Concept Map: Herbal Remedies and Kidney Diseases

Herbal agents are used on a daily basis by many. Risks to the kidney have been identified with some of these agents. Here is a brief concept map of few of the agents have had strong associations with CKD, glomerular disease and electrolyte disorders. Dr Warren Kupin from Miami recently spoke to us about these and I summarize these from his discussion to us.

NKF has a summary as well on this concept.  V Jha has a nice review as well.
Click on image below for larger view of the concept map.

Nephrology at crossroads in 2014-2015

Looking back at the year 2014, where do we stand in terms of Nephrology?

                Compared to last year, this year bought a spectrum of kidney diseases to light and the number of articles published in high impact journals was astounding. NEJM and JAMA had great articles from amazing clinical research done this year in Nephrology.  There has been no research done in hyperkalemia in decades, but of recent, 3 top tier articles with 2 new agents in NEJM and JAMA.  And if you look by category- nephrology in NEJM, this year had 13 original articles, up from 10 in 2013. There was significant review articles as well in NEJM this year on various topics.  Simplicity 3 and CORAL trial being some of the major Hypertension highlights but the JNCVIII also made way to affect the world of Nephrology. The science of nephrology is clearly advancing.  Even though some of the trials were negative trials, we know what DOES NOT work and keep trying rather than doing something based on observational data and then finding out it caused harm.  The renal fellow network has a top 10 nephrology story countdown. Go and vote for your top study.  The new allocation system for transplantation is a positive step for clinical patient care in nephrology.

                In the realm of education, Nephmadness 2014 ( brainchild of Topf and Sparks) was well received with much more participation then 2013 version.  Watch out for the upcoming Nephmadness 2015 this upcoming year.

                The NRMP Nephrology match was met with a debacle and many spots going unfilled. ASN has a special report on this.  While this might be a setback for our field, this should not stop us from continuing what we do best – be passionate of nephrology and continue to shower enthusiasm and knowledge about renal disorders for our trainees.  Trainees ultimately have the right to choose the field that they desire to be happy with.  The last thing we want is “just filling the spots” and unhappy fellows in making.  The ASN is planning to create a match Taskforce to help in this matter.  Tejas Desai, creator of NOD has come up with a creative solution that suggests a short term solution of fixing the match process- decreasing the number of fellowship spots. Which programs should do this and which should not is the question and he address that in his proposal… have a look and comment on what you think?

                So as we look into 2015, think positive and let’s create the same magic as we did in 2014 for science in nephrology. Every field has their bumps and so does nephrology. We shall overcome this barrier as a community as well.  Collectively, we need to inspire students, residents at ground level and every institution needs to light this candle. No large society can make this happen. Even if one person at each institution can inspire students and resident, we will make it happen.  This is a collectively call for all academic, and private practice nephrologists who love what they do to shed their experience and passion to trainees.  For those who don’t like what they do- I have no comments but to ask yourself why you went into it for the first place?

Concept Map: APOL1 Nephropathy

APOL1 gene nephropathy has now emerged as a potential new entity given the linkage to African American ancestry and having these alleles that were protective against sleeping sickness and then leading to more HTN proteinuric and non proteinuric renal disease in AA.  Below is a summary concept map on this topic and how having these alleles and then a SECOND HIT concept might be necessary for disease phenotype.  There are likely two disease phenotypes- FSGS variants and then the tubular non proteinuric variants. African Americans with arterionephrosclerosis who possess two APOL1 risk variants more often lack obsolescent glomerulosclerosis and have greater degrees of (solidified and disappearing) glomerulosclerosis, thyroidization-type tubular atrophy, and microcystic tubular dilation than patients with fewer than two risk variants in the non proteinuric patient lists.  
Also, there is some emerging data that JC and BK virus might be protective for the kidney relatives of patients with APOL1 nephropathy.

