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Renal Pathology
Tuesday, February 14, 2006 - 7:30 PM
International South Room
Autoimmunity and the Kidney
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Moderator:
Agnes Fogo
Vanderbilt University Medical Center
Nashville, TN
Disclosure: The speakers have indicated they have nothing to disclose.
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Clinical histories are printed below.
Click on the case numbers for text and references of each case.
Click on each slide thumbnail image for an enlarged view
 Click here to download handout in 1-per-page format for this case (7.0 MB)
Click here to download handout in 6-per-page format for this case (6.9 MB)
Submitted by:
Fred G. Silva
United States and Canadian Academy of Pathology
Augusta, GA
This 52 year old African American female factory worker was admitted most recently with chest pain/midsternal pressure for one day PTA (10/04). - Past Med Hx: DM type 2 (for a couple of years, most recently started on insulin); Uncontrolled hypertension (160-200/100-130), and hypothyroidism; eye grounds said to be normal
- PE: bipedal edema/EKG and labs: no evidence of MI
- Labs: BUN/serum Cr: 8/0.9 (on 7/04), and on this admission and next few days (10/25-11/10, 2004) was 26-39/2.2-2.8; 4+ proteinuria; remainder normal or negative
- Renal Biopsy: (11/09/04) New onset of renal failure and nephrotic syndrome
(? thought to be too short a duration of DM as a cause)
Other lab tests ordered.
Case 1 - Figure 1 -
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Case 1 - Figure 2 -
Several of the glomeruli appear normal in size and cellularity with patent capillary lumens. PAS reaction.
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Case 1 - Figure 3 -
Higher magnification showing patent glomerular capillaries. There is one or two very small rounded mesangial nodules. PAS reaction.
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Case 1 - Figure 4 -
There is a mild to moderate increase in mesangial matrix with a couple of small founded mesangial nodules. PAS reaction.
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Case 1 - Figure 5 -
Higher magnification of another glomerulus showing a couple of very small rounded mesangial nodules. PAS reaction.
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Case 1 - Figure 6 -
Another glomerulus showing mild to moderate intracapillary hypercellularity with some closure of the glomerular capillaries. H&E
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Case 1 - Figure 7 -
Another glomerulus showing more marked intracapillary hypercellularity with closure of the glomerular capillaries. There is also some prominent visceral epithelial cell change, suggestive of proteinuria. H&E
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Case 1 - Figure 8 -
The glomerulus shows marked closure of the glomerular capillaries with intracapillary hypercellularity and some increase in mesangial matrix. H&E
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Case 1 - Figure 9 -
The glomerulus show some segmental, but marked prominence of the glomerular epithelial cells. PAS reaction.
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Case 1 - Figure 10 -
The low magnification of the glomerulus shows a proliferation/hypercellularity within Bowman’s space (and possibly attached to the glomerular tuft). PAS reaction.
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Case 1 - Figure 11 -
Higher magnification of the glomerulus in slide 1-9. There is a segmental marked hypercellularity (crescent) in Bowman’s Space, apparently attached to the glomerular tuft. PAS reaction.
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Case 1 - Figure 12 -
Another glomerulus showing several moderate sized mesangial nodules (Kimmelstiel-Wilson nodules). Trichrome stain.
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Case 1 - Figure 13 -
Another glomerulus showing Kimmelstiel-Wilson mesangial nodules, suggestive of diabetic nephropathy. Trichrome stain.
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Case 1 - Figure 14 -
Another glomerulus showing Kimmelstiel-Wilson mesangial nodules, suggestive of diabetic nephropathy. Trichrome stain.
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Case 1 - Figure 15 -
The glomerular tuft is somewhat unremarkable. The glomerular capillaries are patent, and the mesangial/GBM regions appear unremarkable. There is a small segmental hypercellularity in Bowman’s Space (?early crescent formation). Silver methenamine stain.
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Case 1 - Figure 16 -
Bowman’s space on the right hand side is filled (about 50% of Bowman’s space) by very prominent epithelioid cells (crescent). Silver methenamine stain.
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Case 1 - Figure 17 -
Another section of the same glomerulus in Slide 1-15 showing what is considered a cellular crescent. Silver Methenamine stain.
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Case 1 - Figure 18 -
There is segmental tubular thinning/degeneration and a sparse interstitial inflammation (lymphocytes). H&E
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Case 1 - Figure 19 -
There is no evidence of vascular disease in the few vessels present in the biopsy. H&E
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Case 1 - Figure 20 -
Electronmicrograph showing patent glomerular capillaries, but a moderate increase in mesangial matrix and especially GBM thickening. No definite electrondense (“immune-type”) deposits were noted anywhere in the glomeruli studied.
