Wednesday, March 21, 2018

Nephmadness 2018

Neph Madness is back with a new twist in 2018! This time, not only is it the fun game we used to playing for the last 6 years but this year there is CME points awarded.  So you learn and get credit for it!

Thanks to AJKD and NKF on this component of the Neph Madness
and check out the website
I just submitted my picks and all I can say is my top player is related to the heart! Let’s see if the best champion wins. 

Novel things this year
1.       Many visual abstracts
2.       Amazing videos
3.       CME credits this time around
4.       Visually appealing more amazing website design
5.       More varied topics including a Pediatric Neph region, transplant region and an interesting basic science and electrolyte region. 

 Here is the amazing blue ribbon panel
Blue Ribbon Panel
Come play the best online game of the year- Nephmadness 2018! 
Check out this amazing editorial on this years games by Sparks and Topf

Thursday, March 15, 2018

Concept Map: Podocytopathies

In last decade, another way to look at podocyte disorders.
Reference of this form of classification comes from
Click on image for larger size view

Tuesday, February 27, 2018

Consult Rounds: Esclicarbazepine induced hyponatremia

Image result for eslicarbazepine

Carbamazepine and oxcarbazepine are the most common anti epileptic drugs( AEDs) which induce hyponatremia in patients with epilepsy. Recently, other AEDs, such as eslicarbazepine(ESL), sodium valproate, lamotrigine, levetiracetam and gabapentin have also been reported to cause hyponatremia.

In a two year, single center open labeled observational study of ESL in patients with imaging proven stroke with new onset post stroke seizure were included. ESL was titrated between 400 mg and 1200 mg once daily during 1 month observation period. The titrated dose of ESL was continued during 96-week maintenance period. The patients were followed up for seizure control and side effects, including serum sodium on first examination, at the end of 1 month and then at three monthly intervals for 24 months (total eight visits). Hyponatremia developed in four out of 32 (12.5%) patients; it was symptomatic in three and asymptomatic in one patient.
In three controlled epilepsy studies, 1/196 patients (0.5%) treated with 400 mg, 4/415 patients (1.0%) treated with 800 mg, and 6/410 patients (1.5%) treated with 1200 mg of ESL had one or more serum sodium values less than 125 mEq/L during treatment whereas none in placebo group. In contrast hyponatremia is the most frequently reported adverse drug reactions in the post-marketing database for Aptoim (ESL brand approved by the US FDA). In this database there were 140 cases of hyponatremia, in half of them hyponatremia occurred within the recommended range of 400-1200mg of ESL and sodium level as low as 103 mEq/L had been reported. In the above study all four patients who developed hyponatremia were in ESL 800 mg group, and lowest sodium level recorded was 113 mEq/L. As hyponatremia develops across all dose ranges of ESL, thus it appears that ESL induced hyponatremia is probably not dose dependent but most appeared in the 800mg group or higher.

What is the mechanism? Possible mechanism of ESL induced hyponatremia can be understood by the mechanism of hyponatremia in oxcarbazepine. Sachdeo et al. found that oxcarbazepine intake results in significant reductions in serum osmolality and serum sodium concentration after a water–load test, This hypotonic hyponatremia, which is not associated with a significant change in serum ADH, is the result of both a relative inability to dilute the urine and a reduction in the percentage of water excreted after the water–load test. He suggested that oxcarbazepine induced hyponatremia is not attributable to the SIADH. Possible mechanisms include a direct effect of the drug on the renal collecting tubules or an enhancement of their responsiveness to circulating ADH. 

It responds well to fluid restriction, salt supplementation with or without ESL withdrawal.

Thursday, February 8, 2018

MGRS and MGUS- the 1/3-2/3 rule of pathology in the kidney?

When someone has MGUS, what is the true incidence of kidney disease? – this has not been answered. An old study from AJKD in 2003 did help us guide the breakdown of kidney diseases when someone has MGUS.  In other words, if someone has MGUS, and there is some form of renal disease- AKI, proteinuria, hematuria and you biopsy them- what percent of the time you will find renal disease associated with proteinuria, what percent of the time you would find diseases other than paraproteinemic disease?

In summary, the AJKD paper looked at a single center experience of their paraprotein related kidney diseases biopsy bank.  Patients who underwent renal biopsy and had monoclonal gammopathy on serum and/or urine electrophoresis and/or had a renal biopsy diagnosis related to paraprotein (cryoglobulinemic glomerulonephritis(cryo) monoclonal immunoglobulin deposition disease [MIDD], light chain cast nephropathy [CN], or light chain amyloidosis [AL]) were identified.  One hundred twenty-one patients met the inclusion criteria and were classified as having renal disease related or unrelated to monoclonal gammopathy. Among 66 cases of renal disease related to monoclonal gammopathy, diagnoses were cryo (30.3%), MIDD (28.8%), CN (19.7%), AL (19.7%), and CN plus MIDD (1.5%).

Among 55 patients with monoclonal gammopathy and unrelated renal disease (63.2% of all patients with monoclonal gammopathy), various lesions were found, including diabetic nephropathy (18.1%), focal segmental glomerulosclerosis (18.1%), arterionephrosclerosis (12.7%), membranous glomerulonephritis (9.0%), minimal change disease (7.3%), various immune complex diseases, interstitial nephritis, or nonspecific changes. MPGN was also included in this group. We know now that MPGN is likely related to MGUS and not a non paraprotein disease.

