ABSTRACT Chronic kidney disease (CKD) is highly prevalent and is predicted to become the fifth highest cause of premature mortality globally by 2040. There are several risk factors for CKD and the environmental conditions play an important role on the development of kidney injury. Due to increasing use of earth’s natural resources and pollutants emissions, extreme weather events are becoming more frequent and severe. These events, such as hurricanes or floods, cause infectious diseases outbreaks that increase the risk of acute kidney injury and chronic kidney disease. In addition, rising average temperatures and heat waves cause a higher incidence of acute kidney injury and nephrolithiasis. Patients with CKD are particularly prone to these events, with a special focus on patients undergoing peritoneal dialysis or hemodialysis. Mitigation plans are needed to reduce the effect of climate change on kidney health. Nephrologists have an important role in both reducing the environmental impact of nephrology and in preparing patients for the effect of climate changes on their diseases and for the accessibility problems to health institutions.

ABSTRACT Introduction: Healthcare facilities are among the greatest contributors to resource consumption and waste generation. Nephrology is one of the most polluting medical areas, mostly due to hemodialysis (HD). Incremental hemodialysis (iHD) has gained attention due to several clinical advantages, by decreasing the number of sessions while the patient still has residual kidney function. Beyond these benefits, this regímen might also be both more economical and environmentally friendly. The aim of this study was to evaluate the potential reduction of resource consumption, waste generation and carbon footprint associated with the implementation of iHD. Methods: We conducted a single-center retrospective analysis of 157 incidental patients initiating HD in our centre in 2019 (pre-pandemic). Retrospectively, a set of criteria identifying eligibility for an iHD program were applied to those patients. Results: Twenty-three patients (15%) would have been eligible for iHD instead of starting a standard HD program. In that scenario, iHD implementation would have reduced from 36 to 85 tons of CO2 equivalent emissions and 4186 kg of contaminated waste yearly, at our unit. iHD would also allow savings of almost 60 000€ and a reduction in water consumption of 418 600 L in one year. Conclusion: This study shows that iHD can significantly attenuate the environmental and economic impact of HD. These findings encourage kidneycare programs and policymakers to adopt greener options but should never be detrimental to the clinical decision of referencing a patient to iHD.

ABSTRACT The rising prevalence of patients living with kidney disease and the recognition of the huge environmental impact of kidney care (mainly dialysis treatments) points to the unsustainability of nephrology in the near future, which has forced the nephrology field to define its sustainability as a priority for this century. In order to face this issue, nephrologists need to recognize the dimension of the environmental footprint of their activities and what topics are associated with a bigger carbon footprint or resource consumption. Nephrologists should be in the center and the driving force for the changes needed.

ABSTRACT Introduction: Healthcare services have a significant environmental impact (EI). The increasing prevalence of chronic kidney disease makes nephrology one of the clinical areas with higher EI. The aim of this study was to document Portuguese nephrologists’ current practice regarding environmental sustainability. Methods: Two surveys were developed: one for chiefs of departments and another for all nephrologists registered in the Portuguese Society of Nephrology. Results: There were 153 responders (25.5% response rate): 17 (11%) were chiefs of departments, 36 (23.5%) nephrologists in coordination roles, 60 (39%) nephrologists and 40 (26%) nephrology fellows. The median priority attributed to environmental sustainability was 4 (IQR 3-5). Only one department had established a green group, but 13 were currently undertaking at least one green project (76.5%). Only 6% of responders (8/136) had received formal training on this topic, but more than 90% would like to have more information. The most reported barriers to environmental sustainability practices were inadequate information, lack of adequate facilities, concerns about security and legal norms. Only two facilities (11.8%) declared that environmental sustainability was considered in procurement decisions. More than 70% of the Units did not have regular access to any kind of environmental sustainability audit. Only 3 surveyed units (17.6%) have set up systems to reuse the reverse osmosis rejected water and only half had local on-line dialysate production (9/17, 53%). Conclusion: Portuguese nephrologists wish to incorporate environmental sustainability in their daily practice, however there is a big gap between their intention and current behavior, likely because of the identified barriers. Keywords: Environment; Medical Waste; Nephrology; Renal Dialysis

