Hypocitraturia as a biomarker of renal tubular acidosis in patients with Sjögren's disease.

INTRODUCTION: Sjögren's disease (SD) is an immune-mediated chronic inflammatory disease that affects epithelial tissues, mainly salivary and lacrimal glands. It also presents extraglandular manifestations. The main renal manifestation is tubulointerstitial nephritis (TIN), which can manifest as renal tubular acidosis (RTA). Urinary citrate may be a biomarker of RTA in these patients. The objective of this study was to evaluate whether hypocitraturia is a predictive biomarker of RTA in a sample of patients with SD in a tertiary hospital in southern Brazil. METHODS: All patients with SD who met the inclusion criteria and who participated in the rheumatology outpatient clinic of the Irmandade Santa Casa de Misericórdia de Porto Alegre were included. Demographic, SD, serological and urinary data were obtained. RTA was considered in those patients who persistently presented urinary pH above 5.5 and serum pH below 7.35. Patients who persistently had urinary pH above 5.5 underwent a urinary acidification test with furosemide and fludrocortisone. These patients received 1 mg of fludrocortisone and 40 mg of furosemide and had their urine samples tested 2, 4 and 6 h after taking the medications. The test was stopped at any urine sample with pH 5.5 or less. The variables were expressed as mean and standard deviation or interquartile range. The association between hypocitraturia and RTA was assessed using the chi-square. RESULTS: Forty-two patients were included, 95.2% female with a median age of 61.73 years. The prevalence of complete distal RTA was 4.88%. Twenty-eight patients underwent urine acidification testing. Five patients had hypocitraturia, and two of them had complete distal RTA. The association between hypocitraturia and RTA was statistically significant (p < 0.012), with a sensitivity of 100%, specificity of 91.2% and accuracy of 91.7%. The negative predictive value was 100%. The global renal assessment of the population demonstrated two patients with RTA, one patient with decreased renal function and six patients with proteinuria greater than 0.5 g/24 h. CONCLUSION: The prevalence of RTA in the studied population was 4.88%. Hypocitraturia had high sensitivity and accuracy for the diagnosis of RTA.

Renal tubular acidosis as the initial presentation of Sjögren's syndrome.

We present a 44-year-old female with an initial presentation with distal renal tubular acidosis (RTA) after she presented with hypokalaemia and normal anion gap acidosis. Three years following the diagnosis, she presented with progressive renal impairment. In the absence of any clinical, biochemical and radiological clues, she underwent a renal biopsy which showed severe tubulitis secondary to lymphocytic infiltration. Serological investigations subsequently revealed positive anti-nuclear, anti-Sjögren's syndrome related antigen A (SS-A), and anti-Sjögren's syndrome related antigen B (SS-B) antibodies, supporting the diagnosis of Sjögren's syndrome. This case is unique in that distal RTA was the presenting clinical manifestation of Sjögren's syndrome. We hope that a consideration for Sjögren's syndrome is made in patients with seemingly idiopathic RTA.

Periodontitis, caries and salivary factors in Sjögren's syndrome patients compared to sex- and age-matched controls.

The aims of this investigation were: (i) to study a group of dry mouth Sjögren's syndrome (SS) patients comprising individuals with pathological and non-pathological amounts of rest saliva and (ii) to compare these two categories of SS patients with a sex- and age-matched control group with respect to their periodontal and dental status. Thirty-three dry mouth patients and 33 sex- and age-matched patients, referred to the same private dental clinic in southern Norway, were examined for rest and stimulated saliva, as well as their dental and periodontal status. All patients were referred to the local hospital for blood and urine examinations. The dry mouth SS patients were all of the secondary type. Volumes of rest and stimulated saliva were significantly lower in the low saliva SS group compared with the high saliva SS group; the values for immunoglobulin G (IgG) and IgA were similarly lower for the low saliva group, but not for IgM which was significantly higher. The two SS subgroups and their controls were compared for the volume of rest and stimulated saliva, which showed a statistically significant lower volumes for the low saliva SS group compared with the control group. None of the subgroups and their controls differed concerning filled or missing teeth, but the total SS group revealed significantly higher number of missing teeth. The periodontal and dental status did not show any statistically significant differences except for a few scattered higher periodontal level losses of attachment in the SS subgroups. The blood and urine analyses showed statistically significant higher values for sedimentation rate, white blood cell count and haemoglobin in the SS low saliva group compared with the control group while anti-streptolysin was lower. In the high saliva SS group only sedimentation rate and white cell count were higher compared with the control. The conclusions is SS patients do not have an increased risk for developing periodontitis.

Treatment with cytotoxic immunosuppression agents increases urinary excretion of JCV in patients with autoimmune disease.

Human JC virus is ubiquitous in human populations and is reactivated frequently in immunosuppressed patients. Fifty-one patients with autoimmune disease receiving immunomodulating therapy were evaluated to study the possible relationship between immunosuppression and JCV viruria. Patients were divided into cytotoxic and noncytotoxic treatment groups based on their prescription. The incidence of JCV viruria in the cytotoxic treatment group was significantly higher than that in the noncytotoxic group (67% vs. 28%; P < 0.05). Most patients with JCV viruria were receiving corticosteroid (P = 0.03 for any dose and P < 0.001 for higher-dose treatments) and cytotoxic agents (P = 0.02). Age, disease duration, and medication duration appeared not to be the precipitating factors of JCV viruria in this study. The results of clinical evaluation indicate that cytotoxic immunosuppression may play an important role in JC virus reactivation.

Risk factors of calcium stone formation in patients with primary Sjögren's syndrome.

