Sjogren's Syndrome and Renal Tubular Acidosis

Primary Sjögren's syndrome (SS) is an autoimmune disease that primarily affects women in their peri-and postmenopausal years in the Caucasian population, but has an earlier onset in India and China. The disease is characterized by lymphocytic infiltration of exocrine glands and glandular dysfunction.  Sicca symptoms are hailed as the most common presenting feature of SS. especially  in the Caucasian population. Extraglandular features are reported in up to 60% of cases. Though it is a relatively common autoimmune disease, it is often underdiagnosed and misdiagnosed. 

Specifically, in the Indian scenario, most patients do not volunteer sicca symptoms. Further, systemic manifestations can precede sicca symptoms and be the presenting feature of the disease, resulting in diagnostic delay or misdiagnosis. Renal tubular acidosis (RTA) is a systemic feature of SS, more commonly reported in the Asian population, particularly Indians. Limited data suggests that patients with SS-RTA mostly present with hypokalemic paralysis, have a younger age at onset, and have a paucity of sicca symptoms. 

Further, data on the outcomes and treatment of SS-RTA is meager. RTA could have a wide range of manifestations, which could make diagnosis challenging. Early diagnosis is essential, as RTA could lead to CKD and other comorbidities. Further, there is a possibility of a window of opportunity where immunosuppression could reverse or halt disease progression in SS-RTA.

Clinical Characterization of Patients with Sjögren's syndrome-Renal Tubular Acidosis

This research initiative, under the aegis of the Sjögren's Syndrome Special Interest Group of the Indian Rheumatology Association, envisages the retrospective collection of  identity-stripped clinical and laboratory data of SS-RTA from different centers in India, which is expected to enhance understanding of clinical and laboratory features.

Join this Collaborative Initiative

To join this collaboration, clarifications and assistance, contact, Dr Pulukool Sandhya ,Email: 
Deadline for Filling in Proforma: June 30th, 2023

When to suspect tubular disease in Sjögren Syndrome? 

Renal tubular disease in SS can also be occult or present with symptoms such as life threatening hypokalemic paralysis, muscle weakness, cramps, renal stones, and pseudofractures. Timely detection can prevent complications. Hence, in every patient with SS, one needs to actively look for renal disease by doing a minimum of these tests: sodium, potassium, chloride, bicarbonate, creatinine( with calculation of eGFR), calcium, phosphate, urine pH, and urinalysis. Even if these tests are normal, in cases of suspicion, ultrasonography and arterial blood gas analysis need to be performed. If renal tubular acidosis (RTA) is suspected, for instance, in a patient with renal stones but normal blood pH the possibility of incomplete RTA needs to be considered. The diagnosis can be established by giving an additional oral acid load (0.1 mg/kg of ammonium chloride) or simultaneous furosemide (40 mg) and fludrocortisone (1 mg) and monitoring urine pH hourly. Failure to acidify urine (urine pH<5.3) is diagnostic of distal RTA.  


The following urinary testing is recommended in a patient with suspected tubular dysfunction in a patient with SS: a 24h urinary volume, proteinuria, glycosuria, creatininuria, calciuria, phosphaturia, citraturia, urinary sediment, and culture. Urinary tract infection with proteus species and other urea-splitting organisms should be excluded in those with high urine pH.

Potassium and Alkali supplementation in Renal Tubular Acidosis

Potassium supplementation must be done in severe hypokalemia prior to the initiation of alkali supplementation. Potassium replacement should follow standard guidelines for treating hypokalemia. Those with potassium <2.5 mEq/L or the presence of arrhythmias, marked muscle weakness, or rhabdomyolysis must be treated with intravenous potassium correction. The goal of alkali therapy is to normalize serum bicarbonate levels (22 to 24 mEq/L). Correction of chronic acidemia prevents the deleterious effect on bone and muscle and decreases stone formation. This can be done with sodium bicarbonate or potassium citrate. Citrate may be more preferred due to fewer gastric adverse effects, and potassium citrate is beneficial for those with stones and corrects hypokalemia as well. However, sodium bicarbonate is cheaper. Higher alkali dosing is required in the proximal RTA as compared to the distal RTA. Distal RTA generally requires alkali replacement of 1-3 mEq/kg/d, whereas 10-15 mEq/kg/d is required in proximal RTA. The total dose is split over 3–4 divided doses. The available preparations and dose equivalences for bicarbonate are listed below. 

1 g of sodium bicarbonate tablet is equal to 11.5 mEq of HCO3-

Potassium citrate solutions contain 1-2 mEq/mL of HCO3-

Shohl's solution contains sodium citrate-citric acid and contains 1 mEq/mL of HCO3-

The dose of alkali and potassium needs to be titrated based on weekly monitoring initially and less frequently once the levels are stabilized. In addition, phosphate and vitamin D supplementation may be required for those with bone disease. 

When to do a renal biopsy?

There is no consensus on the indication for renal biopsy in all pSS patients with abnormal electrolytes. Isolated mild electrolyte imbalances with normal eGFR and no proteinuria may be treated with correction of electrolytes along with  close monitoring of urinalysis and renal function tests. However, in all the scenarios below, a renal biopsy must be considered.

Treatment: Is there an indication for steroids?

In the absence of prospective or randomized trials, there are no clear recommendations on the management of kidney disease in SS. TIN is the most common pathophysiology underlying tubular disorders. However, it should be borne in mind that all TIN is not mild or benign. In most cases, features of chronicity such as interstitial fibrosis and tubular atrophy are seen. The insidious and silent progression of TIN can lead to CKD. Currently, it is unclear if there is a window of opportunity to identify and treat tubular dysfunction in SS, reverse electrolyte imbalance, and further prevent the occurrence of complications. Data from retrospective studies suggest that short courses of steroids (≥0.5 mg/kg) are useful in cases of TIN and could improve or stabilize eGFR even in the presence of interstitial fibrosis in the renal biopsy. Immunosuppressive agents (azathioprine, mycophenolate, cyclophosphamide, and rituximab) have been added upfront or if there is a relapse on steroid tapering. However, the addition of immunosuppressive agents, including rituximab, did not prove to have any added advantage in a large retrospective study. Unlike glomerulonephritis in lupus, the treatment effects are less dramatic, and it is unlikely that proteinuria and renal dysfunction will normalize completely due to the chronicity that has set in by the time the diagnosis is made.

Take home points


For complete publication, list visit the Publications section

Sandhya PUrine concentration defects in patients with Sjögren's syndrome and Renal Tubular Acidosis: Review of published case reportsMinerva Urology and Nephrology (2023) Accepted
Sandhya P, Akaishi T, Fujihara K, Aoki M. 

A novel association of osmotic demyelination in Sjögren's syndrome prompts revisiting role of aquaporins in CNS demyelinating diseases: A literature review. 

Mult Scler Relat Disord. 2022 Dec 11;69:104466. doi: 10.1016/j.msard.2022.104466.
Sandhya P. Comprehensive analysis of clinical and laboratory features of 440 published cases of Sjögren's syndrome and renal tubular acidosis. Int J Rheum Dis. 2022 Nov 2. doi: 10.1111/1756-185X.14483. Epub ahead of print. 
Sandhya P, Danda D, Rajaratnam S, Thomas N .Sjögren's, Renal Tubular Acidosis And Osteomalacia - An Asian Indian Series.Open Rheumatol J. 2014 Dec 19;8:103-9.
Sandhya P, Janardana R, Sudarsanam T, Mahasampath G, Prakash JAJ, Danda DDeterminants of diagnosis and disease course in primary Sjögren's syndrome: Results from datamining of electronic health records.Int J Rheum Dis. 2019