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Clinical Journal of the American... Sep 2014The human kidneys produce approximately 160-170 L of ultrafiltrate per day. The proximal tubule contributes to fluid, electrolyte, and nutrient homeostasis by... (Review)
Review
The human kidneys produce approximately 160-170 L of ultrafiltrate per day. The proximal tubule contributes to fluid, electrolyte, and nutrient homeostasis by reabsorbing approximately 60%-70% of the water and NaCl, a greater proportion of the NaHCO3, and nearly all of the nutrients in the ultrafiltrate. The proximal tubule is also the site of active solute secretion, hormone production, and many of the metabolic functions of the kidney. This review discusses the transport of NaCl, NaHCO3, glucose, amino acids, and two clinically important anions, citrate and phosphate. NaCl and the accompanying water are reabsorbed in an isotonic fashion. The energy that drives this process is generated largely by the basolateral Na(+)/K(+)-ATPase, which creates an inward negative membrane potential and Na(+)-gradient. Various Na(+)-dependent countertransporters and cotransporters use the energy of this gradient to promote the uptake of HCO3 (-) and various solutes, respectively. A Na(+)-dependent cotransporter mediates the movement of HCO3 (-) across the basolateral membrane, whereas various Na(+)-independent passive transporters accomplish the export of various other solutes. To illustrate its homeostatic feat, the proximal tubule alters its metabolism and transport properties in response to metabolic acidosis. The uptake and catabolism of glutamine and citrate are increased during acidosis, whereas the recovery of phosphate from the ultrafiltrate is decreased. The increased catabolism of glutamine results in increased ammoniagenesis and gluconeogenesis. Excretion of the resulting ammonium ions facilitates the excretion of acid, whereas the combined pathways accomplish the net production of HCO3 (-) ions that are added to the plasma to partially restore acid-base balance.
Topics: Acidosis, Renal Tubular; Biological Transport, Active; Humans; Kidney Tubules, Proximal; Phosphates; Sodium Bicarbonate; Sodium Chloride
PubMed: 23908456
DOI: 10.2215/CJN.10391012 -
Archivos Espanoles de Urologia Jan 2021Urolithiasis is a multifactorial and recurrent disease whose incidence is increasing, especially in women but also in the paediatric population. Differences can be found...
Urolithiasis is a multifactorial and recurrent disease whose incidence is increasing, especially in women but also in the paediatric population. Differences can be found between different regions and between different ethnicities, often due to dietary and environmental factors, without forgetting the genetic influence on different types of stones. There are disease sthat require a high index of suspicion in order to reach a diagnosis, such as renal tubular acidosis (RTA), not only for the benefit of the patient but also for their family members in the case a genetic mutation. Calcium-based stones continue to be the most frequent, but with a progressive increase in uric stones...
Topics: Acidosis, Renal Tubular; Calculi; Child; Female; Humans; Incidence; Urolithiasis
PubMed: 33459616
DOI: No ID Found -
The Veterinary Clinics of North... Apr 2022This article overviews metabolic disorders associated with renal disease. Included is a discussion of the pathophysiology, clinical signs, and treatment of... (Review)
Review
This article overviews metabolic disorders associated with renal disease. Included is a discussion of the pathophysiology, clinical signs, and treatment of hyperchloremic metabolic acidosis associated with renal tubular acidosis. Conditions affecting the central nervous system including uremic encephalopathy and hyponatremic encephalopathy secondary to renal disease are presented. Finally, a discussion of the unique features of calcium and phosphorus homeostasis in horses is provided with special emphasis on a recently described syndrome of calcinosis and calciphylaxis of unknown etiology.
Topics: Acidosis, Renal Tubular; Animals; Horse Diseases; Horses
PubMed: 35282958
DOI: 10.1016/j.cveq.2021.11.008 -
Advances in Chronic Kidney Disease Mar 2017Accumulating evidence suggests that the central locus for the progression of CKD is the renal proximal tubule. As injured tubular epithelial cells dedifferentiate in... (Review)
Review
Accumulating evidence suggests that the central locus for the progression of CKD is the renal proximal tubule. As injured tubular epithelial cells dedifferentiate in attempted repair, they stimulate inflammation and recruit myofibroblasts. At the same time, tissue loss stimulates remnant nephron hypertrophy. Increased tubular transport workload eventually exceeds the energy-generating capacity of the hypertrophied nephrons, leading to anerobic metabolism, acidosis, hypoxia, endoplasmic reticulum stress, and the induction of additional inflammatory and fibrogenic responses. The result is a vicious cycle of injury, misdirected repair, maladaptive responses, and more nephron loss. Therapy that might be advantageous at one phase of this progression pathway could be deleterious during other phases. Thus, interrupting this downward spiral requires narrowly targeted approaches that promote healing and adequate function without generating further entry into the progression cycle.
