Venus, Sjogren's and the Kidney

The Williams sisters put yet another Wimbledon doubles tittle into their trophy case over the weekend.  This, just hours after Serena had won the singles competition.  Pretty impressive.

In reading the coverage I learned that during the last year Venus had been diagnosed with Sjogren's syndrome (I know, I know, old news to those paying attention).  There was no mention in any of the reports that Venus has had any kidney problems, her main issues have apparently been with severe fatigue and joint pains.  Although we usually think of dryness in the eyes and mouth when we hear Sjogren's syndrome there are a number of potential renal tip offs to the diagnosis...

Interstitial (and sometimes glomerular) Disease

Interstitial nephritis - Typically mild but can progress to ESRD in rare cases.  In a Mayo Clinic case series 46% and 25% of patients with Sjogren's syndrome who underwent kidney biopsy had chronic or acute interstitial nephritis respectively.  Only one of the 24 patients biopsied had ESRD and this was from a total case series of 7276 patients (there may have been some additional cases of ESRD lurking in the cohort who didn't get biopsied as they didn't have complete clinical data on all the patients).

Glomerular disease - Less common than interstitial disease but does occur. Associations with MPGN (often in association with cryglobulins), FSGS, Membranous and minimal change have all been reported. 

Tubular defects

Distal renal tubular acidosis - An unexplained distal RTA is a invitation to investigate for Sjogren's.  Patients with distal RTAs are prone to nephrolithiasis (typically calcium phosphate stones) and nephrocalcinosis.  Severe associated hypokalemia can also occur with flaccid paralysis having been described as a presenting symptom.

Although the cause of distal RTAs in most patients with Sjogren's syndrome is unknown a few patients have been described who have an absence of the H-ATPase pump on intercalated cells in the collecting duct.  Another hypothesis is that Sjogren's leads to autoantibodies directed against carbonic anhydrase II thus leading to the generation of less protons for excretion.

Proximal RTA and full blown Fanconi's syndrome have also been described.

Nephrogenic diabetes insipidus - Urinary concentrating defects are not uncommon in patients with Sjogren's.  As an example, in an Italian series 21% of patients were noted to have an abnormal urinary concentrating ability.  The cause of this tubular defect is again unknown but histologically clusters of lymphocytic infiltrate can sometimes be seen around collecting ducts which could theoretically interfere with the actions of ADH.

Hypokalemia - This can occur in the absence of RTA and is thought to be due to tubular damage induced sodium wasting with subsequent increased distal sodium delivery.  In the distal nephron increased sodium delivery drives potassium loss in exchange for sodium.  This effect may be amplified by volume depletion with subsequent increased aldosterone levels which again drive sodium absorption and potassium loss.