Sodium-glucose cotransporter 2 inhibition in primary and secondary glomerulonephritis.

BACKGROUND: The role of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in the management glomerular/systemic autoimmune diseases with proteinuria in real-world clinical settings is unclear. METHODS: This is a retrospective, observational, international cohort study. Adult patients with biopsy-proven glomerular diseases were included. The main outcome was the percentage reduction in 24-h proteinuria from SGLT2i initiation to 3, 6, 9 and 12 months. Secondary outcomes included percentage change in estimated glomerular filtration rate (eGFR), proteinuria reduction by type of disease and reduction of proteinuria ≥30% from SGLT2i initiation. RESULTS: Four-hundred and ninety-three patients with a median age of 55 years and background therapy with renin-angiotensin system blockers were included. Proteinuria from baseline changed by -35%, -41%, -45% and -48% at 3, 6, 9 and 12 months after SGLT2i initiation, while eGFR changed by -6%, -3%, -8% and -10.5% at 3, 6, 9 and 12 months, respectively. Results were similar irrespective of the underlying disease. A correlation was found between body mass index (BMI) and percentage proteinuria reduction at last follow-up. By mixed-effects logistic regression model, serum albumin at SGLT2i initiation emerged as a predictor of ≥30% proteinuria reduction (odds ratio for albumin <3.5 g/dL, 0.53; 95% CI 0.30-0.91; P = .02). A slower eGFR decline was observed in patients achieving a ≥30% proteinuria reduction: -3.7 versus -5.3 mL/min/1.73 m2/year (P = .001). The overall tolerance to SGLT2i was good. CONCLUSIONS: The use of SGLT2i was associated with a significant reduction of proteinuria. This percentage change is greater in patients with higher BMI. Higher serum albumin at SGLT2i onset is associated with higher probability of achieving a ≥30% proteinuria reduction.

Long-term follow-up of an IgA nephropathy cohort: outcomes and risk factors.

AIM: IgA nephropathy (IgAN), the most common glomerulopathy worldwide and in Uruguay, raised treatment controversies. The study aimed to analyze long-term IgAN outcomes and treatment. METHODS: A retrospective analysis of a Uruguayan IgAN cohort, enrolled between 1985 and 2009 and followed up until 2020, was performed. The Ethics Committee approved the study. The inclusion criteria were (a) biopsy-proven IgAN; (b) age ≥12 years; and (c) available clinical, histologic, and treatment data. The patients were divided into two groups, with immunosuppressive (IS) or without (NoIS) treatment. Outcomes (end-stage kidney disease/kidney replacement therapy [ESKD/KRT] or all-cause death) were obtained from mandatory national registries. RESULTS: The study population included 241 patients (64.7% men), median age 32 (19.5) years, baseline blood pressure <130/80 mmHg in 37%, and microhematuria in 67.5% of patients. Baseline proteinuria, glomerulosclerosis, and a higher crescent percentage were significantly more frequent in the IS group. Proteinuria improved in both groups. Renal survival at 20 years was 74.6% without difference between groups. In the overall population and in the NoIS group, bivariate Cox regression analysis showed that baseline proteinuria, endocapillary hypercellularity, tubule interstitial damage, and crescents were associated with a higher risk of ESKD/KRT or death, but in the IS group, proteinuria and endocapillary hypercellularity were not. In the multivariate Cox analysis, proteinuria in the NoIS group, crescents in the IS group and tubule interstitial damage in both groups were independent risk factors. CONCLUSION: The IS group had more severe risk factors than the NoIS group but attained a similar outcome.

Which Patients with Obesity Are at Risk for Renal Disease?

Obesity-related glomerulopathy (ORG) is an increasingly recognized cause of end-stage kidney disease. The most common clinical presentation is a slowly increasing nonnephrotic proteinuria that is followed by a progressive decline of kidney function. Key histological findings are glomerulomegaly and lesions of focal and segmental glomerulosclerosis. A central pathogenic mechanism is the increased sodium reabsorption by proximal tubules that typically accompanies obesity. This causes a decrease in the offer of sodium to the macula densa in the distal nephron, which results in a vasodilation of afferent glomerular arterioles and glomerular hyperfiltration. From a clinical point of view, it is essential to differentiate focal segmental glomerulosclerosis secondary to obesity from primary glomerular processes, which requires a careful differential diagnosis. Diet-induced weight loss, bariatric surgery, and renin-angiotensin blockers are the fundamental therapeutic measures in ORG. The recently developed sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 agonist represent a significant advance in renal protection and will probably improve clinical kidney outcomes in ORG.

