Hypertension and nephrology

[Role of calcimimetics in the treatment of secondary hyperparathyroidism in dialysed patients ]

SEPTEMBER 20, 2011

Hypertension and nephrology - 2011;15(04)

[The authors summarize the pathophysiology and main clinical features of the condition which was previously called secondary hyperparathyroidism (sHTP) and renal osteodystrophy (ROD) in chronic kidney disease patients. Recently this entity has been renamed as chronic kidney disease - mineral and bone disorders (CKD-MBD), which more accurately describes the complexity of the condition including changes in laboratory parameters, bone turnover and vascular calcification. The calcium sensing receptor (CaR) plays a central role in the pathophysiology of CKD-MBD. Calcimimetics, which increase the sensitivity of the CaR to calcium, represent a novel and potentially advantageous class of medications for the management of the condition. Currently cinacalcet is the only available calcimimetic for clinical practice. Robust preclinical and human clinical trials have demonstrated that calcimimetics increase the expression of calcium sensing and the vitamin D receptors, attenuate parathyroid hyperplasia, decrease all four laboratory parameters (iPTH, Ca, P and Ca × P), optimize bone turnover and may slow down vascular calcification. As a results, cinacalcet based therapy is preferable and beneficial strategy in the treatment of CKD-MBD in patients on maintenance dialysis.]

COMMENTS

0 comments

Further articles in this publication

Hypertension and nephrology

[Association of body composition and mortality in patients on maintenance dialysis]

UJSZÁSZI Ákos, KALANTAR-ZADEH Kamyar, MOLNÁR Miklós Zsolt

[Overweight [body mass index (BMI) = 25-30 kg/m2] and obesity (BMI ≥30 kg/m2) have become mass phenomena with a pronounced upward trend in prevalence in most countries throughout the world and are associated with increased cardiovascular risk and poor survival. In patients with end stage renal disease (ESRD) undergoing maintenance hemodialysis an “obesity paradox” has been consistently reported, i.e., a higher BMI is incrementally associated with better survival. Whereas this “reverse epidemiology” of obesity is relatively consistent in maintenance hemodialysis patients, studies in peritoneal dialysis patients have yielded mixed results. However, BMI is unable to differentiate between adiposity and muscle mass and may not be an acceptable metric to assess the body composition of ESRD patients. Assessing lean body mass, in particular skeletal muscle, and fat mass separately are needed in ESRD patients using gold standard techniques such as imaging techniques. Alternatively, inexpensive and routinely measured surrogate markers such as serum creatinine, waist and hip circumference or mid-arm muscle circumference can be used. We have reviewed and summarized salient recent data pertaining to body composition and clinical outcomes about the association of survival and body composition in peritoneal and hemodialysis patients.]

Hypertension and nephrology

[Coexistence of diabetes mellitus and (nephrogenic) diabetes insipidus]

RADÓ János

[In this report we describe a patient with nephrogenic diabetes insipidus associated with diabetes mellitus. The 44-year-old patient was seen by us for the first time when she was 5 years old in 1972, as a member of a family with nephrogenic diabetes insipidus associated with other congenital renal diseases. Surveying five generations by family history we found in four genarations (supported with investigations in three genarations) five patients suffering from the combination of renal tubular acidosis, polycystic kidney disease and nephrogenic diabetes insipidus. Nephrogenic diabetes insipidus was confirmed with blood and urine osmolality measurements performed during water deprivation as well as during administration of synthetic vasopressins. Renal tubular acidosis was confirmed with blood and urine gas analysis and bicarbonate and acid loadings. Polycystic kidney disease was diagnosed with physical findings, imaging and in the case of a deceased patient by necropsy. The autosomal dominant trait was obvious in the family characteristic to the distal renal tubular acidosis and polycystic kidney disease. The clinical picture was dominated by the polydipsia and polyuria. Significant interindividual differences were found in vazopressin resistance responsible for the nephrogenic diabetes insipidus. In our patient metabolic syndrome (diabetes mellitus, hypertension, obesity, abnormal lipid and uric acid levels) and disturbances in calcium metabolism (nephrolithiasis and osteomalacia) were associated with renal disorders. The 39 year long observation period (with some discontinuations) the patient was treated almost without pauses with bicarbonate, desmopressin, thiazide, NSAIDs supplemented with the administration of vitamin D3, antidiabetics etc. Despite of the listed and other diseases the patient’s mood is quite good, her physical condition is relatively satisfactory while she is working regularly physically.]

