Recent changes in therapeutic approaches and association with outcomes among patients with secondary hyperparathyroidism on chronic hemodialysis: the DOPPS study.

BACKGROUND AND OBJECTIVES: Elevated parathyroid hormone levels may be associated with adverse clinical outcomes in patients on dialysis. After the introduction of practice guidelines suggesting higher parathyroid hormone targets than those previously recommended, changes in parathyroid hormone levels and treatment regimens over time have not been well documented. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using data from the international Dialysis Outcomes and Practice Patterns Study, trends in parathyroid hormone levels and secondary hyperparathyroidism therapies over the past 15 years and the associations between parathyroid hormone and clinical outcomes are reported; 35,655 participants from the Dialysis Outcomes and Practice Patterns Study phases 1-4 (1996-2011) were included. RESULTS: Median parathyroid hormone increased from phase 1 to phase 4 in all regions except for Japan, where it remained stable. Prescriptions of intravenous vitamin D analogs and cinacalcet increased and parathyroidectomy rates decreased in all regions over time. Compared with 150-300 pg/ml, in adjusted models, all-cause mortality risk was higher for parathyroid hormone=301-450 (hazard ratio, 1.09; 95% confidence interval, 1.01 to 1.18) and >600 pg/ml (hazard ratio, 1.23; 95% confidence interval, 1.12 to 1.34). Parathyroid hormone >600 pg/ml was also associated with higher risk of cardiovascular mortality as well as all-cause and cardiovascular hospitalizations. In a subgroup analysis of 5387 patients not receiving vitamin D analogs or cinacalcet and with no prior parathyroidectomy, very low parathyroid hormone (<50 pg/ml) was associated with mortality (hazard ratio, 1.25; 95% confidence interval, 1.04 to 1.51). CONCLUSIONS: In a large international sample of patients on hemodialysis, parathyroid hormone levels increased in most countries, and secondary hyperparathyroidism treatments changed over time. Very low and very high parathyroid hormone levels were associated with adverse outcomes. In the absence of definitive evidence in support of a specific parathyroid hormone target, there is an urgent need for additional research to inform clinical practice.

Associations of frequency and duration of patient-doctor contact in hemodialysis facilities with mortality.

It is unknown whether regular patient-doctor contact (PDC) contributes to better outcomes for patients undergoing hemodialysis. Here, we analyzed the associations between frequency and duration of PDC during hemodialysis treatments with clinical outcomes among 24,498 patients from 778 facilities in the international Dialysis Outcomes and Practice Patterns Study (DOPPS). The typical facility PDC frequency, estimated by facility personnel, was high (more than once per week) for 55% of facilities, intermediate (once per week) for 24%, and low (less than once per week) for 21%. The mean ± SD estimated duration of a typical interaction between patient and physician was 7.7 ± 5.6 minutes. PDC frequency and duration varied across DOPPS phases and countries; the proportion of facilities with high PDC frequency was 17% in the United States and 73% across the other countries. Compared with high PDC frequency, the adjusted hazard ratio (HR) for all-cause mortality was 1.06 (95% confidence interval [CI], 0.96 to 1.17) for intermediate PDC frequency and 1.11 (95% CI, 1.01 to 1.23) for low PDC frequency (P=0.03 for trend). Furthermore, each 5-minutes-shorter duration of PDC was associated with a 5% higher risk for death, on average (HR, 1.05; 95% CI, 1.01 to 1.09), adjusted for PDC frequency and other covariates. Multivariable analyses also suggested modest inverse associations between both PDC frequency and duration with hospitalization but not with kidney transplantation. Taken together, these results suggest that policies supporting more frequent and longer duration of PDC may improve patient outcomes in hemodialysis.

Regimen complexity and prescription adherence in dialysis patients.

OBJECTIVES: Poor medication adherence is common in end-stage renal disease and may cause suboptimal outcomes and increased healthcare costs. We assessed the association between regimen complexity, perceived burden of oral therapy (BOT) and medication adherence in a large sample of hemodialysis (HD) patients. METHODS: 1,238 HD patients in 54 Italian centers participated. Data were collected on patients' socio-demographic characteristics, perceived BOT, quality of life, healthcare satisfaction, social support and medication adherence with a self-administered questionnaire. Data on medication regimen, comorbidities, hospitalizations, and transplant listing status were provided by the nursing staff. We estimated the adjusted association of regimen complexity, BOT and medication adherence with logistic regression. RESULTS: There were 789 (64%) men and the median age was 67 years. Mean daily burden was 9.7 tablets and 48% of patients were adherent to medication prescriptions. The number of tablets prescribed in the medication regimen was associated to adherence likelihood after adjustment for possible confounders. Perceived BOT moderated the association between tablet count and self-reported adherence. CONCLUSION: Poor adherence was very common in our sample. Reducing tablet burden might help patients be adherent. However, our results suggest that modulating regimen complexity might be ineffective if patients' negative attitudes toward medications are not addressed concurrently.

