A randomized, controlled trial comparing the immunogenecity and safety of a 23-valent pneumococcal polysaccharide vaccination to a repeated dose 13-valent pneumococcal conjugate vaccination in kidney transplant recipients.

BACKGROUND: The risk of invasive pneumococcal disease is significant among solid organ transplant (SOT) recipients. The optimal pneumococcal vaccination strategy for SOT patients is not known. METHODS: The potential kidney transplant recipients in dialysis were randomized into two arms: to receive a 23-valent pneumococcal polysaccharide vaccine (PPV23) before transplantation or to receive a 13-valent pneumococcal conjugate vaccine (PCV13) before transplantation and a second dose of PCV13 six months after the transplantation. Serotype-specific antibody concentrations and opsonophagocytic activity (OPA) were measured before and after the first vaccination (visits V1,V2) and six and seven months after the transplantation, for example, before and after the second PCV13 (visits V3,V4). RESULTS: Out of 133 participants, 48 (PCV13 arm) and 46 (PPV23 arm) received a kidney transplant, and 37 + 37 in both arms completed the study. After the first vaccination, the geometric mean concentrations (GMCs) in the PCV13 arm were significantly higher for 9/13 serotypes and the OPA geometric mean titers (GMTs) were significantly higher for 4/13 serotypes. At V3, the antibody levels had declined but OPA remained significantly higher for 7/13 (PCV13) vs 4/13 (PPV23) serotypes. At V4, the GMCs for 9/13 serotypes and the GMTs for 12/13 serotypes were significantly higher in the PCV13 arm. The GMCs but not GMTs were lower than at V2. There was no difference in adverse effects. No vaccine-related allograft rejection was detected. CONCLUSIONS: The immunogenicity of PCV13 was better in dialysis patients, and revaccination with PCV13 was immunogenic and safe.

Autoantibodies Targeting a Collecting Duct-Specific Water Channel in Tubulointerstitial Nephritis.

Tubulointerstitial nephritis is a common cause of kidney failure and may have diverse etiologies. This form of nephritis is sometimes associated with autoimmune disease, but the role of autoimmune mechanisms in disease development is not well understood. Here, we present the cases of three patients with autoimmune polyendocrine syndrome type 1 who developed tubulointerstitial nephritis and ESRD in association with autoantibodies against kidney collecting duct cells. One of the patients developed autoantibodies targeting the collecting duct-specific water channel aquaporin 2, whereas autoantibodies of the two other patients reacted against the HOXB7 or NFAT5 transcription factors, which regulate the aquaporin 2 promoter. Our findings suggest that tubulointerstitial nephritis developed in these patients as a result of an autoimmune insult on the kidney collecting duct cells.

A narrow-band ultraviolet B course improves vitamin D balance and alters cutaneous CYP27A1 and CYP27B1 mRNA expression levels in haemodialysis patients supplemented with oral vitamin D.

BACKGROUND/AIMS: Chronic kidney disease (CKD) patients on dialysis are prone to vitamin D insufficiency despite oral vitamin D supplementation. Here, we studied whether narrow-band ultraviolet B (NB-UVB) exposures improve vitamin D balance. METHODS: 14 haemodialysis patients and 15 healthy subjects receiving oral cholecalciferol 20 µg daily got nine NB-UVB exposures on the entire body. Serum 25-hydroxyvitamin D (25(OH)D) was measured by radioimmunoassay. Cutaneous mRNA expression levels of CYP27A1 and CYP27B1, two enzymes required for hydroxylation of vitamin D into its active metabolite, were also measured. RESULTS: The baseline serum 25(OH)D concentration was 57.6 ± 18.2 nmol/l in the CKD patients and 74.3 ± 14.8 nmol/l in the healthy subjects. The NB-UVB course increased serum 25(OH)D by 14.0 nmol/l (95% CI 8.7-19.5) and 17.0 nmol/l (CI 13.7-20.2), respectively. At baseline the CKD patients showed significantly increased CYP27B1 levels compared to the healthy subjects. CONCLUSIONS: A short NB-UVB course is an efficient way to improve vitamin D balance in CKD patients on dialysis who are receiving oral vitamin D supplementation. The increased cutaneous CYP27B1 levels in the CKD patients suggest that the loss of renal activity of this enzyme is at least partially compensated for by the skin.

