renal Flashcards
suPAR
FSGS (80%)
independent predictors of cardiovascular disease
albuminuria and eGFR
most helpful in preventing contrast induced nephropathy
sodium bicarbonate
amyloid nephropathy
chronic inflammatory disorder plus proteinuria.
Rapamycin (Sirolimus) side effect?
hyperlipidemia.
glomerular diseases in kidney transplant recipients
IgA nephropathy:
– Most common type of GN worldwide and is the primary cause of renal failure in 20% of kidney transplant recipients.
– Recurrent IgA nephropathy is common after transplantation and recurrence rate reported for patients with renal biopsies for clinical symptoms ranged from 13–50%.
– Clinical manifestations are similar to primary IgA nephropathy and include microscopic hematuria, proteinuria and slow decline in renal function.
Focal and segmental GN:
– Primary FSGS has a recurrence rate of 20–50% after kidney transplantation leading to graft failure in 13–20% of patient in 10 years after kidney transplantation.
– Clinical manifestations of recurrent FSGS include early onset of massive proteinuria, usually within first year post-transplant, hypertension and graft dysfunction.
Membranoproliferative (Mesangiocapillary) GN:
– Both type I (with mesangial and subendothelial deposits) and type II (dense deposit disease) primary MPGN have high rates of recurrence after transplantation.
– Type I MPGN recurs in 20–50% of patients but recurrent disease is much more frequent in type II disease, and up to 80–100% of patients are affected.
– These patients usually present with nonnephrotic range proteinuria within the first year posttransplant and slowly declining renal function.
– Risk factors for recurrence include HLA-B8DR3, living related donors and previous graft loss from recurrence.
– There is no correlation between complement level and recurrence risk.
– Graft loss due to recurrence occur in 15–30% of patients after 5 years.
Membranous GN:
– Idiopathic membranous nephropathy(MN) recurs in 10–30% of patients after kidney transplantation.
– Recurrent disease should be differentiated from de novo MN, which is the most common de novo glomerulopathy in renal allografts.
– The disease is characterized by nephrotic range proteinuria.
– Mean onset time is approximately 10 months post-transplant as compared with the more insidious and later onset of symptoms in de novo MN, an entity thought to be related to chronic rejection.
– Graft failure from recurrence occurs in 10–15% of patients after 10 years.
The occurrence of post-bacterial acute glomerulonephritis on the other hand is rare in renal transplant patients. Though whether this is due to the fact that immunosuppressive therapy impedes the formation of antibodies or is simply due to under-reporting by transplant centers is unknown.
Autosomal dominant polycystic kidney disease
sensitivity of renal ultrasonography for the detection of ADPKD is 100%
Diagnostic criteria require two or more cysts in one kidney and at least one cyst in the contralateral kidney in young subjects(by age 30), but four or more in each kidney for subjects older than 60 years because of the increased frequency of benign simple cysts.
most common opportunistic infection to occur in renal transplant
after 6 months – Aspergillus – Nocardia – BK virus (polyoma) - get nephropathy (deterioration in renal function) – Herpes zoster – Hepatitis B – Hepatitis C
CMV usually occurs between 1-6 months.
Pneumocystis jiroveci also occurs between 1-6 months - more septic any may have CXR changes
membranous nephropathy
PLA2R
Causes of membranous nephropathy:
1) SLE- Class V lupus nephritis
2) Drugs- NSAIDs,penicillamine, gold.
3) Hepatitis B and C
4) Malignancy- solid organ tumors
5) Hematopoetic stem cell transplant and graft versus host disease
6) Kidney transplant
7) Syphilis
Investigations:
- ANA, serum C3, Hep B, Hep C serology
- FOB +/- colonoscopy if age >50
- Mammogram age >40
- PSa age >50
- CXR +/- CT Chest if high risk of lung cancer.
batter/gittleman/gordon/little
Gitelman syndrome = defect in distal tubule = thiazide
Bartter’s syndrome = defect in loop of Henle = frusemide
Liddle syndrome = increased number Na channel in collecting duct which results in increased sodium reabsorption and potassium excretion.
