiac calcium content in uremic patients with multislice computed tomography (MSCT). METHODS: The study has been carried out on 120 uremic and 28 nonuremic patients affected by cardiovascular disease. Serum calcium, phosphorus, calcium-phosphate product, intact PTH were assayed. Several lipidic and nutritional parameters were measured. Calcification values obtained with the MSCT were reported in terms of Agatson scores. RESULTS: We found that the average score values in cohort on uremic was 10 times higher than in nonuremic patients (score values 3.389 vs 328). Cardiac calcification score was found to be correlated significantly to age (P=0.006), HD age (P=0.010), serum calcium (P=0.006), iPTH (P=0.004). Multiregression analysis (MRA) with the cardiac score as dependent variable selected the following variables (R(2) 0.612): age (P=0.002), HD age (P=0.010), serum cholesterol (P<0.000), triglycerides (P=0.001) and inversely HDL cholesterol (P=0.001) and non-HDL cholesterol (P=0.001) as predictive variables for cardiac score. By comparing patients with scores lower and higher than 400, the group with score <400 showed a significantly lower age (P=0.0001), HD vintage (P=0.01) and a significantly higher serum cholesterol (P=0.009), HDL cholesterol (P=0.05) and non-HDL cholesterol (P=0.05). CONCLUSIONS: The MSCT could help in identifying and stratifying high-risk patients to implement preventive strategies. The control of mineral metabolism and of lipid levels is important in prevention of arterial calcification in uremic patients.

Calcinosis↗

Cardiac calcium evaluation in hemodialysis patients with multisection spiral computed tomography.

AIM: The aim of this study is cardiac calcium content evaluation in hemodialysis patients by a new technique, based on ultrafast multisection CT (MTC). METHODS: The study was carried out on 30 HD patients, 14 F and 16 M, average age 57.7 +/- 13.9 years, average HD age 57.3 +/- 47.4 months. The intact PTH levels were 625.4 +/- 571 pg/mL. Serum calcium, phosphate and CaxP product were 9.75 +/- 0.84 mg/mL, 6.21 +/- 1.01 mg/dL and 60.2 +/- 10.7 mg2/dL2, respectively. RESULTS: The values obtained with the MTC technique were reported in terms of Agatson scores. Score values frankly in the pathologic range (>100) were found in 24 patients (80%). Correlation analysis has shown positive and significant correlation coefficients of the score with patients' age (p = 0.003), serum calcium (p = 0.012), CaxP (p = 0.015), iPTH (p = 0.049), and borderline, to HD age (p = 0. 06). CONCLUSION: Risk factors for cardiac calcification are mainly age, degree of hyperparathyroidism, increased CaxP and serum calcium levels. A control of calcium phosphate parameters in hemodialysis patients seems to be mandatory to avoid increased severity of coronary artery disease.

Adult↗

Atherosclerotic ischemic renal disease.

AIM: Atherosclerotic ischemic renal disease is a frequent cause of end-stage renal failure leading to dialysis among the elderly; its prevalence is inferred from autopsy or retrospective arteriographic studies. Screening investigation for ischemic nephropathy on large cohorts, based on non invasive diagnostic techniques, have not so far been published. This study has been conducted on 269 subjects over 50 with hypertension and/or chronic renal failure, unrelated to other known causes of renal disease. METHODS: All 269 patients were studied either by color-flow duplex sonography (n=238) or by renal scintigraphy (n=224), and 199 of the 269 patients were evaluated using both of these techniques. Forty patients, found to have renal artery stenosis, were subjected to 3D-contrast enhancement magnetic resonance angiography (MRA) and/or digital selective angiography (DSA). An additional 23 cases, negative both to scintigraphy and to ultrasound study, underwent renal angiography (MRA and/or DSA). RESULTS: Color-duplex sonography, carried out in 238 patients, revealed 49 cases of renal artery stenosis. MR or DSA was carried out in 35 of these 49 patients, and confirmed the diagnosis in 33. Color-duplex sonography was 91.7% sensitive and 90.9% specific, with positive predictive value of 94.2% and negative predictive value of 86.9%. Specificity and sensitivity of renal scintigraphy, carried out in 224 patients, was significantly lower. Patients with renal artery stenosis showed a higher degree of renal insufficiency compared to non stenotic patients while there were no differences in the extent of proteinuria between the two groups. Renal artery stenosis, based on color-duplex sonography studies, was present in 11% of patients in the age group 50-59, 18% in the 60-69 and 23% at age 70 and above. CONCLUSION: A relatively large percentage of the elderly population with renal insufficiency and/or hypertension is affected by renal artery stenosis and is at risk of developing end-stage renal failure. Color-duplex ultrasonography is a valid routine method of investigation of population at risk for renal artery stenosis.

