Predictors of response and relapse in patients with idiopathic membranous nephropathy treated with tacrolimus.

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.

Late thrombotic complications after SARS-CoV-2 infection in hemodialysis patients.

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.

Proteinuria-Lowering Effects of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors in Chronic Kidney Disease Patients: A Real-World Multicentric Study.

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 < 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.

[Disability as a barrier to drug adherence in polypathological patients: role of main carer]. / La discapacidad como barrera a la adherencia terapéutica en pacientes pluripatológicos: papel del cuidador principal.

OBJECTIVES: To determine which social and individual factors may predict adherence to medication in patients with more than two chronic symptomatic diseases (polypathological patients) under polypharmacy. METHODS: Cross-sectional observational study. In a primary care area assigned to our teaching hospital 265 patients with multiple chronic diseases and polypharmacy were recruited over a 6 month period. 84 patients with uncompleted data or died before finishing our study were excluded. An structured interview performed by a investigator different from responsible physicians was used. Drug adherence was assessed by a subjective method. RESULTS: Disability measured by Barthel index was was the main predictor of drug adherence. Patients without carer support and Barthel Index lower than 100 showed the poorer drug adherence. In the later group number of drugs also affected adherence. However, in patients with carer available, medication adherence was better, mostly in more disabled ones, and unaffected by other factors. CONCLUSIONS: In patients with multiple chronic diseases, social support by a carer may allow disabled patients to overcome the barrier of disability leading to a better drug adherence, even than non-disabled ones. These findings may help to design future prospective studies on medication adherence performed in this peculiar frail population.

Lumbar bone mineral density in renal transplant patients on neoral and tacrolimus: a four-year prospective study.

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<0.001 in both groups). On multivariate analysis, the variables associated with no change or lumbar BMD loss were total prednisone dose in grams at 12 months (OR 1.402; 95% CI 1.038-1.893; P=0.028), calcitriol levels at 12 months (OR 0.936; 95% CI 0.892-0.982; P=0.007) and lumbar BMD at baseline (OR 1.006; 95% CI 1.002-1.010; P=0.002). Late treatment with calcium supplements and calcitriol did not improve osteopenia. CONCLUSIONS: One third of patients had bone loss mainly during the first year of follow-up. Bone loss was associated to higher baseline BMD, high steroid dose, and lower calcitriol levels at 1 year. Late administration of calcitriol and calcium supplements did not improve posttransplant osteopenia. More than 50% of patients were osteopenic 4 years after transplantation.

Kidney injury after sodium phosphate solution beyond the acute renal failure.

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 24ml/min/1.73m(2). 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.

Clinical significance of C-reactive protein in patients on hemodialysis: a longitudinal study.

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.

Reliability of a short questionnaire for the diagnosis of severe disability in polypathological patients attended in hospital setting.

BACKGROUND: A comprehensive evaluation of polypathological patients (PP) should always include a functional evaluation. For this purpose, a modified version of the Barthel Index (BI) is the most applied questionnaire, and it consists of a 10-variable scale. The aim of this study was to develop a screening and confirmation tool to diagnose high disability with the fewest number of dimensions of the BI as possible. METHOD: This present cross-sectional observational multicentre study included PP attended in 36 Spanish hospitals that were divided into two geographical areas (Western and Eastern). The Western area was considered to be the derivation subgroup of PP, and the Eastern area was the validation subgroup. Complete disability for each item (value of 0) was assessed for the diagnosis of severe disability. Diagnostic validity indices (sensitivity, specificity, negative and positive predictive values [NPV and PPV, respectively], and negative and positive likelihood ratios [NLR and PLR, respectively]) were determined for the derivation subgroup. The dimensions with the best diagnostic validity indices were then used to evaluate the validation subgroup. RESULTS: The analysis included 1521 PP, 753 PP from the Western area and 768 PP from the Eastern area. Needing complete help for bathing showed the highest NPV and lowest NLR in the derivation/validation subgroups (NPV 96.87/95.54, NLR 0.07/0.13). Being disabled for feeding alone showed high PPV and PLR values (PPV 97.97/95.65, PLR 109.25/49.62), as did disability for transfers (PPV 98.48/97.96, PLR 143.36/107.68). In addition, complete disability for feeding and transfers had the best PPV and PLR in both subgroups (PPV 100/100, PLR X/0). CONCLUSIONS: A two-dimension mini-Barthel Index may represent a reliable diagnostic test for severe disability in PP.

Effects of renin-angiotensin blockers/inhibitors and statins on mortality and functional impairment in polypathological patients.

BACKGROUND: Frail and polypathological patients (PP) are often undertreated with evidence-based cardiovascular drugs, as their benefits are uncertain in this population. OBJECTIVES: To determine the effects of treatment with renin-angiotensin system blockers/inhibitors (ACEI/ARB), statins and/or beta-blockers on survival rates and functional decline in PP with evidence-based clinical indications for treatment with any of these drug families. METHOD: Prospective observational multicentre cohort study with a 12-month follow-up period. We selected PP with any condition of the following: chronic heart failure, coronary heart disease, chronic renal disease, cerebrovascular disease, peripheral artery disease, diabetes mellitus with any visceral involvement, hypertension, and dyslipidaemia. Clinical, functional (Barthel index), socio-familial risk data and drug prescriptions were measured at baseline. Multivariate Cox proportional hazards and logistic regression models were used to identify variables independently associated with survival and functional decline. RESULTS: The analysis included 1260 PP. The mean age was 79±9.5 years. The mortality rate was 34.5%. Statin (aHR 0.671; P=0.001), beta-blocker plus statin (aHR 0.645; P=0.007), ACEI/ARB plus statin (aHR 0.680; P=0.002), or combined ACEI/ARB plus statin plus beta-blocker (aHR 0.541; P=0.000) prescriptions were associated with longer survival times. Additionally, PP whose Barthel index was ≥60 showed a lower risk of disability progression if treated with statins (aOR=0.476; P=0.000), or their combinations, mainly with ACEI/ARB plus beta-blockers (aOR 0.563; P=0.031). CONCLUSIONS: The prescription of statins, alone or in combination with other drugs, may impact the survival and functional decline in polypathological patients. Further prospective blinded randomised assays are needed to confirm these observations.

Effect of different dialysis modalities on microinflammatory status and endothelial damage.

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

Clinical outcomes and C2 cyclosporin monitoring in maintenance renal transplant recipients: 1 year follow-up study.

BACKGROUND: 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. METHODS: 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. RESULTS: The mean annual C2 blood levels in double therapy patients showed C2 in 23 (24.5%) of <600 ng/ml; in 53 (56.4%) of between 600 and 850 ng/ml; and in 18 patients (19.1%) of >850 ng/ml. In the triple therapy group, C2 in 12 (25%) was <500 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. CONCLUSIONS: 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.