**8. References**

Ahlenstiel, T., Pape, L., Ehrich, J. H., & Kuhlmann, M. K. (2010). Self-adjustment of phosphate binder dose to meal phosphorus content improves management of

for the use in this situation and cost-intensive if used for many years (Kruse et al., 2005;

Therefore, we believe that a good and early control of sHPT prior to kidney transplantation is mandatory. This should be initially done using all medical options including cinacalcet, but if unsuccessful in control of severe sHPT proceeding straight to PTX for an optimal and cost-effective treatment. Randomized clinical trials directly comparing medical with surgical

To avoid severe postoperative hypocalcemia ("hungry bone syndrome), pre-/peri- and postoperative calcium and calcitriol supplementation (e.g. 1 to 2 g elemental calcium thrice a day, 1 to 4 µg calcitriol per day; parenteral calcium substitution if symptomatic hypocalcemia is present with 1 to 2 mg elemental calcium/kg/h) must be guaranteed along with frequent controls of serum calcium levels. In case of recurrent or persistent hyperparathyroidism after parathyroidectomy, cinacalcet has been shown to be a viable and

A near-neutral calcium flux could be expected in patients with a dialysate calcium concentration of 1.25 mmol/L (2.5 mEq/L), although there is considerable interindividual variability among patients (Hou et al., 1991; Argiles et al., 1993). Based on calcium kinetic modelling even lower dialysate calcium concentrations of 1.0 mmol/L (2.0 mEq/L) might be needed to avoid net positive calcium balance (Gotch et al., 2010). The risks of hemodynamic instability and cardiac rhythm disturbances with a very low dialysate calcium concentration must be kept in mind (Drueke & Touam, 2009). Overall calcium balance is influenced by dietary calcium intake, vitamin D level, calcium-containing phosphate binders, use of VDRA and calcimimetics and dialysate calcium concentration. Therefore, selecting an individual dialysate calcium concentration is based on various parameters and must always be a compromise between the need to guarantee cardiovascular stability during the hemodialysis session and the goal to maintain normal bone turnover and mineralization in

Whereas there are insufficient high-quality randomized controlled trials in the field, this shortcoming should not lead to a nihilistic approach to the relevant clinical problems of hemodialysis patients with sHPT. Nevertheless, because of insufficient clinical data, a single treatment modality, be it phosphorus binders, vitamin D substitution with inactive forms or vitamin D receptor activators, calcimimetics or parathyroidectomy may not claim to be uniformly superior to the others, and a wider therapeutic window often prompts the use of a combination of these options and individualization of sHPT management. The ultimate goal is to improve the very poor survival of hemodialysis patients, so any suggested

Ahlenstiel, T., Pape, L., Ehrich, J. H., & Kuhlmann, M. K. (2010). Self-adjustment of

phosphate binder dose to meal phosphorus content improves management of

order to avoid bone pain and fractures but avoid extraskeletal calcification.

approach for the management of sHPT should be tested.

Serra et al., 2005; Srinivas et al., 2006; Zitt et al., 2007).

therapy of sHPT are lacking.

**7. Summary** 

**8. References** 

safe treatment option (Zitt et al., 2010).

**6. Dialysate calcium concentration** 

hyperphosphataemia in children with chronic kidney disease. *Nephrol Dial Transplant* 25(10): pp. 3241-3249


Management of Secondary Hyperparathyroidism in Hemodialysis Patients 345

Giangrande, A., Castiglioni, A., Solbiati, L., & Allaria, P. (1992). Ultrasound-guided

Giovannucci, E. (2008). Vitamin D status and cancer incidence and mortality. *Adv Exp Med* 

Goldsmith, D. J., Covic, A., Fouque, D., Locatelli, F., Olgaard, K., Rodriguez, M., Spasovski,

Goodman, W. G., Goldin, J., Kuizon, B. D., Yoon, C., Gales, B., Sider, D., Wang, Y., Chung, J.,

Gotch, F. A., Kotanko, P., Thijssen, S., & Levin, N. W.. (2010). The KDIGO guideline for

Holick, M. F. (2005). Vitamin D for health and in chronic kidney disease. *Semin Dial* 18(4):

Hou, S. H., Zhao, J., Ellman, C. F., Hu, J., Griffin, Z., Spiegel, D. M., & Bourdeau, J. E. (1991).

Isakova, T., Gutierrez, O. M., Chang, Y., Shah, A., Tamez, H., Smith, K., Thadhani, R., &

Jean, G., Souberbielle, J. C., & Chazot, C. (2009). Monthly cholecalciferol administration in

Johnson, W. J., McCarthy, J. T., van Heerden, J. A., Sterioff, S., Grant, C. S., & Kao, P. C.

