RESUMEN
Na+/H+ exchanger isoform 3 (NHE3) contributes to Na+/bicarbonate reabsorption and ammonium secretion in early proximal tubules. To determine its role in the diabetic kidney, type 1 diabetic Akita mice with tubular NHE3 knockdown [Pax8-Cre; NHE3-knockout (KO) mice] were generated. NHE3-KO mice had higher urine pH, more bicarbonaturia, and compensating increases in renal mRNA expression for genes associated with generation of ammonium, bicarbonate, and glucose (phosphoenolpyruvate carboxykinase) in proximal tubules and H+ and ammonia secretion and glycolysis in distal tubules. This left blood pH and bicarbonate unaffected in nondiabetic and diabetic NHE3-KO versus wild-type mice but was associated with renal upregulation of proinflammatory markers. Higher renal phosphoenolpyruvate carboxykinase expression in NHE3-KO mice was associated with lower Na+-glucose cotransporter (SGLT)2 and higher SGLT1 expression, indicating a downward tubular shift in Na+ and glucose reabsorption. NHE3-KO was associated with lesser kidney weight and glomerular filtration rate (GFR) independent of diabetes and prevented diabetes-associated albuminuria. NHE3-KO, however, did not attenuate hyperglycemia or prevent diabetes from increasing kidney weight and GFR. Higher renal gluconeogenesis may explain similar hyperglycemia despite lower SGLT2 expression and higher glucosuria in diabetic NHE3-KO versus wild-type mice; stronger SGLT1 engagement could have affected kidney weight and GFR responses. Chronic kidney disease in humans is associated with reduced urinary excretion of metabolites of branched-chain amino acids and the tricarboxylic acid cycle, a pattern mimicked in diabetic wild-type mice. This pattern was reversed in nondiabetic NHE3-KO mice, possibly reflecting branched-chain amino acids use for ammoniagenesis and tricarboxylic acid cycle upregulation to support formation of ammonia, bicarbonate, and glucose in proximal tubule. NHE3-KO, however, did not prevent the diabetes-induced urinary downregulation in these metabolites.
Asunto(s)
Equilibrio Ácido-Base , Diabetes Mellitus Tipo 1/metabolismo , Nefropatías Diabéticas/metabolismo , Túbulos Renales/metabolismo , Reabsorción Renal , Intercambiador 3 de Sodio-Hidrógeno/deficiencia , Sodio/orina , Equilibrio Ácido-Base/genética , Aminoácidos de Cadena Ramificada/orina , Amoníaco/orina , Animales , Bicarbonatos/orina , Biomarcadores/orina , Glucemia/metabolismo , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/fisiopatología , Diabetes Mellitus Tipo 1/orina , Nefropatías Diabéticas/genética , Nefropatías Diabéticas/fisiopatología , Nefropatías Diabéticas/orina , Modelos Animales de Enfermedad , Metabolismo Energético/genética , Regulación de la Expresión Génica , Técnicas de Silenciamiento del Gen , Concentración de Iones de Hidrógeno , Túbulos Renales/fisiopatología , Masculino , Metabolómica/métodos , Ratones Endogámicos C57BL , Ratones Noqueados , Transportador 1 de Sodio-Glucosa/genética , Transportador 1 de Sodio-Glucosa/metabolismo , Transportador 2 de Sodio-Glucosa/genética , Transportador 2 de Sodio-Glucosa/metabolismo , Intercambiador 3 de Sodio-Hidrógeno/genéticaRESUMEN
Hyperchloremic metabolic acidosis, particularly renal tubular acidosis, can pose diagnostic challenges. The laboratory phenotype of a low total carbon dioxide content, normal anion gap, and hyperchloremia may be misconstrued as hypobicarbonatemia from renal tubular acidosis. Several disorders can mimic renal tubular acidosis, and these must be appropriately diagnosed to prevent inadvertent and inappropriate application of alkali therapy. Key physiologic principles and limitations in the assessment of renal acid handling that can pose diagnostic challenges are enumerated.
Asunto(s)
Acidosis Tubular Renal/diagnóstico , Alcalosis Respiratoria/diagnóstico , Bicarbonatos/sangre , Equilibrio Ácido-Base , Acidosis Tubular Renal/orina , Bicarbonatos/orina , Diagnóstico Diferencial , Humanos , Concentración Osmolar , Urinálisis , Derivación Urinaria/efectos adversosRESUMEN
With aging there is a chronic low-grade metabolic-acidosis that may exacerbate negative protein balance during weight loss. The objective of this randomized pilot study was to assess the impact of 90 mmolâday-1 potassium bicarbonate (KHCO3) versus a placebo (PLA) on 24-h urinary net acid excretion (NAE), nitrogen balance (NBAL), and whole-body ammonia and urea turnover following short-term diet-induced weight loss. Sixteen (KHCO3; n = 8, PLA; n = 8) older (64 ± 4 years) overweight (BMI: 28.5 ± 2.1 kgâday-1) men completed a 35-day controlled feeding study, with a 7-day weight-maintenance phase followed by a 28-day 30% energy-restriction phase. KHCO3 or PLA supplementation began during energy restriction. NAE, NBAL, and whole-body ammonia and urea turnover (15N-glycine) were measured at the end of the weight-maintenance and energy-restriction phases. Following energy restriction, NAE was -9.8 ± 27.8 mmolâday-1 in KHCO3 and 43.9 ± 27.8 mmolâday-1 in PLA (p < 0.05). No significant group or time differences were observed in NBAL or ammonia and urea turnover. Ammonia synthesis and breakdown tended (p = 0.09) to be higher in KHCO3 vs. PLA following energy restriction, and NAE was inversely associated (r = -0.522; p < 0.05) with urea synthesis in all subjects. This pilot study suggests some benefit may exist with KHCO3 supplementation following energy restriction as lower NAE indicated higher urea synthesis.
