Update sulla letteratura Ca - P 

Grazie a Genzyme

Literature update:


Rodriguez M, Felsenfeld A.

PTH, FGF-23 and early CKD.

Nephrol Dial Transplant 2008;23(11):3391-3.



Bover J, Andres E, Lloret M, Aguilar A, Ballarin J.

Dietary and Pharmacological Control of Calcium and Phosphate Metabolism in Dialysis Patients.

Blood Purif 2009;27(4):369-386.


Chronic kidney disease-mineral and bone disorder is a new term defining a complex syndrome which underlines the need of a systemic approach to disturbances of calcium and phosphate metabolism in patients with renal failure. In recent years, the availability of new phosphorus binders and the appearance of new selective vitamin D receptor activators and calcimimetics have increased our current armamentarium and have changed previous paradigms. All these drugs can be used in combination, acting in distinct yet complementary pathways, with a resultant improvement in their individual clinical profile and reduction in secondary effects, while enhancing the achievement of clinical guideline targets. On the other hand, we should be aware that treatment costs are increasing and most of our knowledge is opinion-based. In this article, we shall consider rational recommendations on the control of calcium, phosphorus and parathyroid hormone while awaiting new evidence. We shall also briefly review some important related issues such as vascular calcification, adynamic bone disease, osteoporosis and the need of parathyroidectomy. Future guidelines may modify current recommendations, but we believe that the lack of an absolute evidence is not equivalent to the lack of awareness of the important problem which chronic kidney disease-mineral and bone disorder represents.



Terai K, Nara H, Takakura K, Mizukami K, Sanagi M, Fukushima S, et al.

Vascular calcification and secondary hyperparathyroidism of severe chronic kidney disease and its relation to serum phosphate and calcium levels.

Br J Pharmacol [Epub ahead of print] 2009:Mar 19.


Background and purpose: Various complications consequent on disordered calcium and phosphate homeostasis occur frequently in chronic kidney disease (CKD) patients. Particularly, vascular calcification has high morbidity and mortality rates. There is a clear need for a better CKD model to examine various aspects of this disordered homeostasis. Experimental approach: Oral dosing with adenine induced CKD in rats in only 10 days. Serum calcium, phosphate and parathyroid hormone were measured and calcification in aorta was assessed histologically. The effects of varying phosphorus content of diet or treatment with phosphate binders or active vitamin D(3) on these parameters were examined. Key results: After adenine dosing, significant hyperphosphatemia, hypocalcemia and secondary hyperparathyroidism (2HPT) were observed during the experimental period of 15 weeks. Aortic calcification was detected in only some of the animals even at 15 weeks ( approximately 40%). Treatment with vitamin D(3) for 18 days, even at a low dose (100 ng.kg(-1), 3-4 times week(-1), p.o), caused aortic calcification in all animals and increases in serum calcium levels up to the normal range. The vitamin D(3)-induced calcification was significantly inhibited by phosphate binders which lowered serum phosphate levels and the calcium x phosphate product, although serum calcium levels were elevated. Conclusions: These data suggest that rats dosed orally with adenine provide a more useful model for analysing calcium/phosphate homeostasis in severe CKD. Controlling serum calcium/phosphate levels with phosphate binders may be better than vitamin D(3) treatment in hyperphosphatemia and 2HPT, to avoid vascular calcification.


Chen Y, Su C, Wang S, Lee H, Lin S.

A Preliminary Investigation of the Association between Serum Uric Acid and Impaired Renal Function.

Chang Gung Med J 2009;32(1):66-71.


Background:Hemodialysis for end-stage renal disease (ESRD) incurs huge medical costs in Taiwan . We set out to determine if it is possible to help control chronic renal disease with early treatment of hyperuricemia. Methods: Data from Taipei Medical University Hospital (TMUH) health center from January 2004 to December 2006 were analyzed to correlate renal function and blood uric acid concentration. Patients were divided into 5 groups according to their serum uric acid concentration (< 4; 4~5.9; 6~7.9; 8~9.9, and > 10 mg/dl). According to our laboratory data, elevated serum creatinine levels (> 1.3 mg/dL) indicated impaired renal function. Results: In total, there were 5722 patients, including 2816 (49.2%) men and 2906 (50.8%) women, with a median age of 67. Impaired renal function was noted in 307 (5.4%) cases. Serum uric acid was significantly correlated with blood urea nitrogen and serum creatinine. Groups with a higher serum uric acid level had an increased risk of impaired renal function. Conclusion: Our purpose in this preliminary observation was to try to define a starting point for the early control of serum uric acid, in order to avoid the development of impaired renal function. We found that serum uric acid level to < 6 mg/dl seemed to be associated with less renal function impairment.