[Kidney transplantation from a living donor: criteria for donor and recipient]. / Munuaissiirto elävältä luovuttajalta: luovuttajan ja vastaanottajan kriteerit.

The annual number of kidney transplantations in Finland is 150 to 200. Successful kidney transplantation improves the patient's quality of life and prognosis and is cost-effective as compared with dialytic therapy. Only a few per cent of transplantations are made from a living donor. Waiting times for kidney transplantations have become longer in the last few years. Whereas attempts should be made to better identify potential brain-dead organ donors in order to increase kidney transplantations, transplantations from living donors could also reduce the disproportion between the availability and the need of organs.

Factors associated with time to first dialysis-associated peritonitis episode: Data from the Peritonitis Prevention Study (PEPS).

INTRODUCTION: Peritonitis remains a potentially serious complication of peritoneal dialysis (PD) treatment. It is therefore important to identify risk factors in order to reduce the incidence of peritonitis. The aim of the present analysis was to identify factors associated with time to first peritonitis episode. METHODS: Incident PD patients from 57 centres in Europe participated in the prospective randomised controlled Peritonitis Prevention Study (PEPS) from 2010 to 2015. Peritonitis-free, self-care PD patients ≥18 years were randomised to a retraining or a control group and followed for 1-36 months after PD initiation. The association of biochemical, clinical and prescription data with time to first peritonitis episode was studied. RESULTS: A first peritonitis episode was experienced by 33% (223/671) of participants. Univariable Cox proportional hazard regression showed a strong association between the time-updated number of PD bags connected per 24 h (PD bags/24 h) and time to first peritonitis episode (HR 1.35; 95% confidence interval (CI) 1.17-1.57), even after inclusion of PD modalities in the same model. Multivariable Cox regression revealed that the factors independently associated with time to first peritonitis episode included age (HR 1.16 per 10 years; 95% CI 1.05-1.28), PD bags/24 h (HR 1.32; 95% CI 1.13-1.54), serum albumin <35 versus >35 g/L (HR 1.39; 95% CI 1.06-1.82) and body weight per 10 kg (HR 1.10; 95% CI 1.01-1.19). CONCLUSION: This study of incident PD patients indicates that older age, greater number of PD bags connected/24 h, higher body weight and hypoalbuminaemia are independently associated with a shorter time to first peritonitis episode.

Narrow-band ultraviolet B exposure increases serum vitamin D levels in haemodialysis patients.

BACKGROUND: Chronic kidney disease (CKD) patients are especially prone to vitamin D insufficiency. Narrow-band ultraviolet B (NB-UVB) treatment increases serum 25-hydroxyvitamin D [25(OH)D] in dermatological patients, and we studied whether it also improves vitamin D balance in CKD patients on haemodialysis. METHODS: Fifteen dialysis patients (mean age 48.3 years) and 12 healthy subjects (mean age 43.6 years) received nine NB-UVB exposures on the upper body. Serum 25(OH)D and 1,25(OH)(2)D were measured before and after the exposures. From skin biopsy specimen messenger RNA (mRNA) expression levels of CYP24A1 and CYP27B1, two enzymes needed for hydroxylation of vitamin D into its active metabolites, and of antimicrobial peptide cathelicidin, were examined. RESULTS: Before NB-UVB, mean serum 25(OH)D was 32.5 ± 10.2 nmol/L in the dialysis patients and 60.2 ± 18.0 nmol/L in the healthy subjects (P < 0.001). After eight NB-UVB exposures, serum 25(OH)D increased by 13.8 nmol/L (43%; P < 0.001) and serum 1,25(OH)(2)D by 3.3 pmol/L (27%; P = 0.002) in the dialysis patients. After NB-UVB exposures, CYP27B1 mRNA was increased (P = 0.04), whereas cathelicidin mRNA was decreased (P < 0.0001) compared to non-treated healthy subjects. One and 2 months after NB-UVB exposure, serum 25(OH)D was still 10% higher than initially in the dialysis patients. CONCLUSIONS: The present study shows that a short course of NB-UVB exposure increases significantly serum 25(OH)D and 1,25(OH)(2)D in dialysis patients. The effect is, however, short lasting suggesting that the patients need cyclic NB-UVB exposure to maintain their improved vitamin D concentration.

