Evaluating candidates for kidney transplantation: some recommendations still lack convincing clinical evidence.

Sir, The paper by Zeier and Ritz in the April 2002 issue of NDT [1]is a good reminder of the importance of evaluation and selectionof kidney transplant candidates. Also, this paper clearly demonstratesthe persisting lack of clinical evidence in this field, whichhas considerable impact on large numbers of end-stage renaldisease patients. We have previously demonstrated the unexplained variations inthe evaluation     

Reports of Large Immunosuppression Trials in Kidney Transplantation: Room for Improvement

The reporting quality of publications of clinical trials can affect the quality of clinical decision-making. We systematically assessed the quality of publications of large multicenter trials evaluating immunosuppressive regimens in de novo kidney transplantation. Study quality, reporting quality and accessibility of the results of 63 publications were assessed independently by three blinded investigators using an instrument combining the Jadad scale with a list of reporting quality items. Study quality was rated with an average of only 2.3 (range 1-5) on the Jadad scale. Unblinded studies were reported in 68.3% of publications and follow-up longer than 12 months was reported for only 13 out of 50 studies. The reviewed publications fulfilled an average of 69.1% of the reporting quality criteria. Fifty-four percent of publications did not report both treated and biopsy-proven rejections. Whether reported graft survival was censored for death could not be determined for 27% of publications. Only a few publications gave confidence intervals (CIs) or stated whether additional analyses were pre-specified. Even the largest trials of immunosuppression in kidney transplantation show considerable quality deficits in their design and publication. Additional efforts are required of investigators, editors and sponsors to achieve maximum study and reporting quality.     

Trends and Predictors for Vagotomy When Performing Oversew of Acute Bleeding Duodenal Ulcer in the United States

Background In the era of Helicobacter pylori treatment, the role of vagotomy in bleeding duodenal ulcers is debatable. National outcomes were evaluated to determine the current surgical treatment and use of vagotomy for bleeding duodenal ulcers. Methods Data from the Nationwide Inpatient Sample (NIS) were used from years 1999 to 2003. Patients were selected using diagnostic codes for acute duodenal ulcer bleed and procedure codes for simple oversew of a bleeding ulcer and vagotomy. Data were analyzed using multiple linear and logistic regression. Results Between 1999 and 2003, 100,931 patients with an acute bleeding duodenal ulcer were identified. Over time, there was a decrease in the number of acute bleeding ulcers (p = 0.027) and a decrease in the number of vagotomies (p = 0.027). A high co-morbidity index [odds ratio (OR), 0.60, p = 0.017], operation in the Midwest (OR 0.50, p < 0.001) and operation in the West (OR 0.68, p = 0.034) were predictive of no vagotomy during surgery for a bleeding duodenal ulcer. Conclusions A vagotomy is not commonly performed during surgical treatment of an acute bleeding duodenal ulcer. This variation in practice was not fully explained by patient characteristics. We must seek new evidence to determine the safety of combined medical and surgical management of this clinical problem. Presented at DDW/SSAT May 20–24, Los Angeles, California.     

Paracrine renal endothelin system in rats with liver cirrhosis.

