Wednesday, December 28, 2011

Tuesday, December 27, 2011

TOPIC DISCUSSION: What about BUN - and when its too low?

Not many studies have looked at causes of low urea nitrogen production. Besides malnutrition, there are certain other conditions that might be very likely to have noted low BUN levels. A study done in 1989 looked at causes of BUN less than 50mg/dl. ( in their lab 50-200mg/dl) was normal.

The causes were:
Alcohol abuse
Intravenous fluids intake
Endocrine disorders
Special Diets
Use of steroids

If we analyze what they found: Alcohol abuse is usually associated with low solute intake and mal nutrition and hence again leading to that as the cause. IVF and special diets can be understood. The endocrine disorders they found were SIADH, hyper and hypothyroidism due to water excess leading to low BUN.  The steroids use ( usually thought to be cause increased BUN), was thought to decrease BUN due to water retention per the authors.

Interesting old study to have a look
Ref: http://www.clinchem.org/content/35/4/639.full.pdf


Sunday, December 25, 2011

Renal Fellow Network: Top nephrology-related stories of 2011

Renal Fellow Network: Top nephrology-related stories of 2011: 2011 proved to be another exciting year in the world of nephrology. 2010 was dominated with big clinical trials (SHARP, FHN, IDEAL), APO...

Saturday, December 24, 2011

Journal Club: FGF-23 and LVH


Left ventricular hypertrophy(LVH) is an important mechanism of cardiovascular disease in CKD that contributes to cardiac events and death. Prevalence of LVH in dialysis population is around 90% and 50-70% in CKD population. Compensatory increases in FGF23 levels help patients with CKD to maintain normal serum phosphate levels, despite even severely reduced renal function. Recent prospective studies of CKD and non-CKD patients demonstrated a dose-dependent association between elevated FGF23 levels and greater risks of major cardiovascular events and mortality.

http://www.ncbi.nlm.nih.gov/pubmed/21903574
http://www.ncbi.nlm.nih.gov/pubmed/18687639
http://www.ncbi.nlm.nih.gov/pubmed/21673295 

A recent study by Faul et al in JCI show the toxicity of elevated FGF-23 levels on LVH in a mice model. They summarize that FGF23 causes pathological cardiac hypertrophy directly. This is mediated by FGFR-dependent activation of the calcineurin-NFAT signaling cascade but do not require klotho as coreceptor. Blocking FGFR signaling can prevent LVH, independent of blood pressure in an established animal model of CKD that is characterized by elevated FGF23 levels, severe hypertension, and LVH. The effect is Klotho independent. First, low-affinity binding of FGF23 to FGFR may be adequate to induce LVH when there is a protracted period of cardiac exposure to high concentrations of FGF23, such as in CKD. FGF23 toxicity : accentuated further in CKD where klotho expression is down-regulated in the kidney and parathyroid glands, which could enhance promiscuous binding of FGF23 to FGFR in other tissues.

Thus, high circulating FGF23 concentrations combined with decreased klotho expression could represent an especially cardio-toxic blend in patients with CKD.

Ref:
http://www.ncbi.nlm.nih.gov/pubmed/21985788
(image courtesy:- JCI article)




Hitesh Patni, MD
Kenar Jhaveri, MD

Friday, December 23, 2011

eAJKD: Test your knowledge on Glomerular Diseases in Sjorgen's syndrome

Check out the latest post on eAJKD re SS and Glomerular Diseases.

eAJKD: Peritoneal Dialysis Strikes Back

In the United States, the number of patients who are offered peritoneal dialysis (PD) has declined over the last decade. The newer generation of Nephrologists may not feel as comfortable with this dialysis modality, and shy away from referring patients towards PD. Check out this latest post regarding an article that opens news ways to increase PD as an option for dialysis to the patients. Visit eAJKD page

Wednesday, December 21, 2011

TRANSPLANT ROUNDS: Test your knowledge of induction agents!

To test your knowledge of induction agents in kidney transplantation, we invite you to complete the following matching quiz. The answers will be posted early next week.
Match the following induction agents with the description that best matches their profile. One description will not be used.

