The Role of Secondary Calciprotein Particles in the Mineralisation Paradox of Chronic Kidney Disease.

Mineralisation paradox is prevalent in chronic kidney disease and ageing where increased vascular calcification is accompanied by reduced bone mineralisation and osteopenia. Secondary calciprotein particles (CPP2), colloidal nanoparticles containing hydroxyapatite crystal stabilised by a protein shell, have been implicated in vascular calcification in chronic kidney disease. Here, we describe the effect of CPP2 on osteoblasts and vascular smooth muscle cells (VSMC) mineralisation in an in vitro model system. The mineralisation paradox can be simulated in vitro by the addition of phosphate ions (Pi, 3 mM) and CPP2 (10 µg/ml of Ca equivalent). Pi alone induced osteoblast mineralisation but had no effect on VSMC mineralisation. CPP2 alone had no effect on mineralisation in either cell line, but when combined with elevated Pi, reduced osteoblast-like mineralisation (P < 0.001) whilst induced VSMC mineralisation (P < 0.001). These results suggest that in an in vitro system the synergistic interaction between Pi and CPP2 could mimic the mineralisation paradox, and may provide a potential mechanistic link to explain these clinical observations.

Is there a role for newer biomarkers in chronic kidney disease-mineral and bone disorder management?

The current management of Chronic Kidney Disease-Mineral Bone Disorder (CKD-MBD) relies largely on clinical judgement and assessment of biochemical parameters including serum calcium, phosphate and intact parathyroid hormone concentrations. In the past two decades, there has been a leap in the understanding of the pathophysiology of CKD-MBD, leading to the discovery of novel biomarkers. The potential utility of these markers in this clinical setting is an area of intense investigation. In the absence of any guidelines aiding the clinician's understanding and application of these markers, we summarise the current available literature surrounding fibroblast growth factor-23, α-Klotho, sclerostin and serum calcification propensity testing and their respective assays in the context of CKD-MBD management.

Protection provided by a herpes simplex virus 2 (HSV-2) glycoprotein C and D subunit antigen vaccine against genital HSV-2 infection in HSV-1-seropositive guinea pigs.

A prophylactic vaccine for genital herpes disease remains an elusive goal. We report the results of two studies performed collaboratively in different laboratories that assessed immunogenicity and vaccine efficacy in herpes simplex virus 1 (HSV-1)-seropositive guinea pigs immunized and subsequently challenged intravaginally with HSV-2. In study 1, HSV-2 glycoproteins C (gC2) and D (gD2) were produced in baculovirus and administered intramuscularly as monovalent or bivalent vaccines with CpG and alum. In study 2, gD2 was produced in CHO cells and given intramuscularly with monophosphoryl lipid A (MPL) and alum, or gC2 and gD2 were produced in glycoengineered Pichia pastoris and administered intramuscularly as a bivalent vaccine with Iscomatrix and alum to HSV-1-naive or -seropositive guinea pigs. In both studies, immunization boosted neutralizing antibody responses to HSV-1 and HSV-2. In study 1, immunization with gC2, gD2, or both immunogens significantly reduced the frequency of genital lesions, with the bivalent vaccine showing the greatest protection. In study 2, both vaccines were highly protective against genital disease in naive and HSV-1-seropositive animals. Comparisons between gD2 and gC2/gD2 in study 2 must be interpreted cautiously, because different adjuvants, gD2 doses, and antigen production methods were used; however, significant differences invariably favored the bivalent vaccine. Immunization of naive animals with gC2/gD2 significantly reduced the number of days of vaginal shedding of HSV-2 DNA compared with that for mock-immunized animals. Surprisingly, in both studies, immunization of HSV-1-seropositive animals had little effect on recurrent vaginal shedding of HSV-2 DNA, despite significantly reducing genital disease.

Relative abundance of fetuin- A in peritoneal dialysis effluent and its association with in situ formation of calciprotein particles: an observational pilot study.

