Skip to main content

Distal renal tubular acidosis presenting with an acute hypokalemic paralysis in an older child with severe vesicoureteral reflux and syringomyelia: a case report

Abstract

Background

Distal renal tubular acidosis (dRTA) is the most common type of renal tubular acidosis (RTA) in children. Pediatric dRTA is usually genetic and rarely occurs due to acquired issues such as obstructive uropathies, recurrent urinary tract infections (UTIs), and chronic kidney disease (CKD). Although persistent hypokalemia frequently occurs with dRTA, acute hypokalemic paralysis is not frequently reported, especially in older children.

Case presentation

An eight-year-old girl presented with an acute first episode of paralysis. A physical examination revealed normal vital signs, short stature consistent with her genetic potential, and decreased muscle strength of her upper and lower extremities. Preexisting conditions included stage 4 CKD due to recurrent UTIs, severe vesicoureteral reflux and bilateral hydronephrosis, neurogenic bladder, and multisegment thoracic syringomyelia. Her laboratory work-up revealed hypokalemic, hyperchloremic metabolic acidosis with a normal anion gap. She also had a urine osmolal gap of 1.9 mOsmol/kg with a high urine pH. Intravenous potassium replacement resulted in a complete resolution of her paralysis. She was diagnosed with dRTA and discharged with oral bicarbonate and slow-release potassium supplementation.

Conclusions

This case report highlights the importance of considering dRTA in the differential diagnosis of hypokalemic acute paralysis in children. Additionally, in children with neurogenic lower urinary tract dysfunction and recurrent UTIs, early diagnosis of spinal cord etiology is crucial to treat promptly, slow the progression of CKD, and prevent long-term complications such as RTA.

Peer Review reports

Introduction

Renal tubular acidosis (RTA) is an inherited or acquired renal tubular defect that compromises the kidney’s ability to absorb filtered bicarbonate and excrete ammonia or titratable acid. The most common pediatric forms are distal (type 1) and proximal (type 2) RTA. Distal RTA (dRTA) is caused by impaired distal acid secretion that results in the inability to secrete hydrogen ions from the distal tubules [1].  The resulting clinical syndrome is characterized by hypokalemic, hyperchloremic metabolic acidosis with a normal anion gap, high urine pH (> 5.5), and in some cases nephrocalcinosis and nephrolithiasis [1,2,3]. 

Clinical manifestations of dRTA in children include polyuria, failure to thrive, constipation, Kussmaul breathing, and persistent hypokalemia [1,2,3,4].  This case report describes a late diagnosis of dRTA in a child previously diagnosed with stage 4 chronic kidney disease (CKD) due to neurogenic lower urinary tract dysfunction (NLUTD) secondary to syringomyelia. dRTA was first suspected when the patient presented with an acute episode of hypokalemic paralysis, a rare condition, particularly in older children.

Case description

An eight-year-old girl was admitted to the emergency department with an acute primary episode of bilateral lower limb paralysis that had begun approximately 9 h prior. There was no history of trauma, loss of consciousness, rapid breathing, fever, seizure, spasm, gastrointestinal tract losses, polyuria, paresthesia, or pain. She had a normal developmental history, normal auditory function, and experienced no leg weakness or sensory loss previously. No family members reported similar medical history or kidney diseases, and her parents were not close relatives. Her physical examination revealed that she was fully alert with normal vital signs. She was well nourished with short stature (height < 3rd percentile) consistent with her genetic potential. She had normal physiological reflexes. Muscle strength was 4/5 for the upper limbs and 3/5 for the lower limbs. No pathological reflexes, clonus, spasticity, or rigidity was found.

The patient had a history of anal atresia with a rectovaginal fistula that was fully corrected when she was 1 year old. She had recurrent urinary tract infections (UTIs) caused by high-grade vesicoureteral reflux (VUR) and severe bilateral hydronephrosis. She was treated with prophylactic antibiotics. When she was 6 years old, a bulking agent was used to treat bilateral VUR. She also received tamsulosin (α-1 blocker) at the age of 6 years which was then discontinued after 3 months due to no improvements. Urodynamics were performed and suggested bladder outlet obstruction with a residual urine volume of 150 mL. Magnetic resonance imaging (MRI) of the spinal cord revealed syringomyelia extending from thoracic spine Th2 to Th7 (Fig. 1). Clean intermittent catheterization (CIC) was initiated and maintained until admission. No breakthrough UTIs were noted. After a 2-year follow-up, the hydronephrosis persisted.

