'Aquaporin-omics': mechanisms of aquaporin-2 loss in polyuric disorders.

Animal models of a variety of acquired nephrogenic diabetes insipidus (NDI) disorders have identified a common feature: all such models are associated with the loss of aquaporin-2 (AQP2) from collecting duct principal cells, explaining the associated polyuria. To discover mechanisms of AQP2 loss, previous investigators have carried out either transcriptomics (lithium-induced NDI, unilateral ureteral obstruction, endotoxin-induced NDI) or proteomics (hypokalaemia-associated NDI, hypercalcaemia-associated NDI, bilateral ureteral obstruction), yielding contrasting views. Here, to address whether there may be common mechanisms underlying loss of AQP2 in acquired NDI disorders, we have used bioinformatic data integration techniques to combine information from all transcriptomic and proteomic data sets. The analysis reveals roles for autophagy/apoptosis, oxidative stress and inflammatory signalling as key elements of the mechanism that results in loss of AQP2. These processes can cause AQP2 loss through the combined effects of repression of Aqp2 gene transcription, generalized translational repression, and increased autophagic degradation of proteins including AQP2. Two possible types of stress-sensor proteins, namely death receptors and stress-sensitive protein kinases of the EIF2AK family, are discussed as potential triggers for signalling processes that result in loss of AQP2. KEY POINTS: Prior studies have shown in a variety of animal models of acquired nephrogenic diabetes insipidus (NDI) that loss of the aquaporin-2 (AQP2) protein is a common feature. Investigations of acquired NDI using transcriptomics (RNA-seq) and proteomics (protein mass spectrometry) have led to differing conclusions regarding mechanisms of AQP2 loss. Bioinformatic integration of transcriptomic and proteomic data from these prior studies now reveals that acquired NDI models map to three core processes: oxidative stress, apoptosis/autophagy and inflammatory signalling. These processes cause loss of AQP2 through translational repression, accelerated degradation of proteins, and transcriptional repression.

Acute Intermittent Porphyria: Complete Phenotype in a Patient with p.Arg173Trp Variant in Thailand.

BACKGROUND Acute intermittent porphyria (AIP) is a rare genetic disease caused by the deficiency of porphobilinogen deaminase enzyme in the heme synthesis pathway. AIP is passed by autosomal dominant inheritance. Heterozygous pathogenic variants in hydroxymethylbilane synthase (HMBS) are associated with AIP. Multisystemic manifestations of acute neurovisceral features exist, which are quite challenging for diagnosis. Currently, few patients worldwide have been reported with AIP. A small number of reports have been published in Thailand, but none have been confirmed by molecular genetics diagnosis. CASE REPORT A 14-year-old female adolescent presented with severe intermittent abdominal pain, vomiting, seizure, posterior reversible encephalopathy syndrome, syndrome of inappropriate antidiuretic hormone, and muscle weakness, which are all classic phenotypes of an acute AIP attack. The patient received several investigations before AIP was suspected. High levels of urine porphobilinogen, high levels of urine aminolevulinic acid, and a heterozygous known pathogenic variant in HMBS: c.517C>T (p.Arg173Trp) were identified. Therefore, AIP was the definitive diagnosis. Then, Sanger sequencing testing was performed for the patient's family; this variant was found in her father, paternal grandmother, and sister, who were all asymptomatic (latent AIP). After the AIP was confirmed, high carbohydrate loading was given as a standard treatment. She had a full recovery; her clinical course of the attack episode lasted for 8 weeks. CONCLUSIONS An early diagnosis of AIP leads to prompt and specific treatment, which can shorten the duration of attacks, prevent complications, reduce the cost of treatment, and reduce the mortality rate.

Expanding phenotypic and mutational spectra of mitochondrial HMG-CoA synthase deficiency.

