Medical kidney diseases

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This article describes medical renal disease or the medical kidney. Much in medical kidney depends on the clinical information. Most of the disease seen by pathologists is... glomerular disease. If in doubt... the answer to most questions is diabetes mellitus or systemic lupus erythematosus. Medical kidney is niche area in pathology. It is one of the few areas that routinely requires electron microscopy.

Normal

Epithelium[1]

  • The glomeruli visceral epithelium is part of the capillary wall (part of the glomerular tuft).
  • The parietal epithelium is part of Bowman's capsule.

Remember: visceral has vessels.

Clinical presentations

Nephrotic syndrome

Features:

  • Anasarca (whole body - edema).
  • Proteinuria (>3.5 g/24h).
  • Hypercholesterolemia.
  • Hypoalbuminemia.

Nephritic syndrome

Features - mnemonic PHAROH:[2]

  • Proteinuria.
  • Hypertension.
  • Azotemia.
  • RBC casts.
  • Oliguria.
  • Hematuria.

Mixed

  • Features of nephritic syndrome and nephrotic syndrome.

Basic approach to renal biopsy

Comment on:

  • Glomeruli.
  • Tubules.
  • Interstitium.
  • Vessels.

Glomeruli

  1. Mesangium
    • Matrix should be: "1 cell thick" (expanded in diabetes mellitus).
    • Cellularity of the mesangium - normal = upto 3 cells (don't count cell abutting the capillary lumen).
  2. Capillary loops "open"
    • Lumina patent? If not patent is it due to matrix or cells (endocapillary hypercellularity).
    • Capillary wall morphology - wavy thin is normal; hulla-hoop/wire-like abnormal (suggestive of immune complex deposition).
  3. Bowman's space (urinary space) - crescents present?
  • Count the number of glomeruli.
  • Count number of the obsolete glomeruli.

Components of the glomeruli (anatomical)

  • Podocyte - rarely affect by disease
    • One notable disease is collapsing glomerulopathy in HIV.[3]
  • Endothelial cell.
  • Mesangial cell.

Vessels

  1. Arteriolar hyalinosis - too much pink stuff???
  2. Intimal hyperplasia.

Consider:

  • Vasculitis? - inflammatory cells in vessel wall.
  • Amyloid? - pink.
  • Rejection? - PMNs.

Tubules & interstitium

Tubules - proximal portion is the most important.

  • Casts?
  • Necrosis?

Interstitium

  • Fibrosis - prognostically important.
    • Grading: mild = <25%, moderate 25-50%, severe >50%.

Important terms/process related

Obsolete glomeruli

  • Completely sclerosed glomeruli are not important - unless present in larger numbers than expected for the age of the patient.
Percent of sclerosed glomeruli = (age in years)/2 - 10%.[4]

Example:

  • It is normal for an 80 year-old to have 30% sclerosed glomeruli.

Glomerular disease terms[5]

  • Global = >50% of glomeruli.
  • Focal = <50% of glomeruli.
  • Segmental = part of glomerulus.
  • Diffuse = most of glomerulus.

Staining

The standard stain in kidney pathology is PAS. Section are usually 1-2 micrometers, as opposed to 4-5 micrometers seen in rountine section of other organs.

Interpretation of medical renal disease more difficult or even impossible if the sections are thicker, as one does not see the glomerular structures well.

In kidney that is cut thick the glomeruli look more nodular and it is more difficult to find open capillary loops.

Immunofluorescence

Routinue (mnemonic GAM CF):

  • IgG.
  • IgA.
  • IgM.
  • C3.
  • Fibrinogen.

Optional:

  • Kappa.
  • Lambda.

Immune complex-related disease

Can be:

  • Subepithelial - distal to basement membrane (BM).
  • Subendothelial - proximal to BM.

Tram-tracking of BM

DDx:[6]

  1. MPGN.
  2. Thrombotic microscopic angiopathy (TMA).
  3. Transplant glomerulopathy (TG).

Arteriolar hyalinosis

DDx:

  • Diabetes mellitus.
  • Hypertension.
  • Aging.
  • Drugs - tarolimus, cyclosporine.

Note:

  • Arteriolar hyalinosis - involves afferent and efferent arterioles in diabetes, in others it is only tha afferent.

Mesangial hypercellularity

Think:

  1. Lupus.
  2. IgA nephropathy.

Mesangial expansion

  • Diabetes mellitus.[7]
  • Immune complex mediated disease (e.g. IgA nephropathy).
  • Henoch-Schoenlein disease.
  • Lupus.