1. Liver cirrhosis was induced in rats by CCl4 administration. We analysed the expression of endothelin receptor subtypes in the renal cortex and medulla using Scatchard analysis and receptor autoradiography, and measured plasma as well as renal-tissue endothelin-1 concentrations using a specific radioimmunoassay. Furthermore, we analysed the effects of the non-selective (A/B) endothelin receptor antagonist, bosentan (6 and 100 mg kg-1 day-1) on mean arterial blood pressure, water and sodium excretion and glomerular filtration rate. 2. Our study revealed an overexpression of the endothelin B receptor (ETB) in the renal medulla of rats with liver cirrhosis (Cir: 2775 +/- 299 fmol mg-1; Con: 1695 +/- 255 fmol mg-1; n = 8; means +/- s.d., P < 0.01), whereas the density of ETB in the cortex and the endothelin A receptor (ETA) in the cortex and medulla were similar in both cirrhotic and control rats. Receptor autoradiography showed that the upregulation of medullary ETB in cirrhotic rats was due to an upregulation of ETB in the inner medullary collecting duct cells. 3. The tissue endothelin-1 concentrations were increased in the renal medulla of cirrhotic rats (Cir: 271 +/- 68 pg g-1wet wt.; Con: 153 +/- 36 pg g-1 wet wt., n = 8; means +/- s.d., P < 0.01). 4. The glomerular filtration rate was slightly decreased in cirrhotic rats but not altered after bosentan treatment in either cirrhotic or control rats. Bosentan decreased sodium excretion to a similar extent in both cirrhotic and control rats, whereas water excretion was significantly reduced by both dosages of bosentan in cirrhotic rats only (Cir + vehicle: 12.5 +/- 0.62 m day-1, Cir + 6 mg kg-1 day-1 bosentan: 8.6 +/- 1.0 ml day-1; Cir + 100 mg kg-1 day-1 bosentan: 7.4 +/- 0.6 ml day-1; n = 10; means +/- s.e.mean). 5. We therefore suggest that the upregulation of the medullary ETB in cirrhotic rats is involved in the regulation of water excretion in rats with CCl4-induced liver cirrhosis.     

Impaired sodium excretion, decreased glomerular filtration rate and elevated blood pressure in endothelin receptor type B deficient rats

The renal endothelin (ET) system, particularly the ET type B receptor, has been implicated in the regulation of sodium excretion and glomerular filtration rate (GFR). We analyzed kidney morphology and function in a rat strain characterized by complete absence of a functional ETB receptor. Due to Hirschsprung's disease limiting lifetime in these rats, studies were performed in 23-day-old rats. Kidney size and morphology (glomerular and interstitial matrix content, glomerular size and cell density and intrarenal vascular morphology) were normal in ETB-deficient rats. There were also no evidence of altered kidney cell cycle regulation in these rats. GFR was significantly lower, by 72% (P<0.001), in homozygous ETB-deficient rats than in wild-type rats. Fractional sodium excretion was likewise markedly reduced by 84% in homozygous ETB-deficient rats (P<0.001 versus wild-type rats). Treatment with the specific epithelial sodium channel blocker amiloride led to a much higher increase in fractional sodium excretion in ETB-deficient rats (934.2+/-73% in ETB-deficient rats versus 297+/-20% in wild-type rats, expressed as percentage of corresponding placebo treated control; P<0.001). Mean arterial blood pressure was elevated by 7.9 mmHg in homozygous ETB-deficient rats (P<0.05 versus wild-type rats). Our study demonstrates that ETB-deficiency causes early onset kidney dysfunction characterized by a markedly reduced sodium excretion, decreased GFR, and slightly elevated blood pressure. The complete absence of the ETB receptor causes in the kidney--in contrast to the colon--a functional rather than a developmental, neural crest cell dependent disease, since kidney morphology was normal in ETB-deficient rats. The much higher increase in the fractional sodium excretion in ETB-deficient rats after pharmacological blockade of the epithelial sodium channel indicates that the decreased fractional sodium excretion in ETB-deficient rats is most probably due to a lack of the inhibitory property of the ETB receptor on the epithelial sodium channel activity.     