ABSTRACT Reports of spontaneous remissions in minimal change disease are rare and often associated with secondary causes. We report the case of a 47-year-old male patient with HIV-HBV/HDV co-infection and cirrhosis, admitted in the emergency department with nephrotic syndrome (hypoalbuminemia 1.2 g/dL and nephrotic range proteinuria 14 440 mg/g of creatinine). Ultrasound showed normal kidneys. Viral load for HIV, HBV, HDV and anti-HCV were negative. Immunologic and dysproteinemia study was normal and there were no signs of malignancy on body computer tomography scan. Abdominal fat pad biopsy was Congo red-stain negative. After initiating an angiotensin-converting enzyme inhibitor, the proteinuria decreased to 3891 mg/g. A kidney biopsy was scheduled, but the patient abandoned follow-up. Two years later, he presented again in anasarca, with mild elevation of transaminases, severe hypoalbuminemia (0.7 g/dL), acute kidney injury (creatinine 2.7 mg/dL) and heavy proteinuria (37 g/24 h). One month after the onset, when referred to a nephrologist, he was in complete remission. A year later, he presented a third episode of abrupt onset nephrotic syndrome. Kidney biopsy revealed minimal change disease. Corticosteroid therapy was withheld, and after one month the patient was again in complete remission. We hypothesize that, in the context of cirrhosis, the clearance of a putative permeability circulating factor may be diminished; hemodynamic changes in renal perfusion in decompensated chronic liver disease may interfere in the glomerular barrier function; and a genetic polymorphism related to podocyte dysfunction could precipitate a nephrotic syndrome that resolves once the liver function resumes its steady state. This case represents an unprecedented report of a minimal change disease in a cirrhotic patient, presenting with recurring episodes of nephrotic syndrome followed by early spontaneous remission.

Resumo Introdução: Danos tubulares são comuns em doenças glomerulares (DG). Glicosúria é um marcador de disfunção tubular e pode detectar lesão tubular e progressão da DRC. O objetivo deste estudo foi avaliar a prevalência e o valor prognóstico da glicosúria no diagnóstico em glomerulopatias primárias (GP). Métodos: Realizamos estudo retrospectivo de 24 meses em pacientes diagnosticados com GP em nosso centro entre 2009-2020. Excluímos pacientes diabéticos, uso de inibidores de SGLT2, pacientes transplantados e DG secundárias. Os pacientes dividiram-se em dois grupos de acordo com seu estado de glicosúria no diagnóstico. Resultados: Estudamos 115 pacientes. A prevalência global de glicosúria foi de 10% (n=11) e a nefropatia membranosa (NM) teve maior prevalência (n=5, 17,9%). Constatamos que pacientes com glicosúria apresentavam creatinina sérica mais elevada (2,4 vs. 1,2 mg/dL, p=0,030), albuminúria mais alta (4,8 vs. 1,9 g/g, p=0,004), e albumina sérica mais baixa (2,3 vs. 3,2 g/dL, p=0,021). Não encontramos associação com fatores prognósticos histológicos. Ao final do acompanhamento, pacientes com glicosúria tiveram maior prevalência do desfecho composto de DRC estágio 5D ou aumento de 50% na CrS basal (45,5% vs. 17,3%, p=0,037). Em pacientes com NM, os resultados foram semelhantes, mas encontramos uma associação de glicosúria com fibrose intersticial mais grave e atrofia tubular (25,0 vs. 0,0 %, p=0,032). Conclusão: 10% de nossos pacientes com GP têm glicosúria. A glicosúria no diagnóstico foi associada a uma apresentação clínica mais grave e pior desfecho renal. A associação com albuminúria mais elevada sugere que a função tubular tem um impacto na gravidade e nos desfechos da GP.

Abstract Introduction: Tubular damage is common in glomerular diseases (GD). Glycosuria is a marker of tubular dysfunction and may be used to detect tubular lesion and CKD progression. The aim of this study was to evaluate the prevalence and prognostic value of glycosuria at the time of diagnosis in primary glomerulopathies (PG). Methods: We conducted a 24-month retrospective study in patients diagnosed with PG in our center between 2009 and 2020. We excluded diabetic patients, use of SGLT2 inhibitors, transplant patients, and secondary GD. Patients were divided in two groups according to their glycosuria status at diagnosis. Results: We studied 115 patients. Global prevalence of glycosuria was 10% (n=11) and membranous nephropathy (MN) had the highest prevalence (n=5, 17.9%). We found that patients with glycosuria had higher serum creatinine (2.4 vs. 1.2 mg/dL, p=0.030), higher albuminuria (4.8 vs. 1.9 g/g, p=0.004), and lower serum albumin (2.3 vs. 3.2 g/dL, p=0.021). We did not find association with histological prognostic factors. At the end of follow-up, patients with glycosuria had higher prevalence of the composite outcome of stage 5D CKD or 50% increase in basal SCr (45.5% vs. 17.3%, p=0.037). In patients with MN, results were similar but we were able to find an association of glycosuria with more severe interstitial fibrosis and tubular atrophy (25.0 vs. 0.0 %, p=0.032). Conclusion: Ten percent of our patients with PG have glycosuria. Glycosuria at the time of diagnosis was associated with more severe clinical presentation and worst renal outcome. The association with higher albuminuria suggests that tubular function has an impact on the severity and outcomes of PG.

