JOURNAL CLUB: Metabolic Acidosis and improving GFR

We discussed a fascinating article from KI at Journal Club this week. It sheds some light on metabolic acidosis in CKD patients.  As we all know metabolic acidosis can cause symptoms and in some studies worsens the progression of CKD.  It also leads to Malnutrition Inflammation syndrome. 
Few papers early in the 1990s showed that if you keep the ph >7.4, there might be hastening of the renal injury. It never cought on the renal community probably for two reasons: NaHCo3- people thought might worsen the HTN of the patient. Na citrate might not be a good combination with then used aluminium binders.
This study ( although small ) with 30-40 patients ( only HTN nephropathy) showed that the rate of GFR decline was slower in the Na citrate treated group after 30 months of treatment.  What showed statistical significance was eGFRcys and Pcys and eGFRcrt and Plasma Crt were almost reaching significance but didn't.  At 6 months, there was no difference. SBP was not different at 6 months and 30 months in both groups. The bicarbonate differnce was 19 vs 23.  They hence suggest keeping bicarbonate >22 with help of Na citrate.
Few points.
1. NaHC03 can also be used. The NACL is what really causes worsening HTN for two reasons, one because of the ECF distribitution of NAHC03 is not as great as NACL. Second, the macula densa really senses Cl and not Na and if you think about it, HTN is more of a CL related problem and not Na.
2. This article touches on a pathophysiology of endothelin. When there is renal injury endothelin in the kidney is produced that can cause more damage. So in summary, CKD can lead to Metabolic acidosis.
Metabolic acidosis on one hand can cause increase kidney H+ and that causes increase endothelin which via ETA receptors leads to IF/TA and via ETB receptors to proximal and distal H secretion to mitigate the metabolic acidosis. On the other hand, this metabolic acidosis leads to increased ammonium production that leds to complement activation and IF/TA and worsening of the CKD. 
3. So aggresively treating the Metabolic acidosis with simple and cheap medications like Nacitrate or Na HCO3 might be helpful.
4. Small study, need larger studies to confirm this as it might not be significant when we bring in Diabetics, other GNs and other CKD patients. at this point, KDOQI does recommend to keep Bicarb around 22 in CKD 3,4,5 and ESRD patients.

A few more references:
http://www.ncbi.nlm.nih.gov/pubmed/2993363
http://www.ncbi.nlm.nih.gov/pubmed/19608703

The Online Transplant Center: Kidney Biopsy in Heart Transplant Candidates?

The Online Transplant Center: Kidney Biopsy in Heart Transplant Candidates?

Kidney Biopsy in Heart Transplant Candidates?

A recent study in Transplantation highlights this issue in detail. Lot of times we have patients with severe CHF and are also going into acute renal failure due to pre renal or what we are now calling cardio renal syndrome sort of in the same fashion as hepatorenal syndrome? When do we think its just ATN or when is it intrinsic renal disease? When can we say this patient needs just a heart transplant and when a combined heart and kidney?

In this study, thirty heart transplant candidates with an GFR < 40 mL/min or proteinuria greater than 500 mg/day or a history of amyloidosis underwent kidney biopsies between June 2001 and March 2009. The renal pathologic diagnosis as well as the percent tubular atrophy and interstitial fibrosis on renal biopsy were assessed. On the basis of the biopsy results, nine patients were listed for only heart transplantation and eight patients were listed for heart and kidney.
Based on this small study, the conclusion was that renal biopsy provides useful diagnostic information to differentiate intrinsic renal disease from renal hypoperfusion and helps guide the decision for OHT alone versus combined HKT.

I think that it makes sense but the sample size here is too small to make a general statement. In general, clinically if the patient is not behaving like CHF induced hypoperfusion, most of us will get a kidney biopsy to make sure no other cause is lingering around.

