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Renal tubular acidosis [keywords]
- [Acute kidney injury in children]. [English Abstract, Journal Article]
- Srp Arh Celok Lek 2014 May-Jun; 142(5-6):371-7.
Acute kidney injury (AKI) is a clinical condition considered to be the consequence of a sudden decrease (> 25%) or discontinuation of renal function. The term AKI is used instead of the previous term acute renal failure, because it has been demonstrated that even minor renal lesions may cause far-reaching consequences on human health. Contemporary classifications of AKI (RIFLE and AKIN) are based on the change of serum creatinine and urinary output. In the developed countries, AKI is most often caused by renal ischemia, nephrotoxins and sepsis, rather than a (primary) diffuse renal disease, such as glomerulonephritis, interstitial nephritis, renovascular disorder and thrombotic microangiopathy. The main risk factors for hospital AKI are mechanical ventilation, use of vasoactive drugs, stem cell transplantation and diuretic-resistant hypervolemia. Prerenal and parenchymal AKI (previously known as acute tubular necrosis) jointly account for 2/3 of all AKI causes. Diuresis and serum creatinine concentration are not early diagnostic markers of AKI. Potential early biomarkers of AKI are neutrophil gelatinase-associated lipocalin (NGAL), cystatin C, kidney injury molecule-1 (KIM-1), interleukins 6, 8 and 18, and liver-type fatty acid-binding protein (L-FABP). Early detection of kidney impairment, before the increase of serum creatinine, is important for timely initiated therapy and recovery. The goal of AKI treatment is to normalize the fluid and electrolyte status, as well as the correction of acidosis and blood pressure. Since a severe fluid overload resistant to diuretics and inotropic agents is associated with a poor outcome, the initiation of dialysis should not be delayed. The mortality rate of AKI is highest in critically ill children with multiple organ failure and hemodynamically unstable patients.
- Combination Therapy with Losartan and α-Tocopherol in Acute Ureteral Obstruction-Induced Renal Excretory Dysfunction and Acidification Defect. [Journal Article]
- Iran J Med Sci 2014 Jul; 39(4):357-66.
Background:Previous study by the authors showed that a-tocopherol prevents oxidative stress but would not improve depressed excretory variables in post-obstructed kidney (POK) after release of 24-h unilateral ureteral obstruction (UUO). This study is a supplementary investigation on the effects of a-tocopherol combined with an antagonist of angiotensin-II type-1 (AT1) receptor on renal dysfunction following release of acute UUO.
Methods:The left ureter was ligated in different groups of male Sprague-Dawley rats that received normal saline, losartan or losartan/a-tocopherol (n=6 in each group). After releasing 24-h UUO, urine of each kidney was separately collected under paraffin during 1-3 h of post-release period and then both kidneys were removed for measuring malondialdehyde (MDA) and ferric reducing/antioxidant power (FRAP).
Results:Losartan-treatment decreased MDA and increased FRAP, creatinine-clearance and sodium-reabsorption in POK, while co-treatment with losartan and a-tocopherol not only augmented improvement in these variables but also elevated potassium-excretion, free-water reabsorption and urine-osmolality. However, UUO-induced fall in urinary pCO2 and rise in pH and bicarbonate-excretion of POK were ameliorated equally with losartan and losartan/a-tocopherol.
Conclusion:Activation of AT1-receptor contributes to the development of renal distal acidification defect induced by acute ureteral obstruction. The co-treatment with losartan and a-tocopherol showed that their effects on preventing oxidative stress along with ameliorating glomerular filtration and tubular fluid-delivery in POK could lead to improvement in tubular transport of sodium and potassium as well as urine-concentrating ability at the early post-release period.
- Acute thiamine deficiency and refeeding syndrome: Similar findings but different pathogenesis. [Journal Article]
- Nutrition 2014 Jul-Aug; 30(7-8):948-52.
