Sorry for delay…better late than never! Thank you to Jill and Emily for presenting a fascinating case of middle aged man with hx of chronic wounds and HCV s/p presenting with foamy urine found to have nephrotic Syndrome, possibly membranous nephropathy based on tempo, demographics and history. Unfortunately patient left the hospital AMA prior to renal biopsy.
HH’s CRANKLES Nephrotic Syndrome Mneumonic: Blast from the past!!!
R – renal vein thrombosis
A – Amylodosis and paraproteinemias
N – MCG, FSGS, Membranous (unusual, but possible to have MPGN or IgA Nephropathy)
K – Kimmelesteil and Wilson nodular intercapillary lesions (Diabetes – most common cause world wide)
L – Lupus
E – Eclampsia
S – Secondary syphilis
Definition: > 3.5 g urine protein/day, hypoalbuminemia (< 3 g/dL), peripheral edema. Associated HLD and thrombosis can be present. Hypertension is more common in nephrotic syndromes.
Differential Diagnosis – see above
Other associated findings: acute kidney injury (not always), thromboembolism (renal vein thrombosis is found disproportionately in patients with membranous nephropathy), infection (due to urinary loss of immunoglobulins), proximal tubular dysfunction
Biopsy is often necessary to reveal the definitive diagnosis. (note this is in contrast to nephritic syndrome, which can be diagnosed with examination of the urine sediment and blood work: serologies). Interestingly, Richards, et al* found that in 28 patients with nephrotic range proteinuria, histologic information obtained via biopsy altered management in 24/28 cases (86%!!!)
Treatment: Diuretics (treat edema), Ace-inhibitor (proteinuria), statin (hyperlipidemia), anticoagulation (hypercoagulability)
In non-diabetics this accounts for up to 1/3 of cases of Nephrotic Syndrome. Especially common among white men.
Breakdown in primary vs secondary causes:
MN is most often primary (idiopathic), associated with the presence of anti-PLA2R antibodies (can be measured in serum); although, it has been associated with a variety of conditions, including hepatitis B antigenemia; autoimmune diseases (eg, lupus); malignancy; and the use of certain drugs such as gold and nonsteroidal antiinflammatory drugs (NSAIDs). MN may also be seen in conjunction with other glomerular diseases such as diabetic nephropathy and crescentic glomerulonephritis.
First pass work-up (per up-to-date)
- CMP + Albumin
- UA with examination of the sediment
- Protein/Creatinine ratio or 24 urine for protein
- Tests for hepatitis B & C & HIV
- Serum C3 and C4 complement levels
- In patients older than 50 years – serum free light chains (SFLCs) and serum protein electrophoresis (SPEP) with immunofixation
- Anti-PLA2R antibody (by enzy
- Based of risk if progression given low risk disease often spontaneously resolves without therapy (see link for more info).
- First-line immunosuppressive therapy consists of cytotoxic drugs (cyclophosphamide) plus glucocorticoids or a calcineurin inhibitor with low-dose or no glucocorticoid.
Intern Report Pearls
Virchow’s Triad – RF for clotting
- Endothelial damage
Phlegmasia cerulea dolens (painful blue edema) is an uncommon severe form of DVT which results from extensive occlusion (blockage by a thrombus) of the major and the collateral veins of an extremity.
Evaluation of Isolated Elevated PTT
- Inhibitor – factor 8 is the most common inhibitor
When concerned about an inhibitor order a mixing study – does not correct with mixing study.
Clotting & Bleeding – Causes
- Liver Disease
Management of Bleeding with Inhibitor
Give factor back or bypass cascade – PCC or FEIBA, Novo 7
Steroids – Prednisone 1 mg/kg per day
Rituximab or Cyclophosphamide
Acquired Inhibitor – Causes • Underlying Cancer
- Exogenous exposures
- Medication related
- Idiopathic – ~50% cases unknown cause