Bilateral Renal Angiomyolipomas and Subependymal Giant Cell Astrocytoma Associated with Tuberous Sclerosis Complex: a Case Report and Review of The Literature.

Tuberous sclerosis complex (TSC) is an autosomal-dominant multi system disorder. The genetic basis of the disorder is mutations in the TSC1 or TSC2 gene, which leads to over activation of the mammalian target of rapamycin (mTOR) protein complex and results in development of benign tumors in different body systems such as brain, skin, lungs and kidney. The mTOR inhibitors are presently the main treatment option for patients with TSC. We here report a 21-year female patient with large bilateral angiomyolipoma (AML) in both kidneys with longest diameter more than 12.3 cm and subependymal giant cell astrocytoma (SEGA). Treatment with everolimus (EVE) was initiated at a dose of 10.0 mg/day and continued during the following 3 years. Magnetic resonance imaging (MRI) was performed before treatment with everolimus was initiated, and consequently at 12 and 36 months for follow-up of the efficacy of the treatment. After 3 years, the total size of largest AML decreased by ~24.0% in the longest diameter. A reduction of the total size of SEGA was also observed. The most common adverse effect of treatment was stomatitis grades 3 to 4 and one febrile episode associated with skin rash that required a reduced dose of EVE. In conclusion, the everolimus treatment improved even such a large renal AML and the effect persisted during the long-term administration with a small number of adverse effects. A positive effect was observed on the brain tumor as well.

Characteristics of high- and low-risk individuals in the PRIORITY study: urinary proteomics and mineralocorticoid receptor antagonism for prevention of diabetic nephropathy in Type 2 diabetes.

AIM: To compare clinical baseline data in individuals with Type 2 diabetes and normoalbuminuria, who are at high or low risk of diabetic kidney disease based on the urinary proteomics classifier CKD273. METHODS: We conducted a prospective, randomized, double-blind, placebo-controlled international multicentre clinical trial and observational study in participants with Type 2 diabetes and normoalbuminuria, stratified into high- or low-risk groups based on CKD273 score. Clinical baseline data for the whole cohort and stratified by risk groups are reported. The associations between CKD273 and traditional risk factors for diabetic kidney disease were evaluated using univariate and logistic regression analysis. RESULTS: A total of 1777 participants from 15 centres were included, with 12.3% of these having a high-risk proteomic pattern. Participants in the high-risk group (n=218), were more likely to be men, were older, had longer diabetes duration, a lower estimated GFR and a higher urinary albumin:creatinine ratio than those in the low-risk group (n=1559, P<0.02). Numerical differences were small and univariate regression analyses showed weak associations (R2 < 0.04) of CKD273 with each baseline variable. In a logistic regression model including clinical variables known to be associated with diabetic kidney disease, estimated GFR, gender, log urinary albumin:creatinine ratio and use of renin-angiotensin system-blocking agents remained significant determinants of the CKD273 high-risk group: area under the curve 0.72 (95% CI 0.68-0.75; P<0.01). CONCLUSIONS: In this population of individuals with Type 2 diabetes and normoalbuminuria, traditional diabetic kidney disease risk factors differed slightly between participants at high risk and those at low risk of diabetic kidney disease, based on CKD273. These data suggest that CKD273 may provide additional prognostic information over and above the variables routinely available in the clinic. Testing the added value will be subject to our ongoing study. (European Union Clinical Trials Register: EudraCT 2012-000452-34 and Clinicaltrials.gov: NCT02040441).

Calcimimetics versus parathyroidectomy: What is preferable?

Secondary hyperparathyroidism (SHPT) is common among patients with end-stage renal disease (ESRD). SHPT is associated with high-turnover bone disease, interstitial and vascular calcifications, cardiovascular morbidity and mortality. The pharmacological management of SHPT has progressed in recent years. The introduction of targeted therapies, such as selective vitamin D receptors activators and calcium-sensing receptor modulators, offers an increased opportunity to adequately control elevated parathyroid hormone (PTH), especially in patients with chronic kidney disease under dialysis treatment. Calcimimetic medications such as cinacalcet negatively feedback on the parathyroid glands and do not have the consequences of calcium augmentation. However, there are no randomised, prospective data that demonstrate improved quality of life, improvement in anemia, reduction in phosphate binders, reduction in use of vitamin D analogs, or reduction in mortality. Literature supports cinacalcet therapy to improve patient outcomes, especially with regard to vascular calcifications and presumably the very lethal condition of calciphylaxis. However, cinacalcet is administered orally and has been associated with gastrointestinal intolerance along with hypocalcemia. In addition, poor adherence has been observed among dialysis patients self-administering oral cinacalcet. On the other hand, successful surgical parathyroidectomy (sPTX) can yield a dramatic reduction in PTH level and clinical symptoms. The advanced pharmacological treatments of SHPT often obviate parathyroidectomy; however, some researchers have reported that sPTX may be more cost-effective than cinacalcet in some patients with ESRD and suffering uncontrolled SHPT.

