Liver transplant outcome: a comparison between high and low MELD score recipients

OBJECTIVE: To compare low and high MELD scores and investigate whether existing renal dysfunction has an effect on transplant outcome. METHODS: Data was prospectively collected among 237 liver transplants (216 patients) between March 2003 and March 2009. Patients with cirrhotic disease submitted to transplantation were divided into three groups: MELD > 30, MELD < 30, and hepatocellular carcinoma. Renal failure was defined as a ± 25% decline in estimated glomerular filtration rate as observed 1 week after the transplant. Median MELD scores were 35, 21, and 13 for groups MELD > 30, MELD < 30, and hepatocellular carcinoma, respectively. RESULTS: Recipients with MELD > 30 had more days in Intensive Care Unit, longer hospital stay, and received more blood product transfusions. Moreover, their renal function improved after liver transplant. All other groups presented with impairment of renal function. Mortality was similar in all groups, but renal function was the most important variable associated with morbidity and length of hospital stay. CONCLUSION: High MELD score recipients had an improvement in the glomerular filtration rate after 1 week of liver transplantation.

Standard surgical treatment for benign prostatic hyperplasia is safe for patients over 75 years: analysis of 100 cases from a high-volume urologic center

OBJECTIVES: In this study, we aimed to determine the complications of standard surgical treatments among patients over 75 years in a high-volume urologic center. METHODS: We analyzed 100 consecutive patients older than 75 years who had undergone transurethral prostatic resection of the prostate or open prostatectomy for treatment of benign prostatic hyperplasia from January 2008 to March 2010. We analyzed patient age, prostate volume, prostate-specific antigen level, international prostatic symptom score, quality of life score, urinary retention, co-morbidities, surgical technique and satisfaction with treatment. RESULTS: Median age was 79 years. Forty-eight patients had undergone transurethral prostatic resection of the prostate, and 52 had undergone open prostatectomy. The median International Prostatic Symptom Score was 20, the median prostate volume was 83 g, 51% were using an indwelling bladder catheter, and the median prostatespecific antigen level was 5.0 ng/ml. The most common comorbidities were hypertension, diabetes and coronary disease. After a median follow-up period of 17 months, most patients were satisfied. Complications were present in 20% of cases. The most common urological complication was urethral stenosis, followed by bladder neck sclerosis, urinary fistula, late macroscopic hematuria and persistent urinary incontinence. The most common clinical complication was myocardial infarction, followed by acute renal failure requiring dialysis. Incidental carcinoma of the prostate was present in 6% of cases. One case had urothelial bladder cancer. CONCLUSIONS: Standard surgical treatments for benign prostatic hyperplasia are safe and satisfactory among the elderly. Complications are infrequent, and urethral stenosis is the most common. No clinical variable is associated with the occurrence of complications.

Untersuchung der Pharmakokinetik von Ciprofloxacin und Piperacillin bei Intensivpatienten mit kontinuierlichen Hämodialyseverfahren