Asunto(s)
Amoníaco/metabolismo , Bicarbonatos/administración & dosificación , Dieta Reductora , Nitrógeno/metabolismo , Compuestos de Potasio/administración & dosificación , Urea/metabolismo , Anciano , Amoníaco/orina , Bicarbonatos/orina , Índice de Masa Corporal , Suplementos Dietéticos , Ingestión de Energía , Glicina , Humanos , Concentración de Iones de Hidrógeno , Masculino , Persona de Mediana Edad , Isótopos de Nitrógeno/orina , Obesidad/dietoterapia , Sobrepeso/dietoterapia , Proyectos Piloto , Placebos , Proteínas/metabolismo , Urea/orina , Pérdida de PesoRESUMEN
Metabolic acidosis is the most common acid-base disorder in septic patients and is associated with increased mortality. Previously, we demonstrated that sepsis induced by cecal ligation and puncture (CLP) impairs [Formula: see text] absorption in the medullary thick ascending limb (MTAL) by 1) decreasing the intrinsic [Formula: see text] absorptive capacity and 2) enhancing inhibition of [Formula: see text] absorption by LPS through upregulation of Toll-like receptor (TLR) 4 signaling. Both effects depend on ERK activation. Monophosphoryl lipid A (MPLA) is a detoxified TLR4 agonist that enhances innate antimicrobial immunity and improves survival following sepsis. Pretreatment of MTALs with MPLA in vitro prevents LPS inhibition of [Formula: see text] absorption. Here we examined whether pretreatment with MPLA would protect the MTAL against sepsis. Vehicle or MPLA was administered to mice 48 h before sham or CLP surgery, and MTALs were studied in vitro 18 h postsurgery. Pretreatment with MPLA prevented the effects of sepsis to decrease the basal [Formula: see text] absorption rate and enhance inhibition by LPS. These protective effects were mediated through MPLA stimulation of a Toll/IL-1 receptor domain-containing adaptor-inducing IFN-ß-(TRIF)-dependent phosphatidylinositol 3-kinase-Akt pathway that prevents sepsis- and LPS-induced ERK activation. The effects of MPLA to improve MTAL [Formula: see text] absorption were associated with marked improvement in plasma [Formula: see text] concentration, supporting a role for the kidneys in the pathogenesis of sepsis-induced metabolic acidosis. These studies support detoxified TLR4-based immunomodulators, such as MPLA, that enhance antimicrobial responses as a safe and effective approach to prevent or treat sepsis-induced renal tubule dysfunction and identify cell signaling pathways that can be targeted to preserve MTAL [Formula: see text] absorption and attenuate metabolic acidosis during sepsis.
Asunto(s)
Acidosis/prevención & control , Bicarbonatos/metabolismo , Lípido A/análogos & derivados , Asa de la Nefrona/efectos de los fármacos , Reabsorción Renal/efectos de los fármacos , Sepsis/tratamiento farmacológico , Equilibrio Ácido-Base/efectos de los fármacos , Acidosis/metabolismo , Acidosis/fisiopatología , Proteínas Adaptadoras del Transporte Vesicular/deficiencia , Proteínas Adaptadoras del Transporte Vesicular/genética , Animales , Bicarbonatos/sangre , Bicarbonatos/orina , Modelos Animales de Enfermedad , Activación Enzimática , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Lípido A/farmacología , Asa de la Nefrona/metabolismo , Asa de la Nefrona/fisiopatología , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Fosfatidilinositol 3-Quinasa/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Sepsis/metabolismo , Sepsis/fisiopatología , Transducción de Señal/efectos de los fármacos , Receptor Toll-Like 4/agonistasRESUMEN
The purpose of this study is to describe a low-cost and simply made instrument capable of measuring the total CO2 content of microliter volumes of biological fluids utilizing a commercially available CO2 sensor based on a NDIR detector. The described instrument is based on transformation of dissolved HCO3- to CO2 by acidification and subsequent measurement of the produced CO2. The instrument has a linear response in the range 0.025-10 µmol HCO3-, which enables measurements in fresh urine and plasma samples down to 5 µl. The values from plasma were compared to measurements made on 65 µl whole blood in an automatic blood gas analyzer and found not to differ significantly. Compared to currently commercially available instruments applying the same principles to measure total CO2, this study provides a simple and robust alternative which even can be used on smaller sample volumes.
