Perspectives in the treatment of renal anaemia new concepts and new drugs.

There are several new erythropoiesis stimulating agents that may potentially improve in the near future the management of anaemia in patients with chronic kidney disease. Some of the new erythropoiesis stimulating agents were synthesised by modification of the aminoacide sequence of the erythropoietin (EPO) molecule and hyperglycosylation and therefore they have improved pharmacokinetics (darbopoietin or CERA) by prolongation of the serum elimination half-life compared to epoietins. These agents may be administered less frequently with better stabilisation of blood haemoglobin concentration. There are a promising attempts to overcome the parenteral way of drug administration. Such non-peptide drugs acts as inhibitors of prolyl hydroxylase and GATA-2 transcription factor enhancing the endogenous EPO synthesis.

Low plasma dehydroepiandrosterone sulfate level and its relationship to adiponectin in hemodialysis patients.

The aim of the present study was to assess the relationship between plasma DHEA-S and adiponectin concentrations in hemodialyses patients (HD). Plasma adiponectin, DHEA-S, cholesterol, and albumin levels were estimated in 94 HD and 46 healthy subjects (HS). In HD, a significantly lower plasma DHEA-S concentration (2.5+/-0.2 vs. 4.7+/-0.4 micromol/L respectively; p = 0.002) but significantly higher plasma adiponectin level (15.0+/-0.7 vs. 8.7+/-0.8 microg/mL respectively; p = 0.004) than in HS were found. Only in uremic patients was a significant negative correlation found between plasma adiponectin and DHEA-S concentrations (tau = -0.210; p = 0.001). Decreased plasma DHEA-S level is associated with increased adiponectinemia in uremic patients.

The influence of a 3-month weight reduction therapy with Orlistat on serum vitamin B12 and folic acid concentration in obese women.

OBJECTIVE: Serum folic acid, but not the vitamin B(12) concentration, was found to be significantly lower in obese subjects than in the control ones. DESIGN: The aim of this study was to examine the levels of serum vitamin B(12) and folic acid in obese women before and after weight reduction therapy with Orlistat in comparison to healthy controls with normal body weight. SUBJECTS: Twenty obese women participated in a 3-month weight reduction therapy. The control group consisted of 20 healthy women. MEASUREMENTS: Body weight and height were measured and BMI was calculated. Body composition was analyzed with the impedance method using a Bodystat analyzer. In all patients before and after 3-month weight reduction therapy, serum concentrations of folic acid and vitamin B(12) were assessed. RESULTS: In obese women, serum concentrations of folic acid and vitamin B(12) did not change significantly after 3-month weight reduction therapy with Orlistat.

[Clinical and biochemical picture of primary hyperparathyroidism based on 155 observed cases]. / Obraz kliniczny i biochemiczny pierwotnej nadczynnosci przytarczyc w swietle 155 obserwowanych przypadków.

In this study, the biochemical and clinical profile of primary hyperparathyroidism, diagnosed in 155 patients (106 females and 49 males) in the Department of Nephrology of the Silesian University School of Medicine in the years 1972-1998 was analyzed. The mean age of patients was 48.5 +/- 12.8 years. In all cases the diagnosis was confirmed by the pathomorphological examination. In the majority of cases PNP was diagnosed in a phase of advanced organic injuries. The leading clinical finding in these patients was nephrolithiasis. Asymptomatic hypercalcemia was diagnosed only in 9% of cases. In the years 1972-1992 elevated serum total calcium concentration was found in 92.6% while after introduction of routine estimation of ionized calcium concentration in 1993, hypercalcemia was found in all patients. The incidence of hypercalciuria increased significantly in patients diagnosed in the period 1993-1998 while in this same period the incidence of impaired renal function declined significantly. The elevated serum PTH was found in 86% of patients regardless whether C-terminal fragments of PTH or intact PTH-1-84 were assessed. Elevated levels of ionized serum calcium with normal or increased plasma iPTH-1-84 level are the most constant symptoms of primary hyperparathyroidism.

