Saturday, March 28, 2015

Clinical Case 87: Answers and Summary

34 y old Indian Male with IgA nephropathy, crt is 2.4mg/dl and 2.5gm of proteinuria: treatment?

RAAS blockade only
  6 (12%)
RAAS blockade and Fish oil
  9 (19%)
Steroids with RAAS blockade
  19 (40%)
Treatment depends on Biopsy Oxford Classification of IgA Nephropathy
  13 (27%)

The KDIGO recommends no specific guidance for treatment with steroids in IgA nephropathy patients when they present with GFR between 30-50cc/min. A recent study published in JASN in 2015 looked at steroid use in IgA Nephropathy patients. It is called the VALIGA study.  A retrospective study that studied over 140 patients with IgA nephropathy from European registry and classified based on Oxford classification MEST score.   46% received immunosuppresive agents and of them 985 were steroids.  The ones who were treated had all the features of clinical progression( rising crt, or proteinuria).  All also received RAAS blockade.  The patients who got steroids had a significant reduction in proteinuria, a slower rate of renal function decline and greater chance of not being on dialysis.  While, initially we had thought that the benefit of such treatment was only in patients with mild- moderate AKI, this study found benefit even in the GFR<50cc/min cohort with levels of proteinuria.  

So in the above patient, the best answer would be Steroids with RAAS blockade. If the biopsy did show crescentic GN, the treatment ofcourse would be with cytotoxic agents in addition. 

Sunday, March 15, 2015

ASN- KSAP First installment

Nephrology Self-Assessment Program (NephSAP) has served for twelve years as a strategy for nephrologists to keep knowledge up-to-date and earn both CME credits.

ASN has recognized a need for material that covers basic principles of clinical nephrology that would be appropriate for individuals who are studying for the In-Training/In-Service examination or preparing for the American Board of Internal Medicine (ABIM) examination in the subspecialty of Nephrology. To this end, the concept of the Kidney Self-Assessment Program (KSAP) was developed.

KSAP is similar to having a Q bank for board preparation and re certification exams.
Please visit and see what you all think

This was must needed and well intended

Tuesday, March 10, 2015

Topic Discussion: Renal Vein Thrombosis in the Allograft

0.5%-4% and frequently results in graft loss

Risk factors:
Technique error
Hypovolaemia Atherosclerosis OKT3 (plus high-dose methylprednisolone) Antiphospholipid antibodies High dose steroids Long cold ischaemia time Delayed graft function recovery

Certain renal diseases( membranous GN, SLE)
Antiphospholipid antibody syndrome
Use of oral contraception, 
Hereditary thrombophilia secondary to protein C or factor V deficiency

Clinical presentation:
Acute anuria, hematuria, graft tenderness, primary non function of the graft

Best test:
Renal sonogram with dopplers waveform evaluation( most important part)
A normal renal arterial waveform in either an allograft or native kidney shows antegrade flow throughout the entire cardiac cycle. Reversal of diastolic flow in the allograft renal artery, although not specific, is considered abnormal. This finding is caused by a significant increase in resistance in small intrarenal or large extrarenal vessels. This sign is not pathognomonic for renal vein thrombosis ( as can be seen with ATN or rejection as well).  Renal vein thrombosis was more likely to occur in the acute (24 hours) and perioperative (30 days) periods. It is important to recognize the abnormal duplex Doppler waveform pattern, reversal of diastolic flow, which is associated with renal vein thrombosis.

Timely returning back to the OR for thrombectomy and or reconstruction of venous component
Streptokinase or urokinase
Percutaneous mechanical thrombectomy and
Localized catheter-directed thrombolysis
But overall, prognosis is poor with many times leading to nephrectomy.

