Although several compensatory mechanisms are employed in the setting of proximal tubule defects (increased bicarbonate reabsorption occurs in the thick ascending limb of the loop of Henle and in the distal parts of the nephron), their capacity is not able to overcome proximal tubule loss, leading to the appearance of symptoms [1]. Proximal renal tubular acidosis (RTA) is most frequently encountered as a constitutive feature of Fanconi's syndrome, a disorder characterized by proximal tubule dysfunction due to mutations in the sodium-phosphate cotransporter (NaPi-II), in which loss of bicarbonate is accompanied by loss of glucose, amino acids, phosphate, uric acid and other electrolytes [1]. In addition, several genetic and acquired etiologies may cause proximal RTA, such as cystinosis, multiple myeloma, wilson disease, sjögren syndrome, primary hyperparathyroidism, drug-induced (gentamicin, ifosfamide, sodium valproate, antiretroviral drugs, and cisplatin are known inducers), cadmium poisoning and several variants of inherited RTA - autosomal dominant and two autosomal recessive forms that presumably occur due to carbonic anhydrase (CA) deficiency and mutations in several other gene families [1] [2] [3] [4]. Nevertheless, the clinical features, because of the extensive nutrient loss, are similar and include growth retardation and short stature in childhood, osteomalacia due to the inability of vitamin D to convert into its active form in the proximal tubule, as well as hypothyroidism, hyperparathyroidism, dental defects and ocular abnormalities (cataracts, glaucoma, keratopathies) [1] [2] [3] [5]. Muscle and generalized weakness, reduced deep tendon reflexes and other signs of hypokalemia may be seen, whereas osteopetrosis and cerebral calcifications are characteristic for certain inherited forms [2].

• Short Stature

  Though rare, recessive SLC4A4 mutations have been reported in patients with proximal renal tubular acidosis, short stature, and ocular pathology. A 27-year-old male presented with these findings. [ncbi.nlm.nih.gov]

• Failure to Thrive

  We think that low doses of alkali are useful in the transient form of proximal renal tubular acidosis to prevent bone lesions and failure to thrive. [ncbi.nlm.nih.gov]

  At 2 months of age, the infant had persistent failure to thrive and a 1-day history of irritability and vomiting and was readmitted for diagnostic evaluation. [pedsinreview.aappublications.org]

  Evaluation of Failure to Thrive: Diagnostic Yield of Testing for Renal Tubular Acidosis. Pediatrics. 2003;112: e463–e466. Belldina EB, Huang MY, Schneider JA, Brundage RC, Tracy TS. [pedclerk.bsd.uchicago.edu]

  The disease results in deposition of crystals throughout the body; if untreated, it leads to failure to thrive, profound metabolic imbalance, early end-stage renal disease, thyroid failure, and multiorgan dysfunction. [doi.org]

• Vomiting

  A 14-year-old girl with paraplegia and absence of deep tendon reflexes in the lower extremities after 2 days of vomiting and diarrhea was referred to our pediatric neurology department with a diagnosis of Guillain-Barré syndrome. [ncbi.nlm.nih.gov]

  Since causes of nausea and vomiting among HIV/AIDS patients are very diverse, awareness of this phenomenon is useful in diagnosing and managing the problem. [bmcpharmacoltoxicol.biomedcentral.com]

  At 2 months of age, the infant had persistent failure to thrive and a 1-day history of irritability and vomiting and was readmitted for diagnostic evaluation. [pedsinreview.aappublications.org]

  For some kids, the first symptom of RTA is kidney stones, which can cause symptoms like: pain in the back or side that spreads to the lower abdomen pain while urinating pee that is red, brown, or cloudy frequent urge to urinate nausea and vomiting Over [kidshealth.org]

  A low or high potassium levels result in the following symptoms: Weakness, fatigue Paralysis Dysrhythmias or irregular heart beat Anorexia, vomiting Abdominal distention Leg cramps Postural hypotension Shallow respirations Lethargy and confusion Causes [ehealthwall.com]

• Nausea

  Since causes of nausea and vomiting among HIV/AIDS patients are very diverse, awareness of this phenomenon is useful in diagnosing and managing the problem. [bmcpharmacoltoxicol.biomedcentral.com]

