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Introduction There is an increased risk of thrombotic complications in patients with COVID‐19. Hemodialysis patients are already at an increased risk for thromboembolic events such as stroke and pulmonary embolism. The aim of our study was to determine the incidence of late thrombotic complications (deep vein thrombosis, pulmonary embolism, stroke, new‐onset vascular access thrombosis) in maintenance hemodialysis patients after recovery from COVID‐19. Methods We performed a retrospective cohort study of 200 prevalent hemodialysis patients in our center at the start of the pandemic. We excluded incident patients after the cohort entry date and those who required hemodialysis for acute kidney injury, and excluded patients with less than 1 month follow‐up due to kidney transplantation or death from non‐thrombotic causes. Findings One‐hundred and eighty five prevalent hemodialysis patients finally met the inclusion criteria; 37 patients (17.6%) had SARS‐CoV‐2 infection, out of which 10 (27%) died during the acute phase of disease without evidence of thrombotic events. There was an increased risk of thrombotic events in COVID‐19 survivors compared to the non‐infected cohort (18.5% vs. 1.9%, p = 0.002) after a median follow‐up of 7 months. Multivariate regression analysis showed that COVID‐19 infection increased risk for late thrombotic events adjusted for age, sex, hypertension, diabetes, antithrombotic treatment, and previous thrombotic events (Odds Ratio (OR) 26.4, 95% confidence interval 2.5–280.6, p = 0.01). Clinical and laboratory markers did not predict thrombotic events. Conclusions There is an increased risk of late thrombotic complications in hemodialysis patients after infection with COVID‐19. Further studies should evaluate the benefit of prolonged prophylactic anticoagulation in hemodialysis patients after recovery from COVID‐19.

Background and Aims There is an increased risk of thrombotic complications in patients with COVID-19. Hemodialysis patients are already at an increased risk for thromboembolic events such as stroke and pulmonary embolism. The aim of our study was to determine the incidence of late thrombotic complications (deep vein thrombosis, pulmonary embolism, stroke, new-onset vascular access thrombosis) in maintenance hemodialysis patients after recovery from COVID-19. Method We performed a retrospective cohort study of 200 prevalent hemodialysis patients in our center at the start of the pandemic. We excluded incident patients after the cohort entry date and those who required hemodialysis for acute kidney injury, and excluded patients with less than 1 month follow-up due to kidney transplantation or death from non-thrombotic causes. Results 185 prevalent hemodialysis patients finally met the inclusion criteria; 37 patients (17.6%) had SARS-CoV-2 infection, out of which 10 (27%) died during the acute phase of disease without evidence of thrombotic events. There was an increased risk of thrombotic events in COVID-19 survivors compared to the non-infected cohort (18.5% vs 1.9%, p=0.002) after a median follow-up of 7 months. Stroke incidence was 38.9 episodes/1000 patient-years in patients infected with SARS-CoV-2, compared to an incidence of 2.8 episodes/1000 patient-years in non-infected patients during the follow-up period. The median time from diagnosis of SARS-CoV-2 to the first thrombotic event was 62 days (interquartile range 5-118 days). Survival analysis with Kaplan-Meier curves revealed an increase in the rate of thrombotic events after SARS-CoV-2 compared to non-infected patients (see Figure 1). Mean survival from thrombotic event was 6.1±0.4 months in the COVID-infected group, compared to 6.97±0.04 months in the non-infected group (p Conclusion There is an increased risk of late thrombotic complications in hemodialysis patients after infection with COVID-19. Further studies should evaluate the benefit of prolonged prophylactic anticoagulation in hemodialysis patients after recovery from COVID-19.

Control of dyslipidemia in chronic kidney disease (CKD) is not always guaranteed with statins and/or ezetimibe. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) have opened up a new era in lipid control, but their effect on renal function and proteinuria in real life have not yet been evaluated. The aim of the present study was to analyze the evolution of renal function and proteinuria in a cohort of CKD patients treated with PCSK9i. This retrospective multicentric cohort study included CKD patients treated with PCSK9i. Baseline epidemiological data, comorbidities and laboratory findings (including estimated glomerular filtration rate [eGFR], proteinuria and lipid profile) were collected. The evolution of renal function, proteinuria and lipid profile was analyzed during the 1-year follow-up. The cohort included 76 patients (68% male, mean age 66 ± 10 years). The mean baseline creatinine was 1.55 ± 0.77 mg/dL, and the mean eGFR was 52 ± 22 mL/min/1.73 m2. Reductions in LDL-cholesterol, total cholesterol and triglycerides during the first month were 51 ± 25%, 32 ± 25% and 11 ± 40%, respectively, levels that remained stable throughout the first year (p &lt, 0.001 for LDL-cholesterol and total cholesterol trends and p = 0.002 for triglyceride trend). During follow-up, proteinuria improved from 57 (9–481) to 30 (7–520) mg/g (p = 0.021). In addition, eGFR remained stable, and no adverse events were reported. In our cohort, dyslipidemia treatment with PCSK9i was associated with decreased proteinuria in CKD patients, an effect that might be due to reduced lipid nephrotoxicity. Clinical trials are needed to further investigate whether this impact on proteinuria can significantly slow CKD progression in the long term.

