Zinc alpha 2 glycoprotein as an early biomarker of diabetic nephropathy in patients with type 2 diabetes mellitus / Zinco-alfa2-glicoproteina (ZAG) como biomarcador precoce de nefropatia diabética em pacientes com diabetes mellitus tipo 2

Abstract Introduction: Although microalbuminuria remains the gold standard for early detection of diabetic nephropathy (DN), it is not a sufficiently accurate predictor of DN risk. Thus, new biomarkers that would help to predict DN risk earlier and possibly prevent the occurrence of end-stage kidney disease are being investigated. Objective: To investigate the role of zinc-alpha-2-glycoprotein (ZAG) as an early marker of DN in type 2 diabetic (T2DM) patients. Methods: 88 persons were included and classified into 4 groups: Control group (group I), composed of normal healthy volunteers, and three patient groups with type 2 diabetes mellitus divided into: normo-albuminuria group (group II), subdivided into normal eGFR subgroup and increased eGFR subgroup > 120 mL/min/1.73m2), microalbuminuria group (group III), and macroalbuminuria group (group IV). All subjects were submitted to urine analysis, blood glucose levels, HbA1c, liver function tests, serum creatinine, uric acid, lipid profile and calculation of eGFR, urinary albumin creatinine ratio (UACR), and measurement of urinary and serum ZAG. Results: The levels of serum and urine ZAG were higher in patients with T2DM compared to control subjects and a statistically significant difference among studied groups regarding serum and urinary ZAG was found. Urine ZAG levels were positively correlated with UACR. Both ZAG levels were negatively correlated with eGFR. Urine ZAG levels in the eGFR ˃ 120 mL/min/1.73m2 subgroup were higher than that in the normal eGFR subgroup. Conclusion: These findings suggest that urine and serum ZAG might be useful as early biomarkers for detection of DN in T2DM patients, detectable earlier than microalbuminuria.

Resumo Introdução: Embora a microalbuminúria continue sendo o padrão ouro para a detecção precoce da nefropatia diabética (ND), ela não é um preditor suficientemente preciso do risco de ND. Assim, novos biomarcadores para prever mais precocemente o risco de ND e possivelmente evitar a ocorrência de doença renal terminal estão sendo investigados. Objetivo: Investigar a zinco-alfa2-glicoproteína (ZAG) como marcador precoce de ND em pacientes com debates mellitus tipo 2 (DM2). Métodos: Os 88 indivíduos incluídos foram divididos em quatro grupos: grupo controle (Grupo I), composto por voluntários saudáveis normais; e três grupos de pacientes com DM2 assim divididos: grupo normoalbuminúria (Grupo II), subdivididos em TFG normal e TFG > 120 mL/min/1,73 m2), grupo microalbuminúria (Grupo III) e grupo macroalbuminúria (Grupo IV). Todos foram submetidos a urinálise e exames para determinar glicemia, HbA1c, função hepática, creatinina sérica, ácido úrico, perfil lipídico, cálculo da TFG, relação albumina/creatinina (RAC) e dosagem urinária e sérica de ZAG. Resultados: Os níveis séricos e urinários de ZAG foram mais elevados nos pacientes com DM2 em comparação aos controles. Foi identificada diferença estatisticamente significativa entre os grupos estudados em relação aos níveis séricos e urinários de ZAG. Os níveis urinários de ZAG foram positivamente correlacionados com a RAC. Ambos os níveis de ZAG foram negativamente correlacionados com TFG. Os níveis urinários de ZAG no subgrupo com TFG ˃ 120 mL/min/1,73m2 foram maiores do que no subgrupo com TFG normal. Conclusão: Constatamos que a ZAG sérica e urinária pode ser um útil biomarcador precoce para detecção de ND em pacientes com DM2, sendo detectável mais precocemente que microalbuminúria.

Serum uric acid and its association with hypertension, early nephropathy and chronic kidney disease in type 2 diabetic patients / Ácido úrico sérico e sua associação com hipertensão, nefropatia precoce e doença renal crônica em pacientes diabéticos tipo 2

Abstract Introduction: Early detection diabetic nephropathy (DN) is important. Whether serum uric acid (SUA) has a role in the development of DN is not known. Objective: To study the relationship between SUA and hypertension, early nephropathy and progression of chronic kidney disease (CKD) in type 2 diabetes mellitus (T2DM). Methods: The total number of the study was 986 participants, according to presence and duration of diabetes were classified into three groups. Group I; including 250 healthy participants. Group II; including 352 with onset of diabetes < 5 years. Group III; including 384, with the onset of diabetes > 5 years. All participants were submitted to complete clinical examination, anthropometric measurements, laboratory investigations, including glycosylated hemoglobin (HbA1C), as well triglycerides to high-density lipoprotein ratios (TG/HDL-C), SUA, urinary albumin/creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR). Results: SUA, BP, HbA1c, TG/HDL-C ratio, and ACR levels were significantly higher in group III than group I, II and in II than I. eGFR significantly lower in group III than group I, II and in II than I (p < 0.001). Age, BMI, BP, HbA1c, TG/HDL-C, ACR, were positively correlated with SUA, while GFR negatively correlated. SUA at level of > 6.1 mg/dl, > 6.2 mg/dl and > 6.5 mg/dl had a greater sensitivity and specificity for identifying hypertension, early nephropathy and decline eGFR respectively. Conclusion: Even high normal SUA level, was associated with the risk of hypertension, early nephropathy and decline of eGFR. Moreover SUA level may identify the onset of hypertension, early nephropathy and progression of CKD in T2DM.