European Renal Best Practice Guideline on kidney donor and recipient evaluation and perioperative care

The European Best Practice Guideline group (EBPG) issued guidelines on the evaluation and selection of kidney donor and kidney transplant candidates, as well as post-transplant recipient care, in the year 2000 and 2002. The new European Renal Best Practice board decided in 2009 that these guidelines needed updating. In order to avoid duplication of efforts with kidney disease improving global outcomes, which published in 2009 clinical practice guidelines on the post-transplant care of kidney transplant recipients, we did not address these issues in the present guidelines.The guideline was developed following a rigorous methodological approach: (i) identification of clinical questions, (ii) prioritization of questions, (iii) systematic literature review and critical appraisal of available evidence and (iv) formulation of recommendations and grading according to Grades of Recommendation Assessment, Development, and Evaluation (GRADE). The strength of each recommendation is rated 1 or 2, with 1 being a 'We recommend' statement, and 2 being a 'We suggest' statement. In addition, each statement is assigned an overall grade for the quality of evidence: A (high), B (moderate), C (low) or D (very low). The guideline makes recommendations for the evaluation of the kidney transplant candidate as well as the potential deceased and living donor, the immunological work-up of kidney donors and recipients and perioperative recipient care.All together, the work group issued 112 statements. There were 51 (45%) recommendations graded '1', 18 (16%) were graded '2' and 43 (38%) statements were not graded. There were 0 (0%) recommendations graded '1A', 15 (13%) were '1B', 19 (17%) '1C' and 17 (15%) '1D'. None (0%) were graded '2A', 1 (0.9%) was '2B', 8 (7%) were '2C' and 9 (8%) '2D'. Limitations of the evidence, especially the lack of definitive clinical outcome trials, are discussed and suggestions are provided for future research.We present here the complete recommendations about the evaluation of the kidney transplant candidate as well as the potential deceased and living donor, the immunological work-up of kidney donors and recipients and the perioperative recipient care. We hope that this document will help caregivers to improve the quality of care they deliver to patients. The full version with methods, rationale and references is published in Nephrol Dial Transplant (2013) 28: i1-i71; doi: 10.1093/ndt/gft218 and can be downloaded freely from http://www.oxfordjournals.org/our_journals/ndt/era_edta.html.

Meeting Report: International nephrology days - In honor of the 75(th) anniversary of acad. Momir Polenakovic and 50 years of scientific work, 26-27 September 2014.

The International Nephrology Days in honor of the 75(th) anniversary of Academician Momir Polenakovic and 50 years of his scientific work were held in the Macedonian Academy of Sciences and Arts (MASA) on 26 and 27 September 2014. Organizers of the meeting were the Macedonian Academy of Sciences and Arts and the Macedonian Society of Nephrology, Dialysis, Transplantation and Artificial Organs (MSNDTAO). The days were programmed with the VII Macedonian-Croatian Nephrology Meeting and the Continuing Medical Education (CME) Course on "Renal Replacement Therapy - when & how - update on the outcome and cost-efficacy" organized by the MSNDTAO in cooperation with the European Renal Association (ERA-EDTA). Prominent academicians, researchers and nephrologists from Europe and neighboring countries contributed with their lectures and discussion at this scientific event. On September 26, 2014 the opening talk was given by Acad. V. Kambovski, President of the MASA, about the Life and Work of Academician Momir Polenakovic. In honor of his anniversary and valuable scientific opus, during the meeting Acad. Momir Polenakovic was awarded with Certificate of the European Renal Association (ERA-EDTA) for his significant role in the development of nephrology in the Balkan region and couple of other diplomas and acknowledgement. Prof. Polenakovic is founder of the MSNDTAO and his lifetime honorary president.

