KidneySZ.com

The new website http://www.kidneysz.com/ has just been launched.

This is the official Nephrology Clinic website platform for Dr Soehardy Zainudin, who is a Consultant Nephrologist and Physician currently practising in Tropicana Medical Centre, Kota Damansara.

A new drug for Diabetic Nephropathy

Researchers at the University of California, San Diego School of Medicine, the National Institutes of Health (NIH) and the Mayo Clinic have published promising results of a clinical study using an experimental anti-fibrotic and anti-inflammatory drug called pirfenidone to treat patients with diabetic nephropathy. Their study will be published in the April 21 issue of the Journal of the American Society of Nephrology (JASN).

Influence of the timing of cardiac catheterization and amount of contrast media on acute renal failure after cardiac surgery

Journal of Research in Medical Sciences, 04/26/2011

MirmohammadSadeghi M et al. –

The patients who progressed to ARF were more likely to have received a higher dose of contrast agent compared to the mean dose. However, the time interval between cardiac surgery and last catheterization was not significantly different between the patients with and without acute renal failure (ARF). Minimizing the amount of contrast agent has a potential role in reducing the incidence of postoperative ARF in patients undergoing cardiac surgery, but delaying cardiac surgery after exposure to these agents might not have this protective effect.

Death rates among those with high blood pressure decreasing, but still high

Death rates have decreased among people with high blood pressure but remain far higher than in those without it, according to research in Circulation: Journal of the American Heart Association.

Researchers examined changes in death rates among adults ages 25 to 74, using results from two national health surveys: The National Health and Nutrition Examination Survey (NHANES) I Epidemiologic Follow-up Study followed participants recruited between 1971 and 1975 and the NHANES III Linked Mortality Study followed participants recruited between 1988 and 1994.

The study found:

• The overall death rate (number of deaths for every 1000 person-years and adjusted for age) was 18.8 among NHANES I participants with high blood pressure — 42% higher than in those without it (13.3).
• From NHANES I until NHANES III, mortality rates had fallen to 14.3 in hypertensive patients — 57% higher than in those without high blood pressure (9.1). 
• Although men were more likely to die than women in both time periods, the decline in deaths among hypertensive men (7.7, a 33% relative reduction) was more than four times larger than among hypertensive women (1.9, a 12% relative reduction).

"On average, hypertensive women had larger declines in their blood pressure than hypertensive men, but didn't do as well in other measures related to heart disease risk," the researchers said. "Compared with hypertensive men, women gained more weight, were more likely to be diagnosed with diabetes and were less likely to quit smoking."
Between the two surveys, hypertensive patients had a:

• 45% smaller reduction in total cholesterol levels
• 30% larger increase in body mass index 
• 3.6 times larger increase in the diagnoses of diabetes 
• 25%larger decrease in the percentage of smokers

End-Stage Renal Failure requiring dialysis

One of the challenges facing a Nephrologist is when breaking news about End-Stage Renal Failure to a patient and telling him or her about the need for life-long haemodialysis 3 times every week.

The reactions I often got out of the patients vary from one of despair to denial to anger. Sometimes it is best to let the patient go through the emotions before they settle down with some degree of acceptance of their disease and the unavoidable treatment.

What is High-Efficiency and what is High-Flux ?

Unusually Low or High Endogenous Creatinine

NKF K/DOQI recommended target ranges

Serum phosphorus 3.5 mg/dL–5.5 mg/dL
Serum calcium 8.4 mg/dL–9.5 mg/dL
Ca X P product <55 mg2/dL2
Intact PTH 150 pg/mL–300 pg/mL
Serum total CO3 >22 mmol/L

these are the targets for Bone Metabolism

Summary of Treatment Recommendations for IgAN

All summarised ....

IgAN latest

Management of IgA nephropathy


ACE-inhibitors, ARBs and ACEI/ARB combinations - beneficial

Steroids
Pozzi et al (vs placebo) - better renal survival with steroids
Katafuchi et al (vs placebo) - similar renal survival
A recent metaanalysis also support use of steroids : reduce proteinuria, prevent progression to ESRD

Oral CYC
Ballardie et al. better 5-year renal survival

Fish Oil - conflicting results
Donadio et al. Mayo Clinic. NEJM 1994 (fish oil better)
Pettersson et al (no benefit, in fact worse)
Hogg et al (no benefit)

MMF - no evidence in IgAN

Membranous nephropathy

Management of membranous nephropathy

Chlorambucil } both proven effective by Ponticelli et al
cyclophospamide }

Cyclosporin A (Cattran et al.KI 2001)
CSA + low dose steroids vs steroids only (n=51)
CSA + low dose steroids - more CR/PR (21/28 vs 5/23)

MMF (only uncontrolled trials)
Choi et al. reduced proteinuria
Miller et al. reduced proteinuria

Rituximab (also uncontrolled trials)
Ruggenenti et al. reduced proteinuria up to 1 year.