Background and objectives Screening colonoscopy with polipectomy reduces colonorectal cancer incidence and mortality. An adequate bowel cleansing is one of the keys to achieving best results with this technique. Oral sodium phosphate solution (OSP) had a widespread use in the 90s decade. Its efficacy was similar to polyethylene glycol (PEG) solution, but with less cost and convenient administration. Series of patients with acute renal failure due to OSP use have been reported. However, large cohorts of patients found no difference in the incidence of renal damage between these two solutions. Methods From 2006 to 2009 we identified twelve cases of phosphate nephropathy after colonoscopy prepared with OSP. All patients were followed up to six months. All patients had received just a single dose. Results We analyzed 12 cases with phosphate nephropathy; three patients debuted with AKI and nine patients had chronic renal injury. Four cases were confirmed with renal biopsy. One patient with AKI needed hemodialysis at diagnosis without subsequent recovery. Two patients (both with chronic damage) fully recovered their previous renal function. The remaining patients (nine) had an average loss of estimated glomerular filtration rate of 24 ml/min/1.73 m2. Conclusions The use of OSP can lead to both acute and chronic renal damage. However, chronic injury was the most common pattern. Both forms of presentation imply a significant and irreversible loss of renal function. Further studies analyzing renal damage secondary to bowel cleaning should consider these two different patterns of injury.

Exercise can induce circadian phase shifts depending on the duration, intensity and frequency. These modifications are of special meaning in athletes during training and competition. Melatonin, which is produced by the pineal gland in a circadian manner, behaves as an endogenous rhythms synchronizer, and it is used as a supplement to promote resynchronization of altered circadian rhythms. In this study, we tested the effect of melatonin administration on the circadian system in athletes. Two groups of athletes were treated with 100 mg day(-1) of melatonin or placebo 30 min before bed for four weeks. Daily rhythm of salivary melatonin was measured before and after melatonin administration. Moreover, circadian variables, including wrist temperature (WT), motor activity and body position rhythmicity, were recorded during seven days before and seven days after melatonin or placebo treatment with the aid of specific sensors placed in the wrist and arm of each athlete. Before treatment, the athletes showed a phase-shift delay of the melatonin circadian rhythm, with an acrophase at 05:00 h. Exercise induced a phase advance of the melatonin rhythm, restoring its acrophase accordingly to the chronotype of the athletes. Melatonin, but not placebo treatment, changed daily waveforms of WT, activity and position. These changes included a one-hour phase advance in the WT rhythm before bedtime, with a longer nocturnal steady state and a smaller reduction when arising at morning than the placebo group. Melatonin, but not placebo, also reduced the nocturnal activity and the activity and position during lunch/nap time. Together, these data reflect the beneficial effect of melatonin to modulate the circadian components of the sleep-wake cycle, improving sleep efficiency.