References:

Pathology of Non proteinuric Renal diseases in APOL1 nephropathy
Second hit concept
Protective viruses for APOL1 nephropathy

Sickle Cell Trait and Renal disease

Are there any association of sickle cell trait( SCT) and renal disease? Sickle cell disease and renal disease has been well established, but SCT and renal disease is an area understudied. A recent JAMA study showed association using a registry data.  Primary outcomes were CKD , incident CKD, albuminuria and decline in eGFR. The study concluded that among African Americans in these cohorts, the presence of SCT was associated with an increased risk of CKD, decline in eGFR, and albuminuria, compared with noncarriers.

What type of diseases do we see with SCT in the kidney? In SCT, injection radiographs demonstrate renal medullary vascular disruption, though to a lesser extent than seen in sickle cell disease, suggesting that sickle hemoglobin may have a dose-dependent relationship with kidney injury.  Our finding that SCT was related to both CKD and albuminuria is consistent with these proposed mechanisms. SCT is 4-5 times more common than sickle cell disease.  Hematuria by far is the most common complication of SCT especially seen in African Americans.  Admission rate in one study with patients with SCT and hematuria was 4%.  

The most common renal involvement in SCT are:

1.    Papillary necrosis ( most common)

2.    Renal infarction

3.    Isosthenuria

4.    Increased risk of exercise induced rhabdomyolysis

5.    Renal medullary carcinoma( very rare)

6.    Earlier onset of ESRD if also have ADPKD

Nephrology Crosswords: Hemodialysis

Check out the next installment of Nephrology Crosswords in Kidney International on
Hemodialysis

Hyperkalemia meets their new K-busters

      Hyperkalemia is a challenge in CKD and ESRD patients. The treatment agents for this complication have been limited to bowel resins, diuretics and dialysis.  There has been some recent interest in novel agents as some evidence suggesting the efficacy of Kayexalate and side effects leading to colonic necrosis in some settings.

Three articles published this week (2 in NEJM and 1 in JAMA) give us trials of using novel K lowering agents in three different settings.

The first trial looked at patiromer use for hyperkalemia in CKD patients on RAAS inhibitors. The active moiety of patiromer for oral suspension is a nonabsorbed polymer that binds potassium in exchange for calcium in the distal colon leading to highest K excretion possible. Patiromer is a dry powder, primarily a spherical bead that is not absorbed and that binds potassium when mixed in small amounts of water. It exchanges potassium for calcium, which would be of some concern if the drug were absorbed. It appears, however, that the drug is not absorbed and that the amount of calcium absorbed is small. In A RCT with placebo, patiromer treatment was associated with a decrease in serum potassium levels and, as compared with placebo, a reduction in the recurrence of hyperkalemia. Mild-to-moderate constipation was the most common adverse event (in 11% of the patients); hypokalemia occurred in 3%.

The second trial looked at zirconium cyclosilicate (ZS-9), a novel selective cation exchanger, could lower serum potassium levels in patients with hyperkalemia. ZS-9 is a compound with a crystalline structure that traps potassium  10 times as much potassium as kayexalate does. It is insoluble and remains in the intestine during transit. This was in a variety of diagnosis leading to hyperkalemia in over 700 patients. There was an initial phase and then a maintenance phase. Patients with hyperkalemia who received ZS-9, as compared with those who received placebo, had a significant reduction in potassium levels at 48 hours, with normokalemia maintained during 12 days of maintenance therapy per their conclusion

The third trial titled HARMONIZE was a phase 3, multicenter, randomized,

double-blind, placebo-controlled trial evaluating zirconium cyclosilicate in outpatients with hyperkalemia (serum potassium_5.1mEq/L) . Among outpatients with hyperkalemia, sodium zirconium cyclosilicate reduced serum potassium to normal levels within 48 hours; compared with placebo, all 3 doses of zirconium cyclosilicate resulted in lower potassium levels and a higher proportion of patients with normal potassium levels for up to 28 days.

