Podocyte Disorders

Glomerular disease review in a nutshell- check out the latest offering from AJKD Core Topics review
http://www.ajkd.org/article/S0272-6386(11)01071-7/fulltext

TOPIC DISCUSSION: Pure Thin Basement Membrane vs " Hereditary Nephritis with Thin Basement like features"

Classically, Hereditary Nephritis or Alports Syndrome shows the basket weaving appearing or thin and think alternating basement membrane.  Early in the course in some males and almost all females, the only finding on kidney biopsy might be thin basement membrane. The pathologist needs to carefully look for any subtle changes in lamination and change in thickness in other areas as it makes it almost impossible in that stage to differentiate from pure Thin Basement Membrane disease.  When its not possible to differentiate its called " Hereditary Nephritis with thin basement membrane phenotype".  Those cases have to be clinically followed closely in case they develop renal insufficiency.

Ref:
ASN Nephsap July 2011, Pathology

Topic Discussion: Proliferative GN with Monoclonal igG Deposits

Classically the dysproteinemias have glomerular involvement as
1. Light chain or Heavy chain deposition diseaese
2. Cryoglobulenemia
3. Amyloidosis
4. Immunotactoid GN
5. Fibrillary GN

Recently, a new entity has been identified called Proliferative GN with dysproteinemias or monoclonal igG deposits ( PGNMID)
Some features
1. MPGN pattern of injury, with endocapilary proliferation.  (Now if we look back at the original papers of secondary MPGN pattern of injury one of the classic causes is dysproteinemias, so unclear why this is a new category)
2. Interestingly, only 50% ended up having a bone marrow proven lymphoma or myeloma diagnosis( so now what do we do?)
3. All had proteinuria
4. 75% or more had hematuria
5. Treatment in this one study with immunomodulators showed no benefit
6.Type 1 Cyro MPGN pattern has to be ruled out.

Ref:
http://www.ncbi.nlm.nih.gov/pubmed/14675039
NephSap July 2011

TOPIC DISCUSSION; Stages of Membranous GN

On Electron microscopy, Membranous is defined by electron dense deposits in the sub epithelial region.

Classically there are 4 stages:
Stage 1:- sparse deposits, LM can even look normal.
Stage 2:- most commonly noted finding, the classic Spikes appearance
Stage 3:- deposits with overlying membrane formation, looks like a chain like formation
Stage 4:- disappearance of the deposits.

Interestingly, these stages don't correlate clinically
Progression from one to another could even mean improvement or worsening of proteinuria
We usually encounter Stage 2 most of the times
But just in one glomerulus, you can find multiple stages!

Ref: Neph Sap July 2011

Nephsap review: Fluids Electrolytes

Another interesting Nephsap teaching point by a question was an under recognized cause of acquired apparent mineralcoritcoid access.
Liver cirrhotic patients with elevated bilirubins and sickle cell crisis patients who have elevated bilirubins have this happen to them.  When total bilirubin levels are very high, it is hypothesized that worsening cholestasis led to greater bile acid inhibition of 11B - HSDH type II in the distal nephron and this allows for K wasting via cortisol mediation and HTN as well.
Case reports have been reported in liver cirrhosis and sickle cell crisis patients?
Wonder if we see this or its noticed in Post BMT - VOD syndrome?

Nephsap review: Fluids Electrolytes

Interesting thing we learned at our Nephsap about why hypomagnesemia causing hypokalemia
1. Intracellular Mg has inhibitory effects on the K secretion of ROMK channels in the distal nephron.
2. A decrease in Intracellular Mg will release this inhibitory effect and cause Renal K excretion.
3. Also Low Mg can lead to increase distal Na delivery and increased aldo as well and K excretion increases.

Nephsap review: AKI and ICU Nephrology

We encountered a question on " osmotic Nephrosis" that led to a discussion.
What is that and what are its causes?
It is renal injury that is "tubular" in nature secondary to hyperosmolar substatnces
You will see vacuolization and swelling of the tubules and a finding that might look very similar to " CNI toxicity" to a certain extent. But CNI injury is different and there other findings in that case.

Why is it called "osmotic" Nephrosis? Who knows. Since the vacuoles are happening due to large amounts of hyperosmolar solutes but these solutes enter the tubular cell via pinocytosis and not osmotic forces.