Roman-Garcia P, Carrillo-Lopez N, Cannata-Andia J.

Pathogenesis of bone and mineral related disorders in chronic kidney disease: key role of hyperphosphatemia.

J Ren Care 2009;35 Suppl 1:34-8.


This paper reviews the pathogenesis of hyperphosphataemia and its role in the regulation of parathyroid hormone synthesis and parathyroid cell proliferation in chronic kidney disease. The association between hyperphosphaemia and vascular calcification, and the interventions that can be used to control plasma phosphate are also discussed.


Sigrist M, Chiarelli G, Lim L, Levin A.

Early initiation of phosphate lowering dietary therapy in non-dialysis chronic kidney disease: a critical review.

J Ren Care 2009;35 Suppl 1:71-8.


Dietary management of hyperphosphatemia and hyperparathyroidism have long been important elements in the clinical management of CKD stage 4 and 5 for the prevention of mineral bone disease. The rationale for phosphate lowering has been further justified, given the accumulating data to support the association of phosphate with vascular damage, in this population who are at high risk of cardiovascular (CV) death. Phosphate is a novel CV risk factor in both CKD and in the general population, and a growing body of literature suggests that high normal serum phosphate may be a risk factor for progression of CKD. Few studies have examined hard outcomes after phosphate lowering. Nonetheless, given the balance of data both in cell, animal and human studies, the use of phosphate lowering strategies at earlier stages of CKD, perhaps even prior to serum phosphate level rising, may well be justified. This review will discuss the complications associated with higher serum phosphate, the potential benefits of early phosphate intervention, practical considerations of low phosphate diets and novel strategies for evaluating these strategies in clinical practice.


Kariyawasam D.

Phosphate management-a dietitian's perspective.

J Ren Care 2009;35 Suppl 1:79-83.


Hyperphosphataemia is a complication of renal failure which can lead to vascular calcification and hyperparathyroidism. Many factors influence phosphate levels, e.g. adherence to a low phosphate diet, adequate dialysis, hyperparathyroidism and concordance with phosphate binders. This article looks at the issues to consider and provides a dietitian's perspective on phosphate management.


Cannata-Andia J, Naves-Diaz M.

Phosphorus and survival: key questions that need answers.

J Am Soc Nephrol 2009;20(2):234-6.



Goldstein-Fuchs J, Fouque D.

The ubiquitous nature and elusive role of phosphorus and vascular calcification.

Am J Kidney Dis 2009;53(3):363-5.



Kanbay M, Goldsmith D, Akcay A, Covic A.

Phosphate - the silent stealthy cardiorenal culprit in all stages of chronic kidney disease: a systematic review.

Blood Purif 2009;27(2):220-30.


BACKGROUND AND AIM: Due to increasing evidence suggesting a link between hyperphosphatemia and cardiovascular disease (CVD), mediated through vascular calcification in patients on dialysis, the following question arises: At what stage of chronic kidney disease (CKD) does the relationship between elevated phosphate levels, vascular calcification and increased cardiovascular mortality begin? Therefore, the purpose of the current study was to critically review the current literature regarding this issue. METHODS: We performed a systematic search of the National Library of Medicine and the Cochrane Library databases from January 1985 to February 2008 to identify clinical studies examining the effects of plasma phosphate on cardiovascular outcome, mortality and progression of kidney disease in subjects with and without CKD who have not yet received dialysis. The primary outcome measure was the development of CVD, mortality and progression of kidney disease. RESULTS: Twelve clinical trials investigated the role of serum phosphate levels and adverse outcome (9 studies examining CVD outcome and 3 examining progression of kidney disease). After adjustment for risk factors for mortality, adverse cardiovascular outcome and progression of kidney disease, all studies found a graded independent significant association between phosphate levels and mortality, development of CVD and progression of kidney disease. There was no such association with plasma calcium levels. CONCLUSIONS: There is a graded independent association between serum phosphate levels and mortality, mainly cardiovascular events, and the progression of renal disease in subjects with and without definable (loss of glomerular filtration rate) CKD.



