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.

The kidney in sickle cell disease

Today, one of my colleagues presented an interesting case of sickle cell disease with microscopic hematuria, nephrotic range proteinuria and elevated serum creatinine. The renal manifestations of sickle cell disease are myriad. There is a nice review article published last year on this topic (Scheinman, Nature Reviews Nephrology 2009). Common renal manifestations of sickle cell disease include:
- Painless microscopic or gross hematuria as a result of RBC sickling in vasa recta in relatively hypoxic renal medulla. More severe ischemia due to vaso-occlusive phenomena in vasa recta can lead to renal papillary necrosis.
- Tubular function defects like hypoesthenuria/impaired concentrating ability (because of involvement of juxtamedually nephron collecting ducts), incomplete distal RTA with hyperkalemia (because of voltage defect), supranormal proximal tubular function in initial stages causing increased sodium & phosphrous reabsorption and increased creatinine/uric acid secretion (?? because of prostaglandins)
- Sickle cell glomerulopathy with nephrosis more common than nephritis. Most common pathological diagnosis is FSGS predominantly involving juxta medually nephrons that are perfused by vasa recta. Medullary fibrosis is prominent.
Other key points:
- Lower incidence of hypertension
- More prone to acute renal failure (In addition to usual causes, keep in mind the renal vein thrombosis and urinary tract obstruction from blood clots)
- Renal medullary carcinoma: rare but exclusive to sickle cell patients
- For ESRD, transplant outcomes are not as good as for other ESRD patients