AVG thrombosis-- can any drug prevent it?

AVG can clot and certain patients, they clot frequently.  What is the data on pharmacological interventions to improve AVG outcomes in terms of preventing further clots?

A recent article in CJASN discusses this nicely via a case of a patient who has numerous AVG and most clot within weeks  of creation. The authors discuss patho-physiology of thrombosis of AVG but then discuss the potential pharmacological options.  I encourage all to look at Table 1 as it summarizes the randomized controlled trials on major agents that we consider are useful in preventing clots.

Apparently, warfarin, ASA + clopidogrel showed no difference and were more harmful in causing bleeding. 

Lowering homocysteine levels by folic acid didn’t do much either. Only trials that showed benefit were the ones that used Fish oil.  One is a small single center trial that showed decrease in thrombosis and other was a multicenter trial that showed that fish oil (four 1-g capsules/day) halved the frequency of the AVG thrombosis and angioplasty.

Worth a read for all nephrologists!

Topic Discussion: Anti-PD-1 Therapy and the Kidney

Anti PD-1 Inhibitors and the Kidney

This includes two proteins called programmed death-1 (PD-1), which is expressed on the surface of immune cells, and programmed death ligand-1 (PD-L1), which is expressed on cancer cells. When PD-1 and PD-L1 join together, they form a biochemical "shield" protecting tumor cells from being destroyed by the immune system. Another protein involved in the pathway and also expressed by cells in the immune system, programmed death ligand -2 (PD-L2).

Anti-PD-1 agents are humanized monoclonal antibodies that bind the PD-1 receptor, which are present on tumor infiltrating lymphocytes and Tregs. They prevent the engagement of PD-1 to its ligand on the tumor cells (PD-L1 and PD-L2) thereby asserting its antitumor activity.

Nivolumab

Nivolumab is the first anti-PD-1 antibody tested initially in melanoma.  In December 2014, the U.S. Food and Drug Administration (FDA) granted an accelerated approval to nivolumab for the treatment of patients with unresectable or metastatic melanoma. Since then, there have been use of this agent’s approval in lymphoma and renal cell cancer as well.  There also has been some interest of this agent to be used in myeloma.

In one trial, there was an increased incidence of elevated creatinine in the nivolumab-treated group as compared to the chemotherapy-treated group (13% vs. 9%).  Steroids help resolve the renal dysfunction in 50% of the cases. It is presumed to be AIN from an immune mediated process. The FDA label has guidelines to start steroids as the creatinine rises rapidly.  A pubmed search revealed no published cases of AIN or acute renal failure in the peer reviewed literature.

Pembrolizumab

Pembrolizumab (MK-3475) is another monoclonal antibody (MAb) therapy designed to directly block the interaction between PD-1 and its ligands, without antibody dependent cell-mediated cytotoxicity (ADCC) or complement dependent cytotoxicity (CDC). This drug also has been used in melanoma and other hematological malignancies since 2014. 

Nephritis occurred in 3 (0.7%) patients, consisting of one case of Grade 2 autoimmune nephritis (0.2%) and two cases of interstitial nephritis with renal failure (0.5%), one Grade 3 and one Grade 4.

The time to onset of autoimmune nephritis was 11.6 months after the first dose of pembrolizumab(5 months after the last dose) and lasted 3.2 months; this patient did not have a biopsy.

Acute interstitial nephritis was confirmed by renal biopsy in two patients with Grades 3-4 renal failure. All three patients fully recovered renal function with treatment with high-dose corticosteroids (greater than or equal to 40 mg prednisone or equivalent per day) followed by a corticosteroid taper.

Mae et al. from Yale presented a poster in ASN Kidney Week 2015 that highlighted 2 cases of biopsy proven AIN from this agent (Abstract: [TH-PO1051).

It’s not just the kidney- apparently this immune mediated reaction that is initiated might be leading to hepatitis, uveitis, pancreatitis, myocarditis and other concerns. 

Literature search thus far has not revealed any published cases of AIN from this agent. Given this immune mediated reaction- the kidney can be a potential target. I won’t be surprised if both vasculitis and allergic nephritis can be noted on kidney biopsies with these agents. 

Washington Univ You Tube based Nephropathology CPC series : Case 1

The Nephrology 2016 Match: Where do we go from here and a call for help!!!