Alemtuzumab
A. This anti CD25 human/ mouse chimeric antibody is almost devoid of side effects. It does not increase the risk for malignancies or infections.
Rituximab
B. This antibody has been used in a recent trial to facilitate positive crossmatch transplantation in living donors by blocking the effector pathway of antibody mediated allograft injury.
Thymoglobulin
C. This agent is used to treat antibody mediated rejection and as induction in sensitized individuals. It decreased the production of anti-HLA antibodies by targeting the CD 20 receptor on B cells and plasma cells.
Daclizumab
D. This antibody targets CD 52. It is FDA approved for the treatment of CLL. It is often used in minimization protocols for kidney transplantation.
Basiliximab
E. This agent when used as an induction agent may increase the risk of cellular rejection.
Atgam
F. This polyclonal antibody preparation targets many different receptors on T cells. It increases the risk of PTLD, and CMV compared to no induction or anti-CD25 induction. However, it has been shown to be a superior agent in reducing rejection episodes and prolonging graft survival especially in high risk individuals.
OK3T
G. This polyclonal antibody preparation came from horses. It has since been largely replaced by another polyclonal T cell preparation.
Eculizumab
H. This agent was a humanized monoclonal antibody that targeted the alpha chain of the IL-2 receptor of T-cells. The manufacturer discontinued its use in January 2009.

I. This monoclonal antibody against the T-cell receptor was the first such antibody used for any clinical indication in the United States. Its current use has been minimized due to severe adverse reactions including serum sickness and pulmonary edema.
Answers soon to follow! Stay tuned.

Monday, December 19, 2011

CONSULT ROUNDS: AA vs AL Amyloidosis

How do we differentiate AA from AL Amyloidosis? 

Accurate typing of amyloid is mandatory because the treatment modalities of various types of amyloid are very different. Renal amyloidosis can at times be easy to classify into AL and AA types depending on immunofluorescence and immunohistochemistry studies. Technically, AL amyloidosis or AH amyloidosis are plasma cell diseases and either light chain or heavy chain disorder that have one chain predominance on IF and then subtypes using staining for AL or AH.  AA amyloidosis is usually secondary to chronic illness such as RA, FMF, Infections, sometimes malignancies like renal cell and Hodgkin's Lymphoma.
A novel technique has come into light in helping diagnosis Amyloidosis. It is the LMD/MS technique or Laser micro dissection combined with mass spectrometry. From the Mayo Clinic, using this technique, they were able to diagnosis even rare cases that might not have been picked up on regular staining via AA or AL and perhaps even medullary Amyloidosis.  They showed that LMD/MS is a useful and sensitive technique for the diagnosis of amyloid and for accurate typing of the amyloidosis, particularly problematic cases of amyloid. To show the usefulness of LMD/MS in typing renal amyloidosis, they demonstrate four cases of renal amyloidosis that were diagnostically challenging.  What is this method?
About 10-μm-thick sections of formalin-fixed paraffin-embedded tissues were stained with Congo red. Glomeruli with positive Congo red areas viewed under a fluorescence light source appeared bright red. The Congo red deposits were identified under fluorescence light and microdissected with LMD.  The microdissected material was collected analyzed by liquid chromatography electrospray tandem mass spect.  The MS result value indicates the total number of mass spectrum collected on the mass spectrometer and matched to the protein using the proteomic software. A higher number of mass spectra is indicative of greater abundance and will typically yield greater amino acid sequence coverage.
Thus specific proteins were identified and diagnosis was made
Check out the two references:

Saturday, December 17, 2011

CONSULT ROUNDS: Calciphylaxis Treatment Options

A Pathophysiology based treatment strategy has been suggested:
1. High bone turnover/ high pth levels:- Therapy that works is cinacalcet, Vitamin D analogs, non calcium based phosphate binders, bisphosphanates, and perhaps surgical parathyroidectomy
2. high calcium phos product:- tight control with daily dialysis, avoiding calcium based binders, low Ca dialysate
3. Extracellular matrix associated soft tissue or vascular calcium deposition effects:- sodium thiosulfate enhances calcium solubility, bisphosphanates via multiple ligand pathways
4. Hypercoagulability mechanism:- avoid warfarin, change to non warfarin based agent, hyperbaric oxygen for wound healing
5. Tissue ischemia mechanism:- hyperbaric oxygen, optimize anemia, sodium thiosulfate
6. Macrophage activation:- avoid biopsies if possible.


