David Tovbin

Hepatitis C virus infection in renal failure patients in the absence of anti-hepatitis C virus antibodies

The magnitude and clinical significance of Hepatitis C virus (HCV) infection in dialysis patients is controversial and underestimated. This study was conducted in order to evaluate the correlation between HCV replication and antibody response to HCV in dialysis patients. HCV infection in dialysis patients was evaluated over a period of 3 years and compared to HCV infection in Liver Clinic patients. Sera were collected from 310 dialysis patients and tested for anti‐HCV and HCV‐RNA. In addition, HCV genotype and HCV viral load were determined in HCV‐RNA‐positive sera. Anti‐HCV was detected in 43 (14%) of the dialysis patients. Of these, 37 (86%) were HCV‐RNA‐positive. Among the 267 HCV‐seronegative dialysis patients, 25 (9%) were found to be HCV‐RNA‐positive in more than one sample during the study. These patients were characterized by low viral load; at least two orders of magnitude lower than in the group of HCV‐seropositives. In contrast, in the Liver Clinic patients, HCV‐RNA was found exclusively in HCV‐seropositive patients. Comparison of the genotype pattern in the two groups did not reveal a difference.  Our results suggest that HCV infection in dialysis units may be underestimated due to cases of low viral load, depending on the method of RNA extraction and sensitivity of the test used. Low viral load might contribute to the lack of humoral immune response seen in some dialysis patients.

High Postdialysis Urea Rebound Can Predict Intradialytic Increase in Intraocular Pressure in Dialysis Patients with Lowered Intradialytic Hemoconcentration

Background: Intradialytic (ID) decrease in intraocular pressure (IOP) parallel to ultrafiltration-induced hemoconcentration has been recently reported. However, exacerbation of glaucoma in hemodialysis (HD) patients during HD sessions is occasionally observed. Postdialysis urea rebound (PDUR) is induced by the lag in urea removal from the cells to urea removal from the extracellular fluid, which when increased can result in ID drag of water to intracellular compartment. It is our hypothesis that similar lag in urea removal from ocular compartments may also be reflected by PDUR, and may induce drag of water into ocular compartments counteracting the effect of hemoconcentration. Our assumption was, therefore, that PDUR might predict ID increase in IOP. Methods: IOP, serum urea and hematocrit levels were measured at the start, end and 1 h postdialysis, in 19 chronic HD patients with normal IOP. Results: PDUR was positively correlated with mean (both eyes) ID changes in IOP (MIDIOP) (r = 0.5, p = 0.03) and % MIDIOP (r = 0.55, p = 0.02). ID increase in IOP was observed only in the 7 patients with relatively higher PDUR (≧9 mg%), who had also a relatively lower % ID change in Hct (<8%). MIDIOP was negatively correlated with % ID changes in Hct (r = –0.65, p = 0.03) in the 12 patients with PDUR ≧9 mg, and positively correlated with PDUR (r = 0.57, p = 0.03) in the 14 patients with % ID change in Hct <8%. Conclusion: High PDUR may predict susceptibility to ID increase in IOP in patients with lowered ID hemoconcentration.