Infektionen zählen bei hämodialysepflichtigen Intensivpatienten zu den häufigsten Todesursachen. Um die Wirksamkeit und Sicherheit der Antibiotikatherapie zu verbessern, müssen verschiedene Faktoren, zum Beispiel die Pharmakodynamik und Pharmakokinetik des Antibiotikums, die Art des Hämodialyseverfahrens, die Art des Dialysefilters und der Zustand des Patienten berücksichtigt werden. Im Rahmen einer klinischen Studie wurde die antibiotische Wirkung von Piperacillin und Ciprofloxacin bei kontinuierlichen Hämodialyseverfahren mittels pharmakokinetischer Methoden bestimmt.Für die klinische Studie wurde eine HPLC-Methode mit kombinierter Festphasenextraktion (SPE) entwickelt und nach den Grenzwerten der EMA Guideline on Bioanalytical Method Validation validiert. Die Methode erwies sich für die gleichzeitige Bestimmung von Piperacillin und Ciprofloxacin in Plasma- und Dialysatproben als valide und zuverlässig. Die ermittelten Konzentrationen der beiden Antibiotika wurden für die Berechnung der pharmakokinetischen Parameter verwendet.In der klinischen Studie wurden bei 24 Intensivpatienten mit kontinuierlicher venovenöser Hämodialyse (CVVHD) bzw. kontinuierlicher venovenöser Hämodiafiltration (CVVHDF), bei denen Piperacillin/Tazobactam, Ciprofloxacin oder eine Kombination dieser Antibiotika indiziert war, die Antibiotikakonzentrationen im Plasma und Dialysat im Steady State gemessen. Unmittelbar vor einer Antibiotikainfusion (0 min) wurde ein Volumen von sechs Milliliter Blut entnommen. Weitere Blutentnahmen erfolgten 30 Minuten nach der Infusion sowie nach 1, 2, 3, 4, 8, 12 und 24 Stunden. Sobald ein Filtratbeutel ausgetauscht wurde, wurden parallel zu den Blutproben Dialysatproben entnommen. Die Konzentrationen von Piperacillin und Ciprofloxacin wurden nach der Festphasenextraktion aus den Plasmaproben mit der validierten HPLC-Methode innerhalb von 15 Minuten zuverlässig bestimmt. Neben den gemessenen Plasmakonzentrationen (Cmax, Cmin) wurden pharmakokinetische Parameter wie t0,5, VdSS, AUC, Cltot, ClCRRT und Clextrarenal berechnet. Für Piperacillin wurde untersucht, ob die Plasmaspiegel der Patienten für das gesamte Dosierungsintervall oberhalb der geforderten vierfachen MHK von 64 mg/l liegen. Für Ciprofloxacin wurde untersucht, ob die aus gemessenen Plasmaspiegeln berechnete AUC den Quotienten aus AUC und MHK (=AUIC) ≥ 125 h erfüllt.Bei zehn der 21 mit Piperacillin behandelten Patienten lagen die Plasmaspiegel unterhalb der angestrebten Konzentration von 64 mg/l für das gesamte Dosierungsintervall. Das Patientenkollektiv wies eine große interindividuelle Variabilität auf. Mit einer Wahrscheinlichkeit von 95 % waren 26 - 70 % der Patienten unterdosiert. In der Gruppe der mit Ciprofloxacin behandelten Patienten wurde die angestrebte AUIC von 125 h nur bei neun der 20 Patienten erreicht. Mit einer Wahrscheinlichkeit von 95 % waren 29 - 76 % der Patienten unterdosiert. Die kontinuierlichen Nierenersatzverfahren hatten nur einen geringen Anteil an der totalen Clearance der untersuchten Antibiotika. Während die Clearance des kontinuierlichen Nierenersatzverfahren bei Piperacillin für ein Drittel der Arzneistoffelimination verantwortlich war, trug diese im Fall von Ciprofloxacin lediglich zu 16 % zur Arzneistoffelimination bei.Die Dosierung von Piperacillin/Tazobactam bzw. Ciprofloxacin sollte bei kritisch kranken Intensivpatienten mit kontinuierlicher Hämodialyse mindestens 4 mal 4/0,5 g pro Tag bzw. 2 mal 400 mg pro Tag betragen. Diese Empfehlungen sind insbesondere für die verwendeten Dialyseverfahren und -bedingungen zutreffend. Zur weiteren Optimierung der Antibiotikatherapie ist ein Therapeutisches Drug Monitoring empfehlenswert.

Outcome a lungo termine dei pazienti pediatrici con rene singolo. Valutazione di marker laboratoristici e strumentali di danno renale