Traditionally above treatments have always been mentioned
Bisphosphanates have now started coming into the literature to be used in this disease entity.


1. Mechanism might be calcium mediated and control of high bone absorption
2. Independent effet on bone and tissue calcification via NF-B pathways and RANKL
3. Inhibition of phosphate transport and calcium phosphate crystal formation
4. Anti inflammatory effects towards macrophages and TNF and interleukins


When to use them?
1. No clinical improvement with above mentioned common therapies
2. Failed 2 weeks of sodium thiosulfate as well
3. Usually use Pamidronate 30mg IV ( 5 doses over 48 days) or Aldentronate 35mg weekly
4. Successful treatment has been described in the literature.


Check out the original references:


http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowPDF&ArtikelNr=332221&Ausgabe=255569&ProduktNr=223979&filename=332221.pdf
http://www.ncbi.nlm.nih.gov/pubmed/18070019
http://www.ncbi.nlm.nih.gov/pubmed/18021849
http://www.ncbi.nlm.nih.gov/pubmed/15252173

Friday, December 16, 2011

eAJKD: Home Hemodialysis

Is there any future for Home Hemodialysis in the US? Check out the commentary from Dr. Mailloux on two recent articles in AJKD Dec 2011 issue on eAJKD

Wednesday, December 14, 2011

eAJKD: IgA Nephropathy and Vitamin D therapy

White vitamin D has shown to be beneficial in reducing proteinuria in patients with chronic kidney disease (CKD), the role of activated vitamin D replacement in IgA Nephropathy is not well studied.  A recent open-label, nonplacebo-controlled randomized study published in the American Journal of Kidney Diseases looks at this particular question.  Check out the latest blog post from eAJKD.

Tuesday, December 13, 2011

CLINICAL CASE 48: Answers and Summary


AFRICAN ANCESTRY GENETIC VARIANT APOL1 GENE HAS BEEN NOW ASSOCIATED WITH GLOMERULAR DISEASES. WHICH OF THE FOLLOWING REGARDING APOL1 ARE TRUE?

1.APOL1 can be localized to podocytes and media of medium artery and arterioles in the kidneys-  22%
2.APOL1 Variants Increase Risk for FSGS and HIVAN but Not IgA Nephropathy -33%

3.African Americans carrying two copies of the G1 APOL1 risk allele need early age hemodialysis -22%
4.Case-control studies suggest that African Americans with genetic variants in both copies of APOL1 
have increased risk for hypertension-attributable ESRD and focal segmental glomerulosclerosis  -77%

5.APOL1 sits next to MYH9 gene  - 100%
6.African americans with APOL1 risk allele have more increased risk of non diabetic CKD - 44%




Gene variants of MHY9 locus were being considered as possible risk factors for FSGS and high incidence of kidney diseases in the african american population for the last decade.  A further risk assessment was just done by the same investigators and 1641 European Americans were compared to 1800 African Americans and new locus was discovered.
This phenomenon might be epigenetic from protection from the Sleeping sickness disease caused by the tsetse fly. Apparently on the same chromosome 22, APOL1(apolipoprotein -1) and MHY9 sit next to each other.  The studies are now showing that due to natural selection and linkage disequilibrium, the APOL1 gene might be the strong candidate for a gene that is responsible for increased incidence of renal disease in African Origin Americans. Recent JASN articles in Nov 2011 issue also shed light on newer findings as described above: Having the APOL-1 variant can lead to more arterilopathy and renal vessel changes and that was confirmed on biopsy findings.  Interestingly, only certain glomerular diseases are at risk- FSGS types including HIVAN but not IgA nephropathy or diabetic nephropathy.  Given the severity of the disease, these patients need dialysis at an earlier age.  More copies of this gene- more you are at risk of FSGS and ESRD.

So all the above statements are correct.