AIM: In patients with renal failure or chronic inflammation, the accumulation of fetuin-A-containing calciprotein particles (CPP) in the extracellular fluid has been implicated in driving inflammatory pathways and extraosseous mineral deposition. We aimed to discover whether CPP are present in the peritoneal dialysis fluid effluent (PDF) of stable peritoneal dialysis (PD) patients, and if so, how these particles might be formed. METHODS: Serum and PDF were sampled from 20 stable PD patients. CPP were quantified by the reduction in fetuin-A concentration after high speed centrifugation. 8-iso-PGF2α in PDF was measured as a marker of oxidative stress. Fetuin-A and phosphate were added to commercially available dialysis fluids to assess their ability to support CPP formation ex vivo. RESULTS: We report that the major protein component of these mineral-containing nanoparticles, fetuin-A, is relatively abundant in PDF and that CPP were present in the PDF of 17/20 PD patients. PDF CPP levels were strongly correlated with 8-iso-PGF2α concentrations. In vitro experiments suggested that commonly used peritoneal dialysate fluids, irrespective of composition, could not sustain appreciable de novo CPP formation ex vivo. CONCLUSION: Fetuin-A is either actively transported or locally produced by the peritoneal membrane in PD patients. The association between fetuin-A-containing CPP and markers of oxidative stress warrants further mechanistic studies.

In search of an effective treatment for recurrent mesangiocapillary glomerulonephritis in the renal allograft.

In patients with end-stage kidney disease (ESKD) secondary to mesangiocapillary glomerulonephritis (MCGN), recurrent disease post transplantation is a common cause of graft loss. We report a case of a 33-year-old female with ESKD due to idiopathic MCGN who developed recurrent disease in two consecutive renal allografts. Recurrent disease was diagnosed two months after receiving her primary transplant from a live related donor. Oral cyclophosphamide was initiated but discontinued after 10 months due to cystitis. This was followed by rapid deterioration in her renal function. Despite salvage therapy with rituximab, the graft was lost 2 years post transplantation. After 7 years on haemodialysis, the patient received a second graft from a deceased donor. Recurrent MCGN was once again diagnosed one year post transplantation. She was treated with plasma exchange and rituximab. Despite ongoing nephrotic range proteinuria, her graft function remained stable 2 years post transplantation. The optimal therapy for recurrent MCGN is unknown at this stage. It is hoped that a better understanding of its pathogenesis will enable the development of more effective and targeted therapies.

Live attenuated herpes simplex virus 2 glycoprotein E deletion mutant as a vaccine candidate defective in neuronal spread.

A herpes simplex virus 2 (HSV-2) glycoprotein E deletion mutant (gE2-del virus) was evaluated as a replication-competent, attenuated live virus vaccine candidate. The gE2-del virus is defective in epithelial cell-to-axon spread and in anterograde transport from the neuron cell body to the axon terminus. In BALB/c and SCID mice, the gE2-del virus caused no death or disease after vaginal, intravascular, or intramuscular inoculation and was 5 orders of magnitude less virulent than wild-type virus when inoculated directly into the brain. No infectious gE2-del virus was recovered from dorsal root ganglia (DRG) after multiple routes of inoculation; however, gE2-del DNA was detected by PCR in lumbosacral DRG at a low copy number in some mice. Importantly, no recurrent vaginal shedding of gE2-del DNA was detected in immunized guinea pigs. Intramuscular immunization outperformed subcutaneous immunization in all parameters evaluated, although individual differences were not significant, and two intramuscular immunizations were more protective than one. Immunized animals had reduced vaginal disease, vaginal titers, DRG infection, recurrent genital lesions, and recurrent vaginal shedding of HSV-2 DNA; however, protection was incomplete. A combined modality immunization using live virus and HSV-2 glycoprotein C and D subunit antigens in guinea pigs did not totally eliminate recurrent lesions or recurrent vaginal shedding of HSV-2 DNA. The gE2-del virus used as an immunotherapeutic vaccine in previously HSV-2-infected guinea pigs greatly reduced the frequency of recurrent genital lesions. Therefore, the gE2-del virus is safe, other than when injected at high titer into the brain, and is efficacious as a prophylactic and immunotherapeutic vaccine.

Urinary neutrophil gelatinase-associated lipocalin may aid prediction of renal decline in patients with non-proteinuric Stages 3 and 4 chronic kidney disease (CKD).

