Short- and mid- term impact of tobacco smoking on donor renal function following living kidney donation at a tertiary referral hospital

Background: The negative impact of tobacco smoking on renal function has been widely studied. However, there is limited knowledge about the effect of smoking on pre-operative and post-operative renal function in living kidney donors. Objective: The objective of the study was to evaluate the short- and mid-term impact of smoking on donor renal function. Methods: This is a retrospective study of 308 patients who underwent living donor nephrectomy (LDN) at a tertiary referral hospital. We compared baseline characteristics as well as functional outcomes following LDN according to history of tobacco smoking. Estimated glomerular filtration rate (eGFR) was calculated with the modification of diet in renal disease equation in 6 time periods: pre-operative, 1 week, 1 month, 6 months, 12 months, and 24 months after surgery. We performed a Kaplan-Meier analysis for chronic kidney disease (CKD) outcome and binary logistic regression analysis to identify risk factors associated with CKD at 24 months of follow-up. Results: Among donors, 106 (34.4%) reported a smoking history before nephrectomy. Smoking donors had worse pre-operative eGFR than non-smokers (90 ± 26.3 mL/min/1.73m2 vs. 96 ± 27 mL/min/1.73 m2, respectively; p = 0.02) and lower eGFR at 1 week (p = 0.01), 1 month (p ≤ 0.01), 6 months (p = 0.01), and 12 months (p = 0.01) after LDN. Tobacco smoking (OR 3.35, p ≤ 0.01) and age ≥ 40 years at donation (OR 6.59, p ≤ 0.01) were associated with post-operative development of CKD at 24 months after LDN. Conclusions: Living kidney donors with a tobacco smoking history had an increased risk of developing chronic kidney disease following nephrectomy. Smoking-cessation strategies should be implemented.

COVID-19 and Kidney: a narrative review / COVID-19 e os rins: uma revisão narrativa

Abstract COVID-19 is a pandemic associated with systemic clinical manifestations. In this study, we aimed to present a narrative review on kidney involvement in COVID-19. Kidney involvement could be derived from direct cytopathic effects, immunological mechanisms, indirect effects on renal tissue through other mediators, and dysfunction or injury of other organs. The evolution of COVID-19 may be complicated with acute kidney injury (AKI) in a significant percentage of patients, and renal dysfunction seems to be associated with worse prognosis. Patients with chronic kidney disease (CKD) seem to be more susceptible to the severe forms of COVID-19. Patients with renal replacement therapy (RRT) are also a vulnerable population as consequence of their advanced age, underlying comorbidities, impaired immune response, and clustering in hemodialysis centers, with requirements for frequent contact with healthcare services. Kidney transplant patients may be at high-risk due to long-term immunosuppression and comorbidities, hence, managing immunosuppression is imperative. Lastly, renal replacement therapy may be required during COVID-19, and different modalities are discussed based on clinical findings and laboratorial aspects. Therefore, COVID-19 seems to affect kidney by different mechanisms, which contributes for AKI development and increases the severity of the disease. Also, patients with CKD and kidney transplant recipients are at higher risk for COVID-19 and mortality.

Resumo COVID-19 é uma pandemia associada a manifestações clínicas sistêmicas. Neste estudo, apresenta-se revisão narrativa acerca do envolvimento renal na COVID-19. Envolvimento renal parece ser relacionado a efeitos citopáticos diretos, mecanismos imunológicos, efeitos indiretos de outros mediadores no tecido renal, além de disfunção e lesão de outros órgãos. A evolução da COVID-19 pode ser complicada por lesão renal aguda (LRA) em percentual significativo dos pacientes, e a disfunção renal parece ser associada a pior prognóstico. Pacientes com doença renal crônica (DRC) parecem ser mais suscetíveis a formas severas da COVID-19. Pacientes em terapia de substituição renal (TSR) contínua também constituem população vulnerável em razão de idade avançada, comorbidades subjacentes, resposta imune disfuncional e aglomeração em unidades de diálise, com necessidade de visitas frequentes aos serviços de saúde. Pacientes transplantados renais podem estar em alto risco dadas imunossupressão a longo prazo e comorbidades; assim, o manejo da imunossupressão é mandatório. Finalmente, TSR pode ser necessária durante a COVID-19, e diferentes modalidades são discutidas conforme manifestações clínicas e aspectos laboratoriais. Assim, COVID-19 parece acometer os rins por diferentes mecanismos, os quais contribuem para o desenvolvimento de LRA e aumento da severidade da doença. Ainda, pacientes com DRC e transplantados renais apresentam elevado risco para desenvolvimento de COVID-19 e de mortalidade.

El riñón del niño prematuro: riesgos a largo plazo / The kidney of the premature child: long-term risks

Resumen: El recién nacido prematuro se enfrenta a las condiciones extrauterinas con sistemas aún inmaduros, tanto anatómica como fisiológicamente. El riñón termina de desarrollarse a finales del tercer trimes tre del embarazo, por lo que está especialmente expuesto a alterar su desarrollo normal en caso de nacer en forma prematura. Esta situación puede condicionar, entre otras consecuencias, una menor masa renal funcional y cambios microvasculares que representan un riesgo elevado de hipertensión arterial y daño renal crónico en el largo plazo. En el presente artículo se analiza la evidencia existente actual sobre estos riesgos en los prematuros y se ofrece un esquema de seguimiento de estos niños desde el punto de vista nefrológico.

