[Kidney involvement in Idiopathic Light Chain disease. Report of one case]. / Enfermedad renal por depósito idiopático de cadenas livianas: Caso clínico.

Idiopathic Light Chain disease (ILCD) is a systemic disease characterized by a deposit in different organs of light chain monoclonal immunoglobulins, produced by an abnormal clone of B cells. It is usually found in the course ofa plasma cell dyscrasia and in other lymphoproliferative alterations; however it may occur in absence of any hematologic disease and is denominated as idiopathic. We report a 51-year-old mole admitted to the hospital due to anasarca. Laboratory evaluation showed a serum creatinine of 1.4 mg/dl, a serum albumin of1.6 g/dl, a serum cholesterol of 687 mg/dl and a proteinuria of 5.3 g/day Light chains with a predominance of a monoclonal component were identified in urinary proteins by electrophoresis and kappa chains were identified by immunofixation. A renal biopsy showed a diffuse nodular glomerulopathy with a 35% tubular atrophy and interstitial sclerosis. Electrón microscopy confirmed light chain deposition. The bone marrow biopsy showed a myeloid hyperplasia. The patient was initially treated with methylprednisolone and plasmapheresis with a reduction in serum creatinine and disappearance of urinary kappa component. Albuminuria persisted and a malnutrition-inflammatory complex syndrome was diagnosed. Hemodialysis with ultrafiltration was started along with cyclophosphamide. The patient received hemodialysis for six months and continued with methylprednisolone.

Pro-calcitonin and inflammation in chronic hemodialysis.

UNLABELLED: Procalcitonin (PCT) has emerged as a marker of infection, a frequent complication in hemodialysis (HD). We analyzed PCT levels in chronic non-acutely infected HD subjects, assessed its correlation with inflammatory and nutritional markers and propose a PCT reference value for non-infected HD patients. In an observational cross-sectional study, 48 chronic HD patients and 36 controls were analyzed. VARIABLES: age, gender, time on HD; diabetes; vascular access, PCT, C-reactive protein (CRP), albumin, malnutrition inflammatory score (MIS), hematocrit, leukocyte count, and body mass index (BMI). Subsequently, control (G1, n = 36, 43%) vs. non-infected patients (G2, n = 48, 57%) groups were compared. In control subjects (G1), age: 54.3 ± 13.7 years, range (r): 30-81; males: 19 (53%); median PCT 0.034 ng/ml (r: 0.02-0.08); median CRP 0.80 mg/ dl (r: 0.36-3.9); p95 PCT level: 0.063 ng/ml. In G2, age: 60.2 ± 15.2 years; males 32 (67%), time on HD: 27.0 ± 24.4; diabetics: 19 (32%); median PCT: 0.26 ng/ml (r: 0.09-0.82); CRP: 1.1 mg/dl (r: 0.5-6.2); p95 PCT level: 0.8 ng/ml. In control subjects, PCT and CRP were significantly lower than in G2: PCT: 0.034 vs. 0.26 ng/ml, p = 0.0001; CRP: 0.8 vs. 1.1 mg/dl, p = 0.0004. PCT-CRP correlation in G2: p = 0.287, p = 0.048. PCT and CRP concentrations are elevated in chronic non-acutely infected HD subjects, independently of infection, diabetes and vascular access. A p95 PCT level of 0.8 ng/ml may be considered as the upper normal reference value in non-acutely infected HD subjects. The PCT cut-off level in HD is yet to be determined in HD.

Central Venous Reflux, a Rare Cause of Neurological Manifestations in Hemodialysis Patients: A Case Report and Literature Review.

Central venous disease (CVD) is a serious complication in hemodialysis patients. Neurological manifestations are rare. We describe a female with end-stage renal disease with throbbing headache accompanied by paresthesia, weakness, and abnormal posture of her right hand during dialysis sessions. Motor symptoms completely resolved after each dialysis session, although the headaches persisted for several hours. No neurological deficit was evidenced on physical examination. Digital subtraction angiography identified an incomplete thrombosis of the left brachiocephalic vein with retrograde flow in the internal jugular vein, sigmoid sinus, and transverse sinus on the left side. This case illustrates that cerebral venous congestion due to CVD can produce neurological symptoms. Furthermore, we systematically review the literature to identify the characteristics of the cases described so far. This allows clinicians to know the entity and have a high index of suspicion in a hemodialysis patient who develops neurological symptoms.

Safety and effectiveness of COVID-19 SPUTNIK V vaccine in dialysis patients.

