Clinical characteristics and risk factors for severe COVID-19 in hospitalized kidney transplant recipients: A multicentric cohort study.

Kidney transplant recipients might be at higher risk for severe coronavirus disease 2019 (COVID-19). However, risk factors for relevant outcomes remain uncertain in this population. This is a multicentric kidney transplant cohort including 104 hospitalized patients between March 4 and April 17, 2020. Risk factors for death and acute respiratory distress syndrome (ARDS) were investigated, and clinical and laboratory data were analyzed. The mean age was 60 years. Forty-seven patients (54.8%) developed ARDS. Obesity was associated to ARDS development (OR 2.63; P = .04). Significant age differences were not found among patients developing and not developing ARDS (61.3 vs 57.8 years, P = .16). Seventy-six (73%) patients were discharged, and 28 (27%) died. Death was more common among the elderly (55 and 70.8 years, P < .001) and those with preexisting pulmonary disease (OR 2.89, P = .009). At admission, higher baseline lactate dehydrogenase (257 vs 358 IU/mL, P = .001) or ARDS conferred higher risk of death (HR 2.09, P = .044). In our cohort, ARDS was equally present among young and old kidney recipients. However, the elderly might be at higher risk of death, along with those showing higher baseline LDH at admission.

Kidney Graft Outcomes in High Immunological Risk Simultaneous Liver-Kidney Transplants.

Recipients of simultaneous liver-kidney transplantations (SLKTs) have a lower risk of rejection compared with recipients of kidney transplants alone. However, there is disagreement about the impact of pretransplant anti-human leukocyte antigen sensitization on patient and kidney graft survival in the long term. The aim of the study was to evaluate the impact of the recipient immunological risk and comorbidities in renal graft outcomes on SLKT. We reviewed the SLKTs performed in our center from May 1993 until September 2017. Patient and graft survival were analyzed according to the immunological risk, comorbidities, liver and kidney rejection episodes, immunosuppression, and infections. A total of 20 recipients of SLKT were considered in the high immunological risk (HIR) group, and 68 recipients were included in the low immunological risk (LIR) control group. The prevalence of hepatitis C virus infection, second renal transplant, and time on dialysis prior to transplantation were significantly higher in the HIR group. The incidence of acute kidney rejection was higher in the HIR group (P<0.01). However, death-censored kidney graft survival as well as the estimated glomerular filtration rate at follow-up were not different between the 2 groups. Comorbidities, but not the immunological risk, impact negatively on patient survival. Despite the higher incidence of rejection in the HIR SLKT group, longterm renal function and graft survival were similar to the LIR group.

Long-term results of a randomized study comparing parathyroidectomy with cinacalcet for treating tertiary hyperparathyroidism.

Tertiary hyperparathyroidism is a common cause of hypercalcemia after kidney transplantation (KT) and has been associated with renal dysfunction, bone mineral density loss, and increased risk of fracture and cardiovascular events. In a previous 12-month clinical trial, we demonstrated that subtotal parathyroidectomy was more effective than cinacalcet for controlling hypercalcemia. In the current study, we retrospectively evaluate whether this effect is maintained after 5 years of follow-up. In total, 24 patients had data available at 5 years, 13 in the cinacalcet group and 11 in the parathyroidectomy group. At 5 years, 7 of 11 patients (64%) in the parathyroidectomy group and 6 of 13 patients (46%) in the cinacalcet group (P = .44) showed normocalcemia. However, recurrence of hypercalcemia was only observed in the cinacalcet group (P = .016). Subtotal parathyroidectomy retained a greater reduction in intact parathyroid hormone (iPTH) compared with cinacalcet group. No differences were observed in kidney function and incidence of fragility fractures between both groups. Cinacalcet was discontinued in 5 out of 13 patients. In conclusion, in kidney transplant patients with tertiary hyperparathyroidism recurrence of hypercalcemia after 5-year follow-up is more frequent in cinacalcet than after subtotal parathyroidectomy.

A Randomized Study Comparing Parathyroidectomy with Cinacalcet for Treating Hypercalcemia in Kidney Allograft Recipients with Hyperparathyroidism.

