Thanks to Dr. Wahba for walking us through his approach to hypercalcemia.
Images courtesy of Choksi P, UMichigan
We also talked about the milk-alkali syndrome (MAS). It was first described in the early 1900s after (Doctor) Sippy (what a great name) came up with a calcium-laden milk and antacid regimen for the treatment of peptic ulcers. The introduction of PPIs and H2 blockers in the 1970s caused a dramatic decline in its incidence, but recent years have seen a resurgence due to the widespread use of Ca carbonate and Vit D supplementation for osteoporosis. It is now thought to be the 3rd most common cause of in-hospital hypercalcemia, after hyperparathyroidism (#1) and malignancy (#2)!
“Old” MAS: middle aged men with GERD taking Tums
“Modern” MAS: older women with osteoporosis, ESRD patients or those on chronic steroids taking Ca/Vit D supplementation. Don’t forget unusual sources of calcium like nicotine gum; also betel nut chewers from East Asia (though obviously a rare population here in Philly)
Pathogenesis of MAS
- dietary input of calcium exceeds excretory capacity (thought to be >4-5g Ca/day, but varies widely)
- Alkalosis further decreases Ca excretion
- Ca leads to natriuresis and diuresis
- pre-existing renal insufficiency and failure to suppress calcitriol levels play a role
- Other meds play a role: NSAIDs, ACEIs, thiazides
The hallmarks of milk alkali syndrome are 1) hypercalcemia, 2) metabolic alkalosis and 3) varying degrees of renal failure. Note that these findings really exist on a continuum (acute, subacute, chronic)
Symptoms of MAS
Early signs: N/V, anorexia, distaste for milk, headache, dizziness, vertigo, apathy, and confusion
Chronic signs: myalgias, psychosis, tremor, polyuria, polydipsia, pruritus, and abnormal calcifications (band keratopathy, soft tissue, etc)
- A careful history identifying heavy calcium and alkali intake is key
- Lab findings: hypercalcemia (can be severe), AKI, metabolic alkalosis, low/normal phosphate, low 1,25-OH Vit D and PTH
- Supportive: treat hypercalcemia, stop calcium/alkali containing supplements, stop NSAIDs, thiazides and other offending meds
Medarov B. The Milk-Alkali Syndrome. Mayo Clin Proc 2009.
For this case, we discussed a 44 year old female who presented to the ED with flank pain, and on CT scan was found to have a unilateral renal infarct. She was discharged with no clear diagnosis and then re-presented a few days later with bilateral infarcts. On review of the scans, it was found that she had bilateral renal artery clots and further history revealed that she was taking increasing doses of sumatriptan for migraines. The most pertinent teaching points were:
- Not all flank pain is a UTI, and having a “positive UA” in the absence of infectious does not denote a urinary tract infection.
- Renal infarcts are a rare presentation, but are most commonly due to Afib. Published case series of patients with renal infarcts has yielded the below differential (although this is by no means all-inclusive), and standard work-up includes TTE, halter monitor, and renal artery imaging.
- Hypercoagulability work-ups are rarely indicated because they rarely change management. They are even more complicated if a patient is anticoagulated. I compiled a list of tests that are the most high yield to send if a patient is anti-coagulated and a work-up must be done. This is a very unique situation, and should be approached with caution.
- Triptans rarely cause non-trigeminal vasoconstriction, but have been implicated in a number of case reports of vasospasm in various organ systems (STEMI, CVA, Mesenteric Ischemia, Splenic Infarct). This should remain on your differential when evaluating patients who are taking Triptans for migraine.
Thanks to Dan Kim for giving a great talk (and to the audience of contributing lots of great learning points!) on a middle aged woman who presented with hypoglycemia after taking a dose of her sulfonylurea.
Recall that sulfonylureas work by inhibiting the ATP-sensitive potassium channel in pancreatic beta cells; this leads to increased endogenous insulin release. Long acting sulfonylureas (ie glyburide) are more likely than short-acting agents (glipizide, glimepiride) to cause hypoglycemia.