Recomendaciones sobre la vacunación contra SARS-CoV-2 / COVID-19 en pacientes con enfermedad renal y trasplante renal / Recommendations for the SARS-CoV-2 vaccination of patients with kidney disease and transplant recipients / Recomendações sobre vacinação contra SARS-CoV-2 / COVID-19 em pacientes com doença renal e transplante renal

Resumen: Este documento de recomendaciones tiene como objetivo orientar a médicos nefrólogos y no nefrólogos que asisten a pacientes con enfermedad renal crónica (ERC) en todas las etapas de la misma, en el proceso de vacunación contra el SARS-CoV-2. Como consecuencia de la situación epidemiológica y de los tiempos del proceso de elaboración de las vacunas disponibles, no se ha generado evidencia lo suficientemente potente, por lo que las recomendaciones no se acompañan del nivel de evidencia. Se fundamenta la necesidad de priorizar la vacunación en este grupo de pacientes en el mayor riesgo de adquirir la infección por SARS-CoV-2, desarrollar la enfermedad COVID-19 con mayor gravedad y presentar una mortalidad más elevada que la población general. Las recomendaciones se organizan por grupos de pacientes considerando pacientes con ERC no dialítica, diálisis y trasplante renal, y pacientes bajo tratamiento inmunosupresor.

Summary The objective of this document containing recommendations is to provide guidelines for nephrologists and non-nephrologists who assist patients with chronic kidney disease (CKD) at all stages of the disease on the vaccination process against SARS-CoV-2. As a consequence of the current epidemiological situation and the timing of the COVID-19 vaccine development -for available vaccines- there is no solid evidence, and thus, recommendations are not accompanied by the due medical proof. The need to prioritize vaccination in this group of patients is based on the increased risk of acquiring the SARS-CoV-2 infection, developing the COVID-19 disease with greater severity and presenting higher mortality rates than the general population. The recommendations are organized by groups of patients, considering patients with non-dialytic CKD, dialysis and kidney transplantation, and patients under immunosuppressive treatment.

Resumo: O objetivo deste documento de recomendações é orientar os nefrologistas e não nefrologistas que atendem pacientes com doença renal crônica (DRC) em todas as fases da doença, no processo de vacinação contra a SARS-CoV-2. Como consequência da situação epidemiológica e do momento do processo de produção das vacinas disponíveis, não foram geradas evidências suficientemente potentes, de modo que as recomendações não são acompanhadas de seu nível de evidência. A necessidade de priorizar a vacinação neste grupo de pacientes baseia-se no maior risco de adquirir a infecção pelo SARS-CoV-2, desenvolver a doença COVID-19 com maior gravidade e apresentar mortalidade superior à da população em geral. As recomendações são organizadas por grupos de pacientes, considerando pacientes com DRC não dialítica, em diálise, com transplante renal, e pacientes em tratamento imunossupressor.

A Personalized Update on IgA Nephropathy: A New Vision and New Future Challenges.

IgA nephropathy (IgAN) is the most common primary glomerulonephritis in the world among patients undergoing renal biopsy. Approximately 30% of patients with IgAN develop end-stage kidney disease 20 years after renal biopsy. It is a glomerulopathy with a very broad clinical presentation, making it difficult to stratify and treat. IgAN is characterized by dysregulation of the immune system, which causes an abnormal synthesis of IgA1 that is deglycosylated causing its mesangial deposition. IgAN pathogenesis is incompletely understood; the current multi-hit hypothesis of IgAN pathogenesis does not explain the range of glomerular inflammation and renal injury associated with mesangial IgA deposition. Although associations between IgAN and glomerular and circulating markers of complement activation are established, the mechanism of complement activation and contribution to glomerular inflammation and injury are not defined. On the other hand, the renal-gut connection can also play an important role in the pathogenesis of IgAN with possible therapeutic implications. In order to standardize the histological findings, the Oxford Classification has allowed clarifying renal lesions that confer potential risk of progression. Currently, except for the blockade of the renin-angiotensin-aldosterone system, no other therapies are available in clinical setting for the treatment of IgAN, although the range of new drugs under investigation is extensive. The incorporation in the next trials of clinical parameters such as the amount of hematuria and histological lesions may allow more personalized therapeutic approaches. To summarize, in recent years, several important efforts have taken place in the understanding of IgAN, but still, further studies are warranted to elucidate the best therapeutic strategies according to the risk to improve the prognosis of this entity.

Estimation of Glomerular Filtration Rate Based on Serum Cystatin C versus Creatinine in a Uruguayan Population.