Savica V, Calo L, Monardo P, Caldarera R, Cavaleri A, Santoro D, et al.

High phosphate content beverages in dialysis patients: relevance for hyperphosphatemia and cardiovascular risk.

Nutr Metab Cardiovasc Dis 2008;18(8):e39-40.




Bellasi A, Kooienga L, Block G, Veledar E, Spiegel D, Raggi P.

How long is the warranty period for Nil or low coronary artery calcium in patients new to hemodialysis?

J Nephrol 2009;22(2):255-62.


Background: Coronary artery calcification (CAC) is common in patients with advanced chronic kidney disease on dialysis. A sizeable proportion of patients has no or minimal CAC at the inception of dialysis, but it is unclear how long they remain free of it. Methods: For the purpose of this study, 36 incident hemodialysis patients were submitted to sequential chest computed tomography to quantify CAC at baseline, 6, 12, 18 and 30 months. Results: Among them, 15 had absent or minimal CAC score (CACS 0 to 30) and 21 had a CACS >30 at baseline. Overall, the median baseline CACS was 129 (interquartile range [IQR] = 0-709) and it increased to 364 (IQR=8.3-1683) at study completion (182% increase). Among the 15 patients with minimal CACS, only 3 progressed and the median CACS increase was 20, as opposed to 15 of 21 patients with a baseline CACS >30 whose median progression was 431 (p<0.02). The 18 patients who had CACS progression were older (68.5 vs. 57.3 years, p=0.0081) and exhibited a poorer control of mineral metabolism (phosphorus 5.2 vs. 4.9 mg/ dL, p=0.048; corrected calcium x phosphorus product [CaxP] 49.3 vs. 46.2 mg2/dL2, p=0.001) than the patients without progression. On multivariable analysis, independent predictors of progression were baseline CACS (p=0.038) and time-averaged Cax;P (p=0.077). Conclusion: These data suggest that absent or low CAC at baseline is associated with minimal progression even up to 30 months. Careful management of mineral metabolism appears to be one of the main factors that limit progression of CAC.


Giachelli C.

The emerging role of phosphate in vascular calcification.

Kidney Int 2009;75(9):890-7.


Vascular calcification is recognized as a major contributor to cardiovascular disease (CVD) in end stage renal disease (ESRD) patients. Susceptibility to vascular calcification is genetically determined and actively regulated by diverse inducers and inhibitors. One of these inducers, hyperphosphatemia, promotes vascular calcification and is a nontraditional risk factor for CVD mortality in ESRD patients. Vascular smooth muscle cells (SMCs) respond to elevated phosphate levels by undergoing an osteochondrogenic phenotype change and mineralizing their extracellular matrix through a mechanism requiring sodium-dependent phosphate cotransporters. Disease states and cytokines can increase expression of sodium-dependent phosphate cotransporters in SMCs, thereby increasing susceptibility to calcification even at phosphate concentrations that are in the normal range.



Kapustin A, Shanahan C.

Targeting vascular calcification: softening-up a hard target.

Curr Opin Pharmacol 2009;9(2):84-9.


Widespread vascular calcification is a ubiquitous feature of aging and is prevalent in association with a number of common pathologies including atherosclerosis, renal failure, and diabetes. Once thought of as innocuous, emerging evidence suggests that calcification is causal in precipitating vascular events and mediating chronic cardiovascular damage, independent of disease context. Importantly, a large body of data has shed light on the factors that favor the formation of calcification in vivo, as well as on the complex mechanisms that initiate and promote it. This has identified some novel targets and allowed for the possibility that calcification can potentially be blocked and ultimately regressed. Targets include local and circulating inhibitors of calcification as well as factors that may ameliorate vascular smooth muscle cell (VSMC) apoptosis. Despite this, the vasculature remains a difficult tissue to target and currently there are no effective treatments in general use. More crucially, any potential treatments will need to be carefully evaluated as they may impinge on bone metabolism. Our best hope for the near future is to normalize factors associated with accelerated calcification in pathologies such as renal failure where, aberrant mineral metabolism, as well as treatment regimes, may contribute to the initiation and progression of calcification.


