This morning we welcomed Dr. Dena Rifkin, nephrologist extraordinaire, to discuss the limitations of serum creatinine and the use of Cystatin C as an alternative for the estimation of renal function. We started by considering a 59-year-old man that presented to primary care clinic to discuss an elevated Cr to 1.43 (eGFR of 46). There was no clear sign of personal risk factors for CKD, although he occasionally used Ibuprofen and had a family history of Type II Diabetes and Hypertension. He had no microalbuminuria and his Cr was stable compared to three years prior. We obtained a Cystatin C level that indicated an eGFR of 82.
We then discussed why serum creatinine needs to be interpreted within the context of the patient’s physiology and how estimation calculators (including the preferred CKD-EPI equation) make adjustments for age, race, and sex. Cystatin C is an alternate biomarker produced by all nucleated cells that is freely filtered by glomeruli that avoids those problematic corrections. Cystatin C allows for increased detection of GFR reductions in the “creatinine blind range” where large changes in GFR are not reflected by substantial changes in GFR. Caution needs to be exercised when using Cystatin C in inflammatory states (infection, malignancy) and obesity as those will create higher levels of the protein. We then went through three patient cases that demonstrate the discrepancy in eGFR when using serum Cr versus CysC.
Cystatin C is available with rapid turnaround times at both the VA and UCSD – use it today!
Tuesday morning report at the VA was all about diuretics. We presented a case of a 73-year-old man with history of CHF, CKD and T2DM who presented with progressive dyspnea, bilateral lower extremity swelling, orthopnea, and abdominal distension. Physical exam showed evidence of volume overload with 3+ pitting edema, elevated JVD, and bibasilar pulmonary crackles. We considered various common triggers of heart failure exacerbation before diving into a discussion of diuretics.
Key points that we highlighted:
Decongestion with resolution of symptoms and edema is achieved through “diuresis” = loss of sodium (natriuresis) + loss of water (diuresis). That is why sodium-limited diet is crucial in treatment of fluid overload.
Loop diuretics function as “threshold” drugs that need to achieve a sufficient concentration in order to work. The natriuretic threshold is higher in patients with acute CHF than in healthy persons. That is why hospitalized patients require loop diuretic doses that are higher than stable outpatient doses.
Loop diuretics exhibit a “ceiling” effect and doses above the ceiling will not increase the amount of natriuresis. Acute CHF shifts the relation between plasma diuretic concentration and sodium excretion to the right and reduces the “ceiling.”
Patients with chronic diuretic use develop post-diuretic sodium retention and decreased efficacy with each subsequent loop diuretic dose. That is why loop diuretics are dosed multiple times daily and why patients need a net negative sodium balance each day.
Chronic loop diuretic use leads to distal tubular hypertrophy and once maximum loop diuretic effect is reached, auxiliary diuretics are sometimes used (thiazide, aldosterone antagonists, carbonic anhydrase inhibitors). We discussed specific situations you may consider using these agents.
Ethacrynic acid is the loop diuretic of choice in patients with sulfa allergy.
For further reading, check out this review from the NEJM:
Ellison DH, Felker GM. Diuretic Treatment in Heart Failure. N Engl J Med. 2017 Nov 16;377(20):1964-1975.
Our amazing resident, Dr. Masih Barat, presented a case of an 88-year old woman with history of HTN and diet controlled T2DM who was prompted to come for evaluation of a low sodium value discovered on outpatient labs. History was notable for non-specific symptoms of subacute loss of energy, nausea, poor appetite, and increased forgetfulness (per family). She was euvolemic on exam and her labs showed a low serum osmolality (consistent with a true hypotonic hyponatremia) and low urine osmolality. This pointed to an ADH-independent cause of hyponatremia. Given her history, these findings led us to determine that food insecurity (“tea and toast” diet) was the cause of her low sodium. We continued the discussion by developing a diagnostic schema for hyponatremia. Thank you to our nephrologist extraordinaire, Dr. Joe Abdelmalek, for sharing clinical pearls and discussing the mechanism behind the body’s sodium and water physiology.
This morning we presented the case of a middle aged man with a history of DM2, CKD for whom the medicine service was consulted due to persistent hyperkalemia. The patient was found to have a notable normal anion gap metabolic acidosis. The patient’s medications and hospital course were reviewed, which were not suggestive of hemolysis, rhabdomyolysis, AKI, which led the team to start considering the possibility of hypoaldosteronism in setting of Type IV RTA. To do this, though we reviewed the different types of RTA and how they may differ on initial work up. We also discussed the Urine Anion Gap = UNa + UK – UCl, and how it is an indirect measure of NH4+ excretion. Very negative UAGs (-20-50) suggest a Type 2 RTA (promixal RTA) due to the preserved ability to excrete acid, which is indirectly reflected in Urine Cl-. Very positive UAGs (+20 and above) suggest either Type 1 (Distal) or Type 4 (Hypoaldosteronism), with the distinguishing factor being whether the serum potassium is elevated (Type 4) or decreased (Type 1).