Things that cause it:

Increased starch in "anything" usually older forms of IVIG
Hetastarch
Mannitol
Contrast dye
Dextran

Its usually reversible and most important preventable

Take a look at the following good references:
http://www.ncbi.nlm.nih.gov/pubmed/18295066
http://www.ncbi.nlm.nih.gov/pubmed/8074604
http://www.ncbi.nlm.nih.gov/pubmed/19435473
Image source:1.Nature.com
2.Renal Fellow Network

Nephsap review: AKI and ICU Nephrology

At Nephsap review of AKI, we came across a question regarding ischemic renal insult and its effect on the rest of the body organs.  AKI induces inflammation and functional changes in many organs and its worth noting the changes that happen in other organs due to AKI.

1. Brain: increased vascular permeability  and disruption of blood brain barrier
2. Lungs: increased vascular permeability and pulmonary edema, increased leukocyte trafficking and altered response to ventilator associated injury
3. Heart:- increased TNF- Alpha and increased apoptosis of heart muscle
4. Bone Marrow:- increased anemia, immune dysfunction and coagulation disorders
5. GI tract:- increased channel inducing factor, and increased k excretion
6. Liver:- increased oxidation products and decreased anti oxidants

Nephrocentric we are!

Nephsap review: Glomerular, vascular and TI disease

In Nephsap review we learned that cancer following cytoxan carries risk due to total dosing amount

low dose of cytoxan usually means < 36gm of total cumulative cytoxan exposure
( this is artbitary)
<36gm group most common cancers were non melenoma skin and basal cell cancers
>36gm group most common cancers were non melenoma skin and basal cell but also saw bladder cancers, AML( which happened after many years)

Nephsap review: Glomerular, vascular and TI disease

In reviewing IgA Nephropathy:
Did you know that besides the pathology related prognostic signs, non traditional factors such as obesity, elevated nocturnal BP and increased uric acid levels and increased C4d mesangial depostion have been associated with a poorer prognosis in igA Nephropathy.  A mild alcohol consumption and mild elevation in bilirubin with a improved outcome.
Interesting ! Likely due to anti oxidant effects of both

Nephsap review: Chronic Kidney Disease : CKD patients are more likely to have proximal coronary lesions???

Did you know that patients with CKD are more likely to have proximal coronary lesions on coronary angiography? This is well summarized in Charytan,et al study in KI 2008. This is in comparison to distal lesions
the pathogenic mechanism behind it might the time that is not enough to form collaterals, uremic mileau, and perhaps other unknown reasons.

Interesting

http://www.ncbi.nlm.nih.gov/pubmed/18818684

Nephsap review: Chronic Kidney Disease: Troponin T vs I in CKD

On review of Nephsap 2009 CKD, here is an interesting topic of discussion that came up after a question we reviewed.
Hayeshi, et al studied the utility of using cardiac troponin t as a tool for predicting asymptomatic coronary artery stenosis in CKD patients on renal replacement therapy. The primary finding was that cardiac troponin t was a more potent independent predictor of asymptomatic multivessel coronary artery disease in late stage CKD patients. This raises an important point and makes us wonder will we be using troponin t as a screening tool for asymptomatic coronary artery disase in the future? Further studies are needed to help us with this.
First we need to understand the different troponins in the picture.

Troponin is a component of thin filaments and is the protein to which calcium binds to accomplish this regulation. Troponin has three subunits, TnC, TnI, and TnT. 

• Troponin C binds to calcium ions to produce a conformational change in TnI
• Troponin T binds to tropomyosin, interlocking them to form a troponin-tropomyosin complex
• Troponin I binds to actin in thin myofilaments to hold the troponin-tropomyosin complex in place.

Some centers use Tropnin I and some T, both are very sensitive and specific for cardiac events.

The question is which one is better in CKD patients.

Another study by Fehr et al in Clinical Nephrology showed that for diagnosis of ACS in HD patients, a combination of cTnT and cTnI may be used, since the former has higher sensitivity and the latter higher specificity. A higher threshold value for cTnT in HD patients could further increase its diagnostic accuracy.

Interesting the differences in the studies, one with CKD and other with ESRD.

http://www.ncbi.nlm.nih.gov/pubmed/18403432

http://www.ncbi.nlm.nih.gov/pubmed/12572929