Aged↗

Could an echo contrast agent be helpful in identifying renal artery stenosis?

BACKGROUND: Diagnosis of renal artery stenosis using echo color-Doppler is subjected to several limitations. The aim of this study was to examine if the routine use of a contrast agent could be helpful in identifying renal artery stenosis (RAS). METHODS: We analysed 35 patients affected by RAS using an echo color-Doppler coupled with a contrast agent. All patients presented arterial hypertension, with a good drugs control, and mean serum creatinine of 1.8 mg/dL. All patients previously underwent angiography. RAS was at the origin of the artery in 27 patients, at the intermediate tract in 8. All patients had already been submitted to a basal echo color-Doppler. RESULTS: The contrast agent determined a significant increase in the average colour signal in all the subjects, and a better evaluation of the spectral waveforms, if compared to the basal examination. CONCLUSIONS: The results obtained showed that the contrast agent doesn't improve the diagnosis of RAS, especially in vascular origin stenosis, while it shows a real advantage in the intermediate or distal stenosis which are better visualized.

Adolescent↗

Histomorphometric assessment of bone turnover in uraemic patients: comparison between activation frequency and bone formation rate.

AIMS: The histomorphometric assessment of bone formation rate (BFR/BS) in bone biopsies from uraemic patients is of crucial importance in differentiating low from high turnover types of renal osteodystrophy. However, since BFR/BS relies on osteoblasts, activation frequency (Ac.f), encompassing all remodelling phases, has recently been preferred to BFR/BS. This study was carried out to consider whether estimation of Ac.f is superior, in practical terms, to that of BFR/BS in distinguishing between different rates of bone turnover in uraemic patients. METHODS AND RESULTS: Bone biopsies from 27 patients in predialysis (20 men and seven women; mean age 53 +/- 12 years) and 37 in haemodialysis (22 men and 15 women; mean age 53 +/- 12 years) were examined. The types of renal osteodystrophy were classified on the basis of morphology. Bone formation rate and Ac.f were evaluated according to standardized procedures. The Ac.f was calculated both as a ratio between BFR/BS and wall thickness (W.Th) and as a reciprocal of erosion, formation and quiescent periods (EP, FP and QP). Patients were affected by renal osteodystrophy with predominant hyperparathyroidism (two predialysis and 16 dialysis), predominant osteomalacia (three predialysis and seven dialysis) or that of advanced (nine predialysis and five dialysis) or mild (seven predialysis and four dialysis) mixed type or adynamic type (six predialysis and five dialysis). Activation frequency, which with either formula requires the measurement of W.Th, i.e. the thickness of bone structural units (BSUs), was not calculated in three dialysis patients with severe hyperparathyroidism and in one predialysis and four dialysis patients with severe osteomalacia, because only incomplete BSUs were found. In dialysis, EP was higher in the adynamic than in the other types of osteodystrophy. During both predialysis and dialysis, FP was higher in osteomalacia than in the other forms of osteodystrophy, and in adynamic osteopathy than in hyperparathyroidism or in advanced and mild mixed osteodystrophy. During predialysis and dialysis, QP was higher in the adynamic than in the other forms of osteodystrophy. Correlations were found between BFR/BS and Ac.f, during predialysis (r=0.97) and dialysis (r=0.95). CONCLUSIONS: The superiority of Ac.f in assessing bone turnover, in comparison to BFR/BS, is conceptual rather than practical. The highest values for FP in osteomalacia and for QP in adynamic bone allow a clearer characterization of these low turnover conditions.

Bone Remodeling↗

Parathyroidectomy in chronic renal failure: short- and long-term results on parathyroid function, blood pressure and anemia.