Asunto(s)
Bicarbonatos/orina , Análisis de los Gases de la Sangre/instrumentación , Líquidos Corporales/química , Dióxido de Carbono/orina , Animales , Productos Biológicos , Análisis de los Gases de la Sangre/métodos , Líquidos Corporales/metabolismo , Dióxido de Carbono/sangre , HumanosRESUMEN
The approach to acid-base chemistry in medicine includes several methods. Currently, the two most popular procedures are derived from Stewart's studies and from the bicarbonate/BE-based classical formulation. Another method, unfortunately little known, follows the Kildeberg theory applied to acid-base titration. By using the data produced by Dana Atchley in 1933, regarding electrolytes and blood gas analysis applied to diabetes, we compared the three aforementioned methods, in order to highlight their strengths and their weaknesses. The results obtained, by reprocessing the data of Atchley, have shown that Kildeberg's approach, unlike the other two methods, is consistent, rational and complete for describing the organ-physiological behavior of the hydrogen ion turnover in human organism. In contrast, the data obtained using the Stewart approach and the bicarbonate-based classical formulation are misleading and fail to specify which organs or systems are involved in causing or maintaining the diabetic acidosis. Stewart's approach, despite being considered 'quantitative', does not propose in any way the concept of 'an amount of acid' and becomes even more confusing, because it is not clear how to distinguish between 'strong' and 'weak' ions. As for Stewart's approach, the classical method makes no distinction between hydrogen ions managed by the intermediate metabolism and hydroxyl ions handled by the kidney, but, at least, it is based on the concept of titration (base-excess) and indirectly defines the concept of 'an amount of acid'. In conclusion, only Kildeberg's approach offers a complete understanding of the causes and remedies against any type of acid-base disturbance.
Asunto(s)
Cetoacidosis Diabética/sangre , Cetoacidosis Diabética/orina , Electrólitos , Riñón/metabolismo , Protones , Equilibrio Ácido-Base , Bicarbonatos/sangre , Bicarbonatos/orina , Análisis de los Gases de la Sangre , Ácido Carbónico/sangre , Ácido Carbónico/orina , Cetoacidosis Diabética/historia , Cetoacidosis Diabética/fisiopatología , Electrólitos/sangre , Electrólitos/orina , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Concentración de Iones de Hidrógeno , Hidróxidos/sangre , Hidróxidos/orina , Riñón/fisiopatologíaRESUMEN
Human stone calcium phosphate (CaP) content correlates with higher urine CaP supersaturation (SS) and urine pH as well as with the number of shock wave lithotripsy (SWL) treatments. SWL does damage medullary collecting ducts and vasa recta, sites for urine pH regulation. We tested the hypothesis that SWL raises urine pH and therefore Cap SS, resulting in CaP nucleation and tubular plugging. The left kidney (T) of nine farm pigs was treated with SWL, and metabolic studies were performed using bilateral ureteral catheters for up to 70 days post-SWL. Some animals were given an NH4Cl load to sort out effects on urine pH of CD injury vs. increased HCO3 (-) delivery. Histopathological studies were performed at the end of the functional studies. The mean pH of the T kidneys exceeded that of the control (C) kidneys by 0.18 units in 14 experiments on 9 pigs. Increased HCO3 (-) delivery to CD is at least partly responsible for the pH difference because NH4Cl acidosis abolished it. The T kidneys excreted more Na, K, HCO3 (-), water, Ca, Mg, and Cl than C kidneys. A single nephron site that could produce losses of all of these is the thick ascending limb. Extensive injury was noted in medullary thick ascending limbs and collecting ducts. Linear bands showing nephron loss and fibrosis were found in the cortex and extended into the medulla. Thus SWL produces tubule cell injury easily observed histopathologically that leads to functional disturbances across a wide range of electrolyte metabolism including higher than control urine pH.
Asunto(s)
Fosfatos de Calcio/orina , Túbulos Renales/metabolismo , Litotricia/efectos adversos , Nefrolitiasis/orina , Eliminación Renal , Cloruro de Amonio/administración & dosificación , Animales , Bicarbonatos/sangre , Bicarbonatos/orina , Femenino , Humanos , Concentración de Iones de Hidrógeno , Túbulos Renales/efectos de los fármacos , Túbulos Renales/lesiones , Túbulos Renales/patología , Túbulos Renales/fisiopatología , Modelos Biológicos , Nefrolitiasis/etiología , Nefrolitiasis/patología , Nefrolitiasis/fisiopatología , Sus scrofa , Factores de Tiempo , Urodinámica , Equilibrio HidroelectrolíticoRESUMEN
OBJECTIVE: To examine the long-term stability and validity of analyte concentrations of 21 clinical biochemistry parameters in 24-h urine samples stored for 12 or 15 yr at -22°C and preservative free. DESIGN AND METHODS: Healthy children's 24-h urine samples in which the respective analytes had been measured shortly after sample collection (baseline) were reanalyzed. Second measurement was performed after 12 yr (organic acids) and 15 yr (creatinine, urea, osmolality, iodine, nitrogen, anions, cations, acid-base parameters) with the same analytical methodology. Paired comparisons and correlations between the baseline and repeated measurements were done. Recovery rates were calculated. RESULTS: More than half of the analytes (creatinine, urea, iodine, nitrogen, sodium, potassium, magnesium, calcium, ammonium, bicarbonate, citric & uric acid) showed measurement values after >10 yr of storage not significantly different from baseline. 15 of the 21 parameters were highly correlated (r=0.99) between baseline and second measurement. Poorest correlation was r=0.77 for oxalate. Recovery ranged from 73% (oxalate) to 105% (phosphate). CONCLUSION: Our results suggest high long-term stability and measurement validity for numerous clinical chemistry parameters stored at -22°C without addition of any urine preservative. Prospective storage of urine aliquots at -22°C for periods even exceeding 10 yr, appears to be an acceptable and valid tool in epidemiological settings for later quantification of several urine analytes.
