Year : 2016 | Volume
: 27 | Issue : 4 | Page : 812--815
Successful treatment of proximal renal tubular acidosis and Fanconi syndrome with vitamin D replacement
Syed Ahsan Ali, Muhammad Tariq
Department of Medicine, Aga Khan University Hospital, Karachi, Pakistan
Syed Ahsan Ali
Department of Medicine, Aga Khan University Hospital, Karachi 74800
Proximal renal tubular acidosis (RTA), also known as Type II RTA, is characterized by a defect in the ability to reabsorb bicarbonate (HCO 3 ) in the proximal tubule. It is usually associated with generalized dysfunction of the proximal tubule as part of Fanconi syndrome. Very few case reports in the literature support Vitamin D deficiency as a cause of proximal RTA. We present a case of a young female who presented with proximal RTA and Fanconi syndrome and excellently responded to Vitamin D replacement. 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.
|How to cite this article:|
Ali SA, Tariq M. Successful treatment of proximal renal tubular acidosis and Fanconi syndrome with vitamin D replacement.Saudi J Kidney Dis Transpl 2016;27:812-815
|How to cite this URL:|
Ali SA, Tariq M. Successful treatment of proximal renal tubular acidosis and Fanconi syndrome with vitamin D replacement. Saudi J Kidney Dis Transpl [serial online] 2016 [cited 2020 Oct 21 ];27:812-815
Available from: https://www.sjkdt.org/text.asp?2016/27/4/812/185270
The importance of Vitamin D deficiency is undebatable. Vitamin D deficiency causes impaired calcium absorption which can lead to osteomalacia in adults and is also associated with extraskeletal sequelae including increased risks of cancer, cardiovascular disease, infection, and autoimmune diseases.  Vitamin D deficiency is quite common among otherwise healthy adults. ,,
Renal tubular acidosis (RTA) is a nonuremic defect of urinary acidification.  Proximal RTA is characterized by a defect in the ability to reabsorb HCO 3 in the proximal tubule. More commonly than being an isolated disorder, proximal RTA is associated with generalized dysfunction of the proximal tubule as part of the Fanconi syndrome. 
Proximal RTA as a cause of Vitamin D deficiency can result in osteomalacia and rickets as documented well in literature. ,,, However, a few case reports in literature support Vitamin D deficiency as a cause of proximal RTA. ,,,
Here, we present a case of proximal RTA with Fanconi syndrome in a patient who initially presented with hypokalemic periodic paralysis. Later, the patient was found to have Vitamin D deficiency and responded well to Vitamin D replacement in terms of correction of electrolytes disturbances including hypophosphatemia.
A 27-year-old female residing in Karachi and working as a school administrator presented with pain and weakness of all four limbs for the last two days. This weakness started gradually and then became so severe that patient was unable to walk or get out of bed. She had moderate aching pain in all four limbs but without numbness or tingling. Two months ago, she had similar pain without any weakness that resolved on taking tizanidine and naproxen. There was no history of joint pain, skin rash, photosensitivity, oral ulcers, dryness of mouth or eyes, Raynaud's phenomenon, sweating, palpitation, weight loss, diarrhea, irritability, pedal swelling, or fever. There was no history of any addiction.
On examination, she was a young female of average height and build lying without stress in bed with normal vital signs. Her neurological examination revealed power of 2/5 in all four limbs with intact reflexes and flexor plantar response with no sensory impairment. The rest of the systemic examination was completely unremarkable.
The laboratory investigations showed blood urea nitrogen 13 mg/dL, creatinine of 0.6 mg/ dL, sodium 137 mmol/L, potassium 2.3 mmol/ L, chloride 122 mmol/L, bicarbonate 7.9 mmol/ L, random blood sugar 118 mg/dL, calcium 9.0 mg/dL, magnesium 2.7 mg/dL (normal 1.7-2.8), and phosphorus 1.0 mg/dL (normal 2.5-4.6). Arterial blood gas done at that time showed pH 7.38, PCO 2 20.6 mm Hg, PO 2 159.2 mm Hg, and bicarbonate 12.2 mEq/L. Thyroidstimulating hormone level was 2.0 μIU (0.4-4.2) and free T4 1.63 ng/dL (0.93-1.7). Blood counts were normal. Urinary CO 2 , bicarbonate, and amino acids could not be done as these tests were not available at our hospital.