To evaluate the long-term results of parathyroidectomy (PTX) on parathyroid function, blood pressure and anemia, data of 45 patients with secondary Hyperparathyroidism in dialysis who had undergone PTX were collected retrospectively from 8 different dialysis units. The patients, 25 M and 20 F, mean age 56 +/- 11 years, who were followed up for an average period of 3.3 +/- 2.3 years, were divided into four groups according to the surgical procedure: 19 patients had had a subtotal PTX; 10 patients had undergone total PTX with autotransplantation (AT); 10 patients had had total PTX without AT, and 6 patients had undergone partial PTX. Taking a reduction in intact PTH > 50% as sign of successful PTX, only 5 patients did not attain this result. Considering values of PTH between 20 and 200 pg/ml at the mid-term observation (1-2 years) as the optimal result, values under 20 pg/ml as an expression of permanent hypoparathyroidism, and those above 200 pg/ml as indicating persistent/recurrent hyperparathyroidism, 65.5% of patients operated with subtotal PTX and total PTX + AT had a therapeutic success, versus 31.2% of patients in the other two groups, due to excess permanent hypoparathyroidism and persistent/recurrent hyperparathyroidism; 20 of 45 patients with preoperative hypertension experienced a statistically and clinically significant decrease in blood pressure levels. An increase in serum hemoglobin was also observed, despite a reduction of administered erythropoietin. In conclusion, the results of PTX obtained from this multicenter study are comparable to those reported by single leading centers. Recommended surgical procedures are subtotal PTX and total PTX with AT. The fall in blood pressure in hypertensive patients is clinically significant, and improvement in anemia is also observed with a reduction in erythropoietin dosage.

Aged↗

Urinary composition and lithogenic risk in normal subjects following oligomineral versus bicarbonate-alkaline high calcium mineral water intake.

OBJECTIVE: A normal dietary calcium intake to reduce intestinal oxalate absorption is essential to avoid recurrence of calcium oxalate stone formation. It is also important in the prevention of osteopenia in idiopathic hypercalciuria. The calcium content of waters used for hydration may vary from very low to relatively high and is an important factor in prevention or additional risk of stone formation. Therefore, the effect of drinking mineral waters of different calcium concentrations on lithogenic risk factors was studied in normal volunteers. MATERIALS AND METHODS: Normal subjects were divided into two groups of 11 and 10 individuals each. All followed a prescribed diet with an average calcium content of 800 mg/day. The water intake for hydration consisted of 2 liters of an oligomineral water with a low calcium content, <20 mg/l (group A) or of a bicarbonate alkaline water with a high calcium content, 370 mg/l (group B). RESULTS: Diuresis increased similarly in both groups; urine calcium increased by about 80 mg/day in group B. A rise in urine oxalate was observed in both groups, along with the increased urine volume. Osmolar excretion increased in group B; urine osmolality decreased significantly only in group A. In spite of the increase in calciuria in group B, Ca/citrate ratio was constant, due to an increase in citrate excretion. Inter-group differences in terms of activity products of calcium phosphate, calculated according with Tiselius's methods, were found. The differences in AP(CaP) index 1 and AP(CaP) index 2 were significant, with higher values in group B, who drank the bicarbonate alkaline mineral water. CONCLUSIONS: Increased water intake between meals to prevent renal stone recurrence should preferably be achieved with a relatively low calcium water and calcium-rich mineral waters should be avoided.

Adult↗

Changes in bone turnover after parathyroidectomy in dialysis patients: role of calcitriol administration.