INTRODUCTION: Given the vulnerability of chronic kidney disease individuals to SARS-CoV-2, nephrology societies have issued statements calling for prioritization of these patients for vaccination. It is not yet known whether COVID-19 vaccines grant the same high level of protection in patients with kidney disease compared to the non-dialysis population. The aims of this study were to evaluate the safety - measured by the adverse events potentially attributed to vaccines (ESAVI) - and the effectiveness - evaluated by the presence of antibodies - in dialysis patients immunized with the COVID-19 Sputnik V vaccine. METHODS: multicenter, observational and analytical study of a prospective cohort of hemodialysis patients from the Ciudad Autónoma de Buenos Aires participating in an official vaccination program. Dialysis requiring individuals older than 18 years, who received both components of the COVID-19 vaccine were included. RESULTS: Data from 491 patients were included in the safety analysis. ESAVI with either the first or second component was detected in 186 (37.9%, 95% CI 33.6%-42.3%). Effectiveness analysis measuring antibodies levels against SARS-CoV-2 were performed in 102 patients; 98% presented these IgG antibodies at day 21 after the second component. In patients with COVID-19 prior to vaccination, antibodies at day 21 after the first component reached almost the highest levels compared to patients without previous COVID-19, but IgG rise among patients with previous COVID-19 was lower than in those without this previous disease. CONCLUSION: The Sputnik V vaccine has been shown to be safe and effective in this patient's population.

Introducción: Dada la vulnerabilidad al SARS-CoV-2 de las personas con enfermedad renal crónica, las sociedades de nefrología han emitido declaraciones pidiendo priorizar a estos pacientes para la vacunación. Aún no se sabe si las vacunas COVID-19 confieren el mismo nivel de protección en pacientes con enfermedad renal. Los objetivos de este estudio fueron evaluar la seguridad, medida por eventos supuestamente atribuidos a las vacunas (ESAVI) y la efectividad, evaluada por la presencia de anticuerpos en pacientes en diálisis inmunizados con la vacuna COVID-19 Sputnik V. Métodos: estudio multicéntrico, observacional y analítico de una cohorte prospectiva de pacientes en hemodiálisis, en la Ciudad Autónoma de Buenos Aires, con plan de vacunación. Se incluyeron pacientes mayores de 18 años en diálisis que recibieron ambos componentes de la vacuna COVID-19. Resultados: 491 pacientes fueron incluidos en el análisis de seguridad. Se detectó ESAVI con el primer o el segundo componente en 186 (37.9% IC 95%: 33.6%-42.3%). La efectividad medida por presencia de anticuerpos IgG contra SARS-Cov-2 se realizó en 102 pacientes, 98% presentaba IgG contra SARS-CoV-2, 21 días después del segundo componente. En pacientes con COVID-19 previo a la vacunación, los anticuerpos al día 21 del primer componente alcanzaron niveles casi mayores que en aquellos que no habían sufrido COVID-19, aunque el aumento de los niveles a los 21 días del segundo componente fue menor que en los pacientes sin COVID-19 previo. Conclusión: Los pacientes en diálisis constituyen una población vulnerable para la infección por SARS-CoV-2, por lo tanto, más allá de las recomendaciones implementadas por las unidades de diálisis, la vacunación completa es mandatoria. Se ha demostrado que la vacuna Sputnik V es segura y eficaz en esta población de pacientes.

Elevated pro-brain natriuretic peptide, troponin T and malnutrition inflammatory score in chronic hemodialysis patients with overt cardiovascular disease.

BACKGROUND: We assessed the relationship between pro-brain natriuretic peptide (pro-BNP), troponin T (TropT) and nutritional status. METHODS: A total of 48 chronic hemodialysis patients were grouped according to the presence [group A (GA); n = 24] or not [group B (GB)] of cardiovascular disease. RESULTS: Compared to GB subjects, GA subjects were older, had been on hemodialysis for a longer period and had higher prevalences of vascular grafts, hypertension and elevated C-reactive protein (CRP) [GA vs. GB: 1.1 (range 0.1-32.9) vs. 0.4 (0-28.1) mg/dl; p = 0.028], malnutrition inflammatory score (MIS) (GA vs. GB: 7.50 vs. 4.00; p = 0.001), pro-BNP [GA vs. GB: 6,760 (601-103,200) vs. 686 (75-83,700) pg/ml; p < 0.001] and TropT [GA vs. GB: 0.3650 (0.011-0.199) vs. 0.010 (0.0-0.290) ng/ml; p = 0.002]. Pro-BNP correlated with TropT (rho 0.539; p < 0.001), MIS (rho 0.502; p < 0.0001), homocysteine (rho 0.321; p = 0.13) and CRP (rho 0.511; p < 0.0001). Pro-BNP levels were lower in GB patients as the body mass index increased; the opposite occurred in GA. CONCLUSIONS: Patients with cardiovascular disease had elevated pro-BNP and TropT levels. In patients without cardiovascular disease, malnutrition and inflammation were associated with vascular prostheses, while pro-BNP was lower in obese patients.