[Kidney transplantation criteria in Finland]. / Kuka munuaissiirtolistalle--kriteerit 2011.

In the treatment of end-stage renal disease, kidney transplantation is the best and most cost-effective alternative with regard to both prognosis and quality of life. Problems arise from the disproportion between the number of available allografts and the patients waiting for the transplantation. There are few absolute contraindications to kidney transplantation. In the assessment of the eligibility for transplantation of patients on dialysis the most important factors include cardiovascular diseases, cancer diseases, other diseases affecting operability and life expectancy, age, excess weight and possible infections.

[The follow-up of kidney transplant patients]. / Munuaissiirtopotilaan seuranta.

Although the results of kidney transplantation have improved markedly, the long-term survival of renal allografts is still a major challenge. The long-term exposure of recipients to chronic renal failure and chronic immunosuppression increases the burden of infections, cardiovascular diseases, malignancies, and renal bone disease. The prevention and adequate treatment of these complications have become increasingly important. During the first months after kidney transplantation patients are followed carefully with short intervals; in stable patients the follow-up frequency is reduced later. Most important laboratory tests in the follow-up include parameters of graft function and pharmacokinetic monitoring of the immunosuppressive drugs.

Retraining for prevention of peritonitis in peritoneal dialysis patients: A randomized controlled trial.

BACKGROUND: Peritonitis is more common in peritoneal dialysis (PD) patients nonadherent to the PD exchange protocol procedures than in compliant patients. We therefore investigated whether regular testing of PD knowledge with focus on infection prophylaxis could increase the time to first peritonitis (primary outcome) and reduce the peritonitis rate in new PD patients. METHODS: This physician-initiated, open-label, parallel group trial took place at 57 centers in Sweden, Denmark, Norway, Finland, Estonia, Latvia, the Netherlands, and the United Kingdom from 2010 to 2015. New peritonitis-free PD patients were randomized using computer-generated numbers 1 month after the start of PD either to a control group (n = 331) treated according to center routines or to a retraining group (n = 340), which underwent testing of PD knowledge and skills at 1, 3, 6, 12, 18, 24, 30, and 36 months after PD start, followed by retraining if the goals were not achieved. RESULTS: In all, 74% of the controls and 80% of the retraining patients discontinued the study. The groups did not differ significantly regarding cumulative incidence of first peritonitis adjusted for competing risks (kidney transplantation, transfer to hemodialysis and death; hazard ratio 0.84; 95% confidence interval (CI) 0.65-1.09) nor regarding peritonitis rate per patient year (relative risk 0.93; 95% CI 0.75-1.16). CONCLUSIONS: In this randomized controlled trial, we were unable to demonstrate that regular, targeted testing and retraining of new PD patients increased the time to first peritonitis or reduced the rate of peritonitis, as the study comprised patients with a low risk of peritonitis, was underpowered, open to type 1 statistical error, and contamination between groups.

Cinacalcet and achievement of the NKF/K-DOQI recommended target values for bone and mineral metabolism in real-world clinical practice--the ECHO observational study.

