Hypokalemia leading to the diagnosis of primary Sjögren’s syndrome: the role of early renal biopsy

Abstract Background Hypokalemia due to distal renal tubular acidosis (dRTA) may represent the earliest manifestation of primary Sjögren’s syndrome (pSS), preceding the recognition of sicca symptoms. We report a case series highlighting the diagnostic challenges, renal manifestations, and clinical implications of renal biopsy in patients presenting with hypokalemia. Methods We retrospectively analyzed four female patients who presented with severe hypokalemia and normal anion gap metabolic acidosis secondary to dRTA, ultimately leading to the diagnosis of pSS. Clinical, biological, immunological, histopathological, therapeutic, and follow-up data were reviewed. One patient presented with concomitant rheumatoid arthritis, and one underwent renal biopsy despite preserved renal function. Results All patients exhibited inappropriate renal potassium wasting and hyperchloremic metabolic acidosis consistent with dRTA. Although sicca symptoms were present in all cases, they had initially been overlooked. Minor salivary gland biopsy demonstrated focal lymphocytic sialadenitis (Chisholm and Mason grades 3–4), while serological testing revealed high-titer anti-SSA and anti-SSB antibodies, fulfilling the 2016 ACR/EULAR classification criteria for pSS. Potassium and alkali supplementation corrected electrolyte disturbances in all patients. Corticosteroid therapy was initiated in every case, and rituximab was administered in one patient with aggressive dual nephropathy combining membranous nephropathy and tubulointerstitial nephritis, raising concern for lymphomatous transformation. Renal and clinical outcomes were favorable during long-term follow-up. Notably, early diagnostic renal biopsy despite preserved renal function in a patient, revealed active tubulointerstitial nephritis despite an apparently silent renal presentation. Conclusions Severe hypokalemia caused by dRTA may be the presenting feature of occult pSS and should prompt a systematic evaluation for autoimmune disease. Our findings emphasize the role of the kidney as an early indicator of systemic autoimmunity and suggest that renal biopsy may provide valuable diagnostic and therapeutic information even in selected patients with preserved renal function. These cases further expand the recognized renal spectrum of pSS by illustrating overlap syndromes and the rare coexistence of dual nephropathy.