K/DOQI (2003). K/DOQI clinical practice guidelines for bone metabolism and disease in

KDIGO (2009). KDIGO clinical practice guideline for the diagnosis, evaluation, prevention,

Kitaoka, M., Fukagawa, M., Ogata, E., & Kurokawa, K. (1994). Reduction of functioning

Koller, H., Zitt, E., Staudacher, G., Neyer, U., Mayer, G.,& Rosenkranz, A. R. (2004). Variable

Kruse, A. E., Eisenberger, U., Frey, F. J., & Mohaupt, M. G. (2005). The calcimimetic

supplementation. *Nephrol Dial Transplant* 24(12): pp. 3799-3805

chronic kidney disease. *Am J Kidney Dis* 42(4 Suppl 3): pp. S1-201

parathyroid hormone assays. *Clin Nephrol* 61(5): pp. 337-343

hyperparathyroidism. *Nephrol Dial Transplant* 20: pp. 1311-1314

hyperparathyroidism. *Nephrol Dial Transplant* 7(5): pp. 412-421

dialysis. *N Engl J Med* 342(20): pp. 1478-1483

*Am J Kidney Dis* 18(2): pp. 217-224

*Kidney Int Suppl*(113): pp. S1-130

*Nephrol* 20(2): pp. 388-396

84(1): pp. 23-32

46(4): pp. 1110-1117

hemodialysis patients. *Kidney Int* 78(4): pp. 343-350

*Biol* 624: pp. 31-42

3831

pp. 266-275

percutaneous fine-needle ethanol injection into parathyroid glands in secondary

G., Urena, P., Zoccali, C., London, G. M., & Vanholder, R. (2010). Endorsement of the Kidney Disease Improving Global Outcomes (KDIGO) Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) Guidelines: a European Renal Best Practice (ERBP) commentary statement. *Nephrol Dial Transplant* 25(12): pp. 3823-

Emerick, A., Greaser, L., Elashoff, R. M., & Salusky, I. B. (2000). Coronary-artery calcification in young adults with end-stage renal disease who are undergoing

dialysate calcium will result in an increased incidence of calcium accumulation in

Calcium and phosphorus fluxes during hemodialysis with low calcium dialysate.

Wolf, M. (2009). Phosphorus binders and survival on hemodialysis. *J Am Soc* 

haemodialysis patients: a simple and efficient strategy for vitamin D

(1988). Results of subtotal parathyroidectomy in hemodialysis patients. *Am J Med*

and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD).

parathyroid cell mass by ethanol injection in chronic dialysis patients. *Kidney Int*

parathyroid hormone(1-84)/carboxylterminal PTH ratios detected by 4 novel

cinacalcet normalizes serum calcium in renal transplant patients with persistent


Cozzolino, M., Mazzaferro, S., & Brandenburg, V. (2011). The treatment of

Culleton, B. F., Walsh, M., Klarenbach, S. W., Mortis, G., Scott-Douglas, N., Quinn, R. R.,

Cunningham, J., Danese, M., Olson, K., Klassen, P., & Chertow, G. M. (2005). Effects of the

Cunningham, J. & Zehnder D. (2011). New Vitamin D analogs and changing therapeutic

Danese, M. D., Belozeroff, V., Smirnakis, K., & Rothman, K. J. (2008). Consistent control of

Drueke, T. B. & Touam M. (2009). Calcium balance in haemodialysis--do not lower the

Evenepoel, P., Claes, K., Kuypers, D., Maes, B., Bammens, B., & Vanrenterghem Y. (2004).

Foley, R. N., Li, S., Liu, J., Gilbertson, D. T., Chen, S. C., & Collins, A. J. (2005). The fall and

Fouque, D., Vennegoor, M.,ter Wee, P., Wanner, C., Basci, A., Canaud, B., Haage, P., Konner,

Fukagawa, M., Tominaga, Y., Kitaoka, M., Kakuta, T., & Kurokawa, K. (1999). Medical and surgical aspects of parathyroidectomy. *Kidney Int Suppl* 73: pp. 65-69 Gagne, E. R., Urena, P., Leite-Silva, S., Zingraff, J., Chevalier, A., Sarfati, E., Dubost, C., &

Gasparri, G., Camandona, M., & Dei Poli, M. (2001). Secondary and tertiary

hemodialysis patients. *J Am Soc Nephrol* 3(4): pp. 1008-1017

randomized controlled trial. *JAMA* 298(11): pp. 1291-1299

*Nephrol Dial Transplant* 26(2): pp. 402-407

paradigms. *Kidney Int* 79(7): 702-707

*J Am Soc Nephrol* 3(6): pp. 1718-1725

*Nephrol* 16(1): pp. 210-218

*Ann Surg* 233(1): pp. 65-69

Suppl 2: pp. 45-87

6(4): pp. 913-921

3(5): pp. 1423-9

pp. 2990-2993

hyperphosphataemia in CKD: calcium-based or calcium-free phosphate binders?

