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- Hyperosmolar Hyperglycemic State: A Historic Review of the Clinical Presentation, Diagnosis, and Treatment. [REVIEW]
- Diabetes Care 2014 Nov; 37(11):3124-3131.
The hyperosmolar hyperglycemic state (HHS) is the most serious acute hyperglycemic emergency in patients with type 2 diabetes. von Frerichs and Dreschfeld described the first cases of HHS in the 1880s in patients with an "unusual diabetic coma" characterized by severe hyperglycemia and glycosuria in the absence of Kussmaul breathing, with a fruity breath odor or positive acetone test in the urine. Current diagnostic HHS criteria include a plasma glucose level >600 mg/dL and increased effective plasma osmolality >320 mOsm/kg in the absence of ketoacidosis. The incidence of HHS is estimated to be <1% of hospital admissions of patients with diabetes. The reported mortality is between 10 and 20%, which is about 10 times higher than the mortality rate in patients with diabetic ketoacidosis (DKA). Despite the severity of this condition, no prospective, randomized studies have determined best treatment strategies in patients with HHS, and its management has largely been extrapolated from studies of patients with DKA. There are many unresolved questions that need to be addressed in prospective clinical trials regarding the pathogenesis and treatment of pediatric and adult patients with HHS.
- Amyloid A amyloidosis with subcutaneous drug abuse. [Journal Article]
- J Renal Inj Prev 2014; 3(1):11-6.
Amyloid A (AA) amyloidosis is a systemic form of amyloidosis secondary to chronic infections and inflammatory disorders. An acute-phase protein produced by the liver, serum amyloid A (SAA) is the precursor of AA amyloid fibrils. AA amyloid deposition occurs predominantly in the kidneys, spleen, adrenal glands, liver and gastrointestinal tract. The manifestations of AA amyloidosis involving the kidneys include proteinuria, tubular dysfunction and progressive loss of renal function.We report a 47-year-old drug addict who developed AA amyloidosis as a result of recurrent suppurative skin infections secondary to subcutaneous drug injection. Elevated C-reactive protein concentrations attested to the presence of a chronic systemic inflammatory state. He suffered from the nephrotic syndrome and insidious loss of renal function. Isosthenuria and glycosuria were indicative of renal tubular dysfunction. Renal biopsy demonstrated AA amyloidosis involving the glomeruli, tubular basement membranes and blood vessel walls.Superimposed acute tubular necrosis due to concomitant endocarditis and cocaine use accelerated his renal disease. CASE presentation is followed by a brief discussion of clinical features, natural history and outcome of AA amyloidosis with a particular emphasis on AA amyloidosis as a complication of subcutaneous drug abuse.
- Novel SLC2 Variants Contribute to Renal Glucosuria in Chinese Families༚Abnormal Expression and Dysfunction of Variant SLC2. [JOURNAL ARTICLE]
- Hum Mutat 2014 Oct 22.
Familial renal glucosuria (FRG) is characterized by persistent glucosuria despite normal serum glucose and the absence of overt tubular dysfunction. Variants in solute carrier family 5 (sodium-glucose co-transporter), member 2 (SLC5A2) have been reported in FRG patients. However, the functional and expression-related consequences of such variants have been scarcely investigated. In the current study, we studied five FRG families and identified six missense mutations, including four novel variants (c.1051T>C/p.(C351R), c.1400T>C/p.(V467A), c.1420G>C/p.(A474P), c.1691G>A/p.(R564Q); RNA not analyzed) and two variants that had been previously reported (c.294C>A/p.(F98L), c.736C>T/p.(P246S); RNA not analyzed). The probands were either heterozygous or compound heterozygous for SLC5A2 variants and had glucosuria of 5.9-19.6 g/day. Human 293 cells were transfected with plasmid constructs to study the expression and function of SLC5A2 Variants in vitro. Western blotting revealed that the expression levels of SLC5A2-351R-GFP, SLC5A2-467A-GFP, SLC5A2-474P-GFP and SLC5A2-564Q-GFP were significantly decreased compared with wild-type SLC5A2-GFP (37-55%). Confocal microscopy revealed that three variants (c.1400T>C, c.1420G>C, c.1691G>A) resulted in a loss of the punctate membrane pattern typical of wild-type SLC5A2. All Variants had a significantly lower transport capacity in than the wild-type control. The current study provides a starting point to further investigate the molecular mechanism of SLC5A2 in FRG families and provides functional clues for anti-diabetes drugs. This article is protected by copyright. All rights reserved.