  Adverse reactions Most common adverse reactions (incidence ≥5%; all grades) in clinical studies through week 96 were diarrhea (6%), nausea (6%), and headache (5%). [businesswire.com]

  For some kids, the first symptom of RTA is kidney stones, which can cause symptoms like: pain in the back or side that spreads to the lower abdomen pain while urinating pee that is red, brown, or cloudy frequent urge to urinate nausea and vomiting Over [kidshealth.org]

  Confusion Nausea Fatigue Vomiting ( 10 ). If your child experiences pain during urination, needs to urinate frequently, has cloudy or red/brown urine then these could be signs of kidney stones and hence RTA. [momjunction.com]

  Some signs and symptoms include tiredness, confusion, weakness, decreased alertness, decreased reflexes, increased breathing rate, increased heart rate, muscle cramps, muscle pain, bone pain, back pain, stomach pain, nausea, vomiting, constipation, slowed [medfriendly.com]

• Constipation

  Muscle weakness, fatigue, hypotonia, and constipation may be present due to hypokalemia. Anorexia, vomiting, and dehydration may also be present. Low normal blood pressure is seen due to hypovolemia. [lecturio.com]

  Some signs and symptoms include tiredness, confusion, weakness, decreased alertness, decreased reflexes, increased breathing rate, increased heart rate, muscle cramps, muscle pain, bone pain, back pain, stomach pain, nausea, vomiting, constipation, slowed [medfriendly.com]

• Lethargy

  We report a 28-year-old woman, gravida 3 para 2, who presented at 30 weeks gestation with lethargy, weakness and generalized myalgia. [ncbi.nlm.nih.gov]

  A low or high potassium levels result in the following symptoms: Weakness, fatigue Paralysis Dysrhythmias or irregular heart beat Anorexia, vomiting Abdominal distention Leg cramps Postural hypotension Shallow respirations Lethargy and confusion Causes [ehealthwall.com]

• Kidney Failure

  If left untreated or if not treated properly, it may cause chronic acidity of the blood leading to bone disease, kidney stones, chronic kidney disease and kidney failure, and growth retardation. [health.in4mnation.com]

  This alkali therapy also helps decrease the development of kidney stones and stabilizes kidney function so kidney failure does not progress. [pediatrics.med.miami.edu]

  Kidney stones can damage the cells of the kidney, leading to long-term kidney failure in the worst case scenario. [medfriendly.com]

  Without treatment, RTA can affect a child's growth and cause kidney stones, fatigue, muscle weakness, and other symptoms. Over time, untreated acidosis can lead to long-term problems like bone disease, kidney disease, and kidney failure. [kidshealth.org]

  […] to thrive and a normal anion gap metabolic acidosis, the following pathologies beyond RTA are in the differential: Congenital hypothyroidism Obstructive uropathy Uremic acidosis (kidney failure) Bicarbonate loss secondary to: Diarrhea, intestinal fistula [pedclerk.bsd.uchicago.edu]

• Nocturia

  Due to potassium depletion : Muscle weakness, polyuria, polydipsia, nocturia. Due to defective Calcium / phosphate / Vitamin D/ Parathormone metabolism : Osteomalacia, other bone disease. [medvin2u.net]

  […] needle biopsy針生検 neobladder 新膀胱 nephrectomy腎摘出［術］、腎摘、腎切除［術］ nephritis腎炎 nephrolithiasis腎結石 nephrology腎臓病学 nephropathy腎症 nephrostomy 腎瘻造設術 nephrotic syndromeネフローゼ症候群 nephrotoxicity腎毒性 neurogenic神経［原］性の neurogenic bladder 神経因性膀胱 neuropathic bladder 神経因性膀胱 nocturia [tokyo-med.ac.jp]