Abstract: The premature newborn faces extrauterine conditions with some systems still immature, both ana tomically and physiologically. The kidney finishes developing at the end of the third trimester of pregnancy, so it is especially exposed to alter its normal development if preterm birth occurs. This si tuation may condition, among other consequences, a lower functional renal mass and microvascular changes comprising a high risk of chronic kidney disease in the long term and arterial hypertension. This article analyzes the current evidence on these risks in premature infants and offers a nephrology follow-up scheme of these children.

Cardiometabolic risk factors associated with renal function in apparently healthy young students: a cross-sectional study

ABSTRACT Background: Cardiometabolic risk factors (CMRFs) appear decades before developing chronic kidney disease (CKD) in adulthood. Objective: The objective of the study was to identify the prevalence and association between CMRFs and kidney function in apparently healthy young adults (18-25 years old). Methods: We included 5531 freshman year students. Data collected on CMRFs included central obesity, high body mass index (hBMI >25), blood pressure, glycemia, lipids, uric acid (UA >6.8 mg/dL), and insulin. Glomerular filtration rate (GFR) was estimated by CKD-Epidemiology Collaboration formula. We used logistic regression and a log linear for odds ratio (OR) (95% confidence level) and probabilities. Results: The presence of any CMRF was observed in 78% (4312) of individuals; GFR ≥120/130 mL/min/1.73 m2sc was found in 33%, GFR <90 mL/min/1.73 m2sc in 3%, and proteinuria in 3%. Factors associated with high GFR were hBMI (OR 1.3 [1.14, 1.47]), UA (OR 0.2 [0.15, 0.26]), high-density lipoprotein (HDL) (OR 1.4 [1.2, 1.6]), and insulin resistance (OR 1.3 [1.05, 1.7]). CMRF associated with low GFR was UA (OR 1.8 [1.3, 2.6]), low-density lipoprotein cholesterol (OR 1.66 [1.05, 2.6]), and proteinuria (OR 3.4 [2.07, 5.7]). Proteinuria was associated with high UA (OR 1.59 [1.01, 2.5]) and hypercholesterolemia (OR 1.8 [1.03, 3.18]). The sole presence of hBMI+UA predicted low GFR with p = 0.6 and hBMI+UA+low HDL predicted proteinuria with p = 0.55. Conclusions: CMRFs were highly prevalent among this freshman student population and were associated with proteinuria and GFR abnormalities. Future studies should focus on public health programs to prevent or delay the development of CKD.

Estudo da morfologia e status oxidativo em rim de ratos com nefropatia isquêmica após tratamento com células-tronco mesenquimais de tecido adiposo / Study of morphology and oxidative status in kidney of rats with ischemic nephropathy after treatment with adipose tissue mesenchymal stem cells

A nefropatia isquêmica é uma doença renal crônica provocada pela redução do fluxo sanguíneo renal que pode progredir para a doença renal terminal, cujo tratamentos disponíveis se baseiam em terapias substitutivas da função renal, como diálise ou transplante renal. No entanto, devido ao alto custo dos tratamentos e a carência de órgãos, se faz necessária a busca por novas terapias, como as células-tronco (CT). Apesar do potencial terapêutico das CT em doenças crônicas, não está claro se essas células mantêm seus efeitos benéficos em órgãos lesionados por tempo prolongado. O objetivo desse estudo foi avaliar os efeitos precoces e tardios do tratamento com células-tronco adiposas (CTA) sobre a morfologia e o status oxidativo em rins de ratos com nefropatia isquêmica. A isquemia renal foi induzida pelo modelo 2rins-1clip (2R1C) e, depois de um mês da clipagem da artéria renal, foram injetadas 106 células-tronco na região subscapsular do rim afetado. Após 15 e 30 dias da injeção das CTA, a morfologia renal foi verificada por meio da análise macroscópica, microscópica e ultraestrutural. Além disso, o status oxidativo foi avaliado no tecido renal através da mensuração da atividade das enzimas antioxidantes catalase e glutationa peroxidase; e de marcadores biológicos de dano oxidativo, como proteínas carboniladas, 3-Nitrotirosina e 4-Hidroxinonenal. Por imunoperoxidase foi possível localizar as células-tronco adiposas GFP+ foram rastreadas e encontradas tanto 15 dias, quanto 30 dias após a injeção na região subcapsular. A restauração da arquitetura renal foi evidenciada 15d após o uso das células, onde detectamos redução na deposição de fibras colágenas no parênquima renal, o que não foi observado 30d após o uso das células. Os resultados também foram confirmados através da análise da ultraestrutura renal que mostraram restauração da arquitetura renal no grupo de 15d, não evidenciada no grupo de 30d. Quanto a análise do status oxidativo, somente os animais com nefropatia isquêmica mais prolongada apresentaram estresse oxidativo com redução da atividade da enzima antioxidante catalase no tecido renal. Além disso, foi observado dano proteico e lipídico, sem melhora dessa condição nos animais 30d após o tratamento com as células-tronco. No modelo de nefropatia isquêmica avaliado, o tratamento com CTA mostrou benefícios na morfologia renal a curto prazo, mas não tardiamente, apesar da permanência dessas células no tecido. Acreditamos que o estresse oxidativo, evidenciado somente no tecido renal com isquemia mais prolongada, possa ter dificultado a ação das células-tronco, contribuindo para tais achados. Esses resultados abrem perspectivas para o aprofundamento do estudo quanto à caracterização dos mecanimos de ação das CTA nas respostas anti-fibrogênicas, assim como o estabelecimento do número, frequência, vias de administração e melhor momento para uso dessas células no tratamento de doenças renais crônicas.

