Author: admin

Posted on

CKD in the NYT

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.

Posted on

MBD and Clinical Practice

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.

Posted on

KDIGO


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

Data Gaps

Evolve is really important, largest prospective clinical trial on dialysis population

Posted on

Renal Adventures in Imaging


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:

  1. Oral sodium phosphorous and nephrocalcinosis
  2. Nephrogenic fibrosing dermopathy

iPhone version
Booklet for printing

Posted on

The blog is sort of a mess.

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.

Posted on

Renal Week 2008: Clotho

Makoto Kuro

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.

Posted on

Renal Week 2008: Acute Kidney Injury Lecture: Can staging guide therapy

Claudio Ronco

We have no data. thank-you.

Various definitions of AKI change the prevalence and prognosis of AKI.

In RIFLE use the worse of cr or u.o to define category

States 200,000 patients have been used to validate RIFLE.

Systemic review of RIFLE in KI in 2008 by Ronco.

AKIN changes R to include increase in Cr of 0.3. Otherwise just sw2ithches I to 2 and F to 3.

Also the two creatines used to determine the 5change must be measured within 48 hours of each other.

Early initiation of RRT has theoretical benefits
Defintion on how to measure/define this are not established

He feels the failure of the ATN is due to Pagamini’s high, medium and low severity argument.

Much better talk

Posted on

Renal Week 2008: Acute Kidney Injury

Mehta

Need to adjust serum Cr for fluid balance. He states that this will allow Cr to determine renal failure 24 hours earlier. He fails to give an equation to do this. Is creatinine distributed in total body water or extracellular water? My guess is total body water.

eGFR would be more helpful in eliminating the curvelinear relationship of GFR and Cr but not validated in ARF.

Jelliffe method takes into account Cr generation and is better in ARF. Fails to provide information on calculating the eGFR by Jelliffe method.

Mentions Thurau’s article on Acute renal success. Am J Med 1976

Shaw in Nephron Physiology article on the time course of AKI as determined by differing etiologies.

Oliguria is bad
diuretic matter, but he wont tell us how.

Mehta is the worst lecturer. He throws a ton of data up and fails to describe any of the implications.

Total crap.