Characteristics and management of thrombotic microangiopathy in kidney transplantation.

Thrombotic microangiopathy is not a rare complication of kidney transplantation and is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury with extensive thrombosis of the arterioles and capillaries. Various factors can cause thrombotic microangiopathy after kidney transplantation, including surgery, warm and cold ischemia-reperfusion injury, exposure to immunosuppressants, infection, and rejection. Many recent studies on atypical hemolytic uremic syndrome have described genetic abnormalities related to excessive activation of the alternative complement pathway. The affected patients' genetic backgrounds revealed significant genetic heterogeneity in several genes involved in complement regulation, including the complement factor H, complement factor H-related proteins, complement factor I, complement factor B, complement component 3, and CD46 genes in the alternative complement pathway. Although clinical studies have provided a better understanding of the pathogenesis of diseases, the diverse triggers present in the transplant environment can lead to thrombotic microangiopathy, along with various genetic predispositions, and it is difficult to identify the genetic background in various clinical conditions. Given the poor prognosis of posttransplant thrombotic microangiopathy, further research is necessary to improve the diagnosis and treatment protocols based on risk factors or genetic predisposition, and to develop new therapeutic agents.

Association between Consumption of Dietary Supplements and Chronic Kidney Disease Prevalence: Results of the Korean Nationwide Population-Based Survey.

Despite the enormous global market of dietary supplements, the impact of dietary supplements on kidney disease is still unclear. Based on the National Health and Nutrition Examination Survey from 2015 to 2017, this study evaluated the association between dietary supplement and chronic kidney disease (CKD) in 13,271 Korean adults. Among the dietary supplements, vitamin and mineral intake was the highest at 61.41%, followed by omega-3 fatty acids at 11.85%, and ginseng at 7.99%. The prevalence of CKD was significantly higher in those who consumed amino acids and proteins, ginseng and red ginseng, and herbal medicine (plant extract)-berries than in those who did not. Conversely, patients who consumed probiotic supplements had a significantly lower prevalence of CKD than those who did not. In the population without CKD risk factors or history of CKD, the prevalence of CKD was high in the group consuming ginseng and red ginseng. After adjusting for covariates, the herbal medicine (plant extract)-berry group showed an independent association with CKD incidence. In conclusion, it is suggested that dietary supplements may affect kidney function. Further large-scale cohort studies are required to elucidate the exact effects of each dietary supplement on CKD.

Perturbation of Circadian Rhythm Is Associated with Increased Prevalence of Chronic Kidney Disease: Results of the Korean Nationwide Population-Based Survey.

Disturbances in circadian rhythms cause several health problems, such as psychosis, metabolic syndrome, and cancer; however, their effect on kidney disease remains unclear. This study aimed to evaluate the association between chronic kidney disease (CKD) and sleep disturbance in a Korean adult population. A total of 17,408 participants who completed the National Health and Nutrition Examination Survey from 2016 to 2018 were assessed for their sleep patterns and renal function. CKD was defined as an estimated glomerular filtration rate ≤ 60 mL/min/1.73 m² or a positive dipstick urinalysis. Sleep onset time and sleep duration showed significant differences between the control and CKD groups (p < 0.001). After adjusting for the covariates, sleep onset time rather than sleep duration was independently associated with incidence of CKD, and this association was more significant in people who were older, in women, and in those with low body mass index and no comorbidities. When comparing the prevalence of newly diagnosed CKD according to sleep onset time in a population with no CKD risk factors or no history of CKD, the early bedtime group showed an independent association with incidence of new CKD (odds ratio (OR), 1.535; 95% confidence interval (CI), 1.011−2.330) even after adjusting for covariates. Impaired circadian rhythm along with sleep disturbance could be associated with CKD development; therefore, sleep disturbance might be an important therapeutic target for CKD.

Pathogens of peritoneal dialysis peritonitis: Trends from a single-center experience over 15 years.

