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Giornale Italiano Di Nefrologia :... 2014Rhabdomyolysis is characterized by skeletal muscle necrosis resulting in release of large amounts of toxic muscle cell components, including electrolytes, myoglobin, and... (Review)
Review
Rhabdomyolysis is characterized by skeletal muscle necrosis resulting in release of large amounts of toxic muscle cell components, including electrolytes, myoglobin, and other sarcoplasmic proteins into circulation. Creatinine phosphokinase (CPK) and myoglobin serum levels constitute the diagnostic hallmark. Nowadays, drugs have become one of the most frequent cause of rhabdomyolysis and acute kidney injury (AKI) is a potential life-threatening complication. The mechanisms involved in the development of AKI in rhabdomyolysis are intrarenal vasoconstriction, direct and ischemic tubule injury and tubular obstruction. According to some clinical series, the mortality rate in patients who develop AKI due to rhabdomyolysis is highly variable. The cornerstone in managing this condition is the early, aggressive repletion of fluids. The composition of replacement fluid remains controversial. Saline and sodium bicarbonate, especially in patients with metabolic acidosis, seem to be a reasonable approach. When AKI produces refractory hyperkalemia, acidosis or volume overload, renal replacement therapy is indicated.
Topics: Acute Kidney Injury; Humans; Nephrology; Physician's Role; Rhabdomyolysis
PubMed: 25504160
DOI: No ID Found -
Pediatric Health, Medicine and... 2018Primary distal renal tubular acidosis (dRTA) is a rare genetic disorder caused by impaired distal acidification due to a failure of type A intercalated cells (A-ICs) in... (Review)
Review
Primary distal renal tubular acidosis (dRTA) is a rare genetic disorder caused by impaired distal acidification due to a failure of type A intercalated cells (A-ICs) in the collecting tubule. dRTA is characterized by persistent hyperchloremia, a normal plasma anion gap, and the inability to maximally lower urinary pH in the presence of systemic metabolic acidosis. Common clinical features of dRTA include vomiting, failure to thrive, polyuria, hypercalciuria, hypocitraturia, nephrocalcinosis, nephrolithiasis, growth delay, and rickets. Mutations in genes encoding three distinct transport proteins in A-ICs have been identified as causes of dRTA, including the B1/ and a4/ subunits of the vacuolar-type H-ATPase (H-ATPase) and the chloride-bicarbonate exchanger AE1/. Homozygous or compound heterozygous mutations in and lead to autosomal recessive (AR) dRTA. dRTA caused by mutations can occur with either autosomal dominant or AR transmission. Red blood cell abnormalities have been associated with AR dRTA due to mutations, including hereditary spherocytosis, Southeast Asia ovalocytosis, and others. Some patients with dRTA exhibit atypical clinical features, including transient and reversible proximal tubular dysfunction and hyperammonemia. Incomplete dRTA presents with inadequate urinary acidification, but without spontaneous metabolic acidosis and recurrent urinary stones. Heterozygous mutations in the AE1 or H-ATPase genes have recently been reported in patients with incomplete dRTA. Early and sufficient doses of alkali treatment are needed for patients with dRTA. Normalized serum bicarbonate, urinary calcium excretion, urinary low-molecular-weight protein levels, and growth rate are good markers of adherence to and/or efficacy of treatment. The prognosis of dRTA is generally good in patients with appropriate treatment. However, recent studies showed an increased frequency of chronic kidney disease (CKD) in patients with dRTA during long-term follow-up. The precise pathogenic mechanisms of CKD in patients with dRTA are unknown.
PubMed: 30588151
DOI: 10.2147/PHMT.S174459 -
Ochsner Journal 2016The term renal tubular acidosis (RTA) describes a group of uncommon kidney disorders characterized by defective acid-base regulation. Reaching the diagnosis of RTA is... (Review)
Review
BACKGROUND
The term renal tubular acidosis (RTA) describes a group of uncommon kidney disorders characterized by defective acid-base regulation. Reaching the diagnosis of RTA is complex and often delayed, resulting in suboptimal treatment.
METHODS
This article provides an overview of the clinical features of RTA and diagnostic approaches in a format accessible to physicians for everyday use.
RESULTS
The 3 major forms of disease are classified by their respective tubular transport defects, each of which produces persistent hyperchloremic metabolic acidosis. Distal RTA is characterized by limited urinary acid secretion, proximal RTA by restricted urinary bicarbonate reabsorption, and hyperkalemic RTA by absolute or relative hypoaldosteronism. RTA is often detected incidentally as a biochemical diagnosis in asymptomatic individuals. When present, clinical features may range from mild nonspecific complaints to life-threatening physiologic disturbances.
CONCLUSION
RTA is a complex condition that requires thoughtful investigation. Physicians should be aware of the presentation of RTA and the investigative options available to confirm the diagnosis.