BACKGROUND: Available data on changes in serum levels of bone markers after parathyroidectomy (PTx) in dialysis patients are not uniform. Changes are thought to be due to either a reduction in PTH activity per se or to a direct effect of vitamin D therapy on bone cells. We aimed to verify whether treatment with vitamin D modifies serum levels of markers of bone synthesis (alkaline phosphatase (AP), osteocalcin (BGP), procollagen type I C-terminal peptide (PICP)) and resorption (collagen type I C-terminal peptide (ICTP)) within a period of 15 days in haemodialysis patients with severe secondary hyperparathyroidism following PTx. METHODS: We randomized two groups (A, treatment and B, placebo, 10 patients each) with comparable basal PTH values and measured bone markers 3, 7 and 15 days after surgery. All patients were treated with calcium supplements (i.v. and p.o.), and group A also received calcitriol (2.4+/-1.0 microg/day, p.o.). RESULTS: In both groups, PTx induced significant changes in all the markers evaluated, except for BGP in group B. Compared to basal values, ICTP decreased from 481+/-152 ng/ml in group A and 277+/-126 ng/ml in group B to 267+/-94 and 185+/-71 ng/ml (M+/-SD) respectively, and PICP increased from 307+/-139 ng/ml in group A and 309+/-200 ng/ml in group B to 1129+/-725 and 1231+/-1267 ng/ml (M+/-SD) respectively, within 3 days of surgery. AP values increased after 15 days from 1115+/-734 mU/ml in group A and 1419+/-1225 mU/ml in group B to 1917+/-1225 and 1867+/-1295 mU/ml (M+/-SD) respectively. On the contrary, mean values of BGP were never different from basal levels after PTx in either group. In the two groups, the pattern of changes of all the bone markers after PTx was almost identical. Group A patients predictably required lower doses of oral calcium supplements to correct hypocalcaemia (16. 9+/-5.7 vs 22.1+/-5.0 g/10 days; M+/-SD, P<0.04). CONCLUSIONS: The opposite behaviour of serum PICP and ICTP after PTx, in both the treated and untreated groups suggests that quantitative uncoupling between bone synthesis and resorption is responsible for hypocalcaemia. This phenomenon, as reflected by the evaluated bone markers, is unaffected by calcitriol. Based on our data we conclude that immediately after parathyroid surgery, vitamin D therapy does not influence bone cell activity, but improves hypocalcaemia mainly through its known effect on intestinal calcium absorption.

Adult↗

Bone markers in the diagnosis of low turnover osteodystrophy in haemodialysis patients.

BACKGROUND: Renal osteodystrophy includes a number of low and high turnover bone histologic patterns which require a bone biopsy for their full identification. The role of intact PTH and several classical and more recent bone markers in the non-invasive diagnosis of renal bone disease in patients with CRF in HD requires further definition since available published data are limited. METHODS: In addition to intact PTH, alkaline phosphatase (AP) and osteocalcin (BGP), bone alkaline phosphatase isoenzyme (BALP), tartrate resistant acid phosphatase (TRAP), C-terminal cross-linked peptide of collagen type 1 (ICTP) and deoxypyridinoline (DPD) were measured in the serum of 41 patients on haemodialysis, subjected at the same time to transiliac bone biopsy for histomorphometric, histodynamic and aluminium histochemical examination. Histodynamic evaluation following double tetracycline label, was carried out in 37 patients. The patients had no evidence of active cytolytic and cholestatic liver disease and a history of very limited aluminium exposure. RESULTS: The patients had differing degrees of hyper-parathyroidism, with intact PTH ranging from normal to very elevated levels. Serum values of the markers BGP, ICTP and DPD, normally excreted through the kidneys, were on average very high. The correlation coefficients of the humoral parameters vs dynamic variables, such as BFR/BS, were high. The highest values were: intact PTH 0.798, AP 0.900, BALP 0.891, ICTP 0.807. The patients, grouped in low turnover osteodystrophy (LTO; 9), mixed osteodystrophy (MO; 9) and prevalent hyperparathyroidism (HP; 23), showed significant difference in the levels of most humoral and static and dynamic parameters (ANOVA). Bone aluminium histochemistry was negative in all cases. Discrimination of LTO patients from the other groups by humoral parameters, at the highest value of accuracy, showed 100% sensitivity and 93.7% specificity with a cut-off of 12.9 ng/ml for BALP; 88.9% sensitivity and 93.7% specificity with a cut-off of 21.5 ng/ml for DPD, and 88.9% sensitivity and 90.6% specificity with a cut-off of 79.7 pg/ml for intact PTH. The other markers had lower values. A standardized z-score approach for evaluation of all humoral parameters was also carried out. Using all variables, a correct classification of MO/HP and of LTO was possible in 93.8 and 88.9% of the cases, respectively. Predictive power was 96.8 and 80%, respectively for MO/HP and LTO. When the only variables used were intact PTH and BALP, a correct classification of MO/HP and LTO was possible in 90.6% and 88.9%, respectively. Predictive value of MO/HP was 96.7% and for LTO 72.7%. Predictive values using PTH and AP were 96.3% and 57.2%, respectively. CONCLUSION: Intact PTH and several relatively new bone markers are of certain value in the non-invasive diagnosis of renal osteodystrophy. However some of the humoral markers carry the same quality of information and the use of intact PTH and BALP may be adequate in the discrimination of bone histologic patterns. In cases exempt from liver disease, PTH and AP may be used as a less costly alternative. Bone biopsy could be chiefly limited to cases with borderline humoral values and to all those with a suspected aluminium overload.

