Concept Map: Cholesterol Embolic Renal Disease

 

Based on a recent study published by Jain et al. 

Consult rounds: Hyperammonemic encephalopathy in the setting of myeloma

Can paraproteinemia cause an elevated ammonia level?

While liver disease and certain medications are known to cause hyperammonemia, myeloma is a rare cause of hyperammonemia. One of the first cases published on this topic was back in 2002 in NEJM.

Here are some cases published in the literature.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891795/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891795/

https://www.amjmed.com/article/S0002-9343(03)00630-2/fulltext

https://diagnosticpathology.biomedcentral.com/articles/10.1186/s13000-022-01285-6

https://pubmed.ncbi.nlm.nih.gov/35871579/

 

 A retrospective study shed more light. In this study of individual patients diagnosed with ammonia related disease from myeloma was evaluated( 27 patients), interesting findings were noted. The mean age was 76 years with a 5:1 male-to-female ratio. All had stage III based on the International Staging Scale (ISS). Bone marrow biopsies demonstrated 54–98% (mean 69%) plasma cell infiltration. IgA subtype was the most common. The mean ammonia level was 113 umol/L. No intracranial processes were detected on imaging. Three patients had improvement in mental status and decreased ammonia levels after chemotherapy; the other three patients declined further interventions. Inpatient mortality was over 66%. 

    The authors also did a MEDLINE search revealing 20 articles originating from the United States and Japan detailing a total of 32 patients who were diagnosed with myeloma induced hyperammonemic encephalopathy. The mean age was 52 years  with an equal distribution between men and women. The average ammonia level amongst these patients was 121 umol/L with as high as 299umol/L.  All these patients had stage III disease by the ISS or the Durie-Salmon system. IgG was the most common subtype at 44% (n=12), followed by IgA with 37% (n=10), light chain multiple myeloma with 11% (n=3), and IgD with 7% (n=2). Of the 25 patients that received chemotherapy, 15 (60%) survived until discharge. The inpatient mortality was 40% (n=10). Those patients who did not receive chemotherapy had a lower rate of survival at 25%.

Some studies report beneficial effects in using hemodialysis to remove excess ammonia. Several others suggest that the initiation of aggressive chemotherapy is the most effective measure to achieve normal ammonia levels and clinical improvement.  Mechanism of this association is still unclear. 

It is important to consider myeloma as a cause of hyperammonemia.

Consult Rounds: Differential Diagnosis of Asterixis

 The differential diagnosis of asterixis is important for a Nephrologists- It is not always Uremia...

Metabolic causes-- Uremia, Liver failure and hypercapnia 
Neuro drugs--Anticonvulsants, Benzos-- classic is phenytoin, carbamazepine, gabapentin, valproic acid, lithium
Antibiotics-- Cefepime, and other cephalosporins
Electrolyte disorders-- Hypomagnesemia, hypokalemia( never seen it there)
Bilateral brain lesions
**Unilateral brain lesions cause unilateral asterixis

Topic Discussion: As needed anti HTN meds in the hospital- can we stop the madness?

 

We often see in the hospital, BP is treated as needed. Often, as nephrologists we have suggested to NOT do this. Outpatient problem that exists for years cannot be corrected in 2 hours by hydralazine or beta blockers so that the "vitals" look good and " numbers" are good for rounds. A recent study published in Hypertension nicely showcases this via a retrospective propensity matched protocol. When compared to scheduled BP meds patients to Scheduled meds and PRN patients ( over 4000 each), risk of AKI, stroke and mortality was higher in the as needed group. In addition, length of stay was higher as well. 

This comes following another recent article in JAMA looking at a similar concept. Among 22,000+ patients studied in hospitals with non cardiac diagnosis, hypertension was treated as needed in several patients.  In a propensity-matched sample controlling for patient and BP characteristics, treated patients had higher rates of subsequent acute kidney injury (466 of 4520 [10.3%] vs 357 of 4520 [7.9%]; P < .001) and myocardial injury (53 of 4520 [1.2%] vs 26 of 4520 [0.6%]; P = .003). There was no BP interval in which treated patients had better outcomes than untreated patients. A total of 1645 of 17 821 patients (9%) with hypertension were discharged with an intensified antihypertensive regimen. Treating with intensification of anti HTN meds without signs of end organ damage lead to worse outcomes.

