Soluble Klotho Protects against Uremic Cardiomyopathy Independently of Fibroblast Growth Factor 23 and Phosphate

Cardiac hypertrophy occurs in up to 95% of patients with CKD and increases their risk for cardiovascular death. In the kidney, full-length membranous Klotho forms the coreceptor for fibroblast growth factor 23 (FGF23) to regulate phosphate metabolism. The prevailing view is that the decreased level of Klotho in CKD causes cardiomyopathy through increases in serum FGF23 and/or phosphate levels. However, we reported recently that soluble Klotho protects against cardiac hypertrophy by inhibiting abnormal calcium signaling in the heart. Here, we tested whether this protective effect requires changes in FGF23 and/or phosphate levels. Heterozygous Klotho-deficient CKD mice exhibited aggravated cardiac hypertrophy compared with wild-type CKD mice. Cardiac magnetic resonance imaging studies revealed that Klotho-deficient CKD hearts had worse functional impairment than wild-type CKD hearts. Normalization of serum phosphate and FGF23 levels by dietary phosphate restriction did not abrogate the aggravated cardiac hypertrophy observed in Klotho-deficient CKD mice. Circulating levels of the cleaved soluble ectodomain of Klotho were lower in wild-type CKD mice than in control mice and even lower in Klotho-deficient CKD mice. Intravenous delivery of a transgene encoding soluble Klotho ameliorated cardiac hypertrophy in Klotho-deficient CKD mice. These results suggest that the decreased level of circulating soluble Klotho in CKD is an important cause of uremic cardiomyopathy independent of FGF23 and phosphate, opening new avenues for treatment of this disease.     

Anticoagulation minimization is safe and effective in albumin liver dialysis using the molecular adsorbent recirculating system

The molecular adsorbent recirculating system (MARS) is a blood purification device with renal and hepatic dialytic effects. This study examined the use of low-dose unfractionated heparin in MARS. This was a prospective, observational study of 15 MARS treatment sessions (mean duration per treatment cycle = 12.2 +/- 4.5 h) in four patients with severe acute decompensation of chronic liver disease (n = 3) and fulminant hepatic failure (n = 1) treated with intermittent MARS. All patients were critically ill (APACHE II 24.8 +/- 3.3). Renal dialysis was with continuous hemofiltration and/or slow low-efficiency dialysis. One MARS session was terminated because of vascular access occlusion (1/15; 6.7%). Bleeding was noted in two sessions (2/15; 13%). Twelve MARS sessions were heparin-free and three treatments were with mean heparin dose of 833 +/- 382 IU. Serum biochemical parameters pre- and post-MARS were total bilirubin (micromol/L): 409.4 +/- 141.6 versus 282.9 +/- 90, P < 0.05; plasma ammonia (micromol/L): 44.3 +/- 21.2 versus 28.8 +/- 20.2, P = 0.002; urea (mmol/L): 15.9 +/- 11.8 versus 7.9 +/- 6.6, P = 0.002; creatinine (micromol/L): 252.4 +/- 151.9 versus 150.1 +/- 96.6, P = 0.003. Pre-MARS versus post-MARS systolic (SBPs) and diastolic (DBPs) blood pressures (mm Hg) were SBP = 129.2 +/- 27.7 versus 124 +/- 25, P = 0.838; and DBP = 60.7 +/- 15.3 versus 56 +/- 13, P = 0.595. Prothrombin time (PT), activated partial thromboplastin time (aPTT) and platelet count (Plt) pre- and post-MARS were PT(s): 22 +/- 7.9 versus 23.8 +/- 10.2, P = 0.116; aPTT (s): 64.5 +/- 40.9 versus 85.5 +/- 50.6, P = 0.092; and Plt (x10(3)/mm(3)): 87 +/- 67.6 versus 68.8 +/- 39, P = 0.098. MARS priming with heparin saline was safe. Heparin-minimized MARS did not compromise circuit function and longevity in extended intermittent MARS.     