Background/Aim: The levels of C-reactive protein (CRP) have been related to hypoalbuminemia and the necessity of erythropoietin in patients on maintenance hemodialysis. However, in several studies, the patients’ clinical situation is not taken into account. The aim of the present work was to analyze the relationship between CRP and serum albumin and hemoglobin and the erythropoietin resistance index (ERI) in a population of patients on chronic hemodialysis classified according to their clinical situation. Methods: In a cohort of 53 patients followed for 12 months, we analyzed the CRP level and its association with albumin and hemoglobin levels and the ERI (ratio of total weekly erythropoietin dose in units/weight to hemoglobin concentration in g/dl) at the start of the study and at 6 and 12 months thereafter. The patients were divided into three groups based on the presence of inflammatory/infectious disorders during the 4 weeks prior to CRP determination (group A) or the use of a jugular catheter (group B) or an arteriovenous fistula (group C) as vascular access for hemodialysis. Results: At baseline, the CRP levels (47.1 mg/l in group A, 30.7 mg/l in group B, and 9.4 mg/l in group C) and the ERI (23.9 in group A, 24.6 in group B, and 10.7 in group C) were higher in groups A and B than in group C (p < 0.001 for both parameters). Serum albumin (3.9 g/dl in group A, 4.1 g/dl in group B, and 4.4 g/dl in group C) and hemoglobin (10.4 g/dl in group A, 11.3 g/dl in group B, and 12 g/dl in group C) were lower in groups A and B than in group C (p < 0.05 for serum albumin and p < 0.01 for hemoglobin). In all patients, the baseline CRP level correlated with the albumin level (r = –0.3853, p < 0.01), with the hemoglobin level (r = –0.2950, p < 0.05), and with the ERI (r = 0.4378, p < 0.01). However, if we only considered the group C patients, there was no correlation between baseline CRP and albumin, hemoglobin, and ERI. Similar results were observed at 6 and 12 months. Conclusions: The CRP, albumin, and hemoglobin levels and the ERI mostly depend on the existence of ongoing inflammatory/infectious disorders and the use of a catheter as vascular access. In the absence of these clinical conditions, we could not correlate the CRP level with the other parameters. The relationship between CRP, albumin, and anemia may be an epiphenomenon

Background Although tacrolimus is recommended by KDIGO Clinical Practice Guideline for Glomerulonephritis for the treatment of idiopathic membranous nephropathy (MN), little is known about factors that influence response and relapse of the disease after tacrolimus therapy. Methods Multicentre study that collected 122 MN patients with nephrotic syndrome and stable renal function treated with tacrolimus. Duration of treatment was 17.6 ± 7.2 months, including a full-dose and a tapering period. Results The percentage of remission was 60, 78 and 84% after 6, 12 and 18 months of treatment, respectively. The amount of proteinuria at baseline significantly predicted remission, the lower the baseline proteinuria the higher the probability of remission. Only 10 patients (8%) received concomitantly corticosteroids, and their rate of remission was similar (80% at 18 months). Among responders, 42% achieved complete remission (CR) and 58% partial remission (PR). Almost half (44%) of the responder patients relapsed. The amount of proteinuria at the onset of tacrolimus tapering was significantly higher in relapsing patients. By multivariable analysis, the presence of a PR versus CR at the onset of tacrolimus tapering and a shorter duration of the tapering period significantly predicted relapses. Tolerance was good and the number of adverse events low. Conclusions Tacrolimus monotherapy is an effective and safe option for the treatment of MN with stable renal function. Relapses are frequent in patients with PR and can be partially prevented by a longer tapering period.

Cancer has been reported to be more common among kidney transplant recipients than waiting-list patients or the general population. Use of anticalcineurin agents and azathioprine are relevant risk factors. Nine renal allograft recipients (seven men and two women) of mean age 67.6 (55-77) years and mean time after transplantation of 30.7 (58-216) months were switched to everolimus-based immunosuppression because of the presence of biopsy-proven malignancies (eight patients) or neurological tacrolimus toxicity (one patient). One patient with posttransplant lymphoproliferative disease also received chemotherapy with a good evolution at 6 months. He showed an initial increase in the protein to creatinine ratio (peak 3.3 mg/mg at 3 months) that was controlled by increasing the enalapril dose. One patient with skin cancer and severe atheromatosis (baseline SCr 2.5 mg/dL, creatinine clearance 17 mL/min, and protein to creatinine ratio 3.2 mg/mg), had cyclosporine and everolimus overlapped for 25 days, showing a continued poor evolution requiring dialysis initiation at 3 months after switch. The other six patients with recurrent skin cancers had good cancer evolution, with no new skin tumors and regression of skin lesions in three, including not biopsied actinic keratosis. Sudden switching from calcineurin inhibitors to everolimus is safe and may be used in long-term transplant recipients with malignancies. In patients with advanced chronic nephropathy this approach appeared to be less beneficial.