Fig. 1
figure 1

Sagittal T2-weighted whole spine magnetic resonance imagings (MRIs) of the patient indicating syringomyelia at T2–T7 level (arrow)

Initial laboratory investigations revealed a normal complete blood count and electrolyte imbalances, notably hypokalemia (K 2.4 mEq/L). Urinalysis revealed a UTI (Table 1). The electrocardiogram (ECG) indicated a normal heart rate and T wave inversions. The patient had decreased kidney function corresponding to an estimated glomerular filtration rate (eGFR) of 25 mL/min per 1.73 m2  (Table 1). She was treated with intravenous (IV) potassium chloride, sodium chloride, and cefotaxime and investigated for possible etiologies of hypokalemic paralysis. On the third day of hospitalization, her venous blood gasses and electrolytes indicated hyperchloremic metabolic acidosis with hypokalemia and a normal anion gap. The urine pH was 6.5 with a positive urine anion gap. Her urinary pH before this admission has ranged from 7.0 to 7.5. The urinary calcium creatinine ratio was 0.19 mg/g. Thyroid function was within the normal range. Urine osmolal gap (UOG) when she was free from UTI was 1.9 mOsmol/kg (Table 2). Kidney ultrasonography (US) did not document any nephrocalcinosis.

Table 1 Laboratory investigation on admission
Table 2 Subsequent laboratory investigation

dRTA was therefore diagnosed. The paralysis resolved completely, the urinalysis normalized, and the patient was discharged with oral bicarbonate 500 mg every 8 h and potassium slow release (KSR) 1200 mg every 12 h.

Discussion

Our patient was hospitalized after her first episode of acute hypokalemic paralysis. Based on her history and physical examination, we concluded that she had a lower motor neuron type paralysis originating from the muscles along with hypokalemia (K 2.4 mEq/L), suggesting an acute hypokalemic paralysis. The possible cause of hypokalemia was investigated, primarily the possibility of potassium loss from the kidneys. The occurrence of hypokalemia and metabolic acidosis suggests the possibility of a gastrointestinal loss of bicarbonate or RTA [5].  In this case, RTA was considered the possible cause due to the patient’s obstructive uropathy and the absence of gastrointestinal loss. All forms of RTA induce normal anion gap (hyperchloremic) metabolic acidosis, but the hallmark of dRTA is impaired urine acidification [5,6,7].  The findings of hyperchloremic metabolic acidosis, a normal anion gap, a positive UAG, a UOG of < 150 mOsmol/kg, and a high urine acidity (pH > 5.5) support the diagnosis of dRTA. Urine anion gap and UOG are indirect markers of urine acidification that estimate urinary ammonium (NH4+), which represents a major portion of net acid excretion (NAE) [6, 7].  The urine acidification impairment in dRTA and CKD patients is associated with positive UAG and a decrease in UOG, with both markers are well correlated with urine NH4+ and NAE [67]. However, UOG provides a better estimation of urinary NH4+ excretion than UAG in RTA, due to the latter becoming a less reliable predictor of urinary NH4+ excretion in patients with acute or chronic kidney disease [8, 9].

Hypokalemic paralysis is a relatively uncommon clinical manifestation of hypokalemia in patients with dRTA, and usually presents in cases of severe hypokalemia [2,3,4, 10]. In this case, however, hypokalemic paralysis occurred with a moderate level of hypokalemia. This may be due to chronic hypokalemia that was late to be discovered. In our setting, the limited availability of supporting diagnostic tools and laboratories has been a major constraint that has frequently caused diagnosis and treatment delays, particularly in patients living in remote areas, such as our current case [11, 12] .

Pediatric dRTA can be genetic or acquired. Genetic causes are most often reported in pediatric cases, although the condition can also occur due to drugs and toxins (e.g., amphotericin B and lithium), obstructive uropathies, pyelonephritis, interstitial nephritis, CKD of any cause, or autoimmune diseases (e.g., Sjögren syndrome and systemic lupus erythematosus) [1, 3]. The clinical manifestations of dRTA are further classified based on the underlying etiology. The recessive genetic form presents in infancy and is associated with more severe symptoms, while the dominant form presents later in life as a milder disease [1, 2].  Acquired dRTA may occur at any age, depending on the timing of the tubular injury of the kidneys [1].

