Detection of JCV or BKV viruria and viremia after kidney transplantation is not associated with unfavorable outcomes.

Studies analyzing the relationship between BK polyomavirus (BKV) or JC polyomavirus (JCV) infection and kidney transplant (KT) long term clinical outcomes are scarce. Therefore, we evaluated this relationship in a single-center retrospective cohort of 288 KT patients followed for 45.4(27.5; 62.5) months. Detection of BKV viremia in two consecutive analyses led to discontinuation of antimetabolite and initiation of mammalian target of rapamycin inhibitor. Outcome data included de novo BKV and/or JCV viremia and/or viruria after KT, death-censored graft survival and patient survival. BKV viruria and viremia were detected in 42.4% and 22.2% of KT recipients, respectively. BKV viremic patients had higher urinary BKV viral loads at the onset of viruria, when compared to nonviremic patients (7 log10 vs. 4.9 log10 cp/mL, p < 0.001). JCV viruria was identified in 38.5% of KT patients; the 5.9% of KT recipients who developed JCV viremia had higher JCV urinary viral loads at the onset of viruria, when compared to non-viremic patients (5.3 vs. 3.7 log10 cp/mL, p = 0.034). No differences were found in estimated glomerular filtration rate at the end of follow up, when comparing BKV or JCV viruric or viremic patients with nonviremic patients. No association was found between JCV or BKV viruria or viremia and death/graft failure. Therefore, higher BKV urinary viral loads at the onset could serve as an early maker of over immunosuppression. JCV and BKV replication was not associated with inferior clinical outcomes in KT patients with the above-mentioned immunosuppression strategy.

Torquetenovirus viral load is associated with anti-spike antibody response in SARS-CoV-2 mRNA BNT162b2 vaccinated kidney transplant patients.

INTRODUCTION: Kidney transplant patients (KT) are at high risk for severe COVID-19 and presented attenuated antibody responses to vaccination when compared to immunocompetent individuals. Torquetenovirus (TTV) has recently gained attention as a potential surrogate marker of the net state of immunosuppression. We evaluated the association between pre-vaccination TTV viral load and anti-spike total antibody response to SARS-CoV-2 vaccination in KT. MATERIAL AND METHODS: The 114 adult KT recipients enrolled in this prospective single-center cohort study received two doses of SARS-CoV-2 mRNA BNT162b2 vaccine. Serum samples were collected immediately before vaccination at the days when patients received both the first (T0) and the second dose (T1) and 16-45 days after the second dose (T2). Primary endpoint was the development of anti-spike total antibodies after vaccination. Demographic, clinical, and laboratorial parameters were compared between patients with and without detectable SARS-CoV-2 antibodies at T2. RESULTS: Ninety-nine patients (86.8%) were naïve for SARS-CoV-2 before vaccination. Fifty-six (56.6%) patients developed anti-spike total antibodies at T2. The use of mTOR inhibitors was associated with a favorable response (p = .005); conversely, mycophenolic acid (MPA) was associated with a negative response (p = .006). In a multivariable model, the presence of TTV at T0 ≥ 3.36 log10 cp/ml was associated with unfavorable vaccine response (OR: 5.40; 95% CI: 1.47-19.80; p = .011), after adjusting for age and eGFR at T0. CONCLUSIONS: Higher TTV viral loads before vaccination are associated with reduced anti-spike total antibody response in SARS-CoV-2 mRNA BNT162b2 vaccinated KT patients. The association between TTV viral load and vaccine response may be an added-value in the optimization of vaccination regimens in KT.

Prognostic Value of the Malnutrition-inflammation Score in Hospitalization and Mortality on Long-term Hemodialysis.