- Transient renal dysfunction with reversible splenial lesion. [Journal Article]
- Pediatr Int 2014 Oct; 56(5):e68-71.
We report the case of a 6-month-old boy with transient renal dysfunction who had an intensified signal in the splenium of the corpus callosum on magnetic resonance imaging. He presented to hospital with fever and sudden disturbance of consciousness. Cerebrospinal fluid analysis did not show pleocytosis. The mild consciousness disturbance disappeared after 30 min, but the splenial signal persisted even after 8 days. Further, renal glucosuria, increased excretion of select amino acids, and abnormal fractional excretion of electrolytes were observed, indicating renal tubular dysfunction. The abnormal urinary findings spontaneously resolved by day 9 of hospitalization. The splenial lesion took 21 days to normalize. There were no signs of neurological complications 2 months later. This case suggests the possibility of renal involvement in splenial lesions.
- Common mutation causes cystinosis in the majority of black South African patients. [JOURNAL ARTICLE]
- Pediatr Nephrol 2014 Oct 18.
The mutations responsible for cystinosis in South African patients are currently unknown. A pertinent question is whether they are similar to those described elsewhere in the world.Children who were being managed for cystinosis in the Western Cape Province of South Africa between 2002 and 2013 were studied. All underwent molecular analysis to detect sequence variations in the cystinosis gene.This cohort study included 20 patients, 13 of whom were Xhosa-speaking black South Africans and seven were Cape Coloureds (mixed race); none were Caucasian. All had nephropathic infantile-type cystinosis with evidence of proximal tubulopathy, with glycosuria and renal phosphate wasting. Diagnosis was confirmed in 19 cases by demonstrating an elevated cystine concentration in leukocytes. Molecular analysis of the cystinosin gene revealed that 19 patients had a G > A mutation in intron 11 (CTNS-c.971-12G > A p.D324AfsX44) which caused an out-of-frame 10-bp insertion. Of these 19 patients, 16 were homozygous for this mutation, which was the most frequent mutation identified in the alleles of the black South African and Cape Coloured patients (96 and 71 %, respectively).We recommend that black South African and Cape Coloured patients presenting with cystinosis be tested for CTNS-c.971-12G > A in the first instance, with the possibility of prenatal testing being offered to at-risk families.
- Long-term assessment of glucosuria in captive okapi (Okapia johnstoni) after a dietary change. [Journal Article]
- J Zoo Wildl Med 2014 Sep; 45(3):632-4.
Glucosuria in okapis (Okapia johnstoni) was first documented in 1980, yet the etiology remains unclear. In August 2006, an attempt to lower glucosuria in captive okapi by diet modification (omitting all fruit and adding unmolassed beet pulp) was started at the Antwerp Zoo. To study the possible relationship between glucosuria and diet, stress, and/or pregnancy, four okapis were monitored over a period of 4.5 yr. One animal, born in 2006, became glucosuric near the age of three. Three okapis were adults at the start of the study and had been glucosuric for more than 5 yr. The glucose/creatinine urinary ratio values of these four glucosuric animals did not change considerably over time despite dietary changes. Stress did not appear to influence glucosuria in these okapi. Urinary ratio decreased during the second half of pregnancy in two females. In conclusion, the diet change did not reduce glucosuria, but pregnancy appeared to lower urinary glucose in okapis.
- [Executive summary of the recommendations on the evaluation and management of renal disease in human immunodeficiency virus-infected patients.] [JOURNAL ARTICLE]
- Enferm Infecc Microbiol Clin 2014 Oct 7.
The aim of this article is to update the 2010 recommendations on the evaluation and management of renal disease in human immunodeficiency virus (HIV)-infected patients. Renal function should be monitored in all HIV-infected patients. The basic renal work-up should include measurements of serum creatinine, estimated glomerular filtration rate by CKD-EPI, urine protein-to-creatinine ratio, and urinary sediment. Tubular function tests should include determination of serum phosphate levels and urine dipstick for glycosuria. In the absence of abnormal values, renal screening should be performed annually. In patients treated with tenofovir, or with risk factors for chronic kidney disease (CKD), more frequent renal screening is recommended. In order to prevent disease progression, potentially nephrotoxic antiretroviral drugs are not recommended in patients with CKD or risk factors for CKD. The document provides indications for renal biopsy and advises on the optimal time for referral of a patient to the nephrologist. The indicat6ions for and evaluation and management of dialysis and renal transplantation are also addressed.
