Tuesday, February 25, 2014

eJC: Provider and Care Characteristics With Timing on Dialysis

CJASN's eJC feature is doing a hosting the journal club article at different institutions and sharing their thoughts on the manuscript on their eJC website.  Jan 2014 topic is a study that looked at provider and care characteristics with timing on dialysis. This is an interesting topic is discussed in a retrospective cohort manner and showed that provider factors are associated with timing of dialysis in the US.
The renal fellow network has commented on this article along with a discussion that took place at Duke Nephrology Journal club. Visit and log in via your ASN membership to eJC website of CJASN and provide your thoughts. If your institution does this for journal club, then post a summary statement of thoughts you all had regarding this study.

Thursday, February 20, 2014

Complement system in ANCA vasculitis

          Classically associated with a pauci immune RPGN, ANCA disease has traditionally been not associated with complement activation. Recent data in JASN 2014 from the UNC group suggests otherwise.  Passive transfer of anti MPO in mice induced ANCA associated necrotizing crescentic GN with activation of alternate complement system.  The researcher highlighted the role of C5a receptor in the mediation of this disease. As we know, C5 has a role more downstream close to the MAC system in the complement cascade.  Hence blocking C5a receptor will halt alternate pathway.  The researchers then showed that C5a receptor/CD88 engagement enhances the inflammation and C5L2 ( C5 a like receptor) suppresses inflammation.  Given an oral agent that blocks C5a receptor/CD88 ameliorated the GN in the mouse model. No human trials have been suggested yet but pharmaceuticals are already on the go for this proof of concept.
          In a different study, the elevated plasma and urinary C5a levels indicated complement activation in human ANCA disease. CD88 expression was downregulated, and C5L2 was upregulated in ANCA-associated glomerulonephritis.

          The role of complement in ANCA disease is not completely novel. If C5A receptor can be of help, why not block C5 directly with an agent we already have for C3GN, DDD, PNH and aHUS: eculizumab.
Looking at clinicaltrials.gov, we find a withdrawn study.( thanks to anonymous for pointing this out)

Tuesday, February 18, 2014

Clinical Case 80: Answers and Summary

Which statement best describes the relationship of microalbuminuria and cardiovascular disease?

Microalbuminuria causes cardiovascular disease
Atherothrombosis causes microalbuminuria
A common risk factor causes both microalbuminuria and cardiovascular disease
A common pathophysiological process such as endothelial dysfunction might lead to 
both microalbuminuria and cardiac disease

Most of you got this one correct. The age old question is " is microalbuminuria cardio toxic?" This is tough. Is it a surrogate marker of inflammation as some believe it is the ESR for the kidney or is it truly a risk factor for cardiac disease?  A paper in JASN many years ago looked at 4 potential mechanism of how these two might be related. The 4 mechanisms are listed above as your 4 choices. 

There is no direct evidence that supports statement " microalbuminuria causes cardiovascular disease".  The second statement may be partially true based on the authors argument but not many times hence atherothrombosis causing microalbuminuria might not be the problem either. Clearly common risk factors do exist with these two condition such as insulin resistance and or metabolic syndrome, and no one has looked at whether the association of the two conditions disappears when adjusted for insulin resistance and or other variables that are common risk factors. 

Hence, the most likely statement that makes sense is a common process that leads to endothelial damage leads to both microalbuminuria and cardiac disease.  Endothelial damage makes most sense as we as nephrologist see this all the time:- both diabetics get proteinuria and then the SLE patients with endothelial damage and then the pre eclamptics with endothelial damage. 

Sunday, February 16, 2014

Dream RCT contest- Dream it- Do it for the sake of Nephrology

The DreamRCT is a great online project spearheaded by Jordan Weinstein at UKidney and Joel Topf at PBFluids. Nephrology bloggers have all pitched in.
It is to stimulate ideas for a potential big project in clinical nephrology. For those new to this, these are NEW ideas that have never been studied before- innovation in the making!
The voting is going to begin on Monday Feb 17th 2014.  Go to Ukidney.com for the final voting.
The final contestants are:

1. NOMAD trial
2. CA-HIL study
4. URIC ACID-CKD connection
5. International Glomerular Disease trial network
6. PHANTOM-1 Study
7. Prevent DeaDD
8. Phosphate Trial

Check them all out and vote for the most likely to be doable and likely needed in nephrology.

Wednesday, February 12, 2014

#Dream RCT: Ca-HIL Study ( diuretic use in hypercalcemia)

#DreamRCT: Ca-HIL Study

Dream RCT is a project that many of us online are involved in. The assignment is to target the most important question you see in nephrology today and design a trial to answer it. Per Dr Topf, “Money no object, forget about pesky IRBs, let your mind free and create the trial which will meaningfully push back the walls of knowledge.

After you post your entry at your site of choice, UKidney will host a summary with a link for each entry and gather votes for the best. Check out what others have proposed. This is a novel project on ideas online for nephrology projects.
Here is my entry.

My idea for a dream RCT is very simple. There are many simple questions unanswered in nephrology.
Hypercalcemia is a common problem we encounter in the hospital setting. The most common cause usually is malignancy. While the long term treatment is dependent on the cause, the initial treatment is usually IV fluids and diuretics, calcitonin and so forth.  The data to give IVF followed by diuretics have been questioned. The initial observational experiences of many physicians have driven this practice.

