Reverse epidemiology in ESRD: Digoxin

Conventional risk factors of cardiovascular disease and mortality in the general population such as obesity, hypercholesterolemia, and hypertension appear to be paradoxically protective and are associated with increased survival among dialysis patients (Kalantar-Zadeh et al, Kidney Int. 2003). Also, it was reported recently that there is paradoxical increase in the risk of stroke among dialysis patients receiving warfarin therapy for atrial fibrillation (Chan et al, JASN Oct 2009). Now there is an addition to the list of reverse epidemiology in ESRD. In the current issue of JASN, Chan and colleagues report increased mortality with digoxin use in ESRD patients (Chan et al, JASN, June 2010). In this study, authors compared 4549 dialysis patients on digoxin with 116,315 dialysis patients who were not on digoxin. This is a retrospective study. However, authors did propensity score analysis to match patients with similar comorbidities in both groups. It was found that digoxin use was associated with 28% increased risk of death. This was most pronounced in patients with lower predialysis serum potassium of less than 4.3 mEq/L. It is likely that hypokalemia, which frequently occurs immediately post dialysis in our ESRD patients, enhances the toxicity of digoxin. In conclusion, we all apply same principles of medicine learnt from general population to our dialysis patients. It seems we have to re-examine everything in our ESRD population.

Survey on innovative teaching tools

Dr. Jhaveri of Nephron Power and Online Transplant Center is conducting a survey on innovative teaching tools. Please see the link - http://www.surveymonkey.com/s/vrnjjx3

Billing and Coding Seminars

Renal Physicians Association (RPA) has excellent series of presentations on billing, coding and documentation. These are very helpful for all practicing nephrologists especially for those going to practice in the community.

SNP of Caveolin-1 gene is associated with renal allograft function

Caveolin-1 is the primary structural component of caveolae which are cell membrane invaginations on endothelial cells, adipocytes, fibroblasts and pneumocytes etc. It is anti-fibrotic and is shown to be reduced in conditions such as scleroderma and idiopathic pulmonary fibrosis. In a recently published JAMA paper (Moore et al, JAMA, April 2010), it was shown that donor single nucleotide polymorphism in gene encoding for Caveolin-1 was associated with long term renal transplant outcomes. Authors investigated this SNP in 785 white kidney transplant donors and their respective recipients with median follow up of 81 months post transplantation. It was found that donor genotype AA, compared to AC and CC genotypes, was associated with increased risk of allograft failure (Hazard ratio of about 2). The findings were confirmed in another independent cohort within UK. This is an interesting study that may not alter our clinical practice at present but will atleaset open new avenues in renal fibosis research if the findings are replicable in other studies.

Renal outcomes after preeclampsia

Recently, I had to look up this topic after one of my patients posed this question. In the largest study that I could find on this topic (Vikse et al, NEJM, Aug 2008), outcomes data on 570,433 women from national registries of Norway were reviewed. The relative risk of ESRD among women with history of preeclampsia was 3.2 to 6.7 compared to women without history of preeclampsia, with risk being higher in women who had preeclampsia in more than one pregnancy or if preeclampsia resulted in low birth weight or preterm infant. This translates into an absolute risk of less than 1% after a mean time of 17 years after first pregnancy. The main limitation of this study is that it is based on administrative database and is not a prospective study. There is a systematic review and metanalysis on this topic in the current issue of AJKD (McDonald et al, AJKD, June 2010). In this review, data from 7 cohort studies involving 273 patients with preeclampsia and 333 patients with uncomplicated pregnancies were analyzed. It was found that, after a mean of 7.1 years postpartum, 31% of women with history of preeclampsia had microalbuminuria compared to 7% of controls.

MICA antibodies

Please refer to the Online Transplant Center for my post on MICA antibodies.

ISBP Annual Conference 2010

Dr. Gura from UCLA forwarded a brochure regarding upcoming annual meeting of International Society of Blood Purification (ISBP) on September 24-26, 2010 in Marina del Rey, California. I have not attended this conference before but heard that it is a good one. If you are interested, please refer to brochure for details.

Vitamin D attenuates renal fibrosis

In addition to pleiotropic beneficial effects of vitamin D on musculoskeletal system, immune system, cancer prevention, mortality, cardiovascular and mental health, there is increasing evidence in the recent years for its role in attenuating renal fibrosis in various animal models. An article by Zhang and colleagues in the current issue of JASN (Zhang et al JASN, June 2010) is the latest in the series. In this study, Vitamin D Receptor (mediator of action of active vitamin D) knock out mice developed more severe renal damage, compared to wild type mice, following unilateral ureteral obstruction. There was significant induction of fibrogenic and inflammatory mediators like fibronectin, collagen I, TGF-b, MCP-1 etc. Administration of Losartan eliminated the difference in fibrosis between VDR knockout and wild type mice. There are also handful of human studies that showed antiproteinuric effect of active vitamin D. The trial with largest number of patients was published in 2005 (Agarwal et al, Kidney Int. 2005). In this study, 220 stage 3 and 4 CKD patients with secondary hyperparathyroidism were randomized to oral paricalcitrol or placebo. There was reduction of proteinuria independent of use of RAAS blockers. Do these data support a role for active vitamin D in attenuating progression of CKD? May be.

Urine NGAL in AKI: Journal Club

Urine NGAL Moderately predicts Acute Kidney Injury in critically ill adults

Journal Club Presentation

View more presentations from Anand Reddy.

Intragraft gene expression can predict graft loss

In an article just published in 'Journal of Clinical Investigation' (Einecke et al, JCI: June 2010), intragraft molecular signature was found to predict late graft loss. Authors perfomed microarrays to analyze gene expression in 105 'for-cause' biopsies taken 1 to 31 years after kidney transplantation. Based on this, authors derived a molecular risk score (comprising of 30 genes related to tissue injury, epithelial dedifferentiation, matrix remodelling and TGF-beta) that was associated with future graft failure. This molecular risk score was superior to classical features associated with progression to renal failure (histological findings, proteinuria and low eGFR at the time of biospy) in predicting incipient graft loss. The main limitation of this study is that it was not a prospective study. However, the important point here is that intragraft gene expression studies will likely help us in prognosticating, identifying pathogenic mechanisms, initiate specific therapy if available (personalized therapy rather than one-size-fits-all approach) and develop potential new therapies.