Thursday, May 31, 2012

KDIGO Glomerular Disease Guidelines: ANCA vasculitis


Pauci immune focal and segmental necrotizing GN guidelines by KDIGO


1. Initial treatment( cyclophosphamide and steroids) ( Grade 1A)
2. Rituximab and steroisd be used as alternative when above is contraindicated ( Grade 1B)
3. Plasmapheresis be added if there is rapid rise in crt or on dialysis (Grade 1C)
4. Plasmapheresis be added for pulmonary hemorrhage( Grade 2C)
5. Overlap diseases of ANCA and anti GBM - use plasmapheresis (Grade 2D).
6. If dialysis dependent for 3 months, stop cyclophosphamide if no extra renal manifestations( Grade 2C).
7. Maintenance therapy should be used if achieved remission ( Grade 1B)
8. Continue maintenance therapy for 18 months who achieved remission ( Grade 2D).
9. No maintenance in dialysis dependence and no extra renal manifestations ( Grade 1C)
10. Azathioprine is first choice at 1-2mg/kg/day orally as maintenance therapy ( Grade 1B)
11. MMF up to 1mg BID if above not possible( Grade 2C)
12. Bactrim use as adjunct( Grade 2B)
13. Methotrexate for maintenance  if intolerant to azathioprine and MMF if GFR >60 ( Grade 1C)
14. Etanercept should not be used as adjunct therapy ( Grade 1A).
15. Severe Relapse should be treated just like initial disease ( Grade 1C)
16. Other relapses should mean to re starting maintenance therapy ( Grade 2C)
17. Resistant disease:- Rituximab should be used ( 1C), IVIG( 2C) and plasmapheresis (2D)
18. ANCA titer alone should not change therapy ( Grade 2D)
19. Delaying transplantation till complete extrarenal manifestations have been in remission for 12 months( Grade 1C)
20. Not delaying transplantation for those in complete remission but still ANCA positive( Grade 1C).

For full details: http://www.nature.com/kisup/journal/v2/n2/pdf/kisup201226a.pdf
Image source: UNC kidney center website

Wednesday, May 30, 2012

KDIGO Guidelines for Glomerular Diseases: LUPUS NEPHRITIS

KDIGO is publishing guidelines in Glomerular Diseases in Kidney International

Topic: Lupus Nephritis


1. Class I LN be treated by extra renal manifestations rather than renal ( 2D)
2. Class II LN - No specific renal treatment if <1gm of proteinuria( 2D)
3. Class II LN- Proteinuria >3gm be treated with steroids or CNI like a minimal change disease (2D)
4. Class III LN- Steroids (1A) + either cyclophosphamide or MMF (1B)
5. Class III LN- if first option is not working to change to the alternative option above in 3 months (2D)
6. Class III Maintenance - Imuran or MMF ( 1B) and low dose steroids for one year (2D)
7. Class IV - same as Class III as above
8. Class V- If normal kidney function, and non nephrotic range proteinuria, conservative management and treatment dictated by extra renal manifestations( 2D)
9. Class V- persistent proteinuria:- steroids + cyclophosphamide and or CNI or MMF or Imuran ( 2D)
10. All patients should be on hydroxycholoroquine (2C)

For other detailed recommendations look at http://www.nature.com/kisup/journal/v2/n2/pdf/kisup201225a.pdf

Monday, May 28, 2012

KDIGO Guidelines for Glomerular Diseases: HSP

KDIGO released guidelines for glomerular diseases in Kidney International this year.

Topic: Henoch Schonlein Purpura Nephritis


1. HSP nephritis and persistant proteinuria of 0.5-1g/d be treated with ACEI or ARB( Grade 2D)
2. If proteinuria is >1gm, to be treated just like IgA nephropathy with steroids for 6 months
3. Steroids should not be used to prevent HSP Nephritis ( Grade 1B)
4. Crescentic HSP Nephritis should be treated with Steroids and alkylatic agents( Grade 2D)

For full article , look at
http://www.nature.com/kisup/journal/v2/n2/pdf/kisup201224a.pdf

Sunday, May 27, 2012

Healthcare in India exposed!