We also discussed the etiologies of each of the RTAs:
The patient’s work up revealed very low plasma renin activity and low aldosterone, as well as a positive UAG. Presumptive diagnosis was Type IV RTA, which can be seen in renal insufficiency in context of DM. Given that the patient was not hypertensive, florinef was started, which successfully reduced the patient’s serum K from 6.1 to mid 4.
Take Home Points:
Non-gap acidosis work up should include review of the usual suspects including GI losses, acid loads, medications, but if not revealing may need to consider RTAs.
UAG can be helpful to distinguish different types of RTA, though need to be aware that unaccounted acid buffers (phosphate and sulfates) which accumulate in CKD may negate the diagnostic effectiveness of UAG.
Treatment of Type IV Hyperkalemic RTA consists of removal of any of the large group of offending agents, or treatment with mineralocorticoid replacement in settings of primary adrenal insufficiency or hyporeninemic hypoaldosteronism. Thiazide diuretics and/or loop diuretics, in lieu of mineralocorticoids, can be used in settings of concomitant HTN or CHF.
Thank you to Viet Nguyen (Renal Fellow) to helping with this challenging case!
Today, the help of our amazing discussant Dr. Tomaz Beben, we discussed the case of an elderly gentleman who had recently undergone renal transplantation and presented with asymptomatic hemoglobin drop picked up on routine lab monitoring. We used this time to discuss some of the unique aspects of transplant medicine including additional questions to ask in the history as well as a review of some common immunosuppression (IS) medications. Ultimately, our patient was ruled out for GI bleed, and his hemoglobin drop was attributed to several of his transplant medications!
Consider some of the unique features of transplant medicine including donor recipient CMV status, peri-operative complications, history of previous rejection, and changes to IS regimen.
Most transplants require an induction phase (usually in the OR) with high dose steroids or anti-thymocyte globulin to prevent acute rejection, followed by a maintenance phase (started POD #1) which usually stabilizes by 6 months post-op.
Most maintenance IS regimens will contain glucocorticoids (lowest-tolerable dose), a calcineurin inhibitor (tacrolimus, cyclosporine), and an antimetabolite (mycophenolate).
Keep in mind some of the more common IS meds and their side-effects: Tacrolimus can cause neurotoxicity (ask about tremor), AKI, HTN, and hyperkalemia. Mycophenolate can cause diarrhea and cytopenias.
Today at the VA for our Maputo Case Conference, Dr. Neal Jones presented a fascinating case of an elderly gentleman presenting with subacute URI symptoms and progressive gross hematuria. He was found to have an AKI, pulmonary infiltrates on CXR, and multiple large renal cysts on CT. The patient was also noted to have significantly elevated CRP and ESR. He was initially treated for suspected pneumonia and infected renal cyst, but after several days without improvement and a steadily increasing creatinine, the work-up for his hematuria revealed PR3/C-ANCA positivity. A subsequent renal biopsy demonstrated diffuse crescentic glomerulonephritis, consistent with rapidly progressive GN 2/2 GPA! Dr. Tomasz Beben, nephrologist extraordinaire, then walked us through the nuances of GPA diagnosis and management. Our patient ultimately demonstrated signs of renal recovery after receiving high-dose methylprednisolone, rituximab, and several sounds of plasmapheresis. Thank you Drs. Jones and Beben for a great case presentation and excellent discussion!
Take Home Points:
GPA is uncommon, but with a constellation of sinopulmonary and renal findings, it should always be on the differential.
In the past, the diagnosis of GPA was made exclusively by renal biopsy, but many nephrologists are moving towards treatment after confirmed PR3/C-ANCA positivity.
Patients with GPA require pulse dose and then prolonged steroid use. For severe cases, there is also a movement to use rituximab rather than cyclophosphamide as an adjunct to steroids based on similar outcomes and a better side effect profile. Plasmapheresis may also be considered in severe cases!
This morning, one of our fantastic third year residents, Dr. Pokala presented a case of a young male with a history of IVDU who presented with acute onset right sided hemiplegia and aphasia and was found to have what appeared to be a brain abscess on CT Head, with evidence of midline shift and uncal herniation. After initial attempts to reduce intracranial pressure with mannitol and hypertonic saline were unsuccessful in maintaining a durable response, the patient was taken for urgent craniotomy and abscess aspiration revealing Strep sanguinis. The patient’s subsequent ICU course was complicated by resistant hyponatremia, which we discussed.