TOPIC DISCUSSION: Cellular Senescence and Renal Aging

Yesterday, we discussed an interesting topic called cellular senescence and how it matters in renal disease.
1. What is senescence: some cells drop out completely, some persist in damaged form (atrophic tubular cells) and others remain as senescent cells that show limited function and are unable to proliferate.
2. These senescent cells compromise the integrity of the tissue as a result and this is part of the process of aging.
3. The cells have altered morphology, greater heterogeneity, expression of associated ß-galactosidase (SA-ß-GAL) & accumulation of lipofuscin granules.
4. Several candidate genes p21 and p16 have been also reported to play a role in senescence
5. A special case for a possible interaction of underlying renal senescence imposed stresses might be the poor performance of transplanted kidneys from older donors, particularly cadaveric donors. Poorer graft survival might be secondary due to older kidneys with increased senescent cells. These showed increased P16 activity and increased IF/TA.
6. Studies have shown that certain things stress and cause accelerated senescence. Hypertension is one of those things.
7. Telomere knock out mice showed less of chronic changes and less senescent cells. Perhaps a future pathway to NOT age????

Some interesting stuff. Few references below:
Image source: cartoonstock.com

http://www.ncbi.nlm.nih.gov/pubmed/19133932
http://www.ncbi.nlm.nih.gov/pubmed/14717921
http://www.ncbi.nlm.nih.gov/pubmed/11158231
http://www.ncbi.nlm.nih.gov/pubmed/19959722

CLINICAL CASE 12

Which one of these statements regarding Toll like receptors is false? They are key players in innate immunity	1 (14%)
The pathogenesis seen in many renal conditions is due to underactivation of these receptors	4 (57%)
They play a key role in adaptive immunity	1 (14%)
They are expressed on mast cells	1 (14%)
They are expressed on dendritic cells

Nice work everyone. This is a growing field in nephrology. Please see the recent Nature Review Nephrology review on Toll like receptors and kidney disease.  In general, these receptors recognize pathogen associated molecular patterns and molecules that are released from damaged cells.  They are key players in innate immunity, and also play a role in adaptive immunity. They are expressed in variety of immune cells including mast cells, macrophages, dendritic cells, T and B lymphocytes and granulocytes.  Overactivation, not underactivation of these receptors  might contribute to pathogenesis of few renal diseases such as rejection, immune complex glomerulonephritis, ischemic ATN and perhaps even UTIs and renal leptospirosis.
Some recent data also suggests some role of TLR inhibitors as a therapy for above diseases.


Image source: Nature Review Immunology.
Good reference: http://www.ncbi.nlm.nih.gov/pubmed/20177402

CLINICAL CASE 11

Which one of these mechanisms is responsible for sodium retention in cirrhosis and hepatorenal syndrome?

Decreased " effective " plasma volume 64%

Increased vascular capacitance 0%

Cirrhosis alone 0%

Abnormal hepatic vascular function and hepatic vascular sensor 14%

jury still out 21%

Tough question. There might be no right or wrong answer but I think the best answer is the jury is still out.

I defer you to the above linked recent Kidney International article that reviews the latest research in hepatorenal syndrome. 

some points to make:

1. The "effective" plasma volume concept has been the one that most people think of as the cause of this syndrome.  The questions really are to ask where is this effective plasma volume decreased. In recent studies, patients with cirrhosis, plasma volume remained unchanged after ascites removal and there was some thought that the renal salt and water retention preceded ascites and edema.  Another study, showed that measures total plasma volume had really increased in most subjects and even in the splanchnic and non splanchnic beds. This study showed that it was the ascites and edema in cirrhosis resulted from a positive sodium and water balance. 

http://www.ncbi.nlm.nih.gov/pubmed/5771197

http://www.ncbi.nlm.nih.gov/pubmed/596455

2. The concept of increased vascular capacitance is there. This in contrast to the above "overfilling" , is the under filling hypothesis. Here the primary event in edema formation is really systemic vasodilation caused by cirrhosis itself perhaps via nitric oxide.  This leads to the edema due to underfilling and a results " low plasma volume" and salt retention.  This has been a newer hypothesis.