Aamir Khan( a well known Bollywood star) exposes indian societal issues nicely in this TV show.
His latest episode was on health care and he addresses multiple issues that Indian Healthcare is behind.
1. Corruption
2. Medical Mistakes
3. No punishment for corrupt and mal practice doctors
4. Rise of private medical colleagues and their costs.

Interestingly one of the topics in the discussion was on kidney and pancreas transplantation.
Have a look

Saturday, May 26, 2012

KDIGO Glomerular Diseases Guidelines: IgA Nephropathy


KDIGO just released guidelines for GN in a supplement in KI

Topic: IgA Nephropathy


1. Long term ACEI or ARB for proteinuria >1gm( Grade 1B)
2. ACEI or ARB treatment if proteinuria between 0.5gm to 1gm ( Grade 2D)
3. Patients with persistent proteinuria >1g/d despite 3-6 months of conservative management, and GFR >50ml/min get 6 month course of steroids (Grade 2C)
4. Not use cyclophosphamide or aza in IgA unless there is RPGN with crescents ( Grade 2D)
5. Not use cytotoxic agents for GFR< 30ml/min unless there is RPGN ( Grade 2C)
6. Fish oil is recommended if proteinuria is >1gm/d ( Grade 2D).
7. Not using antiplatelet agents in IgA( Grade 2C).
8. Minimal change with IgA:- treat like minimal change ( Grade 2B)
9. AKI associated with MCD:- perform a kidney biopsy in AKI with macroscopic hematuria if no change in renal function for 5 days
10. General supportive care for AKI in IgA for biopsy showing ATN( Grade 2C)
11. Steroids and cyclophosphamide in crescentic IgA( Grade 2D).
12. Tonsillectomy is not recommended ( Grade 2C)

For full recs see http://www.nature.com/kisup/journal/v2/n2/pdf/kisup201223a.pdf

Friday, May 25, 2012

KDIGO Guidelines for Glomerular diseases: Infection related GN


KDIGO guidelines published this year in KI supplement.
TOPIC: Infection related GN

1. Treat the underlying infectious disease for the following: Post streptococal GN, infective endocarditis related GN and shunt nephritis.
2. For Hep C related GN, and CKD stage 1 and 2, combined treatment with anti virals ( Grade 2C).
3. For Hep C related GN, CKD stage 3,4,5- suggest monotherapy with pegylated interferon with dose adjustment ( Grade 2D).
4. For Hep C with mixed cryo with nephrotic proteinuria or progressive renal disease: plasmapheresis, rituximab or cyclophosphamide  in conjunction with IV steroids and antiviral therapy( Grade 2D).
5. For Hep B related GN, treatment of Hep B with interferon alpha ( Grade 1C).
6. For HIV associated GN, anti retro virals are the most important regardless of CD4 count ( Grade 1B).

http://www.nature.com/kisup/journal/v2/n2/pdf/kisup201222a.pdf

Thursday, May 24, 2012

KDIGO Guidelines for Glomerular Diseases: MPGN

  KDIGO guidelines are proposed this year in recent Kidney International on glomerular disease.
Topic: MPGN

1. It is very important to evaluate for secondary causes
2. Conditions to consider are: Infections like Hepatitis C,  autoimmune diseases, MGUS, complement dysregulation and chronic thrombotic microangiopathy and to treat those underlying conditions.
3. Adults and children with idiopathic MPGN with nephrotic syndrome and progressive decline in renal function receive oral cyclophosphamide or MMF with low dose alternating steroid for 6 months( Grade 2D).












