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Journal of Internal Medicine 1996 ; 239 : 483–488 Urolithiasis and distal renal tubular acidosis preceding primary Sjo $ gren’s syndrome : a retrospective study 5–53 years after the presentation of urolithiasis PER ERIKSSON,* TORSTEN DENNEBERG,SVERKER ENESTRO > M,BJO > RN JOHANSSON,FOLKE LINDSTRO > M§ & THOMAS SKOGH§ From the *Department of Internal Medicine, Jo X nko X ping Hospital, Jo X nko X ping ; and the Departments of Nephrology and Urology, Pathology, §Ophthalmology, and Rheumatology, University Hospital, Linko X ping, Sweden Abstract. Eriksson P, Denneberg T, Enestro $ m S, Johansson B, Lindstro $ m F, Skogh T (Jo $ nko $ ping Hospital and University Hospital Linko $ ping, Sweden). Urolithiasis and distal renal tubular acidosis preceding primary Sjo $ gren’s syndrome : a retrospective study 5–53 years after the presentation of urolithiasis. J Intern Med 1996 ; 239 : 483–8. Objectives. Distal renal tubular acidosis (dRTA) can be associated with autoimmune diseases such as primary Sjo $ gren’s syndrome (SS). Our objective was to study SS-associated symptoms, autoantibodies and renal histopathology in patients with urolithiasis and dRTA. Setting. The patients were from the Departments of Nephrology and Rheumatology, University Hospital of Linko $ ping, which is a tertiary referral hospital, as well as a secondary referral centre for the immediate area around the city of Linko $ ping. Subjects. Ten female patients with dRTA, who presented with urolithiasis and not with subjective sicca symptoms, were from the Department of Neph- rology, University Hospital, Linko $ ping. Autoanti- bodies were detected in eight of these patients, and Introduction Distal renal tubular acidosis (dRTA) is characterized by an inability to lower urine pH despite spontaneous or ammonium-chloride-induced metabolic acidosis. dRTA is frequently associated with urolithiasis [1]. dRTA can be hereditary or acquired [2], and the latter can be associated with autoimmune disease, hypercalcaemia and different types of tubulointer- stitial renal disease [3]. Primary Sjo $ gren’s syndrome they were studied with respect to clinical and laboratory evidence of SS (urolithiasis group). Fifteen women with SS, who presented with sicca symptoms and not with urolithiasis or dRTA, served as the reference group. Results. In the urolithiasis group, all of the eight patients had anti-SS-A antibodies, and SS (or possible SS) developed in seven of the eight patients 1–48 (mean 15) years after the onset of urolithiasis. Histological features of tubulointerstitial nephritis were found in four of five biopsied patients in the urolithiasis group, and in two of four patients (with dRTA) in the reference group. Conclusions. Urolithiasis and dRTA can precede subjective sicca symptoms, and patients with dRTA may have SS in the absence of subjective sicca symptoms. Anti-SS-A antibodies are common in patients with urolithiasis and dRTA. Therefore, we hypothesize the possibility of a Sjo $ gren-related renal disease in these patients. Keywords : primary Sjo $ gren’s syndrome, renal tubular acidosis, urolithiasis. (SS), SLE, hypergammaglobulinaemic purpura, rheumatoid arthritis, and autoimmune diseases of the liver and the thyroid gland are some of the diseases reported in association with dRTA [1, 3–5]. Sjo $ gren’s syndrome is an autoimmune disease characterized by xerostomia and keratoconjunctivitis sicca. Autoantibodies, including rheumatoid factor, anti-nuclear antibodies (ANA), anti-SS-A and anti- SS-B antibodies are often present [6]. dRTA has been reported in 15–50% of patients with SS, where it is # 1996 Blackwell Science Ltd 483

Urolithiasis and distal renal tubular acidosis preceding primary Sjögren's syndrome: a retrospective study 5–53 years after the presentation of urolithiasis

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Journal of Internal Medicine 1996; 239 : 483–488