Adult↗

Ischemic nephropathy in an elderly nephrologic and hypertensive population.

BACKGROUND: Atherosclerotic renovascular disease is a frequent cause of end-stage renal failure leading to dialysis in the elderly population. Its prevalence is known from autopsy or retrospective arteriographic investigations. This prospective study was conducted in 133 subjects with the inclusion criteria of hypertension and/or chronic renal failure starting after 50 years of age. Renal failure was unrelated to other known causes of renal disease. METHODS: The patients were subjected to echo-color doppler ultrasonography of renal arteries (104) and/or to renal scintigraphy (112). Thirteen of 27 patients with positivity using one or both noninvasive techniques were subjected to digital selective angiography. RESULTS: All the patients with positivity of echo-color doppler technique were true positives, with a consequent predictive value reaching 100%. Renal scintigraphy was of markedly lower predictive value. Based on the echo-color doppler investigation, percentage positivity for hemodynamically significant stenosis (> 50%) was 3.2 (16.3% had mild nonsignificant stenosis of renal arteries) in the 50- to 59-year-old group, 20% (plus 12.5% with nonsignificant stenosis) in the 60- to 69-year-old group and 25% (plus 17.8% nonsignificant stenosis) in the > 70-year age group. Patients with significant stenosis also had a significantly higher degree of renal insufficiency and received a higher number of hypotensive drugs (p < 0.013). The percentage of hypertensive patients was not different in the stenotic and nonstenotic groups. CONCLUSIONS: A large percentage of the elderly population is affected by renal vascular obstructive disease and is at risk of developing end-stage renal failure. Considering the wide number of cases with foreseeable renal arterial stenosis in the vast population meeting the selection criteria, it is possible to conclude that not all cases evolve to renal failure due to different rates of progression or to untimely nonrenal death.

Aged↗

Relative roles of intestinal absorption and dialysis-fluid-related exposure in the accumulation of aluminium in haemodialysis patients.

BACKGROUND: A recent retrospective study has clearly demonstrated a reduction of cases with positive bone aluminium (Al) staining in the Italian dialysis population, which in general has had a low prevalence of bone Al toxicity. In the present study we tried to better address the relative role played, in our study population, by enteral and parenteral exposure to Al in reducing bone accumulation. METHODS: We retrospectively examined the data of 105 DFO tests and bone Al determinations performed in dialysis patients from 1984 to 1995. Enternal exposure was analysed by accurate anamnestic records, while parenteral exposure was evaluated by the determination of Al content in dialysis fluids. Bone Al content was assayed chemically and histochemically, while serum Al was assayed spectrophotometrically. Data pertinent to the patients were allotted into three period groups: 1984-1987; 1988-1991; 1992-1995. As for Al concentrations in dialysis fluids, the interval 1980-1983 (immediately before the start of our study), which could clearly have influenced bone Al content, was also considered. RESULTS: Basal serum Al showed some fluctuations (42.7 +/- 34.1; 24.8 +/- 21.9 and 38.9 +/- 34.9 micrograms/l respectively in the three groups, ANOVA P < 0.01) but only values of the period 1988-1991 were significantly lower than those of the period 1984-1987 (P < 0.05). Increments after DFO did not differ in the three periods (136.5 +/- 105.7; vs 98.7 +/- 91.7 and 106.1 +/- 96.2 micrograms/l respectively, P = n.s.). Enteral exposure to drugs containing Al was comparable (4.1 +/- 2.9 vs 4.0 +/- 4.6 and 5.8 +/- 7.9 total kg ingested respectively; P = n.s.), but bone Al was dramatically reduced (from 60.7 +/- 43.0 to 29.0 +/- 24.4 and 31.9 +/- 29.9 mg/kg/dw respectively; P < 0.0001), along with the definite disappearance of Aluminon-positive cases and Al-related bone disease (ARBD) after 1991. Parenteral exposure through the dialysate dropped from a mean of 26 +/- 14 micrograms/l in the 4-year period prior the start of the study (1980-1983) to 9 +/- 6 micrograms/l in the period 1984-1987 and to 4.9 +/- 2.1 micrograms/l and 5.0 +/- 2.0 micrograms/l respectively thereafter (P < 0.0001). CONCLUSIONS: Despite the persistence of oral exposure to Al, responsible for the observed stability of serum Al levels, a definite reduction of bone Al content has been recorded in our dialysis population, and ARBD has disappeared. This result has to be referred essentially to the optimal control of Al content in dialysis fluids, which is confirmed as a major factor for Al intoxication.

