Sumanth R. Daram

High-dose N-acetylcysteine for the Prevention of Contrast-induced Nephropathy

BACKGROUND Whether N-acetylcysteine is beneficial for the prevention of contrast-induced nephropathy is uncertain. METHODS We conducted a meta-analysis to evaluate the efficacy of high-dose N-acetylcysteine for the prevention of contrast-induced nephropathy. Our prespecified inclusion criteria were as follows: adult subjects; English language literature; administration of high-dose N-acetylcysteine a priori defined as a daily dose greater than 1200 mg or a single periprocedural dose (within 4 hours of contrast exposure) greater than 600 mg; prospective trials of individuals randomized to N-acetylcysteine, administered orally or intravenously, versus a control group; and trials that included the end point of the incidence of contrast-induced nephropathy. Trials that compared N-acetylcysteine with another active treatment were excluded. RESULTS Sixteen comparisons of patients randomized to high-dose N-acetylcysteine versus controls met our prespecified inclusion criteria with a total sample size of 1677 subjects (842 assigned to high-dose N-acetylcysteine and 835 assigned to the control arm). The average population age was 68 years, 38.7% were diabetic, and the majority was male (67.8% of reported instances). The weighted mean baseline creatinine of the overall population was 1.58 mg/dL. No significant heterogeneity was detected (P = .09; I(2) = 34%). The overall effect size assuming a common odds ratio revealed an odds ratio of 0.46 (95% confidence interval [CI], 0.33-0.63) for the occurrence of contrast-induced nephropathy with the use of high-dose N-acetylcysteine. The results of the more conservative random effects approach were similar (odds ratio = 0.52; 95% CI, 0.34-0.78). There was no evidence of publication bias (P = .34). CONCLUSION Our results suggest that high-dose N-acetylcysteine decreases the incidence of contrast-induced nephropathy.

Thrombotic thrombocytopenic purpura without schistocytes on the peripheral blood smear.

A hallmark of the clinical syndrome of thrombotic thrombocytopenic purpura (TTP) is evidence of microangiopathic hemolytic anemia. The presence of schistocytes on the peripheral blood smear, elevated plasma lactic dehydrogenase, and decreased haptoglobin concentration are used as evidence of microangiopathic hemolytic anemia to make a diagnosis of TTP. This report describes a case of recurrence of TTP in the absence of schistocytes in the peripheral blood smear during the recurrent episode. Although careful attention should be paid to microscopic examination of a blood smear in any patient presenting with acute renal failure and thrombocytopenia, this case emphasizes the need to consider TTP-hemolytic uremic syndrome in the differential diagnosis, even in the absence of peripheral schistocytosis.

Thyroid dysfunction and the coagulation system: the often ignored link.

The relationship between thyroid dysfunction and coagulation abnormalities has been known for a very long time. These coagulation abnormalities have been in the form of thrombotic disorders as well as bleeding diatheses. Most of the abnormalities of the coagulation system might stem from the direct action of thyroid hormones on the synthesis of coagulation factors and/or the effect of thyroid hormones on immune function. Immune disorders such as idiopathic thrombocytopenic purpura, secondary antiphospholipid antibody syndrome, and acquired hemophilia have been described in association with thyroid disorders. Coagulation disorders reported in association with thyroid dysfunction have ranged from clinically nonsignificant laboratory abnormalities to significant bleeding abnormalities and thrombotic disorders. While large, well-performed studies on the association between the type of thyroid dysfunction (hypothyroidism versus hyperthyroidism) and the clinical manifestation of the coagulation disorder (bleeding versus thrombosis) are lacking, a bleeding tendency has been noted in patients with hypothyroidism as opposed to an increased risk of thrombosis in patients with hyperthyroidism. In this issue of the SMJ, an interesting case of disseminated intravascular coagulation (DIC) occurring in association with overt hyperthyroidism has been described. As rightly pointed out by the authors, the possibility of septicemia in this patient cannot be entirely ruled out even though all cultures were negative. However, the more interesting aspect of the case is the occurrence of DIC in the setting of overt hyperthyroidism/thyroid storm. The improvement in the coagulation abnormalities as well as the overall clinical condition of the patient lends credence to the fact that thyroid dysfunction might indeed have triggered the DIC in this patient. The underlying pathophysiology in this patient can possibly be gleaned from two intervention studies which reported an increase in the levels of Factor VIII, von Willebrand antigen and activity, in healthy volunteers who were administered the thyroid hormone. Mouton et al reported 4 cases of cerebral venous thrombosis in the setting of hyperthyroidism, and also demonstrated elevated levels of factor VIII in these patients. An acquired von Willebrand syndrome is thought to mediate the abnormal bleeding associated with hypothyroidism. The above case highlights the relationship between thyroid dysfunction and abnormalities of the coagulation system. Clinicians need to be aware of this link, so that appropriate therapy can be begun as soon as this link is established in a given case. Prospective clinical studies in this area are needed to further delineate the degree of coagulation abnormalities associated with the level of thyroid dysfunction, and also to discern whether the underlying etiology of thyroid dysfunction has a bearing on disorders of the coagulation system.

Bleeding complications associated with percutaneous renal biopsy using Biopince® needle.

Renal biopsy is a valuable tool in the diagnosis of renal diseases; however, bleeding remains a serious complication of the procedure [1–4]. We have used 18-G BioPince (Full Core Biopsy Instrument; Medical Device Technologies Inc. Gainesville, FL) needle for performing renal biopsies in the recent years. BioPince technology is built around a tri-axial ‘‘Cut and Trap’’ cannula system, which is designed to cut the specimen and hold it in the cannula. This mechanism supposedly delivers cylindrical, full-length specimens that are complete and largely undamaged, thereby greatly improving the diagnostic value of the sample. This instrument is also claimed to result in less trauma to the patient, and less crush artifact and tissue fragmentation. We retrospectively studied bleeding complications, after kidney biopsy with 18-G Biopince needle, in 66 consecutive patients (33 males) who had undergone a real-time ultrasound-guided biopsy of native (n = 47) or transplant (n = 19) kidneys and compared the results with our earlier experience using either 15-G or 18-G ASAP (Meditech; Boston Scientific Co. Watertown, MA) needles [5]. Predictors of post-biopsy bleeding were assessed by linear regression analysis. All renal biopsies were performed at bedside by clinical nephrology fellows under the direct supervision of experienced faculty nephrologists at the Saint Louis University. Following the biopsy, patients laid in bed supine for 24 h with strict bed rest for the first 6 h. In 17 (26%) patients, there was a marked (C10%) decrease in the hematocrit (Hct) at 18–24 h postbiopsy, necessitating transfusion in 6 (9%) patients. This was similar to 25% (P [ 0.5) incidence of marked decline in Hct and a 3.6% (P [ 0.10) incidence of transfusion requirement with the ASAP needle. Gross hematuria occurred in 11 (17%) biopsies with Biopince versus 3.6% historically with ASAP needle (P \ 0.01). There was an average of 5.9% decline in the Hct at 18–24 h that was very similar to 6.1% decline with ASAP needle. There was a linear correlation between the decline in Hct at 6 h and the decline in Hct at 18–24 h (R = 0.29). None of our patients needed angiography or nephrectomy, and no deaths occurred. S. R. Daram Department of Internal Medicine, Saint Joseph Regional Medical Center and Medical College of Wisconsin, Milwaukee, WI, USA