Biopsy of the transplanted kidney--role of protocol biopsies.

Traditionally, renal allograft biopsies were performed mainly in the setting of acute graft dysfunction. Recently, there has been a change of paradigms. Several reports suggested that acute rejection of the graft and chronic allograft nephropathy are often subclinical without any deterioration in the graft function. This raises the issue of biopsies in functionally stable allografts (e.g. protocol biopsies) and the clinically useful information they provide. Namely, recent reports provide evidence in favour of treating biopsy-proven subclinical rejections. Moreover, by early identification of chronic histological lesions, protocol biopsies give an opportunity for individualized immunosuppressive regimen and use of targeted therapeutic strategies, in order to prevent chronic allograft dysfunction and improve long-term graft outcome. In this review, diagnostic, therapeutic and research benefit information on protocol biopsies performed in stable kidney recipients are described.

Kidney transplantation in emerging countries: do we know all issues?

Although it seems that end stage renal disease (ESRD) therapies gradually become more accessible in the developing world, yet, the vast majority of people living in those areas do not have access to dialysis and especially transplantation because of the economic and technological inequality as compared with the developed world. Despite the great advantage in survival and considerable socioeconomic advantages of transplantation vs. dialysis, there is a widespread recognition that the growing gap between organ supply and demand will continue into the foreseeable future. Several reasons might be considered in this regard as: insufficient data on the topic in the public domain, inadequate governmental financial resources, lack of public awareness, education and motivation for organ donation as well as the low number of organized teams of transplant surgeons and nephrologists, and lack of organizational infrastructure, i.e. coordinators. The defined priorities for the future in terms of improving living donor transplantation, composition of the official waiting lists and registries of transplant recipients and living donors and the role of transplant professionals have been discussed. In conclusion, whatever the governmental support is, as professionals, we should just reinforce our efforts to help our patients as best as we can in the current situation.

Efficacy and tolerability of hyaluronic acid, tea tree oil and methyl-sulfonyl-methane in a new gel medical device for treatment of haemorrhoids in a double-blind, placebo-controlled clinical trial.

Topical formulations are widely used in anti-haemorrhoidal treatment, but often lacking controlled clinical trials. Here, we report the results from a controlled clinical trial performed with a new gel medical device (Proctoial) containing hyaluronic acid with tea tree oil and methyl-sulfonyl-methane as major components. The total number of 36 haemorrhoidal patients (grade 1-3) was enrolled in a double-blind, placebo-controlled clinical trial and divided into 2 equal parallel groups. The anal pain, pain during defecation, visible bleeding, pruritus and irritation/inflammation were recorded before and after 14-day treatment using a visual analogue scale both by the investigators and by the patients. Safety and tolerability of the treatments were also recorded. The new gel medical device statistically significantly reduced all the symptoms after the treatment compared to placebo. The results indicated also a very good tolerability and safety of the treatments.

Achievements in CKD-MBD guidelines targets: is there a progress in the implementation practice?

BACKGROUND: Guidelines should help the practicing nephrologists to reduce the variability in diagnostic and treatment strategies, and achieve the best possible patients' outcomes. The aim of our study was to look at the treatment strategies and the shortcomings in the implementation of the chronic kidney disease mineral and bone disorder (CKD-MBD) KDOQI guidelines in dialysis units across the Republic of Macedonia in 2009, and to analyze trends with regard to our previous analysis from 2005. METHODS: A questionnaire was sent in 2009 to all dialysis units in our country for data concerning CKD-MBD in dialysis patients. This study included 742 patients, comparable with the reply we got on the same our 2005 survey, with a total of 588 patients. We collected the last 6 months mean values of biochemical parameters [calcium (Ca), phosphate (P), and intact parathyroid hormone (iPTH)], as well as treatment data including dialysate Ca concentration, phosphate binding agents, and vitamin D doses. RESULTS: The majority of patients in both surveys had values within the target ranges for all parameters, except for iPTH, which was <150 pg/ml in most patients, in both reports. Compared to the 2005 study, in 2009 we found a significantly improved control of all four biochemical parameters, but a greater proportion of patients within guidelines targets was found only for serum Ca (79 vs. 67.4%, P<0.05). Treatment with low Ca dialysate concentration of 1.25 mmol/L continued to be an underused option (3.7 vs. 6.1%), while the 1.75 mmol/L was still the standard dialysate in the majority of patients (57.7 vs. 64.2%). The dose of calcium carbonate was significantly reduced (2.77±1.71 vs. 3.06±1.54, P<0.01) in 2009 compared to 2005. The mean of the achieved targets increased significantly in 2009 (2.33±1.05 vs. 2.13±1.03, P<0.01). CONCLUSION: There was an improved control of all bone and mineral parameters in our dialysis units, following the publication of the CKD-MBD KDOQI guidelines. In order to improve the iPTH values, a more frequent use of low Ca dialysate (1.25 mmol/L) and of non-calcium-based phosphate binders in this small subset of patients should be implemented, as recommended by the guidelines. Individualization of the CKD-MBD management may be successful, even when newer treatment options are not available. Finally, the guidelines implementation process should be a continuous and self-monitored process, with the help of periodic surveys.