Urolithiasis and distal renal tubular acidosis preceding

primary Sjo$ gren’s syndrome: a retrospective study 5–53

years after the presentation of urolithiasis

PER ERIKSSON,* TORSTEN DENNEBERG,† SVERKER ENESTRO> M,‡ BJO> RN JOHANSSON,¶

FOLKE LINDSTRO> M§ & THOMAS SKOGH§From the *Department of Internal Medicine, JoX nkoX ping Hospital, JoX nkoX ping ; and the Departments of †Nephrology and Urology, ‡Pathology,

§Ophthalmology, and ¶Rheumatology, University Hospital, LinkoX ping, Sweden

Abstract. Eriksson P, Denneberg T, Enestro$ m S,

Johansson B, Lindstro$ m F, Skogh T (Jo$ nko$ ping

Hospital and University Hospital Linko$ ping, Sweden).

Urolithiasis and distal renal tubular acidosis

preceding primary Sjo$ gren’s syndrome: a

retrospective study 5–53 years after the presentation

of urolithiasis. J Intern Med 1996; 239 : 483–8.

Objectives. Distal renal tubular acidosis (dRTA) can

be associated with autoimmune diseases such as

primary Sjo$ gren’s syndrome (SS). Our objective was

to study SS-associated symptoms, autoantibodies and

renal histopathology in patients with urolithiasis and

dRTA.

Setting. The patients were from the Departments of

Nephrology and Rheumatology, University Hospital

of Linko$ ping, which is a tertiary referral hospital, as

well as a secondary referral centre for the immediate

area around the city of Linko$ ping.

Subjects. Ten female patients with dRTA, who

presented with urolithiasis and not with subjective

sicca symptoms, were from the Department of Neph-

rology, University Hospital, Linko$ ping. Autoanti-

bodies were detected in eight of these patients, and

Introduction

Distal renal tubular acidosis (dRTA) is characterized

by an inability to lower urine pH despite spontaneous

or ammonium-chloride-induced metabolic acidosis.

dRTA is frequently associated with urolithiasis [1].

dRTA can be hereditary or acquired [2], and the

latter can be associated with autoimmune disease,

hypercalcaemia and different types of tubulointer-

stitial renal disease [3]. Primary Sjo$ gren’s syndrome

they were studied with respect to clinical and

laboratory evidence of SS (urolithiasis group). Fifteen

women with SS, who presented with sicca symptoms

and not with urolithiasis or dRTA, served as the

reference group.

Results. In the urolithiasis group, all of the eight

patients had anti-SS-A antibodies, and SS (or possible

SS) developed in seven of the eight patients 1–48

(mean 15) years after the onset of urolithiasis.

Histological features of tubulointerstitial nephritis

were found in four of five biopsied patients in the

urolithiasis group, and in two of four patients (with

dRTA) in the reference group.

Conclusions. Urolithiasis and dRTA can precede

subjective sicca symptoms, and patients with dRTA

may have SS in the absence of subjective sicca

symptoms. Anti-SS-A antibodies are common in

patients with urolithiasis and dRTA. Therefore, we

hypothesize the possibility of a Sjo$ gren-related renal

disease in these patients.

Keywords : primary Sjo$ gren’s syndrome, renal

tubular acidosis, urolithiasis.

(SS), SLE, hypergammaglobulinaemic purpura,

rheumatoid arthritis, and autoimmune diseases of

the liver and the thyroid gland are some of the

diseases reported in association with dRTA [1, 3–5].

Sjo$ gren’s syndrome is an autoimmune disease

characterized by xerostomia and keratoconjunctivitis

sicca. Autoantibodies, including rheumatoid factor,

anti-nuclear antibodies (ANA), anti-SS-A and anti-

SS-B antibodies are often present [6]. dRTA has been

reported in 15–50% of patients with SS, where it is

# 1996 Blackwell Science Ltd 483

484 P. ERIKSSON et al.

often associated with tubulointerstitial nephritis

(TIN) [7]. We have recently reported reduced glom-

erular filtration rate in 33% of 27 SS patients as well

as signs of distal and proximal tubular dysfunction

[8, 9]. A common finding in these patients was

hypocitraturia and}or dRTA, and the determination

of urinary excretion of citrate was found to be a

useful indicator of renal disease in SS [8].