Asunto(s)
Bancos de Muestras Biológicas , Congelación , Toma de Muestras de Orina/métodos , Orina/química , Compuestos de Amonio/orina , Bicarbonatos/orina , Calcio/orina , Química Clínica/métodos , Niño , Preescolar , Ácido Cítrico/orina , Creatinina/orina , Femenino , Humanos , Yodo/orina , Magnesio/orina , Masculino , Nitrógeno/orina , Potasio/orina , Estudios Prospectivos , Reproducibilidad de los Resultados , Sodio/orina , Factores de Tiempo , Urea/orina , Ácido Úrico/orinaRESUMEN
BACKGROUND: The exact frequency of distal and proximal renal tubular acidosis (RTA) in Sjögren's syndrome is unknown. Other features of Sjögren's syndrome like polyuria, glomerular manifestations, familial occurrence and pregnancy are not widely reported. The aim was to prospectively study the clinical features and outcome of distal and proximal RTA in Sjögren's syndrome and also report on other renal manifestations of Sjögren's syndrome. METHODS: The present study is a prospective consecutive case series of patients who presented with a history suggestive of RTA and Sjögren's syndrome. All patients were followed for 1 year. The diagnosis of RTA was by fractional excretion of bicarbonate. The diagnosis of Sjögren's syndrome was according to the American-European classification system [modified by Tzioufas and Voulgarelis: Best Pract Res Clin Rheumatol 2007;21:989-1010]. RESULTS: The total number of RTA patients diagnosed during this period was 149. Sjögren's syndrome accounted for 34.8% (52 of 149) of RTA patients. The important symptoms and laboratory parameters were oral and ocular symptoms in 23 (44.2%), dental caries in 12 (23%), body pains in 47 (90.3%), mean serum pH 7.202 ± 0.03, mean serum bicarbonate, 14.03 ± 1.66 mmol/l, and mean urine pH, 7.125 ± 0.54. There were 30 (57.6%) patients with distal RTA and 22 (42.3%) patients with proximal RTA. CONCLUSIONS: The clinical implication of the present study is that RTA is a common feature of Sjögren's syndrome. It may be missed if the presentation is not due to oral and ocular symptoms. The present study is also the only one with a 1-year follow-up.
Asunto(s)
Acidosis Tubular Renal/etiología , Síndrome de Sjögren/complicaciones , Acidosis Tubular Renal/diagnóstico , Acidosis Tubular Renal/tratamiento farmacológico , Adolescente , Adulto , Anticuerpos Antinucleares/sangre , Bicarbonatos/sangre , Bicarbonatos/orina , Niño , Enfermedad Crónica , Caries Dental/etiología , Femenino , Humanos , Concentración de Iones de Hidrógeno , Hipopotasemia/sangre , Recién Nacido , Infertilidad Femenina/etiología , Masculino , Persona de Mediana Edad , Nefritis Intersticial/etiología , Muerte Perinatal , Poliuria/etiología , Embarazo , Estudios Prospectivos , Síndrome de Sjögren/diagnóstico , Síndrome de Sjögren/inmunología , Adulto JovenRESUMEN
BACKGROUND: The clinical dehydration scale (CDS) is a quick, easy-to-use tool with 4 clinical items and a score of 1-8 that serves to classify dehydration in children with gastroenteritis as no, some or moderate/severe dehydration. Studies validating the CDS (Friedman JN) with a comparison group remain elusive. We hypothesized that the CDS correlates with a wide spectrum of established markers of dehydration, making it an appropriate and easy-to-use clinical tool. METHODS: This study was designed as a prospective double-cohort trial in a single tertiary care center. Children with diarrhea and vomiting, who clinically required intravenous fluids for rehydration, were compared with minor trauma patients who required intravenous needling for conscious sedation. We compared the CDS with clinical and urinary markers (urinary electrolytes, proteins, ratios and fractional excretions) for dehydration in both groups using receiver operating characteristic (ROC) curves to determine the area under the curve (AUC). RESULTS: We enrolled 73 children (male = 36) in the dehydration group and 143 (male = 105) in the comparison group. Median age was 32 months (range 3-214) in the dehydration and 96 months (range 2.6-214 months, p < 0.0001) in the trauma group. Median CDS was 3 (range 0-8) within the dehydration group and 0 in the comparison group (p < 0.0001). The following parameters were statistically significant (p < 0.05) between the comparison group and the dehydrated group: difference in heart rate, diastolic blood pressure, urine sodium/potassium ratio, urine sodium, fractional sodium excretion, serum bicarbonate, and creatinine measurements. The best markers for dehydration were urine Na and serum bicarbonate (ROC AUC = 0.798 and 0.821, respectively). CDS was most closely correlated with serum bicarbonate (Pearson r = -0.3696, p = 0.002). CONCLUSION: Although serum bicarbonate is not the gold standard for dehydration, this study provides further evidence for the usefulness of the CDS as a dehydration marker in children. TRIAL REGISTRATION: Registered at ClinicalTrials.gov (NCT00462527) on April 18, 2007.