PubMed: 27999512
DOI: No ID Found -
Clinical Journal of the American... Feb 2015Intercalated cells are kidney tubule epithelial cells with important roles in the regulation of acid-base homeostasis. However, in recent years the understanding of the... (Review)
Review
Intercalated cells are kidney tubule epithelial cells with important roles in the regulation of acid-base homeostasis. However, in recent years the understanding of the function of the intercalated cell has become greatly enhanced and has shaped a new model for how the distal segments of the kidney tubule integrate salt and water reabsorption, potassium homeostasis, and acid-base status. These cells appear in the late distal convoluted tubule or in the connecting segment, depending on the species. They are most abundant in the collecting duct, where they can be detected all the way from the cortex to the initial part of the inner medulla. Intercalated cells are interspersed among the more numerous segment-specific principal cells. There are three types of intercalated cells, each having distinct structures and expressing different ensembles of transport proteins that translate into very different functions in the processing of the urine. This review includes recent findings on how intercalated cells regulate their intracellular milieu and contribute to acid-base regulation and sodium, chloride, and potassium homeostasis, thus highlighting their potential role as targets for the treatment of hypertension. Their novel regulation by paracrine signals in the collecting duct is also discussed. Finally, this article addresses their role as part of the innate immune system of the kidney tubule.
Topics: Acid-Base Equilibrium; Acidosis, Renal Tubular; Animals; Cell Differentiation; Cell Lineage; Epithelial Cells; Humans; Immunity, Innate; Kidney Tubules, Collecting; Phenotype; Renin-Angiotensin System
PubMed: 25632105
DOI: 10.2215/CJN.08880914 -
Kidney Research and Clinical Practice Mar 2017The electrogenic sodium/bicarbonate cotransporter 1 (NBCe1) on the basolateral side of the renal proximal tubule plays a pivotal role in systemic acid-base homeostasis.... (Review)
Review
The electrogenic sodium/bicarbonate cotransporter 1 (NBCe1) on the basolateral side of the renal proximal tubule plays a pivotal role in systemic acid-base homeostasis. Mutations in the gene encoding NBCe1 cause severe proximal renal tubular acidosis accompanied by other extrarenal symptoms. The proximal tubule reabsorbs most of the sodium filtered in the glomerulus, contributing to the regulation of plasma volume and blood pressure. NBCe1 and other sodium transporters in the proximal tubule are regulated by hormones, such as angiotensin II and insulin. Angiotensin II is probably the most important stimulator of sodium reabsorption. Proximal tubule AT receptor is crucial for the systemic pressor effect of angiotensin II. In rodents and rabbits, the effect on proximal tubule NBCe1 is biphasic; at low concentration, angiotensin II stimulates NBCe1 via PKC/cAMP/ERK, whereas at high concentration, it inhibits NBCe1 via NO/cGMP/cGKII. In contrast, in human proximal tubule, angiotensin II has a dose-dependent monophasic stimulatory effect via NO/cGMP/ERK. Insulin stimulates the proximal tubule sodium transport, which is IRS2-dependent. We found that in insulin resistance and overt diabetic nephropathy, stimulatory effect of insulin on proximal tubule transport was preserved. Our results suggest that the preserved stimulation of the proximal tubule enhances sodium reabsorption, contributing to the pathogenesis of hypertension with metabolic syndrome. We describe recent findings regarding the role of proximal tubule transport in the regulation of blood pressure, focusing on the effects of angiotensin II and insulin.
PubMed: 28428931
DOI: 10.23876/j.krcp.2017.36.1.12 -
Nephrology, Dialysis, Transplantation :... May 2022
Topics: Acidosis; Acidosis, Renal Tubular; Humans; Kidney Diseases
PubMed: 33313681
DOI: 10.1093/ndt/gfaa309 -
Nephrology, Dialysis, Transplantation :... Aug 2021Distal renal tubular acidosis (dRTA) is characterized by an impaired ability of the distal tubule to excrete acid, leading to metabolic acidosis. Associated...
Distal renal tubular acidosis (dRTA) is characterized by an impaired ability of the distal tubule to excrete acid, leading to metabolic acidosis. Associated complications include bone disease, growth failure, urolithiasis and hypokalaemia. Due to its rarity, there is limited evidence to guide diagnosis and management; however, available data strongly suggest that metabolic control of the acidosis by alkali supplementation can halt or revert almost all complications. Despite this, cohort studies show that adequate metabolic control is present in only about half of patients, highlighting problems with treatment provision or adherence. With these clinical practice points the authors, part of the working groups tubulopathies in the European Rare Kidney Disease Reference network and inherited kidney diseases of the European Society for Paediatric Nephrology, aim to provide guidance for the management of patients with dRTA to facilitate adequate treatment and establish an initial best practice standard against which treatment of patients can be audited.
