Long-term effects of reducing the dialysate calcium concentration on bone biomarkers in adult patients on peritoneal dialysis

Introduction: Patients on peritoneal dialysis (PD) are usually exposed to a high dialysate calcium concentration (D[Ca]), which is associated with undesirable effects. Low D[Ca] might overstimulate parathyroid hormone (PTH), as shown by previous studies carried out before the incorporation of calcimimetics in clinical practice. We hypothesized that a reduction in D[Ca] is safe and without risk for a rise in serum PTH. Methods in this prospective study, the D[Ca] was reduced from 1.75 mmol/L to 1.25 mmol/L for one year in prevalent patients on PD. Demographic, clinical, and biochemical parameters were evaluated at baseline, 3, 6, and 12 months of follow-up. Results Patients (N = 20) aged 56 ± 16 years, 50% male, 25% diabetic. There was no significant change in calcium, phosphate, alkaline phosphatase, 25(OH)-vitamin D or PTH over time. Medication adjustments included an increase in calcitriol and sevelamer. After 1 year, absolute and percentual change in PTH levels were 36 (-58, 139) pg/ml, and 20% (-28, 45) respectively. The proportion of patients with PTH > 300 pg/ml did not change during the follow-up (p = 0.173). Conclusion Low D[Ca] concentration should be considered to patients on PD as a valuable and safe option. Medication adjustments to detain PTH rising, however, are advised.

Effect of citric-acid dialysate on the QTC-interval

Lower dialysate calcium (dCa) concentration and dialysate citric-acidification may positively affect calcification propensity in serum of haemodialysis (HD) patients. However, the accompanying lower ionized blood calcium concentration may lead to a prolonged cardiac action potential, which is possibly pro-arrhythmic. The aim of this study is to investigate the influence of citric-acid dialysate on the QT-interval corrected for heart rate (QTc) compared to conventional dialysate with different dCa concentrations. We conducted a four-week multicentre, randomized cross-over trial. In week one and three patients received acetic-acid dialysate with a dCa of 1.50 mmol/l (A1.5), in week two and four acetic-acid dialysate with a dCa of 1.25 mmol/l (A1.25) or citric-acid dialysate (1.0 mmol/l) with a dCa of 1.50 mmol/l (C1.5) depending on randomization. Patients had continuous ECG monitoring during one session in week one, two and four. The data of 13 patients were available for analysis. Results showed a significant though limited increase of QTc with C1.5 (from 427 to 444 ms (start to end); p = 0.007) and with A1.25 (from 431 to 449 ms; p < 0.001), but not with A1.5 (from 439 to 443 ms; p = 0.13). In conclusion, we found that the use of C1.5 or A1.25 is associated with a significant prolongation of QTc which was however relatively limited.

Skeletal and cardiovascular consequences of a positive calcium balance during hemodialysis

Patients on hemodialysis are exposed to calcium via the dialysate at least three times a week. Changes in serum calcium vary according to calcium mass transfer during dialysis, which is dependent on the gradient between serum and dialysate calcium concentration (d[Ca]) and the skeleton turnover status that alters the ability of bone to incorporate calcium. Although underappreciated, the d[Ca] can potentially cause positive calcium balance that leads to systemic organ damage, including associations with mortality, myocardial dysfunction, hemodynamic tolerability, vascular calcification, and arrhythmias. The pathophysiology of these adverse effects includes serum calcium changes, parathyroid hormone suppression, and vascular calcification through indirect and direct effects. Some organs are more susceptible to alterations in calcium homeostasis. In this review, we discuss the existing data and potential mechanisms linking the d[Ca] to calcium balance with consequent dysfunction of the skeleton, myocardium, and arteries.

