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21st European Congress of Pathology
Istanbul, Turkey, September 08-13, 2007
http://www.ecp2007istanbul.org/
Slide Seminar 11, September 12th
Diagnostic Challenges in Nephropathology
Chairperson: D. Ferluga |
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Case 2
Presented by: Dusan Ferluga
Clinical History
A 45-year-old female patient with a very long clinical history is presented. Diagnosis of juvenile rheumatoid arthritis was established at the age of 13 yrs. During the next 9 years, she was treated intermittently with corticosteroids, gold therapy and nonsteroidal anti-inflammatory drugs. At the age of 22 yrs, she fulfilled ARA criteria for a diagnosis of overlapping systemic lupus erythematosus (SLE) (butterfly rush, arthritis, positive antinuclear antibodies, positive anti-ds DNA at a titer of 0.98, and kidney involvement with proteinuria of 1.1 g/24h, erythrocituria and leukocyturia). The first kidney biopsy was performed at 22 yrs age (see histologic findings). She received cyclophosphamide pulses and corticosteroids. Remission of the most SLE symptoms and a release of laboratory findings were achieved, but in the next year a diagnosis of antiphospholipid syndrome was made due to a recurrent deep vein thrombosis and a high titer of the IgG anti-cardiolipin antibodies. A long-term antithrombotic therapy with varfarine was introduced. Except for suffering of polyarthritic symptoms, she was doing acceptably well during the next 15 years.
At age 28, laboratory investigation revealed in addition to positive antinuclear antibodies positive anti-dsDNA antibodies in low titer of 0.45. At age 39, a skin biopsy revealed positive lupus band test and cyclosporin A was introduced although her urinalysis and serum creatinine were normal. For a short period of time, she became hypertensive, but after a withdrawal of cyclosporin A due to its side effects she remained normotensive throughout the time of clinical observation.
At age 40, antinuclear antibodies (1:640), ENA (HTE1), anti-dsDNA (0.86), IgG anticardiolipin antibodies (>30) were found positive and cyclosporin A was replaced with methotrexate, but shortly stopped because of its side effects. Chloroquine 250 mg per day was introduced and she received in 5 years this drug in a cumulative dose of 450 g. She was feeling fairly well during this time and her joint swelling and pain were reduced. The laboratory parameters of inflammation (SR, CRP) were low. However, at age 45, during the last few months, she complained about fatigue and myalgias. Laboratory testing showed increased serum creatinine 152 mol/L, reduced creatinine clearance 0.4 ml/s, proteinuria of 0.25 – 0.5 g per day, mild erythrocyturia and leukocyturia. ARA criteria for SLE were not fulfilled at the time of her second kidney biopsy.
Fig 1: First kidney biopsy, Fig 2 & 3: second biopsy
Only snapshots available
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Diagnosis & discussion |
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Case 3
Presented by: Helen Liapis
Clinical History
A 12-year old girl presented to a pediatric nephrology clinic after proteinuria was detected during a routine sports physical. Her past medical history was significant for asthma, eczema, recurrent otitis media and environmental allergies to cats and trees. Her medications included polyhistine, Ventolin inhaler, and Vanceril. The patient had no history of edema, gross hematuria, hypertension, hearing loss, joint problems or rashes. Her family history was significant for asthma and environmental allergies as well as end stage renal disease as a complication of diabetes in a maternal uncle.
Physical examination was largely unremarkable. Her vital signs included a blood pressure of 128/90 and pulse of 76. The patient had a height and weight of 168.5 cm and 70.2 kg, respectively (>95th percentile for both height and weight; BMI of 24.6 kg/m2). Her lung examination was significant for diffuse wheezes and slightly prolonged expiration. Her cardiac examination was without murmurs and she had no peripheral edema. Her abdomen was non-tender without masses. The patient did not have any lymphadenopathy.
In-clinic urinalysis revealed 4+ proteinuria and trace blood. Previous urinalysis had revealed 3+ proteinuria. Serum creatinine was 0.8 mg/dL. 24-hour urine collection revealed 1.8 grams of total protein with a creatinine clearance of 159 ml/min/1.73m2. Renal ultrasound showed increased bilateral renal echogenicity with diminished corticomedullary differentiation consistent with medical renal disease. Kidney size was not enlarged (right kidney: 48 x 115 x 51 mm, left kidney: 50 x 110 x 51 mm). The collecting system and ureters were not dilated. Renal biopsy was performed.
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Diagnosis & discussion |
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Case 4
Presented by: Laura Barisoni
Clinical History
An 18 month old patient presented with periorbital and lower extremities edema. At that time he had proteinuria > 10 g/day, serum cholesterol > 500 mg/dl and albumin < 1.5 g/dl. Serology was negative for Hepatitis B virus, Hepatitis C virus, EBV, HIV, and parvovirus B19. The patient’s parents are from Romania and non consanguineous. Parents and a brother are all healthy.
The patient was treated with Prednisone 2.3 mg/kg/day, diuretics and infusions of albumin. After four weeks of therapy, his edema increased and he developed anasarca. ACE inhibitors were added to the therapy and a renal biopsy was performed. Because of severe unremitting proteinuria, the patient underwent nephrectomy. Both, biopsy and nephrectomy specimens were sent in consultation and for additional studies to the Nephropathology Laboratory at NYU.
