[Changes to calcium-phosphate metabolism associated with chronic nephropathies]. / Zmeny kalcium-fosfátového metabolizmu pri chronických nefropatiích.

The paper discusses bone mineral and bone disorders associated with chronic nephropathies that are a logical consequence of reduced renal function. These are principally driven by changes in parathormone production and vitamin D synthesis. Bones are usually affected by renal osteopathy - osteodystrophy with abnormities of bone turnover, mineralization and volume, and with growth retardation in children. Extra-skeletal calcifications may occur, of which vascular wall localization is the most serious. A collection of pathologies develops, now termed chronic kidney disease - mineral and bone disorder (CKD-MBD).

[Hypogonadism, a serious complication of chronic renal insufficiency]. / Hypogonadizmus--závazná komplikate chronické nedostatecnosti ledvin.

Hypogonadism is a frequent complication in patients with chronic renal insufficiency (CHRI). From a pathogenetic point of view, it is a disorder at the level of the hypothalamus caused by central inhibition of the pulsatile generation of gonadotropin releasing hormone (GnRH) and by a primary disorder of gonads. The cause of hypogonadism in dialysed patients is not completely known. The effect of inhibition of erythropoietin production is believed to be one of the factors, as well as the adverse effects of complicated therapeutic procedures and malnutrition. In men, the affection manifests itself as a disorder of sexual functions, inhibition ofspermatogenesis, premature andropause and severe fatigue syndrome. Menstruation disorders, premature menopause and anovulation cycles are frequent symptoms in dialysed women. Androgen or estrogen substitution improves the quality of life in both sexes and slows down the loss of bone mass. Complete remission of hypogonadism is obtained, in the majority of patients, by renal transplant. The overview study deals with the pathogenesis, diagnosis and treatment of hypogonadism in dialysed patients.

[Viability of parathyroid gland tissue measured by flow cytometry]. / Viabilita tkáne prístítných telísek merená prutokovou cytometrií.

BACKGROUND: Postoperative hypoparathyroidism after the total parathyroidectomy (PTX) remains a problem, no matter our experiences with 243 operations on parathyroid glands (PG). Implantation of "fresh" tissue, cryopreservation and reimplantation of cryopreserved tissue are performed with uncertain results. The aim of this project was to compare viability of cryopreserved tissue of parathyroid glands with "fresh" tissue obtained during parathyreoidectomy and with tissue from cadaverous donors. METHODS AND RESULTS: Group 1 included 55 cryopreserved samples obtained from 41 patients after PTX (22M, 19F, a mean age of 46 +/- 11 years). Average duration of storage in liquid nitrogen was 84 +/- 49 months. Group 2 included "fresh" tissue of PG, harvested during PTX. Viability was measured in different time in samples from 42 patients with hyperparathyroidism (11M, 31F, a mean age of 55 +/- 13 years). Group 3 included tissue of 14 cadaverous donors obtained during multiorgan harvesting (7M, 7F, a mean age of 31 +/- 5 years, WIT 32 min). Viability was measured by flow cytometry with propidium iodide after dissociation of tissue. Evaluation of PG tissue was proven by histology. Average viability in group 1 was 36.9 +/- 24.7%, no correlation with the duration of storage in liquid nitrogen was found. Average viability in group 2 was 51.4 +/- 24%. Viability in group 3 was 66.8 +/- 32%. Group 1 vs. group 2 were different with p < 0.05, group 2 vs. 3 did not reach significance (with marginal p = 0.06) and group 1 vs 3 were different with p < 0.001. CONCLUSIONS: The highest viability was found in tissue of cadaverous donors, the lowest in cryopreserved tissue (with no correlation to the duration of storage in liquid nitrogen).

[Disorders of parathyroid function in patients on regular dialysis therapy and after kidney transplantation]. / Poruchy funkce prístítných telísek u nemocných v pravidelném dialyzacním lécení a po transplantaci ledviny.