Inaba M.

[Chronic kidney disease (CKD) and bone. Impact of diabetes mellitus on the development of CKD-MBD].

Clin Calcium 2009;20(4):502-7.


Chronic kidney disease-mineral and bone disorder (CKD-MBD) develops as renal function deteriorates. The presence of diabetes mellitus as comorbidity modulates the severity of CKD-MBD. The prevalence of vascular calcification, which becomes higher in diabetic CKD patients than in non-CKD counterparts, increases cardiovascular mortality in diabetic patients. The main factor which causes vascular calcification in diabetic CKD patients is poor glycemic control, in contrast to hyperphosphatemia in non-diabetic CKD patients. Diabetes directly impairs osetoblasts to decrease bone mass, suppresses bone turnover to impair bone quality by impairing secretion of parathyroid hormone and increase AGE-modification of bone collagen. Therefore, therapeutic regimens for CKD-MBD should be considered specifically for diabetic CKD patients since the mode of its development differs between diabetic and non-diabetic CKD patients.



Yokoyama K.

[Chronic kidney disease (CKD) and bone. Vascular calcification in CKD.].

Clin Calcium 2009;20(4):552-8.


Vascular calcification is associated with the mortality of patients with chronic kidney disease (CKD) . Susceptibility to vascular calcification is genetically determined and actively regulated by diverse inducers and inhibitors. One of these inducers, hyperphosphatemia, promotes vascular calcification and is a nontraditional risk factor for CVD mortality in CKD patients. Hyperphosphatemia promotes vascular calcification in part by promoting VSMCs to undergo an osteochondrogenic phenotype change through a mechanism requiring sodium-dependent phosphate cotransporters. Recent randomized clinical trials showed that lowering serum phosphate levels with a non-calcium containing phosphate binder slows progression of vascular calcification in ESRD patients. Moreover, calcimimetics reduce arterial remodeling and calcification in rats with subtotal nephrectomy. Whether this difference will also be found in humans and will ultimately translate into less CV events in calcimimetics treated uremic patients is for a matter for speculation. Calcium and phosphate load are an important driver of vascular calcification.


Levey AS.

A new equation to estimate glomerular filtration rate.

Ann Intern Med 2009;150(9):604-612.


The objective of this study was to develop and validate a new estimating equation, the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation, based on the serum creatinine level that would be as accurate as the MDRD Study equation at a GFR <60 mL/min per 1.73 m2 and more accurate at a higher GFR.


        This was a cross-sectional analysis with separate pooled data sets for equation development and validation and a representative sample of US population for prevalence estimates (n=8,254). The authors utilized an additional data set to validate there analysis (n=3896).


        The new CKD-EPI equation estimates the NHANES median eGFR at 9.5 ml/min per 1.73 m higher and therefore would estimate the prevalence in the US population would be decreased by 1.6% (11.5% vs. 13.1%)


        The overall burden of the disease would be reduced and more accurate dosing of medications critical to patients early CKD health could continue.


renal newsletter n 2

Taylor J, Bushinsky D.

Calcium and phosphorus homeostasis.

Blood Purif 2009;27(4):387-94.


Calcium and phosphorus homeostasis relies on a complex, tightly regulated system involving many ions and hormones. The regulation of calcium and phosphorus is controlled by the actions of these ions and hormones on the intestine, kidneys and bone. Disturbances in the serum level of calcium and/or phosphorus can lead to significant pathology, including kidney stones and bone disease. In addition to parathyroid hormone and vitamin D, recently identified factors such as fibroblast growth factors and klotho play an important role in maintaining mineral ion homeostasis. The identification of subfamily V transient receptor potential cation channels (TRPV channels), Na/P(i) cotransporters, the vitamin D receptor and the calcium-sensing receptor have further advanced our understanding of this complex physiology. In this review we discuss the current understanding of the relationships between the ions, hormones, and transporters that maintain calcium and phosphorus homeostasis.


Frazao J, Martins P.

Adynamic bone disease: clinical and therapeutic implications.