Signs and symptoms of proximal renal tubular acidosis are non-specific, but with a high dose of clinical suspicion, a presumptive diagnosis of electrolyte imbalance can be made. Moreover, a detailed physical examination and a thoroughly obtained patient history may reveal key information, such as recent use of drugs that are known inducers of proximal RTA, the presence of similar symptoms in siblings, parents or close relatives, or confirmed underlying disorders that can predispose to electrolyte imbalance. Laboratory evaluation and urinalysis, however, are the mainstay during workup. Assessment of sodium, potassium, bicarbonate, calcium and phosphorus in serum is detrimental to make the diagnosis and proximal RTA manifests as a normal anion gap metabolic acidosis [1] [2] [5]. A low urine pH (< 5.5) and a very low bicarbonate in serum strongly suggests defects of the proximal tubule, and probes such as administration of sodium bicarbonate (NaHCO3) can be performed to solidify the diagnosis [5]. When NaHCO3 is administered, urine pH markedly increases (pH > 7.5) due to the inability of the proximal tubule to absorb bicarbonate (HCO3), and a fractional excretion of HCO3 of more than 15% is considered diagnostic for proximal RTA [1] [5]. The test must be done cautiously and with potassium supplementation, as severe hypokalemia can occur and cause severe cardiac and skeletal abnormalities. Additional findings from urinalysis include glycosuria, hyperphosphaturia, and proteinuria [1]. If the underlying cause is not disclosed, a full laboratory workup, comprised of thyroid and parathyroid hormones, vitamin D levels, renal and hepatic function tests, arterial blood gasses (ABGs), and a complete blood count (CBC), should be performed.

• Nephrolithiasis

  It may lead to hypercalcinuria, nephrolithiasis, and renal failure. [icd10data.com]

  Kaplan, Charles Stanley and Lester Baker, Nephrolithiasis, hypocitraturia, and a distal renal tubular acidification defect in type 1 glycogen storage disease, The Journal of Pediatrics, 122, 3, (392), (1993). W. C. C. [doi.org]

  Evaluate for nephrocalcinosis/nephrolithiasis. Table 1: Diagnostic evaluation results for the various sub-types of RTA. Adapted from Soriano JR. Renal Tubular Acidosis: The Clinical Entity. [pedclerk.bsd.uchicago.edu]

  Unlike distal RTA, nephrolithiasis is absent in proximal RTA. If associated with the specific syndrome, additional signs and symptoms of the syndrome are present. [lecturio.com]

  Clinical clues: nephrolithiasis, nephrocalcinosis, confirm medications (NSAIDs, amiloride, ifosfamide). 1. Historical information important in the diagnosis of this problem. [clinicaladvisor.com]

• Hypophosphatemia

  Hypophosphatemia during the follow-up period was more frequent for FS than PRTA (69.2+/-26.1% vs. 7.0+/-25.8%, P [ncbi.nlm.nih.gov]

  Fanconi's syndrome, with generalized proximal tubular dysfunction, causes glycosuria, aminoaciduria, hypophosphatemia, and rickets. [nmckk.jp]

  Symptoms of distal RTA Normal anion gap metabolic acidosis Urinary stones as a result of alkaline urine Hypokalemia Nephrocalcinosis Bone demineralization as a result of hypophosphatemia (rickets in children and osteomalacia in adults) b. [ehealthwall.com]

  → vitamin D -resistant rickets / osteomalacia Epidemiology X-linked hypophosphatemic rickets (XLH) accounts for ∼ 80% of all familial causes of hypophosphatemia. [amboss.com]

  Failure to thrive Acidosis Low blood potassium (hypokalemia) High blood chloride (hyperchloremia) Symptoms of the generalized proximal renal tubule dysfunction seen in Fanconi syndrome include the following: Low blood phosphate (hypophosphatemia) Increased [news-medical.net]

• Hypophosphatemia

  Hypophosphatemia during the follow-up period was more frequent for FS than PRTA (69.2+/-26.1% vs. 7.0+/-25.8%, P [ncbi.nlm.nih.gov]

  Fanconi's syndrome, with generalized proximal tubular dysfunction, causes glycosuria, aminoaciduria, hypophosphatemia, and rickets. [nmckk.jp]

  Symptoms of distal RTA Normal anion gap metabolic acidosis Urinary stones as a result of alkaline urine Hypokalemia Nephrocalcinosis Bone demineralization as a result of hypophosphatemia (rickets in children and osteomalacia in adults) b. [ehealthwall.com]

  → vitamin D -resistant rickets / osteomalacia Epidemiology X-linked hypophosphatemic rickets (XLH) accounts for ∼ 80% of all familial causes of hypophosphatemia. [amboss.com]