 Usually aggressive IV hydration is warranted sometimes even at 150-200-250 CC/HR. 
Once volume depletion is addressed, a loop diuretic MAY be used for augmentation of calcium excretion.
A recent review and analysis published in Annals of Internal Medicine sheds some light about use of loop diuretic in this setting.

The review suggests the following points:

1. Aggressive hydration is necessary
2. Use of diuretics without aggressive hydration might be harmful
3. Found only 9 articles documenting the use of furosemide in hypercalcemia and latest one published in 1983 and total was only 37 patients.
4. Average dose was 1120mg over 24 hours ( really??)
5. Normalization of Ca occurred in only 14 of 39 cases
6. Study with lower doses didn't achieve normalization ( and what do we use????)
7. Complications of other electrolyte disorders ensued
8. Finally, recommended against the use of this agent routinely except for cases of volume overloaded with hypercalcemia.
I think the tile of the paper listed below nicely puts it:- Furosemide in hypercalcemia is an unproven but common practice ( really not evidence based)
·                     My suggestion is we study this in a standardized fashion: Hypercalcemia IVF and Lasix  ( HIL study)

Venue: Multi Center
Design: Randomized control trial
Primary end point:   1. AKI  2. Need for HD
Secondary end points: 1. Length of stay, 2. Mortality
Monitor closely other electrolyte disorders in both cohorts.

·                     Inclusion Criteria
o                  Age >18
o                  Sex males and females
o                  Primary known history of a malignancy related hypercalcemia

·                     Exclusion Criteria
o                  Other causes of hypercalcemia
o                  Hypercalcemia requiring dialysis at first visit with nephrologist
o                  History of known CHF requiring diuretics on a chronic basis.

Enroll all patients with acute hypercalcemia that are inpatient setting that are initially evaluated for treatment with aid of a nephrologist. To make it a uniform setting, perhaps only hypercalcemia of malignancy should be considered ( most common cause anyway). 

Randomize to IVF ( normal saline) alone for 48 hours followed by long term therapy with bisphosphanates, steroids or denosunab.
Or IVF (normal saline) for 48 hours and furosemide ( dose dependent escalation) followed by long term therapy with similar agents

I think this study or a variant of this concept should answer the question of need and use of diuretics in treatment of hypercalcemia.  Problem is who is going to fund this? 

Monday, February 10, 2014

Consult rounds: Electrolyte abnormalities associated with Primary hyperparathyroidism

Classically, we are notified to see a patient with hypercalcemia and one of the diagnosis that is made is primary hyperparathyroidism (PHPT). Due to the elevated PTH, what other electrolytes can go out of order?
1.       Hypophosphatemia:  Elevated PTH levels tend to lead to phosphate wasting in the urine.  Proximal tubular absorption of phosphorus( Na –Phos co transporter)  is blocked leading to renal wasting.
2.       Hypomagnesemia: This one is interesting as hypercalcemia would lead to decrease magnesium absorption via Ca-Sensing receptor in the TAL but PTH would increase magnesium absorption.  But net effect usually is “ hypercalcemia” wins leading to mg wasting as well. This in turn might lead to hypokalemia as well.

3.       Metabolic acidosis: Elevated PTH levels lead to decrease proximal bicarbonate absorption and leading to mild metabolic acidosis. This is usually seen when you have AKI as well compounding this problem.

Thursday, February 6, 2014

Topic Discussion: Glomerular Diseases and Pregnancy

Many times, primary GN presents during pregnancy and diagnosis is tough. Other times, patients with known primary GN get pregnant.  Three questions come to mind.

1.       Does the pregnancy change the natural course of the glomerular disease?

A study done in over 120 pregnancies looked at this question. The clinical course of 123 pregnancies in 86 patients with biopsy-proven glomerular diseases was evaluated. No complications were observed in more than half of the pregnancies. The lowest incidence of complications was observed in patients with membranous nephropathy and the highest in membranoproliferative glomerulonephritis(MPGN) patients. Renal function deteriorated in 10 cases during pregnancy. The authors note that in most patients pregnancy did not change the natural history of glomerular disease.

2.       What are the risk factors in GN with pregnancy for maternal and fetal outcomes?

Hypertension and impaired renal function at conception seem to carry increased risk for mothers and fetuses. A study done at a single center looked at these complications. 24 pregnancies in 17 women with biopsy-proven glomerular disease was analyzed. The underlying renal histology was IgA nephropathy in 8 cases, lupus nephritis in 7, MPGN in 1, and focal segmental glomerulosclerosis in 1.
                Fetal survival rate was 75%. The perinatal mortality was 5.5%. De novo hypertension occurred in 8 pregnancies (33.3%). In 11 pregnancies (46%) increased proteinuria was diagnosed and in 6 (25%) a decline in maternal renal function was recorded. Maternal hypertension and renal function impairment were found to lead to more ob complications.  

3. Which GN fare the worse?

Many GN have been reported with pregnancy( Membranous GN, MCD, MPGN, IgA, FSGS). A single center study looked at outcomes based on type of GN in pregnancy. In all cases diagnoses were established by biopsy before pregnancy. They were: MPGN in 16 patients, focal glomeruloesclerosis in 13, IgA nephropathy in 10, membranous nephropathy in seven and focal glomerulonephritis in two women. Women with membranoproliferative glomerulonephritis appeared to fare worse, and those with IgA nephropathy and membranous nephropathy better than the rest.

All Posts

Search This Blog