Curr Opin Nephrol Hypertens [Epub ahead of print] 2009:May 6.


PURPOSE OF REVIEW: Adynamic bone disease has recently been associated with increased risk of vascular calcification. This review focuses on the emerging data in adynamic bone disease, its clinical consequences and therapeutic implications. RECENT FINDINGS: There is a lack of good biochemical markers of parathyroid status, bone formation and reabsorption to allow a secure diagnosis of bone disease. Recent data have suggested a possible link between bone activity and vascular calcification. Cardiovascular calcification is an independent predictor of mortality. Adynamic bone is associated with a very low capacity of bone to incorporate calcium in the bone compartment and inability to handle an extra calcium load. A positive association between vascular calcifications and low bone turnover has been suggested. Calcium-containing phosphate binders, active vitamin D therapy and high calcium dialysate may enhance vascular calcifications in the presence of adynamic bone disease. SUMMARY: There is recent evidence suggesting a negative impact of calcium load in the progression of vascular calcification in dialysis patients with chronic kidney disease stage 5 with adynamic bone disease. The current therapeutic approach to these patients should focus on reduction of calcium and vitamin D load to restore parathyroid activity.


Ketteler M, Biggar P.

Dietary and pharmacological control of calcium and phosphate metabolism in predialysis stages of chronic kidney disease.

Blood Purif 2009;27(4):345-9.


Data on calcium and phosphate metabolism in the predialysis stages of chronic kidney disease (CKD) are scarce when compared with the available information on patients on dialysis. Visible derangements of calcium and phosphate levels start to become apparent when GFR falls below 40 ml/min. In some but not all patients, hyperphosphatemia may be a mortality risk predictor in CKD stages 4-5. There are only few treatment studies targeting hyperphosphatemia in these CKD stages. However, the RIND study, evaluating progression of coronary artery calcification in incident hemodialysis patients, demonstrated that vascular calcification processes manifest in predialysis stages in the majority of patients, which may well be linked to deranged calcium and phosphate homeostasis. Novel insights into the pathophysiology of calcium and phosphate handling, especially the discovery of the phosphatonin FGF23, suggest that a more complex assessment of phosphate balance is warranted. This assessment should include measurements of fractional phosphate excretion and phosphatonin levels to objectively judge and effectively correct phosphate overload.


Nikolov I, Mozar A, Drueke T, Massy Z.

Impact of disturbances of calcium and phosphate metabolism on vascular calcification and clinical outcomes in patients with chronic kidney disease.

Blood Purif 2009;27(4):350-9.


Chronic kidney disease (CKD) is frequently complicated by arterial calcification. The latter is part of the associated mineral and bone disorder (CKD-MBD). Hypercalcemia and hyperphosphatemia have long been known to play a major role in the occurrence of vascular and other soft tissue calcification in patients with CKD, together with endocrine disturbances including vitamin D, parathyroid hormone, fibroblast growth factor-23, and klotho. In addition, many other systemic and local promoters, including inflammation and uremic toxins, contribute to the occurrence of vascular calcification, despite a powerful defense system made up of systemic and local inhibitors, as demonstrated in elegant experimental studies done in vitro and in vivo. Most importantly, several reports have shown that both hyperphosphatemia and hypophosphatemia, and to a lesser degree hypercalcemia and hypocalcemia, are associated with an increased relative risk of mortality in patients with CKD. However, all these reports were observational in nature and must therefore be considered as hypothesis generating. It remains to be demonstrated in prospective randomized trials whether normalization of serum phosphorus and/or calcium leads to better patient outcome. In order to improve outcome in patients with CKD-MBD, early medical intervention is of utmost importance.


Articolo su Sevelamer e infiammazione:


Sevelamer hydrochloride use and circulating endotoxin in hemodialysis patients: a pilot cross-sectional study

Phyllis P. Sun, MS, RD, Mary C. Perianayagam, PhD, and Bertrand L. Jaber, MD, MS

Objective: There is a growing interest in the potential anti-inflammatory properties of sevelamer hydrochloride, a commonly used phosphate binder for patients with chronic kidney failure. This study explores the hypothesis that sevelamer hydrochloride binds bacterial endotoxin in the intestinal tract, leading to lower circulating endotoxin levels, and offering a novel anti-inflammatory mechanism.