Adult↗

Fracturing osteoporosis after kidney transplantation--what are the options?

The patient who receives a renal graft does not have virgin bones. Renal transplantation must be performed in a patient with pre-existing bone disease, i.e. renal osteodystrophy, characterized by secondary hyperparathyroidism, calcitriol deficiency, phosphate retention, metabolic acidosis and possibly aluminium accumulation. These pathomechanisms are further modulated by factors such as duration of dialysis, type of dialysis, diet, control of serum phosphate, use phosphate-binding agents etc.

Animals↗

Renal bone disease in 76 patients with varying degrees of predialysis chronic renal failure: a cross-sectional study.

BACKGROUND: Renal osteodystrophy has been studied less extensively in predialysis than in dialysis patients. Different types or histological patterns in their natural evolution from moderate to advanced severity of renal insufficiency are only partially known, with special regard to adynamic bone disease and its relationship with osteomalacia. METHODS: We conducted a cross-sectional retrospective study on 76 unselected patients with chronic renal failure undergoing conservative treatment, with a wide range of severity of renal insufficiency. All the patients were subjected to bone biopsy for histological and histomorphometric evaluation. The patients, 44 males and 32 females ranging in age from 18 to 72 years and with serum creatinine 1.2-11.4 mg/dl, had not been exposed to aluminium-containing drugs and had never been treated with vitamin D or calcitriol. RESULTS: Ten patients had normal bone, nine were diagnosed with adynamic bone disease, 26 with mild mixed osteodystrophy, seven with predominant osteomalacia, 22 with advance mixed osteodystrophy, and two with predominant hyperparathyroidism. Patients with adynamic bone disease had less severe chronic renal failure than the other pathological subgroups, intact PTH above the upper limit of normal, normocalcaemia, and reduced serum osteocalcin in line with a significantly lower ObS/BS. Osteomalacia was found in a more advanced stage of chronic renal failure with relative hypocalcaemia and more severe metabolic acidosis. A creatinine clearance of 20 ml/min served as a clear demarcation between this histological group and adynamic bone disease. CONCLUSIONS: It is postulated that adynamic bone disease is a form of renal osteodystrophy, separate from osteomalacia, appearing when bone resistance to PTH develops, probably a transient stage to more hyperparathyroid histological classes with increasing severity of chronic renal failure.

Adolescent↗

Extent of alkaline phosphatase cytochemistry vs. extent of tetracycline fluorescence in the evaluation of histodynamic variables of bone formation.

Alkaline phosphatase (ALP) activity is a new histomorphometric index of the extent of osteoblastic surfaces involved in mineralization. To assess its validity in the evaluation of bone formation, we carried out a comparative study between histomorphometric values obtained on the basis of the extent of tetracycline labeling and of the length of ALP-positive endosteal surfaces. The following variables were compared (indicated by ALP when based on the extent of ALP positivity): trabecular mineralizing surface (MS/BS vs. ALP.S/BS); osteoid mineralizing surface (MS/OS vs. ALP.S/OS); bone formation rate (BFR/BS vs. ALP.BFR/BS); and adjusted appositional rate (Aj.AR vs. ALP.Aj.AR). Bone biopsies from 39 patients with chronic renal failure and different types of renal osteodystrophy were considered (48 +/- 12 years of age; 19 men and 20 women). Patients were double labeled with tetracycline and biopsies were embedded in glycol-methacrylate at +4 degrees C. Patients showed various types of renal osteodystrophy and were assigned to different groups of pathologies. Although it differed in incidence according to the different groups, ALP activity was found in typical plump osteoblasts bordering osteoid seams and in flat cells, either in contact with osteoid or along the quiescent surfaces of bone in continuity with it. Tetracycline codistributed with all these features to variable extents, according to groups. In all patients, however, ALP.S/BS and ALP.S/OS respectively exceeded MS/BS and MS/OS. In consequence of this, ALP.BFR/BS and ALP.Aj.AR were greater than BFR/BS and Aj.AR, respectively. For each of the variable considered, differences among groups of patients with different types of renal osteodystrophy were highly significant. Good correlations were found between the variables measured with the two methods.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Metabolic acidosis and osteodystrophic bone disease in predialysis chronic renal failure: effect of calcitriol treatment.