OBJECTIVE: Since its development, cumulative evidence has accumulated regarding the prognostic value of the Malnutrition-Inflammation Score (MIS/Kalantar score) prognostic value; however, there is a shortage of recent and large studies with comprehensive statistical methodologies that contribute to support a higher level of evidence and a consensual cutoff. The aim of this study was to assess the strength of MIS association with hospitalization and mortality in a nationwide cohort. METHODS: This was a historical cohort study of hemodialysis patients from 25 outpatient centers followed up for 48 months. Univariable and multivariable Cox additive regression models were used to analyze the data. The C-index was estimated to assess the performance of the final model. RESULTS: Two thousand four hundred forty-four patients were analyzed, 59.0% males, 32.0% diabetic, and median age of 71 years (P25 = 60, P75 = 79). During a median period of 45-month follow-up, with a maximum of 48 months (P25 = 31; P75 = 48), 875 patients presented an MIS <5 (35.8%) and 860 patients (35.2%) died. The proportion of deaths was 23.1% for patients with the MIS <5 and 41.9% if the MIS ≥5 (P < .001). A total of 1,528 patients (62.5%) were hospitalized with a median time to the first hospitalization of 26 months (P25 = 9; P75 = 45). A new cutoff point regarding the risk of death, MIS ≥6, was identified for this study data set. In multivariable analysis for hospitalization risk, a higher MIS, higher comorbidity index, and arteriovenous graft or catheter increased the risk, whereas higher Kt/V and higher albumin had a protective effect. In multivariable analysis for mortality risk, adjusting for age, albumin, normalized protein catabolic rate, Charlson comorbidity index, interdialytic weight gain, Kt/V, diabetes, hematocrit, and vascular access, patients with the MIS ≥6 showed a hazard ratio of 1.469 (95% confidence interval: 1.262-1.711; P < .001). Higher age, higher interdialytic weight gain, higher comorbidity index, and catheter increased significantly the risk, whereas higher Kt/V, higher albumin, and higher normalized protein catabolic rate (≥1.05 g/kg/d) reduced the risk. CONCLUSION: The MIS maintains its relevant and significant association with hospitalization and mortality.

Kinetics of torquetenovirus DNA load in a recent kidney transplant recipient with mild SARS-CoV-2 infection and a failed antibody response.

Kidney transplant (KT) recipients are at an increased risk for severe COVID-19 because of their immunosuppressed state. A 42-year-old KT patient was diagnosed with COVID-19 three months after KT. Despite lymphopenia and several risk factors, he had a mild disease course. Nasopharyngeal real-time reverse transcriptase polymerase chain reaction for SARS-CoV-2 became negative 48 days after detection. SARS-CoV-2 IgG antibodies became negative after day 40. TTV DNA load increased with the onset COVID-19 and reduced after its resolution. This is the first report where TTV DNA load was measured during the course of COVID-19.

High-grade urothelial carcinoma in a kidney transplant recipient after JC virus nephropathy: The first evidence of JC virus as a potential oncovirus in bladder cancer.

Kidney transplant (KT) recipients have an increased risk for urothelial carcinoma. A role for JC virus (JCV) in human cancers is not yet proved but there is an increasingly reported association between BK virus (BKV) nephropathy and renourinary neoplasms. We report a KT recipient who developed a high-grade urothelial carcinoma 5 years after a diagnosis of JCV nephropathy and 9 years after kidney transplantation. Neoplastic tissue was positive for JCV DNA by real-time polymerase chain reaction (PCR). Immunochemical staining showed strong positivity for cell cycle markers (p16, p53, and Ki67) and for early viral protein JCV large T antigen (JCV LTag; using a broad polyomavirus antibody); however, late viral protein (VP1) stained negative. In contrast, in non-neoplastic urothelium, JCV DNA and all immunochemical markers were negative. These facts suggest that malignancy was induced by JCV. To the best of our knowledge, this is the first report of urothelial high-grade carcinoma associated with JCV nephropathy in a KT recipient.

Risk of hepatitis B reactivation in hepatitis B surface antigen seronegative and core antibody seropositive kidney transplant recipients.