["Malnutrition-inflammation complex syndrome" in chronic hemodialysis]. / "Sindrome complejo de malnutricion e inflamacion" en la hemodialisis cronica.

Protein-energy wasting (PEW) and inflammation are usually common and concurrent conditions in maintenance dialysis patients and associated with poor prognosis. Low appetite and hypercatabolic states are common features. In dialysis patients, the former has been suggested to be secondary to inflammation; however, the evidence is not conclusive. Hence, the term malnutrition-inflammation complex syndrome (MICS) was coined to include this clinical entity, regardless the original causes. Possible causes of MICS include comorbid illnesses, oxidative stress, nutrient loss through dialysis, hyporexia, uremic toxins, decreased clearance of inflammatory cytokines, volume overload, increased blood phosphate and dialysis-related factors. MICS is believed to be the main cause of erythropoietin hypo-responsiveness, cardiovascular atherosclerotic disease, decreased quality of life, hospitalization and increased mortality in dialysis patients. Because MICS leads to a low body mass index, hypocholesterolemia, decrease in muscle mass, hypocreatininemia and hypohomocysteinemia, a "reverse epidemiology" phenomenon of cardiovascular risk factors can occur in dialysis patients. Therefore, obesity, hypercholesterolemia, and increased blood levels of creatinine and homocysteine, within certain limits, appear to be protective and paradoxically associated with a better outcome. There is no consensus about how to determine the degree of severity of MICS or how to manage it. Several diagnostic tools and treatment modalities are discussed in this paper. The correct management of MICS may diminish the cardiovascular disease, main cause of death in this population.

[COVID-19 infection in chronic dialysis patients in Argentina]. / Infección por COVID-19 en pacientes en diálisis crónica en Argentina.

The report of the preliminary data of the Argentine Registry of COVID in chronic dialysis is presented, from April 10, 2020 to April 9, 2021 and includes all dialysis centers in the country. In the study period, 36 918 prevalent patients on chronic dialysis were registered. COVID-19 infection was confirmed in 3709 patients (10% of prevalent patients), of which 1675 patients (45.2%) required hospitalization, and of these, 39% (550 patients) required ICU admission. 62% of those admitted to the ICU (339 patients) required mechanical ventilation (MV). 1307 patients died (35.24%). Multivariate analysis showed as factors associated with mortality from COVID in dialysis patients, age greater than 60 years (OR 2.6; 95% CI 2.2-3.1); diabetes (OR 1.5; 95% CI 1.3-1.8); time on dialysis greater than 55 months (OR 1.5; 95% CI 1.2-1.7); cerebrovascular disease (OR 1.6; 95% CI 1.1-2.3); neoplasia (OR 1.7; 95% CI 1.1-2.6); hospitalization requirement (OR 3.4; 95% CI 2.8-3.9); ICU admission (OR 1.8; 95% CI 1.3-2.5); need of MV (OR 11.8; 95% CI 6.9-20.2). The population on chronic dialysis in Argentina, as shown in the rest of the world, is highly vulnerable to COVID infection, showing a lethality 12 times higher than the general population. The measures implemented in dialysis units, patient care and their family environment, and above all priority vaccination are essential in this vulnerable population of patients.

Se presentan los datos preliminares del Registro Argentino de COVID en diálisis crónica, desde el 10 de abril de 2020 al 9 de abril 2021 que incluye todos los centros de diálisis crónica del país. En el período de estudio se registraron 36 918 pacientes prevalentes en diálisis crónica. La infección por COVID-19 fue confirmada en 3709 pacientes (10% prevalentes), de los cuales 1675 (45.2%) requirieron internación, y de éstos el 39% (550) internación en UTI. El 62% de los ingresados a UTI (339) requirió asistencia respiratoria mecánica (ARM). Fallecieron 1307 pacientes (35.24 %). El análisis multivariado, mostró como factores asociados a mortalidad por COVID en diálisis crónica, la edad mayor a 60 años (OR 2.6; IC 95% 2.2-3.1); la diabetes (OR 1.5; IC 95% 1.3-1.8); tiempo en diálisis mayor a 55 meses (OR 1.5; IC 95% 1.2-1.7); enfermedad cerebrovascular OR 1.6; IC 95% 1.1-2.3); neoplasia (OR 1.7; IC 95% 1.1-2.6); requerimiento de internación (OR 3.4; IC 95% 2.8-3.9); internación en UTI (OR 1.8; IC 95% 1.3-2.5); necesidad de ARM (OR 11.8; IC 95% 6.9-20.2). La población en diálisis crónica en Argentina, como se muestra en el resto del mundo, es altamente vulnerable a la infección COVID, mostrando una letalidad 12 veces mayor que la población general. Las medidas implementadas en las unidades de diálisis, los cuidados de los pacientes y su entorno familiar, y por sobre todo la vacunación prioritaria, son fundamentales en esta población vulnerable de pacientes.