3,4 There is data now coming out that the liver itself has intra hepatic vascular sensors that sense and regulate renal function, thirst and salt appetite.  So basically, there are baroreceptors capable of regulating renal sympathetic activity. Its possible that this baroreflex remains active during cirrhosis and continues to cause this increased renal sympathetic activity as a result.

http://www.ncbi.nlm.nih.gov/pubmed/7631798

So i guess after all this, probably, we still don't know!

IN THE NEWS ---> Vancomycin and the kidney

A recent review in Kidney International May 2010 issue talks about the recent changes in vancomycin dosing and how it is affecting the renal community. Due to increase in vancomycin resistance and treatment failure, the infectious disease societies have advocated new guidelines to keep levels of the drug at 15-20 from the older 10-14 ranges.  The articles reviews that these high trough levels might be associated with nephrotoxicity.
Just in the recent 2010 NKF spring meetings, I saw a poster presentation that talked about a series of vancomycin induced ATN toxicity likely as a result of this high trough range.  The risk is incremental and the higher the trough levels and longer the duration of vancomycin use puts you at a higher risk.  This paper suggests that perhaps patients with already existing renal disease as well as patients with acute renal failure and critically ill might be more prone to get worsening renal damage.
A nice table in the paper reviews the studies that showed these nephrotoxicities. How this will affect the ESRD patients is still unclear.

image source: www.3dchem.com

TOPIC DISCUSSION: Smoking and Kidney Disease

Does chronic smoking predispose you to kidney disease? Why not? perhaps an ischemic related injury from chronic ischemia would make sense. Or athrescloerotic disease that can be seen in the entire body affects the kidney vessels as well.  There has been a Glomerulonephritis described in non diabetic smokers as well. A nice review is linked here from JASN in 2007.The authors in that paper described the largest series, describing 23 cases allowing recognition of common clinical and pathologic features. The patients were most frequently older caucasian men who presented with renal failure and proteinuria. Most of them had in common was history of smoking and hypertension. The pathology shows many of the characteristic findings of diabetic nephropathy including diffuse mesangial expansion with nodules, microaneurysms, capsular drops, and hyaline arteriolosclerosis. We have to remember to rule out other causes of nodular GN, like amyloid, immunotactoid and mainly hidden diabetes.


Regardless a nice read!

The Online Transplant Center: Dual Liver and Kidney Transplantations

The Online Transplant Center: Dual Liver and Kidney Transplantations

The Online Transplant Center: HIV and the Kidney Transplant

The Online Transplant Center: HIV and the Kidney Transplant

The Online Transplant Center: Obesity and Kidney Transplantation

The Online Transplant Center: Obesity and Kidney Transplantation

Dual Liver and Kidney Transplantations

Tips from the NKF 2010 sessions


1. When to do both and when to do just Liver? It’s hard to figure this out as most of the kidney damage in liver associated kidney injury is ischemia and we don’t have good markers
2. A good strategy suggested was using biopsy as a guide and using the Interstitial fibrosis, tubular injury as a tool for seeing if they need a SLK or just a liver transplant.
3. When this strategy was used in some centers, and crt compared after going ahead with a respective transplants ( SLK or just liver), crt were 1.2 at 6 months in both groups.
4. Most common biopsy finding: ischemic ATN, followed by other primary GNs, (MPGN, IgA, FSGS, TMA) and vascular disease
5. If the patient has ESLD and is on dialysis < 6 weeks, perhaps just a liver is fine but otherwise might need a SLK. But with the biopsy method, we might achieve more accuracy

HIV and the Kidney Transplant

What I learned at the NKF 2010 , some few points.


1. A large NIH sponsored study basically showed that the outcomes of large number of patients when compared to non hiv patients transplanted was no different.
2. The 3 year follow up showed no major difference in graft survival
3. HIV disease didn’t progress either, perhaps because they didn’t get induction therapy or they were carefully selected patients or there is data that almost all immunosuppresive drugs we use has anti HIV viral activity from cellcept to CNI to sirolimus
4. The major problems people run into these transplants are drug toxicities as anti retrovirals have significant effect on CNI levels and high doses of CNI and increased intervals are needed.
5. There is usually more rejection in these patients,perhaps because of point number 5, but also perhaps because they don’t get much induction
6. Some centers are using induction with thymo, but their acute bacterial infection rates are high. Ideally, a anti CD20 induction is a good choice.


