High Plasma Levels of Fibroblast Growth Factor 23 Are Associated with Increased Risk of COVID-19 in End-Stage Renal Disease Patients on Hemodialysis: Results of a Prospective Cohort.

End-stage renal disease (ESRD) patients are a population with high rates of COVID-19 and mortality. These patients present a low response to anti-SARS-CoV-2 immunization, which is associated with immune dysfunction. ESRD patients also present high plasma titers of Fibroblast Growth Factor 23 (FGF23), a protein hormone that reduces immune response in vivo and in vitro. Increased FGF23 levels associate with higher infection-related hospitalizations and adverse infectious outcomes. Thus, we evaluated whether ESRD patients with high FGF23 titers have an increased rate of SARS-CoV-2 infection. METHODS: We performed a prospective cohort of ESRD patients in hemodialysis who had measurements of plasma intact FGF23 in 2019. We determined COVID-19 infections, hospitalizations, and mortality between January 2020 and December 2021. RESULTS: We evaluated 243 patients. Age: 60.4 ± 10.8 years. Female: 120 (49.3%), diabetes: 110 (45.2%). During follow-up, 45 patients developed COVID-19 (18.5%), 35 patients were hospitalized, and 12 patients died (mortality rate: 26.6%). We found that patients with higher FGF23 levels (defined as equal or above median) had a higher rate of SARS-CoV-2 infection versus those with lower levels (18.8% versus 9.9%; Hazard ratio: 1.92 [1.03-3.56], p = 0.039). Multivariate analysis showed that increased plasma FGF23 was independently associated with SARS-CoV-2 infection and severe COVID-19. DISCUSSION: Our results suggest that high plasma FGF23 levels are a risk factor for developing COVID-19 in ESRD patients. These data support the potential immunosuppressive effects of high circulating FGF23 as a factor implicated in the association with worse clinical outcomes. Further data are needed to confirm this hypothesis.

[Effectiveness of regional citrate anticoagulation in continuous renal replacement therapy]. / Efectividad de anticoagulación regional con citrato en terapia de reemplazo renal continua.

BACKGROUND: Anticoagulation in continuous renal replacement therapy (CRRT) is essential to counteract the coagulation cascade activation, induced by the dialysis circuit. Heparin is the most widely used anticoagulant, followed by regional citrate anticoagulation (RCA). AIM: To determine the effectiveness and safety of anticoagulant treatment with citrate in CRRT. MATERIAL AND METHODS: Retrospective study of adults in CRRT hospitalized between the years 2014 and 2020 in critical units, who required change to RCA according to established protocols. RESULTS: We studied 24 patients aged 63 ± 13 years (12 females). The reasons for admission were acute kidney injury (AKI) in 80% and stage 5 chronic kidney disease in 20%. The indication of RCA in 75% of patients was by coagulation of more than 3 circuits in 24 hours. The duration of the circuit in RCA was 18.5 ± 4.8 hours versus 11.9 ± 4.9 hours with heparin (p < 0.0001). There were 19 mild complications that did not affect the RCA. CONCLUSIONS: RCA is feasible to perform, it is a safe and efficient procedure if it is protocolized, allowing a longer duration of the dialysis circuit.

Efectividad de anticoagulación regional con citrato en terapia de reemplazo renal continua / Effectiveness of regional citrate anticoagulation in continuous renal replacement therapy

BACKGROUND: Anticoagulation in continuous renal replacement therapy (CRRT) is essential to counteract the coagulation cascade activation, induced by the dialysis circuit. Heparin is the most widely used anticoagulant, followed by regional citrate anticoagulation (RCA). AIM: To determine the effectiveness and safety of anticoagulant treatment with citrate in CRRT. Material and Methods: Retrospective study of adults in CRRT hospitalized between the years 2014 and 2020 in critical units, who required change to RCA according to established protocols. RESULTS: We studied 24 patients aged 63 ± 13 years (12 females). The reasons for admission were acute kidney injury (AKI) in 80% and stage 5 chronic kidney disease in 20%. The indication of RCA in 75% of patients was by coagulation of more than 3 circuits in 24 hours. The duration of the circuit in RCA was 18.5 ± 4.8 hours versus 11.9 ± 4.9 hours with heparin (p < 0.0001). There were 19 mild complications that did not affect the RCA. Conclusions: RCA is feasible to perform, it is a safe and efficient procedure if it is protocolized, allowing a longer duration of the dialysis circuit.

[Renal involvement in antineutrophil cytoplasmic antibodies (ANCA) associated vasculitides. Recommendations of the Chilean Societies of Nephrology and Rheumatology]. / Compromiso renal en vasculitis asociadas a anticuerpos anticitoplasma de neutrófilos. Recomendaciones de consenso de las Sociedades Chilenas de Nefrología y Reumatología.