H1N1 infection and the kidney in critically ill patients.

BACKGROUND: Acute renal failure due to viral infections is rare. We assessed the development of acute kidney injury (AKI) in critically compromised patients due to the H1N1 influenza virus. METHODS: All patients with a PCR -confirmed diagnosis of H1N1 influenza infection admitted to the intensive care unit between May and July 2009 were retrospectively studied. Thereafter, the risk factors associated with the development of acute renal injury, the requirements of acute hemodialysis (HD) and death were analyzed. RESULTS: Twenty-two patients with H1N1 pneumonia were included: age: 52.91 ± 18.89 years; gender: males 11 (50%); chronic airway disease: 9 (41%); oncohematological disease: 8 (36.7%); cardiovascular disease 5 (22.7%); chronic renal insufficiency: 4 (18.2%); obesity 3 (13.6%); concomitant pregnancy: 2 (9.1%); diabetes mellitus: 2 (9.1%); previous influenza A vaccination: 9 (41%). All patients received oseltamivir within 48 hours of presumed diagnosis. Seventeen patients (77.3%) developed fever initially. Six patients (27.3%) required noninvasive ventilation assistance and 15 patients (68.2%) received invasive ventilatory support. Mean days on mechanical respiratory assistance: 11 ± 10.35. Arterial partial pressure of oxygen/fraction of inspired oxygen ratio: 140.11 ± 83.03 mmHg. Inotropic drugs were administered to 15 patients (68.2%). Fourteen patients (63.6%) developed AKI. Mean highest creatinine levels: 2.74 ± 2.83 mg/dl. Four patients (18.2%) needed renal replacement therapy with a mean duration of 15 ± 12 days. Six patients (42.9%) recovered renal function. AKI was associated with pregnancy, immunosuppression, high APAC HE, SOFA and MURRA Y scores, and less time on mechanical ventilation assistance, hemodynamical instability and thrombocytopenia. HD requirements were associated with elevated SOFA scores (12.25 ± 1.75 vs. 6.22 ± 0.8, p<0.05), elevated creatine phosphokinase (933 ± 436.6 vs. 189.9 ± 79.3 U/L, p<0.05) and alanine transferase levels (843.3 ± 778.8 vs. 85.33 ± 17.4 U/L, p<0.05). Twelve patients died (54.6%), 10 of whom had acute renal failure (83.3%) and 3 had been on acute HD (25%). Mortality was associated with higher APACHE, SOFA and Murray scores, a higher oseltamivir dose (253.1 ± 25.8 vs. 183.8 ± 27.6 mg, p<0.05), lower oxygen inspired fraction/alveolar pressure ratio (99.3 ± 12.2 vs. 196.3 ± 33.9 mmHg, p<0.01), thrombocytopenia (88966 ± 22977 vs. 141200 ± 17282 mm3, p<0.05), hypoalbuminemia (1.82 ± 0.1 vs. 2.61 ± 0.2 g/dl, p<0.01), acute renal failure (10 vs. 4, p<0.05), oligoanuria (5 vs. 0, p<0.05) and lack of recovery of renal function (2 vs. 4, p<0.01). Three out of 4 (75%) of the hemodialyzed patients died. CONCLUSIONS: In the critically ill due to H1N1 pneumonia, renal insufficiency was a frequent complication, demanding renal replacement therapy in 18% of cases. The need for HD was associated with an elevated risk of death. Mortality was mainly associated with multiple organ failure, oligoanuria, acute renal injury and a lack of recovery of renal function.

[Des-resuscitation in the overload of fluids associated with acute kidney injury]. / Des-resucitación en la sobrecarga de fluidos asociada a la lesión renal aguda.

In the last few years the general results in the treatment of acute kidney injury has improved constantly, without a complete comprehension of its pathophysiology. With this paradigm in mind, in these last few years we have seen an evolving comprehension of the possible answers that may be based on recognizing the more proactive role of fluid management in the resuscitation of critical patients, not limited only to the delivery of fluids, but also to their active removal, having as the principal objective the improvement of tissue perfusion. The key role of vascular integrity in fluid overload is discussed, emphasizing the role of the endothelial glycocalyx. Active desresuscitation maneuvers with diuretics or with renal support therapies could be increasingly recognized instruments in the management of fluid overload, particularly in those patients with acute kidney injury.