[Influence of long-term treatment with human recombinant erythropoietin on secretion of hormones regulating carbohydrate metabolism in hemodialyzed patients with chronic uremia]. / Wplyw dlugotrwalego leczenia ludzka rekombinowana erytropoetyna na wydzielanie hormonów regulujacych przemiane Weglowodanowa u hemodializowanych chorych z przewlekla mocznica.

The study aimed to assess the influence of long-term rhuEPO treatment on secretion of pancreatic hormones (insulin, glucagon). A total of 27 haemodialyzed and 9 healthy subjects were examined. Nine patients with uraemic anaemia were treated with rhuEPO for 12 months (EPO group) while another nine patients did not receive rhu-EPO (non-EPO group), but were monitored biochemically and clinically as patients of the EPO group. The third group (HD) comprised nine haemodialyzed patients with a haematocrit value of > 30%, without rhu-EPO therapy. In all subjects plasma levels of glucose, insulin (IRI) and glucagon (Glu) were estimated before and after administration of the test meal. Patients of the EPO and non-EPO group were examined before and after 6 and 12 months of rhu-EPO treatment (EPO group) or clinical monitoring (non-EPO group) respectively, while only one test was performed in patients of the HD group and healthy subjects. During the observation period fasting glicaemia did not change. Six months of rhu-EPO therapy was followed by an increase of fasting insulinaemia and decrease of basal plasma level of glucagon. At that time point rhu-EPO therapy also increased the response of IRI and Glu to the test meal and the insulin/glucose index. After 12 months of rhu-EPO therapy basal insulinaemia and insulin/glucose index returned to the pretreatment value while plasma level of glucagon and the response to the test meal were lower than pretreatment one. Our results suggest that rhu-EPO treatment exerts a profound effect on carbohydrate metabolism and secretion of IRI. Glu, which seems to be dependent upon duration of rhu-EPO therapy and not only, or exclusively to improvement of the haematological status.

[levels of erythropoietin in serum of patients with primary hyperparathyroidism]. / Stezenie erytropoetyny w surowicy u chorych na pierwotna nadczynnosc przytarczyc.

UNLABELLED: The present study aimed assess the relationship between erythropoietin (EPO) and parathormone (PTH) secretion in patients with primary hyperparathyroidism (PHP). Seventeen patients with PHP and 24 patients with uncomplicated cholelithiasis were examined before and during 14 days after surgical treatment. In PHP patients plasma EPO levels were significantly higher than in patients with cholelithiasis (31.5 + 4.3 vs 14.1 + 0.9 mU/ml, p < 0.01). After cholecystectomy transient increase of plasma EPO level was noticed postoperatively during the first 6 days. Such an increase of plasma EPO was absent in PHP patients after removal of the cause of primary hyperparathyroidism. Only in PHP patients a significant negative correlation was found preoperatively between plasma EPO level and Hct value or creatinine clearance respectively. CONCLUSIONS: 1. Patients with PHP are characterized by significantly elevated plasma EPO levels which are related to the degree of anaemia and decrease of GFR. 2. In patients with PHP presence of significant relationship between EPO and PTH secretion could not be proven.

[Influence of long-term human recombinant erythropoietin treatment on secretion of pancreatic polypeptide and gastrin in hemodialysed patients with chronic renal failure]. / Wplyw dlugotrwalego leczenia ludzka rekombinowana erytropoetyna na wydzielanie polipeptydu trzustkowego i gastryny u hemodializowanych chorych z przewlekla mocznica.