The role of metabolic acidosis on osteodystrophic bone lesions of chronic renal failure has been studied retrospectively in 24 patients, divided into two equal groups of 12, one with normal acid-base equilibrium (group A) and one with metabolic acidosis (group B). The two groups were found to differ significantly in serum levels of BGP (23.7 +/- 18 vs. 42.3 +/- 24 ng/ml, p < 0.02) and in several bone histomorphometric parameters such as osteoid volume (4.5 +/- 3.4 vs. 10.2 +/- 6.6%, p < 0.01), osteoid surface (27.7 +/- 18 vs. 48.4 +/- 19%, p < 0.01), single-labelled surface (7.94 +/- 2.9 vs. 15.8 +/- 9.9%, p < 0.02), mineralizing surface (60.69 +/- 26 vs. 30.89 +/- 15.8%, p < 0.003) and mineralization lag time (56.5 +/- 54 vs. 170.5 +/- 189 days, p < 0.05), with the acidotic group showing excess osteoid and a defect in mineralization. Osteomalacia was found only in the acidotic group, while the only 2 cases of adynamic bone disease (ABD) were in the nonacidotic group. Calcitriol administration, 0.25 micrograms daily for a period of 1 year, in 5 cases in group A and 6 cases in group B induced significant improvement of bone lesions mainly in group A. Two of these patients following treatment acquired the characteristics of ABD. In group B, the response to treatment was very limited, with 5 patients still showing persistence of the histological mixed type of bone disease. In conclusion, metabolic acidosis is accompanied by osteomalacia, pure or mixed variety, and shows a relative resistance to calcitriol administration. Normal acid-base equilibrium is more frequently associated with mild hyperparathyroidism and ABD, spontaneously or as a consequence of calcitriol administration.

Acid-Base Equilibrium↗

Procollagen type 1 C-terminal extension peptide serum levels following parathyroidectomy in hyperparathyroid patients.

Procollagen type 1 is mainly synthesized by osteoblasts and, after cleavage of the N- and C-terminal extension peptides, is utilized for collagen fibril deposition in the osteoid tissue. Serum levels of C-terminal extension peptide (Pcoll-1-C) of the procollagen molecule has been considered a useful marker for the evaluation of the rate of osteoblastic procollagen synthesis. To appraise whether in vivo parathyroid hormone (PTH) plays a suppressive role in the synthesis of procollagen type 1, a study has been carried out in 16 patients, 10 with severe secondary hyperparathyroidism of chronic renal failure and 6 with primary hyperparathyroidism. Following parathyroidectomy (PTX), in chronic renal failure patients a 94% fall in serum intact iPTH and a decline of serum calcium to hypocalcemic levels requiring calcitriol administration were observed. Serum Pcoll-1-C increased markedly with a peak after 7 days and a subsequent decline. Similar changes were observed for alkaline phosphatase and osteocalcin. In primary hyperparathyroidism, PTX was followed by an 88% drop in iPTH and mild hypocalcemia not requiring calcitriol administration. Also in this group serum Pcoll-1-C increased significantly with the same time course, unaccompanied by changes in alkaline phosphatase and osteocalcin. In 4 unsuccessfully neck-operated control patients no change in serum Pcoll-1-C levels was recorded during a period of 2 weeks postoperatively. In conclusion, acute withholding of parathyroid hypersecretion is accompanied by an abrupt and transitory increase of serum Pcoll-1-C, not dependent on calcitriol administration. Hypocalcemia following PTX may in part be due to uncoupling of bone formation and resorption.

Adult↗