Tertiary hyperparathyroidism is a common cause of hypercalcemia after kidney transplant. We designed this 12-month, prospective, multicenter, open-label, randomized study to evaluate whether subtotal parathyroidectomy is more effective than cinacalcet for controlling hypercalcemia caused by persistent hyperparathyroidism after kidney transplant. Kidney allograft recipients with hypercalcemia and elevated intact parathyroid hormone (iPTH) concentration were eligible if they had received a transplant ≥6 months before the study and had an eGFR>30 ml/min per 1.73 m(2) The primary end point was the proportion of patients with normocalcemia at 12 months. Secondary end points were serum iPTH concentration, serum phosphate concentration, bone mineral density, vascular calcification, renal function, patient and graft survival, and economic cost. In total, 30 patients were randomized to receive cinacalcet (n=15) or subtotal parathyroidectomy (n=15). At 12 months, ten of 15 patients in the cinacalcet group and 15 of 15 patients in the parathyroidectomy group (P=0.04) achieved normocalcemia. Normalization of serum phosphate concentration occurred in almost all patients. Subtotal parathyroidectomy induced greater reduction of iPTH and associated with a significant increase in femoral neck bone mineral density; vascular calcification remained unchanged in both groups. The most frequent adverse events were digestive intolerance in the cinacalcet group and hypocalcemia in the parathyroidectomy group. Surgery would be more cost effective than cinacalcet if cinacalcet duration reached 14 months. All patients were alive with a functioning graft at the end of follow-up. In conclusion, subtotal parathyroidectomy was superior to cinacalcet in controlling hypercalcemia in these patients with kidney transplants and persistent hyperparathyroidism.

Epicardial adipose tissue in long-term hemodialysis patients: its association with vascular calcification and long-term development.

BACKGROUND: Epicardial adipose tissue (EAT) is associated with coronary artery disease (CAD) in the general population. EAT is suggested to promote CAD by paracrine mechanisms and local inflammation. We evaluated whether in chronic hemodialysis (HD) patients EAT associates with CAD, how the amount of EAT develops over time, and if EAT independently predicts the mortality risk. METHODS: Post-hoc analysis of a prospective study in 59 chronic HD patients who underwent non-enhanced multi-slice computed tomography (MSCT) at baseline. Thirty-seven patients underwent another MSCT after 24 ± 5 months. We measured EAT volume (cm³) and Agatston calcification scores of coronary arteries (CAC) and aortic valves (AVC). All-cause mortality was assessed after a follow-up of 88 months (IQR 52-105). RESULTS: Baseline EAT was 128.2 ± 60.8 cm³ and significantly higher than in a control group of non-renal patients (94 ± 46 cm³; p < 0.05). Median Agatston score for CAC was 329 (IQR 23-1181) and for AVC was 0 (IQR 0-25.3) in HD patients. We observed significant positive correlations between baseline EAT and age (r = 0.386; p = 0.003), BMI (r = 0.314; p = 0.016), CAC (r = 0.278; p = 0.03), and AVC (r = 0.282; p = 0.03). In multivariate analysis, age, BMI and AVC remained as significant predictors of EAT (p < 0.01). Calcification scores significantly increased over 2 years; in contrast EAT change was not significant (+11 %, IQR -10 to 24 %; p = 0.066). The limited patient number in the present study precludes analysis of the EAT impact upon survival. CONCLUSION: EAT correlated significantly with cardiovascular calcification in long-term HD patients. Mean EAT did not significantly change over 2 years.

Changes in bone mineral metabolism parameters, including FGF23, after discontinuing cinacalcet at kidney transplantation.

Little is known about the effects of the administration of cinacalcet in dialytic patients who are scheduled for kidney transplantation, and in particular about the changes in FGF23 and other mineral metabolism parameters after surgery compared with recipients not on cinacalcet at kidney transplantation. We performed a prospective observational cohort study with recruitment of consecutive kidney transplant recipients at our institution. Patients were classified according to whether they were under treatment with cinacalcet before transplantation. Bone mineral metabolism parameters, including C-terminal FGF23, were measured at baseline, on day 15, and at 1, 3, and 6 months after transplantation. In previously cinacalcet-treated patients, cinacalcet therapy was discontinued on the day of surgery and was not restarted after transplantation. A total of 48 kidney transplant recipients, 20 on cinacalcet at surgery and 28 cinacalcet non-treated patients, completed the follow-up. Serum phosphate declined significantly in the first 15 days after transplantation with no differences between the two groups, whereas cinacalcet-treated patients showed higher FGF23 levels, although not significant. After transplantation, PTH and serum calcium were significantly higher in cinacalcet-treated patients. We conclude that patients receiving cinacalcet on dialysis presented similar serum phosphate levels but higher PTH and serum calcium levels during the initial six months after kidney transplantation than cinacalcet non-treated patients. The group previously treated with cinacalcet before transplantation showed higher FGF23 levels without significant differences, so further studies should investigate its relevance in the management of these patients.