BACKGROUND: Parathyroids dysfunction is a key disorder in the spectrum of renal osteopathy, occurring after renal transplantation and, occasionally, after parathyroidectomy. In our subjects, dysfunction is understood as plus or minus activity. METHODS AND RESULTS: Parathyroidectomy as the primary procedure was performed in 179 patients for all types of hyperparathyrodism. In 70% of cases the secondary hyperparathyroidism was treated, believed to be the most severe condition. Present assessment was focused on postoperative parathyroid hormone levels (pg/ml) in three groups of patients (n = 92). Group 1 with parathyroid gland autoimplants following total parathyroidectomy; Group 2 after partial or subtotal surgery; Group 3 after autologous implantation of cryopreserved parathyroid glands in severe hypoparathyroidism. Group 1 (32 dialysis and 9 non-dialysed patients): 228.9 vs 85.9 pg/ml; ns; hypofunction in 50% and in 33% respectively, afunction in 12.5% of dialysed patients, in non-dialysed patients it was not detected. Group 2 (25 dialysis and 24 non-dialysed patients): 603.3 vs 169.8 (pg/ml); p = 0.01; hypofunction in 16% and in 8% respectively, afunction was not detected. Complete groups 1 and 2 of patients: 197.5 vs 382.3 pg/ml (p = 0.0016). Dialysed patients in Group 1 and 2: 228.9 vs 603.3 pg/ml (p = 0.007); non-dialysed patients: 85.9 vs 169.8 pg/ml; ns. Group 3 (15 dialysed patients): 63.0; hypofunction and afunction in 40%. This group (63.0 pg/ml) vs Groups 1 and 2 of dialysed patients (p = 0.031 and 0.0004), respectively. Basic laboratory findings before operations of tertiary hyperparathyroidism were shown. CONCLUSIONS: After total parathyroidectomy with parathyroids autoimplantation, parathyroid hormone is acceptable to dialysis and non-dialysis patients. Partial parathyroidectomy prevents development of hypoparathyroidism. It is associated, however, with a risk because of hyperparathyrodism recurrence. Cryopreserved autologous parathyroids reach lower parathyroid levels compared with "fresh" parathyroid tissue autoimplants. Parathyroidectomy after successful renal transplantation may be indicated.

[Surgical treatment of hyperparathyroidism--personal experience]. / Chirurgická lécba hyperparatyreózy--nase zkusenosti.

The authors submit their own experience with the surgical treatment of all types of hyperparathyroidism (HPT). Since 1992 till the end of April 2002 in the Institute of Clinical and Experimental Medicine 151 operations were performed in 132 patients, in particular secondary HPT (69.8%). Among surgical operations partial parathyroidectomy (PTE) predominated, as a rule without peroperative implantation of parts of the removed parathyroid glands(PT)(64.8%). The high ratio of this type of operations was due among others to a recent increase of tertiary posttransplantation HPT. Advanced secondary HPT of haemodialyzed patients was treated by total PTE with implantation of PT tissue. The incidence of surgical complications was low (7.1%) and insignificant from the aspect of the long-term postoperative condition. Persisting or relapsing HPT was revised in 15 patients (in 12.6% of all operations).

[Secondary hyperparathyroidism in a female patient with six parathyroid glands]. / Sekundární hyperparatyreóza u nemocné se sesti prístítnými telsky.

The authors present the case-history of a female patient with chronic renal failure and manifest signs of secondary hyperparathyroidism. The patient was repeatedly subjected to surgical operations during which eventually six hyperplastic parathyroid glands were removed.

[Pulsed doses of calcitriol in the treatment of secondary hyperparathyroidism in patients on hemodialysis]. / Nárazové dávky kalcitriolu pri lécení sekundární hyperparatyreózy u hemodialyzovaných nemocných.

