Category Archives: Nephrology

VA Ambulatory Report 10.4.17 – Nephrotic Syndrome

Thanks to Akshai for presenting an interesting case of a 41 yo F with subacute bilateral leg swelling found to have nephrotic syndrome in the process of being evaluated for the underlying cause.



  • Proteinuria can be broken into 4 causes: Overflow, glomerular, tubular, post-renal
  • When concerned about a glomerular process use your clinical findings and UA to help you determine if the picture is more consistent with nephritic vs. nephrotic
  • Nephritic Syndrome is often diagnosed with lab tests whereas nephrotic syndrome usually needs a biopsy to confirm the underlying cause
  • Treatment of nephrotic syndrome: ACEi/ARB for proteinuria, loop diuretic and salt restriction for edema, statin if hyperlipidemia does not resolve, warfarin if thrombosis.


What is the usefulness of BNP for lower extremity edema?

  • Breathing Not Properly Study: In a patient presenting with dyspnea a BNP cut off of > 100 can be helpful in determining heart failure over pulmonary cause of dyspnea
  • The ACC/AHA 2017 Focused Update gives a Class I recommendation for measurement of BNP in patients presenting with dyspnea, to support a diagnosis or exclusion of HF.
  • No studies have looked at BNP in a patient presenting with lower extremity edema as a predictor for heart failure
  • Can be elevated for a variety of reasons:  renal failure, cirrhosis, sepsis, anemia, stroke, OSA, PE and more.


Causes of Proteinuria (Forgive my powerpoint nephron drawing!)

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Nephritic vs. Nephrotic?

Disease of the glomerulus can be nephrotic or nephritic.  Use your clinical findings and UA to help you differentiate.

  Clinical Findings UA and urine sediment Findings Histology Findings
Mild Nephritic Asymptomatic microscopic hematuria and proteinuria

Occassionally gross hematuria

RBCs, dysmorphic RBCs, RBC casts

Mild proteinuria

Inflammatory lesions in less than one half of glomeruli
Severe Nephritic Edema


Renal Insufficiency

RBCs, dysmorphic RBCs, RBC casts

Heavy Proteinuria (>1.5g/day)

Diffuse glomerular disease
Severe Nephrotic Hyperlipidemia


Thrombotic disease

Heavy proteinuria (oftenr >3.5g/day)

Few casts or cells

Varies based on underlying cause


Nephrotic Range Proteinuria work-up for the PCP:

  • Send ANA, A1c, HIV, RPR, and Hepatitis serologies.
  • Refer to renal for likely renal biopsy.
  • Renal biopsy is often needed in adults whereas children are often treated with empiric steroids for presumed minimal change disease.


Treatment of Nephrotic Syndrome

  • Proteinuria
    • The degree of proteinuria is a predictor of renal failure. Treatment can reduce progression.
    • ACEi/ARBs – BP effects are immediate but proteinuria effects can take days-weeks
  • Volume Overload:
    • Due to sodium retention (not oncotic pressure from protein loss)
    • Diuretics; Slow diuresis to prevent hypovolemia, start with loop diuretics but may also need thiazide diuretics
  • Hyperlipidemia
    • Often reverse when underlying cause is treated and reversed
    • Most patients will need statin
    • Dietary modification does not help
  • Hypercoagulability
    • More common in membranous nephropathy
    • If thrombosis, treat with warfarin
    • Unclear if prophylactic anticoagulation benefit outweighs risks, practice varies amongst nephrologists
  • Treat underlying cause if identified


Hey everyone! Thanks to Luis for presenting a case of a middle-aged man with infectious symptoms and NSAID use who developed a complex renal picture of AKI, proteinuria/hematuria, white cell casts, and confusing hepatitis serologies. We touched on nephrotic syndrome and AIN.


Top Pearls:

  1. WBC casts usually indicate interstitial nephritis but can also represent glomerulonephritis.
  2. Only 3% of AIN patients have WBC casts in their urine. Eek!
  3. Only 10% of AIN patients have the classic triad of rash, fever, and eosinophilia.


For those who want more info:

WBC casts are insensitive, and also not totally specific, for AIN. Only 3% of AIN patients have WBC casts in their urine, and WBC casts can rarely represent glomerulonephritis even though we usually think of GN associated with RBC casts.

We have covered nephrotic syndrome a fair number of times in report this year. Check it out:

Also here is a prior discussion of causes of interstitial nephritis, also touching on low anion gap which came up today:

Additionally, the classic AIN triad of clinical manifestations is rash, fever, and eosinophilia. However, the incidence of each of these findings, as well as the full triad, is not very high:

Rash- 15%

Fever- 27%

Eosinophilia- 23%

Triad- 10%

Lastly, we talked about NSAID-induced renal dysfunction, which is reviewed here:

*Pearl: NSAID-induced AIN does NOT usually present with the classic manifestations noted above.




Have a great day everyone!


MOFFITT RENAL REPORT PEARLS 2/24/17: Myeloma Kidney!

