Vascular calcification in peritoneal dialysis patients and its association with bone-derived molecules and bone histomorphometry / Calcificación vascular en pacientes en diálisis peritoneal y su asociación con moléculas derivadas de hueso e histomorfometría ósea

Introduction: Data regarding vascular calcification (VC) in contemporary peritoneal dialysis (PD) patients is scarce. Bone–vascular axis has been demonstrated in hemodialysis (HD). However, studies showing the link between bone disease and VC in PD patients are lacking. The role of sclerostin, dickkopf-related protein 1 (DKK-1), receptor activator for nuclear factor kB ligand and osteoprotegerin (OPG) in VC in PD remains to clarify. Materials and methods: Bone biopsy was performed in 47 prevalent PD patients with histomorphometric analysis. Patients were submitted to pelvis and hands X-ray to evaluate VC using the Adragão score (AS). Relevant clinical and biochemical data was collected. Results: Thirteen patients (27.7%) had positive AS (AS≥1). Patients with VC were significantly older (58.9 vs. 50.4 years, p=0.011), had a lower dialysis dose (KT/V 2.0 vs. 2.4, p=0.025) and a higher glycosylated hemoglobin (7.2 vs. 5.4%, p=0.001). There was not any laboratorial parameter of mineral and bone disease used in clinical practice different between patients with or without VC. All diabetic patients had VC but only 8.1% of non-diabetic had VC (p<0.001). Patients with VC showed significantly higher erythrocyte sedimentation rate (ESR) (91.1 vs. 60.0mm/h, p=0.001), sclerostin (2250.0 vs. 1745.8pg/mL, p=0.035), DKK-1 (1451.6 vs. 1042.9pg/mL, p=0.041) and OPG levels (2904.9 vs. 1518.2pg/mL, p=0.002). On multivariate analysis, only ESR remained statistically significant (OR 1.07; 95% CI 1.01–1.14; p=0.022). Bone histomorphometric findings were not different in patients with VC. There was no correlation between bone formation rate and AS (r=−0.039; p=0.796). Conclusion: The presence of VC was not associated with bone turnover and volume evaluated by bone histomorphometry. Inflammation and diabetes seem to play a more relevant role in VC in PD. (AU)

Introducción Los datos sobre calcificación vascular (CV) en pacientes contemporáneos en diálisis peritoneal (DP) son escasos. En pacientes en hemodiálisis, se ha demostrado la existencia de una conexión entre hueso y sistema vascular; sin embargo, faltan estudios que muestren el vínculo entre la enfermedad ósea y la CV en pacientes en DP. Si la esclerostina, la proteína relacionada con Dickkopf 1 (DKK-1), el ligando del receptor activador para el factor nuclear κB (RANKL) y la osteoprotegerina (OPG) tienen un papel en la CV en pacientes en DP aún no está claro. Materiales y métodos Se realizó biopsia ósea en 47 pacientes prevalentes en DP y se analizó mediante histomorfometría. También se tomaron radiografías de pelvis y manos a los pacientes para evaluar la CV mediante el Índice de Adragão (IA). Además, se analizaron datos clínicos y bioquímicos relevantes. Resultados: Trece pacientes (27,7%) tuvieron IA positivo (IA ≥ 1). Los pacientes con CV eran significativamente mayores (58,9 vs 50,4 años, p=0,011) tenían menor dosis de diálisis (KT/V 2,0 vs 2,4, p=0,025) y niveles más elevados de hemoglobina glicosilada (7,2 vs 5,4%, p=0,001). No hubo ningún parámetro de laboratorio de enfermedad mineral y ósea utilizado en la práctica clínica diferente entre pacientes con o sin CV. Todos los pacientes diabéticos mostraron CV, sin embargo, solo el 8,1% de los no diabéticos tenían CV (p <0,001). Además, los pacientes con CV mostraron una velocidad de sedimentación globular más elevada (VSG) (91,1 vs. 60,0mm/h, p=0,001) y mayores concentraciones séricas de esclerostina (2.250,0 vs. 1.745,8 pg/ml, p=0,035), DKK-1 (1451,6 vs 1042,9 pg/ml, p=0,041) y OPG (2.904,9 vs. 1.518,2 pg/ml, p=0,002). En el análisis multivariante, solo la VSG fue estadísticamente significativa (OR 1,07; IC del 95%: 1,01-1,14; p=0,022)... (AU)

The Association of Leptin with Left Ventricular Hypertrophy in End-Stage Kidney Disease Patients on Dialysis.

