Patrick Saudan

IV N-Acetylcysteine and Emergency CT: Use of Serum Creatinine and Cystatin C as Markers of Radiocontrast Nephrotoxicity

OBJECTIVE The purpose of this study was to assess the effect of i.v. administration of N-acetylcysteine (NAC) on serum levels of creatinine and cystatin C, two markers of renal function, in patients with renal insufficiency who undergo emergency contrast-enhanced CT. SUBJECTS AND METHODS Eighty-seven adult patients with renal insufficiency who underwent emergency CT were randomized to two groups. In the first group, in addition to hydration, patients received a 900-mg injection of NAC 1 hour before and another immediately after injection of iodine contrast medium. Patients in the second group received hydration only. Serum levels of creatinine and cystatin C were measured at admission and on days 2 and 4 after CT. Nephrotoxicity was defined as a 25% or greater increase in serum creatinine or cystatin C concentration from baseline value. RESULTS A 25% or greater increase in serum creatinine concentration was found in nine (21%) of 43 patients in the control group and in two (5%) of 44 patients in the NAC group (p = 0.026). A 25% or greater increase in serum cystatin C concentration was found in nine (22%) of 40 patients in the control group and in seven (17%) of 41 patients in the NAC group (p = 0.59). CONCLUSION On the basis of serum creatinine concentration only, i.v. administration of NAC appears protective against the nephrotoxicity of contrast medium. No effect is found when serum cystatin C concentration is used to assess renal function. The effect of NAC on serum creatinine level remains unclear and may not be related to a renoprotective action.

Risk factors for early failure of native arteriovenous fistulas.

Introduction: Current guidelines recommend native arteriovenous fistulas (AVF) as the vascular access of choice for hemodialysis on account of the lower incidence of complications. However, this kind of vascular access has a high rate of early failure (early thrombosis or non-maturation). Our aim was to examine whether clear risk factors for early AVF failure could be identified in our patients. Subjects and Methods: Data of all patients who underwent creation of an AVF at the Geneva University Hospital from January 1998 to December 2002 were reviewed. Early failure was defined as a non-functioning fistula (thrombosis or absence of fistula maturation). Results: 119 patients underwent the creation of 148 native AVF, 88 (59.5%) in the forearm and 60 (40.5%) in the upper arm. 48 (32.4%) fistulae were created in diabetic patients. In a multiple logistic regression analysis, significant predictive factors of early failure were a distal location (adjusted odds ratio (aOR) = 8.21, 95% CI = 2.63–25.63, p < 0.001), female gender (aOR = 4.04, 95% CI = 1.44–11.30, p = 0.008), level of surgical expertise (aOR = 3.97, 95% CI = 1.39–11.32, p = 0.010) and diabetes mellitus (aOR = 3.19, 95% CI = 1.17–8.71, p = 0.024). Conclusion: Early failure of AVF occurs mainly in forearm sites among women and diabetic patients. Surgical expertise has also a significant influence. These results suggest that selection of a distal site for a native AVF has to be rigorously made for women and diabetic patients and that surgeon’s dedication is of primary importance to avoid early AVF failure occurrence.

Renal replacement therapy in acute kidney injury: controversy and consensus.

Renal replacement therapies (RRTs) represent a cornerstone in the management of severe acute kidney injury. This area of intensive care and nephrology has undergone significant improvement and evolution in recent years. Continuous RRTs have been a major focus of new technological and treatment strategies. RRT is being used increasingly in the intensive care unit, not only for renal indications but also for other organ-supportive strategies. Several aspects related to RRT are now well established, but others remain controversial. In this review, we review the available RRT modalities, covering technical and clinical aspects. We discuss several controversial issues, provide some practical recommendations, and where possible suggest a research agenda for the future.

Long-term prognosis after acute kidney injury requiring renal replacement therapy

BACKGROUND Data on the long-term survival and renal function of patients with acute kidney injury (AKI) treated with continuous renal replacement therapy are scarce. METHODS We investigated the 3-year survival and need for chronic dialysis in critically ill patients, who had survived an episode of AKI requiring continuous renal replacement therapy. RESULTS A total of 206 ICU patients with AKI were randomized in a trial comparing haemofiltration versus haemodiafiltration. Of these, 95 (46%) survived at 90 days. Post-discharge information relating to 3-year survival and renal function was successfully obtained in 89 (94%) of the patients. Of the 89 patients studied, chronic kidney disease (CKD) was present in 32 subjects from the onset, and CKD developed de novo in 25 patients following AKI. End-stage renal disease (ESRD) developed in 9 patients (of whom 8 had pre-existing CKD) and 29 patients died. Three-year survival was 67% overall; the mortality at 3 years was 50% for those with pre-existing kidney disease, and 71 and 82% for those with de novo and without CKD, respectively. CONCLUSION After an episode of AKI necessitating a continuous renal replacement therapy, rapid progression to ESKD is commonly observed in patients with pre-existing chronic renal impairment. Medical care with an emphasis on nephroprotection is necessary in these patients.