Administration of pulse doses of calcitriol is a better way of conservative treatment of secondary hyperparathyroidism (2HPT), making use of the direct suppression of parathormone (PTH) secretion. In a group of 29 haemodialyzed patients the authors evaluated during a six-month follow-up the effect of intravenous Calcijex in 12 and of oral Rocaltrol in 8 subjects. In responders of the calcijex group the PTH level declined by 67.6%, the mean baseline PTH value being 787.8 pg/ml, as compared with non-responders where the decline of PTH at the end of the investigation was 7.5%, the baseline PTH being 1296.4 pg/ml. The difference was significant (p < 0.05). In patients treated with Rocaltrol the therapeutic effect was apparent also in subjects with a lower baseline PTH. An associated phenomenon of treatment are as a rule parallel changes of kALP and ACP levels with those of PTH. It was however revealed that the drop of serum activities can occur also without a concurrent drop of PTH which indicates a dissociation between the level of bone metabolism and PTH secretion. The therapeutic effect can be influenced not only by the stage of 2HPT but also by the route of administration and quantity of calcitriol doses, as ensues from a long-term follow up of one patient. Moreover, the morphological substrate of the hyperplastic tissue of the parathyroid gland and their receptors for 1,25(OH)2D3 must be taken into account. Successfully performed parathyroidectomy, a still justified therapeutic step, is associated as a rule with rapid restoration of PTH levels. TO CONCLUDE: Pulse doses of calcitriol seem to be at present the effective treatment of diagnosed 2HPT, conventional oral calcitriol doses are useful in 2HPT prophylaxis. 2. The i.v. form should be the last resort of conservative treatment before parathyroidectomy. 3. Calcitriol treatment should attempt to maintain slightly raised PTH levels. 4. The limiting indicators of treatment are hypercalcaemia, hyperphosphataemia and the development of extraosseous calcifications. 5. In order to adhere to these criteria it is necessary to use dietary provisions, the dialyzation technique and check biochemical indicators of bone metabolism and possibly change doses of pharmaceutical preparations.

[Relation between parathormone and 1,25-dihydroxyvitamin D3 in chronic kidney failure]. / Vztahy parathormonu a 1,25-dihydroxyvitaminu D3 za chronického selhání ledvin.

The author gives an account of the basic relations of calcium homeostasis ensuing from the action of calcitropic hormones under physiological conditions and during chronic renal failure. The following are evaluated in relation to the pathogenesis of secondary hyperparathyroidism: a decline of glomerular filtration, the relationship of serum calcium levels and PTH secretion along with analyses of so-called S curves, calcitriol deficit and impaired function of the appropriate receptors, phosphate retention, effect of metabolic acidosis, participation of retained aluminium, possible importance of calcitonin and genetic abnormality, corticoid administration and abolition of oestrogen function.

Adenohypophyseal-gonadal dysfunction in male haemodialyzed patients before and after subtotal parathyroidectomy.

The function of the adenohypophyseal-gonadal axis in haemodialyzed male patients is modified: the serum testosterone level is low, and the gonadotropin levels are increased. The pathogenetic role of secondary hyperparathyroidism in this disorder has not previously been defined. The area under the curve (AUC) and the secretion kinetics of testosterone, luteinizing hormone (LH), and follicle-stimulating hormone after administration of LH-releasing hormone were examined in 7 dialyzed men with secondary hyperparathyroidism (mean age 36.2, range 20-47 years) before and 3 and 6 months after parathyroidectomy (PTX). The operation was successful in all 7 patients, as intact parathyroid hormone declined markedly during both postoperative periods as compared with the values before PTX: 81 +/- (SEM) 34 and 138 +/- 57 ng/1 versus 965 +/- 116 ng/l (p < 0.01 and p < 0.0l). The testosterone AUC prior to PTX (63 +/- 115 nmol/l x min) and 3 months (-4 +/- 36 nmol/l x min) and 6 months after PTX (-62 +/- 69) did not differ significantly, as was the case with LH AUC (1,110 +/- 223 and 1,214 +/- 331 and 1,020 +/- 314 U/l x min, respectively) and follicle-stimulating hormone AUC (525 +/- 334 and 634 +/- 347 and 533 +/- 264 U/l x min, respectively). The secretion kinetics of all three hormones was atypical as compared with healthy men of similar age, but it did not change after PTX. There were no correlations between the sexual indicators and parathyroid hormone, 1,25(OH)2D3, calcium, or phosphate during the individual periods. These findings indicate that secondary hyperparathyroidism is probably not involved in the dysfunction of the adenohypophyseal-gonadal axis in dialyzed men.

Use of the low-dose desferrioxamine test to diagnose and differentiate between patients with aluminium-related bone disease, increased risk for aluminium toxicity, or aluminium overload.