Methods: We performed a cross-sectional study in medically stable patients with chronic kidney failure undergoing maintenance hemodialysis. Blood samples were collected before 2 consecutive dialysis sessions, and plasma was tested for endotoxin, interleukin-6 and C-reactive protein. Linear regression analyses were used to examine patient-related and dialysis-related factors associated with plasma endotoxin level.

Results: Forty-six patients met our eligibility criteria. Their mean age was 62 years, 41% were diabetic, and 65% reported the use of sevelamer hydrochloride. The mean plasma endotoxin level was significantly lower in patients using sevelamer hydrochloride compared with those who were not (0.2360.01 vs. 0.3060.01 EU/mL, P5.001). However, plasma interleukin-6 and C-reactive protein levels were not significantly different between the two groups.

According to multivariate analysis, the use of sevelamer hydrochloride was associated with a lower plasma endotoxin level after adjustment for race, gender, age, dialysis vintage, total cholesterol level, and white blood cell count.

Conclusions: This proof-of-concept pilot study demonstrates that the use of sevelamer hydrochloride is associated with a lower plasma endotoxin level, supporting the hypothesis that this agent binds to endotoxin in the intestinal lumen. Although this may be an important mechanism by which sevelamer hydrochloride attenuates systemic inflammation, a clinical trial is required to test this hypothesis.


renal newsletter n 3

Ketteler M.

The control of hyperphosphatemia in chronic kidney disease: which phosphate binder?

Int J Artif Organs 2009;32(2):95-100.


Hyperphosphatemia is currently regarded as a key mortality risk predictor in late CKD stages and especially in patients on dialysis. Fortunately, the armatorium to effectively treat hyperphosphatemia in end-stage renal disease has grown in recent years, and we gained an improved understanding of potential benefits and harms of specific compounds. Most interestingly, novel insights into the pathophysiology of calcium and phosphate handling, especially, the discovery of the phosphatonin FGF23, suggest a more complex assessment of phosphate balance especially in predialysis stages is warranted. This assessment should probably include measurements of fractional phosphate excretion and phosphatonin levels to objectively judge and effectively correct phosphate overload, however, clinical data on calcium and phosphate metabolism in CKD stages 3 - 4 are still scarce. This overview will both discuss aspects of pathophysiology of phosphate regulation and current and future clinical treatement approaches.


Bellotti G, Presta P, Panzino T, Capria M, Caglioti A, Riccio M, et al.

[Multiple peritrochanteric and pubic calcifications in a young woman on hemodialysis with severe renal osteodystrophy successfully treated with sevelamer+cinacalcet+paracalcitol combination therapy.].

G Ital Nefrol 2009;26(3):372-6.


Secondary hyperparathyroidism is a frequent complication of chronic renal failure that can induce severe bone disease and negatively influence the cardiovascular outcome. Therefore, nephrologists should attempt to reach the targets recommended by national and international guidelines using all the available therapeutic strategies. We describe the case of a 37-year-old woman affected by spina bifida and myelomeningocele who had been on hemodialysis since 1993. In July 2006 she developed secondary hyperparathyroidism complicated by peritrochanteric calcifications which did not respond to standard therapy. Because it was impossible to perform a parathyroidectomy, we started medical therapy with a combination of sevelamer hydrochloride, paracalcitol and cinacalcet, which resulted in progressive improvement of laboratory data and osteodystrophy. A diagnosis of mixed secondarytertiary hyperparathyroidism was made, but a progressive increase in iPTH to very high levels suggested a rapid evolution toward a pure tertiary form.


Imanishi Y.

[Clinical aspect of recent progress in phosphate metabolism. Phosphate retension, a powerful risk factor for mortality in chronic kidney disease (CKD)].

Clin Calcium 2009;19(6):828-35.


Higher levels of serum phosphate are associated not only with progression of secondary hyperparathyroidism but also adverse cardiovascular outcomes, such as ectopic calcifications, cardiovascular events its death. The treatments of hyperphosphatemia with phosphate binders were shown to be effective on a risk factor for cardiovascular disease and mortality on hemodialysis patients.


Reddy V, Symes F, Sethi N, Scally A, Scott J, Mumtaz R, et al.