Management of secondary hyperparathyroidism in Italy: results of the Italian FARO survey.

AIMS: In recent years, treatment options for secondary hyperparathyroidism (SHPT) have increased (e.g., paricalcitol, calcimimetics). To determine the impact these new treatments have on achieving K/DOQI targets, an observational, prospective survey was undertaken. METHODS: Four 6-month time-spaced surveys of 2,637 patients in 28 Italian dialysis units were performed. Patient demographic information; use of vitamin D or calcimimetics; and changes in parathyroid hormone (PTH), calcium (Ca) and phosphate (P) levels were evaluated. RESULTS: Over the course of the survey, use of calcitriol decreased (from 62.1% at baseline to 44.5% at month 18; p<0.001), while use of paricalcitol (from 19.9% to 36.9%; p<0.001) and calcimimetics (from 6.4% to 10.8%; p<0.001) increased. This was associated with a decrease in mean PTH values (from 310.3 ± 292.4 pg/mL at baseline to 279.5 ± 250.1 pg/mL at month 18; p=0.0002), while mean Ca and P remained steady. The percentage of patients achieving K/DOQI ranges for PTH (from 26.8% at baseline to 32.0% at month 18, p<0.001), Ca (from 50.4% at baseline to 55.9% at month 18, p<0.001) and the 3 targets combined (PTH, Ca and P; from 8.8% at baseline to 11.5% at month 18, p=0.003) significantly increased (p<0.05). Despite the introduction of newer agents, two thirds of patients did not achieve target levels. CONCLUSIONS: Increased awareness and newer treatment options for chronic kidney disease patients with SHPT have changed treatment policy and number of patients achieving K/DOQI target levels in Italy. However, the majority of patients did not meet the target ranges, suggesting that new drugs and strategies are still warranted for optimal management of SHPT in chronic kidney disease.

[50 years of nephrology: between science and organizing activities]. / 50 anni di nefrologia: tra scienza e sviluppo organizzativo.

The contribution of Italians to the development of nephrology has been very important but not always recognized. Thus, historical accounts do not mention the fact that the concept of short dialysis (4 hours 3 times weekly) was invented in Parma in 1971 by the Italian nephrologist V. Cambi at the nephrology unit of the University Hospital chaired by Prof. L. Migone, although short dialysis is now the standard dialysis all over the world. Poorly known facts concerning the Italian Society of Nephrology (SIN) described in this paper include the proposal, in 1980, of the creation of a new scientific society of nephrology made up only of university doctors, which was rejected but a college of university professors of nephrology created instead; and the reduction, in 1986, of the duration of the term of office of the SIN president from 3 to 2 years, with a hospital and a university nephrologist serving alternating terms. Poorly known facts concerning EDTA-ERA include the action to involve the presidents of the national societies of nephrology in Europe in the organization of EDTA congresses to prevent the creation of a new European society of nephrology, the result of which was the transformation, in 1983, of EDTA into EDTA-ERA (European Renal Association). On 20 November 2001 the Fondazione Italiana del Rene (FIR) was founded in Naples, which subsequently (on 16 September 2009) became a foundation of the SIN.

A translational approach to micro-inflammation in end-stage renal disease: molecular effects of low levels of interleukin-6.