Two accompanying editorials are in NEJM and JAMA as well

Few questions still remain and are a concern:

Since all 3 trials were pharmaceutical company sponsored, placebo was used to compare the agents for efficacy. Why not kayexalate?- it works and it’s cheaper. The authors in one study did state that the agent was not compared to sodium or calcium polystyrene  since prospective studies are lacking in the later and also agents cause bowel necrosis.

But there are significant years of experience and pathophysiology that it works.  Side effects are part and parcel of every agent. The above agents had constipation as side effect, and some might have calcium and magnesium concerns if used long term given how they work. Also all three trials were very short term and long term trials are needed still.  FDA approval is also warranted before any use.

Nevertheless, the patients we have that have CKD and or heart failure and we really want them to be on ACEI, ARB or aldactone but cannot due to K related concerns and or require diuretics with them:- now we may have an alternative option for the situation. 

Pause to think about POISE

One of the largest AKI trials was presented at ASN Kidney week 2014 and just published in JAMA as well- POISE 2.  It was a trial to look at a preventive strategy for AKI in non cardiac surgery setting.   An international trial, with 88 centers, 22 countries, from 2011-2013 of over 6000 patients was done to see if ASA or clonidine given prior to surgery prevented AKI post surgery.  Not to my surprise, a mong patients undergoing major noncardiac surgery, neither aspirin nor clonidine administered perioperatively reduced the risk of acute kidney injury. In addition, the ASA group had more risk of bleeding and the clonidine arm had more risk of hypotension. 

The logic behind using this strategy doesn’t make sense to me.  There are few trials in the surgical literature that might have prompted this trial.

The ASA data
The Clonidine data

The funding was provided by the CIHR, Spanish ministry of health and few other funding pharm agencies.  A multi international trial of AKI that might be one of the largest to date is an amazing ordeal but the concept seemed less likely to have worked.  A drug that causes bleeding and another one that causes hypotension is more likely to cause harm then benefit.  Ischemic re conditioning or sonogram might have been an interesting approach.  

ASN Nephrology Fellow's Events 2014

Welcome reception: Nov 12th: 6-7PM
Marriott Downtown, Grand Ballroom, Salon H

Fellows In Training Bowl( Mystery Case Debate): Nov 14th 2-3PM
Convention Center, Room  119A

Fellows In Training Bowl( Jeopardy game Nephrology Challenge): Nov 14th 3-4PM
Convention Center, Room  119A

Meet the Experts Session Nov 15th  9:30AM - 10:30AM( Meeting the ASN Award Winners)
Convention Center, Hall D

Fellows Forum Nov 15th 10:30-11:30AM
Convention Center, Room 203

Fellows Poster Discussion Section Nov 15th 2-3PM
Convention Center, Room 112

ASN 2014 Abstracts

ASN abstracts 2014 are now online and available for review.
Posters on demand will also have online posters for viewing soon as well.

For those interested in Social media and education in nephrology, few special sessions being held this year

1. Tweets, likes and Blogs: How to use social media for your patients and your benefit.Nov 13, 1030-12:30PM

2.Boost your teaching skills to become a contemporary nephrology educator. Nov 14, 2-4PM
3. Case Based Debates ( Fellows in training bowl)- Mystery case competition Nov 14, 2-3PM
4. Nephrology fellows jeopardy- Nov 14, 3-4PM

IS CKD-MBD a syndrome?

 

Is it a syndrome? An article in NDT addresses this entity as a possible syndrome in CKD

When one looks at nephrotic syndrome or metabolic syndrome, those entities usually fulfill the criteria for calling it a “syndrome” as most patients would fit that criteria and prognosis and treatment would be resulted.  In CKD-MBD, this article argues against it being a potential syndrome in CKD but perhaps might be.  CKD-MBD represents a synopsis of three closely related disease conditions: laboratory abnormalities indicative of disturbed bone and mineral metabolism; renal osteodystrophy summarizing the variety of bone lesion subtypes occurring in CKD; cardiovascular disease representing accelerated arteriosclerosis, left ventricular hypertrophy and a variety of additional pathologies in the vasculature and the heart in patients with CKD.