BACKGROUND: Aiming at a safe method in the diagnosis of aluminium-related bone disease (ARBD)/aluminium overload the low-dose desferrioxamine (DFO) test was developed. In a multicentre study histological and histochemical data and aluminium bulk analysis of bone biopsies of 77 dialysis patients were correlated with the results of both the 5 mg/kg and 10 mg/kg DFO tests. METHODS: ARBD was considered to be present when > 15% of the bone surface was positively stained for aluminium and the bone formation rate was below 220 microns 2/mm2/day. Patients in which the Aluminon staining was positive (> 0%) were considered at an increased risk for aluminium toxicity independent of the type of renal osteodystrophy. Patients were considered aluminium overloaded when the bone aluminium content was > 15 micrograms/g wet weight and/or the Aluminon staining was positive (> 0%). RESULTS: Using the proposed criteria 15 patients were found to have ARBD; 13 of them presenting with a serum iPTH below 150 ng/l. In conjunction with an iPTH measurement the DFO test had a more than acceptable sensitivity and specificity in the diagnosis of ARBD. The test was considered positive when a post-DFO serum aluminium increment (delta sA1) above 50 micrograms/l (5 mg/kg) or 70 micrograms/l (10 mg/kg) together with a serum iPTH below 150 ng/l was found. Using these cut-off levels the 5 and 10 mg/kg tests in the diagnosis of ARBD had a sensitivity of 87% and a specificity of 95% and 92% respectively whereas the predictive value for a positive test for the population under study was 80% (5 mg/kg). Not a single patient with a serum iPTH > 650 ng/l had a positive staining (> 0%) even when the bone aluminium level was elevated (> 15 micrograms/g wet weight). In the detection of patients at risk for aluminium toxicity delta sA1 thresholds of 50 micrograms/l (5 mg/kg) and 70 micrograms/l (10 mg/kg) in combination with a serum iPTH < 650 ng/l had a sensitivity of 92% and specificity of 86% and 84% respectively. In the clinical setting of aluminium overload, threshold delta sA1 levels of 50 micrograms/l (5 mg/kg) and 70 micrograms/l (10 mg/kg) had a sensitivity of 91% and a specificity of 95% and 90% respectively. CONCLUSIONS: The low-dose DFO test is a reliable test for the detection of aluminium overload; however, it is not specific enough to differentiate between ARBD, increased risk of aluminium toxicity, and aluminium overload unless it is used in combination with a serum iPTH measurement. In conjunction with a serum iPTH measurement it is an important tool in the differential diagnosis and may avoid the necessity of a bone biopsy in the majority of patients. Data obtained in the present study have allowed us to update the strategies for monitoring, diagnosis and patient follow-up proposed at the Consensus Conference on Diagnosis and Treatment of Aluminium Overload in End-Stage Renal Failure; Paris, 1992.

Effect of parathyroidectomy on thyrotropic and lactotropic function in patients with renal osteopathy.

To test the effect of parathyroidectomy on thyrotropic and lactotropic function, a thyrotropin-releasing hormone (TRH) test was performed before and between the 2nd and 3rd month after operation in 13 haemodialysed patients with secondary hyperparathyroidism. The thyrotropin response to TRH was higher in the postoperative period as compared with the values before the operation (p < 0.01). The prolactin response to TRH did not differ from the values before the operation. No correlations between thyrotropin response and serum parathyroid hormone (PTH), ionised calcium and haemoglobin or haematocrit were found. The lower sensitivity of the thyrotropic system to TRH in patients with renal osteopathy is not dependent on serum PTH or calcium.

[Dynamic bone scintigraphy in the diagnosis of renal osteopathy]. / Pouzití dynamické kostiní scintigrafie v diagnostice renální osteopatie.

UNLABELLED: A study was undertaken to assess types of RO by a dynamic modification of osteoscintigraphy 53 pts dialyzed for 27-75 mths, 19-52 yrs old were divided, according to histological bone pictures, into 4 groups: I) 11 pts with hyperparathyroidism, II) 12 pts with osteomalacia, III) 11 pts with mixed RO, IV) 11 pts were after parathyroidectomy (PTE) and 13 controls. INVESTIGATIONS: the rate of 99mTc-Sn-HEDP accumulation in the skeleton, skeletal/background radioactivity index both registered for 60 min. (parameters K and P), serum levels of C-PTH, bone isoenzyme of alkaline phosphatase (bALP), acid phosphatase (ACP), free hydroxyproline (S-Hypro). RESULTS: 1. compared to controls: elevations of K and all biochemical parameters, P in groups I and III (p < 0.01 - < 0.001) were found. 2. Group 1 was characterized by the highest values of all parameters compared to groups II and IV (p < 0.01). 3. Linear relationships were found between K and bALP (p < 0.01), P and bALP, ACP, S-Hypro (p < 0.01) in pts of groups I, II, III. 4. PTE in group IV was followed by a decrease in all parameters (p < 0.01) compared to values of the same pts in group I. Aluminum osteopathy was present in 2/3 of cases in group II showing the lowest values of all parameters. CONCLUSION: DBS is a sensitive method for assessing bone turnover rate according to the degree of skeletal uptake of radionuclide. In this manner it is possible to determine both the type of RO and it's further development in repeated measurements.