Background and objectives: We studied the relationship between microinflammation and endothelial damage in chronic kidney disease (CKD) patients on different dialysis modalities. Design, setting, participants, & measurements: Four groups of CKD stage 5 patients were studied: 1) 14 nondialysis CKD patients (CKD-NonD); 2) 15 hemodialysis patients (HD); 3) 12 peritoneal dialysis patients with residual renal function >1 ml/min (PD-RRF >1); and 4) 13 peritoneal dialysis patients with residual renal function ≤1 ml/min (PD-RRF ≤1). Ten healthy subjects served as controls. CD14+CD16+ cells and apoptotic endothelial microparticles (EMPs) were measured by flow cytometry. Serum vascular endothelial growth factor (VEGF) was measured by ELISA. Results: CKD-NonD and HD patients had a higher percentage of CD14+CD16+ monocytes than PD groups and controls. CD14+CD16+ was similar in the PD groups, regardless of their RRF, and controls. The four uremic groups displayed a marked increase in apoptotic EMPs and VEGF compared with controls. Apoptotic EMPs and VEGF were significantly higher in HD patients than in CKD-NonD and both PD groups. However, there were no significant differences between CKD-NonD and the two PD groups. There was a correlation between CD14+CD16+ and endothelial damage in CKD-NonD and HD patients, but not in PD and controls. Conclusions: There was an increase in CD14+CD16+ only in CKD-NonD and HD patients. In these patients, there was a relationship between increased CD14+CD16+ and endothelial damage. These results strongly suggest that other factors unrelated to the microinflammatory status mediated by CD14+CD16+ are promoting the endothelial damage in PD, regardless of their RRF.

Mycophenolate mofetil (MMF) reduces acute rejection episodes (AREs) and may be associated with better renal graft survival than azathioprine. However, MMF-related adverse events are frequent; dose reduction or even withdrawal are quite common. Between 1999 and 2003, 115 renal transplantation patients were treated with tacrolimus, MMF, and steroids. An observational study was undertaken until graft loss (n = 7), death with a functioning graft (n = 2), or October 31, 2005 (mean follow-up-50 months). We assessed MMF dose reductions due to adverse events with the possible consequences on AREs and graft function. Treated acute ARE occurred in 11.3% of recipients, all of which were steroid-responsive. The median MMF initial daily dose was 1000 mg. In 44 patients (38.3%), the MMF dose was not changed; in 48 (41.7%) it was reduced; and in 23 (20%), withdrawn. The causes for dose modification were diarrhea (n = 33, 28.7% of all patients), leukopenia (n = 22, 19.1%), both of these (n = 7, 6.1%), or other events (n = 9, 7.8%). No AREs were attributed to MMF dose changes. Tacrolimus blood levels were higher at 3 years and serum creatinine values at 4 years among patients with dose changes (8.43 +/- 2.42 vs 7.37 +/- 2.23 ng/mL; P = .051 and 1.75 +/- 0.71 vs 1.48 +/- 0.38 mg/dL; P = .038, respectively). The need for MMF dose reduction or withdrawal was frequent in our patients with diarrhea or leukopenia during treatment with tacrolimus, MMF, and steroids. These adverse event-related changes were not associated with AREs, but produced deleterious effects on long-term graft function.

Background. This prospective study was designed to investigate the long-term evolution of bone mineral density (BMD) in kidney transplant recipients. Methods. In 86 patients with functioning grafts, 65 on tacrolimus-based immunosuppression and 21 on cyclosporine-based immunosuppression, laboratory parameters and BMD measurements in lumbar spine (L2-L4) and femoral neck (FN) were performed by DEXA in the first month after transplantation (baseline) and yearly thereafter up to the fourth year. Results. BMD did not change at 12 months in lumbar spine nor in the FN. Detailed analysis identified three patterns of BMD in lumbar spine at 12 months: BMD remained stable in 27 patients (31.4%), decreased >2% in 31 (36.0%) and increased >2% in 28 (32.6%). Patients with no change or gain presented a parallel increase of BMD in FN (P

Omeprazole is a proton pump inhibitor with a number of pharmacokinetic drug interactions due to interference with cytochrome P450. Some studies show absence of relevant interaction between omeprazole and cyclosporine, but little is known about possible interactions between omeprazole and tacrolimus. In vitro studies suggest such interference, but no clinical data are available so far. We assessed interactions between omeprazole and tacrolimus among patients fulfilling two criteria: (1) renal allograft recipients receiving immunosuppression based on tacrolimus and acid-related disorder prophylaxis with omeprazole 20 mg/d since the day of the transplant procedure and (2) stopped omeprazole when it was considered unnecessary. Fifty-one transplant recipients received concomitant immunosuppression with MMF-prednisone (n = 47) or azathioprine-prednisone (n = 1), or rapamycin-prednisone (n = 2) or only prednisone (n = 1). omeprazole was stopped after 6.2 +/- 3 months of treatment. Tacrolimus doses and levels were recorded during 3 outpatient visits before omeprazole withdrawal (Pre3/Pre2/Pre1), at the withdrawal visit (Susp), and at 3 visits after withdrawal (Pos1/Pos2/Pos3). Weight gain was significant (72.5 +/- 13 kg Pre3; 73.4 +/- 13 kg Susp; 74 +/- 12.9 kg Pos3, P < .0001) and serum creatinine (SCr) decreased (1.70 +/- 0.49 mg/dL Pre3; 1.63 + 0.49 Susp; 1.58 +/- 0.48 Pos3, P < .0001). The progressive decrease in tacrolimus doses and levels was significant (ANOVA including the 7 visits

