-
Advances in Chronic Kidney Disease Jul 2018Renal tubular acidosis (RTA) represents a group of diseases characterized by (1) a normal anion gap metabolic acidosis; (2) abnormalities in renal HCO absorption or new... (Review)
Review
Renal tubular acidosis (RTA) represents a group of diseases characterized by (1) a normal anion gap metabolic acidosis; (2) abnormalities in renal HCO absorption or new renal HCO generation; (3) changes in renal NH, Ca, K, and HO homeostasis; and (4) extrarenal manifestations that provide etiologic diagnostic clues. The focus of this review is to give a general overview of the pathogenesis of the various clinical syndromes causing RTA with a particular emphasis on type I (hypokalemic distal RTA) and type II (proximal) RTA while reviewing their pathogenesis from a physiological "bottom-up" approach. In addition, the factors involved in the generation of metabolic acidosis in both type I and II RTA are reviewed highlighting the importance of altered renal ammonia production/partitioning and new HCO generation. Our understanding of the underlying tubular transport and extrarenal abnormalities has significantly improved since the first recognition of RTA as a clinical entity because of significant advances in clinical acid-base chemistry, whole tubule and single-cell H/base transport, and the molecular characterization of the various transporters and channels that are functionally affected in patients with RTA. Despite these advances, additional studies are needed to address the underlying mechanisms involved in hypokalemia, altered ammonia production/partitioning, hypercalciuria, nephrocalcinosis, cystic abnormalities, and CKD progression in these patients.
Topics: Acid-Base Imbalance; Acidosis, Renal Tubular; Ammonia; Ammonium Compounds; Animals; Bicarbonates; Biological Transport; Calcium; Citric Acid; Humans; Hypercalciuria; Hypokalemia; Ketoglutaric Acids; Kidney Tubules, Distal; Kidney Tubules, Proximal; Sodium-Bicarbonate Symporters
PubMed: 30139460
DOI: 10.1053/j.ackd.2018.05.005 -
Pediatric Nephrology (Berlin, Germany) Aug 2024Cystinosis is a rare autosomal recessive disease with an incidence 1 per 100,000-200,000 live births. It is caused by pathogenic variants of the cystinosin (CTNS) gene... (Review)
Review
Cystinosis is a rare autosomal recessive disease with an incidence 1 per 100,000-200,000 live births. It is caused by pathogenic variants of the cystinosin (CTNS) gene that lead to impaired cystine transport from lysosomes to cystosol, resulting in cystine accumulation in lysosomes and subsequent cellular dysfunction. The initial manifestation, cystine accumulation in proximal tubular cells (PTCs), causes renal Fanconi syndrome, which presents with proximal renal tubular acidosis and generalized dysfunction of the proximal tubule, including the presence of polyuria, glycosuria, phosphaturia, aminoaciduria, tubular proteinuria, growth retardation, and rickets. Eventually, glomerular involvement, glomerular proteinuria, focal segmental glomerulosclerosis (FSGS), and progression to kidney failure occur. Although the kidneys are the first organs affected, and play a key role in morbidity and mortality, extrarenal multiorgan involvement can occur in patients with cystinosis, which is seen not only in adults but in early ages in untreated patients, patients with insufficient treatment, and in those that don't comply with treatment. The treatment of cystinosis consists of supportive treatment for Fanconi syndrome, and specific lifelong cystine-depleting therapy using oral cysteamine. There is strong evidence that as early as possible, initiation and ongoing appropriate therapy with cysteamine are essential for delaying the progression to kidney failure, end-organ damage, and extrarenal involvement. The present review aimed to evaluate the extra renal complications of cystinosis.
Topics: Humans; Cystinosis; Fanconi Syndrome; Cysteamine; Cystine Depleting Agents; Amino Acid Transport Systems, Neutral
PubMed: 38127152
DOI: 10.1007/s00467-023-06225-0 -
World Journal of Pediatrics : WJP Oct 2019Distal renal tubular acidosis (dRTA) is a kidney tubulopathy that causes a state of normal anion gap metabolic acidosis due to impairment of urine acidification. This... (Review)
Review
BACKGROUND
Distal renal tubular acidosis (dRTA) is a kidney tubulopathy that causes a state of normal anion gap metabolic acidosis due to impairment of urine acidification. This review aims to summarize the etiology, pathophysiology, clinical findings, diagnosis and therapeutic approach of dRTA, with emphasis on genetic causes of dRTA.
