Alpha-klotho and peritoneal membrane status: A hypothesis generating study.

BACKGROUND: Long-term success of peritoneal dialysis relies on the integrity of the peritoneal membrane. This proof-of-concept study addressed the hypothesis that fibrosis is already present in the membrane at pre-dialysis and that the membrane status is related to the individual's uraemic fingerprint. METHODS: A clinical-mechanistic, transversal, single-centre study was conducted. Pre-dialysis peritoneal biopsies were scored considering the submesothelial compact zone thickness (STM), vasculopathy and inflammation. We investigated if the membrane status could be inferred from a panel of proteins (α-Klotho, Galectin-3, FGF21, FGF23, Tweak, TNFα and hsPCR) in blood. RESULTS: A total 58 incident patients aged 56 ± 15 years old were included, 31% female, 55% hypertension, 29% diabetic and 24% obese. Person-to-person STM was found to be highly variable and 38% of patients were fibrosis positive. Both α-Klotho (Spearman r = -.7491, p < 0.001) and FGF21 (Spearman r = -.5102, p < 0.001) were negatively associated with STM. α-Klotho, but not FGF21, was able to discriminate fibrosis from nonfibrosis with/without inflammation and vasculopathy. PLS models identified α-Klotho as the protein most relevant for fibrosis. α-Klotho was independently associated with fibrosis of the peritoneal membrane (OR = .991 (.896-.997), p = 0.002). CONCLUSION: Before the start of dialysis in incident patients, some patients already present fibrosis of the peritoneal membrane and other patients do not. Our findings suggest that α-Klotho may be implicated in fibrosis of the peritoneal membrane.

Fibrosis of Peritoneal Membrane, Molecular Indicators of Aging and Frailty Unveil Vulnerable Patients in Long-Term Peritoneal Dialysis.

Peritoneal membrane status, clinical data and aging-related molecules were investigated as predictors of long-term peritoneal dialysis (PD) outcomes. A 5-year prospective study was conducted with the following endpoints: (a) PD failure and time until PD failure, (b) major cardiovascular event (MACE) and time until MACE. A total of 58 incident patients with peritoneal biopsy at study baseline were included. Peritoneal membrane histomorphology and aging-related indicators were assessed before the start of PD and investigated as predictors of study endpoints. Fibrosis of the peritoneal membrane was associated with MACE occurrence and earlier MACE, but not with the patient or membrane survival. Serum α-Klotho bellow 742 pg/mL was related to the submesothelial thickness of the peritoneal membrane. This cutoff stratified the patients according to the risk of MACE and time until MACE. Uremic levels of galectin-3 were associated with PD failure and time until PD failure. This work unveils peritoneal membrane fibrosis as a window to the vulnerability of the cardiovascular system, whose mechanisms and links to biological aging need to be better investigated. Galectin-3 and α-Klotho are putative tools to tailor patient management in this home-based renal replacement therapy.

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.

Diuretic-resistant heart failure and the role of ultrafiltration: A proposed protocol.

Acute heart failure (HF) decompensation generally manifests with signs and symptoms of congestion that strongly predict poor poor patient outcome. Loop diuretics are the cornerstone of therapy to counteract fluid overload and are widely used for acute management and chronic stabilization of HF. However, a diminished response to loop diuretics is a common problem, affecting the patient's clinical course and potentially prolonging hospitalization. Diuretic resistance is defined as failure to decongest despite appropriate and escalating loop diuretic therapy. We propose a protocol for the management of diuretic resistance. The initial approach should include an assessment of causes of pseudo-diuretic resistance. Adjustments to loop diuretic therapy, such as increasing doses and frequency of administration and sequential nephron blockade, may be successful. For hospitalized patients with progressive disease there are more invasive methods for fluid removal. Switching from oral to intravenous loop diuretics is essential to avoid variable absorption and for symptomatic relief. Extracorporeal ultrafiltration is also an option since this technique is highly effective at removing plasma fluid from blood. While extracorporeal ultrafiltration is an invasive solution, peritoneal dialysis is a home-based, intermittent therapeutic option that can enable efficient management of fluid overload, preventing HF-related hospital admission, and improving quality of life. As a last resort for fluid removal, a peritoneal dialysis regimen should fully exploit its decongestive properties and should be tailored to the patient's characteristics and clinical needs.

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.

Peritoneal dialysis-associated peritonitis caused by Enterococcus avium.