The 2016 match for nephrology was just released. This is the first year following the ALL-in policy for the nephrology match. Clearly, this is a great way to benefit the candidate and the candidate get’s to see all programs and ranks based on their choice. 

ASN just released the key points that the match data revealed.

You can find the PDF of the information on this link. 

1.     There was a increase in programs (18%) and positions certified in the match.  Well this is because it was an ALL IN process so most programs participated. No big deal.

2.     The number of matched fellows increased—great! That is good news but this doesn’t imply increased interests.

3.     The number of applicants rose 11%- Perhaps reflection that we had ALL –in process and last few years-we never saw those candidates data. Since both the numerator and the denominator increased- we are counting candidates that we hadn't accounted for years ago. Not really an improvement!!

4.     Slight uptick in USA grads applying and major down trend in IMGs applying- big loss as they were the main stay for nephrology workforce last few years.

5.     Unfilled positions rose to a new high 58%-- biggest bummer of this process

Good news:

More US grads. More overall applicants( skeptic on that one as data is now due to ALL-in)

Bad news:

Still many more unmatched spots and programs. There are programs in the country unmatched 100%.

Do we have solutions?

While increasing interest in med school and residency is important and critical- clearly it is NOT working at a national level.  At the end of the day, re-imbursement of nephrologists calls the shots. We need to really push hard on the government level for more reimbursement for renal physicians.  A shortage will happen eventually, there will be a major medical need crisis and then hopefully there will be an uptrend in the salaries of nephrologists—even that is a dream in never never land.

What are programs going to do? Many programs fear- "they might be next."  Downsizing fellowship spots is an option and perhaps hiring physician assistants to help out with day to day duties.  Researchers will be asked to more clinical time, clinical educators will have to more clinical time and teach less--- all trickling down to less innovation and research in nephrology and less time with trainees.

Applicants to research positions are down-trending. This means that pure clinical fellowships that are big university centers( 2 year)- will fill.  The ones that won’t will be large research positions and or small community programs( perhaps).  Perhaps programs need to cater towards what the applicants want out of a renal fellowship-- times have changed( Nephrology was not what it was 20 years ago).

Time will change this. As any ups and downs in an economy- there will be eventually a shortage of nephrologists as this trend continues and eventually, there will be an upswing.

Clearly, I am being schizophrenic in this post but I am happy and sad with these results.

Clearly, the national strategy we have might not be working.  We need to all put our heads together( both academic and private nephrologists) to really come up with OUT of box ideas to change this trend.  

It’s a call for HELP and we need it soon!

Quizlet: Parasitic Infections and the Kidney

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC88933/pdf/cm000055.pdf

B cell malignancies and the Kidney

B cell malignancies and the Kidney from kdj200

Topic Discussion: What causes glomerulomegaly?

What causes glomerulomegaly?

Congenital cyanotic heart disease
Cor pulmonale
Obesity and Sleep apnea
Sickle cell disease
Polycythemia vera
Alcoholism
Hepatic steatosis
Cystic fibrosis

What is the most common physiological abnormality in all of the above

Hypoxemia! Perhaps a combination of metabolic demands of some of these illnesses, hypertrophy of the erythropoietin producing cells, passive congestion causes in the systemic circulation and increased viscosity all might be leading to glomerular damage and proteinuria as a result.

What does glomerulomegaly mean on pathology?

There is going to be focal and diffuse hypercellularity, segmental or global sclerosis, mesangial thickening
Vessels:- capillary congestion, hyalinization of afferent and efferent arterioles
Tubular atrophy
Interstitial Fibrosis

Reference: http://www.ncbi.nlm.nih.gov/pubmed/9402101

IN the NEWS: ESRD re-admissions: where do we stand and what can we do?

ESRD re-admissions are a major concern. A recent KI paper discusses what the nephrology literature has found regarding this very important issue. Unfortunately, no studies have tested interventions in how to avoid re-admissions for our dialysis patients.  The authors propose certain areas for research.

An interesting concept that is discussed in table 3 of the paper is the potential places where the factors might be of the risk and how we can target our research in those 5 areas.

