A peptide fraction from hardened common beans (Phaseolus vulgaris) induces endothelium-dependent antihypertensive and renal effects in rats.

Beans reached the research spotlight as a source of bioactive compounds capable of modulating different functions. Recently, we reported antioxidant and oxidonitrergic effect of a low molecular weight peptide fraction (<3 kDa) from hardened bean (Phaseolus vulgaris) in vitro and ex vivo, which necessitate further in vivo assessments. This work aimed to evaluate the hypotensive effect and the involved physiological mechanisms of the hardened common bean peptide (Phaseolus vulgaris) in normotensive (Wistar) and hypertensive (SHR) animals. Bean flour was combined with a solution containing acetonitrile, water and formic acid (25: 24: 1). Protein extract (PV3) was fractioned (3 kDa membrane). We assessed PV3 effects on renal function and hemodynamics of wistar (WT-normotensive) and spontaneously hypertensive rats (SHR) and measured systemic arterial pressure and flow in aortic and renal beds. The potential endothelial and oxidonitrergic involvements were tested in isolated renal artery rings. As results, we found that PV3: I) decreased food consumption in SHR, increased water intake and urinary volume in WT, increased glomerular filtration rate in WT and SHR, caused natriuresis in SHR; II) caused NO- and endothelium-dependent vasorelaxation in renal artery rings; III) reduced arterial pressure and resistance in aortic and renal vascular beds; IV) caused antihypertensive effects in a dose-dependent manner. Current findings support PV3 as a source of bioactive peptides and raise the potential of composing nutraceutical formulations to treat renal and cardiovascular diseases.

Glomerular filtration in the aging population.

In the last decades, improvements in the average life expectancy in the world population have been associated with a significant increase in the proportion of elderly people, in parallel with a higher prevalence of non-communicable diseases, such as hypertension and diabetes. As the kidney is a common target organ of a variety of diseases, an adequate evaluation of renal function in the approach of this population is of special relevance. It is also known that the kidneys undergo aging-related changes expressed by a decline in the glomerular filtration rate (GFR), reflecting the loss of kidney function, either by a natural senescence process associated with healthy aging or by the length of exposure to diseases with potential kidney damage. Accurate assessment of renal function in the older population is of particular importance to evaluate the degree of kidney function loss, enabling tailored therapeutic interventions. The present review addresses a relevant topic, which is the effects of aging on renal function. In order to do that, we analyze and discuss age-related structural and functional changes. The text also examines the different options for evaluating GFR, from the use of direct methods to the implementation of several estimating equations. Finally, this manuscript supports clinicians in the interpretation of GFR changes associated with age and the management of the older patients with decreased kidney function.

Gdnf Acts as a Germ Cell-Derived Growth Factor and Regulates the Zebrafish Germ Stem Cell Niche in Autocrine- and Paracrine-Dependent Manners.

Glial cell line-derived neurotrophic factor (GDNF) and its receptor (GDNF Family Receptor α1-GFRα1) are well known to mediate spermatogonial stem cell (SSC) proliferation and survival in mammalian testes. In nonmammalian species, Gdnf and Gfrα1 orthologs have been found but their functions remain poorly investigated in the testes. Considering this background, this study aimed to understand the roles of the Gdnf-Gfrα1 signaling pathway in zebrafish testes by combining in vivo, in silico and ex vivo approaches. Our analysis showed that zebrafish exhibit two paralogs for Gndf (gdnfa and gdnfb) and its receptor, Gfrα1 (gfrα1a and gfrα1b), in accordance with a teleost-specific third round of whole genome duplication. Expression analysis further revealed that both ligands and receptors were expressed in zebrafish adult testes. Subsequently, we demonstrated that gdnfa is expressed in the germ cells, while Gfrα1a/Gfrα1b was detected in early spermatogonia (mainly in types Aund and Adiff) and Sertoli cells. Functional ex vivo analysis showed that Gdnf promoted the creation of new available niches by stimulating the proliferation of both type Aund spermatogonia and their surrounding Sertoli cells but without changing pou5f3 mRNA levels. Strikingly, Gdnf also inhibited late spermatogonial differentiation, as shown by the decrease in type B spermatogonia and down-regulation of dazl in a co-treatment with Fsh. Altogether, our data revealed that a germ cell-derived factor is involved in maintaining germ cell stemness through the creation of new available niches, supporting the development of spermatogonial cysts and inhibiting late spermatogonial differentiation in autocrine- and paracrine-dependent manners.

Lrig1 and Lrig3 cooperate to control Ret receptor signaling, sensory axonal growth and epidermal innervation.