But do all patients with CKD have all the bone parameters abnormal; and if they do, what is the CVD risk and prognosis?  But it’s worth some thought of this potentially being a syndrome.

Have a look at the full paper.

http://m.ndt.oxfordjournals.org/content/29/10/1815.full.pdf
A workshop is being held in Europe to further define this

C-KIN( Cancer and Kidney International Network)

The first ever international society specifically for onconephrology has been created.
It's called the C-KIN( Caner and Kidney International Network).
Check out the their twitter feed at https://twitter.com/CKINnews and their annual conference schedule and abstract details as well. C-KIN aims at improving patient care through better knowledge, education and awareness on cancer and the kidney related issues and research.

Clinical Case 85: Answers and Summary ( iron use in ESRD)

ESRD patient with anemia, Fe sats of 12%, Ferritin 450 needs IV iron. Patient has bacteremia.

A. Proceed to give IV iron as anemia and low Fe sats demands it.  (2%)

B. Given active infection, do not give IV iron till 2 weeks after infection resolved (73%)

C. Given active infection, do not give IV iron till 4 weeks after infection resolves. (24%)

There have been no clinical trials of adequate sample size and duration to provide us sufficient understanding of the safety of intravenous iron. Is bolus iron better or continuous form? Is iron infusion pose an infection risk?

Brookhart et al. retrospectively studied patients on dialysis treated at Davita Inc. dialysis facilities and found that patients receiving 200mg intravenous iron per month had an increased risk for hospitalization or death because of infection. They also found that bolus dosing was more associated with infection. More recently, A CJASN study by Miskulin et al. found a increased risk for infection-related mortality when cumulative iron dose exceeded 1050 mg over 3 months or 2100 mg over 6 months( not statistical but a trend). In an accompanying editorial to the Miskulin study, Fishbane et al (must read) discuss what the USRDS data suggests. As the mean serum ferritin of United States patients on dialysis approximately doubled from 1993 to 2001, the rate of bacteremia/sepsis increased approximately by 40%. From 2001 to 2010, serum ferritin stabilized, and soon enough the bacteremia/sepsis rate also stabilized. In light of these above findings, it is advisable to hold iron infusions in setting of active bacteremia.  

What about other active infections such as cellulitis or pneumonias? No data exists for those at this point. How long do we wait is a good question. Most likely choice is 2 weeks but data for that is not clear. Some of you chose 4 weeks: might also be a reasonable choice.  Another concern might be catheter use.  Infection risk as stated by the Brookhart study that risks are largest among patients with a catheter and the ones with a recent infection. 

Topic Discussion: Ebola and the Kidney

Ebola is a RNA virus that has a high rate of transmission.  As we have now noted the world’s largest outbreak of this virus to date, the cure for this entity remains a mystery.  Ebola hemorrhagic fever is a severe infection. It can have a mortality rate of up to 70-90%. The infection can occur in humans and animals. The virus family is Filoviridae and genus Ebolavirus. It was first discovered in 1970s near Ebola river in Congo.  Since then most of the outbreaks have been in Africa.  While the natural reservoir host of Ebola remains unknown, some believe it might be bats.

How does the kidney get involved? Severe volume depletion from this hemorrhagic disease leads to acute kidney injury.  Electrolyte abnormalities such as hyponatremia, hypokalemia and so forth can be noted as well.  Renal failure was described in this entity in early 1980s. DIC ensues and a shock state leads to AKI. Prior animal studies have shown that there is some necrosis and calcification in tubules and glomerular tufts of kidney. The first victim in the US in Texas was on dialysis as well.

While some treatments and preventions are being considered, there is only supportive therapy that can be offered at this time. However, survival is improved by early supportive care with rehydration and symptomatic treatment. Early intensive care therapy might be necessary.