Renal involvement is a frequent complication in antineutrophil cytoplasmic antibodies (ANCA)associated vasculitides, adding morbidity and mortality, such as chronic kidney disease and the need for renal replacement therapy. With the aim of reaching a consensus on relevant issues regarding the diagnosis, treatment and follow-up of patients with these diseases, the Chilean Societies of Nephrology and Rheumatology formed a working group that, based on a critical review of the available literature and their experience, raised and answered consensually a set of questions relevant to the subject. This document includes aspects related to the clinical diagnosis, the histological characteristics, the therapeutic alternatives to induce and maintain the remission of the disease, relapse surveillance strategies and complementary therapies.

Compromiso renal en vasculitis asociadas a anticuerpos anticitoplasma de neutrófilos. Recomendaciones de consenso de las Sociedades Chilenas de Nefrología y Reumatología / Renal involvement in antineutrophil cytoplasmic antibodies (ANCA) associated vasculitides. Recommendations of the Chilean Societies of Nephrology and Rheumatology

Renal involvement is a frequent complication in antineutrophil cytoplasmic antibodies (ANCA)associated vasculitides, adding morbidity and mortality, such as chronic kidney disease and the need for renal replacement therapy. With the aim of reaching a consensus on relevant issues regarding the diagnosis, treatment and follow-up of patients with these diseases, the Chilean Societies of Nephrology and Rheumatology formed a working group that, based on a critical review of the available literature and their experience, raised and answered consensually a set of questions relevant to the subject. This document includes aspects related to the clinical diagnosis, the histological characteristics, the therapeutic alternatives to induce and maintain the remission of the disease, relapse surveillance strategies and complementary therapies.

Human Peritoneal Mesothelial Cell Death Induced by High-Glucose Hypertonic Solution Involves Ca2+ and Na+ Ions and Oxidative Stress with the Participation of PKC/NOX2 and PI3K/Akt Pathways.

Chronic peritoneal dialysis (PD) therapy is equally efficient as hemodialysis while providing greater patient comfort and mobility. Therefore, PD is the treatment of choice for several types of renal patients. During PD, a high-glucose hyperosmotic (HGH) solution is administered into the peritoneal cavity to generate an osmotic gradient that promotes water and solutes transport from peritoneal blood to the dialysis solution. Unfortunately, PD has been associated with a loss of peritoneal viability and function through the generation of a severe inflammatory state that induces human peritoneal mesothelial cell (HPMC) death. Despite this deleterious effect, the precise molecular mechanism of HPMC death as induced by HGH solutions is far from being understood. Therefore, the aim of this study was to explore the pathways involved in HGH solution-induced HPMC death. HGH-induced HPMC death included influxes of intracellular Ca2+ and Na+. Furthermore, HGH-induced HPMC death was inhibited by antioxidant and reducing agents. In line with this, HPMC death was induced solely by increased oxidative stress. In addition to this, the cPKC/NOX2 and PI3K/Akt intracellular signaling pathways also participated in HGH-induced HPMC death. The participation of PI3K/Akt intracellular is in agreement with previously shown in rat PMC apoptosis. These findings contribute toward fully elucidating the underlying molecular mechanism mediating peritoneal mesothelial cell death induced by high-glucose solutions during peritoneal dialysis.

[Encapsulating peritoneal sclerosis]. / Diagnóstico y seguimiento de 12 casos de peritonitis esclerosante asociada a diálisis peritoneal crónica en Chile: Experience in 12 patients on peritoneal dialysis.

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is a complication of peritoneal dialysis (PD) with a low prevalence but high mortality. It is characterized by peritoneal inflammation and fibrosis with subsequent development of intestinal encapsulation. It is associated with a long lapse on PD, frequent episodes of peritonitis, high glucose solution use, and high peritoneal transport status. AIM: To report the clinical features of patients on PD, who developed EPS. MATERIAL AND METHODS: Review of medical records of 12 patients aged 43 ± 10 years (eight women) who developed EPS. RESULTS: The mean time spent on PD was 98 months. The main clinical manifestations were abdominal pain in 82% and ultrafiltration failure in 63%. In 92%, there was a history of peritonitis and 75% had high peritoneal transport at the time of diagnosis. The main findings in computed tomography were peritoneal calcification and thickening. There was a biopsy compatible with the diagnosis in 10 cases. Treatment consisted in withdrawal from PD, removal of PD catheter and the use of corticoids and tamoxifen. After withdrawal from PD 50% of patients became asymptomatic. The rest had intermittent abdominal pain and altered bowel movements. Two patients died (17%). CONCLUSIONS: EPS is a serious complication of PD, which should be suspected in any patient with compatible clinical symptoms, long time on PD, multiple episodes of peritonitis and high peritoneal transport profile.

