Prospective Assessment of Hepcidin in Relation to Delayed or Immediate Graft Function in Patients Undergoing Kidney Transplantation.

BACKGROUND: Hepcidin is a peptide hormone that regulates iron homeostasis. Hepcidin may represent an early, predictive biomarker of acute kidney injury, another model of ischemia-reperfusion injury. Urinary hepcidin-25 has been shown to be elevated in patients who do not develop acute kidney injury. Creatinine is an unreliable indicator during acute changes in kidney; therefore, the aim of the study was to assess whether hepcidin could predict renal outcome in 31 consecutive patients undergoing kidney allograft transplantation. Serum hepcidin was evaluated before and after 1, 3, 6, and 10 days after kidney transplantation, using commercially available kits. Serum creatinine was assessed at the same time. METHODS: We found a significant decrease in serum hepcidin, as early as after 1 day after kidney transplantation. Before transplantation, serum hepcidin was related to creatinine. In patients with delayed graft function, there was no decrease in serum hepcidin. RESULTS: Our findings may have important implications for the clinical treatment of patients undergoing kidney transplantation. The "window of opportunity" is narrow in delayed graft function to distinguish between acute rejection and calcineurin inhibitors nephrotoxicity, and time is limited to introduce proper treatment after initiating insult. CONCLUSIONS: Hepcidin must be investigated as a potential early marker for delayed graft function, especially in the upcoming setting of early dialysis treatment or anti-rejection therapy and might contribute to early patient risk stratification.

Blood pressure control according to the prevalence of diabetes in renal transplant recipients.

Hypertension is one of the most frequent complications of renal transplantation. About 70% to 90% of this population display either high blood pressure (BP) or require antihypertensive therapy. Diabetes mellitus is also a common finding among kidney transplant recipients. The aim of the study was to assess the BP control among kidney transplant recipients according to the prevalence of diabetes. This retrospective analysis included 172 renal transplant recipients of overall mean age 50 years and 51% males. Hypertension was present in 79% of patients. About one-third of the studied population showed abnormal blood pressures based on office measurements. The cohort was divided into two groups according to the presence of diabetes: group 1, diabetic patients (n = 14) versus group 2, nondiabetics (n = 158). Nondiabetic patients were significantly older than diabetic ones (61.5 versus 49 years; P < .05) and their time after renal transplantation was longer (98.83 versus 67.33 months, P < .05). There was no difference in regard to hypertension prevalence, mean BP value, percentage of abnormal (≥ 140/90 mm Hg) BP values or glomerular filtration rate. Diabetic patients were prescribed less steroid. The main hypotensive drug used in whole cohort and in no-diabetic patients was a beta-blocker (n = 64, 37%; n = 4, 28%), patients with diabetes used beta-blockers and angiotensin-converting enzyme inhibitors at the same frequency (n = 60, 37%). The main causative factor for hypertension appeared to be the calcineurin inhibitor. More aggressive antihypertensive treatment using combined drugs, including RAS blockers, might provide adequate BP control among renal transplant subjects with high cardiovascular risk.

Hemojuvelin and iron metabolism in kidney and heart allograft recipients.

INTRODUCTION: Hemojuvelin plays an essential role in the regulation of hepcidin expression, specifically in the iron-sensing pathway. Dietary iron sensing and inflammatory pathways converge in the regulation of the key regulator hepcidin. Hepcidin is a small defensin-like peptide whose production by hepatocytes is modulated in response to anemia, hypoxia, or inflammation. We studied correlations of hemojuvelin with markers of iron status and of inflammation among 61 prevalent kidney allograft recipients and 136 prevalent heart transplant recipients. METHODS: Complete blood count, urea, serum lipids, fasting glucose, and creatinine were measured using standard laboratory methods in the central laboratory of the hospital. Hepcidin, soluble transferin receptor (sTFR), interleukin-6 (IL-6) and hemojuvelin were assayed by enzyme immunosorbent assay using commercially available kits. RESULTS: Among heart transplant recipients hemojuvelin correlated strongly with kidney function, transferrin saturation and white blood cell count; moderately with red blood cell count, hepcidin, IL-6, high-sensitivity C-reactive protein (hsCRP) and weakly with sTfR. Multiple regression analysis revealed the predictors of hemojuvelin to be kidney function and TSAT, explaining 79% of the variations among hemojuvelin values in heart transplant recipients. Among kidney transplant recipients hemojuvelin correlated with kidney function, TSAT, hepcidin and hsCRP, and tended to correlate with IL-6. Predictors of hemojuvelin on multiple regression analysis were TSAT and creatinine. CONCLUSIONS: Elevated hemojuvelin as well as hepcidin levels in kidney or heart transplant recipients may be due to the impaired kidney function and disturbed iron status frequently encountered among this population.