Negative feedback loops represent a regulatory mechanism that guarantees that signaling thresholds are compatible with a physiological response. Previously, we established that Lrig1 acts through this mechanism to inhibit Ret activity. However, it is unclear whether other Lrig family members play similar roles. Here, we show that Lrig1 and Lrig3 are co-expressed in Ret-positive mouse dorsal root ganglion (DRG) neurons. Lrig3, like Lrig1, interacts with Ret and inhibits GDNF/Ret signaling. Treatment of DRG neurons with GDNF ligands induces a significant increase in the expression of Lrig1 and Lrig3. Our findings show that, whereas a single deletion of either Lrig1 or Lrig3 fails to promote Ret-mediated axonal growth, haploinsufficiency of Lrig1 in Lrig3 mutants significantly potentiates Ret signaling and axonal growth of DRG neurons in response to GDNF ligands. We observe that Lrig1 and Lrig3 act redundantly to ensure proper cutaneous innervation of nonpeptidergic axons and behavioral sensitivity to cold, which correlates with a significant increase in the expression of the cold-responsive channel TrpA1. Together, our findings provide insights into the in vivo functions through which Lrig genes control morphology, connectivity and function in sensory neurons.

Principles of Kidney Pharmacotherapy for the Nephrologist: Core Curriculum 2021.

Medications are an important part of the management of patients with kidney disease. When used appropriately, pharmacotherapy can slow disease progression and reduce morbidity and mortality. Unfortunately, reduced kidney function can significantly alter the pharmacokinetics and pharmacodynamics of many medications, putting patients at risk for drug toxicity if modifications to therapy are not appropriately managed. Adding complexity to the appropriateness of medication and dosage selection is the difficulty in estimating kidney function and the discordance between the Cockcroft-Gault-derived dosing cut points in most medication package inserts and the estimations of glomerular filtration rate by newer and generally more accurate guideline-recommended equations. This installment of the AJKD Core Curriculum in Nephrology provides recent updates and practical considerations for designing optimal medication regimens. Given the prevalence of abnormal kidney function and its importance in medication selection and dose adjustment, additional focus and specific recommendations are provided for anticoagulant, anti-infective, analgesic, antidiabetic, and antihypertensive agents.

Assessing Renal Function for Kidney Donation. How Low Is Too Low?

Kidney transplantation (KT) is the treatment of choice for patients with end-stage kidney disease (ESKD) with decreased morbi-mortality, improved life quality, and reduced cost. However, the shortage of organs from deceased donors led to an increase in KT from living donors. Some stipulate that living donors have a higher risk of ESKD after donation compared with healthy non-donors. The reason for this is not clear. It is possible that ESKD is due to the nephrectomy-related reduction in glomerular filtration rate (GFR), followed by an age-related decline that may be more rapid in related donors. It is essential to assess donors properly to avoid rejecting suitable ones and not accepting those with a higher risk of ESKD. GFR is a central aspect of the evaluation of potential donors since there is an association between low GFR and ESKD. The methods for assessing GFR are in continuous debate, and the kidney function thresholds for accepting a donor may vary according to the guidelines. While direct measurements of GFR (mGFR) provide the most accurate evaluation of kidney function, guidelines do not systematically use this measurement as a reference. Also, some studies have shown that the GFR decreases with age and may vary with gender and race, therefore, the lower limit of GFR in patients eligible to donate may vary based on these demographic factors. Finally, it is known that CrCl overestimates mGFR while eGFR underestimates it, therefore, another way to have a reliable GFR could be the combination of two measurement methods.

Simultaneous Treatment with Soluble Forms of GAS1 and PTEN Reduces Invasiveness and Induces Death of Pancreatic Cancer Cells.

INTRODUCTION: Pancreatic carcinoma cells exhibit a pronounced tendency to invade along and through intra and extrapancreatic nerves, even during the early stages of the disease, a phenomenon called perineural invasion (PNI). Thus, we sought to determine the effects of the simultaneous expression of soluble forms of GAS1 and PTEN (tGAS1 and PTEN-L) inhibiting tumor growth and invasiveness. MATERIALS AND METHODS: We employed a lentiviral system to simultaneously express tGAS1 and PTEN-L; in order to determine the effects of the treatments, cell viability and apoptosis as well as the expression of the transgenes by ELISA and intracellular signaling as ascertained by the activation of AKT and ERK1/2 were measured; cell invasiveness was determined using a Boyden chamber assay; and the effects of the treatment were measured in vivo in a mouse model. RESULTS: In the present work, we show that the combined treatment with tGAS1 and PTEN-L inhibits the growth of pancreatic cancer cells, by reducing the activities of both AKT and ERK 1/2, decreases cell invasiveness, and restrains tumor growth in a mouse model. CONCLUSION: The combined administration of tGAS1 and PTEN-L could be a valuable adjunct therapy for the treatment of pancreatic cancer.

