Concept map: Osmolar gap and Anion gap made simple

CONSULT ROUNDS: TINU

Tubular interstitial disease and Uvietis (TINU) 
Some interesting facts:

1. First described in 1975
2. Usually seen in young females more than males
3. Usually uvietis occurs 2-3 months prior to the renal disease but can be as late as a year after renal disease.
4. Elevated ESR and b2 microglobulin levels might be the only lab clue
5. Sarcoidosis and Sjorgren's syndrome have to be ruled out
6. There is some indication that this might fit into the big category of IgG4 related diseases
7. Not uncommon to see proximal tubular dysfunction.
8. Treatment is steroids for 3-6 months.

International Update on Glomerular Diseases: A conference

We are hosting an international conference on glomerular diseases(ISN and NKF endorsed) as part of our division with exceptional speakers. All interested in learning about the conference and to register, can see the entire brochure online at the listed website of NSLIJ CME. Online registration is offered.

An International Update on Glomerular Diseases

Saturday, April 27, 2013

North Shore University Hospital

Rust Auditorium

300 Community Drive

Manhasset, NY 11030

Program of the Day | April 27, 2013 • 7:30 am - 4:00 pm
7:30 am Registration, Continental Breakfast and Exhibitors
8:00 am Welcome and Introduction to Glomerular Diseases
Kenar D. Jhaveri, MD and
Steven Fishbane, MD
8:15 am Minimal Change Disease and FSGS: An Update
Daniel Cattran, MD
8:45 am Clinical Approach to Membranous Nephropathy
Claudio Ponticelli, MD
9:45 am MPGN: The New Classification and Emergence of C3 Nephropathy
Naveed Masani, MD
10:15 am BREAK AND EXHIBITORS
10:30 am HIV Associated Glomerular Diseases
Pravin C. Singhal, MD
11:00 am Treatment of ANCA Associated Vasculitis
Fernando Fervenza, MD, PhD
11:30 am Cancer and Glomerular Diseases
Hitesh H. Shah, MD
12:00 pm LUNCH
1:00 pm Lupus Nephritis: Lessons Learned From Clinical Trials
Richard Furie, MD
1:30 pm Paraproteins and Glomerular Disease
Kenar D. Jhaveri, MD
2:00 pm New Diagnostic Tests and Therapies of IgA Nephropathy
Gerald Appel, MD
2:30 pm Pathology-Based Case Discussion
Glen Markowitz, MD and Panel
4:00 pm Closing Remarks and Adjourn
Kenar D. Jhaveri, MD and Steven Fishbane, MD

Concept Map: Monoclonal Gammopathy of Renal Significance (MGRS)

FSGS: A novel finding

FSGS has been the most researched glomerular disease from a basic science perspective. A recent urge in studying micro RNAs has led to some interesting new findings re glomerular diseases. A recent Nature paper discuses microRNA-miR-193a as a potentially inducing FSGS with extensive podocyte foot process effacement. This was elegantly done using transgenic mice of this expression of miRNA.

There has been data on wilm's tumor protein(WT-1) being central in podocyte integrity. It allows for differentiation of podocyte and classically this has been studied most in collapsing variant of FSGS where the podocytes are presumed to be dedifferentiated and loose that WT-1 marker. miR-193a inhibits the expression (WT1). Decreased expression levels of WT1 lead to downregulation of its target genes podocalyxin and nephrin leading to podocyte damage. The current study compared individuals with FSGS and normal kidneys and this expression of micro RNA. 

Check out the full study at Nature.

MGRS: We need to think a new way!

Many times we have come across monoclonal deposition in the kidney of Ig and there is no bone marrow or blood findings to suggest malignancy.  Lately, there has been findings of association of many such instances with glomerular diseases:

1. MGUS with MPGN
2. New findings of proliferative GN with monoclonal deposits( but no real bone marrow findings)
3. Immunotactoid GN and its's perhaps relationship with CLL and monoclonality
4. Fibrillary GN and similar findings ( less often than immunotactoid GN)
5. LCDD but no BM findings fully suggestive of >10% plasma cells to make a Myeloma diagnosis.

Clearly, there is monoclonal gammopathy of RENAL significance(MGRS) in all above states and perhaps we need to re look at a group of these disease states more carefully. Unfortunately, no studies exist to tell us how to treat them. Do we treat them as denovo renal diseases or treat the underlying plasma cell or B cell clone?

Some recent articles are worth a read to perhaps start some thought provoking discussions re these associations.

Glucoretics have arrived: A new class of anti diabetic drugs

The U.S. Food and Drug Administration approved the drug, Invokana, after data showed it was effective in lowering blood sugar in patients with Type 2 diabetes.
Known chemically as canagliflozin, Invokana is a member of a new class of diabetes treatments called sodium-glucose co-transporter-2 (SGLT2) inhibitors that lower blood sugar by blocking reabsorbtion of glucose and increasing its excretion in urine.
To me this sounds like a glucoretic. 

Some of the animal data had shown promise and then these class of drugs came into trials. Preclinical and clinical research has demonstrated that inhibition of SGLT2, the major pathway of renal glucose reabsorption, leads to increased urinary glucose excretion with concomitant reductions in fasting and postprandial plasma glucose levels, HbA1c levels and body mass. In animal studies, the drugs have been correlated with an increase in urinary volume and a reduction in body fat but not water content.They do mention that it is contra indicated in CKD and ESRD patients( well if you don't make urine, this will not be working for sure).

Why is this drug important for nephrologists? Well increased osmotic diuresis can perhaps lead to a pre renal insults, more urinary tract infections( due to the glucorectic effect), perhaps proximal tubular dysfunction or better yet- maybe it gives additional benefit of water loss leading to good blood pressure control. A recent study already looked at the drug's effect on CKD stage 3 patients. It was deemed safe in CKD Stage 3 based on that one study. 

Novel mechanism, lets wait and watch.