Asunto(s)
Bicarbonatos/orina , Deshidratación/diagnóstico , Deshidratación/orina , Índice de Severidad de la Enfermedad , Sodio/orina , Adolescente , Biomarcadores/orina , Presión Sanguínea , Niño , Preescolar , Creatinina/orina , Deshidratación/etiología , Femenino , Fluidoterapia , Gastroenteritis/complicaciones , Frecuencia Cardíaca , Humanos , Lactante , Masculino , Potasio/orina , Estudios Prospectivos , Curva ROCRESUMEN
Na(+)-glucose cotransporter 1 (SGLT1)-mediated glucose uptake leads to activation of Na(+)-H(+) exchanger 3 (NHE3) in the intestine by a process that is not dependent on glucose metabolism. This coactivation may be important for postprandial nutrient uptake. However, it remains to be determined whether SGLT-mediated glucose uptake regulates NHE3-mediated NaHCO3 reabsorption in the renal proximal tubule. Considering that this nephron segment also expresses SGLT2 and that the kidneys and intestine show significant variations in daily glucose availability, the goal of this study was to determine the effect of SGLT-mediated glucose uptake on NHE3 activity in the renal proximal tubule. Stationary in vivo microperfusion experiments showed that luminal perfusion with 5 mM glucose stimulates NHE3-mediated bicarbonate reabsorption. This stimulatory effect was mediated by glycolytic metabolism but not through ATP production. Conversely, luminal perfusion with 40 mM glucose inhibited NHE3 because of cell swelling. Notably, pharmacologic inhibition of SGLT activity by Phlorizin produced a marked inhibition of NHE3, even in the absence of glucose. Furthermore, immunofluorescence experiments showed that NHE3 colocalizes with SGLT2 but not SGLT1 in the rat renal proximal tubule. Collectively, these findings show that glucose exerts a bimodal effect on NHE3. The physiologic metabolism of glucose stimulates NHE3 transport activity, whereas, supraphysiologic glucose concentrations inhibit this exchanger. Additionally, Phlorizin-sensitive SGLT transporters and NHE3 interact functionally in the proximal tubule.
Asunto(s)
Glucosa/metabolismo , Túbulos Renales Proximales/metabolismo , Transportador 1 de Sodio-Glucosa/metabolismo , Transportador 2 de Sodio-Glucosa/metabolismo , Intercambiadores de Sodio-Hidrógeno/metabolismo , Adenosina Trifosfato/biosíntesis , Animales , Bicarbonatos/metabolismo , Bicarbonatos/orina , Galactosa/metabolismo , Inmunohistoquímica , Túbulos Renales Proximales/efectos de los fármacos , Masculino , Metilglucósidos/metabolismo , Modelos Biológicos , Presión Osmótica , Florizina/farmacología , Ratas , Ratas Wistar , Transportador 1 de Sodio-Glucosa/antagonistas & inhibidores , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Intercambiador 3 de Sodio-HidrógenoRESUMEN
BACKGROUND AND OBJECTIVES: For accurate measurement of pH, urine collection under oil to limit the escape of CO(2) on air exposure is recommended. This study aims to test the hypothesis that urine collection under oil is not necessary in acidic urine in which bicarbonate and CO(2) are minor buffers, because loss of CO(2) would have little effect on its pH. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: One hundred consecutive random urine samples were collected under oil and analyzed for pH, pCO(2), and HCO(3)(-) immediately and after 5 minutes of vigorous shaking in uncovered flasks to allow CO(2) escape. RESULTS: The pH values in 97 unshaken samples ranged from 5.03 to 6.83. With shaking, urine pCO(2) decreased by 76%, whereas urine HCO(3)(-) decreased by 60%. Meanwhile, urine baseline median pH (interquartile range) of 5.84 (5.44-6.25) increased to 5.93 (5.50-6.54) after shaking (ΔpH=0.12 [0.07-0.29], P<0.001). ΔpH with pH≤6.0 was significantly lower than the ΔpH with pH>6.0 (0.08 [0.05-0.12] versus 0.36 [0.23-0.51], P<0.001). Overall, the lower the baseline pH, the smaller the ΔpH. CONCLUSIONS: The calculation of buffer reactions in a hypothetical acidic urine predicted a negligible effect on urine pH on loss of CO(2) by air exposure, which was empirically proven by the experimental study. Therefore, exposure of urine to air does not substantially alter the results of diagnostic tests for urine acidification, and urine collection under oil is not necessary.
Asunto(s)
Aire , Manejo de Especímenes , Urinálisis/métodos , Orina/química , Adulto , Anciano , Bicarbonatos/orina , Tampones (Química) , Dióxido de Carbono/orina , Humanos , Concentración de Iones de Hidrógeno , Masculino , Persona de Mediana Edad , Aceites , Parafina , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Factores de TiempoRESUMEN
To determine the clinical profile and progression of renal dysfunction in distal renal tubular acidosis (dRTA), we retrospectively studied 96 consecutive cases of dRTA diagnosed at our center. Patients with unexplained metabolic bone disease, short stature, hypokalemia, re-current renal stones, chronic obstructive uropathy or any primary autoimmune condition known to cause dRTA were screened. Distal RTA was diagnosed on the basis of systemic metabolic acidosis with urine pH >5.5 and positive urine anion gap. In those patients who had fasting urine pH >5.5 with normal baseline systemic pH and bicarbonate levels (incomplete RTA), acid load test with ammonium chloride was done. A cause of dRTA could be established in 53 (54%) patients. Urological defect in children (22/44) and autoimmune disease in adults (11/52) were the commonest causes. Hypokalemic paralysis, proximal muscle weakness and voiding difficulty were the common modes of presentation. Doubling of serum creatinine during the study period was noted in 13 out of 27 patients who had GFR <60 mL/min at presentation whereas in only one of the 70 with initial GFR >60 mL/min (P <0.005). In conclusion, urological disorders were the commonest cause of dRTA in children while autoimmune disorders were the commonest asso-ciation in adults. Worse baseline renal function, longer duration of disease and greater frequency of nephrolithiasis/nephrocalcinosis and urological disorders were noted in those who had wor-sening of renal dysfunction during the study period.