Cistatina C: marcador de laboratorio precoz de enfermedad renal en pacientes con depranocitosis / Cystatin C: early laboratory marker of renal disease In sickle cell disease

La enfermedad renal en el paciente con drepanocitosis es una consecuencia de su complejo proceso fisiopatológico, por lo que es importante disponer de un grupo de parámetros de laboratorio que, junto a la evaluación clínica, permita determinar de forma precoz la presencia de esta complicación. La cistatina C ha demostrado ser uno de los parámetros que con mayor exactitud aporta evidencia temprana de daño renal en este grupo de pacientes y al mismo tiempo constituye un posible indicador de pronóstico de gran importancia(AU)

Renal disease in patients with sickle cell disease is a consequence of its complex pathophysiological process, so it is important to have a set of laboratory parameters that, together with the clinical evaluation, allow the early detection of this complication. Cystatin C has been shown to be one of the parameters that provides, with greater accuracy, early evidence of kidney damage in this group of patients and at the same time constitutes a possible indicator of prognosis of great importance(AU)

Cistatina C: marcador de laboratorio precoz de enfermedad renal en pacientes con depranocitosis / Cystatin C: early laboratory marker of renal disease In sickle cell disease

La enfermedad renal en el paciente con drepanocitosis es una consecuencia de su complejo proceso fisiopatológico, por lo que es importante disponer de un grupo de parámetros de laboratorio que, junto a la evaluación clínica, permita determinar de forma precoz la presencia de esta complicación. La cistatina C ha demostrado ser uno de los parámetros que con mayor exactitud aporta evidencia temprana de daño renal en este grupo de pacientes y al mismo tiempo constituye un posible indicador de pronóstico de gran importancia(AU)

Renal disease in patients with sickle cell disease is a consequence of its complex pathophysiological process, so it is important to have a set of laboratory parameters that, together with the clinical evaluation, allow the early detection of this complication. Cystatin C has been shown to be one of the parameters that provides, with greater accuracy, early evidence of kidney damage in this group of patients and at the same time constitutes a possible indicator of prognosis of great importance(AU)

GDNF/GFRα1 Complex Abrogates Self-Renewing Activity of Cortical Neural Precursors Inducing Their Differentiation.

The balance between factors leading to proliferation and differentiation of cortical neural precursors (CNPs) determines the correct cortical development. In this work, we show that GDNF and its receptor GFRα1 are expressed in the neocortex during the period of cortical neurogenesis. We show that the GDNF/GFRα1 complex inhibits the self-renewal capacity of mouse CNP cells induced by fibroblast growth factor 2 (FGF2), promoting neuronal differentiation. While GDNF leads to decreased proliferation of cultured cortical precursor cells, ablation of GFRα1 in glutamatergic cortical precursors enhances its proliferation. We show that GDNF treatment of CNPs promoted morphological differentiation even in the presence of the self-renewal-promoting factor, FGF2. Analysis of GFRα1-deficient mice shows an increase in the number of cycling cells during cortical development and a reduction in dendrite development of cortical GFRα1-expressing neurons. Together, these results indicate that GDNF/GFRα1 signaling plays an essential role in regulating the proliferative condition and the differentiation of cortical progenitors.

ST-elevation myocardial infarction risk in the very elderly.

BACKGROUND: Despite the high incidence and mortality of ST-segment elevation myocardial infarction (STEMI) among the very elderly, risk markers for this condition remain poorly defined. This study was designed to identify independent markers of STEMI among individuals carefully selected for being healthy or manifesting STEMI in < 24 h. METHODS: We enrolled participants aged 80 years or older of whom 50 were STEMI patients and 207 had never manifested cardiovascular diseases. Blood tests, medical and psychological evaluations were obtained at study admission. Odds Ratio (OR) and attributed risk (AR) were obtained by multivariate regression models using STEMI as dependent variable. RESULTS: Low glomerular filtration rate (GFR) [OR:4.41 (1.78-10.95); p = 0.001], reduced levels of HDL-C [OR:10.70 (3.88-29.46); p = 0.001], male gender [OR:12.08 (5.82-25.08); p = 0.001], moderate to severe depressive symptoms [OR:10.00 (2.82-35.50); p = 0.001], prior smoking [OR:2.00 (1.05-3.80); p = 0.034] and current smoking [OR:6.58 (1.99-21.70); p = 0.002] were significantly associated with STEMI. No association was found between STEMI and age, diabetes, hypertension, mild depressive symptoms, triglyceride or LDL-C. CONCLUSIONS: This is the first case-control study carried out with very elderlies to assess STEMI risk. Our findings indicate that reduced HDL-C, GFR, male gender, smoking habits and moderate to severe depressive symptoms are markers of STEMI in this age group. GENERAL SIGNIFICANCE: In Individuals aged 80 or more years, a greater attention must be paid to low HDL-C and GFR at the expense of conventional STEMI risk factors for younger adults such as diabetes mellitus, hypertension and high LDL-C or triglyceride.