BACKGROUND: Concerns are increasing about the emergence of pathogens with antibiotic resistance in peritoneal dialysis (PD) peritonitis. We investigated the current pathogen trends and risk factors in PD peritonitis. METHODS: We conducted a retrospective study analyzing data from 643 patients who maintained PD over 3 months between January 2001 and December 2015. The isolated pathogens from PD peritonitis were compared between period A (2001-2008) and period B (2009-2015). RESULTS: Among 643 PD patients, 252 patients experienced one or more episodes of PD peritonitis (total 308 episodes) during the median follow-up of 66 months. In both periods, gram-positive bacteria were the dominant pathogens (22.2% vs. 53.8%, P < 0.01). Gram-negative bacteria showed an increasing tendency in period B, but without statistical significance (17.0% vs. 23.7%, P = 0.15). The culture-negative rate was improved from 57% in period A to 18% in period B (P < 0.01). There was no increase in the prevalence of resistant pathogens such as methicillin-resistant Staphylococcus epidermidis (MRSE), Staphylococcus aureus (MRSA) and extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli between periods A and B. Preserved residual renal function was associated with a lower risk of PD peritonitis (odds ratio, 0.53; 95% confidence interval, 0.31-0.88; P = 0.01). CONCLUSION: Over the past two decades, the pathogens of PD peritonitis have not significantly changed in Korea. Gram-positive organisms remained dominant, with S. epidermidis being the most common pathogen. Resistant bacteria such as MRSE, MRSA, ESBL-producing Gram-negative bacilli did not increase, but should be monitored.

The role of senescence of bone marrow cells in acute kidney injury.

BACKGROUND: The prevalence of acute kidney injury (AKI) in elderly patients has grown considerably. Age-associated changes in the immune system can be one of the critical factors determining AKI outcomes. This study aimed to investigate the role of senescence of bone marrow (BM)-derived cells in the development of AKI, focusing on the immune response. METHODS: Female 7-week-old C57BL/6 mice were irradiated and treated with BM cells from either 48-week-old or 8-week-old male mice. Ischemia-reperfusion injury (IRI) was induced, and their functional deterioration, histological tubular damage, and inflammatory responses were compared. For the in vitro study, lipopolysaccharide (LPS)-stimulated cytokine production by BM cells from old and young mice were examined. RESULTS: At 24 hours after IRI, there was no significant difference in the number of circulating immune cells between the mice transplanted with old or young BM cells. However, the mice with old BM cells showed less functional deterioration and histological tubular injury than those with young BM cells. Moreover, macrophage infiltration and renal cytokine interleukin (IL)-12 levels were lower in the mice with old BM cells at 24 hours post-IRI. Consistently, the in vitro study showed that LPS-induced production of cytokines interferon-γ, monocyte chemoattractant protein-1, and IL-10 was attenuated in cultured old BM cells, suggesting that age-related functional changes in these cells may lead to reduced inflammation in IRI. CONCLUSION: Immunosenescence could affect the susceptibility and response to renal IRI. Further studies specifically addressing age-related alterations can help in the development of treatment strategies for elderly patients with AKI.

Fate of Neutrophils during the Recovery Phase of Ischemia/Reperfusion Induced Acute Kidney Injury.

Effective clearance of inflammatory cells is required for resolution of inflammation. Here, we show in vivo evidence that apoptosis and reverse transendothelial migration (rTEM) are important mechanisms in eliminating neutrophils and facilitating recovery following ischemia/reperfusion injury (IRI) of the kidney. The clearance of neutrophils was delayed in the Bax knockout (KO)(BM) → wild-type (WT) chimera in which bone marrow derived cells are partially resistant to apoptosis, compared to WT(BM) → WT mice. These mice also showed delayed functional, histological recovery, increased tissue cytokines, and accelerated fibrosis. The circulating intercellular adhesion molecule-1 (ICAM-1)⁺ Gr-1⁺ neutrophils displaying rTEM phenotype increased during the recovery phase and blockade of junctional adhesion molecule-C (JAM-C), a negative regulator of rTEM, resulted in an increase in circulating ICAM-1⁺ neutrophils, faster resolution of inflammation and recovery. The presence of Tamm-Horsfall protein (THP) in circulating ICAM-1⁺ neutrophils could suggest that they are derived from injured kidneys. In conclusion, we suggest that apoptosis and rTEM are critically involved in the clearance mechanisms of neutrophils during the recovery phase of IRI.