What might be of interest to us as nephrologists is the use of dialysis modalities to help clear the virus. Hemopurifier, a device from  Aethlon Medical (San Diego, CA) that’s capable of filtering blood of impurities like viruses is available. Apparently it is being used currently ( per their report) for filtering the blood of an infected doctor with the virus in Germany. The device can be used with standard dialysis and continuous renal replacement therapy (CRRT) machines and doesn’t require any special hardware upgrades.

More information regarding this can be found at the website

http://www.medgadget.com/2014/10/aethlon-hemopurifier-now-filtering-blood-of-ebola-patient.html

New York Society of Nephrology 2014-2015 Lecture series

New York Society of Nephrology  2014-2015 lecture series for this upcoming academic calender.
If you are around, come join this amazing group of speakers( basic science and clinical).  This happens at the Faculty Club at Weill Cornell Medical Center

http://nysn-online.org/lecture.html

October 22, 2014

2014 Gibbs Awardee Lecture **NYAM

Fred Coe on Renal Stones

December 3, 2014 ( Hypertension and kidney disease)

1. JNC VIII update.  Ray Townsend 
2. Update on APOL1-associated nephropathy; The search for modifiable “second hits”    Barry Freedman

January 7, 2015 

1. IgA nephropathy: Beyond KDIGO. Dan Cattran
2.  The Burton Rose Neprhology Lecture: Orsen Moe

February 4, 2015( GN/Onco-nephrology)

1. Glomerular cell regeneration in disease-what we should be doing for patients.  Stuart Shankland
2. Paraproteinemic renal diseases: an update   Nelson Leung

March 4, 2015 ( Acute Kidney Injury)

1. New Insights Into Tubule Cell Injury and Death During Acute Kidney Injury". Joel Weinberg
2. Acute Kidney Injury Associated with Cardiac Surgery. Mitch  Rosner. 

April 22, 2015( Transplantation)

1. Update in Antibody Mediated Rejection. MillieSamaneigo.  
2. Regulatory B cells in Transplant Tolerance. David Rothstein.

May 20, 2015 

Fellows’ Night NYAM

TOPIC DISCUSSION: IgA nephropathy and FSGS

What is the significance of findings of FSGS in biopsies that are predominately IgA nephropathy?

Two studies have looked into this matter in 2009 and 2011.

The NDT study in 2009 looked at 75 patients ( split into IGA with FSGS, IGA without FSGS).  In the multivariate model, the FSGS+ group showed a worse GFR decline.  It is no surprise that when there is sclerotic lesions, the prognosis is going to be worse. The question arises if this is part of IGA progression or it is two processes happening independently? Would steroids be indicated in such settings?

The KI study from 2011 looked at over 100 patients and used the Oxford classification for IgA and Columbia classification for FSGS to evaluate the two seen in the same biopsy.  Collapsing FSGS with IgA had worse outcomes.  Overall, worse outcomes were noted with any form of FSGS was present when compared to IgA alone.  In addition, when FSGS was present with any other glomerular findings( mesangial hypercellularity, necrosis, deposits), outcomes were worse compared to “pure” FSGS.
Staining studies they performed showed that the changes related to the podocytopathy were present even with mild IgA disease suggesting that the two processes might be independent and not just an end pathway for any glomerular disease. 

IgA can present with preserved renal function and MCD like podocytopathy.  Presenting with FSGS is more challenging and treatment may be difficult to decide upon.  If there is good preservation of IFTA on biopsy and if there is >1gm of proteinuria, perhaps it’s worth treating with steroids or at least a trial of steroids.  

In the NEWS: FSGS and CD40- a potential new finding

A new potential culprit might have been found for the recurrence of FSGS post transplant. A recent article evaluated pathogenic antibodies in 141 serum samples over 64 patients and looked at many potential culprits such as CD40, PTPRO, CGB5.etc and pre transplant elevation of anti CD40 alone was the best predictor of FSGS recurrence after transplantation.  Another study highlight is the observation that patient-derived antibodies against CD40 functionally cooperate with a previously identified culprit of FSGS called soluble urokinase plasminogen activator receptor (suPAR). Co-injection of patient-derived CD40 anti-autobodies and suPAR caused enhanced kidney filter failure more than each component did by itself.