Endoscopic transthoracic sympathectomy: current indications and techniques

Zusammenfassung GRUNDLAGEN: Die endoskopische thorakale Sympathektomie (ETS) existiert seit 60 Jahren als effektive Therapie der primären Hyperhidrose. Nach wie vor gibt es in der medizinischen Welt teils Vorbehalte, teils Unwissen über die Methode selbst, ihre Erfolgs- und Komplikationsraten sowie Nebenwirkungen. METHODIK: Nach Einführung in die Symptome und Behandlung der primären Hyperhidrose (konservativ und chirurgisch) werden Operationsmethoden und Langzeitergebnisse der ETS-Operation vorwiegend anhand der Daten aus der eigenen Abteilung präsentiert. ERGEBNISSE: Von 1965–2001 wurden 734 Sympathikotomien (ETS2–4) und bis 2003 weitere 103 Sympathikusblockaden (ESB4) bei Patienten mit primärer palmarer und axillärer Hyperhidrose durchgeführt. Die Konversionsrate betrug 0,1 %. Seit Einführung der Video-Thorakoskopie 1991 trat kein postoperatives Horner-Syndrom auf (zuvor 2,2 %), Drainage-pflichtige Pneumothoraces waren in 1,1 % zu verzeichnen. Nach einem medianen Follow-up von 16 Jahren waren 93 % der Extremitäten trocken, 5 % fast trocken und 2 % feucht. Nebenwirkungen traten in Form von kompensatorischem Schwitzen am Stamm (55 % insgesamt, davon 5 % stark) und gustatorischem Schwitzen (33 %) auf. Seit Einführung der limitierten Sympathikusblockade auf Höhe T4 (ESB4) konnte (bei naturgemäß kurzer Nachbeobachtungszeit) das kompensatorische Schwitzen auf 8,5 % und das gustatorische Schwitzen auf 2,1 % gesenkt werden. Mit dem postoperativen Ergebnis waren 100 % der Patienten nach ESB4 zufrieden, nach ETS2–4 waren 80 % zufrieden, 14 % teilweise zufrieden und 6 % unzufrieden (meist wegen starken kompensatorischen Schwitzens). SCHLUSSFOLGERUNGEN: Die ETS-Operation bietet hohe langfristige Erfolgsraten bei niedrigen Komplikationsraten. Patienten sollten über die zu erwartenden Nebenwirkungen genau aufgeklärt werden, für unzufriedene Patienten mit starkem kompensatorischem Schwitzen besteht nun die Möglichkeit der thorakoskopischen Klip-Entfernung.     

The sympathetic trunk and its neural pathway to the upper limb: review of the literature

Zusammenfassung GRUNDLAGEN: Kenntnisse der Anatomie des Truncus sympathicus und des autonomen Nervensystems sind von großer Bedeutung in der Sympathikuschirurgie. Allerdings existiert eine Vielzahl an unterschiedlichen sympathischen Nervenverbindungen zur oberen Extremität, wobei der Großteil im ersten Zwischenrippenraum zu liegen kommt. Aus unterschiedlichsten Gründen führt die chirurgische Sympathektomie im Bereich der oberen thorakalen Ganglien zu einer Unterbrechung der sympathischen Innervation der oberen Extremität. Entscheidend ist, diese variablen Verbindungen zu durchtrennen, um optimale chirurgische Ergebnisse zu erzielen. METHODIK: Diese Arbeit basiert auf einer Durchsicht der Literatur der letzten 80 Jahre über die Anatomie des kranialen thorakalen Truncus sympathicus und seiner Verbindungen, die in der Sympathikuschirurgie von besonderer Bedeutung sind. Die Evaluation basiert auf einer Literaturrecherche in der Medline, ergänzt um Wissen aus Anatomiebüchern; es wird zudem eine Übersicht über die historische Entdeckung des sympathischen Systems gegeben. ERGEBNISSE: Zwei wichtige Ergebnisse liegen vor. 1. Intrathorakale Nervenverbindungen zwischen zweitem und erstem intrathorakalen Nerv dürften sympathische Fasern der oberen Extremität zuführen. Diese Verbindungen kommen bei mehr als 50 % der Menschen vor und dürften für Misserfolge und/oder Rezidive nach Sympathektomie verantwortlich sein. 2. Aktuelle chirurgische Studien weisen darauf hin, dass das Hauptganglion für die sympathische Innervation der oberen Extremität im Segment T4 liegen könnte. Dies steht jedoch im Gegensatz zur bisher anerkannten Ansicht, dass das Hauptganglion der sympathischen Innervation für die obere Extremität das T2-Ganglion sei. Bislang können diese klinischen Erkenntnisse nicht durch anatomisches Wissen erklärt werden. SCHLUSSFOLGERUNGEN: Profunde anatomische Kenntnisse sind eine unabdingbare Voraussetzung, um in der Sympathikuschirurgie optimale Ergebnisse zu erzielen.