Obiettivi: valutare in pazienti con rene singolo congenito la correlazione tra il filtrato glomerulare misurato con il DTPA (DTPA-VFG) e 1) marker laboratoristici di danno renale (creatinina, cistatinaC, proteinuria) 2) formule per stimare il filtrato glomerulare 3) parametri di valutazione della crescita renale ecografica. Materiali e metodi: Sono stati arruolati 118 pazienti con rene singolo congenito tra 0 e 18 anni. Sono stati valutati a ogni visita altezza, creatinina, cistatinaC, proteinuria e lunghezza ecografica renale. E’ stato calcolato il filtrato stimato con formule basate sulla creatinina (Schwartz), sulla cistatina C (Zappitelli, Filler, Grubb e Bokenkamp) e su entrambe (equazione di Zappitelli). La crescita renale è stata valutata come rapporto lunghezza ecografica/altezza corporea (USL/H), differenza percentuale tra lunghezza renale misurata e attesa per età (delta%) e presenza o meno d’ipertrofia compensatoria. In 74 bambini è stata misurata la DTPA-VFG. Risultati: Il follow-up è di 2.1 ± 0.9 anni. Il 65% sono maschi. Nessun paziente ha sviluppato danno renale cronico. La media del DTPA-VFG era di 135±44ml/min/1.73m², il valore medio della creatinina 0.47±0.17mg/dl e di cistatinaC di 1±0.4mg/L. La lunghezza ecografica renale media era di 100±17 mm, il rapporto USL/H medio di 0.8±0,1 e il delta% di 1,13±11,4, il 66% presentava ipertrofia renale. Le uniche correlazioni significative con DTPA-VFG sono inversa con la creatinina (p=<.001) e lineare con USL/H (p=<.001). Discussione: Lo studio ha mostrato che come per altre nefrouropatie, la creatina e l’ecografia renale siano due strumenti validi per il follow-up dei pazienti con rene singolo congenito. Il limite principale è dovuto al fatto che nessuno dei pazienti ha sviluppato danno renale cronico e pertanto non è stato possibile stabilire dei cutt-off di rischio per parametri quali USL/H.

Retrospective analysis of patients for development of nephrogenic systemic fibrosis following conventional angiography using gadolinium-based contrast agents

The purpose was to retrospectively review the data of 27 patients with renal insufficiency who underwent conventional angiography with gadolinium-based contrast agents (GDBCA) as alternative contrast agents and assess the occurrence of nephrogenic systemic fibrosis (NSF) together with associated potential risk factors.

Hemolytic-uremic syndrome in Switzerland: a nationwide surveillance 1997-2003

Hemolytic-uremic syndrome (HUS) is a leading cause of acute renal failure in childhood. In its typical presentation, it is preceded by an episode of diarrhea mostly due to Shiga-toxin-producing Escherichia coli. There is important geographical variation of many aspects of this syndrome. Nationwide data on childhood HUS in Switzerland have not been available so far. In a prospective national study through the Swiss Pediatric Surveillance Unit 114 cases (median age 21 months, 50% boys) were reported between April 1997 and March 2003 by 38 pediatric units (annual incidence 1.42 per 10(5) children < or =16 years). Shiga-toxin-producing E. coli were isolated in 32 (60%) of tested stool samples, serotype O157:H7 in eight. Sixteen children presented with only minimal renal involvement, including three with underlying urinary tract infection. Six patients presented with atypical hemolytic-uremic syndrome, and six with HUS due to invasive Streptococcus pneumoniae infection. Mortality was 5.3%, including two out of six children with S. pneumoniae infection. The severity of thrombocytopenia and the presence of central nervous system involvement significantly correlated with mortality. In conclusion, childhood HUS is not rare in Switzerland. Contrasting other countries, E. coli O157:H7 play only a minor role in the etiology. Incomplete manifestation is not uncommon.

[Partial clinical remission of chronic IgA nephropathy with therapy of tuberculosis]

A 36-year-old patient suffered from repeated exsudative pleural effusions and renal insufficiency (serum creatinine 1.9 mg/dl) combined with glomerular erythrocyturia, proteinuria and renal hypertension.

Fondaparinux - data on efficacy and safety in special situations

New anticoagulants promise to have better efficacy, more safety and/or a better manageability than traditional anticoagulants. However, knowledge is limited regarding special situations such as renal insufficiency, obesity, pregnancy, long-term therapy, heparin-induced thrombocytopenia, treatment in patients with mechanical heart valves, use for children, and in patients with a high risk of thromboembolic complications. These situations have rarely or even never been the objective of randomised controlled trials. The purpose of the present article is to summarize and discuss available data on efficacy and safety in these special situations for one of the first new anticoagulants, the indirect factor-Xa inhibitor fondaparinux. Furthermore, we discuss safety in licensed indications and management of bleeding complications and comment on measuring of drug concentration in plasma.