Ischemic nephropathy is a chronic kidney disease caused by reduced kidney blood flow that can progress to end stage kidney disease, whose available treatments are based on kidney function replacement therapies, such as dialysis or kidney transplantation. However, due to the high cost of treatments and the lack of organs, it is necessary to search for new therapies, such as stem cells (SC). Despite the therapeutic potential of SC in chronic diseases, it is unclear whether these cells maintain their beneficial effects on injured organs for a long time. The aim of this study was to evaluate the early and late effects of adipose-derived stem cells (ADSC) treatment on the morphology and oxidative status in kidneys of rats with ischemic nephropathy. Renal ischemia was induced by the 2kidneys-1clip (2K1C) model and, after a month of clipping the renal artery, 106 stem cells were injected into the subscapsular region of the affected kidney. After 15 and 30 days of ADSC injection, renal morphology was verified by macroscopic, microscopic, and ultrastructural analysis. In addition, oxidative status was assessed in renal tissue by measuring the activity of the antioxidant enzymes catalase and glutathione peroxidase; and biological markers of oxidative damage, such as carbonylated proteins, 3-nitrotyrosine and 4-hydroxynonenal. By immunoperoxidase, it was possible to locate GFP + adipose-derived stem cells that were tracked and found both 15 days and 30 days after injection in the subcapsular region. The restoration of the renal architecture was evidenced 15d after the use of the cells, where we detected a reduction in the deposition of collagen fibers in the renal parenchyma, which was not observed 30d after the use of the cells. The results were also confirmed by analyzing the renal ultrastructure, which showed restoration of the renal architecture in the 15d group, not evidenced in the 30d group. Regarding the analysis of oxidative status, only animals with more prolonged ischemic nephropathy presented oxidative stress with reduced activity of the antioxidant enzyme catalase in renal tissue. In addition, protein and lipid damage was observed, with no improvement in this condition in the animals 30d after treatment with stem cells. In the evaluated ischemic nephropathy model, treatment with ADSC showed benefits in renal morphology in the short term, but not late, despite the permanence of these cells in the tissue. We believe that oxidative stress, evidenced only in renal tissue with more prolonged ischemia, may have hindered the action of stem cells, contributing to such findings. These results open perspectives for further study on the characterization of ADSC mechanisms of action in anti-fibrogenic responses, as well as the establishment of the number, frequency, routes of administration and the best time to use these cells in the treatment of chronic kidney diseases.

SGLT-2 inhibitors in diabetes: a focus on renoprotection

SUMMARY Type 2 diabetes mellitus is an important public health problem, with a significant impact on cardiovascular morbidity and mortality and an important risk factor for chronic kidney disease. Various hypoglycemic therapies have proved to be beneficial to clinical outcomes, while others have failed to provide an improvement in cardiovascular and renal failure, only reducing blood glucose levels. Recently, sodium-glucose cotransporter-2 (SGLT2) inhibitors, represented by the empagliflozin, dapagliflozin, and canagliflozin, have been showing satisfactory and strong results in several clinical trials, especially regarding the reduction of cardiovascular mortality, reduction of hospitalization due to heart failure, reduction of albuminuria, and long-term maintenance of the glomerular filtration rate. The benefit from SGLT2 inhibitors stems from its main mechanism of action, which occurs in the proximal tubule of the nephron, causing glycosuria, and a consequent increase in natriuresis. This leads to increased sodium intake by the juxtaglomerular apparatus, activating the tubule glomerular-feedback and, finally, reducing intraglomerular hypertension, a frequent physiopathological condition in kidney disease caused by diabetes. In addition, this class of medication presents an appropriate safety profile, and its most frequently reported complication is an increase in the incidence of genital infections. Thus, these hypoglycemic agents gained space in practical recommendations for the management of type 2 diabetes mellitus and should be part of the initial therapeutic approach to provide, in addition to glycemic control, cardiovascular outcomes, and the renoprotection in the long term.

Metabolic and volume status evaluation of hemodialysis patients with and without residual renal function in the long interdialytic interval / Avaliação metabólica e volêmica no maior intervalo interdialítico de pacientes em hemodiálise com e sem função renal residual

Abstract Introduction: It is unclear whether residual renal function (RRF) in dialysis patients can attenuate the metabolic impact of the long 68-hour interdialytic interval, in which water, acid, and electrolyte accumulation occurs. Objective: to evaluate serum electrolyte levels, water balance, and acid-base status in dialytic patients with and without RRF over the long interdialytic interval (LII). Methodology: this was a single-center, cross-sectional, and analytical study that compared patients with and without RRF, defined by diuresis above 200 mL in 24 hours. Patients were weighed and serum samples were collected for biochemical and gasometric analysis at the beginning and at the end of the LII. Results: 27 and 24 patients with and without RRF were evaluated, respectively. Patients without RRF had a higher increase in serum potassium during the LII (2.67 x 1.14 mEq/L, p < 0.001), reaching higher values at the end of the study (6.8 x 5.72 mEq/L, p < 0.001) and lower pH value at the beginning of the interval (7.40 x 7.43, p = 0.018). More patients with serum bicarbonate < 18 mEq/L (50 x 14.8%, p = 0.007) and mixed acid-base disorder (57.7 x 29.2%, p = 0.042), as well as greater interdialytic weight gain (14.67 x 8.87 mL/kg/h, p < 0.001) and lower natremia (137 x 139 mEq/L, p = 0.02) at the end of the interval. Calcemia and phosphatemia were not different between the groups. Conclusion: Patients with RRF had better control of serum potassium, sodium, acid-base status, and volemia throughout the LII.