Los resultados generales del tratamiento de la lesión renal aguda en los últimos años han mejorado casi de manera constante, aunque sin una comprensión completa de su fisiopatología. La respuesta a este interrogante radicaría en la comprensión del rol proactivo en lo que hace a la administración / remoción de los fluidos, abarcando todo el proceso de reanimación de los pacientes críticos, es decir no limitándose a la administración sino también al momento oportuno de la remoción de los mismos, buscando como principal objetivo mejorar la perfusión tisular. Se discute entre otros el papel clave que ejerce la integridad vascular en la sobrecarga de fluidos, haciendo hincapié en el papel del glicocálix endotelial. Las maniobras de des-resucitación activa con diuréticos o con terapias de soporte renal, podrían ser instrumentos cada vez más reconocidos en la aplicación de la sobrecarga de fluidos, en particular en aquellos pacientes con lesión renal aguda.

[Acute kidney injury in severe sepsis]. / Injuria renal aguda en la sepsis grave.

Sepsis affects 40% of critically ill patients, with a reported mortality of approximately 30% in severe sepsis, raising to 75% when acute kidney injury ensues, which occurs in about 20-51% of cases. The present study consists on a one-year prospective, observational, longitudinal trial undergone in 80 severe septic patients to determine the risk of development of acute kidney injury and its relationship with mortality; the association of the clinical course and blood parameter variations with mortality; the severe sepsis mortality rate; an eventual correlation between death and septic focus, and to assess mortality predictibility based on initial creatinine levels and final variations. Two groups were defined: Dead (n=25) and Not-dead (n=55). According to creatinine on admission, 39 subjects presented with normal creatinine levels (10 deaths) and 41 presented elevated creatinine measurements (15 deaths); regarding final creatinine levels, 48 presented normal levels and 7 patients died, while 32 developed acute kidney injury, with 18 deaths. Of the total of 25 deaths, 72% presented renal injury. Seven alive patients and 2 deceased patients required hemodialysis. The most frequent primary septic focus was the airway (26.4%). The development of kidney injury is a high predictor of mortality in sepsis, independent of initial serum creatinine levels. Older patients, hypertension, a higher APACHE score, a more severe degree of anemia, hypoalbuminemia, hyperphosphatemia and hyperkalemia were associated with a higher mortality rate. The global mortality was: 31.3%. The failure to identify the primary septic focus was associated with higher mortality. The respiratory focus was related with a higher risk to require hemodialysis.

Early decrease in the podocalyxin to synaptopodin ratio in urinary Fabry podocytes.

BACKGROUND: In Fabry nephropathy, podocyturia is an early event that may lead to glomerulosclerosis and chronic kidney disease. The glycocalyx is a potential podocyte damaged compartment in glomerulopathies. We investigated glycocalyx podocalyxin in urinary detached podocytes compared with cytoplasmic synaptopodin. METHODS: This was a cross-sectional study including 68 individuals: Controls (n = 20) and Fabry patients (n = 48), 15 untreated and 33 treated. Variables included age, gender, urinary protein/creatinine ratio (UPCR), estimated glomerular filtration rate (eGFR), lyso-triasocylsphingosine (lyso-Gb3) levels and enzyme replacement therapy (ERT). Podocyturia was assessed by immunofluorescence and podocyte subpopulations were analyzed. RESULTS: Fabry patients displayed higher podocyturia than controls. Fabry treated subjects (n = 33) presented significantly higher UPCR compared with untreated ones (n = 15); podocyturia, eGFR and lyso-Gb3 levels were not different. All control podocytes colocalized synaptopodin and podocalyxin; 13 Fabry patients (27%) colocalized these proteins, while 35 (73%) were only synaptopodin positive. No podocalyxin-positive/synaptopodin-negative cells were encountered. In Fabry patients, podocyturia was significantly higher and proteinuria lower in those that colocalized. CONCLUSION: Fabry patients present higher podocyturia and a presumably more damaged glycocalyx assessed by podocalyxin. Treated patients had significant higher proteinuria suggesting ERT is initiated late, at advanced stages. The degree of podocalyxin-negative podocytes was similar in both groups, but colocalization was associated with lower proteinuria. Podocyturia assessed by podocalyxin alone may be underestimated. The implications of podocyte glycocalyx damage deserve further investigations.

Dual renin-angiotensin system blockade plus oral methylprednisone for the treatment of proteinuria in IgA nephropathy.