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Case 1 - Figure 21 -
Higher magnification of a glomerulus, showing only increased thickening of the GBM. No electrondense (“immune-type”) deposits were noted anywhere. There are some visceral epithelial changes (segmental “effacement”, etc).
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Figures 22-29: The IF stains (antibodies) were interpreted as essentially negative. No definite immune-complex-like deposition was identified with any of the immunoglobulin or complement immunoreactants.
There was a mild “linear” staining of some GBMs, Bowman’s capsules, and TBMs for IgG and albumin.
Submitted by:
Gilbert Moeckel
Vanderbilt University Medical Center
Nashville, TN
M.G. is an 11 year old African American girl who presented with fever, joint pain, rash and fatigue. Her physical examination was notable for a blood pressure of 138/78 mmHg, periorbital edema, clear lungs, normal heart sounds with a II/VI systolic murmur, a soft abdomen with right upper quadrant tenderness without guarding or rebound, and nonpitting peripheral edema. Laboratory studies included BUN 88 mg/dl, creatinine 8.3 mg/dl, WBC 13,200/mm3, hemoglobin 6.4 gm/dl, platelet count 515,000/mm3 and reticulocytes 11.6 %. The peripheral blood smear showed schistocytes, spherocytes, anisocytosis and poikilocytosis. Urinalysis showed specific gravity of 1.015, pH 5, 1+ protein, 1+ blood, 2-5 RBC/hpf, rare WBCs, granular casts and rare tubular epithelial cells. Additional laboratory tests included albumin 2.4 gm/dl, LDH 1672 U/L (normal 372-744), C3 52 mg/dl, C4 11 mg/dl, rheumatoid factor < 11 IU/ml (normal 0-15), ANA titer > 1:160 in a smooth/speckled pattern, anti-DNA titer > 1:160, negative ANCA, negative cryoglobulins, negative lupus anticoagulant panel, fibrinogen 565 mg/dl (normal 185-400) and a negative direct Coombs test. On renal ultrasound her kidneys measured 10 cm in length with normal echogenicity and no hydronephrosis. On doppler examination, the renal arteries and veins were patent with diminished diastolic flow. She was started on methylprednisolone 100 mg i.v. daily. Over the next 2 days she remained markedly oliguric, her creatinine increased to 9.7 mg/dl, and she underwent a percutaneous renal biopsy.
Case 2 - Figure 1 -
Glomerulus with segmental endocapillary proliferation (H&E, x 400).
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Case 2 - Figure 2 -
Interlobular artery with lymphocytic infiltrate of intima and fibrinoid necrosis (H&E, x 400).
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Case 2 - Figure 3 -
Interlobular artery with myointimal proliferation, foam cell formation and almost complete occlusion of vascular lumen (H&E, x 200).
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Case 2 - Figure 4 -
Immunofluorescence microscopy. Vascular lesions show strong, chunky staining for IgM (Original magnification x 400).
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Case 2 - Figure 5 -
Immunofluorescence microscopy. Vascular lesions show strong, chunky staining for IgA (Original magnification x 400).
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Case 2 - Figure 6 -
Immunofluorescence microscopy. Vascular lesions show strong, chunky staining for IgG (Original magnification x 400).
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Case 2 - Figure 7 -
Immunofluorescence microscopy. Vascular lesions show strong staining for C1q (Original magnification x 400).
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Case 2 - Figure 8 -
Immunofluorescence microscopy. Vascular lesions show strong staining for C3 (Original magnification x 400).
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Case 2 - Figure 9 -
Electron microscopy. Ultrastructural examination of an arteriole shows multiple small to medium size immune complex deposits within its wall. There are also small areas of necrosis. (Original magnification x 8000).
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Submitted by:
Carmen Avila-Casado
Instituto Nacional de Cardiología Ignacio Chávez
Mexico City, Mexico
The patient, a 50 year old Hispanic women presented with dry mouth, dry eyes, Raynaud phenomenon, a sensitive neuropathy of the lower limbs and enlargement of parotid glands, over several weeks. One year latter, she complained also of polyarthralgia, and easy fatigue.
