Miriam Alvo

Effect of a Simultaneous Potassium and Carbohydrate Load on Extrarenal K Homeostasis in End-Stage Renal Failure

Patients with chronic renal failure (CRF) are continuously exposed to hyperkalemia. In these patients the extrarenal disposal of a potassium load may be very important to determine the plasma potassium levels. We studied the effect of a combined oral load of potassium (0.5 mEq/kg body weight) and carbohydrate (0.5 g/kg body weight) to mimic normal ingestion of potassium. Eight CRF patients and 5 control subjects were studied. The maximal increase in plasma potassium levels achieved was significantly higher in the patients (1.07 +/- 0.1 mEq/l) than in controls (0.39 +/- 0.05 mEq/l). Basal insulin levels were higher in the CRF patients and increased with the oral potassium and carbohydrate load in both controls and patients. In the CRF patients only 58.9 +/- 3% of the potassium load was translocated to the intracellular space compared to 81 +/- 6% in the controls. No correlation was found between the acid base status and maximal potassium increase. We conclude that patients with CRF exhibit an impaired extrarenal handling of potassium and that this abnormality does not appear to be related to insulin secretion or acid base status.

Enfermedad renal crónica: Clasificación, identificación, manejo y complicaciones

The key messages of these guidelines on chronic kidney disease are: • Chronic kidney disease (CKD) is a public health problem due to its wide distribution, high rate of complications and cost. • CKD is a common condition, its prevalence being about 10%, and is treatable if it is detected on time. • A patient with CKD has a higher risk of cardiovascular mortality than of progression of its underlying renal disease. • A new definition of CKD, based on estimated Glomerular Filtration Rate (eGFR) and kidney damage, facilitates its detection and management. • CKD is detected with three simple tests: 1) Blood pressure measurement, 2) Detection of proteinuria or albuminuria in an isolated urine sample, and 3) Estimation of renal function (eGFR), based on serum creatinine, age, gender and race. • The CKD risk groups are individuais with diabetes, hypertension and a family history of renal disease. • The most cost-effective measures are to detect and treat diabetic and hypertensive patients in the community. • Therapy must emphasize the maximal reduction of cardiovascular risk. • The complications of CKD such as anemia and renal osteodystrophy can be identified and treated on time. • Most patients with chronic kidney disease are detected in the community, therefore their initial care must be organized at the level of primary care, along with programs for hypertension and diabetes

Outbreak of Paecilomyces variotii Peritonitis in Peritoneal Dialysis Patients after the 2010 Chilean Earthquake

Fungal peritonitis (FP) accounts for 3 - 6% of all peritonitis episodes in chronic peritoneal dialysis (PD), being associated with high morbidity and mortality. Mortality rates are in the range of 15 - 50%, and loss of the peritoneal membrane function can be over 40% (1). The most common cause of the disease is Candida species (C. albicans, C. parapsilosis, C. glabrata). Other yeasts and filamentous fungi such as Aspergillus, Paecilomyces, Penicillium, and Zygomycetes are found less frequently. The strongest risk factors for FP in PD patients are prolonged use of antibiotics and previous bacterial peritonitis (2). Other suggested risk factors are immunosuppression, malnutrition, bowel perforation, diverticulitis, and, possibly, certain comorbidities such as diabetes or neoplastic diseases (1). Paecilomyces spp is a filamentous fungus like the genus Penicillium and Aspergillus. It is found in soil and water and is one of the main dwellers of house dust. It is rarely associated with human infections. When a disease does occur, it is more often related to foreign bodies or immunosuppressed patients (3,4). After the earthquake of February 27, 2010, in Chile, there was an increase in the rate of FP from 1% to 6%, due to the appearance of 6 cases caused by Paecilomyces variotti (5). Here we describe the clinical characteristics and outcomes of 3 of these patients. Although there was no proof of the precise route of infection in our patients, in all 3 cases there was a major alteration in the storage of the PD fluid bags, resulting especially in exposure to excessive dust and destruction of the architecture of the storage holds. It is quite possible that in the context of a natural disaster like a big earthquake, the risk of infections associated with this fungus could increase because of the excessive dust in the environment.