Peritonitis remains a common and serious complication of peritoneal dialysis. Peritonitis caused by gram-positive organisms includes coagulase-negative staphylococci, Streptococcus spp and Enterococcus spp. We present a rare case of peritoneal dialysis-associated peritonitis, where persisting abdominal pain and worsening laboratory findings despite antibiotic therapy led to the identification of Enterococcus avium, requiring Tenckoff catheter removal and temporary transfer to haemodialysis. The available literature reports only few cases where peritonitis is caused by this agent, underlining the need to consider atypical microbial agents when heterogeneous clinical course is presented.

Tubulointerstitial nephritis and uveitis syndrome in a female adult.

Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare disease characterised by the association of acutetubulointerstitial nephritis and uveitis. It affects mainly children and young women. Drugs and infections may be precipitating factors. It is a diagnosis of exclusion. The mainstays of treatment are topical and systemic corticosteroids. Prognosis is usually favourable. We report a case of TINU which occurred in our unit. A 37-year-old woman presented with an influenza-like illness, bilateral ocular pain and blurred vision. Ophthalmological evaluation revealed bilateral anterior uveitis and later renal involvement was seen as acute tubulointerstitial nephritis. A diagnosis of TINU was assumed after exclusion of other systemic diseases. She was treated with topical corticosteroids for the uveitis and evolved favourably, with resolution of ocular symptoms and normalisation of serum creatinine and proteinuria. This case highlights the importance of a high degree of clinical suspicion to make the diagnosis of TINU syndrome.

Impact of Transcatheter Aortic Valve Implantation on Kidney Function.

BACKGROUND: Chronic kidney disease (CKD) is frequently present in patients with aortic valve disease. Decreased kidney perfusion as a consequence of reduced cardiac output may contribute to renal dysfunction in this setting. OBJECTIVE: Given the potential reversibility of kidney hypoperfusion after valve repair, this study aimed to analyze the impact of percutaneous transcatheter aortic valve implantation (TAVI) on kidney function. METHODS: We performed a retrospective analysis of 233 consecutive patients who underwent TAVI in a single center between November 2008 and May 2016. We assessed three groups according to their baseline estimated glomerular filtration rate (eGFR) (mL/min/1.73 m2): Group 1 with eGFR ≥ 60; Group 2 with 30 ≤ eGFR < 60; and Group 3 with eGFR < 30. We analyzed the eGFR one month and one year after TAVI in these three groups, using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula to calculate it. RESULTS: Patients from Group 1 had a progressive decline in eGFR one year after the TAVI procedure (p < 0.001 vs. pre-TAVI). In Group 2 patients, the mean eGFR increased one month after TAVI and continued to grow after one year (p = 0.001 vs. pre-TAVI). The same occurred in Group 3, with the mean eGFR increasing from 24.4 ± 5.1 mL/min/1.73 m2 before TAVI to 38.4 ± 18.8 mL/min/1.73 m2 one year after TAVI (p = 0.012). CONCLUSIONS: For patients with moderate-to-severe CKD, kidney function improved one year after the TAVI procedure. This outcome is probably due to better kidney perfusion post-procedure. We believe that when evaluating patients that might need TAVI, this 'reversibility of CKD effect' should be considered.

SARS-CoV-2 infection in kidney transplant recipients: clinical impact and outcomes - a single center experience / Infecção por SARS-CoV-2 em receptores de transplante renal: impacto clínico e outcomes - uma experiência de centro único

ABSTRACT 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.

RESUMO Introdução: Receptores de transplante renal são um subgrupo de doentes com maior risco de apresentar formas críticas de infecção por Síndrome Respiratória Aguda Grave pelo Coronavirus-2 (SARS-CoV-2) e piores outcomes devido ao tratamento imunossupressor. Aqui, apresentamos dados de uma coorte de um único centro de receptores de transplante renal com infecção por SARS-CoV-2. Métodos: Num estudo prospectivo, características basais, características clínicas, adaptação da terapêutica antiviral e de imunossupressão foram comparados entre doentes seguidos em ambulatório e doentes hospitalizados durante um período de um ano. Resultados: Foram analisados setenta e sete receptores de transplante renal, incluindo doentes de ambulatório e hospitalizados, com idade média de 57,7 (IIQ 49,7-64,9) anos. Vinte e oito (36,4%) foram tratados em ambulatório enquanto 49 (63,6%) doentes necessitaram de internação hospitalar. Entre os doentes hospitalizados, 18,4% foram admitidos na UTI, 49% apresentaram LRA, e 20,4% morreram. Foram realizados ajustes de imunossupressão em 95,9% dos pacientes hospitalizados, com dose de antimetabólitos ajustada em 83,7%, inibidores de mTOR em 14,3%, inibidores de calcineurina em 12,2%, e terapia com corticosteroides em 81,6%. Conclusão: Entre os pacientes hospitalizados, a optimização da terapêutica imunossupressora incluiu redução ou retirada de antimetabólito e aumento da dose de corticosteroides. A LRA ocorreu em quase metade dos pacientes e a mortalidade em pacientes hospitalizados atingiu 20%, refletindo uma maior gravidade da doença em relação à população em geral.