Asunto(s)
Equilibrio Ácido-Base , Acidosis Tubular Renal/diagnóstico , Acidosis Tubular Renal/epidemiología , Acidosis Tubular Renal/etiología , Acidosis Tubular Renal/fisiopatología , Acidosis Tubular Renal/orina , Adolescente , Adulto , Factores de Edad , Anciano , Bicarbonatos/orina , Biomarcadores/sangre , Biomarcadores/orina , Calcio/orina , Niño , Preescolar , Creatinina/sangre , Progresión de la Enfermedad , Femenino , Tasa de Filtración Glomerular , Humanos , Concentración de Iones de Hidrógeno , India/epidemiología , Lactante , Riñón/fisiopatología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Urinálisis , Adulto JovenRESUMEN
Exposure to lead has been reported to have adverse health implications. An assessment of renal function in people occupationally exposed to lead was carried out using the following biochemical markers urea, creatinine, sodium, potassium, chloride and bicarbonate. A total of 53 test subjects (mean age 30.9 ± 7.7) were randomly selected among some workers occupationally exposed to lead in Osogbo city and 42 apparently healthy subjects (mean age 30.1 ± 1.2) were used as controls. The plasma urea, creatinine, chloride and bicarbonate concentration were determined using modified Berthelot method, Jaffe's reaction, Schales and Schales method and back titration methods, respectively. The plasma sodium and potassium concentrations were determined using flame emission spectrophotometry while blood lead level was also determined using atomic absorption spectrophotometry. The result showed significant increases in mean plasma concentration of creatinine (84.9 ± 13.6-97.4 ± 28.7 µmol/L), sodium (131.9 ± 3.9-134.8 ± 3.7 mmol/L) and chloride (98.2 ± 4.0-100.4 ± 3.9 mmol/L) in test subjects when compared with controls (p < 0.05). Furthermore, significant increases (p < 0.01) were observed in mean plasma concentration of urea (4.7 ± 1.2-5.7 ± 1.3 mmol/L) and blood lead levels (18.5 ± 3.5-69.7 ± 13.2 mg/L) in test subjects in comparison with controls. In contrast, there were no significant differences observed when mean plasma potassium and bicarbonate levels in test subjects were compared with controls (p > 0.05). These results indicate that occupational exposure to lead may compromise renal function.
Asunto(s)
Riñón/patología , Plomo/toxicidad , Exposición Profesional/efectos adversos , Adulto , Bicarbonatos/sangre , Bicarbonatos/orina , Biomarcadores/sangre , Biomarcadores/orina , Estudios de Casos y Controles , Cloruros/sangre , Cloruros/orina , Creatinina/sangre , Creatinina/orina , Países en Desarrollo , Humanos , Pruebas de Función Renal , Masculino , Nigeria , Potasio/sangre , Potasio/orina , Sodio/sangre , Sodio/orina , Espectrofotometría Atómica/métodos , Urea/sangre , Urea/orina , Adulto JovenRESUMEN
A prospective examination of 103 newborns with hypoxic damage of the central nervous system of moderate severity was conducted on the 4-7, 10-14 and 21-28 days after birth and included clinical examination, neurosonographic study with dopplerography of great brain arteries and biochemical study of venous blood and urine. Children with ventriculomegalia were treated with diacarb. A control group included 15 newborns without signs of survived hypoxia. Ventriculomegalia was found in 29% of children in the main group and remained till the end of neonatal period in 15%, with moderate and large dilatation in 63,5% and mild dilatation of anterior horns of lateral ventriculars in 36,5%. The markers of development and long remaining ventriculomegalia are specified as follows: the morphofunctional immaturity of the brain (RR=1,7; 95%CI 1,16-2,45), absence of compensatory reduction of resistance index (RI) in anterior brain arteries on 4-7 days of life (RR=3,03; 95%CI 2,11-4,31), metabolic acidosis - the bicarbonate level in the venous blood less than 21 mmol/l (RR=2,9; 95% CI 1,66-5,02), carbanhydrase activation - bicarbonate concentration in the urine less than 5 mmol/mcmol of creatinine on 4-7 days of life (RR=3,81; 95%CI 2,87-5,02). Diacarb in ventriculomegalia should be prescribed only in case of disturbance of the organism compensatory reaction because it causes the significant increase of compensatory reduced RI. The drug has a nephrotoxic effect and causes metabolic acidosis.
