Tuesday, July 31, 2012

Clinical Case 59: Answers and Summary


In nephrotic syndrome(albumin 2-3 range), VLDL produced by the liver are rapidly metabolized so that the LDL concentrations rise whereas VLDL remain normal (13%)
Cholesterol increases but TG remain normal(30%)
With severe nephrotic syndrome, < albumin 1.0g/dl, VLDL accumulate and LDL decline and TG start rising (21%)
When proteinuria is massive, the apoprotein CII are lost and contribute to accumulation of VLDL as well (43%)
No consistent pattern of HDL serum conceontrations has been identified in nephrotic syndromes(26%)

Under normal circumstances, VLDL produced by the liver is hydrolyzed to IDL and HDL by lipoprotein lipases situated in a number of extrahepatic sites including endothelium and adipose tissue.  IDL then gets converted to LDL by the liver. In nephrotic syndromes with moderate hypoalbuminemia (2-3g/dl), VLDL produced by the liver is rapidly metabolized so that the LDL concentrations rise whereas VLDL remain relatively normal.  Cholesterol increases and TG might stay normal.  With severe hypoalbuminemia(<1g/dl), VLDL accumulate and LDL concentrations fall and hence TG rise higher.  This might be because inhibition of lipoprotein lipase is seen by free fatty acids that normally bind to albumin and accumulate in adipose tissue as albumin falls. When there is massive amounts of proteinuria, apoprotein CII, a normal component of VLDL and stimulator of lipoprotein lipase may also contribute in accumulation of VLDL. 
What about HDL? Since HDL have molecular sizes comparable to albumin, it may be reduced in nephrotic syndrome due to urinary losses. Also, accumulation of unbound lysolecithin may decrease the synthesis of HDL. Even with these two mechanisms, one would predict low HDL levels but mixed patterns have been noted in nephrotic syndromes. 

Sunday, July 29, 2012


Arterial blood gas is gold standard to get the oxygenation and acid base information. Venous blood gas has been tried for patient comfort. How does VBG compare to ABG?
Check out the a post by a NYU resident on this topic. Very informative.


Wednesday, July 25, 2012

IN the News: Phosphate binders and CKD

A recent publication in JASN by Block et al compared >100 patients head to head on placebo, lanthanum, sevelamer and calcium acetate and looked at few end points:- Change in mean serum phosphorus, urinary phos, pth, 1,25 vitamin D levels, FGF23 levels and vascular calcifications and bone density scores in CKD patients. The study proposes that although the parameters in above all improved, there was a concern that binders might progress vascular calcifications.

Few take home points
1. Mean phos levels did decline in all groups compared to placebo.
2. Urinary phos levels were also different in active vs placebo group.
3. PTH levels increased with placebo and remained stable with active therapy
4. FGF-23 were elevated at baseline and didn't change much in both active and placebo groups
5. Bone mineral density improved in active patients
6. Active therapy resulted in significant increases in median annual percent change in coronary artery and abdominal aorta.

Few inferences and discussion points
1. Although randomized and controlled, this study has a small n and once distributed had only few patients <50 per group.
2. Baseline phos levels to begin with were in 4.0 range suggesting good control already
3. There were less patients with CHF and HTN in the placebo group ( perhaps effecting the results?)
4. Vascular calcifications noted in coronary and abdominal aorta might not truly reflect cardiac events.
5. Commendable work but more larger studies need to be done to confirm these findings.
6. Just like anemia story, perhaps the Phos study might have the same ending.

Monday, July 23, 2012

Is Iron The answer?