BACKGROUND: The use and effectiveness of cinacalcet in 'real-world' clinical practice was investigated in a pan-European observational study in dialysis patients with secondary hyperparathyroidism (SHPT) of varying severity. METHODS: Adult patients with chronic kidney disease on dialysis who had initiated cinacalcet treatment were enrolled. Data were collected 6 months before initiating cinacalcet, at baseline (initiation of cinacalcet) and up to 12 months after cinacalcet initiation. RESULTS: A total of 1865 patients [mean (SD) age 58 (15) years] were enrolled from 187 sites in 12 countries. Most patients had a dialysis vintage of > or =1 year (1-5 years, n = 833; >5 years, n = 748 versus <1 year, n = 265). The patients generally had severely uncontrolled intact parathyroid hormone (iPTH) serum levels (median 721 pg/ml) and elevated phosphorus (median 5.9 mg/dl) and calcium (median 9.6 mg/dl) at baseline, despite being prescribed conventional therapies. The proportions of patients achieving the recommended [NKF-K/DOQI(TM) (KDOQI(TM))] targets increased from baseline [4%, 39%, 40% and 46% for iPTH, phosphorus, calcium and calcium-phosphorus product (Ca x P), respectively] to Month 12 (28%, 48%, 51% and 68%, respectively). At Month 12, 18% of patients had achieved the combined target for iPTH + Ca x P compared with 2% at baseline. Most patients (65%) received <60 mg/day cinacalcet at Month 12. Vitamin D sterol use remained fairly stable throughout the study. There was a 13% decrease in prescribed sevelamer; use of calcium-based phosphate binders increased by 5.6%. There was no unexpected safety or tolerability concerns. CONCLUSION: This analysis of current European clinical practice shows that-consistent with findings from randomized controlled trials and retrospective observational studies-cinacalcet improves attainment of KDOQI bone metabolism targets in dialysis patients with various stages of SHPT.

Impact of vitamin D dose on biochemical parameters in patients with secondary hyperparathyroidism receiving cinacalcet.

BACKGROUND/AIMS: The calcimimetic cinacalcet (Mimpara/Sensipar) simultaneously lowers parathyroid hormone (PTH), phosphorus (P) and calcium (Ca) levels in patients with secondary hyperparathyroidism. The OPTIMA study demonstrated that cinacalcet and adjusted doses of vitamin D maximized control of these parameters. This post-hoc analysis of OPTIMA data assessed the impact of reducing or increasing the dose of concomitant vitamin D on PTH, P and Ca in patients receiving cinacalcet. METHODS: Dialysis patients with mean baseline intact PTH (iPTH) 300-800 pg/ml (31.8-84.8 pM) received doses of cinacalcet titrated to achieve an iPTH of 150-300 pg/ml (15.9-31.8 pM). The dose of vitamin D could then be decreased to further reduce serum P or Ca, or increased/initiated to further decrease PTH levels if iPTH >300 pg/ml or to increase Ca if Ca <8.0 mg/dl (2.0 mM). RESULTS: Vitamin D dose was assessed for 345 patients during a 23-week period. A total of 91 and 129 patients had an increase or decrease in vitamin D dose, respectively. By study end, mean iPTH, P, and Ca were similar in both vitamin D groups, although there were differences in biochemical parameters between groups at the start of the study. There were statistically significant reductions from baseline to study end in iPTH and Ca in both groups (p < 0.001). Although P was significantly reduced by week 23 in the group in which vitamin D dose was decreased (p = 0.007), the reduction in P was less and did not achieve significance in the group in which vitamin D dose was increased (p = 0.71). CONCLUSIONS: After initiating cinacalcet, the dose of vitamin D can be adjusted to maximize reductions in PTH, P and Ca; however, vitamin D-induced decreases in PTH need to be balanced with the diminished response in P and Ca.

Valvular calcification and its relationship to atherosclerosis in chronic kidney disease.