Symptoms of hypoglycemia; remember that it can mimic virtually any neurologic condition
When thinking about hypoglycemia, it helps to think in terms of whether the patient is ill-looking or not
- drugs (insulin or insulin secretagogue, alcohol, ?others)
- Sepsis/critical illness
- Hormone deficiency (cortisol, glucagon or epinephrine)
- Endogenous hyperinsulinism
- post-gastric bypass hypoglycemia
- antibodies to insulin or insulin receptor
- Surreptitious/factitious hypoglycemia
Sulfonylurea toxicity is generally a clinical diagnosis based on history. There are sulfonylurea assays that can be sent, but they generally take too long to result and are thus of limited use
Management of sulfonylurea toxicity
- D5 or D10 gtt
- should not be used as monotherapy for sulfonylurea toxicity, as it will cause transient hyperglycemia that triggers insulin release and further episodes of hypoglycemia
- works by decreasing insulin release from beta cells
- Give for the first 24h, and then stop; can restart if hypoglycemia recurs
- NB: very short acting, so should only be used as a temporizing measure while getting IV access or some other longer-acting source of glucose
Activated charcoal can be used within 2-3h of the ingestion, but hemodialysis has not been shown to be effective. Diazoxide, an older drug which also inhibits pancreatic insulin release, used to be used, but is less effective than octreotide and can cause hypotension.
We talked briefly about the threshold effect with loop diuretics:
The inflection point where the blue line takes off is the ‘threshold’, and is largely determined by the rate at which the diuretic gets to its site of action. HF patients show resistance at any given diuretic dose due to Na reabsorption at other segments of the nephron. Brater 1983.
Lastly, this study compared bolus vs continuous infusion of lasix in patients with ADHF, and found that there was no real difference between the two dosing strategies. However, keep in mind that this was part of a research setting, where even bolus doses were probably timed perfectly. In real life, doses may be given late (ie beyond the point that the previous dose is effective), so continuous diuretic infusion may still have a role in clinical practice.
- Oh S et al. Loop Diuretics In Clinical Practice. Electrolyte Blood Press 2015.
- Felker et al. Diuretic Strategies in Patients with Acute Decompensated Heart Failure. NEJM 2011.
- Brater DC, Day B, Burdette A, et al. Kidney Int 1984; 26:183.
Today we were joined by faculty expert Dr. George to discuss a case of scleroderma renal crisis. We spent some time discussing hypertensive emergency, which was this patient’s initial presentation — that has been addressed in earlier blog posts so we will focus on the diagnosis of scleroderma renal crisis (SRC) in this post.
There are three major diagnostic considerations for scleroderma renal crisis in a patient with signs or symptoms of scleroderma:
- abrupt onset of moderate/severe HTN (from increased plasma renin activity)
- NOTE: approximately 10% of patients are normotensive when presenting with SRC, so do not completely dismiss this dx from your differential in a normotensive patient! They have a worse prognosis than hypertensive patients, possibly due to delayed recognition and treatment!
- Acute kidney injury
- Urinalysis is usually unremarkable, though may have a few cells/casts and mild proteinuria
Scleroderma renal crisis is thought to be caused by pathology in the renal vasculature, specifically intimal proliferation and thickening that leads to narrowing and obliteration of the vascular lumen. Some people suggest conceptualizing this as a similar pathophysiologic process to bilateral renal artery stenosis.
- Almost always occurs within 5 years of onset of scleroderma
- Diffuse systemic sclerosis (much more common than limited)
- Glucocorticoid use (especially doses >15mg prednisone daily)
- Rapid progression of skin involvement
- Positive RNA polymerase III antibody
- NOT risk factors: pre-existing HTN, elevated Cr, or abnormal UA
In patients diagnosed with scleroderma, it is recommended to perform frequent BP checks (daily if high risk) and further workup if sustained increase in SBP >/20 or DBP >/ 10. They should also have urine dip and Cr checked every 3 months.
ACE Inhibitors are the mainstay of treatment in SRC. There have not been randomized controlled trials to support this treatment, but several observational studies noted improved outcomes. ACE Inhibitors should be initiated immediately, and usually captopril is used during inpatient treatment due to rapid effect and ability to titrate quickly.
All patients with SRC should be on lifelong ACE inhibitor therapy, even patients who present normotensive or those who go on to have improvement in renal function and HTN. Long acting formulations can be used for better adherence.
Many patients will require transient or permanent renal replacement therapy. Some will go on to get renal transplants, although other systemic manifestations of scleroderma can be contraindications. The grafts do not survive as well as in other indications for renal transplant.
We discussed an elderly woman with ESRD who presented with progressive abdominal pain, distention and fevers and was diagnosed with PD (peritoneal dialysis-associated) peritonitis, which was ultimately found to be due to TB!