Circulating cell-free DNA in hemodialysis patients predicts mortality

BACKGROUND Circulating cell-free DNA (CFD) appears following cell damage and DNA release, and increases in hemodialysis (HD) patients particularly following HD. We hypothesized that CFD is an integrative marker of tissue damage and can be an independent predictor for all-cause mortality in HD patients. METHODS In a prospective study, CFD levels before and after HD were evaluated in 31 chronic HD patients with no acute disease, using the reported rapid non-cumbersome inexpensive fluorometric assay developed in our laboratory. Follow-up levels were assessed at 18 months in 22 patients. All-cause mortality was a primary endpoint. RESULTS During 42 months of follow-up, 13 of the 31 (41.9%) patients died. The decedents were older than the survivors (mean age 69.9 versus 61.5 years, P = 0.06), but did not differ in end-stage renal disease (ESRD) duration, gender, albumin and hemoglobin, diabetes mellitus and weight. Post-dialysis CFD levels were significantly lower in survivors (median 688 versus 880 ng/mL, P = 0.01). The sensitivity and specificity of CFD levels of 850 ng/mL to predict 42 months (3.5 years) mortality were 73 and 75%, respectively, and the area under the receiver-operating characteristic curve was 0.77 [95% confidence interval (CI) 0.60-0.94]. The Cox proportional hazard regression model showed that CFD higher than 850 ng/mL adjusted for age, ESRD duration, weight and creatinine (stepwise model) was highly predictive of all-cause death with a hazard ratio of 8.0 (95% CI 2.3-28.5, P = 0.001). CONCLUSIONS Post-dialysis CFD level is an independent predictor of all-cause mortality in patients undergoing HD. We propose that CFD detection is an inexpensive applicable tool for identifying patients at risk and their follow-up.

Role of haptoglobin phenotype in end-stage kidney disease.

Background: We recently reported that haptoglobin (Hp) phenotype 1-1 is protective against the development of nephropathy in normal creatinine diabetics. In the present study, we sought to determine if Hp phenotype also plays a role in renal deterioration by determining Hp phenotypes in a consecutive series of patients with chronic renal failure (CRF) in hemodialysis (HD) and predialysis clinics. Methods: Three hundred and ninety-two patients on HD for less than 2 years and 182 predialysis patients (creatinine clearance time [CCT] <35 ml/min) were subjected to Hp phenotyping. Age, gender and presence of diabetes or hypertension were recorded. Patients were stratified according to age (above and below 60 years) and severity of renal dysfunction (CRF or HD). Results: We observed a markedly lower prevalence of the Hp 1-1 phenotype in HD patients under 60 years of age compared to patients with CRF or compared to the general population. This was not due to differences in the threshold for dialysis initiation among patients with different Hp types or to decreased survival of patients with Hp 1-1 prior to entering HD. In HD patients 60 years and over, Hp 1-1 prevalence was increased, as observed with other diseases in this age group. Conclusions: The prevalence of Hp 1-1 is decreased in HD patients less than 60 years of age. This may be due to a fundamental difference in the rate of renal deterioration in patients with different Hp types. In addition, Hp 1-1 may provide a protective effect against mortality in elderly patients.

Haptoglobin phenotype as a predictive factor of mortality in diabetic haemodialysis patients

Introduction: The mortality rate in diabetic dialysis patients (DDPs) is over 15% per year, with the cause of death most often attributed to cardiovascular disease (CVD) or bacterial infection (sepsis). Identification of genetic markers predictive of early mortality would be useful in the evaluation of therapies for the reduction of mortality rate in this population. Haptoglobin (Hp) is a polymorphic protein which appears to confer differential susceptibility to bacterial infection and CVD. We therefore proposed that Hp phenotype can predict mortality in DDPs. Methods: We tested this hypothesis prospectively in a longitudinal study of 392 dialysis patients from eight medical centres in Israel. Hp was determined by polyacrylamide gel electrophoresis. Patients were followed for all-cause mortality over a 3-year period. Results: We found that Hp phenotype was a significant predictor of mortality in DDPs stratified by age. In diabetic individuals over 60 years of age there was a decrease in mortality associated with the Hp 1-1 phenotype (P = 0.03). However, in younger DDPs the Hp 2-2 phenotype was associated with a decreased mortality rate (P = 0.003). Conclusion: Hp phenotype may be useful in the risk stratification algorithm and management of DDPs.