Left ventricular hypertrophy (LVH) is a common cardiovascular complication in end-stage kidney disease (ESKD) patients. We aimed at studying the association of LVH with adiponectin and leptin levels, cardiovascular stress/injury biomarkers and nutritional status in these patients. We evaluated the LV mass (LVM) and calculated the LVM index (LVMI) in 196 ESKD patients on dialysis; the levels of hemoglobin, calcium, phosphorus, parathyroid hormone, albumin, adiponectin, leptin, N-terminal pro B-type natriuretic peptide (NT-proBNP) and growth differentiation factor (GDF)-15 were analyzed. ESKD patients with LVH (n = 131) presented higher NT-proBNP and GDF-15, lower hemoglobin and, after adjustment for gender, lower leptin levels compared with non-LVH patients. LVH females also showed lower leptin than the non-LVH female group. In the LVH group, LVMI presented a negative correlation with leptin and a positive correlation with NT-proBNP. Leptin emerged as an independent determinant of LVMI in both groups, and NT-proBNP in the LVH group. Low hemoglobin and leptin and increased calcium, NT-proBNP and dialysis vintage are associated with an increased risk of developing LVH. In ESKD patients on dialysis, LVH is associated with lower leptin values (especially in women), which are negatively correlated with LVMI, and with higher levels of biomarkers of myocardial stress/injury. Leptin and NT-proBNP appear as independent determinants of LVMI; dialysis vintage, hemoglobin, calcium, NT-proBNP and leptin emerged as predicting markers for LVH development. Further studies are needed to better understand the role of leptin in LVH in ESKD patients.

Vascular calcification in peritoneal dialysis patients and its association with bone-derived molecules and bone histomorphometry.

INTRODUCTION: Data regarding vascular calcification (VC) in contemporary peritoneal dialysis (PD) patients is scarce. Bone-vascular axis has been demonstrated in hemodialysis (HD). However, studies showing the link between bone disease and VC in PD patients are lacking. The role of sclerostin, dickkopf-related protein 1 (DKK-1), receptor activator for nuclear factor kB ligand and osteoprotegerin (OPG) in VC in PD remains to clarify. MATERIALS AND METHODS: Bone biopsy was performed in 47 prevalent PD patients with histomorphometric analysis. Patients were submitted to pelvis and hands X-ray to evaluate VC using the Adragão score (AS). Relevant clinical and biochemical data was collected. RESULTS: Thirteen patients (27.7%) had positive AS (AS≥1). Patients with VC were significantly older (58.9 vs. 50.4 years, p=0.011), had a lower dialysis dose (KT/V 2.0 vs. 2.4, p=0.025) and a higher glycosylated hemoglobin (7.2 vs. 5.4%, p=0.001). There was not any laboratorial parameter of mineral and bone disease used in clinical practice different between patients with or without VC. All diabetic patients had VC but only 8.1% of non-diabetic had VC (p<0.001). Patients with VC showed significantly higher erythrocyte sedimentation rate (ESR) (91.1 vs. 60.0mm/h, p=0.001), sclerostin (2250.0 vs. 1745.8pg/mL, p=0.035), DKK-1 (1451.6 vs. 1042.9pg/mL, p=0.041) and OPG levels (2904.9 vs. 1518.2pg/mL, p=0.002). On multivariate analysis, only ESR remained statistically significant (OR 1.07; 95% CI 1.01-1.14; p=0.022). Bone histomorphometric findings were not different in patients with VC. There was no correlation between bone formation rate and AS (r=-0.039; p=0.796). CONCLUSION: The presence of VC was not associated with bone turnover and volume evaluated by bone histomorphometry. Inflammation and diabetes seem to play a more relevant role in VC in PD.

Evaluation of Renal Osteodystrophy and Serum Bone-Related Biomarkers in a Peritoneal Dialysis Population.

The spectrum of renal osteodystrophy (ROD) in peritoneal dialysis (PD) patients remains to be clarified. Ideal intact parathormone (iPTH) levels range is still not defined. The role of sclerostin, dickkopf-related protein 1, osteoprotegerin, and receptor activator for nuclear factor κB ligand for the diagnosis of ROD needs to be elucidated. In this cross-sectional study, tetracycline double-labeled bone biopsy was performed in 49 patients with histomorphometric analysis according Kidney Disease Improving Global Outcomes (KDIGO) guidelines. All patients were treated with biocompatible PD solutions, with calcium concentration of 1.25 mmol/L. Adynamic bone was the most frequent diagnosed pattern (42.9%) followed by hyperparathyroid-related bone disease (28.6%). Twenty-two percent of patients had normal bone. In patients with iPTH within the KDIGO recommended range for dialysis patients, adynamic bone was found in 59% of cases. Median (range) iPTH in patients with adynamic bone was 312 (60-631) pg/mL. Median (range) levels of sclerostin varied from 1511.64 (458.84-6387.70) pg/mL in patients with hyperparathyroid bone disease to 2433.1 (1049.59-11354.52) pg/mL in patients with adynamic bone. Sclerostin/iPTH ratio was the best marker of low turnover disease but iPTH performed best in the diagnosis of high turnover disease. Calcium mass transfer was positive in patients with low bone volume. Adynamic bone is the most frequent ROD pattern in contemporary PD. Our results suggest the need to review the iPTH target range for this population. The sclerostin/iPTH ratio showed improved performance compared to iPTH for the diagnosis of low turnover bone. © 2022 American Society for Bone and Mineral Research (ASBMR).

Clearing the clouds: Case-report and review of the literature.