1.       The patient related risk factors ( socio-demographics, social support .etc)

2.       Index hospitalization( the first hospitalization and how to void re-admissions related to that admission, med reconciliation, structured communication from inpatient to outpatient units)

3.       Nephrologist ( timing of first visit post discharge, extra weekly visit for the hospitalized patient, effect of targeted structured eval only addressing certain key variables such as dry weight, access, medications changes)

4.       Dialysis unit- coordination with inpatient dialysis unit and ER of the hospital

5.       Payment structure- effect of resource redistribution in different payer models

Check out the paper here.

In the News: Regenerative Medicine in Nephrology

Chronic kidney disease (CKD) is a major global public health problem.  In the US, about 11% of adults have CKD as of 2012, and CKD accounts for $41 billion in Medicare expenditures (17%).   When patients with CKD progress to end-stage renal disease (ESRD), the options for treatment are limited to dialysis and kidney transplantation.  Dialysis is associated with significant morbidity and mortality, and kidney transplantation is limited by the supply of organs as well as the need for patients to take immunosuppressive medications for the rest of their lives.  There is a need for new, innovative therapies to treat CKD and ESRD.  One promising approach is to rebuild or repair cells, tissues, or organs to restore proper function.  This exciting new area of medicine has been termed “Regenerative Medicine.” 

We have been working for the last seven years on developing strategies to differentiate human pluripotent stem cells, particularly human embryonic stem (ES) cells and human induced pluripotent stem (iPS) cells, into cells of the kidney lineage for the purposes of kidney regeneration and kidney disease modeling.  We believe that the successful derivation of functional kidney cells and structures from human pluripotent stem cells will have an enormous impact on a variety of clinical and translational applications, including kidney tissue bioengineering to replace lost kidney tissue, renal assist devices to treat acute and chronic kidney injury, drug toxicity screening, screening for novel therapeutic agents, and human kidney disease modeling.

Our primary goal was to develop a highly efficient, chemically defined method of differentiating human pluripotent stem cells into kidney tissue.  The normal kidney consists of approximately one million nephrons (the functional units of the kidney).  During normal kidney development, nephron progenitor cells (NPCs) give rise to nearly all the epithelial cells of nephrons.  Nephrons are highly complex structures with multiple segments, each of which performs a set of specific physiologic functions of the kidney such as salt and water regulation and waste product elimination.  While previous studies, including work from our own lab, have demonstrated the ability to generate NPCs from human pluripotent stem cells, efficiencies have been low.  Furthermore, while these NPCs have been able to differentiate into rudimentary structures of the nephron, none of the prior studies have demonstrated the ability to form a complete, mature nephron from NPCs.

We hypothesized that a much higher efficiency of NPC generation and formation of kidney units could be achieved by following nature’s normal differentiation pathway. We therefore set out to establish a differentiation protocol that would mimic the stages of nephron formation as closely as possible.  Our approach in recapitulating the steps of kidney development as precisely as possible resulted in a highly robust recipe for generation of kidney organoids. To our knowledge, this is the most efficient method for generating complex kidney structures from human pluripotent stem cells. The ability to do this using induced pluripotent stem cells, which are derived from skin or blood cells of patients, allows creation of kidney tissue without ethical concerns and allows the tissue to be “personalized”, that is, generated from a particular patient.  If in the future the tissue is re-implanted back into the patient, the immune response may then be very limited since the tissue will be recognized as self.

Finally, we tested our nephron organoids for the ability to model human kidney development and drug toxicity to the kidneys.  Kidney development is an important medical topic since it has been increasingly recognized that individuals can be born with fewer functional kidney units and these patients are plagued by an increased chance of hypertension and kidney disease in later life.  By altering the environment of the NPC-derived renal vesicles with drugs that are known to affect kidney development, we found that the proximal tubule structures are greatly affected. This finding indicated that the nephron organoids are usable for the study of human kidney development, for which no “ex vivo” models currently exist.  With this model system we have a tool to evaluate potential therapeutic agents.

In addition, we tested nephron organoids for drug toxicity.  The kidney organoids were treated with the nephrotoxicants gentamicin and cisplatin.  Both nephrotoxicants induced segment-specific injury to nephron structures within organoids in a pattern that is consistent with what is observed in the clinical setting.  Given the individual variation in drug sensitivity in humans, the generation of these nephron organoids from human iPSCs would enable drug testing in a patient-specific manner.