Resumo Introdução: A detecção precoce da nefropatia diabética (ND) é importante. O ácido úrico sérico (AUS) tem um papel ainda desconhecido no desenvolvimento de ND. Objetivo: Estudar a relação entre AUS e hipertensão, nefropatia precoce e progressão da doença renal crônica (DRC) no diabetes mellitus tipo 2 (DM2). Métodos: O estudo contou com 986 participantes, de acordo com a presença e a duração do diabetes, os pacientes foram classificados em três grupos. O Grupo I incluiu 250 participantes saudáveis. O Grupo II incluiu 352 pacientes com início de diabetes < 5 anos. O Grupo III incluiu 384 pacientes com o aparecimento de diabetes > 5 anos. Todos os participantes foram submetidos a exame clínico completo, medidas antropométricas, exames laboratoriais - incluindo hemoglobina glicosilada (HbA1C), bem como a razão entre triglicérides e lipoproteína de alta densidade (TG/HDL-C), AUS, razão creatinina/albumina (RCA) urinária, e taxa estimada de filtração glomerular (eTFG). Resultados: A razão AUS, PA, HbA1c, TG/HDL-C e RCA foi significativamente maior no grupo III do que no grupo I, II e em II do que I. A eTFG foi significativamente menor no grupo III do que nos grupos I, II e no II do que no I (p < 0,001). Idade, IMC, PA, HbA1c, razão TG/HDL-C, RCA, foram positivamente correlacionados com AUS, enquanto que a TFG esteve negativamente correlacionada. O AUS a níveis > 6,1 mg/dl, > 6,2 mg/dl e > 6,5 mg/dl apresentou maior sensibilidade e especificidade para identificar hipertensão, nefropatia precoce e declínio da eTFG, respectivamente. Conclusão: Mesmo elevados níveis de AUS, foi associado ao risco de hipertensão, nefropatia precoce e declínio da eTFG. Além disso, o nível de AUS pode identificar o início da hipertensão, nefropatia precoce e progressão da DRC em DM2.

Acido úrico, aterosclerosis y calcificaciones vasculares en enfermedad renal crónica / Uric acid, atherosclerosis and vascular calcifications in chronic kidney disease

Estudios clínicos y epidemiológicos han demostrado que la enfermedad cardiovascular está relacionada con un aumento en la tasa de mortalidad en los pacientes con enfermedad renal crónica (ERC). Las complicaciones vasculares son principalmente secundarias a calcificaciones y ateroesclerosis. En los últimos años se ha renovado el interés por la asociación entre niveles de ácido úrico y riesgo cardiovascular. El objetivo de esta investigación fue relacionar la presencia de calcificaciones vasculares (CV) y aterosclerosis, evaluadas mediante ecografía carotídea, con niveles de ácido úrico en pacientes con ERC estadio 5 en diálisis. Se observaron CV en 56% de los pacientes; 46% tuvo criterios ecográficos para aterosclerosis con un promedio general de 0,89 mm (DE: ± 0,28), siendo mayor en los pacientes con hipertensión arterial y diabetes mellitus; este grupo también mostró mayor predisposición para CV (p= 0,01). Los niveles de urea (141,3 mg/dL) (p= 0,01) y ácido úrico (6,9 mg/dL) (p= 0,04) mostraron asociación estadísticamente significativa con la presencia de CV. Los eventos cardiovasculares adversos predominaron en los pacientes con aterosclerosis y CV (p= 0,01). Esta investigación demostró que un incremento en los niveles de ácido úrico por encima de 6 mg/L está relacionado con mayor riesgo de presentar calcificaciones y eventos cardiovasculares adversos en pacientes con ERC.

Epidemiological and clinical studies have shown that cardiovascular disease is associated with an increase in mortality in patients with chronic kidney disease (CKD). Vascular complications are mainly secondary to calcification and atherosclerosis. Interest in the association between uric acid levels and cardiovascular risk has been renewed in recent years. The objective of this research was to determine the relation between vascular calcification (VC) and atherosclerosis, through carotid ultrasound, with uric acid levels in patients with CKD in dialysis. VCs were observed in 56% of patients, 46% had ultrasound criteria for atherosclerosis with an overall average of 0.89 mm (SD ± 0.28), being higher in patients with hypertension and diabetes; this group also showed increased susceptibility to VC (p= 0.01). The levels of urea (141.3 mg/dL) (p= 0.01) and uric acid (6.9 mg/dL) (p= 0.04) showed significant association with the presence of VC. Adverse cardiovascular events were observed mainly in patients with atherosclerosis and VC (p= 0.01). This investigation showed that an increase in uric acid levels above 6 mg/dL is associated with an increased risk of calcification and cardiovascular adverse events in CKD patients in dialysis.