Gordon syndrome = effect is OPPOSITE thiazide or Gitelman’s
Types of transplant rejection
1) Hyperacute rejection:
– Rare. Occurs very early and is untreatable.
– Due to preformed antibodies. On table black kidney.
– Predictable by cytotoxic cross match
2) Acute rejection (up to 25%):
– Occurs early but treatable.
– T cell mediated vs Antibody mediated
– Diagnosis by biopsy
Pathology:
– T cell mediated:
– Cellular/ interstitial- tubulitis, infiltrate.Vascular/glomerular- endothelialitis
– Antibody mediated: PMNs, deposition of complement component C4d+
Differential diagnoses: – Volume depletion – ATN – Interstitial nephritis – Drugs: Calcineurin toxicity, Bactrim. – Obstruction – HUS – Infection with CMV, BK virus (beyond 4 weeks)
3) Chronic rejection (30%): – Occurs late. no specific treatment. – Unknown etiology. – Progressive renal dysfunction, proteinuria, hypertension. – Diagnosed clinically from biopsy
– DDX: GN, drugs, HT.
Management of acute rejection:
1) Obtain tissue diagnosis.
2) IV methylprednisone 500-1000 mg daily for 3 days.
3) Failure to respond is an indication for antibody therapy, usually with OKT3 or antithymocyte depleting antibodies.
4) +/- increase in Calcineurin inhibitor (only if levels subtherapeutic)
5) Plasma exchange, IVIG or Rituximab for antibody mediated rejection
6) Rescue: Refractory or recurrent rejection- use high dose Tacrolimus or MMF.
Practice Points:
– Clinical evidence of rejection is rarely characterized by fever, swelling, and tenderness over the allograft.
– Rejection may present only with a rise in serum creatinine, with or without a reduction in urine volume
– Diagnostic ultrasound is the procedure of choice to rule out urinary obstruction or to confirm the presence of perirenal collections of urine, blood, or lymph.
– Diagnosis of rejection is by renal biopsy.
– Calcineurin inhibitors have an afferent arteriolar constrictor effect on the kidney and may produce permanent vascular and interstitial injury after sustained high-dose therapy.
– Features to suggest calcineurin inhibitor toxicity include interstitial fibrosis, isometric tubular vacuolization, and thickening of arteriolar walls.
– Basically, if the biopsy does not reveal moderate and active cellular rejection activity, the serum creatinine will most likely respond to a reduction in dose.
Type of amyloidosis:
1) AL (light chain)-most common.
- Heavy chain is rare and is associated with multiple myeloma, plasma cell disorder and lymphoma.
2) SAA (Serum Amyloid A)- secondary to chronic inflammatory states
3) FA Familal Amyloidosis (autosomal-dominant disorder caused by deformities of transthyretin.)
amyloidosis
Clues to diagnosis of AL Amyloidosis:
– fatigue, weight loss, enlarged tongue, and easy bruising,hepatomegaly
– Presence of urine monoclonal protein.
– Kidney involvement -nephrotic syndrome with large amounts of non-light-chain proteinuria, and azotemia develops late in the disease course.
– Cardiac involvement- thickening of the septum resulting in heart failure and arrhythmias. (Digoxin is contraindicated)
– Peripheral nerve involvement-sensorimotor neuropathy.
– A bleeding diathesis also may be present.
Clues to diagnosis of AA Amyloidosis:
– History of chronic inflammatory disorders and chronic infection
– Often presents with chronic kidney disease, with hepatomegaly and splenomegaly.
– Macroglossia is not a feature and cardiac involvement is rare.
Detection of monoclonal immunoglobulin in serum, blood, or tissues differentiates AL amyloidosis from other forms of amyloidosis.
The presence of a serum or urine monoclonal protein and amyloid deposition seen on a tissue biopsy specimen is diagnostic of AL amyloidosis.
Treatment of AL Amyloidosis:
– High-dose melphalan plus high-dose dexamethasone
– Bone marrow stem cells transplantation
Treatment of AA Amyloidosis:
– TNF alpha blocker, improves the renal function in AA-type renal amyloidosis, as well as suppresses the inflammatory reactions in patients with rheumatoid arthritis.
Treament of FA Amyloidosis:
– Liver transplant is definitive therapy.