Brain natriuretic peptide between traditional and nontraditional risk factors in hemodialysis patients: analysis of cardiovascular mortality in a two-year follow-up.

BACKGROUND: The ability of brain natriuretic peptide (BNP) together with other traditional and nontraditional risk factors to predict cardiovascular (CV) mortality in hemodialysis (HD) patients has not been well established. The aim of this prospective study was to determine the predictive cutoff values of baseline measurement of BNP along with the known CV disease risk factors to predict all-cause and CV mortality in HD patients. METHODS: BNP concentration before HD was measured in 125 prevalent HD patients (age 53.0 ± 13.5 years, HD vintage 75.2 ± 61.0 months). In addition, several traditional CV risk factors (blood pressure, dyslipidemia, diabetes mellitus, body mass index, left ventricular hypertrophy) and uremia/dialysis-related CV risk factors (anemia, calcium and phosphate impairment, malnutrition, inflammation, ultrafiltration, HD duration, Kt/V) were examined. RESULTS: During the 2-year follow-up, we lost 28 out of 125 patients (22.5%), with CV disease (65.7%) being the main cause of mortality. The cutoff point for BNP, as predictor of the clinical outcome, according to the ROC curve was 1,194 pg/ml for CV mortality with sensitivity and specificity of 63 and 65%, respectively (AUC 0.61 and confidence interval (CI) 95% 0.47-0.75). Kaplan-Meier analysis showed that all-cause (log-rank, p = 0.002) and CV mortality (log-rank, p = 0.001) were the cause of a significantly lower survival in patients with a mean BNP >1,200 pg/ml. The univariate Cox regression analysis found the following factors to be predictors of all-cause mortality: hemoglobin (<110 g/l), phosphorus (>1.78 mmol/l), albumin (<40 g/l), C-reactive protein (CRP ≥ 10 mg/l), BNP (>1,200 pg/ml) and cardiac ejection fraction (≤ 55%). The multivariate Cox regression analyses demonstrated that only CRP ≥ 10 mg/l with a hazard ratio (HR) 6.82 (CI 95% 1.86-24.9, p = 0.004) and BNP >1,200 pg/ml with HR 5.79 (CI 95% 1.58-21.3, p = 0.004) were predictors of all-cause mortality. BNP >1,200 pg/ml with HR 13.52 (CI 95% 1.68-108.9, p = 0.014) was found to be an even stronger predictor of CV mortality than CRP ≥ 10 mg/l with HR 6.53 (CI 95% 1.35-31.6, p = 0.020). CONCLUSIONS: Our study pointed out that BNP >1,200 pg/ml as a marker of cardiac dysfunction and CRP ≥ 10 mg/l as a marker of inflammation identify HD patients at increased risk of CV mortality.

Unusual clinical presentation of brown tumor in hemodialysis patients: two case reports.

