Sjogren's Syndrome and Renal Tubular Acidosis

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 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. 

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.

• Severe electrolyte imbalance

• Proteinuria/hematuria

• Impaired renal function

• Suspicion of glomerular disease

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.