Thanks to Dr. Gluck for presenting an interesting case of AKI on CKD, as well as megaloblastic anemia, who turned out to have newly diagnosed multiple myeloma! Pearls below:


Top Pearls:

  1. Renal biopsy is usually indicated to prove the association between myeloma and renal injury.
  2. Treatment of myeloma kidney is chemotherapy, steroids, hydration, and possibly plasmapheresis.


For those who want more info:

Multiple myeloma is a popular topic at Moffitt! Here are some previous blog posts:

Since this was renal report, let’s review myeloma kidney!

Kidney disease is one of the most common complications of MM due to a wide range of mechanisms and usually occurring in patients with large tumor burden.

In MM patients, AKI is most commonly due to light chain cast nephropathy, hypercalcemia, and nephrotoxic agents (e.g. NSAIDs). MM is also a cause of nephrotic syndrome!

Most patients with MM who have kidney disease undergo renal biopsy to confirm the association between monoclonal protein and kidney disease (some exceptions).

Treatment for AKI due to MM light chain cast nephropathy is chemotherapy and steroids, in addition to hydration, correction of hypercalcemia, and discontinuation of nephrotoxic agents (NSAIDs, ACEs, ARBs).

There is some data for plasmapheresis to remove light chains, which has shown a possible reduction in dialysis dependency among survivors, but this is controversial.

Dialysis indications are the same as in non-myeloma patients.




Have a great day everyone!



Osmotic Demyelination Syndrome

Thank you Teja, for presenting a case during our Renal Report today – a middle aged woman with post-operative hyponatremia. We discussed the basics of hyponatremia work-up/management, with an interesting discussion on osmotic demyelination syndrome.


  • Osmotic demyelination syndrome (ODS) is a very rare, but potentially fatal complication of overly rapid correction of hyponatremia.
  • Our brains start to adapt to hypotonicity/hyponatremia almost immediately, and this adaptation is complete in 2 days. Hence, in patients where hyponatremia has been present for > 2 days, slow correction of hyponatremia is critical in reducing the risk of ODS.

Osmotic Demyelination Syndrome

  • Why does it happen?
    • IMPORTANT to note that the brain begins to adapt to hypotonicity almost immediately after a fall in serum sodium, and the adaptation in complete within 2 days. This process is referred to as “cerebral adaptation to hyponatremia,” and includes processes such as loss of solutes from the brain cells, to allow for osmotic movement of water out of the cells. This is the brain’s mechanism to actively reduce cerebral edema that may occur in the setting of hyponatremia.
    • This cerebral adaptation to hyponatremia is what paradoxically leads to osmotic demyelination syndrome when hyponatremia is corrected too quickly. When hyponatremia is corrected (too quickly), the water leaves the brain cells by osmosis. These brain cells (that have already lost many of its solutes as part of their adaptation), cannot replace their osmolytes as quickly in response to the correction of hyponatremia. This leads to a rapid fall in brain volume, which results in demyelination.
    • Exactly how fall in brain volume leads to demyelination is unknown.
  • Risk Factors for Osmotic Demyelination
    • Risk increases with lower Na levels; majority of cases occur when initial Na concentrations are < 105 mEq/L
    • Duration of hyponatremia is important! Hyponatremia must have persisted for more than 1-2 days (enough time for brain to have adapted to hyponatremia).
    • Overly rapid rate of correction. Do not exceed correction rate of 6-8 mEq/L/day.
    • Alcoholism
    • Malnutrition
    • Liver disease
    • Concomitant hypokalemia
  • Clinical Manifestations:
    • Clinical manifestations are typically delayed for 2-6 days after overly rapid elevation of serum Na
    • Symptoms are often irreversible and include dysarthria, dysphagia, paraparesis, quadriparesis, behavioral disturbances, movement disorders, seizures, lethargy, confusion, disorientation, obtundation, and coma
    • When hyponatremia is corrected (too quickly), the brain volume shrinks in response à this rapid fall in brain volume results in demyelination. Exactly how this occurs is not completely understood.



Evernote Link:

Moffitt Renal Report Pearls 1/13/17: Metabolic Changes Following Urinary Diversion


Today we discussed the case of an elderly man with history of CAD and prostate cancer who developed AKI and non-gap metabolic acidosis following his ureteroileal anastomosis. We learned a lot about metabolic derangements following a urinary diversion!


  • Diarrhea is quite a common symptom following urinary diversion (due to diminished bile salt and fat absorption)
  • Hyperchloremic metabolic acidosis is encountered in almost all patients that undergo urinary diversion
  • In patients with CKD, bicarbonate replacement is used to both 1) mitigate the extra-renal manifestations of metabolic acidosis; and 2) slow the progression of CKD. We usually target a bicarb level of > 20.