The study aimed to assess the influence of long-term rhu-EPO treatment on secretion of pancreatic polypeptide (PP) and gastrin. A total of 27 haemodialysed patients and nine healthy subjects were examined. Nine patients with uraemic anaemia were treated with rhu-EPO for 12 months (EPO group), while another nine patients did not receive rhu-EPO (non-EPO group), but were monitored biochemically and clinically as patients of the EPO group. The third group (HD) comparised nine haemodialysed patients with a haematocrit value > or = 30% without rhu-EPO therapy. In all subjects plasma levels of PP and gastrin were estimated before and after administration of a test meal. Patients of the EPO and non-EPO group were examined before and after 6 and 12 months of rhu-EPO therapy (EPO group) or clinical monitoring (non-EPO group) respectively, while only one test was performed in patients of the HD group and healthy subjects. Six months rhu-EPO therapy was followed by an decrease of basal plasma level of PP and increased response of gastrin to the test meal. After 12 months of rhu-EPO therapy basal plasma level of PP was still lower, the response of PP secretion to a test meal was higher, while that of gastrin secretion lower that the pretreatment ones. Our results suggest, that rhu-EPO treatment exerts effect on secretion of PP and gastrin. These alterations seem not to be related to improvement of the haematological status.

[A case of kidney stone with unusual frequency of renal colic--possible influence of environment on lithogenesis]. / Przypadek kamicy nerkowej o niezwyklej czestotliwosci napadów kolki nerkowej--mozliwy wplyw srodowiska na litogeneze.

In the present paper we described a 36 years old female, who expelled approximately 2000 stones from the urinary tract during the last 18 years. According to the clinical and laboratory tests the lithogenic factors such as abnormalities of calcium, phosphate, oxalate, magnesium and purine metabolism were excluded. The cystinuria and other forms of tubular nephropathies did not exist. Taking into account two following facts: 1) no evidence of renal calculi when the patient was outside her own house and 2) very high concentration of calcium in her home tap water, the role of environmental factors in the pathogenesis of nephrolithiasis in presented patient is very likely.

Influence of long-term erythropoietin treatment on insulin, glucagon, pancreatic polypeptide, and gastrin secretion in haemodialysed patients.

As already reported short-term rHuEpo treatment influences plasma insulin, glucagon, pancreatic polypeptide (PP), and gastrin secretion in haemodialysed patients. The present study aimed to assess the influence of long-term rHuEpo treatment on secretion of above mentioned hormones. A total of 27 haemodialysed patients and nine healthy subjects were examined. Nine patients with uraemic anaemia were treated with rHuEpo for 12 months (Epo group) while another nine patients did not receive rHuEpo (non-Epo group), but were monitored biochemically and clinically as patients of the Epo group. The third group (HD) comprised nine haemodialysed patients with a haematocrit value of > or = 30% without rHuEpo therapy. In all subjects plasma levels of insulin, glucagon, gastrin, and PP were estimated before and after administration of a test meal. Patients of the Epo group were examined before and after 6 and 12 months of rHuEpo treatment (patients of the Epo group) or clinical monitoring (patients of the non-Epo group) respectively, while only one test was performed in patients of the HD group and healthy subjects. Six months of rHuEpo treatment was followed by an increase of fasting insulinaemia and a decrease of basal plasma level of glucagon and PP. At that time point rHuEpo therapy also increased the response of insulin, glucagon, and gastrin to the test meal.(ABSTRACT TRUNCATED AT 250 WORDS)

[Efficacy of recombinant human erythropoietin (rhuEPO) in treatment of anemia in patients with myelodysplastic syndrome]. / Skutecznosc ludzkiej rekombinowanej erytropoetyny (rhuEPO) w leczeniu niedokrwistosci u chorych z zespolem mielodysplastycznym.

This paper summarizes results of rhuEPO--treatment obtained by different authors in 27 patients with a myelodysplastic syndrome (MDS). Only 1/3 of all patients with a MDS were responsive to rhuEPO treatment, while in 2/3 of these subjects no amelioration of anaemia was noticed, even after extremely high doses of this hormone. A detailed description of a patient with MDS, which was observed by the authors, is presented. In this patient the anaemia was refractive even after very high doses of rhuEPO administered for 10 weeks.

Influence of long-term erythropoietin therapy on endocrine abnormalities in haemodialyzed patients.