In an abstract from 1990, Gobert et al. reported

three patients with urolithiasis, dRTA, absence of

subjective symptoms from eyes or mouth but with

objective signs of SS [10]. We wanted to extend these

observations to a larger number of dRTA}urolithiasis

patients. Our objective was to study SS-associated

symptoms, autoantibodies and renal histopathology

in a group of patients with urolithiasis and dRTA,

who presented with urolithiasis without sicca symp-

toms. For comparison, we used a reference group of

SS patients without urolithiasis or known dRTA

when they presented with sicca symptoms.

Patients and methods

In the area around Linko$ ping, patients with uroli-

thiasis are referred to and subsequently seen regu-

larly by the Department of Urology, University

Hospital of Linko$ ping, and only selected patients are

referred to the Department of Nephrology. All 10

patients with dRTA and without spontaneously

reporting sicca symptoms at the presentation of

urolithiasis, who were followed regularly for 1–23

years (mean 10±4 years) by the Department of

Nephrology, were studied after informed consent.

Two of ten patients had no detectable autoantibodies ;

they were diagnosed as having Cushing’s syndrome

(case no. 4), and hereditary dRTA (case no. 1). These

two patients were not further evaluated.

Urolithiasis group

Various autoantibodies were detected in eight female

patients, and these patients constitute the urolithiasis

group. Ages at the time of the present study ranged

from 32 to 79 (mean 53±1) years, and Fig. 1 shows

the ages for seven of the eight patients. Urolithiasis

(any calcifications in the urinary tract) was radio-

graphically demonstrated in all patients, and nephro-

calcinosis (renal parenchymatous calcifications) was

found in two patients (case nos 2 and 3) when seen

*

Fig. 1 The figure shows the age at the study, and at the

presentation of urolithiasis and sicca symptoms, of the seven

patients who developed SS or possible SS in the urolithiasis

group. dRTA was diagnosed 1–48 (median 8) years after the

presentation of urolithiasis. (* Possible SS). D, Age at first

urolithiasis ; *, age at first sicca; ^, age at study.

at the first time with urolithiasis. dRTA was in-

complete in six patients and complete in two patients,

and it was diagnosed 1–48 (median 8) years after the

presentation of urolithiasis.

Reference groups

All 20 patients who first presented with sicca

symptoms and not with urolithiasis or dRTA, and

who were followed at the Department of Rheu-

matology, were asked to participate. Five patients

declined, and the remaining 15 female SS patients

served as reference patients after their informed

consent was obtained. Excretion urography or plain

films of the urinary tract were performed in all

reference patients. Urolithiasis could not be demon-

strated in any of them, but one woman had

experienced one single episode of stone passage after

the presentation of sicca symptoms. All 15 patients

were evaluated with respect to dRTA, which was

diagnosed in seven of them (six with incomplete

dRTA and one with complete dRTA). These seven

patients constituted reference group A, and the eight

patients without dRTA constituted reference group

B. Ages ranged from 44 to 78 (mean 64±6) years.

Seven of the patients in the urolithiasis group and

all patients in the reference groups belong to a group

of 27 patients in whom renal functions have been

studied and reported previously [8, 9]. The time at

which subjective sicca symptoms from the eyes or

mouth presented, a well as the time of the first

# 1996 Blackwell Science Ltd Journal of Internal Medicine 239 : 483–488

UROLITHIASIS–SJO> GREN’S SYNDROME 485

urolithiasis, was judged from information in the

patient records of the Departments of Nephrology

and Rheumathology, and by interviewing the

patients with a standardized questionnaire.

The classification criteria described by Daniels &

Talal [11] were used, because these criteria differ

between definite SS and possible SS. Kerato-

conjunctivitis siccas was established by a positive

Rose–Bengal staining and Schirmer test !5 mm per

5 min or reduced tear meniscus and reduced tear

film break-up time (BUT) %10 s. The oral component

of the syndrome was confirmed by labial salivary

gland biopsy demonstrating focal sialoadenitis with a

focus score above 1. Biopsy was carried out only in

patients with sialometry showing reduced, whole

unstimulated saliva (!1±5 mL 15 min−"). A diag-

nosis of possible SS was established if only the oral or

ocular component was confirmed, and if auto-

antibodies, hypergammaglobulinemia, or interstitial

nephritis}dRTA was demonstrated.