Diabetes y hemodiálisis. Caracterización de una cohorte y seguimiento a cuatro años

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% had to enter dialysis as an emergency. Mean glycosilated hemoglobin was 7.7% and 58% 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 inverted exclamation markate to the nephrologist, the dialysis dose is insufficient and they have a high mortality.

Vitamin B12 deficiency is associated with geographical latitude and solar radiation in the older population.

BACKGROUND Vitamin B12 and folic acid deficiency are common in the older and are associated with several conditions including anaemia, cardiovascular disease, cognitive impairment and cancer. Evidence from in vitro studies suggests that solar radiation can degrade both vitamins in the skin. Chile is the longest country in the world running perfectly North-South making it an ideal place to study potential associations of latitude and solar radiation on vitamin B12 and folic acid deficiency. OBJECTIVES The objective was to examine the association between vitamin B12 and folic acid deficiencies and latitude. METHODS Plasma samples were collected from Chileans aged 65+ years (n=1013) living across the whole country and assayed for vitamin B12 and folic acid concentrations as part of the Chilean Health Survey 2009-2010, which is a national representative sample study. RESULTS Overall, the prevalence of vitamin B12 deficiency was 11.3%, with the prevalence in the North of the country being significantly greater than in the Central and South zones (19.1%,10.5%, and 5.7%, respectively; P<0.001). The prevalence of folic acid deficiency in the whole cohort was 0.7% with no difference between the 3 geographical zones. Using logistic regression analyses, vitamin B12 deficiency was significantly associated with geographical latitude (OR 0.910 [95% confidence intervals 0.890-0.940], P<0.001) and solar radiation (OR 1.203 [95% confidence intervals 1.119-1.294], P<<0.001). These associations persisted after adjustments for confounders (OR 0.930, P<0.001 and 1.198, P=0.002, respectively). CONCLUSIONS In the Chilean population of 65+, the prevalence of vitamin B12 deficiency is associated with living closer to the Equator and solar radiation. Although degradation by solar radiation might explain this observation, further work is required to establish the potential mechanisms. In countries that routinely fortify food with folic acid, efforts to identify vitamin B12 deficiency might be more cost-efficiently targeted in areas closest to the Equator.

Associations of Blood Pressure With Geographical Latitude, Solar Radiation, and Ambient Temperature: Results From the Chilean Health Survey, 2009–2010

Mean blood pressure and the prevalence of hypertension vary widely throughout the world (1). Geographical latitude has been cited as a possible explanation for this variance (2– 5), with increasing distance from the equator being associated with higher blood pressures. However, these statements are often not referenced (3) or refer to data from a post-hoc analysis of the International Study of Sodium, Potassium, and Blood Pressure (INTERSALT) (2, 4), which was published as a hypothesis paper in which the authors did not adequately report the methodology so as to allow others to assess the validity of the results (6). In other studies in which similar findings were reported, the differences observed were either explained by factors such as salt intake (7) or were confounded by other significant differences in characteristics such as renal function, diabetes prevalence, lifestyle, and diet (8–12). Ambient temperature and number of daylight hours have also been reported to affect blood pressure and the prevalence of hypertension (13–15). Chile is the longest country in theworld; it runs almost perfectly north to south for 4,250 km (Web Figure 1, available at http://aje.oxfordjournals.org/). It also has a genetically homogeneous population. These factors combined make it an ideal country in which to study the associations of latitude, solar radiation, and ambient temperature with blood pressure (16–19).

Recomendaciones sobre el manejo del compromiso renal del lupus eritematoso sistémico: Documento de Consenso de las Sociedades Chilenas de Nefrología y Reumatología

Renal involvement affects over one half of patients with Systemic Lupus Erythematosus increasing their mortality and morbidity, including chronic renal disease and the need of renal replacement therapies. Aiming to achieve a consensus in the most relevant topics on diagnosis, therapy and follow-up of patients with lupus renal disease, the Chilean Societies of Nephrology and Rheumatology constituted a workgroup that, based on a critical review of the available literature and their experience, raised and answered by consensus a set of relevant questions. This document includes aspects related to the clinical diagnosis, the importance of a suitable histological classification, therapeutic alternatives to induce and maintain disease remission, strategies for follow-up, additional therapies and gynecological-obstetric issues.Renal involvement affects over one half of patients with Systemic Lupus Erythematosus increasing their mortality and morbidity, including chronic renal disease and the need of renal replacement therapies. Aiming to achieve a consensus in the most relevant topics on diagnosis, therapy and follow-up of patients with lupus renal disease, the Chilean Societies of Nephrology and Rheumatology constituted a workgroup that, based on a critical review of the available literature and their experience, raised and answered by consensus a set of relevant questions. This document includes aspects related to the clinical diagnosis, the importance of a suitable histological classification, therapeutic alternatives to induce and maintain disease remission, strategies for follow-up, additional therapies and gynecological-obstetric issues.