Blocking junctional adhesion molecule C promotes the recovery of cisplatin-induced acute kidney injury.

BACKGROUND/AIMS: Recent findings have demonstrated the occurrence of neutrophil transendothelial migration in the reverse direction (reverse TEM) and that endothelial junctional adhesion molecule C (JAM-C) is a negative regulator of reverse TEM. In this study, we tested the effects of a JAM-C blocking antibody on the resolution of kidney injuries and inflammation in a mouse model of cisplatin-induced acute kidney injury (AKI). METHODS: Cisplatin was administered via intraperitoneal injection. A JAM-C blocking antibody or a control immunoglobulin G was administered intraperitoneal at 1.5 mg/kg, with the injection being delayed until day 4 following cisplatin administration to restrict the effect of antibodies on recovery. RESULTS: After cisplatin injection, serum creatinine and histologic injuries peaked on day 4. Treatment with a JAM-C blocking antibody on days 4 and 5 promoted the functional and histologic recovery of cisplatin-induced AKI on days 5 and 6. Facilitating recovery with a JAM-C blocking antibody correlated with significantly increased circulating intercellular adhesion molecule 1+ Tamm-Horsfall protein+ neutrophils and significantly decreased renal neutrophil infiltration, indicating that facilitating reverse the TEM of neutrophils from the kidney to the peripheral circulation partially mediated the resolution of inflammation and recovery. CONCLUSIONS: These results demonstrated that reverse TEM is involved in the resolution of neutrophilic inflammation in cisplatin-induced AKI and that JAM-C is an important regulator of this process.

Risk factors and outcomes of acute renal infarction.

BACKGROUND: Renal infarction (RI) is an uncommon disease that is difficult to diagnose. As little is known about clinical characteristics of this disease, we investigated its underlying risk factors and outcomes. METHODS: We performed a retrospective single-center study of 89 patients newly diagnosed with acute RI between January 2002 and March 2015 using imaging modalities. Clinical features, possible etiologies, and long-term renal outcome data were reviewed. RESULTS: The patients' mean age was 63.5 ± 15.42 years; 23.6% had diabetes and 56.2% had hypertension. Unilateral and bilateral involvements were shown in 80.9% and 19.1% of patients, respectively; proteinuria and hematuria were reported in 40.4% and 41.6%, respectively. Cardiovascular disease was the most common underlying disease, followed by renal vascular injury and hypercoagulability disorder. Fourteen patients had no specific underlying disease. At the time of diagnosis, acute kidney injury (AKI) was found in 34.8% of patients. Univariate analysis revealed diabetes mellitus (DM), leukocytosis, and high C-reactive protein (CRP) as significant risk factors for the development of AKI. On multivariate analysis, DM and high CRP levels were independent predictors for AKI. During follow-up, chronic kidney disease developed in 27.4% of patients. Univariate and multivariate Cox regression analyses showed old age to be an independent risk factor for this disease, whereas AKI history was a negative risk factor. CONCLUSION: DM patients or those with high CRP levels should be observed for renal function deterioration. Clinicians should also monitor for RI in elderly patients.

Advanced chronic kidney disease: a strong risk factor for Clostridium difficile infection.