ABSTRACT Metabolic acidosis is a usual complication of progressive chronic kidney disease and is associated with morbidity and mortality. The correction of metabolic acidosis is a main goal of dialysis. In prevalent hemodialysis patients, acid-base homeostasis depends on many factors, mainly net acid production, amount of alkali given by the dialysate bath and duration of the interdialytic period. At present, the main concern in prevalent hemodialysis patients is not over patients with metabolic acidosis, but rather about the growing numbers of patients with metabolic alkalosis. Several large cohort studies have shown significant associations between high predialysis bicarbonate, as well as blood pH, and morbidity and mortality risk. Based on recent guidelines, we should keep predialysis serum bicarbonate concentrations at 24-26 mEq/L, although this is opinion-based and there is no consensus on the issue. Furthermore, there should be specific focus on the patient´s nutritional status and reversible comorbidities.

Stone formers have lower urinary magnesium than healthy people. Higher urinary magnesium levels are associated with lower incidence of kidney stones, and hypomagnesuria has been described as a lithogenic risk factor. Magnesium can have direct and indirect inhibitory effects on lithogenesis: decreasing the absorption of oxalates in the intestine; forming magnesium oxalate complexes which reduces the saturation of calcium oxalate; increasing the urinary citrate and inhibiting the conversion of the calcium oxalate in its monohydrated form. Oral supplementation with magnesium is an effective way to correct hypomagnesuria. However, oral magnesium supplementation in recurrent stone formers with hypomagnesuria is still a subject of ongoing debate, and physicians treating these patients underestimate its potential preventive effects. Oral magnesium supplementation can be used as an adjuvant therapy to the standard prophylactic therapy, mainly in association with an alkali salt. It is well tolerated and has few adverse effects.

RESUMO Introdução: Um débito de sangue de acesso arteriovenoso (AV) (Qa) de 400 mL/min é geralmente suficiente para uma hemodiálise (HD) eficaz, mas alguns acessos continuam se desenvolvendo e se tornam acessos de alto débito (AAD). Alguns autores postularam que um AAD poderia desviar uma porção significativa do sangue dialisado do débito cardíaco, o que poderia diminuir a eficiência da HD e levar à sobrecarga de volume. Objetivo: O objetivo do nosso estudo foi avaliar se o AAD está associado à redução da eficiência da HD e/ou à sobrecarga de volume em pacientes prevalentes em HD. Métodos: Foi realizado um estudo retrospectivo de 1 ano, e avaliada a eficiência da HD pela porcentagem de sessões em que o Kt/V > 1,4 e a sobrecarga de volume avaliada pela bioimpedância. Resultados: O estudo incluiu 304 pacientes prevalentes em HD, com média de idade de 67,5 anos; 62,5% eram do sexo masculino; 36,2% eram diabéticos, com uma mediana de tempo em HD de 48 meses. Dezesseis por cento dos pacientes apresentavam AAD (definida como Qa > 2 L/min). Na análise multivariada, os pacientes com AAD apresentaram maior risco de sobrecarga de volume (OR = 2,67; IC95% = 1,06-6,71) e sobrecarga severa de volume (OR = 4,06; IC95% = 1,01-16,39) e atingiram o peso seco com menor frequência (OR = 0,37, IC 95% = 0,14-0,94). No entanto, o AAD não foi associado uma menor razão Kt/V. Conclusão: Nossos resultados sugerem que pacientes com AAD apresentam maior risco de sobrecarga de volume. No entanto, ao contrário do que foi postulado, o AAD não foi associado à diálise menos eficiente, medida pelo Kt/V. Ensaios clínicos randomizados são necessários para esclarecer essas questões.

