Hypertension and nephrology

[The role of vitamin D receptor and the risk reducing effect of vitamin D receptor agonists in chronic kidney disease]

KISS István, KULCSÁR Imre, BARABÁS Noémi, KERKOVITS Lóránt

OCTOBER 20, 2010

Hypertension and nephrology - 2010;14(05)

[Vitamin D3 is produced in the skin and is modified in the liver and kidney to the active metabolite form, 1,25-dyhydroxyvitamin D3 (calcitriol). Calcitriol binds to a nuclear receptor, the vitamin D receptor (VDR), and activates processes that bind to vitamin D. The classical effects of vitamin D receptor activator or agonist (VDRA) therapy for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease primarily involves suppressive effects on the parathyroid gland, and regulation of calcium and phosphorus absorption in the intestine an mobilization in bone. Several VDR agonists have been developed for the treatment of osteoporosis, hyperparathyroidism secondary to chronic kidney disease (CKD), and psoriasis. Secondary hyperparathyroidism (SHPT) is a common and serious consequence of CKD. SHPT is a complex condition characterized by a decline in 1,25-dihidroxi vitamin D and consequent VDR activation, abnormalities in serum calcium and phosphorus levels, parathyroid gland hyperplasia, elevated parathyroid hormone (PTH) secretion, and systemic mineral and bone abnormalities. There are three classes of drug used for treatment of SHPT (non-selective and selective VDR activators, and calcimimetics). Observational studies in hemodialysis patients report improved cardiovascular and allcause survival among those received VDRA therapy compared with those not on VDRA therapy. The survival benefits of selective VDRA paricalcitol appear to be linked to "non classical" action of VDRA, possibly through VDRA-mediated modulation of gene expression. VRDAs are reported to have beneficial effects such as anti-inflammatory and antithrombotic effects, inhibition of vascular calcification and stiffening, inhibition of vascular smooth muscle cell proliferation, and regression of left ventricular hypertrophy. VDRA are also reported to negatively regulate the renin-angiotensin system, which plays a key role in hypertension, myocardial infarction and stroke. Data from epidemiological, preclinical and clinical studies have shown that vitamin D and/or 25(OH) vitamin D deficiency is associated with increased risk for cardiovascular disease (CVD). The selective VDR agonists are associated direct protective effects on glomerular architecture and antiproteinuric effects in response to renal damage. Emerging evidence suggest that VDR plays important roles in modulating cardiovascular, immunological, metabolic and other function. Paricalcitol may prove to have a substantial beneficial effect on cardiac disease and its outcome in patients with CKD.]

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Hypertension and nephrology

[Recent developments in the diagnosis and therapy of haemolytic uremic syndrome. Part 1: Diagnosis and initial therapy]

PROHÁSZKA Zoltán, SZILÁGYI Ágnes, SZABÓ Melinda Zsuzsanna oh., RÉTI Marienn, REUSZ György

[In this summary an overview is offered on the recent developments of the investigation and the treatment of hemolytic uremic syndrome. Based on the recent developments in the understanding of the pathogenesis and on the novel diagnostics there is an increasing ability to identify the etiology of specific diagnostic sub-groups of the disease. This molecular etiology-based classification and sub-group diagnosis has substantial influence on the short-term and long-term management of the affected patients. The first part of our review focuses on the steps of first and second line diagnosis and the selection between available therapeutic options, and provides flow-charts for the daily work. The various aspects of the long-term management and disease monitoring in hemolytic uremic syndrome will be reviewed in a second article in the future.]

Hypertension and nephrology

[Biosimilar erythropoietins in nephrology - benedictio seu maledictio?]

KISS István

[Biological medicines of protein or polypeptide origin produced with biotechnology are far more complex in structure than the low molecular weight chemical ones. In conjunction with chemical drugs generic copies are completely the same, while in the field of biological medicines only similarity can be stated, as identical molecules cannot be produced. Spatial structure, isomers and side chains cause difference and for this reason these are called biosimilar drugs. Immunogenity of biosimilar drugs is very different and the risk of antibody production against them is diverse. Pure red cell aplasia, a rare side effect of erythropoietins is a life-threatening condition so every effort must be done for its prevention. Biosimilar drugs are not to be replaced with each other, and even the reference drugs should not be substituted in order to identify easily the side effects of each drug. Importantly financing should support these clinical principles namely a cheaper drug could be started as a new treatment but a former treatment should not be replaced because of cost sensitivity. It is important to provide the availability of the very expensive biologically active drugs to each patient but it is acceptable that the treatment should be as cost-effective as possible. Similarly to the generic copy program of chemical drugs biosimilar drugs are also important for the clinical practice, however their use needs appropriate regulation and farmacovigilance.]

