Is one kidney enough for me?

Well, Iam doing Transplant Nephrology right now. So I though I will chip in with this topic ....that many patients ask about. These are some of the facts that we know about donating a kidney......

Usually donors have be healthy..and ideally free of chronic problems especially Diabetes, cancer, strong family history of renal disease ending on dialysis, and without anatomical abnormalities like Polycystic kidneys.

So we are dealing with a group of healthy people. Consequences of donating may be divided into two...for the ease of explaining..

1. Issues with surgery - The surgery for removing is mostly done laparoscopically these days.(usually left kidney is removed due to ease of removal ). On a recent study in JAMA ,the mortality in the first 90 days is around 3/10,000 patients. Mostly due to bleeding, thromboembolic disease etc. After 1 year the mortality equals the mortality with a comparable healthy cohort.

2. Issues with loss of kidney mass -  Since 50% of the nephron mass is lost, its expected that their left over kidney swells up a little to compensate, and creatinine can theoretically double. But usually creatinine goes back to normal or settles within 40% above baseline. The other theoretical risks that need to be watched for over the next 2 years are 1.Hypertension ( not significantly high than in normal population)
                                       2. Protenuria (significance is not really known)
 As I mentioned above, the mortality is the same for these people as for someone who has 2 kidneys.

One advantage of donating a kidney is...if in case the donor ends on Dialysis either due to trauma, cancer or CKD), then they will be considered as high priority, and will get transplanted (if they dont have a living donor) within 6 months.

So..go ahead ..encourage patients to donate...if they can...!!!!

Hepatitis C and its transmission........something to know!

I came across this article from Yale(presented at the 17th CROI in Feb 2010), where they did a research on the Survival of hepatitis C virus in the syringes ..mainly with respect to intravenous drug users, as the main form of transmission of Hep C in US is intravenous drug abuse(IVDA). Eventhough HIV and HCV almost have the same mode of trasmission, there are differences in their prevalance.For example...in places where HIV prevalance is 1-10 %,the HCV prevalance has been around 40-50%. This is likely due to longer survival of HCV.

Ok...what they studied in Yale is ....loading insulin and tuberculin syringes (both are commonly used by IVDA) with a lab strain of Hepatits C virus, and they stored the syringes at varying temperatures of 4 C(fridge temp), 22 C(room temp), and 37 C(autoclave temp) for up to 63 days. They checked for viability of HCV. The insulin syringes did not show viable HCV beyond day 1 at all temp except 4C where it was viable until Day 7
The tuberculin syringes there was 96%, 71% & 52% viability for HCV at temp of 4C, 22C, & 37C respectively, at 7 days.
This is likely due to the high void volume ( volume left in syringe after injection) in case of the tuberculin syringe.This study gives us some idea about the transmission of HCV on syringes. Since this study has been done on lab strains, it may not apply for the actual HCV. With this ..I will leave you to decide on the final sentence..

This gives us something to add to our history taking skills..when it comes to IVDA. And we can add this to our counselling skills as well (if we have time!!). Preventing needles is the best way to prevent HCV.But if not possible..then may be using an Insulin syringe instead of a tuberculin syringe may help. This will be a advice from me to my patients until we have any further compelling evidence to change this.

Obstructive Sleep Apnea - More than about sleep!!

Sleep apnea has long been considered something that improves the quality of life for patients. However, it's becoming more clearer that OSA obviously has metabolic effects way more important than just helping people sleep and feel better in the morning.

Severity of OSA correlates with diabetes control. According to a study published just last December 2009 at AJRCCM, compared with patients without OSA, the adjusted mean HbA1c was increased by 1.49% in patients with mild OSA, 1.93% in patients with moderate OSA, and 3.69% in patients with severe OSA (P < 0.0001 for linear trend).

Treating heart failure patients with OSA can actually improve CHF. In the first randomized trial involving 24 patients with heart failure (EF < 45%) and moderate to severe OSA, 30 days of CPAP lowered daytime heart rate and systolic BP and increased ejection fraction by 9%. In contrast, there was no change in any of these variables in the 12 patients in the control group.

Lastly treating OSA actually helps with atherosclerosis! A small Brazilian study of 24 patients published in AJRCCM showed that 4 months of CPAP in people with OSA made a significant decrease occurred in carotid intima-media thickness, pulse-wave velocity , C-reactive protein , and catecholamines after 4 months of CPAP.