Glycemic and lipidic profile in diabetic patients undergoing dialysis / Controle glicêmico e lipídico no paciente diabético em diálise

OBJECTIVE: The aim of this study is to assess the clinical care pattern and to compare the lipid and glycemic profile in a group of diabetic patients undergoing both hemodialysis (HD) and peritoneal dialysis (PD) and to correlate these data using biomarkers of cardiovascular risk. SUBJECTS AND METHODS: The first phase consisted in performing a survey on demographic data, questions about the medical team and glycemic control. In the second phase, patients were assessed through laboratorial data on their glycemic and lipid profile at a single center for HD and PD. RESULTS: 91 patients was the total population; 70 patients (77 percent) answered the survey; 66 patients (94 percent) considered the nephrologist the physician responsible for caring for their glycemic control. Second phase: 59 patients were assessed, 29 undergoing HD and 30 undergoing PD. Fifty-seven percent of the patients had HbA1c above 7 percent; the level of glycemic markers in patients undergoing peritoneal dialysis was significantly higher than in patients undergoing hemodialysis: HbA1c (9.37 ± 0.5) vs. (7.37 ± 0.49) p < 0.01; fasting glycemia (170 ± 15) vs. (126 ± 15) mg/dL p < 0.05. We found a positive correlation between HbA1c and hyperfibrinogenemia (r = 0.4437, p < 0.0005). CONCLUSIONS: The data reveal that glycemic control in diabetic patients undergoing renal replacement therapy (RRT) is neglected. Peritoneal dialysis is related to the worst level of glycemic markers, possibly due to the glucose content in the dialysis solution, and higher levels from HbA1c have a positive correlation with hyperfibrinogenesis in this population.

OBJETIVO: Avaliar as características dos cuidados clínicos dos pacientes em diálise, comparar o controle glicêmico e lipídico entre os pacientes diabéticos em hemodiálise (HD) e em diálise peritoneal (DP) e correlacionar os dados laboratoriais com biomarcadores de risco cardiovascular. SUJEITOS E MÉTODOS: A primeira etapa consistiu de um questionário abordando variáveis demográficas, questões sobre a equipe multidisciplinar, incluindo a equipe médica e sobre o controle glicêmico. Na segunda, os pacientes foram avaliados com exames laboratoriais para controle glicêmico e perfil lipídico numa unidade de HD e DP. RESULTADOS: Dos 91 pacientes avaliados, setenta (77 por cento) responderam ao questionário. Destes, 66 (94 por cento) consideraram o nefrologista o médico responsável pelo cuidado do seu controle glicêmico. Na segunda etapa, foram avaliados 59 pacientes: 29 em HD e 30 em DP. Cinquenta e sete por cento dos pacientes diabéticos em diálise apresentaram HbA1c acima de 7 por cento, sendo que aqueles em diálise peritoneal apresentam níveis de marcadores glicêmicos significativamente piores do que os pacientes diabéticos em HD, HbA1c: (9,37 ± 0,5) vs. (7,37 ± 0,49) p < 0.01; glicemia de jejum: (170 ± 15) vs. (126 ± 15) mg/dL, p < 0.05. Encontramos uma correlação positiva entre HbA1c e hiperfibrinogenemia (r = 0.4437, p < 0.0005). CONCLUSÕES: Nossos dados permitem inferir que o controle glicêmico da população diabética em terapia renal de substituição (TRS) é negligenciado. A diálise peritoneal está relacionada com piora nos níveis de marcadores glicêmicos, possivelmente em decorrência do conteúdo de glicose das soluções de diálise, e os níveis elevados de HbA1c estão associados com hiperfibrinogenemia nesta população.

Diabetes y hemodiálisis. Caracterización de una cohorte y seguimiento a cuatro años / Assessment and follow up of diabetic patients in hemodialysis

Background: Despite a better management of the variables that influence the development of diabetic nephropathy there is a progressive increase in the prevalence of terminal renal failure among diabetics, whose cause is not clear. Aim: To study in a group of patients in hemodialysis, the quality of diabetes control previous to the entry to dialysis, their physical condition and their evolution. Material and methods: Diabetic patients with at least three months of hemodialysis answered a questionnaire about diabetes control quality previous to dialysis and had physical and laboratory assessment. They were followed for at least four years thereafter. Results: Fifty seven patients aged 62±11 years were studied. Eighty four percent had some degree of disability. Eighty seven percent had high blood pressure and 73 percent had to enter dialysis as an emergency. Mean glycosilated hemoglobin was 7.7 percent and 58 percent had a dialysis dose with a Kt/Vofless than 1.2. Fifty eight percent died during follow up. No relationship between mortality and age, blood pressure, glycosilated hemoglobin of Kt/V, was observed. Conclusions: There is an inadequate management of blood glucose and blood pressure of diabetic patients before entry to dialysis. They are referred ¡ate to the nephrologist, the dialysis dose is insufficient and they have a high mortality.