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Proximal Renal Tubular Acidosis

Renal Tubular Acidosis Type 2

Proximal renal tubular acidosis, also known as type 2 renal tubular acidosis, is distinguished by the impaired absorption of bicarbonate in the proximal tubule of the nephron. Wasting of bicarbonate, as well as other electrolytes, proteins and glucose in the proximal tubule lead to symptoms. Urinalysis is needed to make the diagnosis.


Presentation

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].

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]
  • 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.[content.nejm.org]
  • 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]
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]
Cyanosis
  • Despite a Blalock's fistula there was evidence of chronic hypoxia with cyanosis, clubbing of fingers and toes and very elevated blood hematocrit values.[ncbi.nlm.nih.gov]
Corneal Opacity
  • The prolonged survival time uncovered the development of corneal opacities due to corneal edema.[ncbi.nlm.nih.gov]
Corneal Edema
  • The prolonged survival time uncovered the development of corneal opacities due to corneal edema.[ncbi.nlm.nih.gov]
Guillain-Barré Syndrome
  • 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]
Kidney Failure
  • If treated early and properly, chances for developing permanent kidney failure will be none. However, the patient will need checkups throughout his/her life.[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]
  • If treated early, most people with RTA will not develop permanent kidney failure. The longer the condition goes untreated, however, the greater the likelihood of permanent kidney failure.[medfriendly.com]
  • Over time, untreated acidosis can lead to long-term problems like bone disease, kidney disease, and kidney failure.[kidshealth.org]
  • failure) Bicarbonate loss secondary to: Diarrhea, intestinal fistula, and medications (cholestyramine, magnesium sulfate, calcium chloride, acetazolamide) Acid loading with accompanying chloride (ammonium chloride, arginine hydrochloride) Laboratory[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]

Workup

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
  • 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]
  • It may lead to hypercalcinuria, nephrolithiasis, and renal failure.[icd10data.com]
  • 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]
  • Nephrocalcinosis and nephrolithiasis are possible complications of hypercalciuria and hypocitraturia if urine is relatively alkaline. This syndrome is rare.[merckmanuals.com]
  • Clinical clues: nephrolithiasis, nephrocalcinosis, confirm medications (NSAIDs, amiloride, ifosfamide). 1. Historical information important in the diagnosis of this problem.[clinicaladvisor.com]
Hypouricemia
  • Laboratory studies revealed a hyperchloremic metabolic acidosis without aciduria, hypokalemia, hypouricemia with uricosuria, hypercalciuria, LMW proteinuria, phosphaturia, and generalized aminoaciduria.[link.springer.com]
  • […] 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]
Hyponatremia
  • It is associated with increased renin activity, hyponatremia, hyperkalemia and volume depletion.[netscut.templaro.com]

Treatment

  • Our patient was started on treatment with apremilast 2 weeks before his admission.[ncbi.nlm.nih.gov]
  • After treatment, metabolic acidosis and hypercalciuria improved, and the patient had a catch-up growth phase.[ncbi.nlm.nih.gov]
  • The height standard deviation score (SDS) at the start of treatment was significantly lower in FS than in PRTA.[ncbi.nlm.nih.gov]
  • Treatment consists of oral bicarbonate supplementation. However, this will increase urinary bicarbonate wasting and may well promote a bicarbonate diuresis.[en.wikipedia.org]
  • When restudied at 33 months of age, the threshold had risen to 20 mEq/liter, but this was still abnormal and supplemental treatment was required to keep the serum concentration of bicarbonate above 20 mEq/liter.[ncbi.nlm.nih.gov]

Prognosis

  • 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]
  • Long term prognosis varies from one case to another, and cases of both full recovery and fatalistic implications have been recorded.[hxbenefit.com]

Etiology

  • 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]
  • 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.[ncbi.nlm.nih.gov]
  • Etiologies of proximal RTA may be divided into primary, isolated causes and secondary causes, or those related to another disease. Primary causes are frequently single gene hereditary disorders.[en.wikipedia.org]
  • 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[symptoma.com]

Epidemiology

  • 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, rheumatoid[unboundmedicine.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]
Sex distribution
Age distribution

Pathophysiology

  • These results have implications for understanding the role of kNBC1 in the pathophysiologic processes of pRTA associated with ocular abnormalities and mental retardation.[ncbi.nlm.nih.gov]
  • 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]
  • Describe Thyrotoxic hypokalemic paralysis and its pathophysiology unusual manifestation of hyperthyroidism, seen mostly in Asian patients.[quizlet.com]
  • 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]
  • 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 dominant[amboss.com]

Prevention

  • 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]
  • 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]
  • 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]
  • Correcting acidosis and low potassium levels restores normal growth patterns, allowing bone to mature while preventing further renal disease. Vitamin D supplements may also be needed to help prevent bone problems.[pediatrics.med.miami.edu]

References

Article

  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.

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Last updated: 2019-07-11 20:09