Inflammation plays a key role in the progression of cardiovascular disease, the leading cause of mortality in ESRD (end-stage renal disease). Over recent years, inflammation has been greatly reduced with treatment, but mortality remains high. The aim of the present study was to assess whether low (<2 pg/ml) circulating levels of IL-6 (interleukin-6) are necessary and sufficient to activate the transcription factor STAT3 (signal transducer and activator of transcription 3) in human hepatocytes, and if this micro-inflammatory state was associated with changes in gene expression of some acute-phase proteins involved in cardiovascular mortality in ESRD. Human hepatocytes were treated for 24 h in the presence and absence of serum fractions from ESRD patients and healthy subjects with different concentrations of IL-6. The specific role of the cytokine was also evaluated by cell experiments with serum containing blocked IL-6. Furthermore, a comparison of the effects of IL-6 from patient serum and rIL-6 (recombinant IL-6) at increasing concentrations was performed. Confocal microscopy and Western blotting demonstrated that STAT3 activation was associated with IL-6 cell-membrane-bound receptor overexpression only in hepatocytes cultured with 1.8 pg/ml serum IL-6. A linear activation of STAT3 and IL-6 receptor expression was also observed after incubation with rIL-6. Treatment of hepatocytes with 1.8 pg/ml serum IL-6 was also associated with a 31.6-fold up-regulation of hepcidin gene expression and a 8.9-fold down-regulation of fetuin-A gene expression. In conclusion, these results demonstrated that low (<2 pg/ml) circulating levels of IL-6, as present in non-inflamed ESRD patients, are sufficient to activate some inflammatory pathways and can differentially regulate hepcidin and fetuin-A gene expression.

The burden of amputation among hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS).

BACKGROUND: Hemodialysis patients are at increased risk of amputation, particularly those with diabetes. Limited data exist about the prevalence, incidence, risk factors for, and sequelae of amputation in hemodialysis patients. STUDY DESIGN: A prospective observational study of hemodialysis practices and outcomes. SETTING & PARTICIPANTS: Data from 29,838 patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS) from 1996 to 2004 were analyzed. PREDICTOR/FACTOR: Demographic factors, comorbid conditions, laboratory values, years since end-stage renal disease onset, and currently prescribed medications at study enrollment. OUTCOME: Prior amputation at study enrollment by using logistic regression and amputation during follow-up by using Cox models. Amputation was ascertained from medical record review. RESULTS: There was a high prevalence (6%) and incidence (2.0 events/100 patient-years at risk) of amputation in hemodialysis patients; patients with diabetes had a more than 9 times greater incidence of new amputation. Wide variations among countries were observed in risk of amputation, with the lowest prevalence in Japan and the highest in Belgium, France, and Germany. Traditional cardiovascular risk factors, such as age, peripheral vascular disease, and smoking were predictive of amputation, as were such risk factors related to hemodialysis as altered mineral metabolism and years of hemodialysis therapy. In patients with diabetes, greater relative risks of amputation were observed in men, smokers, and those with other diabetic complications, anemia, and malnutrition. The relative risk of mortality after amputation was 1.54 (95% confidence interval, 1.41 to 1.68; P < 0.001) with a mean survival of 2.0 versus 3.8 years. LIMITATIONS: The database does not differentiate between types of amputations; some amputations may have concerned the upper limbs and could have been linked to ischemia related to vascular access. CONCLUSIONS: Amputation in hemodialysis patients is a very frequent event, particularly in patients with diabetes, and is associated with both traditional cardiovascular risk factors and factors linked to kidney failure treated by hemodialysis. Interventional trials are needed to reduce the burden of amputation.

Prescription of antihypertensive agents to haemodialysis patients: time trends and associations with patient characteristics, country and survival in the DOPPS.

BACKGROUND: Haemodialysis patients were studied in 12 countries to identify practice patterns of prescription of antihypertensive agents (AHA) associated with survival. METHODS: The sample included 28 513 patients enrolled in DOPPS I and II. The classes of AHA studied were beta blocker (BB), angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), peripheral blocker, central antagonist, vasodilator, long-acting dihydropyridine calcium channel blocker (CCB), short-acting dihydropyridine CCB and non-dihydropyridine CCB. To reduce bias due to unmeasured confounders, the associations with mortality were assessed by separate Cox models based on patient-level prescription and facility prescription practice. RESULTS: An increase in prescription of ARBs (9.5%) and BBs (9.1%) was observed from DOPPS I to II. Prescription of AHA classes varied significantly by country, ranging for BBs from 9.7% in Japan to 52.7% in Sweden and for ARBs from 5.5% in Italy to 21.3% in Japan in DOPPS II. Facilities that treated 10% more patients with ARBs had, on average, 7% lower all-cause mortality, independent of patient characteristics and the prescription patterns of other antihypertensive medications (P = 0.05). Significant and independent associations with reduction in cardiovascular mortality were observed for ARBs (RR = 0.79; P = 0.005) and BBs (RR = 0.87, P = 0.004) in analyses of patient-level prescriptions. These associations in the facility-level model followed the same direction. CONCLUSIONS: DOPPS data show large variations across countries in AHA prescription for haemodialysis patients. The data suggest an association between ARB use and reduction in all-cause mortality, as well as with the use of BBs and reduction in cardiovascular mortality among haemodialysis patients.

