Removal of vancomycin in sustained low-efficiency dialysis (SLED): a need for better surveillance and dosing.

AIMS: This study was designed to evaluate the extent of vancomycin removal from the blood compartment during sustained low-efficiency dialysis (SLED) and the efficacy of our current vancomycin dosing practice. MATERIAL: 10 ICU patients were selected. They all had oliguric renal failure requiring SLED and were on vancomycin therapy. SLED was provided with the Fresenius 2000K machine and used an AV400 polysulfone dialyzer (sieving coefficient for vitamin B12 = 1, and surface area = 0.7 m2). METHOD: SLED prescriptions were individualized for each patient but the duration for all was at least 8 hours. The blood flow rate (Qb) and dialysate flow rate (Qd) did not vary between patients by greater than 100 cc per minute. Blood samples were drawn at 0, 2, 4, and 8 hours to determine the extent of reduction in vancomycin level. RESULTS: The total reduction of vancomycin was about 36% with an 8-hour treatment, when following a typical SLED prescription. Serum vancomycin levels dropped below the therapeutic window (< 15 mcg/ml) at the end of an 8-hour SLED session in almost half of the patients. Drug removal was greatest during the first 4 hours (29.5 +/- 6.5%) compared to the last 4 hours (9.1 +/- 7.4%) of SLED. CONCLUSIONS: Vancomycin removal during a typical 8-hour SLED treatment approaches 36%. SLED patients are at risk for undertreatment of their infections. A redosing strategy should be considered if the estimated or measured predialysis level is 20 - 30 mcg/ml. Vancomycin should be redosed with at least 500 mg in most patients at the completion of the SLED. Therapeutic drug monitoring (TDM) is an essential part of any dosing scheme, until further studies are done.

Large atrial thrombus formation associated with tunneled cuffed hemodialysis catheters.

AIMS: In the existing literature, there is a paucity of data regarding large atrial thrombus (AT) formation occurring as a complication of tunneled cuffed hemodialysis catheter (TCC) use. This study was performed to determine the risk factors, mortality and the appropriate management of TCC-AT. METHODS: We report 6 new cases of TCC-AT and have amalgamated these data with data from 16 previously published cases of TCC-AT found by performing a PubMed literature search (total of 22 cases). Demographic data were collected prospectively over 2 years in 85 consecutive patients initiating hemodialysis who were using a TCC as their primary vascular access, so that comparisons could be made between the 6 patients with TCC-AT versus all patients with a TCC at our center. RESULTS: In patients with TCC-AT, the mean time from TCC insertion was 4.5 months, and infection was present at the time of diagnosis in 68% of cases. The mean thrombus size was 3.7 cm, range 1.5-8 cm. All but 1 case were visualized by echocardiography; the remaining case required magnetic resonance imaging. Management included TCC removal and thrombectomy (n = 9), TCC removal and anticoagulation (AC) (n = 6), TCC removal alone (n = 5), and no intervention (n = 2). The overall mortality was 27%, and 5 of the 6 deaths (83%) occurred in patients with bacteremia. The mortality associated with each management strategy was as follows: TCC removal and thrombectomy (0%), TCC removal and AC (33%), TCC removal alone (40%), and no intervention (100%). CONCLUSIONS: AT is a serious complication of TCC use in hemodialysis patients and may be associated with a high mortality rate. TCC-AT may occur more commonly than previously reported and therefore warrants a high index of suspicion.

Novel WT1 mutation (C388Y) in a female child with Denys-Drash syndrome.

We report the identification of a novel Wilms tumor suppressor gene mutation in a 5-month-old girl who presented with unilateral Wilms tumor (WT) and renal diffuse mesangial sclerosis typical of Denys-Drash syndrome (DDS). The patient did not have ambiguous genitalia and the karyotype (by amniocentesis) was 46, XX. A de novo constitutional heterozygous mutation in WT1 gene exon 9 coding for the third zinc-finger (1163G-->A, C388Y) was identified. This mutation affects a cysteine residue involved in the coordination of the zinc atom, confirming the importance of these residues in the biological function of WT1 protein.