Wednesday, May 23, 2012

KDIGO Guidelines for Glomerular Diseases: Membranous Nephropathy


KDIGO guidelines have been now published on glomerular diseases in KI this year
(image source: kidneypathology.com)
Topic: Membranous Nephropathy

1. Initial therapy should only be started on patients with nephrotic syndrome and one of the following: more than 4g/day of proteinuria AND remains over 50% of the baseline value, AND does not show progressive decline, during anti hypertensive and proteinuric therapy with 6 months of observation( Grade 1B) or presence of disabling or severe complication of nephrotic syndrome( clot, significant edema)( Grade 1C) or rise in creatinine by 30% or more in 6-12 months from time of diagnosis (Grade 2C).

2. Immunosuppresive therapy to be not used if chronic disease found with small kidneys on sonogram.
3. 6 months of modified Pontecelli regimen ( oral or IV cyclophosphamide and steroids) for 6 months( Grade 1B) as initial therapy. Steroid month starts with IV steroids (1gm) for 3 days followed by oral steroids( 0.5mg/kg/day) for 27 days. The cyclo month starts and finishes with 2.0mg/kg/day of oral for 30 days.
4. CNI can be used for 6 months if cannot use above Pontecelli regimen( Grade 1C). CNI dose be reduced by month 2 to a level of about 50% of starting dose provided remission is maintained and no treatment related nephrotoxicity is develping( Grade 2C).
5. For resistant cases, suggesting switching from alkylating regimen based to CNI based and vice versa.
6. Relapses should be treated with the same therapy that worked ( Grade 2D).
7. If an alkylating therapy was used initially, then that regimen should only be used one more time again. (Grade 2B).
8. Nephrotic syndrome with albumin <2.5g/dl and additional risks for thrombosis,may benefit from warfarin ( 2C).

For full paper see: http://www.nature.com/kisup/journal/v2/n2/pdf/kisup201220a.pdf

Tuesday, May 22, 2012

KDIGO Guidelines for Glomerular Diseases: FSGS in adults


KDIGO released guidelines in glomerular diseases in a Kidney International supplement this year.( image source: RFN)


Topic: FSGS in Adults

1. Exclude secondary causes of FSGS , genetic testing not required routinely
2. Steroids at 1mg/kg daily as initial treatment ( 2C) if idiopathic
3. Minimum 4 week course but up to 16 weeks if not responding in 4 weeks
4. Taper over 6 months after response( Grade 2D)
5. Contraindication to steroids: use CNI( Grade 2D)
6. Relapsing FSGS should be treated just like relapsing MCD( with cyclosporine instead) for 4-6 months
7. If there is partial or complete remission, continue CNI till 12 months( 2D)
8. If cannot tolerate CNI, use combination of MMF with steroids ( 2C)

For full recommendations see: http://www.nature.com/kisup/journal/v2/n2/pdf/kisup201219a.pdf

Monday, May 21, 2012

KDIGO Guidelines for Glomerular Diseases 2012: Minimal Change Disease




KDIGO Kidney International supplementary material released the guidelines for management of glomerular diseases. ( image source: http://library.med.utah.edu/WebPath/RENAHTML/RENAL102.html)

Topic: Minimal change disease in Adults

1. Initial treatment - Steroids ( Grade 1C) 1mg/kg or alternating 2mg/kg QOD for 4 weeks minimum if complete remission achieved and 16weeks if complete remission not achieved (2C)
2. Taper after remission over 6 months( Grade 2D)
3. If cannot tolerate steroids, oral cyclophosphamide or CNIs can be used( Grade 2D)
4. For relapses, use the same steroid protocols
5. For frequently relapsing and or steroid dependent minimal change, oral cylcophosphamide can be used at 2-2.5mg/kg.day  for 8 weeks( 2C)
6. For frequently relapsing and or steroid dependent minimal change, oral cyclosporine can be used at 3-5mg/kg.day or tacrolimus 0.05-0.1mg/kg/day in divided doses for 1-2 years (2C)
7. MMF 500-1000mg BID for 1-2 years for intolerance also to 5,6 ( 2D)
8. Re-evaluate patients with resistant minimal changes for secondary causes.
9. For initial episode of nephrotic syndrome associated with MCD, statins and ACEI/ARBS not be used in normotensive individuals for proteinuria ( 2D).
10. MCD with AKI, treat with renal repalcement therapy if need be but with steroids.