Falsely high ankle-brachial index predicts major amputation in critical limb ischemia

Falsely high ankle-brachial index (ABI) values are associated with an adverse clinical outcome in diabetes mellitus. The aim of the present study was to verify whether such an association also exists in patients with chronic critical limb ischemia (CLI) with and without diabetes. A total of 229 patients (74 +/- 11 years, 136 males, 244 limbs with CLI) were followed for 262 +/- 136 days. Incompressibility of lower limb arteries (ABI > 1.3) was found in 45 patients, and was associated with diabetes mellitus (p = 0.01) and renal insufficiency (p = 0.035). Limbs with incompressible ankle arteries had a higher rate of major amputation (p = 0.002 by log-rank). This association was confirmed by multivariate Cox regression analysis (relative risk [RR] 2.67; 95% CI 1.27-5.64, p = 0.01). The relationship between ABI > 1.3 and amputation rate persisted after subjects with diabetes and renal insufficiency had been removed from the analysis (RR 3.85; 95% CI 1.25-11.79, p = 0.018). Dividing limbs with measurable ankle pressure according to tertiles of ABI, the group in the second tertile (0.323 < or = ABI < or = 0.469) had the lowest amputation rate (4/64, 6.2%), and a U-shaped association between the occurrence of major amputation and ABI was evident. No association was found between ABI and mortality. In conclusion, this study demonstrates that falsely high ABI is an independent predictor of major amputation in patients with CLI.

Invasive sphenoidal aspergillosis: successful treatment with sphenoidotomy and voriconazole

Treatment of invasive sphenoidal aspergillosis is surgical, followed by antifungal therapy, mostly amphotericin B. To optimize the adjuvant antifungal treatment, which is often limited by severe side effects, the new triazole antifungal agent voriconazole with broad coverage of fungal pathogens including Aspergillus was investigated in a study of 4 patients with clinical, radiological and histological signs of invasive sphenoidal aspergillosis. They first underwent endoscopic sphenoidotomy with drainage and extraction of the fungal mass. Postoperatively, 2 patients were immediately treated with voriconazole. Two patients initially received amphotericin B; but this treatment had to be stopped because of acute renal toxicity. Finally, all patients were treated orally with 200 mg voriconazole twice a day for 12-14 weeks. After this combined treatment all patients were asymptomatic and there were no endoscopic or radiological signs of residual fungal disease. The only side effects were nausea in one and transient visual disturbances in 2 other patients. In the 4 patients presented and treated, voriconazole was shown to be effective and less toxic than amphotericin B in adjuvant treatment of invasive sphenoidal aspergillosis. Copyright (c) 2007 S. Karger AG, Basel.

A case report of Clarkson's disease: If you don't know it, you'll miss it

The systemic capillary leak syndrome (SCLS), also known as Clarkson's disease, is a rare disorder characterized by paroxysmal capillary hyperpermeability with a shift of plasma fluid from the intravascular to the interstitial space. A 35-year-old previously healthy woman was admitted with rapidly developing hypovolemic shock syndrome, rhabdomyolysis, and diffuse edema. Laboratory analysis revealed a severe hemoconcentration, renal insufficiency, and paraproteinemia. After exclusion of infection, allergy, burning or drug-induced conditions, the clinical presentation was consistent with the diagnosis of SCLS. Though this is a rare entity, the substantial morbidity and mortality associated with it necessitate the physician's awareness in order to provide timely therapy. This report is meant to enhance awareness of SCLS.

Paracellin-1 gene mutation with multiple congenital abnormalities

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis is an autosomal recessive renal tubular disorder characterized by renal magnesium wasting, hypercalciuria, advanced nephrocalcinosis and progressive renal failure. Mutations in the paracellin-1 (CLDN16) gene have been defined as the underlying genetic defect. The tubular disorders and progression in renal failure are usually resistant to magnesium substitution and hydrochlorothiazide therapy, but hypomagnesemia may improve with advanced renal insufficiency. We present a patient with a homozygous truncating CLDN16 gene mutation (W237X) who had early onset of renal insufficiency despite early diagnosis at 2 months. He also had additional abnormalities including horseshoe kidney, neonatal teeth, atypical face, cardiac abnormalities including coarctation of the aorta associated with atrial and ventricular septal defects, umbilical hernia and hypertrichosis. To the best of our knowledge, this is the youngest case diagnosed as familial hypomagnesemia with hypercalciuria and nephrocalcinosis and the first case having such additional congenital abnormalities independent of the disease itself.