As restrictions have arose in using of erythropoietin agents in dialysis patients, the use of IV iron has risen in the nephrology community. What are the rates of iron overload in such instances?
Studies have shown that excessive use of iron can intensify the oxidative stress associated with chronic kidney disease, and promote endothelial dysfunction and cardiac disease. Excessive iron reduces iron utilization and is involved in the generation of intracellular reactive oxygen species, which induce cell injury; the risk of subtle toxicity from iron excess exists. Unnecessary iron supplementation accelerates hepcidin  production. This effect on ferroportin 1 (FP-1), keeps intracellular iron from being carried even if the iron storage is adequate; it also decreases iron absorption from the intestine.In the most recent issue of the Am J of Medicine, an editorial to a  study done prospectively found that there was iron overload in 84% of a 119 stable HD patients. Some of the amount of iron reached the levels found in hemochromotosis. A prior study had shown that the risk factors were ferritin >500.   The Japanese Society for Dialysis Therapy Guidelines has proposed that a minimal amount of iron should be given to chronic kidney disease patients. Japanese clinicians believe that the risk/benefit ratio for iron supplementation is higher than that accepted in Western countries. So now what?
A proper attention to body's individual iron stores and ferritin levels along with perhaps hepcidin information might be a more prudent way to decide iron treatment. More robust guidelines might be needed.

Saturday, July 21, 2012

IN THE NEWS: Walking and Hypertension assessment

Hypertension is tough to manage in the elderly as no one really knows what the target blood pressures should be in the age >80.  The standard guidelines might not really be correct in the very elderly population.
Perhaps a slightly higher blood pressure might be more prudent in the very elderly. Prior studies have shown increase mortality in over management of HTN in the elderly.
A recent study has an interesting way to look at HTN. Using walking speeds to assess the risk of HTN management in the elderly is a novel concept.  The association between BP and mortality varied by walking speed.  The fast walkers(≥0.8 m/s for a 20ft walk) with with elevated systolic BP (≥140 mm Hg) had a greater adjusted risk of mortality compared with those without.  Among slower walkers, neither elevated systolic nor diastolic BP (≥90 mm Hg) was associated with mortality. Interestingly, they also found elevated systolic and diastolic BP was strongly and independently associated with a lower mortality  in people who didn't complete the walking test. These findings are consistent with prior studies that have found that the association of BP and mortality diminishes with age. HTN management might change as frailty increases with age. 
Testing walking speeds for the hypertension management and assessing risk might be an easy tool to use.
Any comments?

Thursday, July 19, 2012

Arsenic and the Kidney

Arsenic is an environmental pollutant and can be found in drinking water in many countries.  Chronic exposure can cause DM, neurotoxicity, liver injury and nephrotoxicity.  Cancers of certain organs have also been found. In the past, accidental contamination of beer in England had resulted in many deaths in 1900s. The kidneys are the site for elimination of most of the arsenic concentrates.  Arsenic induced oxidative stress induces expression of HO-1 and MAPK which activate many transcription factors and eventually leading to tubular damage in the proximal component.  Kimura et al had shown that interferon gamma played a protective role in sodium arsenite induced renal injury by up regulating the intra renal multi drug resistance associated protein-1 expression. Acute tubular necrosis findings that dates back to 1900s is the commonly found renal toxicity finding. Cases of acute hemolysis related injury has been described as well.  Chronic tubular and interstitial damages have been described as well in survivors. Glomerular damage has been seen in one case. Cortical necrosis is a rare finding to begin with and rarely observed in current era, has been described in this toxin as well.  One interesting case found bilateral acute cortical necrosis, which is even a rarer event.
Isn't arsenic used as a chemotherapy agent for acute promyelocytic leukemia(APL)?  In combination with trans retinoic acid and gemtuzumab, studies have shown effective treatment of this cancer.  In the one study that showed the promise of above regimen, Grade 3 and 4 adverse events of the agents were noted.  Overall, of the 80+ patients, 4 had "renal failure" in that one study.
A toxin to the kidney that we must be at a constant watch for.

