A case of rhabdomyolysis with fatal outcome after a treatment with levofloxacin

Fluoroquinolones are known to cause rhabdomyolysis. Levofloxacin is a recent fluoroquinolone and its muscular toxicity is not well documented. We describe the case of a 77-year-old female patient, who presented with an acute rhabdomyolysis after treatment with levofloxacin. She had a background of serious cardio-pulmonary disease. She received an oral ambulatory treatment with levofloxacin for pulmonary infection. After 6 days, she presented with severe rhabdomyolysis, resulting in complete anuria with hyperkalaemia, complicated with acute liver cytolysis and respiratory failure. The treatment was a daily repeated haemodialysis. She presented with a fatal myocardial infarction 13 days after admission. The medical history inclines us to strongly suspect levofloxacin as the cause of this severe adverse drug reaction. We also reviewed 27 other suspect cases reported in the database provided by the World Health Organization Collaborating Centre for Drug Monitoring (Uppsala, Sweden). We conclude that rhabdomyolysis can be a rare, severe adverse effect of levofloxacin, as well as the other fluoroquinolones.     

Nephrotoxic effects of lead nitrate in<Emphasis Type="Italic"> Rana ridibunda</Emphasis>

The impact of lead (Pb) on kidney histopathology of the frog Rana ridibunda was investigated. Female frogs were exposed for 4, 10 and 30 days to 14 ppm lead (as lead nitrate). All the lead concentrations and many histological changes were time dependent. Light microscopy of kidney revealed morphological changes mainly in the proximal convoluted tubule (PCT) cells. The most severe changes such as vacuolation, Perl's stained material, infiltration, brush border destruction and proximal tubule damage were detected in the animals exposed for 10 and 30 days. Karyomegaly was highest at 10-days exposure, probably as a result of intense stress caused by the lead. Some PCT in the 30-days-exposed animals were von Kossa's method positive, suggesting the presence of calcium. The possibility is discussed that some of these changes, such as karyomegaly and intranuclear inclusions, might be preneoplastic if lead was supplied at high concentrations and for long time.     

Resistance of CD28-deficient mice to autologous phase of anti-glomerular basement membrane glomerulonephritis

Background. The engagement of CD28 on T cells provides an essential costimulatory signal for T-cell activation and differentiation. Recent studies suggest that CTLA4Ig inhibits T-cell activation in vitro and in vivo, prevents acute and chronic allograft rejection, and induces tolerance in some experimental transplantation models.Methods. The present study examined the role of the CD28 costimulatory pathway in the induction of experimental anti-glomerular basement membrane (GBM) glomerulonephritis (GN). An accelerated type of anti-GBM GN was induced in wild-type mice and CD28-deficient (KO) mice. After 7 and 14 days, functional parameters, such as serum creatinine, amount of proteinuria, and serum mouse IgG levels were assessed. Histological studies were performed simultaneously to examine glomerular changes by light microscopy and immunoglobulin deposition by immunofluorescence staining. Flow cytometric analysis was undertaken to assess I-A^b antigen expression on spleen cells.Results. Anti-GBM GN induction was almost completely prevented in CD28-KO mice. CD28-KO mice had impaired ability to evoke B-cell activation, and developed lower mouse anti-rabbit IgG antibody titers in their serum than wild-type C57BL/6 mice. Furthermore, glomerular deposition of mouse anti-rabbit IgG was not detectable in CD28-KO mice after immunization with anti-GBM antibody.Conclusions. This is the first demonstration that the CD28 costimulatory pathway plays a critical role in autologous antibody production in anti-GBM GN, and suggests that effective inhibition of CD28-dependent autologous antibody production could be useful in the treatment of antibody-dependent GN in humans.     

Interim evidence of the renoprotective effect of the angiotensin II receptor antagonist losartan versus the calcium channel blocker amlodipine in patients with chronic kidney disease and hypertension: a report of the Japanese Losartan Therapy Intended for Global Renal Protection in Hypertensive Patients (JLIGHT) Study