Renal acidification capacity

Complete dRTA was diagnosed in patients with

metabolic acidosis (blood base excess below

®6 mmol L−" in at least two different specimens) and

a urine pH above 5±5. An oral ammonium chloride

loading test was performed in all patients with a

urine pH above 5±5 if complete dRTA was absent

[12, 13]. Incomplete dRTA was diagnosed if urine

pH did not decrease below 5±5 during ammonium

chloride loading.

Kidney biopsy

A kidney biopsy was done after informed consent. It

was performed in patients with reduced glomerular

filtration rate (GFR) and}or tubular defects including

dRTA. The histopathological examinations, which

were performed by the same kidney pathologist

(S.E.), included immunohistochemistry for detection

of deposits of immunoglobulins (IgG, IgM, IgA),

complement factors (C3, C1q) and fibrinogen. 1–2

µm sections for light microscopy were stained

according to the periodic acid-Schiff and periodic acid-

silver methenamine methods. The nephron, vessels

and the interstitium were analysed for inflammatory,

atrophic, fibrotic and atherosclerotic lesions. The

diagnosis of chronic TIN was based on the presence

of mononuclear interstitial inflammation and varying

degrees of interstitial fibrosis and tubular atrophy in

the absence of atherosclerotic lesions.

Other tests

Serum levels of total IgG were measured by a

nephelometric method (normal range: 7±0–

15±0 g L−"). Antinuclear antibodies (ANA), anti-

mitochondrial antibodies (AMA), and anti-smooth

muscle antibodies (SMA) of IgG class were analysed

by indirect immunofluoroscence (IIF) microscopy

using unfixed cryostat sections of rat tissues (liver,

kidney and stomach) as antigen substrates [14]. Sera

containing ANA were further analysed by IIF mi-

croscopy for the presence of antibodies against

double-stranded (ds) DNA using Chritidia luciliae as

antigen substrate (Sci MedX, Denville, NJ, USA).

Anti-SS-A and anti-SS-B antibodies were detected by

means of double radial immunodiffusion (Immuno-

concepts, Sacramento, CA, USA). Anti-thyroid micro-

somal antibodies of IgG class were analysed by IIF

microscopy using acetone-fixed cryostat sections of

human thyroid, and anti-thyroglobulin antibodies

were detected by passive haemagglutination (Murex

Diagnostics Ltd, Dartford, UK). Rheumatoid factor

(RF) was determined by a latex bead agglutination

method (Roche, Basel, Switzerland). Anti-cardiolipin

antibodies of IgG class were analysed by enzyme-

linked immunosorbent assay (ELISA) [15]. Auto-

antibody tests were considered positive at titres of &1:100 for ANA, SMA, AMA, and antibodies against

cytoplasmatic thyroid antigens, and at titres of

&1:10 for anti-dsDNA antibodies and antibodies

against thyroglobulin. RF was considered positive at

values &30 WHO units, and anti-cardiolipin anti-

bodies at values "3 units. Anti-SS-A}SS-B were

considered positive when undiluted patient serum

caused precipitation of the antigens.

Statistics

Fischer’s exact test was used for comparison of

frequencies, and Student’s t-test was used for com-

parison of serum IgG in the two groups (computer

program: StatView 4.0).

