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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

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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

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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.

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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.

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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

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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.

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Renal Week 2008: CVD and CKD: Case 7

66 yo woman with ESRD due to analgesic nephropathy. Hx of Crohn’s Disease. Extended criteria deceased donor allograft transplant 1.5 yrs ago.

Now SBP of 160.

Next Speaker Ojo. Greatest name in Nephrology.

CVD and CKD in Transplantation

Progressive reduction of acute rejection since 2000 from 17.4 to 10.3% at one year. This should improve outcome of graft and patient; however post-transplant life-span has decreased from 14 in 1995 to 12.7 in ’06.

CVD is the explanation for this conundrum.

After the first year the most common cause of loss of graft is: death with a functioning graft (56%). This is twice as common as number 2, chronic rejection (21%).

43.5% die of CVD.

Hypertension, DM, hypercholesterolemia, obesity, and anemia are all more prevalent in transplant patients than transplant candidates or prevalent dialysis patients.

Focus on immunosupressant drugs

  • In HIV patients with lower cd4 have higher higher CVD death rate
  • Same relationship of CD4 to CVD is seen in patients with radiation exposure (Hiroshima) causing lower cd4 counts
  • also seen in transplant patients.

Rabbit data showing that increased cholesterol plaques with concurrent CSA, without change in lipid profile. Roselaar jci 1995 96 1389.

Steroids are dangerous even at low doses in the normal population.

CSA increase BP.

CSA also causes endothelial dysfunction.

Sirolimus is antiatherogenic, as seen in cardiac stents.
MMF also appears to reduce cholesterol plaque Romero Atherosclerosis 2000: 152:127-133.

Cr alone is a predictor of CVD independent of immunosupression and traditional risk factors.

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Renal Week 2008: CKD and CVD: Antihypertensive therapy

Case report of a patient with HTN
Ray Townsend is the MC (sweet). He presnts a patient with HTN and modest CKD. Cr 1.4 up from 0.9 in 2001.

Ray passes off to Domenic Sica.

Antihypertensive Drug Therapy in patients with HTN and CKD.

Volume expansion

  • Patient was on 25 mg of HCTZ. No need to change to loop if the patient is euvolemic. Chlorathalidone vs hctz
  • Ernst HTN 2006. chlorathalidone reduced 24hr mean bp more (7 vs 12) non-ckd patients. night time bp drop was even more pronounced 6 vs 13 mmHg.
  • Recommends switch within class from hctz to chlorthalidone
  • the increase in calcium may help with PTH. interesting.
  • elison JCI 83: 113; 1989 images of hypertrophy of DCT with loop diuretics
  • He’s pushing torsemide
  • Using FeNa to determine if patient is responding to loops (look for fena>3%)
  • Why is there variability in bioavailability of furosemide: floculation of pills stops some absorption. Use of liquid furosemide doesn’t help because of only a limited area of absorbtion: early duodenum only.
  • He likes the torsemide

Drug accumulation

At gfr 30-50 need to think about dose adjustment.
Renally cleared: atenolol, nadolol, betaxolol

Hepatically cleared
propanolol, metoprolol, carvedilol

Dose response to beta-blockers is flat in CKD.

Don’t titrate atenolol. It is renally cleared and patients are already retaining the drug before you increase the dose. Though the BP effect is not dose dependent, the adverse effects are.

Aldosteronism

  • 20% of patients with CKD.
  • Likely this patient will have aldo level of 14-20 and renin less than 1
  • Aldosterone antagonists (AA) reduce proteinuria
  • Need diuretic on board to get much BP effect
  • Half-life of spironolactone is 24 hours, in liver disease 120 hours, and in CKD multiple days. These figures include active metabolites. He feels eplerenone is safer because you won’t get accumulation.
  • Consider qod dosing of spironolactone. Consider 12.5 mg qd
  • beware of heparin causing hyperkalemia with AA
  • Similar warning for ACEi, ARB, TMP/SMX

Clonidine

  • in CKD clonidine is renally cleared. This decreases rebound htn by extending the half life
  • initially clonidine has a steep dose responce at low doses but then flattens
  • causes dose dependent volume retension. this is worse with TTS
  • at higher doses the peripheral alpha stimulation will overcome the central reduction in alpha activity so patients get increase in BP. This is seen in clonidine OD or with autonomic dysfunction.

CCB

  • Amlodipine has half-life of 40 hours
  • nifedipine’s half-life goes from 2 to 4 hours in renal failure
  • Edema with CCB is worse in patients with CKD because they already have increased volume

ACEi

  • 10 in the US
  • fosinopril and trandolopril have significant hepatic clearance
  • ARB are not renally excreted
  • dialyzable: captopril, enalepril, lisinopril. Use in overdose.

Statin

  • AUC of simva increases 4 fold with diltiazem
  • Cool case report of a patient on 80 of simva who was admitted for A-fib with RVR and gets started on a diltiazem gtt. He developed rhabdo a few days later.

That’s it. Question time.