In the NEWS: mTOR inhibitors and ATN

MTOR inhibitors are widely used in many GU cancers and in kidney transplantations. mTOR inhibitors are known to cause proteinuria and many cases of biopsy proven FSGS, collapsing GN and TMA. There is always a risk of AIN with any drug. Of note, recently, in a manuscript in the Ann of Oncology, Izzedine et al present 4 cases of biopsy proven ATN from mTOR inhibitors. 

A kidney biopsy showed acute tubular necrosis (ATN) with prominent tubular dysfunction. Withdrawal of the drug leads to a rapid recovery in two cases. However, a fixed renal dysfunction was noted in the other two cases, one of which will remained dialysis-dependent. Two cases used A TORC1/TORC2 inhibitor and one case of everolimus and one of temsirolimus. 
A toxicity to watch out for all transplant and onco-nephrologists. 

TOPIC DISCUSSION: Risk factors for UTI in Transplant patients

What are independent risk factors for early urinary tract infections in renal transplants?

1. Female Gender
2. Prolonged use of foley
3. Stent use
4. Older age
5. Delayed Graft function.

These findings are summarized in a recent study by Lee et al. Interestingly, they also found that untreated UTI was associated with risk of acute cellular rejection.

Dr. House, Sherlock Holmes and Medical Education

Medical TV shows such as Dr. House and detective books such as of Watson and Holmes have now entered medical education literature to deduce their use in deductive reasoning and diagnostic skills. Can they be used to teach students about diagnosis and how to think? Dr. House exemplifies rare diseases states most of the episodes presenting even in a more atypical manner. Can this teach students to diagnose more common entities?

A recent study in AJM this year from France analyzed 18 episodes of Dr.House and found that strategies used in the show were unrealistic and there is an information bias in the show and costs, risks and failures of treatments are not taken into account. Here is another perspective on this topic.
Interesting to see a physician's account of each and every episode of Dr.House.

Regardless of the shortcomings, many of us get joy and excitement from watching the sleuth diagnose yet another rare disorder: and to top it all- he is a framed as a board certified specialist in  infectious disease and nephrology!!

Message from the NRAA regarding a medical director workshop meeting in Fall 2013.

NRAA Announces Physician Panel for Medical Director Workshop & Nephrology Symposium

NRAA, introduces the physician-led panel for the Medical Director Workshop & Nephrology Symposium  at the 2013 NRAA Annual Conference, in joint sponsorship with the Cleveland Clinic, on September 25, 2013, in Seattle, WA.

The NRAA has gathered expert speakers to offer a Physicians’ Track for Dialysis providers.  This unique opportunity brings colleagues and industry experts together to discuss improving patient care, USRDS trends and key findings, and an open forum for providers to share best practices.

Allan Collins, MD, FACP will give an overview of CMO symposium and lead a discussion about the problem from the USRDS perspective. Richard Glassock, MD will advise about when to start and what not to do, in addition to sharing recommendations on volume management.

Diane Wish will address how to decrease hospitalization rates.  Brigitte Schiller, MD, FACP, FASN will co-present with Doug Johnson, MD on how to increase PD among ESRD patients and discuss nutritional supplements and sodium management with Raymond Hakim, MD.

Leanna B. Tyshler, MD and Doug Johnson, MD plan to address CKD Education, followed by a discussion on Urgent Start Peritoneal Dialysis with Steven Guest, MD and Leanna B. Tyshler, MD.

These nephrology experts will provide a platform to discuss what the future holds for the treatment of kidney disease.  This workshop is a must for all medical directors who aim to improve dialysis organizations.

 www.nraa.org/fallconference.