A nice website to look at is: hivtransplant.com

Obesity and Kidney Transplantation

What I learned at the NKF 2010. Some key points

1. BMI < 18 and >30 are both associated with worsening graft survival
2. Why does obesity affect transplant outcomes: The risk factors after few studies have been: increased insulin resistance, increased BP, hyperlipidemia, increased proteinuria and development of NODAT

3. There has been a higher incidence of acute rejection in high BMI patients? The reason: obesity has been associated with mild continuous chronic inflammation and increased proteinuria.

4. Should obese patients be trasnplanted? Yes as a comparative study showing how they do on dialysis still shows they do better on transplant. Yes, when compared to non obese patients getting transplanted, the risk is low, the overall benefit vs dialysis is more.
5. Should their immunosuppresion be treated differently? No real headway. When compared steroid free vs steroid + protocols in obese patients, no difference was noted in outcomes.

In the News: ASN website for Renal Fellows

The ASN just launched a renal fellows website. Its a fascinating tool that should be used by all fellows.
I think it will grow and become a good resource for all renal fellows around the world.
Great work!

TOPIC DISCUSSION: Adolescents and Disease

We all have trouble managing patients who are in the late teens/ youths 18-22 as they themselves are in transition and its hard to connect with them.
Recently at the NKF meetings, I heard a great talk about this and learned some take home points.

1. Its hard for them to deal with Kidney disease, coming for dialysis  or taking their transplant medications
2. Rule of thumb is that , non adherence is fairly common than we think.
3. This non adherence has been well studied in Type 1 Diabetics ( 50% ) are non adherent and this might apply to ESRD/Transplant as well.
4. The best measure of non adherence is clinic attendance, followed by family,self and team reporting non adherence. The main problem we have with transplant is that the drug regimens are not simple.

TOPIC DISCUSSION: Why do AVG and AVF get stenosis?

What I learned at the NKF.. about this.

1. Veins are not arteries and they are more prone to endothelial dysfunction
2. ESRD is a state of worsening endothelial dysfunction
3. ESRD and graft formation leads to neointimal hyperplasia and less NO production leading to endothelial damage
4. Most of these grafts and fistulas have a flow pattern that is more " turbulent rather than laminar" causing more sheer stress leading to endothelial dysfunction.

A nice summary of this is below
http://www.ncbi.nlm.nih.gov/pubmed/19695501

NKF reports

Check out the East Carolina University Website for brief snippets of recent NKF meeting at Orlando, Fl

CONSULT ROUNDS

A nice review was presented at our rounds on how myeloma can affect the kidney.
There are lot of ways myeloma can affect the kidney.
Just want to list the different presentations myeloma can have on the kidney that you might encounter.
1. Fanconi Syndrome or biopsy proven newly called Light chain proximal tubulopathy
2. Cast Nephropathy ( usually light chain)
3. Amyloidosis ( AL or sometimes even AH)
4. Monoclonal immunoglobulin depositon disease--> which includes heavy chain or light chain deposition disease or mixed chain deposition disease
5. Cryoglobulenemic GN
6. Proliferative GN ( described by Nasr et al)
7. Distal Tubular Dysfunction
8. Hypercalcemia
9. Interstitial Nephritis
10. Plasma cell invasion or infiltration related damage
11. Hyperviscosity Syndrome
12. Crystalglobulinemia