Topics: Acute Kidney Injury; Animals; Cell Dedifferentiation; Disease Progression; Extracellular Matrix; Fibrosis; Homeostasis; Humans; Hyperplasia; Kidney Tubules, Proximal; Nephritis, Interstitial; Renal Insufficiency, Chronic
PubMed: 28284376
DOI: 10.1053/j.ackd.2016.11.011 -
The Journal of the Royal College of... Sep 2020Tenofovir disoproxil fumarate (TDF) is the foundation nucleotide reverse-transcriptase inhibitor in the recommended first-line regimen for all naive human...
Tenofovir disoproxil fumarate (TDF) is the foundation nucleotide reverse-transcriptase inhibitor in the recommended first-line regimen for all naive human immunodeficciency virus-1 (HIV-1) patients whose age is more than 10 years and body weight is more than 30 kg. Although it has a good safety profile overall, nephrotoxicity is a concern and its overall incidence is 1-6% with a long period of clinical latency. Nephrotoxicity may manifest as either proximal renal tubule dysfunction in the form of a partial or complete Fanconi syndrome or as decreased renal function leading to acute or chronic kidney injury. Osteomalacia can also develop secondary to complicating hypophosphataemia and low calcitriol levels. Here we report a 50-year-old HIV-positive male on tenofovir who presented with proximal renal tubular acidosis and fracture of left neck of femur four years after initiation of the drug.
Topics: Child; Fanconi Syndrome; HIV Infections; Humans; Incidence; Male; Middle Aged; Osteomalacia; Tenofovir
PubMed: 32936106
DOI: 10.4997/JRCPE.2020.316 -
Advances in Chronic Kidney Disease Jul 2018
Topics: Acidosis, Renal Tubular; Career Choice; Humans; Nephrology; Teaching
PubMed: 30139457
DOI: 10.1053/j.ackd.2018.05.002 -
Postgraduate Medicine Apr 2019Hyperchloremic metabolic acidosis of renal origin results from a defect in renal tubular acidification mechanism, and this tubular dysfunction can consist of an altered... (Review)
Review
Hyperchloremic metabolic acidosis of renal origin results from a defect in renal tubular acidification mechanism, and this tubular dysfunction can consist of an altered tubular proton secretion or bicarbonate reabsorption capability. Studies have documented that all forms of renal tubular acidosis (RTA), type I to IV, are documented in kidney transplant patients. Among RTA pathophysiologic mechanisms have been described the renal mass reduction, hyperkalemia, hyperparathyroidism, graft rejection, immunologic diseases, and some drugs such as renin-angiotensin-aldosterone blockers, and calcineurin inhibitors. RTA can lead to serious complications as is the case of muscle protein catabolism, muscle protein synthesis inhibition, renal osteodystrophy, renal damage progression, and anemia promotion. RTA should be treated by suppressing its etiologic factor (if it is possible), avoiding hyperkalemia, and/or supplying bicarbonate or a precursor (citrate). In conclusion: Hyperchloremic metabolic acidosis of renal origin is a relatively frequent complication in kidney transplantation patients, which can be harmful, and should be adequately treated in order to avoid its renal and systemic adverse effects.
Topics: Acidosis, Renal Tubular; Humans; Kidney; Kidney Transplantation
PubMed: 30924703
DOI: 10.1080/00325481.2019.1592360 -
American Journal of Nephrology 2022In metabolic acidosis, a negative calcium balance is induced by decreased renal tubular calcium reabsorption. This occurs independently of the action of parathyroid... (Review)
Review
BACKGROUND
In metabolic acidosis, a negative calcium balance is induced by decreased renal tubular calcium reabsorption. This occurs independently of the action of parathyroid hormone or vitamin D and was attributed to a direct action of metabolic acidosis on the renal tubular cells. The latter has been verified by recent studies on the molecular levels in the kidney.
