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- Lower urinary tract symptoms in women with diabetes mellitus: a current review. [Journal Article]
- Curr Urol Rep 2014 Oct; 15(10):440.
A literature review of the most current publications studying lower urinary tract symptoms (LUTS) and findings in diabetic women was conducted including articles from January 2013 to April 2014. Current reports consistently note that aging and obesity are significantly associated with worsened LUTS in diabetic women. Glucosuria has variable effects on urodynamic parameters and LUTS, but has a significant association with urinary tract infection (UTI) and incontinence at clinically relevant numbers, such as HbA1C values. The presence of severe nocturia in diabetic patients warrants careful surveillance for cardiovascular risks given the significant association with mortality. Diabetics appear to be at higher risk for colonization with the virulent, extended-spectrum, β-lactamase-producing Escherichia coli and Klebsiella species in UTI. Novel therapies in glycemic control and for diabetic bladder dysfunction are undergoing animal model trials with encouraging results. The most promising of these includes stem cell therapy, although a need exists for human studies.
- An uncommon presentation of Sjögren's syndrome and brucellosis. [JOURNAL ARTICLE]
- Transfus Apher Sci 2014 Jul 23.
We describe herein a case of hypokalemia due to proximal renal tubular acidosis (RTA) and Fanconi's syndrome (FS) and nephrogenic diabetes insipidus with DIC - a rare complication of Sjögren's syndrome (SS) and brucellosis. The interesting feature of this case was the presentation with severe hypokalemia, causing acute flaccid quadriparesis with cardiac arrest which is extremely rare. The patient was a 48-year-old woman who suffered cardiopulmonary arrest an hour after hospitalization. Analysis of a blood sample obtained before her cardiopulmonary arrest yielded surprising results: laboratory investigations showed profound hypokalemia (1.1 mEq/L) with renal K wasting, hyperchloremic metabolic acidosis with normal anion gap, hypophosphatemia with hypouricemia, glucosuria, and proteinuria. A diagnosis of RTA and FS were made. On the seventh day, she looked acutely ill, temperature 38.8 °C and pale, and her physical examination revealed purpuric skin lesions on both legs. The serum antibrucella titration agglutination test was found to be 1 of 160 positive with a nosocomial infection. The clinical and laboratory findings were consistent with disseminated intravascular coagulation (DIC). She was unable to concentrate her urine and so a diagnosis of nephrogenic diabetes insipidus (NDI) was reached. A thorough survey for the cause of FS, RTA and NDI revealed that she had xerophthalmia and xerostomia accompanied by high anti-Ro antibody, positive Schirmer test, confirming the diagnosis of SS.
- The role of the kidneys in glucose homeostasis in type 2 diabetes: Clinical implications and therapeutic significance through sodium glucose co-transporter 2 inhibitors. [REVIEW]
- Metabolism 2014 Jul 2.
The kidneys play an important role in regulating glucose homeostasis through utilization of glucose, gluconeogenesis, and glucose reabsorption via sodium glucose co-transporters (SGLTs) and glucose transporters. The renal threshold for glucose excretion (RTG) is increased in patients with type 2 diabetes mellitus (T2DM), possibly due to upregulation of SGLT2 and SGLT1 expression. The resulting increase in renal glucose reabsorption is thought to contribute to the maintenance of hyperglycemia in patients with T2DM. Selective SGLT2 inhibitors reduce the RTG, thereby increasing glucosuria, and have demonstrated favorable efficacy and safety in patients with T2DM inadequately controlled with diet and exercise and other glucose-lowering treatments.
- Novel Antiretroviral Drugs and Renal Function Monitoring of HIV Patients. [JOURNAL ARTICLE]
- AIDS Rev 2014 Aug 7; 16(3)
Chronic kidney disease is a major comorbidity in patients affected by HIV infection. In addition, the introduction of new antiretroviral agents that interact with creatinine transporters is raising some concerns. In this review we analyze the currently available data about three new antiretroviral drugs and one new pharmacokinetic enhancer. Three of them (rilpivirine, cobicistat, dolutegravir) have shown some interactions with renal function, while tenofovir alafenamide fumarate reduces the plasmatic concentration of the parent drug. The future use of tenofovir alafenamide seems to be encouraging in order to reduce the renal interaction of tenofovir. Rilpivirine, cobicistat, and dolutegravir reduce the tubular secretion of creatinine, inducing a decrease of estimated glomerular filtration rate according to creatinine. Rilpivirine and dolutegravir block the uptake of creatinine from the blood, inhibiting organic cation transporter 2, and cobicistat interacts with the efflux inhibiting multidrug and toxin extrusion protein 1. This effect can then be considered a "reset" of the estimated glomerular filtration rate according to creatinine. However, clinicians should carefully monitor renal function in order to identify possible alterations suggestive of a true renal functional impairment. Owing to the interference of these drugs with creatinine secretion, an alternative way of estimation of glomerular filtration rate would be desirable. However, at the moment, other methods of direct glomerular filtration rate measurement have a high impact on the patient, are not readily available, or are not reliable in HIV patients. Consequently, use of classic formulas to estimate glomerular filtration rate is still recommended. Also, tubular function needs to be carefully monitored with simple tests such as proteinuria, phosphatemia, urinary excretion of phosphate, normoglycemic glycosuria, and excretion of uric acid.