Albumin dialysis in critically ill patients: use versus omission of intradialytic heparin

Albumin liver dialysis using the Molecular Adsorbent Recirculating System (MARS) (Teraklin AG, Rostock, Germany) is used in severe acute liver failure (ALF). We hypothesized that intradialytic heparin worsens preexisting hemostatic defects without enhancing system longevity or therapeutic efficacy. This was a retrospective, single center study of 10 critically ill patients (M : F = 8:2; mean age 58.5 +/- 16.5 years old; Acute Physiology and Chronic Health Evaluation II 25.0 +/- 3.5) treated with 31 MARS sessions (intradialytically heparinized : nonheparinized = 18:13). Mortality in this cohort was 80%. All MARS circuits were primed with dilute heparinized saline before commencement. However, intradialytic, intermittent, bolus heparin was administered on an ad hoc basis with circuit saline flush where indicated. Acute renal replacement therapy was instituted where indicated. Average total intradialytic heparin used was 757 +/- 389 IU. Circuit pressures were stable with or without intradialytic heparin. Significant reductions in serum urea, creatinine, ammonia, and total bilirubin were achieved using intradialytically heparinized and nonheparinized MARS. Thrombocytopenia and elevated activated partial thromboplastin time (aPTT) were further deranged post-MARS for both circuit types, but significantly so in intradialytically heparinized MARS: pre- versus post-MARS aPTT (s) 57.8 +/- 17.6 versus 88.7 +/- 48.0, P = 0.011, and platelet count (x 10(3)/L) 102.9 +/- 61.1 versus 84.4 +/- 50.5; P = 0.009. The use of low dose, intradialytic heparin during MARS exacerbates preexisting severe coagulopathy and thrombocytopenia in patients with severe ALF without enhancing circuit function and longevity. However, the role and safety of heparinized saline prime need further investigation.     

Management of Patients after Renal Graft Loss: An Open Question for Nephrologists

Patients undergoing renal graft failure and returning to dialysis are often regarded to like facing for the first time a substitutive treatment, without considering the technical complications, the economical impact, and the psychological implications. This review attempt, to give answers to various questions, concerning the management of vascular access, the immunosuppressive therapy, the transplantectomy, the emotional and neuropsychic aspects, and the quality of life of graft-failed patients.     

The heterogeneity of premature ovarian failure:A report with six cases

Objective:To investigate the heterogeneity of premature ovarian failure(POF).Methods:A retrospective study was carried out in Peking Union Medical College Hospital(PUMCH),two hundred and forty-five women with POF were retrospectively analyzed in the reproductive endocrinology clinic in PUMCH from 1988 to 2008.Results:During the hormone replacement therapy,ovarian function recovery was observed in 6 idiopathic POF cases,3 out of these 6 got pregnaney and regular menses with elevated estradiol and decreased follicular stimulating hormone(FSH).The spontaneous pregnancy in the group was 1.22%(3/245).It is indicated that even women di-agnosed as POF still have the possibility of spontaneous ovulation.Conclusions:POF is a kind of disease with heterogeneity.We must give the individualized therapy to POF pa-tients.     

Factors associated with primary and secondary graft failure following cadaveric kidney transplant

The risk profile for primary renal graft failure is largely unknown because of its inclusion with secondary failures or its exclusion from analysis. This study compares characteristics of the cadaveric transplant recipients who experienced primary failure, secondary failures or survived with a functioning graft for at least 6 months. Medical records of all cadaveric kidney-transplant patients performed in Israel over a 3-yr period 1997-2000 were reviewed. Fisher's exact test and multinomial regression models were used to assess the association of demographic, pre-operative and operative risk factors with the two types of failure outcomes. Of 325 grafts, 54 (16.6%) failed of which half were primary failures. Univariate analysis demonstrated a significant trend of increasing proportion of patients with specific risk factors from the functioning grafts group to the secondary and to the primary graft failure groups. Independent risk factors for primary graft failure included 'surgical complications', 'donor's age > or =60 yr', 'waiting for transplant > or =6 yr', and 'human leukocyte antigen-DR (HLA-DR) mismatch', based on the multivariate model. These factors may reflect the scarcity of organ donations in Israel, which leads to a prolonged waiting time, higher tolerance for HLA-DR mismatches, and utilization of kidneys from elderly donors.     