Renin-angiotensin system inhibition is a widely accepted approach to initially deal with proteinuria in IgA nephropathy, while the role of immunosuppressants remains controversial in many instances. A prospective, uncontrolled, open-label trial was undertaken in patients with biopsy-proven IgA nephropathy with proteinuria > 0.5 g/day and normal renal function to assess the efficacy of a combination treatment of angiotensin converting enzyme inhibitors plus angiotensin receptor blockers enalapril valsartan coupled with methylprednisone to decrease proteinuria to levels below 0.5 g/day. Twenty patients were included: Age 37.45 +/- 13.26 years (50% male); 7 patients (35%) were hypertensive; proteinuria 2.2 +/- 1.86 g/day; serum creatinine 1.07 +/- 0.29 mg/dl; mean follow-up 60.10 +/- 31.47 months. IgA nephropathy was subclassified according to Haas criteria. Twelve patients (60%) were class II; seven (35%) were class III and one (5%) class V. All patients received dual renin-angiotensin system blockade as tolerated. Oral methylprednisone was started at 0.5 mg/kg/day for the initial 8 weeks and subsequently tapered bi-weekly until the maintenance dose of 4 mg was reached. Oral steroids were discontinued after 24 weeks (6 months) of therapy but renin-angiotensin inhibition remained unchanged. At 10 weeks of therapy proteinuria decreased to 0.15 +/- 0.07 g/day (P < 0.001) while serum creatinine did not vary: 1.07 +/- 0.28 mg/dl (P = ns). After a mean follow-up of 42.36 +/- 21.56 months urinary protein excretion (0.12 +/- 0.06 g/day) and renal function (serum creatinine 1.06 +/- 0.27 mg/dl) remained stable. No major side effects were reported during the study. Renin-angiotensin blockade plus oral steroids proved useful to significantly decrease proteinuria to < 0.5 g/day in patients with IgA nephropathy without changes in renal function.

In IgA Nephropathy, Glomerulosclerosis Is Associated with Increased Urinary CD80 Excretion and Urokinase-Type Plasminogen Activator Receptor-Positive Podocyturia.

BACKGROUND: Podocyturia may determine the evolution to podocytopenia, glomerulosclerosis, and renal failure. According to the Oxford classification of IgA nephropathy (IgAN), the S1 lesion describes glomerulosclerosis. Urokinase-type plasminogen activator receptor (uPAR) participates in podocyte attachment, while CD80 increases in glomerulosclerosis. We measured uPAR-positive urinary podocytes and urinary CD80 (uCD80) in controls and in IgAN subjects with M1E0S0T0 and M1E0S1T0 Oxford scores to assess a potential association between podocyturia, inflammation, and glomerulosclerosis. METHODS: The groups were as follows: controls (G1), n = 20 and IgAN group (G2), n = 39, subdivided into M1E0S0T0 (G2A), n = 21 and M1E0S1T0 (G2B), n = 18. Among the included variables, we determined uPAR-positive podocytes/gram of urinary creatinine (gUrCr) and uCD80 ng/gUrCr. Biopsies with interstitial fibrosis and tubular atrophy <10% were included. RESULTS: Groups were not different in age and gender; urinary protein-creatinine (uP/C) ratio, Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation, uPAR-positive podocytes/gUrCr, and uCD80 were significantly increased in G2 versus G1. G2A and G2B were not different in age, gender, hypertension, and follow-up. G2B displayed significantly higher uP/C, uPAR-positive podocytes, uCD80, and lower CKD-EPI versus G2A. Strong significant correlations were encountered between uCD80 and podocyturia in G2A and G2B. However, when G1 was compared to G2A and G2B separately, the differences with respect to uP/C, uPAR-positive podocytes, and podocyturia were significantly stronger versus G2B than versus G2A. CONCLUSIONS: IgAN presents elevated uCD80 excretion and uPAR-positive podocyturia, while CD80 correlates with podocyturia. Glomerulosclerosis (S1) at the time of biopsy is associated with higher uP/C, lower renal function, increased uPAR-positive podocyturia, and CD80 excretion, and is independent of M1. In IgAN, uPAR may participate in podocyte detachment.

Expression of uPAR in Urinary Podocytes of Patients with Fabry Disease.

Background. Despite enzyme replacement therapy, Fabry nephropathy still progresses. Podocyturia is an irreversible event that antedates proteinuria and leads to chronic renal failure. We evaluated a potential mechanism of podocyte detachment via the expression of the urokinase-type Plasminogen Activator Receptor (uPAR) in urinary podocytes of Fabry patients. Methods. This is a cross-sectional study that included controls (n = 20) and Fabry patients (n = 44) either untreated (n = 23) or treated with agalsidase-ß (n = 21). Variables. Variables are estimated glomerular filtration rate (eGFR), urinary protein : creatinine ratio, and urinary uPAR+ podocyte : creatinine ratio. uPAR mRNA expression in response to lyso-Gb3, a bioactive glycolipid accumulated in Fabry disease, was studied in cultured human podocytes. Results. Controls and Fabry patients had similar age, gender, and renal function. Urinary uPAR+ podocytes were higher in patients than in controls. Untreated patients were significantly younger; had more females, and presented lower urinary protein : creatinine ratios and significantly higher urinary uPAR+ podocytes than treated subjects. In treated patients, urinary uPAR+ podocytes correlated with urinary protein : creatinine ratio (ρ = 0.5; p = 0.02). Lyso-Gb3 at concentrations found in the circulation of Fabry patients increased uPAR expression in cultured podocytes. Conclusions. Urinary podocytes expressing uPAR are increased in Fabry patients, especially in untreated patients. The potential contribution of uPAR expression to podocyte detachment merits further studies.