Kidneys are the most commonly transplanted organs, but demand far outweighs supply.  While the human kidney does have the capacity to repair itself after injury, it is not able to regenerate new nephrons, the individual functional units that make up the kidney. Human pluripotent stem cells are the only human cells we can grow in the laboratory with the potential to generate new functional kidney tissue. Previously, researchers have been able to differentiate pluripotent stem cells into heart, liver, pancreas, or nerve cells by adding certain chemicals, but it has been challenging to turn these stem cells into kidney. Using normal kidney development as a roadmap, we developed the most efficient method for converting human pluripotent stem cells into kidney stem cells that will give rise to nearly all the functional cells of the kidney. These kidney stem cells organize into mature kidney structures that resemble the structures found in a normal human kidney. This gives us hope that, one day, we might be able to create kidney tissues that could function in a human patient and would be 100% immunocompatible with that patient.

Check out the manuscript here.

Ryuji Morizane, MD, PhD

Postdoctoral fellow, Renal Division, Brigham and WOmen's Hospital

Albert Q. Lam, MD

Associate Physician, Renal Division, Brigham and Women's Hospital

Joseph V. Bonventre, MD, PhD

Chief, Renal Division, Brigham and Women's Hospital

Consult Rounds: Cancer Drug induced Thrombotic microangiopathies

Cancer Drug induced TMA come in 2 variants

1.       Type 1 TMA:- onset is delayed, usually 6-12 months after starting therapy

Cumulative dose related

Clinically, could be permanent and irreversible renal damage

Would avoid rechallenge

High incidence of acute mortality and may require dialysis even after stopping agent

Thrombi in both arteriole and glomerular capillary

Examples: Mitomycin C and gemcitabine induced

2.       Type 2 TMA:- onset is more acute and only at time of initiation of agent.

Not dose related

High likelihood of recovery

Some evidence of safe rechallenge

Thrombi in glomerular capillary mainly

Patient and kidney survival excellent

Examples:  anti VEGF and TKI agents induced

Ref: http://www.ncbi.nlm.nih.gov/pubmed/25943718

Topic Discussion: CLL and the kidney

Classically, it's well know that infiltrative disease is seen with CLL and the kidney leading to AKI.
What other diseases can you see with CLL and the kidney?

A recent paper by The Leung group at Mayo discusses the Mayo clinic experience of CLL and monocloncal B cell lymphocytosis patients that had a kidney biopsy.

Most common findings:
20% had MPGN
12% had infiltration of CLL
12% had TMA from chemotherapy -- classically related to pentostatin
10% had Minimal change disease

Other less commonly observed findings were AIN, AL lamda amyloidosis, light chain cast nephropathy, membranous GN and mesangial proliferative GN.

Other unrelated biopsy findings were diabetic nephropathy, obesity related FSGS, and HTN nephropathy.

Topic Discussion: Non Dilated Obstructive Uropathy

Anuric renal failure has very few causes. The top three are usually: hydronephrosis, hydronephrosis and hydronephrosis! But sometimes, it’s the sonogram and imaging that sways you away from the diagnosis. The sonogram reads- no hydronephrosis and or dilatation.  But clinically, the only thing that makes sense to you is obstruction? What do you do then?

Non dilated obstruction is not uncommon especially in patients with cancer that effects the retroperitoneal regions. There is so much cancer mass that there is no ROOM for the kidney to expand. But doesn’t mean that hydronephrosis is not present. The syndrome of non-dilated obstructive uropathy (NDOU) and AKI is well reported. However, the literature suggests that this syndrome is rare, accounting for less than 5% of cases of urinary obstruction.

One of the earlier studies had looked at a series of patients at a single center and found that most common cause of these type of situations were cancers ( likely RP related)- so prostate, colon, bladder, lymphomas and other series have found cervical cancer as well.  Antegrade urography had found the obstruction in all of the cases in that one series. 

The first ever case of this was described by Ormand in 1948 with someone with retroperitoneal fibrosis.

A more recent study from Mayo Clinic has a case series of 3 cases. Despite the absence of dilatation on renal imaging, strong suspicion for NDOU led to decompression procedures with prompt recovery of kidney function in all three patients - two required percutaneous nephrostomy tube placements and/or ureteric stents and one responded to simple Foley catheter drainage. Here is another case series summarizing the data.