Hypertension and nephrology

[Advantages of fixed combinations in the treatment of hypertensive patients]

FARSANG Csaba

[In 60-70% of patients with hypertension, a significant decrease in blood pressure can only be achieved by a combination of antihypertensive drugs. International as well as national guidelines emphasise the numerous advantages and the importance of combination treatment. Fixed combinations are particularly advantageous, as their use improves patients’ compliance. This paper summarises the available information on the possible combinations of the nine major antihypertensive drug groups distributed in Hungary, and for details the results published on the recently approved and introduced fixed combination of telmisartan and amlodipine.]

Hypertension and nephrology

[Two cases of hyponatremic hypertensive syndrome due to unilateral stenosis of the renal artery]

LAKATOS Orsolya, GYÖRKE Zsuzsanna, VAJDA Péter, JUHÁSZ Zsolt, DEGRELL Péter, SULYOK Endre, MOLNÁR Dénes

[Eighty percent of secondary hypertension in childhood is of a renal cause, and ten percent of these cases are due to renovascular disease. Rarely, unilateral stenosis of the renal artery can lead to hyponatremic hypertensive syndrome as a consequence of critical renal ischemia, which is characterized by serious hypertension, electrolyte disturbances (hyponatremia, hypokalemia), polyuria and increased activity of the renin angiotensin aldosterone system. The authors review the cases of a 27-month-old and a 3-year-old boy, in whom HHS developed due to a severe stricture of the renal artery. With the removal of the nonfunctioning kidney, polyuria and electrolyte disturbances resolved, the level of renin normalised, and anti-hypertensive therapy could be gradually ceased. The authors emphasize that the measurement of blood pressure in children is crucial, especially in cases of polyuria, polydipsia, proteinuria and failure to thrive. Early recognition is very important, and a kidney with a function under ten percent must be removed before hypertension can be stabilized. In case of an electrolyte disturbance associated with hypertension, the possibility of hyponatremic hypertensive syndrome must be considered in childhood as well.]

Hypertension and nephrology

[Prominents in Hungarian nephrology Professor Gyula Petrányi (1912–2000). I. part]

SZALAY László

[A nation can only survive and keep its identity through its traditions. This is why the initiative to launch this series coming from professor János Radó is worthy of attention. Gyula Petrányi is an outstanding personality in 20th century internal medicine, to be more precise in nephrology and immunology, his activity being wide-ranging. The first part of the current summmary of his work deals with a tribute to his personality, and his role in immunomodularity treatment in glomerulonephritis. The second part shall cover his role in spreading renal biopsy, screening and caring kidney patients, dialysis, in developing kidney patients’ care, furthermore in clinicopharmacology and renal transplantation.]

All articles in the issue

Related contents

Hypertension and nephrology

[Prevalence of bone abnormalities and soft tissue calcification and their determining factors in dialyzed patients]

KISS Zoltán, AMBRUS Csaba, SZABÓ András, SZEGEDI János, BALLA József, TÖRÖK Marietta, LADÁNYI Erzsébet, CSIKY Botond, ÁRKOSSY Ottó, TÚRI Sándor, KULCSÁR Imre, KISS István