DATA SOURCES
Literature reviews and original research articles from databases, including PubMed and Google Scholar. Manual searching was performed to identify additional studies about dRTA.
RESULTS
dRTA is characterized as the dysfunction of the distal urinary acidification, leading to metabolic acidosis. In pediatric patients, the most frequent etiology of dRTA is the genetic alteration of genes responsible for the codification of distal tubule channels, whereas, in adult patients, dRTA is more commonly secondary to autoimmune diseases, use of medications and uropathies. Patients with dRTA exhibit failure to thrive and important laboratory alterations, which are used to define the diagnosis. The oral alkali and potassium supplementation can correct the biochemical defects, improve clinical manifestations and avoid nephrolithiasis and nephrocalcinosis.
CONCLUSIONS
dRTA is a multifactorial disease leading to several clinical manifestations. Clinical and laboratory alterations can be corrected by alkali replacement therapy.
Topics: Acidosis, Renal Tubular; Adolescent; Anion Exchange Protein 1, Erythrocyte; Child; Humans; Mutation; Vacuolar Proton-Translocating ATPases
PubMed: 31079338
DOI: 10.1007/s12519-019-00260-4 -
The Journal of International Medical... Mar 2021We report the case of a family in which two sisters have distal renal tubular acidosis (dRTA). Familial dRTA is a rare disorder, with both autosomal dominant and...
We report the case of a family in which two sisters have distal renal tubular acidosis (dRTA). Familial dRTA is a rare disorder, with both autosomal dominant and recessive transmission. This is a report of familial dRTA from China.
Topics: Acidosis, Renal Tubular; China; Humans; Mutation
PubMed: 33726529
DOI: 10.1177/03000605211000533 -
Acta Paediatrica (Oslo, Norway : 1992) Nov 2020To describe incomplete distal renal tubular acidosis (iDRTA) in paediatric patients, a term used for the diagnosis of patients who do not develop spontaneous overt... (Review)
Review
AIM
To describe incomplete distal renal tubular acidosis (iDRTA) in paediatric patients, a term used for the diagnosis of patients who do not develop spontaneous overt metabolic acidosis but are unable to acidify the urine in response to an ammonium chloride load.
METHODS
Tests used to explore urinary acidification were revised. In addition, publications in English extracted from 161 entries yielded by a PubMed database search, using 'incomplete distal renal tubular acidosis' as keyword, were reviewed.
RESULTS
Incomplete distal renal tubular acidosis has mostly been identified in adults with autoimmune diseases, nephrolithiasis, nephrocalcinosis and/or osteopenia. iDRTA has been reported in few paediatric patients with rickets, congenital abnormalities of kidney and urological tract and/or growth failure. The pathophysiological mechanisms potentially responsible for the defect of urinary acidification are discussed as well as the clinical and biochemical findings of iDRTA described in children.
CONCLUSION
The presentation of iDRTA in children differs from adults. The clinical and biochemical features of iDRTA are not well characterised in paediatric patients. The detection of iDRTA in groups of population such as heterozygous carriers of primary DRTA gene mutations and children with hypocitraturia or hypercalciuria might be of clinical interest to better know the pathophysiology and natural history of iDRTA.
Topics: Acidosis, Renal Tubular; Adult; Child; Heterozygote; Humans; Hypercalciuria; Kidney Calculi; Rickets
PubMed: 32212394
DOI: 10.1111/apa.15269 -
Advances in Chronic Kidney Disease Jul 2018In contrast to distal type I or classic renal tubular acidosis (RTA) that is associated with hypokalemia, hyperkalemic forms of RTA also occur usually in the setting of... (Review)
Review
In contrast to distal type I or classic renal tubular acidosis (RTA) that is associated with hypokalemia, hyperkalemic forms of RTA also occur usually in the setting of mild-to-moderate CKD. Two pathogenic types of hyperkalemic metabolic acidosis are frequently encountered in adults with underlying CKD. One type, which corresponds to some extent to the animal model of selective aldosterone deficiency (SAD) created experimentally by adrenalectomy and glucocorticoid replacement, is manifested in humans by low plasma and urinary aldosterone levels, reduced ammonium excretion, and preserved ability to lower urine pH below 5.5. This type of hyperkalemic RTA is also referred to as type IV RTA. It should be noted that the mere deficiency of aldosterone when glomerular filtration rate is completely normal only causes a modest decline in plasma bicarbonate which emphasizes the importance of reduced glomerular filtration rate in the development of the hyperchloremic metabolic acidosis associated with SAD. Another type of hyperkalemic RTA distinctive from SAD in which plasma aldosterone is not reduced is referred to as hyperkalemic distal renal tubular acidosis because urine pH cannot be reduced despite acidemia or after provocative tests aimed at increasing sodium-dependent distal acidification such as the administration of sodium sulfate or loop diuretics with or without concurrent mineralocorticoid administration. This type of hyperkalemic RTA (also referred to as voltage-dependent distal renal tubular acidosis) has been best described in patients with obstructive uropathy and resembles the impairment in both hydrogen ion and potassium secretion that are induced experimentally by urinary tract obstruction and when sodium transport in the cortical collecting tubule is blocked by amiloride.