Background. Estimation of glomerular filtration rate (eGFR) from biomarkers has evolved and multiple equations are available to estimate renal function at bedside. Methods. In a random sample of 119 Uruguayans (54.5% women; 56.2 years (mean)), we used Bland and Altman's method and Cohen's kappa statistic to assess concordance on a continuous or categorical (eGFR < 60 versus ≥60 mL/min/1.73 m(2)) scale between eGFRcys (reference) and eGFR derived from serum creatinine according to the Modification of Diet in Renal Disease (eGFRmdrd) or the Chronic Kidney Disease Epidemiology Collaboration equations (eGFRepi) or from both serum cystatin C and creatinine (eGFRmix). Results. In all participants, eGFRmdrd, eGFRepi, and eGFRmix were, respectively, 9.7, 11.5, and 5.6 mL/min/1.73 m(2) higher (P < 0.0001) than eGFRcys. The prevalence of eGFR <60 mL/min/1.73 m(2) was the highest for eGFRcys (21.8%), intermediate for eGFRmix (11.8%), and the lowest for eGFRmdrd (5.9%) and eGFRepi (3.4%). Using eGFRcys as reference, we found only fair agreement with the equations based on creatinine (Cohen's kappa statistic 0.15 to 0.23). Conclusion. Using different equations we reached clinically significant differences in the estimation of renal function. eGFRcys provides lower estimates, resulting in higher prevalence of eGFR <60 mL/min/1.73 m(2).

Rabdomiólisis por hipopotasemia severa: Report of six cases / Severe hypokalemic rhabdomyolysis

Rhabdomyolysis results from acute necrosis of skeletal muscle fibers and consequent leakage of muscle constituents into the circulation. It ranges from an asymptomatic state to a severe condition associated with extreme elevations in creatine kinase and acute renal failure. Reported etiologies of rhabdomyolysis include alcohol abuse, drugs, muscle trauma and muscle overexertion. Less common causes include muscle enzyme deficiencies, electrolyte abnormalities, infectious causes, toxins and endocrine disorders. Hypokalemia is a rare cause of rhabdomyolysis. We report six patients aged 31 to 57 years (three women) with a severe hypokalemic rhabdomyolysis, secondary to chronic diarrhea in two patients, treatment with loop diuretics in one and Gitelman syndrome in three. Rhabdomyolysis may be underdiagnosed in the context of hypokalemia, because the neuromuscular symptoms can be attributed solely to the electrolyte disorder.

Calcium citrate improves the epithelial-to-mesenchymal transition induced by acidosis in proximal tubular cells / Citrato de cálcio melhora a transição epitélio-mesenquimal induzida por acidose em células do túbulo proximal

INTRODUCTION: Epithelial-to-mesenchymal transition (EMT) is a key event in renal fibrosis. The aims of the study were to evaluate acidosis induced EMT, transforming-growth-factor (TGF) β1 role and citrate effect on it. METHODS: HK2 cells (ATCC 2290) were cultured in DMEM/HAM F12 medium, pH 7.4. At 80% confluence, after 24 hr under serum free conditions, cells were distributed in three groups (24 hours): A) Control: pH 7.4, B) Acidosis: pH 7.0 and C) Calcium citrate (0.2 mmol/L) + pH 7.0. Change (Δ) of intracellular calcium concentration, basal and after Angiotensin II (10-6M) exposition, were measured to evaluate cellular performance. EMT was evaluated by the expression of α-smooth muscle actin (α-SMA) and E-cadherin by immunocytochemistry and/or Western blot. TGF-β1 secretion was determined by ELISA in cell supernatant. RESULTS: At pH 7.0 HK2 cells significantly reduced E-cadherin and increased α-SMA expression (EMT). Supernatant TGF-β1 levels were higher than in control group. Calcium citrate decreased acidosis induced EMT and improved cells performance, without reduction of TGF-β production. CONCLUSIONS: Acidosis induces EMT and secretion of TGF-β1 in tubular proximal cells in culture and citrate improves cellular performance and ameliorates acidosis induced EMT.

INTRODUÇÃO: A transição epitélio-mesenquimal (TEM) é um evento chave na fibrose renal. Os objetivos do estudo foram avaliar se o citrato seria capaz de reverter a TEM induzida por acidose, e qual seria o papel do fator de crescimento transformador (TGF) β1 neste evento. MÉTODOS: Células de túbulo proximal (HK2) foram cultivadas em meio DMEM-F12, pH 7,4. Após confluência, as células foram distribuídas em três grupos A) controle: pH 7,4, B) Acidose: pH 7,0 e C) Acidose: pH 7,0 + citrato de cálcio (0,2 mmol/L). A variação na concentração de cálcio intracelular, antes e após a adição de angiotensina II (10-6M) foi medida para avaliar o desempenho celular. TEM foi avaliada pela expressão de α-actina de músculo liso (α-SMA) e E-caderina por imunocitoquímica e/ou de Western blot. A secreção de TGF-β1 foi determinada por ELISA no sobrenadante. RESULTADOS: Em pH 7,0, houve redução significante na expressão de E-caderina e aumento de α-SMA indicando a presença de TEM e a concentração de TGF-β1 foi maior do que no grupo controle. O citrato de cálcio melhorou TEM induzida pela acidose e a resposta das células à angiotensina II, sem redução do TGF-β. CONCLUSÕES: Acidose induz TEM e secreção de TGF-β1 em células tubulares proximais em cultura e o citrato melhora o desempenho celular e a TEM induzida por acidose.