Mitochondrial 3-hydroxy-3 methylglutaryl-CoA synthase-2 deficiency (HMGCS2D) is a rare autosomal recessive inborn error of hepatic ketogenesis, caused by mutations in HMGCS2. As its clinical and laboratory manifestations resemble many other metabolic disorders, HMGCS2D definite diagnosis presents a challenge, frequently requiring molecular tests. Only 26 patients with HMGCS2 mutations have been previously described, and this study reports the first two unrelated Thai patients, a 9-month-old male and an 8-month-old female, with HMGCS2D. During acute episodes, steatorrhea and dyslipidemia occurred, both previously unreported. Increased serum levels of triglycerides, very low density lipoproteins (VLDL), and low density lipoproteins (LDL), along with a decreased serum level of HDL were found. Both patients had hypophosphatemic encephalopathy, and the female had metabolic acidosis without hypoglycemia. Trio whole-exome sequencing (WES) revealed that the male harbored two HMGCS2 mutations, a novel c.1480C>T (p.Arg494*) and a previously reported c.1502G>C (p.Arg501Pro), while the female was compound heterozygous for the c.1502G>C (p.Arg501Pro) and a previously reported mutation, c.520T>C (p.Phe174Leu). Interestingly, c.1502G>C (p.Arg501Pro) was not only found in both of our patients but also detected heterozygously in 9 out of 1081 unrelated individuals (allele frequency of 9/2162; 0.42%) in our in-house Thai exome database. Discovery of this common mutation suggests there could be about 14 babies with HMGCS2D within 800,000 newborns in Thailand annually. Therefore, awareness of HMGCS2D among medical personnel in Thailand should be raised.

Bilateral ureteral obstruction is rapidly accompanied by ER stress and activation of autophagic degradation of IMCD proteins, including AQP2.

After the release of bilateral ureteral obstruction (BUO), postobstructive diuresis from an impaired urine concentration mechanism is associated with reduced aquaporin 2 (AQP2) abundance in the inner medullary collecting duct (IMCD). However, the underlying molecular mechanism of this AQP2 reduction is incompletely understood. To elucidate the mechanisms responsible for this phenomenon, we studied molecular changes in IMCDs isolated from rats with 4-h BUO or sham operation at the early onset of AQP2 downregulation using mass spectrometry-based proteomic analysis. Two-hundred fifteen proteins had significant changes in abundances, with 65% of them downregulated in the IMCD of 4-h BUO rats compared with sham rats. Bioinformatic analysis revealed that significantly changed proteins were associated with functional Gene Ontology terms, including "cell-cell adhesion," "cell-cell adherens junction," "mitochondrial inner membrane," "endoplasmic reticulum chaperone complex," and the KEGG pathway of glycolysis/gluconeogenesis. Targeted liquid chromatography-tandem mass spectrometry or immunoblot analysis confirmed the changes in 19 proteins representative of each predominant cluster, including AQP2. Electron microscopy demonstrated disrupted tight junctions, disorganized adherens junctions, swollen mitochondria, enlargement of the endoplasmic reticulum lumen, and numerous autophagosomes/lysosomes in the IMCD of rats with 4-h BUO. AQP2 and seven proteins chosen as representative of the significantly altered clusters had a significant increase in immunofluorescence-based colocalization with autophagosomes/lysosomes. Immunogold electron microscopy confirmed colocalization of AQP2 with the autophagosome marker microtubule-associated protein 1A/1B-light chain 3 and the lysosomal marker cathepsin D in IMCD cells of rats with 4-h BUO. We conclude that enhanced autophagic degradation of AQP2 and other critical proteins, as well as endoplasmic reticulum stress in the IMCD, are initiated shortly after BUO.

RNA-Seq and protein mass spectrometry in microdissected kidney tubules reveal signaling processes initiating lithium-induced nephrogenic diabetes insipidus.

Lithium salts, used for treating bipolar disorder, frequently induce nephrogenic diabetes insipidus (NDI) thereby limiting therapeutic success. NDI is associated with loss of expression of the gene coding for the molecular water channel, aquaporin-2, in the renal collecting duct (CD). Here, we use systems biology methods in a well-established rat model of lithium-induced NDI to identify signaling pathways activated at the onset of polyuria. Using single-tubule RNA-Seq, full transcriptomes were determined in microdissected cortical collecting ducts (CCDs) of rats after 72 hours without or with initiation of lithium chloride administration. Transcriptome-wide changes in mRNA abundances were mapped to gene sets associated with curated canonical signaling pathways, showing evidence for activation of NF-κB signaling with induction of genes coding for multiple chemokines and most components of the Major Histocompatibility Complex Class I antigen-presenting complex. Administration of anti-inflammatory doses of dexamethasone to lithium chloride-treated rats countered the loss of aquaporin-2. RNA-Seq also confirmed prior evidence of a shift from quiescence into the cell cycle with arrest. Time course studies demonstrated an early (12 hour) increase in multiple immediate early response genes including several transcription factors. Protein mass spectrometry in microdissected CCDs provided corroborative evidence and identified decreased abundance of several anti-oxidant proteins. Thus, in the context of prior observations, our study can be best explained by a model in which lithium increases ERK activation leading to induction of NF-κB signaling and an inflammatory-like response that represses Aqp2 transcription.