Vitamin D, vitamin D receptor and the importance of its activation in patients with chronic kidney disease.

Vitamin D deficiency has been linked to many different pathologies, especially with morbimortality in patients with chronic kidney disease. The progressive loss of renal function leads to calcitriol deficiency and homeostatic changes in calcium, phosphorus, FGF-23 and PTH, among others. All these changes can also influence vitamin D receptor (VDR) activation and the development of secondary hyperparathyroidism (SHPT). The biologic actions of both vitamin D and its synthetic analogues are mediated by binding to the same VDR, acting on different genes. There is a narrow relationship between low levels of calcitriol and SHPT. The combined approach of VDR activation and phosphate restriction, among others, plays an important role in the early treatment of the chronic kidney disease-mineral and bone disorder (CKD-MBD). The Spanish Society of Nephrology, in order to reduce the uniform and significant association with CKD-associated mortality, calcidiol and high phosphate levels suggests normalization of phosphate as well as calcidiol levels in both CKD and dialysis patients. Moreover, it considers that, in addition to selective/non selective activation of VDR for the prevention and treatment of SHPT, VDR could be activated in dialysis patients by native vitamin D or even low paricalcitol doses, independently of PTH levels, as some cohort studies and a recent metaanalysis have found an association between treatment with active vitamin D and decreased mortality in patients with CKD. In general it is considered reasonable to use all this information to individualise decision making.

Rapid calcitriol increase and persistent calcidiol insufficiency in the first 6 months after kidney transplantation.

INTRODUCTION: Vitamin D deficiency or insufficiency is prevalent in kidney transplant recipients. Little is known about post-transplantation changes in vitamin D forms, which are essential for bone health and other health outcomes. The aim was to measure the levels of calcidiol and calcitriol during the first 6 months after kidney transplantation and examine their relation with other bone mineral metabolic parameters. PATIENTS AND METHODS: A prospective study was performed on 98 patients recruited between April 2010 and June 2011. Calcidiol and calcitriol levels were measured at baseline and at days 15, 30, 90, and 180 after kidney transplantation. RESULTS: Serum calcidiol levels remained persistently low: 14.3 (9-22) ng/ml at baseline and 16.3 (10.1-20.6) ng/ml at 6 months (P=0.641). At 6 months, calcidiol levels showed an inverse correlation with simultaneously measured parathyroid hormone levels. Calcidiol showed a trend to be higher in patients transplanted in spring but with no statistically significant difference. Calcitriol levels increased from 17 (13-23.7) pg/ml at baseline to 24 (16-32) pg/ml (P=0.002) in the first 2 weeks after transplantation and reached 37 (25-50) pg/ml (P=0.000) after 6 months. During the follow-up, calcitriol levels showed a significant inverse correlation with baseline fibroblast growth factor-23 levels. At month 6, calcitriol levels were inversely correlated with baseline fibroblast growth factor-23 levels and directly correlated with calcidiol levels. CONCLUSION: In most patients, calcidiol levels remain low 6 months after kidney transplantation, whereas calcitriol levels rapidly return to normal. Lower calcidiol blood levels promoted lower calcitriol blood levels and higher parathyroid hormone concentrations.

Successful treatment of calcific uraemic arteriolopathy with bisphosphonates.

BACKGROUND AND OBJECTIVES: Calcific uraemic arteriolopathy (CUA), also known as calciphylaxis, is a rare but life-threatening condition that almost exclusively affects patients with chronic kidney disease. Several therapies have been employed to treat this disease but with irregular results. We report a prospective case series of eight patients diagnosed with CUA in our unit between 2002 and 2010. MATERIAL AND METHOD: The series consisted of eight patients with CUA (including 4 men, 5 dialysis patients and 3 with functioning allografts) who were treated with bisphosphonates. The diagnosis was by clinical suspicion and a confirmatory biopsy. Five patients had a previous history of high calcium-phosphorus product, 6 had a history of high parathyroid hormone levels (>800pg/ml), 4 had undergone parathyroidectomy, 5 had a history of high cumulative doses of steroids, and 6 patients were under dicoumarin treatment. None of the patients were obese or had diabetes mellitus. RESULTS: In all patients, progression of skin lesions stopped between 2 to 4 weeks after starting bisphosphonate therapy, with no changes in blood levels of calcium and phosphate. Improvement in pain and lesions was faster in patients receiving intravenous ibandronate. All of these patients remained on bisphosphonate treatment for at least 6 months until the wounds healed completely. No recurrences have been observed after follow-up periods between 1 and 9 years. Renal function remained stable in transplant recipients. The treatment was well tolerated and no adverse effects were observed. CONCLUSIONS: Bisphosphonates could be a new and attractive alternative to treat CUA.