Importancia del examen médico preventivo para el diagnóstico precoz de enfermedad renal en Uruguay.: Programa Nacional de Salud Renal / Importance of preventive medical examination for early diagnosis of renal disease in Uruguay.: The National Renal Health Program

Introducción: El Programa Nacional de Salud Renal (PNSR) mostró que la enfermedad renal crónica (ERC) puede estabilizarse en la evolución. Objetivo: evaluar el tamizaje de Enfermedad Renal Crónica presuntiva (ERCp) en población ambulatoria de una Clínica Preventiva con tirilla reactiva para proteinuria (TPu) y determinación de creatinina. Método. Estudio observacional, descriptivo, de corte transversal, entre 1/1/2008 y 31/12/2012 en 83.912 personas que se realizaron Carné de Salud (edad media =34.4años). Se consideró proteinuria positiva (Pu+) si TPu ≥1+ o ≥ 0.3 g/l. Se realizó TPu a todos y dosificación de creatinina para estimación Filtrado Glomerular (TFGe) en subpoblación con factores de riesgo (FR) como hipertensión o diabetes. Se evaluó proteinuria según edad y presencia o no de FR. En 11.161 individuos con determinación de creatinina se estimó el TFGe por fórmula CKD-EPI, (edad media=44.7años) se estimó prevalencia de ERCp mediante Pu+ TFGe<60 ml/min aisladas o en conjunto según grupos con FR, en base de datos no identificados de la Clínica Preventiva. Se utilizó el software estadístico SPSS 15.0 y regresión logística para análisis multivariado. Resultados: La prevalencia total de Pu+ fue de 6% (5.5% en grupo sin FR, 6.7% en hipertensión-sin-diabetes, 9.2% en diabetes-sin-hipertensión y 13.6% con ambos FR). Se desconocen falsos positivos. La prevalencia de TFGe<60 ml/min fue de 1.8%, siendo edad e hipertensión FR independientes para TFGe descendido. Considerados en conjunto Pu+ y TFGe<60 ml/min la prevalencia de ERCp alcanza 9.2%. Los FR aumentan la frecuencia de ERCp (p<0.05). Con Pu+ aislada se detecta ERCp entre el 85-90% según tengan o no FR; por grupos etarios la Pu+ aislada detecta el 100% de individuos con ERCp <20 años, es >90% en <50 años y cae a 30% en >70 años, donde cobra importancia la TFGe: 21.9% en con FR. Conclusiones: La población del Carné de Salud es útil para el tamizaje de ERCp temprana. Este estudio permitió identificar los mejores marcadores de ERCp para segmentos diferentes de población: la Pu+ aislada detecta ERCp en más del 90% de las personas <50 años y la TFGe adquiere importancia en añosos.

Introduction: The National Renal Health Program showed that chronic kidney disease (CKD) can be stabilized in the outcome. Objective: To assess screening Chronic Kidney Disease presumptive (pCKD) in an outpatient population of a Preventive Clinic with dipstick proteinuria (TPu) and/or eGFR <60 ml/min. Method: It is an observational, descriptive and cross sectional study. Between 1/1/2008 and 12/31/2012 was performed medical check to 83.912 individual (average age=34.4 years) from a Preventive Clinic with a proteinuria by TPu. In a selective population with predominant hypertension and diabetes (n 11.161 individuals, age 44.7 years odl) was performed determination of creatina and eGFR was estimated by CKD-EPI formula. pCKD prevalence was assessed by Pu + and/or eGFR<60 ml/min/1.73m2 alone or combined. We analyzed the risk factors (RF) for pCKD with SPSS 15.0 statistical software and logistic regression was used for multivariate analysis. Results: The prevalence of Pu + in total population was 6% (5.5% in the reference group, 6.7% in hypertension-without-diabetes, 9.2% in diabetes-without-hypertension and 13.6% in both RF group); the risk of Pu+ was increased in the previous groups (p < 0.05). Pu + false positives were unknown. The prevalence of eGFR< 60 ml/min was 1.8%, and age and hypertension were independent risk factors. When Pu + and/or eGFR<60 ml/min are considered together, the prevalence of pCKD reaches 9.2%. RF increases the frequency of pCKD (p < 0.05). With isolated Pu +, pCKD is detected between 85-90% according to whether or not they have RF; by age groups the isolated Pu + detects 100% of individuals with pCKD <20 years, is > 90% in those with <50 years and drop to 30% at 70 years or more, where is relevant the eGFR: 21.9% in RF group. Conclusions: The Preventive Clinic population is a useful place for screening early pCKD. This study identified renal markers of pCKD for different population segments: isolated Pu + detects pCKD in more than 90% of people < 50 years and the eGFR makes it in aged people.