- Proximal Renal Tubular Dysfunction Related to Antiretroviral Therapy Among HIV-Infected Patients in an HIV Clinic in Mexico. [JOURNAL ARTICLE]
- AIDS Patient Care STDS 2014 Aug 7.
Abstract Proximal renal tubular dysfunction (PRTD) of varying severity has been associated with antiretroviral toxicity, especially related to the use of tenofovir (TDF). The aim of this study was to investigate whether HIV-infected patients who use a tenofovir-based regimen are at increased risk of tubular dysfunction. We conducted an observational, comparative, longitudinal, prospective study. Estimated glomerular filtration rate (eGFR) and markers of tubular damage to assess tubular dysfunction (fractional excretion of phosphate and uric acid, glycosuria, and proteinuria) were measured at baseline and at weeks 12 and 24. Of 111 participants, PRTD was found in 6.3% at week 12 and 9% at week 24, with no statistically significant difference between those on an abacavir (ABC)-containing regimen or a TDF-containing regimen. We also found an increase in triglycerides associated with the ABC-containing regimen compared with the TDF group. The use of an ABC- or TDF-containing regimen was independently associated with tubular dysfunction, but we found no significant differences between these groups, except when TDF was combined with a protease inhibitor. A better and more complete assessment of renal function is needed, because the presence of tubular dysfunction and proteinuria without impairment of eGFR may affect the renal safety of HIV-infected patients.
- Severe oral and intravenous insecticide mixture poisoning with diabetic ketoacidosis: a case report. [JOURNAL ARTICLE]
- BMC Res Notes 2014 Jul 31; 7(1):485.
The widespread use of pesticides in public health protection and agricultural pest control has caused severe environmental pollution and health hazards, especially in developing countries, including cases of severe acute and chronic human poisoning. Diabetic ketoacidosis is an uncommon manifestation of acute pesticide poisoning. Suicidal pesticide poisoning by injection is also an unusual way to take poison. We report a severe pesticide mixture poisoning case with diabetic ketoacidosis in an adult with improved outcome after supportive treatment and large doses of atropine.A 30-year-old unmarried Moroccan Arab male with a previous history of active polysubstance abuse and behavior disorders had ingested and self injected intravenously into his forearm an unknown amount of a mixture of chlorpyrifos and cypermethrin. He developed muscarinic and nicotinic symptoms with hypothermia, inflammation in the site of the pesticide injection without necrosis. Red blood cell cholinesterase and plasma cholinesterase were very low (<10%). By day 3, the patient developed stroke with hypotension (80/50 mmHg) and tachycardia (143 pulses /min). Laboratory tests showed severe hyperglycemia (4.49 g/dL), hypokaliemia (2.4 mEq/L), glycosuria, ketonuria and low bicarbonate levels (12 mEq/L) with improvement after intensive medical treatment and treatment by atropine.Suicidal poisonings with self-injection of insecticide were rarely reported but could be associated with severe local and systemic complications. The oxidative stress caused by pyrethroids and organophosphates poisoning could explain the occurrence of hyperglycemia and ketoacidosis.
- Renal tight junction proteins are decreased in cisplatin-induced nephrotoxicity in rats. [JOURNAL ARTICLE]
- Toxicol Mech Methods 2014 Aug 11.:1-9.
Abstract Cisplatin (CP) is an antineoplastic agent that induces nephrotoxicity and oxidative stress. It is unknown whether renal tight junction (TJ) proteins expression and localization are modified in CP-induced nephrotoxicity. Objective: To study if the expression of the TJ proteins occludin, claudin-2, claudin-5 and zonula occludens-1 (ZO-1) is modified in rats with CP-induced nephrotoxicity. Materials and methods: Male Wistar rats (n = 5/group) were injected with saline solution (V group), and the other group (CP group) was injected with a single dose of saline solution and CP (7.5 mg/kg i.p.). Rats were sacrificed 72 h after CP injection and blood, and 24-h urine samples were collected. Several plasma and urinary injury biomarkers as well as renal histopathology lesions, oxidative and nitrosative stress markers were evaluated, and protein levels of ocludin, claudin-2, claudin-5, ZO-1 were measured by Western blot. Statistically significant changes noted with different p < 0.05 versus V. Results: Nephrotoxicity was evident by histological alterations, glycosuria, decrease in creatinine clearance, increase in fractional excretion of sodium, serum creatinine and kidney injury molecule-1. These changes were associated with oxidative/nitrosative stress (increased renal abundance of 3-nitrotyrosine and protein kinase Cβ2 and decreased renal expression of nuclear factor-erythroid-2-related factor 2) and decreased activity of antioxidant enzymes. Finally, it was found that CP-induced renal damage was associated with decreased renal expression of occludin and claudin-2. Discussion and conclusion: CP altered the TJ proteins expression and localization in the proximal tubule that was associated with oxidative/nitrosative stress.
