Abstract Background The existence of adynamic bone disease (ABD) as most prevalent form of renal osteodystrophy in recent years and its reduced ability to handle an exogenous calcium load has implied ...a higher risk for vascular and soft-tissue calcifications. The effect of low dialysate calcium (LCD) on parathyroid hormone (PTH) secretion in ABD patients has not yet sufficiently been clarified. This randomized, prospective study aimed to compare the effects of LCD and high calcium dialysate (HCD) on the evolution of bone and mineral parameters related to ABD in dialysis patients. Methods 52 out of 60 patients with predialysis intact PTH < 100 pg/ml completed this study and were equally distributed over LCD (1.25 mmol/l) or HCD (1.75 mmol/l) treatment. The duration of the study was 6 months and the only peroral phosphate binder administered was calcium carbonate. Total and ionised calcium were measured monthly in serum before and after dialysis while serum parameters relevant to bone were measured at the enrollment and at 3-month intervals. Results There were no differences in predialysis mean phosphate or calcium × phosphorus product (Ca × P). The most common side effects of both treatments were comparable. Hypotension occurred in 16% and 17% and cramps in 6% and 8% of the dialysis sessions, in the HCD and LCD group, respectively. The groups did not differ in the mean tCa before dialysis, but this parameter was significantly higher in the HCD group vs. LCD at the end of dialysis (2.59 ± 0.18 vs. 2.44 ± 0.19 mmol/l; p < 0.01). The patients of the HCD group also had a significantly higher mean iCa both before (1.08 ± 0.05 vs. 1.04 ± 0.06 mmol/l; p = 0.02) and at the end of dialysis (1.18 ± 0.04 vs. 1.48 ± 0.04 mmol/l; p < 0.01). There were no differences within the LCD group between baseline and end of dialysis treatment values of tCa and iCa. However, the mean tCa and iCa were markedly increased at the end of dialysis in the HDC group 2.40 ± 0.21 vs. 2.59 ± 0.18 mmol/l ( p < 0.01); 1.08 ± 0.05 vs. 1.18 ± 0.04 mmol/l ( p < 0.01). Mean serum levels of iPTH and total alkaline phosphatase in the LCD group were increased at 3 months and at the end of the study compared with the baseline levels (38.6 ± 22.9 vs. 63.3 ± 46.0 vs. 78.6 ± 44.7 pg/ml); (59.5 ± 18.7 vs. 75.9 ± 26.7 vs. 84.0 ± 35.4 U/l), respectively, and bone alkaline phosphatase increased also only after 6 months of treatment (23.4 ± 7.3 U/l vs. 35.6 ± 22.3). The bone markers in the HCD group did not change. At the end of the study all bone parameters in the LCD group were significantly higher than in the HCD group. Conclusion There was an evolution towards parameters reflecting higher bone turnover in patients treated with dialysate calcium of 1.25 mmol/l, probably by prevention of a positive calcium balance and enabling sustained stimulation of PTH secretion. Hence, LCD might be considered a valuable therapeutic option for ABD patients.
Purpose
The complexity of chronic kidney disease–mineral and bone disorder (CKD–MBD) led to many preclinical and clinical trials. The role of sclerostin in renal pathophysiology remained unresolved, ...and question whether sclerostin is related to cardiovascular (CV) outcome in patients with CKD is still open. Our aim was to evaluate the possible association between serum sclerostin levels and carotid intima-media thickness (CIMT) in CV pathophysiology through various CKD stages.
Methods
Eighty-eight patients in various CKD stages were involved in this analysis. CKD-EPI (Chronic kidney disease Epidemiology Collaboration Equation) was used to estimate glomerular filtration rate (eGFR). CKD–MBD parameters were determined in patients’ serum after an overnight fasting. Early atherosclerosis was assessed by ultrasound measurement of CIMT. In order to assess the association between serum sclerostin with other CKD–MBD parameters and CIMT, correlation and regression analyses were performed.
Results
Mean age was 62.84 ± 11.37 years and 56% were female. Mean values of serum sclerostin were 1.67 ± 0.44 ng/ml. Negative correlation was noticed with serum calcium and phosphate product (CaxP), alkaline phosphatase (ALP), intact parathyroid hormone (iPTH), serum creatinine, and HbA1c level. There was no association with FGF23, CIMT, and carotid atherosclerotic plaque occurence. Serum levels of sclerostin were significantly higher in female patients compared to males (
p
< 0.001).