Finally, another study in 2019 in JAMA found that among older adults hospitalized for noncardiac conditions, prescription of intensified anti-hypertensives at discharge was not associated with reduced cardiac events or improved BP control within 1 year but was associated with an increased risk of readmission and serious adverse events within 30 days.

So basically, let's not try to treat a number but the patient and let's not make a chronic problem a priority in the admission that doesn't warrant too many changes. That may be doing some harm!

Topic Discussion: Remdesivir in CKD and ESRD patients- what is the data thus far

Acute kidney injury (AKI) occurs at a rate of 30-40% in hospitalized patients with COVID-19.
Chronic kidney disease (CKD) and ESKD are also common comorbidities in patients who develop severe COVID-19. Data on use of these agents in CKD and ESRD is limited. 

The active metabolite of remdesivir is eliminated by the kidneys and can accumulate in patients with reduced estimated glomerular filtration rate (eGFR); moreover, the sulfobutylether-β-cyclodextrin (SBECD)carrier is known to accumulate in these patients. 

The largest clinical trials evaluating the use of this agent in COVID-19 excluded patients with stage 4 CKD or those requiring dialysis.

A multicenter study from Northwell health, BWH, MGH and U of Miami( of 18 patients) and a large study from India (46 patients) recently looked at use of remdesivir in CKD, AKI and ESKD patients. All patients studied had eGFR<30cc/min. 

In the USA study, treatment was well-tolerated, with few other AEs attributed to remdesivir. Five patients discontinued remdesivir early, only 2 of them due to AEs attributed to remdesivir (burning at IV site during the final dose and worsening kidney function); the remainder stopped due to improved clinical status (N=2) or patient preference (N=1). Overall 28-day mortality was 44% (8/18). Among patients requiring intensive care at the time of remdesivir initiation, 8 of 11 died. All 7 patients who were not requiring intensive care at baseline survived to 28 days.

In the India study, most patients tolerated the infusion well. Liver function remained stable in 28 (60.9%) cases. No patient had a severe rise in AST/ALT >5 times the upper limit of normal, therefore therapy was not required to be discontinued for this reason in any of the patients. No kidney function abnormalities attributable to drug were observed. Fourteen (30.4%) patients died, 24 (52.2%) patients were discharged from the hospital after recovery.

 

Publication	USA( Estiverne et al)	India ( Thakare et al)
Total # of AKI on dialysis	3	19
Total # of AKI non on dialysis	5	11( 5 transplant patients)
Total # of CKD patients	8	15
Total # of ESKD patients	2	16
LFT abnormalities attributed to agent	3	3
Remdesivir induced AKI	1	0
Got 5 days course	16	46
Got 10 days course	2	0

Consult Rounds: Hyponatremia from Anti depressants

 As nephrologists we often get called on SIADH from medications. Anti depressants a class of agents that we do consider to cause hyponatremia. Which ones are more likely vs others has always been interesting to know? A study from Denmark has a detailed look into this matter. 

The odds of developing hyponatremia in one large study was the highest in clomipramine, followed by nortriptyline, citalopram, paroxetine, duloxetine, venlafaxine, sertraline and amitriptyline. It had the least odds of association with mirtazapine, mianserin and escitalopram. The development was highest in the first 2 weeks of starting treatment( with the highest incidence of hyponatremia in the first 2 weeks in citalopram and lowest in mianserin. 

So, SSRI had the most association, SNRIs had slightly lower and non adrenergic specific serotogenic antidepressants had the least association. 

In the News: Nephrologists take care of the most complex patients

As a nephrologist, I always wondered , “ too many med reconciliations, so many co morbidities and I feel like I am taking care of so many complex patients.”  A study from Canada confirmed my assumption. This study was a population-based retrospective cohort study of 2 597 127 residents of the Canadian province of Alberta aged 18 years and older with at least 1 physician visit between April 1, 2014 and March 31, 2015. Data were analyzed in September 2018. When types of physician were ranked according to patient complexity across all 9 markers, the order from most to least complex was nephrologist, infectious disease specialist, neurologist, pulmonologist, hematologist, rheumatologist, gastroenterologist, cardiologist, general internist, endocrinologist, allergist/immunologist, dermatologist, and family physician.