BACKGROUND: Chronic kidney disease (CKD) is an increasing public health issue. It is therefore potentially highly advantageous to identify patients at risk of accelerated renal progression and death. Neutrophil gelatinase-associated lipocalin (NGAL) is an established urinary biomarker for acute kidney injury, but it is not known whether adding urinary NGAL (uNGAL) measurements to conventional risk factors will improve risk assessment in the setting of chronic disease. METHODS: This is a prospective observational cohort study of 158 patients with Stage 3 or 4 CKD. The ability of baseline uNGAL to improve prediction of outcome was assessed by multivariate modelling and a number of metrics including net reclassification analysis. A primary composite endpoint of all-cause mortality or progression to end-stage renal disease (ESRD) requiring renal replacement therapy (RRT) at 2 years and a secondary endpoint of ≥5 mL/min/1.73 m(2) decline in the estimated glomerular filtration rate (eGFR) after 1 year were considered. RESULTS: Forty patients (25%) reached the primary composite endpoint, 20 of whom died. Twenty-seven patients (19%) reached the secondary endpoint of a ≥5 mL/min/1.73 m(2) decline in the eGFR. The baseline uNGAL-to-creatinine ratio (uNCR) was associated with the combined endpoint of death or initiation of RRT (HR per 5 µg/mmol increase 1.27, 95% CI: 1.01-1.60, P = 0.036) independent of conventional cardiovascular and renal risk factors, including proteinuria. In separate analysis of these two competing endpoints, however, uNCR only remained associated with increased risk of progression to ESRD requiring RRT. Higher baseline uNCR was also independently predictive of rapid renal decline over 1 year (HR per 5 µg/mmol increase 1.47, 95% CI: 1.06-2.06, P = 0.022). Addition of uNCR to the base model resulted in a significant increase in discrimination for the secondary (C-statistic 0.76-0.85, P = 0.001) but not the primary endpoint (P = 0.276). Reclassification analysis on the other hand, demonstrated an improvement in risk predication of both primary and secondary endpoints by incorporating uNCR into the base model, but only in those with low-level urine protein excretion (<28 mg/mmol), with category-free net reclassification improvement (NRI) scores of 64% (95% CI: 8-70; P = 0.019) and 79% (95% CI: 12-83; P = 0.009), respectively. CONCLUSION: The utilization of uNCR in addition to conventional established cardiovascular and renal risk factors may improve the prediction of disease progression in elderly Caucasian pre-dialysis CKD patients with low-grade proteinuria.

Fetuin-A-containing calciprotein particle levels can be reduced by dialysis, sodium thiosulphate and plasma exchange. Potential therapeutic implications for calciphylaxis?

Calciprotein particles (CPP) are a novel marker of mineral stress. High levels of CPP are found in patients with calciphylaxis, a condition associated with marked vascular calcification and a poor prognosis. We report substantial reductions in CPP levels in a dialysis patient having combined haemodialysis (HD) and plasma exchange (PEx) prior to an ABO-incompatible kidney transplant. We also report the effects of the same treatments combined with sodium thiosulphate (STS) in a patient newly diagnosed with calciphylaxis. Combining HD with intra-dialytic STS and PEx we achieved a significant reduction in CCP with the least rebound between treatment sessions. After 6 weeks of treatment, the CPP reduction was paralleled by clinical improvement. Measurement of CPP may be an attractive marker for monitoring the effectiveness of calciphylaxis therapy.

Serum fetuin-A concentration and fetuin-A-containing calciprotein particles in patients with chronic inflammatory disease and renal failure.

AIM: Fetuin-A (Fet-A) is an important regulator of extracellular matrix mineralization. Fet-A plays a critical role in the formation and stabilization of high molecular weight colloidal protein-mineral complexes known as calciprotein particles (CPP). The aim of this study was to examine the effects of inflammation, renal function and dialysis modality on serum Fet-A and CPP. METHODS: This is an observational study of patients with chronic kidney disease (CKD) and those with chronic inflammatory disease (CID) but normal renal function. Serum CPP were quantified indirectly by analysing the apparent reduction in serum Fet-A concentration (reduction ratio, RR) after high-speed centrifugation. RESULTS: Serum total Fet-A concentrations are reduced in renal disease and in patients with CID. CPP were not detectable in the serum of normal individuals. CPP represent an increasing percentage of total circulating Fet-A concentrations in patients with CID (RR, 13.3 ± 8.5%), as well as in patients with pre-dialysis CKD (12.4 ± 7.3%) and those undergoing peritoneal dialysis (RR, 22.8 ± 6.0%) or haemodialysis (RR, 38.1 ± 12.8%). The highest Fet-A RR were found in patients with calcific uraemic arteriolopathy (CUA) on haemodialysis (73.9 ± 15.6%). Serum total Fet-A concentrations and Fet-A reduction ratios decreased during a single haemodialysis session, by 24% (P < 0.001) and 34% (P < 0.001), respectively. CONCLUSION: Inflammation appears to be associated with mineral stress even in the absence of renal dysfunction. Patients with CUA on haemodialysis have very high serum Fet-A reduction ratios, suggesting that this measurement may have a prognostic/diagnostic role in this condition.

pH changes in radicular dentine associated with calcium hydroxide and corticosteroid/antibiotic pastes.