ABSTRACT Introduction: An arteriovenous (AV) access flow (Qa) of 400 mL/min is usually sufficient for an effective hemodialysis (HD), but some accesses continue developing and become high flow accesses (HFA). Some authors postulated that an HFA might shift a significant portion of dialyzed blood from the cardiac output, which could decrease HD efficiency and lead to volume overload. Objective: The aim of our study was to evaluate if HFA is associated with reduced HD efficiency and/or volume overload in prevalent HD patients. Methods: We performed a 1-year retrospective study and assessed HD efficiency by the percentage of sessions in which the Kt/V > 1.4 and volume overload by bioimpedance spectroscopy. Results: The study included 304 prevalent HD patients with a mean age of 67.5 years; 62.5% were males, 36.2% were diabetics, with a median HD vintage of 48 months. Sixteen percent of the patients had a HFA (defined as Qa > 2 L/min). In multivariate analysis, patients with HFA presented higher risk of volume overload (OR = 2.67, 95%CI = 1.06-6.71) and severe volume overload (OR = 4.06, 95%CI = 1.01-16.39) and attained dry weight less frequently (OR = 0.37, 95%CI = 0.14-0.94). However, HFA was not associated with lower Kt/V. Conclusion: Our results suggest that patients with HFA have higher risk of volume overload. However, contrarily to what has been postulated, HFA was not associated with less efficient dialysis, measured by Kt/V. Randomized controlled trials are needed to clarify these questions.

Abstract Background: Albuminuria was widely considered as the first clinical sign of diabetic kidney disease (DKD), which is why it has traditionally been used as a screening test for DKD. However, increasing evidence has shown that a significant number of type 2 diabetes mellitus (DM) patients have a decreased glomerular filtration rate (GFR) without significant albuminuria, known as non-albuminuric DKD (NA-DKD). The aim of this study was to determine the prevalence and the demographic and clinical characteristics of patients with NA-DKD. Methods: This was a 1-year retrospective study that included 146 type 2 diabetic patients with GFR < 75 mL/min followed-up in a diabetes outpatient department. Patients were divided into two groups according to their ACR status - NA-DKD and albuminuric DKD (A-DKD). Results: Of the 146 patients included in the study, 53.4% had A-DKD and 46.6% had NA-DKD. According to the multivariable analysis performed, patients with NA-DKD tended to be older (p = 0.021), female (p = 0.045) and with a lower GFR (p = 0.004) than A-DKD patients. There was no difference between the groups in terms of body mass index, metabolic control of DM, duration of DM diagnosis and prevalence of metabolic syndrome. Conclusions: The majority of patients with DKD had albuminuria, but a significant proportion had a non-albuminuric phenotype (46.6% in this population). These patients exhibit distinct clinical features that could have screening, therapeutic and prognosis implications.

Resumen Introducción: La albuminuria fue ampliamente considerada como el primer signo clínico de la enfermedad renal diabética (DKD), por lo que se ha utilizado tradicionalmente como prueba de detección para DKD. Sin embargo, el aumento de la evidencia ha demostrado que un número importante de pacientes con diabetes mellitus tipo 2 (DM) tenían disminución de la filtración glomerular (TFG), sin albuminuria significativa (DKD sin albuminuria (NA-DKD). El objetivo de este estudio fue determinar la prevalencia y las características demográficas y clínicas de los pacientes con NA-DKD. Métodos: Este fue un estudio retrospectivo de un año que incluyó a 146 diabéticos tipo 2 con TFG < 75 ml/min seguidos en el departamento de diabetes. Los pacientes fueron divididos en 2 grupos de acuerdo a su estado de ACR NA-DKD y DKD albuminúrica (A-DKD). Resultados: De los 146 pacientes incluidos en el estudio, 53,4% tienen A-DKD y 46,6% tienen a NA-DKD. En comparación con los pacientes con A-DKD, aquellos con NA-DKD eran más propensos a ser de mayor edad (p = 0,021), a ser mujeres (p = 0,045) y tenían una TFG menor (p = 0,004), datos confirmados en el análisis multivariante. El índice de masa corporal, el control metabólico de la DM, la duración del diagnóstico de DM y la prevalencia de síndrome metabólico no fueron diferentes entre los grupos. Conclusiones: La mayoría de los pacientes con DKD presentan albuminuria, pero una proporción significativa tiene un fenotipo de no albuminuria (46,6% en esta población). Estos pacientes presentan características clínicas diferentes, lo que podría tener relevancia en la proyección, el pronóstico o implicaciones terapéuticas.