Dietitian-led education program to improve phosphate control in a single-center hemodialysis population.

J Ren Nutr 2009;19(4):314-20.


OBJECTIVE: We sought to analyze the effect of a structured, dietitian-led education program on patients' general knowledge of phosphate and phosphate binders, and its impact on serum phosphate concentrations in a single-center hemodialysis population. DESIGN: We compared subjects before and after intervention. SETTING: This study involved two dialysis units operated by a single center. PATIENTS: One hundred and fifteen hemodialysis patients consented to participate in this study (54% male; mean age, 61.1 years; 32% Asian). Patients acted as their own controls. One hundred and eight patients completed the study. INTERVENTION: All patients completed a questionnaire to assess their knowledge of phosphate and phosphate-binder therapy. Small group teaching sessions were then delivered to patients by a single dietitian, with the aid of a hospital interpreter as required. Patients also received information booklets or audio cassettes translated into Urdu. A second identical questionnaire was completed a month later. MAIN OUTCOME MEASURES: Outcome measures involved pre-education and posteducation knowledge scores, monthly measurements of serum phosphate, calcium, and mean Kt/V, and parathyroid hormone concentrations every 3 months during the 5 month run-in period and subsequent 5-month study period. RESULTS: The education program significantly improved patients' general knowledge of phosphate and of phosphate-binders (P < .001), especially in patients with a low pretest score and those of South Asian origin. This result was associated with a significant reduction in serum phosphate in patients with hyperphosphatemia (P = .032). CONCLUSIONS: These findings suggest that a combination of educational initiatives is effective in enhancing patients' knowledge of phosphate and phosphate-binders, and consequently in improving serum phosphate levels in patients with hyperphosphatemia.



David S, Kumpers P, Eisenbach G, Haller H, Kielstein J.

Prospective evaluation of an in-centre conversion from conventional haemodialysis to an intensified nocturnal strategy.

Nephrol Dial Transplant 2009;24(7):2232-40.


INTRODUCTION: Under physiological conditions kidneys work continuously, 168 h/week. In contrast, patients with end-stage renal disease are usually dialyzed only 12-15 h/ week. This unphysiological dialysis dose, even if considered adequate by current Kt/V-based dose estimates, is just capable to maintain the alterations of multiple metabolic parameters at a level that permits an unacceptable annual mortality rate of 10-20%, mainly due to cardiovascular events, protein energy wasting and infections. PATIENTS AND METHODS: Thirteen haemodialysis patients were converted from conventional (3 x 4 h/week) to an intensified nocturnal (3 x 8 h/week) dialysis and were longitudinally followed up for 12 months. Different parameters were evaluated before treatment conversion and quarterly during the follow-up period [i.e. dialysis efficacy (eKt/V), mean arterial pressure (MAP), antihypertensive drug score, extra-cellular volume (ECV), haemoglobin, transferrin saturation, ferritin, dose of erythropoiesis-stimulating agents (ESA), iron requirement, parameters of nutrition (body weight (BW), albumin, protein, normalized protein catabolic rate (nPCR), bioelectrical impedance analysis (BIA)), C-reactive protein, calcium-phosphate product, alkaline phosphatase (AP), intact parathyroid hormone (iPTH) and amount of phosphate-binding pharmacotherapy]. RESULTS: The calculated dialysis efficacy rose after switching the treatment mode (eKt/V 1.87 versus 2.7, P < 0.0001). Further, a significantly decreased MAP in the pre- (100 versus 89 mmHg) and postdialytic period (97 versus 83 mmHg), and a decreased ECV (13.8 versus 13.2 L; P = 0.03) even though antihypertensive pharmacotherapy could be substantially reduced (P < 0.0001), was found. Concomitant with a reduction of ESA (66.5 versus 45.2 IU/ kg/week; P = 0.006), the haemoglobin level rose significantly (11.4 versus 12.5 g/dL, P = 0.01). Nutritional status assessed by BW (70.9 +/- 20.2 versus 72.1 +/- 19.8 kg, P = 0.02), nPCR (1.39 versus 2.25 g/kg/day, P = 0.02) and BIA (phase angle: 6.2 versus 6.9 degrees, P < 0.001) improved. The calcium-phosphate product slightly declined, without changes in the dose of any phosphate binders. Surprisingly, iPTH of those patients with intact parathyroid glands (n = 7) increased approximately 3-fold (27.9 versus 59.35 pmol/L, P = 0.009), while the AP was found stable. CONCLUSION: This study demonstrates improvements in numerous dialysis-associated metabolic variables after intensification of HD time. Of note, an increase of iPTH was detected in those patients with intact parathyroid glands.



