Renal Pathology review

2012

Student version

Case 1 • A 16-year-old girl notes the sudden onset of periorbital

edema and dark maroon urine. This is a rather frightening experience for the patient and her parents and it prompts an immediate visit to the emergency ward.

• The patient had been in good health until 3 weeks prior to

consultation, when she developed a sore throat in connection with a respiratory tract infection. This was accompanied by persistent fever, forcing her to miss school for 3 days. The fever and the respiratory symptoms resolved spontaneously.

• Physical exam revealed an elevated blood pressure of

150/105mmHg, edema of the face, and only minimal inflammation of the pharynx

• Blood and urine tests reveal:

Case 1 continued

• BUN = 32mg/dL • Creatinine = 2.1mg/dL • Albumin = 3.7g/dL (N=3.5-5.0g/dL) • Urinalysis

– 1+ protein, 4+ blood by dipstick – Sediment: multiple red cells (most of which have a

dysmorphic appearance: acanthocytes) and occasional red cell and red granular (HGB) casts

– Active urine sediment • A renal biopsy was performed on the 3rd day

when she developed pulmonary infiltrates. • Biopsy results are on next slide • What is this?

Hypercellularity Inflammation IgG granular pattern

Diffuse AND?

EM: electron dense immune deposits on both sides PMN inflammatory cell in lumen of capillary

Case 2 • A 27-year-old man consults his family physician

because of a recent onset of edema. He has not other relevant history and the physical exam is remarkable only for significant pitting edema in the lower extremities. His blood pressure is 135/80

• Blood and urine tests reveal:

– BUN: 15mg/dL – Creatinine: 0.9mg/dL – Albumin: 1.7g/dL (normal = 3.5-5g/dL) – Urinalysis = 4+ protein (by dipstick)

• Sediment = oval fat bodies, occasional hyaline casts, rare rbcs

• Inactive urine sediment (no inflammatory cells)

– Renal Biopsy found on next slide: what do you predict?

Thickened BM compared to tubular membrane Immunoglobulins in

thickened BM

EM: Spikes and characteristic subepithelial deposits No inflammatory cells

Figure 9.9 from Renal Pathophysiology: The Essentials: 2nd Edition by H. Rennke and B. Denker p. 244

Table 9.3 from Renal Pathophysiology: The Essentials: 2nd Edition by H. Rennke and B. Denker p. 245

Nephrotic vs. Nephritic

Nephrotic

• Insidious onset

• 4+ edema

• Normal BP

• 4+ proteinuria

• +/- hematuria

• No RBC casts

• Low serum albumin

Nephritic

• Abrupt onset

• 2+ edema

• Hypertension

• Trace to 1+ proteinuria

• 3+ hematuria

• RBC casts present

• Normal/slightly low serum albumin

Young 3-y-o male child; dark urine, 3+protein; fatigue; and scrotal edema biopsy: light microscopy: glomeruli normal; Put on course of steroids, problem clears up after 6 weeks; Electron micrograph seen: What is seen in this EM? Which of the following is the most likely diagnosis in this patient?

A. Anti-GBM w/ Goodpastures B. Acute post strep glomerulonephritis C. Focal segmental GN D. Membranous glomerulopathy E. Minimal change disease

HIV positive 32-y-o man: eGFR reduced; BP 160-110; Urinalysis shows 2+protein; not steroid responsive; biopsy H&E shown; Fluorescence stain shows: IgM and C3 deposits

A. Anti-GBM w/ Goodpastures B. Acute post strep glomerulonephritis C. Focal segmental GN D. Membranous glomerulopathy E. Minimal change disease

38-yo female; labs: hypocomplementemia, azotemia, positive for Hepatitis B; Description of biopsy: Not hypercellular glomeruli; diffuse global capillary wall thickening; PAS stain: thick membranes and membranous ‘spikes’; Fluorescence: ‘granular’ IgG deposits along GBM

A. Anti-GBM w/ Goodpastures B. Acute post strep glomerulonephritis C. Focal segmental GN D. Membranous glomerulopathy E. Minimal change disease

23-yo female with dark urine and complaining of fatigue and chest pain Labs: hypocomplementemia; Urinalysis: 4+protein and 1+hematuria Biopsy: seen in photo; cellularity? Mesangial increase? EM: tram tracks: reduplication of basement membrane

A. Diabetic nephropathy B. Focal segmental GN C. Membranous glomerulopathy D. Membranoproliferative GN E. Minimal change disease

45-yo female; complaining of fatigue and exercise intolerance; persistent high BP (165/110); oliguria and weight gain Labs: glucose 220mg/dL and albumin 2.0g/dL; eGFR 29mL/min; UA: 2+protein ; trace blood; Light biopsy seen below: What are the circled structures called? EM: both subepithelial and subendothelial deposits seen What drug do we use to slow this progression?

A. Amyloidosis B. Diabetic nephropathy C. Focal segmental GN D. Membranous glomerulopathy E. Membranoproliferative GN

79-yo male suffering from Waldenstrom’s macroglobulinemia for 10 years; What is this? complaints: swelling of lower legs, oliguria and fatigue and chest pain. Light biopsy seen in A; EM seen in B and ‘apple green’ fluorescence seen in C

A. Amyloidosis B. Diabetic nephropathy C. Focal segmental GN D. IgA nephropathy E. Membranoproliferative GN

A

B C

27-yo soldier during annual physical: has rash and dark colored urine Labs: Creatinine 3.5mg/dL; BUN 35mg/dL; albumin 2.4g/dL; UA: 3+RBC and 1+ protein Light biopsy: mesangial proliferation; IgA staining Fluorescence pattern?