BACKGROUND: Previous contact with Hepatitis B virus (HBV) is common in patients undergoing hemodialysis. Literature has shown conflicting results on the risk of HBV reactivation in kidney transplant (KT) recipients with serologic evidence of past HBV infection. METHODS: We reviewed 631 consecutive KT recipients and selected 70 patients simultaneously HBsAg negative and anti-HBc positive before KT, regardless of hepatitis B surface antibody (anti-HBs) status. Demographic characteristics, coinfection with other viruses, the presence of a previous KT, induction and maintenance immunosuppression, length of follow up, biopsy-proven acute rejection episodes, incidence of impaired liver function, and causes of graft loss and mortality were collected. Hepatitis B virus reactivation was defined as detection of HBV DNA viral load >2000 IU/mL during follow up. Outcome data included HBV reactivation episodes, graft function, and patient survival. RESULTS: Median follow-up was 151 months; 91.4% of patients were positive to anti-HBs prior to KT. No patient received HBV prophylaxis and 11 patients (15.7%) received rituximab as part of induction therapy. Anti-HBs titers remained stable in all patients throughout the observation period but two patient showed evidence of HBV reactivation after KT. CONCLUSION: Hepatitis B virus reactivation in HBsAg-negative and anti-HBc-positive after KT is rare but possible. We suggest evaluating HBV serologies, HBV DNA viral load, and liver enzymes before KT and routinely monitoring serologic HBV markers after KT. As only two patients experienced HBV reactivation, it is neither possible to define risk factors for HBV reactivation nor to evaluate the impact of different immunosuppressants or the benefit of prophylactic regimens. Further studies regarding HBV reactivation in solid organ transplant recipients are necessary.

Peritoneal dialysis is a reasonable option in patients with cardiovascular disease
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INTRODUCTION: Peritoneal dialysis (PD) has been proposed as a therapeutic option for patients with end-stage renal disease (ESRD) and cardiovascular (CV) disease. The study presented here aimed to compare incident PD patients with and without CV disease at baseline, in order to determine the impact of CV disease in the outcomes of long-term PD patients. METHODS: This is a prospective cohort study performed at a single PD unit where 112 consecutive incident patients admitted to the PD program during 5 years were studied. The background of CV disease at PD initiation was defined as: presence of coronary artery disease, cerebrovascular disease, heart failure, or peripheral arterial disease. Laboratory measurements as well as PD adequacy were obtained at the beginning of PD and at the last evaluation. The outcomes examined were patient and technique survival, hospitalization and peritonitis rate. RESULTS: Prevalence of diabetes was higher in patients with CV disease (53.3% vs. 31.7%, p = 0.036). Patients who suffered from CV disease were, on average, older (62.8 ± 13.1 vs. 49.7 ± 15.7 years, p < 0.05). There were no significant differences in other demographic or clinical variables, including hospital admissions (0.99 vs. 0.72 episodes/patient-year, p = 0.057) or peritonitis rates (0.69 vs. 0.61 episodes/patient-year, p = 0.652). The overall rates of PD technique failure were similar between both groups (CV disease patients: 12.7 transfers to hemodialysis (HD)/100 patient-years vs. CONTROL: 13.7 transfers to HD/100 patient-year; p = 0.54). Diabetes and age were independently associated with the presence of CV disease (p = 0.011), in a model adjusted for time on PD. The mortality rate was higher in CV disease patients (14.9 vs. 0.8 deaths/100 patient-years, p = 0.000) and 75% of all-cause mortality occurred in diabetic patients. In a multivariate analysis, diabetes (hazard ratio (HR): 5.5, confidence interval (CI): 0.84 - 36.29, p = 0.049) and age (HR: 1.07, CI: 1.0 - 1.13, p = 0.047) were independent predictors of death in a model adjusted for residual diuresis, body mass index, and time on PD. CONCLUSIONS: This study compared incident PD patients with and without CV disease. CV disease patients were older but clinical and laboratorial targets, peritonitis rates, hospitalizations, and technique survival were similar between both groups, suggesting PD as an effective therapy for patients with CV comorbidities.
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Peritoneal dialysis as a successful treatment in patients with refractory congestive heart failure: a one-center experience.

INTRODUCTION: Ultrafiltration (UF) technique is a valuable alternative to pharmacological therapy in the treatment of patients with refractory congestive heart failure (HF). The aim of this study was to describe a single-center experience in the treatment of refractory HF patients with peritoneal dialysis (PD). METHODS: Retrospective study of 5 patients included in a single PD Unit, showing symptoms and signs of severe refractory congestive HF to optimal pharmacological therapy (NYHA class IV). Clinical and laboratory parameters, survival, hospitalization, and peritonitis rates were recorded. RESULTS: Patients were followed for 9.36 (± 6.36) months; population mean age was 62 (± 16) years and Charlson's comorbidity index was 7.2 (± 2.1). After PD therapy, functional class of NYHA significantly improved (class IV to class II in 4 patients). Doppler-echocardiography improved in terms of ejection fraction (EF) or systolic pressure of the pulmonary artery (SPPA) in 3 patients. No patient was readmitted due to HF. Hospitalization days substantially decreased in 4 patients. One patient presented with peritonitis episodes. Three patients died but the mean survival was higher than expected according to their comorbidity index. CONCLUSION: PD, applied to refractory HF in addition to optimal pharmacological therapy, improves quality of life and functional class and reduces hospitalization days due to HF.

