IN the NEWS: Balanced solutions all the way- do we need more studies?

Balanced fluids such as lactate ringers have made it to the medicine literature finally.
This week in Annals of Internal Medicine, a meta analysis showed that balanced fluids trumped normal saline in sepsis treatment.  Normal saline, initially invented during the cholera epidemic has come a long way in medicine literature.

Solution	pH	Na+	Cl-	K+	Ca++	Lactate	Glucose	Osmolality	Other
0.9% normal saline	5.0	154	154	0	0	0	0	308	0
LR	6.5	130	109	4	3	28	0	275	0

A landmark trial in JAMA in 2012 showed that chloride based fluids might not have that great of renal outcomes.  Another one showed increased renal blood flow.

In addition, this year in Nephmadness 2014, balanced solutions was a top match. 

Clinical Case 84: Answers and Summary

What is the pathology seen in the kidney in Mesoamerican nephropathy?

Chronic glomerular damage	1 (5%)
Chronic tubulo interstitial damage	13 (72%)
Chronic thrombotic microangiopathy	0 (0%)
Chronic nodular sclerosis	4

The correct answer is tubulo interstitial disease.  The best summary of this entity was recently discussed in the online nephrology journal club ( NephJC).  

http://www.nephjc.com/hyperosmolarity-ckd/ is the full link

This link also goes over the discussion re this entity on twitter. 

https://storify.com/nephondemand/meso-american-nephropathy

Tubuloreticular inclusions related nephropathy: Should we look at it that way?

Tubuloreticular inclusions (TRI)s are sub-cellular organelles characterized by small clusters of anastomosing tubule-like structures within cisternae of endoplasmic reticulum and are considered footprints of biological activity of the alpha or beta interferons (IFN-α and INF-β). These structures have been described with collagen vascular diseases (Eg, SLE, systemic sclerosis, MCTD etc.), HIV associated nephropathy and during systemic treatment with interferons. However, the role of TRIs as a reliable indicator of secondary glomerular process with a wide spectrum of etiologies has not been fully studied.

Production of IFNs requires stimulation by viruses, microbial products or specific chemicals via triggering the signaling systems linked to toll-like receptors (TLRs). Both in systemic diseases and viral infections, it’s the IFN-α and INF-β that are most associated with TRI formation. While we have literature supporting some secondary causes that have been associated with TRIs, are we still missing other causes that may lead to a secondary form of GN such as membranous GN, minimal change disease or proliferative GN. 

Does the presence of TRI prompt one to look for a secondary cause? What if the only finding you have is TRI with membranous GN and or TRI with MCD? Should a viral etiology or cancer or systemic lupus be considered?  Or are we dealing with it backwards.  Should we be classifying some of these entities as TRI Nephropathy and then appropriately look for a secondary cause. 

In the literature, only one study has looked at TRIs specifically in reference to this question. It was evaluating Membranous GN with TRIs.  Most of the cases did lead to a secondary cause but 1/3 had no etiology found( or perhaps we don’t know yet about this virus or systemic disease).  Another study did a more wider search and found causes we had already known. Other diverse conditions where TRIs have been described include inclusion body myositis , Kaposi's sarcoma, gliomas and sarcomas. Some of these findings are not in the kidney but in the brain or eye. Perhaps we need to elaborate on disease states that form TRIs and are we missing a bigger entity of TRI related diseases?  Inflammatory myopathies are something to strongly consider. Overall, if there is a high IFN-α and INF-β state in the body from any known or unknown cause- chances that it might lead to TRI formation in the kidney and a podocytopathy which can manifest as MCD, Membranous GN, FSGS or proliferative GN. 

CONCEPT MAP: Gap acidosis- GOLDMARK

Based on Lancet Article that gives a better ddx for Gap acidosis
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(08)61398-7/fulltext

Topic Discussion: Stones: HEART of the MATTER

Last year, a prospective study was published in JAMA suggesting that having a history of kidney stones as an independent risk factor for cardiac disease (CHD). 

            In short, this was a prospective study of 45 748 men and 196 357 women in the United States without a history of CHD at baseline who were participants in the three study cohort registries. Coronary heart disease was defined as fatal or nonfatal myocardial infarction (MI) or coronary revascularization. The outcome was identified by biennial questionnaires and confirmed through review of medical records.

            Of a total of over 240,000 participants, over 19,000 reported a history of kidney stones. After up to 24 years of follow-up in men and 18 years in women, 16 838 incident cases of CHD occurred. After adjusting for all confounders, amongst the 2 cohorts of women, a history of kidney stones was associated with a modest but statistically significantly increased risk of CHD; there was no significant association in a separate cohort of men.

