Arsenic-mediated nephrotoxicity.

Chronic kidney disease (CKD) is an important global health problem that affects 8-15% of the population according to epidemiological studies done in different countries. Essential to prevention is the knowledge of the environmental factors associated with this disease, and heavy metals such as lead and cadmium are clearly associated with kidney injury and CKD progression. Arsenic is one of the most abundant contaminants in water and soil, and many epidemiological studies have found an association between arsenic and type 2 diabetes mellitus, hypertension and cancer; however, there is a scarcity of epidemiological studies about its association with kidney disease, and the evidence linking urinary arsenic excretion with CKD, higher urinary excretion of low molecular proteins, albuminuria or other markers of renal in injury is still limited, and more studies are necessary to characterize the role of arsenic on renal injury and CKD progression. Global efforts to reduce arsenic exposure remain important and research is also needed to determine whether specific therapies are beneficial in susceptible populations.

Tubular dysfunction and non-albuminuric renal disease in subjects with type 2 diabetes mellitus.

INTRODUCTION: Micro-albuminuria is considered an early marker of glomerular injury in patients with diabetes but it has yet to be determined whether testing for markers of tubular injury can also identify people who are at risk of progressive renal disease. OBJECTIVE: To evaluate markers of tubular injury and renal characteristics in a sample of community treated type 2 diabetic subjects. MATERIAL AND METHODS: We carry-out an assessment of a group of community diabetic patients, anthropometric measures, creatinine clearance, HbA1c, lipid profile, the mean fast serum glucose levels, albuminuria and α1-microglobulin (α1M) urine excretion were evaluated. RESULTS: From 95 included patients, 45.2% had α1M urinary excretion ≥ 10 µg/gCr, 23.1% micro-albuminuria, 9.6% macroalbuminuria and 27.2% had a GFR < 60 mL/min. The most important risk factor associated with a1M excretion was fasting glucose level (OR 4.3, 95IC 1.7-11.1 p = 0.001); HbA1c ≥ 8% and age were the most important risk factors associated with GFR ≤ 60 mL/min. Most of patients had uncontrolled glucose levels and 45.1% patients with albuminuria were not receiving any drug with anti-proteinuric effects. CONCLUSIONS: Fasting glucose levels was the most important risk factor associated with tubular dysfunction; non-albuminuric presentation of CKD defined as GFR < 60 mL/min was frequent in our population, so is necessary to implement different strategies for surveillance in patients with type 2 diabetes aiming to delay progression to CKD.

[Brief history of lead poisoning: from Egyptian civilization to the Renaissance]. / Breve historia de la intoxicación por plomo: de la civilización egipcia hasta el Renacimiento

The exposition to lead in the Antiquity is one of the first environmental health risks in the history of the mankind. In the ancient cultures of Egypt, Crete and Sumer there was no reports of an important exposition to this metal. The first clinical data is described in the Corpus Hipocraticcus, however was Nicandrus of Colophon the first to make a thorough description of the clinical manifestations of this disease. There was an increase in the exposition to this metal in times of the Roman empire and even some researchers propose that Julius Cesar and Octavio had clinical manifestations associated with lead poisoning. Paul of Aegina in the 7th century (a.C.) describes the first epidemic associated with lead intoxication, however in the Middle Ages the use of lead decrease until the Renaissance period in which lead poisoning affects mostly painters, metal-smithers and miners. Some studies done in the ice-layers of Greenland showed that the environmental pollution by lead during the Roman empire and the Renaissance was important.

Prevalence of thyroid function test abnormalities and anti-thyroid antibodies in an open population in Central México.

OBJECTIVE. To examine the prevalence of abnormal thyroid function tests and positive anti-thyroid antibodies in two Central Mexican cities. MATERIAL AND METHODS. Subjects 18 to 70 years old were randomly selected to participate in this survey. A questionnaire was given and blood samples were taken to measure TSH and free T4 levels as well as anti-TPO and anti- Tg antibodies. RESULTS. The mean TSH level in subjects without existing thyroid disease was 1.72 mIU/L; 0.64 and 3.74 mIU/L were the 2.5th and 97.5th percentiles. The mean free T4 level was 1.02 ng/dL, and the 2.5th and 97.5th percentiles were 0.78 and 1.31 ng/dL, respectively. There was a 2.5% prevalence of former diagnosed thyroid diseases, 3.9% of individuals were sub-hypo, and 1.1% had overt hypothyroidism. Total hypothyroidism prevalence was 7.48% (when we considered TSH levels greater than 4.5 mIU/L), but it was 11.03% when diagnosed with TSH values greater than 3.5 mIU/L. Factors associated with hypothyroidism were older age, positive family background of thyroid disease, and positive anti- TPO and anti-Tg antibodies. Subclinical and overt hyperthyroidism were found in 1.7% of participants. CONCLUSIONS. Abnormal thyroid function test prevalence in this population was high, but few participants were aware of having a thyroid disease. The prevalence of positive anti-thyroid antibodies was high. More studies are necessary to elucidate the effects of thyroid abnormalities on other aspects of health status and quality of life.