Ref:

Monday, December 12, 2011

TOPIC DISCUSSION: Lithium and timing of dialysis?

Since 1870s, lithium has been around to help physicians deal with many issues including gout, cluster headaches and neutropenia.  Then it became the standard of care treatment for bipolar disorder.  This agent is water soluble and not protein bound hence easily dialyzed.
What are the indications for dialysis in a patient who comes in with lithium toxicity?

1. Lithium toxicity and acute renal injury
2. Patients with normal renal function and cannot tolerate aggressive fluid therapy or GI decontamination due to either cardiac or liver disease
3. Severe neurological presentations of altered mental status and seizures.
4. Acute presentation with even mild symptoms but level >4.0mEq/L
5. Chronic use of lithium but level >2.5mEq/L
6. Be careful of rebound phenomenon as it is released from adipose tissue as being removed by dialysis.

Points 4+5 might be controversial as many won't believe in just using a number to arbitrarily start dialysis. There are also some who have advocated CVVH in this setting as it will prevent the rebound regardless of the volume status of the patient. Some might argue that if presenting acutely, to just hydrate and follow serial levels ask lithium follows a two compartment model. Its initially high in the blood and then high in the tissue. Dialysis won't be effective in removing the intracellular lithium.  As a result, early levels could be misleading.

Lets go through an exercise of why dialysis is so effective in removing lithium. It has to do with the volume of distribution(Vd). It is the amount of drug/ plasma concentration.  Or L/kg.  Some drugs such as opioids and anti depressants have large Vd and lithium, alcohols and salicylate have small Vd.

So think of this way: If your clearance is 200ml/min using dialysis or native GFR of 100ml/min
and you have a drugA with 500L of Vd and another with 50L of Vd( lithium).  Then the fractional elimination in 60 min of dialysis will be 1% for drugA and 17% for drug B (Half life is 0.693 Vd/Clearance)

Friday, December 9, 2011

IN THE NEWS: Transplantation and hypotension




We often encounter patients who have very low blood pressures on dialysis for unclear reasons, perhaps there is a component of amyloidosis but functioning is normal with these low bp in SBP 70-90s.  What happens to them when they get transplanted?  Do they have more risk of ischemic re perfusion injury, more rejection? Or primary non function (PNF).
A recent study in Transplantation 2011 confirms a primary non function of these grafts. PNF is a devastating outcome after kidney transplantation and is more common with kidneys from donors who are cardiac death or extended criteria. Recipient criteria have not been explored.  A case-control study design and matched for the source of organ and year of transplantation was done in this paper retrospectively.  Among the factors analyzed, the mean systolic BP , diastolic BP, and mean arterial pressure (MAP)) during the 3 months before transplantation were significantly lower in the PNF cases compared with the controls without PNF. The paper supports the hypothesis that the average MAP less than or equal to 80 mm Hg during the 3 months before kidney transplantation is a risk factor for PNF.
What does this mean? Should we not transplant this subgroup? Should they be given pressors prior to surgery? Should they be made volume dependent ( more then they are perhaps) like pheochromocytoma surgeries?  Unclear what those changes might do.

Check out the full article at:

Thursday, December 8, 2011

TOPIC DISCUSSION: FUROSEMIDE in HYPERCALCEMIA

Treatment of symptomatic hypercalcemia is treating the underlying cause but also some symptomatic management.  Usually aggressive IV hydration is warranted sometimes even at 150-200-250 CC/HR.
Once volume depletion is addressed, a loop diuretic MAY be used for augmentation of calcium excretion.
A recent review and analysis published in Annals of Internal Medicine sheds some light about use of loop diuretic in this setting.
The review suggests the following points:

1. Aggressive hydration is necessary
2. Use of diuretics without aggressive hydration might be harmful
3. Found only 9 articles documenting the use of furosemide in hypercalcemia and latest one published in 1983 and total was only 37 patients.
4. Average dose was 1120mg over 24 hours ( really??)
5. Normalization of Ca occurred in only 14 of 39 cases
6. Study with lower doses didn't achieve normalization ( and what do we use????)
7. complications of other electrolyte disorders ensued
8. Finally, recommended against the use of this agent routinely except for cases of volume overloaded with hypercalcemia.
I think the tile of the paper listed below nicely puts it:- Furosemide in hypercalcemia is an unproven but common practice ( really not evidence based)

Ref: http://www.ncbi.nlm.nih.gov/pubmed/18711156

eAJKD: PTLD quiz!