Diagnóstico y seguimiento de 12 casos de peritonitis esclerosante asociada a diálisis peritoneal crónica en Chile: Experience in 12 patients on peritoneal dialysis / Encapsulating peritoneal sclerosis

Background: Encapsulating peritoneal sclerosis (EPS) is a complication of peritoneal dialysis (PD) with a low prevalence but high mortality. It is characterized by peritoneal inflammation and fibrosis with subsequent development of intestinal encapsulation. It is associated with a long lapse on PD, frequent episodes of peritonitis, high glucose solution use, and high peritoneal transport status. Aim: To report the clinical features of patients on PD, who developed EPS. Material and Methods: Review of medical records of 12 patients aged 43 ± 10 years (eight women) who developed EPS. Results: The mean time spent on PD was 98 months. The main clinical manifestations were abdominal pain in 82% and ultrafiltration failure in 63%. In 92%, there was a history of peritonitis and 75% had high peritoneal transport at the time of diagnosis. The main findings in computed tomography were peritoneal calcification and thickening. There was a biopsy compatible with the diagnosis in 10 cases. Treatment consisted in withdrawal from PD, removal of PD catheter and the use of corticoids and tamoxifen. After withdrawal from PD 50% of patients became asymptomatic. The rest had intermittent abdominal pain and altered bowel movements. Two patients died (17%). Conclusions: EPS is a serious complication of PD, which should be suspected in any patient with compatible clinical symptoms, long time on PD, multiple episodes of peritonitis and high peritoneal transport profile.

Recomendaciones sobre el manejo del compromiso renal del lupus eritematoso sistémico: Documento de Consenso de las Sociedades Chilenas de Nefrología y Reumatología / A consensus of the Chilean Nephrology and Rheumatology Societies on renal involvement in systemic lupus erythematosus

Renal involvement affects over one half of patients with Systemic Lupus Erythematosus increasing their mortality and morbidity, including chronic renal disease and the need of renal replacement therapies. Aiming to achieve a consensus in the most relevant topics on diagnosis, therapy and follow-up of patients with lupus renal disease, the Chilean Societies of Nephrology and Rheumatology constituted a workgroup that, based on a critical review of the available literature and their experience, raised and answered by consensus a set of relevant questions. This document includes aspects related to the clinical diagnosis, the importance of a suitable histological classification, therapeutic alternatives to induce and maintain disease remission, strategies for follow-up, additional therapies and ginecological-obstetric issues.

[A consensus of the Chilean Nephrology and Rheumatology Societies on renal involvement in systemic lupus erythematosus]. / Recomendaciones sobre el manejo del compromiso renal del lupus eritematoso sistémico: Documento de Consenso de las Sociedades Chilenas de Nefrología y Reumatología.

Renal involvement affects over one half of patients with Systemic Lupus Erythematosus increasing their mortality and morbidity, including chronic renal disease and the need of renal replacement therapies. Aiming to achieve a consensus in the most relevant topics on diagnosis, therapy and follow-up of patients with lupus renal disease, the Chilean Societies of Nephrology and Rheumatology constituted a workgroup that, based on a critical review of the available literature and their experience, raised and answered by consensus a set of relevant questions. This document includes aspects related to the clinical diagnosis, the importance of a suitable histological classification, therapeutic alternatives to induce and maintain disease remission, strategies for follow-up, additional therapies and gynecological-obstetric issues.

Vitamin B12 deficiency is associated with geographical latitude and solar radiation in the older population.

BACKGROUND: Vitamin B12 and folic acid deficiency are common in the older and are associated with several conditions including anaemia, cardiovascular disease, cognitive impairment and cancer. Evidence from in vitro studies suggests that solar radiation can degrade both vitamins in the skin. Chile is the longest country in the world running perfectly North-South making it an ideal place to study potential associations of latitude and solar radiation on vitamin B12 and folic acid deficiency. OBJECTIVES: The objective was to examine the association between vitamin B12 and folic acid deficiencies and latitude. METHODS: Plasma samples were collected from Chileans aged 65+ years (n=1013) living across the whole country and assayed for vitamin B12 and folic acid concentrations as part of the Chilean Health Survey 2009-2010, which is a national representative sample study. RESULTS: Overall, the prevalence of vitamin B12 deficiency was 11.3%, with the prevalence in the North of the country being significantly greater than in the Central and South zones (19.1%,10.5%, and 5.7%, respectively; P<0.001). The prevalence of folic acid deficiency in the whole cohort was 0.7% with no difference between the 3 geographical zones. Using logistic regression analyses, vitamin B12 deficiency was significantly associated with geographical latitude (OR 0.910 [95% confidence intervals 0.890-0.940], P<0.001) and solar radiation (OR 1.203 [95% confidence intervals 1.119-1.294], P<<0.001). These associations persisted after adjustments for confounders (OR 0.930, P<0.001 and 1.198, P=0.002, respectively). CONCLUSIONS: In the Chilean population of 65+, the prevalence of vitamin B12 deficiency is associated with living closer to the Equator and solar radiation. Although degradation by solar radiation might explain this observation, further work is required to establish the potential mechanisms. In countries that routinely fortify food with folic acid, efforts to identify vitamin B12 deficiency might be more cost-efficiently targeted in areas closest to the Equator.

