Long-term evolution, secular trends, and risk factors of renal dysfunction following cardiac transplantation.

Recent reports suggest that individuals who underwent heart transplantation in the last decade have improved post-transplant kidney function. The objectives of this retrospective study were to describe the incidence and to identify fixed and time-dependent predictors of renal dysfunction in cardiac recipients transplanted over a 25-year period (1983-2008). To illustrate temporal trends, patients (n = 306) were divided into five groups based on year of transplantation. The primary endpoint was the estimated glomerular filtration rate (eGFR) at year 1. Secondary endpoints were time to moderate (eGFR <60 ml/min/1.73 m(2) ) and severe renal dysfunction (eGFR <30 ml/min/1.73 m(2) ). Risk factor analyses relied on multivariable regression models. Kidney function was mildly impaired before transplant (median eGFR=61.0 ml/min/1.73 m(2) ), improved at discharge (eGFR=72.3 ml/min/1.73 m(2) ; P < 0.001), decreased considerably in the first year (eGFR = 54.7 ml/min/1.73 m(2) ; P < 0.001), and deteriorated less rapidly thereafter. At year 1, 2004-2008 recipients exhibited a higher eGFR compared with all other patients (P < 0.001). Factors independently associated with eGFR at year 1 and with moderate and severe renal dysfunction included age, gender, pretransplant eGFR, blood pressure, glycemia, and use of prednisone (P < 0.05). In summary, kidney function worsens constantly up to two decades after cardiac transplantation, with the greatest decline occurring in the first year. Corticosteroid minimization and treatment of modifiable risk factors (hypertension, diabetes) may minimize renal deterioration.

PRKCB is associated with calcineurin inhibitor-induced renal dysfunction in heart transplant recipients.

OBJECTIVES: Single nucleotide polymorphisms (SNPs) in the transforming growth factor-ß1 gene (TGFB1) have been inconsistently associated with calcineurin inhibitor (CNI)-induced renal dysfunction following cardiac transplantation. The impact of genetic variants related to the renin-angiotensin-aldosterone system (RAAS) and natriuretic peptides, which are implicated in CNI nephrotoxicity, is unknown. The primary objective of this study was to validate the association between two common variants in TGFB1 (rs1800470, rs1800471) and postcardiac transplant renal function. The secondary objective was to investigate the effect of candidate genes related to the RAAS, natriuretic peptides, and other elements involved in the intracellular signaling of these pathways. METHODS: We conducted a retrospective cohort study of 158 heart transplant recipients treated with CNIs, and evaluated the association between select SNPs and the estimated glomerular filtration rate as calculated by the Modification of Diet in Renal Disease simplified formula. A total of 273 SNPs distributed in 44 genes were tested. RESULTS: No association was observed between TGFB1 variants and renal function. One polymorphism in the protein kinase C-ß gene (PRKCB; rs11074606), which is implicated in the RAAS intracellular signaling, was significantly associated with post-transplant estimated glomerular filtration rate after adjusting for possible confounders (P=0.00049). This marker is in linkage disequilibrium with two variants located in putative regulatory regions of the gene (rs2283541, rs1013316). CONCLUSION: Our results suggest that PRKCB may be a potential predictor of CNI-induced nephrotoxicity in heart transplant recipients, and could therefore be a promising candidate to identify patients who are most susceptible to this adverse drug reaction.

Oral ferrous sulfate does not increase preoperative hemoglobin in patients scheduled for hip or knee arthroplasty.