Safety and effectiveness of COVID-19 SPUTNIK V vaccine in dialysis patients / Seguridad y efectividad de vacuna COVID-19 SPUTNIK V en pacientes en diálisis

Abstract Introduction: Given the vulnerability of chronic kidney disease individuals to SARS-CoV-2, nephrology societies have issued statements calling for prioritization of these patients for vaccination. It is not yet known whether COVID-19 vaccines grant the same high level of protection in patients with kidney disease compared to the non-dialysis population. The aims of this study were to evaluate the safety - measured by the adverse events potentially attributed to vaccines (ESAVI) - and the effectiveness - evaluated by the presence of antibodies - in dialysis patients immunized with the COVID-19 Sputnik V vaccine. Methods: multicenter, ob servational and analytical study of a prospective cohort of hemodialysis patients from the Ciudad Autónoma de Buenos Aires participating in an official vaccination program. Dialysis requiring individuals older than 18 years, who received both components of the COVID-19 vaccine were included. Results: Data from 491 patients were included in the safety analysis. ESAVI with either the first or second component was detected in 186 (37.9%, 95% CI 33.6%-42.3%). Effectiveness analysis measuring antibodies levels against SARS-CoV-2 were performed in 102 patients; 98% presented these IgG antibodies at day 21 after the second component. In patients with COVID-19 prior to vaccination, antibodies at day 21 after the first component reached almost the highest levels compared to patients without previous COVID-19, but IgG rise among patients with previous COVID-19 was lower than in those without this previous disease. Conclusion: The Sputnik V vaccine has been shown to be safe and effective in this patient's population.

Resumen Introducción: Dada la vulnerabilidad al SARS-CoV-2 de las personas con enfermedad renal crónica, las sociedades de nefrología han emitido declaraciones pidiendo priorizar a estos pacientes para la vacunación. Aún no se sabe si las vacunas COVID-19 confieren el mismo nivel de protección en pacientes con enfermedad renal. Los objetivos de este estudio fueron evaluar la seguridad, medida por eventos supuestamente atribuidos a las vacunas (ESAVI) y la efectividad, evaluada por la presencia de anticuerpos en pacientes en diálisis inmuniza dos con la vacuna COVID-19 Sputnik V. Métodos: estudio multicéntrico, observacional y analítico de una cohorte prospectiva de pacientes en hemodiálisis, en la Ciudad Autónoma de Buenos Aires, con plan de vacunación. Se incluyeron pacientes mayores de 18 años en diálisis que recibieron ambos componentes de la vacuna COVID-19. Resultados: 491 pacientes fueron incluidos en el análisis de seguridad. Se detectó ESAVI con el primer o el segundo componente en 186 (37.9% IC 95%: 33.6%-42.3%). La efectividad medida por presencia de anticuerpos IgG contra SARS-Cov-2 se realizó en 102 pacientes, 98% presentaba IgG contra SARS-CoV-2, 21 días después del segundo componente. En pacientes con COVID-19 previo a la vacunación, los anticuerpos al día 21 del primer componente alcanzaron niveles casi mayores que en aquellos que no habían sufrido COVID-19, aunque el aumento de los niveles a los 21 días del segundo componente fue menor que en los pacientes sin COVID-19 previo. Conclusión: Los pacientes en diálisis constituyen una población vulnerable para la infección por SARS-CoV-2, por lo tanto, más allá de las recomendaciones implementadas por las unidades de diálisis, la vacunación completa es mandatoria. Se ha demostrado que la vacuna Sputnik V es segura y eficaz en esta población de pacientes.

Biomarkers in acute kidney injury: Evidence or paradigm? / Biomarcadores en la lesión renal aguda: ¿ paradigma o evidencia?

Acute kidney injury in the critically ill represents an independent risk factor of morbidity and mortality in the short and long terms, with significant economic impacts in terms of public health costs. Currently its diagnosis is still based on the presence of oliguria and/or a gradual increase in serum creatinine, which make the diagnosis a delayed event and to detriment of the so-called 'therapeutic window'. The appearance of new biomarkers of acute kidney injury could potentially improve this situation, contributing to the detection of 'subclinical acute kidney injury', which could allow the precocious employment of multiple treatment strategies in order to preserve kidney function. However these new biomarkers display sensitive features that may threaten their full capacity of action, which focus specifically on their additional contribution in the early approach of the situation, given the lack of specific validated treatments for acute kidney injury. This review aims to analyze the strengths and weaknesses of these new tools in the early management of acute kidney injury.