Molecular Diagnosis of Solute Carrier Family 4 Member 1 (SLC4A1) Mutation-Related Autosomal Recessive Distal Renal Tubular Acidosis.

BACKGROUND: Two common mutations of the solute carrier family 4 member 1 (SLC4A1) gene, namely, Southeast Asian ovalocytosis (SAO) and band 3 Bangkok 1 (G701D), cause autosomal recessive distal renal tubular acidosis (AR dRTA) in ethnic Southeast Asian populations. In this study, we applied the high-resolution melting (HRM) method for screening of AR dRTA associated with SLC4A1 mutations in 10 new patients with unknown cause(s) of AR dRTA. METHODS: We analyzed SAO and G701D mutations in the patients and their family members using HRM. The results were confirmed by polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) and DNA sequencing techniques. RESULTS: All patients carried homozygous G701D mutation, whereas their family members had heterozygous G701D or homozygous wild-type. CONCLUSIONS: Homozygous G701D is a common cause of AR dRTA in ethnic Thai pediatric populations. HRM can be used as a rapid screening method for common SLC4A1 mutations that cause AR dRTA in Southeast Asian and other populations.

The First Report of Multicentric Carpotarsal Osteolysis Syndrome Caused by MAFB Mutation in Asian.

Multicentric carpotarsal osteolysis syndrome (MCTO) is a rare skeletal disorder characterized by aggressive osteolysis associated with progressive nephropathy. The early clinical presentation can mimic polyarticular juvenile idiopathic arthritis. Since 2012, MAFB mutations have been discovered in all MCTO patients. Therefore, the early diagnosis can be made based on genetic confirmation. We report the clinical manifestation of mineral bone disease and the molecular genetic study of a Thai female adolescent with MCTO. She presented with end-stage renal disease, bilateral wrist and ankle joint deformities, and subtle facial dysmorphic features. We identified a heterozygous missense MAFB mutation at nucleotide 197 from C to G (NM_005461.4; c.197C>G), predicting the change of amino acid at codon 66 from serine to cysteine (p.Ser66Cys), and the mutation was absent in the parents, indicating a de novo mutation. This report confirms the previous link between MAFB mutation and MCTO. Her unexplained hypercalcemia after a regular dose of calcium and active vitamin D supported an important role of MafB in the negative regulation of RANKL-mediated osteoclast differentiation. Therefore, we would encourage the physicians who take care of MCTO patients to closely monitor serum calcium level and perform a genetic study as a part of the management and investigation.

Corrigendum to "Dual Inhibiting Senescence and Epithelial-to-Mesenchymal Transition by Erythropoietin Preserve Tubular Epithelial Cell Regeneration and Ameliorate Renal Fibrosis in Unilateral Ureteral Obstruction".

[This corrects the article DOI: 10.1155/2013/308130.].

Hypercalcemia induces targeted autophagic degradation of aquaporin-2 at the onset of nephrogenic diabetes insipidus.