Thursday, July 12, 2012

The "surprise" question in Nephrology

"Would I be surprised if this patient died in the next year?" is the surprise question. This notion has made way into the palliative care and nephrology world thanks to it's introduction by Dr.Alvin Moss. Recent news has mentioned this concept as well. A study published in CJASN in 2008 showed that the answer to this question was more predictive of identifying sicker patients on dialysis who have a risk of early mortality and need for palliative care consults.  In this study, the group that answered "no" to the question had higher mortality, older patients and more co morbid conditions.  The surprise question predicted status at 1 year better than age, time on dialysis, gender, hemoglobin, serum albumin, and quality of life scores. Given this surprising simple question as a good screening tool, many other fields of medicine such as pulmonary and oncology have embraced this technique. These studies tell us that the most important is learning how to assess the patient's prognosis.  A touchcalc program utilizes this method in the mortality calculation as well. Please review the RPA summary on palliative care for dialysis patients and shared decision making.

Wednesday, July 11, 2012

Less is more: Nephrology point of view

To dialyze or not to dialyze is the question that we face sometimes in the elderly and AKI in severe sepsis or cancer with no chance of recovery. What is the evidence that dailysis is going to prolong life or give a quality of life in these individuals? Sometimes we feel that we have to offer something. Offering "no dialysis" should also be an option.  It all depends on the medical issues involved and overall prognosis, a combined team decision involving all members involved including patient or family might be needed. A recent CJASN attending rounds issue discusses the dialysis question in AKI with metastatic cancer with poor prognosis in the ICU.  Dr Moss takes the readers to a  7 step process of how to ethically make a decision that is optimal for patient care. The four topics that are extremely important are: Medical indications, patient preferences, quality of life and contextual features. Now, perhaps in some countries, economics might even play a larger role. A recent Newsweek article also shares a similar story of the costs involved in end of life care for a loved one in USA.
A shared decision making algorithm as proposed by Moss's article should be a must read for all.
Why is that nephrologist are not comfortable in not offering aggressive therapy? How do they compare to their counterparts in oncology, cardiology, and critical care?  Is it their medical school training, residency training or fellowship experiences? We must answer these questions to better improve training of nephrologist and make them better equipped to handle palliative decision making.  Please take our survey on this topic if you are a fellow in training. A similar survey being performed for program directors and fellows on hospice as well, please take that as well.

Other articles to consider for a read on this topic

Monday, July 9, 2012

In The News: GFR from Creatinine and cystatin C

Cystatin C has been eyed as the novel troponin of the kidney attack in recent years. CKD-EPI equation has slowly emerged as another player in the equations that are used to measure GFR.  A recent publication in NEJM discusses three equations

1. CKD-EPI creatinine based
2. CKD-EPI cystatin C based
3. CKD-EPI creatinine and cystatin C based

The third one listed performed the best with more precision and accuracy for GFR <60.
It was across range of GFRs and subgroups and demographics and lower BMIs( which the prior methods were deficient in)
Certain limitations that the authors do mention are: no racial or ethnic minorities other than AA were used in the development so can't be used for others. No transplant patients were included in the analysis.

Nevertheless, we are slowly and surely reaching a new troponin for the kidney attack.


Friday, July 6, 2012

Clinical Case 58: Answers and Summary


False positive tests for semiquantitative tests for proteinuria are not uncommon.  Patients with small volume of urine with concentrated urine are more likely to have these false positives.  A urine with specific gravity of >1.025 and 1+ protein should raise some suspicion for false positive test. 

Gross hematuria and pyuria are other potential confounders as they are related to cellular element breakdown leading to proteinaceous components leading to false positive testing.  
When urine is highly alkaline, pH>8, dipstick can lead to false positive findings as the buffer component of the indicator dye is possibly overwhelmed by an actual shift in pH.  This is usually seen in UTI with urea splitting organisms. Although, a recent rat study showed that the pH didn't matter in terms of urinary proteinuria estimate using dipstick. 