Go test your knowledge of PTLD at the eAJKD blog site

Tuesday, December 6, 2011

Azathioprine vs MMF: Transplantation for the society?

Every year, our fellows do role playing as part of their transplantation training lectures. Last week, the fellows were assigned immunosuppressive agents and each played a specific drug that was "assigned to them" based on their personality. 
What was very fascinating to me was that fellows bring articles that are supporting their existence and what can make their agent more superior.  In our vast medical literature, one can always find articles that support one side and then enough to support the other. Debates as a result lead to a more fun and exciting discussion that enhances learning.
One of the most interesting debates was AZA vs MMF.  The AZA arm pulled out these two articles that were very interesting. 


Article 1: MYSS trial from LANCET 2004: Mycophenolate mofetil has replaced azathioprine in immunosuppression regimens worldwide to
prevent graft rejection. The mycophenolate steroids sparing multicentre, prospective, randomised, parallel-group trial compared acute rejections and adverse events in recipients of DDRT over 6-month treatment with MMF or azathioprine along with Neoral and steroids (phase A), and over 15 more months without steroids (phase B). The primary endpoint was occurrence of acute rejection episodes. This trial showed no major advantage to preventing acute rejection when MMF was used.  

Article 2: MYSS trial follow up results: In kidney transplantation, the long-term risk/benefit profile of MMF andazathioprine therapy in combination with cyclosporine Neoral is similar. In view of the cost, standard immunosuppression regimens for kidney transplantation should perhaps include azathioprine rather than MMF.

The cost to oneself vs cost to the society is the question when we embark on expensive therapies that are equal to a cheaper alternative.  Nevertheless, MMF has fewer side effects and less interactions with other medications.  

If you needed a transplant:- what would you choose to have? MMF or AZA?

eAJKD: family history of ESRD- what does that mean?

Check out the latest author oriented discussion on eAJKD on ESRD family history as a risk factor for kidney disease. This is an under studied area.
http://ajkdblog.org/2011/12/06/family-history-of-end-stage-renal-disease-what-does-it-mean-for-esrd-risk/

Monday, December 5, 2011

The Call of Renin!




Authors: Kellie Calderon, MD and Kenar Jhaveri, MD




















Using creative writing to teach Nephrology: http://www.ncbi.nlm.nih.gov/pubmed/21671849

Saturday, December 3, 2011

QUIZ:What causes Green urine? Answers


QUIZ : What causes Green urine?

Blue or green urine may be caused by:
1.    Dyes such as methylene blue, indigo carmine
2.    Bladder irritation decreasing meds:- pyridium(usually orange but also green), uroblue, trac tabs
3.    The infamous propofol, has also been reported to cause green coloration of the urine
4.    Amitriptyline, indomethacin, resorcinol, triamterine, cimetidine, Phenergan, rifampin
5.    B vitamins especially.
6.    An inherited form of high calcium (called "familial hypercalcemia") can result in blue urine, which has lent this disease the nickname "blue diaper syndrome"
7.    Indicanuria,
8.    Pseudomonas  infection
9.    Pneumaturia: can be caused by bile when there is a fistula between the urinary tract the intestines.
Some good references:
Slawson M. Thirty-three drugs that discolor urine and/or stools. RN. 1980 8. 9.
Blakey SA, Hixson-Wallace JA. Clinical significance of rare and benign side effects: propofol and green urine. Pharmacotherapy. 2000 Sep;20(9):1120-2.