Pulse pressure and presence of coronary artery calcification.

BACKGROUND: Coronary calcification (CAC) is found in early stages of CKD. Pulse pressure (PP) predicts CAC in dialysis patients. This study evaluates the accuracy of PP in predicting CAC in patients not yet on dialysis (CKD patients). METHODS: CKD patients (n = 388) underwent coronary calcium score (CAC score) and abdominal x-ray (n = 128) for estimating aorta calcification (AAC). Biochemistry and PP were measured every 3 and 6 months in patients with stage 4 to 5 and 2 to 3 CKD, respectively. The accuracy of PP and AAC was assessed by receiver operating characteristics analysis. RESULTS: PP correlated with CAC score in the whole cohort and in patients with stages 2 to 3 and stages 4 to 5 CKD. PP >60 mmHg predicted CAC score >0 (OR: 2.14; P < 0.001), > or =100 (OR: 2.92; P < 0.001), > or =400 (OR: 6.17; P < 0.001) after multivariable adjustment. Area under the curve (AUC) was 0.626 for CAC score >0, 0.676 for score >100, and 0.746 for score >400. PP >60 mmHg reduced the rate of event-free survival. AAC was found in 58% of patients and correlated with CAC score. AUC was 0.628 for CAC score >0, 0.652 for score >100, 0.831 for score >400. CONCLUSION: PP may identify CKD patients with subclinical CAC who need further evaluation. Accuracy of PP and AAC is nearly similar in predicting CAC. High PP indicates vessel wall alterations leading to adverse outcome.

Beneficial effects of better control of secondary hyperparathyroidism with paricalcitol in chronic dialysis patients.

BACKGROUND: Treatment of secondary hyperparathyroidism (SHPT) with calcitriol is often limited by the occurrence of hypercalcemia, hyperphosphatemia and risk of vascular calcifications. Paricalcitol, a vitamin D analogue with lower calcemic and phosphatemic effects, is successfully utilized in dialysis patients, although some uncertainty remains about the optimal dosage. Amelioration of survival in hemodialysis patients has been correlated to the use of calcitriol and, even better, paricalcitol. METHODS: We evaluated 1-year treatment with paricalcitol in 12 chronic hemodialysis patients with moderate-severe SHPT previously treated with intravenous calcitriol. Starting dose of paricalcitol was calculated according to the severity of the disease by the formula: intact parathyroid hormone (iPTH)/80, and successive titration performed according to the NKF-DOQI guidelines. RESULTS: Paricalcitol caused a rapid decrease in serum levels of iPTH with a consistent percentage of values falling below 150 pg/mL in the first months of treatment. Although the occurrence of hypercalcemia was not significantly different between treatment with calcitriol and paricalcitol, a slight but significant increase in mean calcium levels was observed during paricalcitol treatment. A significant amelioration of erythropoiesis and acid-base balance was observed during paricalcitol treatment. CONCLUSIONS: Paricalcitol efficiently suppresses PTH secretion in dialysis patients with SHPT, with a moderate calcemic, but not a phosphatemic, effect. The dose of paricalcitol calculated as iPTH/80 may cause acute lowering of bone turnover. The improvement of anemia control and the amelioration of acid-base balance are 2 important additive effects of the better control of SHPT that may improve survival of hemodialysis patients.

Sleep quality predicts quality of life and mortality risk in haemodialysis patients: results from the Dialysis Outcomes and Practice Patterns Study (DOPPS).

BACKGROUND: Poor sleep quality (SQ) affects many haemodialysis (HD) patients and could potentially predict their morbidity, mortality, quality of life (QOL) and patterns of medication use. METHODS: Data on SQ were collected from 11,351 patients in 308 dialysis units in seven countries in the Dialysis Outcomes and Practice Patterns Study (DOPPS) between 1996 and 2001 through a patient self-reported SQ scale, ranging from 0 (worst) to 10 (best). A score of <6 reflected poor SQ. Sleep disturbance was also assessed by self-reported daytime sleepiness, feeling drained and nocturnal awakening. Logistic and multiple linear regression were used to assess predictors of SQ and associations with QOL. Cox regression examined associations with mortality. Analyses accounted for case-mix, facility clustering and country. RESULTS: Nearly half (49%) of patients experienced poor SQ. Mean SQ scores varied by country, ranging from 4.9 in Germany to 6.5 in Japan. Patients with poor SQ were more likely to be prescribed antihistamines, antidepressants, anti-inflammatories, narcotics, gastrointestinal (GI) medications, anti-asthmatics or hypnotics. Physical exercise at least once a week (vs < once a week) was associated with lower odds of poor SQ (AOR = 0.55-0.85, P < 0.05). Poorer SQ was associated with significantly lower mental and physical component summary (MCS/PCS) scores (MCS scores 1.9-13.2 points lower and PCS scores 1.5-7.7 points lower when SQ scores were <10 vs 10). The RR of mortality was 16% higher for HD patients with poor SQ. CONCLUSIONS: Poor SQ is common among HD patients in DOPPS countries and is independently associated with several QOL indices, medication use patterns and mortality. Assessment and management of SQ should be an important component of care.