Schlieper G, Brandenburg V, Djuric Z, Damjanovic T, Markovic N, Schurgers L, et al.

Risk factors for cardiovascular calcifications in non-diabetic caucasian haemodialysis patients.

Kidney Blood Press Res 2009;32(3):161-168.


Background/Aims: Dialysis patients display an increased mortality which is associated with cardiovascular calcifications. Diabetes mellitus and ethnicity are known factors that affect the extent of cardiovascular calcifications. However, most studies have investigated mixed cohorts with diabetics and/or mixed ethnicity. Methods: Cardiovascular calcifications were assessed in non-diabetic Caucasian haemodialysis patients by the semiquantitative Adragao calcification score (X-ray pelvis and hands) and a novel composite calcification score encompassing the Adragao score as well as calcifications detected by X-ray of the fistula arm, echocardiography of heart valves and carotid ultrasound. Results: Using multivariate analysis, age, male gender, dialysis vintage, lower Kt/V, calcium-phosphate product, smoking and high-sensitivity CRP were independent risk factors for cardiovascular calcifications as assessed by the Adragao or the composite score. Pulse wave velocity was independently related to both calcification scores. Body mass index, cholesterol, triglycerides, iPTH and serum levels of fetuin-A and uncarboxylated matrix Gla protein were not associated with cardiovascular calcifications. Conclusions: In our cohort of non-diabetic Caucasian haemodialysis patients, age, male gender, dialysis vintage, smoking, calcium-phosphate product, high-sensitivity CRP and lower Kt/V were independent risk factors for cardiovascular calcifications. Whether lowering the calcium-phosphate product and increasing dialysis efficiency can reduce cardiovascular calcifications in dialysis patients remains to be determined.


Petrovic D, Obrenovic R, Stojimirovic B.

Risk factors for aortic valve calcification in patients on regular hemodialysis.

Int J Artif Organs 2009;32(3):173-9.


Introduction: Aortic valve calcification (AVC) accelerates development of aortic valve stenosis and cardiovascular complications. Hyperphosphatemia is one of the key risk factors for aortic valve calcification. Aim: The aim of this study was to evaluate the prevalence of AVC in patients on regular hemodialysis and to assess the impact of different factors on its appearance. Method: The study investigated a total of 115 patients treated in the Hemodialysis Department of the Urology and Nephrology Clinic at the Kragujevac Clinical Center in Serbia . The variables investigated were: serum albumin, C-reactive protein (CRP), homocysteine, total cholesterol, LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), triglycerides (TG), Apolipoprotein A-I (Apo A-I), Apolipoprotein B (Apo B) and lipoprotein (a), calcium, phosphate and parathormone, and calcium-phosphorus product (Ca x P). Patients were evaluated by echocardiography for AVC. Statistical analysis included univariate and multivariate logistic regression analysis. Results: Univariate regression analysis showed that serum phosphate levels and Ca x P are the most important risk factors for AVC (p<0.001). Multivariate logistic regression analysis revealed that hyperphosphatemia is an independent risk factor for AVC (p<0.001). Conclusion: Hyperphosphatemia is an independent risk factor for aortic valve calcification.



CME/CE Programs Online:

        ASN Renal Week 2008 Official Symposia now available to view (click on title for link):

Managing CKD-MBD Through the Disease Continuum (H. Malluche, MD; R. Thadhani, MD; B. Kestenbaum, MD, MS)    


New Frontiers in Phosphorus Homeostasis in CKD (H. Malluche, MD; D. Quarles , MD ; M. Wolf, MD)


        A Summary of Key Insights from ASN Renal Week 2008:

All-Stage Management of CKD-MBD: Insights From Renal Week 2008 (C. Langman, MD; B. Kestenbaum, MD, MS Anjay Rastogi, MD, PhD)