Topics: Acidosis, Renal Tubular; Aldosterone; Animals; Epithelial Sodium Channels; Humans; Hydrogen-Ion Concentration; Hyperkalemia; Membrane Potentials; Nephrons; Potassium; Pseudohypoaldosteronism; Renal Insufficiency, Chronic; Sodium; Ureteral Obstruction
PubMed: 30139459
DOI: 10.1053/j.ackd.2018.05.004 -
Advances in Chronic Kidney Disease Jul 2018Renal tubular acidosis (RTA) is comprised of a diverse group of congenital or acquired diseases with the common denominator of defective renal acid excretion with... (Review)
Review
Renal tubular acidosis (RTA) is comprised of a diverse group of congenital or acquired diseases with the common denominator of defective renal acid excretion with protean manifestation, but in adults, recurrent kidney stones and nephrocalcinosis are mainly found in presentation. Calcium phosphate (CaP) stones and nephrocalcinosis are frequently encountered in distal hypokalemic RTA type I. Alkaline urinary pH, hypocitraturia, and, less frequently, hypercalciuria are the tripartite lithogenic factors in distal RTA (dRTA) predisposing to CaP stone formation; the latter 2 are also commonly encountered in other causes of urolithiasis. Although the full blown syndrome is easily diagnosed by conventional clinical criteria, an attenuated forme fruste called incomplete dRTA typically evades clinical testing and is only uncovered by provocative acid-loading challenges. Stone formers (SFs) that cannot acidify urine of pH < 5.3 during acid loading are considered to have incomplete dRTA. However, urinary acidification capacity is not a dichotomous but rather a continuous trait, so incomplete dRTA is not a distinct entity but may be one end of a spectrum. Recent findings suggest that incomplete dRTA can be attributed to heterozygous carriers of hypofunctional V-ATPase. The value of incomplete dRTA diagnosis by provocative testing and genotyping candidate genes is a valuable research tool, but it remains unclear at the moment whether they alter clinical practice and needs further clarification. No randomized controlled trials have been performed in SFs with dRTA or CaP stones, and until such data are available, treatment of CaP stones are centered on reversing the biochemical abnormalities encountered in the metabolic workup. SFs with type I dRTA should receive alkali therapy, preferentially in the form of K-citrate delivered judiciously to treat the chronic acid retention that drives both stone formation and bone disease.
Topics: Acidosis, Renal Tubular; Humans; Hydrogen-Ion Concentration; Hyperkalemia; Hypokalemia; Kidney Calculi; Kidney Tubules, Distal; Kidney Tubules, Proximal; Urine
PubMed: 30139463
DOI: 10.1053/j.ackd.2018.05.007 -
International Journal of Surgery... Dec 2016Renal stones are common and are usually secondary to risk factors affecting the solubility of substances in the urinary tract. Primary, that is genetic, causes are rare... (Review)
Review
Renal stones are common and are usually secondary to risk factors affecting the solubility of substances in the urinary tract. Primary, that is genetic, causes are rare but nevertheless are important to recognise so that appropriate treatments can be instigated and the risks to other family members acknowledged. A brief overview of the investigation of renal stones from a biochemical point of view is presented with emphasis on the problems that can arise. The genetic basis of renal stone disease caused by (i) derangement of a metabolic pathway, (ii) diversion to an insoluble product, (iii) failure of transport and (iv) renal tubular acidosis is described by reference to the disorders of adenine phosphoribosyl transferase (APRT) deficiency, primary hyperoxaluria, cystinuria and autosomal dominant distal renal tubular acidosis.