Brown tumor or osteoclastoma is a lytic bone tumor, which is common in secondary hyperparathyroidism (1.5-13%) in chronic dialysis patients, mainly in those with untreated renal osteodystrophy. Brown tumor appears as a result from excess osteoclast activity and consists of collections of osteoclasts intermixed with fibrous tissue and poorly mineralized woven bone. It can be manifested as a single or multiple bone lesions. Although invasive, it has no malignant potential and should be distinguished from giant cell tumors of the bone. Two unusual cases of brown tumor in dialysis patients are reported. We present a first patient with five subtotal parathyroidectomies between 2002 and 2009 and a tendency toward recurrence of secondary hyperparathyroidism (sHPTH). The double MRI check up could not reveal any ectopic parathyroid gland. Although the patient had permanently high PTH values, serum calcium level was never above the normal range. However, the brown tumor in the cervical spine was destructing the cervical vertebrae and required surgical intervention. Despite the conservative treatment with calcium and non-calcium-based binders and various forms of vitamin D, the patient's clinical and biochemical condition improved only after the use of cinacalcet. The second patient, a 58-years-old female on chronic hemodialysis since 1998, was found with high PTH serum levels in 2009. The development of sHPTH was scintigraphically confirmed and surgically treated. During the late 2008, she started feeling pain, numbness and swelling of the 3rd right hand finger, prior to the full clinical manifestation of the tumor. The CT scan of the right hand showed osteolytic changes and soft tissue destruction of the middle phalanx of the 3rd right hand finger. This formation corresponded to an unusual presentation of brown tumor associated with sHPTH. As expected, after the parathyroidectomy, there was no marked change in the destructed bone of the 3rd right hand finger middle phalanx, but only a gradual improvement in the subjective clinical condition of the patient. Based on these two reports, we would recommend that in cases of severe or recurrent sHPTH either total parathyroidectomy or early administration of calcimimetics should be considered. Furthermore, the implementation of regular checkup and treatment according to the KDIGO guidelines should be advised and clinical appearance of any bone tumor immediately checked for an association with sHPTH, which is a rather common entity in dialysis patients.

Screening for prostate cancer: a controversy or fact.

BACKGROUND: Adenocarcinoma of the prostate is the most frequent malignancy in men and the second leading cause of death in the male population worldwide. The screening for prostate cancer allows early diagnosis of prostate malignancy before the individual presents with symptoms. The early stage of the disease is easier to manage by different therapeutic modalities. AIM: The aim of this review is to evaluate the reasons and facts for enthusiasm and positive approach towards the clinical decision about whether to screen or not male patients for early detection of prostate cancer. METHODS: We performed a computerized MEDLINE search followed by a manual bibliographic review of cross-references. These reports were analyzed and the important findings were summarized. We analyzed the methods and schedule of screening, as well as advantages and disadvantages of the prostate cancer screening. RESULTS: There were more than a hundred studies on prostate cancer screening performed but only a few are eligible for a decisive conclusion concerning the prostate cancer screening issue. We reviewed the screening methods, the schedule of screening, the advantages and disadvantages of prostate cancer screening. CONCLUSION: The role for prostate cancer screening is not established yet. Definite proof of screening should be assumed as a decrease in the death rate of that cancer due to screening activity.

Does prostate specific antigen density correlates with aggressiveness of the prostate cancer?

BACKGROUND: As already documented, a high prostate specific antigen in men with normal size of prostate gland is more likely to be associated with an aggressive cancer as compared to others with the same prostate specific antigen and a large gland size. In this retrospective study we tested the association between Prostate Specific Antigen Density (PSAD) and tumor aggressiveness in patients with clinically localized Prostate Cancer (PCa) surgically treated by radical prostatectomy. METHODS: We evaluated data from patients records in a cohort of 72 patients who underwent radical prostatectomy between January 2000 and June 2007. PSAD was calculated as ratio between the preoperative total prostatic specific antigen (PSA) in nanograms per milliliter with the prostate weight (PW) of prostatectomized specimen in grams or prostate volume measured with ultrasound (US). The patients were stratified into four PSAD categories: 0.1-0.15, 0.16- 0.20, 0.21-0.5 and greater than 0.51 ng/ml/gr. Parameters that were included into analysis were: PSA, measurement of the prostate volume by ultrasound (preoperatively) and prostate weight, pathological tumor stage, Gleason sum, Gleason grade, metastatic lymph nodes, seminal vesicle involvement and organ confine disease (postoperatively). Worsening of the clinicopathological properties was defined as aggressiveness. RESULTS: There was a significant correlation between US-PSAD and PW-PSAD (p<0.001). In US-PSAD categories the statistic tests found significant correlation with the primary tumor (R=0.303, p<0.01), metastatic lymph nodes (R=0.331, p<0.01), and the organ confine disease (R=0.296, p<0.05). The PW-PSAD categories correlated significantly with the pathologic findings from other parameters. Hence, a statistically significant correlation was found with Gleason sum (R=0.246, p<0.05), Gleason grade (R=0.234, p<0.05), primary tumor (R=0.285, p<0.05), metastatic lymph node (R=0.287, p<0.05) and organ confine disease (R=0.303, p<0.01). CONCLUSIONS: Prostate specific antigen density measurement is useful tool for the assessment of the degree of aggressiveness in clinically localized prostate cancer, and further investigation regarding its possible use as a prediction marker is justified.