BACKGROUND: Low hemoglobin (Hb) concentrations before lower limb joint replacement are associated with the need for blood transfusions and increased mortality. To optimize preoperative Hb, blood conservation protocols often recommend oral iron supplements, even in nonanemic patients. OBJECTIVE: To investigate the impact of ferrous sulfate on the change in Hb prior to hip or knee arthroplasty and evaluate the effect of oral iron on hematocrit, mean corpuscular volume (MCV), ferritin, and transferrin saturation, as well as its tolerability and treatment adherence. METHODS: We conducted a prospective, observational cohort study of adults with Hb concentrations between 10 and 15 g/dL who received iron supplementation prior to hip or knee arthroplasty. Systemic inflammatory diseases, vitamin B(12) or folate deficiency, and current use of iron supplements, intravenous iron, or erythropoietin were exclusion criteria. All participants were prescribed ferrous sulfate 300 mg 3 times daily for a minimum of 3 weeks. Complete blood cell counts and iron studies were performed before therapy and surgery. RESULTS: Eighty-seven patients with a mean (SD) Hb of 13.47 (0.84) g/dL were included in the study. Preoperative Hb decreased after treatment with iron (-0.14 [0.53] g/dL, p = 0.015). Hematocrit also declined (-0.6% [1.8%], p = 0.002), whereas ferritin increased (25.8 [38.6] ng/mL, p < 0.001). No significant change was seen in MCV and transferrin saturation. The most common adverse effects were constipation (33.3%), heartburn (13.8%), and abdominal pain (12.6%). The adherence rate was 67.1%. CONCLUSIONS: Oral ferrous sulfate supplementation is not an effective method to increase preoperative Hb in patients scheduled for hip or knee arthroplasty, and its use is associated with adverse effects.

Temporal Changes on the Risks and Complications of Posttransplantion Diabetes Mellitus Following Cardiac Transplantation.

BACKGROUND: Recent changes in the demographic of cardiac donors and recipients have modulated the rate and risk, associated with posttransplant diabetes mellitus (PTDM). We investigated the secular trends of the risk of PTDM at 1 year and 3 years after transplantation over 30 years and explored its effect on major outcomes. METHODS: Three hundred and three nondiabetic patients were followed for a minimum of 36 months, after a first cardiac transplantation performed between 1983 and 2011. Based on the year of their transplantation, the patients were divided into 3 eras: (1983-1992 [era 1], 1993-2002 [era 2], and 2003-2011 [era 3]). RESULTS: In eras 1, 2, and 3, the proportions of patients with PTDM at 1 versus 3 years were 23% versus 39%, 21% versus 26%, and 33% versus 38%, respectively. Independent risk factors predicting PTDM at one year were recipient's age, duration of cold ischemic time, treatment with furosemide, and tacrolimus. There was a trend for overall survival being worse for patients with PTDM in comparison to patients without PTDM (p = 0.08). Patients with PTDM exhibited a significantly higher rate of renal failure over a median follow-up of 10 years (p = 0.03). CONCLUSION: The development of PTDM following cardiac transplantation approaches 40% at 3 years and has not significantly changed over thirty years. The presence of PTDM is weakly associated with an increased mortality and is significantly associated with a worsening in renal function long-term following cardiac transplantation.

Risk Factors for Chronic Renal Insufficiency Following Cardiac Transplantation.

Although previous publications have discussed kidney disease in nonrenal solid-organ transplantation, none has reviewed thoroughly the potential predictors of long-term renal impairment in cardiac recipients. Thus, the purpose of this review article is to summarize the current state of knowledge on risk factors of chronic renal insufficiency in heart transplant patients. An English language Medline literature search (1946-April 2014) was conducted using the search terms renal insufficiency, kidney failure, kidney diseases, nephrotoxi$ ($ for truncation), creatinine, glomerular filtration rate, heart transplantation and organ transplantation. Additional references were identified from a review of literature citations. A total of 74 articles discussing key risk factors were included in the manuscript.         The existing literature reveals that several recipient characteristics (age, female sex, pretransplant/early post-transplant kidney impairment, diabetes, and hypertension) increase the risk of renal insufficiency after transplantation. Current data also indicate that, while cyclosporine and tacrolimus are most likely major determinants of post-transplant kidney failure, the effects of calcineurin inhibitor doses and concentrations remain unclear. A small number of studies suggest that tacrolimus could possibly induce less nephrotoxicity than cyclosporine, but meta-analyses of randomized controlled trials show the opposite with comparable incidences of dialysis after cardiac transplantation. Finally, the role of genetic variations has only been explored to a limited extent in heart transplant patients. This growing body of evidence should ultimately lead to a better risk prediction regarding chronic renal insufficiency following cardiac transplantation and a more personalized tailoring of immunosuppressive regimens.