Lack of appetite in haemodialysis patients--associations with patient characteristics, indicators of nutritional status and outcomes in the international DOPPS.

BACKGROUND: Identification of haemodialysis patients with problems related to lack of appetite should help prevent adverse outcomes. We studied whether a single question about being bothered by lack of appetite within the prior 4 weeks is related to nutritional status, inflammation and risks of death and hospitalization. Additionally, we assessed associations of lack of appetite with depression, dialysis dose and length of haemodialysis. METHODS: This study is an analysis of baseline and longitudinal data from 14 406 patients enrolled in the Dialysis Outcomes and Practice Pattern Study. Cox regression was used to assess whether the degree (not, somewhat, moderately, very much, extremely) that patients were bothered by lack of appetite is an independent predictor of death and hospitalization. Logistic regression was used to identify baseline characteristics associated with being bothered by lack of appetite. RESULTS: The risk of death was more than 2-fold higher [relative risk (RR) = 2.23; 95% confidence interval (CI) = 1.90-2.62] and the risk of hospitalization 33% higher (RR = 1.33; 95% CI = 1.19-1.48) among patients extremely bothered, compared with not bothered, by lack of appetite. These associations followed a dose-response fashion and remained statistically significant after adjustments for 14 comorbidities. Depression, shorter haemodialysis session, hypoalbuminaemia, lower concentration of serum creatinine and normalized protein catabolic rate, lower body mass index and higher leucocyte and neutrophil counts were independently associated with higher odds of being bothered by lack of appetite. CONCLUSIONS: The data suggest that a single question about lack of appetite helps identify haemodialysis patients with poorer nutritional status, inflammation, depression and higher risks of hospitalization and death. The study calls attention to a possible beneficial effect of longer haemodialysis on appetite.

Fetuin-A gene expression, synthesis and release in primary human hepatocytes cultured in a galactosylated membrane bioreactor.

This paper reports on human hepatocytes cultured in a galactosylated membrane bioreactor in order to explore the modulation of the effects of a pro-inflammatory cytokine, Interleukin-6 (IL-6) on the liver cells at molecular level. In particular the role of IL-6 on gene expression and production of a glycoprotein, fetuin-A produced by hepatocytes, was investigated by culturing hepatocytes in the membrane bioreactor, both in the absence and presence of IL-6 (300 pg/ml). IL-6 modulated the fetuin-A gene expression, synthesis and release by primary human hepatocytes cultured in the bioreactor. A 75% IL-6-induced reduction of fetuin-A concentration in the medium was associated with a 60% increase of C-reactive protein in the same samples. Real-time-PCR demonstrated an 8-fold IL-6-induced reduction of fetuin-A gene expression. These results demonstrate that the hepatocyte galactosylated membrane bioreactor is a valuable tool to study IL-6 effects and gave evidence, for the first time, that IL-6 down-regulates the gene expression and synthesis of fetuin-A by primary human hepatocytes. The human hepatocyte bioreactor behaves like the in vivo liver, reproducing the same hepatic acute-phase response that occurs during the inflammatory process.

A project to prevent renal diseases in the general population.