Celecoxib versus ibuprofen in the prevention of heterotopic ossification following total hip replacement: A PROSPECTIVE RANDOMISED TRIAL

We examined whether a selective cyclooxygenase-2 (COX-2) inhibitor (celecoxib) was as effective as a non-selective inhibitor (ibuprofen) for the prevention of heterotopic ossification following total hip replacement. A total of 250 patients were randomised to receive celecoxib (200 mg b/d) or ibuprofen (400 mg t.d.s) for ten days after surgery. Anteroposterior radiographs of the pelvis were examined for heterotopic ossification three months after surgery. Of the 250 patients, 240 were available for assessment. Heterotopic ossification was more common in the ibuprofen group (none 40.7% (50), Brooker class I 46.3% (57), classes II and III 13.0% (16)) than in the celecoxib group (none 59.0% (69), Brooker class I 35.9% (42), classes II and III 5.1% (6), p=0.002). Celecoxib was more effective than ibuprofen in preventing heterotopic bone formation after total hip replacement.

Epoetin administrated after cardiac surgery: effects on renal function and inflammation in a randomized controlled study

BackgroundExperimentally, erythropoietin (EPO) has nephroprotective as well as immunomodulatory properties when administered after ischemic renal injury. We tested the hypothesis that different doses of recombinant human EPO administered to patients after cardiac surgery would minimize kidney lesions and the systemic inflammatory response, thereby decreasing acute kidney injury (AKI) incidence.MethodsIn this double-blinded randomized control study, 80 patients admitted to the ICU post-cardiac surgery were randomized by computer to receive intravenously isotonic saline (n = 40) versus α-Epoetin (n = 40): either 40000 IU (n = 20) or 20000 IU (n = 20). The study lasted one year. The primary outcome was the change in urinary NGAL concentration from baseline and 48 h after EPO injection. Creatinine, cystatine C and urinary NGAL levels were measured on the day of randomization and 2–4 days after EPO injection. To assess acute inflammatory response, serum cytokines (IL6 and IL8) were measured at randomization and four days after r-HuEPO injection. Patients and care-takers were blinded for the assignment.ResultsNo patient was excluded after randomization. Patient groups did not differ in terms of age, gender, comorbidities and renal function at randomization. The rate of AKI assessed by AKIN criteria was 22.5% in our population. EPO treatment did not significantly modify the difference in uNGAl between 48 hours and randomization compared to placebo [2.5 ng/ml (−17.3; 22.5) vs 0.7 ng/ml (−31.77; 25.15), p = 0.77] and the incidence of AKI was similar. Inflammatory cytokines levels were not influenced by EPO treatment. Mortality and hospital stays were similar between the groups and no adverse event was recorded.ConclusionIn this randomized-controlled trial, α-Epoetin administrated after cardiac surgery, although safe, demonstrated neither nephroprotective nor anti-inflammatory properties.Trial registration numberNCT00676234

Olfactory function improves following hemodialysis

Olfactory function has been shown to be affected in chronic kidney disease; however, studies are contradictory and little is known on the effects of dialysis. To resolve these issues we tested olfactory function in 24 healthy controls and in 28 patients with chronic kidney disease receiving hemodialysis (20 patients) or peritoneal dialysis (the other 8). As assays for olfactory function we measured smell identification, n-butanol and acetic acid thresholds, Kt/V urea, percentage reduced urea, and weights before and after dialysis. Olfactory function was also self-rated by the participants. Compared to healthy controls, predialysis olfactory function was moderately but significantly decreased in the two dialysis groups, with hemodialysis patients being more affected. Patients self-rated olfactory function similar to that of healthy controls, suggesting that patients are unaware of the olfactory decrease. Olfactory function was significantly improved by one hemodialysis session. Neither body mass index, total volume loss, nor any other dialysis parameter correlated with olfactory function or its restitution following hemodialysis. The observed pattern of improvement suggests underlying mixed peripheral and central mechanisms. Thus, olfactory dysfunction in patients with chronic kidney disease is readily reversible by hemodialysis.