Metabolic Changes of Urinary Diversion

Bowel Dysfunction/Malabsorption

  • Diarrhea is one of the main reasons for diminished quality of life after urinary diversion.
  • Resection of ileum results in diminished bile salt and fat absorption à Fat malabsorption leads to steatorrhea à bile salts reach the colon and act as irritants, causing diarrhea

Acid Base Abnormalities

  • Hyperchloremic metabolic acidosis is encountered in all patients that undergo urinary diversion, and 10% of patients with ileal conduit have clinically important metabolic acidosis at 1 year.
  • Mechanism: In the bowel, Na is secreted in exchange of hydrogen, and bicarbonate is secreted in exchange of chloride. In parts of bowel that are exposed to urine à H+ and Cl- are re-absorbed à resulting in hyperchloremic, metabolic acidosis
  • Alkalinizing therapy with oral bicarbonate is effective in treating acidosis
  • Note, hypokalemia, hypocalcemia, and hypomagnesemia can also occur due to both intestinal & renal losses

Calculi Formation

  • Incidence of renal stone formation increases in patients with intestinal urinary diversion! Presence of hyperchloremic metabolic acidosis results in calcium phosphate and/or calcium oxalate stone formation.


Renal Dysfunction

  • Main factors that impair renal function after urinary diversion are ureteral obstruction (stenosis), recurrent infection, and urinary lithiasis



Moffitt AM Renal Report Pearls 12/2/16: Membranous Nephropathy

Today, we discussed the case of an elderly man with remote history of treated TB, who presented with new nephrotic syndrome. We had an interesting discussion on approach to nephrotic syndrome in general, with a specific emphasis on membranous nephropathy.



  • Like many other etiologies of nephrotic syndrome, membranous nephropathy (MN) can be divided into primary versus secondary MN
  • Patients with primary MN have a more precipitous onset of symptoms, whereas secondary MN patients have more insidious onset of symptoms.



Membranous Nephropathy (MN)

  • MN is one of the most common causes of nephrotic syndrome in non-diabetic adults.
  • MN can be divided into primary (idiopathic) or secondary.
  • Most commonly, MN is primary (75% of cases).
    • There are epitopes that have recently been discovered to be associated with primary GN (Thanks Chi, for sharing these with us):
      • Phospholipase A2 receptor: transmembrane receptor highly expressed in glomerular podocytes and is a major antigen in human idiopathic MN
      • Thrombospondin type-1 domain-containing 7A (THSD7A): another transmembrane protein expressed on podocytes
      • Neutral endopeptidase (NEP): associated with rare antenatal form of MN
  • Secondary MN can be caused by many causes – drugs (gold, penicillamine, NSAIDs), SLE, malignancy (colon ca), HBV, HCV, thyroiditis, Syphilis, etc.
  • Clinical manifestations: Most patients with MN (~80%) present with nephrotic syndrome. Remainder are diagnosed with MN after evaluation for asymptomatic proteinuria.
  • Treatment
    • General therapeutics for nephrotic syndrome: diuresis, angiotensin inhibition, treat hyperlipidemia, supportive care
    • Specific therapies for primary MN: – majority of patients will undergo spontaneous remission with supportive care alone! – For those with progressive disease, can use: cyclophosphamide, cyclosporine, tacrolimus, rituximab, etc (per discussion with Nephrology)


See these prior Moffitt pearls on nephrotic syndrome:


Evernote Link:


MOFFITT RENAL REPORT PEARLS 11/18/16: V-fib Arrest and Renal Failure!

Hi Everyone! Thanks to Rabih for presenting the case of a young man with sudden V-fib arrest and anuric renal failure. It was unclear whether pre-existing CKD might have contributed to his cardiac arrest or if all of the renal injury was a consequence of the arrest. Pearls below!


Top pearls:

  • Think about sudden cardiac death in terms of structural and non-structural cardiac causes, as well as non-cardiac causes.
  • Structural: HOCM, DCM, valve disease, scar, congenital coronary abnormalities
  • Non-structural: Ischemia, channelopathies (QT, Brugada), myocarditis
  • Non-cardiac: PE, intracranial hemorrhage, medications/drugs


For those who want more info:

See these pearls from earlier in the year about sudden cardiac death in a young patient and ARVD:


The most common cause of renal injury after cardiac arrest is ATN due to renal hypoperfusion. In this case, there was a suggestion that the patient may have had pre-existing CKD.

We also discussed some congenital abnormalities that could lead to cardiac and renal problems:

  • LCAT deficiency
  • Fabry disease
  • Tuberous sclerosis


LCAT deficiency (autosomal recessive) leads to very low HDL, severe corneal opacities (“fish eye syndrome”), normocytic anemia and target cells on blood smear, as well as proteinuria and CKD. Premature CAD can result but is unusual.

Fabry disease (X-linked recessive) is the 2nd most common lysosomal storage disease (after Gaucher disease). Defect is in alpha-Gal A which results in accumulation of Gb3 within lysosomes in the vascular endothelium and smooth muscle, renal cells (glomerular, tubular, and interstitial), as well as cardiac muscle cells and conduction fibers (among others). Severe neuropathic pain and telangiectasias/angiokeratomas are commonly seen early in life. Cardiac, renal, cerebral, and dermatologic involvement is common in adulthood.

Tuberous sclerosis (autosomal dominant) is caused by mutations in TSC1 or TSC2, usually characterized by benign tumors in multiple organs and skin manifestations. Most have epilepsy and cognitive deficits. Benign cardiac rhabdomyomas and renal angiomyolipomas are common. CKD in the absence of renal tumors is possible, even progressing to ESRD.



Have a great day everyone!