BACKGROUND/AIMS: It has been suggested that chronic kidney disease (CKD) is a risk factor for Clostridium difficile infection (CDI) and is associated with increased mortality among patients infected with C. difficile. However, recent studies of the clinical impact of CKD on CDI in Asians are still insufficient. We sought to determine the relationship between CKD and CDI in a Korean population. METHODS: This was a single-center, retrospective case-control study. In total, 171 patients with CDI were included as cases and 342 age- and gender-matched patients without CDI were used as controls. We compared the prevalence of CKD in the study sample and identified independent risk factors that could predict the development or prognosis of CDI. RESULTS: Independent risk factors for CDI included stage IV to V CKD not requiring dialysis (odds ratio [OR], 2.90) and end-stage renal disease requiring dialysis (OR, 3.34). Patients with more advanced CKD (estimated glomerular filtration rate < 30) and CDI showed higher in-hospital mortality and poorer responses to the initial metronidazole therapy. CONCLUSIONS: More advanced CKD is an independent risk factor for CDI and is associated with higher in-hospital mortality and poor treatment responses in CDI patients. Thus, in CKD patients, careful attention should be paid to the occurrence of CDI and its management to improve the outcome of CDI.

The Role of M2 Macrophages in the Progression of Chronic Kidney Disease following Acute Kidney Injury.

INTRODUCTION: Acute kidney injury (AKI) is a major risk factor in the development of chronic kidney disease (CKD). However, the mechanisms linking AKI to CKD remain unclear. We examined the alteration of macrophage phenotypes during an extended recovery period following ischemia/reperfusion injury (IRI) and determine their roles in the development of fibrosis. METHODS: The left renal pedicle of mice was clamped for 40 min. To deplete monocyte/macrophage, liposome clodronate was injected or CD11b-DTR and CD11c-DTR transgenic mice were used. RESULTS: Throughout the phase of IRI recovery, M2-phenotype macrophages made up the predominant macrophage subset. On day 28, renal fibrosis was clearly shown with increased type IV collagen and TGF-ß. The depletion of macrophages induced by the liposome clodronate injection improved renal fibrosis with a reduction of kidney IL-6, type IV collagen, and TGF-ß levels. Additionally, the adoptive transfer of the M2c macrophages partially reversed the beneficial effect of macrophage depletion, whereas the adoptive transfer of the M1 macrophages did not. M2 macrophages isolated from the kidneys during the recovery phase expressed 2.5 fold higher levels of TGF-ß than the M1 macrophages. The injection of the diphtheria toxin into CD11b or CD11c-DTR transgenic mice resulted in lesser depletion or no change in M2 macrophages and had little impact on renal fibrosis. CONCLUSION: Although M2 macrophages are known to be indispensible for short-term recovery, they are thought to be main culprit in the development of renal fibrosis following IRI.

Relationship between pulmonary hypertension, peripheral vascular calcification, and major cardiovascular events in dialysis patients.

BACKGROUND: Pulmonary hypertension (PHT) is a recently recognized complication of chronic kidney disease. In this study, we investigated the association between PHT, peripheral vascular calcifications (VCs), and major cardiovascular events. METHODS: In this retrospective study, we included 172 end-stage renal disease (ESRD) patients undergoing dialysis [hemodialysis (HD)=84, peritoneal dialysis=88]. PHT was defined as an estimated pulmonary artery systolic pressure>37 mmHg using echocardiography. The Simple Vascular Calcification Score (SVCS) was measured using plain radiographic films of the hands and pelvis. RESULTS: The prevalence of PHT was significantly higher in HD patients (51.2% vs. 22.7%). Dialysis patients with PHT had a significantly higher prevalence of severe VCs (SVCS≥3). In multivariate analysis, the presence of severe VCs [odds ratio (OR), 2.68], mitral valve disease (OR, 7.79), HD (OR, 3.35), and larger left atrial diameter (OR, 11.39) were independent risk factors for PHT. In addition to the presence of anemia, severe VCs, or older age, the presence of PHT was an independent predictor of major cardiovascular events in ESRD patients. CONCLUSION: The prevalence of PHT was higher in HD patients and was associated with higher rates of major cardiovascular events. Severe VCs are thought to be an independent risk factor for predicting PHT in ESRD patients. Therefore, in dialysis patients with PHT, careful attention should be paid to the presence of VCs and the occurrence of major cardiovascular events.