[Hyperparathyroidism and parathyroidectomy in dialyzed patients]. / Hyperparatyreóza a paratyroidektomie u dialyzovaných nemocných.

The authors present older and more recent views regarding the pathogenesis of hypocalcaemia and secondary hyperparathyroidism in patients with chronic renal failure with emphasis on the impact of inorganic phosphate retention and lack of 1,25-dihydroxyvitamin D3 in body fluids. As regards therapeutic procedures the initial problem is to control hyperphosphataemia and to suppress the increased parathormone secretion in particular in dialyzed patients. When treating hyperphosphataemia it is necessary with regard to the severity of the finding to use concurrently several procedures and avoid aluminium phosphate binders. Aimed reduction of high parathormone levels in the blood stream can be achieved by medicamentous--pharmacological means, using 1,25 (OH)2 D3 or surgery of the hypertrophic parathyroid glands. The term parathyroidectomy can comprise also percutaneous infiltration of the parathyroid glands with ethanol. From this aspect under certain circumstances a combination of different therapeutic procedures may prove useful. In the conclusion the authors mention basic data on para-thyroidectomies performed in their department: the favourable long-term results of operations amounted to 80.4%.

[Changes in plasma renin and aldosterone after parathyroidectomy in patients with hyperparathyroidism]. / Zmeny plazmatického reninu a aldosteronu po paratyroidektomii u nemocných s hyperparatyrózou.

The plasma renin activity and its changes after parathyroidectomy indicate a preserved internal secretory renal function in dialyzed patients. The PRA values before parathyroidectomy are not unequivocally related to the blood pressure reading. After parathyroidectomy during the initial months the renin and aldosterone plasma levels decline in patients with secondary and primary HPT (p < 0.001), the urinary Na/K quotient rises in primary HPT (p < 0.05) and the systemic blood pressure declines in dialyzed patients with secondary HPT (p < 0.001). The findings suggest relations between the two hormonal systems during hyperparathyroidism and in the early stage after parathyroidectomy. Parathormone probably stimulates renin secretion. After a prolonged time interval following operation the parathormone levels in the blood steam reach normal levels and the same probably applies to intracellular calcium in cells of the iuxtaglomerular apparatus along with PRA.

31P magnetic resonance spectroscopy investigation of skeletal muscle metabolism in uraemic patients.

Using the method of in vivo magnetic resonance spectroscopy we examined 17 patients with moderately advanced chronic renal insufficiency, 21 patients with chronic renal failure treated by haemodialysis, and 15 dialyzed patients with symptomatic renal osteopathy. The ratios of intracellular phosphocreatine and inorganic phosphate concentrations of these subjects measured at rest were compared with those found in healthy controls. While we noted significantly lower (p < 0.01) ratio values in all patients, subjects with osteopathy showed a lower value than dialyzed patients free of bone disease. Haemodialysis improved the result of examination in 7 patients. The results can be summarized as follows: (1) patients with altered renal function have significantly impaired energy metabolism of skeletal muscle, and (2) the disorder is more severe in patients with renal osteopathy than in those free of it.

[Computer tomography in the diagnosis of hyperparathyroidism]. / Výpocetní tomografie v diagnostice hyperparathyreoidismu.

The paper presents long-term experience in the diagnosis of hyperparathyroidism by means of computer tomography. A large number of examinations (164) of parathyroid glands, the possibility of verification and comparison with sonography or with other diagnostic methods of visualization make it possible to define the role of computer tomography in hyperparathyroidism and to show advantages and limitations of the method. For the high diagnostic precision the CT examination may be considered to be the reliable method in the demonstration of enlarged parathyroid glands.

