Decreased Renal Expression of H&lt;sup&gt;+&lt;/sup&gt;-ATPase and Pendrin in a Patient with Distal Renal Tubular Acidosis Associated with Sj&amp;ouml;gren's Syndrome

Kim, Ha Yeon; Kim, Sung Sun; Bae, Eun Hui; Kwon, Seong; Kim, Soo Wan

doi:10.2169/internalmedicine.54.4821

Cited by 12 publications

(19 citation statements)

References 30 publications

(23 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Most RTAs in pSS are associated with TIN, which resembles lymphocyte infiltration in the exocrine glands. In these cases, the decreased expression of both H+-ATPase and anion exchanger 1 (AE1) in α-intercalated cells has been well observed without the presence of autoantibodies against those transporters 6 7 8) . However, underlying cellular events linking TIN and the absence of those two transport proteins have yet to be discovered.…”

Section: Discussionmentioning

confidence: 99%

Renal Tubular Acidosis in Patients with Primary Sjögren's Syndrome

Jung

Park

Kim

et al. 2017

Electrolyte Blood Press

View full text Add to dashboard Cite

Primary Sjögren's syndrome (pSS) is characterized by lymphocytic infiltration of the exocrine glands resulting in decreased saliva and tear production. It uncommonly involves the kidneys in various forms, including tubulointerstitial nephritis, renal tubular acidosis, Fanconi syndrome, and rarely glomerulonephritis. Its clinical symptoms include muscle weakness, periodic paralysis, and bone pain due to metabolic acidosis and electrolyte imbalance. Herein, we describe the cases of two women with pSS whose presenting symptoms involve the kidneys. They had hypokalemia and normal anion gap metabolic acidosis due to distal renal tubular acidosis and positive anti-SS-A and anti-SS-B autoantibodies. Since one of them experienced femoral fracture due to osteomalacia secondary to renal tubular acidosis, an earlier diagnosis of pSS is important in preventing serious complications.

show abstract

Section: Discussionmentioning

confidence: 99%

Renal Tubular Acidosis in Patients with Primary Sjögren's Syndrome

Jung

Park

Kim

et al. 2017

Electrolyte Blood Press

View full text Add to dashboard Cite

show abstract

“…First, various articles have shown the apical H + ATPase ( Figure 2 ) on membranes of αICCs to be absent via immunostaining, 14 - 16 although the αICCs are otherwise present and morphologically normal. This has been speculated to be due to immune cell infiltration (as seen on histological examination), with general injury to α-intercalated cells (αICCs).However, distal RTA in some Sjögren patients do not have evidence of interstitial infiltration, 16 suggesting a more targeted destruction of the H + ATPase pumps. Kim et al explored whether autoantibodies in the serum may be responsible for this process, but incubation of the patient’s serum with control human and rat kidney failed to show any cross reactivity.…”

Section: Pathogenesis Of Distal Rta and Subsequent Hypokalemia In Sjömentioning

confidence: 99%

“…Kim et al explored whether autoantibodies in the serum may be responsible for this process, but incubation of the patient’s serum with control human and rat kidney failed to show any cross reactivity. 16 Other unproven theories of the (presumed acquired) loss include defects in expression, assembly, or insertion of the pump into the apical membrane. As the H + ATPase actively secretes protons, loss of this pump leads to metabolic acidosis and inappropriately alkaline urine.…”

Section: Pathogenesis Of Distal Rta and Subsequent Hypokalemia In Sjömentioning

confidence: 99%

“…Second, distal RTA in Sjögren patients is also marked by the absence of Pendrin ( Figure 2 ), a Cl − /HCO 3 − antiporter on the apical membrane of Type B intercalated cells (βICC) which functions to secrete bicarbonate. 16 A possible explanation for this is that the process underlying the destruction of H + ATPase on αICCs also affects Pendrin. An alternative possibility, however, may be that loss of H + ATPase on αICCs which lead to metabolic acidosis may cause βICCs to compensate by downregulating Pendrin to reduce secretion of bicarbonate.…”

Section: Pathogenesis Of Distal Rta and Subsequent Hypokalemia In Sjömentioning

confidence: 99%

“…An alternative possibility, however, may be that loss of H + ATPase on αICCs which lead to metabolic acidosis may cause βICCs to compensate by downregulating Pendrin to reduce secretion of bicarbonate. 16 If the loss of Pendrin is due to compensation, it is likely incomplete if the state of metabolic acidosis persists. 16 It is thus interesting to speculate that perhaps more patients with Sjögren than we observe have diminished H + ATPase, as those who completely compensate do not come to clinical attention with significant metabolic acidosis.…”

