Title: The%20Kidney%20in%20Autoimmune%20Diseases%20Renal%20involvement%20in%20primary%20Sjogren
1The Kidney in Autoimmune DiseasesRenal
involvement in primary Sjogrens syndrome
- Eva Honsová
- Institute for Clinical and Experimental Medicine
- Prague, Czech Republic
2 Sjogrens syndrome
- Chronic inflammatory disorder
- Diminished function of the lacrimal and salivary
glands (sicca syndrome) - autoimmune predominantly in females
- presence of
autoantibodies - anti-Ro/SSA, anti-La/SSB
- Sjs may occur in a primary form or as a secondary
form that complicates other autoimmune diseases
most frequently RA. There is also evident overlap
of SjS with subset of SLE.
3 A prophet is without honor
in his own home
-
- The disease eponym
is associated with - Swedish
ophthalmologist Henrik - Sjögren. In 1933,
he presented 19 - patients with
diminished tear production - and proposed the
term - keratoconjunctivitis.
- Only when his thesis was translated into English
in 1943 (by - Bruce Hamilton), the eponym Sjogrens sy began to
appear in - the medical literature.
-
Henrik Samuel Conrad Sjogren
4 Sjogrens syndrome clinical features
- The precise etiology and pathogenesis remain
elusive. - Some authors suggested that primary SjS develops
through three stages defined by the extent of
organ damage during the progression of the
disease. - Stage I, only sicca syndrome without systemic
involvement (45 of cases). - Stage II, apart from sicca syndrome, organ
involvement kidneys, liver, thyroid gland or
pancreas (approx. 50 of cases). - Stage III, about 5 of patients develop lymphoma.
5Sjogrens syndrome diagnosis
CD138
- The American-European criteria (Ann Rheum Dis
200261664-558), 6 inclusion criteria, 5 focus
on glandular involvement, remaining one is
presence of anti-Ro/La antibodies. - Exlusion criteria (sarcoidosis, prior head and
neck irradiation, recent use of anticholinergic
drugs, HCV, AIDS) - Dg. is made if clinical symptoms are compatible
with the laboratory results and when other causes
of ocular and/or oral dryness have been excluded.
6Sjogrens syndrome renal involvement
- a frequent extraglandular manifestation of
primary SjS. Clinical signs and renal pathology
are heterogeneous and variable. - The main clinical manifestation is presented by
renal tubular dysfunction, especially by distal
renal tubular acidosis (RTA) type I. - SjS represents a rare indication for the
performance of a renal biopsy - Maripuri et al. Renal involvement in Primary SjS.
Clin J Am Soc Nephrol.2009, Aug. - 7 276 patients/ 24 with a biopsy (0.3).
7Sjogrens syndrome renal involvement
von Kossa stain
- Distal RTA is a disease of defective urinary
acidification that is caused by dysfunction of
a-intercalated cells. - RTA is characterized by hypocalemic metabolic
acidosis - An impairment of H excretion into the tubules is
associated with higher - excretion of potassium and hypokalaemia. Instead
of the bicarbonates, which - are lost in the urine, chlorides enter the blood
and this type of defective - function may leads to hyperchloremic and
hypokalaemic metabolic acidosis. - As it is necessary to buffer acid ions, calcium
is mobilized from the bones - nephrocalcinosis or nephrolithiasis.
8Sjogrens syndrome renal involvementDevuyst O,
Lemaire M et al. Autoantibodies against
intercalated cells in Sjogrens sy. Kidney Int
200976229.
- Authors incubated control human kidney with IgG
extracted from this - patient (g,h, ICs positive staining with
autoantibodies). Identification of - ICs was performed on serial section with IH
apical H-ATPase (i,j), and EM. - No signal was obtained with control human IgG (k).
9Sjogrens syndrome renal involvement
- Biopsy samples of patients suffering from SjS
with dRTA showed frequently tubulointerstitial
nephritis - focally dense infiltrates of
lymphocytes, monocytes and plasma cells, - - varying degrees of tubulitis, - tubular
atrophy, and interstitial fibrosis. - Dif. dg. different types of TIN, IgG4-related
sclerosing autoimmune disease
10Sjogrens syndrome IgG4-related sclerosing
autoimmune disease
- Kamisawa et al. IgG4-related sclerosing disease.
World J Gastroenterol 200814(25)3948-55. - Systemic disease characterized in histology by
extensive number of IgG4-positive plasmocytes,
high level of IgG, excellent response to the
steroid therapy - Major clinical manifestations
- - pancreatico-hepato-biliary (AIP)
- - salivary glands
- - retroperitoneum
- - kidney and lungs
AIP
sialadenitis
Sclerosing cholangitis
Retroperitoneal fibrosis
11Sjogrens syndrome IgG4-related sclerosing
autoimmune disease
Detail
- Histology inflammatory destruction of tissue
which is followed - by fibrosis. Peri-ductal infiltrate with
numerous IgG4 positive - plasmocytes. Obliterative flebitis.
12Sjogrens syndrome IgG4-related sclerosing
autoimmune disease
13Sjogrens syndrome IgG4-related sclerosing
autoimmune disease
Kidney
14Sjogrens syndrome renal involvement
- Only small percentage of patients develops
immune-complex-mediated GN . Bossini (Nephrol
Dial Transplant 2001 162328-2336) the incidence
of GN was 5, and in the study of Ren (J
Rheumatol 2008 35278-284) it was 4.6. - All types of GNs were reported MGN, MPGN, FSGS,
IgA GN and also pauciimunne GN with positive ANCA
antibodies. - In several cases, the glomerular lesion, usually
MPGN, was associated with cryoglobulinemia - overlap of SjS with a subset of SLE
15Sjogrens syndrome liver involvement
- Liver is a common target in SjS (2002 Kaplan
49.1 patients abnormal liver tests) - PBC and AIH
- PBC is the most common autoimmune liver disease,
affecting up to 1 in 1000 women over 40 years of
age. - SjS and PBC share several features are common,
and affecting the same group of patients, are
associated with autoantibodies, but the titre is
not related either to the activity or to the
prognosis. Therapy is only symptomatic.
16Sjogrens syndrome heart involvement
- women with primary SjS and positive anti-Ro/SSA
antibodies are at risk of giving birth to babies
with neonatal lupus that is associated with
congenital heart block. That risk is
approximately 4. - Heart block can also occur in SjS patients later
in life, in adulthood, and their serological
examination may reveal antibodies against
Purkinje fibers, muscarinic M1 receptors, and
anti-La/SSB antibodies.
17 Sjogrens syndrome Conclusion
- Enigmatic disease autoimmune epithelitis
- Kidney involvement is frequent SjS is one of the
leading cause of acquired type I RTA - Asymptomatic, rare indication for renal biopsy,
in cases of SjS associated RTA, TIN is the most
frequent diagnosis. - Only small percentage of patients with primary
SjS develops immune-complex-mediated GN. All
types of GNs were reported - IgG4-related sclerosing autoimmune disease
18Endemic to the pathology department, IKEM