Title

A Rare Clinical Entity: Liddle’s-Like Syndrome due to Membranous Nephropathy

Authors

Dharam R Patel, DO, Roshny A George, MD

Introduction

Liddle-Like Syndrome secondary to Nephrotic Syndrome is an extremely rare presentation with few case reports in published literature. [3,4,5] Our patient’s presentation is unique in that RAAS blockade alone was effective in improving symptoms. Thus, indicating that the inhibition of aldosterone mediated ENac channel activation is sufficient for initial treatment until the underlying cause is treated. This differs from Liddle Syndrome as direct ENac inhibitors are the mainstay of therapy.

Case Presentation

Our Patient is a 40-year-old male without any significant past medical history and no medication use who was admitted for bilateral lower extremity weakness and anasarca. Patient was noted to be hypertensive on admission with blood pressure of 168/92 but otherwise normal vitals and BMI of 29.6. He denied symptoms of shortness of breath, chest pain, polyuria, nausea, vomiting, diarrhea or laxative abuse, alcohol or drug use, NSAID use, history of obstructive sleep apnea, beta blocker or insulin use. Lab abnormalities revealed potassium of 1.9meq/L, Creatinine of 1.76 mg/dL, glucose of 102 mg/dL, bicarbonate of 32meq/L, AST of 104 IU/L, Albumin of 2.3 g/dL with corrected calcium within normal limits, total protein of 4.6 g/dL, CK of 3863 IU/L, Hgb of 12.1 g/dL, urinalysis with >300g within nephrotic range. Subsequent lipid panel revealed mixed hyperlipidemia. It is important to note plasma renin level 0.3ng/mL/hr and aldosterone of 3.4ng/dL were low with normal TSH. Urine drug screen was negative. Given the severity of metabolic alkalosis and lack of tachypnea indicative of respiratory alkalosis, urine electrolyte studies were obtained. Urine K+ of 17.7 meq/L, Cl- of 81 meq/L, and Na+ of 67.7 meq/L, 102.8 mg/dL, and urine-protein-creatinine-ratio of 10.09. Urine K+/Creatinine ration of 0.17 which is less than 1.5 indicating either GI losses, poor PO intake, or shift of potassium intracellularly. Patient was finishing his meals entirely and had no diarrhea or emesis during his hospital course. Given lack of explanation for his elevated creatinine with unknown baseline, the following work-up was pursued. Urine Immunofixation, serum protein electrophoresis, C3 and C4 complement levels, hepatitis panel, HIV antibodies, c-ANCA, p-ANCA, ds-DNA antibodies resulted negative. PLA2R antibodies returned positive as well as positive ANA with speckled pattern 1:640. Patient underwent kidney biopsy revealing Primary Membranous Nephropathy. The patient was initiated on lisinopril and spironolactone in addition to low sodium diet for renin-angiotensin aldosterone system blockade with improvement of clinical symptoms, hypertension, and electrolyte disturbances.

Discussion

The patient’s presentation is consistent with Liddle-Like Syndrome caused by activation of ENac channels secondary to significant proteasuria. [1] All criteria were met, including nephrotic syndrome, hypertension, hypokalemia, low serum renin and aldosterone levels, metabolic alkalosis, in addition to the condition improving with the use of potassium sparing diuretics as well as a low sodium diet. It is important to note that spironolactone or lisinopril has no effect in true Liddle’s Syndrome, however, is effective in Liddle-Like Syndrome as in this patient which is an important distinguishing factor. [2]

References

1. Artunc, F. (2020). Proteolytic activation of the epithelial sodium channel in nephrotic syndrome by Proteasuria: Concept and therapeutic potential. Turkish Journal of Nephrology, 29(1), 59–65. https://doi.org/10.5152/turkjnephrol.2020.4227 2. Enslow, B. T., Stockand, J. D., & Berman, J. M. (2019). liddle’s syndrome mechanisms, diagnosis and management. Integrated Blood Pressure Control, Volume 12, 13–22. https://doi.org/10.2147/ibpc.s188869 3. Kashif Nadeem, M., & Ling, C. (2012). Liddle’s-like syndrome in the elderly. The Journal of Clinical Hypertension, 14(10), 728–728. https://doi.org/10.1111/j.1751-7176.2012.00683.x 4. Sinada, N., & Bhimma, R. (2022). Liddle’s-Like Syndrome Associated With Nephrotic Syndrome in a Pediatric Patient. Journal of Pediatric Nephrology, 10(1), 39–46. https://doi.org/https://doi.org/10.22037/jpn.v10i1.36352 5. Yamaguchi, E., Yoshikawa, K., Nakaya, I., Kato, K., Miyasato, Y., Nakagawa, T., Kakizoe, Y., Mukoyama, M., & Soma, J. (2018). Liddle’s-like syndrome associated with nephrotic syndrome secondary to membranous nephropathy: The first case report. BMC Nephrology, 19(1). https://doi.org/10.1186/s12882-018-0916-3