Friday, December 2, 2011

CONSULT ROUNDS: Renal Infarcts


Renal Infarcts: Differential Diagnosis

1.      Embolic( A fib, endocarditis)
2.      Embolic
3.      Embolic
4.      Sepsis, hypotension
5.      Trauma
6.      Auto immune diseases ( PAN, antiphospholipid syndrome, Takayasu)
7.      Amyloidosis
8.      Fibromuscular Dysplasia
9.      Connective Tissue Disorders( Marfans, Ehlers Danlos Syndrome)

Wednesday, November 30, 2011

eAJKD: Cardiac biomarkers in CKD

Troponin T and N-terminal pro brain natriuretic peptide are potential markers of cardiac injury that are often measured in the inpatient setting. Can these markers be used in the outpatient setting to predict risk of developing ESRD in patients with diabetic kidney disease? Check it out in an exclusive interview on eAJKD. 
Ref:

http://ajkdblog.org/2011/11/29/cardiac-biomarkers-in-ckd-and-esrd-what-to-make-of-them/

Tuesday, November 29, 2011

CONSULT ROUNDS: Sjogren's Syndrome and Glomerular Diseases?

What is the association of Sjogren's Syndrome(SS) with any glomerular disease..


Well, besides few cases reports scattered in the literature, there are two large case series that highlight this nicely.


In 2001, Bossini et al described the clinical and morphological features of kidney involvement in SS.  Sixteen patients (27%) had laboratory evidence of tubular and/or glomerular dysfunction.  Renal biopsies from nine patients showed tubulointerstitial nephritis in six and glomerular disease in three. The three diagnosis were MPGN, mesangiproliferative and membranous. Patients with renal involvement had a significantly shorter disease duration compared with patients without renal abnormalities.
A more recent study in CJASN looked at more number of patients and at least 24 biopsies of SS patients showing mostly tubular interstitial disease but the glomerular disease was a mixed bag: FSGS, mild mesangial sclerosis, MPGN, minimal change disease( 1 case), membranous, were the ones reported. The paper is free access ( look below). Four patients (17%) were diagnosed with lymphoma during their follow-up. Below is a pie chart from the paper that had 24 cases and the distribution on the biopsy. Overall, not a very common thing to see in SS, but glomerular disease is likely.



From CJASN 2009


Monday, November 28, 2011

Access educational Tool


The AV fistula first website has developed some really good teaching resources for fistula and graft management and access care.  The videos that are very educational and helpful are the link below:
have a look:
http://www.fistulafirst.org/HealthcareProfessionals/FFBIChangeConcepts/ChangeConcept9.aspx

Saturday, November 26, 2011

Friday, November 25, 2011

Complement Component Quiz Answers


Question:



Match the following complement components with their function in the complement cascade

C5a
Membrane attack complex

DAF
Initiates the alternative complement pathway

C5b-9
Initiates the classical complement pathway

Factor H
Byproduct of the classical complement pathway

C5
Potent inflammatory mediator

C1q
Membrane bound complement regulatory protein 

C4d
Blockade of this complement component is the treatment for PNF

C3b
Deficiency results in atypical HUS

Answers:
C5a – Potent inflammatory mediator
DAF (decay accelerating factor) – membrane bound complement regulatory protein
C5b-9 – membrane attack complex (MAC)
Factor H – Deficiency results in atypical HUS (hemolytic uremic syndrome)
C5 - Blockade of this complement component is the treatment for PNF (paroxysmal nocturnal hematuria)
C1q – Initiates the classical complement pathway
C4d - Byproduct of the classical complement pathway
C3b - Initiates the alternative complement pathway

Post by
Vinay Nair 

Thursday, November 24, 2011

eAJKD: Pemetrexed Nephrotoxicity

Pemetrexed is an antifolate agent approved for the treatment of advanced lung cancer.A recent publication in American Journal of Kidney Diseases discusses potential nephrotoxicity of this drug. Kidney biopsy specimens showed tubulointerstitial injury with tubular simplification, shrinkage, loss of brush border, and tubular atrophy in a more advanced case.  eAJKD did an exclusive video blog with the authors Dr. Ilya Glezerman( Renal service, Memorial Sloan Kettering Cancer Center, NY) and Dr.Surya Seshan( Chief of Renal Pathology, Professor of Pathology, Weill Cornell Medical Center, NY)
Check it out
http://ajkdblog.org/2011/11/23/pemetrexed-nephrotoxicity/

Wednesday, November 23, 2011

Clinical case 47: Answers and Summary


WHICH OF THE FOLLOWING ELECTROLYTE ABNORMALITIES HAS BEEN ASSOCIATED WITH PARAPROTEINS?