Tonelli, M., Donnelly, S., Friedrich, M. G., Kumar, A., Mahallati, H., Hemmelgarn, B. R., & Manns, B. J. (2007). Effect of frequent nocturnal hemodialysis vs conventional hemodialysis on left ventricular mass and quality of life: a

calcimimetic cinacalcet HCl on cardiovascular disease, fracture, and health-related quality of life in secondary hyperparathyroidism. *Kidney Int* 68(4): pp. 1793-1800 Cunningham, J., Locatelli, F., & Rodriguez, M. (2011). Secondary hyperparathyroidism:

pathogenesis, disease progression, and therapeutic options. *Clin J Am Soc Nephrol* 

mineral and bone disorder in incident hemodialysis patients. *Clin J Am Soc Nephrol* 

dialysate calcium concentration too much (con part). *Nephrol Dial Transplant* 24(10):

Natural history of parathyroid function and calcium metabolism after kidney transplantation: a single-centre study. *Nephrol Dial Transplant* 19: pp. 1281-1287 Fishbane, S., Shapiro, W. B., Corry, D. B., Vicks, S. L., Roppolo, M., Rappaport, K., Ling, X.,

Goodman, W. G., Turner, S., & Charytan, C. (2008). Cinacalcet HCl and concurrent low-dose vitamin D improves treatment of secondary hyperparathyroidism in dialysis patients compared with vitamin D alone: the ACHIEVE study results. *Clin* 

rise of parathyroidectomy in U.S. hemodialysis patients, 1992 to 2002. *J Am Soc* 

K., Kooman, J., Martin-Malo, A., Pedrini, L., Pizzarelli, F., Tattersall, J., Tordoir, J., & Vanholder, R. (2007). EBPG guideline on nutrition. *Nephrol Dial Transplant* 22

Drueke, T. B. (1992). Short- and long-term efficacy of total parathyroidectomy with immediate autografting compared with subtotal parathyroidectomy in

hyperparathyroidism: causes of recurrent disease after 446 parathyroidectomies.


Management of Secondary Hyperparathyroidism in Hemodialysis Patients 347

Noori, N., Kalantar-Zadeh, K., Kovesdy, C. P., Bross, R., Benner, D., & Kopple, J. D. (2010).

mortality in hemodialysis patients. *Clin J Am Soc Nephrol* 5(4): pp. 683-692 Pelletier, S., Roth, H., Bouchet, J. L., Drueke, T., London, G., & Fouque, D. (2010). Mineral

Raggi, P., Boulay, A., Chasan-Taber, S., Amin, N., Dillon, M., Burke, S. K., & Chertow, G. M.

Rodriguez, M. & Lorenzo V. (2009). Parathyroid hormone, a uremic toxin. *Semin Dial* 22(4):

Serra, A. L., Schwarz, A. A., Wick, F. H., Marti, H.P., & Wuthrich, R. P. (2005). Successful

persistent hyperparathyroidism. *Nephrol Dial Transplant* 20: pp. 1315-1319 Sherman, R. A. & Mehta O. (2009). Dietary phosphorus restriction in dialysis patients:

Sherman, R. A. & Mehta O. (2009). Phosphorus and potassium content of enhanced meat

Shiizaki, K., Hatamura, I., Negi, S., Narukawa, N., Mizobuchi, M., Sakaguchi, T., Ooshima,

Shinaberger, C. S., Greenland, S., Kopple, J. D., Van Wyck, D., Mehrotra, R., Kovesdy, C. P.,

Souberbielle, J. C., Roth, H., & Fouque, D. P. (2010). Parathyroid hormone measurement in

Sprague, S. M., Evenepoel, P., Curzi, M. P., Gonzalez, M. T., Husserl, F. E., Kopyt, N.,

Srinivas, T. R., Schold, J. D., Womer, K.L., Kaplan, B., Howard, R. J., Bucci, C. M., & Meier-

Sullivan, C., Sayre, S. S., Leon, J. B., Machekano, R., Love, T. E., Porter, D., Marbury, M., &

transplantation. *Clin J Am Soc Nephro* 1: pp. 323-326.