Asunto(s)
Acetazolamida/uso terapéutico , Isquemia Encefálica/etiología , Circulación Cerebrovascular/fisiología , Diuréticos/uso terapéutico , Hidrocefalia/complicaciones , Bicarbonatos/sangre , Bicarbonatos/orina , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/tratamiento farmacológico , Ventrículos Cerebrales/irrigación sanguínea , Ventrículos Cerebrales/diagnóstico por imagen , Creatinina/sangre , Creatinina/orina , Estudios de Seguimiento , Edad Gestacional , Humanos , Hidrocefalia/diagnóstico , Hidrocefalia/tratamiento farmacológico , Recién Nacido , Pronóstico , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Ultrasonografía Doppler TranscranealRESUMEN
BACKGROUND: Dietary acid charge enhances bone loss. Bicarbonate or alkali diet decreases bone resorption in humans. We compared the effect of an alkaline mineral water, rich in bicarbonate, with that of an acid one, rich in calcium only, on bone markers, in young women with a normal calcium intake. METHODS: This study compared water A (per litre: 520 mg Ca, 291 mg HCO(3)(-), 1160 mg SO(4)(-), Potential Renal Acid load (PRAL) +9.2 mEq) with water B (per litre: 547 mg Ca, 2172 mg HCO(3)(-), 9 mg SO(4)(-), PRAL -11.2 mEq). 30 female dieticians aged 26.3 yrs (SD 7.3) were randomized into two groups, followed an identical weighed, balanced diet (965 mg Ca) and drank 1.5 l/d of the assigned water. Changes in blood and urine electrolytes, C-telopeptides (CTX), urinary pH and bicarbonate, and serum PTH were measured after 2 and 4 weeks. RESULTS: The two groups were not different at baseline, and showed a similar increase in urinary calcium excretion. Urinary pH and bicarbonate excretion increased with water B, but not with water A. PTH (p=0.022) and S-CTX (p=0.023) decreased with water B but not with water A. CONCLUSION: In calcium sufficiency, the acid calcium-rich water had no effect on bone resorption, while the alkaline water rich in bicarbonate led to a significant decrease of PTH and of S-CTX.
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Álcalis/uso terapéutico , Resorción Ósea/tratamiento farmacológico , Huesos/metabolismo , Calcio de la Dieta/uso terapéutico , Aguas Minerales/uso terapéutico , Adolescente , Adulto , Bicarbonatos/orina , Huesos/patología , Colágeno Tipo I/sangre , Ayuno/orina , Femenino , Pruebas Hematológicas , Humanos , Concentración de Iones de Hidrógeno , Persona de Mediana Edad , Hormona Paratiroidea/sangre , Péptidos/sangre , UrinálisisRESUMEN
We aimed to compare the recent practical method of capillary beta-hydroxy butyrate (betaOHB) measurement with the widely used urinary ketone measurement in monitoring metabolic status of the patient during treatment of diabetic ketoacidosis (DKA) and diabetic ketosis (DK). Patients with DKA and DK admitted to the hospital were followed with simultaneous measurements of capillary betaOHB by electrochemical method (Medisense Optium, Abbott), and urinary ketone by semi-quantitative method. Blood gases were measured in 2-4 h intervals. Fourteen patients with DKA/DK (7 males and 7 females, age: 9.2 +/- 4.2 years) were included with 50 simultaneous measurements of capillary and urinary ketone. No correlation was detected between urinary ketone and blood pH (P = 0.06) and HCO3 (P = 0.79), whereas a significant negative correlation was found between capillary betaOHB and blood pH (r = -0.41, P < 0.05) and HCO3 (r = -0.35, P < 0.05). Capillary betaOHB and urinary ketone levels did not correlate at the beginning and 3.3 +/- 1.4 h after treatment, but did correlate in the third samples taken 7.8 +/- 2.0 h after treatment (r = 0.8, P < 0.05). Capillary betaOHB levels show good correlation with the degree of acidosis (pH and HCO3). Capillary betaOHB measurement is more sensitive than urinary ketone measurement in reflecting the patient's metabolic status and improvement during treatment.
Asunto(s)
Capilares/fisiología , Cetoacidosis Diabética/sangre , Cetonas/sangre , Adolescente , Bicarbonatos/sangre , Bicarbonatos/orina , Niño , Preescolar , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/orina , Cetoacidosis Diabética/orina , Electroquímica/métodos , Humanos , Concentración de Iones de Hidrógeno , Cetonas/orina , Registros MédicosRESUMEN
BACKGROUND: Inherited proximal renal tubular acidosis (pRTA) is commonly associated with more generalized proximal tubular dysfunctions and occasionally with other organ system defects. Inherited combined pRTA and distal RTA with osteopetrosis and pure pRTA associated with ocular abnormalities, a rare disease which has been recently described. Only one family with pure isolated pRTA has been reported so far and the genetic cause for this disease is unknown. Objectives. We report a unique family with isolated pRTA. The aim of the project was to define the phenotype and to try to find the gene defect causing the disease. METHODS: Clinical and metabolic evaluation of all family members was performed and a family pedigree was constructed. DNA was extracted from blood samples of affected and unaffected family members. We amplified by PCR and sequenced the coding areas and splice-sites of the genes that contribute to HCO(-)(3) reclamation in the proximal tubule. The genes studied were as follows: CA II, CA IV, CA XIV, NCB1, Na(+)/H(+) exchanger (NHE)-3, NHE-8, the regulatory proteins of NHE3, NHRF1 and NHRF2 and the Cl(-)/HCO(-)(3) exchanger, SLC26A6. RESULTS: The father and all four children had RTA with blood HCO(-)(3) levels of 11-14 meq/l and urine pH of 5.3-5.4. Increased HCO(-)(3) fractional excretion after bicarbonate loading to 40-60% confirmed the diagnosis pRTA. No other tubular dysfunction was found, and no organ system dysfunction was detected, besides short stature. No mutation was found in all candidate genes studied. CONCLUSIONS: We presented a second family in the literature with familial isolated pure pRTA. The mode of inheritance is compatible with an autosomal dominant disease. Because of the small size of the family, wide genome search was not applicable and the gene candidate approach was chosen. Nine important candidate genes were extensively studied but the molecular basis of the disease was not yet found and genotyping nine important gene candidates were negative.