A randomized trial of minidose warfarin for the prevention of late malfunction in tunneled, cuffed hemodialysis catheters.

BACKGROUND: Minidose warfarin (1 mg/day) has been associated with a 74% reduction in the thrombosis rate of central venous catheters used in oncology patients. To determine the efficacy of minidose warfarin on late malfunction caused by thrombosis or fibrin sheath formation in tunneled, cuffed catheters (TCC) used for hemodialysis (HD), we performed a randomized, placebo-controlled trial. METHODS: One hundred five chronic HD patients with TCCs were initially randomized. Of these, 85 (warfarin 41 and placebo 44) completed the first two weeks of the protocol and were followed for the first year of TCC life or until TCC removal. RESULTS: Sixteen TCCs failed with late TCC malfunction, eight in each group. In a multivariate analysis, there was no significant effect of warfarin on thrombosis-free TCC survival or time to the first urokinase (UK) instillation for incipient thrombosis. The presence of a low hemoglobin (Hgb; <10.5 g/dL) or a low international normalized ratio (INR; <1.00) was significantly associated with a higher risk of late TCC malfunction (RR 5.2 and 4.0, respectively), a higher risk of incipient TCC thrombosis requiring UK (RR 2.0 and 2.8, respectively), and higher rates of UK dosing. Diabetics had a 3.6-fold higher risk of late TCC malfunction and a twofold higher risk of incipient thrombosis requiring UK, although these findings were not statistically significant. Aspirin use, race, age, number of hospitalizations, erythropoietin dose, intradialytic heparin dose, serum albumin, and the number of episodes of TCC-associated infection were not significantly associated with late TCC malfunction. CONCLUSIONS: Thrombosis prophylaxis using fixed minidose warfarin is not efficacious in TCCs used for HD. However, the present data suggest improved TCC survival in patients with an INR> 1.00. Patients with diabetes and those with a low Hgb or INR have a higher risk of late TCC malfunction.

Uterus didelphys with obstructed hemivagina and ipsilateral renal agenesis. A case report.

BACKGROUND: Uterus didelphys with obstructed hemivagina and ipsilateral renal agenesis usually presents after menarche with progressive abdominal pain during menses secondary to hematocolpos. We describe a case with the unique presentation of rectal pain and constipation. CASE: A 13-year-old girl presented to the emergency department complaining of lower abdominal and rectal pain and constipation of two weeks' duration. Pelvic ultrasound, physical examination and laparoscopic findings established a diagnosis of hematometracolpos secondary to uterus didelphys with unilateral imperforate hemivagina. An incision in the vaginal septum allowed drainage of the hematocolpos, providing relief of the patient's symptoms. CONCLUSION: Uterus didelphys with unilateral imperforate hemivagina and ipsilateral renal agenesis may present with apparent gastrointestinal symptoms. With increased awareness of this problem, timely diagnosis may be achieved.

Preexisting stress urinary incontinence: a predictor of discontinuation with pessary management.

OBJECTIVE: To identify variables predictive of pessary discontinuation in the treatment of pelvic organ prolapse. METHODS AND MATERIALS: Forty-two women with symptomatic pelvic organ prolapse presenting at a hospital-based urogynecology practice without a prior history of pessary use who opted for this form of management were included in the study. Data collected included vaginal paritye, presence or absence of symptomatic urinary incontinence, and previous pelvic surgery. RESULTS: Of the 42 patients, 24 (57%) were successfully managed with a pessary while 18 (43%) discontinued pessary use and were categorized as failures. Patients with preexisting urinary incontinence were more likely to discontinue pessary usage (OR 10.2 [1.06-240.96]). Logistic regression analysis indicated that stress urinary incontinence was the only significant type of incontinence predictive of discontinuation of pessary usage (p = .04). CONCLUSIONS: Preexisting stress urinary incontinence may be an independent predictor of pessary failure in the management of pelvic organ prolapse.

Podocyte cell cycle regulation and proliferation in collapsing glomerulopathies.