Kinetics of Torque Teno Virus Viral Load Is Associated with Infection and De Novo Donor Specific Antibodies in the First Year after Kidney Transplantation: A Prospective Cohort Study.

Torque teno virus (TTV) was recently identified as a potential biomarker for the degree of immunosuppression, and potentially as a predictor of rejection and infection in solid organ transplant patients. We evaluated TTV viral load in kidney transplant (KT) patients during the first year post-transplant to examine overall kinetics and their relationships with deleterious events, including episodes of infection and the formation of de novo donor-specific antibodies (DSAs). In a single-center, prospective observational cohort study, 81 KT patients were monitored at baseline, week 1, and month 1, 3, 6, 9 and 12, post-KT, and whenever required by clinical events. Kidney function, plasma TTV load, immunoglobulins and lymphocyte subpopulations were assessed at each time point. Twenty-six patients (32.1%) presented a total of 38 infection episodes post-KT. Induction immunosuppression with thymoglobulin, compared to basiliximab, was not associated with more infections (p = 0.8093). Patients with infectious events had lower T-cells (p = 0.0500), CD8+ T-cells (p = 0.0313) and B-cells (p = 0.0009) 1 month post-KT, compared to infection-free patients. Patients with infection also showed higher increases in TTV viral loads between week 1- month 1, post-KT, with TTV viral load variations >2.65 log10 cp/mL predicting the development of infectious events during the 12-month study period (p < 0.0001; sensitivity 99.73%; specificity 83.67%). Patients who developed de novo DSAs had lower TTV DNA viral loads at month 12 after KT, compared to patients who did not develop DSA (3.7 vs. 5.3 log10 cp/mL, p = 0.0023). Briefly, evaluating early TTV viremia is a promising strategy for defining infectious risk in the 1st year post-KT. The availability of standardized commercial real-time PCR assays is crucial to further validate this as an effective tool guiding immunosuppression prescription.

Ankle--brachial index, vascular calcifications and mortality in dialysis patients.

BACKGROUND: The ankle-brachial index (ABI) is a noninvasive method to evaluate peripheral artery disease (PAD). ABI <0.9 diagnoses PAD; ABI >1.3 is a false negative caused by noncompressible arteries. The aim of this study is to evaluate the association between ABI with vascular calcifications (VC) and with mortality, in haemodialysis (HD) patients. METHODS: We studied 219 HD patients (60% male; 20% diabetic). At baseline, ABI was evaluated by a Doppler device. VCs were evaluated by two methods: the abdominal aorta calcification score (AACS) in a lateral plain X-ray of the abdominal aorta and the simple vascular calcification score (SVCS) in plain X-rays of the pelvis and hands. VC were also classified by their anatomical localization in main vessels (aorta and iliac-femoral axis) and in peripheral or distal vessels (pelvic, radial or digital). The cutoff values for the different VC scores in relation with ABI were determined by receiver operating characteristic curve analysis. Biochemical parameters were time averaged for the 6 months preceding ABI evaluation. RESULTS: An ABI <0.9, an ABI >1.3 or a normal ABI were found, respectively, in 90 (41%), in 42 (19%) and in 87 (40%) patients. AACS ≥6 and SVCS >3 were found, respectively, in 98 (45%) and 95 (43%) patients. The adjusted odds ratio (OR) for having an ABI <0.9 was 2.5 (P = 0.007) for AACS ≥6 and 4.5 (P < 0.001) for iliac-femoral calcification score (CS) ≥2. The adjusted OR for having an ABI >1.3 was 4.2 (P = 0.003) for pelvic CS and 3.7 (P = 0.006) for hand CS ≥2. During an observational period of 28.9 months, all-cause and cardiovascular mortality occurred, respectively, in 50 (23%) and in 29 (13%) patients. Adjusting for age, diabetes, P levels, HD duration and cardiovascular disease at baseline, an ABI <0.9 [hazard ratio (HR) = 3.9, P < 0.001] and an ABI >1.3 (HR = 2.7, P = 0.038) were associated with all-cause mortality; an ABI <0.9 (HR = 7.2, P = 0.002) and an ABI >1.3 (HR = 5.1, P = 0.028) were associated with cardiovascular mortality. CONCLUSIONS: Both low and high ABI were independent predictors of all-cause and cardiovascular mortality. VC in main arteries were associated with an ABI <0.9. VC in peripheral and distal arteries were associated with an ABI >1.3. ABI is a simple and noninvasive method that allows the identification of high cardiovascular risk patients.