Resumo Introdução: Não se sabe ao certo se a função renal residual (FRR) de pacientes dialíticos pode atenuar o impacto metabólico do maior intervalo interdialítico (MII) de 68 horas, no qual ocorre acúmulo de volume, ácidos e eletrólitos. Objetivo: Avaliar os níveis séricos de eletrólitos, balanço hídrico e status ácido-básico de pacientes dialíticos com e sem FRR ao longo do MII. Metodologia: Tratou-se de estudo unicêntrico, transversal e analítico, que comparou pacientes com e sem FRR, definida como diurese acima de 200 mL em 24 horas. Para tal, os pacientes foram pesados e submetidos à coleta de amostras séricas para análise bioquímica e gasométrica no início e fim do MII. Resultados: Foram avaliados 27 e 24 pacientes com e sem FRR, respectivamente. Pacientes sem FRR apresentaram maior aumento de potássio sérico durante o MII (2,67 x 1,14 mEq/L, p < 0,001) atingindo valores mais elevados no fim (6,8 x 5,72 mEq/L, p < 0,001); menor valor de pH no início do intervalo (7,40 x 7,43, p = 0,018), maior proporção de pacientes com bicarbonato sérico < 18 mEq/L (50 x 14,8 %, p = 0,007) e distúrbio ácido-básico misto (70,8 x 42,3 %, p = 0,042), além de maior ganho de peso interdialítico (14,67 x 8,87 mL/kg/h, p < 0,001) e menor natremia (137 x 139 mEq/L, p = 0,02) no fim do intervalo. A calcemia e fosfatemia não foram diferentes entre os grupos. Conclusão: Pacientes com FRR apresentaram melhor controle dos níveis séricos de potássio, sódio, status ácido-básico e da volemia ao longo do MII.

Antioxidant effect of endothelin-1 receptor antagonist protects the rat kidney against chronic injury induced by hypertension and hyperglycemia / Efeito antioxidante de antagonista dos receptores de endotelina-1 protege ratos contra lesão renal crônica induzida por hipertensão e hiperglicemia

ABSTRACT Hypertension and Diabetes mellitus are the two main causes of chronic kidney disease that culminate in the final stage of kidney disease. Since these two risk factors are common and can overlap, new approaches to prevent or treat them are needed. Macitentan (MAC) is a new non-selective antagonist of the endothelin-1 (ET-1) receptor. This study aimed to evaluate the effect of chronic blockade of ET-1 receptor with MAC on the alteration of renal function observed in hypertensive and hyperglycemic animals. Genetically hypertensive rats were divided into control hypertensive (HT-CTL) group, hypertensive and hyperglycemic (HT+DIAB) group, and hypertensive and hyperglycemic group that received 25 mg/kg macitentan (HT-DIAB+MAC25) via gavage for 60 days. Kidney function and parameters associated with oxidative and nitrosative stress were evaluated. Immunohistochemistry for neutrophil gelatinase-associated lipocalin (NGAL), ET-1, and catalase in the renal cortex was performed. The HT+DIAB group showed a decrease in kidney function and an increase in NGAL expression in the renal cortex, as well as an increase in oxidative stress. MAC treatment was associated with attenuated ET-1 and NGAL production and increases in antioxidant defense (catalase expression) and nitric oxide production. In addition, MAC prevented an increase in oxidant injury (as measured by urinary hydroperoxide and lipid peroxidation), thus improving renal function. Our results suggest that the antioxidant effect of the ET-1 receptor antagonist MAC is involved in the improvement of kidney function observed in hypertensive and hyperglycemic rats.

RESUMO Hipertensão e Diabetes Mellitus figuram como as duas principais causas de doença renal crônica que culmina em doença renal terminal. Uma vez que os dois fatores de risco são comuns e podem se sobrepor, novas abordagens preventivas e terapêuticas se fazem necessárias. O macitentan (MAC) é um novo antagonista não-seletivo dos receptores da endotelina-1 (ET-1). O presente estudo teve como objetivo avaliar os efeitos do bloqueio crônico dos receptores da ET-1 com MAC sobre a alteração da função renal em animais hipertensos e hiperglicêmicos. Ratos geneticamente hipertensos foram divididos em grupos com animais hipertensos de controle (HT-CTL), hipertensos e hiperglicêmicos (HT+DIAB) e hipertensos e hiperglicêmicos tratados com 25 mg/kg de macitentan (HT-DIAB+MAC25) via gavagem por 60 dias. Foram avaliados função renal e parâmetros associados ao estresse oxidativo e nitrosativo. Exames de imunoistoquímica foram realizados para lipocalina associada à gelatinase neutrofílica (NGAL), ET-1 e catalase no córtex renal. O grupo HT+DIAB exibiu diminuição da função renal e aumento na expressão de NGAL no córtex renal, bem como estresse oxidativo aumentado. O tratamento com MAC foi associado a atenuação da produção de ET-1 e NGAL e maior ativação das defesas antioxidantes (expressão de catalase) e elevação da produção de óxido nítrico. Além disso, o MAC evitou exacerbação da lesão oxidante (medida por hidroperóxidos urinários e peroxidação lipídica), melhorando assim a função renal. Nossos resultados sugerem que o efeito antioxidante do antagonista dos receptores da ET-1 MAC esteja imbricado no aprimoramento da função renal observada em ratos hipertensos e hiperglicêmicos.