Vitamin D, race, and risk for anemia in children.

OBJECTIVE: To examine the association between 25-hydroxyvitamin D [25(OH)D] deficiency and anemia in a cohort of otherwise-healthy children and to determine whether race modifies the association between 25(OH)D status and hemoglobin (Hgb). STUDY DESIGN: Cross-sectional study of 10,410 children and adolescents ages 1-21 years from the 2001-2006 National Health and Nutrition Examination Survey. Anemia was defined as Hgb less than the 5th percentile for age and sex based on National Health and Nutrition Examination Survey III (1988-1994) data. RESULTS: Lower 25(OH)D levels were associated with increased risk for anemia; <30 ng/mL, adjusted OR 1.93, 95% CI 1.21-3.08, P = .006, and <20 ng/mL, OR 1.47, 95% CI 1.14-1.89, P = .004. In linear regression, small but significant increases in Hgb were noted in the upper quartiles of 25(OH)D compared with the lowest quartile (<20 ng/mL) in the full cohort. Results of race-stratified linear regression by 25(OH)D quartile in white children were similar to those observed in the full cohort, but in black children, an increase in Hgb in the upper 25(OH)D quartiles was only apparent compared with the lowest black race-specific quartile (<12 ng/mL). CONCLUSION: 25(OH)D deficiency is associated with increased risk of anemia in healthy US children, but the 25(OH)D threshold levels for lower Hgb are lower in black children in comparison with white children.

Height-independent estimation of glomerular filtration rate in children: an alternative to the Schwartz equation.

OBJECTIVE: To compare the diagnostic performance of 2 height-independent equations used to calculate estimated glomerular filtration rate (eGFR), those of Pottel (eGFR-Pottel) and the British Columbia Children's Hospital (BCCH) (eGFR-BCCH), with the commonly used Schwartz equation (eGFR-Schwartz). STUDY DESIGN: We externally validated eGFR-Pottel and eGFR-BCCH in a well-characterized pediatric patient population (n = 152) and compared their diagnostic performance with that of eGFR-Schwartz using Bland-Altman analysis. All patients underwent glomerular filtration rate measurement using the gold standard single-injection inulin clearance method (GFR-inulin). RESULTS: Median GFR-inulin was 92.0 mL/min/1.73 m² (IQR, 76.1-107.4 mL/min/1.73 m²). Compared with GFR-inulin, the mean bias for eGFR-Schwartz was -10.1 mL/min/1.73 m(2) (95% limits of agreement [LOA], -77.5 to 57.2 mL/min/1.73 m(2)), compared with -12.3 mL/min/1.73 m² (95% LOA, -72.6 to 47.9 mL/min/1.73 m(2)) for eGFR-Pottel and -22.1 mL/min/1.73 m² (95% LOA, -105.0 to 60.8 mL/min/1.73 m(2)) for eGFR-BCCH. eGFR-Pottel showed comparable accuracy to eGFR-Schwartz, with 77% and 76% of estimates within 30% of GFR-inulin, respectively. eGFR-BCCH was less accurate than eGFR-Schwartz (66% of estimates within 30% of GFR-inulin; P < .01). CONCLUSION: The performance of eGFR-Pottel is superior to that of eGFR-BCCH and comparable with that of eGFR-Schwartz. eGFR-Pottel is a valid alternative to eGFR-Schwartz in children and could be reported by the laboratory if height data are not available.