Based on newer guidelines published in JASN in 2017, a new diagnostic algorithm for interpreting hyponatremia has made some significant changes to the way we think about working up this complicated electrolyte disturbance– namely, there has been some data to suggest that the use of volume status to service as a the primary arbitrator of etiology has been difficult to employ. The new guideline uses more objective criteria such as Urine Osm and Urine Na to help guide the diagnosis as well as early recognition of symptomatic acute hyponatremia as an entity that requires immediate intervention.
We also discussed the rationale of maintaining normo- to slight hypernatremia in neurocritical care settings to avoid the deleterious consequences of acute hyponatremia with regards to cerebral edema, possible herniation, risk of coma and seizure. We further discussed the etiologies of SIADH, of which include CNS disturbance, malignancy with ectopic ADH production, surgery and its associated pain afferent triggers, pulmonary processes, HIV infection, hypothyroidism, hypopituitarism, and a multitude of medications.
Finally, we discussed the treatment modalities useful in correcting hyponatremia secondary to SIADH, focusing on treating the underlying medical process, fluid restriction. In more severe cases, use of high solute intake through salt tabs, urea tabs, hypertonic saline, and/or loop diuretics to augment free water excretion can be helpful and effective strategies.
Thank you Kusuma for a fantastic teaching case, and thanks to Dr Tyler Woodell for his expert input and helping us make sense of a confusing, yet vital core medical concept!
Second year resident Mark Rolfsen presented an excellent case of hypertensive emergency that merited a work up for secondary hypertension. Our own Dr. Joseph Abdelmalek was on hand to discuss indications for a secondary hypertension work up including: resistant hypertension (persistently above goal on 3 drugs, including 1 diuretic), absent risk factors (age <30, non-African American, non-obese, no family history), hypertensive emergency, and concomitant hypokalemia with metabolic alkalosis.
We then discussed the differential for secondary hypertension and how measurements of aldosterone and renin (and more importantly their ratio) can help differentiate between primary hyperaldosteronism, renovascular hypertension and Cushing’s disease.
The patient was found to have an elevated aldosterone-renin ratio (ARR), which was concerning for primary hyperaldosteronism with a subsequent CT abdomen revealing multiple adrenal nodules. Dr. Rolfsen is following this patient in his primary care clinic and will be discussing adrenal vein sampling soon!
Today Dr. David Malinak, one of our fabulous primary care track PGY-3’s, lead us through a fascinating case of a man who had prior anoxic brain injury and was largely bedbound, who presented with weight loss, and altered mentation. In looking at his labs, we discovered he was hypovolemic on exam and among his laboratory derangements, he had a serum sodium of 170!
We went through our diagnostic schema for how to think about hypernatremia, specifically thinking about why patients might be water deficit out of proportion to water intake (and to a lesser extent, if they might have increased sodium intake ) with the help of our expert nephrology discussant, Dr. Mullaney. We also got information that he had polyuria (~7L loss daily!) with low urine sodium and low urine osm. Based on his clinical picture (being bedbound with poor PO intake) we were concerned about diabetes insipidus being the cause of his polyuria, as he was not primarily taking in excess fluids. In fact, he was not at all thirsty, which is concerning as usually hypernatremia >150 generally triggers a thirst drive in addition to activation of RAAS pathway and retention of water with ADH.
With test administration of DDAVP, this patient had correction of his polyuria as well as decreased sodium levels, leading to the final diagnosis of diabetes insipidus. It is important to note that you should not see hypernatremia like you would in this patient, unless there is an impaired thirst drive to prevent the polydipsia that usually accompanies the condition (adipsic DI in this case!) . This patient ultimately was discharged on DDAVP replacement therapy as part of his medication regimen. Dr. Mullaney also reminded us we do not have cautiously correct hypernatremia over the span of 24-48 hrs in adult patients (see attached article: https://cjasn.asnjournals.org/content/14/5/656), like we do in hyponatremia.
Thank you again, Dr. David Malinak for guiding us through an interesting case and to Dr. Scott Mullaney for his fabulous clinical pearls!
Third year resident and rising chief, Dr. Samantha Spilman presented a great case of metformin-associated lactic acidosis (MALA). We discussed the work up and differential of lactic acidosis. Most importantly, rule out the much more common Type A lactic acidosis due to either global or regional hypoperfusion. In this case, the patient underwent an exploratory laparotomy due to high suspicion for mesenteric ischemia (regional intestinal hypoperfusion). When this was negative, the next step was to think about the differential for Type B lactic acidosis (See diagrams below). After identifying MALA the cause, the patient was started on CRRT and was discharged home!
Our own Internal Medicine and Endocrinology graduate Dr. Schafer Boeder was on hand and discussed the need to consider the risk of patient’s developing lactic acidosis prior to starting patients on metformin (most importantly the risk for renal insufficiency). We also discussed the low incidence of MALA (4.3/100,000 patient years), which is compounded by the frequency of metformin prescriptions (>50 million/year) and mortality (45%).