Endocrine abnormalities in patients with chronic renal failure are well documented. The present study aimed to assess the influence of long-term erythropoietin (EPO) therapy on endocrine abnormalities in haemodialyzed patients. Two groups of haemodialyzed patients, each of which comprised 17 subjects, were examined. The first one treated by EPO (EPO group) while the second one did not receive this hormone (NO-EPO group). A complete biochemical and hormonal check-up was performed before and at the 3, 6, 9 and 12 months of the study period. Normal values for the estimated parameters were obtained in appropriately selected sex and age-matched healthy subjects. After EPO therapy an increase of the haematocrit value from 21.8 +/- 0.9% to 32.6 +/- 0.9% was observed which was accompanied by a significant decline of plasma ferritin and saturation of transferrin. In patients of the NO-EPO group a significant although less marked rise of the haematocrit value (21.4 +/- 0.4% to 24.2 +/- 0.6%) was also noticed. EPO therapy did not change electrolytes (Na, K, Ca, inorganic phosphate), osteocalcin, creatinine, glucose and alkaline phosphatase plasma levels as well as plasma concentrations of calcium related hormones (PTH, calcitonin, 1.25(OH)2D3) and vasopressin (AVP). EPO treatment induced a significant decline of somatotropin (HGH), prolactin (PRO), follitropin (FSH), lutropin (LH), ACTH, cortisol, plasma renin activity, aldosterone, insulin (IRI), glucagon (IR-G), pancreatic polypeptide (PP) and gastrin plasma levels and an increase of plasma estradiol, testosterone and atrial natriuretic peptide (ANP). These EPO induced endocrine alterations were restricted mostly to the first 6 months of EPO administration.(ABSTRACT TRUNCATED AT 250 WORDS)

[Hypercalciuria and primary hyperparathyroidism in patients with kidney calculi. I. Hypercalciuria]. / Wystepowanie hiperkalciurii i pierwotnej nadczynnosci przytarczyc u chorych na kamice nerkowa. Czesc I. Hiperkalciuria.

In 1819 patients with active or non active respectively nephrolithiasis the following parameters were assessed: plasma level of calcium, phosphate, and uric acid and urinary excretion of calcium, phosphate, oxalate, uric acid and creatinine. These parameters were estimated after 5 days of diet containing 400 mg of calcium, 800 mg of phosphate, 100 mg of purines and 40 g of proteins. In 3/4 of all examined patients at least one lithogenic factor was present. More than 40% of patients showed presence of hypercalciuria. Among these patients in 68% renal in 17% absorptive and in 15% undefined hypercalciuria was diagnosed. Patients with active nephrolithiasis showed a similar frequency of hypercalciuria but more profound abnormalities of Ca P metabolism than patients with non active renal stone disease.

[Hypercalciuria and primary hyperparathyroidism in patients with kidney calculi. II. Primary hyperparathyroidism]. / Wystepowanie hiperkalciurii i pierwotnej nadczynnosci przytarczyc u chorych na kamice nerkowa. Czesc II. Pierwotna nadczynnosc przytarczyc (P.N.P.)

Among 1819 patients with renal stone disease 44 cases with primary hyperparathyroidism (p.h.p.) were diagnosed. In all cases the diagnosis of php was confirmed by histomorphological examination. In 34 patients with php solitary adenoma was found, in 5 patients an adenoma with concomitant hyperplasia of the parathyroid glands, in 2 patients hyperplasia and in 3 patients carcinoma of the parathyroid glands. Hypercalcemia was found in 86% of patients, while elevated plasma levels of PTH in 90% of patients with php. Not in all patients PTH secretion was entirely autonomous. No significant correlation was found between plasma levels of PTH and kind of pathology of the parathyroid glands as well as clinical feature of php respectively.

[Selected parameters of calcium and phosphate metabolism in patients after kidney transplantation and administration of azathioprine or cyclosporin A]. / Zachowanie sie wybranych parametrów gospodarki wapniowo-fosforanowej u chorych po przeszczepieniu nerki leczonych azatiopryna lub cyklosporyna A.