Two great reviews:

Wednesday, February 25, 2015

Risk factors for BK virus infection post transplantation

Transplant related risk

1.       Acute rejection episodes
2.       Cold ischemia time( the longer the more likely)
3.       Delayed graft function
4.       Ureteral stent placement
5.       Thymoglobulin induction
6.       Tacro/ MMF based regimen

Recipient related risk
1.       Older age
2.       Male
3.       Non African American
4.       DMII

Donor related risk ( now this is fascinating)
1.       BK Virus + donor
2.       Degree  of HLA mismatch
3.       HLA C7

Apparently there is growing evidence that the donor kidney might be the source of the BK virus.  Pre- transplant BK Screening of donors might identify the risked recipients post transplant.  Recipients of BK + donors developed BK viremia at earlier transplant time-points, had higher viral loads and slower clearing of the virus.  Even a recent study provides more evidence of this concept.

Overall, a nice review of BK Nephropathy was just published in NDT, where these risk factors are summarized.

Tuesday, February 24, 2015

Topic Discussion: MGUS and kidney transplantation

MGUS is defined as having a monoclonal protein in a small but abnormal concentration( <3g/dl). But the bone marrow doesn’t meet criteria for plasma cell percentage that qualifies for myeloma.  The incidence of MGUS is around 3.2% especially in the age >50 and the incidence rises as you age. Given the number of renal transplants are increasing especially in the age >50, it is evident that this entity comes up now frequently at transplant selection meetings.  What do we do? Is it a risk factor? Should we be worried?
MGRS( monoclonal gammopathy of renal significance) is a term now used to describe entities that have renal damage from MGUS. A recent KI paper sheds more light on the pathology of such cases. High rates of recurrence and the recurrence is early and more severe than in the native kidney. ( 40-60%) if MGUS had presented as MGRS( or some folks might want to call is MGKS).  Risk is especially high when there is a circulating Monoclonal immunoglobulins still around.  Recurrence is early and much more severe than the native disease.

Soltero et al. looked at transplant candidates with MGUS between 2000 and 2007 in a single center study.  MGUS that received a KT were compared with MGUS that were not transplanted.( similar age and CV risks) . Of 1215 KT candidates, 34 were found to have MGUS  (11%). The gammopathy was monoclonal in 76% of the cases. Nine patients with MGUS were transplanted. Following transplantation, the MGUS group had a lower survival than the non-transplanted group. (p = 0.0008).  Follow-up of 18.7 ±  15.4 months, seven patients (78%) died. Causes of death were cerebral abscess, lung cancer, sepsis, melanoma, bacterial meningitis, myocardial infarction. They had requested UNOS database from 1987-2003 and only found two reported cases of MGUS to UNOS.  Hence data might not be possible to be obtained from UNOS as not many centers are asking this information.
There are cases of LCDD, MPGN and proliferative GN with monoclonal deposits recurring after transplant. Most of the cases had untreated monoclonal clones prior to transplantation. They would now be classified as MGRS cases.

Is MGUS a risk factor for development of MM post transplantation?  A study from Mayo Clinic had indentified patients who had MGUS either before or after transplant. Of the 3518 patients who underwent transplantation, MGUS was found in 42 patients( 23 pre and 19 post).  They were followed for 8 years.  17% of pre transplant MGUS patients developed malignancies such as smoldering myeloma and other hematologic cancers.  None of the patients who developed MGUS post transplant progressed to MM.
Another more recent study by the Mayo group looked at newly diagnosed MM cases post transplantation. 7 cases were identified and 4 of them had MGUS pre transplant and two of them had clonal plasma cells in bone marrow. They concluded that MGUS prior to transplant was a risk factor for MM post transplant.

Garcia et al showed recently that MGUS following transplantation is a different phenomenon. It was  >100 times more frequent in transplant patients than in general population. Of their small subset of 11 patients with post transplant MGUS, only one developed PTLD.  In contrast to MGUS  in general population, progression to plasma cell dyscrasias was absent and it’s incidence is unknown A longitudinal study in 55 patients demonstrated that most of the MG reflected transient B-cell monoclonal proliferations, probably due to an immunodeficiency. Usually associated with intense immunosuppression and M protein is usually small and multiple bands.