- SGLT2 inhibitor lowers serum uric acid through alteration of uric acid transport activity in renal tubule by increased glycosuria. [JOURNAL ARTICLE]
- Biopharm Drug Dispos 2014 Jul 7.
Sodium glucose cotransporter 2 (SGLT2) inhibitors have been reported to lower the serum uric acid (SUA) level. To elucidate the mechanism responsible for this reduction, we analyzed SUA and the urinary excretion rate of UA (UEUA ) after the oral administration of luseogliflozin, an SGLT2 inhibitor, to healthy subjects. After dosing, SUA decreased, and a negative correlation was observed between the SUA level and the UEUA , suggesting that SUA decreased as a result of the increase in the UEUA . The increase in UEUA was correlated with an increase in urinary D-glucose excretion, but not with the plasma luseogliflozin concentration. Additionally, in vitro transport experiments showed that luseogliflozin had no direct effect on the transporters involved in renal UA reabsorption. To explain that the increase in UEUA is likely due to glycosuria, we focused on the facilitative glucose transporter 9 isoform 2 (GLUT9ΔN, SLC2A9b), which is expressed at the apical membrane of the kidney tubular cells and transports both UA and D-glucose. We observed that the efflux of [(14) C]UA in Xenopus oocytes expressing GLUT9 isoform 2 was trans-stimulated by 10 mM D-glucose, a high concentration of glucose that existed under SGLT2 inhibition. On the other hand, uptake of [(14) C]UA by oocytes was cis-inhibited by 100 mM D-glucose, a concentration assumed to exist in collecting ducts. In conclusion, it was demonstrated that the UEUA could be potentially increased by luseogliflozin-induced glycosuria, with alterations of UA transport activity because of urinary glucose. This article is protected by copyright. All rights reserved.
- New Treatments for Type 2 Diabetes: Cardiovascular Protection Beyond Glucose Lowering? [REVIEW]
- Heart Lung Circ 2014 Jun 10.
The health burden of type 2 diabetes mellitus (T2DM) is increasing worldwide, with a substantial portion of this burden being due to the development of cardiovascular (CV) disease. Multiple individual randomised clinical trials of intensive versus conventional glucose control, based on the use of traditional oral hypoglycaemic agents, have failed to convincingly show that intensive glucose control significantly reduces CV disease outcomes. In recent times, two new approaches to lowering glucose levels have become available. One targets the "incretin effect" which involves the modulation of peptide hormones that normally regulate glucose levels when nutrients are given orally. The other approach is based on inhibiting the sodium-glucose co-transporter 2 (SGLT-2) in the tubules of the kidney to promote glycosuria. Incretin-based therapies, especially glucagon-like peptide-1 receptor analogues, reduce glucose levels, with a low risk of hypoglycaemia, by increasing insulin secretion, inhibiting glucagon release and increasing satiety. Clinical and experimental studies have also shown favourable effects on CV disease risk factors such as dyslipidaemia, blood pressure, and improvements in endothelial function and cardiac contractility. Similarly, SGLT-2 inhibitors reduce glucose levels with a low risk for hypoglycaemia and have positive effects on multiple CV disease risk factors. Whether the beneficial effects of these new glucose lowering approaches on surrogate markers of CV disease risk translates to an improvement in CV events remains unknown. Several CV outcome trials are currently being performed to show that at a minimum, these novel glucose lowering agents are safe, but also have positive CV benefits.
- Supplemental iron intake and the risk of glucose intolerance in pregnancy: re-analysis of a randomised controlled trial in Finland. [JOURNAL ARTICLE]
- Matern Child Nutr 2014 Jul 4.
Observational studies suggest that high iron intake during pregnancy is associated with the risk of gestational diabetes. As such studies are prone to bias, we re-analysed data from a randomised controlled trial of iron supplementation to see whether it supports the risk found in observational studies. The trial was conducted in primary health care setting in five municipalities in Finland in 1985-1986. The participants were 2944 women (95% of pregnant women in the area) who were randomly allocated either to (1) the selective iron group (elemental iron 50 mg twice a day only if diagnosed as anaemic, continuing until their haemoglobin increased to 110 g L(-1) ) or (2) the routine iron group (elemental iron 100 mg day(-1) throughout the pregnancy regardless of haemoglobin level). The numbers of women in the analyses were 1358 and 1336, respectively. The main outcome measure was a composite variable including any glucose intolerance-related outcome (e.g. glucosuria, gestational diabetes, large-for-gestational-age child) in mothers' or children's patient records during pregnancy and post-partum. There were no statistically significant differences in the incidence of the primary outcome between the selective iron and the routine iron groups (13.0 vs. 11.0%, P = 0.12). The most common outcome was large-for-gestational-age calculated from children's hospital data (8.3 vs. 8.2%, P = 0.95). The results were mainly similar when stratified by the mothers' baseline haemoglobin level, body mass index or gestational weight gain. Routine iron supplementation throughout pregnancy did not increase the risk of glucose intolerance during pregnancy. The results need to be confirmed in future trials.