A multicenter study on the affects of lanthanum carbonate (Fosrenol™) and calcium carbonate on renal bone disease in dialysis patients.
Lanthanum carbonate (LC) (Fosrenol™) is a novel new treatment ...for hyperphosphatemia. In this phase III, open-label study, we compared the effects of LC and calcium carbonate (CC) on the evolution of renal osteodystrophy (ROD) in dialysis patients.
Ninety-eight patients were randomized to LC (N = 49) or CC (N = 49). Bone biopsies were taken at baseline and after one year of treatment. Acceptable paired biopsies were available for static and dynamic histomorphometry studies in 33 LC and 30CC patients. Blood samples were taken at regular intervals for biochemical analysis and adverse events were monitored.
LC was well tolerated and serum phosphate levels were well controlled in both treatment groups. The incidence of hypercalcemia was lower in the LC group (6% vs. 49% for CC). At baseline, subtypes of ROD were similarly distributed in both groups, with mixed ROD being most common. At one-year follow-up in the LC group, 5 of 7 patients with baseline low bone turnover (either adynamic bone or osteomalacia), and 4 of 5 patients with baseline hyperparathyroidism, had evolved toward a normalization of their bone turnover. Only one lanthanum-treated patient evolved toward adynamic bone compared with 6 patients in the CC group. In the LC group, the number of patients having either adynamic bone, osteomalacia, or hyperpara decreased overall from 12 (36%) at baseline to 6 (18%), while in the calcium group, the number of patients with these types of ROD increased from 13 (43%) to 16 (53%).
LC is a poorly absorbed, well-tolerated, and efficient phosphate binder. LC-treated dialysis patients show almost no evolution toward low bone turnover over one year (unlike CC-treated patients), nor do they experience any aluminum-like effects on bone.
Abnormal bone in chronic kidney disease (CKD) may adversely affect vascular calcification via disordered calcium and phosphate metabolism. In this context, bone health should be viewed as a ...prerequisite for the successful prevention/treatment of vascular calcification (VC) along with controlled parathyroid hormone (PTH) secretion, the use of calcium-based phosphate binders and vitamin D therapy. In CKD patients, VC occurs more frequently and progresses more rapidly than in the general population, and is associated with increased cardiovascular disease (CVD) morbidity and mortality. A number of therapies aimed at reducing PTH concentration are associated with an increase of calcaemia and Ca x P product, e.g. calcium-containing phosphate binders or active vitamin D. The introduction of calcium-free phosphate binders has reduced calcium load, attenuating VC and improving trabecular bone content. In addition, a major breakthrough has been achieved through the use of calcimimetics, as first agents which lower PTH without increasing the concentrations of serum calcium and phosphate. Nowadays, it is becoming evident that even early stage CKD is recognised as an independent CVD risk factor. Moreover, the excess of CVD among dialysis patients cannot be explained entirely on the basis of abnormal mineral and bone metabolism. Hence, much controversy has surrounded the cost-effectiveness of treatment with the new phosphate-binding drugs as well as new vitamin D analogs and calcimimetics. Thus, it seems prudent and reasonable that maintaining bone health and mineral homeostasis should rely on some modifications of standard phosphate binding and calcitriol therapy. Hypophosphataemia and hypercalcaemia in adynamic bone disease (ABD) might be treated by reducing the number of calcium carbonate/acetate tablets in order to increase serum phosphate and decrease serum calcium, which, in turn, might positively stimulate PTH secretion. The same rationale is assumed for the use of a low calcium dialysate. On the other hand, secondary hyperparathyroidism with hyperphosphataemia and hypocalcaemia should be treated with a substantial number of calcium carbonate/acetate tablets in combination with calcitriol and low calcium dialysate in order to decrease serum phosphate and maintain the Ca x P product within K/DOQI guidelines (<4.4 mmol l(-1)). Finally, it becomes apparent that prevention, with judicious use of calcium-based binders, vitamin D and a low calcium dialysate without adverse effects on Ca x P or oversuppression of PTH, provides the best management of VC and mineral and bone disorder in CKD patients.
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.
