GN from the KSAP Flashcards
Causes of Drug Induced ANCA vasculitis
Numerous other drugs have been implicated as causes of ANCA vasculitis, including minocycline, levamisole-adulterated cocaine, and propylthiouracil.
27 year old - abdominal pain, bloody diarrhoea, fever, SOB, on diet eating raw foods
Schistocyes, low platelets. LDH up
- Eculizmab
- Supportive care
- Methylpred
- Platelet transfusion
- Plasmapheresis
Supportive care.
This is diarrhoeal HUS NOT TTP or atypical
Primary HUS = Atypical HUS (abnormalities of the alternative complement pathway = Can use eculizumab
Secondary HUS is attributed to an additional cause such as an infection (including STEC, HIV and Streptococcus pneumoniae), medications (including calcineurin inhibitors and chemotherapy), pregnancy, and stem cell transplant. Some patients who present with secondary HUS are later identified to have occult abnormalities of the alternate complement cascade. Treatment of STEC HUS is supportive, volume resusc and RRT if necessary
How frequently does ESRD occur in patients with HIV associated nephropathy, and how long is renal survival?
60%
40 months
What are the biopsy findings of HIV associated nephropathy?
Biopsy findings in HIVAN include glomerular capillary collapse, podocyte hypertrophy and proliferation, interstitial fibrosis and edema, and tubular microcystic dilation. Electron microscopy frequently reveals endothelial tubuloreticular inclusions (TRIs).
Risk factors for progression of membranous
High levels of proteinuria (>8 g/d), older age at onset (>50 years), baseline CKD, and male sex are independent risk factors for progression to advanced CKD.
Does diltiazem have an antiproteinuric effect?
Yes
Patient with anti GBM disease requires dialysis at presentation - and has crescents on her biopsy. Is she likely to improve or continue needing dialysis?
One of the largest cohort studies of patients with anti-GBM disease demonstrated that patients who required immediate dialysis and had 100% crescents on their kidney biopsy remained dialysis-dependent. Patients who presented with serum creatinine values <5.7 mg/dL were likely to have renal recovery. Patients with serum creatinine of >5.7 mg/dL but who did not require dialysis immediately had an 82% chance of renal survival at 1 year. Those patients who required dialysis on presentation, such as this patient, had a poor renal prognosis with only a small minority achieving dialysis independence.
What is the normal expected creatinine generation rate in a day?
The normal expected creatinine generation rate is 15–25 mg/kg per day, with rates in women and elderly people toward the lower end of this range.
Lupus nephritis patient - who had diffuse proliferative LN has more protein on dipstick and on uPCR
- Do you repeat uPCR in a fortnight
- Do a kidney biopsy
- Change her treatment
- Do a 24 hour urine collection
The accuracy of a UPCR depends on a steady excretion of both urinary protein and creatinine. UPCR has been found to be reasonably accurate for classification of CKD, but the correlation is weaker for glomerular diseases and particularly for lupus nephritis. Urinary protein excretion follows an hour-to-hour circadian rhythm, which can be influenced by diet, posture, and exercise, making a single mid-day UPCR vulnerable to error. The first morning void UPCR is thought to be the most reliable predictor of 24-hour excretion and is preferred over other, random collection times.
In addition, dilute urine samples (specific gravity <1.005) tend to overestimate urinary protein excretion, particularly when urine creatinine levels are <39 mg/dL. For these reasons, it would be prudent to confirm by 24-hour urine collection that the elevated UPCR in this patient actually represents worsening proteinuria. Repeating UPCR in 2 weeks would still be subject to the interpretation challenges outlined and would delay the evaluation.
Resuming prednisone or adjusting the mycophenolate mofetil dose may be necessary if a lupus nephritis flare is confirmed, but such a step should wait until an increase in proteinuria is confirmed by a 24-hour collection.
Because this patient was in complete remission, as defined by having proteinuria <500 mg/d, an increase in urine protein value would reasonably prompt another biopsy if the increased proteinuria were confirmed by 24-hour collection.
Which has a better prognosis - Immunotactoid or fibrillary GN?
Parallel arrays of microtubules with a diameter usually >30 nm are seen in immunotactoid GN. Patients with this disorder have a more favorable prognosis compared with that of fibrillary GN.
What is collagenofibrotic GN?
Collagenofibrotic glomerulopathy is a rare glomerulopathy with organized deposits. These deposits are composed of type III collagen. The pathognomonic finding is a transverse band pattern of fibrils approximately 60 nm in diameter on electron microscopy. Light microscopy shows a lobular appearance of glomeruli that can be confused with Kimmelstiel-Wilson nodules. Immunofluorescence is generally unremarkable. Pathogenesis of this disease is unknown.
Note distinction-
What size are tubules of collagenofibrotic GN
Cryoglobulinaemic GN
Collagenofibrotic GN - 60
Curved microtubules around 30 nm in diameter, often described to resemble a fingerprint pattern, are typical of GN related to cryoglobulinemia.
Amyloid (10) Fibrillary (15- 20) Immunotactoid ( >30) Cryoglobulinaemic are around 30 and Collagenofibrotic 60
MPGN on kidney biopsy related to hep C
MPGN related to hepatitis C (with or without cryoglobulins) is associated with the deposition of polyclonal immune complexes, and shows granular deposition of IgM, C3, and relatively equal kappa and lambda; IgG deposition is variable
Does treatment of Hep C always clear cryoglobulins?
It is important to note that because of independent B-cell proliferation, cryoglobulins can persist even after HCV has been eradicated by antiviral therapy. Treatment for cryoglobulinemia that persists or appears after antiviral therapy may include steroids, rituximab, and plasma exchange in severe cases.
What are the different types of cryoglobulinaemia?
Cryoglobulins are immunoglobulins that precipitate at a temperature lower than 37oC. There are 3 types of cryoglobulins, as shown below:
Classification of cryoglobulins
Type Composition Notes
I Isolated monoclonal immunoglobulin Composed of a single monoclonal immunoglobulin paraprotein (usually IgM), commonly caused by Waldenström macroglobulinemia, multiple myeloma, or chronic lymphocytic leukemia.
II Mixture of both a monoclonal component and a polyclonal component The monoclonal component is usually IgM that has rheumatoid factor activity and binds to either intact polyclonal IgG or a component of IgG fragment to form IgM-IgG complexes. Strongly associated with hepatitis C infection.
III Polyclonal IgG and IgM(no monoclonal component) Also has rheumatoid factor activity.May be associated with an autoimmune disorder or persistent infection such as hepatitis C.
Cryoglobulinemia can be asymptomatic or result in tissue damage from hyperviscosity (mainly with type I) or immune-complex mediated inflammation (mainly type II, strongly associated with HCV infection). Other associated conditions include infections, such as hepatitis B virus and HIV, and autoimmune disorders, such as Sjögren syndrome, systemic lupus erythematosus, and rheumatoid arthritis.
Renal manifestations of cryoglobulinemia may include hematuria, proteinuria, hypertension, and AKI. Hypocomplementemia, especially C4 depletion, and elevated rheumatoid factor are common. Blood cryoglobulin levels (sometimes referred to as the “cryocrit”) can be high, but reliable detection requires appropriate collection in pre-warmed syringes. The light microscopic appearance of a kidney biopsy specimen most commonly shows a membranoproliferative pattern, but may also show vasculitis, hyaline thrombi, and crescents. Immunofluorescence reveals deposition of immune complexes in the mesangium and subendothelium that are often IgM-dominant; electron microscopy may reveal substructure to the electron-dense deposits with a microtubular or fibrillary pattern.