Conclusion
Advanced CKD showed a trend of declining sclerostin levels and significantly higher CIMT levels. Serum sclerostin was not associated with CIMT. More studies are needed in order to reveal the exact role of sclerostin in the complexity of CKD–MBD pathophysiological mechanism.
Various biochemical markers have been evaluated in dialysis patients for the diagnosis of renal osteodystrophy (ROD). However, their value in predialysis patients with end-stage renal failure (ESRF) ...is not yet clear.
Bone histomorphometric evaluation was performed and biochemical markers of bone turnover were determined in serum of an unselected predialysis ESRF population (N = 84).
Significant (P < 0.005) differences between the five groups with ROD (ie, normal bone N = 32, adynamic bone ABD; N = 19, hyperparathyroidism N = 8, osteomalacia OM; N = 10, and mixed lesion N = 15) were noted for intact parathyroid hormone, total (TAP) and bone alkaline phosphatase (BAP), osteocalcin (OC), and serum calcium levels. Serum creatinine and (deoxy)pyridinoline levels did not differ between groups. For the diagnosis of ABD, an OC level of 41 μg/L or less (≤7.0 nmol/L) had a sensitivity of 83% and specificity of 67%. The positive predictive value (PPV) for the population under study was 47%. The combination of an OC level of 41 ng/L or less (≤7.0 nmol/L) with a BAP level of 23 U/L or less increased the sensitivity, specificity, and PPV to 72%, 89%, and 77%, respectively. ABD and normal bone taken as one group could be detected best by a BAP level of 25 U/L or less and TAP level of 84 U/L or less, showing sensitivities of 72% and 88% and specificities of 76% and 60%, corresponding with PPVs of 89% and 85%, respectively. In the absence of aluminum or strontium exposure, serum calcium level was found to be a useful index for the diagnosis of OM.
OC, TAP, BAP, and serum calcium levels are useful in the diagnosis of ABD, normal bone, and OM in predialysis patients with ESRF.
Background. During the last few years the spectrum of renal osteodystrophy (ROD) in dialysis patients has been studied thoroughly and the prevalence of the various types of ROD has changed ...considerably. Whereas until a decade ago most patients presented with secondary hyperparathyroidism (HPTH), adynamic bone (ABD) has become the most common lesion within the dialysis population over the last few years. Much less is known about the spectrum of ROD in end‐stage renal failure (ESRF) patients not yet on dialysis. Methods. Transiliac bone biopsies were taken in an unselected group of 84 ESRF patients (44 male, age 54±12 years) before enrolment in a dialysis programme. All patients were recruited within a time period of 10 months from various centres (n=18) in Macedonia. Calcium carbonate was the only prescribed medication in patients followed up by the outpatient clinic. Results. HPTH was found in only 9% of the patients, whilst ABD appeared to be the most frequent renal bone disease as it was observed in 23% of the cases next to normal bone (38%). A relatively high number of patients (n=10; 12%) fulfilled the criteria of osteomalacia (OM). Mixed osteodystrophy (MX) was diagnosed in 18% of the subjects. There was no significant difference between groups in age, creatinine, or serum and bone strontium and aluminium levels. Patient characteristics associated with ABD included male gender and diabetes, whilst OM was associated with older age (>58 years). Conclusions. In an unselected population of ESRF patients already, 62% of them have an abnormal bone histology. ABD is the most prevalent type of ROD in this population. In the absence of aluminium or strontium accumulation the relatively high prevalence of a low bone turnover as expressed by either normal bone or ABD and OM is striking.
Abstract
Background and Aims
HLA compatibility between donor and recipient is an important factor that influences graft outcomes after kidney transplantation. Increasing number of class I (HLA-AB) ...and class II (HLA-DR) mismatches are associated with an increased risk of acute rejection and graft loss. Recent developments have increased our understanding of the structural basis of HLA antigenicity and may allow accurate evaluation of the immunogenic potential of broad antigen HLA mismatches.
The immunogenicity of HLA antigens is determined by continuous and discontinuous short sequences of amino acids that form the antibody-accessible regions within each HLA allele known as epitopes. HLAMatchmaker, a computer algorithm that calculates the number of epitope mismatches between donors and recipients by considering each HLA allele as a combination of distinct epitopes known as triplets (continuous amino acid sequences) or eplets (closely located contiguous amino acid sequences).