Strategies to manage low-bone turnover.

A change in paradigm occurred lately whereby not hypocalcemia but hypercalcemia and positive calcium balance were considered negative factors. Namely, the use of calcium- based binders in combination with vitamin D analogues, has been shown to lead to an over-suppression of parathyroid hormone (PTH) and development of low-bone turnover adynamic bone disease (ABD). The changing prevalence of various types of bone diseases from a high to low-bone turnover goes in line with the presence of increased risk for vascular calcification (VC), morbidity and mortality in the dialysis population. The attenuation of the previous great expectations in calcium-based phosphate binders and vitamin D-analogues entailed a new treatment strategy to preserve bone and vascular health. Hence, a new evidence for treatment of ABD with various types of non calcium based binders and low calcium dialysate is presented. Sevelamer treatment has reduced calcium concentration and increased PTH levels, resulting in the improvement of markers of bone turnover, increased bone formation and improved trabecular architecture, providing a slower progression of VC. Data on lanthanum beneficial effect on ABD histology have been demonstrated in long-term clinical studies. Although there is a slow release of lanthanum from its bone deposits after discontinuation of the treatment and no association with aluminium- like bone toxicity, there is still an ongoing scientific debate about its long-term toxic potential. Finally, reducing the number of calcium based binders and low calcium dialysate (1.25 mmol/l) has been reported to have an impact on the evolution towards markers reflecting higher bone turnover. Then, adoption of the non calcium-based binders should be reserved to high risk patients with ABD and progression of vascular calcifications associated with increased morbidity and mortality.

Factors associated with various arterial calcifications in haemodialysis patients.

BACKGROUND: Haemodialysis (HD) patients are at increased risk of the development of arterial intimal (AIC) and medial calcification (AMC). The aim of our study was to analyze the association between the pre-defined potential risk factors and the status of various arterial calcifications in our HD patients. METHODS: In a cross-sectional study of 150 patients (91 male, mean age 54.55 +/- 12.46 yrs, HD duration 104.77 +/- 68.02 mths) we first determined the presence of AIC and AMC using plain radiography of the pelvis. We then compared the percentages of different radiogram findings in patients stratified according to various cut-off levels or the codes of each clinical and biochemical parameter (mean value of one year laboratory data recorded in the files). RESULTS: We determined arterial calcifications in 77.3% of our patients (AIC in 45.3%, AMC in 32%). The significantly higher frequencies of arterial calcifications of both groups (AIC and/or AMC) and isolated AIC presence were found in patients older than 55 at inclusion and 45 at the start of treatment with HD, with a serum C-reactive protein (CRP) > 4.5 mg/L, predominantly of male gender with diabetes. The patients with a significantly higher occurrence of arterial calcifications had lower percentages of total serum calcium (Ca) levels but within the K/DOQI guideline recommendations. Also, we found a significantly higher proportion of isolated AIC presence in the group of patients with corrected total serum Ca levels > 2.35 mmol/L and serum intact parathyroid hormone (iPTH) levels out of the range proposed by K/DOQI guidelines. In parallel, a significantly higher percentage of absence of arterial calcifications (ACA) was obtained in the patients with corrected total serum Ca levels < 2.35 mmol/L, body mass index (BMI) < 23 kg/m(2), mean pulse pressure < 60 mmHg, blood leucocytes < 6.5 x 10(9)L and serum triglycerides < 1.8 mmol/L. Finally, we found a significantly higher presence of isolated AMC in patients with mean Kt/V < 1.3 (poor dialysis adequacy), serum triglycerides > 1.8 mmol/L and outside K/DOQI guideline achievements for corrected total serum Ca. In the 12 month period data analyzed, there were no significant differences in other risk factors such as the dose of prescribed calcium carbonate and vitamin D3, serum levels of albumin, cholesterol, phosphate (P) and Ca x P product. CONCLUSIONS: AIC and AMC were frequently present in our HD population. Age, gender, BMI, diabetes, pulse pressure, dialysis adequacy, serum CRP, triglycerides, Ca and iPTH, as well as blood leucocyte levels were associated with the occurrence of arterial calcifications in our HD patients.