Non-calcium-containing phosphate binders: comparing efficacy, safety, and other clinical effects.

Phosphate-binder therapy for hyperphosphataemia is key to the treatment of patients with chronic kidney disease (CKD)-mineral and bone disorder (MBD). Calcium-free phosphate binders are increasingly favoured since calcium-based agents potentially cause harmful calcium overload and vascular calcification that confound the benefits of reducing serum phosphorus. Several calcium-free phosphate binders are available, including the non-absorbed agent sevelamer and the absorbed agents, e.g. lanthanum and magnesium salts. Randomised controlled studies consistently show that sevelamer and lanthanum carbonate offer equivalent lowering of serum phosphorus and often effectively achieve phosphorus targets versus calcium salts, with sevelamer having a positive effect on bone disease, vascular calcification, and patient-level outcomes in dialysis patients in several trials. There is also evidence that lanthanum carbonate can improve bone health, but data are limited to its effects to vascular calcification or patient-level outcomes. Magnesium salts have also been shown to reduce serum phosphorus levels, but clear evidence is lacking on bone, vascular, or clinical outcomes. It also remains to be established whether long-term systemic accumulation of lanthanum and magnesium, in tissues including bone, has clinically relevant toxic effects. This review summarises the evidence of efficacy and safety for newer calcium-free phosphate binders in CKD-MBD management.

JCV viruria associates with suboptimal recovery of kidney function three years after living kidney donation.

INTRODUCTION: Few studies have investigated pre-donation factors that could affect renal recovery after living kidney donation (LKD). We retrospectively investigated the role of John Cunningham virus (JCV) infection and other pre-donation factors on the magnitude of kidney function decline after LKD. METHODS: Urine JCV viral loads, glomerular filtration rate, and blood pressure were evaluated in 60 consecutive LK donors before donation. Suboptimal compensatory hypertrophy was defined as an eGFR <60% of the pre-donation eGFR. RESULTS: LKD (40% JCV infected) were followed for 3.2±1.6 years. No association was found between age, gender, and baseline hypertension with 1st, 2nd, 3rd, and 4th years post-donation eGFR <60% of the pre-donation eGFR. Mean eGFR recovery at the 3rd year after donation was lower in JCV infected donors vs non-infected donors (61.8% vs 71.0%, p=0.006). CONCLUSION: We hypothesized that JCV could shift glomeruli into a hyperfiltration state before nephrectomy, modulating the magnitude of compensatory hypertrophy after donation. Conversely, JCV might curtail the ability of the remaining kidney to promote hyperfiltration. Longer follow up is needed to determine whether JCV viruria ultimately leads to lower eGFR over time or if it is a protective factor for the remaining kidney.

SARS-CoV-2 infection in kidney transplant recipients: clinical impact and outcomes - a single center experience.

INTRODUCTION: Kidney transplant recipients are a subgroup of patients at higher risk of critical forms of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection and poor outcomes due to immunosuppression treatment. Herein, we present data from a single center cohort of kidney transplant recipients with SARS-CoV-2 infection. METHODS: In a prospective study, baseline characteristics, clinical features, antiviral and immunosuppression management were compared between outpatients and hospitalized patients, during a one-year period. RESULTS: Seventy-seven kidney transplant recipients were analyzed, including outpatients and hospitalized patients, with a median age of 57.7 (IQR 49.7-64.9) years. Twenty-eight (36.4%) were managed as outpatients, while 49 (63.6%) patients required hospital admission. Among hospitalized patients, 18.4% were admitted in ICU, 49% had AKI, and 20.4% died. Immunosuppression adjustments were performed in 95.9% of hospitalized patients, with dose of anti-metabolites adjusted in 83.7%, mTOR inhibitors in 14.3%, calcineurin inhibitors in 12.2%, and corticosteroid therapy in 81.6%. CONCLUSION: Among hospitalized patients, immunosuppression management included reduction or withdrawal of anti-metabolite and increase of corticosteroid dose. AKI occurred in almost half of patients and mortality in hospitalized patients reached 20%, reflecting greater disease severity than the general population.