The aim was to compare hydroxyl ion diffusion through dentine following placement of calcium hydroxide and Ledermix paste. Thirty-six teeth were divided into one control (n = 6) and three experimental (n = 10) groups - (i) Pulpdent paste; (ii) Pulpdent/Ledermix pastes; (iii) Ledermix paste and (iv) Saline. pH was measured in inner and outer dentine cavities over 12 months. Inner dentine time to maximum pH (Tmax ) was 1 week for Pulpdent and 2 weeks for Pulpdent/Ledermix. Pulpdent's outer dentine Tmax was 4 weeks and Pulpdent/Ledermix was 10 weeks. After day 1, Pulpdent pH was higher and this continued for 12 months. Pulpdent's outer dentine pH was higher than Ledermix and controls, but not significantly different from Pulpdent/Ledermix. Pulpdent/Ledermix had significantly higher pH than controls and Ledermix from day 5 until 10 months when Pulpdent/Ledermix outer dentine pH decreased and became similar. In all groups, pH reduced after 3 months.

Immunization with a vaccine combining herpes simplex virus 2 (HSV-2) glycoprotein C (gC) and gD subunits improves the protection of dorsal root ganglia in mice and reduces the frequency of recurrent vaginal shedding of HSV-2 DNA in guinea pigs compared to immunization with gD alone.

Attempts to develop a vaccine to prevent genital herpes simplex virus 2 (HSV-2) disease have been only marginally successful, suggesting that novel strategies are needed. Immunization with HSV-2 glycoprotein C (gC-2) and gD-2 was evaluated in mice and guinea pigs to determine whether adding gC-2 to a gD-2 subunit vaccine would improve protection by producing antibodies that block gC-2 immune evasion from complement. Antibodies produced by gC-2 immunization blocked the interaction between gC-2 and complement C3b, and passive transfer of gC-2 antibody protected complement-intact mice but not C3 knockout mice against HSV-2 challenge, indicating that gC-2 antibody is effective, at least in part, because it prevents HSV-2 evasion from complement. Immunization with gC-2 also produced neutralizing antibodies that were active in the absence of complement; however, the neutralizing titers were higher when complement was present, with the highest titers in animals immunized with both antigens. Animals immunized with the gC-2-plus-gD-2 combination had robust CD4+ T-cell responses to each immunogen. Multiple disease parameters were evaluated in mice and guinea pigs immunized with gC-2 alone, gD-2 alone, or both antigens. In general, gD-2 outperformed gC-2; however, the gC-2-plus-gD-2 combination outperformed gD-2 alone, particularly in protecting dorsal root ganglia in mice and reducing recurrent vaginal shedding of HSV-2 DNA in guinea pigs. Therefore, the gC-2 subunit antigen enhances a gD-2 subunit vaccine by stimulating a CD4+ T-cell response, by producing neutralizing antibodies that are effective in the absence and presence of complement, and by blocking immune evasion domains that inhibit complement activation.

The value of simultaneous measurements of urinary albumin and total protein in proteinuric patients.

BACKGROUND: Proteinuria is a common pathological finding in renal disease. Examining the urinary protein electrophoretic pattern gives clues to the site of origin of the protein. We hypothesized that the type of proteinuria, classified by urine protein electrophoresis and immunofixation (uPEI), may be predicted by simply examining the proportion of higher molecular weight protein (e.g. albumin) in urine total protein content. METHODS: One thousand and eleven patients, whose urine had been sent to the pathology department for uPEI, were analysed for total protein and albumin to creatinine ratio (uPCR and uACR) and the ratio reported as the albumin to total protein ratio (uAPR). In a group of renal outpatients (n=248), we also specifically measured tubular proteins (N-acetyl-ß-D-glucosaminidase, NAG, and ß2-microglobulin) and expressed these as ratios to creatinine (uNCR and uß2CR). To validate these findings, we correlated these measurements with 68 patients in whom we also had renal biopsy data. RESULTS: In receiver operating characteristic (ROC) curve analysis, the AUC for uAPR was 0.84 for predicting tubular proteinuria pattern on uPEI. In the renal outpatient subgroup, uAPR predicted a tubular pattern of urinary protein equally as well as testing for specific tubular protein markers (uNCR and uß2CR). In the validation cohort, a uAPR cut-off of <0.40 was 88% sensitive and 99% specific for the diagnosis of primary tubulointerstitial disorders on renal biopsy. CONCLUSIONS: Useful information about the origins of urinary protein may be inferred by measuring uAPR, the measurement of which is both simple and inexpensive.