Analysis of the intronic single nucleotide polymorphism rs#466452 of the nephrin gene in patients with diabetic nephropathy

We present the analysis of an intronic polymorphism of the nephrin gene and its relationship to the development of diabetic nephropathy in a study of diabetes type 1 and type 2 patients. The frequency of the single nucleotide polymorphism rs#466452 in the nephrin gene was determined in 231 patients and control subjects. The C/T status of the polymorphism was assessed using restriction enzyme digestions and the nephrin transcript from a kidney biopsy was examined. Association between the polymorphism and clinical parameters was evaluated using multivariate correspondence analysis. A bioinformatics analysis of the single nucleotide polymorphism rs#466452 suggested the appearance of a splicing enhancer sequence in intron 24 of the nephrin gene and a modification of proteins that bind to this sequence. However, no change in the splicing of a nephrin transcript from a renal biopsy was found. No association was found between the polymorphism and diabetes or degree of renal damage in diabetes type 1 or 2 patients. The single nucleotide polymorphism rs#466452 of the nephrin gene seems to be neutral in relation to diabetes and the development of diabetic nephropathy, and does not affect the splicing of a nephrin transcript, in spite of a splicing enhancer site.

A pilot study on genetic variation in purine-rich elements in the nephrin gene promoter in type 2 diabetic patients

Diabetic nephropathy (DN) is one of the major complications of type 2 diabetes and is associated with coronary disease. Nephrin, a protein mainly expressed in glomeruli, is decreased in DN and other kidney diseases. Since insulin levels are misregulated in type 2 diabetes, a possible connection between DN and its decreased nephrin expression could be the presence of regulatory elements responsive to insulin in the nephrin gene (NPHS1) promoter region. In this work, using bioinformatic tools, we identified a purine-rich GAGA element in the nephrin gene promoter and conducted a genomic study in search of the presence of polymorphisms in this element and its possible association with DN in type 2 diabetic patients. We amplified and sequenced a 514 bp promoter region of 100 individuals and found no genetic variants in the purine-rich GAGA-box of the nephrin gene promoter between groups of patients with diabetes type 2 with and without renal and coronary complications, control patients without diabetes and healthy controls.

Human peritoneal mesothelial cell death induced by high-glucose hypertonic solution involves Ca2+ and Na+ ions and oxidative stress with the participation of PKC/NOX2 and PI3K/Akt pathways

Chronic peritoneal dialysis (PD) therapy is equally efficient as hemodialysis while providing greater patient comfort and mobility. Therefore, PD is the treatment of choice for several types of renal patients. During PD, a high-glucose hyperosmotic (HGH) solution is administered into the peritoneal cavity to generate an osmotic gradient that promotes water and solutes transport from peritoneal blood to the dialysis solution. Unfortunately, PD has been associated with a loss of peritoneal viability and function through the generation of a severe inflammatory state that induces human peritoneal mesothelial cell (HPMC) death. Despite this deleterious effect, the precise molecular mechanism of HPMC death as induced by HGH solutions is far from being understood. Therefore, the aim of this study was to explore the pathways involved in HGH solution-induced HPMC death. HGH-induced HPMC death included influxes of intracellular Ca2+ and Na+. Furthermore, HGH-induced HPMC death was inhibited by antioxidant and reducing agents. In line with this, HPMC death was induced solely by increased oxidative stress. In addition to this, the cPKC/NOX2 and PI3K/Akt intracellular signaling pathways also participated in HGH-induced HPMC death. The participation of PI3K/Akt intracellular is in agreement with previously shown in rat PMC apoptosis. These findings contribute toward fully elucidating the underlying molecular mechanism mediating peritoneal mesothelial cell death induced by high-glucose solutions during peritoneal dialysis.