New aspects of treatment of renal bone disease in dialysis patients.

The abnormalities in bone and mineral metabolism in chronic kidney disease patients are associated with an increased risk of fractures, vascular calcifications and cardiovascular diseases. A few decades ago hyperphosphatemia and the common development of secondary hyperparathyroidism were thought to be the main problem to deal with. Since dietary phosphate restriction and haemodialysis were not proven to be sufficient measures to reduce phosphorus, phosphate-binding therapy has been widely instituted as a treatment option. Various types of phosphate binders employed over the years have contributed to the changing spectrum of renal osteodystrophy from high to low bone turnover along with the shift from hypocalcemia and negative calcium balance towards hypercalcemia and the positive calcium balance. Thus, hypercalcemia instead of hyperphosphatemia is nowadays associated with the increased risk of vascular calcification, morbidity and mortality in the dialysis population. Besides the very expensive non-calcium based phosphate binders, at least two common tools may be helpful in the treatment of hypercalcemia and adynamic bone. A reduced daily use of calcium carbonate/acetate up to 1g per main meal is an easily manageable and inexpensive tool. The second option for stimulation of parathyroid gland activity and bone turnover is the lowering of the dialysate calcium concentration. In conclusion, an aggressive treatment of hyperphosphatemia and calcium overload might lead towards an opposite effect of hypoparathyroidism and hypercalcemia. Reasonable treatment strategies based on a careful monitoring should be employed in order to prevent related consequences and to contribute to a better long-term quality of life and survival of dialysis patients.

Radiological and "imaging" methods in TNM classification of non-small-cell lung cancer.

Lung cancer is the most common worldwide malignant disease according to its incidence and mortality. The aim of our study was to evaluate the diagnostic value of the radiological and imaging methods, according to the TNM classification, compared to postoperative histological diagnosis. Thirty-seven patients with pulmonary carcinoma were studied prospectively using native chest radiography (PA and LL view), computed tomography (CT) and magnetic resonance imaging (MRI) during ten days before thoracotomy. Radiological and imaging findings were reviewed separately and results were compared with surgical and pathohistological findings on the basis of the TNM classification. All patients underwent chest x-rays, CT was performed in 36 patients and MRI in 12 of them. Imaging methods (CT and MRI) showed more accuracy in sensitivity and specificity compared with the native chest radiography in a great percentage. Generally no statistically significant differences were found between the two imaging methods for the evaluation of tumour extent (T) or lymph node metastases (N). MRI was slightly superior to CT in determination of the chest wall extent of the tumour. In conclusion CT remains the imaging modality of choice both for assessing patients with abnormal chest radiographs suspected of having lung cancer, and in staging patients with histologically proven pulmonary carcinoma.

Do we have to treat subclinical rejections in early protocol renal allograft biopsies?

The aim of the present study was to evaluate whether treatment of subclinical, borderline rejections (SR/BR) or histological findings of chronic allograft nephropathy (CAN) in protocol biopsies in the first month posttransplantation after living related kidney transplantation has a beneficial effect on graft histology and renal function at 6 months. Among the 40 paired biopsies, only 6/80 showed no histological lesions. BR was found in 13/40 and 12/40, and SR in 15/40 and 21/40 of patients on the 1- and 6-month biopsies, respectively. The mean histological index/total sum of scores for acute and chronic changes (HI) increased at 6-month biopsy: 5.3 +/- 2.9 vs 7.8 +/- 3.6 (P < .001). Similarly, the mean sum of histological markers for chronicity (CAN score) of 2.1 +/- 1.5 increased to 4.6 +/- 2.3 (P < .001) on the 6-month biopsy. When divided according to whether there was treatment of BR and SR, the treated BR/SR group on 1-month biopsy had a mean HI score of 7.11 +/- 1.9, which remained almost the same (7.11 +/- 2.32) at 6 months. Among the untreated BR/SR group it increased from 4.95 +/- 1.99 to 8.16 +/- 4.30. However, there was no difference in graft function between the groups from 1 to 6 months. In conclusion, a protocol 1-month biopsy may be valuable to establish the prevalence of BR/SR in stable allografts. The presence of an untreated BR/SR upon a 1-month biopsy showed greater susceptibility for histological deterioration on the 6-month biopsy due to an accelerated CAN process.