Topics: Acidosis, Renal Tubular; Adenine Phosphoribosyltransferase; Adult; Genetic Predisposition to Disease; Humans; Hyperoxaluria, Primary; Kidney Calculi; Metabolism, Inborn Errors; Urolithiasis
PubMed: 27838384
DOI: 10.1016/j.ijsu.2016.11.015 -
Archivos Espanoles de Urologia Jan 2021Renal tubular acidosis (RTA) is a set of raredis orders in which the renal tubule is unable to excreteacid normally and there by maintain normal acid-basebalance,...
Renal tubular acidosis (RTA) is a set of raredis orders in which the renal tubule is unable to excreteacid normally and there by maintain normal acid-basebalance, resulting in a complete or incomplete metabolicacidosis. In distal RTA (dRTA, also known as classicalor type 1 RTA), there is a defect in excreting H+ ionsalong the distal nephron (distal tubule and collectingduct), leading to an alkaline urinary pH with calcium phosphate precipitation and stones. Causes of dRTAinclude genetic mutations, autoimmune disease, and some drugs.Clinical manifestations of the genetic forms of dRTA typically occur during childhood and may vary from mildclinical symptoms, such as a mild metabolic acidosis, hypokalaemia,and incidental detection of kidney stones, to more serious manifestations such as failure to thrive,severe metabolic acidosis, rickets and nephrocalcinosis.Progressive hearing loss may develop in patients withrecessive dRTA, which, depending the causative genemutation, can be present at birth or develop later in adolescence or early adulthood. Diagnosis of dRTA can be challenging, since it requires a high index of suspicion and/or measurement of urinary pH after an acid load, usually in the form of oral ammonium chloride; this should normally acidify the urine to pH below 5.3. In dRTA, urinary citrate levels a real so low and patients are at increased risk of for mingkidney stones from a combination of alkaline urine and low citrate. Ideally, affected patients need regular outpatient follow-up by a urologist and nephrologist. Thus, any patient found to have a calcium phosphate kidney stone, low urinary citrate, and raised urinary pH, especially with an early morning pH >5.5, should be evaluated for underlying dRTA. Patients with complete dRTA will have a low (<20 mmol/L) plasma or serum bicarbonate concentration, whereas in those with incomplete dRTA, bicarbonate levels are usually normal. Oral alkali as potassiumcitrate is still the mainstay of treatment in dRTA.
Topics: Acidosis, Renal Tubular; Adolescent; Adult; Ammonium Chloride; Child; Citric Acid; Humans; Hydrogen-Ion Concentration; Kidney Calculi
PubMed: 33459628
DOI: No ID Found -
Kidney Research and Clinical Practice Sep 2019Proximal renal tubular acidosis (RTA) is caused by a defect in bicarbonate (HCO) reabsorption in the kidney proximal convoluted tubule. It usually manifests as normal... (Review)
Review
Proximal renal tubular acidosis (RTA) is caused by a defect in bicarbonate (HCO) reabsorption in the kidney proximal convoluted tubule. It usually manifests as normal anion-gap metabolic acidosis due to HCO wastage. In a normal kidney, the thick ascending limb of Henle's loop and more distal nephron segments reclaim all of the HCO not absorbed by the proximal tubule. Bicarbonate wastage seen in type II RTA indicates that the proximal tubular defect is severe enough to overwhelm the capacity for HCO reabsorption beyond the proximal tubule. Proximal RTA can occur as an isolated syndrome or with other impairments in proximal tubular functions under the spectrum of Fanconi syndrome. Fanconi syndrome, which is characterized by a defect in proximal tubular reabsorption of glucose, amino acids, uric acid, phosphate, and HCO, can occur due to inherited or acquired causes. Primary inherited Fanconi syndrome is caused by a mutation in the sodium-phosphate cotransporter (NaP-II) in the proximal tubule. Recent studies have identified new causes of Fanconi syndrome due to mutations in the and the genes. Fanconi syndrome can also be one of many manifestations of various inherited systemic diseases, such as cystinosis. Many of the acquired causes of Fanconi syndrome with or without proximal RTA are drug-induced, with the list of causative agents increasing as newer drugs are introduced for clinical use, mainly in the oncology field.
PubMed: 31474092
DOI: 10.23876/j.krcp.19.056