SUMMARY
Whereas the regulatory role of urinary calcium excretion was traditionally assigned to the transcellular calcium transport in the distal convoluted tubule (DCT) and connecting tubule (CNT), most of the calcium reabsorption from the glomerular filtrate paracellularly occurs through the tight junctions in the proximal tubule (PT) and the thick ascending limb (TAL) of Henle's loop. Interestingly, all these nephron segments participate in producing hypercalciuria caused by metabolic acidosis. Claudin-2 is the major route of paracellular calcium transport in the PT and was downregulated in rats with 5 days' NH4Cl loading. In the TAL, the lumen-positive voltage produced by apical K+ recycling drives paracellular reabsorption of Ca2+ and Mg2+ via the claudin-16/19 complex. Activation of calcium-sensing receptor (CaSR) by extracellular calcium upregulates claudin-14, which in turn interacts with the claudin-16/19 complex and inhibits its cation permeability. This TAL CaSR-claudins axis was activated by chronic NH4Cl loading in rats. Finally, the major transcellular calcium transporters TRPV5 and 28K calcium-binding protein in the DCT-CNT were also downregulated by NH4Cl or acetazolamide administration in mice.
KEY MESSAGES
Both paracellular and transcellular calcium transport pathways in the kidney are regulated by metabolic acidosis and lead to renal calcium wasting. In the PT, claudin-2 is downregulated by acidic pH. In the TAL of Henle's loop, CaSR is stimulated by the ionized calcium released from bone and upregulates claudin-14, which in turn inhibits the claudin-16/19 complex and leads to calcium and magnesium wasting. Finally, the transcellular calcium transporters, TRPV5 and calbindin-D28K, are downregulated by metabolic acidosis in the DCT and CNT.
Topics: Mice; Rats; Animals; Calcium; Hypercalciuria; Claudin-2; Claudins; Kidney; Acidosis
PubMed: 36450225
DOI: 10.1159/000528089 -
Current Opinion in Nephrology and... Mar 2023The present review summarizes findings of recent studies examining the epidemiology, pathophysiology, and treatment of type 4 renal tubular acidosis (RTA) and uric acid... (Review)
Review
PURPOSE OF REVIEW
The present review summarizes findings of recent studies examining the epidemiology, pathophysiology, and treatment of type 4 renal tubular acidosis (RTA) and uric acid nephrolithiasis, two conditions characterized by an abnormally acidic urine.
RECENT FINDINGS
Both type 4 RTA and uric acid nephrolithiasis disproportionately occur in patients with type 2 diabetes and/or chronic kidney disease. Biochemically, both conditions are associated with reduced renal ammonium excretion resulting in impaired urinary buffering and low urine pH. Reduced ammoniagenesis is postulated to result from hyperkalemia in type 4 RTA and from insulin resistance and fat accumulation in the renal proximal tubule in uric acid nephrolithiasis. The typical biochemical findings of hyperkalemia and systemic acidosis of type 4 RTA are rarely reported in uric acid stone formers. Additional clinical differences between the two conditions include findings of higher urinary uric acid excretion and consequent urinary uric acid supersaturation in uric acid stone formers but not in type 4 RTA.
SUMMARY
Type 4 RTA and uric acid nephrolithiasis share several epidemiological, clinical, and biochemical features. Although both conditions may be manifestations of diabetes mellitus and thus have a large at-risk population, the means to the shared biochemical finding of overly acidic urine are different. This difference in pathophysiology may explain the dissimilarity in the prevalence of kidney stone formation.
Topics: Humans; Uric Acid; Diabetes Mellitus, Type 2; Acidosis, Renal Tubular; Hyperkalemia; Hydrogen-Ion Concentration; Kidney Calculi; Nephrolithiasis
PubMed: 36683539
DOI: 10.1097/MNH.0000000000000859 -
Journal of the American Society of... Dec 2016Metabolic acidosis is associated with increased urinary calcium excretion and related sequelae, including nephrocalcinosis and nephrolithiasis. The increased urinary... (Review)
Review
Metabolic acidosis is associated with increased urinary calcium excretion and related sequelae, including nephrocalcinosis and nephrolithiasis. The increased urinary calcium excretion induced by metabolic acidosis predominantly results from increased mobilization of calcium out of bone and inhibition of calcium transport processes within the renal tubule. The mechanisms whereby acid alters the integrity and stability of bone have been examined extensively in the published literature. Here, after briefly reviewing this literature, we consider the effects of acid on calcium transport in the renal tubule and then discuss why not all gene defects that cause renal tubular acidosis are associated with hypercalciuria and nephrocalcinosis.
Topics: Acid-Base Imbalance; Acidosis; Bone Diseases; Calcium; Humans; Hypercalciuria; Kidney Tubules; Nephrocalcinosis
PubMed: 27468975
DOI: 10.1681/ASN.2016030305