Hypercalcemia can cause renal dysfunction such as nephrogenic diabetes insipidus (NDI), but the mechanisms underlying hypercalcemia-induced NDI are not well understood. To elucidate the early molecular changes responsible for this disorder, we employed mass spectrometry-based proteomic analysis of inner medullary collecting ducts (IMCD) isolated from parathyroid hormone-treated rats at onset of hypercalcemia-induced NDI. Forty-one proteins, including the water channel aquaporin-2, exhibited significant changes in abundance, most of which were decreased. Bioinformatic analysis revealed that many of the downregulated proteins were associated with cytoskeletal protein binding, regulation of actin filament polymerization, and cell-cell junctions. Targeted LC-MS/MS and immunoblot studies confirmed the downregulation of 16 proteins identified in the initial proteomic analysis and in additional experiments using a vitamin D treatment model of hypercalcemia-induced NDI. Evaluation of transcript levels and estimated half-life of the downregulated proteins suggested enhanced protein degradation as the possible regulatory mechanism. Electron microscopy showed defective intercellular junctions and autophagy in the IMCD cells from both vitamin D- and parathyroid hormone-treated rats. A significant increase in the number of autophagosomes was confirmed by immunofluorescence labeling of LC3. Colocalization of LC3 and Lamp1 with aquaporin-2 and other downregulated proteins was found in both models. Immunogold electron microscopy revealed aquaporin-2 in autophagosomes in IMCD cells from both hypercalcemia models. Finally, parathyroid hormone withdrawal reversed the NDI phenotype, accompanied by termination of aquaporin-2 autophagic degradation and normalization of both nonphoshorylated and S256-phosphorylated aquaporin-2 levels. Thus, enhanced autophagic degradation of proteins plays an important role in the initial mechanism of hypercalcemic-induced NDI.

Autophagic degradation of aquaporin-2 is an early event in hypokalemia-induced nephrogenic diabetes insipidus.

Hypokalemia (low serum potassium level) is a common electrolyte imbalance that can cause a defect in urinary concentrating ability, i.e., nephrogenic diabetes insipidus (NDI), but the molecular mechanism is unknown. We employed proteomic analysis of inner medullary collecting ducts (IMCD) from rats fed with a potassium-free diet for 1 day. IMCD protein quantification was performed by mass spectrometry using a label-free methodology. A total of 131 proteins, including the water channel AQP2, exhibited significant changes in abundance, most of which were decreased. Bioinformatic analysis revealed that many of the down-regulated proteins were associated with the biological processes of generation of precursor metabolites and energy, actin cytoskeleton organization, and cell-cell adhesion. Targeted LC-MS/MS and immunoblotting studies further confirmed the down regulation of 18 selected proteins. Electron microscopy showed autophagosomes/autophagolysosomes in the IMCD cells of rats deprived of potassium for only 1 day. An increased number of autophagosomes was also confirmed by immunofluorescence, demonstrating co-localization of LC3 and Lamp1 with AQP2 and several other down-regulated proteins in IMCD cells. AQP2 was also detected in autophagosomes in IMCD cells of potassium-deprived rats by immunogold electron microscopy. Thus, enhanced autophagic degradation of proteins, most notably including AQP2, is an early event in hypokalemia-induced NDI.

Dual inhibiting senescence and epithelial-to-mesenchymal transition by erythropoietin preserve tubular epithelial cell regeneration and ameliorate renal fibrosis in unilateral ureteral obstruction.

This study aims to investigate the renoprotective effect of recombinant human erythropoietin (rhEPO) treatment could preserve tubular epithelial cell regeneration and ameliorate renal fibrosis by dual inhibition of stress-induced senescence and EMT in unilateral ureteric obstruction (UUO) mouse model. UUO or sham-operated mice were randomly assigned to receive rhEPO or vehicle treatment and were sacrificed on days 3, 7, and 14. Kidney specimens were fixed for histopathological and immunohistochemical study. The expression of S100A4, TGF-ß1, BMP-7, Smad2/3, Smad1/5/8, and p16(INK4a) was determined by western blot and real-time RT-PCR. Vehicle treated UUO mice had increased tubular atrophy and interstitial fibrosis within 3 to 14 days. An increase in TGF-ß1, Smad2/3, S100A4, and p16(INK4a) expression and a decrease in BMP-7 and Smad1/5/8 expression were observed in the obstructed kidneys. p16(INK4a) was positively correlated with TGF-ß1/Smad2/3 and negatively correlated with BMP-7/Smad1/5/8 in UUO mice. rhEPO treatment significantly suppressed the upregulation of TGF-ß, Smad2/3, S100A4, and p16(INK4a) and preserved the downregulation of BMP-7 and Smad1/5/8, resulting in markedly reduced TA/IF compared to the vehicle treated mice. The renoprotective effects of rhEPO could ameliorate renal TA/IF by modulating senescence and EMT which could be a part of therapeutic option in patients with chronic kidney disease.