In peritoneal dialysis (PD), a cloudy dialysate is an alarming finding. Bacterial peritonitis is the most common cause, however, atypical infections and non-infectious causes must be considered. A 46-year-old man presented with asthenia, paraesthesia, foamy urine and hypertension. Laboratory testing revealed severe azotaemia, anaemia, hyperkalaemia and nephrotic-range proteinuria. Haemodialysis was started through a central venous catheter. Later, due to patient preference, a Tenckhoff catheter was inserted. Conversion to PD occurred 3 weeks later, during hospitalization for a presumed central line infection. A month later, the patient was hospitalized for neutropenic fever. He was diagnosed an acute parvovirus infection and was discharged under isoniazid for latent tuberculosis. Four months later, the patient presented with fever and a cloudy effluent. Peritoneal fluid (PF) cytology was suggestive of infectious peritonitis, but the symptoms persisted despite antibiotic therapy. Bacterial and mycological cultures were negative. No neoplastic cells were detected. Mycobacterium tuberculosis eventually grew in PF cultures, despite previous negative molecular tests. Directed therapy was then initiated with excellent response. Thus, facing a cloudy effluent, one must consider multiple aetiologies. Diagnosis of peritoneal tuberculosis is hampered by the lack of highly sensitive and specific exams. Here, diagnosis was only possible due to positive mycobacterial cultures.

Peritoneal Dialysis Cuff-Shaving-A Salvage Therapy for Refractory Exit-Site Infections.

Introduction:Cuff-shaving has been described as a salvage technique for refractory exit-site infections, with conflicting data regarding infection and catheter outcomes. We describe our experience with cuff-shaving as a rescue therapy for exit-site infections unresponsive to systemic therapy.Methods:We retrospectively reviewed patients who underwent cuff-shaving between January 2012 and June 2017. Refractory exit-site infection was defined as purulent discharge from the exit site with no clinical response after 3 weeks of systemic antibiotic treatment.Results:Fifty-three cuff-shavings were included, mean age was 53.4 ± 13.4 years, 26 patients were male. Median dialysis vintage was 29 months (interquartile range [IQR] 14.3 - 38), and 39 (73.6%) were on continuous ambulatory peritoneal dialysis (CAPD). The exit-site infection rate before cuff-shaving was 1.12 episodes per patient-year and the median time from infection to shaving was 52 days (IQR 35 - 76). The most frequent agents were Staphylococcus aureus (34%), Corynebacterium spp. (17%) and Pseudomonas aeruginosa (15%). Median follow-up was 9 months (IQR 1 - 18.5), during which time 35 catheters were removed, 5 due to non-infectious reasons. Using the Kaplan-Meier survival analysis, median catheter survival was 24 months (95% confidence interval [CI] 4.17 - 43.83). At 12 months, the probability of catheter survival was 54% and was not statistically different between gram-positive and gram-negative agents, although it was significantly shorter for fungal agents.Conclusion:Cuff-shaving is a feasible rescue therapy to treat refractory exit-site infections. In our experience, it allowed resolution of infections in a significant proportion of cases, except for fungal agents, and therefore extended catheter survival time, besides being associated with a small rate of complications.

Planning Vascular Access in Peritoneal Dialysis-Defining High-Risk Patients.

BACKGROUND: Peritoneal dialysis (PD) is an effective renal replacement technique. However, every year a considerable number of patients are transferred to hemodialysis (HD). Our aim was to identify those at risk, in order to place an arteriovenous fistula (AVF). METHODS: Case-control study enrolling all prevalent patients in 2014 and 2015 in our clinic. Groups: 72 case patients who were transferred definitively to HD, 111 control patients (remaining on PD, transplanted, recovered renal function, or deceased). RESULTS: A total of 183 patients were eligible, with a mean age of 55.2 ± 14.8 years, 56.3% male, 31.1% diabetic, and 49.7% on continuous ambulatory PD. The mean follow-up time was 42.1 ± 25.6 months. Eighty-five patients had an AVF. The groups differed in diabetic nephropathy etiology, and in some PD-related characteristics (Kt/V, creatinine clearance, residual renal function, mean ultrafiltration, natriuretic peptide, peritonitis, hospitalizations, and hypervolemia). In multivariate analysis, Kt/V < 1.7 (odds ratio [OR] 3.00, 95% confidence interval [CI]: 1.20 - 7.50], albumin < 35 g/L (OR 4.03, 95% CI: 1.26 - 12.92), number of hospitalizations 1 to 3 (OR 2.74, 95% CI: 1.15 - 6.53) and 4 or more (OR 10.48, 95% CI: 3.62 - 30.36), and 2 or more peritonitis episodes (OR 2.50, 95% CI: 1.03 - 6.07) were predictors of PD transfer to HD. In those patients who were transferred to HD, 34 initiated HD by AVF, 2 needed a catheter due to a non-functioning AVF, and 36 did not have an AVF needing catheter placement. CONCLUSIONS: Low Kt/V, low albumin, higher number of hospitalizations, and peritonitis were factors associated with PD transfer to HD, probably indicative of a high-risk PD population where arteriovenous access should be weighed.