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Acidosis Tubular Renal/genética , Biomarcadores/sangre , ADN/genética , Marcadores Genéticos/genética , Predisposición Genética a la Enfermedad , Mutación , Linaje , Equilibrio Ácido-Base , Acidosis Tubular Renal/metabolismo , Proteínas de Transporte de Anión/sangre , Proteínas de Transporte de Anión/genética , Bicarbonatos/sangre , Bicarbonatos/orina , Biomarcadores/orina , Anhidrasa Carbónica II/sangre , Anhidrasa Carbónica II/genética , Anhidrasa Carbónica IV/sangre , Anhidrasa Carbónica IV/genética , Anhidrasas Carbónicas/sangre , Anhidrasas Carbónicas/genética , Femenino , Haplotipos , Humanos , Recién Nacido , Túbulos Renales Proximales/metabolismo , Masculino , Proteínas de Transporte de Membrana/sangre , Proteínas de Transporte de Membrana/genética , Fenotipo , Reacción en Cadena de la Polimerasa , Simportadores de Sodio-Bicarbonato/sangre , Simportadores de Sodio-Bicarbonato/genética , Intercambiador 3 de Sodio-Hidrógeno , Intercambiadores de Sodio-Hidrógeno/sangre , Intercambiadores de Sodio-Hidrógeno/genética , Transportadores de SulfatoRESUMEN
Forty-two lactating Holstein cows 188 +/- 59 d in milk were used in an 8-wk randomized complete block trial with a 2 x 3 factorial arrangement of treatments. The objective was to determine the effects of high dietary cation-anion difference (DCAD) and K:Na ratio on milk yield and composition and blood acid-base chemistry. Treatments included DCAD concentrations of 45 or 60 mEq (Na + K -Cl)/100 g of feed dry matter and K:Na ratios of 2:1, 3:1, or 4:1. Mean DCAD values were later determined to be 41 and 58. Dry matter intake was similar across treatments. Yield of milk and energy corrected milk were lower for the 3:1 K:Na ratio compared with 2:1 and 4:1 ratios. Blood urea N was lower for the highest DCAD, suggesting that DCAD possibly reduced protein degradation or altered protein metabolism and retention. Mean temperature-humidity index was 75.6 for the duration of the trial, exceeding the critical value of 72 for all weeks during the treatment period. Cows maintained relatively normal body temperature with mean a.m. and p.m. body temperature of 38.5 and 38.7 degrees C, respectively. These body temperatures suggest that cows were not subject to extreme heat stress due to good environmental control. Results of this trial indicate that the greatest effect on milk yield occurs when either Na or K is primarily used to increase DCAD, with the lowest yield of energy-corrected milk at a 3:1 K:Na ratio (27.1 kg/d) compared with ratios of 2:1 (29.3 kg/d) and 4:1 (28.7 kg/d). Results also suggest that greater DCAD improves ruminal N metabolism or N utilization may be more efficient with a high DCAD.
Asunto(s)
Equilibrio Ácido-Base/fisiología , Bovinos/fisiología , Calor , Lactancia/fisiología , Potasio en la Dieta/administración & dosificación , Sodio en la Dieta/administración & dosificación , Amoníaco/sangre , Animales , Aniones , Bicarbonatos/sangre , Bicarbonatos/orina , Nitrógeno de la Urea Sanguínea , Peso Corporal , Cationes , Dieta , Ambiente , Femenino , Humedad , Leche/químicaRESUMEN
Dietary protein as casein (CAS) augments intrinsic acid production, induces endothelin-mediated kidney acidification, and promotes kidney injury. We tested the hypothesis that dietary CAS induces endothelin-mediated kidney injury through augmented intrinsic acid production. Munich-Wistar rats ate minimum electrolyte diets from age 8 to 96 weeks with 50 or 20% protein as either acid-inducing CAS or non-acid-inducing SOY. Urine net acid excretion and distal nephron net HCO3 reabsorption by in vivo microperfusion (Net J(HCO3)) were higher in 50 than 20% CAS but not 50 and 20% SOY. At 96 weeks, 50% compared the 20% CAS had higher urine endothelin-1 excretion (U(ET-1)V) and a higher index of tubulo-interstitial injury (TII) at pathology (2.25+/-0.21 vs 1.25+/-0.13 U, P<0.03), but each parameter was similar in 50 and 20% SOY. CAS (50%) eating NaHCO3 to reduce intrinsic acid production had lower Net J(HCO3), lower U(ET-1)V, and less TII. By contrast, 50% SOY eating dietary acid as (NH4)2SO4 had higher Net J(HCO3), higher U(ET-1)V, and more TII. Endothelin A/B but not A receptor antagonism reduced Net J(HCO3) in 50% CAS and 50% SOY+(NH4)2SO4 animals. By contrast, endothelin A but not A/B receptor antagonism reduced TII in each group. The data support that increased intake of acid-inducing dietary protein induces endothelin B-receptor-mediated increased Net J(HCO3) and endothelin A-receptor-mediated TII through augmented intrinsic acid production.