Quantitative protein and mRNA profiling shows selective post-transcriptional control of protein expression by vasopressin in kidney cells.

Previous studies in yeast have supported the view that post-transcriptional regulation of protein abundances may be more important than previously believed. Here we ask the question: "In a physiological regulatory process (the response of mammalian kidney cells to the hormone vasopressin), what fraction of the expressed proteome undergoes a change in abundance and what fraction of the regulated proteins have corresponding changes in mRNA levels?" In humans and other mammals, vasopressin fulfills a vital homeostatic role (viz. regulation of renal water excretion) by regulating the water channel aquaporin-2 in collecting duct cells. To address the question posed, we utilized large-scale quantitative protein mass spectrometry (LC-MS/MS) employing stable isotopic labeling in cultured mpkCCD cells ('SILAC') coupled with transcriptomic profiling using oligonucleotide expression arrays (Affymetrix). Preliminary studies analyzing two nominally identical control samples by SILAC LC-MS/MS yielded a relative S.D. of 13% (for ratios), establishing the precision of the SILAC approach in our hands. We quantified nearly 3000 proteins with nontargeted SILAC LC-MS/MS, comparing vasopressin- versus vehicle-treated samples. Of these proteins 786 of them were quantified in each of 3 experiments, allowing statistical analysis and 188 of these showed significant vasopressin-induced changes in abundance, including aquaporin-2 (20-fold increase). Among the proteins with statistically significant abundance changes, a large fraction (at least one-third) was found to lack changes in the corresponding mRNA species (despite sufficient statistical power), indicating that post-transcriptional regulation of protein abundance plays an important role in the vasopressin response. Bioinformatic analysis of the regulated proteins (versus all transcripts) shows enrichment of glutathione S-transferase isoforms as well as proteins involved in organization of the actin cytoskeleton. The latter suggests that long-term regulatory processes may contribute to actomyosin-dependent trafficking of the water channel aquaporin-2. The results provide impetus for increased focus on translational regulation and regulation of protein degradation in physiological control in mammalian epithelial cells.

Henoch-Schonlein purpura in Thai children: a report from single center.

Henoch Schonlein Purpura (HSP) is the most common vasculitis in childhood. It is a self-limited disease. Recurrent HSP is not uncommon. Colchicine, an anti-inflammatory drug, has been used in prolonged HSP in only a few patients with good response. The present study described pediatric HSP patients in a single center, Thailand. To determine the epidemiology, clinical manifestations, treatments, and outcomes of HSP patients, the authors retrospectively studied 26 patients (age < 15 years) diagnosed with HSP at Thammasat University Hospital, from January 01, 2004 through December 31, 2010. The mean age was 7.2 +/- 3.8 years; median (range) follow-up was 2 (0.5-39) months. Fifteen (57.7%) patients were female. Clinical manifestations were skin (100%), joint (69.2%), gastrointestinal symptoms (50%) and renal involvement (19.2%). Symptoms lasted within 8 weeks in 21 (80%) patients. Recurrences identified in 5 (19%) patients with a mean of 4.8 +/- 2.4 times. The clinical outcome was excellent without major complication. Colchicine induced remission of severe and recurrent petechiae in one patient who developed methemoglobinemia after dapsone therapy. Colchicine may be an effective drug for prolonged HSP without renal involvement. The controlled studies to establish benefit effect and optimal regimen of colchicine in HSP is required.

Transient hyperkalemic distal renal tubular acidosis with bicarbonate wasting in a young child.

Distal renal tubular acidosis is a clinical syndrome characterized by inability to acidify urine in the presence of metabolic acidosis. Classic dRTA patients exhibit failure to thrive, polyuria, metabolic acidosis and hypokalemia. Hyperkalemic dRTA without underlying disease is very rare. Transient bicarbonate wasting accompanied with hypokalemic dRTA was reported in infants. Herein, a transient hyperkalemic dRTA with bicarbonate wasting was reported in a young child.

Impaired trafficking and intracellular retention of mutant kidney anion exchanger 1 proteins (G701D and A858D) associated with distal renal tubular acidosis.