黄芪注射液治疗慢性肾衰竭合并心力衰竭的临床疗效

目的:观察黄芪注射液治疗慢性肾衰竭合并心力衰竭的疗效。方法:将60例慢性肾衰合并心力衰竭病人分为两组。对照组30例予西医治疗。治疗组30例在西医治疗基础上加用黄芪注射液30 ml溶入10％G.S 250 ml中静脉滴注,qd连用10 d。结果:治疗组心功能明显改善,总有效率90％,明显高于对照组(P<0.05);治疗组左室射血分数(LVEF)和左室短轴缩短率(ΔD％)均显著提高(P<0.05)。结论:黄芪注射液能明显改善慢性肾衰病人的心功能。     

Revascularizing Effect of Diaphragm Graft on Ischaemic Myocardium:An Experimental Study in the Dog

A method for revascularizing ischaemic myocardium by means of diaphragm graft is presented. In an experimental series the graft healed to the myocardium in 9 of 11 dogs. The revascularizing effect could be demonstrated by coronary arteriography and/or internal mammary arteriography intra vitam and postmortem, and by gross and microscopic examination. All of the 11 animals in the experimental series survived high ligation of the left anterior descending (LAD) coronary artery, whereas a high frequency of large infarctions and deaths occurred in the two control series in which no diaphragm graft had been transplanted to the heart muscle.     

胸部开放伤后海水浸泡对实验犬呼吸功能的影响

目的 探讨胸部开放伤后海水海泡所致呼吸功能障碍的病理生理特点,为研究早期救治方案提供依据。方法 实验犬致伤后随机分为对照组（n-10)和海水浸泡组（n=10)。海水浸泡组;犬于致伤后置入人工配制的海水中,于致伤前及入海水后即刻、30分钟和45分钟取动脉血测定血气分析变化,同时监测通气功能和换气功能变化。对照组：不浸泡海水,于致伤前、致伤后即刻、30分钟、45分钟、1小时、2小时、3小时和4小时进行监测,处理同海水浸泡组。结果 海水浸泡组的呼吸功能衰竭明显重于对照组,表现在严重的低氧血症和高碳酸血症,处理同海水浸泡 组。结果 海水浸泡组的呼吸功能衰竭明显重于对照组,表现在严重的低氧血症和高碳酸血症,而且出现的时间早。对照组低氧血症的主要原因是以通气／灌注比率失调为主的换气功能障碍,同时并存一定程度的限制性通气功能障碍;而造成海水浸泡组低氧血症和高碳酸血症的主要原因是以严重肺泡通气不足为主的通气功能障碍和肺内分流引起的换气功能障碍。结论 胸部开放伤后海水浸泡组与对照组所造成呼吸功能障碍的机制有所不同,前者可造成严重的Ⅱ型呼吸衰竭,对生命威胁更大。     

Liver transplantation for fulminant hepatic failure: importance of renal failure

Abstract One hundred eighty-one consecutive patients with fulminant hepatic failure (FHF) presenting in a 2-year period were reviewed. In this cohort we examined the impact of pretransplant renal failure on mortality and morbidity following orthotopic liver transplantation (OLTx). Twenty-seven patients (18 female, 9 male) with a median age of 43.5 years (range 19–65 years) underwent OLTx. FHF was due to idiosyncratic drug reaction ( n = 4), paracetamol overdose ( n = 3), seronegative hepatitis ( n = 17), hepatitis B ( n = 1), veno-occlusive disease ( n = 1), and Wilson's disease ( n = 1). Renal failure was present in 14 patients, 7 of whom died (whereas there was 100 % survival in patients without renal failure). Pretransplant renal failure was associated with prolonged mechanical ventilation (13 days vs 6 days, P = 0.05), prolonged intensive care stay (17 days vs 8 days, P - 0.01) and prolonged hospital stay (27 vs 21 days, P = NS). Pretransplant renal failure did not predict renal dysfunction at 1 year after OLTx. We conclude that the survival of patients transplanted for FHF is inferior to that of patients transplanted for chronic liver disease (67 % vs 88 % 1-year survival in Birmingham). For patients with FHF undergoing transplantation, pretransplant renal failure strongly predicts poor outcome with significantly greater consumption of resources.     