BACKGROUND: Early identification of subjects unaware of hypertension, diabetes and urinary abnormalities may prevent and/or reduce the onset and progression of kidney disease and ameliorate outcomes. In this study, the presence of hypertension, diabetes and urinary abnormalities was checked in subjects walking in a large square of Naples. METHODS: Data on age, habits and history of hypertension and/or diabetes were collected. Systolic and diastolic blood pressure were recorded. Protein, glucose, leukocytes and red blood cells were measured in urine. RESULTS: Participants numbered 698. Smoking (past or current smoking) was reported by 77%. Many of the participants with hypertension (35%) showed uncontrolled hypertension despite antihypertensive therapy. Hypertension was found for the first time in 154 subjects, and was confirmed in 28% of them afterwards; 23 participants (15% of hypertensive subjects) did not recheck blood pressure (BP) despite our summons. Proteinuria was found in 18% of new hypertensive participants. In 14 out of 17 diabetic participants without history of hypertension, hypertension was found for the first time and confirmed thereafter. Urinary abnormalities were present in more than one half of the participants, and were more prevalent in women and diabetics. Diabetics numbered 55 out of 698 subjects. In spite of therapy, glucosuria was present in almost one third of diabetics. Glucosuria was found in 6 participants with no history of diabetes (0.9% of all subjects). CONCLUSIONS: These data demonstrate that (a) many persons with hypertension are not aware of it; (b) control of hypertension is inadequate in most treated hypertensive patients and even worse in diabetics; (c) urinary abnormalities are frequently present in otherwise healthy subjects; (d) projects with the aim of raising awareness of hypertension, urinary abnormalities and diabetes in out-clinic subjects should be supported; (e) the use of a transportable clinic parked in residential areas of cities appears a suitable way for promoting evaluation of BP and urine test in subjects unaware of disease.

Factors associated with health-related quality of life among hemodialysis patients in the DOPPS.

OBJECTIVE: To identify modifiable factors associated with health-related quality of life (HRQOL) among chronic hemodialysis patients. METHODS: Analysis of baseline data of 9,526 hemodialysis patients from seven countries enrolled in phase I of the Dialysis Outcomes and Practice Patterns Study (DOPPS). Using the Kidney Disease Quality of Life Short Form (KDQOL-SF(TM)), we determined scores for 8 generic scale summaries derived from these scales, i.e., the physical component summary [PCS] and mental component summary [MCS], and 11 kidney disease- targeted scales. Regression models were used to adjust for differences in comorbidities and sociodemographic and treatment factors. The Benjamini-Hochberg procedure was used to correct P-values for multiple comparisons. RESULTS: Unemployment and psychiatric disease were independently and significantly associated with lower scores for all generic and several kidney disease-targeted HRQOL measures. Several other comorbidities, lower educational level, lower income, and hypoalbuminemia were also independently and significantly associated with lower scores of PCS and/or MCS and several generic and kidney disease-targeted scales. Hemodialysis by catheter was associated with significantly lower PCS scores, partially explained by the correlation with covariates. CONCLUSION: Associations of poorer HRQOL with preventable or controllable factors support a greater focus on psychosocial and medical interventions to improve the well-being of hemodialysis patients.

Progression of coronary artery calcification in predialysis patients.

BACKGROUND: In patients on dialysis coronary artery calcification (CAC) rapidly proceeds due to impaired mineral metabolism and/or exogenous calcium load. Progression has not been assessed in patients with chronic kidney disease not yet requiring dialysis (CKD patients). In this study, rate and determinants of CAC progression have been evaluated in CKD patients who are exposed to minor derangement of mineral metabolism and calcium load. METHODS: Consecutive patients were enrolled. Exclusion criteria were: symptomatic coronary disease, arrhythmia, myocardial infarction, and diabetes. Serum calcium, phosphorus, parathyroid hormone, homocysteine, C-reactive protein, triglycerides, total cholesterol, high- and low-density lipoprotein cholesterol were serially measured. Fetuin-A was assessed at entry into the study. CAC progression was detected by measuring total calcium score (TCS) with computed tomography. Initial and final scans were obtained. Predictive factors of progression were investigated. RESULTS: Fifty-three patients had CKD (stage 3-5 CKD; K-DOQI classification) not yet requiring dialysis, and 60 patients had normal renal function (NRF patients). Follow-up lasted 24 +/- 4.2 months (mean +/- SE). Patients with CAC were older with lower serum fetuin-A. TCS increased from 73 +/- 17 to 80 +/- 20 (mean +/- SE; p = NS) in NRF patients, and from 384 +/- 116 to 602 +/- 140 (mean +/- SE; p < 0.01) in CKD patients. Serum phosphorus [OR = 1.97 (1.14-3.41, 95% CI); p = 0.015] was the only variable that was associated with CAC progression. Cardiovascular events occurred in CKD patients with CAC. CONCLUSION: CAC progression was prominent in CKD patients and correlated with serum phosphorus. Fatal and nonfatal cardiovascular events were more frequent in CKD patients. Studies are required to ascertain whether the attainment of serum phosphorus concentration lower than that suggested by current guidelines may reduce CAC progression and ultimately mortality.