  Failure to thrive Acidosis Low blood potassium (hypokalemia) High blood chloride (hyperchloremia) Symptoms of the generalized proximal renal tubule dysfunction seen in Fanconi syndrome include the following: Low blood phosphate (hypophosphatemia) Increased [news-medical.net]

• Hyperchloremia

  It is suggested that this defect represents an exaggeration of the physiological effect of parathormone on bicarbonate reabsorption and may be responsible for the frequent finding of hyperchloremia in association with primary hyperparathyroidism as well [ncbi.nlm.nih.gov]

  Vitamin D]]) Physiology Proximal Convoluted Tubule is the Main Site of Bicarbonate Reabsorption In proximal RTA, proximal tubular bicarbonate absorption is impaired, resulting in renal bicarbonate loss: bicarbonate is replaced by chloride (producing hyperchloremia [mdnxs.com]

  Normal anion gap metabolic acidosis/acidemia Hypokalemia, Hypocalcemia, Hyperchloremia Urinary stone formation (related to alkaline urine, hypercalciuria, and low urinary citrate). [en.wikipedia.org]

  Failure to thrive Acidosis Low blood potassium (hypokalemia) High blood chloride (hyperchloremia) Symptoms of the generalized proximal renal tubule dysfunction seen in Fanconi syndrome include the following: Low blood phosphate (hypophosphatemia) Increased [news-medical.net]

  Medication-induced (ACE inhibitors, NSAIDs) Clinical Features In general, pediatric patients with RTA will present with: Failure to thrive and a generally ill appearance Normal anion gap metabolic acidosis (either compensated or uncompensated) with associated hyperchloremia [pedclerk.bsd.uchicago.edu]

• Hypouricemia

  […] low-molecular-weight proteinuvia. 1995 Research Grants & Projects Molecular analysis of Dent's disease Inactivating mutations of NBC cause permanent isolated pRTA Pathogenesis of hemolytic uremic syndrome The mechanism of acute renal failure after exercise in renal hypouricemia [researchmap.jp]

  Laboratory studies revealed a hyperchloremic metabolic acidosis without aciduria, hypokalemia, hypouricemia with uricosuria, hypercalciuria, LMW proteinuria, phosphaturia, and generalized aminoaciduria. [link.springer.com]

• Hyponatremia

  It is associated with increased renin activity, hyponatremia, hyperkalemia and volume depletion. [netscut.templaro.com]

Our patient was started on treatment with apremilast 2 weeks before his admission. [ncbi.nlm.nih.gov]

Links: aetiology investigation clinical features treatment and prognosis renal tubular acidosis [gpnotebook.co.uk]

Prognosis of PRTA Although the underlying cause of proximal renal tubular acidosis may go away by itself, the effects and complications can be permanent or life-threatening. Treatment is usually successful. [medvin2u.net]

Since the ultimate prognosis seems to vary with the site of the acidification deficit, this distinction has more than academic importance. [doi.org]

Outlook (Prognosis) Although the underlying cause of proximal renal tubular acidosis may go away by itself, the effects and complications can be permanent or life-threatening. Treatment is usually successful. [coordinatedhealth.com]

TREATMENT & PROGNOSIS 60. • The aims of treatment for RTA are not only to correct as much as possible the biochemical abnormalities but to fundamentally improve growth in children and to prevent the progression of nephrocalcinosis and the development [slideshare.net]

Abstract Our aim in this article is to propose a new hypothesis concerning the etiology of renal tubular acidosis (RTA) in that subgroup of patients who have the isolated, primary type of proximal RTA. [ncbi.nlm.nih.gov]

[…] of an RTA is generally performed by a pediatric nephrologist Listed below are a few simple tests that can help delineate the etiology of the underlying RTA The interpretation of the following evaluations is summarized in Table 1. [pedclerk.bsd.uchicago.edu]

References: [1] [2] [3] [4] Type 1 renal tubular acidosis Pathophysiology : inability of the intercalated cells of the distal tubu le to secrete H + Etiology Sporadic type 1 RTA ( idiopathic ) Familial type 1 RTA (inherited genetic defects) Autosomal [amboss.com]