TOPIC DISCUSSION: Asymptomatic Hyponatremia

A nice editorial in my favorite journal Nephrology Nature Reviews talks about the " asymptomatic hyponatremia" syndrome.  When we see a calcium > 11 and no symptoms, we admit and treat. When we see a K of >6.0, we treat, so when we see an asymptomatic hyponatremia say of 130, why don't we treat? is what is asked in this editorial. The editorial brings in the points of 30% of elderly population in nursing homes having low Na levels and increase risk of falls and fractures.  The cirrhotics, CHF patients who run in NA 130-135 but are having no symptoms, should they be treated? and with what. With the new agents out now ( V2 receptor antagonists, FWR or lasix) will be the other question?
This has to be further studied and looked at in my opinion.
At least in part, perhaps culprit agents should be discontinued - such as SSRIs, HCTZ to start with
and prevent worsening perhaps of the hyponatremia.
Check out this nice editorial, a must read

IN THE NEWS- RENAL ANGINA SYNDROME

Nephrologists are trying to catch up with the cardiologist. We are in the midst for a search for a troponin for kidney injury and this is important. several markers are being studied but none really validated and ready for clinical use yet.
What do we really need: How can we suspect renal injury early enough to trigger biomarker testing and more aggressive renal monitoring?
They suggest an angina equivalent for kidney injury....
What is that?
Oliguria, fluid overload and small changes in crt being renal angina equivalents. If these occur in an ICU patient, a more aggressive monitoring should be employed: urine chemistries, more frequent crt monitoring, cystatin C testing and perhaps an early renal consultation

CLINICAL CASE 10, ANSWER AND SUMMARY

Fun with numbers.. Na 140 mmol/L K 4.0 mmol/L Cl 110 mmol/L pH 7.0 pCO2 35 mmHg pO2 75 mmHg HCO3 8 mmol/L. What is the disorder?

In this case, we see that the ph is 7.0 suggesting acidosis as a primary disorder and HCO3 is 8 as well suggesting a metabolic acidemia.  

1. Calculate AG= 22

So there is an anion gap metabolic acidosis

2. Then lets do the Winter's formula

which is 3/2 * bicarb +8 +-2 = PC02. In this case, 3/2 *8= 12+ 8= 20. So the PCO2 expected should be 20 but here its 35.  Hmm. so there is more PCO2 production when it should be suggesting a superimposed

Resp acidosis.

3. A delta delta should be performed to make sure there isn't a third disorder.  Change in your AG is 22-12= 10. So your bicarbonate should be 24(normal) -10= 14. But your bicarbonate here is 8, more lower than expected suggesting another significant non gap acidosis.

So this patient has a severe acidosis--> AG+ non gap + respiratory acidosis.

TOPIC DISCUSSION: PHOSPHATE BINDERS

Check out this week's NEJM issue:It has a nice drug review on Oral Phosphate Binders in patients with kidney diseases.
It highlights the history of binders, cost differences and basic characteristics of types of binders
1. Ca based
2. Sevelamer family
3. Mg Based
4. Lanthanum
5. Aluminium based

What was more fascinating is whats under development.
**Fermagate ( a new mg based binder)
**Colestilan ( non metallic anion exchange resin)
**Niacin and Nicotinamide
What is also interesting is the point that patients with advanced kidney diseases have elevated salivary phosphate concentration.  And no matter what they eat, that gets absorbed. A study showed that chewing gum containing a novel chitosan compound was effective in lowering serum phosphate levels and salivary phosphate levels.
http://www.ncbi.nlm.nih.gov/pubmed/19121775
A good review for fellows!

TOPIC DISCUSSION: A rare case of statin induced rhabdomyolysis leading to respiratory failure and hemodialysis

Someone with hypercholesterolemia and chronic lower back pain on simvastatin 80mg develops Rhabdomyolysis. Over next few days, develops progressive ascending weakness and dysphagia limiting oral intake. Muscle weakness was pronounced with proximal emphasis. Respiratory failure ensues and intubation happens.  Peak CPK of 88747 in spite of aggressive hydration and subsequently required hemodialysis. Hepatitis was severe as well. A quadriceps muscle biopsy demonstrated fragments of muscle with fiber loss and dropout, no significant inflammatory changes. Nerve conduction studies showed motor greater than sensory neuropathy affecting both the upper and lower extremities.