take a look at full recommendations at http://www.nature.com/kisup/journal/v2/n2/pdf/kisup201218a.pdf

Wednesday, May 16, 2012

Clinical Case 56: Answers and Summary


NAME THE AGENT: 45 Y OLD MALE WITH SARCOMA GETS WORSENING RENAL FAILURE AFTER CHEMOTHERAPY X. LABS SHOW PERSISTENT HYPOURICEMIA, HYPOKALEMIA, HYPOPHOSPHATEMIA AND NON GAP ACIDOSIS AS WELL. URINE PH VALUES ARE IN 6-7 RANGE.


The case presents a fanconi's syndrome. This is classically seen in Ifosfamide toxicity. This can also be seen in cisptatin or methotrexate toxicity. Carmustine cause a more slow interstitial injury. Cetuximab is usually associated with pure hypomagnesemia.  Sunitinib is a tyrosine kinase inhibitor that can cause thrombotic microangiopathy, proteinuria or interstitial disease. A concept map of chemotherapy induced kidney disease can be found here.

Tuesday, May 15, 2012

CJASN Journal Club

The May eJournalClub of CJASN selection, "Efficacy and Tolerance of Urea Compared with Vaptans for Long-Term Treatment of Patients with SIADH" by  Alain Soupart, MD and colleagues


Check it out at http://ejc.cjasn.org/phpBB3/

Monday, May 14, 2012

IN THE NEWS: OBESITY and ORGAN POOL DONATION




Besides causing many other problems, obesity is leading to 

Friday, May 11, 2012

Geriatric Workforce Shortage: What can we learn?


Recently articles in the medical literature shed light on an important shortage besides nephrology- geriatricians. Geriatric medicine was founded as a specialty in 1988 and a fellowship track was created. With the baby boomers growing older and human lifespan expanding, multiple medical problems, geriatric medicine is an important field of medicine that should attract many applicants. But just like Nephrology, there is a major workforce shortage the geriatricians are facing today in the United States. Why is that and can this field survive?
Apparently, just like Nephrology, geriatric medicine is an unpopular career choice for medical students and residents due to perceived low prestige, low salaries and complicated patients.  Nephrology has many older patients, not very high salaries and similarly complicated patients to take care of.  American Society of Nephrology has created a committee on the Workforce shortage and ways to come up with ideas on how to increase interest in Nephrology. You can watch a recent video clip from ASN regarding this.



The article in annals proposes potential solutions on how to increase interest in geriatrics and improve geriatrics care. Perhaps Nephrology can learn from them
The suggestions are:

1********Geriatric focus models (ACOs) might help relieve some of that frustration. A similar proposal has been made in Nephrology.
2*********  “Gerontologize” teaching incentives. If the residents and medical students are not taking geriatrics as careers and fellowships are vacant, then perhaps energy should be redirected in geriatric educational resources towards teaching non geriatricians to be better geriatricians.   Nephrology is part and parcel of UGE and GME- unclear if this strategy will work in our field.  Will there ever be a point in time when general internists might have to do some basic nephrology care given lack of experts in the field.  In parts of the world, pediatric nephrologists are only found in academic centers, and initial treatments of many diseases including nephrotic syndrome is initiated by general pediatricians. 
3******** Train non geriatricians in geriatric medicine to deliver this education to the UGE and GME.  It appears that the field of geriatrics is not really focusing on how to increase interest but to shift gears and allow others to take charge and teach and practice geriatrics as part of their general medical practice. Given there is technical issues with dialysis and immunosuppresion management in transplantation, would a general internist be comfortable? Hard to see this happen in Nephrology

“It appears that if there is no increase in compensation, or professional recognition, the field of geriatric medicine is in for extinction.” – The article states. Should society needs and demands  be considered when making career choices? The society is going to need geriatricians and nephrologists, there is going to be a major shortage. Students in medicine and residents in medicine, should try to consider these fields of choices as they will be fulfilling a major need for the society as well.  