Because of the limited chance of receiving a kidney transplant (for several well-known reasons), a lot of desperate dialysis patients procure an unrelated donor kidney transplant against all medical ...advice. This type of renal paid transplantation is associated with many surgical complications and invasive opportunistic infections that increase the morbidity and mortality in this group of transplant recipients. In this report, we describe a case of a 22-year-old girl with a segmental infarction of the graft lower pole and a complete pyelo-ureteral necrosis as a consequence of some vascular damage, complicated by a pathohistological finding of an invasive candidiasis. Despite the successful surgical pyelovesical anastomosis and the good recovery of the patient and the kidney, long term prognosis remains poor. The lack of information from the transplanting center regarding both donor and recipient and the associated, unacceptable risks on the graft and patient survival in unrelated, paid transplant recipients reinforce the standpoint that this practice should be abandoned.
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.
Bone biopsy in the diagnosis of renal osteodystrophy Spasovski, Goce B
Prilozi - Makedonska akademija na naukite i umetnostite. Oddelenie za biološki i medicinski nauki,
2004, Volume:
25, Issue:
1-2
Journal Article
When renal disease develops, mineral and vitamin D homeostasis is disrupted, resulting in diverse manifestations in bone cells and structure as well as the rate of bone turnover. In ESRF when ...patients require chronic maintenance dialysis, nearly all of them have abnormal bone histology named renal osteodystrophy (ROD). On the other hand, survival rates of patients on dialysis have increased with improved dialytic therapy and the resultant increased duration of dialysis has led to a rise in renal osteodystrophy. Because this metabolic bone disease can produce fractures, bone pain, and deformities late in the course of the disease, prevention and early treatment are essential. Serum PTH levels are commonly used to assess bone turnover in dialyzed patients. However, it is found that serum PTH levels between 65 and 450 pg/ml seen in the majority of dialysis patients are not predictive of the underlying bone disease. To date, bone biopsy is the most powerful and informative diagnostic tool to provide important information on precisely the type of renal osteodystrophy affecting patients, the degree of severity of the lesions, and the presence and amount of aluminum and strontium deposition in bone. Bone biopsy is not only useful in clinical settings but also in research to assess the effects of therapies on bone. Although considered as an invasive procedure, bone biopsy has been proven as safe and free from major complications besides pain, haematoma or wound infections, but the operator's experience and skill is important in minimizing morbidity. Alternatives to bone biopsy continue to be pursued, but the non-invasive bone markers have not been proven to hold sufficient diagnostic performance related to the bone turnover, mineralization process and bone cell abnormality. At present however, the transiliac bone biopsy remains the golden standard in the diagnosis of renal osteodystrophy.
Abstract
The strengths and the limitations of research activities currently present in Europe are explored in order to outline how to proceed in the near future. Epidemiological and clinical research ...and public policy in Europe are generally considered to be comprehensive and successful, and the European Renal Association – European Dialysis and Transplant Association (ERA-EDTA) is playing a key role in the field of nephrology research. The Nephrology and Public Policy Committee (NPPC) aims to improve the current situation and translation into public policy by planning eight research topics to be supported in the coming 5 years by ERA-EDTA.
The General Data Protection Regulation (GDPR) became binding law in the European Union Member States in 2018, as a step toward harmonizing personal data protection legislation in the European Union. ...The Regulation governs almost all types of personal data processing, hence, also, those pertaining to biomedical research. The purpose of this article is to highlight the main practical issues related to data and biological sample sharing that biomedical researchers face regularly, and to specify how these are addressed in the context of GDPR, after consulting with ethics/legal experts. We identify areas in which clarifications of the GDPR are needed, particularly those related to consent requirements by study participants. Amendments should target the following: (1) restricting exceptions based on national laws and increasing harmonization, (2) confirming the concept of broad consent, and (3) defining a roadmap for secondary use of data. These changes will be achieved by acknowledged learned societies in the field taking the lead in preparing a document giving guidance for the optimal interpretation of the GDPR, which will be finalized following a period of commenting by a broad multistakeholder audience. In parallel, promoting engagement and education of the public in the relevant issues (such as different consent types or residual risk for re-identification), on both local/national and international levels, is considered critical for advancement. We hope that this article will open this broad discussion involving all major stakeholders, toward optimizing the GDPR and allowing a harmonized transnational research approach.
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