Point of care ultrasonography as the new "Laennec Sthetoscope".

Point of care ultrasonography (POCUS) has evolved to become the fifth pillar of the conventional physical examination, and use of POCUS protocols have significantly decreased procedure complications and time to diagnose. However, lack of experience in POCUS by preceptors in medical schools and nephrology residency programs are significant barriers to implement a broader use. In rural and low-income areas POCUS may have a transformative effect on health care management.

Appendicular Muscle Mass Index as the Most Important Determinant of Bone Mineral Content and Density in Small for Gestational Age Children.

Preterm small for gestational age (SGA) children are at increased risk for low bone mineral content later in life; however, data on SGA children born at term are scarce. We included 44 SGA and 57 adequate for gestational age (AGA) children aged 6 to 11 years to compare bone mineral density (BMD) and bone mineral content (BMC) and to identify which anthropometric and biochemical values influence bone mineralization in these children. Fat mass, appendicular skeletal muscle mass index (ASMMI), BMC, and BMD were significantly lower in SGA children than in AGA (P ≤ .005). Appendicular muscle mass index correlated with BMC(TBLH,FN,L1-L4) and BMD(TBLH,FN,L1-L4) in both groups (r2 = 0.7, P < .05). In multivariate analysis, ASMMI was strongly associated with BMC and BMD in both groups. There were no differences in clinical biomarkers, calcium intake, and physical activity between the groups. Achieving adequate muscle mass contributes to adequate bone mineralization and a lower risk for low BMC and BMD in SGA children.

Tight junction disruption and the pathogenesis of the chronic complications of diabetes mellitus: A narrative review.

The chronic complications of diabetes mellitus constitute a major public health problem. For example, diabetic eye diseases are the most important cause of blindness, and diabetic nephropathy is the most frequent cause of chronic kidney disease worldwide. The cellular and molecular mechanisms of these chronic complications are still poorly understood, preventing the development of effective treatment strategies. Tight junctions (TJs) are epithelial intercellular junctions located at the most apical region of cell-cell contacts, and their main function is to restrict the passage of molecules through the paracellular space. The TJs consist of over 40 proteins, and the most important are occludin, claudins and the zonula occludens. Accumulating evidence suggests that TJ disruption in different organs, such as the brain, nerves, retina and kidneys, plays a fundamental pathophysiological role in the development of chronic complications. Increased permeability of the blood-brain barrier and the blood-retinal barrier has been demonstrated in diabetic neuropathy, brain injury and diabetic retinopathy. The consequences of TJ disruption on kidney function or progression of kidney disease are currently unknown. In the present review, we highlighted the molecular events that lead to barrier dysfunction in diabetes. Further investigation of the mechanisms underlying TJ disruption is expected to provide new insights into therapeutic approaches to ameliorate the chronic complications of diabetes mellitus.

The biology of epithelial cell tight junctions in the kidney.

Nearly 50 years have lapsed since the tight junction between epithelial cells was first identified by electron microscopy. The tight junction was once viewed as a static structure providing a barrier to paracellular movement and restricting proteins to the apical or basolateral membrane. Recent insights into the molecular composition of tight junctions reveal surprising complexity and dynamic regulation. Epithelia along the nephron exemplify a diversity of tight junctions that contribute to more than a 100-fold difference in permeability from the proximal tubule to the collecting duct. Tight junctions along the nephron form during kidney development and must reassemble after tubular injury. Hereditary diseases, animal models, and cell culture studies provide a variety of new perspectives on the function of tight junctions in health and disease.

Urinary arsenic levels and risk of renal injury in a cross-sectional study in open population.