Novel compound heterozygous mutations, G701D, a recessive mutation, and A858D, a mild dominant mutation, of human solute carrier family 4, anion exchanger, member 1 (SLC4A1) were identified in two pediatric patients with distal renal tubular acidosis (dRTA). To examine the interaction, trafficking, and cellular localization of the wild-type and two mutant kidney AE1 (kAE1) proteins, we expressed the proteins alone or together in human embryonic kidney (HEK) 293T and Madin-Darby canine kidney (MDCK) epithelial cells. In individual expressions, wild-type kAE1 was localized at the cell surface of HEK 293T and the basolateral membrane of MDCK cells. In contrast, kAE1 G701D was mainly retained intracellularly, while kAE1 A858D was observed intracellularly and at the cell surface. In co-expression experiments, wild-type kAE1 formed heterodimers with kAE1 G701D and kAE1 A858D, and promoted the cell surface expression of the mutant proteins. The co-expressed kAE1 G701D and A858D could also form heterodimers but showed predominant intracellular retention in HEK 293T and MDCK cells. Thus impaired trafficking of the kAE1 G701D and A858D mutants would lead to a profound decrease in functional kAE1 at the basolateral membrane of alpha-intercalated cells in the distal nephron of the patients with dRTA.

Tamm-Horsfall protein and urinary exosome isolation.

Urinary exosomes have been proposed as starting material for discovery of protein biomarkers of kidney disease. Current protocols for their isolation use a two-step differential centrifugation process. Due to their low density, exosomes are expected to remain in the low-speed (17,000 x g) supernatant and to sediment only when the sample is spun at high speed (200,000 x g). Analysis using western blot and electron microscopy found that urinary exosomes are also present in the low-speed pellet entrapped by polymeric Tamm-Horsfall protein, thus diminishing the procedure's reproducibility. Here we show that addition of dithiothreitol to the low-speed pellet disrupted the polymeric network, presumably by reduction of disulfide bonds linking the monomers. This modification shifted the exosomal proteins from the low- to the high-speed pellet. Also, by shifting the Tamm-Horsfall protein to the high-speed pellet, the use of dithiothreitol makes it feasible to use Tamm-Horsfall protein to normalize excretion rates of exosomal proteins in spot urines. We tested this by western blot, and found that there was a high degree of correlation between exosomal proteins and Tamm-Horsfall protein in the high-speed pellet. Since the yield of exosomes by differential centrifugation can be increased by chemical reduction, Tamm-Horsfall protein may be a suitable normalizing variable for urinary exosome studies when quantitative urine collections are not practical.

Pediatric systemic lupus erythematosus in Thammasat University Hospital.

Systemic lupus erythematosus (SLE) is a common autoimmune disease in children. Current standard therapies carry high adverse effects. Refractory SLE to conventional therapies is not uncommon. Rituximab, anti-CD20 monoclonal antibody, has been used as an adjunctive therapy in children with refractory SLE with limited reports. This study described pediatric SLE patients in a single center, Thailand. To determine the clinical manifestations, treatments, and outcome of SLE patients, the authors retrospectively studied 19 patients (age <15 years) diagnosed with SLE at Thammasat University hospital, from January 01, 2002 through March 31, 2010. The mean age was 12.9 +/- 1.6 years; mean follow-up 3.3 +/- 2.6 years. Seventeen (89.5%) patients were female. Clinical manifestations were hematological (89.5%), dermatologic (73.7%), and renal involvement (68.4%). SLE was diagnosed 1 year after systemic onset juvenile rheumatoid arthiris in one patient. Lupus nephritis (LN) class II was observed in 30.8%, class III (15.4%), and class IV (53.8%) of patients with LN. Overall, mean SLEDAI score at presentation was 14.9 +/- 2.2 and significantly decreased to 6.8 +/- 1.6 (p < 0.0001) at 1 month after treatment. Complete remission at 1 year demonstrated in 11 (68.7%) patients. Infection was the most common complication followed by ophthalmological complications. All patients survived during follow-up period. Rituximab induced remission of SLE after refractory diffuse alveolar hemorrhage in one patient, and rapidly progressive glomerulonephirits leading to end stage renal failure in one patient. Clinical outcome of pediatric SLE was favorable in the present study. Complications from corticosteroid and anti-inflammatory therapy were high. Rituximab may be a good adjunctive therapy for refractory SLE in children. Large controlled trials to establish safety profile and optimal regimen of rituximab in childhood SLE are required.