The impact of OSA on cardiovascular disease and stroke is so profound that the AHA/ACC actually produced a consensus statement about this.

So, treating OSA should be as much of a priority as those pills everybody likes prescribing!!

Some more indications for Statin

As we all know, we are getting more and more new information on the benefits of Statins independent from their ability to inhibit HMG CoA reductase and reduce LDL cholesterol. 

There has been a great interest in high CRP levels and their relation to increased coronary events, even in the absence of hyperlipidemia. The study done on nearly 500 patients who had MI showed nicely that Pravastatin reduced the median and mean CRP levels significantly, compared to placebo, over a period of 5 years.(E.Braunwald - same person who contributed a lot to Harrison's Textbook). With this background, PROVE IT-TIMI 22 trial recruited nearly 4000 pts, and showed that pts with low CRP levels after statin therapy have a better clinical outcome than if CRP level is high. 
Given these stimulating results, investigators tried to apply this in the primary prevention of CAD. And guess what...two studies with slightly different population (AFCAPS- low risk pts, and JUPITER- intermediate and high risk ...due to 10% 10 yr Framingham risk score) showed significant reduction in the first coronary event in patients whose CRP level decreased while on statin. All the participants didn't have hyperlipidemia. The Canadian Heart Guidelines have already included CRP in risk stratifying pts for primary prvention. 


Statins also reduce the incidence of DVT/PE as shown in a meta analysis of nearly 1 million pts done at U Conn. JUPITER trial was included in this meta analysis, as this is the only randomised trial to show reduction in DVT ( but not significant for reduction in PE).


Now this is the latest on the list of benefits from Statin ---- A meta analysis looking at incidence of ventricular arrhythmias(VF/VT) among pts with CAD on a statin Vs no statin, has shown a 31% reduction in ventricular arrhythmic events in the statin group. This has previously been shown in a subgroup from MADIT-II trial.
So ...what about Atrial Fibrillation. Well there were many studies on Statins and maintaining sinus rythm in A fib...with conflicting results. A recent meta analysis showed that Statins does not help maintain sinus rythm in patients who underwent elective DC cardioversion. 


This list of benefits might increase every day....... keep checking!!

Confounded by Delirium

Ok so not everybody is interested in this, but there was an excellent review in JAMA recently which went over the evidence on the accuracy of several instruments in diagnosing delirium in adults.

As we all know, delirium is an indepenent marker for increased mortality, longer hospital stay, increased complications, persistent cognitive devicits and increased discharge rates to long term care.

So when you get a patient who is clearly "out of it".. what does the regular intern reflexively do. MMSE right? NO! According to the review, the MMSE was the LEAST useful for identifying patients with delirium (LR 1.5 for a score of less 24> better than guessing).

The study included 11 bedside delirium instruments. One instrument stood out: the Confusion Assessment Method (CAM) which has a +LR of 7.3 and -LR 0.08 and may be the most convenient because it can be performed in less than 5 minutes, and can be applied by nongeriatricians.

Some training is recommended and an instruction manual is available online. The algorithm is based on only 4 elements of the DSM-III-R criteria: acute onset and fluctuating course, inattention, disorganized thinking and altered level of consciousness(see inset).

ACE-i - a wonder drug for Heart failure

ACE-inhibitors have long been used in heart failure due to their many beneficial effects.  Angiotensin II has shown to activate growth factors in myocardium. So blocking the RAAS with ace-i helps with regression of LV hypertrophy. As we all know, LVH is associated with increased incidence of heart failure, MI or sudden cardiac death. ace-i as we all know....are related to cough due to to inhibition of bradykinin degradation. But this is also the reason how it improves insulin sensitivity, as bradykinin increases Insulin dependent glucose uptake by cells.

With regards to clinical outcomes in patients with Heart failure, how do ace-i perform?
In 1987, CONSENSUS trial was published in NEJM. 260 patients with NYHA class 3 & 4 heart failure were randomised to enalapril Vs placebo. Cardiovascular mortality was reduced by 30% in enalapril group. There was also a significant decrease in cardiac size, and in NYHA symptoms. 7 pts in enalapril group had to stop it due to hypotension Vs none in placebo arm.

