Review

Authors: Biff F Palmer, Ellie Kelepouris, Deborah J Clegg...

Renal tubular acidosis (RTA) occurs when the kidneys are unable to maintain normal acid-base homeostasis because of tubular defects in acid excretion or bicarbonate ion reabsorption. Using illustrative clinical cases, this review describes the main types of RTA observed in clinical practice and provides an overview of their diagnosis and treatment. The three major forms of RTA are distal RTA (type 1; characterized by impaired acid excretion), proximal RTA (type 2; caused by defects in reabsorption of filtered bicarbonate), and hyperkalemic RTA (type 4; caused by abnormal excretion of acid and potassium in the collecting duct). Type 3 RTA is a rare form of the disease with features of both distal and proximal RTA. Accurate diagnosis of RTA plays an important role in optimal patient management. The diagnosis of distal versus proximal RTA involves assessment of urinary acid and bicarbonate secretion, while in hyperkalemic RTA, selective aldosterone deficiency or resistance to its effects is confirmed after exclusion of other causes of hyperkalemia. Treatment options include alkali therapy in patients with distal or proximal RTA and lowering of serum potassium concentrations through dietary modification and potential new pharmacotherapies in patients with hyperkalemic RTA including newer potassium binders.

Topics: Acidosis, Renal Tubular; Bicarbonates; Humans; Hyperkalemia; Kidney; Potassium

PubMed: 33367987
DOI: 10.1007/s12325-020-01587-5

Review

Authors: Salim Lim

Acute metabolic acidosis is frequently encountered in critically ill patients. Metabolic acidosis can occur as a result of either the accumulation of endogenous acids that consumes bicarbonate (high anion gap metabolic acidosis) or loss of bicarbonate from the gastrointestinal tract or the kidney (hyperchloremic or normal anion gap metabolic acidosis). The cause of high anion gap metabolic acidosis includes lactic acidosis, ketoacidosis, renal failure and intoxication with ethylene glycol, methanol, salicylate and less commonly with pyroglutamic acid (5-oxoproline), propylene glycole or djenkol bean (gjenkolism). The most common causes of hyperchloremic metabolic acidosis are gastrointestinal bicarbonate loss, renal tubular acidosis, drugs-induced hyperkalemia, early renal failure and administration of acids. The appropriate treatment of acute metabolic acidosis, in particular organic form of acidosis such as lactic acidosis, has been very controversial. The only effective treatment for organic acidosis is cessation of acid production via improvement of tissue oxygenation. Treatment of acute organic acidosis with sodium bicarbonate failed to reduce the morbidity and mortality despite improvement in acid-base parameters. Further studies are required to determine the optimal treatment strategies for acute metabolic acidosis.

Topics: Acidosis; Acidosis, Lactic; Acidosis, Renal Tubular; Acute Disease; Bicarbonates; Diabetic Ketoacidosis; Humans; Risk Factors; Sodium Bicarbonate

PubMed: 17936961
DOI: No ID Found

Review

Authors: Salim Lim

Hypokalemia is frequently encountered in clinical practice. It can be due to either potassium deficiency (inadequate potassium intake or excessive potassium loss) or to net potassium shifts from the extracellular to the intracellular compartment. Inadequate dietary intake of potassium alone rarely causes hypokalemia since kidney is able to lower potassium excretion below 15 mmol per day. Hypokalemia due to excessive potassium loss can be due to renal or extrarenal losses. It is not necessary to wait for a timed urine collection for potassium to determine the etiology of hypokalemia. Measurement of spot urine for potassium and creatinine as well as evaluation of acid-base status can be used as an initial step in the diagnosis of hypokalemia. Subsequent evaluations such as measurement of spot urinary chloride, blood pressure, serum aldosterone, renin and cortisol levels may be needed in certain circumstances.

Topics: Acidosis, Renal Tubular; Humans; Hypokalemia; Potassium; Risk Factors

PubMed: 17297212
DOI: No ID Found

Review

Authors: Sabrina Giglio, Giovanni Montini, Francesco Trepiccione...

Renal tubular acidosis (RTA) comprises a group of disorders in which excretion of hydrogen ions or reabsorption of filtered HCO is impaired, leading to chronic metabolic acidosis with normal anion gap. In the current review, the focus is placed on the most common type of RTA, Type 1 RTA or Distal RTA (dRTA), which is a rare chronic genetic disorder characterized by an inability of the distal nephron to secrete hydrogen ions in the presence of metabolic acidosis. Over the years, knowledge of the molecular mechanisms behind acid secretion has improved, thereby greatly helping the diagnosis of dRTA. The primary or inherited form of dRTA is mostly diagnosed in infancy, childhood, or young adulthood, while the acquired secondary form, as a consequence of other disorders or medications, can happen at any age, although it is more commonly seen in adults. dRTA is not as "benign" as previously assumed, and can have several, highly variable long-term consequences. The present review indeed reports and summarizes both clinical symptoms and diagnosis, long-term outcomes, genetic inheritance, epidemiology and current treatment options, with the aim of shedding more light onto this rare disorder. Being a chronic condition, dRTA also deserves attention in the transition between pediatric and adult nephrology care, and as a rare disease it has a place in the European and Italian rare nephrological diseases network.

Topics: Acid-Base Equilibrium; Acidosis, Renal Tubular; Adult; Biological Transport; Child; Humans; Young Adult

PubMed: 33770395
DOI: 10.1007/s40620-021-01032-y

Review

Authors: Samuel Sherng Young Wang, Haoming Tang, Wen Qi Jane Ho...

Renal tubular acidosis is a group of disorders characterised by metabolic acidosis, hyperchloraemia, normal anion gap, and potassium imbalance. Genetic mutations, drugs or acquired disorders disrupt the function of various transport proteins and enzymes in the renal tubules, causing diminished bicarbonate reabsorption or inability to excrete hydrogen ions, leading to proximal (type 2) and distal (type 1) renal tubular acidosis, respectively. These conditions are typically associated with hypokalaemia, which, if severe, can cause muscle paralysis and dangerous cardiac arrhythmias. A rare mixed variant (type 3), including features of both type 1 and type 2 renal tubular acidosis, has also been described. On the other hand, aldosterone deficiency or resistance leads to the hyperkalaemic form of renal tubular acidosis (type 4). If untreated, renal tubular acidosis can lead to long-term severe complications such as growth retardation, osteoporosis, rickets, osteomalacia, and renal calculi. Moreover, renal tubular acidosis might be the initial presentation of a more severe underlying pathology, such as autoimmune disease or plasma cell dyscrasias. A better understanding of the condition can help physicians diagnose and treat it early and prevent adverse outcomes.

Topics: Acidosis, Renal Tubular; Humans; Hypokalemia

PubMed: 39475030
DOI: 10.12968/hmed.2024.0290

Review

Authors: Ira Kurtz

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

Review

Authors: Daniel G Fuster, Orson W Moe

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

Authors: Daniel Batlle, Sheeba Habeeb Ba Aqeel, Alonso Marquez...

Topics: Acid-Base Equilibrium; Acidosis, Renal Tubular; Ammonium Compounds; Humans; Kidney Diseases

PubMed: 29311217
DOI: 10.2215/CJN.13791217

Review

Authors: Emmanuel A Adomako, Naim M Maalouf

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

Authors: Giulia Magni, Robert J Unwin, Shabbir H Moochhala...

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