Frail Renal Phenotype

Frailty in the elderly or any patient leading towards ESRD is a tough combination. Renal physicians should not consider dialysis as the de facto treatment for all patients and in certain patients that meet some frailty criteria, perhaps non dialysis modalities with multi team approach and renal palliative care might be better options. Recent article in CJASN explores the Frail Renal Phenotype

1. Karnofsky score <50( requires special care)
2. Older age compared 80-84 : 85-89 years
3. Presence of geriatric factors and syndromes: Dementia, non ambulatory status, positive frailty test, low serum albumin, symptom burden that is high.
4. " Would you be surprised if this patient died in the next year?" answer being No
5. Low survival probability by comorbid scores, hemodialysis mortality index, and nursing four chronic conditions and nursing home patient.

Take a look at the full article at CJASN 2013

Coffee, tea, or soda: are they going to cause kidney stones?

Beverages and risk of kidney stones has been a recently studied topic.
Recently published studies and most recent being in CJASN by Curhan's group suggested the following:

1. Sugar sweetened sodas was associated with higher incidence of stones( as fructose increased urinary ca excretion and uric acid excretion).
2. Consumption of sugar sweet soda and punch was associated with highest risk of stone formation.
3. Coffee and tea drinking was associated with lower risk of stone formation( coffee and tea act as diuretics and diuresis via both proximal and distal tubules)- mainly due to caffeine related effect.
4. Interestingly, decaffeinated coffee was also associated with lower incidence of stones ( perhaps an anti oxidant effect suggested by the authors)
5. Wine and alcohol ingestion was associated with lower incidence of stones( diuretic effect)- interesting find but still needs to be studied further.
6. Orange juice intake was associated with lower incidence of stones( has K citrate and fructose in it). K citrate wins out! Some juices such as apple juice has more fructose than K citrate and hence there have been more stones in those drinkers.

Consult Rounds: Psoriasis and kidney disease

Psoriasis is an immune-mediated chronic inflammatory disorder of the skin. Association with kidney disease has been debated for a long time. Secondary renal amyloidosis in psoriatic arthropathy and drug-induced renal lesions secondary to methotrexate or cyclosporine are accepted accompaniments of

psoriasis. IgA nephropathy is also known to occur in psoriatic patients with HLA B27 genetic sharing. 

Are there GN that have been associated with psoriasis. One interesting report I found describes three findings: IgA, FSGS and membranous GN. All of them improved with treatment of the skin condition and ACEI/ARB therapy. The authors label the entity as  ‘‘psoriatic nephropathy’’ or ‘‘psoriatic kidney disease.’’ but with some doubt and a "?"

Other studies have looked at this association. Microalbuminuria has been studied as a potential link with psoriasis. In that one study, when abnormal urinary findings were compared to another cohort, patients with psoriasis had an increased prevalence of pathologic albuminuria compared with controls.  Of the eight patients with psoriasis who had urinary abnormalities, four underwent renal biopsy. Two of them had biopsy-proven glomerulonephritis: mesangial proliferative glomerulonephritis in one and IgA nephropathy in the other. Another study had looked at this connection.

But recently in JAMA dermatology, psoriasis was linked with many co morbid conditions including kidney disease. In a large cohort of over 9,000 patients, psoriasis overall was associated with higher prevalence of chronic pulmonary disease, diabetes mellitus, diabetes with systemic complications, mild liver disease , myocardial infarction,  peptic ulcer disease ,peripheral vascular disease , renal disease , and rheumatologic disease. Trend analysis revealed significant associations between psoriasis severity and each of the above comorbid diseases.  Potential confounding factors, such as hypertension, diabetes, and the use of nephrotoxic psoriasis treatments should be kept in mind when making this connection. A topic worth further studying.

Concept map: C3 Glomerulopathy

C3 Glomerulopathy can be divided into three distinct clinico-pathological entities. Hope this concept map helps simplify this novel disease entities.

In the NEWS: How many dialysis patients do you have?