Treatment is usually diagnostic.  Given the pathology and the cause of the obstruction being present after the ureteral stents are placed, they usually only temporize the treatment. Percutaneous nephrostomy is usually the best procedure in such situations. 

When one encounters such cases, Urology and IR help is critical in getting the right diagnosis and prompt treatment.  

TOPIC DISCUSSION: MEMS and ESRD

The NYHA heart failure patients have a new device that is useful in predicting their volume status. A Lancet article in 2013 showed that this device called the CARDIOMEMS ( implantable hemodynamic monitoring).  This big study showed that it reduced hospitalizations of heart failure patients.  This device measures the pulmonary artery pressures (PAP) via remote monitoring.  The device is placed via interventional means and the remote box predicts the PAP. Based on that the physician can assess volume status and increase or decrease diuretics or give fluids preventing inpatient visits. 

The holy grail of ESRD patients has been the dry weight and how do we know they are more volume overloaded or need more UF.   MEMS or microelectromechanical systems can perhaps play a major role in renal care.  MEMS offers a potential to predict volume status in ESRD patients.  The current use of drt weight comes with fluctuations, errors and not much reliability.  This device could be planted in HD patients and perhaps we could remotely monitor their fluid status and call for extra UF sessions, or remove less fluid and so forth and perhaps even prevent hospitalizations.  

Kim and Ray summarize the use of potential of MEMs in the nephrology world.

What an amazing achievement by the cardiologists.

Onconephrology CME: Sept 26th one day symposium: First of it's kind

One last push for a plug in for the first ever one day CME on onconephrology.  It's ASN, ISN, NKF and C-KIN endorsed event.  

We are conducting a one day symposium on OncoNephrology: Cancer, chemotherapy and the Kidney at Hofstra NSLIJ School of Medicine on Sept 26th, 2015 from 7:30AM to 4PM
The conference will highlight and review the latest happenings in OncoNephrology

WHY to attend:

1. First of it's kind in USA to focus on this topic
2. We shall be using innovative technology to allow for a fun and interactive conference( polleverywhere, joinme and so forth)
3. A chance to win few nephrology textbooks as a raffle during the day
4. FREE to attend for any trainee ( student, fellows or residents)
5. Live tweeting of conference will be available via AJKDblog


Talks and Speakers highlighted;

AKI in Cancer Patients;  Joseph Bonventre, Harvard Medical School
Chemotherapy Toxicities:  Mark Perazella, Yale University
Targeted Therapy and the Kidney: Kenar Jhaveri, Hofstra University
Hypercalcemia of Malignancy: Naveed Masani, Winthrop University
Anemia, CKD, ESKD and cancer: Steven Fishbane, Hofstra University
Renal Cancer, an update: Thomas Bradley, Hofstra University, NSLIJ Cancer Institute
Paraneoplastic GN; Hitesh H Shah, Hofstra University
TMA:  Bradley Dixon, Cincinnati Children Hospital
Post Kidney Transplant Cancers: Vinay Nair, Mt Sinai Medical Center
Paraproteinemias, an update: Gerald Appel, Columbia University Medical Center
Cases with the Onconephropathologist: Glen Markowitz, Columbia Medical Center

Course directors:  Kenar Jhaveri, Steven Fishbane and Thomas Bradley( Division of Nephrology and Hematology/Oncology at Hofstra NSLIJ School of Medicine)
Planning committee: Kenar Jhaveri, Steven Fishbane and Thomas Bradley, Hitesh H Shah, Pravin Singhal, Jyotsana Thakkar and Rimda Wanchoo( all from Division of Nephrology, Hofstra NSLIJ School of Medicine)

To Register: go here

TOPIC DISCUSSION: Mnemonic for toxins that are removed by hemodialysis

Toxins that are removed by hemodialysis

Here is a mnemonic I found online

I   STUMBLE

I = Isopropanol
S= Salicylates
T = Theophyline
U = Uremia
M= Methanol
B= Barbituates, beta blockers (water soluble ones such as atenolol)
L= Lithium
E= Ethylene glycol

Source: http://crashingpatient.com/toxicology/general-toxicology-random-drugs.htm/

Nephrology Crosswords: Diabetic Nephropathy

Check out the next installments of our crosswords in Kidney International on Diabetic Nephropathy

Topic Discussion: Cocaine and the Kidney

Cocaine and it's effect on the kidney. A quick bullet point list of what cocaine can do to the kidney.