Results

Eight of 10 patients with dRTA had different autoanti-

bodies, and these eight patients constituted the

# 1996 Blackwell Science Ltd Journal of Internal Medicine 239 : 483–488

486 P. ERIKSSON et al.

Table 1 Results of anti-SS-A, anti-SS-B, ANA, ocular and oral tests in the urolithiasis group. Diagnosis according to Daniels–Talal

criteria is also noted

Break-up

Schirmer time

Unstimulated Focus right}left right}left SS

Case no. Anti-SS-A Anti-SS-B ANA saliva (mL}15 min) score Rose-Bengal (mm}5 min) (s) (Daniels–Talal)

2 ­ ® ® 0±0 0 ® 21}16 15}18 No

3 ­ ­ ® 0±0 4±0 ­ 4}3 10}10 Yes

5 ­ ® ® 0±6 2±4 ­ 8}7 "20}20* Yes

6 ­ ­ ­ 0±0 3 ­ 4}3 "20}20 Yes

7 ­ ­ ­ 0±9 7±6 ­ 10}17 "15}"15 Possible

8 ­ ­ ­ 0±0 10±0 ­ 7}4 5–10}5–10* Yes

9 ­ ­ ® 0±0 4±0 ­ 1}3 "15}"15 Yes

10 ­ ® ­ 0±3 2±3 ­ 3}8 5–10}5–10 Yes

­ Pathological ; ® normal or negative.

* Reduced tear meniscus.

urolithiasis group. Anti-SS-A antibodies were detec-

ted in eight patients, anti-SS-B antibodies in five

patients, antinuclear antibodies (ANA) in four

patients, rheumatoid factor in seven patients, anti-

bodies to cytoplasmatic thyroid antigen in one

patient, anti-thyroglobulin in two patients, and anti-

cardiolipin in two patients. Mean value (SD) of serum

IgG was 23±3 (11±8) g L−".

In the urolithiasis group, most patients showed

evidence of xerostomia and keratoconjunctivitis

sicca, with unstimulated saliva less than

0±1 mL min−" in 8}8, salivary gland biopsy focus

score above 1 in 7}8, Rose–Bengal staining of the

eyes positive in 7}8, Schirmer test 5 mm per 5 min

or less in 5}8, and reduced break-up time or tear

meniscus in 4}8 (Table 1).

Six of 10 dRTA-patients had definite SS and one

patient (case no. 7) had possible SS according to the

criteria of Daniels & Talal [11]. Case no. 5 had no

subjective sicca symptoms, but oral and ocular tests

confirmed SS. Case no. 2 had anti-SS-A antibodies

but the criteria of SS were not fulfilled. No one had

secondary Sjo$ gren’s syndrome.

As shown in Fig. 1, subjective sicca symptoms

developed 1–48 (mean 15) years after the first kidney

stone.

Comparison between the urolithiasis group and the

reference groups

Subjective oral sicca symptoms were significantly

more common in the reference groups than in the

urolithiasis group (15}15 vs. 5}8; P¯0±03). In

other respects there were no statistical differences

between the urolithiasis group and the reference

groups with regard to the frequencies of symptoms

and signs associated with SS (ocular sicca symptoms,

leucopenia, parotid swelling, hypothyroidism, epi-

sodic purpura, arthralgia), or the occurrence of

autoantibodies (ANA, anti-dsDNA, anti-SS-A, anti-

SS-B, SMA, AMA, anti-cytoplasmatic thyroid anti-

gen, anti-thyroglobulin, anti-cardiolipin, RF) or the

mean levels of serum IgG. A higher frequency of

family history of urolithiasis was noted in the

urolithiasis group (6}8 vs. 3}15; P¯0±02).

Kidney biopsies were performed in five patients in

the urolithiasis group, and in four patients with a

recently diagnosed dRTA}decreased GFR in reference

group A. Infiltrates of lymphocytes and plasma cells

were found in 5}5 in the urolithiasis group and in

3}4 in reference group A. Interstitial fibrosis and

tubular atrophy were slightly more frequent in the

urolithiasis group.

Immunohistochemistry revealed sparse glomeru-

lar deposits of immunoglobulins (IgG, IgA or IgM)

and complement (C3 and}or C1q) in 2}5 of the

biopsies in the urolithiasis group and in 2}4 of the

biopsies in reference group A. Cell proliferation in the

glomeruli was not seen in any group and only few

glomeruli were sclerotic. Thus, the histopathological

findings were similar in both groups and consistent

with different degrees of chronic TIN in 4}5 patients

in the urolithiasis group and in 2}4 patients in

reference group A. Histopathological findings con-

sistent with nephrosclerosis were found in the fifth

patient in the urolithiasis group, and normal histo-

pathological findings were recorded in two patients

in reference group A.