Trastornos glomerulares en la práctica médica / Glomerulopathies in the medical practice

RESUMEN Las glomerulopatías agrupan varias nefropatías con lesiones fundamentalmente del corpúsculo renal y que se expresan principalmente por proteinuria, hematuria, edemas e hipertensión arterial. La presentación clínica varía en dependencia del tipo de enfermedad de que se trate. Constituye la causa más frecuente de enfermedad renal crónica en adultos jóvenes, por lo que su estudio resulta imprescindible sobre todo para el nivel primario de salud. El propósito fue actualizar consideraciones pertinentes sobre la conducta diagnóstica y terapéutica integral ante una glomerulopatía y valorar emisión de recomendaciones al respecto. Se realizó una búsqueda, análisis y síntesis de información a través de Bases de datos ScieLO Cuba, ScieLO regional, Pubmed, Cumed, Clinical Key en el período 2012-2017 con las palabras clave: síndrome nefrótico, glomerulonefritis, diagnóstico, terapéutica, atención integral. El abordaje en las glomerulopatías es integral, multidisciplinario e individualizado. En Cuba constituyen la cuarta causa de enfermedad renal crónica y predomina el síndrome nefrítico agudo postinfeccioso. El método clínico juega en ello un papel trascendental a la hora de reconocer y registrar sus aspectos clínicos, su etiología, su fisiopatología, y los exámenes complementarios que confirman su presencia o sus complicaciones, así como un tratamiento oportuno que garanticen el perfeccionamiento asistencial. El arma más poderosa ante el reto de los trastornos glomerulares es la visión integradora y con enfoque individual y social protagonizado por el médico ante este grupo de nefropatías en adultos.

ABSTRACT Glomerulopathies encompass a group of several renal disorders with lesions, mainly in the renal corpuscle, expressed in proteinuria, hematuria, edemas and arterial hypertension. Their clinical manifestations change in dependence of the kind of disease. They are the most frequent cause of chronic renal disease in young adults; therefore their study is very important above all in the health care primary level. The aim was updating pertinent considerations on the diagnostic behavior and comprehensive therapy in the case of glomerulopathy, and evaluating the emission of recommendations regarding to them. A search, analysis and synthesis of information was carried out in the databases ScieLO Cuba, ScieLO regional, Pubmed, Cumed, and Clinical Key in the period 2012-2017, using the key words nephrotic syndrome, glomerulonephritis, diagnosis, therapeutics, comprehensive care. The approach to glomerulopathies is comprehensive, multidisciplinary and individualized. They are the fourth cause of chronic renal disease; the acute post-infectious nephritic syndrome predominates. The clinical method plays a transcendental role at the moment of recognizing and registering their clinical characteristics, etiology and physiopathology, while complementary tests confirm their presence or complications, and therefore an opportune treatment guarantying the healthcare improvement. The most powerful weapon against the challenge of the glomerular disorders is the integrated vision with an individual and social approach led by the physician in the case of these nephropathies in adults.

The preoperative stratification of patients based on renal scan data is unable to predict the functional outcome after partial nephrectomy

ABSTRACT Introduction: eGFR-categories are used to predict functional outcome after partial nephrectomy (PN); no study categorized patients according to preoperative renal scan (RS) data. Aim of the study was to evaluate if stratification of patients according to RS is a reliable method to predict minor/major loss of renal function after PN. Materials and Methods: We considered patients who underwent PN and RS pre-/post-PN for T1 tumor in our Institution (2007-2017). Demographics, perioperative and specifically functional data were analysed. On the basis of the baseline Split Renal Function (SRF), patients were stratified into risk-categories: 1) baseline operated-kidney SRF range 45-55%; 2) baseline operated-kidney SRF <45%. Risk categories were analysed with postoperative functional outcome: postoperative operated-kidney SRF decrease below 90% of baseline was considered significant loss of function. Contingency tables and univariate/multivariate regression were analysed looking for independent factors of postoperative functional impairment. Results: 224 patients were analysed, 125 (55.8%) maintained >90% of their baseline function. Worse probability of maintaining ≥90 baseline renal function was found in patients with Charlson's Comorbidity Index (CCI≥3) (p=0.004) and patients with PADUA score ≥8 (p=0.023). After stratification by baseline renal function, ischemia was the only independent factor: no effect on patients with poorer baseline renal function. Patients with baseline SRF 45-55% who did not experience ischemia had the highest probability to maintain ≥90% baseline SRF (p=0.028). Ischemia >25 minutes was detrimental (p=0.017). Conclusions: Stratification of patients by SRF before PN is not a reliable predictor of renal functional outcome. Ischemia seems to scarcely influence patients with poorer renal function.

Marcadores de daño renal en pacientes con factores de riesgo de enfermedad renal crónica / Markers of renal damage in patients with risk factors of chronic renal disease

Se efectuó un estudio descriptivo y transversal de 46 pacientes con más de 18 años de edad, pertenecientes al consultorio 34 del área de salud del municipio de Majagua, provincia Ciego de Ávila, desde septiembre de 2015 hasta febrero de 2016. A todos los integrantes de la serie se les indicaron exámenes complementarios, tales como microalbuminuria, filtrado glomerular, creatinina, conteo de Addis y urea. No se realizaron estudios imagenológicos debido a la lejanía, las dificultades con el transporte y el equipo de ultrasonografía. La alteración de los marcadores renales estuvo presente en la mitad de los afectados con factores de riesgo, lo cual permitió detectar la enfermedad renal crónica de manera precoz en ese grupo poblacional