Mortality in dialysis patients may not be associated with ESA dose: a 2-year prospective observational study.

BACKGROUND: Anaemia of chronic kidney disease increases the risk of death and adverse events, but can be managed using erythropoiesis stimulating agents (ESAs). However, recent evidence suggests that targeting a higher haemoglobin concentration ([Hb]) increases mortality risk, and both higher [Hb] targets and ESA doses have been implicated. Nonetheless, a causative role has not been demonstrated, and this potential relationship requires further appraisal in such a complex patient group. METHODS: The relationship between the haematopoietic response to ESAs and patient survival in 302 stable, prevalent dialysis patients was explored in a prospective, single-centre study. Clinical and laboratory parameters influencing mortality and ESA resistance were analysed. Patients were stratified into 5 groups, according to their [Hb] and ESA dosage, and were followed for 2 years. RESULTS: Little difference in co-morbidities between groups was identified. 73 patients died and 36 were transplanted. Initial analysis suggested a direct relationship between mortality and ESA dosage. However, Cox proportional hazards multivariate analysis demonstrated mortality risk was associated only with age (adjusted HR per year: 1.061, 95% CI 1.031-1.092), dialysis duration (adjusted HR: 1.010, 95% CI 1.004-1.016), peripheral vascular disease (adjusted HR: 1.967, 95% CI 1.083-3.576) and CRP (adjusted HR: 1.024, 95% CI 1.011-1.039). Mortality was increased in patients poorly responsive to ESAs (55.5%). CONCLUSION: ESA dose does not appear to contribute substantially to mortality risk in dialysis patients. Instead, age and co-morbidities appear to be the critical determinants. A poor response to ESAs is a marker of overall poor health status.

Hyperparathyroidism in chronic kidney disease: complexities within the commonplace.

Secondary hyperparathyroidism in patients with chronic kidney disease (CKD) is common and usually caused by associated metabolic abnormalities, in particular, hypocalcaemia and hyperphosphataemia. Nevertheless, other causes of hyperparathyroidism can exist concurrently with CKD, challenging diagnostic interpretation and therapeutic intervention. We present four cases of hyperparathyroidism in patients with CKD that highlight some of these dilemmas.

ATM-TCR: TCR-Epitope Binding Affinity Prediction Using a Multi-Head Self-Attention Model.

TCR-epitope pair binding is the key component for T cell regulation. The ability to predict whether a given pair binds is fundamental to understanding the underlying biology of the binding mechanism as well as developing T-cell mediated immunotherapy approaches. The advent of large-scale public databases containing TCR-epitope binding pairs enabled the recent development of computational prediction methods for TCR-epitope binding. However, the number of epitopes reported along with binding TCRs is far too small, resulting in poor out-of-sample performance for unseen epitopes. In order to address this issue, we present our model ATM-TCR which uses a multi-head self-attention mechanism to capture biological contextual information and improve generalization performance. Additionally, we present a novel application of the attention map from our model to improve out-of-sample performance by demonstrating on recent SARS-CoV-2 data.

Effect of nutritional calcium and phosphate loading on calciprotein particle kinetics in adults with normal and impaired kidney function.

Plasma approaches metastability with respect to its calcium and phosphate content, with only minor perturbations in ionic activity needed to sustain crystal growth once nucleated. Physiologically, calcium and phosphate are intermittently absorbed from the diet each day, yet plasma concentrations of these ions deviate minimally post-prandially. This implies the existence of a blood-borne mineral buffer system to sequester calcium phosphates and minimise the risk of deposition in the soft tissues. Calciprotein particles (CPP), endogenous mineral-protein colloids containing the plasma protein fetuin-A, may fulfill this function but definitive evidence linking dietary mineral loading with their formation is lacking. Here we demonstrate that CPP are formed as a normal physiological response to feeding in healthy adults and that this occurs despite minimal change in conventional serum mineral markers. Further, in individuals with Chronic Kidney Disease (CKD), in whom mineral handling is impaired, we show that both fasting and post-prandial levels of CPP precursors are markedly augmented and strongly inversely correlated with kidney function. This study highlights the important, but often neglected, contribution of colloidal biochemistry to mineral homeostasis and provides novel insight into the dysregulation of mineral metabolism in CKD.