[Aluminum osteopathy]. / Hliníková osteopatie.

Histochemical study of 155 bone biopsies from dialyzed patients revealed 43 cases with aluminium deposits in bone trabeculae localized along the mineralization line or in phagolysosomes of bone marrow macrophages. Aluminium was limited to macrophages in 5 cases, to mineralization line in 23 cases, and found in both localities in 15 patients. Patients with a positive finding mostly had osteomalacia (8 times) which was combined in some cases (35 times) with mild fibrous osteodystrophy. Authors failed to prove histochemically positive deposits in dialyzed patients with serious parathyroidism. Simultaneous deposits of aluminium and hemosiderin were found in the mineralization line in three patients. Bone deposition of aluminium seems to influence somehow the bone lesion but precise interpretation of the phenomenon has not been given.

[Ultrasonography in the diagnosis of hyperparathyroidism]. / Ultrasonografie v diagnostice hyperparathyreoidismu.

Ultrasonography is a direct method of representation, giving various advantages over other methods in the examination of parathyroid glands: it is rapid, non-radiation and economically undemanding. Dynamic examination by means of the linear electronic transducer of 3.5 MHz and the use of water path was used in 37 patients. In 7 patients with primary hyperparathyroidism was the examination rapid and the pictures of the adenomas were persuasive. In 30 patients with secondary hyperparathyroidism were found characteristic pictures, if the glands were enlarged to 8 mm or more. For the diagnosis of smaller glands a high resolution transducer will be necessary. Histological finding was available in 21 patients undergoing operation, and easily available method and it is therefore the procedure of the first choice.

[Personal experience with surgical treatment of hyperparathyroidism in chronic kidney failure. I. Etiopathogenesis of secondary hyperparathyroidism, preoperative findings, indications for parathyroidectomy]. / Nase zkusenosti s chirurgickým lécením hyperparatyreoidismu pri chronickém selhání ledvin. I. Etiopatogeneze sekundárního hyperparatyreoidismu, predoperacní nálezy, indikace k paratyreoidektomii.

The authors give an account of the fundamental relations of the calcium-phosphate metabolism in conjunction with the development of secondary HPT in chronic renal failure. The authors analyzed a group of 20 patients operated on account of secondary and tertiary forms of HPT as regards preoperative findings. The analysis comprised the clinical condition, biochemical, radiological and histological findings pertaining to bone, along with evidence of enlarged parathyroid glands by computed tomography and ultrasonography. The mentioned findings supplemented by some findings from the literature are the sum of indications for PTE. From the practical aspect they are indicators of the affection, of a high total ALP blood level and X-ray evidence of subperiostal absorption.

[Personal experience with surgical treatment of hyperparathyroidism in chronic kidney failure. II. Surgical technic, postoperative course and the state of bone metabolism after parathyroidectomy]. / Nase zkusenosti s chirurgickým lécením hyperparatyreoidismu pri chronickém selhání ledvin. II. Technika operacního výkonu, pooperacní prubeh a stav kostního metabolismu po paratyreoidektomii.

In 20 haemodialyzed patients operated on account of HPT, in 12 instances total PTE was performed with autotransplantation of portions of the parathyroid gland and in 8 patients so-called partial PTE was performed, leaving one parathyroid gland (in one instance two). Histomorphological examination revealed diffuse to nodular hyperplasia and twice an adenoma of the parathyroid; the mean weight of the excised tissue was 4000 mg. The follow-up period after operation varied from two months to 36 months. After total PTE the regression of HPT is more marked and more rapid. Possible relapses are more probable after partial PTE, also the possible development of hyperplasia of the implanted tissue cannot be ruled out. A new rise of C-HPT levels precedes changes of the clinical picture and a rise of indicators of bone metabolism. From linear correlations between serum levels of the ALP bone fraction, total ACP, free OH-P and values of C-PTH (p less than 0.01-0.001) conclusions can be drawn on regression or progress of the osseous finding after PTE. Data on the possible participation of aluminum osteopathy are essential, as in the florid stage it is a contraindication of PTE. The positive effect of operation recorded in 17 patients comprised not only restoration of a satisfactory mobility but also an improved mental condition. Surgical treatment of advanced forms of HPT in dialyzed patients is therefore still considered an indicated operation, provided these patients receive subsequently further aimed care.