   
Paraproteins may cause abnormal laboratory findings in 3 ways: 1) through the disease 
process itself; 2) by interacting with the target of an assay; 3) by creating spurious results due to their 
interference with the assay method. Paraproteins have been shown to cause interference with the 
assays of multiple laboratory tests, including blood counts, sodium, calcium, phosphorus, lipids, 
coagulation profiles, iron studies, blood urea nitrogen, creatinine, bilirubin, c-reactive protein, 
glucose, uric acid, lactate dehydrogenase, alkaline phosphatase. 


All the above listed findings have been described with paraproteins except the hypermagnesemia.  Obviously, the most commonly discussed on board questions is pseudohyponatremia but that we don't see that often. Given the burden of light chains, usually one now encounters the others.  See the references below for full primary data on these.  IgM, given its size, is usually the big culprit but igG and igA have also been described.  Paraproteins exert biphasic interference on serum phosphate levels, usually resulting in factitious hyperphosphatemia but occasionally in hypophosphatemia. Pseudohyperphosphatemia may be seen in patients with IgM, IgA, or IgG paraproteins. In addition, hypophosphatemic patients showing falsely “high” levels of phosphate may be labeled as pseudonormophosphatemic, and this may be just as clinically relevant as pseudohyperphosphatemia. Deproteination can usually correct this artifact.

Previous SectionNext Section
Pseudohyponatremia, pseudohypochloridemia, and reduced anion gap have also been described when using the indirect ion-specific electrode method.  Pseudohypercalcemia due to an IgM paraprotein has been reported in two cases in the literature.
Previous Section
Next Section


Ref:

http://www.ncbi.nlm.nih.gov/pubmed/20118906
http://www.ncbi.nlm.nih.gov/pubmed/18251580
http://www.ncbi.nlm.nih.gov/pubmed/21849226
http://www.ncbi.nlm.nih.gov/pubmed/19141380



eAJKD: Sulodexide in Diabetic Nephropathy: Is There a Role for This Novel Agent?

Check out the latest offering from eAJKD:
http://ajkdblog.org/2011/11/22/sulodexide-in-diabetic-nephropathy-is-there-a-role-for-this-novel-agent

Tuesday, November 22, 2011

Journal Club: Tolvaptan in ADPKD


Tolvaptan in Autosomal Dominant Polycystic Kidney Disease: Three Years Experience
CJASN Oct 2011
ADPKD is an inherited disorder resulting in renal cysts, urinary concentrating defects, hypertension, and ESRD. The clinical manifestations include back pain from cyst hemorrage, stones, and infection. Extrarenal manifestations include cerebral aneurysms and can be life threatening .
A recent study evaluated the potential use of Tolvaptan, a V2 receptor antagonist, for the purpose of delaying progression of this disease.  The concept behind its use was based on animal studies that showed suppression of vasopressin by forced hydration or V2 receptor blockade reduced cyst burden and protected renal function.
                Total Kidney Volume (TKV) is a measurable end point that reflects outcomes in ADPKD including pain, hypertension, renal insufficiency, and ESRD. The current study explored if the use of V2 receptor antagonism in ADPKD pts could slow the rate of TKV expansion and decline in GFR.  There was one treatment arm in which all patients carried the diagnosis of ADPKD and were treated with tolvaptan. These patients were randomized in a 1:2 ratio to historical controls obtained from the MDRD and CRISP trials. These controls had ADPKD and were managed with blood pressure control. The treatment and control arms were followed for three years and endpoints included rate of TKV growth and rate of decline in eGFR. Results showed statistically significant differences in TKV growth with the treatment arm showing slower progression. Additionally rate of decline in eGFR was slower in the treatment arm in comparison to controls. However the absolute mean differences in eGFR decline were not significantly different suggesting that over a longer period of time, perhaps that effect would be realized.
                Over the course of the study all treated patients experienced mild side effects consistent with the mechanism of action of tolvaptan. Twelve patients in the treatment arm withdrew and six of them withdrew secondary to side effects which included renal impairment, acute renal failure, benign pituitary tumor, TIA, eye swelling, and subarachnoid hemorrhage with a fatal outcome.
                This study seems to be a proof of concept that perhaps V2 receptor antagonism may be an avenue for therapy in this disease population. A more rigorous and better designed study is underway with over 1400 ADPKD patients concurrently randomized into a treatment and control arm with long term follow up.    