Past history:
She had no medical history of exposure to radiation, continuous antinflammatory drug therapy or pyelonephritis
Laboratory evaluation disclosed:
Arterial blood pH 7.32
Hematocrit 33%
Hemoglobulin 9.8 g/dL
Creatinine Clearance 35mL/min
Serum Creatinine 2.4 mg/dL
Urinalysis: specific gravity 1.005, pH 8, proteinuria ++
24-Hour proteinuria of 1.8 g/24 h
Rheumatoid factor 1/640
ANA 1/1,280
Anti-Ro (SSA) and Anti-La (SSB) antibodies
Low C4
Positive Schrimer test I
Positive Rose Bengal test
Case 3 - Figure 1 -
The sample consists of renal cortex. There were, on average, twenty glomeruli in the sample submitted for light microscopy. In this field, seven (7) glomeruli are present; two (2) of them are globally sclerosed. The interstitium reveals focal and mainly periglomerular inflammation.( PAS 10X)
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Case 3 - Figure 2 -
Other low power field showing three (3) glomeruli that appeared slightly increased. A focal area of inflammation is also observed. (PAS 10X)
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Case 3 - Figure 3 -
Interstitial fibrosis affected less than 10% of the sample as evidenced on the trichrome stain (Masson 10X)
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Case 3 - Figure 4 -
Glomerulus showing open capillary loops and the absence of inflammatory infiltrates. Glomerular basement membranes appear normal without wrinkling or double contours. One capillary loop appears aneurysmatic. A small synechia and hypertrophy of the yuxtaglomerular apparatus are also observed. (PAS 400X)
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Case 3 - Figure 5 -
A detail of the inflammatory infiltrate surrounding the glomeruli, Glomeruli show small synechya to the Bowman's capsule.
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Case 3 - Figure 6 -
Small foci of mononuclear inflammatory infiltrates in the interstitium in different fields. These inflammatory cells correspond to lymphocytes and plasma cells and are often seen infiltrating tubular epithelial cells. (PAS 40 X)
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Case 3 - Figure 7 -
Small foci of mononuclear inflammatory infiltrates in the interstitium in different fields. These inflammatory cells correspond to lymphocytes and plasma cells and are often seen infiltrating tubular epithelial cells. (PAS 40 X)
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Case 3 - Figure 8 -
Small foci of mononuclear inflammatory infiltrates in the interstitium in different fields. These inflammatory cells correspond to lymphocytes and plasma cells and are often seen infiltrating tubular epithelial cells. (PAS 40 X)
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Case 3 - Figure 9 -
Small foci of mononuclear inflammatory infiltrates in the interstitium in different fields. These inflammatory cells correspond to lymphocytes and plasma cells and are often seen infiltrating tubular epithelial cells. (PAS 40 X)
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Case 3 - Figure 10 -
Tubular atrophy was difficult to find although isolated tubules with luminal hyaline casts and others presenting thickening of the tubular basement membrane where also observed. This field also shows and small area of scarring with some inflammatory infiltrate.
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Case 3 - Figure 11 -
The sections were incubated with antibodies specific for the heavy chains of IgG, IgA, and IgM; for kappa and lambda light chains, C3c, C1q, Albumin and fibrin-related antigens. Sample for immunofluorescence contained ten (10) glomeruli. There were no significant immune deposits present. Arterioles show focal C3
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Case 3 - Figure 12 -
The sections were incubated with antibodies specific for the heavy chains of IgG, IgA, and IgM; for kappa and lambda light chains, C3c, C1q, Albumin and fibrin-related antigens. Sample for immunofluorescence contained ten (10) glomeruli. There were no significant immune deposits present. Arterioles show focal C3
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Submitted by:
Terence Cook
Hammersmith Hospital
London, U.K.
The patient is a 74 year old Caucasian male. He first presented in January 2004 having noticed increasing ankle oedema over the previous 2 months
On examination:
Wt 78Kg, BP 142/90 mmHg
Chest, abdomen, Nervous system – no abnormalities
Marked pedal and pre-tibial oedema
Urinalysis 4+ prot, + rbc's no wbc's no casts
24 hour urine protein 5.5g
Serum albumin 22g/l
Serum creatinine 80mmol/l (0.9 mg/dl)
ANA negative, Anti DNA negative
HBSAg , HCV, ASLO, ANCA all negative
SPEP-UPEP no monoclonal spike, complement normal
The patient was treated conservatively with diuretics.