Rhabdomyolosis can be dangerous. As we know that statins can cause renal damage and hepatitis but degree of other muscle damage is rare to see. This is an unusual case vignette of both severe rhabdomyolysis with possible diaphragmatic and accessory muscle involvement. Muscle involvement in statin toxicity has typically been skeletal, it is likely that the respiratory muscles had widespread involvement which led to respiratory failure. In general, Patients respond to drug cessation and therapy with steroids or immunosuppressive agents. This case highlights the need to screen patients in the setting of a recently introduced or dose escalated statin therapy especially in the elderly. Severe skeletal myositis should prompt the treating clinician to monitor the respiratory status carefully. Clinicians should also be vigilant for visceral (liver ,kidney) and smooth muscle ( bowel,bladder) involvement. 

.

IN THE NEWS: GLOSEN Study

Idiopathic Membranous Nephropathy:- to treat with immunosuppresion or not to treat is the question at hand.
The classic division has been via the Toronto Registry of breaking down in terms of low risk of progression, medium risk and high risk based on degrees of proteinuria.
This landmark paper just published in JASN April issue really questions the need for treatment early on.
This retrospective trial, very large set of patients showed that spontaneous remission (SR) occurred in 30% of patients; but the decline in proteinuria might take up to a year.  What was more interesting is that, despite remission in the low proteinuria group, a significant number in the moderate proteinuria and 22% in the >12gm of proteinuria had SR as well.
This is different than what was previously thought. SR is not very common in patients with >12gm of proteinuria. On the other hand, this study showed the opposite and that significant amount of these patients had a SR.
From the point of a physician deciding when to start immunosuppresion in this high risk category., this study might shed some more light.  Four features that defined early remission were female gender, lower proteinuria, lower serum crt and treatment with ACEI/ARB.
What this study might teach us is that:- Perhaps the first 6-9 months is a wait and watch period for that high risk >12gm group. If there is a decline by 50% in proteinuria, perhaps a SR is coming on and not to initiate immunosuppresive therapy; just continue anti proteinuria regimen like ACEI/ARB.  If in those 6 months, proteinuria doesn't improve and other complications of nephrotic syndrome ensue, renal function is declining, immunosuppresive therapy might be needed.
A nice editorial is also a good read with this study. Keep in mind its still a retrospective study, but might give some answers that we didn't have for a long time.

IN THE NEWS: Dialysis Time

Interesting article in Kidney Internationa looking dialysis time (in-center, thrice weekly) comparing standard 4hours to shorter treatment and looking at outcomes. They found that patients with shorter treatment times had higher all cause mortality at 1 year, and this was a potentially independent variable.

The study design was observational in nature, looking at session length as a time varying exposure (rather than just baseline), and looking at only incident patients. Finally they analyzed the data to adjust for time varying confounders.

The article also suggests reasons as to why this might be (all reasons we would expect). Although recent studies suggest more dialysis does not translate to significant clinical outcomes in the setting of AKI, chronic dialysis seems to benefit from more dialysis (e.g. nocturnal dialysis)

TOPIC DISCUSSION: Albuminuria and Proteinuria

Few days ago, we discussed what is the normal for albumin amount in your urine and total protein amount?


In a 24 hour urine collection, it would be considered normal to have up to150 mg per day of protein, of which approximately 10 mg is albumin. 
Normal urine albumin to creatinine ratio is <17 mg albumin/g creatinine for men, < 25 mg albumin/g creatinine for women. The normal urine protein to creatinine ratio is < 200 mg protein/gram creatinine.
Urinary protein can be comprised of both albumin and other proteins.Therefore, the urine albumin would not account for all protein excretion.
Microalbuminuria refers to albumin excretion of 30-300 mg/day, which correlates to a urine albumin:creatinine ratio of 17-250 mg/g for men and 25-355 mg/g for women.

The Online Transplant Center: Antibody Mediated Rejection Review

The Online Transplant Center: Antibody Mediated Rejection Review

Antibody Mediated Rejection Review

https://www.pediatric-nephrology.com/daily-updates/2010/04/04/175-amrcedars.html

Check out the link to this nice review posted on a pediatric nephrology blog.
A nice read!

