The%20Kidney%20in%20Autoimmune%20Diseases%20Renal%20involvement%20in%20primary%20Sjogren

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The Kidney in Autoimmune DiseasesRenal
involvement in primary Sjogrens syndrome

• Eva Honsová
• Institute for Clinical and Experimental Medicine
• Prague, Czech Republic

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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.

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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
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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.
  

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Sjogrens 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.
  

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Sjogrens 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).

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Sjogrens 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.

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Sjogrens 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).

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Sjogrens 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

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Sjogrens 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
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Sjogrens 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.

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Sjogrens syndrome IgG4-related sclerosing
autoimmune disease
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Sjogrens syndrome IgG4-related sclerosing
autoimmune disease
Kidney
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Sjogrens 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

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Sjogrens 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.

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Sjogrens 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.

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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

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Endemic to the pathology department, IKEM