Hypertension and nephrology

[Chronic kidney disease and atherosclerosis]

REIBER István

[Accelerated cardiovascular disease is a frequent complication of chronic kidney disease. Chronic kidney disease promotes hypertension and dyslipidaemia, which in turn can contribute to the progression of renal failure. Diabetic nephropathy is a leading cause of renal failure. Hypertension, dyslipidaemia and diabetes together are the major risk factors of the development of endothelial dysfunction and progression of atherosclerosis. Inflammatory mediators are often elevated and the renin-angiotensin system is frequently activated in chronic kidney disease. Promoters of calcification are increased and inhibitors are reduced, which favors vascular calcification, an important cause of vascular injury associated with end-stage renal disease. Accelerated atherosclerosis will then lead to increased prevalence of coronary artery disease, heart failure, stroke and peripheral arterial disease.]

Hypertension and nephrology

[Kidney transplantation in Hungary, 2010]

LANGER Róbert, TORONYI Éva

[Hungarian kidney transplantation has been established with three milestone operations. In 1902 Emerich Ullmann showed the technical feasibility of renal transplantation on dogs, and later the living donor transplant of András Németh in 1962 and the program starting operation of Ferenc Perner in 1973 already meant the real possibility for Hungarian patients. More than 5000 kidney transplantations were done since, and the operations are now made at the four university medical schools centers. In 2009 248 renal transplantations were done in our country (Budapest: 148, Szeged: 51, Pécs: 39, Debrecen: 34), from which 24 were living donor and nine combined kidney-pancreas cases. Despite the worsening financing situation in the health care system the numbers of transplantations are stable within a 15 year period, but this means a marked decrease in international comparison. In our country, the ratio of living donation is low, there is no paired donation, incompatible transplantation, the problems of hypersensitive patients are unresolved, and there is no old-for-old program. The solution to all of these problems could be joining to Eurotransplant, which is the definite wish of the transplant society based on the positive Slovenian and Croatian examples.]

Hypertension and nephrology

[Dialysis in Hungary: 2003-2009]

KULCSÁR Imre, SZEGEDI János, LADÁNYI Erzsébet, TÖRÖK Marietta, TÚRI Sándor, KISS István

[The authors show the data of Hungarian dialysis statistics from 2003 to 2009. The questionnaire-based data collection was made by the Dialysis Committee of the Hungarian Society of Nephrology. The number of all patients entered in the dialysis program increased by 45.2% over six years (an average of 7.5% per year) and the number of new ones increased by 51.2% (8.5% per year). The increase in number of patients treated with haemodialysis was 39% (6.5% per year) in this period. The increase in the number of patients in the peritoneal dialysis program was extremely high: 80.6% (an average of 13.4% per year). The population incidence of new dialysed patients was 332/1 million in 2003 and 483/1 million in 2009. The population point prevalence at the end of the year was 437/1 million in 2003, but 607/1 million in 2009. The penetrance of peritoneal dialysis was 12.8% in 2009. Differences exist among the regions of Hungary in the number of patients, the penetrance of peritoneal dialysis and the prevalence of renal replacement therapies. Among patients suffering in conditions which lead to end stage renal disease the proportion of patients with diabetic or hypertensive nephropathies is increasing and the proprtion of patients with glomerular or tubulointerstitial damage is decreasing. The number (and rate) of the elderly people is growing continuously year by year. The rate of patients on waiting list for renal transplantation is decreasing (the rate was 20% in 2003, but only 10.7% in 2009). There is also a slow decrease in the number of the annual renal transplantations. The mortality rate of chronically dialysed patients shows a little increase. Five dialysis centres for paediatric patients and 58 for adults have been functioning in Hungary by the end of 2009. In average 106 patients have been treated by each Hungarian dialysis centre in contrast to the optimal of 60 persons. The number of nephrologists increased between 2003 and 2007, but slightly decreased since then. The case is similar regarding nephrological nurses.]

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