The influence was studied of the type of immunosuppression on calciuria, phosphaturia, and on the levels of parathyroid hormone (PTH), calcitonin (CT), 25-hydroxycholecalciferol (25/OH/D), total calcium, magnesium, and alkaline phosphatase activity in 24 patients after renal transplantation. Twelve of these patients received cyclosporin with prednisone (group CyA) and other 12 were treated with azathioprine and prednisone (group Aza). Independently of the type of immunosuppression used, in both groups a significantly higher concentration of PTH, CT, 25/OH/D and greater activity of alkaline phosphatase were demonstrated in relation to healthy controls. In both studied groups the patients had also a significantly reduced calciuria and phosphatemia than controls. In group Aza the patients had a significantly lower phosphaturia and significantly higher magnesemia than in group CyA. The results of these investigations suggest a certain influence of the type of immunosuppression on the intensity of calcium-phosphate metabolism in renal graft recipients.

Endocrine function of the pancreas and gastrin secretion in patients with a kidney transplant.

In 24 patients with a kidney transplant and in 10 healthy subjects the test meal response of immunoreactive insulin (IRI), glucagon (IR-G), pancreatic polypeptide (IR-PP) and gastrin (IR-Ga) was studied. Patients with a kidney transplant showed significantly elevated basal plasma glucagon levels but normal levels of plasma IRI, IR-PP and IR-Ga. After administration of a test meal a significantly suppressed response of IRI, IR-PP and IR-Ga secretion was observed both in the patients treated with azathioprine as well as those treated with ciclosporin. In patients of the ciclosporin group the compromised response of IR-Ga and IRI secretion was significantly more marked than in subjects in the azathioprine group. From the results obtained in this paper it follows that the type of immunosuppressive drugs (azathioprine or ciclosporin) seems to be of minor importance in the pathogenesis of the described endocrine abnormalities.

[Adrenal cortex function in patients after kidney transplantation treated with cyclosporin A with prednisone or Azathioprine with prednisone]. / Czynnosc kory nadnerczy u chorych po przeszczepieniu nerki leczonych cyklosporyna A z prednisonem lub azatiopryna z prednisonem.

Cortisol and aldosterone secretion following an intravenous injection of 0.25 mg of Synacthen was investigated in 12 patients with renal transplants, treated with azathioprine and prednisone (the "azathioprine group") and in 16 kidney-transplanted patients treated with cyclosporin A and prednisone (the "cyclosporin group"), as well as in 12 healthy control subjects. Statistically significant low cortisol and aldosterone levels under basal conditions was found in both groups of patients with renal transplants as well as a significantly lower reactivity of cortisol secretion and a moderately lower reactivity of aldosterone secretion after Synacthen administration. The protocol of the immunosuppression employed had no effect on the severity of the hormonal abnormalities found.

Does the kind of immunosuppressive therapy influence plasma renin activity, aldosterone and vasopressin in patients with a kidney transplant?

In 24 patients with a functioning kidney transplant and in 33 healthy subjects plasma renin activity (PRA), plasma aldosterone and vasopressin (AVP) levels were assessed under basal conditions and after dietary sodium restriction. Twelve patients were treated with azathioprine and another 12 with cyclosporine A. From the results obtained it seems that immunosuppressive drugs used in transplanted patients ar involved in the pathogenesis of endocrine abnormalities and that the kind of immunosuppressive therapy is of minor importance in their development of maintenance. Transplanted kidneys show a preserved reaction pattern of renin secretion to sodium deprivation and upright position.

Influence of type of immunosuppressive therapy on secretion of somatotropin and function of the pituitary-adrenal and pituitary-gonadal axis in patients with a kidney transplant.

In 24 patients with a functioning kidney transplant, hypoglycemia-induced somatotropin (STH), adreno-corticotropin and cortisol secretion was studied. In a further 24 transplanted patients, secretion of lutropin, follitropin and testosterone after the intravenous administration of luliberin was assessed. Data obtained in this paper suggest the presence of abnormal function of the pituitary-adrenal and pituitary-gonadal axis and abnormal STH secretion in patients with a functioning transplant. Type and duration of immunosuppressive therapy seem to influence the intensity of the above-mentioned endocrine abnormalities.