8 months later he re-presented complaining of nausea and vomiting. He had been anuric for 48 hours; BP180/110 mmHg; Serum albumin 18g/l; Serum creatinine 1400 mmol/l (15.8mg/dl);
A renal biopsy was performed
Case 4 - Figure 1 -
Low power view of the renal cortex. The glomeruli are difficult to make out but do not appear normal. There is mild focal tubular dilatation (H&E)
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Case 4 - Figure 2 -
Low power view of renal cortex. In this silver stain it is clear that all the glomeruli are involved by cellular crescents (Methenamine silver)
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Case 4 - Figure 3 -
Medium power view showing two glomeruli with cellular crescents. At this power the tubules are seen to be dilated with flattened epithelium (H&E)
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Case 4 - Figure 4 -
Medium power view showing four glomeruli with cellular crescents. All the crescents appear to be of a similar age (Methenamine silver)
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Case 4 - Figure 5 -
Two glomeruli with cellular crescents. Where the glomerular capillary walls can be made out they appear slightly thickened. (H&E)
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Case 4 - Figure 6 -
Three glomeruli with cellular crescents. In one there is extensive destruction of Bowman's capsule (Methenamine silver)
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Case 4 - Figure 7 -
The glomerulus shows a circumferential cellular crescent (Methenamine silver)
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Case 4 - Figure 8 -
The glomerulus shows extensive fibrinoid necrosis, a circumferential cellular crescent and rupture of Bowman's capsule (Methenamine sliver)
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Case 4 - Figure 9 -
At high power the glomerular capillary wall is seen to be thickened with an irregular outer aspect with segmental spike formation (Methenamine silver)
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Case 4 - Figure 10 -
At high power the glomerular capillary wall is seen to be thickened with an irregular outer aspect with segmental spike formation (Methenamine silver)
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Case 4 - Figure 11 -
IgG shows a granular pattern of localisation along the capillary wall (IgG immunofluorescence)
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Case 4 - Figure 12 -
C3 shows a similar pattern to IgG with predominantly granular capillary wall staining (C3 immunofluorescence)
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Submitted by:
J. Charles Jennette
University of North Carolina School of Medicine
Chapel Hill, NC
A 28 year old Hispanic female developed trace proteinuria and hypertension (blood pressure 120/90 mmHg) 8 weeks into a pregnancy. She had no history of hypertension prior to the pregnancy and no family history of kidney disease or hypertension. Laboratory data at that time included serum creatinine 0.7, normal liver function tests and normal platelet count. Anti-hypertensive therapy was begun with labetalol. At 19 weeks gestation, her hypertension had worsened to 160/100 mmHg and she had developed 2+ lower extremity edema, malaise and headaches. The hypertension could not be controlled with a calcium channel blocker, labetalol and magnesium. Laboratory results at that time included 19 g/day proteinuria, oval fat bodies and fatty casts in the urine, 1+ hematuria with no RBC casts, serum creatinine 0.6, BUN 7, albumin 2.3, glucose 81, negative ANA, normal C3, slightly low C4, platelet count 80K, elevated LDH, no anemia, no schistocytes, and mildly elevated liver function tests. The following were negative or normal: lupus anticoagulant, anti- cardiolipin antibodies, factor V Leiden, HIV testing, and hepatitis A/B/C serology. Fetal and placental ultrasound was unremarkable. The clinical differential diagnosis was early onset preeclampsia/HELLP syndrome versus thrombotic microangiopathy versus focal segmental glomerulosclerosis versus other kidney disease. A renal biopsy was performed.
Case 5 - Figure 1 -
Two "bloodless" glomeruli with obliteration of capillary lumens caused by swollen endothelial cells and expansion of the subendothelial zone. Note the unremarkable tubulointerstitial compartment. (H&E stain)
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Case 5 - Figure 2 -
This higher magnification of one of the glomeruli in figure 5-1 shows the pale acidophilic consolidation with slight vacuolization that is characteristic for eclampsia/preeclampsia. (H&E stain)
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Case 5 - Figure 3 -
Masson trichrome stained glomeruli with obscured capillary lumens, but no hypercellularity. Note again the unremarkable tubulointerstitial compartment.
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Case 5 - Figure 4 -
This higher magnification of one of the glomeruli in figure 5-3 revealing the somewhat "bubbly" appearance in the consolidated areas. This is caused more by swollen endothelial cells and podocytes rather than increase in matrix material and thus does not stain as intensely blue as increased matrix would. (Masson trichrome stain)
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Case 5 - Figure 5 -
PAS-stained glomerulus showing extensive delicate replication of glomerular basement membranes, which forms some clear ovals that resemble "pearls".
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Case 5 - Figure 6 -
Jones silver methenamine stain showing the same glomerular changes illustrated in figure 5-5 as well as herniation of the tip of the swollen glomerulus into the proximal tubule, which is a characteristic but not specific feature of preeclampsia/eclampsia.
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Case 5 - Figure 7 -
High magnification of a Jones silver methenamine stain-stained glomerulus showing extensive remodeling of glomerular basement membranes.
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Case 5 - Figure 8 -
Masson trichrome stain showing profiles of small arteries and arterioles that have no changes indicative of a thrombotic microangiopathy or of chronic hypertension.
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Case 5 - Figure 9 -
Electron micrograph showing obliteration of a glomerular capillary lumen by a combination of endothelial swelling and expansion of the subendothelial zone by slightly electron-dense material.
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Case 5 - Figure 10 -
Electron micrograph showing marked narrowing of a glomerular capillary lumen predominantly by endothelial swelling (endotheliosis).
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Case 5 - Figure 11 -
Electron micrograph of a capillary wall that is thickened by multiple events, including endothelial swelling and subendothelial invagination, subendothelial mesangial interposition, and accumulation of subendothelial extracellular material. These ultrastructural changes are the basis for the light microscopic capillary wall abnormalities seen in figure 5-7.
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