This is fascinating as can anti CD40 therapies then lead to preventing FSGS in kidney transplantation?

Abatacept or belatacept may have some role in FSGS treatment. A recent study showed the success of using such agents in minimal change disease. It is interesting to note that in presence of cd40 auto antibody, the wild type suPAR becomes pathogenic to the podocyte.  There seems to be an on/off switch for suPAR perhaps with Cd40 and a trial of belatacept in FSGS might be warranted.  

Would co stimulating blockade agents be sufficient as their interaction as an anti CD40 is possible?- as we use those in transplant anyway? Perhaps, looking at the recurrence of FSGS in patients on belatacept might be a good start.  Or are we specifically going to look at ant CD40 agents( some of which are being studied as anti cancer agents in colon cancer and others)

There is some data of use of this agent in panc transplantation as well.

http://www.jimmunol.org/content/166/1/89.abstract

http://www.bloodjournal.org/content/102/4/1449?sso-checked=true

http://cancerimmunolres.aacrjournals.org/content/early/2013/10/19/2326-6066.CIR-13-0067

For full paper look here

http://stm.sciencemag.org/content/6/256/256ra136

IN the NEWS: End of Fenoldopam in prevention of AKI following CT surgery

Fenoldopam has been advocated in prior studies to prevent AKI following surgery: specially studied the most in cardiac surgery.  The most recent issue of JAMA gives us the first randomized multi center placebo controlled trial on use of fenoldopam in CT surgery patients for prevention of AKI. 

Key points:

This study assigned >600 patients to placebo or fenoldopam that were admitted to CT ICU following cardiac surgery with early AKI.  30 day follow up was done.

The primary outcome was need for RRT and mortality was the secondary outcome/ rate of hypotension during infusion.

Patient characteristics appeared equal. There seemed to be more patients with A fib in treatment arm, more pulm HTN and MI in control arm.

Types of surgeries were equal in both( CABG, MVR, AVR, TVR, aorta surgery, and others)

CKD stages based patients were equal in both.  There was 13 CKD IV patients in control  and 19 CKD IV patients in fenoldopam arm.  But majority of them initially had GFR >90. 

Conclusions: Among patients with AKI after CT surgery, fenoldopam infusion compared to placebo showed no benefit in need for RRT or 30 day mortality.

In addition, the infusion caused some harm and led to hypotension episodes compared to placebo arm. 

A prior study had shown similar findings from AJKD.

Is this the end of fenoldopam in prevention of AKI in CT surgery?  Largest study, multi centered and good power showing harm more than benefit. I think we have our answer.  

Full article

http://jama.jamanetwork.com/article.aspx?articleid=1910563

Consult Rounds: Dialysis in the Acute Brain Injury patient

Standard hemodialysis can increase cerebral water content and lead to edema. The pressure in the brain or ICP shouldn’t have too many influences.  There is strong buffer system in the brain but if that fails- then the ICP can increase rapidly.  It has been noted that even small subclinical cerebral edema that occurs in IHD can slowly raise the ICP.  Why is that and how does the BP and acidosis make this possible?

A review by Davenport on this topic suggests few cautions:

1.      Drops in blood pressure or intradialytic hypotension can lead to ICP rises( Figure 1 from the Davenport review)

2.      Big fluctuations in urea shifting

3.      Intracellular acidosis in the brain as CO2 is removed in dialysis leads to paradoxical Co2 absorption in the brain and causing imbalance.

4.      Exogenous substances can enter brain ( albumin) during brain injury as BBB is broken and lead to worsening edema.

Above Figure from Davenport article.

Some key points regarding what should be done then?