Prognosis of acute kidney injury requiring renal replacement therapy in solid organ transplanted patients.

Solid organ transplanted patients represent a complex and multi‐morbid population with potential acute illness. They are at high risk not only for chronic renal failure (CRF), but also for acute kidney injury (AKI) and little is known about the overall epidemiology or prognosis. We conducted a retrospective review of all solid organ transplant patients who required emergency renal replacement therapy (RRT) for AKI during a period of 7.5 years. We identified 53 episodes of AKI requiring RRT occurring in 51 transplanted patients, and 58.5% of them were freshly (<48 h) transplanted when admitted in ICU. The majority of episodes were a result of cardio‐circulatory or septic events (84%), and a large proportion of the AKI episodes were a result of multifactorial causes (27%). Overall 90 days mortality was 49%, and no difference was detected between kidney and nonkidney transplants. On univariate analysis, the risk factors for death were smoking status [OR = 4.09 (CI 95%: 1.16–14.43); P = 0.028] and sepsis [OR = 4.90 (CI95%: 1.39–17.31); P = 0.014]. Transplanted patients with AKI are younger, more prone to be diabetic and to have previous chronic renal failure compared with the general ICU population, possibly in part because of their immunosuppressive therapy. Nevertheless, they have the same prognosis.

Contribution of interferon-γ release assays (IGRAs) to the diagnosis of latent tuberculosis infection after renal transplantation.

Background Renal transplant recipients (RTRs), as all immunosuppressed patients, are at increased risk of reactivating latent tuberculosis infection (LTBI). Detecting LTBI in this population is therefore important to prevent active TB. The tuberculin skin test (TST) has a poor sensitivity in this setting. Methods The aim of this prospective study was to compare the diagnostic performance of the TST and two interferon-&ggr; release assays (IGRAs): T-SPOT.TB (Oxford Immunotec, Oxford, UK) and QuantiFERON Gold In-Tube (QGIT; Cellestis, Australia), performed simultaneously, for the detection of patients with risk factors for LTBI or a definite history of TB among RTRs under stable immunosuppression. Results Two hundred five patients (ages 59±13 years, tested 10.4±7.1 years after transplantation) were studied. Positivity rate was 4.5% for TST, 20.5% for T-SPOT.TB, and 23.5% for QGIT. Agreement between IGRAs was fair (&kgr;=0.71). Sensitivity of T-SPOT.TB and QGIT for detection of prior active TB was 55.6% (95% confidence interval [CI], 21.2–86.3) and 44.4 (95% CI, 13.7–78.8), respectively. Sensitivity of both IGRAs for detection of risk factors for LTBI was 33.3% (95% CI, 19.6–49.5). Specificity was 85.5% (95% CI, 78.9–90.7) for T-SPOT.TB and 80.1% (95% CI, 72.9–86.2) for QGIT. Combining IGRAs did not significantly improve sensitivity. Conclusions Because their sensitivity for detecting prior active TB and probable LTBI in RTRs is very low, IGRAs cannot be used to exclude LTBI. These results emphasize the limitations of IGRAs in the setting of chronic immunosuppressive therapy.

Increased Synthesis of Liver Erythropoietin with CKD

Anemia of CKD seems to be related to impaired production of renal erythropoietin (Epo). The glycosylation pattern of Epo depends on the synthesizing cell and thus, can indicate its origin. We hypothesized that synthesis of Epo from nonkidney cells increases to compensate for insufficient renal Epo production during CKD. We determined plasma Epo levels and Epo glycosylation patterns in 33 patients with CKD before undergoing dialysis and nine patients with CKD undergoing dialysis. We compared these values with values obtained in healthy volunteers and other controls. Although patients with CKD before undergoing dialysis had median (interquartile range) Epo levels higher than those of healthy controls (13.8 IU/L; interquartile range, 10.0-20.7 IU/L versus 8.4 IU/L; interquartile range, 7.6-9.0 IU/L; P<0.01), these patients were moderately anemic (mean±SD; hemoglobin =118±17 g/L). Detected as the percentage of migrated isoforms (PMI), Epo glycosylation in patients with CKD before undergoing dialysis (PMI=36.1±11.7%) differed from that in healthy controls (PMI=9.2±3.8%; P<0.01) but not from that in umbilical cord plasma (PMI=53.9±10.6%; P>0.05), which contains mainly liver-derived Epo. Furthermore, glycosylation modification correlated with eGFR loss. These results suggest that patients with CKD maintain persistent Epo synthesis despite declining renal function, and this maintenance may result in part from increased liver Epo synthesis.