Thursday, May 10, 2012

IN the NEWS: Intensive treatment during end of life for dialysis patients?



Type of careDialysis patientsCancer patients
Hospitalization76.0%61.3%
Average number of days hospitalized9.85.1
Intensive care unit48.9%24.0%
Average number of days in ICU3.51.3
Ventilator, feeding tube or CPR29.0%9.0%
Hospice20.0%55.0%
In-hospital death44.8%29.0%
This is a table just seen in a recent article in Archives of Internal medicine on intensity of treatment at the end of life in older adults receiving long term dialysis.  It is an interesting comparison of cancer patients to dialysis patients and one notices that while cancer patients are sick, dialysis patients are sicker and have a higher mortality. Hospitalizations are more, average length of stay and even average intensive care stays are higher. Hospice is rarely offered or chosen in dialysis patients. Check out a post regarding this topic recently as well. Part of this is perhaps Nephrologists are not comfortable offering end of life care to the elderly sick patients during their end of life. Forgoing dialysis is hard for the practicing Nephrologists. 
Are our Nephrologists in training comfortable in dealing with end of life issues and providing "No dialysis" in the right circumstance. 
And how are they compare to their counterparts in cardiology, oncology, and critical care? 
We don't know. 
For that, we have created a survey for our fellows to take. Please pass this along to all nephrology fellows you know as this is very important question to answer.

eAJKD: Live NKF coverage

Check out next 4 days live blog posts, videos, audios and tweeter feeds from NKF by Dr.Tejas Desai as part of eAJKD

Wednesday, May 9, 2012

IN THE NEWS:ACR Lupus Nephritis Guidelines

Expert panel published recently the first ever guide to Lupus Nephritis treatment. The medical news community and lay press has mentioned it at numerous occasions already
Some summary points after looking at it

1. Definition of Lupus Nephritis included the usual persistent proteinuria, active sediment but noted that if a kidney biopsy showed immune complex mediated GN compatible with lupus nephritis would also qualify for the diagnosis. Finally, an opinion of the nephrologist or rheumatologist was good as well.
2. The panel recommended that all with active lupus nephritis, previously untreated undergo a renal biopsy but evidence for this was LEVEL C.
3. Treatment of disease be based on the class of lupus identified on biopsy.
4. Class I and II- conservative management and no active treatment ( Level C evidence)
5. Class III, IV and V- require treatment
6. Class III and IV- MMF induction or IV CYC along with steroids ( Level A evidence based on ALMS trial)
7. Myfortic was mentioned by the expert panel as equivalent to MMF in inducing lupus nephritis
8. Euro Lupus ( 500mg of IV CYC every 2 weeks) for total of 6 doses be used for Caucasians and patients of European origin and the NIH protocol( 500-1000mg/m2 IV once a month for 6 doses) be used for the rest.
9. Pulse IV steroids for 3 doses and then 0.5mg-1mg/kg daily dosing is needed( level C evidence)
10. Induction for Class IV/V with crescents included steroids but no recommendations made strongly regarding use of IV CYC or MMF for this group.  Both are mentioned.
11. Pure Class V:- MMF with steroids ( PO only) ( level A evidence)
12. AZA or MMF can be used for maintenance therapy ( level A evidence)

Some of the other things the task force discusses is changing regimen when initial treatment fails, pregnancy related to SLE treatment options and monitoring of lupus nephritis.

Take a look at the original article 
Take a look at a critical review by the Kidney Doctor Blog.