不同缺血方式对大鼠肾脏损伤作用的实验研究

目的 研究在总缺血时间一定的情况下不同缺血方式对肾脏的损伤程度及其作用机理。方法 ４５只Ｗｉｓｔａｒ大鼠制备成肾缺血动物模型。Ａ组为正常对照组（ｎ＝１０）;Ｂ组为持续缺血组（ｎ＝１０）;Ｃ组为间断缺血组（ｎ＝１０）;Ｄ组为缺血预处理组（ｎ＝１０）;Ｅ组为缺血预处理延迟效应组（ｎ＝５）。手术后动态观察各组动物肾功能改变、组织学以及肾组织再灌注前后ＭＤＡ含量变化。结果 （１）Ｃ组术后肾功能各项指标与Ａ     

Mortality in Elderly Patients with Acute Renal Failure

In a retrospective study, we identified 55 elderly patients with acute renal failure (ARF) admitted to our hospital during an 8-year period from 1985 to 1993. Information about the etiology, complications, laboratory data, and treatment course were obtained from the clinical history. Of the 200 patients with ARF admitted to the hospital during this period, 28% were patients more than 60 years old (41 male and 14 female) with an average age of 68.5 ± 7 years. The main causes of ARF were sepsis, volume depletion, low cardiac output, arterial hypotension, nephrotoxicity by antibiotics, and obstructive uropathy. The global mortality of elderly patients with ARF was 53%. The mortality rate of the different types of the ARF were: prerenal 35%, intrinsic 64% (oliguric 76%, nonoliguric 50%), and postrenal 40%. Mortality as a result of sepsis occurred in 18 patients (62%), by cardiovascular disease in 4 patients (13%), by acute respiratory failure in 2 patients (7%), and by other causes in 5 patients (18%). In the cases of sepsis, Pseudomonas was detected in 7 cases (39%), Escherichia coli in 2 cases (11%), Gram-negative nonspecific in 3 cases (17%), Klebsiella in 1 case (5%), and in 5 cases (16%), the hemoculture was negative. The patient survival rate was 47% (26 of 55 patients). Of these patients, 19 recovered their normal renal function (73%), but 7 patients remained with renal failure (27%). In conclusion, the global mortality in the elderly patients without considering the types of ARF was 53%. The oliguric form had the highest mortality rate with 76%. The main causes for mortality were sepsis with 62%, cardiovascular disease with 13%, and other causes 18%.     

Rhabdomyolysis and secondary renal failure in critically ill surgical patients

Background

Rhabdomyolysis accounts for up to 28% of the causes of posttraumatic acute renal failure requiring dialysis. Clinically significant rhabdomyolysis is poorly characterized biochemically and difficult to diagnose.

Methods

A retrospective review of all surgical, trauma, burn, and pediatric surgical patients admitted to Grady Memorial Hospital in Atlanta, GA, from January 1995, through April 2002 was performed. Patients were screened for serum creatinine, base deficit, serum creatine kinase (CK) ≥1,000, presence of myoglobinuria, or if they had a clinical diagnosis of rhabdomyolysis by an attending surgeon.

Results

The sequential addition of admission laboratory values for serum creatinine ≥1.5 mg/dL (positive predictive value [PPV] = 33%), base deficit ≤−4 (PPV = 52%), serum CK level ≥5,000 U/L (PPV = 80%), and myoglobinuria increases the ability to predict which patients will develop dialysis-requiring acute renal failure after an episode of rhabdomyolysis. Patients with maximum CK ≥5,000 are also at increased risk for persistent renal insufficiency (Cr ≥2.0 mg/dL).

Conclusions

An algorithm for testing at-risk surgical patients was developed and may aid in the early diagnosis of clinically significant rhabdomyolysis.     

Aetiology and outcome of acute renal failure secondary to war related trauma and infectious disease in Croatia

Summary: The aim of our study was to explore the aetiology and the outcome of acute renal failure (ARF) during the war in Croatia. of the 2132 patients admitted to our hospital between April 1990 and November 1992 due to war related trauma, 11 (0.5%) developed ARF. We believe that the development of ARF in these patients was secondary to an overwhelming septic process. Most of our patients suffered from multiple organ failure. of the 11 patients suffering from ARF due to war related trauma only four recovered (63.6% had died). We attribute the lethal outcome to the progression of the septic process. Patients who developed ARF due to infectious diseases unrelated to trauma had a different prognosis. Acute renal failure caused by the Hantan virus ran a benign course, in both its oliguric and non-oliguric form. Patients who developed ARF as a complication of leptospirosis also had a good prognosis. Although ARF is usually of a multifactorial genesis, our study aimed to emphasize the importance of disseminated septic processes as a cause of ARF.     