Distal renal tubular acidosis (dRTA), which occurs in patients with primary Sjögren's syndrome (SS), is a risk factor for the development of urolithiasis. Twenty-seven patients with SS were evaluated with respect to biochemical risk factors of calcium stone formation. Sixteen had no history of urolithiasis (group 1) whereas 11 had such a history (group 2). The stone composition was known for seven of the patients, and calcium phosphate was the major stone constituent in all of them. dRTA was present in all patients in group 2, and in 7 of the 16 patients in group 1. Hypocitraturia was common in both groups, and the urinary excretion of citrate did not differ between the two groups. There was a higher urinary excretion of calcium and urate in group 2 and this group also had a higher urine volume. The risk of forming a urine supersaturated with calcium oxalate (CaOx) expressed in terms of AP(CaOx)index(s), which is an approximate estimate of the ion-activity product of CaOx calculated for a 24-h urine volume of 1500 ml, was higher in stone formers. A similarly derived estimate of the ion-activity product of calcium phosphate, AP(CaP)index(s), was calculated for a urine pH of 7. Although AP(CaP)index(s) was not significantly higher in group 2, there was a good correlation between AP(CaP)index(s) and AP(CaOx)index(s). We conclude that the urine composition in patients with SS, dRTA and urolithiasis is similar to that of other stone-forming patients with dRTA, and recurrence preventive therapy can be designed as for these patients.

Sjögren's syndrome in one of two sisters with idiopathic renal hypouricemia.

Concomitance of idiopathic hypouricemia and Sjögren's syndrome is reported. A 37-year-old Japanese woman with Sjögren's syndrome and her 39-year-old sister without this syndrome both had extremely low levels of serum uric acid. Markedly increased urinary excretion of uric acid and poor response to the pyrazinamide suppression test revealed that the hypouricemia in these sisters was caused by a defect in the pre-secretory reabsorption of uric acid. It is categorized as idiopathic renal hypouricemia than hypouricemia rather secondary to Sjögren's syndrome. Thus, idiopathic renal hypouricemia should be considered even in cases with autoimmune diseases.

Increased incidence of urinary tract infection in patients with rheumatoid arthritis and secondary Sjögren's syndrome.

The incidence of lower urinary tract infection in 120 women with rheumatoid arthritis and secondary Sjögren's syndrome was evaluated retrospectively. Thirty one patients (26%) had secondary Sjögren's syndrome. Recurrent urinary tract infection was significantly more common in these patients (11/31) than in patients without Sjögren's syndrome (4/89). Habitual leucocyturia was also more common in patients with secondary Sjögren's syndrome (18/31) than in patients with rheumatoid arthritis without Sjögren's syndrome (8/89). Of seven patients with vaginal sicca symptoms, six had recurrent urinary tract infection. Urinary 24 hour mucopolysaccharide excretion in 20 patients with Sjögren's syndrome was similar to the excretion in 10 patients without Sjögren's syndrome. These results show that recurrent urinary tract infection is significantly more common in women with rheumatoid arthritis and secondary Sjögren's syndrome. A local deficit in protective urinary mucosal secretion or other immune mechanisms may be responsible for this susceptibility.

Renal tubular dysfunction in primary Sjögren's syndrome: clinical studies in 27 patients.

Kidney involvement in Sjögren's syndrome (SS) including renal tubular disorders are well recognized but little is known about frequency and extent of such dysfunction in the general population of patients with primary SS, due to a lack of group studies. We studied 27 patients with primary SS and without other possible causes of tubular dysfunction. Increased urinary beta 2M excretion, due to proximal tubular dysfunction, was present in 26% of patients. Inadequate urine acidification after oral NH4 Cl, proving distal tubular dysfunction, was found in 12% of the patients studied. Concentrating ability, tested by thirst, was decreased in 44% of patients studied. Abnormal renal tubular tests correlated with presence of ANA (p = 0.05) but not with other clinical parameters. In conclusion demonstrable renal tubular dysfunctions occur in over half the patients with primary SS. Literature concerning this subject is discussed.

Urinary monoclonal free light chains in primary Sjögren's syndrome: an aid to the diagnosis of malignant lymphoma.

Three patients, two with typical primary Sjögren's syndrome (SS) and the third with several features of SS, including abnormal sialography and reduced tear secretion, developed B cell non-Hodgkin's lymphoma (NHL) of parotid or lung, or both. Isoelectric focusing of concentrated urine specimens in agarose, followed by immunofixation, demonstrated the presence in each patient's urine of monoclonal free light chains of the same class as that shown on the tumour cells. In one patient the level of urinary free light chains was monitored and found to correlate with disease activity. Similar techniques showed no monoclonal light chains in the urine from a further 26 cases of SS with no clinical evidence of lymphoma. The detection of monoclonal urinary free light chains may provide an early diagnostic clue to the development of lymphoma in patients with SS and be a means of tumour monitoring.

Demonstration and identification of monoclonal proteins in the urine of patients with Sjögren's syndrome.

Fresh sera and concentrated urine from 17 patients with primary Sjögren's syndrome (SS) were fractionated by high-resolution agarose electrophoresis to investigate the presence of monoclonal immunoglobulins or their components. Homogeneous protein bands were found in the gamma-globulin region in 47% of serum samples and 76% of urine specimens of all patients tested. These monoclonal proteins were detected more often in patients with extraglandular SS (77% in serum, 100% in the urine) than in patients with glandular SS (14% in serum, 43% in the urine). Immunofixation electrophoresis showed that the majority of these monoclonal proteins were free kappa or lambda light chains. Fractionation of unconcentrated parotid salivas from five SS patients failed to reveal the presence of monoclonal light chains or immunoglobulins. The present findings further substantiate our previous observation that a monoclonal process coexists with the polyclonal activation in SS patients.