Background. Insufficiency of renal function and high blood pressure influence each other and eventually result in life-threatening endstage renal disease. It has been proposed that proteinuria per se is a determinant of the progression of chronic kidney disease (CKD). The therapeutic strategy for patients with proteinuric CKD and hypertension should therefore be targeted with a view not merely toward blood pressure reduction but also toward renoprotection. Methods. We examined the effect of the angiotensin (AT)₁ receptor antagonist losartan and the calcium channel blocker amlodipine, throughout a period of 12 months, on reduction of blood pressure and renoprotection. This was done by assessing amounts of urinary protein excretion, serum creatinine (SCr), and creatinine clearance (CCr) in patients with hypertension (systolic blood pressure [SBP] 140mmHg or diastolic blood pressure [DBP] 90mmHg) and CKD (male, body weight [BW] 60kg: 1.5 SCr < 3.0mg/dl; female or male BW < 60kg: 1.3 SCr < 3.0mg/dl), manifesting proteinuria of 0.5g or more/day. Losartan was administered once daily at doses of 25 to 100mg/day, and amlodipine was given once daily at 2.5 to 5mg/day. No antihypertensive combination therapy was allowed during the first 3-month period. Results. A 3-month interim analysis revealed that, despite there being no difference in blood pressure between the two groups, there was a significant reduction in 24-h urinary protein excretion in the losartan group (n = 43), but there was no change in the amlodipine group (n = 43). Analysis of stratified subgroups with proteinuria of 2g or more/day and less than 2g/day showed that losartan lowered proteinuria by approximately 24% in both subgroups, while amlodipine lowered proteinuria by 10%, but only in the subgroup of less than 2g/day (NS). SCr and CCr did not change throughout the period of 3 months in either group. No severe or fatal adverse event was experienced in either group during the study period. Conclusions. Losartan appeared to be efficacious for renoprotection in patients with proteinuric CKD and hypertension, with the mechanism being independent of its antihypertensive action.     

内皮素受体拮抗剂对单侧输尿管梗阻大鼠肾间质纤维化的保护作用

目的　观察非选择性内皮素受体拮抗剂波生坦对单侧输尿管梗阻大鼠肾间质纤维化的作用。方法　制作单侧输尿管梗阻 (UUO)大鼠模型 ,给或不给波生坦干预 ,于造模第 7天取梗阻肾进行如下试验 :( 1)逆转录多聚酶链反应法 (RT PCR) :观察梗阻肾实质前内皮素 1原 (preproET 1)、Ⅰ型胶原 (ColⅠ )、转化生长因子 β1(TGF β1)、金属蛋白酶组织抑制物 1(TIMP 1)及Ⅰ型纤溶酶原激活物抑制物 (PAI 1)mRNA的表达。 ( 2 )免疫组织化学法 :观察梗阻肾脏肾小管 间质内皮素 1(ET 1)、ColⅠ、TGF β1、TIMP 1及PAI 1蛋白质的表达。 结果　 ( 1)与假手术组大鼠相比 ,UUO大鼠肾实质preproET 1、ColⅠ、TGF β1、TIMP 1、PAI 1mRNA表达 ,及肾小管 间质ET 1、ColⅠ、TGF β1、TIMP 1、PAI 1蛋白质表达均明显上调 (P <0 0 5 )。 ( 2 )波生坦能够显著下调梗阻肾的ColⅠ、TGF β1、TIMP 1mRNA和蛋白质的表达 (P <0 0 5 ) ;而对preproET 1、PAI 1mRNA及ET 1、PAI 1蛋白质表达无显著影响 (P >0 0 5 )。结论　ET 1可能参与UUO大鼠的肾间质纤维化过程 ,而波生坦有可能通过抑制TGF β1和TIMP 1而拮抗纤维化。     

老年活体供肾移植术后供者安全性及受者移植效果的分析

Objective To investigate the safety for donors and the effectiveness for recipients of living-related donor (LRD) kidney transplantation from elder donors. Methods 251 cases of LRD kidney transplantation were reviewed. According to the age of LRDs, the patients were divided into 2 groups:≥55 years group (group A) and <55 years (group B). The parameters studied included serum creatinine (Cr), glomerular filtration rate (GFR), creatinine clearance (Ccr), perioperative complications, average hospital stay, and acute rejection rate of LRDs and recipients were compared. Results (1)There was no significant difference in serum Cr between groups A and B at different time points (P>0.05). (2)There was no significant difference in Ccr between two groups pre-donation (P = 0.45). But at the 10th day after the donor nephrectomy, Ccr level in group A was significant lower than in group B (P<0.01). (3)Total GFR pre-donation, remaining renal GFR, and remaining renal GFR on the day 10 after donation had no significant difference in both groups A and B (P>0.05). Remaining renal GFR on the day 10 before and after donation had no significant difference in group A (P>0.05), but on the day 10 after donation that was significantly increased in group B as compared with that pre-donation (P<0.01). (4) The serum Cr of recipients at different time points after transplantation had no significant difference between two groups (P>0.05). (5) The mean hospital stay after donation of LRDs and recipients had no significant difference between two groups. (6) The incidence of recipients" acute rejection was 6.50 % (5/77) in group A, and 5.75%(10/174) in group B within 6 months after operation (P = 0.95). Conclusion Transplantations performed from the elderly donors will yield similar results from younger donors if the eider donors are evaluated or assessed as the standards.     