INTRODUCTION: Arsenic (As) is one of the most ubiquitous elements in nature, and a prolonged exposure has been associated with an increase in the risk of cancer, diabetes mellitus, hypertension and cardiovascular disease. There are few studies addressing the effects of As on albuminuria, tubular injury and biochemical variables as uric acid. AIM. To analyze the association between urinary As levels, albuminuria, and al-microglobulin as marker of tubular injury. MATERIAL AND METHODS: This is a cross-sectional, and comparative study done in 5 communities localized close to Queretaro City. Subjects with no antecedents of renal disease, diabetes, hypertension, or industrial exposure to As were included. A questionnaire about risk factors for arsenic exposure was done, blood was taken for biochemical analysis and a spot urine sample was collected for albumin, alpha1-microglobulin, and As measurements. RESULTS: A total of 90 adult persons were included with no antecedents of renal disease, diabetes or hypertension; the mean age was 40.9 +/- 12.9 years and the median for urinary As levels was 15 microg/gr Cr (range 0.56-89.2 microg/gr Cr), 10 (11.1%) persons had critical levels > 50 microg/gr Cr. Age more than 50 years old [OR 2.48 IC95 (0.9-6.6)] and place of residence were the most important risk factors associated with higher levels of As. There was association between urinary As levels and al-microglobulin urinary excretion (r2 = 0.07, p = 0.01) but not with albuminuria or other biochemical variables. CONCLUSIONS: This is the first study in Mexico to show an association between As and urinary excretion of al-microglobulin as marker of early renal injury. We did not found association with albuminuria or other serum biochemical variables. Arsenic may be considered as a risk factor for tubular injury.

Liposoluble vitamins A and E in kidney disease.

Kidney disease (KD) is characterized by the presence of elevated oxidative stress, and this is postulated as contributing to the high cardiovascular morbidity and mortality in these individuals. Chronic KD (CKD) is related to high grade inflammatory condition and pro-oxidative state that aggravates the progression of the disease by damaging primary podocytes. Liposoluble vitamins (vitamin A and E) are potent dietary antioxidants that have also anti-inflammatory and antiapoptotic functions. Vitamin deficits in CKD patients are a common issue, and multiple causes are related to them: Anorexia, dietary restrictions, food cooking methods, dialysis losses, gastrointestinal malabsorption, etc. The potential benefit of retinoic acid (RA) and α-tocopherol have been described in animal models and in some human clinical trials. This review provides an overview of RA and α tocopherol in KD.

Neuroimmunoendocrine Link Between Chronic Kidney Disease and Olfactory Deficits.

Chronic kidney disease (CKD) is a multifactorial pathology that progressively leads to the deterioration of metabolic functions and results from deficient glomerular filtration and electrolyte imbalance. Its economic impact on public health is challenging. Mexico has a high prevalence of CKD that is strongly associated with some of the most common metabolic disorders like diabetes and hypertension. The gradual loss of kidney functions provokes an inflammatory state and endocrine alterations affecting several systems. High serum levels of prolactin have been associated with CKD progression, inflammation, and olfactory function. Also, the nutritional status is altered due to impaired renal function. The decrease in calorie and protein intake is often accompanied by malnutrition, which can be severe at advanced stages of the disease. Nutrition and olfactory functioning are closely interconnected, and CKD patients often complain of olfactory deficits, which ultimately can lead to deficient food intake. CKD patients present a wide range of deficits in olfaction like odor discrimination, identification, and detection threshold. The chronic inflammatory status in CKD damages the olfactory epithelium leading to deficiencies in the chemical detection of odor molecules. Additionally, the decline in cognitive functioning impairs the capacity of odor differentiation. It is not clear whether peritoneal dialysis and hemodialysis improve the olfactory deficits, but renal transplants have a strong positive effect. In the present review, we discuss whether the olfactory deficiencies caused by CKD are the result of the induced inflammatory state, the hyperprolactinemia, or a combination of both.

Nephroprotective Plants: A Review on the Use in Pre-Renal and Post-Renal Diseases.

Kidney diseases are expected to become the fifth leading cause of death by 2040. Several physiological failures classified as pre-, intra-, and post-renal factors induce kidney damage. Diabetes, liver pathologies, rhabdomyolysis, and intestinal microbiota have been identified as pre-renal factors, and lithiasis or blood clots in the ureters, prostate cancer, urethral obstructions, prostate elongation, and urinary tract infections are post-renal factors. Additionally, the nephrotoxicity of drugs has been highlighted as a crucial factor inducing kidney injuries. Due to the adverse effects of drugs, it is necessary to point to other alternatives to complement the treatment of these diseases, such as nephroprotective agents. Plants are a wide source of nephroprotective substances and can have beneficial effects in different levels of the physiological pathways which lead to kidney damage. In traditional medicines, plants are used as antioxidants, anti-inflammatories, diuretics, and anticancer agents, among other benefits. However, the mechanism of action of some plants empirically used remains unknown and scientific data are required to support their nephroprotective effects. The present work reviewed the plants with a beneficial effect on kidney diseases. The classification of nephroprotective plants according to the clinical definition of pre-renal, intrinsic, and post-renal factors is proposed to orient their use as complementary treatments.

Chronic kidney disease and the olfactory system. / Enfermedad renal crónica y olfato.