A. Amyloidosis B. Diabetic nephropathy C. Focal segmental GN D. IgA nephropathy E. Membranoproliferative GN

25-yo male: clinical symptoms: hemoptysis; dark urine, oliguria; Light biopsy: shown; fluorescence shown; What immunoglobulin/complement seen in B? Confirmatory testing?

A. Anti-GBM w Goodpastures B. Diabetic nephropathy C. Focal segmental GN D. IgA nephropathy E. Membranoproliferative GN F. Post-strep GN

B

12-yo male: 2 weeks after URI with sore throat; complaints: shoes are tight and ‘peeing’ dark red urine (coffee grounds); Labs: Positive ASO titer; Serum alb: 2.1g/dL; UA: 4+blood and 2+protein with RBC casts and acanthocytes Light biopsy seen (A and B): taken 1 month apart Fluorescent: lumpy bumpy IgG and C3 Describe deposits seen in A and C What is the prognosis in this child? And why?

A. Anti-GBM w Goodpastures B. Diabetic nephropathy C. Focal segmental GN D. IgA nephropathy E. Membranoproliferative GN F. Pauci-immune GN G. Post-strep GN

First biopsy 1 month ago

A

B

C What is the cause of the low serum alb?:

22-yo male: Oliguria, Creatinine 4.0mg/dL; eGFR 10mL/min UA: 4+blood and 2+protein with RBC casts and acanthocytes No fluorescent staining; What is the test that is seen in B-1?

A. Anti-GBM w Goodpastures B. Diabetic nephropathy C. Focal segmental GN D. Lupus E. Membranoproliferative GN F. Pauci-immune GN G. Post-strep GN

A

B-1 B-2

28-yo woman: malar rash; photosensitivity; pains in joints; dark- colored urine and oliguria Lab: positive for anti-double stranded-DNA Renal biopsy: full-house staining What does this mean?

A. Anti-GBM w Goodpastures B. Diabetic nephropathy C. Focal segmental GN D. Lupus E. Membranoproliferative GN F. Pauci-immune GN G. Post-strep GN

Mary, a 77 year old widow, presented to the urgent care with the complaint of rash, fever and malaise for 24 hours Mary had seen her primary care physician the week prior for increasing fatigue. Up until then, she had been quite active, going out with friends and spending time with her grandchildren. Mary considered herself quite healthy, only having to take Lisinopril for high blood pressure and omeprazole for gastroesophageal reflux disease.

A. Acute post-strep GN B. Acute interstitial nephrosis C. Acute tubular necrosis D. Focal segmental GN E. Systemic erythematosus

What are the diagnostic cells in this biopsy? What are the most common causes of this disease?

Harold Poulin A 68-year-old man recently diagnosed with colon cancer was admitted for colon resection. The surgery is complicated by some intra-operative bleeding and intermittent periods of hypotension. Postoperatively, the patient again developed hypotension. Labs: UA: 1+protein, 1+ blood; negative for nitrites and leukocytes + see microscopic picture: What are these called? Serum creatinine: 3.2mg/dL; BUN 35mg/dL; Alb 2.4mg/dL

A. Acute post-strep GN B. Acute interstitial nephrosis C. Acute tubular necrosis D. Focal segmental GN E. Systemic erythematosus

Acute vs. chronic pyelonephritis

Acute

• Urine: WBC’s and leukocyte ‘casts’

• Fever, chills, sweats, malaise and flank pain

• In kids: vesico-ureteral reflux: urine refluxes back up towards kidneys

• Papillary necrosis

• Kidneys normal size

Chronic

• Urine not always a good diagnostic tool

• Recurrent and persistent bacterial infection secondary to UTI obstruction or urine reflux or both

• Progressive atrophy and scarring with contraction of tissue

• Kidneys small and atrophied

UTI

• Definition: infection of the bladder; can occur alone or in conjunction with pyelonephritis

• Pathogens: E. coli in 85% of uncomplicated cases; Staphylococcus saprophyticus; Proteus mirabilis; Klebsiella

• Urinalysis classic findings: blood, WBC, and protein often positive; leukocyte esterase positive; nitrite often positive (gram neg bacteria); motile bacteria; budding yeast

Pyelonephritis

• Gross pathology: kidneys appear pocketed

• Urinalysis: WBCs & WBC casts, bacteria

• Affects cortex with relative sparing of glomeruli/vessels

Disorder Presentation/ Symptoms

Causes: pathogenesis/ pathology

Notes

Stress Incontinenance

Leak of urine Pelvic support structure weakened (childbirth, menopause, age, obesity) -Sphincter does not close fully during periods of increased pressure (coughing, sneezing)

Overactive Bladder

Leak of urine -Detrusor muscle doesn’t contract when it should – it contracts before bladder is full

-Treatment: muscarinic antagonists block the effect of parasympathetic activation and promote storage; Ditropan, Detrol LA, Vesicare

Enlarged Prostate (BPH)

-Weak stream, increased frequency, nocturia

-Obstruction to urine low leads to lower urinary tract symptoms -Leads to urinary retention

-Affects 60% of men by age 65 -Treatment: alpha adrenergic antagonists open smooth muscle in the prostate; Flomax, Uroxatral

Ureteral Obstruction

-Flank pain -Groin pain

-Most commonly caused by kidney stones -Physiologic response: initially, increased ureteral pressure and increased RBF (1.5 hours); second phase, increased ureteral pressure and decreased RBF (5 hours); third phase, decreased RBF and ureteral pressure