Case 92: Answer and Discussion

The prevalence of non dipping of blood pressure increases with loss of renal function.

— Kenar Jhaveri (@kdjhaveri) September 27, 2018

Nondipping is more prevalent in CKD than in non-CKD patients or patients with essential HTN.  The prevalence of non dipping does increase as GFR declines. The prevalence of  reverse-dippers also increases progressively as stage of CKD progresses.

Reference: https://www.ncbi.nlm.nih.gov/pubmed/23595357
 

Topic Discussion: CABG( off pump vs on pump) and AKI

CABG induced AKI is fairly common.  Traditionally CABG is performed with bypass machine. Last decade has noted a surge in doing CABG via an off pump method. So you can get a CABG either off PUMP vs on PUMP.  If the pump is the problem and being on the bypass machine is what leads to the AKI, off PUMP CABG should have less AKI?

What is the data?

In 2010, a meta-analysis published in CJASN showed that off-pump CABG may be associated with a lower incidence of postoperative AKI but may not affect dialysis requirement, a serious complication of cardiac surgery. However, the different definitions of AKI used in individual trials and methodological concerns preclude definitive conclusions.

Then in 2014, Garg’s group from Canada did a large study looking at this question in the CORONARY study group in JAMA. They found that the use of off-pump compared with on-pump CABG surgery reduced the risk of postoperative acute kidney injury, without evidence of better preserved kidney function with off-pump CABG surgery at 1 year.

Another meta-analysis in 2015 from the Mayo clinic group showed a beneficial effect of off‐pump CABG on the incidence of AKI. However, this meta‐analysis does not show benefits of the need of dialysis or survival among patients undergoing off‐pump CABG.

In 2017, an Asian study published in Medicine found that among the 3 surgical methods( off pump, on pump with arrest heart, on pump with beating heart), off pump surgery resulted in lower AKI incidence. The short term outcome, including kidney function, of on pump beating heart surgery is similar to that of the off pump group.

The reasons that are proposed for higher AKI in on-pump CABG patients include renal hypoperfusion, hypotension, inflammation and oxidant stress. Compared to on-pump surgery, off pump surgery has potential benefits of reduced AKI risk and reduced cerebral dysfunction and reduced ICU stay and reduced mortality.

However, KDIGO guideline suggests that “off pump CABG not be selected for the purpose of reducing perioperative AKI or need for dialysis.”

Crystals in the urine Quiz Flash cards

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: Common Nephrotoxic drugs and their mode of enteries

Common Renal toxic drugs and their mode of entering the tubule and mechanism of toxicity

Drug Name	Mode of entry	Mechanism	Clinical Presentation(s)
Tenofivir(TDF)	Secreted via the basolateral side via OAT and then enters lumen via MRP2 in the urine.	Mitochondrial dysfunction	ATI Proximal tubulopathy Diabetes Insipidus(rare)
Gentamicin(Aminoglycosides)	They are all filtered and they are attracted to negative phospholipids and bind to megalin cubulin receptor and enter the cell.	Lysosomes binding and then cause mitochondrial damage and tubular injury—myelin bodies	ATI Bartter’s syndrome( via activating of the CaSR in the TAHL) Fanconi syndrome(rare)
Polymixin	All filtered, punch holes enter cells via organic cationic transporter(OCT) on apical surface	Apoptosis and necrosis	ATI
Vancomycin	Unclear how it enters	Complement activation Activation of reactive oxygen species Mitochondrial injury Vancomycin cast formations	ATI Worse when combined with Piperacillin / Tazobactam
Amphotericin B	Unclear how it enters	Principal cell defect via holes in the apical membrane	Distal hypokalemic RTA ATI Hypomagnesemia Nephrogenic DI
Heta-Starch, Dextran, Sucrose, Mannitol	Filtered and enter proximal cell – pinocytosis and build up and swell up cells. Cannot be metabolized	Osmotic nephrosis	ATI
Atazanavir	Minimal renal excretion, poorly soluble in urinary ph- leading to crystallization	Crystal formation	Crystal Nephropathy
Cisplatin	Enters via OCT on the basolateral side, enters and activates apoptosis	Oxidative stress	ATI Hypomagnesemia Proximal tubulopathy Salt wasting nephropathy Nephrogenic DI
Ifosfamide	Enters proximal tubular cell via OCT on the basolateral side and then metabolized to its metabolized that causes the damage	Increased oxidative stress and mitochondrial injury	ATI Fanconi syndrome

In the NEWS: Atypical parvovirus causing interstitial fibrosis and AKI

An interesting pathology study just got published in Cell.  It describes an atypical parvovirus infection in the kidney presenting as interstitial disease and fibrosis. Classically, the three lesions that have been described with parvovirus B19 infection are collapsing GN, FSGS and Minimal change disease. Both native kidneys and post transplant cases have been described.