The knowledge of history of kidney stones was obtained via an independently validated survey.

When looking at the covariates, most risk variants of both formation of kidney stones and CHD were evaluated and controlled for.

Why this risk?

1.    CHD and stone formers share the same risk factors- obesity, metabolic syndrome, DMII, HTN, high lipids but when controlled for all this, the risk of getting CHD was independently associated with history of stones

2.    Perhaps common dietary factors- sugary drinks, low calcium diet, high protein diet, but dietary adjustments were also made in the study.

3.    One adjustment that was not made was renal disease. Stone formers can perhaps have CKD and CKD becomes then a CHD risk factor.  This was not analyzed per authors in the manuscript.

What is the mechanism?

1.    Perhaps there is a unknown metabolic state that is both a risk factor for stones and CHD

2.    The stone might increase some other factor that we don’t know that leads to CHD

3.    There might be some other confounding factor we haven’t found.

Why Women: - No clear explanation can be found, perhaps an unknown factor that is not clear yet.

Major limitations: Self reported questionnaire, stone analysis not clear, most patients were white and not many blacks, Asians or Hispanics.

Very fascinating study but leaves us with more questions than answers.  At this point, would not make any major statements based on this observational study re risk of cardiac disease and stones.

Cisplatin-induced acute kidney injury (AKI): Why is magnesium balance important?

Cisplatin is one of the most commonly used chemotherapeutic agents.  In the US, there are more than 2000 ongoing clinical trials investigating cisplatin in patients with ovarian, testicular, bladder, cervical, and head/neck cancers, among others.  Unfortunately, approximately 25-30% of patients receiving cisplatin suffer nephrotoxicity despite its potency as an anti-tumor agent. This is a challenge in the oncology clinical setting where either dose reductions or discontinuation of cisplatin are often required to salvage the kidneys leaving the patient and clinician with limited options given the efficacy and affordability of this drug.  An important contributor to cisplatin-mediated nephrotoxicity is the accompanying electrolyte imbalances, including hypomagnesemia. Magnesium (Mg) is an essential dietary mineral required for normal body functioning and cellular processes.  Surprisingly, Mg consumption (via foods and supplements) among most Americans, particularly the elderly, is below the recommended daily allowance. In addition, many medications and disease conditions reduce the availability of dietary Mg. Therefore, we sought to examine the effects of Mg deficiency and Mg supplementation following Mg deficiency on cisplatin-mediated acute kidney injury (AKI) using a mouse model.  We observed that Mg deficiency exacerbates cisplatin-induced AKI, whereas correction of Mg status protects against cisplatin-mediated AKI.  Additional studies detail the cellular and molecular mechanisms by which Mg provides renoprotection, namely by attenuating cisplatin-induced inflammation, oxidative stress and apoptosis. In addition, we show for the first time that Mg supplementation reduces the platinum accumulation in the kidneys possibly by affecting the efflux of cisplatin by the renal epithelial cells.  While protecting the kidneys, Mg supplementation did not compromise cisplatin-induced cytotoxicity using several human cancer cell lines, suggesting the Mg does not interfere with the chemotherapeutic efficacy of cisplatin in vitro. The results of this study warrant future large scale clinical studies to better monitor patients’ Mg status prior to and during cisplatin treatment and to develop improved Mg supplementation protocols that provide nephroprotection without compromising cisplatin’s potent chemotherapeutic efficacy.

For full link of paper click below

http://www.ncbi.nlm.nih.gov/pubmed/24944268

Post By:

Malvika Solanki, MD

The First Ever Nephrology Spelling Bee

The First Ever Nephrology Spelling Pee Bee

For the first time ever ( to my knowledge), we conducted a Nephrology Spelling Bee competition for our residents and trainees.  It was like the ESPN format of the show.  Nephrology faculty prepared tough nephrology entity related words. Residents were allowed 1 minute to try to spell the word. They could ask 2 questions regarding pronunciation and using it in a sentence.  If they got it, they moved to the next round. If they got it wrong, they got eliminated. 

Following the word, a PowerPoint slide was shown with the correct spelling followed by an academic question attached to the word for the trainees. The correct answer to that question would win a nephrology text book.  The final spelling bee winner won Tennis US Open tickets. 

While it was a fun event, there was teaching through the academic questions attached through the words.  A surprise host of the show was Sameer Mishra, prior national spelling bee winner from 2008( the real deal).  Check out his you tube video of the winning word.

Some of the words we used were:  amyloidosis,belatacept, podocalyxin, pseudopheochromocytoma to name a few.