BACKGROUND: Mature podocytes are growth-arrested because of the expression of cyclin-dependent kinase inhibitors. Under pathological conditions, podocytes may undergo mitosis, but not cell division. Exceptions to this rule are collapsing glomerulopathies (CGs), including HIV-associated nephropathy (HIVAN) and idiopathic CG, where podocytes undergo a dysregulation of their differentiated phenotype and proliferate. METHODS: To shed light on the mechanism underlying podocyte proliferation in CG, we analyzed the expression of the proliferation marker Ki-67, cyclins (A, D1), cyclin-dependent kinase inhibitors (p27, p57), and podocyte differentiation marker synaptopodin in eight cases of HIVAN and two cases of idiopathic CG. Normal fetal and adult kidneys served as controls. RESULTS: Both HIVAN and idiopathic CG showed a marked reduction in the expression of p27, p57, and cyclin D1 (absent in 69, 62, and 80% of all glomeruli, respectively). Cyclin A and Ki-67 were expressed in 11 and 29% of all glomeruli. Moreover, there was partial loss of synaptopodin and cyclin D1 expression in nonaffected glomeruli. CONCLUSIONS: The loss of p27 and p57 leading to expression of cyclin A may account for the activation of podocyte proliferation in CG. Furthermore, the loss of cyclin D1 from histologically normal glomeruli suggests a possible role of cyclin D1 in mediating the dysregulation of the podocyte cell cycle in CG. These novel findings offer insight into the molecular regulation of mature podocyte differentiation. Podocyte proliferation in CG provides evidence in support of a previously underestimated plasticity of mature podocytes.

Plasma exchange for the removal of digoxin-specific antibody fragments in renal failure: timing is important for maximizing clearance.

Life-threatening digoxin toxicity may be effectively treated with digoxin-specific antibody fragments (Fab). However, in end-stage renal disease, the digoxin-Fab complexes persist in the circulation and dissociate, potentially resulting in rebounding free digoxin levels and the recurrence of symptomatic toxicity. To prevent this rebound phenomenon, plasma exchange (PE) has been implemented for the removal of the digoxin-Fab complexes in renal failure. However, there is only one case report describing its use in this setting. To better determine the optimal timing of PE after Fab administration, we performed two PE treatments (each preceded by Fab) in a patient with acute renal failure and acute digoxin poisoning. The admission serum digoxin level was 21 ng/mL. The timing of the PE treatments relative to Fab dosing was as follows: the first PE was performed 26 hours post-Fab, and the second PE was performed 2.5 hours post-Fab. The plasma ultrafiltrate digoxin concentration was 2.5-fold greater when PE was performed 2.5 hours versus 26 hours after Fab administration (19.9 versus 8.1 ng/mL). The combined total amount of digoxin removed in the ultrafiltrate plasma was minimal (0.13 mg), less than 1% of the total amount of ingested drug. We conclude that the optimal timing of PE is within the first 3 hours after Fab administration. Although PE is efficacious for removing digoxin-Fab complexes, thus preventing rebound digoxin toxicity, it is not efficacious for improving total digoxin clearance because of the large apparent volume of distribution of digoxin (5 to 8 L/kg).

Lactic acidosis associated with stavudine administration: a report of five cases.

Type "B" lactic acidosis has been described in patients receiving the nucleoside analogs zidovudine, didanosine, and fialuridine. Lactic acidosis has also been described in 4 patients receiving combination therapy with stavudine and lamivudine. We describe the development of chronic type "B" lactic acidosis in 3 patients receiving stavudine as a single agent and in 2 patients receiving combination therapy with stavudine and either lamivudine or delavirdine, a nonnucleoside analog. All patients presented with abdominal pain, vomiting, and hepatic steatosis. Other signs of mitochondrial toxicity included pancreatitis and myopathy (2 cases). The mean duration of stavudine therapy was 9.4 months, and the mean observed peak lactate level+/-SD was 10.3+/-5 mmol/L. After discontinuation of stavudine treatment, lactic acidosis improved in 4 patients after 4-60 weeks, and 1 patient died. Evaluations for other causes of lactic acidosis, including hypoxemia, malignancy, sepsis, and cardiogenic shock, were negative.

Human immunodeficiency virus-associated nephropathy in the Bronx: low prevalence in a predominantly Hispanic population.

