FRAX prognostic and intervention thresholds in the management of major bone fractures in hemodialysis patients: A two-year prospective multicenter cohort study.

PURPOSE: The usefulness of FRAX in predicting major bone fractures in patients with end-stage kidney disease on maintenance hemodialysis treatment has been confirmed in previous studies. For meaningful clinical use, the prognostic and intervention FRAX thresholds need to be established. METHODS: The primary aim of our study was to calculate the optimal cut-off point of FRAX for the best prediction of an increased bone fracture risk in dialysis patients and additionally, to propose its intervention threshold, indicating the need for antifracture pharmacological treatment. The study included 718 hemodialysis patients, who were followed up for two years. Thirty low-energy major bone fractures were diagnosed during the study period. We used the Polish version of FRAX (without the DXA examination) and some particular variables of the FRAX calculator. The optimal cut-off point for prediction of an increased major bone fracture risk was based on the analysis of the sensitivity and specificity curves of FRAX. RESULTS: The analysis revealed FRAX >5% (sensitivity of 70.0%, specificity of 69.8%) as the prognostic threshold for major bone fractures. Its sensitivity for bone fracture prediction was significantly higher, but specificity lower than those of FRAX ≥10%, used in general Polish population. The reason for this can be an underestimation of bone fracture risk with FRAX in dialysis patients. CONCLUSIONS: We conclude that the FRAX prognostic threshold for identification of an increased risk of major bone fractures in hemodialysis patients is >5%. We propose to use this specific value of FRAX as an intervention threshold for pharmacological antifracture treatment in hemodialysis patients.

[Effect of salmon calcitonin on bone mineral density and calcium-phosphate metabolism in chronic hemodialysis patients with secondary hyperparathyroidism]. / Wplyw lososiowej kalcytoniny na gestosc mineralna kosci oraz metabolizm wapnia i fosforu u chorych z wtórna nadczynnoscia przytarczyc przewlekle hemodializowanych.

UNLABELLED: The aim of the study was to evaluate the effect of salmon calcitonin on bone mineral density, parathyroid and thyroid C cells, and calcium-phosphate metabolism in chronic hemodialysis patients with uremic hyperparathyroidism. Forty five patients with serum 1-84 PTH >220 pg/ml were divided into 2 groups: group I (n = 25), treated with intranasal salmon calcitonin (200 IU, thrice a week) and control group II (n = 20). Patients received calcium carbonate (up to 6 g/d) alone or with aluminum hydroxide (up to 3 g/d) as phosphate binders; dialysate calcium was 1.75-2 mmol/l. The observation period was 12 months. The following parameters were measured: bone mineral density (BMD) with dual-energy X-ray absorptiometry in: lumbar spine (L2-L4), femoral neck and total body, before and after the study; serum endogenous calcitonin, before and after the study; serum PTH, alkaline phosphatase and total hydroxyproline, before and after 1, 3, 6, and 12 months; and serum calcium and phosphate monthly. During 12 months of the study, a substantial reduction in BMD was observed in all examined regions in group II (-2.8 +/- 2.1%; p<0.01 in L2-L4, -2.4 +/- 2.0%; p<0.01 in femoral neck, and -1.9 +/- 1.4%; p<0.01 in total body), whereas in group I a slight increase of bone mineral was noted, however insignificant. The inhibition of bone resorption was accompanied by a marked decrease in serum hydroxyproline. No changes in parathyroid activity were noted nor any decrease in serum phosphate. The treatment had no influence on serum endogenous calcitonin; initial concentrations were elevated in 47% of patients. CONCLUSION: Intranasal salmon calcitonin: 1) has no influence on bone mineralization in dialysis patients with uremic hyperparathyroidism; 2) has no significant effect on serum phosphate concentration; 3) provided adequate calcium supplementation doesn't stimulate parathyroid glands; 4) has no influence on endogenous calcitonin secretion.

Endometrial morphology and pituitary-gonadal axis dysfunction in women of reproductive age undergoing chronic haemodialysis--a multicentre study.