Nephropathy following Type 2 diabetes mellitus in Tunisian population / Nefropatía tras la diabetes mellitus tipo 2 en la población Tunesina

OBJECTIVE: The purpose was to compare the characteristics of Tunisians with Type 2 diabetes mellitus (Type 2 DM) and nephropathy with those without nephropathy. This study assessed whether or not phenotypic characteristics can predict nephropathy development in Type 2 DM. The prevalence of nephropathy in Tunisian Type 2 DM patients, and their relationship with clinical and biochemical factors as well as chronic complications of the disease were determined. METHODS: This was a cross-sectional study of patients with diabetes diagnosed between January 2008 and December 2010. Altogether, 73 Type 2 DM and 42 healthy volunteers from the Basic Health Group of Sousse, were targeted for the study. Clinical, biochemical data, as well as complications of diabetes were collected. Kidney malfunction was defined by glomerular filtration rate (GFR). RESULTS: Diabetic patients were older. Diabetic women were more likely to have higher body mass index than men (p = 0.004). Obesity was more in women than men (60/23%). Complications including hypertension and dyslipidaemia were co-associated in women. Urinary creatinine clearance in Type 2 DM patients without nephropathy was significantly lower than in healthy participants (p < 0.0001). Microalbuminuria and urinary creatinine clearance were associated only in women with Type 2 DM with nephropathy (R² = 0.95); 1.5% of Type 2 DM patients without nephropathy had GFR < 60 mL/min/1.73m² and 76% had a GFR between 60 and 89 mL/min/1.73m². Glomerular filtration rate difference between Type 2 DM patients with/without nephropathy, as well as between Type 2 DM patients with nephropathy/Type 2 DM without nephropathy, and with retinopathy was not significant. CONCLUSIONS: By analysing factors associated with nephropathy in Type 2 DM Tunisian patients, this study demonstrated their susceptibility to nephropathy. In addition, retinopathy is potentially associated with incipient nephropathy in Type 2 DM Tunisian patients.

OBJETIVO: El propósito fue comparar las características de los tunesinos con diabetes mellitus tipo 2 (DMT2) y nefropatía, con aquéllos que no padecen nefropatía. Este estudio evaluó la posibilidad de saber si las características fenotípicas pueden predecir el desarrollo de una nefropatía en pacientes de DMT2. Se determinó la prevalencia de la nefropatía en los pacientes tunesinos con DMT2, y su relación con factores clínicos y bioquímicos, así como las complicaciones crónicas de la enfermedad. MÉTODOS: Se realizó un estudio transversal de pacientes con diabetes diagnosticada entre enero de 2008 y diciembre de 2010. En total, 73 voluntarios con DMT2 y 42 saludables del Grupo Básico de Salud de Sousse, fueron escogidos para el estudio. Se recogieron los datos clínicos y bioquímicos, así como las complicaciones por diabetes. El grado de mal funcionamiento renal fue determinado por la tasa de filtrado glomerular (GFR). RESULTADOS: Los pacientes diabéticos tenían más edad. Las mujeres diabéticas presentaban una mayor probabilidad de tener un índice de masa corporal más alto que los hombres (p = 0.004). Hubo mayor obesidad en las mujeres que en los hombres (60/23%). Las complicaciones - incluyendo hipertensión y dislipidemia - estuvieron co-asociadas en las mujeres. La depuración de la creatinina urinaria en los pacientes de DMT2 sin nefropatía fue significativamente más baja (p < 0.0001) que en los participantes saludables. La microalbuminuria y la depuración de la creatinina urinaria estuvieron asociadas en las mujeres con DMT2 con nefropatía (R² = 0.95); 1.5% de los pacientes con DMT2 sin nefropatía, tuvo una tasa GFR < 60 mL/min/1.73m² y 76% tuvo una GFR entre 60 y 89 mL/min/1.73m². La diferencia de la tasa de filtrado glomerular entre los pacientes de DMT2 con/sin nefropatía, así como entre los pacientes de DMT2 con nefropatía/DMT2 sin nefropatía, y con retinopatía, no fue significativa. CONCLUSIONES: Analizando factores asociados con la nefropatía en pacientes tunesinos con DMT2, este estudio demostró que estos últimos son susceptibles a la nefropatía. Además, la retinopatía se halla potencialmente asociada con la nefropatía incipiente en los pacientes tunesinos que padecen DMT2.