Reports of human immunodeficiency virus-associated nephropathy (HIVAN) occurring in Hispanics, females and heterosexuals are scarce. We reviewed 858 charts from our total HIV population to determine the prevalence and epidemiology of HIVAN at our center, and to evaluate the renal and patient survival among individual groups, according to race, sex and HIV risk factor. The prevalence of HIVAN was low (1.9%), relative to other centers (4-13%). Although Hispanics accounted for 56% of the HIV population, only 38% of HIVAN patients were Hispanic. The absolute risk of HIVAN in blacks was 3. 6%, and in Hispanics was 1.3%. The relative risk of blacks vs. Hispanics was 2.8% (p < 0.04). Women and men were represented equally in both the HIVAN and HIV populations. The mean (+/- SE) rate of decline in glomerular filtration rate was 3.7 +/- 0.9 ml/min/month, and patient survival following the onset of HIVAN was 23.6 +/- 4.8 months. We found no difference in renal or patient survival between individual groups. In summary, the risk of HIVAN in Hispanics is similar to that for whites. Male sex is not an independent risk factor. Both renal and patient survival are similar in blacks and Hispanics, and in men compared to women.

Estrogen and progesterone receptors in the uterosacral ligament.

OBJECTIVE: To evaluate steroid hormone receptor status in the uterosacral ligament, a structure that contributes to pelvic support. METHODS: A descriptive study was conducted by sampling the uterosacral ligaments from 25 consecutive women undergoing hysterectomy by the primary author for nonmalignant conditions. Using immunohistochemical staining techniques, uterosacral ligaments were assessed for the presence and location of estrogen and progesterone receptors. Positive and negative controls were used. Confirmation of the uterosacral ligament was performed histologically. RESULTS: Using commercially available monoclonal antibodies, estrogen and progesterone receptors were detected in the nuclei of smooth muscle cells of the uterosacral ligament in all patients, regardless of variations in age, race, menopausal status, parity, body mass index, and medications affecting serum steroid hormone levels. Hormone receptors were not found in the collagen, vascular, or neuronal components. CONCLUSION: The presence of estrogen and progesterone receptors in the uterosacral ligaments means that this structure may be a target for estrogen and progesterone. This finding might suggest a possible role for steroid hormones in pelvic support.

Protein losses in continuous renal replacement therapies.

Continuous renal replacement therapy (CRRT) has become a popular treatment modality but may have the disadvantage of producing substantial protein losses. With use of the Biuret method, a relatively insensitive assay, dialysate/ultrafiltrate protein losses have been reported to be as high as 1.3 g/L. With CRRT outputs of up to 50 L/day, these values would amount to protein losses of up to 65 g/day. In this study, dialysate/ultrafiltrate protein losses were reanalyzed by using a highly sensitive microprotein reagent (pyrogallol red) considered to be more accurate than previously available methods. Twenty-two dialysate/ultrafiltrate samples were obtained from Amicon-20 Diafilters or Fresenius F-80 dialyzers during continuous venovenous hemofiltration (CVVH) or continuous venovenous hemodialysis/hemodiafiltration (CVVHD/F). Mean hourly output for all treatments was 1637 +/- 694 mL/h. Mean protein concentration for all 22 dialysate/ultrafiltrate samples was 4.2 +/- 4.0 mg/dL. Mean dialysate/ultrafiltrate protein concentrations were similar for the Amicon 20 (3.4 +/- 4.4 mg/dL, N = 9) and the Fresenius F-80 (4.7 +/- 3.9 mg/dL, N = 13) (P = not significant). Protein losses were higher during convection-based CVVH (6.0 +/- 5.1 mg/dL, N = 10; range, 1 to 15 mg/dL) than during the mixed convection and diffusion-based CVVHD/F (2.7 +/- 1.9 mg/dL, N = 12; range, 0 to 6 mg/dL) (P = 0.049). Mean serum protein concentration at the time of dialysate/ultrafiltrate sampling was 4.7 +/- 1.8 g/dL. There was a weak, but statistically significant correlation between the dialysate/ultrafiltrate samples and the corresponding value for serum protein (r = 0.468, P < 0.03). It was concluded that protein losses during CRRT treatments are substantially lower than previously reported, are dependent on the serum protein concentration and the predominant nature of solute removal (convection versus diffusion), and can vary between 1.2 and 7.5 g/day.