Osteopenia is a common complication after transplantation. However, prospective long-term studies are scarce and most were performed in patients on cyclosporine and high-dose steroids. In 65 patients with functioning grafts, 41 males and 24 females, 50 on tacrolimus-based immunosuppression and 15 on cyclosporine-based immunosuppression, bone mineral density (BMD) was measured in the lumbar spine (L2-L4) and femoral neck (FN) using dual X-ray absorptiometry (DEXA) in the first month after transplantation (baseline) and at 1, 2, and 3 years. At baseline, BMD was similar to the control population both in L2-L4 (z score = -0.421) and in FN (z score = -0.518). During the follow-up, 3 types of patterns were identified: BMD increased in L2-L4 in 25 patients (38.5%), remained stable in 20 patients (30.8%), and decreased in 20 patients (30.8%). BMD losses appeared mainly during the first year (0.964 +/- 0.162 baseline; 0.904 +/- 0.161 at 1 year, 0.886 +/- 0.140 at 3 years; analysis of variance [ANOVA] P.001). However, the improvement was maintained throughout the follow-up (0.860 +/- 0.176 g/cm2 at baseline; 0.901 +/- 0.161 at 1 year; 0.954 +/- 0.178 at 3 years; ANOVA P.001) and there was a parallel increase of BMD in FN (0.712 +/- 0.144 at baseline; 0.744 +/- 0.249 at 1 year; 0.826 +/- 0.184 at 3 years; ANOVA P.01). There were no differences between both groups in graft function, intact parathyroid hormone (iPTH) levels, number of postmenopausal women, or steroid doses. About one third of patients had bone loss during the first year after transplantation. We were unable to identify any risk factor for this complication in patients on low-dose steroids.

Cyclosporin A (CsA) concentration monitoring with 2 h post-dosing levels (C2) correlates with the incidence of rejection and graft outcome in de novo renal transplant patients. The advantages of this policy beyond the first 12 months remain a matter of debate. The purpose of the present work was to evaluate the C2 target ranges on CsA monitoring after the first year in stable kidney transplant patients.We studied 142 patients, 94 on CsA-steroids and 48 on triple therapy (CsA-azathioprin-steroids), transplanted for 104+/-42 months and with a serum creatinine of 1.53+/-0.52 mg/dl. C2 and C0 measurements were performed at baseline and at least twice more during the year of follow-up.The mean annual C2 blood levels in double therapy patients showed C2 in 23 (24.5%) of600 ng/ml; in 53 (56.4%) of between 600 and 850 ng/ml; and in 18 patients (19.1%) of850 ng/ml. In the triple therapy group, C2 in 12 (25%) was500 ng/ml, in 24 (50%) between 500 and 700 ng/ml and in 12 patients (25%)700 ng/ml. In both groups, higher C2 levels were associated with a better absorption of the drug measured by the ratio C2/C0 and C2/dose. There were no differences in incidence of infections, need for hospitalization and the presence of hypertension, hyperuricaemia, hypercholesterolaemia or diabetes between patients with low and high C2 blood levels. However, serum creatinine was higher in triple therapy patients with lower C0 levels (P = 0.004). In 135 patients (90 on double and 45 on triple therapy), renal function remained stable during follow-up and 120 of them (89%) had C2 values under the recommended ranges.C2 monitoring in maintenance patients enabled us to identify overexposure to CsA. Target levels of C2 should be adjusted according to the immunosuppressive regime. C2 levels between 600 and 800 ng/ml in double therapy patients and between 500 and 700 ng/ml in triple therapy patients are sufficient to give an adequate immunosuppression. The superiority of C2 with respect to C0 levels could not be demonstrated.