Intra-abdominal hypertension does not predict renal recovery or in-hospital mortality in critically ill patients with acute kidney injury.

BACKGROUND: Although emerging evidence suggests that intra-abdominal hypertension (IAH) is a predictor of the development of acute kidney injury (AKI), it remains unclear whether the presence of IAH is a predictor of prognosis in patients with AKI. The purpose of this study was to assess whether the presence of IAH could predict prognosis in critically ill patients with AKI. The prognostic value of urinary biomarkers was also determined. METHODS: In this prospective observational study, we enrolled 57 patients with established AKI, who were admitted to the intensive care unit between February 2012 and June 2014. IAH was defined as a sustained elevation in intra-abdominal pressure of ≥12 mmHg, in three consecutive measurements performed daily on the first 3 days. Urinary neutrophil gelatinase-associated lipocalin (NGAL), liver-type fatty acid-binding protein, and simplified acute physiology score II score at the time of admission were also examined. RESULTS: IAH was observed in 78.9% of patients. The in-hospital mortality was 21.1%, and renal recovery during hospitalization was achieved in 40.4% of patients. Although high urinary NGAL [odds ratio (OR), 1.015] and liver-type fatty acid-binding protein (OR, 1.003) were found to be independent predictors of renal recovery, IAH was not. High urinary NGAL (OR, 1.003) and a high simplified acute physiology score II score (OR, 1.102) were independent predictors of in-hospital mortality, while IAH or urinary liver-type fatty acid-binding protein was not. CONCLUSION: Although IAH is prevalent in critically ill patients with AKI, it did not predict AKI prognosis. However, urinary NGAL was found to be a useful predictor of both renal recovery and in-hospital mortality.

Renal Klotho expression in patients with acute kidney injury is associated with the severity of the injury.

BACKGROUND/AIMS: The potential physiologic roles of Klotho in acute kidney injury (AKI) have recently been demonstrated in animal models. However, to date, there have been no human studies investigating the expression of renal Klotho in AKI. METHODS: We retrospectively collected biopsy specimens and clinical data of AKI patients between January 2001 and December 2012. Klotho expression was determined by immunohistochemical staining, and the clinical-pathological correlation was examined. RESULTS: Among the 34 patients diagnosed with acute tubular necrosis or acute tubulointerstitial nephritis, 21 patients without chronic histological lesions were included. The mean age was 37.3 ± 18.5 years and the mean peak creatinine level was 8.2 ± 5.5 mg/dL. In total, 10 patients (47.6%) received temporary renal replacement therapy (RRT); however, 17 patients (81%) showed functional recovery with creatinine levels of < 1.3 mg/dL after 1 month. The intensity of Klotho expression was scored as a percentage of Klotho-positive area. The renal Klotho score showed a significant negative correlation with the initial or peak creatinine level. When the patients were divided into three groups according to the Klotho score (low, middle, high), the low group had a significantly higher peak creatinine level and a more frequent requirement for RRT. However, the Klotho score was not a significant predictor of renal recovery. CONCLUSIONS: The results demonstrated that renal Klotho expression in humans decreased significantly according to the severity of AKI, regardless of the etiology, and that low expression was associated with a poor short-term outcome.

A single-center experience of overseas kidney transplant for immunologically high-risk patients.