P1417ALTERED CATHEPSIN-K LEVELS REFLECT SEVERITY OF MINERAL BONE DISEASE AND INFLAMMATION IN CHRONIC HEMODIALYSIS PATIENTS

Background and Aims Mineral bone disease (MBD) and chronic inflammation are key triggers of the exceeding cardiovascular risk that characterizes dialysis patients. Cathepsin-K (Cts-K) is a lysosomal cysteine protease involved in bone remodeling and resorption, whose expression is promoted particularly by inflammation and whose involvement in bone and cardiovascular disorders has previously been demonstrated. We set out to undertake an exploratory, observational study to assess the possible clinical significance of Cts-K in dialysis patients. Method Eighty-five chronic HD patients (mean age 67±12, median dialysis vintage 3.2 yrs) with stable dry weight were studied. Cts-K was measured in peripheral blood samples before a mid-week dialysis session together with standard biochemical parameters. Twenty-six healthy subjects, matched with HD patients for age and gender, served as controls. Results Cts-K was statistically higher in HD patients than in controls (median 340, IQR 170-835 vs. 190 IQR 20-120 pg/mL, p&lt;0.0001). At univariate analyses, Cts-K levels were significantly associated with ALP (r=0.50, p&lt;0.001), CRP (r=0.46, p&lt;0.001), PTH (r=0.24,p=0.02), presence of diabetes (r=0.28,p&lt;0.001),peripheral vasculopathy (r=0.20, p=0.05) and dialysate calcium concentration (r=-0.28,p&lt;0.001). In a multivariate model including all univariate predictors (R2=61%, p&lt;0.001) only ALP (β=0.70,p&lt;0.001), CRP (β=0.49,p&lt;0.001) and dialysate calcium concentration (β -0.40,p=0.04) remained significantly associated with Cts-K levels. Interestingly, Cts-K levels were significantly higher among individuals who were under active calcimimetic therapy (n=28; p&lt;0.001) but significantly lower among those who previously underwent parathyroidectomy (n=8; p&lt;0.001) (Figure 1). Conclusion Cathepsin-K is a biomarker at the crossroads of bone and inflammatory disorders in chronic hemodialysis patients. Future research is needed to clarify the exact pathophysiological role of this protein and to test its potential usefulness as a marker for managing MBD therapy and complications.

Pneumocystis jirovecii pneumonitis: cause of acute hypercalcaemia in chronic haemodialysis patient

A 76-year-old renal transplant patient due to autosomal dominant polycystic kidney disease who resumed chronic haemodialysis was admitted to our hospital for confusion and lassitude. He was afebrile and physical examination revealed diffuse bilateral rales with decreased respiratory sounds in lower right lung. Laboratory data showed hypercalcaemia (total calcium 3.92 mmol/L (normal range 2.2–2.6 mmol/L), ionised calcium 1.87 mmol/L (1.15–1.35 mmol/L)), low intact parathyroid hormone (iPTH) 15 ng/L, (15–65 ng/L) and high 1,25(OH)2D3 128.9 pg/mL, (15.2–90.1 pg/mL). Chest CT-scan revealed bilateral apical lung lesions after 15 days of antibiotics. Bronchoalveolar sample was PCR positive for Pneumocystis jirovecii. He was treated with an extra session of haemodialysis with 1.25 mmol/L dialysate calcium concentration, oral trimethoprim-sulfamethoxazole was started and oral corticosteroid dose increased to 1 mg/kg for 1 week. Hypercalcaemia decreased progressively after initiation of these treatments. We concluded a case of hypercalcaemia secondary to P. jirovecii infection.

A hemodialysis patient with bone disease after pregnancy: a case report

Background Pregnancy is rare in women on hemodialysis. Recommendations for the treatment of secondary hyperparathyroidism (sHPT) and preservation of bone health in pregnant dialysis patients are lacking. Case presentation We present the case of a young woman with end-stage kidney disease (ESKD) due to lupus nephritis, who developed multiple brown tumors while on hemodialysis during her second pregnancy. During her first pregnancy sHPT was well controlled and no skeletal complications occurred. Before the second pregnancy she developed severe sHPT. During pregnancy, dialysis time was increased to 24 h per week, the patient was given oral calcitriol, and the dialysate calcium concentration was set at 1.5 mmol/l. In week 20 the patient complained about bone pain in her left hip. Magnetic resonance imaging revealed a cystic lesion compatible with a brown tumor. The baby was delivered in the 36th week by cesarean section. Further assessment identified multiple brown tumors of her skeleton, including the acetabulum, tibia, ribs, skull, thoracic spine and thumb. She required multiple orthopedic surgeries. Three months after pregnancy, etelcalcetide was started, which brought about a gradual improvement in her sHPT. Conclusions This case demonstrates that the combination of pregnancy and severe sHPT in dialysis patients can have deleterious consequences for bone health.