Infección por COVID-19 en pacientes en diálisis crónica en Argentina / COVID-19 infection in chronic dialysis patients in Argentina

Resumen Se presentan los datos preliminares del Registro Argentino de COVID en diálisis crónica, desde el 10 de abril de 2020 al 9 de abril 2021 que incluye todos los centros de diálisis crónica del país. En el período de estudio se registraron 36 918 pacientes prevalentes en diálisis crónica. La infección por COVID-19 fue confirmada en 3709 pacientes (10% prevalentes), de los cuales 1675 (45.2%) requirieron internación, y de éstos el 39% (550) internación en UTI. El 62% de los ingresados a UTI (339) requirió asistencia respiratoria me cánica (ARM). Fallecieron 1307 pacientes (35.24 %). El análisis multivariado, mostró como factores asociados a mortalidad por COVID en diálisis crónica, la edad mayor a 60 años (OR 2.6; IC 95% 2.2-3.1); la diabetes (OR 1.5; IC 95% 1.3-1.8); tiempo en diálisis mayor a 55 meses (OR 1.5; IC 95% 1.2-1.7); enfermedad cerebrovascular OR 1.6; IC 95% 1.1-2.3); neoplasia (OR 1.7; IC 95% 1.1-2.6); requerimiento de internación (OR 3.4; IC 95% 2.8-3.9); internación en UTI (OR 1.8; IC 95% 1.3-2.5); necesidad de ARM (OR 11.8; IC 95% 6.9-20.2). La población en diálisis crónica en Argentina, como se muestra en el resto del mundo, es altamente vulnerable a la infección COVID, mostrando una letalidad 12 veces mayor que la población general. Las medidas implementadas en las unidades de diálisis, los cuidados de los pacientes y su entorno familiar, y por sobre todo la vacunación prioritaria, son fundamentales en esta población vulnerable de pacientes.

Abstract The report of the preliminary data of the Argentine Registry of COVID in chronic dialysis is presented, from April 10, 2020 to April 9, 2021 and includes all dialysis centers in the country. In the study period, 36 918 prevalent patients on chronic dialysis were registered. COVID-19 infection was confirmed in 3709 patients (10% of prevalent patients), of which 1675 patients (45.2%) required hospitalization, and of these, 39% (550 patients) required ICU admission. 62% of those admitted to the ICU (339 patients) required mechanical ventilation (MV). 1307 patients died (35.24%). Multivariate analysis showed as factors associated with mortality from COVID in dialysis patients, age greater than 60 years (OR 2.6; 95% CI 2.2-3.1); diabetes (OR 1.5; 95% CI 1.3-1.8); time on dialysis greater than 55 months (OR 1.5; 95% CI 1.2-1.7); cerebrovascular disease (OR 1.6; 95% CI 1.1-2.3); neoplasia (OR 1.7; 95% CI 1.1-2.6); hospitalization requirement (OR 3.4; 95% CI 2.8-3.9); ICU admission (OR 1.8; 95% CI 1.3-2.5); need of MV (OR 11.8; 95% CI 6.9-20.2). The population on chronic dialysis in Argentina, as shown in the rest of the world, is highly vulnerable to COVID infection, showing a lethality 12 times higher than the general population. The measures implemented in dialysis units, patient care and their family environment, and above all priority vaccination are essential in this vulnerable population of patients.

Belatacept and mediastinal histoplasmosis in a kidney transplant patient.

BACKGROUND: In transplantation immunosuppression enhances the appearance of opportunist infections. An ideal balance between the prevention of rejection, the lowest risk of infections and the highest rates of graft survival is a continuous challenge. Lower doses of immunosuppression may diminish the risk of infections, metabolic and hemodynamic complications or even of malignancy, but may expose patients to episodes of acute rejection. New drugs are being developed to improve graft survival at the lowest risk of side effects. Belatacept has recently been introduced in kidney transplantation to inhibit the co-ligand signal of T cell stimulation. It is a drug with a safe profile, is well-tolerated and appears to improve long-term survival of kidney grafts. However, there may be an increase in opportunistic infections which may be facilitated by T cell depression, as Aspergillus sp., Cryptococcus neoformans or tuberculosis. CASE PRESENTATION: We describe a 59-year-old female who developed fever, clinical wasting and a mediastinal mass 31 months after receiving a living non-related kidney transplant while on belatacept therapy. A mediastinal node biopsy disclosed the presence of Histoplasma capsulatum. Infection successfully resolved after appropriate antifungal treatment. CONCLUSIONS: To our knowledge, this is the first reported case of Histoplasma capsulatum in a kidney transplanted patient on belatacept therapy.