BACKGROUND AND AIM OF THE STUDY: Cardiovascular calcification is a common complication in patients with chronic kidney disease (CKD). The study aim was to identify the characteristics and risk factors of valvular calcification, and its relationship to atherosclerosis, in CKD. METHODS: In this cross-sectional study, a total of 135 patients with CKD (mean age 52 +/- 11 years) included 58 pre-dialysis patients, 36 dialysis patients, and 41 renal transplant recipients. A control group of 58 subjects was also examined. The characteristics of valvular calcification were assessed using transthoracic echocardiography. RESULTS: The combined prevalences of mitral or aortic valve calcification were 31% in pre-dialysis patients, 50% in dialysis patients, 29% in renal transplant recipients, and 12% in controls (p = 0.001). The prevalences of mitral annular calcification were 17%, 31%, 27% and 2%, respectively (p = 0.001). In multivariate analysis, the risk factors for valvular calcification in CKD were age, duration of dialysis treatment and interleukin-6 level. Mitral annular calcification proved to be five-fold more common in diabetic patients than among non-diabetics. A close association between valvular calcification and patients with or without increased carotid intima-media thickness (44% versus 15%, p < 0.001), carotid plaque (77% versus 49%, p = 0.002), calcified carotid plaque (65% versus 26%, p = 0.001), coronary artery disease (40% versus 15%, p = 0.003) and peripheral arterial disease (46% versus 9%, p < 0.001) was found. CONCLUSION: Valvular calcification is common in CKD, and is closely associated with findings of intimal arterial disease. The presence of inflammation and the duration of dialysis treatment contribute to this complication. Diabetes is also a prominent risk factor for mitral annular calcification in CKD.

Treatment of experimental renal osteodystrophy with pamidronate.

We evaluated the effects of the bisphosphonate pamidronate on bone histomorphometry, structure and strength in male rats with uninephrectomy or with chronic renal disease induced by 5/6 nephrectomy. In rats with chronic renal disease the plasma urea, phosphate and parathyroid hormone levels were significantly increased compared to rats with a uninephroctomy and none of these parameters was affected by pamidronate treatment. In the femoral midshaft, chronic renal disease reduced cortical bone mineral density and content. No difference was observed in the breaking load of the femoral midshaft. In the distal femur, a high-turnover renal osteodystrophy was found but pamidronate suppressed this bone turnover and increased bone mineral content. Treatment had no effect on chronic disease-induced augmentation of osteoid volume or fibroblast surface. These studies show that in this model of stage 3 renal disease, pamidronate increased mineral content in the femoral midshaft and distal metaphysis primarily by adding bone to endocortical and trabecular surfaces but did not reduce osteitis fibrosa.

Measurement of the kidney function in patients with rheumatoid arthritis: plasma cystatin C versus 51Cr-EDTA clearance.

BACKGROUND/AIM: Knowledge of the usefulness of cystatin C measurement in the detection of chronic kidney disease in patients with rheumatoid arthritis (RA) is scant. The purpose of this study was to evaluate the ability of plasma cystatin C- and creatinine-based methods to predict glomerular filtration rate (GFR) and classify chronic kidney disease in RA patients. METHODS: The study population consisted of 64 RA patients aged 41-86 years. Comparisons were made between measured plasma creatinine, cystatin C, creatinine clearance and GFR estimated by the Cockcroft-Gault (CG) and the Modification of Diet in Renal Disease (MDRD) formulas. The plasma clearance of (51)Cr-EDTA served as a reference. RESULTS: The Pearson correlation coefficients between plasma clearance of (51)Cr-EDTA and the markers of GFR were calculated. The correlation coefficients were 0.800 for plasma creatinine, 0.863 for cystatin C, 0.866 and 0.904 for GFR values estimated by MDRD and CG and 0.922 for plasma creatinine clearance. Statistically significant differences were detected between the correlation coefficients of plasma creatinine and GFR estimated by CG (p = 0.0412) and plasma creatinine and creatinine clearance (p = 0.0099). Creatinine clearance and the MDRD and CG formulas proved to be better at identifying GFR <90 ml/min than plasma creatinine or cystatin C. CONCLUSION: We recommend using the CG formula or creatinine clearance for the estimation of the GFR of RA patients instead of solely creatinine or cystatin C in clinical work.

Abdominal Aortic Calcifications Predict Survival in Peritoneal Dialysis Patients.