Topics: Acidosis; Acidosis, Renal Tubular; Child; Cohort Studies; Humans; Hypokalemia; Kidney
PubMed: 33914889
DOI: 10.1093/ndt/gfab171 -
F1000Research 2016Urinary stone disease is a very common disease whose prevalence is still increasing. Stone formation is frequently associated with other diseases of affluence such as... (Review)
Review
Urinary stone disease is a very common disease whose prevalence is still increasing. Stone formation is frequently associated with other diseases of affluence such as hypertension, osteoporosis, cardiovascular disease, metabolic syndrome, and insulin resistance. The increasing concentration of lithogenic solutes along the different segments of the nephron involves supersaturation conditions leading to the formation, growth, and aggregation of crystals. Crystalline aggregates can grow free in the tubular lumen or coated on the wall of the renal tubule. Plugs of crystalline material have been highlighted in the tubular lumen in some patients, but crystalline growth starting from plaques of calcium phosphate within the renal papillae has been demonstrated in others. Urinary supersaturation is the result of a complex interaction between predisposing genetic features and environmental factors. Dietary intake is certainly the most important environmental risk factor. In particular, an insufficient intake of dietary calcium (<600 mg/day) can increase the intestinal absorption of oxalate and the risk of calcium oxalate stone formation. Other possible risk factors that have been identified include excessive intake of salt and proteins. The potential role of dietary acid load seems to play an important role in causing a state of subclinical chronic acidosis; therefore, the intake of vegetables is encouraged in stone-forming patients. Consumption of sugar-sweetened soda and punch is associated with a higher risk of stone formation, whereas consumption of coffee, tea, beer, wine, and orange juice is associated with a lower risk. A high fluid intake is widely recognized as the cornerstone of prevention of all forms of stones. The effectiveness of protein and salt restriction has been evaluated in some studies that still do not allow definitive conclusions to be made. Calcium stone formation can be prevented by the use of different drugs with different mechanisms of action (thiazide diuretics, allopurinol, and potassium citrate), but there is no ideal drug that is both risk free and well tolerated.
PubMed: 27134735
DOI: 10.12688/f1000research.7126.1 -
Therapeutische Umschau. Revue... Jun 2021Metabolic investigation of stone formers Once a kidney stone has passed, patients must be carefully evaluated in order to identify the underlying cause of the disease...
Metabolic investigation of stone formers Once a kidney stone has passed, patients must be carefully evaluated in order to identify the underlying cause of the disease and to guide preventive measures and treatment. General recommendations can be offered to all kidney stone formers, but personalized counseling and follow-up adaptations need to be guided by in-depth assessment. Metabolic evaluation for recurrent stone formers is based on 24 h urine collection. This allows a comprehensive understanding of the dietary habits of the patient and helps identifying treatable metabolic diseases and renal tubulopathies. Additional specific assessments may include urine acidification test (in case of suspected partial renal distal tubular acidosis), characterization of hypercalciuria or osteodensitometry. Metabolic evaluation often needs to be repeated over time to guide therapeutic interventions, both dietetic and drug-related.
Topics: Acidosis, Renal Tubular; Humans; Kidney Calculi; Risk Factors
PubMed: 34032135
DOI: 10.1024/0040-5930/a001266 -
American Journal of Physiology. Renal... Jun 2023Phosphoenolpyruvate carboxykinase 1 (PCK1 or PEPCK-C) is a cytosolic enzyme converting oxaloacetate to phosphoenolpyruvate, with a potential role in gluconeogenesis,...
Phosphoenolpyruvate carboxykinase 1 (PCK1 or PEPCK-C) is a cytosolic enzyme converting oxaloacetate to phosphoenolpyruvate, with a potential role in gluconeogenesis, ammoniagenesis, and cataplerosis in the liver. Kidney proximal tubule cells display high expression of this enzyme, whose importance is currently not well defined. We generated PCK1 kidney-specific knockout and knockin mice under the tubular cell-specific PAX8 promoter. We studied the effect of PCK1 deletion and overexpression at the renal level on tubular physiology under normal conditions and during metabolic acidosis and proteinuric renal disease. PCK1 deletion led to hyperchloremic metabolic acidosis characterized by reduced but not abolished ammoniagenesis. PCK1 deletion also resulted in glycosuria, lactaturia, and altered systemic glucose and lactate metabolism at baseline and during metabolic acidosis. Metabolic acidosis resulted in kidney injury in PCK1-deficient animals with decreased creatinine clearance and albuminuria. PCK1 further regulated energy production by the proximal tubule, and PCK1 deletion decreased ATP generation. In proteinuric chronic kidney disease, mitigation of PCK1 downregulation led to better renal function preservation. PCK1 is essential for kidney tubular cell acid-base control, mitochondrial function, and glucose/lactate homeostasis. Loss of PCK1 increases tubular injury during acidosis. Mitigating kidney tubular PCK1 downregulation during proteinuric renal disease improves renal function. Phosphoenolpyruvate carboxykinase 1 (PCK1) is highly expressed in the proximal tubule. We show here that this enzyme is crucial for the maintenance of normal tubular physiology, lactate, and glucose homeostasis. PCK1 is a regulator of acid-base balance and ammoniagenesis. Preventing PCK1 downregulation during renal injury improves renal function, rendering it an important target during renal disease.
Topics: Animals; Mice; Acidosis; Glucose; Kidney; Lactates; Mitochondria; Phosphoenolpyruvate; Phosphoenolpyruvate Carboxykinase (GTP)
PubMed: 37102687
DOI: 10.1152/ajprenal.00038.2023