BACKGROUND: Although disorders of the reproductive system are very common in women undergoing chronic haemodialysis, this issue remains a neglected area. The aim of the study was to evaluate the endometrial morphology and its relationship with pituitary-gonadal axis dysfunction in uraemic women of reproductive age undergoing haemodialysis. METHODS: The baseline survey with determination of the sex hormones concentrations was performed in 75 haemodialysed women aged 18-45 years. The control group consisted of 33 healthy premenopausal women, aged 18-45 years, with normal menstruation. Then, 40 haemodialysis women, who met the inclusion criteria and gave their informed consent, underwent endometrium suction biopsy. RESULTS: The pathological endometrial morphology was observed in 80% of biopsied subjects. Atrophia or subatrophia was recognized in almost half of the cases, and proliferative changes in one-third of them. Full atrophia with no mitotic figures was found in all but one non-menstruating woman. In one case, adenocarcinoma in situ was diagnosed and successfully treated. The analysis of the relationship between hormonal status and endometrial morphology revealed the substantial influence of oestradiol on endometrium as a target organ. In women with atrophic changes, oestradiol concentrations were significantly decreased, whereas in the remaining subjects, the increase of serum oestradiol seemed to be accompanied by a shift in endometrium morphology from secretional pattern, through proliferative changes to glandular hyperplasia. Mean serum 17-beta oestradiol was decreased in women with amenorrhoea, and increased in those with eumenorrhoea (P<0.001). Except women with regular menses, mean serum progesterone concentrations were in the lower normal range. Seventy-five percent of the studied population had menstrual disorders, and amenorrhoea constituted almost a half of them. CONCLUSIONS: Pathological endometrium morphology is very common in uraemic women of reproductive age undergoing haemodialysis, with proliferative changes in one-third and atrophia in almost a quarter of them. The results of the study suggest a preserved normal reactivity of endometrium on circulating oestrogens.

[Heart failure in advanced age]. / Niewydolnosc serca u pacjentów w wieku podeszlym.

In Europe, 20% of the populations is over 65 years of age. About 5% of the older adults have heart failure. Heart failure (HF) in the elderly is an increasing public health problem, leading cause of hospitalization in older patients and a major cause of morbidity and mortality. Prognosis has improved only slightly during the past decade. Typically, heart failure occurs when ventricles do not fill (diastolic heart failure - DHF) or empty blood (systolic heart failure - SHF) properly. Transthoracic echocardiography is the key investigation to confirm the underlying structural and functional abnormalities of the heart. Patients with heart failure due to left ventricular systolic dysfunction should be treated with a diuretic, an angiotensin converting enzyme inhibitor, and a beta-blocker (unless contraindicated). Several epidemiologic studies have recently shown that more than 50% of older patients who present with symptoms of HF have DHF. While numerous large trials have established specific therapies for SHF, such trials are lacking for DHF. The finding of similar key pathophysiologic abnormalities in DHF and SHF suggests the possibility that therapies that have been successful for SHF may have a role in therapy for DHF. A recent survey showed that despite physicians' awareness of the benefits of beta-blocker therapy, only minority of patients with heart failure are treated with beta-blocker or combination of ACE inhibitors and beta-blocker.

[Red cell zinc protoporphyrin and its ratio to serum ferritin (ZPP/logSF index) in the detection of iron deficiency in patients with end-stage renal failure on hemodialysis]. / Stezenie cynkowej protoporfiryny w erytrocytach i jego stosunek do stezenia ferrytyny w surowicy (indeks ZPP/logSF) w niedoborze zelaza u hemodializowanych chorych z powodu schylkowej niewydolnosci nerek.