Pathologic DDx

The clinical presentations suggest a pathologic DDx.[8]

Nephritic

  • Post-infectious glomerulonephritis,
    • Classically streptococcal
  • Crescentic glomerulonephritis (AKA rapidly progressive glomerulonephritis (RPGN)),
    • Anti-GBM disease,
    • ANCA disease (e.g. Wegener's granulomatosis),
    • Goodpasture's syndrome.

Nephrotic

  • Minimal segmental disease (MSD) - AKA minimal change disease (MCD),
  • Focal segmental glomerulosclerosis (FSGS),
  • Membranous nephropathy.

Mixed presentation

  • IgA nephropathy,
  • Focal proliferative glomerulosclerosis (FPGS),
  • Membranoproliferative glomerulonephritis (MPGN).

Nephrotic syndrome

A broad classification of nephrotic syndrome based on etiology:

 
 
 
Nephrotic
syndrome
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Primary
 
 
 
Secondary

In children nephrotic syndrome is assumed to be minimal change disease. Biopsies are done only there is no response to steriods.

Diabetes

  • Most common cause of end stage renal disease (ESRD).
  • Rarely biopsied.
  • Leads to nodular glomerulosclerosis.

Histology

  • Thick glomerular basement membrane (GBM).
  • Mesangial matrix expansion - leads to nodule formation Kimmelstiel-Wilson nodules.

Image: Nodular glomerulosclerosis (WP).

IgA nephropathy

  • Diagnosis based on immunofluorescence (IgA+).

Histology

  • Mesangial hypercellularity - may be only light microscopy finding.

Membranous nephropathy

  • Presents as nephrotic syndrome.

Histology

  • Subepithelial immunocomplex deposition, spike forming.

Membranoproliferative glomerulonephritis

  • Abbrev. MPGN.
  • In adults most common cause: hepatitis C.

Histology

  • Endothelial cell proliferation.
  • Basement membrane double layering (tram-tracking).
  • Mesangial hypercellularity.

Lupus nephritis

Five classes:

  • Diffuse mesangial 2 vs. 4.
  • Focal patch mesangial 3.
  • Membranous 5 ???

Fabry disease

General

  • Rare X-linked genetic disease.
    • Caused by defect in alpha-galactosidase A gene.
    • Women partially affected
  • Lysosomal storage disorder -- 2nd in prevalence only to Gaucher disease.
  • Multisystem disease affecting small vessels and kidney.

Presentation

  • Women: usually proteinuria.
  • Men: angiokeratomas (skin lesion), proteinuria.

Microscopy

LM:[9]

  • Foamy podocyte inclusions, best visualized with toluidine blue.
  • Mild mesangial hypercellularity.

EM:[9]

  • Myelin-like inclusions.
    • Concentric bodies with an onion-skin-like appearance.
  • Zebra bodies.
    • Ovoid inclusions with striped pattern.

Note:

  • Myelin-like inclusion are not pathognomonic for Fabry disease; they may result from drug use:[9]
    • Amiodarone,
    • Aminoglycosides,
    • Chloroquine.

Tx

  • Symptomatic treatment.
  • Enzyme replacement - agalsidase alpha (Replagal) or agalsidase beta (Fabrazyme).

Acute tubular necrosis

  • Best diagnosed clinically (using urine R&M) - hemegranular casts are diagnostic.
  • Often abbreviated ATN.

Histopathology

Features:[10]

  • Hemegranular casts in the lumen.
  • Regenerative activity (mitoses).

Hepatorenal syndrome

  • Acute renal failure due secondary to cirrhosis or fulminant liver failure.

Clinical

  • Urine sodium is low,[11] unlike in ATN (the main DDx).

Pathophysiology

  • Renal vasoconstriction.[12]

Histology

  • Normal.

Treatment

Medical and surgical:[13]

  • Vasoconstrictors (e.g. midodrine, terlipressin (counteracts splanchnic vasodilation), norepinephrine).
  • Albumin.
  • TIPS (transjugular intrahepatic portosystemic shunt).
  • Liver transplantation.

Note:

  • I suspect a portal vein pump would work... it reduces portal pressure and would likely increase hepatic function.

Alport disease

Clinical

  • Hearing loss (sensorineural).
  • Hematuria - usually preceeds hearing loss.[14]
  • Can be thought of a pathologic form of thin basement membrane disease.[15]

Etiology

  • Genetic defect - collagen type IV.

Inheritance:[14]

  • X-linked - 80%.
  • Autosomal recessive - 15%.
  • Autosomal dominant - 5%.

Polycystic kidney disease

Types:

  • Adult onset - autosomal dominant polycystic kidney disease (ADPKD).
  • Childhood onset - autosomal recessive polycystic kidney disease (ARPKD).

ADPKD

Etiology

  • Mutation in PKD1 gene or PKD2 gene.
  • Is classified in a large group of diseases - ciliopathies.