Refeeding syndrome can occur in several contexts of relative malnutrition in which an overaggressive nutritional support is started. The consequences are life threatening with multiorgan impairment, and severe electrolyte imbalances. During refeeding, glucose-involved insulin secretion causes abrupt reverse of lipolysis and a switch from catabolism to anabolism. This creates a sudden cellular demand for electrolytes (phosphate, potassium, and magnesium) necessary for synthesis of adenosine triphosphate, glucose transport, and other synthesis reactions, resulting in decreased serum levels. Laboratory findings and multiorgan impairment similar to refeeding syndrome also are observed in acute thiamine deficiency. The aim of this study was to determine whether thiamine deficiency was responsible for the electrolyte imbalance caused by tubular electrolyte losses.We describe two patients with leukemia who developed acute thiamine deficiency with an electrolyte pattern suggestive of refeeding syndrome, severe lactic acidosis, and evidence of proximal renal tubular dysfunction.A single thiamine administration led to rapid resolution of the tubular dysfunction and normalization of acidosis and electrolyte imbalance. This demonstrated that thiamine deficiency was responsible for the electrolyte imbalance, caused by tubular electrolyte losses.Our study indicates that, despite sharing many laboratory similarities, refeeding syndrome and acute thiamine deficiency should be viewed as separate entities in which the electrolyte abnormalities reported in cases of refeeding syndrome with thiamine deficiency and refractory lactic acidosis may be due to renal tubular losses instead of a shifting from extracellular to intracellular compartments. In oncologic and malnourished patients, individuals at particular risk for developing refeeding syndrome, in the presence of these biochemical abnormalities, acute thiamine deficiency should be suspected and treated because it promptly responds to thiamine administration.
- Roles of Renal Proximal Tubule Transport in Acid/Base Balance and Blood Pressure Regulation. [REVIEW]
- Biomed Res Int 2014.:504808.
Sodium-coupled bicarbonate absorption from renal proximal tubules (PTs) plays a pivotal role in the maintenance of systemic acid/base balance. Indeed, mutations in the Na(+)-HCO3 (-) cotransporter NBCe1, which mediates a majority of bicarbonate exit from PTs, cause severe proximal renal tubular acidosis associated with ocular and other extrarenal abnormalities. Sodium transport in PTs also plays an important role in the regulation of blood pressure. For example, PT transport stimulation by insulin may be involved in the pathogenesis of hypertension associated with insulin resistance. Type 1 angiotensin (Ang) II receptors in PT are critical for blood pressure homeostasis. Paradoxically, the effects of Ang II on PT transport are known to be biphasic. Unlike in other species, however, Ang II is recently shown to dose-dependently stimulate human PT transport via nitric oxide/cGMP/ERK pathway, which may represent a novel therapeutic target in human hypertension. In this paper, we will review the physiological and pathophysiological roles of PT transport.
- The Case | Renal tubular acidosis and eye findings. [Journal Article]
- Kidney Int 2014 Jul; 86(1):217-8.
- Mutation analysis and audiologic assessment in six Chinese children with primary distal renal tubular acidosis. [JOURNAL ARTICLE]
- Ren Fail 2014 Jun 30.:1-7.
Abstract The objective of this study is to identify ATP6V1B1, ATP6V0A4 and SLC4A1 genes mutations and assess audiologic characteristics in six Chinese children with primary distal renal tubular acidosis from four unrelated families between the ages of 2 and 13 years. Both ATP6V0A4 and ATP6V1B1 genes were preferentially screened in all index cases by direct sequence analysis. If inconclusive then SLC4A1 gene should be analyzed for mutation. Their clinical features, hearing status and inner ear imaging structure were also investigated. Six loss-of-function mutations were identified in six patients. Two novel mutations were identified in either of ATP6V0A4 and ATP6V1B1 genes, respectively. Two probands from different kindreds with mutations in ATP6V1B1 presented early onset profound sensorineural hearing loss (SNHL) and enlarged vestibular aqueduct (EVA). Two from different families carrying ATP6V0A4 mutations manifested early onset moderate mixed HL and moderate SNHL, respectively, the former comorbid with EVA, while the latter not; however, both their elder sisters showed normal hearing and inner ear. These findings expand the spectrum of mutations in the ATP6V0A4 and ATP6V1B1 genes associated with primary dRTA. Our study confirms the association of EVA and mutations in either of these two genes. More studies are necessary to clarify the relationship between dRTA, SNHL, EVA, and gene mutations.