OBJECTIVES: We report our experience in treating Mongolian patients transferred to our center in Korea to undergo kidney transplants, including immunologically high-risk patients. MATERIALS AND METHODS: Between September 2009 and February 2013, thirty-three Mongolian patients underwent kidney transplants at our center with the approval of the Korean Network for Organ Sharing. Their clinical data were retrospectively collected and analyzed. RESULTS: The mean age of the transplant recipients was 38.8 ± 10.5 years, and the causes of end-stage renal disease were glomerulonephritis (5), diabetes mellitus (2), hypertension (3), and unknown (25). These cases included ABO incompatibility, high levels of sensitization, and retransplant, at frequencies of 9, 12, and 9. Basiliximab (30) or antithymocyte globulin (2) was administered as the induction therapy, and combination regimens of plasmapheresis with or without intravenous immunoglobulins and/or rituximab were used in some high-risk patients. The mean follow-up after kidney transplant was 12.87 ± 11.7 months. During the follow-up, antibody-mediated rejection and graft failure occurred in 2 patients. In addition, cytomegalovirus infection, calcineurin inhibitor toxicity, and BK viremia developed in 1 patient each. The mean estimated glomerular filtration rates at 1, 6, and 12 months after kidney transplant were 88.2 ± 26.9 mL/min/1.73 m2, 67.5 ± 14.9 mL/min/1.73 m2, and 63.9 ± 21.1 mL/min/1.73 m2. In addition, subgroup analysis revealed that ABOincompatible and immunologically high-risk recipients had comparable renal function status during the follow-up. CONCLUSIONS: We found that an overseas kidney transplant program in Korea could be conducted safely, even in high-risk patients. Therefore, a proper cooperation and transfer system for these high-risk patients between neighboring countries might help in providing improved medical care in this setting.

The incidence and risk factors of acute kidney injury after hepatobiliary surgery: a prospective observational study.

BACKGROUND: Although intraperitoneal surgery is a major operation associated with postoperative acute kidney injury (AKI), the incidence, risk factors, and long-term renal outcome are not well known. We aimed to determine the risk factors and 6 months renal outcome in patients with clinical or subclinical AKI after hepatobiliary surgery. We also assessed the validity of urine neutrophil gelatinase-associated lipocalin (NGAL) in the early detection of AKI or prediction of renal outcome. METHODS: This prospective observational study enrolled patients with normal renal function who underwent hepatobiliary surgeries. Urine and serum samples were collected for NGAL measurement. RESULTS: Among 131 patients, 10 (7.6%) developed postoperative AKI. Urine NGAL at 12 h postsurgery was the most predictive parameter for the diagnosis of AKI (cutoff, 92.85 ng/mL). With the cutoff value, subclinical AKI was diagnosed in 42 (32.1%) patients. Patients with clinical AKI and those with subclinical AKI were assigned to the AKI group. The AKI group had significantly higher model for end-stage liver disease and sodium (MELD-Na) score, lower albumin level, and longer hospital stay after surgery than the non-AKI group. Older age and higher MELD-Na score were independent risk factors for the development of postoperative AKI. At 6 months postsurgery, the estimated glomerular filtration rate (eGFR) in the AKI group was significantly lower than that in the non-AKI group, although the baseline eGFR was not different. In multiple linear regression analysis, the maximum urine NGAL level during 24 h postsurgery, intraoperative fluid balance, and having liver transplantation were significantly associated with a poor 6 months renal outcome. CONCLUSION: Urine NGAL was useful in the early diagnosis of postoperative AKI as well as in predicting the 6 months renal outcome after hepatobiliary surgery. A considerable proportion of patients developed subclinical AKI, and these patients showed worse renal outcome compared with the non-AKI group.

Polymicrobial Peritonitis with Lactococcus lactis in a Peritoneal Dialysis Patient.

Lactococcus lactis (L. lactis) is an important gram-positive bacterium in dairy products. It is a rare cause of opportunistic infections with only four cases of Lactococcus peritoneal dialysis (PD) peritonitis reported in the literature. In Korea, L. lactis infection was first reported in a liver abscess patient in 2010; however, PD peritonitis with Lactococcus has not been reported in Korea. Recently, we experienced a case of Lactococcus-associated polymicrobial PD peritonitis. The patient was initially managed with broad-coverage antibiotics; however, owing to a poor response, the PD catheter was removed and the patient was switched to hemodialysis. We discuss this case and review the literature.