The patient was diagnosed as hypokalemic periodic paralysis with proximal RTA II. Diagnosis of Fanconi syndrome was considered due to significantly low phosphorus levels. She was treated aggressively with intravenous potassium chloride and bicarbonate. Her symptoms improved in the next few days with moderate improvement in electrolytes. After 10 days of admission, her potassium was 3.5 mmol/L, bicarbonate was 14.0 mmol/L, and phosphorus was 2.9 mg/dL. At this stage, her urine showed a pH of 6.0 and trace proteinuria with no glucosuria. The patient was then discharged home on oral potassium and bicarbonate supplements. She remained compliant to bicarbonate and potassium supplements. Her electrolytes were done several times during her follow-up. Her potassium was 3.4 mmol/L, bicarbonate 13 mmol/L, and phosphate 2.4 mg/ dL after four months of discharge. Similarly, her potassium was 3.8 mmol/L, bicarbonate 20.6 mmol/L, and phosphate 2.6 mg/dL after eight months. Her potassium was 2.2 mmol/L, bicarbonate 14.1 mmol/L, and phosphate 1.4 mg/dL after one year. After two years, her potassium was 2.8 mmol/L, bicarbonate 16.3 mmol/L, and phosphate 1.7 mg/dL. Her urinalysis was done after one month, two years, and 2½ years during follow-up. All these showed a urinary pH of 7.0.
After around four years of admission, the patient again complained of generalized muscular pains. At that time, her Vitamin D level was 8.19 ng/mL (normal >30 ng/mL). At that time, her other laboratory investigations showed potassium 4.0 mmol/L, bicarbonate 17.9 mmol/L, calcium 8.9 mg/dL, and phosphate 2.7 mg/ dL. She was treated with 600,000 IU of intramuscular Vitamin D 3 (cholecalciferol). Just after a single dose of Vitamin D, her electrolytes showed dramatic improvement within two months. Her potassium increased to 4.1 mmol/L, bicarbonate 23.7 mmol/L, and phosphorus 3.3 mg/dL. She remained on potassium and bicarbonate supplements for eight months. Her latest potassium was 3.3 mmol/L, bicarbonate 17.7 mmol/L, and phosphate 1.6 mg/dL, and she was asymptomatic as well. This slight drop in her potassium, bicarbonate, and phosphate level was probably due to a recent noncompliance by her to sodium bicarbonate and potassium supplements. Now, she was restarted on these supplements.
The diagnosis of proximal RTA should be considered whenever a patient presents with normal anion gap metabolic acidosis, hypokalemia, and urinary pH >5.3. The diagnosis is confirmed by an increase in urinary pH and fractional excretion of bicarbonate (>15%) after bicarbonate infusion, , and urinary PCO 2 >70 mm Hg. 
Decreased serum calcium and increased parathyroid hormone levels associated with Vitamin D deficiency probably reduce the bicarbonate reabsorption at the proximal tubules of kidney. 
Despite having ample sunlight exposure throughout the year in all over Pakistan, Vitamin D deficiency is prevalent in this part of the world. The exact etiology of this is still not completely understood with some blames on inadequate food fortification, increased pigmentation, major chunk of women in general not going outside home for work and possibly altered physiology of Vitamin D metabolism in Pakistanis. 
Our patient presented with hypokalemic periodic paralysis and found to have proximal RTA II. We labeled her as Fanconi syndrome due to the presence of coexistent very low phosphorus levels and trace proteinuria though she did not reveal glucosuria. After bicarbonate therapy, her urinary pH was 6.0, which is also a supportive evidence of proximal RTA. Although this high urinary pH may be due to coexistent distal RTA I.  Despite the fact that we could not confirm the diagnosis by measuring fractional excretion of bicarbonate after intravenous bicarbonate infusion, we were able to establish vitamin D deficiency as a cause of proximal RTA. Our patient remained on oral bicarbonate and potassium supplements for around four years till she incidentally was found to have low vitamin D levels, and supplementation with vitamin D cured the patient.
There are several shortcomings in this case report. Due to unavailability, we were not able to check aminoaciduria, urinary PCO 2, and fractional excretion of bicarbonate. Similarly, urinalysis, which would have been shown urinary pH, was not done at the time of admission before start of bicarbonate infusion. All these would help in confirming the diagnosis of proximal RTA. Despite these caveats, we believe that the information obtained from this case report will help to increase our knowledge about curable causes of proximal RTA.
If a patient presents with proximal RTA in an area where vitamin D deficiency is common, then vitamin D deficiency should be included in the differential diagnosis. Vitamin D levels of such patients should always be checked because vitamin D replacement in such patients can be curative.
Conflict of interest: None declared.
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