In a recent study reported in JASN 2013, dialysis patients receiving treatment from kidney specialists with a higher patient caseload have a greater risk of dying prematurely than those receiving care from specialists with a lower caseload.  Now this makes intuitive sense. The researchers examined the patterns of 41 Nephrologists in their health system and compared the ones with highest mortality rate to lowest mortality rates. You have less patient load, you spend more time with them and can think about them and allow for better decision making. As you caseload increases, time per patient might decrease. This is the ultimate battle of quality vs quantity based care model. It’s about time we moved to a quality based care and Nephrologists get paid by their quality of care and not the number of patients. Nephrologists whose dialysis patients had the best survival over six years had a significantly lower patient caseload than Nephrologists whose patients had the worst survival. Their study quotes “Nephrologists with the lowest patient mortality rates had significantly lower patient caseloads than Nephrologists with the highest mortality rates65 [55–76] versus 103 [78–144] patients per Nephrologist, respectively; P<0.001.”  This is not a story that is true just for dialysis patients but in medicine in general.  What do others think?

Concept Map: Acute Kidney Injury in HIV

Adapted and updated from recent article on this by Hartle et al in JASN 2013: AKI in an HIV patient.

Click to enlarge the image.

Clinical Case 73: Answers and Summary

Which of the following statements are true regarding bile cast nephropathy?

It is also called cholemic nephrosis

  10 (41%)

 

It is no different than hepatorenal syndrome

  2 (8%)

 

The casts that form in the kidney are correlated with higher total and direct bili levels

  12 (50%)

 

Mechanism of the casts is similar to myeloma casts or myoglobin casts

  5 (20%)

 

It is also called jaundice associated nephrosis

  4 (16%)

 

No such entity exists

  4 (16%)

 

Bile cast nephropathy has been described in older literature as cholemic nephrosis or jaudice associated nephrosis. In the most latest publication in KI 2013, this entity takes a new leap and re introduction to the nephrology world. This entity represents a spectrum of disease from proximal tubulopathy to intrarenal bile cast formation found in patients with severe liver dysfunction. The researchers looked at 44 cases and found that 24 patients had bile casts with involvement of distal nephron segments in 18 mild cases and extension to proximal tubules for 6 severe cases. Eleven of 13 patients with hepatorenal syndrome(HRS) and all 10 with alcoholic cirrhosis had tubular bile casts. These casts significantly correlated with higher serum total and direct bilirubin levels, and a trend toward higher serum creatinine, AST, and ALT levels. Bile casts may contribute to the kidney injury of severely jaundiced patients by direct bile and bilirubin toxicity, and tubular obstruction. The mechanisms are analogous to the injury by myeloma or myoglobin casts. It is different from HRS as in HRS, the injury is more pre renal and kidney biopsy is usually normal. 

IN THE NEWS: New NKF recommendations for screening

Based on some new findings in a recent AJKD study, the National Kidney Foundation now recommends annual screening with a simple urine albumin test that checks for protein in the urine, in specific high-risk groups. 

These include adults with:

• Diabetes
• High blood pressure
• Age 60 years or older
• Family history of kidney failure requiring dialysis or transplantation

The entire manuscript is in on AJKD website.  

Diabetes, HTN and family history of kidney disease makes sense and has always been part of the screening for kidney disease in past. Now, we are adding age >60 years or older based on the significantly high finding of >50% of americans likely to develop lifetime risk of CKD. The risk was higher in women. How do the authors come up with this risk? They used the current CKD prevalence rate of Americans with CKD and used the Markov chain model ( random process with memorylessness) to come up with statistics to detect the future risk. It is a model use to predict events in the future as a process moves in time. So in this case, current CKD prevalence using this model can predict what it could be based on risk factors and prediction of events what the CKD status would be years from now? The model is like the "drunkard walk" and how with each step, the position may change by +1 or −1 with equal probability. A use in medicine of this model can be found here and here. 

Nephrology Crosswords: Onco-Nephrology: Chemotherapy related toxicity

Check out the next KI Nephrology Crosswords on Chemotherapy related renal toxicities.