Anemia control in renal transplant recipients receiving continuous erythropoietin receptor activator (C.E.R.A.) treatment: the AnemiaTrans Study.

INTRODUCTION: Continuous erythropoietin receptor activator (C.E.R.A.) effectively enables anemia control in patients with chronic kidney disease, but little information is available in renal transplant recipients. The authors aimed to evaluate the effect of C.E.R.A. under clinical practice conditions on anemia control in renal transplant recipients. METHODS: This was a multicenter, retrospective, observational study carried out in adult renal transplant patients in the immediate posttransplant period and at late posttransplant period receiving C.E.R.A. in clinical practice. Patients' data were retrieved from their medical charts at baseline and months 1, 3, and 6. RESULTS: A total of 318 evaluable patients were enrolled into the study: 32 in the immediate posttransplant period and 286 at late posttransplant period (erythropoiesis-stimulating agent [ESA]-naïve, n = 44; converting from other ESAs, n = 242). Patients in the immediate posttransplant period experienced a significant increase in hemoglobin (Hb) levels from baseline to month 1 (9.9±1.5 g/dL vs. 11.5±1.4 g/dL; P< 0.001). ESA-naïve patients showed increasing mean Hb levels from baseline to month 6 (10.1±0.7 g/dL vs. 11.7±1.0 g/dL; P < 0.001) and 94.7% achieved Hb ≥11 g/dL during the study. In patients converted from other ESAs, the percentage of patients with Hb between 11-13 g/dL was maintained from baseline to month 6 with no significant differences (61.0% vs. 62.4%). Mean monthly doses of C.E.R.A. at baseline were 134.4±56.4 µg, 81.3±28.1 µg, and 93.0±44.2 µg in immediate posttransplant, ESA-naïve, and converted patients, respectively. C.E.R.A. was well tolerated. CONCLUSION: C.E.R.A. enables anemia control in renal transplant recipients, allowing target Hb levels to be achieved and maintained with doses even below those described in the Summary of Product Characteristics.

Prevalence, clinical correlates and therapy cost of mineral abnormalities among haemodialysis patients: a cross-sectional multicentre study.

BACKGROUND: This study evaluated the proportion of patients who met National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI) guidelines for mineral status, and assessed the cost of therapy for mineral management of patients under haemodialysis treatment in Spain. METHODS: Demographic and biochemical data were collected for 1312 patients undergoing standard three-times weekly maintenance haemodialysis at six Spanish centres during December 2003. Age, gender, diabetic nephropathy, haemodialysis duration, serum calcium, phosphorus, calcium-phosphorus product (Ca x P), and intact parathyroid hormone (iPTH) levels were monitored. Exploratory analyses of associations between demographic and biochemical parameters, were undertaken using bivariate and multivariate regression techniques. RESULTS: Mean age of patients was 62 years. 97% were Caucasian, 23% were diabetic. In total, 51% of patients received calcium binders, 21% sevelamer, 16% aluminium hydroxide, and 29% received no binders; 33% of patients received calcitriol. Prevalence of patients outside K/DOQI targets was: calcium 50%, phosphorus 46%; Ca x P 33%; iPTH 77%. Elevated phosphorus (>5.5 mg/dl) was independently associated with younger age [OR 0.972 (95% CI 0.963-0.980), P<0.001] and higher iPTH [OR 1.0005 (95% CI 1.0002-1.0008), P<0.001]. Elevated Ca x P (>or=55 mg(2) x dl(2)) showed a similar relationship. High iPTH levels (>300 pmol/l) were associated with female gender [OR 1.574 (95% CI 1.213-2.041), P<0.001], high serum phosphorus [OR 1.230 (95% CI 1.130-1.338), P<0.001], and longer duration of dialysis [OR 1.003 (95% CI 1.001-1.005), P<0.01]. Poorly controlled serum phosphorus, Ca x P and iPTH were associated with more expensive therapy for mineral management. CONCLUSIONS: One in three haemodialysis patients in Spain remains above the upper target range defined in current mineral metabolism guidelines. This abnormal profile is more common in younger patients and females and therapy is more expensive in younger patients.