This study had some interesting findings:

1.      They used 2 different methods of sensitivity analysis making their discovery a strong finding, which were consistent with both methods

2.      In terms of mean number of comorbid conditions a specialists deals with, Nephrologists were the highest followed by Infectious diseases

3.      Nephrologists took care of sick patients with mental conditions as well- not a surprise to most of us ( followed by ID and Neurology in the lead)

4.      We also dealt with patients that were prescribed the most medications( not just by us but by all physicians they see). I can attest to that as doing a med recon on most takes a lot of time as there are many medications. As a result, med discrepancies are not uncommon in our patients

5.      Most patients referred to renal also had a higher mean of seeing other physicians, a close second to ID

6.      Mean number of days spent in hospital, we were also on top with ID, this is part of the fact that many have co morbid conditions such as CAD, CHF and access infections and so forth

7.      Strikingly, we also had the patients with the highest mortality( significantly higher than other fields)

What is more important is not where we stand in the ranking but that there is such a wide variation of types of complexities of patients all fields are seeing and taking care of. As authors suggest, this impacts education and health policy.

Should residents applying for ID and Nephrology be involved in learning about complex disease models? Is this perhaps a major reason why residents are scared to go into these fields? Complexity and curiosity drove me to Nephrology but for some – might scare them.

In addition, the reimbursement in the US doesn’t reflect complexity of the patient. There is no question that patient complexity requires time (including the time required to communicate with the multiple other doctors), expertise, and resources to optimize management. However, reimbursement of physicians and facilities in North America is most commonly based on

fee-for-service compensation. The complexity of medical decision making is addressed by assessing the number of diagnoses and management options that are considered, the medical risks, and the amount of data to be reviewed. Adjusting payments to encourage physicians to spend more time and resources caring for patients at highest risk of complications makes sense from a health care payer perspective. This is important in Nephrology as there is declining interest in this field and changes in reimbursement might help change that trend.

As ESRD and transplant physician, internal medicine is part of our core and most often, we are in charge of the medical management of these individuals. Due to the fact that we take care of the most complex patients, most nephrologists are good leaders. Leading the dialysis unit, dealing with multiple physicians, and communicating with all types of doctors makes us ideal in leading an administration. Hence, many Nephrologists also take on administrative roles and fit well in them. A recent ACKD series of articles highlight these non-traditional roles of the Nephrologist.

Nephrologists are in a very crossroads of a complex field in medicine, with high regards from many fields of medicine. We should take pride in this and allow for an ongoing dialogue with the payers that complexity takes time and dealing with complex sick patients is equally as hard as doing an interventional procedure.

Topic Discussion: Hormonal levels with various RAAS blockade medications

Class of RAAS agent	Renin level	Plasma renin activity	Ang II level	Aldosterone level
Renin inhibitor	Elevated	Low	Low	Low
ACEI inhibitor*	Elevated	Elevated	Low	Low
ARB*	Elevated	Elevated	Elevated	Low
Aldo receptor blocker	Elevated	Elevated	Elevated	Elevated

* after being on ACEI/ARB for long periods, due to aldosterone breakthrough, aldosterone levels could be high in some cases.

Topic Discussion: Intravenous Fluids and the Kidney

Specific fluid	Fluid Type	Effect on the kidney	Evidence
Lactate Ringers	Crystalloid	None	SMART  and SALT-ED trial, NEJM 2018 and SPLIT trial JAMA 2015
0.9% Saline	Crystalloid	? more metabolic acidosis, ?AKI	SMART and SALT-ED trial, NEJM 2018 and SPLIT trial JAMA 2015
Albumin	Colloid	None to our knowledge	SAFE study, FEAST study
Hydroxyethyl starch	Colloid	Bad, AKI, osmotic nephrosis leading to more RRT	Perner et al, NEJM 2012
Pentastarch( low molecular weight Hydroxyethyl starch)	Colloid	Bad, AKI, osmotic nephrosis leading to more RRT	VISEP study NEJM 2008
Dextrand	Colloid	Bad, AKI, osmotic nephrosis	First described by Mailloux et al,  NEJM 1967
PlasmaLyte	Crystalloid	None	Shaw et al, Ann Surg 2012