Patients with the recessive genetic form of dRTA may present with severe hyperchloremic metabolic acidosis, moderate to severe hypokalemia, nephrocalcinosis, vomiting, dehydration, poor growth, rickets disease, and/or bilateral sensorineural hearing loss [1,2,3,4].  In comparison, the dominant genetic form is usually associated with milder disease: the most frequent initial finding is kidney stones or nephrocalcinosis, and patients typically have mild metabolic acidosis and mild to moderate hypokalemia [1, 2]. The underlying pathophysiology of dRTA consisted of decreased net activity of proton pumps and increased luminal membrane hydrogen ion permeability [5, 6]. The secretion of H+ into the lumen of the distal tubule is accomplished by type A intercalated cells of tubules via H-ATPase and H-K-ATPase pumps, which secrete H+ and reabsorb potassium [13]. Defects in these proton pumps reduce H + secretion and increase net potassium excretion by decreasing potassium reabsorption, causing potassium wasting and subsequently, hypokalemia [5, 6]. Hypokalemic paralysis usually presents in those with moderate to severe hypokalemia (K < 2.5 mEq/L).4 The defective H-ATPase also generates sodium wasting [14]. In addition, the state of metabolic acidosis may inhibit a component of the proximal tubule for sodium reabsorption [15]. The luminal membrane of the distal nephron is required to be relatively permeable to H + and carbonic acid to generate and maintain highly acidic urine. In dRTA, there is an increased permeability that results in back-leak of secreted H + from the urine into the extracellular fluid, which reduces urine acid excretion [9]. Therefore, the initial findings of hyperchloremic metabolic acidosis, hypokalemia, and hyponatremia in our patient.

The decrease in kidney function in our patient was a consequence of recurrent complicated UTIs due to severe bilateral VUR and hydronephrosis due to chronic NLUTD. The syringomyelia on the T2–T7 vertebrae segment is linked as the underlying etiology for her NLUTD. Recurrent UTIs in children with structural kidney and urinary tract abnormalities are a major risk for CKD [16]. NLUTD and obstructive uropathy have also been reported as significant causes of end-stage kidney disease in children, including in our country [17, 18].

Cases of syringomyelia presenting with neurogenic bladder have rarely been reported. Reports of dRTA secondary to obstructive uropathies due to spinal cord diseases are particularly rare [19].  dRTA in children is typically a primary genetic defect. However, we consider our case to be acquired dRTA due to the obstructive uropathies and history of recurrent UTIs. Genetic testing was not performed because the clinical history completely explained her clinical presentation. Additionally, the patient lacked any hearing impairment, nephrocalcinosis, or rickets, which are hallmarks of the genetic forms of dRTA.

Our patient was discharged after a complete resolution of symptoms due to potassium administration. She is being maintained on lifelong supportive treatments with regular oral potassium and bicarbonate supplementations. Other urinary alkalinizer such as sodium citrate (Shohl’s solution) and potassium citrate are commonly used for the treatment of dRTA as they have an additional benefit to reduce the risk of urinary tract stones formation [20, 21]. However, Shohl’s solution is not available in Indonesia, whereas potassium citrate is exclusively available only in our center with an inconsistent supply. Therefore, our case was discharged with oral bicarbonate and KSR. The parents were informed about the general management, the importance of adherence to long-term treatment, and possible poor prognosis of stage 4 CKD. Metabolic profiles and kidney function need to be monitored regularly to prevent recurrence of symptoms, future nephrocalcinosis, bone deformities, and growth retardation which may occur in the untreated dRTA [22].

This case report highlights the importance of considering dRTA in the differential diagnosis of hypokalemic acute paralysis in children. Additionally, in children with neurogenic lower urinary tract dysfunction and recurrent UTIs, early diagnosis of spinal cord etiology is crucial to treat promptly, slow the progression of CKD, and prevent long-term complications such as RTA.