In this study, using metagenomics, the authors identified a spontaneous nephropathy with intranuclear inclusions and the causative agent as an atypical virus, termed “mouse kidney parvovirus” (MKPV), belonging to a divergent genus of Parvoviridae. Detailed analysis of the clinical course and histopathological features demonstrated a stepwise progression of pathology ranging from sporadic tubular inclusions to tubular degeneration and interstitial fibrosis and culminating in AKI. 

Below is the visual abstract of the study from the journal abstract.

Courtesy: Journal Article from Cell

This study highlights an interstitial inclusion type nephritis associated with parvovirus in mice. While clinically, to my knowledge, interstitial nephritis like this has not been reported with parvovirus.

A recent online discussion on twitter regarding this paper is linked below.

Fellow nephrons have you seen inclusion body nephritis in mice?
An Atypical Parvovirus Drives Chronic Tubulointerstitial Nephropathy and Kidney Fibrosis https://t.co/afcgYrILuV pic.twitter.com/ffa0wYnXZ8

— Katalin Susztak (@KSusztak) September 14, 2018

Conceptually we have always known that in humans viruses can induce kidney disease and fibrosis such as seen in BK, CMV, Parvovirus and so forth. This is definitely worth studying in humans.

Concept Map: NSAIDS and their effects on the Kidney

Consult rounds: CRRT calculations primer

Two must know concepts in CRRT is clearance and filtration fraction.

How does one calculate clearance in CRRT?

Let’s start with convection first- so mainly CVVH (like you are making coffee) 

Clearance = V (u/p) but here dialysate/plasma eventually equilibrates, so the Clearance =Volume. What is your volume in CVVH? – IT is your total effluent—so it is your Replacement fluid rate + UF rate

If you had post filter replacement- just add replacement fluid rate + UF

If you had pre filter replacement- you need to have a correction factor, because the blood that enters the filter pre filter has a different concentration and gets diluted. The correction factor is an equation that reduced the replacement fluid rate by a certain percentages that includes the blood flow rate.
The formula for the fudge factor is BFR/ BFR+ Replacement fluid rate. An amazing you tube video explaining this concept.

Now let’s do the diffusive clearance (like making tea with a tea bag) - you need to basically add all the rates- DFR+ UFR+ post filter rate. You tube video link for this calculation.

So the Clearance = Diffusive + convective if it’s CVVHD ( Remember to only add UFR once)

Here is an example of a patient getting CVVHDF with order set

BFR=100cc/min or 6000cc/hr
DFR= 1400cc/hr
Pre filter- 800cc/hr
Post filter- 200cc/hr
UFR-100cc/hr

Let’s do diffusive first.  Clearance = DFR+ UFR = 1400+ 100= 1500cc/hour =25cc/min
Convective = pre filter + post filter +UFR( but we already counted UFR above) so can’t count again.
Also, pre filter needs a correction factor. 

The correction factor is Blood flow/ Blood flow +replacement fluid rate.  So that is 6000/6800= 0.88 for the pre filter part. So here the pre filter part will be 800 *0.88=705.

So the convective clearance = 705+ 200= 905cc/hr =15cc/min

So total prescribed dose gives you a clearance of 25+ 15= 40cc/min

So if this individual was 85kg

It would be 1500+ 905 cc/hr = 2405/85=28 cc/kg/hr

How does one calculate Filtration fraction?(FF)

FF===Effluent flow / blood flow with correction factor

Your effluent will include the DFR+UFR. You want the FF <20% to avoid clotting. So if you increase the numerator, your FF increases or if you decrease the denominator, FF increases. So, basically, you have to keep the blood flow high if you want to increase UFR or DFR to avoid the increased concentration of the plasma and increase clotting risk. Here is the FF YouTube video explanation.