Tuesday, May 8, 2012

Friday, May 4, 2012

Topic Discussion: Hyperkalemia in Bartter Syndrome

Bartter syndrome is an autosomal recessive disorder characterized by renal salt wasting, hypokalemic metabolic alkalosis, and normotensive hyperreninemic hyperaldosteronism. Five variants of Bartter syndrome have been identified depending on the affected protein in the thick ascending limb of the loop of Henle:

·        Type 1: Inactivating gene mutation that encodes the  Na+-K+-2Cl- contransporter (NKCC2)
·        Type 2: Inactivating gene mutation that encodes the apical  K+ channel (ROMK)
·        Type 3: Inactivating gene mutation that encodes the  basolateral Cl- channel (ClCNKB)
·        Type 4: Inactivating gene mutation that encodes a basolateral accessory Cl- channel subunit Barttin (BSND)
·        Type 5: Inactivating gene mutation that encodes the  basolateral Calcium sensing receptor (CASR)

Apical ROMK ensures functioning of the NKCC2 cotransporter by recycling potassium back into the renal tubular lumen so hypokalemia in patients with defects in ROMK (Bartter's type II) is relatively mild compared with that in the other forms of Bartter's syndrome.
The mechanism of hypokalemia in Bartter syndrome is thought to be increased distal potassium secretion in the CCD caused by increased distal Na+ delivery in the setting of high aldosterone levels and also by activation of the flow-mediated K+ channels (Maxi-K or BK channels).

However, it has been recognized that Type 2 Bartter syndrome can sometimes course with hyperkalemia. The reason for this can be found in the developmental aspects of potassium secretion. Satlin et al have shown that CCDs isolated from newborn rabbits and studied by in vitro microperfusion show no net K+ secretion until after the third week of postnatal life; net K+ secretory rates increase to adult levels by 6 weeks of age. The role of the maxi-K channels appears to assume great importance in regulating K+ homeostasis under conditions where ROMK K+ secretion is limited like in Type 2 Bartter syndrome. Maxi-K channels are not consistently detected in the CCD until the 4th week of life. This is worsened by the fact that children with type 2 Bartter syndrome are usually born prematurely.

Although patients with type 2 Bartter syndrome may exhibit severe hyperkalemia during the first few days of life, the hyperkalemia is usually transitory. In fact, these patients typically exhibit modest hypokalemia beyond the neonatal period probably due to maturation and presence of Maxi-K channels after the 4th week.

Hyperkalemia during neonatal period has also been described in type I pseudohypoaldosteronism (type I PHA). However, in type I PHA hyperkalemia is sustained beyond the neonatal period and is associated with metabolic acidosis

Post by
Dr. Helbert Rondon

Thursday, May 3, 2012

IN THE NEWS: Treating Cast Nephropathy without treating the myeloma!


Myeloma kidney is a common complication of multiple myeloma (MM).  There has been data now that supports that free light chains co precipitate with Tamm Horsfall gycoprotein (THP) in the lumen of the distal nephron and leading to intratubular obstruction leading to clinically evident cast nephropathy.  Ying et al show in  this elegant paper in JCI about inhibiting this interaction of free light chains with THP.  There is an area on the free light chains called the complementarity determining region 3(CDR3) that is very important to allow interaction with the THP.  To demonstrate further, the investigators show that when you competitively inhibit that peptide, the free light chains did not bind to the THP in vitro.  Then in a rodent model of cast nephropathy, this inhibitor of CDR3 prevented cast formation and prevented manifestations of the kidney injury in vivo.


This is an interesting study as it doesn't treat the underlying disease which is MM but is attempting to treat in an animal model a consequence of the disease.  Cast nephropathy which leads to intra tubular obstruction can quickly lead to dialysis in many cases.  This is a study that shows by using the CDR3 inhibitor, we prevent this bad light chain and THP combo and prevent the precipitation in the tubules.  We also know that the free light chains behave differently in each MM case. In some cases, we get cast nephrpathy and in some cases we get light chain deposition disease and some amyloidosis.  It appears to be characteristics of the specific light chains produced. While this method might be optimal for cast nephrpathy cases, don't know if this will prevent all MM associated renal diseases.  Regardless, this study might lead to growing MM related cast nephropathy studies with this inhibitor; hopefully.


Ref:
http://www.ncbi.nlm.nih.gov/pubmed/22484815

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