1. Acute renal failure due to Rhabdomyolysis
2. Renal infarction 
3. Severe HTN and eventually chronic renal disease---> ESRD
4. TMA
5. Severe arterioscloerosis
6. Levamisol adulterated cocaine leading to ANCA vasculitis


Few nice reviews
http://ndt.oxfordjournals.org/content/15/3/299.full
http://www.ncbi.nlm.nih.gov/pubmed/15335299
http://www.nejm.org/doi/full/10.1056/NEJM200108023450507

Concept Map: AKI in Liver Failure

This concept map was created by Dr Daniel Ross based on the Kidney International Article

Consult Rounds: Scleroderma and the Kidney: Not just Renal Crisis

Scleroderma and the Kidney: Not just Renal Crisis

Not all renal failure in scleroderma is HTN related renal crisis. While renal TMA and endothelial damage is a common cause of AKI in scleroderma, other interesting cause to keep in mind is vasculitis.

Of all the vasculitides, small vessel ANCA vasculitis is noted to be seen with scleroderma. 

 A study by Rho et al. found 31 reports containing 63 cases of ANCA vasculitis with scleroderma up to 1994.  Fifty of the 63 cases provided sufficient clinical and laboratory information and were included in the analysis. Eighty-four percent were women with a mean age of 57.1 years.  Over 70% had ANA positive and 70% with anti-Scl-70 antibody, and 72% with positive anti-MPO antibody. The most common end-organ involvement included kidneys (82%) and lungs (70% had pulmonary fibrosis). Mortality was highest in the first year. 

A more recent review has 11 more cases that also were reported.  Most were females, all had anti MPO titers and 9 /11 cases had renal involvement with crescentic GN. 

These findings highlight the importance of considering crescentic GN related to ANCA vasculitis as a potential cause of renal insufficiency in scleroderma. Classically, scleroderma renal crisis occurs in up to 20% of patients with diffuse scleroderma, and renal involvement manifesting as hypertension, proteinuria, or azotemia can be found in 45–60%. However, causes other than scleroderma renal crisis should be considered as a differential diagnosis, especially in settings of normal blood pressure or ANCA positivity.

Onconephrology Textbook

I would like to introduce my first edited textbook on my topic of interest- onconephrology. The book is a question/answer board style material with all topics that relate to cancer and the kidney.  The book ends with a list of concept maps that summarize few of the chapters.

Thank you to Springer for giving me this opportunity

Any comments welcomed

The link to the book on Springer's website 
The link on amazon.com 

Drug induced renal injury:- a consensus classification.

A recent article in KI 2015 discusses categorizing all drug induced AKI based on certain types and following few strict guidelines.  This ensures that the effect was clearly to a culprit drug and gives an idea of type of injury.

1.       Phenotype description: Glomerular, tubular dysfunction, AKI and nephrolithiasis/crystalluria

2.       Tubular dysfunction refers to RTA, Fanconis, SIADH, DI, phosphate wasting

3.       AKI refers to ATN, AIN or osmotic nephrosis. While not discussed in article- pre renal insult from pharmacologic agents might be under this category as well

4.       The mechanism then is divided in two types A and B.  Type A reaction are dose dependent toxicities and that are predictable based on drug exposure and pharmacology of agent for example aminoglycoside.  Type B reaction is unpredictable such as AIN from PPI or any agent for the matter.  A Type B reaction in glomerular category would be hydralazine or PTU induced lupus nephritis.

5.       Same drug can cause Type A or B reaction.

6.       Time course:  Acute ( 1-7 days),  sub acute (8-90 days) and chronic(>90 days).

7.       Setting: Hospitalized vs outpatient setting.  Outpatient setting drug injury is the most missed type as not easy to recognize as compared to inpatient setting as more reliable and easily visible data by consultants.