A case of lupus-like glomerulonephritis in an HIV patient with nephrotic range proteinuria, purpura, and elevated IgA level.

Human immunodeficiency virus (HIV) infection is growing medical concern worldwide. There are many types of glomerulonephritis which are associated with HIV infection. We report a case of a 53-year-old Korean man with an HIV infection, who was developed nephritic range proteinuria and purpura with elevated IgA level rasing a possibility of Henoch-Schölein Purpura (H-S purpura). However, renal biopsy showed "lupus-like feature" glomerulonephritis without clinical or serologic evidence of systemic lupus erythematosus. Although baseline renal function was maintained without further need for maintenance dialysis following anti-retroviral therapy (ART) and steroid, patient died from uncontrolled gastrointestinal bleeding.

Role of inflammation in the pathogenesis of cardiorenal syndrome in a rat myocardial infarction model.

BACKGROUND: Cardiorenal syndrome is now frequently recognized, and the combined dysfunction of heart and kidney increases morbidity and mortality. This study aimed to investigate possible mechanisms that underlie renal damage following heart dysfunction using a rat myocardial infarction model, focusing on the inflammatory pathway. METHODS: Rats were randomized into four groups: normal, volume depletion, sham operation and myocardial infarction (MI). MI was induced by the ligation of the left coronary artery and a volume depletion model was produced by low-salt diet and furosemide injection. Biochemical, histological and flow cytometric analyses were performed at 3 days and 4 and 8 weeks after MI. RESULTS: On Day 3 following MI, the development of subclinical acute kidney injury was identified through significantly increased serum and urine neutrophil gelatinase-associated lipocalin level. We detected the increase of activated monocytes (CC chemokine receptor 2(+) ED-1(+)) in peripheral blood, along with the infiltration of ED-1(+) macrophages and the increment of nuclear p65 in the kidney of MI rats, suggesting the contribution of nuclear factor-kappa B-mediated inflammation in the development of Type 1 cardiorenal syndrome (CRS). The inflammatory cytokines, interleukin-6 and tumour necrosis factor-α (TNF-α) mRNA expression, as well as microvascular endothelial permeability and tubular cell apoptosis, significantly increased in the kidneys of MI rats. At 4 and 8 weeks after MI, tubular cell apoptosis, ED-1(+) macrophage infiltration and interstitial fibrosis increased in MI rats, and these chronic changes were significantly mitigated by systemic monocyte/macrophage depletion using liposome clodronate. CONCLUSION: This study identifies the possible important role of inflammatory response as a mediator of heart-kidney crosstalk in CRS.

The role of urinary liver-type fatty acid-binding protein in critically ill patients.

Although several urinary biomarkers have been validated as early diagnostic markers of acute kidney injury (AKI), their usefulness as outcome predictors is not well established. This study aimed to determine the diagnostic and prognostic abilities of urinary liver-type fatty acid-binding protein (L-FABP) in heterogeneous critically ill patients. We prospectively collected data on patients admitted to medical and surgical intensive care units (ICUs) from July 2010 to June 2011. Urine neutrophil gelatinase-associated lipocalin (NGAL) and L-FABP at the time of ICU admission were quantitated. Of the 145 patients, 54 (37.2%) had AKI defined by the Acute Kidney Injury Network (AKIN) criteria. AKI patients showed significantly higher level of urinary NGAL and L-FABP and also higher mortality than non-AKI patients. The diagnostic performances, assessed by the area under the ROC curve, were 0.773 for NGAL and 0.780 for L-FABP, demonstrating their usefulness in diagnosing AKI. In multivariate Cox analysis, urinary L-FABP was an independent predictor for 90-day mortality. Urinary L-FABP seems to be promising both for the diagnosis of AKI and for the prediction of prognosis in heterogeneous ICU patients. It needs to be further validated for clinical utility.