In 1991, SOLVD trial was published in NEJM. 2500 pts with LVEF < 35% and NYHA class 2 & 3 were randomised to enalapril Vs placebo. Follow up for 3.5 years. Enalapril had a 15% reduction in mortality compared to placebo. But in this study patients with creatinine >2 mg/dl or who had a tendency to increased creatinine during the run-in phase ,were excluded from the study.
In both the above studies ..the reduction in deaths were largely due to reduction in deaths due to pump failure.

In 1992, AIRE study was published in LANCET. 2000 pts were randomised to receive Enalapril Vs placebo 3-10 days after an acute MI and showing signs of Heart failure. F/U for 6 mon - 1 year. There was a 27% risk reduction in mortality, with enalapril compared to placebo. The beneficial effect was evident as early as in 30 days. An AIRE extension study (AIREX) found that the benefit extended upto 3 years after the study.

Then in 2000, HOPE trial was published in NEJM! 9000 high risk pts (age > 55) with evidence of vascular disease( CAD, PVD, stroke) or diabetes with 1 additional risk(HTN, hyperlipidemia, smoking ) were randomised to Ramipril Vs placebo. F/U for 5 years. There was a 22% reduction in cardiovascular mortality with Ramipril compared to placebo. Note that 7% of Ramipril patients stopped it due to cough.

All these studies(and many more) have shown beyond doubt, the usefulness of ACE- inhibitors along the whole spectrum of heart failure. As we all are aware of, they also have a renoprotective effect (thats an extensive topic!!). It has become such a wonder medication for Cardiologists, Internist, nephrologist, endocrinologists.........

metformin and lactic acidosis- How strong of a relation?

How much should we be worried about.I felt that lactic acidosis has been hyped a little by everyone in clinical practice. In fact I am yet to see a case of lactic acidosis that can be attributed to Metformin use.
The relation between the two is a legacy of Phenformin, which was taken out of market in 1978 due to high incidence of lactic acidosis.It is still prescribed in Brazil ,Greece, China & Portugal.
Metformin also possesses this risk, but to a lesser extent, mainly because it is not metabolised in the liver(as phenformin).


Lets recap lactic acid metaboism....
Lactic acid is the a dead end product beacuse pyruvate, its immediate precursor is also its only route of metabolism. Lactate is buffered by equal amount of HCO3, and the liver's job is to oxidise the lactate and replace the HCO3.This is a formidable task, as 1400 mmol of lactate are produced everyday, but the plasma concentration is maintained around 1 mmol. The kidneys are responsible for excretion of 10 -20% of lactate. If we look at the picture above, increase in NADH (from alcohol) or pyruvate(from glycolysis) would shift the reaction towards lactate. Metformin may inhibit oxidative metabolism and increase NADH, and thus worsen lactic acidosis. But this happens usually if excretion or buffering is deficient.


Lets look at some data. Of the first one million patients who took Metformin in US, 47 developed lactic acidosis. Of them 43 had renal failure or CHF. Only 4 didn't have any other reason apart from Metformin, and these were not fatal (NEJM 98). Based on this observation, CHF was included in the CI list for Metformin.
Another study done my Bristol Meyers (COSMIC study) comparing 1 year treatment of 7200 pts on Metformin Vs 1500 pts on other antdiabetics showed no cases of lactic acidosis. A meta analysis in 2003, of 194 studies didn't reveal any case of lactic acidosis in 36,893 pt years in Metformin group Vs 30,109 pt years in non-metformin group. Many of the studies in this analysis were of short duration, and included very few number of patients though.
The most recent Cochrane review 2008 on this subject concluded "There is no evidence from prospective comparative trials or from observational cohort studies that metformin is associated with an increased risk of lactic acidosis" . 


The main accusations on Metformin and lactic acidosis have been only from case reports, and they still continue to be reported. 
Usually pts on Metformin who develop lactic acidosis are sick, and have other underlying problems.I will go back to my first statement,that this relation has been overhyped, and that Metformin does not seem to cause lactic acidosis IF USED IN THE RIGHT POPULATION.( avoid if CKD 4 & 5, caution in CKD 3, avoid if Creat >1.3 in females, and >1.4 in males, CHF, and any underlying reason that can cause tissue hypoxia--> lactic acidosis)