Once you go beyond the modified Ponticelli, the treatment of idiopathic membranous feels like hunting in the woods. I have a woman in her late thirties who I have been treating for almost three years. She has between 6 and 10 grams of proteinuria, no renal failure (Cr or 0.8 and stable) no hypertension, and a middling albumin with terrible lipids. She doesn’t get much edema and is able to limit her use of loop diuretics to very occasionally.
We started with conservative therapy for 6 months to see where the proteinuria is going. After that we decided to give treatment a try because of the heavy proteinuria. She also had high levels of urinary IgG and urine beta-microglobulin.
She was reluctant to use cyclophosphamide because of concerns about future fertility. And I’m reluctant to use it in a young patient especially for a disease which is causing her minimal problems right now.
We started with MMF. Little effect.
We then gave a trial of CSA. Little effect.
We gave a trial of Pentoxifylline (Trental). little effect
What now? Tacro? Rituximab?
Anyone have any experience with ACTH?
I must say I have been seduced by the preliminary data (case series, rct) on ACTH. To me it looks more compelling than the alternatives (rituximab and tacro). The fact you have to go to a specialty pharmacy to get the stuff is a little intimidating.
Link to a description of membranous nephropathy from a lecture I give on Hep B, C and HIV associated renal pathology.
Just saw this post on the Renal Fellow’s Network. I appreciate his flippant attitude toward renal vitamins as they are so routine as to invite disregard but they may have an effect on mortality.
This 2004 article based on the DOPPS database shows a significant reduction in mortality (RR 0.84) associated with use of water soluble vitamins.
I always have a healthy skepticism for DOPPS data as they have been on the wrong side of the anemia, Kt/V and statin debate. Each time being refuted by the RCT. But I’ll take the position that since no one will ever do a randomized controlled trial we should go forward with the renal vitamins.
I first heard about this data on renal vitamins during the at the Easterling Lecture given by Eric Young for the Michigan NKF in 2003. At the time this was explained by the reduction of homocysteine induced by the folate in the vitamin. Since that has also fallen to the blade of the RCT, I wonder what componant of the renal vitamin explains the benefit.
Kidney Disease a Takes a Growing Toll
Nice article on the increasing prevelance of chronic kidney disease. They even mention the controversy of geriatric CKD, one of my newest interests.
The article mentions the NKF of Michigan’s project to raise awareness of CKD by using hair dressers. I am the newest member of the NKF of Michigan’s Scientific Advisory Board.
Also the article has a quote by Steven Fadem, a nephrologist I shared a limo with last week at the EVOLVE Primary Investigator’s Meeting. Crazy small world.
Glen Chertow on MBD and clinical practice.
Starts with the high mortality of CVD in ESRD slide shown at every gatheriong of nephrologists.
MBD as a non-traditional risk factor for CVD
HEMO, 4D, Wrone on homocysteine, D-COR all RCT, All negative. [should add correction of anemia study]
45% drop out in D-COR lead to a loss of power and contributed to negative trial.
Cinacalcet approved based on its ability to get the PTH down and get patient to guidelines but we are missing the information on whether this helps patients.
Power is the probablity of detecting the treatment affect if it really exists. 90% power means that 9 out of 10 times you will detect a treatment effect if it exists.
With 3883 patients EVOLVE had 88% power to detect 20% reduction in cardiovascular disease. If the benefit is 15%, which would phenomenally important to our patients, we may not be able to detect it.
bill goodman talking on KDIGO. Goodman wrote the article that interested me in the topic of vascular calcification and binder choice.
What is KDIGO
Kidney Disease Improving Global Outcomes
established in 2003
Independent non-profit, established by the NKF
The concept was to take K/DOQI and generalize the guidelines for a global audience.
The KDIGO mission is to provide:
- Clinical Practice Guidelines
- Guideline database
- Work groups
- Controversy conferences
- Mineral and bone inititative (in draft)
- Hepatitis C in kidney disease (coming)
- Care of transplant patient (coming)
- Acute kidney disease (coming)
CKD Mineral and Bone Disease
A rose from the perception that international perspective needed to define renal osteodystrophy
use the phrase ROD exclusively to define: alterations in bone morphology in patients with CKD
classification based on bone histology, bone turnover, mineralization and volume.
CKD-MBD is a systemic disorder of mineral and bone metabolism due to ckd manifested by either one or a combination of the following:
- abnormalities of Ca, Phos, PTH, Vitamin D
- abnormal bone turnover, mineralization, volume, linear growth or strength
- vascular or soft tissue calcification
KDIGO revisited the concept of guidelines
They graded evidence and created their guidelines by limitting the data to:
- RCT of at least six months in duration
- N>50 excepts for pediatrics and bone biopsy
- Intermediate endpoints including: BMD, bone biopsy, vascular calcification and biochemical endpoints are not considered unless they have been validated prospectively [unclear if any surrogates have been validated]
- Observational studies acceptable if a clinical outcome examined conducted with a high methodological quality and had a relative risk of >2.0 or <0.5
treatment of CKD-MBD
- lowering high phos
- abnormal PTH levels in CKD-MBD
- treatment of bone and bisphosphonates, other osteoporosis medication and growth hormone
- evaluation and treatment of kidney transplant bone disease
there is little evidence to provide guidance for a specific therapeutic target range for any biochemical parameter
- extreme values are associated with greater mortality risk
- little evidence to support preferred treatments
KDIGO concluded that PTH guidelines are mainly opinion based and not informed by randomized clinical trials
150-300 is based on evidence just not rct and outdated
phos and calcium guidelines are loose
repeated emphasis through out document on the lack of evidence from RCT with hard outcomes
Evolve is really important, largest prospective clinical trial on dialysis population
Dr. Dhungal did the interesting case conference this morning. He did a great job.
Here are the slides used by Dr. Kayal to support his comprehensive talk on anion gap metabolic acidosis.
One of my favorite lectures. I’m supposed to give an hour lecture on contrast nephropathy but I find that the residents have excellent knowledge and instincts on this topic so I expand it in two other areas they are less well versed:
- Oral sodium phosphorous and nephrocalcinosis
- Nephrogenic fibrosing dermopathy
Booklet for printing
I tried doing some “live” blogging of the ASN and use the blog to take notes during some of the lectures I attended. I would judge that effort to be a failure. I’ll spend the next few days trying to clean up some of these posts.
Emerging role of Klotho
Klotho mouse has accelerated aging
due to insertion of gene missiong gene X by accident.
first model of human aging with multiple phenotypes.Question what is gene X
single pass transmembrain protein
it has some siaqlidase activity
gene expressed predominantly in the kidney and a little in the brain
does over expression of klotho surpress aging?
over expression extends mouse life by 30%
expressed in the distal convoluted tubules with weak expression in PT
the extracellular domain is clipped by ADAM 10 and then is a soluble factor
klotho -/- has similar phenotypes as FGF23 -/-
FGF is phophaturic hormone from the bones
gain of function causes hypophosphatemic rickets (vit D resistant)
FGF23 binds to FGF23 receptor plus Klotho
FGF23 requires klotho to activate FGF signaling
FGF lowers 1-alpha hydroxylase and increases 24-hydroxylase (deacticvate 1,25)
FGF?Klotho system surpresses PTH
agiing like phenotypes are caused by phosphate toxicity
soluble/secreted klotho independent of FGF23 increases renal phosphate wasting
sialidase activity activates TRPV5 which increases Ca current.
Link between |Klotho and CKD.
Mice lacking Klotho and ESRD share: casc calcification and hyperphosphatemia
mice with over expression of klotho are more resistant to vasc calcification and hyperphosphatemia in CKD model.