# 1996 Blackwell Science Ltd Journal of Internal Medicine 239 : 483–488

UROLITHIASIS–SJO> GREN’S SYNDROME 487

Discussion

Distal renal tubular acidosis (dRTA) is sometimes

associated with primary Sjo$ gren’s syndrome [1]. We

have recently studied dRTA in 27 SS patients [8], but

in the present study the problem was approached

from a different perspective : 10 patients with uro-

lithiasis and dRTA but without subjective symptoms

of SS at the time of the first urolithiasis were

investigated. During the study period, a diagnosis of

SS or possible SS was established in 7}10 dRTA

patients. In three other reports on dRTA patients

with 44, 48 and 87 patients studied, the pathogenesis

of dRTA was judged as immune-related in 25, 23

and 39%, respectively [1, 16, 17]. Our material is

smaller but the results agree with these reports in

which immune-related dRTA was the commonest

form of dRTA seen in adults.

We found that subjective sicca symptoms presented

1–48 (mean 15) years after the first episode of

urolithiasis. Renal disease preceding the onset of

classical manifestations of SS has also been reported

by Tu et al. [18] and by Moutsopoulos et al. [19].

Objective ocular and oral tests during the period

when the patients were followed would possibly have

shown signs of Sjo$ gren’s syndrome earlier. This is

illustrated by case no. 5, who had no subjective sicca

symptoms, but SS was diagnosed according to the

Daniels–Talal criteria [11]. At least six similar

patients with dRTA and objective signs of SS, but

without subjective sicca symptoms, have been re-

ported previously [10, 20, 21]. Thus, SS can be

diagnosed in dRTA patients even in the absence of

subjective sicca symptoms. In our study, anti-SS-A

antibodies were present in eight of 10 patients with

urolithiasis and dRTA, one of which (case no. 2) did

not fulfil the SS criteria. Anti-SS-A is unusual in a

normal population [22, 23].

ANA was found in found in four patients in the

urolithiasis group, but in no instance were anti-DNA

antibodies recorded and none of the patients fulfilled

the criteria for having SLE. Also, in contrast to SS,

isolated TIN in uncommon in SLE [24].

Are there any differences between the urolithiasis

group and the reference groups of SS patients? To

look for possible differences between the two groups,

clinical and laboratory features, as well as renal

histopathology, were compared.

Except for the occurrence of oral sicca symptoms,

the frequencies of various autoantibodies and SS-

related symptoms, as well as serum levels of IgG,

were similar in the groups. The data of renal

histopathology show that chronic TIN was present

in four of five patients in the urolithiasis group and in

two of four SS patients in reference group A. Renal

histopathological findings have previously been re-

ported in dRTA patients without sicca symptoms.

Feest et al. reported that interstitial lymphocyte

infiltration and fibrosis consistent with chronic TIN

were common findings both in dRTA patients with,

and in those without immunological abnormalities

[25]. Similar results have been reported by others

[20, 21, 26]. In patients with sicca symptoms and

dRTA due to SS, a few reports of renal histo-

pathological findings exist : chronic TIN was present

in most cases [18, 27–29]. Thus, the histopatho-

logical findings seem to be similar in patients

presenting with urolithiasis}dRTA and in those

presenting with subjective sicca symptoms, and later

developing dRTA.

In summary in this study, features of SS and}or

presence of anti-SS-A antibodies were common in a

group of female patients with urolithiasis and dRTA;

we also found that dRTA and urolithiasis can precede

subjective sicca symptoms, and that patients with

dRTA may have SS in the absence of subjective sicca

symptoms. Except for oral sicca symptoms and a

family history of urolithiasis there were no clinical

differences between the urolithiasis group and the

reference groups of SS patients. We hypothesize the

possibility of a Sjo$ gren-related renal disease, charac-

terized by urolithiasis and}or dRTA and antibodies to

SS-A, whether subjective sicca symptoms are pre-

sent or not. Further investigation will be needed to

prove whether the renal disease precedes SS, or

whether it is related to subclinical SS with auto-

antibodies but without subjective or objective sicca

symptoms.