Low-dose aspirin does not affect the renal function of microalbuminuric type 2 diabetic patients / Aspirina em baixa dosagem não afeta a função renal de pacientes com diabete melito tipo 2 microalbuminuricos

Low-grade inflammation has been implicated in the pathogenesis of diabetic nephropathy, and anti-inflammatory drugs could be potentially useful as a therapeutic tool. The aim of this study was to analyze the effect of low-dose aspirin (300 mg/d) on urinary albumin excretion (UAE) and glomerular filtration rate (GFR) levels of microalbuminuric type 2 DM patients. Methods: in this randomized, double-blind, crossover, placebo-controlled study, 18 microalbuminuric (UAE=30-300 mg/24 h) type 2 DM patients received aspirin (300 mg/d) or identical placebo for 8 weeks, with a 6-week washout period. The patients were aged 56±9 years, had a diabetes duration of 16±7.5 years; 11 (61%) were female, and they were all using enalapril 10 mg bid. GFR was measured by 51Cr-EDTA single-injection method and UAE by immunoturbidimetry. The sample-size calculation showed that 17 patients were needed to detect a 30% change in UAE (α= 0.05 and β= 0.20). Results: after 8 weeks of treatment, there were no significant differences between placebo and aspirin, respectively, regarding UAE [57.7 (8.9-420.0) vs. 63 (8.2-272.0) mg/24 h; P=0.45] and GFR (108±34 vs. 111±47 ml/min/1.73 m2; P=0.90). Glycemic control was stable throughout the C-reactive protein levels [2.72 (0.34-10.3) vs. 2.03 (0.25-10.3) μg/l; P=0.21] were comparable after placebo and aspirin, respectively. There were no period (P=0.41) or carry-over effects (P=0.49). Conclusion: low-dose aspirin did not affect GFR and UAE levels of microalbuminuric type 2 DM. It seems that the putative low-grade inflammation of diabetic nephropathy does not respond to these low doses of the drug

A inflamação em baixo grau tem sido implicada na patogênese da nefropatia diabética e o uso de anti-inflamatórios poderia ser potencialmente útil como terapêutica. Objetivo: o objetivo deste estudo foi analisar o efeito de baixas doses de aspirina sobre a excreção urinária de albumina (EUA) e taxa de filtração glomerular (TFG) de pacientes com diabete melito(DM) tipo 2 microalbuminuricos. Métodos: neste estudo randomizado, duplo-cego, cruzado, controlado com placebo, 18 pacientes DM tipo 2 microalbuminuricos (EUA = 30-300 mg/24 h) receberam aspirina (300 mg/dia) ou placebo idêntico por 8 semanas, com um período de washout de 6 semanas. Os pacientes tinham idade de 56±9 anos, duração diabetes de 16±7,5 anos, 11 (61%) eram do sexo feminino, e todos estavam usando 20 mg de enalapril/dia. A TFG foi medida pelo 51Cr-EDTA e a EUA por imunoturbidimetria. O calculo do tamanho da amostra: 17 pacientes para detectar uma alteração de 30% na EUA (α=0,05 e β=0,20). Resultados: após 8 semanas, não houve diferenças significativas entre placebo e aspirina, respectivamente, em relação a EUA [57,7 (8,9-420,0) vs. 63 (8,2-272,0) mg/24 h;P=0,45] e TFG (108±34 vs. 111±47 ml/min/1,73 m2; P=0,90). O controle glicêmico manteve-se estável. Os níveis de proteína C reativa [2,72 (0,34-10,3) vs. 2,03 (0,25-10,3) mg/l; P=0,21] foram semelhantes após placebo e aspirina, respectivamente. Não houve efeito de período (P=0,41) ou carry-over (P=0,49). Conclusão: a inflamação de baixo grau descrita na patogênese da nefropatia diabética não responde a baixas doses de aspirina

Monitoring renal function: measured and estimated glomerular filtration rates: a review

Chronic kidney disease (CKD) is a wrld-wide public health problem, with adverse outcomes of kidney failure, cardiovascular disease, and premature death. This finding has led to the hypothesis that earlier recognition of kidney disease and successful intervention may improve outcome. The National Kidney Foundation, through its Kidney Disease Outcomes Quality Initiative (K/DOQI), and other National institutions recommend glomerular filtration rate (GFR) for the definition, classification, screening, and monitoring of CKD. Blood creatinine clearance, the most widely used clinical marker of kidney function, is now recognized as an unreliable measure of GFR because serum creatinine is affected by age, weight, muscle mass, race, various medications, and extra-glomerular elimination. Cystatin C concentration is a new and promising marker for kidney dysfunction in both native and transplanted kidneys. Because of its low molecular weight, cystatin C is freely filtered at the glomerulus and is almost completely reabsorbed and catabolized, but not secreted, by tubular cells. Given these characteristics, cystatin C concentration may be superior to creatinine concentration in detecting chronic kidney disease. This review aims to evaluate from recent literature the clinical efficiency and relevance of these GFR markers in terms of screening CKD.