BACKGROUND: Peripheral arterial disease and vascular calcifications contribute significantly to the outcome of dialysis patients. The aim of this study was to evaluate the prognostic role of severity of abdominal aortic calcifications and peripheral arterial disease on outcome of peritoneal dialysis (PD) patients using methods easily available in everyday clinical practice. METHODS: We enrolled 249 PD patients (mean age 61 years, 67% male) in this prospective, observational, multicenter study from 2009 to 2013. The abdominal aortic calcification score (AACS) was assessed using lateral lumbar X ray, and the ankle-brachial index (ABI) using a Doppler device. RESULTS: The median AACS was 11 (range 0 - 24). In 58% of the patients, all 4 segments of the abdominal aorta showed deposits, while 19% of patients had no visible deposits (AACS 0). Ankle-brachial index was normal in 49%, low (< 0.9) in 17%, and high (> 1.3) in 34% of patients. Altogether 91 patients (37%) died during the median follow-up of 46 months. Only 2 patients (5%) with AACS 0 died compared with 50% of the patients with AACS ≥ 7 (p < 0.001). The adjusted hazard ratio for all-cause mortality was 4.85 (95% confidence interval [CI] 1.94 - 24.46) for aortic calcification (AACS ≥ 7), 2.14 for diabetes (yes/no), 0.93 for albumin (per 1 g/L), and 1.04 for age (per year). A low or high ABI were not independently associated with mortality. CONCLUSIONS: Severe aortic calcification was a strong predictor of all-cause mortality in PD patients. The evaluation of aortic calcifications by lateral X ray is a simple method that allows the identification of high-risk patients.

Nephropathy advancing to end-stage renal disease: a novel complication of lysinuric protein intolerance.

OBJECTIVE: To analyze systemically the prevalence of renal involvement in a cohort of Finnish patients with lysinuric protein intolerance (LPI) and to describe the course and outcome of end-stage renal disease in 4 patients. STUDY DESIGN: The clinical information in a cohort of 39 Finnish patients with LPI was analyzed retrospectively. RESULTS: Proteinuria was observed in 74% of the patients and hematuria was observed in 38% of the patients during follow-up. Elevated blood pressure was diagnosed in 36% of the patients. Mean serum creatinine concentration increased in 38% of the patients, and cystatin C concentration increased in 59% of the patients. Four patients required dialysis, and severe anemia with poor response to erythropoietin and iron supplementation also developed in these patients. CONCLUSIONS: Our findings suggest that renal function of patients with LPI needs to be carefully monitored, and hypertension and hyperlipidemia should be treated effectively. Special attention also should be paid to the prevention of osteoporosis and carnitine deficiency in the patients with end-stage renal disease associated with LPI. The primary disease does not prohibit treatment by dialysis and renal transplantation.

Implications of levels of serum mineral metabolism markers, albumin and C-reactive protein for treatment costs of patients on maintenance dialysis.

BACKGROUND: Secondary hyperparathyroidism, malnutrition and inflammation have been reported to associate with adverse outcomes in dialysis patients. However, little is known about the implications of these conditions for treatment costs. METHODS: The cost data of all adult patients who had entered dialysis therapy at Tampere University Hospital between 1991 and 1996 and had remained on dialysis for at least 1 year were collected. results of measurements of parathyroid hormone (PTH), calcium, phosphorus, albumin and C-reactive protein (CRP) were obtained from the database of the hospital. RESULTS: Patients (n = 109), aged 57.0 +/- 14.9 years, included 57% men and 37% diabetics; 62% started on hemodialysis and 38% on peritoneal dialysis. Average daily costs were USD 161 (range 95-360). After controlling for patients' age, body mass index, gender, dialysis modality and primary renal disease, there was a positive correlation between average CRP and average costs and a negative correlation between albumin and costs. Correlations between mineral metabolism markers and costs were not found, but there was a trend towards lower cost among patients who achieved the Kidney Disease Outcomes Quality Initiative targets of calcium, phosphorus and PTH (USD 145 +/- 31) compared with those with nonoptimal levels (USD 165 +/- 48; p = 0.095). Costs of patients with at least one in-target PTH measurement were lower than costs of patients with constantly low PTH (USD 148 +/- 31 vs. 170 +/- 48; p = 0.01). CONCLUSION: Serum levels of albumin and CRP correlated with dialysis patients' treatment costs. Achieving the Kidney Disease Outcomes Quality Initiative targets may be associated with lower costs.