PKD1 related disease:[16]

  • Encodes polycystin.
  • Death at ~53 years.
  • Assoc. with cerebral aneurysms.

PKD2 related disease:[17]

  • Death at ~69 years.
  • Assoc. with colonic diverticula, aortic aneurysm, mitral valve prolapse.

Liver and PKD

Complications:[18]

  1. Infected cyst.
  2. Cholangiocarcinoma.

Cysts:

  • Cysts in the liver, like the kidney, are thought to enlarge with age.

Von Meyenburg complexes:

  • Cluster of dilated ducts with "altered" bile.
  • Surrounded by collagenous stroma.

See also: Medical liver disease.

Transplant - rejection

  • Associated with C4d+ IHC.[19]
  • Mean graft survival is ~4 years for C4d+ interstitial capillaries vs. ~8 years for C4d- renal grafts.[20]

See also

References

  1. ↑ Robbins p.956.
  2. ↑ URL: http://www.google.com/url?sa=t&source=web&ct=res&cd=12&ved=0CAkQFDABOAo&url=http%3A%2F%2Fbooks.google.com%2Fbooks%3Fid%3D5bmg8xiLxkMC%26pg%3DPA249%26lpg%3DPA249%26dq%3DNephritic%2Bsyndrome%2BPHAROH%26source%3Dbl%26ots%3DjNOpOusIu0%26sig%3DTBRPjGRx5B6pBV516Ssz7PBx1vs%26hl%3Den%26ei%3DYwogS6fqF5X7nAfij6nWDQ%26sa%3DX%26oi%3Dbook_result%26ct%3Dresult%26resnum%3D2%26ved%3D0CAoQ6AEwATgK&rct=j&q=Nephritic+syndrome+PHAROH&ei=YwogS6fqF5X7nAfij6nWDQ&usg=AFQjCNF9hJwXFKoe2_TgHMCud8140qPskg. Accessed on: 9 December 2009.
  3. ↑ AH. 13 August 2009.
  4. ↑ Fogo AB, Kashgarian M. Diagnostic Atlas of Renal Pathology. Elsevier. 2005. Page 16.
  5. ↑ Fogo AB et al.. Fundamentals of Renal Pathology. Springer. 2006. p. 82. ISBN: 978-0387-31126-5.
  6. ↑ AH. 17 July 2009.
  7. ↑ Fioretto P, Mauer M (March 2007). "Histopathology of diabetic nephropathy". Semin. Nephrol. 27 (2): 195-207. doi:10.1016/j.semnephrol.2007.01.012. PMID 17418688.
  8. ↑ [1][2]
  9. ↑ 9.0 9.1 9.2 Fischer EG, Moore MJ, Lager DJ (October 2006). "Fabry disease: a morphologic study of 11 cases". Mod. Pathol. 19 (10): 1295-301. doi:10.1038/modpathol.3800634. PMID 16799480. http://www.nature.com/modpathol/journal/v19/n10/abs/3800634a.html.
  10. ↑ PS April 2009.
  11. ↑ Epstein M, Oster JR, de Velasco RE (March 1976). "Hepatorenal syndrome following hemihepatectomy". Clin. Nephrol. 5 (3): 129-33. PMID 1261103.
  12. ↑ Angeli P, Merkel C (2008). "Pathogenesis and management of hepatorenal syndrome in patients with cirrhosis". J. Hepatol. 48 Suppl 1: S93-103. doi:10.1016/j.jhep.2008.01.010. PMID 18304678.
  13. ↑ Wong F (February 2008). "Hepatorenal syndrome: current management". Curr Gastroenterol Rep 10 (1): 22-9. PMID 18417039.
  14. ↑ 14.0 14.1 http://emedicine.medscape.com/article/981126-overview
  15. ↑ AM. 13 August 2009.
  16. ↑ MacSween 5th Ed. PP. 174-5.
  17. ↑ MacSween 5th Ed. PP. 174-5.
  18. ↑ MacSween 5th Ed. PP. 174-5.
  19. ↑ Vascular deposition of complement-split products in kidney allografts with cell-mediated rejection. Feucht HE, Felber E, Gokel MJ, Hillebrand G, Nattermann U, Brockmeyer C, Held E, Riethmüller G, Land W, Albert E. Clin Exp Immunol. 1991 Dec;86(3):464-70. PMID 1747954.
  20. ↑ Impact of humoral alloreactivity early after transplantation on the long-term survival of renal allografts. Lederer SR, Kluth-Pepper B, Schneeberger H, Albert E, Land W, Feucht HE. Kidney Int. 2001 Jan;59(1):334-41. PMID 11135088.
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