Impact of Transcatheter Aortic Valve Implantation on Kidney Function / Impacto do Implante Percutâneo de Válvula Aórtica na Função Renal

Abstract Background: Chronic kidney disease (CKD) is frequently present in patients with aortic valve disease. Decreased kidney perfusion as a consequence of reduced cardiac output may contribute to renal dysfunction in this setting. Objective: Given the potential reversibility of kidney hypoperfusion after valve repair, this study aimed to analyze the impact of percutaneous transcatheter aortic valve implantation (TAVI) on kidney function. Methods: We performed a retrospective analysis of 233 consecutive patients who underwent TAVI in a single center between November 2008 and May 2016. We assessed three groups according to their baseline estimated glomerular filtration rate (eGFR) (mL/min/1.73 m2): Group 1 with eGFR ≥ 60; Group 2 with 30 ≤ eGFR < 60; and Group 3 with eGFR < 30. We analyzed the eGFR one month and one year after TAVI in these three groups, using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula to calculate it. Results: Patients from Group 1 had a progressive decline in eGFR one year after the TAVI procedure (p < 0.001 vs. pre-TAVI). In Group 2 patients, the mean eGFR increased one month after TAVI and continued to grow after one year (p = 0.001 vs. pre-TAVI). The same occurred in Group 3, with the mean eGFR increasing from 24.4 ± 5.1 mL/min/1.73 m2 before TAVI to 38.4 ± 18.8 mL/min/1.73 m2 one year after TAVI (p = 0.012). Conclusions: For patients with moderate-to-severe CKD, kidney function improved one year after the TAVI procedure. This outcome is probably due to better kidney perfusion post-procedure. We believe that when evaluating patients that might need TAVI, this 'reversibility of CKD effect' should be considered.

Resumo Fundamento: Pacientes com doença valvar aórtica frequentemente apresentam doença renal crônica (DRC). Diminuição da perfusão renal como consequência da redução do débito cardíaco pode contribuir para a disfunção renal neste cenário. Objetivo: Dado o potencial de reversibilidade da hipoperfusão renal após o reparo valvar, este estudo teve o objetivo de analisar o impacto do implante percutâneo de válvula aórtica (TAVI - transcatheter aortic valve implantation) na função renal. Métodos: Foi realizada uma análise retrospectiva de 233 pacientes consecutivos submetidos ao TAVI em um único centro, entre novembro de 2008 e maio de 2016. Três grupos foram avaliados de acordo com a taxa de filtração glomerular estimada (TFGe) basal (mL/min/1,73 m2): Grupo 1 com TFGe ≥ 60; Grupo 2 com 30 ≤ TFGe < 60; e Grupo 3 com TFGe < 30. O TFGe foi analisado nestes três grupos um mês e um ano após o TAVI e calculado usando a fórmula do Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI). Resultados: Os pacientes do Grupo 1 tiveram um declínio progressivo da TFGe um ano após o procedimento TAVI (p < 0,001 vs. pré-TAVI). Nos pacientes do Grupo 2, a média da TFGe aumentou um mês depois do TAVI e continuou crescendo depois de um ano (p = 0,001 vs. pré-TAVI). O mesmo ocorreu no Grupo 3, com a média da TFGe subindo de 24,4 ± 5,1 mL/min/1,73 m2 antes do TAVI para 38,4 ± 18,8 mL/min/1,73 m2 um ano após o TAVI (p = 0,012). Conclusões: Em pacientes com DRC moderada a grave, a função renal melhorou um ano após o procedimento TAVI. Este resultado é provavelmente devido à melhora da perfusão renal pós-procedimento. Acredita-se que, ao avaliar pacientes que possam precisar de TAVI, este 'efeito de reversibilidade da DRC' deva ser considerado.