- Low body weight and tenofovir use are risk factors for renal dysfunction in Vietnamese HIV-infected patients. A prospective 18-month observation study. [JOURNAL ARTICLE]
- J Infect Chemother 2014 Oct 6.
The use of tenofovir has been rapidly increasing in Vietnam. Several studies identified low body weight as a risk factor for tenofovir-induced nephrotoxicity. However, little is known about the impact of tenofovir on renal function in HIV-infected Vietnamese with generally low weight.An observational single-center cohort of adult HIV-infected patients on antiretroviral therapy at National Hospital of Tropical Diseases, Hanoi. Patients on tenofovir or with creatinine clearance ≤60 ml/min at baseline were excluded. The incidence of renal dysfunction was compared between patients who switched to tenofovir and those who did not. Renal dysfunction was defined as 25% decline of creatinine clearance from baseline. Time to renal dysfunction was analyzed by the Kaplan-Meier method between the two groups. The Cox hazard model was used to determine risk factors for renal dysfunction in uni- and multivariate analyses.Of 556 patients enrolled in this study, 403 were non-tenofovir group while 153 were the tenofovir-switched group. Renal dysfunction occurred at a higher rate in the tenofovir-switched group (92.5 per 1000 person-years) than the non-tenofovir group (47.8 per 1000 person-years)(p = 0.023, Log-rank test). Multivariate analysis confirmed that tenofovir use, low body weight and glucosuria were significant risk factors for renal dysfunction (hazard ratio = 1.980; 95% confidential interval, 1.094-3.582, HR = 1.057; 95%CI, 1.016-1.098, HR = 5.202; 95%CI, 1.245-21.738, respectively).Tenofovir use, low body weight and glucosuria were significant risk factors for renal dysfunction. We suggest close monitoring of renal function in patients with these risk factors even in resource-limited setting.
- Activation of Protein Kinase C-α and Src Kinase Increases Urea Transporter A1 α-2, 6 Sialylation. [JOURNAL ARTICLE]
- J Am Soc Nephrol 2014 Oct 9.
The urea transporter A1 (UT-A1) is a glycosylated protein with two glycoforms: 117 and 97 kD. In diabetes, the increased abundance of the heavily glycosylated 117-kD UT-A1 corresponds to an increase of kidney tubule urea permeability. We previously reported that diabetes not only causes an increase of UT-A1 protein abundance but also, results in UT-A1 glycan changes, including an increase of sialic acid content. Because activation of the diacylglycerol (DAG)-protein kinase C (PKC) pathway is elevated in diabetes and PKC-α regulates UT-A1 urea transport activity, we explored the role of PKC in UT-A1 glycan sialylation. We found that activation of PKC specifically promotes UT-A1 glycan sialylation in both UT-A1-MDCK cells and rat kidney inner medullary collecting duct suspensions, and inhibition of PKC activity blocks high glucose-induced UT-A1 sialylation. Overexpression of PKC-α promoted UT-A1 sialylation and membrane surface expression. Conversely, PKC-α-deficient mice had significantly less sialylated UT-A1 compared with wild-type mice. Furthermore, the effect of PKC-α-induced UT-A1 sialylation was mainly mediated by Src kinase but not Raf-1 kinase. Functionally, increased UT-A1 sialylation corresponded with enhanced urea transport activity. Thus, our results reveal a novel mechanism by which PKC regulates UT-A1 function by increasing glycan sialylation through Src kinase pathways, which may have an important role in preventing the osmotic diuresis caused by glucosuria under diabetic conditions.
- [Severe hypernatremia due to sea water ingestion in a child.] [JOURNAL ARTICLE]
- Arch Pediatr 2014 Oct 1.
Drowning in sea water is an unusual cause of severe hypernatremia. We report the case of a 3.5-year-old boy who died 11h after drowning in sea water, with a serum sodium level of 178mmoL/L. In this case, hypernatremia was aggravated by diarrhea and hyperglycemia with glycosuria. Usually, correction of acute hypernatremia must be quick and early, aiming at a reduction of serum sodium concentration of up to 1-2mmoL per liter per hour.