Analysis of the intronic single nucleotide polymorphism rs#466452 of the nephrin gene in patients with diabetic nephropathy.

We present the analysis of an intronic polymorphism of the nephrin gene and its relationship to the development of diabetic nephropathy in a study of diabetes type 1 and type 2 patients. The frequency of the single nucleotide polymorphism rs#466452 in the nephrin gene was determined in 231 patients and control subjects. The C/T status of the polymorphism was assessed using restriction enzyme digestions and the nephrin transcript from a kidney biopsy was examined. Association between the polymorphism and clinical parameters was evaluated using multivariate correspondence analysis. A bioinformatics analysis of the single nucleotide polymorphism rs#466452 suggested the appearance of a splicing enhancer sequence in intron 24 of the nephrin gene and a modification of proteins that bind to this sequence. However, no change in the splicing of a nephrin transcript from a renal biopsy was found. No association was found between the polymorphism and diabetes or degree of renal damage in diabetes type 1 or 2 patients. The single nucleotide polymorphism rs#466452 of the nephrin gene seems to be neutral in relation to diabetes and the development of diabetic nephropathy, and does not affect the splicing of a nephrin transcript, in spite of a splicing enhancer site.

[Clinical guidelines on identification, management and complications of chronic kidney disease]. / Enfermedad renal crónica: clasificación, identificación, manejo y complicaciones.

The key messages of these guidelines on chronic kidney disease are: Chronic kidney disease (CKD) is a public health problem due to its wide distribution, high rate of complications and cost. CKD is a common condition, its prevalence being about 10%, and is treatable if it is detected on time. A patient with CKD has a higher risk of cardiovascular mortality than of progression of its underlying renal disease. A new definition of CKD, based on estimated Glomerular Filtration Rate (eGFR) and kidney damage, facilitates its detection and management. CKD is detected with three simple tests: 1) Blood pressure measurement, 2) Detection of proteinuria or albuminuria in an isolated urine sample, and 3) Estimation of renal function (eGFR), based on serum creatinine, age, gender and race. The CKD risk groups are individuals with diabetes, hypertension and a family history of renal disease. The most cost-effective measures are to detect and treat diabetic and hypertensive patients in the community. Therapy must emphasize the maximal reduction of cardiovascular risk. The complications of CKD such as anemia and renal osteodystrophy can be identified and treated on time. Most patients with chronic kidney disease are detected in the community, therefore their initial care must be organized at the level of primary care, along with programs for hypertension and diabetes.

Enfermedad renal crónica: Clasificación, identificación, manejo y complicaciones / Clinical guidelines on identitication, management and complications of chronic kidney disease

The key messages of these guidel ines on chronic kidney disease are: • Chronic kidney disease (CKD) is a public health problem due to its wide distribution, high rate of complications and cost. • CKD is a common condition, its prevalence being about 10 percent, and is treatable if it is detected on time. • A patient with CKD has a higher risk of cardiovascular mortality than of progression of its underlying renal disease. • A new definition of CKD, based on estimated Glomerular Filtration Rate (eGFR) and kidney damage, facilitates its detection and management. • CKD is detected with three simple tests: 1) Blood pressure measurement, 2) Detection of proteinuria or albuminuria in an isolated urine sample, and 3) Estimation of renal function (eGFR), based on serum creatinine, age, gender and race. • The CKD risk groups are individuáis with diabetes, hypertension and a family history of renal disease. • The most cost-effective measures are to detect and treat diabetic and hypertensive patients in the community. • Therapy must emphasize the maximal reduction of cardiovascular risk. • The complications of CKD such as anemia and renal osteodystrophy can be identified and treated on time. • Most patients with chronic kidney disease are detected in the community, therefore their initial care must be organized at the level of primary care, along with programs for hypertension and diabetes.