First two AB-incompatible living kidney transplantations in the Balkans--should it be a procedure of choice in a developing country?

Kidney transplantation is the best available medical intervention for the treatment of end-stage renal failure. However, as a consequence of the growing gap between organ supply and demand, many patients die waiting for an organ each year. In order to increase the number of organs, living donor (LD) transplantation from unrelated and ABO-incompatible (ABOi) donors have been introduced over the last few decades. While in the past ABOi transplantation resulted in hyperacute or acute antibody-mediated rejection, the tremendous progress in this area in recent years has shown that it can be overcome by careful patient management, including protocols to remove or lower antibodies, along with stronger immunosuppression and intensive monitoring. The organ shortage problem is even more prominent in regions such as the Balkans where cadaver transplantation has not been well developed. In addition to the introduction of expanded criteria for living donation (elderly and marginal donors), we performed the first two ABOi/LD transplantations in the Balkans in the last 2 years using an already established preconditioning regimen and maintenance therapy with cyclosporine, mofetil mycophenolate and prednisolon. We report our modest experience of a case in which the patient developed lymphadenopathy, sarcomatosis and died after one year; and a second case with accelerated acute rejection and hemorrhagic necrosis with explantation of the graft after a month. Taking into account the high cost of the desensitization procedure and induction therapy as well as the need for intensive monitoring throughout the standardized procedures and facilities, we might reconsider whether ABOi living kidney transplantation should be a procedure of choice in developing countries.

Epidemiology of severe poisonings caused by ingestion of caustic substances.

Acute poisoning with corrosive substances can cause severe chemical injuries of the upper part of the gastrointestinal tract. They are most frequently localized in the oesophagus and stomach. If the patient survives the acute phase of poisoning, the regenerative response can result in oesophageal and/or gastric stenosis and a higher risk of oesophageal and stomach cancer. Seven-years clinical material was evaluated for this study (2000-2006) with a total number of 517 patients, hospitalized and treated at the Urgent Internal Medicine and Toxicology Clinic, University Clinical Centre, Skopje, Republic of Macedonia. The evaluation of the caustic poisonings was followed on the basis of anamnesis and hetero-anamnesis, physical examination of the patient, and status of the local changes to the oral mucosae, tongue, palate, and pharynx. The patients were assessed by the following techniques of visualization: urgent oesophagoduodenoscopy in the first 24 hours after the ingestion, control oesophagoduodenoscopy (15 and 25 days after ingestion), X-ray of oesophagus, gaster and duodenum with gastrograph (25-30 days after the ingestion), as well as a routine laboratory examination (blood count, urea, creatinine, enzyme, protein and lipid status, serum transferin, etc), following also the actual body mass index (BMI). The presented results show that the dominating patients were female [n = 368 patients (71.79 %), p < 0.001] and Christian by religion [n = 263 (50.87 %), p > 0.05], with the majority having had secondary education [n = 322 (62.28 %), p = 0.001]. The most frequently misused substance was chlorine hydrogen acid [n = 245 patients (47.38%)]., At the first urgent oesophagoduodenoscopy examination the majority of patients had II A (n = 190) and II B (n = 136) grade damage (x(2) = 44.0; p < 0.05). One hundred patients, or 19.34 %, were dismissed from the hospital with stenosis of the oesophagus and stomach. The high percentage of stenosis was the major factor in the invalidity of these patients. A high mortality of 8.69 % (p > 0.05) was also stated. Of 517 patients, 62 (11.99 %) were poisoned with concentrated acetic acid. In 37 patients (59.67 %) acute renal failure developed as an acute complication and four patients (6.5 %) died as a consequence of the disordered renal function and the need for active dialysis treatment. Recovery of the renal function was established in 93.5 % of the patients. A total number of 138 haemodialyses (3.7/patients) were performed. Acute corrosive poisonings represent a serious socio-economic problem, as well as a diagnostic and therapeutic problem. They appear most frequently in a population that is in a period of life when the person is most creative and efficient in terms of working capacity. The treatment is expensive and is an economic burden on the social community. Despite all the current therapeutic treatments and efforts made to decrease the mortality and late morbidity, intoxication with corrosive substances remains a difficult medical problem.