Monitoring of iron metabolism has become a major clinical issue in end-stage renal patients undergoing hemodialysis. It can be done at three levels: storage, transport and marrow availability. The objective of that study was to evaluate if a combination of an iron storage marker, serum ferritin (SF) with red cell zinc protoporphyrin (ZPP), a marker of iron availability for erythron, will improve diagnostic value of both tests. In a baseline survey in the population of 186 haemodialysis patients (75% treated with rHuEpo), the following parameters were determined: complete blood count, serum transferrin saturation (TSAT), transferrin, SF, hypochromic red cells % (HRC) and ZPP; the ZPP/logSF ratio was calculated. Iron deficiency was defined as a fernitin saturation--TSAT < 20%. In the second part of the study, 24 pts with SF < 50 ng/ml were given 50 mg of i.v. iron weekly for three months, then the same tests were repeated. During that time the doses of rhuEpo were stable. An increase in hemoglobin of > 1.0 g/dl was considered as a positive response. In 186 studied patients mean SF was 274 +/- 335 ng/ml, and mean ZPP was 68 +/- 44 mumol/mol heme. A ZPP/logSF ratio > or = 40 had the best combination of diagnostic sensitivity and specificity in detecting iron deficiency (76% and 83% vs: 56% and 89% for ZPP > 90 mumol/mol heme, 84% and 34% for HRC > 5%, 68% and 58% for HRC > 10%) and the strong correlations with all other examined parameters were found. The index showed also the highest correlation with the response to the i.v. iron (r = 59; p < 0.01) of the tests evaluated. After three months the values of ZPP/logSF ratio decreased from 80 +/- 105 to 39 +/- 19 (p < 0.01). A significant difference between responders and nonresponders was found for basal ZPP/logSF (p < 0.05) but not for ZPP. Our data suggest that the ZPP/logSF index provides a new valuable parameter for the identification of hemodialysis patients with iron deficiency and the prediction an erythropoietic response to iron supplementation.

[Menstrual disturbances and alternations in hypophyseal gonadal axis in end-stage premenopausal women undergoing hemodialysis: a multi-center study]. / Zaburzenia miesiaczkowania i osi przysadkowo-gonadalnej u kobiet w wieku rozrodczym hemodializowanych z powodu schylkowej niewydolnosci nerek--badanie wieloosrodkowe.

The results of the studies of hypophyseal-gonadal axis in dialysis women are not uniform. Mostly the increased serum concentrations of prolactine and pituitary gonadotropins are observed; the data about ovarian secretion are much more scanty and contradictory. The aim of this crossectional study was to assess changes in sexual hormones secretion and their associations with menstrual disturbations in premenopausal women with end-stage renal failure undergoing hemodialysis. Sixty three women from six mazovian dialysis units, aged 18-45 years (mean 35 +/- 7 years) were enrolled into the study. They were divided into four groups according to their menstrual pattern: I--eumenorrhoea (n = 17), II--polymenorrhoea (n = 9), III--oligomenorrhoea (n = 16) i IV--amenorrhoea n = 21). There were no differences between both groups in respect to age, age of menarche, time on hemodialysis, and body mass index. In all subjects gynecological examination was performed and serum prolactin, FSH, LH, estradiol, progesterone and testosterone concentrations were assayed. In 49% women high serum prolactin concentrations were noted (the highest in group IV--1699 +/- 1022 vs 441 +/- 205 microIU/ml in group I; p < 0.05). Mean serum FSH and LH were increased in group IV only (33 +/- 59 and 22 +/- 31 mIU/ml); no significant differences among groups examined were seen. Serum estradiol was increased in groups I-III (95 +/- 46, 72 +/- 33, and 83 +/- 55 pg/ml, respectively) and decreased in group IV (27 +/- 22 pg/ml; p < 0.001 in respect to remaining groups). Mean serum progesterone and testosterone concentrations were normal in all four groups, but serum progesterone was significantly lower in groups II-IV than in group I (p < 0.05). No differences in hormonal status between patients receiving and not receiving rHuEpo were observed. Menstrual disturbances are common (73%) in premenopausal women with end-stage renal failure, with amenorrhea constituting a half of them. Hyperprolactinemia is the most frequently seen alteration in their hormonal profile with the highest concentrations in those with secondary amenorrhea. Increased serum gonadotropins and reduced serum estradiol concentrations are mostly seen in amenorrheic women, whereas in menstruating women serum estradiol is often slightly increased.