Outcomes of Living Kidney Donor Candidates and Living Kidney Recipient Candidates with JC Polyomavirus and BK Polyomavirus Viruria.

INTRODUCTION: Recent data have emerged about a protective association between JCV viruria and chronic kidney disease (CKD). Material and Methods. Single-center retrospective cohort study; 230 living kidney donors (LKD) candidates and 59 potential living kidney receptors (LKR) were enrolled. Plasma and urinary JCV and BKV viral loads were measured in all LKD candidates and in nonanuric LKR candidates. Twenty-six living kidney transplant surgeries were performed. LKR were followed in order to evaluate BKV and JCV viremia and urinary viral shedding after KT. RESULTS: In LKD candidates, JCV viruria was negatively associated with proteinuria of >200 mg/24 hours (JC viruric LKD: 12.5% vs JCV nonviruric LKD: 26.7%, p=0.021, OR:0.393; 95% CI: 0.181-0.854). In a multivariate analysis, LKD candidates with JCV viruria had a lower risk of proteinuria of >200 mg/24 hours (p=0.009, OR: 0.342, 95% CI: 0.153-0.764), in a model adjusted for age, gender, presence of hypertension, and eGFR <80 mL/min. Prevalence of JCV viruria was higher in LKD candidates when compared with LKR candidates (40.0% vs 1.7%, p < 0.001). Among the 26 LKR, 14 (53.8%) KT patients evolved with JCV viruria; 71.4% received a graft from a JCV viruric donor. CONCLUSION: Our data corroborate the recent findings of an eventual protective association between JCV viruria and kidney disease, and we extrapolated this concept to a South European population.

Can an intradialytic snack model compensate the catabolic impact of hemodialysis?

BACKGROUND AND AIMS: Hemodialysis (HD) has a catabolic effect caused by alterations in protein metabolism, increase in resting energy expenditure (REE) and protein needs due to inflammation, HD circuit blood and heat losses, protein losses to dialysate and HD filter membrane biocompatibility. We aim to determine, as a proof of concept, whether a standardized intradialytic snack model is adequate to compensate the catabolic impact of HD. METHODS: Cross sectional analysis of patients' chosen intradialytic intake according to a snack model, at the day of blood sample collection of three different months. As targets for the compensation of the catabolic impact of HD, we considered 316.8kCal (1.32 (±0.18) kcal/min - 240' of HD) for the estimated increase in REE and at least 7 g of protein losses/HD treatment. RESULTS: A total of 448 meals were analyzed, with 383 given during daytime shifts. No intolerances were registered. The mean nutritional profile of the daytime shifts intakes was 378.8 (±151.4) kcal, 13.5 (±7.2) g of protein, 676 (±334) mg of sodium (Na), 361.0 (±240.3) mg of potassium (K) and 249.3 (±143.0) mg of phosphates (P). We found that 68% of the meals provided an intake ≥316.8kCal and 82% a protein intake ≥ 7 g, with a significant association found between treatment shift and energy (p < 0.028), protein (p < 0.028), lipids (p < 0.004), Na (p < 0.004), K (p < 0.009) and P (p < 0.039) intakes. CONCLUSIONS: We found that this intradialytic snack model meets the target for the treatment-related increases in protein and energy needs. Although sodium intake was found to be high, potassium and phosphate intake was considered adequate.

[Vascular calcification in chronic kidney disease]. / La calcificazione vascolare nel paziente con insufficienza renale cronica.