Peripheral vascular disease in diabetic peritoneal dialysis patients.

In the present article, we review current knowledge of the epidemiology, diagnosis, and treatment of peripheral vascular disease in patients with end-stage renal disease. The main focus is placed on diabetic patients receiving peritoneal dialysis, but studies on patients receiving hemodialysis are also reviewed, because most reports involve this patient group, and the number of reports on peripheral vascular disease in PD patients alone is limited.

Comparison of calcium phosphate product values using measurement of plasma total calcium and serum ionized calcium.

Calcium phosphate product (Ca x Pi) is a clinically relevant tool to estimate the cardiovascular risk of patients with renal failure. In reports, mostly total serum calcium has been used. As measurement of serum ionized calcium has some benefits and is being used increasingly, we estimated the respective levels of calcium phosphate product using both total (t-Ca x Pi) and ionized calcium (ion-Ca x Pi). Fifty-eight healthy individuals and 180 hemodialysis (HD) patients from 2 centers were studied. Diagnostic accuracies for corresponding values of the t-Ca x Pi and ion-Ca x Pi were calculated using a GraphROC program. Of HD patients, 64% had t-Ca x Pi <4.4 mmol(2)/L(2) regarded as a desirable goal, and 10% had values over 5.6 mmol(2)/L(2) associated with a high cardiovascular risk. Based on GraphROC analysis, t-Ca x Pi of 4.4 mmol(2)/L(2) corresponded to a value of 2.2 mmol(2)/L(2) of ion-Ca x Pi and, respectively, t-Ca x Pi of 5.6 mmol(2)/L(2) corresponded 2.8 mmol(2)/L(2) of ion-Ca x Pi. Owing to the good agreement between the results in the 2 centers, these values for risk levels can be used in both centers. When measurement of ionized calcium is used, Ca x Pi values of 2.2 and 2.8 mmol(2)/L(2) can be used instead of generally used values of 4.4 and 5.6 mmol(2)/L(2) with total calcium.

Renal insufficiency-induced bone loss is associated with an increase in bone size and preservation of strength in rat proximal femur.

Chronic renal insufficiency (CRI) results in phosphate retention and secondary hyperparathyroidism, the treatment of which is largely based on the use of calcium salts as phosphate binders. Advanced CRI causes bone fragility, but information about bone geometry and strength in moderate CRI is scarce. We assigned 39 8-week-old male Sprague-Dawley rats to sham-operation (Sham) or 5/6 nephrectomy (NTX). Four weeks later, the rats were randomized to 0.3% calcium (Sham, NTX) or 3.0% calcium diet (Sham + Calcium, NTX + Calcium). After 8 weeks, the animals were sacrificed, plasma samples collected, and femora excised for neck and midshaft analyses: dual-energy X-ray absorptiometry, peripheral quantitative computed tomography, and biomechanical testing. The NTX increased plasma urea and PTH 1.6-fold and 3.6-fold, respectively, whereas high calcium intake suppressed PTH to 30% of controls. Total femoral bone mineral content decreased (-6.3%) in the NTX group, while this deleterious effect was reversed by high calcium diet. In the site-specific analysis of the femoral neck, the volumetric bone density (-6.5%) was decreased in the NTX group but not NTX + Calcium group. However, in the nephrectomized rats, there was also a concomitant increase in the cross-sectional area (+15%), and, despite the decrease in bone density, the mechanical strength of the femoral neck was maintained. In the midshaft, NTX decreased cortical volumetric bone density (-1.2%), but similar to the femoral neck, no differences were found in the mechanical strength. In conclusion, a decrease in bone mass in moderate experimental CRI was associated with a concomitant increase in bone size, and maintenance of mechanical competence. Although high calcium diet suppressed plasma PTH to under normal physiological levels, it prevented the CRI-induced loss of bone mass without an adverse influence on bone strength.