Alterations in the sense of smell (dysosmia, anosmia, hyposmia) are frequently experienced by patients with chronic kidney disease. However, currently, the aetiology and consequences are poorly understood, with no effective treatments available to address such impairment. In general, the capacity of olfactory perception is affected in patients with chronic kidney disease (even in those who have not undergone dialysis therapy), and whether these alterations improve after dialysis is disputed. Patients in peritoneal dialysis and haemodialysis have the same olfactory perception defects. Kidney transplantation improves olfactory perception, and one important consequence of such impairment is the potential impact on the patient's nutritional status.

Cell-cell interactions in the kidney: inducible expression of mutant G protein alpha-subunits in Madin-Darby canine kidney cells for studies of epithelial cell junction structure and function.

Disrupted epithelial cell junctions are a hallmark of numerous disease processes. The signaling mechanisms regulating barrier function and re-establishment of intact junctions after injury and during development are complex and tightly regulated. We have shown that heterotrimeric G proteins regulate assembly and maintenance of epithelial cell barrier in cultured Madin-Darby canine kidney (MDCK) cells. The inducible expression of mutant signaling molecules (constitutively active or dominant negative) in polarized cells is a useful strategy for elucidating the role(s) for specific proteins. Using tetracycline-off inducible expression of wild-type and constitutively active Galpha12, we have demonstrated a fundamental role for Galpha12 in regulating the junction of MDCK cells. Inducible expression permits the comparison of the identical cell line in the presence and absence of the protein of interest and minimizes variation arising from distinct clones. The methods described here are applicable to virtually any protein that may regulate maintenance or assembly of the epithelial cell junctional complex.

[Molecular physiopathology of Bartter's syndrome]. / Fisiopatología molecular del síndrome de Bartter.

Bartter's syndrome is an autosomic recessive disease characterized by hypokalemic metabolic alkalosis accompanied with hypercalciuria, polyuria and hypotension due to volume depletion. The pathophysiology of this hereditary disease was largely unknown until the last few years in which inactivating mutations in up to five different genes have been shown to produce or be associated with the development of this syndrome. All the involved proteins are expressed either in the apical or basolateral membrane of the thick ascending limb of Henle's loop. These clinical and molecular findings have increased our understanding of the Bartter's disease and also of the thick ascending limb physiology.

[Early referral to the nephrologist: impact on initial hospitalization and the first 6 months of continuous ambulatory peritoneal dialysis]. / Referencia temprana al nefrólogo: impacto sobre la hospitalización inicial y los seis primeros meses en diálisis peritoneal continua ambulatoria.

BACKGROUND: The prognosis and outcome in patients with end stage renal disease is significantly related to the predialysis care and early or late nephrological referral. Late nephrological referral has been associated with more hospital admissions and mortality at six months after the dialysis was initiated. We lack information about the role of early nephrological referral and its impact in biochemical variables and first hospitalization in our country. METHODS: The charts of all patients that were admitted to peritoneal dialysis in the period 01/1999-06/2001 were reviewed. We divided the population in group A with patients referred to nephrologist more than 3 months before the start of dialysis (early referral) and group B with those patients referred for a period shorter than three months or no referred before the start of dialysis (late referral or no referral). The patient's characteristics, laboratory values, characteristics of the first hospitalization and drugs were analyzed when dialysis was initiated and after six months of follow-up. RESULTS: Patients in group A were older and the percentage of patients with diabetes and hypertension was higher. The patients with early referral started dialysis with higher levels of hemoglobin (9.2 vs. 8.3 g/dL, p = 0.01) and with lower serum levels of BUN (91 vs. 122.5 mg/dL, p = 0.0001), creatinine (8.4 vs. 12.8 mg/dL, p = 0.0002) and phosphorus (6.4 vs. 7.7 mg/dL, p = 0.01). The length of the first hospitalization was shorter in patients of Group A (5.7 vs. 10.5 days, p = 0.004) and the emergency department was less used to peritoneal catheter placement in this group (46.3 vs. 86.9%, p = 0.01). There were not differences in hospitalization between the two groups after six months. CONCLUSION: Patients with early referral to a nephrologist show better biochemical variables, shorter first hospitalization length and higher percentage of elective placement of catheter.

Renal health and the environment: heavy metal nephrotoxicity.

We currently recognise that environmental toxins such as cadmium, lead, and arsenic play a significant role in the development of chronic renal failure. Epidemiological studies have shown a strong association between exposure to these metals and the presence of chronic kidney injury. The physiopathological mechanisms behind metal-induced kidney injury are complex, and some aspects of their metabolism and damage mechanisms remain unknown. This review aims to analyse the physiopathological mechanisms of kidney injury due to cadmium, lead and arsenic.