Testing for anti-SS-A is a valuable tool in the

diagnosis of SS in patients with urolithiasis and

dRTA. Patients with anti-SS-A antibodies should be

tested further for keratoconjunctivitis sicca and}or

xerostomia, even in the absence of subjective sicca

symptoms. At present, SS cannot be cured, but it

seems important to establish a correct diagnosis, as

other manifestations of SS such as vitamin B"#

deficiency [30] and thyroid hypofunction secondary

to autoimmune thyroiditis [31] can be effectively

treated.

# 1996 Blackwell Science Ltd Journal of Internal Medicine 239 : 483–488

488 P. ERIKSSON et al.

Acknowledgements

This work was supported by Grants from the County

Council of O> stergo$ tland, the University Hospital,

Linko$ ping and the Faculty of Health Science, Uni-

versity of Linko$ ping, Sweden.

The authors wish to thank medical student Peter

Christakos, College of Medicine, University of

Vermont, for correcting to the language in the

manuscript.

References

1 Caruana RJ, Buckalew VM. The syndrome of distal (type 1)

renal tubular acidosis. Medicine 1988; 67 : 84–99.

2 Buckalew VM. Calcium nephrolithiasis and renal tubular

acidosis. In : Coe FL, Favus MJ, eds. Disorders of Bone and

Mineral Metabolism, 1st edn. New York: Raven Press, 1992;

729–56.

3 Wrong OM, Feest TG. The natural history of distal renal

tubular acidosis. Contrib Nephrol 1980; 21 : 137–44.

4 Mason AMS, Golding PL. Hyperglobulinemic renal tubular

acidosis : a report of nine cases. Br Med J 1970; 3 : 143–6.

5 McCurdy DK, Cornwell GG, DePratti VJ. Hyperglobulinemic

renal tubular acidosis. Ann Intern Med 1967; 67 : 110–17.

6 Hansen B, Manthorpe R. Antibodies against SS-B}La and SS-

A}Ro antigens in patients with primary Sjo$ gren’s syndrome.

Scand J Rheumatol 1986; Suppl. 61: 93–7.

7 Winer RL. Sjo$ gren’s syndrome. In: Grishman E, Churg J,

Needle MA, Venkataseshan VS, eds. The Kidney in Collagen

Vascular Diseases. New York: Raven Press, 1993, 179–87.

8 Eriksson P, Denneberg T, Larsson L, Lindstro$ m F. Biochemical

markers of renal disease in Primary Sjo$ grens’s syndrome.

Scand J Urol Nephrol 1994 (in press).

9 Eriksson P, Denneberg T, Granerus G, Lindstro$ m F. Glomerular

filtration rate in Primary Sjo$ gren’s Syndrome with renal

disease. Scand J Urol Nephrol 1995; 29 : 383–92.

10 Gobert P, Vanhille Ph, Mougenot B, Lemaı# re V, Fleury D.

Nephrolithiasis revealing Sjo$ gren’s syndrome. Kidney Int

1990; 38 : 1237–8.

11 Daniels TE, Talal N. Diagnosis and differential diagnosis in

Sjo$ gren’s syndrome. In: Talal N, Moutsopoulos HM, Kassan

SS, eds. SjoX gren’s Syndrome : Clinical and Immunological Aspects.

Berlin : Springer Verlag, 1987; 193–9.

12 Backman U, Danielsson BG, Sothell M. A short duration renal

acidification test. Scand J Urol Nephrol 1976; Suppl. 35:

33–48.

13 Backman U, Danielsson BG, Johansson G, Ljunghall S,

Wikstro$ m S. Incidence and clinical importance of renal tubular

defects in recurrent renal stone formers. Nephron 1980; 25 :

96–101.

14 Vrethem M, Skogh T, Berlin G, Ernerudh J. Autoantibodies

versus clinical symptoms in blood donors. J Rheumatol 1992;

19 : 1919–21.