1.         All standard intermittent therapies, hemofiltration, hemodialysis, and hemodiafiltration, will lead to increased cerebral swelling, and if the patient has suffered a severe injury and is unconscious, then most centers would deem continuous renal replacement or hybrid therapies as the preferred treatment. ICPs have shown to remain much more preserved and constant in CRRT forms rather than IHD forms of therapy.

2.         Treatment should be designed to both slow down the rate of change of serum urea and osmolality, and to maintain cardiovascular stability( so perhaps daily IHD might be needed to minimize BUN shifts and prevent edema from getting worse)

3.         Given breakdown of BBB, avoid heparin based dialysis in this setting

4.         If doing HD, would do daily and use a lower BFR and cooler dialysate( 35C), smaller dialyzer and high Na bath(≤10 mEq/L above serum sodium), bicarb of 30meq/l , higher K and calcium baths).

5.         Some might suggest keeping a pre dialysis BUN low( less osmotic shifts – close to 30 and keep on supplemental oxygen.

Interestingly, regarding cooled dialysis- a recent JASN 2014 article sheds some light on that as well. In total, 73 patients on incident hemodialysis starting within 6 months were randomized to dialyze with a dialysate temperature of either 37°C or 0.5°C below the core body temperature and followed up for 1 year. Cooled dialysate improved hemodynamic tolerability, and changes in brain white matter were associated with hemodynamic instability and patients who dialyzed at 0.5°C below core body temperature exhibited complete protection against white matter changes at 1 year.

Preventing hypotension and rapid osmotic shifts is essentially what is required. 

Nephrology physiology videos by a fellow in training

 John Roberts, a nephrology fellow at Duke, recently produced a collection of short (10-15min) videos on renal physiology to simplify nephrology. They are "khan academy" type videos.  Medical students, residents and fellows can benefit from this basic physiology review. 

Tubular Transport 1 
Tubular Transport 2
Regulation of Body Fluid Osm 1 
Regulation of Body Fluid Osm 2 
Body Fluid Compartments: Regulation of ECFV 1 
Body Fluid Compartments: Regulation of ECFV 2 
Potassium 1
Potassium 2
Acid Base Physiology 1 
Acid Base Physiology 2 
Acid Base Physiology 3
Action of Diuretics

TOPIC DISCUSSION: Crystalglobulinemia and prarproteins and the kidney

Crystalglobulin induced nephropathy is a known complication of paraproteinemias.  A recent review In JASN focuses on this presentation of kidney damage from paraproteins. Monoclonal proteins can also deposit in the kidney as crystals and cause tissue damage. This happens in cases of  light chain proximal tubulopathy, crystal-storing histiocytosis, and crystalglobulinemia. Crystalglobulinemia is a rare complication of multiple myeloma that results from crystallization of monoclonal proteins in the systemic vasculature, leading to vascular injury, thrombosis, and occlusion. One can observe diffuse rectangular, rhomboid and sharp needle shaped hyaline-like  crystals depositing in multiple organ systems, including the kidneys, myocardium, coronary arteries, tricuspid and  pulmonary valves, lungs, bone marrow and other organs. Usually, this is a quick and drastic leading to AKI, and ESRD. The reason why this happens is unclear.  It is possible that it related to the abnormal glycosylation of light chains and their interactions with albumin.  IgG k and IgG lambda chains both have been reported to be involved. Heavy chains have also been reported.  Both cases of MM and MGRS have been reported to be present with crystalglobulinemia.

Fig 1: Crystals in urinary space

Fig 2: Intracardiac crystalline deposits 

Telenephrology: Is this the answer?

Chronic kidney disease (CKD) is a common medical condition, affecting approximately 26 million adults in the U.S. Parallel to the increasing prevalence of CKD, a record number of patients now have end stage renal disease (ESRD). In 2007, 368 544 patients were on dialysis—a striking 54% increase from one decade earlier. Meanwhile, mortality rates for dialysis patients have declined, and approximately 775 000 people are expected to be alive with ESRD in the year 2020.