Vasodilator provocation of occult urinary tract hemorrhage.

This case demonstrates the use of vasodilators to reactivate an intermittent urinary tract hemorrhage. The site of bleeding was demonstrated and treated with subselective embolization.

Transient central diabetes insipidus in the setting of underlying chronic nephrogenic diabetes insipidus associated with lithium use.

Nephrogenic diabetes insipidus (NDI) is a well-documented complication of lithium use. The association of central diabetes insipidus (CDI) with lithium use is rare. We report a patient receiving chronic lithium therapy who presented with a transient CDI occurring in the setting of underlying chronic NDI. To the best of our knowledge, this is the first case of lithium-associated CDI and NDI presenting concurrently. Potential mechanisms regarding the pathophysiology of lithium-associated CDI are discussed. This case emphasizes the importance of the evaluation of lithium-associated polyuria with a direct measurement of plasma vasopressin, interpreted with simultaneous plasma and urine osmolality to secure the correct diagnosis and ensure appropriate therapeutic management.

Thrombotic thrombocytopenic purpura in pregnancy: successful treatment with plasma exchange. Case report and review of the literature.

Thrombotic thrombocytopenic purpura (TTP) is a rare syndrome which presents typically with thrombocytopenia, microangiopathic hemolytic anemia, central nervous system symptoms, fever, and renal abnormalities. The diagnosis of TTP in pregnancy previously carried a poor prognosis and a high fetal mortality when presenting early in gestation. This case report describes the earliest presentation of TTP in pregnancy (6 weeks of gestation) we could identify in the literature treated successfully with a prolonged course of plasma exchange. The differential diagnosis and the pathogenesis of TTP in pregnancy are reviewed. Therapeutic options and data regarding the removal of pregnancy-related hormones by plasma exchange are presented.

Therapeutic plasma exchange: complications and management.

Therapeutic plasma exchange is a treatment modality used in a variety of disease states, some of which are characterized by renal involvement (ie, Goodpasture's syndrome, multiple myeloma, cryoglobulinemia, and thrombotic thrombocytopenic purpura). To investigate the safety of this procedure we evaluated all patients receiving plasma-pheresis at the University of Connecticut from January 1988 to June 1991. Sixty-eight adverse reactions occurred in 699 treatments, resulting in an incidence of 9.7%. The most frequent complications were symptoms of hypocalcemia, hypovolemia, and anaphylactoid reactions. The incidence of hypocalcemic symptoms was lowered with the prophylactic administration of calcium. Without calcium prophylaxis the incidence of symptoms was 9.1% (six in 66 treatments), whereas with calcium prophylaxis the incidence was reduced to 1% (six in 633 treatments) (P < 0.01). Treatments in which albumin was administered as volume replacement were associated with fewer adverse reactions when compared with those using fresh-frozen plasma (1.4% v 20%). Our experience, combined with the 15,658 procedures reported in the literature, reveals that serious complications do not commonly occur. These are characterized by cardiovascular events (0.2%), respiratory events (0.2%), and anaphylactoid reactions (0.25%). Hemorrhage and infection are rare, each occurring at a rate of 0.02%. Death was reported in eight of 15,658 procedures (0.05%). We conclude that therapeutic plasma exchange is relatively safe and alterations in plasma proteins generally are well tolerated. Prophylactic calcium administration lowers the incidence of hypocalcemic symptoms. Adverse reactions are associated more commonly with the administration of fresh-frozen plasma.

Renal malacoplakia with papillary necrosis and renal failure.

Renal parenchymal malacoplakia is a rare cause of renal failure. Patients presenting with renal failure carry a poor prognosis, the majority either dying or requiring chronic dialysis. In this report, we describe an alcoholic man who presented with renal failure due to bilateral renal parenchymal malacoplakia and papillary necrosis. The patient, who initially required dialysis, partially recovered renal function following prolonged antibiotic treatment with a fluoroquinolone antibiotic.