25(9): pp. 3062-3070

pp. 363-836

992-1003

*Transplant* 13(8): pp. 2037-2040

*Am J Kidney Dis* 54(1): pp. 18-23

*Nephrol* 4(8): pp. 1370-1373

*Clin Nutr* 88(6): pp. 1511-1518.

4(9): pp. 1465-1476

635

CKD. *Kidney Int* 77(2): pp. 93-100

Association of dietary phosphorus intake and phosphorus to protein ratio with

and bone disease pattern in elderly haemodialysis patients. *Nephrol Dial Transplant*

(2002). Cardiac calcification in adult hemodialysis patients. A link between endstage renal disease and cardiovascular disease? *J Am Coll Cardiol* 39(4): pp. 695-701 Ribeiro, S., Ramos, A., Brandao, A., Rebelo, J. R., Guerra, A., Resina, C., Vila-Lobos, A.,

Carvalho, F., Remedio, F., & Ribeiro, F. (1998). Cardiac valve calcification in haemodialysis patients: role of calcium-phosphate metabolism. *Nephrol Dial* 

treatment of hypercalcemia with cinacalcet in renal transplant recipients with

potential impact of processed meat, poultry, and fish products as protein sources.

and poultry products: implications for patients who receive dialysis. *Clin J Am Soc* 

A., & Akizawa, T. (2003). Percutaneous maxacalcitol injection therapy regresses hyperplasia of parathyroid and induces apoptosis in uremia. *Kidney Int* 64(3): pp.

& Kalantar-Zadeh, K. (2008). Is controlling phosphorus by decreasing dietary protein intake beneficial or harmful in persons with chronic kidney disease? *Am J* 

Sterling, L. R., Mix, C., & Wong, G. (2009). Simultaneous control of PTH and CaxP Is sustained over three years of treatment with cinacalcet HCl. *Clin J Am Soc Nephrol*

Kriesche, H. U. (2006). Improvement in hypercalcemia with cinacalcet after kidney

Sehgal, A. R. (2009). Effect of food additives on hyperphosphatemia among patients with end-stage renal disease: a randomized controlled trial. *JAMA* 301(6): pp. 629-


Lacson, E., Jr., Ikizler, T. A., Lazarus, J. M., Teng, M., & Hakim, R. M. (2007). Potential

Lindberg, J. S., Culleton, B., Wong, G., Borah, M. F., Clark, R. V., Shapiro, W. B., Roger, S. D.,

Malberti, F., Marcelli, D., Conte, F., Limido, A., Spotti, D., & Locatelli, F. (2001).

Malluche, H. & Faugere M. C. (1990). Renal bone disease 1990: an unmet challenge for the

Meola, M., Petrucci, I., & Barsotti, G. (2009). Long-term treatment with cinacalcet and

Messa, P., Macario, F., Yaqoob, M., Bouman, K., Braun, J., von Albertini, B., Brink, H.,

Muller, D., Mehling, H., Otto, B., Bergmann-Lips, R., Luft, F., Jordan, J., Kettritz, R. (2007).

Navaneethan, S. D., Palmer, S. C., Craig, J. C., Elder, G. J., & Strippoli, G. F. (2009). Benefits

Naves-Diaz, M., Alvarez-Hernandez, D., Passlick-Deetjen, J., Guinsburg, A., Marelli, C.,

Nemeth, E. F., Steffey, M. E., Hammerland, L. G., Hung, B. C., Van Wagenen, B. C., DelMar,

secondary hyperparathyroidism. *Clin J Am Soc Nephrol* 3(1): pp. 36-45 Moe, S., Drueke, T., Cunningham, J., Goodman, W., Martin, K., Olgaard, K., Ott, S., Sprague,

hyperparathyroidism. *Nephrol Dial Transplant* 24(3): pp. 982-989

Outcomes (KDIGO). *Kidney Int* 69(11): pp. 1945-1953

controlled trials. *Am J Kidney Dis* 54(4): pp. 619-637

*Clin J Am Soc Nephrol* 2(6): pp. 1249-1254

double-blind, multicenter study. *J Am Soc Nephrol* 16(3): pp. 800-807 Locatelli, F., Dimkovic, N., Pontoriero, G., Spasovski, G., Pljesa, S., Kostic, S., Manning, A.,

and treatment costs. *J Ren Nutr* 17(6): pp. 363-371

study. *J Am Soc Nephrol* 12(6): pp. 1242-1248

nephrologist. *Kidney Int* 38(2): pp. 193-211

581

1070-1078

625-629

impact of nutritional intervention on end-stage renal disease hospitalization, death,