Hydroxyl Ion Diffusion through Radicular Dentine When Calcium Hydroxide Is Used under Different Conditions.

Calcium hydroxide's anti-bacterial action relies on high pH. The aim here was to investigate hydroxyl ion diffusion through dentine under different conditions. Teeth were divided into control (n = 4) and four experimental groups (n = 10): Group 1-no medicament; Group 2-Calmix; Group 3-Calmix/Ledermix; Group 4-Calasept Plus/Ledermix; Group 5-Pulpdent/smear layer. Deep (inner dentine) and shallow (outer dentine) cavities were cut into each root. pH was measured in these cavities for 12 weeks. The inner and outer dentine pH in Group 2 was significantly higher than all groups. Inner dentine pH in Group 3 was slightly higher than that in Group 4 initially but subsequently comparable. After Day 2, Group 5 had significantly lower pH than Groups 3 and 4. The outer dentine pH in Group 3 started higher than that in Groups 4 and 5, but by Day 28 the difference was insignificant. The time for the inner dentine to reach maximum pH was one week for Group 2 and four weeks for Groups 3 and 4. The time for the outer dentine to reach maximum pH was eight weeks for all experimental groups. Mixing different Ca(OH)2 formulations with Ledermix gave similar hydroxyl ion release but pH and total diffusion was lower than Ca(OH)2 alone. The smear layer inhibited diffusion.

High-intensity physical exercise increases serum α-klotho levels in healthy volunteers.

The recently discovered klotho proteins have roles in a diverse range of metabolic processes with the oldest protein, α-klotho, implicated in various cellular pathways in energy, glucose, and phosphate metabolism. Circulating soluble klotho (sKl), derived from membrane α-klotho cleavage, not only has effects on ion channels and insulin signaling pathways, but is inversely associated with mortality. Effects of physical exercise on sKl have not been well studied. The effect of a single high-intensity standardized exercise on sKl and serum phosphate (sPi) levels in healthy adults was investigated. A standard Bruce protocol treadmill exercise was undertaken by 10 fasting healthy volunteers. sKl, sPi, and blood glucose levels were measured in samples collected 1-week prior, immediately pre (Tpre), 0 (Tpost), 30 (T30), 240 (T240) min, and 1-week after exercise. Median (interquartile range) age of participants was 47.5 (44-51) years; five (50%) were male. All study participants achieved at least 90% predicted maximum heart rate (MHR). sKl increased acutely after exercise (Tpre median 448 pg/mL vs. Tpost median 576 pg/mL; p < 0.01). There was a nonsignificant sPi decline at T30 (Tpre 0.94 ± 0.12 mmol/L vs. T30 0.83 ± 0.22 mmol/L). Exercise led to a reduction in blood glucose by T240 with median glucose levels at Tpre, Tpost, T30, and T240 of 6.0, 6.5, 6.3, and 5.7 mmol/L, respectively. In conclusion, a single high-intensity exercise session is associated with a transient increase in sKl, a delayed reduction in blood glucose, and a nonsignificant decrease in sPi levels in healthy adults. The evaluation of long-term effects of cardiovascular fitness programs on sKl and sPi in healthy individuals and disease cohorts are required to identify potential lifestyle modifications to help improve chronic disease management and long-term outcomes.

Calciprotein Particle Formation in Peritoneal Dialysis Effluent Is Dependent on Dialysate Calcium Concentration.

BACKGROUND: The accumulation of fetuin-A-containing calciprotein particles (CPP) in the serum of patients with renal disease and those with chronic inflammation may be involved in driving sterile inflammation and extraosseous mineral deposition. We previously showed that both fetuin-A and CPP were present in the peritoneal dialysis (PD) effluent of stable PD patients. It is unknown whether different PD fluids might affect the formation of CPP in vivo. METHOD: Peritoneal effluent from 12 patients was collected after a 6-hour dwell with 7 different commercial PD fluids. Calciprotein particles and inflammatory cytokines were measured by flow cytometry. RESULTS: High inter-subject variability in CPP concentration was observed. Peritoneal dialysis fluids containing 1.75 mmol/L calcium were associated with enhanced formation of CPP in vivo, compared with fluids containing 1.25 mmol/L calcium. Osmotic agent, fluid pH, and glucose concentration did not affect CPP formation. Peritoneal dialysis effluent CPP levels were not associated with changes in inflammatory cytokines. CONCLUSION: High calcium-containing PD fluids favor intraperitoneal CPP formation. This finding may have relevance for future PD fluid design.