The Online Transplant Center: Bone marrow transplantation and solid organs

The Online Transplant Center: Bone marrow transplantation and solid organs

Bone marrow transplantation and solid organs

The recent issue of Transplantation embarks on two articles on simultaneously doing a bone marrow transplantation and pancreas and islet cell respectively.
The first paper is a basic science study that showed bone marrow derived pancreatic cells are mobilized into injured pancreatic tissue and contribute to β-cell regeneration. Transplantation of BM-derived cells improved the function of injured pancreas, although the response is not sufficient to restore sustained normoglycemia is their conclusion.
The second paper was on islet cell transplants, another basic science study. Cotransplantation of bone marrow cells with islets was associated with enhanced islet graft vascularization and function in this paper.


This concept of bone marrow transplantation along with solid organs is not novel now. It was first reported few years ago in NEJM of actual 5 cases of kidney transplants along with bone marrow and the need for immunosuppresion was eliminated in these patients.  This is true thinking out of the box. Long terms outcomes of these patients is still underway.

IN THE NEWS: Tyrosine Kinase Inhibitors and CKD

A recent retrospective study in Annals of Oncology takes on the use of the tyrosine kinase inhibitors sunitinib and sorafenib in the CKD patients and even patients on dialysis.  Onco-Nephrology or the role of the nephrologists in the care of the cancer patients is becoming more and more important as most new chemo drugs are known to cause some degree of renal damage.
Tyrosine kinase inhibitors have anti VEGF effects and now have known to cause AKI, AIN, proteinuria, HTN and sometimes a pre eclampsia like syndrome as well.
Using them in CKD patients would scare me.  This study , although retrospective showed that with dose modifications, even patients on dialysis and CKD received it with no renal toxicity.  Perhaps dialysis removes some metabolite that might be reno toxic.
This is more and more important as nephrologist we might get scared of few cases in the literature causing injury but for that specific patient with cancer, these drugs might be those few months of quality of life and hope.
Having studies like these are important to stress that in the big scheme of things, these drugs still are good for treating Renal Cell Cancer and just because they have renal side effects, we should not avoid them. Rather, use them with caution and watch for changes in crt, HTN and proteinuria and monitor patients more closely.

Other key references:
http://www.ncbi.nlm.nih.gov/pubmed/20142724
http://www.ncbi.nlm.nih.gov/pubmed/19421832
http://www.ncbi.nlm.nih.gov/pubmed/18709027
http://www.ncbi.nlm.nih.gov/pubmed/19054798

IN THE NEWS- MORE NEPHROLOGY CONSULTS

A recent study in JAMA March 2010 issue suggests that the use of eGFR is making people question the results and send more referrals to Nephrology by 70%.
Is that a good thing or bad thing?
The study was a community based cohort study with time series analysis and from 2003-2007.  They found that the first visit nephrology consults were increased significantly among patients with severe kidney disease, middle aged women and the very elderly, and severe comorbidities.  No outcome measures were done.

This raises a few concerns and questions. A nice editorial in the same issue of JAMA, was even more fun to read.
Does one reading of eGFR enough? Do we classify people in one ready or one calculation at one period in time. GFR separated by 3 months might be better, 2 months or 1 month? Based on KQIGO, direct measurements of estimated GFR seprated by more than or equal to 3 months would be preferred.
The editorial points out that these studies don't define outcome. Calling someone CKD with GFR less than 60 has been challenged before and especially in extremes of ages as there is a natural decline in GFR as we age.
What the editorial nicely stresses is perhaps in the older age population, a GFR less than 45cc.min/1.73m2 is a better cut off. This might not hold true for someone with proteinuria, hematuria or strong family history of kidney disease.
What the problem is the measurements of GFR - we don't have a good method yet?
Neither of the GFR calculators are perfect, nor is the basis of it- Creatinine. but that's the best marker we have. Till we find a troponin for the kidney, we are going to run into this problem for a while.