Patients affected by chronic kidney disease (CKD) suffer by secondary hyperparathyroidism and hyperphosphatemia. The new KDIGO guidelines identify a new definition in CKD-MBD (Mineral Bone Disorder), in which vascular calcification plays a central role. In fact, CKD patients that present vascular calcification have highest risk of cardiovascular morbility and mortality. Recently, it has been elucidated that the control of phosphate is one of the major problems for the nephrology community. Furthermore, new markers, such as FGF-23, have been identified as inducers of vascular calcification and cardiovascular disease in CKD. Therefore, the use of calcium-free phosphate-binders may reduce the risk of cardiovascular disease by reducing both serum phosphate and FGF-23 levels.

A plain X-ray vascular calcification score is associated with arterial stiffness and mortality in dialysis patients.

BACKGROUND: Vascular calcifications are highly prevalent in dialysis patients and are associated with arterial stiffness and mortality. The use of simple and inexpensive methods to evaluate arterial stiffness and vascular calcifications is desired. The objective of this study was to evaluate the relationship of a simple vascular calcification score (SVCS) with pulse wave velocity (PWV) and pulse pressure (PP) and to evaluate their association with all-cause mortality. METHODS: 101 haemodialysis patients (71 men; 19% diabetic) were evaluated. At baseline, arterial stiffness was measured by PP and by PWV with Complior. SVCS was evaluated in plain X-ray of pelvis and hands. RESULTS: During a 43-month observational period, 31 patients died. By Kaplan-Meier analysis, SVCS >3 (P = 0.001), PP > 70 mmHg (P = 0.001) and PWV > 10.5 m/s (P < 0.001) were found to be associated with lower cumulative survival. Adjusting for multiple variables, association with mortality was maintained for SVCS >3 (HR = 3.308, P = 0.032) and PP > 70 mmHg (HR = 3.227, P = 0.031) in all patients and for PWV > 10.5 m/s (HR = 2.981, P = 0.047) in non-diabetic patients. Age (P < 0.001), systolic pressure (P = 0.004) and SVCS > 3 (P = 0.032) were associated with PWV. Diabetes (P = 0.031), calcium carbonate dose (P = 0.009) and SVCS > 3 (P = 0.012) were associated with PP. CONCLUSION: Higher SVCS, PWV and PP were associated with higher mortality in this population. SVCS was associated with arterial stiffness. Simple and inexpensive methods such as PP or SVCS may be used to detect mortality risk and to provide important information that may be relevant for guiding therapeutic intervention in dialysis patients.

Inferring disease mechanisms from epidemiological data in chronic kidney disease: calcium and phosphorus metabolism.

BACKGROUND/AIMS: By applying numerical filtering to epidemiological data of 2,512 chronic kidney disease patients, we aimed to identify some of the underlying mechanisms of the calcium/phosphorus metabolism perturbations. METHODS: The measured variables, serum calcitriol, calcidiol, total calcium ([Ca](s)) and phosphorus ([P](s)) and the urinary excretions of calcium and phosphorus, were paired in the same patients with the glomerular filtration rate (GFR) or the serum concentrations of parathormone (i[PTH](s)) (used as independent variables) numerically filtered with a moving average and partitioned into 15-25 frequency classes. All variables exhibited unimodal frequency distributions. RESULTS: There was a steep fall of i[PTH](s), [P](s), and urinary excretion fractions of Ca and P up to a value of GFR in the range of 25-45 ml/min/1.73 m2. The increase in the phosphorus urinary excretion preceded the steep increase in i[PTH](s). Except [Ca](s), all factors exhibited their physiological correlation with i[PTH](s) when GFR was above 90 ml/min/1.73 m2 and reverted to a feedback correlation below 80 ml/min/1.73 m2. CONCLUSION: The perturbation of mineral metabolism in chronic kidney disease results in the maintenance of a normal range of [Ca](s) and [P](s) acting as the controlled factors at the cost of large variations of i[PTH](s), and calcium and phosphate urinary excretions behaving as controlling factors.

Evaluation of vascular calcifications in CKD patients.

In observational studies on dialysis patients, there has been a consistent association between vascular calcifications and mortality. Hyperphosphatemia and calcium treatment are some of the factors associated with development of vascular calcifications, especially in the presence of low bone turnover disease. Several non-invasive imaging techniques have been used to screen for the presence of vascular calcifications: plain X-Ray, echocardiography, ultrasonography, and computed tomography. Presence of vascular calcifications is a warning sign for increased cardiovascular risk and this information may be relevant for choosing the most suitable treatment for dialysis patients.