Treatment of anemia with erythropoietin-stimulating agents in kidney transplant recipients and chronic kidney disease-another drawback of immunosuppression?

Anemia is more prevalent in allograft recipients compared with glomerular filtration rate (GFR) matched patients with chronic kidney diseases. There is a paucity of data concerning the correction of anemia in the posttransplant period with erythropoietin-stimulating agents (ESA). The aim of this study was to compare the iron status, kidney function, inflammatory state, use of drugs affecting erythropoiesis (immunosuppressants ACEi/ARB) and correction of anemia using ESA in a chronic kidney disease (CKD) population versus kidney transplant recipients. We included 67 patients treated with ESA including 17 after kidney transplantation. CKD Patients with native kidneys were significantly older than allograft recipients (mean age 69 versus 51 years; P < .001, and despite similar serum creatinine and iron parameters showed an estimated lower GFR (19 mL/min versus 23 mL/min; P < .05). Median time of ESA therapy was similar among patients with native kidney CKD versus kidney recipients, but they achieved a significantly higher hemoglobin (11.04 versus 10.36 g/dL; P < .05). There was no difference between patients administered or not a mammalian target of rapamycin antagonist. None of the patients with native kidney CKD received immunosuppressive therapy, but they were prescribed ACEi more often than kidney recipients. The higher degree of anemia in kidney allograft recipient is the most probably attributed to the use of immunosuppressive drugs, despite their better kidney function and comparable iron status. This study suggested that higher doses of ESA should be employed to anemia in kidney transplant recipients.

Prevalence of iron deficiency in heart and kidney allograft recipients.

BACKGROUND: Functional iron deficiency is characterized by the presence of adequate iron stores as defined by conventional criteria, but insufficient iron mobilization to adequately support erythropoiesis. The aim of this study was to assess the prevalence of functional iron deficiency in heart and kidney transplant recipients based on data from recent medical records. METHODS: Using standard laboratory methods obtained during routine checkups, we assessed iron status by determinations of serum iron, total iron-binding capacity, ferritin and total saturation of transferrin (TSAT), as well as complete blood count and creatinine. RESULTS: Iron parameters were available for 62% of heart transplant recipients, but only for 26% of kidney transplant recipients. Absolute iron deficiency was observed in 35% of the heart and 8% of the kidney transplant recipients (P<.001). Functional iron deficiency was present in 4% of the heart and 6% of the kidney transplant recipients. Functional iron deficiency was associated with significantly higher serum ferritin and lower TSAT. In addition, although their hemoglobin values did not differ significantly, heart transplant recipients with absolute iron deficiency showed lower erythrocyte blood counts, were younger, and had a shorter time after transplantation. CONCLUSIONS: Iron parameters are assessed infrequently, particularly among kidney transplant recipients. Iron deficiency was present in a considerable group of heart transplant recipients. This population should be carefully screened for possible reversible causes of iron deficiency to slow or to minimize anemia development.

Iron metabolism in kidney allograft recipients: still a mystery?

INTRODUCTION: All living organisms have evolved sophisticated mechanisms to maintain appropriate iron levels in their cells and within their body. Recently our understanding of iron metabolism has dramatically increased. Overt labile plasma iron (LPI) represents a component of non-transferrin-bound iron (NTBI) that is both redox active and chelatable, capable of permeating into organs and inducing tissue iron overload. LPI measures the iron-specific capacity of a given sample to produce reactive oxygen species. We studied NTBI correlations with markers of iron status and inflammation in prevalent kidney allograft recipients. METHODS: Complete blood count, urea, creatinine, serum lipids, fasting glucose, ferritin, serum iron, and total iron-binding capacity (TIBC) were studied by standard laboratory method in the hospital central laboratory. NTBI was assessed by FeROS eLPI kit by Aferrix Ltd (Tel Aviv, Israel). A test result of 0.6 U of LPI or more indicated a potential for iron-mediated production of reactive oxygen species in the sample. RESULTS: In kidney transplant recipients NTBI was correlated with TIBC (r=.46, P<.001) and ferritin (r=.31, P<.05), with tendencies to correlate with C-reactive protein. Patients with LPI units≥0.6 showed higher serum iron (P<.05), TIBC (P<.05), ferritin (P<.001) and mean corpuscular volume. High ferritin values together with elevated NTBI content were observed among patients undergoing multiple transfusions before and/or after transplantation. CONCLUSIONS: Elevated NTBI as well as ferritin levels in kidney transplant patients may be due to disturbed iron metabolism, since the human body has no possibility to remove an iron excess. NTBI could be responsible for excessive synthesis of reactive oxygen species. Therefore, it may be linked to complications such as atherosclerosis, which is frequently encountered among this population.