Method
A total number of 55 adult patients with LDKT were included in the study. The inclusion criteria: first transplantation of one organ - kidney, use of living donor related or unrelated, emotionally related (spouses) donor. Data concerning donor - sex, age of the donor, type of donation (related or unrelated donor), and data concerning the recipients: sex, age, hemodialysis vintage, underlying disease, type of immunosuppressive therapy, were analyzed. The number of eplet HLA mismatches for each recipient and donor pair at HLA class I (HLA-AB) and class II (HLA-DR) loci was calculated using HLAMatchmaker (Version 1.2)
Results
In our study we have included 55 patients. 44 patients have related and 11 have unrelated donors. From the group of related donors 31 patients were haploidentycal, with 3 HLA miss match, in the group of unrelated donors-recipients 5 of them have 6 miss match. According HLA MM triplets Class 1 + 2 < or> 20 we have devided 2 groups, but no statistical difference on the graft function was observed in the follow up period.
Three acute rejections were reported in the group of patients with HLA miss match triplets Class 1 + 2> 20.
Conclusion
An increasing number of epitope HLA mismatches is associated with an increased risk of acute rejection. Triplet HLA mismatches may provide better risk stratification for acute rejection and graft survival among those who are otherwise classified as low immunological risk at the broad antigen level.
Abstract Prof. Dr. Dimitar T. Hrisoho was born on June 11, 1924 in Bitola, R. Macedonia. He died in Struga on September 22, 1986, and was buried in Skopje. He completed primary and secondary ...education in Bitola. He graduated from the Medical Faculty in Belgrade in 1951 as one of the best students of his generation (average grade of 9.75). In 1953 he was employed at the Internal Clinic of the Medical Faculty in Skopje, where in 1955 he passed the specialist exam in internal medicine. He successfully defended his habilitation “Polyarthritis chronica evolutiva” and his doctoral dissertation “Clinical features of Vitina nephropathy”. The doctoral dissertation indicates that Vitina nephropathy is a new site of the Balkan Endemic Nephropathy entity and that more genetic testing of patients were needed. Based on numerous clinical and scientific researches published in over 200 papers, he was elected a Full Professor of internal medicine at the Medical Faculty of the Ss. Cyril and Methodius University in Skopje in 1971. In 1970, he formed the nephrology section of the Macedonian Medical Association (MMA), which grew into the nephrology Association of MMA. Through the Association, the education of the medical staff from the field of nephrology was performed. He also set up a bio-cybernetics association. He achieved his vision and desire to transfer and apply the achievements of modern nephrology in the diagnosis and treatment of kidney patients in Macedonia at the Clinic of Nephrology of the Medical Faculty in Skopje, which was the first specialized institution established for examination and treatment of kidney patients in the former Yugoslavia and the Balkans. The Clinic educated nephrological staff and examined and treated kidney patients with new methods and drugs that positively affected the development of nephrology as a subspecialty of the internal medicine. D. Hrisoho was actively involved in the introduction of new methods for examination of kidney patients, as well as in the treatment of patients with acute and chronic renal insufficiency with dialysis since 1965. He also participated in the first two kidney transplantations from living donors performed in 1977. He wrote a chapter on “kidney examination”, printed in the book of Prof. A. J. Ignjatovski “Fundamentals of Internal Propedeutics” Part III, published by “Prosvetno delo”, 1963, in Skopje. This is the first text to investigate a patient with kidney disease published in a textbook in R. Macedonia. In 1984 he published the textbook “Clinical Nephrology” printed by the University of the Ss. Cyril and Methodius University in Skopje. Prof. D. Hrisoho organized the First Scientific Meeting of Yugoslav Nephrologists with international participation, from 26 to 28 September 1977, in Struga, R. Macedonia. The meeting was attended by prominent nephrologists from the former Yugoslavia, the Balkans, Europe and the United States, among them: J.S. Cameron from UK, J.L. Funck-Brentano from France, M. Burg and P. Ivanovich from the USA, R. Kluthe from Germany and A. Puchlev from Bulgaria. The scientific meeting was the largest nephrology event until then organized in the former Yugoslavia. The meeting provided an exchange of experiences with world-renowned nephrologists. D. Hrisoho presented the paper Artificial intelligence in nephrology. The author tried to apply bio-cybernetics in nephrology. Prof. D. Hrisoho was Vice Dean of the Medical Faculty in Skopje in the period 1963-1965 and Vice Rector of the University of the Ss. Cyril and Methodius University in Skopje in the period 1974-1975. Prof. Hrisoho was also active in socio-political organizations. For his medical, educational and scientific activities he received several awards and recognitions in the country and abroad. Thus, the work of Prof. D. Hrisoho was permanently embedded in the nephrology of R. Macedonia.
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