A descriptive and cross-sectional study of 46 patients older than 18 years, belonging to the doctor's office 34 of the health area in Majagua, Ciego de Ávila, was carried out from September, 2015 to February, 2016. The complementary tests were indicated to all the members of the series, such as microalbuminuria, glomerular filtration rate, creatinine, Addis and urea counts . The imagenologic studies were not carried out due to the long distance, difficulties with the transportation and the ultrasonography equipment. The disorder of renal markers was present in half of those affected patients with risk factors, which allowed to detect earlier the chronic renal disease in that population group

Interaction of Gender and Hepatitis C in Risk of Chronic Renal Failure After Liver Transplantation

ABSTRACT Background. Chronic renal failure (CRF) is a significant cause of morbidity and mortality in post-liver transplantation (LT) recipients. The risk factors associated with the development of renal dysfunction are not clearly elucidated. Objectives. To examine the risk factors in the development of CRF in these patients. Material and methods. Retrospective case-cohort of liver transplant patients without baseline kidney dysfunction who developed chronic renal failure during their follow-up. Results. Of 370 patients, 254 met the inclusion criteria. 30% (76) of these patients had CRF of which 57% (43) were male. Age, estimated glomerular filtration rate (eGFR) at discharge, and HCV infection were found to be risk factors for CRF post-LT. The odds ratio of developing CRF was 1.4 (0.6-3.3) in males with HCV, 1.6 (0.7-3.9) in females without HCV and 4.4 (1.5-13.2) among females with HCV when compared to men without HCV. Conclusions. In this cohort of LT receipients of a major Canadian city, age, eGFR, and HCV infection were risk factors for CRF. Female gender and HCV increased this odds by a factor of more than 4.

When kidneys get old: an essay on nephro-geriatrics / Quando os rins envelhecem: um ensaio em nefro-geriatria

Abstract Aging is a nearly universal phenomenon in biology only partially controlled by genetic endowment. Individuals and their organs age at varying rates. The kidneys manifest the aging process by steady loss of nephrons and a corresponding decrease in glomerular filtration rate (GFR) beginning about age 30 years. The mechanisms responsible for this observation is are elusive. However, defining chronic kidney disease based on arbitrary, fixed thresholds of GFR in the later phases of life can be problematical as it may over-diagnosis CKD in the elderly. A modest, persisting reduction of GFR (around 45-59 ml/min/1.73m2) without abnormal proteinuria does not seem to confer much of an adverse effect on mortality and remaining life expectancy in older adults and the development of end-stage renal disease in such subjects is very uncommon. Old kidneys should not be equated with "diseased" kidneys.

Resumo O envelhecimento é um fenômeno quase universal na biologia, apenas parcialmente controlado pela dotação genética. Os indivíduos e seus órgãos envelhecem em taxas variáveis. Os rins manifestam o processo de envelhecimento por perda constante de néfrons e uma diminuição correspondente na taxa de filtração glomerular (TFG) a partir dos 30 anos. Os mecanismos responsáveis por essa observação são elusivos. No entanto, a definição de doença renal crônica com base em limiares arbitrários e fixos de TFG nas últimas fases da vida pode ser problemática, pois pode levar a um excessivo diagnóstico de DRC em idosos. Uma modesta e persistente redução da TFG (cerca de 45-59 ml/min/1,73 m2) sem proteinúria anormal não parece conferir grande parte do efeito adverso sobre a mortalidade e expectativa de vida remanescente em adultos mais velhos; e o desenvolvimento de doença renal em fase terminal em tais indivíduos é muito incomum. Rins mais velhos não devem ser equiparados a rins "doentes".

Conversion to Mycophenolate Mofetil Monotherapy in Liver Recipients: Calcineurin Inhibitor Levels are Key

Abstract: The use of calcineurin inhibitors (CNI) after liver transplantation is associated with post-transplant nephrotoxicity. Conversion to mycophenolate mofetil (MMF) monotherapy improves renal function, but is related to graft rejection in some recipients. Our aim was to identify variables associated with rejection after conversion to MMF monotherapy. Conversion was attempted in 40 liver transplant recipients. Clinical variables were determined and peripheral mononuclear blood cells were immunophenotyped during a 12-month follow- up. Conversion was classified as successful (SC) if rejection did not occur during the follow-up. MMF conversion was successful with 28 patients (70%) and was associated with higher glomerular filtration rates at the end of study. It also correlated with increased time elapsed since transplantation, low baseline CNI levels (Tacrolimus ≤ 6.5 ng/mL or Cyclosporine ≤ 635 ng/mL) and lower frequency of tacrolimus use. The only clinical variable independently related to SC in multivariate analysis was low baseline CNI levels (p = 0.02, OR: 6.93, 95%, CI: 1.3-29.7). Mean baseline fluorescent intensity of FOXP3+ T cells was significantly higher among recipients with SC. In conclusion, this study suggests that baseline CNI levels can be used to identify recipients with higher probability of SC to MMF monotherapy. Clinicaltrials.gov identification: NCT01321112.