Abbreviations

CIC:

Clean intermittent catheterization

CKD:

Chronic kidney disease

dRTA:

Distal renal tubular acidosis

ECG:

Electrocardiogram

eGFR:

Estimated glomerular filtration rate

IV:

Intravenous

MRI:

Magnetic resonance imaging

NAE:

net acid excretion

NLUTD:

Neurogenic lower urinary tract dysfunction

RTA:

Renal tubular acidosis

UAG:

Urine anion gap

UOG:

Urine osmolal gap

US:

Ultrasonography

UTIs:

Urinary tract infections

VUR:

Vesicoureteral reflux

References

  1. Besouw MTP, Bienias M, Walsh P, Kleta R, van’t Hoff WG, Ashton E, et al. Clinical and molecular aspects of distal renal tubular acidosis in children. Pediatr Nephrol. 2017;32:987–92. https://doi.org/10.1007/s00467-016-3573-4.

    Article  PubMed  Google Scholar 

  2. Palazzo V, Provenzano A, Bacherucci F, Sansavini G, Mazzinghi B, Orlandini V, et al. The genetic and clinical spectrum of a large cohort of patients with distal renal tubular acidosis. Kidney Int. 2017;91:1243–55. https://doi.org/10.1016/j.kint.2016.12.017.

    Article  CAS  PubMed  Google Scholar 

  3. Yaxley J, Pirrone C. Review of the diagnostic evaluation of renal tubular acidosis. Ochsner J. 2016;16:525–30. PMID: 27999512.

    PubMed  PubMed Central  Google Scholar 

  4. Giglio S, Montini G, Trepiccione F, Gambaro G, Emma F. Distal renal tubular acidosis: A systematic approach from diagnosis to treatment. J Nephrol. 2021;26:1–7. https://doi.org/10.1007/s40620-021-01032-y.

    Article  CAS  Google Scholar 

  5. Forero-Delgadillo JM, Gil-Pena H, Alonso-Varela M, Santos F. Kidney function in patients with primary distal renal tubular acidosis. Pediatr Nephrol. 2021;36:1931–5. https://doi.org/10.1007/s00467-021-05068-x.

    Article  PubMed  Google Scholar 

  6. Bagga A, Bajpai A, Menon S. Approach to renal tubular disorders. Indian J Pediatr. 2005;72:771–6. https://doi.org/10.1007/BF02734150.

    Article  PubMed  Google Scholar 

  7. Kim GH, Han JS, Kim YS, Joo KW, Kim S, Lee JS. Evaluation of urine acidification by urine anion gap and urine osmolal gap in chronic metabolic acidosis. Am J Kidney Dis. 1996;27:42–7. https://doi.org/10.1016/s0272-6386(96)90029-3.

    Article  CAS  PubMed  Google Scholar 

  8. Santos F, Ordóñez FA, Claramunt-Taberner D, Gil-Peña H. Clinical and laboratory approaches in the diagnosis of renal tubular acidosis. Pediatr Nephrol. 2015;30:2099–107. https://doi.org/10.1007/s00467-015-3083-9.

    Article  PubMed  Google Scholar 

  9. Batlle D, Ba Aqeel SH, Marquez A. The urine anion gap in context. Clin J Am Soc Nephrol. 2018;13:195–7. https://doi.org/10.2215/CJN.13791217.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Gomez-Conde S, Garcia-Castano A, Guirre M, Hererro M, Gondra L, Garcia-Perez N, et al. Molecular aspects and long term outcome of patients with primary distal renal tubular acidosis. Pediatr Nephrol. 2021;33881640. https://doi.org/10.1007/s00467-021-05066-z.

  11. Ambarsari CG, Cahyadi D, Sari L, Satria O, Sahli F, Darmadi TL, Kadaristiana A. Late diagnosis of Lesch–Nyhan disease complicated with end-stage renal disease and tophi burst: A case report. Ren Fail. 2020;42(1):113–21. https://doi.org/10.1080/0886022X.2020.1713805.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Ambarsari CG, Sindih RM, Saraswati M, Trihono PP. Delayed admission and management of pediatric acute kidney injury and multiple organ dysfunction syndrome in children with multiple wasp stings: a case series. Case Rep Nephrol Dial. 2019;9:137–48. https://doi.org/10.1159/000504043.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Giebisch G, Wang W. Potassium transport: from clearance to channels and pumps. Kidney Int. 1996;49:1624–31. https://doi.org/10.1038/ki.1996.236.