8.       The authors propose that drug induced kidney injury meet the following criteria:

a.       The drug exposure must be 24 hours before renal event

b.      Reasonable evidence for biological plausibility for the casual drug

c.       Complete data( full medication list, biomarker comparison)

d.      Strength of the relationship between attributable drug and phenotype should be based on drug exposure and duration, extent of primary and secondary criteria met and the time course of injury.

9.       Transient factors that affect change is important to know- BP trends, infections, and medications that can alter hemodynamics

10.   Kidney biopsy should be used to define ATN vs AIN or Gn to better get the phenotype.

11.   In patients with CKD, reference baseline crt might be used to use as value to which crt might return back to.  In cases of AIN, the crt may take much longer to return to baseline—making it a sub acute injury.

12.   Tools such as the Naranjo scale can be used to help guide but sometimes with multi drug exposure and other events, this might be not that helpful.

13.   This is an interesting start to a common problem we face. Sometimes biopsies are not that easy in the sick patient and guidance tools as this paper might be useful.    

Journal Club: CAPTAIN TRIAL: ACEI /ARB pre cardiac cath: Hold or not to hold

There is unclear evidence on holding ACEi/ ARB prior to coronary angiography reduces contrast induced nephropathy (CIN). The CAPTAIN trail just published in the American Heart Journal was a randomized trial to investigate whether holding ACEi/ ARB prior to cardiac catheterization reduces the incidence of contrast-induced AKI in patients with chronic kidney disease (CKD).

Some key points:

Total of 208 patients underwent randomization over 6 years with CKD as defined - creatinine >1.7mg/dl w/in 3 months before  cardiac catheterization and/or serum creatinine > 1.5 mg/dl w/in 1 week before cardiac catheterization

Primary outcome: incidence of AKI defined as an absolute rise in Scr of >0.5 mg/dl from baseline and/or a relative rise in Scr of > 25% compared with baseline at any time between 48 and 96 hrs post-cardiac catheterization.

Secondary outcome: absolute difference in post-procedure creatinine compared with baseline creatinine

Safety outcome was a composite of CHF or hypertension after the procedure

Results of the study demonstrate that in patients with CKD, holding compared w/ continuing ACEi/ARB prior to cardiac catheterization, with-holding ACEi/ARB resulted in a:

1.       Non-significant reduction in contrast-induced AKI

2.       Significant reduction in post-procedural rise of creatinine.

3.       Study demonstrated a strong trend toward improved clinical outcomes when ACEi/ARB was held before angiography.

4.       No adverse events were reported in the hold ACEi/ARB group

5.       Safety: no rise in CHF or HTN with holding ACEi/ARB therapy

This randomized trial does suggest that in CKD patients, it might be beneficial to hold the ACEI/ARB pre cardiac cath for some potential benefit.  A larger N would have perhaps been important to do to get a better sense of this protective effect. A multi center study would have been useful as well. 

Consult Rounds: Ifosfamide Toxicity

Ifosfamide induced renal damage comes in 6 flavors. The toxic agent is metabolite chloroacetaldehyde rather than the parent drug to the tubular cells of the kidney.

1.     Pure hypophosphatemia – this is due to direct proximal damage

2.     Fanconi syndrome

3.     Pure renal potassium wasting syndrome leading to hypokalemia

4.     ATN

5.     Distal RTA

6.     Nephrogenic Diabetes insipidus

In the NEWS: Amyloidosis and potential novel treatment

Systemic amyloidosis contains non fibrillar protein called serum amyloid P ( SAP).   Novel agent that is called CPHPC depletes SAP from the plasma but leaves some SAP in the amyloid deposits.  Following giving CPHPC, if given anti SAP antibodies, it can clear the remainder of the free SAP. A recent study in NEJM did an open label single dose phase 1 trial to look at 15 patients with systemic amyloidosis using the above strategy and there was clearance of amyloid deposits from liver and other tissues.

Few interesting and key points
What type of amylodosis: the patients included had AA, AFib, AL, AApoA1 type of amyloidosis.

What tissues involved: Liver, spleen, kidney, bone marrow, ( no patients with cardiac or severe renal involvement)

Any renal adverse events:- None in liver or kidney

This is a fascinating new pathway of treating patients with fibril based disease like amyloidosis. Wonder if this similar approach might be useful in other renal fibril forming disease such as fibrillary GN or immunotactoid GN.