Association Between Hepatitis B Virus and Chronic Kidney Disease: a Systematic Review and Meta-analysis

Abstract: Background. Hepatitis B virus infection and chronic kidney disease are prevalent and remain a major public health problem worldwide. It remains unclear how infection with hepatitis B virus impacts on the development and progression of chronic kidney disease. Aim. To evaluate the effect of infection with HBV on the risk of chronic kidney disease in the general population. Material and methods. We conducted a systematic review of the published medical literature to determine if hepatitis B infection is associated with increased likelihood of chronic kidney disease. We used the random effects model of DerSimonian and Laird to generate a summary estimate of the relative risk for chronic kidney disease (defined by reduced glomerular filtration rate and/or detectable proteinuria) with hepatitis B virus across the published studies. Meta-regression and stratified analysis were also conducted. Results. We identified 16 studies (n = 394,664 patients) and separate meta-analyses were performed according to the outcome. The subset of longitudinal studies addressing ESRD (n = 2; n = 91,656) gave a pooled aHR 3.87 (95% CI, 1.48; 6.25, P < 0.0001) among HBV-infected patients and no heterogeneity was recorded. In meta-regression, we noted the impact of male (P = 0.006) and duration of follow-up (P = 0.007) upon the adjusted hazard ratio of incidence of chronic kidney disease (including end-stage renal disease). No relationship occurred between HBV positive status and prevalent chronic disease (n = 7, n = 109,889 unique patients); adjusted odds ratio, were 1.07 (95% CI, 0.89; 1.25) and 0.93 (95% CI, 0.76; 1.10), respectively. Conclusions. HBV infection is possibly associated with a risk of developing reduced glomerular filtration rate in the general population; no link between HBV sero-positive status and frequency of chronic kidney disease or proteinuria was noted in cross-sectional surveys.

Hypercalcemia and renal function impairment associated with vitamin D toxicity: case report / Hipercalcemia e prejuízo de função renal associados à intoxicação por vitamina D: relato de caso

Abstract Nowadays vitamin D (25-OHD) deficiency is supposed to be a global epidemic condition. Expectedly, vitamin D measurement and intake exponentially increased in Brazil in this decade. Although the benefit of vitamin D to general health is still in debate, its indiscriminate use potentially may lead to enhance the incidence of vitamin D intoxication, which is considered a rare disorder. We report a case of a 70 year old diabetic male with chronic renal disease (blood creatinine of 1.6 mg/dL) who progressed suddenly to acute kidney injury (blood creatinine of 5.7 mg/dL) associated with hypercalcemia and high blood levels of vitamin D. Vitamin D and calcitriol were discontinued and hypercalcemia was managed by hydration followed by furosemide. Thereafter, disodium pamidronate was administered and the patient did not undergo on dialysis. It took approximately 14 months to normalize 25-OHD levels and blood creatinine returned to basal levels only after 24 months. The indicated labeling dosage was 2000 IU, but most likely the vitamin D manipulated preparation was higher as the vitamin D blood levels were very high. Although rare, vitamin D intoxication is becoming more frequent as the patients use frequently manipulated preparations that could be subject to errors in the manufacturing and labeling of the tablets or capsules. The present report alerts to the potential increase in the incidence of severe vitamin D intoxication due to the frequent use of this secosteroid as a nutritional supplement. At the same time, it is necessary to improve regulation on the nutrient supplement market.

Resumo Atualmente, muitos brasileiros têm utilizado vitamina D (25-OHD) como suplemento vitamínico para prevenção de diversas doenças crônicas, apesar da falta de dados científicos consistentes sobre o papel deste secosteroide na prevenção de doenças que não as do metabolismo mineral. A intoxicação por vitamina D é rara, mas devido ao seu uso indiscriminado tem ocorrido com maior frequência. Nesse relato, um homem diabético de 70 anos de idade com doença renal crônica (creatinina sérica de 1,6 mg/dL) passou a fazer uso de colecalciferol e calcitriol para recomposição dos níveis de 25-OHD, que eram de 16 ng/mL. O mesmo desenvolveu quadro de lesão renal aguda (creatinina = 5,7 mg/dL), após 45 dias. Este processo emergiu em paralelo ao surgimento de hipercalcemia e níveis circulantes elevados de vitamina D. Foram suspensas a administração de vitamina D e calcitriol, a hipercalcemia foi tratada com hidratação endovenosa, seguida de diurético de alça e posteriormente pamidronato. O paciente, que havia sido encaminhado para diálise, não necessitou desse tratamento. Os níveis de 25-OHD voltaram ao normal 14 meses após a sua suspensão, e os níveis de creatinina voltaram aos patamares anteriores 24 meses após esse evento. A dose prescrita de vitamina D correspondeu a 2000 UI/dia, a qual não é considerada inadequada segundo recomendações atuais. Existe, no entanto, na literatura controvérsia quanto à sensibilidade individual à vitamina D. Não pode ser descartado o uso inapropriado pelo paciente e nem eventual erro de manipulação. Embora raro, o quadro de intoxicação por vitamina D é grave e potencialmente pode levar a complicações clínicas irreversíveis.

Characterization of an experimental model of progressive renal disease in rats

ABSTRACT PURPOSE: To characterize an experimental model of progressive renal disease induced by different degrees of nephrectomy in rats. METHODS: Eighty male Wistar rats were divided into four experimental groups (n=20/group): sham surgery (control group), progressive degrees of nephrectomy leading to mild uremia (group 1), moderate uremia (group 2) and severe uremia (group 3). Ten animals of each group were followed for two or four weeks. At the end, blood and 24-hour urine samples were collected to determine renal function parameters. Urine output and water and food intake were daily monitored. RESULTS: In rats of group 1, serum levels of creatinine and urea and microalbuminuria were increased, while reduced creatinine clearance (p<0.05, compared with control group), without changing blood pressure. Animals of group 2 had more accentuated alterations: increases in urinary output, blood pressure, serum concentrations of urea, creatinine, sodium, potassium, and in microalbuminuria, and reduction of creatinine clearance (p<0.05). Group 3 exhibited even more increased serum concentrations of urea, creatinine, sodium and potassium, blood pressure and microalbuminuria, and decreased creatinine clearance (p<0.05) in comparison with control group and unilateral nephrectomy. CONCLUSION: Progressive nephrectomy in rats seems to be useful to study the physiopathology of chronic kidney disease and its mechanisms of progression.