What is peritoneal dialysis?
In the simplest terms, PD involves the instillation of dialysis fluid into the peritoneum with the goal of achieving solute clearance and ultrafiltration across the peritoneal membrane.
Dialysis fluid ‘dwells’ in the peritoneum while solute and volume move into it; it is then removed via the peritoneal catheter at the end of the dwell
There are three specific infectious complications of PD catheters: 1) PD peritonitis, 2) tunnel infection and 3) exit site infection
The microbiology of PD peritonitis differs somewhat from spontaneous bacterial peritonitis (SBP).
Microbiology of PD peritonitis. Glickman 2017
- NB: unlike SBP, where >250 PMNs or a +culture is necessary for the diagnosis, about 10% of patients with PD peritonitis present without >100 WBCs, so it’s important to have a high suspicion for it
- It’s often a difficult decision as to whether to try to preserve the catheter or to pull it. In general, fungal, mycobacterial and pseudomonal peritonitis necessitate catheter removal.
- You can try to treat through other forms of bacterial PD peritonitis, unless it’s a recurrent or refractory infection
- Recurrent episodes of peritonitis can make the abdomen less hospitable to PD, and can even lead to the development of peritoneal sclerosis, which may lead to small/large bowel obstruction, constipation, malnutrition and death
This patient ultimately had her peritoneal fluid tested for adenosine deaminase (ADA) given the concern for TB. A few quick notes:
- It can be used to distinguish between tuberculous and malignant causes of lymphocytic pleural effusions/ascites, etc.
- Test characteristics vary somewhat between different body sites, but for tuberculous ascites, ADA (particularly values >35) has a ~95% sensitivity and 96% specificity, a positive likelihood ratio of ~16 and a NLR of 0.09!
- Akoh JA. Peritoneal dialysis associated infections: An update on diagnosis and management. World J Nephrol 2012.
In a delayed posting — I’d like to thank Lindsey Haddock for her excellent lecture on CKD Complete with picture-worthy whiteboard drawings!
Lindsey started off her overview highlighting the various stages of CKD and the importance of referring to nephrology when patients are stageIIIb (GFR 30-44) so that they can begin the vascular workup/preparations for dialysis.
Next Lindsey tackled WHY patient’s get CKD with Hypertension and Diabetes taking the largest piece of the etiology pie at 30% and 45% respectively.
Importantly we reviewed the work up necessary and appropriate treatments/screening needed for the various sequelae of CKD including anemia, mineral bone disease and metabolic acidoses.
Thanks again for a great lecture Lindsey — always proving that a picture is DEFINITELY worth a thousand words.
Today we discussed a case of acute kidney injury and proteinuria in a patient with well-controlled HIV, who was ultimately diagnosed with IgA nephropathy. It is important to remember that patients with well-controlled HIV have pretty much the same differential for glomerular disease as the general population.
In general, we classify glomerular diseases based on whether all glomeruli (diffuse) or only some (focal) are involved, and within each individual glomerulus whether the entire unit (global) or only part (segmental) is effected.
There are two broad syndromes of glomerular disease: nephrotic syndrome (which is characterized primarily by proteinuria >3.5 g/day) and nephritic syndrome (glomerular inflammation). Urinalysis findings of erythrocyte casts or dysmorphic red cells have a high specificity for glomerular pathology, which can also be suggested by hematuria and proteinuria.
Nephrotic syndrome can be a primary glomerular pathology, or it can be secondary to a systemic disease process (infectious, malignant, or medication-induced). Here is a basic differential for nephrotic syndrome:
- Minimal change disease
- Focal segmental glomerular sclerosis
- Membranous glomerulopathy
- Diabetic nephropathy
Nephritic syndrome can be conceptualized based on mechanism of disease into three categories – pauci-immune (minimal immune cell infiltration), immune complex deposition, and anti-glomerular basement membrane antibody-mediated.
Pauci immune: seen in vasculitis (MPA, GPA, eGPA)
Anti-GBM antibodies: can have pulmonary manifestations (Goodpasture’s syndrome). Inherited collagen IV disorders can also effect renal function.
Immune complex deposition
- IgA nephropathy
- SLE nephritis
- Infection-related glomerulonephritis
- Membranoproliferative glomerulonephritis
In our patient, renal biopsy made the diagnosis of IgA nephropathy!