Unilateral acute renal cortical necrosis correlative imaging

Bilateral acute cortical necrosis is a rare form of acute renal failure characterized by necrosis of the renal cortex and sparing of the medulla. Little information on the imaging presentation of bilateral acute renal cortical necrosis is available. The enhanced CT appearance is pathognomonic and diagnostic. The unilateral presentation of acute cortical necrosis is extremely rare, and no imaging methods have been described. The authors chose to apply scintigraphic evaluation to this unique condition complementary to CT to confirm the diagnosis. Mercaptoacetylglycine (T3) was selected to assess tubular damage, in contrast to the pure glomerular agent DTPA. Evidence of some tubular function and clear delineation of the shrunken kidney was found. Conversely, in the DTPA study the kidney was not visualized. A DMSA scan was performed for assessment of viability of the renal cortex and showed a photopenic halo around the small area of the viable cortex of the upper pole. The halo sign represents a cortical loss. The visualization of the upper pole as evidence of cortical viability as a consequence of collateral blood flow from capsular vessels was seen on angiography. Radiographic and scintigraphic correlation of this rare condition may be an effective means to confirm the diagnosis and to establish the extent of involvement. However, contrast CT remains the preferred method in the diagnosis of acute cortical necrosis.

Intradialytic Hypercapnic Respiratory Failure Managed by Noninvasive Assisted Ventilation

We report a hemodialysis patient with acute hypercapnic respiratory failure managed on noninvasive intermittent positive pressure ventilation and progressive metabolic acidosis. Dialysate bicarbonate concentration of 25 mEq/l was associated with exacerbation of metabolic acidosis, while higher dialysate bicarbonate concentration of 30 mEq/l induced a dangerous increase in PCO2 level. Excessive bicarbonate buffering and CO2 production induced by severe metabolic acidosis, malnourishment and tissue hypoxia, could explain inadequate correction of metabolic acidosis and worsening of hypercapnia in this patient. Our findings suggest the need for close monitoring of blood gases and cautious modulation of dialysate bicarbonate concentration in the presence of progressive metabolic acidosis in hypercapnic hemodialysis patients.

High incidence of severe twin hemodialysis catheter infections in elderly women. Possible roles of insufficient nutrition and social support.

Background: Cuffed-tunneled hemodialysis (HD) catheters are recommended as a bridging therapy until peripheral access is available, but their long-term use is controversial. Aim: To evaluate the complications and lifetime of twin-tunneled HD catheters and to identify parameters which could predict their outcome. Methods: 29 chronic HD patients (19 female and 10 male) were inserted with twin hemodialysis catheters (28 Tesio, 1 Schon Duoflow), followed for up to 9 months or until catheter loss, and evaluated for severe catheter-related complications necessitating catheter removal. Since the most common severe complication was catheter-related infection, we retrospectively examined whether parameters such as age, gender, duration of end-stage renal disease, delivered dose of dialysis, nutrition, diabetes and indices of social support correlate with this outcome. Results: Severe catheter infection requiring catheter removal occurred in 11 patients (10 female). Of these infected female patients, 9 were elderly (≧67 years) and in 6 of those, catheter infection was fatal (54% of infected cases). At 9 months, severe catheter infection and related patient death rates were 38 and 21%, respectively. Severe catheter infection was significantly related to less social support (p < 0.005), older age, female gender, lower nPCR (all p < 0.05), and tended to be related to shorter end-stage renal disease duration prior to catheter insertion (p = 0.06). Conclusion: This study demonstrated that twin HD catheters are associated with a high incidence of severe catheter-related infections which was most significantly related to social-support as well as inadequate nutrition, older age and female gender. Therefore, we suggest early removal of the catheter, enhancement of social support and dietary counseling for the elderly and lonely HD patients using this type of catheter.

Renal Transplant Dysfunction due to Severe Aorto-Iliac Atherosclerosis in the Presence of Patent Renal Transplant Artery

We report a case of progressive deterioration in renal function and decreased renal graft perfusion induced by extensive aorto-iliac atherosclerotic lesions proximal to a patent renal graft artery. Significant improvement in kidney graft function followed left axillo-femoral bypass graft surgery, which to the best of our knowledge, has never been performed previously for permanent maintenance of renal transplant perfusion.