FSGS latest update

Management of FSGS

Steroid-resistant FSGS
Cyclosporin A vs placebo (Cattran et al. KI 1999)
CR/PR : 70% vs 4% (CSA much better)

MMF : Choi et al (n=18) but not controlled. New NIH multicenter RCT ongoing
Sirolimus : no evidence

PD Guidelines : Quick Summary

European Best Practice Guidelines

UF > 1L/day
Kt/V > 1.7 per week

UK Renal Guidelines

CCr 50L/week
Kt/V > 1.7 per week

KDOQI Guidelines

CCr 50-60L/week
Kt/V > 2.0 per week

Strategies to Expand Living Donor Pool

Due to the lack of living donors here, this is something we need to know :

What are the strategies available to expand Living Donor Pool?

1) Use of genetically unrelated donors such as a spouse, friend or acquaintance (emotionally related donors) or a stranger(altruistic or living nondirected donors [LNDs])

2) Paired-donor kidney exchanges, either direct (living-donor–living-donor) exchanges (kidney-paired donation) or indirect (living-donor–deceased-donor) exchanges (list-paired donation)

3) Integration of paired exchanges with LND donation, as either domino-paired donation (LND donation plus direct exchanges) or chain-paired donation (LND donation plus direct and indirect exchanges)

4) Transplantation across ABO or HLA barriers using desensitization techniques

5) Use of expanded-criteria living donors including hypertensive donors, obese donors and elderly donors

Lupus Nephritis Maintenance Trials (Revision)

OK, yesterday I posted on Induction trials. Now lets look at Maintenance of LN.

Remember the name ....
Contreras et al.
n=59
After induction with IV CYC (4-7 monthly doses),
split into 3 arms:
1) continue IV CYC (3-monthly doses)- 2 years
2) Azathioprine (1-3mg/kg/day)- 2 years
3) MMF (0.5-3gm/day) - 2 years

IV CYC arm : more reached end point (death/CRF) compared to Aza or MMF
Aza and MMF arms : more relapse-free survival
Mortality increased with IV CYC

Limitations : large % of Hispanics/Blacks

... Watch out for upcoming trial MAINTAIN Nephritis Trial (comparing aza to MMF as maintenance)

Lupus Nephritis Induction Trials (revision)

OK guys. Time for lupus revision. OK we all know that the NIH protocol for INDUCTION has both short-term and long-term adverse effects of Cyclophosphamide (CYC). What else is there?

For exam purposes ;

CYCLOPHOSPHAMIDE
Euro Lupus Nephritis Trial (Houssiau et al)
(n=90)class IV LN receive either high-dose (monthly pulses x 6 followed by quarterly pulses x 2) or low-dose (500 mg biweekly × 6 pulses) IV CYC induction followed by azathioprine (AZA) maintenance in a dose of 1 mg/kg/day
Result : No difference in remissions. No difference in flares. Less infections with low dose. Limitation : milder disease, almost all causasians (no blacks)

Cellcept / MMF
Chan et al. (n=42)DPLN receive 6 months of induction with MMF (2 g/day) or oral CYC (2.5 mg/kg/day), both with concurrent prednisolone.During the maintenance phase, those in the MMF arm continued the drug at a reduced dose (1 g/day)and those in the CYC arm switched to AZA (1.5 mg/kg/day)for 6 months.
Result: At 12 months, there were no differences in CR, PR or relapse.
.... they added another 22 patients, followed up 5 years.
Result: same, no difference as above. Fewer infections with MMF arm.

Hu et al. 6 months MMF vs conventional IV CYC. Result : MMF better

Ginzler et al. (n=140) majority Class IV. MMF vs standard IV CYC (6 months). Crossover allowed at 3 months.
Result: MMF better at 6 months(CR, PR, infection rate). At 3 years, no difference (death, flare, renal failure)

... watch out for Aspreva (IV CYC vs MMF 6 months) ... but after that MMF vs Aza (i think i can predict the result ... clear winner in MMF ... but imagine if there is no difference between MMF and aza .... hehehe.

Another basic problem ... Dialysis Cramps

Aetiology - unclear (likely volume depletion and tissue hypoxia) and usually due to requirement for large volume removal.

Management options :

1) administration of hypertonic fluid, most commonly 50% dextrose (50mls), in order to raise plasma osmolality.

2) Quinine 200-300mg before dialysis or at bedtime can be tried but is unproven

3) Oral agents such as clonazepam, vitamin E, carnitine, or anti-convulsants are sometimes used as prophylaxis.

4)Limitation of inter-dialytic weight gains, ensuring that post-dialysis dry weight is correct and the use of an appropriate dialysate sodium are the best means to prevent this problem. Remember that a higher dialysate sodium will reduce intra-dialytic symptoms at the expense of thirst and weight gains; the converse holds true for a lower dialysate sodium. Sodium profiling may again be of benefit.