Aproximación clínica al consumo de sodio / Clinical approach to sodium consumption

Introducción: el consumo de sodio se vincula directamente a las cifras de presión arterial y adicionalmente incide en el manejo de diversas enfermedades. En el año 2003, la Organización Mundial de la Salud (OMS) propone reducir el consumo poblacional de sal a menos de 5 g/día. En Uruguay no contamos con datos de mediciones directas del consumo de sodio. La medición del sodio en la orina de 24 horas es el método patrón para la determinación del consumo diario, sin embargo es un método poco usado en la prácticaclínica debido en parte a lo engorroso que resulta para el paciente. Objetivo: determinar el consumo de sodio de un grupo de voluntarios a través de la natriuria de 24 horas. Encontrar una relación entre la natriuria de una muestra de orina (spot) y la natriuria de 24 horas. Material y método: se reclutaron estudiantes de cuarto año de la carrera de Doctor en Medicina de la Universidad de la República. Se registraron antecedentes médicos, medidas antropométricas, y de presión arterial en consultorio y se recolectó la orina de 24 horas. El análisis de la relación entre el contenido de sodio en el spot y en la orina de 24 horas serealizó mediante prueba de chi cuadrado.Resultados: 33 de 45 estudiantes completaron el estudio. El consumo promedio de sodio fue de 2,9±1,1 g/día. Una natriuria en el spot mayor a 75 mEq/L se asoció a un consumo de sodiomedido por natriuria de 24 horas mayor de 100 mEq/día (p<0,005), con una sensibilidad de 95% y especificidad de 63%.

Introduction: sodium consumption is closely related to blood pressure rates and it additionally affects the handlingof different diseases. In 2003, the World Health Organization (WHO) encouraged people to reduce the consumption of sodium to under 5 g/day. In Uruguay there is no data resulting from direct measurement of sodium consumption. Measuring sodium in the 24 hour urine is the standard method to determine daily consumption, although this method is rarely used in the clinical practice due to its being bothersome for patients. Objective: to determine sodium consumption for agroup of volunteers through 24 hours natriuria. To find a relationship between spot tests of urine natriuria and 24-hour urine natriuria. Method: fourth year medical students were recruited from the School of Medicine at the University of the Republic. Medical history, anthropometric measures and blood pressure in the polyclinic were recorded and the urine was collected during 24 hours. The analysis of the relationship between the content of sodium in the spot and in the 24- hour urine was performed through square chi.Results: 33 out of 45 students completed the study. Average consumption of sodium was 2.9 2,9±1,1 g/day. Natriuria in the spot greater than 75 mEq/L was associated to sodium consumption measured by 24-hour natriuria greater than 100 mEq/día (p<0,005), with a sensitivity of95% and a specificity of 63%.

Introdução: o consumo de sódio está diretamente relacionado aos valores da pressão arterial e também tem influenciasobre o manejo de varias doenças. Em 2003, a Organização Mundial da Saúde (OMS) lançou uma proposta para reduzir o consumo de sal da população aum valor inferior a 5 g/dia. No Uruguai não estão disponíveis dados de medições diretas do consumo de sal. O método padrão para determinação de consumo diário é o exame da urina de 24 horas; no entanto não é um método muito utilizado na prática clínica por ser muito trabalhoso para o paciente. Objetivo: conhecer o consumo de sódio de um grupo de voluntários determinando a natriúria de 24 horas. Encontrar uma relação entre a natriúria de uma amostra de urina (ôspotõ) e a natriúria de 24 horas. Material e método: foram recrutados estudantes doquarto ano do curso de Medicina da Universidad de la República. Foram registrados sus antecedentes médicos,medidas antropométricas, e pressão arterial no consultório e se realizou a coleta de urina de 24 horas. A análise darelação entre o conteúdo de sódio no ôspotõ e na urina de 24 horas foi realizado utilizando a prova do X quadrado. Resultados: 33 dos 45 estudantes completaram o estudo. O consumo médio de sódio foi de 2,9±1,1 g/dia. Uma natriúria do ôspotõ superior a 75 mEq/L foi associada ao consumo de sódio medido por natriúria de 24 horas superior a 100 mEq/dia (p<0,005), com uma sensibilidadede 95% e especificidade de 63%.