But what about patient’s with MGUS and true MGRS- what I calculated from the paper was around 22( either had cyro, CN, AL or MIDD) patients and if we remove MPGN from the current 55 patients stated above, would be 52 patients.  This makes it a 1/3-2/3 rule.  So if there is MGUS or smoldering MM and some form of renal disease on clinical presentation , there is 1/3 chance that their disease would be paraprotein related in the kidney if you did a kidney biopsy. But majority of the time, it would be a non paraprotein mediated disease.

While this paper looks at it at a single center, it gives some insight into the incidence of true MGRS when there are renal clinical presentations. 

Sunday, February 4, 2018

#Nephrocards2018 CME on March 10th 2018

Northwell health in Long Island New York will host a one-day symposium aimed at providing updates on the Nephro-Cardiology on Saturday March 10th( #nephrocards2018)

Go to this link for more information and to register. Fellow, Students and Residents registration is free

ASN, ISN, NKF and Cardio-renal society of America endorsed

Below is the itinerary

7:30am Registration, Breakfast and Exhibits

8am Contrast Nephropathy? Does it Exist-The Latest Update and Prevention
Paul M. Palevsky, MD

9am Cardio-Renal Syndrome
Jai Radhakrishnan, MD, MS, MRCP

9:30am TAVR and the Kidney
a. Basics of Transcatheter Aortic Valve Replacement: A Primer
Bruce Rutkin, MD

b. The Renal Effects of Transcatheter Aortic Valve Replacemen
Kenar D. Jhaveri, MD

10:30am Break

10:45am Left Ventricular Assist Devices
a. Basics of Left Ventricular Assist Devices
David Majure, MD

b. Left Ventricular Assist Devices and the Kidney
Daniel W. Ross, MD

11:30am Novel Agents Used in Hyperkalemia - What Cardiologists and Nephrologists Need to Know
Steven Fishbane, MD

12:15pm Interventional Therapies for Refractive Hypertension
Avneet Singh, MD

12:40pm Lunch 1:30pm Novel Anticoagulants and the Kidney
Nupur N. Uppal, MD

2pm Cardiac Workup of the Kidney Transplant Patient
Alexander Lee, MD

2:30pm Cardiac Surgery and the Kidney
Mitchell H. Rosner, MD

3:30pm Panel Discussion

4pm Program Conclusion

Sunday, January 28, 2018

Topic Discussion: Gemcitabine induced TMA- what to do?

Thrombotic microangiopathy (TMA) can come in many forms- HUS and TTP might being the two most extreme versions. Gemcitabine induced TMA is a drug induced TMA that can result from dose dependent use of the agent or an immune mediated phenomenon.

In immune-mediated TMA, the drug induces formation of antibodies that react with multiple cells, including platelets, neutrophils, and endothelial cells, but strong binding only occurs in the presence of the drug (or drug metabolite). Therefore, these antibodies are described as drug-dependent antibodies. Toxicity-mediated (ie, non-antibody-mediated) TMA may develop by multiple mechanisms. Many cases are dose related, occurring only after large cumulative exposure over a period of time or exposure to large single doses of a drug. Gemcitabine induced TMA is thought to be due to both the above mechanisms.

Recent review found that of 78 substances to have previously been reported to cause thrombotic microangiopathy (TMA), 22 had definite evidence supporting causal association. However, 9 (clopidogrel, cyclosporine, estrogen/progesterone, gemcitabine, interferon, mitomycin, quinine, tacrolimus, and ticlopidine) accounted for 76% of reports.

Initial management involves immediate discontinuation of suspected drug, or reduction of dose when discontinuation is not a medical option.

What about pheresis or anti complement therapy specifically for Gemcitabine induced TMA?

A twitter pole I did showed these results

Here is the summary from the Pheresis society guidelines

In all cases of Gemcitabine induced TMA, ADAMTS13 levels were typically normal. In literature review, among 26 patients not treated with pheresis, 56% recovered from TMA, whereas 30% of 18 patients who received TPE. So based on that data, doubt pheresis will help TMA associated with gemcitabine.

There have been reports of patients with toxicity-mediated DITMA attributed to gemcitabine, case reports have described patients with acute kidney injury attributed to gemcitabine who improved after treatment with anti-complement therapy. However, these case reports do not provide confidence that anti-complement therapy is appropriate. Often the patients have received multiple chemotherapeutic agents, and the selection of gemcitabine as the possible cause-effect cannot be confirmed.

Often a kidney biopsy to document TMA has not been done. Although these preliminary observations do not provide confidence that anticomplement therapy is appropriate, some experts do feel it might be reasonable to consider the use of eculizumab in persistent drug toxicity-mediated TMA that does not improve with supportive care and withdrawal of the offending agent and especially if there is risk for progressive CKD.

So in summary

1. Most important- stop the offending agent
2. Data on use of pheresis- poor and in some instances might be not recommended
3. Data on use of complement inhibitor- poor and unclear at this point- probably would avoid but there might be mixed opinion on this matter in the literature.

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