Prevalence and management of anemia in pre-dialysis Malaysian patients: A hospital-based study / Anemia em pacientes pré-diálise: prevalência, gravidade, manejo

Summary Objective: Anemia, a common complication of chronic kidney diseases (CKD), is involved in significant cardiovascular morbidity. Therefore, the objective of our study was to investigate the prevalence and severity of anemia in pre-dialysis patients, as well as to determine the predictors of anti-anemic therapy. Method: A retrospective, observational study was conducted on adult pre-dialysis patients receiving treatment at the Hospital Universiti Sains Malaysia from January 2009 to December 2013. Results: A total of 615 eligible cases were included. The mean age of patients was 64.1±12.0 years. The prevalence of anemia was 75.8%, and the severity of anemia was mild in 47.7% of the patients, moderate in 32.2%, and severe in 20%. Based on morphological classification of anemia, 76.9% of our patients had normochromic-normocytic anemia whereas 21.8 and 1.3% had hypochromic-microcytic anemia and macrocytic anemia, respectively. Oral iron supplements were prescribed to 38.0% of the patients and none of the patients was given erythropoietin stabilizing agents (ESA) or intravenous iron preparations. In logistic regression, significant predictors of anti-anemic preparation use were decreased hemoglobin and hematocrit, and advanced stages of CKD. Conclusion: The results of the present study suggest that the prevalence of anemia in pre-dialysis patients is higher than currently accepted and it is found to be correlated with renal function; prevalence increases with declined renal function. An earlier identification as well as appropriate management of anemia will not only have a positive impact on quality of life but also reduce hospitalizations of CKD patients due to cardiovascular events.

Resumo Objetivo: anemia é uma complicação comum de doenças renais crônicas (DRC) e está significativamente envolvida na morbidade cardiovascular. O objetivo de nosso estudo foi investigar a prevalência e a gravidade da anemia em pacientes adultos pré-diálise, bem como determinar fatores preditores da terapia antianêmica. Método: estudo retrospectivo observacional foi realizado em pacientes pré-diálise adultos que recebiam tratamento no Hospital Universiti Sains Malaysia de janeiro de 2009 a dezembro de 2013. Resultados: ao todo, 615 casos elegíveis foram incluídos. A idade média dos pacientes foi de 64,1±12,0 anos. A prevalência de anemia foi de 75,8%, e a gravidade da anemia foi considerada leve em 47,7%, moderada em 32,2% e grave em 20% dos pacientes. Com base nas características morfológicas da anemia, os pacientes foram classificados em anemia normocrômica normocítica (76,9%), anemia hipocrômica microcítica (21,8%) e anemia macrocítica (1,3%). Suplementos de ferro oral foram prescritos para 38% dos pacientes e a nenhum dos pacientes foram dados eritropoietina, agentes estabilizadores (ESA) e preparações de ferro por via intravenosa. Na regressão logística, os preditores significativos de utilização da preparação antianêmica foram diminuição da hemoglobina e do hematócrito e estágios avançados da DRC. Conclusão: os resultados do presente estudo sugerem que a prevalência de anemia em pacientes pré-diálise é maior do que o atualmente aceito e está associado com a função renal; a prevalência aumenta com a diminuição da função renal. A identificação precoce e o manejo adequado da anemia não só terão um impacto positivo na qualidade de vida, mas também reduzirão internações de pacientes com DRC decorrentes de eventos cardiovasculares.

Um caso de recuperação da função renal na síndrome hemolítico-urêmica tratada com eculizumab / A case of renal recovery in atypical hemolytic uremic syndrome treated with eculizumab

Resumo A síndrome hemolítico-urêmica atípica (SHUa) é uma doença grave, pouco prevalente, com acometimento em qualquer idade e apresentação esporádica ou familiar. A SHUa é causada por uma ativação descontrolada do sistema complemento. A plasmaférese foi o tratamento padronizado por anos, com resultados desfavoráveis, levando à doença renal crônica terminal ou morte em aproximadamente 40% dos pacientes durante as primeiras manifestações clínicas. O Eculizumab é um anticorpo monoclonal humanizado contra o componente C5 do complemento e nos últimos anos vem sendo utilizado como novo arsenal terapêutico com resultados promissores. O presente caso descreve uma paciente adulta tratada com eculizumab em que se obteve resultados satisfatórios evitando-se potenciais riscos e aumento da morbidade com o procedimento de plasmaférese.

ABSTRACT Atypical Hemolytic Uremic Syndrome (aHUS) is a rare, life-threatening disease that can occur at any age and be sporadic or familial. aHUS is caused by an uncontrolled activation of the complement system. Plasma Exchange (PE) has been the standard treatment for years with poor results, leading approximately 40% of patients to end-stage renal disease (ESRD) or death during the first clinical manifestation. Eculizumab, an humanized monoclonal antibody directed against complement component C5, has emerged in the last few years as a new therapheutic aproach with promising results. Our goal is to present a case of an adult patient where eculizumab was sucessfully used as upfront therapy avoiding the potential significant morbidity of PE.