Volatile Anesthetics and AKI: Risks,Mechanisms, and a Potential Therapeutic Window

AKI is a major clinical problem with extremely high mortality and morbidity. Kidney hypoxia or ischemia-reperfusion injury inevitably occurs during surgery involving renal or aortic vascular occlusion and is one of the leading causes of perioperative AKI. Despite the growing incidence and tremendous clinical and financial burden of AKI, there is currently no effective therapy for this condition. The pathophysiology of AKI is orchestrated by renal tubular and endothelial cell necrosis and apoptosis, leukocyte infiltration, and the production and release of proinflammatory cytokines and reactive oxygen species. Effective management strategies require multimodal inhibition of these injury processes. Despite the past theoretical concerns about the nephrotoxic effects of several clinically utilized volatile anesthetics, recent studies suggest that modern halogenated volatile anesthetics induce potent anti-inflammatory, antinecrotic, and antiapoptotic effects that protect against ischemic AKI. Therefore, the renal protective properties of volatile anesthetics may provide clinically useful therapeutic intervention to treat and/or prevent perioperative AKI. In this review, we outline the history of volatile anesthetics and their effect on kidney function, briefly review the studies on volatile anesthetic-induced renal protection, and summarize the basic cellular mechanisms of volatile anesthetic-mediated protection against ischemic AKI.     

Liver transplantation for fulminant hepatic failure: Importance of renal failure

One hundred eighty-one consecutive patients with fulminant hepatic failure (FHF) presenting in a 2-year period were reviewed. In this cohort we examined the impact of pretransplant renal failure on mortality and morbidity following orthotopic liver transplantation (OLTx). Twenty-seven patients (18 female, 9 male) with a median age of 43.5 years (range 19–65 years) underwent OLTx. FHF was due to idiosyncratic drug reaction (n = 4), paracetamol overdose (n = 3), seronegative hepatitis (n = 17), hepatitis B (n = 1), veno-occlusive disease (n = 1), and Wilson's disease (n = 1). Renal failure was present in 14 patients, 7 of whom died (whereas there was 100% survival in patients without renal failure). Pretransplant renal failure was associated with prolonged mechanical ventilation (13 days vs 6 days,P = 0.05), prolonged intensive care stay (17 days vs 8 days,P = 0.01) and prolonged hospital stay (27 vs 21 days,P = NS). Pretransplant renal failure did not predict renal dysfunction at 1 year after OLTx. We conclude that the survival of patients transplanted for FHF is inferior to that of patients transplanted for chronic liver disease (67% vs 88% 1-year survival in Birmingham). For patients with FHF undergoing transplantation, pretransplant renal failure strongly predicts poor outcome with significantly greater consumption of resources.     

Longitudinal evaluation of ventricular ejection fraction and NT-proBNP across heart failure subgroups

Objectives: Left ventricular ejection fraction (EF) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are important surrogate markers of cardiac function and wall stress. Randomized trials of heart failure (HF) have shown improvements in survival in patients with reduced EF (<40%, HFrEF) but not with preserved EF (≥50%, HFpEF) or mid-range EF (40-49%, HFmrEF). Limited information is available on the trajectory of EF in contemporary heart failure management programs (HFMPs).

Design: 201 HF patients consecutively enrolled 2010–2011 in the outpatient-based HFMP of Skåne University Hospital in Lund were included in the study. Probable etiology, EF, NT-proBNP and medications were assessed at baseline and 1 year after enrollment.

Results: HFrEF was the most common heart failure subgroup (78.1% of patients) in this HFMP, followed by HFmrEF (14.9%) and HFpEF (7.0%). The most common etiology was ischemic heart disease (IHD, 40.8%).

Complete recovery of EF (>50%) was rare (14.1% of patients with HFrEF and 26.7% with HFmrEF), some degree of improvement was observed in 57.7% and 46.7% of patients. LVEF improved on average 9.1% in patients with HFrEF (p?p?Conclusions: This study provides estimates of the improvement in LVEF and NT-proBNP that can be expected with contemporary management across subgroups of HF and different etiologies in a contemporary HFMP.