    Article  CAS  PubMed  Google Scholar 

  14. Gueutin V, Vallet M, Jayat M, Peti-Peterdi J, Cornière N, Leviel F, et al. Renal β-intercalated cells maintain body fluid and electrolyte imbalance. J Clin Invest. 2013;123:4219–31. https://doi.org/10.1172/JCI63492.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Wang T, Egbert AL Jr, Aronson PS, Giebisch G. Effect of metabolic acidosis on NaCl transport in the proximal tubule. Am J Physiol. 1998;274:1015–9. https://doi.org/10.1152/ajprenal.1998.274.6.F1015.

    Article  Google Scholar 

  16. Salo J, Ikaheimo R, Tapiainen T, Uhari M. Childhood urinary tract infections as a cause of chronic kidney disease. Pediatrics. 2011;128(5):840–7. https://doi.org/10.1542/peds.2010-3520.

    Article  PubMed  Google Scholar 

  17. Ambarsari CG, Hidayati EL, Trihono PP, Saraswati M, Rodjani A, Wahyudi I, Situmorang GR, Kim JJ, Mellyana O, Kadaristiana A. Experience of the first 6 years of pediatric kidney transplantation in Indonesia: A multicenter retrospective study. Pediatr Transpl. 2020;00:e13812. https://doi.org/10.1111/petr.13812.

    Article  Google Scholar 

  18. Palupi-Baroto R, Hermawan K, Murni IK, Nurlitasari T, Prihastuti Y, Sekali DRK, Ambarsari CG. High fibroblast growth factor 23 as a biomarker for severe cardiac impairment in children with chronic kidney disease: a single tertiary center study. Int J Nephrol Renovasc Dis. 2021;14:165–71. https://doi.org/10.2147/IJNRD.S304143.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Geljic A, Abdovic S, Stampalija F, Loncar L, Tripalo B, Cuk M. An unsual case of syringohydromyelia presenting with neurogenic bladder. Eur J Pediatr Surg Rep. 2019;7(1):79–82. https://doi.org/10.1055/s-0039-1697925.

    Article  Google Scholar 

  20. Glassman K. Metabolic acidosis: Got bicarbonate? Pract Gastroenterol. 2020;203:26–33.

    Google Scholar 

  21. Lopez-Garcia SC, Emma F, Walsh SB, Fila M, Hooman N, Zaniew M, et al. Treatment and long-term outcome in primary distal renal tubular acidosis. Nephrol Dial Transplant. 2019;34:981–91. https://doi.org/10.1093/ndt/gfy409.

    Article  CAS  PubMed  Google Scholar 

  22. Kedsatha P, Shin HY, Choi Y, Cheong H, Cho T, Yi E, et al. A pediatric case of long-term untreated distal renal tubular acidosis. Child Kidney Dis. 2020;24(2):115–9. https://doi.org/10.3339/jkspn.2020.24.2.115.

    Article  Google Scholar 

Download references

Acknowledgements

Not applicable.

Funding

The authors received no specific funding for this work.

Author information

Authors and Affiliations

Authors

Contributions

DNS and CGA performed the literature search, data collection, analysis, and interpretation, and wrote the first draft of the manuscript. FAGS performed data collection and analysis. DNS, FAGS, and CGA critically reviewed the manuscript. All authors read and approved the final version of the manuscript.

Corresponding author

Correspondence to Cahyani Gita Ambarsari.

Ethics declarations

Ethics approval and consent to participate

This study was performed in line with the principles of the Declaration of Helsinki. Informed consent was obtained from the patient’s caregiver for publication of this case report.

Consent for publication

Written informed consent for the publication of this case report and accompanying images was obtained from the patient’s guardian. A copy of the written consent is available for review from the editor of this journal.

Competing interests

The authors have no conflict of interests to report.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Santoso, D.N., Sinuraya, F. & Ambarsari, C. Distal renal tubular acidosis presenting with an acute hypokalemic paralysis in an older child with severe vesicoureteral reflux and syringomyelia: a case report. BMC Nephrol 23, 248 (2022). https://doi.org/10.1186/s12882-022-02874-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12882-022-02874-9

Keywords

  • Anion gap
  • Chronic kidney diseases
  • Hydronephrosis
  • Intermittent urethral catheterization
  • Metabolic acidosis
  • Neurogenic urinary bladder
  • Spinal cord diseases
  • Urinary tract infections