Dialysis Rounds: Management of Hypoalbuminemia and Malnutrition in an End‐Stage Renal Disease Patient with Crohn's Disease and Amyloidosis

A 57-year-old man was admitted due to one month of progressive diarrhea, abdominal pain and weight loss, with fever and vomiting 3 days prior to admission. The patient had a 30 year history of Crohn’s disease. On physical examination, patient appeared weak and dehydrated; blood pressure was 95/55 mm Hg; pulse rate 100 beats/min; temperature 37.8 °C; respiratory rate 20/min; weight 60 kg and skin turgor was poor. Laboratory values showed a serum creatinine of 4.1 mg/dL (1.9 mg/dL and 1.4 mg/dL, 1 month and 2 years earlier). Complete blood count showed leukocytosis of 117,000/mL with left shift, thrombocytosis of 653,000/mL and anemia with an initial hematocrit of 32%, which stabilized at 27% after fluid replacement. Serum blood urea level (BUN) was 12.1 mg/dL, albumin 2 g/dL and proteinuria of 4 g/day. Vitamin B 12 levels were 80 pg/mL (normal values: 200–880) and carotene 12 mg/dL (normal values: 50–250). Long standing Crohn’s disease was indicated by barium studies showing tubular changes in the ileum and computed abdominal tomography suggesting small bowel loop adhesions. When no improvement was observed with fluid therapy and serum creatinine rose to 6 mg/dL after 2 weeks, a kidney biopsy was performed that showed amyloidosis and extensive interstitial nephritis. Steroid therapy was initiated and the patient stabilized on creatinine of 4 mg/dL and albumin of 2 g/dL. Two weeks later, the patient was readmitted with pneumococccal meningitis, sepsis and coma. The clinical course was complicated by deterioration in renal function, severe upper gastrointestinal (GI) bleeding and bilateral deep vein thrombosis which necessitated Greenfield filter insertion and omeprazole therapy. The patient improved considerably and was discharged, but his nutritional status continued to deteriorate, parallel to continued proteinuria, metabolic acidosis, maintenance steroid therapy and further decrease in renal function. When his serum albumin level fell to 1.1 g/dL and serum creatinine and BUN levels rose to 8.2 mg/dL and 62 mg/dL, respectively, cuffed hemodialysis (HD) catheters were implanted. The patient began HD on a low flux biocompatible dialyzer (F5Fresenius) without reuse. Oral naproxen was started in order to reduce proteinuria, which was 3g/day even at this low level of renal function. Intradialytic parenteral nutrition (IDPN) was initiated with 335 mL of 8.5% amino acids, 125 mL of glucose 50%, which provided 326 Kcal and 28.5 g protein with gradual increase in volume and rate of infusion; after 8 therapeutic sessions fat emulsion was added. The final maximal volume was achieved at the twelfth IDPN session, contained 655 mL of 8.5% amino acid, 245 mL of glucose 50% and 250 mL of 20% fat emulsion and provided 1090 Kcal and 55.6 g protein. This therapy combined with intradialytic 100 g albumin infusions during the first 2 weeks, was associated with an increase in serum albumin level to 2 g/dL and 2.4 g/dL in 2 and 6 weeks, respectively (Table 1). Within 10 weeks of initiating therapy, dry weight increased from 55 to 59 kg (from 20% to 13% below desired weight—68 kg at height of 179 cm). Although patient’s systolic blood pressure remained constant at 70–85 mmHg in the presence of normal cardiac function on echocardiography, fluid removal of 12.5 kg to dry weight was achieved in 2 weeks. In addition to using sodium profiling and low temperature dialysate, albumin infusions in the first 2 weeks helped to stabilize blood pressure during the dialyzes sessions. The patient ate and felt well, but lower than expected urea levels and continued diarrhea suggested that GI absorption was still impaired and the relative contribution of IDPN was probably much higher than its actual percentage of the total intake. The patient resumed full time work and could drive his car after two weeks of HD and IDPN. Address correspondence to: David Tovbin MD, Nephrology Division, Soroka Medical University Center, Beer Sheva, Israel, 84101. E-mail:: dtovbin@bgumail.bgu.ac.il Seminars in Dialysis—Vol 12, No 3 (May–June) 1999 pp. 202–204