Section: Pathogenesis Of Distal Rta and Subsequent Hypokalemia In Sjömentioning

confidence: 99%

See 2 more Smart Citations

Complete Hypokalemic Quadriparesis as a First Presentation of Sjögren Syndrome

Braam

2018

Can J Kidney Health Dis

View full text Add to dashboard Cite

Rationale:We hope to increase awareness that hypokalemic paralysis may be the first presentation of Sjögren syndrome, for which potassium-sparing diuretics can be an effective adjunct to potassium replenishment.Presenting concerns:A 73-year-old female presented to a peripheral hospital with quadriparesis and a critically low serum potassium of 1.6 mmol/L with U waves on the electrocardiogram (ECG). The initial arterial blood gas showed a pH of 7.19, bicarbonate of 13 mEq/L, and a CO2 of 35 mm Hg. Over the next 6 days, she was administered a total of 450 mEq of potassium supplements. Despite this, her potassium never increased above 2.9 mmol/L and was thus transferred to the University Hospital for further management. On arrival, her vital signs were within normal limits. Her only other symptoms were fatigue and ocular dryness. Physical exam showed slightly weakened quadriceps muscles bilaterally, graded 4/5. Examination was otherwise unremarkable. Admission investigations included a potassium of 2.8 mmol/L, chloride 118 mmol/L, sodium 136 mmol/L, and eGFR 48 mL/min/1.73 m2. Renin aldosterone ratio was normal.Diagnoses:Distal renal tubular acidosis (RTA) was diagnosed based on a normal anion gap metabolic acidosis, positive urine anion gap, and elevated urine potassium to creatinine ratio. Investigation of underlying causes revealed a positive Antinuclear antibody (ANA), elevated rheumatoid factor, and high anti-Ro/SSA titre which directed us toward a unifying diagnosis of Sjögren syndrome. A renal biopsy was undertaken as an outpatient and demonstrated severe interstitial nephritis with acute and chronic components, parenchymal scarring, atrophy, and small vessel arteriosclerosis.Interventions:In the acute setting, the patient was treated with bicarbonate and amiloride in addition to potassium supplementation.Outcomes:The patient’s hypokalemic paralysis and metabolic acidosis were corrected.Lessons Learned:Severe hypokalemic paralysis in distal RTA associated with Sjögren syndrome can be successfully treated with amiloride in addition to potassium supplementation. We also review the literature on the aberrancies seen in H+ATPase, Band 3, Pendrin, and carbonic anhydrase that may underlie the pathogenesis of distal RTA in Sjögren syndrome.

show abstract

Renal involvement in primary Sjogren’s syndrome: a prospective cohort study

et al. 2018

View full text Add to dashboard Cite

The objective of the study is to prospectively evaluate the spectrum of clinical and subclinical renal involvement in patients with primary Sjogren's syndrome (pSS). Of the 174 patients screened, seventy patients with pSS underwent renal function tests, urine examination, renal ultrasound, arterial blood gases, urine pH followed by urine acidification test and renal biopsy (if indicated). Renal tubular acidosis (RTA) was treated with alkali replacement and moderate-severe tubulointerstitial nephritis (TIN) was treated with oral prednisolone. Sixty-two patients completed 1-year follow-up. A comparison was made between patients with and without renal involvement. Thirty-five (50%) patients had renal involvement. They had a lower baseline eGFR (71.85 ± 18.04 vs. 83.8 ± 17, p = 0.005). Twenty-nine patients had RTA (25 complete and 4 incomplete). Eleven patients had urinary abnormalities. Patients with RTA (n = 29) were younger (34.9 ± 9 vs. 42 ± 11.3, p = 0.006), had fewer articular (34% vs. 78%, p = 0.001) and ocular sicca (62% vs. 88%, P = 0.01) than those without RTA (n = 41) and commonly presented with hypokalemic paralysis. On biopsy, TIN (9/17) and IgA nephropathy (3/17) were most common. On follow-up, there was no clinically significant change in eGFR; however, one patient with renal calculi and incomplete distal renal tubular acidosis (dRTA) progressed to complete dRTA. Two patients treated with steroids had marginal improvement in eGFR. Renal involvement in pSS is under-recognized with the most common manifestation being RTA presenting with hypokalemic paralysis. These patients are younger with less articular and sicca symptoms. Subclinical RTA may progress to complete RTA. Renal biopsy should be considered in all patients with renal involvement.

show abstract

Decreased Renal Expression of H<sup>+</sup>-ATPase and Pendrin in a Patient with Distal Renal Tubular Acidosis Associated with Sjögren's Syndrome

Cited by 12 publications

References 30 publications

Renal Tubular Acidosis in Patients with Primary Sjögren's Syndrome

Renal Tubular Acidosis in Patients with Primary Sjögren's Syndrome

Complete Hypokalemic Quadriparesis as a First Presentation of Sjögren Syndrome

Renal involvement in primary Sjogren’s syndrome: a prospective cohort study

Contact Info

Product

Resources

About