The nephrologist—a central provider for patients with CKD, ESRD, or kidney transplants—assumes a critical role in addressing the primary care needs of these patients, who tend to require frequent follow-ups. To meet the projected need for nephrologists inthe United States, fellowship programs should have produced an estimated 436new nephrologists each year since 2000. During the past decade, however, the American Board of Internal Medicine (ABIM) only certified an annual average of 382 nephrologists. This is despite the organizations many efforts and initiatives to recruit physicians to the field of nephrology.  If you do the math, the deficit is alarming.

Telemedicine is the practice of medicine using modern communication technologies when the physician and the patient are separated by distance. The modern communication technologies involved are nothing more intimidating than the telephone, e-mail and videoconferencing. Formally defined by the American Telemedicine Association, telemedicine is the use of medical information exchanged from one site to another via electronic communications to improve a patient’s clinical health status. It has been applied to other specialties, particularly neurology, radiology, psychiatry, ophthalmology, and high-risk obstetrics but nephrology has been a slow starter. Indeed, as a specialty, nephrology may be very suitable for this type of medicine. 

Nephrology is a visual and auditory rather than tactile subject – the skill is in recognizing diseases principally from a history, backed up by demonstrating basic physical signs in an examination and established by laboratory tests. So, if nephrologists based in urban centers can deal with renal patients in distant parts of the country, or even different countries, by means of communication technology, then the problem of reduced access to specialist care may be lessened, if not solved.

Post By Judy K. Tan MD

Mount Sinai Medical Center, New York, New York

Twice weekly, three times weekly or daily dialysis- where do we stand?

While observational trials had shown that there is much more benefit in daily dialysis (improved phos control, better HTN control, anemia), the FHN trial in NEJM proved some of the hunch that more dialysis was better in terms of cardiac remodeling and quality of life. This study compared in center patients to standard HD vs daily dialysis.  These were prevalent patients and not incident patients with some residual renal function.  

A recent editorial in AJKD sheds some light on residual renal function as an important predictor of renal survival.  The authors suggest that thrice weekly might rapidly decline renal function compared to perhaps twice a weekly dialysis sessions. But does that matter compared to cardiac outcomes.  The second FHN trial in Kidney international showed that the more intensive nocturnal HD group failed to show benefit compared to the three times a week dialysis.  Interestingly, this was in all incident patients with residual renal function.  The study found that the more intensive HD group lost residual renal function faster and in addition no difference in cardiac remodeling and quality of life. More vascular interventions were also performed in the more intensive arm. 

Finally, the most recent AJN article published this week, a single center study from China shows that twice a week HD preserves residual renal function.  They examined 85 HD patients; 30 of them were initiated with twice-weekly HD for 6 months or longer and 55 patients were started and maintained on thrice-weekly HD treatment. Then a subcohort study in 48 incident HD patients was implemented to assess the independent risk factors responsible for RKF decline during the first year of HD therapy. Clinical outcomes were the same in both groups. The multivariate analysis showed that factors such as the male gender, HD frequency, URR and intradialytic hypotension episode were associated with residual renal function loss. This study’s main outcome was residual renal function and not mortality.  It will be interesting to see and follow these patients to see the mortality data regarding this.

What does this lead us to believe? One size DOES NOT fit all. Perhaps initially, HD should be catered to preserving residual renal function and start slowly. Some patients might require twice a week HD, some three times a week and some perhaps more such as 4-6 times a week.  Should we be doing HD just as we do PD? When we calculate PD related CRCL, we use the residual renal function clearance and then the peritoneal clearance and add them to get to our expected/desired kt/v.  Why shouldn’t we do that in HD as well?  Incident patients might benefit from less intensive HD and prevalent patients who have lost residual renal function, might benefit from more intensive HD.  More studies are needed to answer these questions that the FHN and other studies have raise.