[Disturbances of bone and mineral metabolism are frequent complications of chronic kidney disease. In the last decades, increasing evidence of both pathophysiological and epidemiological nature support the relationship between bone disease and soft tissue calcification. In this current research, we analysed characteristics, determining factors and relationship of these two complications in a nationwide, cross-sectional cohort of dialysed patients. We collected demographical data (age, gender, body weight, height, diabetes, type of dialysis), laboratory results (serum parathormone, calcium, phosphat, albumin levels) and the presence of diabetes mellitus, bone abnormalities and soft-tissue calcification in patients on maintenance dialysis in 2010. The prevalence of bone abnormalities and soft tissue calcification followed similar pattern: both prevalences were high when parathormone <150 pg/ml (42.9% and 51.5%, respectively) or >500 pg/ml (44.2% and 55.5%) and they were significantly lower when parathormone was between 150-500 pg/ml (30.7% and 47.4%). In a multivariate logistic regression model, independent predictors of bone abnormalities were low (<150 pg/ml) and high (>500 pg/ml) parathormone levels (p<0.001), orhemodialysis (vs peritoneal dialysis) (p<0.001), age (p<0.001) and diabetes (p<0.001). In a similar statistical model, predictors of soft tissue calcification were also low (<65 pg/ml) (p<0.01) and high (>500 pg/ml) parathormone levels (p<0.001), hemodialysis (p<0.001), age (p<0.001), diabetes (p<0.001) and serum calcium level greater than 2.4 mmol/l (p<0.05). In summary, there was a U-shaped relationship between increasing serum parathormone levels and prevalence of bone abnormalities and soft tissue calcification in ESRD patients on maintenance dialysis. Further research and long term follow up are needed in order to reveal more detailed relationship among the two diseases and their determining factors.]

Hypertension and nephrology

[Terciary hyperparathyreosis or not? ? You cannot solve it alone: combined treatment in severe osteitis fibrosa cystica]

HERSZÉNYI Eszter, PATÓ Éva, SZALAY László, BÍRÓ Zsolt, György Andrea, DEÁK György

[Phosphate retention, consequential rise of the phosphaturic fibroblast growth factor-23 that decreases the level of calcitriol resulting in hypocalcemia facilitates the development of secondary hyperparathyroidism (sHPT) in chronic kidney disease (CKD). Hyperphosphatemia, hypocalcemia and low calcitriol level result in increasing secretion of parathormone (PTH). While sHPT occures frequently in CKD, the development of therapy-resistant and hypercalcemic tertiary hyperparathyroidism is rare due to current therapeutic approaches. We present the case of a 41 year old, treated schizophrenic, hemodialized male patient with severe osteitis fibrosa cystica, severe hyperparathyroidism (PTH 2500 pg/ml) - considered to be tertiary - and with repeated pathologic fractures. While hospitalized, the patient was under supervised, combined therapy with the vitamin D receptor activator paricalcitol and the calcimimetic cinacalcet that resulted in marked decrease of PTH level to 1589 pg/ml. However, after discharge from the hospital due to the lack of compliance he failed to take his medications and PTH had risen to the initial level. This case demonstrates that severe hyperparathyroidism thought to be therapy resistant responds well to a combination of paricalcitol and cinacalcet however, patient compliance is essential to therapeutic success.]

Ca&Bone

[The pathophysiological role of the cell surface calcium-sensing receptor New clinical entities and drugs, potential therapeutic targets]

TÓTH Miklós

[The extracellular calcium-sensing receptor (CaSR) was recognized and cloned a decade ago. It is a G-proteincoupled receptor that plays an essential role in the regulation of extracellular calcium homeostasis. Diseases known as familial hypocalciuric hypercalcemia, neonatal severe primary hyperparathyroidism and autosomal dominant hypocalcemia are the consequences of naturally occurring mutations of the CaSR. However, the spectrum of the CaSR diseases became more complex with the recognition of both hypo- and hypercalcemic states caused by anti-CaSR autoantibodies. Activating anti-CaSR autoantibodies have been implicated in the pathogenesis of isolated idiopathic hypoparathyroidism and of hypoparathyroidism associated with autoimmune polyglandular syndromes. Inactivating CaSR autoantibodies may cause fluctuating hypercalcemic disorder that resembles primary hyperparathyroidism. The CaSR recently became one of the most intensively investigated target of potential new drugs. Cinacalcet has been approved for the treatment of secondary hyperparathyroidism associated with chronic renal insufficiency and for the management of inoperable or metastatic parathyroid carcinoma.The CaSR may be one of the main molecular target of strontium ranelate, wich is a new antiosteoporotic compound.]