A first case of congenital TTP on the African continent due to a new homozygous mutation in the catalytic domain of ADAMTS13

Hereditary thrombotic thrombocytopenic purpura (TTP) is a rare disorder characterized by occlusive microvascular thrombosis, consumptive thrombocytopenia, and microangiopathic hemolytic anemia. Homozygous or compound heterozygous mutations in the ADAMTS13 gene result in a congenital severe ADAMTS13 deficiency and subsequent accumulation of ultra-large von Willebrand factor multimers, which tend to form platelet thrombi in the microcirculation. We report a first case of congenital TTP on the African continent with a new, homozygous mutation in the metalloprotease domain of ADAMTS13. An initially oligo-symptomatic presentation was followed by acute exacerbation with ischemic stroke and acute renal failure highlighting the severity of this syndrome.

Modulation of chemokine gene expression by Shiga-toxin producing Escherichia coli belonging to various origins and serotypes

Infection with Shiga-toxin producing Escherichia coli (STEC) may result in the development of the haemolytic-uremic syndrome (HUS), the main cause of acute renal failure in children. While O157:H7 STEC are associated with large outbreaks of HUS, it is difficult to predict whether a non-O157:H7 isolate can be pathogenic for humans. The mucosal innate immune response plays a central role in the pathogenesis of HUS; therefore, we compared the induction of IL-8 and CCL20 in human colon epithelial cells infected with strains belonging to different serotypes, isolated from cattle or from HUS patients. No correlation was observed between strain virulence and chemokine gene expression. Rather, the genetic background of the strains seems to determine the chemokine gene expression profile. Investigating the contribution of different bacterial factors in this process, we show that the type III secretion system of O157:H7 bacteria, but not the intimate adhesion, is required to stimulate the cells. In addition, H7, H10, and H21 flagellins are potent inducers of chemokine gene expression when synthesized in large amount.

Effects of a non-selective COX inhibitor and selective COX-2 inhibitors on contractility of human and porcine ureters in vitro and in vivo

BACKGROUND AND PURPOSE: Anti-inflammatory drugs are used in the treatment of acute renal colic. The aim of this study was to investigate the effects of selective COX-2 inhibitors and the non-selective COX inhibitor diclofenac on contractility of human and porcine ureters in vitro and in vivo, respectively. COX-1 and COX-2 receptors were identified in human ureter and kidney. EXPERIMENTAL APPROACH: Human ureter samples were used alongside an in vivo pig model with or without partial ureteral obstruction. COX-1 and COX-2 receptors were located in human ureters by immunohistochemistry. KEY RESULTS: Diclofenac and valdecoxib significantly decreased the amplitude of electrically-stimulated contractions in human ureters in vitro, the maximal effect (Vmax) being 120 and 14%, respectively. Valdecoxib was more potent in proximal specimens of human ureter (EC50=7.3 x 10(-11) M) than in distal specimens (EC50=7.4 x 10(-10) M), and the Vmax was more marked in distal specimens (22.5%) than in proximal specimens (8.0%) in vitro. In the in vivo pig model, parecoxib, when compared to the effect of its solvent, significantly decreased the maximal amplitude of contractions (Amax) in non-obstructed ureters but not in obstructed ureters. Diclofenac had no effect on spontaneous contractions of porcine ureter in vivo. COX-1 and COX-2 receptors were found to be expressed in proximal and distal human ureter and in tubulus epithelia of the kidney. CONCLUSIONS AND IMPLICATIONS: Selective COX-2 inhibitors decrease the contractility of non-obstructed, but not obstructed, ureters of the pig in vivo, but have a minimal effect on electrically-induced contractions of human ureters in vitro.