In summary, MGRS may not be a contraindication to kidney transplantation as risk of dying from their clone is low.  No data to suggest that small B-cell clones are truly curable but there might be a high rate of recurrence in certain types. While LCDD and amyloidosis might have a slower recurrence rate, proliferative GN with monoclonal deposits might be must faster. MGUS might be a risk factor for development of active hematologic disease post kidney transplant.  The decision to transplant might depend on considering the underlying MGRS characteristics, initial therapeutic response, extrarenal manifestations, and the patient’s status. Risk of graft loss, its link with the B-cell clone and the potential need for reintroduction of chemotherapy should be explained to the recipient and the donor.

The field is still unsure on the question asked? 

Saturday, February 21, 2015

Nephmadness 2015: A novel theme

NephMadness began in March 2013 as a social media education project of the AJKD blog.  From the beginning, we envisioned NephMadness as an ambitious month long social media campaign, featured in multiple AJKD blog posts that encouraged deep engagement. Two years and still running with power and fuel, the game has become a monster on it's own in the social media world in nephrology.

Welcome to 2015 now. The theme for NephMadness 2015 is nephrology’s connections with other specialties. The 8 topics are  listed below.  A detail account of history of Nephmadness and how to play the game is now available in an editorial in AJKD. In addition, check out for ongoing details and brackets appearing starting March 1st 2015.

1. Obstetric Nephrology
2. Infectious Disease and Nephrology
3. The Heart and Kidney Connection
4. Nephrology and Nutrition
5. Genetic Nephrology
6. Critical Care Nephrology
7. Nephrology and Vascular Surgery
8. Onconephrology

Let the madness begin!!

Sunday, February 15, 2015

Clinical Case 86: Answers and Summary

Which one of the following chemotherapy agents cause solitary hypophosphatemia?(select more than 1)

  7 (38%)
  2 (11%)
  7 (38%)
  4 (22%)

While many chemotherapy agents cause electrolyte disorders, hypophosphatemia is a rare occurrence.

Let’s take each chemotherapy agent at a time that is listed above.
Cisplatin classically is known to cause AKI and proximal tubular damage and hypomagnesemia but sole hypophosphatemia is rarely reported. Usually, a classic Fanconi syndrome has been described
So, choice A is less likely to cause solitary hypophosphatemia.

Sorafenib, a multikinase inhibitor targeting the c-Kit, RAF, VEGF and PDGF pathways, is approved for the treatment of patients with hepatocellular carcinoma and renal cell carcinoma, with a broad spectrum of activity also including selected sarcoma subtypes, thyroid cancers and melanoma. Sorafenib induces pancreatic exocrine dysfunction, leading to vitamin D malabsorption and secondary hyperparathyroidism. Patients receiving sorafenib can develop hypophosphatemia and vitamin D deficiency.

Of the 4 listed above, imatinib has been most well described with this electrolyte disorder. In NEJM, Berman and colleagues reported their findings regarding the development of hypophosphatemia and associated changes in bone and mineral metabolism in patients with either chronic myelogenous leukemia or gastrointestinal stromal tumors who are taking imatinib. A nice review article discusses the effect of all tyrosine kinase inhibitors such as imatinib and sorafenib and their effects on bone health. By inhibiting platelet-derived growth factor receptors expressed on osteoclasts, these agents cause a subsequent decrease in bone resorption and decreased calcium and phosphate egress from the bone. As a result, PTH levels increase and phosphaturia follows.

Lenalidomide and hypophosphatemia has been described in conjunction with other therapies and sole effect. It appears to be a potential renal loss mechanism. It is hard in this drug as myeloma is the primary cancer and the cancer itself can cause this electrolyte disorder. A Fanconi syndrome has also been described. 

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