Radiographic contrast agents, high urinary levels of penicillins and or cephaosporins and sulfonamide metabolites in urine can result in false positives in the precipitation method of urinary protein detection but not in the dipstick evaluation.   Protein precipitation techniques includes precipitation with sufosalicylic acid, heat and acetic acid or concentrated nitric acid.


Thursday, July 5, 2012

Nephrology education: Where do we stand?

Nephrology is facing a workforce shortage. Desai et al  have estimated this via a prediction model as well and confirmed the ASN predictions.  While we are trying to tackle the workforce matters, are we watching out for our renal fellows in training? The nephrology fellowship format hasn't changed much in many years. Satisfaction of our fellows might be perceived to be optimal but is it? A recent study published in CJASN by our group shows otherwise. While good amount of fellows are satisfied, fair amount are not.  While we keep increasing interest in nephrology among residents and medical students, we have to make sure our own fellows remain satisfied. They are THE NEPHROLOGY representation to the residents and students.

In addition, are our fellows getting the right amount of inpatient and outpatient experience? Since the inception of nephrology fellowship, lot has changed in the field of nephrology. Now fellows are spread between dialysis, transplant, research and might not have the same amount of time they had to do pure consult months and outpatient experience as previously perceived.  A recent editorial in AJKD proposes a novel format. Are fellows willing to change to that format? We would like to hear from the fellows about this.
Novel ways to teach our fellows is required. Using e learning or other means, try utilizing these in your institutions.

While our fellowship possibly get re examined, medical residents rotations might need changes as well. A study by us published in AJKD compared a combined inpatient and outpatient rotation to pure inpatient rotations and the residents knowledge and perception of nephrology was improved with the combined rotation. Larger more robust studies might be needed to prove this.

Tuesday, July 3, 2012

A fictional story on dialysis care

Kamal Shah from the blog " Kamal Shah's blog" writes a fictional 11 part short story that is set at a dialysis unit in India. Kamal, who blogs on a daily basis has creatively addressed some concerns that many places have in dialysis units.  The 11 part series is a quick read and commenting  is free.
The story highlights the frustration, and anger that many patients might feel during dialysis and also the constant stress that the staff entail when dealing with such complex patient population.

Give it a read and see what you think.
The title is " In you we trust" 

Monday, July 2, 2012

Eculizumab and what we see post treatment?

C3 glomerular diseases and dense deposit disease, novel entities that have been successfully treated now with eculizumab.  A recent article in JASN summarizes what we see on kidney biopsies in cases that have been successfully treated with eculizumab.  C3 glomeluar disease is manifested like MPGN pattern of injury but mainly with c3 deposits and no significant Ig staining.
The researchers found:

1. One year post treatment biopsies still showed no reduction in C3 or C5b-9 and EM showing deposits still being present( they postulate this being from long half lives).
2. Interestingly, all biopsies showed new denovo monoclonal staining for IgG-kappa in the same distribution as C3 and C5b-9, like a monoclonal deposition disease and paraprotein disease.
3. Staining of the Y heavy chain was restricted to  the IgG2 and IgG4 subclasses.

This is interesting as by the new IF based definition  of MPGN pattern, C3 glomerularopathy is defined by no IF staining for Ig.  After treated, most of these cases showed staining for Ig.  The investigators suggest this might be a monoclonal binding of the eculizumab antibody itself due to an inflammatory response.  The staining was exclusive in IgG2, IgG4 and kappa and the authors propose that this is exactly what would be detected if eculizumab were being deposited in tissues.  Even a case of aHUS who got this drug showed this finding post treatment( with no prior EM deposits).
It appears that this drug binds and deposits within glomeruli, thin basement membrane and vessel walls of treated patients and results in this pattern of Ig that the investigators are seeing. This should be careful put in the differential when we biopsy someone who had eculizumab in the past and not call this MIDD or new signs of paraprotein mediated disease. Presumably, a bone marrow would have been negative in theses cases.

For the full paper look at

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