Post by Dr. Ezra Israel
Nephrology Fellow, Hofstra NSLIJ

Monday, November 21, 2011

Frequent Hemodialysis Trials: ASN 2011 update


The effects of frequent nocturnal home hemodialysis: the Frequent Hemodialysis Network Nocturnal Trial. This trial was launched because it was noticed from small studies that more frequent nocturnal dialysis may help improve outcomes in dialysis patients. A multicenter study headed by Dr. Rocco et al where 87  patients randomized to three times per week conventional hemodialysis or to nocturnal hemodialysis six times per week, all with single-use high-flux dialyzers. The 45 patients in the frequent nocturnal arm had a 1.82-fold higher mean weekly stdKt/V(urea).  NO significant effect of nocturnal hemodialysis for either of the two coprimary outcomes (death or left ventricular mass (measured by MRI) was found. Secondary outcomes included cognitive performance, self-reported depression, laboratory markers of nutrition, mineral metabolism and anemia, blood pressure and rates of hospitalization, and vascular access interventions. Patients in the nocturnal arm had improved control of hyperphosphatemia and hypertension, but no significant benefit among the other main secondary outcomes. There was a trend for increased vascular access events in the nocturnal arm. Sample size was small which could have been a reason of these negative result.

A sister of this trial was conducted: this time it was morning dialysis ( not nocturnal) but daily vs conventional hd on 245 patients. Compared two groups 6times weekly vs 3times weekly. This was an in-center trial. Average delivered 5.2 days vs 2.9 days in the two arms respectively. The time was shorter in the daily so the total hours were only 20% more in the daily arm overall. However patients in the daily arm still did better compared with the conventional group. Both primary outcomes and secondary outcomes were the same as for the nocturnal trial but they were significantly better for the latter(during the day). The reason for the discordance is being investigated.( of note the nightly dialysis received much more time on dialysis than either daily frequent or conventional)
Final note :
"FHN participants were younger and the racial composition for each study was different from the racial composition of the aggregate US dialysis population. Catheters for vascular access were more common in FHN Nocturnal Trial participants."

Post by
Dr. Azzour Hazzan
Hofstra NSLIJ Nephrology

Saturday, November 19, 2011

TOPIC DISCUSSION: SIADH diagnosis

We always struggle to diagnosis this entity in few cases of hyponatremia. Measurement of AVP can prove challenging due to problems of ordering and time it takes to come back. Measurement of copeptin( a 39 amino acid glycopeptide) which is derived from the same precursor peptide as AVP and released in equimolor amounts as AVP might be measurable.  Is that been studied? You bet!

In this one prospective observational study, 106 consecutive hyponatremic patients were classified based on their history, clinical evaluation, and laboratory tests. In patients and 32 healthy control subjects, plasma copeptin concentration and standard biochemical parameters were tested for their utility of diagnosing SIADH.



Plasma copeptin levels were significantly higher in patients with hypo- and hypervolemic hyponatremia compared with SIAD (P < 0.005, respectively) and primary polydipsia (P < 0.001). The copeptin to U-Na ratio differentiated accurately between volume-depleted and normovolemic disorders (area under the receiver-operating characteristic curve 0.88, 95% confidence interval 0.81-0.95; P < 0.001), resulting in a sensitivity and specificity of 85 and 87% if a cutoff value of 30 pmol/mmol was used.  This ratio differentiated between volume-depleted and normovolemic disorders resulting in good specificity and sensitivity in this one study. It did better than copeptin alone as well. Another small swiss study felt that it added very little to the sodium balance information. I guess not much out in the literature. Lets see where this story unfolds and how this becomes real in clinical use.










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