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Diagnosis & discussion |
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Slide 5a1 |
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Slide 5a2 |
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Slide 5b |
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Slide 5c1 |
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Slide 5c2 |
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Case 5
Presented by: Eva Honsova
Clinical History
A 19-year-old woman was admitted to the hospital for oliguric acute renal failure. The patient had been in excellent health until five weeks earlier, when she began to have respiratory symptoms with tonsilitis that was weakly responsive to antibiotics. During ATB therapy she suffered from nausea and vomiting, and one-day diarrhea. At the same time, she began to have mild arthralgias and weakness. The physical examination was normal except peripheral edema. There was no fever, lymphadenopathy or rush. No complaints of dysuria. Her blood pressure was 125/80 mm Hg. She took no chronic medication, except birth control pills during the previous year.
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Diagnosis & discussion |
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Case 6
Presented by: V. Nickeleit and M. Latour
Clinical History
The patient is a 71 year-old woman with a history of smoking and “chronic pulmonary disease”. Aged 62 at an outside institution she underwent a left nephrectomy for a renal cell carcinoma (clear cell type) and subsequently presented at age 68 with “advanced” abdominal metastases (jejunum, mesentery, one mesenteric lymph node). Surgical intervention resulted in incomplete tumor resection. No additional therapeutic intervention was tried (i.e. no chemotherapy and no radiation) until at age 69 when treatment with “Sunitinib” (Sutent/SU11248), a tyrosine kinase inhibitor with receptor inhibition of VEGFR and PDGFR was initiated. At this time renal function tests of the right kidney were within normal limits and the patient’s blood pressure was well controlled. The treatment was given in cycles, each cycle consisting of 28 days followed by 15 days without medication. Altogether 10 cycles were administered that resulted in complete tumor regression the next year. However, under Sunitinib therapy, in particular during the 28 days of the treatment cycles with Sunitinib administration, the patient rapidly developed severe hypertension requiring additional antihypertensive therapy with multiple drugs (Hydralazine, Clonidine, Spironolactone, Metropolol and Toxazosin). The same year she presented with new onset severe nephrotic syndrome including anasarca and pleural effusions. Proteinuria (3.4gm/24 hours) was associated with mild renal dysfunction, i.e. an increase in serum creatinine up to 1.5mg/dl. The urine sediment was bland and all serologic work-ups including ANA and ANCA tests were within normal limits. There was no evidence of an infection. A diagnostic renal biopsy was performed in order to determine the cause of the proteinuria.
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Diagnosis & discussion |
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Case 7
Presented by: Ingeborg Bajema
Clinical History
A 58 year old male
Nephrotic syndrome, proteinuria: 39 mg/L; oedema: +++, blood pressure: 130/55
Serum creatinine: 80, clearance: 90 ml/min
urine sediment: some erythrocytes, no leucocytes
ANF and ANCA: negative
A renal biopsy was performed.
In the accompanying files, immunofluoresence for IgG is shown, and EM
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Diagnosis & discussion |
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Case 8
Presented by: Eva Honsova
Clinical History
A 31-year-old woman had been suffering from diabetes mellitus type I since the age of 16. Because of severe organ complications of DM, she underwent cadaveric kidney-pancreas transplantation at age 23.
She had been immunosuppressed with Tacrolimus and Mycophenolate Mofetil. The patient had a histologically verified episode of acute rejection of the pancreas on the 15th day after transplantation (grade II, using Drachenberg’s criteria) and was treated with steroids with good response.
During the following 3 years she was treated for repeated urinary tract infections. She was admitted to the hospital for the same complaints at age 25.
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Diagnosis & discussion |
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Case 9
Presented by: Heinz Regele
Clinical History
Patient H.H., male, 64 years old at time of biopsy
Native kidney disease: unknown, no Bx available
1st dialysis 1986
1st renal Tx in 1988
Tx failure in 1995 (chronic rejection and membranous glomerulonephritis)
Dialysis from 1995-1999
07/99: 2nd renal Tx, 95% PRA (panel reactive antibodies). Desensitisation treatment consisting of pre- and post-Tx immunoadsorption and additional induction therapy with ALG was started according to a local protocol.
The patient suffered from delayed graft function but could be discharged from the hospital at 3 weeks post Tx with SCr of 1,2mg%
12/2001: Tx-Bx (SCr 2,2mg%): Banff borderline lesion.
2003: increasing proteinuria, an allograft biopsy did not contain diagnostically adequate tissue.
02/2004: Tx-Bx performed during surgical intervention required for perirenal hematoma causing hydronephrosis and oliguria (patient is on oral anticoagulation (Cumarin) for atrial fibrillations)
Other clinical data at time of Bx:
SCr 4,9mg%
Proteinuria 7g/24h
Hepatitis C with high virus load
03/2004: Patient returns to dialysis
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Diagnosis & discussion |
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Case 10
Presented by: Eugen Mandache
Clinical History
A fifty-two year old female has received a donor kidney from a living relative, 7 months before the present biopsy was performed. The patient had a glomerulonephritis of unknown origin followed by renal failure and secondary hypertension.
After the transplant the patient was immuno-suppressed with Prograf and MMF.
During this treatment a slow rise of the serum creatinine value appeared (1.5 – 3 mg %) and the patient was suspected of a graft rejection. The patient had no proteinuria.
Three weeks after the kidney biopsy the patient died of pneumonia, although she was unsuccessfully treated with several antibiotics for 14 days.
Only snapshots available
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Diagnosis & discussion |
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