15 Vrethem M, Ernerudh J, Lindstro$ m F, Olsson JE. Cerebral

ishemia associated with anti-cardiolipin antibodies. Acta

Neurol Scand 1992; 85 : 412.

16 Harrington TM, Bunch TW, van der Berg CJ. Renal tubular

acidosis – a new look at treatment of musculoskeletal and

renal disease. Mayo Clin Proc 1983; 58 : 354–60.

17 Wrong OM, Feest TG, MacIver AG. Immune-related potassium-

losing interstitial nephritis : a comparison with distal renal

tubular acidosis. Q J Med 1993; 86 : 513–34.

18 Tu WH, Shearn MA, Lee JC, Hopper J. Interstitial nephritis in

Sjo$ gren’s syndrome. Ann Intern Med 1968; 6 : 1163–70.

19 Moutsopoulos HM, Cledes J, Skopouli FN, Elisaf M, Youinou P.

Nephrocalcinosis in Sjo$ gren’s syndrome: a late sequela of

renal tubular acidosis. J Intern Med 1991; 230 : 187–91.

20 Andrassy K, Gebest J, Tan E, Thoenes W, Ritz E. Interstitial

nephritis in a patient with atypical Sjo$ gren’s syndrome. Klin

Wochenschr 1980; 58 : 563–7.

21 Shioji R, Furuyama T, Onodera S, Sito H, Ito H, Sasaki Y.

Sjo$ gren’s syndrome and renal tubular acidosis. Am J Med

1970; 48 : 456–63.

22 Calmes M, Bartholomew B. SS-A (Ro) antibody in random

mother-infant pairs. J Clin Pathol 1985; 38 : 73–5.

23 Lindstro$ m F, Eriksson P, Tejle K, Skogh T. IgG subclasses of

anti-SS-A}Ro in patients with primary Sjo$ gren’s syndrome.

Clin Immunol Immunopathol 1994; 73 : 358–61.

24 Graninger WB, Steinberg AD, Meron G, Smolen JS. Interstitial

nephritis in patients with systemic lupus erythematodes : a

manifestation of concomitant Sjo$ gren’s syndrome? Clin Exp

Rheumatol 1991; 9 : 41–5.

25 Feest TG, Lockwood CM, Morley AR, Uff JS. Renal histology

and immunopathology in distal renal tubular acidosis. Clin

Nephrol 1978; 10 : 187–90.

26 Pasternack A, Linder E. Renal tubular acidosis : an immuno-

pathological study on four patients. Clin Exp Immunol 1970;

7 :115–23.

27 Matsumura R, Kondo Y, Sugiyama T, Sueishi M, Koike T,

Takabayashi K et al. Immunohistochemistical identification of

infiltrating mononuclear cells in tubulointerstitial nephritis

associated with Sjo$ gren’s syndrome. Clin Nephrol 1988; 30 :

335–40.

28 Siamopoulos KC, Mavridis AK, Elisaf M, Drosos AA,

Moutsopoulos HM. Kidney involvement in primary Sjo$ gren’s

syndrome. Scand J Rheumatol 1986; Suppl 61: 156–60.

29 Talal N, Zisman E, Schur PH. Renal tubular acidosis, glomeru-

lonephritis and immunologic factors in Sjo$ gren’s syndrome.

Arthritis Rheum 1968; 11 : 774–86.

30 Wegelius O, Fyhrquist F, Adner P-L. Sjo$ gren’s syndrome

associated with vitamin B"#

deficiency. Acta Rheumatol Scand

1970; 16 : 184–90.

31 Karsh J, Pavlidids N, Weintraub BD, Moutsopoulos HM.

Thyroid disease in Sjo$ gren’s syndrome. Arthritis Rheum

1980; 23 : 1326–9.

Received 15 August 1995; accepted 30 November 1995.

Correspondence : Dr Per Eriksson MD, Department of Internal

Medicine, La$ nssjukhuset Ryhov, S-551 85 Jo$ nko$ ping, Sweden.

# 1996 Blackwell Science Ltd Journal of Internal Medicine 239 : 483–488