Category Archives: Nephrology

Moffitt Renal Report Pearls– 11.17.17

Thank you to HH and Katie for co-presenting a case of a young woman with T1DM, CKD presenting with a severe non-anion gap metabolic acidosis with a pH of 7 and a Bicarb of 6! Overall, it was felt that her initial presentation was 2/2 to a mix of GI losses given her profound diarrhea and renal losses of bicarb in early renal dysfunction.

Key Pearls:

  1. When calculating the serum anion gap, there’s no need to correct serum sodium for hyperglycemia. The osmotic pull of water would dilute all of the electrolytes in an equal manner, so the sodium, potassium, and chloride are all relatively dilute, and the anion gap calculation would not change.
  2. When trying to determine where a patient is losing bicarbonate – you can calculate a urine anion gap UAG – see more below.
  3. In a patient with normally functioning kidneys, they will secrete ketones in their urine. In patients with DKA, this can eventually result in a non-anion gap acidosis.
  1. Remember risk factors for central pontine demyelination with rapid correction > 10 in 24 hours include: very low sodium levels < 110 (in most cases), premenopausal females and severe malnutrition.

Urine Anion Gap (UAG)

Na +  K  –  Cl = Ur Anion Gap (this is calculating unmeasured anions NH4+ primarily)


  • Assumes that the patient is volume replete (Una > 20) and is without an anion gap acidosis
  • If UAG + in setting of non-gap metabolic acidosis this suggests the kidneys are FAILING to excrete ammonia à renal tubular acidosis
    • DDx: RTAs (see below)
  • If UAG zero or negative, suggests bicarbonate losses from GI tract (this means the kidneys are appropriately getting rid of NH4+ to compensate for acidosis).
    • DDx: GI losses (diarrhea or fistulas), early renal failure& ingestions
  • These labs must be interpreted in the context of patient’s presentation and there are not strict cut-offs.
  • Depending on the severity of the metabolic acidosis, if you have normal kidneys, the urine anion gap should be even more negative (kidney is responding appropriately to excrete NH4+).
  • If you have severe metabolic acidosis, and the urine anion gap is zero or only slightly negative, this suggests a mixed picture – in that there are GI losses, but the kidney’s are not responding as robustly as they should to get rid of NH4+. With excretion of NH4+ the CL- amount increases and this should drive the equation above more and more negative.

Non-Gap Acidosis Ddx

  • GI losses of HCO3- Diarrhea, fistulas/drainage
    • Proximal (Type II): decreased reabsorption & then loss of HCO3-
    • Distal (Type I): defect in H+ excretion (hence profound acidosis)
    • Hypoaldo (Type IV): acidosis 2/2 to inability to excrete acid
  • Early renal failure – impaired generation of NH4+ (this is the KEY to understanding the physiology per above)!
  • Ingestions – acetazolamine, sevelamer, toluene
  • Dilution – rapid infusion of bicarb free IVFs
  • Post-hypocapnia – Rapid correction of respiratory alkalosis -> renal wasting og HCO3 needs to be regenerated
  • RTAs
Location Type Acidosis UAG U pH FeHco3 Serum K
Proximal II Moderate +/- <5.3 > 15% LOW
Distal I Severe + > 5.3 < 3% Variable
Hypoaldo IV Mild + > 5.3 < 3% HIGH





Moffitt Pearls 10/30/17 – Palpable Purpura + AKI

Thank you, Lily for presenting a case this morning of a middle-aged woman from Mexico being treated for a metastatic GI malignancy p/w flank pain, AKI and palpable purpura found to have obstructive nephropathy and candiduria .

Key Pearls:

  1. Classic approach to AKI: pre-, intrinsic-, post-renal hold-up even when the patient becomes more complicated. Always remember to consider carefully a patient’s volume status and run the med list.
  2. The DDx for purpura can be broken down first by whether or not the lesions are palpable. If NOT palpable, we call these petechiae or ecchymoses based on the size (<3mm = petechiae). This should prompt consideration of the coagulation cascade, platelets, uremia. If palpable, this suggests inflammation and a possible vasculitis. See an approach to palpable purpura below.
  3. Yeast in urine is usually a colonizer and not a pathogen. However, treatment for funguria is indicated in patients with renal transplant and immunosuppression. See link for more info
Candiduria: A Review of Clinical Significance and Management – Zakeya Abdulbaqi Bukhary

Selected Highlights:

  • Treatment of Candida can be guided by in vitro susceptibility testing (although all labs do not send these).
  • Fluconazole gains high concentrations of active drug in the urine, is better tolerated and is less likely to be associated with the emergence of resistance during therapy.
  • The greatest concern for fluconazole resis­tance is related to C. glabrata and C. krusei isolates which require maximal doses of amphotericin B.
  • As HH mentioned – Echi­nocandin anti fungal agents (caspofungin, micafungin, and anidulafungin) can be used although low sub-therapeutic levels are achieved in the urine because the drug has poor glomerular filtration with subsequent diminished tubular secretion. 

More Info at:


Causes of Non-Palpable Purpura based on size of lesion

  • Remember these lesions are macular and are typically NOT inflammatory
  • Petechiae (small lesions < 3 mm)
    • Abnormal palatele function
    • Increased intravascular pressures
    • Thrombocytopenia
      • Idiopathic
      • Drug-induced
      • Thrombotic
    • DIC and infection
  • Ecchymoses (larger lesions > 5 mm)
    • Coagulation defects
    • DIC and infection (purpura fulminas)
    • External trauma
    • Hypergammaglobulinemic purpura

See the following link for more information in a case based ppt from the American Academy of Dermatology Titled “Petechiae, Purpura and Vasculitis.”

Break down Vasculitis based on vessel size



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!)

Screen Shot 2017-10-06 at 10.10.50 AM.png

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