Husserl, F. E., Klassen, P. S., Guo, M. D., Albizem, M. B., & Coburn, J. W. (2005). Cinacalcet HCl, an oral calcimimetic agent for the treatment of secondary hyperparathyroidism in hemodialysis and peritoneal dialysis: a randomized,

Sano, H., & Nakajima, S. (2010). Effect of MCI-196 on serum phosphate and cholesterol levels in haemodialysis patients with hyperphosphataemia: a doubleblind, randomized, placebo-controlled study. *Nephrol Dial Transplant* 25(2): pp. 574-

Parathyroidectomy in patients on renal replacement therapy: an epidemiologic

conventional therapy reduces parathyroid hyperplasia in severe secondary

Maduell, F., Graf, H., Frazao, J. M., Bos, W. J., Torregrosa, V., Saha, H., Reichel, H., Wilkie, M., Zani, V. J., Molemans, B., Carter, D., & Locatelli, F. (2008). The OPTIMA study: assessing a new cinacalcet (Sensipar/Mimpara) treatment algorithm for

S., Lameire, N., & Eknoyan, G. (2006). Definition, evaluation, and classification of renal osteodystrophy: a position statement from Kidney Disease: Improving Global

Niacin lowers serum phosphate and increases HDL cholesterol in dialysis patients.

and harms of phosphate binders in CKD: a systematic review of randomized

Rodriguez-Puyol, D., & Cannata-Andia, J. B. (2008). Oral active vitamin D is associated with improved survival in hemodialysis patients. *Kidney Int* 74(8): pp.

E. G., & Balandrin, M. F. (1998). Calcimimetics with potent and selective activity on the parathyroid calcium receptor. *Proc Natl Acad Sci U S A* 95(7): pp. 4040-4045 Neyer, U., Hoerandner, H., Haid, A., Zimmermann, G., & Niederle, B. (2002). Total

parathyroidectomy with autotransplantation in renal hyperparathyroidism: low recurrence after intra-operative tissue selection. *Nephrol Dial Transplant* 17(4): pp.


**19** 

**Lipid and Lipoprotein** 

**Insufficiency: Review** 

*1Šafárik University, Medical School, Košice* 

*2Railway Hospital, Košice 3University of Prešov,* 

*Slovak Republic* 

*Faculty of Health Care, Prešov* 

**Abnormalities in Chronic Renal** 

Oliver Rácz1, Rudolf Gaško2 and Eleonóra Klímová3

**1. Introduction** 

**1.1 Kidney disease and cardiovascular mortality** 

quarter (Great Britain) or even two thirds (USA) of cases.

and Beaglehole, 2001, Go et al, 2004).

particular condition.

Cardiovascular disease is a leading case of mortality not only in the whole population but also in groups with different, noncardiovascular chronic conditions. Kidney disease is one of these and many patients with kidney disease paradoxically do not die from end stage kidney failure but from cardiovascular causes. Already mild or moderate renal impairment represents a considerable excess risk of cardiovascular mortality. The probability of premature death is even more striking in some subgroups of kidney patients – e.g. the cardiovascular mortality rate of young end stage renal disease (ESRD) patients is 500 times higher as compared with an age-matched control group. The situation is moreover complicated by the fact that traditional risk factors (the "Framingham factors") are of lesser predictive value in kidney disease than in general population (Foley et al, 1998, Magnus

To explain this dismal picture it is not sufficient to disclose that chronic kidney disease (CKD) and chronic renal insufficiency (CRI) is associated with accelerated atherosclerosis and abnormal lipid/lipoprotein metabolism (Felström et al., 2003, Lacquaniti, 2010). One should keep in mind that "CKD", "CRI" and "ESRD" are collective terms and the actual diseases and conditions behind them are manifold (Table 1). Some of them (e.g. diabetes mellitus and hypertension) have a profound effect on lipid metabolism and atherosclerosis independently from kidney function already before the manifestation of renal impairment. From the data in Table 1 is evident that diabetes and hypertension is behind ESRD in one

The natural history of each underlying disease is dependent on a wide range of factors and although the K/DOQI classification based on glomerulal filtration rate is a very useful one from practical point of view it does not reveal anything about the pathogenesis of the