Calibração da creatinina sérica com uso de equação de regressão: influência na performance da fórmula do estudo MDRD / Serum creatinine calibration with regression equation: influence on MDRD formula performance

Diferenças nos métodos de medida da creatinina sérica podem determinar amplas variações na taxa de filtração glomerular (TFG) estimada com fórmulas. Para a padronização da medida da creatinina, deve ser usado método calibrado rastreável para medida de referência com ID-MS (isotope dilution mass spectrometry). Objetivo: Avaliar a TFG estimada com a equação MDRD (Modification of Diet in Renal Disease) original (MDRDo, creatinina método não calibrado) e a equação MDRD re-expressa (MDRDr, método calibrado por ID-MS), comparando-as com a TFG medida pelo 51Cr-EDTA (método padrão) em indivíduos normais. Métodos: Foram avaliados 101 indivíduos, com idade média de 38±12 anos, sendo 45 homens. A TFG foi medida pela técnica de injeção única do 51Cr-EDTA (TFG 51Cr-EDTA) e estimada pelas equações MDRDo: 186 x creatinina sérica-1,154 x idade-0,203 x 0,742 (se mulher) x 1,210 (se negro) e MDRDr, substituindo-se o valor 186 por 175 na equação. A creatinina sérica foi medida pelo método de Jaffe não calibrado e transformada em calibrado com a fórmula: y=1,07x-0,249, obtida previamente por regressão. A concordância entre os métodos foi avaliada através da análise de Bland&Altman. Resultados: Os valores médios para as TFG 51Cr-EDTA, MDRDr e MDRDo foram de 105±18, 102±21 e 84±13 ml/min/1,73 m², respectivamente. Acurácia (percentual de casos de TFG estimada que não desviam em mais de 15% do valor medido) foi maior com o uso da MDRDr em relação à MDRDo (57% vs. 35%, P=0,002). O viés (diferença entre TFG medida e estimada) para 51Cr-EDTA e MDRDr foi de 3±23 ml/min/1,73 m². Para 51Cr-EDTA e MDRDo o viés foi significativamente maior, sendo de 21±18 ml/min/1,73 m². No entanto, a precisão, avaliada como desvio padrão do viés indicou elevada dispersão nos dois casos. Conclusão: O uso da equação re-expressa do MDRD, empregando a creatinina calibrada, produz uma estimativa mais acurada da TFG do que a equação original do MDRD.

Differences in methods of measurement of serum creatinine may provide wide variations in glomerular filtration rate (GFR) estimated with formulas. To standardize the measurement of creatinine, calibrated methods should be used, traceable to the reference ID-MS (isotope dilution mass spectrometry) method. Aim: To evaluate the performance of GFRs estimated with the original Modification of Diet in Renal Disease study equation (MDRDo; non-calibrated creatinine method) and with the re-expressed MDRD equation (MDRDr; ID-MS creatinine), comparing them with the GFR measured by 51Cr-EDTA (standard method ) in normal adults. Methods: 101 subjects, aged 38±12 years, 45 (45%) men were evaluated. GFR was measured by single-injection 51Cr-EDTA (GFR 51Cr-EDTA) technique and estimated by the following equations - MDRDo: 186 x serum creatinine-1. 154 x age-0.203 x 0.742 (if female) x 1.210 (if black), and MDRDr, replacing the value 186 by 175 in the equation. Serum creatinine was measured by a non-calibrated Jaffe’s method and transformed into calibrated with the formula: y=1.07x-0.249, previously obtained by regression. The agreement between methods was assessed by the Bland&Altman analyses. Results: The mean GFR 51Cr-EDTA, MDRDr and MDRDo were 105±18, 102±21 and 84±13 ml/min/1, 73 m2, respectively. There was no agreement between 51Cr-EDTA and MDRDo GFR (P <0.001), but it was present between 51Cr-EDTA and MDRDr GFR (P=0.149). Accuracy (percentage of cases of estimated GFR within 15% of measured value) was higher with the use of MDRDr in comparison to MDRDo (57% vs. 35%, P=0.002). Bias (diference between measured and estimated GFR) for 51Cr-EDTA and MDRDr was 3±23 ml/min/1.73 m². For 51Cr-EDTA and MDRDo the bias was significantly higher, 21±18 ml/min/1.73 m². However, the precision, evaluated as standard deviation of bias indicated a huge variation in both cases. Conclusion: The re-expressed MDRD equation, using calibrated creatinine, is a more accurate estimation of GFR than.