A study on the efficacy and safety of losartan in elderly patients with mild to moderate essential hypertension

Despite progress in the detection and treatment of hypertension the percentage of patients with controlled hypertension has failed to increase. The problem of poor blood pressure control is even more serious in elderly hypertensives than in the rest of the population. The antihypertensive drugs of the AIIRA (non-peptide angiotension II receptor antagonist) class are drugs whose use and experience are increasing and whose properties make them particularly useful in the elderly. We tried to assess the efficacy of treatment with losartan, the first AIIRA drug in a cohort of elderly patients with essential hypertension and to assess the percentage of patients achieving optimum BP control and to evaluate its safety, tolerability and metabolic effects. The intervention proved to be highly effective, achieving the anticipated blood pressure levels in the elderly in 77% of subjects after a 16-week follow-up, with very good tolerability. Renal function remained unchanged, as did the subjects' lipid profile.     

Renal dysfunction but not cystic change is ameliorated by neonatal epidermal growth factor in bpk mice

BALB/c mice homozygous for the bpk gene exhibit a form of autosomal recessive (AR) polycystic kidney disease (PKD) with massive collecting duct cysts, common bile duct dilation and chaotic intrahepatic bile ducts/portal triads. The combined renal and biliary pathology mimics much of the pathology seen in human ARPKD. Murine models of ARPKD generally have a reduced renal expression of epidermal growth factor (EGF) and an increased expression of EGF receptors (EGF-R). However, the role that EGF and EGF-R play in the progression of PKD has been unclear. Evidence from various model systems/ages of treatment produces conflicting results. Treating neonatal C57BL/6J-cpk mice with EGF ameliorates the renal pathology and dysfunction while treating 2- and 3-week-old bpk mice with an EGF-receptor tyrosine kinase inhibitor also ameliorates ARPKD. Therefore, to determine whether neonatal EGF treatment would accelerate or inhibit the progression of the PKD in bpk mice, we administered exogenous EGF (1 μg/g body weight subcutaneously) daily from postnatal days 3–9 (a critical period for tubule maturation). Neonatal EGF treatment but not sham treatment retarded the development of azotemia and common bile duct dilation and the chaotic hepatic triad changes in cystic mice. However, EGF treatment neither reduced the severity of the renal cystic pathology nor reduced the degree of cystic enlargement of the kidneys. Cystic mice treated past 9 days of age died prior to their scheduled termination at 21 days of age. The role of EGF in the progression of polycystic kidney disease in bpk mice is relatively complicated, with neonatal treatment being associated with some amelioration of the renal dysfunction and extrarenal pathology without an effect on the renal pathology. Continuation of treatment beyond 9 days increased morbidity. Therefore, in discussing the role of EGF or EGF receptor in mediating the pathophysiology of PKD, the stage of development may be an important consideration. Received: 8 March 2000 / Revised: 29 August 2000 / Accepted: 30 August 2000     

Renal hemodynamic effect of tacrolimus in renal transplanted children

Like cyclosporine (CsA), tacrolimus acts through the inhibition of renal phosphatase calcineurin. CsA induces reversible vasoconstriction, causing a transient reduction of renal plasma flow in patients with renal transplantation. The aim of this study was to determine the effect of tacrolimus on renal plasma flow in renal transplanted children. Eight children were studied with a median age of 10.6 years, a mean glomerular filtration rate (inulin clearance) of 55 ml/min per 1.73 m² (range 29–95), and a mean follow-up after transplantation of 5.6 months. Effective renal plasma flow (ERPF) was studied in each patient for 12 h after tacrolimus administration. Clearan- ces were obtained every 2 h for 12 h after drug administration. Tacrolimus pharmacokinetics was also studied. Average ERPF at the start of the test was 289 ml/min per 1.73 m² (range 177–404, SD±106). Variation in each of the 2-h periods was not significant, although a mild reduction of plasma flow was observed in three of the eight children. No correlation was found between tacrolimus AUC, peak, or trough levels and renal blood flow variations. Despite the relatively small number of patients studied, these data suggest that, in vivo, a therapeutic oral dose of tacrolimus is not necessarily followed by a significant reduction of ERPF in renal transplanted children. Received: 15 November 2000 / Revised: 3 April 2001 / Accepted: 16 May 2001