5)Patients who experience cramps at night may benefit from muscle-stretching for a minute or two. Heat and massage for the camping muscle can help.

Personally, I haven't tried numbers 2) and 3), and 4) makes you spend a lot of time counselling patients (who still end up not following your advice!)but there are some good obedient patients... usually adjusting dry weight and IDWG helps .... and sodium profiling seems to be useful too. I usually advocate linear sodium profiling for such problematic patients (ie start Na 140 or 145 and end up with 135)and the patients have less problems - not sure if it is just psychological. I wonder if anyone else has encountered same experience with sodium profiling in this situation?

Intradialytic Hypotension (IDH) ... what can we do about it?

Hi team,

time for some basic dialysis stuff for revision. I'm revising on intradialytic complications now and one of the commonest complication is IDH (intradialytic hypotension).

Usually occurs for one of three broad reasons:

1) Patient is below dry weight (q.v.)
2) Fluid removal is faster than redistribution can occur (eg, too large weight gains, unstable circulation)
3) Some effect of dialysate/ membrane/ extracorporeal circuit on cardiac output and/or peripheral resistance

... and of course sometimes anti-hypertensive accidentally served in the morning!

What can we do?

1) Advise patient about fluid, salt, etc

2) Review dry weight

3) Consider longer, slower dialysis (unpopular with patients understandably)

4) Consider serial ultrafiltration followed by isovolaemic dialysis (lengthens dialysis again; can be used for a time to get nearer to dry weight)

5) Review haemoglobin (effect of anaemia possibly via cardiac oxygenation)

6) Consider providing oxygen during dialysis

7) Tricks with dialysate:
(a) cooling (causes increased peripheral resistance);
(b) sodium profiling, or ramping, in which the dialysate sodium is altered during dialysis. A higher dialysate Na reduces hypotension (probably by maintaining ECF osmolality) - but reduces Na removal. Start high Na, lower Na later helps (ie linear profiling). Ultrafiltration rate can also be profiled on some machines.

8)Avoid eating and drinking before/during dialysis (reduces peripheral resistance by causing splanchnic vasodilation)

9)Omit hypotensive agents on the morning (or evening) before dialysis

10) Oral midodrine, an a1 adrenergic agonist (I don't think it is available here though)

11) Consider haemofiltration or haemodiafiltration (different membranes, but in the case of haemofiltration, also usually a slower treatment - and possibly with more cooling of blood)

Physiological levels of Haemoglobin increase mortality in CKD?

Risk for all-cause mortality was significantly higher in patients with anemia caused by chronic kidney disease (CKD) who were treated with erythropoiesis-stimulating agents (ESAs) to higher rather than lower hemoglobin targets, according to a meta-analysis of 9 randomized controlled trials and more than 5000 patients.

The study, (published 3rd February 2007 in Lancet), also found that patients in the higher hemoglobin-target group were at increased risk for arteriovenous access thrombosis and poorly controlled hypertension.

"The most important of our findings is the significant increase in the risk of all-cause mortality seen when a target hemoglobin concentration of 120 to 160 g/L is achieved," despite this being within the normal physiologic range, the researchers from Monash University in Melbourne in Australia said.

The Cardiovascular Risk Reduction by Early Anemia Treatment with Epoetin Beta (CREATE) and the Correction of Hemoglobin and Outcomes in Renal Insufficiency (CHOIR) also raised this issue.

Take note that there is another study coming up ....The Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT), which is investigating darbepoetin. This will provide further insight into optimal target levels.

So how do we apply this in clinical practice???

The editorialists conclude: "The question has been answered: higher hemoglobin-target concentrations increase mortality via cardiovascular end points. Partial, rather than complete correction of anemia is appropriate, although commercially less attractive, and it is time to move on."

Dr. Strippoli said: "Treat patients with CKD to a hemoglobin target of 100 to 120 g/L; if patients have severe cardiopathy, treat them to a hemoglobin target of 100 to 105 g/L."

"First, hemoglobin-target trials should be stopped, or their aims need to be strongly reassessed; second, a trial of different doses of erythropoietin is needed, because what is causing harm to the patients is probably that many of them do not respond to these drugs properly and higher doses are used."

DOPPS : European study

This was what they did .... 4 groups (total n=2165) from 5 european countries:

1) low flux HD
2) high flux HD
3) low efficiency HDF
4) high efficiency HDF

.... it turned out that high-efficiency HDF had 35% lower mortality rates than low flux HD (p=0.01). These observational results suggest that HDF may improve patient survival independently of its higher dialysis dose .... but more randomised controlled trials are needed before clinical recommendation. but looks like HDF is the way to go ....

This was published 26th April last year.