- Hypokalaemic paralysis and normocalcaemic tetany--a rare presentation of Sjogren's syndrome. [Journal Article]
- J Assoc Physicians India 2013 Nov; 61(11):818-20.
38 year old woman was admitted with acute onset of quadriplegia. Biochemical investigation revealed severe hypokalaemia with hyperchloraemic metabolic acidosis, alkaline urine, and positive urinary anion gap which are the hallmark of distal tubular acidosis. In addition she also had hypophosphataemia, normoglycaemic glycosuria, aminoaciduria, and hyperphosphaturia suggestive of proximal tubular dysfunction. Further evaluation confirmed the diagnosis of Sjogren's syndrome. Interestingly our patient also had carpopedal spasm despite normal calcium and magnesium level. Quadriplegia and carpopedal spasm improved with correction of hypokalaemia and acidosis. Proximal tubular abnormalities (except albuminuria) were normalised at the time of discharge. Distal tubular acidosis is a well known renal manifestation of Sjogren's syndrome. But this type of transient proximal tubular dysfunction with distal tubular acidosis in Sjogren's syndrome is very rare and hypokalaemic tetany also deserves mention.
- Metabolic acidosis in the first 14 days of life in infants of gestation less than 26 weeks. [JOURNAL ARTICLE]
- Eur J Pediatr 2014 Jun 27.
Extremely immature newborns develop a self-limiting normal anion gap metabolic acidosis in early life. This study examined the natural history of this acidosis in a population of infants of gestation less than 26 weeks in the first 14 days of life. The acidosis was maximal on day 4 with a mean base deficit of 10.6 mmol/l and had resolved in 90 % of infants by day 11. Dopamine usage was the only independent predictor of the acidosis. Its use was associated with a greater degree of acidosis. Conclusion: Extremely preterm infants experience a self-limiting normal anion gap metabolic acidosis in the first 2 weeks of life which is consistent with renal tubular immaturity.
- DEGRADATION MECHANISM OF A GOLGI-RETAINED DISTAL RENAL TUBULAR ACIDOSIS MUTANT OF THE KIDNEY ANION EXCHANGER 1 IN RENAL CELLS. [JOURNAL ARTICLE]
- Am J Physiol Cell Physiol 2014 Jun 11.
Distal renal tubular acidosis (dRTA) can be caused by mutations in the SLC4A1 gene encoding the anion exchanger 1. Both recessive and dominant mutations result in mistrafficking of proteins preventing them from reaching the basolateral membrane of renal epithelial cells where their function is needed. In this study, we show that two dRTA mutants are prematurely degraded. We therefore investigated the degradation pathway of kAE1 G701D mutant that is retained in the Golgi. Little is known about degradation of non-native membrane proteins from the Golgi compartments in mammalian cells. Here, we show that the kAE1 G701D mutant is poly-ubiquitylated and degraded by both the lysosome and the proteosome. This mutant reaches the plasma membrane where it is endocytosed and degraded by the lysosome via a mechanism dependent on the peripheral quality control machinery. Furthermore, we show that the function of the mutant is rescued at the cell surface upon inhibition of the lysosome and incubation with a chemical chaperone. We conclude that modulating the peripheral quality control machinery may provide a novel therapeutic option for the treatment of patients with dRTA due to a Golgi-retained mutant.