A fluctuation of serum osmolality inducing osmotic demyelination syndrome.

Osmotic demyelination syndrome (ODS) is an uncommon acute demyelinating process which involves the central nervous system. Rapid correction of chronic hyponatremia with increasing serum osmolality is the most common cause of ODS. We report the first case of an infant with moderate dehydration and initially normal serum Na who developed ODS associated with a fluctuation of serum osmolality. We present the lowest decreasing rate of serum Na level ever reported causing ODS. The fluctuation of serum osmolality in this case expands the list of precipitating causes of ODS in children. The case also highlights the appropriate intravenous fluid for initial rehydration in infant.

Hypertension in Thai children: a report from a hospital in suburban area.

Hypertension in children is the major risk for cardiovascular disease in adult. Limited data are available for hypertension in children in Southeast Asia. To determine the cause, treatment, and long-term outcome of hypertension in Thai Children, the authors retrospectively studied 62 patients (age <15 years) diagnosed with hypertension at Thammasat University hospital, from December 01, 2004 through November 30, 2009. The mean age was 9.2 +/- 4.2 years; median follow-up 8 months. Fifty five (88.7%) patients had secondary hypertension. Patients presented with stage 2 hypertension (67.7%), and hypertensive emergency (9.7%). Renal parenchymal disease caused 67.3% of secondary hypertension. End organ damage included left ventricular hypertrophy (11.3%) and hypertensive retinopathy (6.4%). Hypertensive emergency was caused mostly by acute poststreptococcal glmoerulnephritis (APSGN, 66.7%). Intravenous diuretic coupled with oral antihypertensive drugs gave uncontrolled blood pressure in APSGN with hypertensive emergency. Seventy percents of patients with essential hypertension had obesity. Majority of the patients had controlled hypertension without medication. Acute poststreptococcal glomerulonephritis remained the common cause of transient hypertension and hypertensive emergency in Thai children. The high incidence of obesity among essential hypertension in children demonstrated in the present study should alert Thai pediatrician to measure blood pressure in every obese child. Treatment of childhood hypertension was associated with good long-term outcome.

The fractional excretion of urea in the differential diagnosis of prerenal failure and acute tubular necrosis in neonates.

BACKGROUND: Acute renal failure (ARF) in a newborn is a common problem. Fractional excretion of sodium (FENa) has been used to distinguish between the two main causes of ARF, prerenal failure and acute tubular necrosis (ATN). However, the clinical usefulness of FENa could be limited by furosemide diuretic that are commonly prescribed inARF patients. In contrast, urea is not reabsorbed significantly in the distal nephron, thus the fractional excretion of urea (FE UN) should not be affected by furosemide. OBJECTIVE: To test the hypothesis that FE UN is not effected by furosemide and useful in differentiating between prerenal failure and ATN. MATERIAL AND METHOD: Neonates admitted to the Department of Pediatrics, Thammasat University Hospital from August 2007-May 2009 were studies prospectively for ARF which is defined as urine output < 0.5 ml/kg/hr after the 1st day and serum creatinine > 1.5 mg/dl with normal maternal renal function. FENa and FEUN were performed on the initial time of diagnosis and were repeated on two consecutive days. RESULTS: Neonates with ARF were classified as prerenal failure (n=38) and ATN (n=5). The prerenal failure neonates were divided into two groups: those prerenal failure without furosemide (n=27), those prerenal failure with furosemide (n=11). The FENa at the initial time of diagnosis and the two consecutive days in prerenal failure neonates (0.33 +/- 0.57, 10.1 +/- 2.73, 0.8 +/- 1.32%, respectively) were lower than ATN neonates (4.74 +/- 6.12, 5.05 +/- 4.03, 3.98 +/- 2.47%, respectively) significantly. Both FENa and FE UN were no statistical difference between the two prerenal failure groups and ATN neonates. CONCLUSION: A FE Na in prerenal failure is significantly lower than ATN. A FE UN has no benefit in distinguishing between prerenal failure and ATN. Furosemide has no effect on both FENa and FE UN.