Thus, work-up for the etiology of proximal RTA should include Vitamin D levels since replacement of this vitamin in those who are deficient can lead to cure of such patients. [ecommons.aku.edu]

References: [6] [7] Bartter syndrome Definition : : a group of rare genetic disorders ; ( autosomal recessive or dominant ) that affect chloride reabsorption in the ascending limb of the loop of Henle Epidemiology Prevalence : 1/1,000,000 Etiology Type [amboss.com]

Urine pH usually is Epidemiology Incidence Predominant age: all ages Predominant sex: male > female (with regard to type II RTA with isolated defect in HCO 3 reabsorption) Etiology and Pathophysiology Type I RTA Autoimmune diseases: Sjögren syndrome, [unboundmedicine.com]

Epidemiology of Renal Tubular Acidosis Type 2 and 3 The exact prevalence of RTA type 2 and type 3 are unknown. It may occur as a single entity or a part of a generalized dysfunction (e.g. Fanconi’s syndrome). Isolated primary proximal RTA is rare. [lecturio.com]

Renal Tubular Acidosis Epidemiology All forms of RTA are uncommon. However, it is difficult to trace the exact rate of prevalence of these conditions as they are often under-reported and the incomplete forms are frequently not recognized. [hxbenefit.com]

Pathophysiologic and therapeutic aspects D. Rosti, A. De Vecchi, G. Graziani Istituto Clinico Humanitas Research output: Contribution to journal › Article › peer-review Translated title of the contribution Primary proximal renal tubular acidosis. [moh-it.pure.elsevier.com]

Describe Thyrotoxic hypokalemic paralysis and its pathophysiology unusual manifestation of hyperthyroidism, seen mostly in Asian patients. [quizlet.com]

In summary, the pathophysiology of pRTA caused by the R881C mutation is likely due to a deficit of NBCe1-A at the proximal tubule basolateral membrane, rather than a defect in the transport activity of individual molecules. [ncbi.nlm.nih.gov]

The kidney: Physiology and pathophysiology, New York: Ravan Press, 1491-1525 [ PM ] [ EČ ][ GS ] Kraut, J.A., Madias, N.E. (2010) Metabolic acidosis: pathophysiology, diagnosis and management. Nature reviews. [scindeks.ceon.rs]

Prevention of Renal Tubular Acidosis Prevention of RTA includes measures to prevent the causes. It is essential to maintain good hydration by increasing fluid intake to prevent stasis of byproducts in the kidneys. [ehealthwall.com]

We think that low doses of alkali are useful in the transient form of proximal renal tubular acidosis to prevent bone lesions and failure to thrive. [ncbi.nlm.nih.gov]

Get medical help right away if any of the following emergency symptoms develop: Decreased alertness or disorientation Decreased consciousness Seizures Prevention Most of the disorders that cause proximal renal tubular acidosis are not preventable. [coordinatedhealth.com]

The medicine helps prevent bone disease caused by too much acid, such as rickets, and to allow normal growth. Thiazide diuretics are also frequently used to preserve bicarbonate in the body. [nlm.nih.gov]

Type II renal tubular acidosis is caused by a defect in the proximal convoluted tubule which prevents the normal reabsorption of bicarbonate ions. [gpnotebook.co.uk]

1. Haque SK, Ariceta G, Batlle D. Proximal renal tubular acidosis: a not so rare disorder of multiple etiologies. Nephrol Dial Transplant. 2012;27(12):4273-4287.
2. Pereira PC., Miranda D., Oliveira E., Silva ACS e. Molecular Pathophysiology of Renal Tubular Acidosis. Curr Genomics. 2009;10(1):51-59.
3. Ali Y, Parekh A, Baig M, Ali T, Rafiq T. Renal tubular acidosis type II associated with vitamin D deficiency presenting as chronic weakness. Ther Adv Endocrinol Metab. 2014;5(4):86-89.
4. Katzir Z, Dinour D, Reznik-Wolf H, Nissenkorn A, Holtzman E. Familial pure proximal renal tubular acidosis--a clinical and genetic study. Nephrol Dial Transplant. 2008;23(4):1211-1215.
5. Igarashi T, Sekine T, Watanabe H. Molecular basis of proximal renal tubular acidosis. J Nephrol. 2002;15(5):S135-141.