Impedance ratio: a novel marker and a powerful predictor of mortality in hemodialysis patients.

PURPOSE: Impedance ratio (Imp-R) obtained by multifrequency bioimpedance analysis (BIA) has been shown to be associated with volume and nutrition status. In this prospective study, the predictive role of Imp-R for mortality in hemodialysis (HD) patients was investigated. METHODS: Multifrequency (5-50-100-200 kHz) BIA was applied to 493 prevalent HD patients in March-April 2006. Imp-R was defined as the ratio of 200-5 kHz impedance values. Demographical, clinical and laboratory data at the time of the analysis were recorded. All-cause and cardiovascular (CV) mortality were assessed during 3 years of follow-up. RESULTS: Mean age was 57.7 ± 13.9 years, HD duration 52.1 ± 42.6 months and prevalence of diabetes 21.7 %. Imp-R was negatively correlated with nutritional markers including albumin, creatinine and hemoglobin levels. In addition, there was a positive correlation between Imp-R and age, ratio of extracellular water to total body water and high-sensitive C-reactive protein. Over a mean follow-up period of 27.9 ± 11.1 months, 93 deaths (52 from CV reasons) were observed. In the multivariate analysis, Imp-R was significantly associated with all-cause and CV mortality after adjustments [HR 1.13, 95 % CI (1.04-1.23); p = 0.004 and HR 1.15, 95 % CI (1.03-1.27); p = 0.01, respectively]. The risk of all-cause mortality was 3.4 times higher in the fourth quartile of Imp-R (>83.5 %) compared to the first Imp-R quartile (<78.8 %) as reference. Cutoff value of Imp-R for all-cause mortality was 82.0 % with a sensitivity of 65.5 % and specificity of 64 %. CONCLUSION: Impedance ratio measured by multifrequency in standardized conditions BIA is an independent and powerful predictor of both all-cause and CV mortality in hemodialysis patients.

Biochemical parameters, renal function, and outcome of pregnancy in kidney transplant recipient.

INTRODUCTION: The number of women who would like to have a baby after renal transplantation has increased. The aim of this study was to evaluate the effects of pregnancy on the lipid profiles and renal functions among transplantation patients as well as the maternal and fetal results of pregnancy. MATERIALS AND METHODS: We searched files of female patients who underwent renal transplantation between 1998 and 2008 to discover 31 pregnancies among 24 women. RESULTS: Mean duration of dialysis and age at transplantation for the 24 cases were 22.7 ± 24.1 months (range, 0-72) and 21.2 ± 4.6 years (range, 13-34), respectively. The time between transplantation and conception as well as age at conception were 5.2 ± 1.9 and 26.4 ± 4.4 years, respectively. Creatinine levels in the second trimester were significantly lower (P = .000). Gestational bicarbonate and albumin levels were significantly lower (P = .009 and P = .001, respectively). There were significant differences between the preconception triglyceride (TG) and those in the second and third trimesters (P = .006 and P = .00, respectively). TG levels increased as trimesters progressed (P = .000). Moreover, TG levels were higher among patients taking cyclosporine. Of pregnancies that passed the first trimester, 88.4% resulted in live births. There were 23 (74.19%) live births among 31 pregnancies with a cesarean section rate of 58%. Of the cases, 16.1% delivered preterm and 19.4% of babies had low birth weights. CONCLUSION: We believe that women with renal transplants can have healthy babies with close monitoring during pregnancy and without any effect on graft survival.

Plasmapheresis therapy in renal transplant patients: five-year experience.

INTRODUCTION: Plasma exchange (PE) and double-filtration plasmapheresis (DFPP) have been used successfully in renal transplant patients as well as those with various other diseases over the last decade. In this retrospective study, we sought to explore the outcomes of plasmapheresis in renal transplant patients. PATIENTS AND METHODS: We investigated 58 patients who received PE or DFPP therapy between 2005 and 2010. PE was performed using a Fresenius AS.TEC 204 device and DFPP, by an INFOMED HF 440 device. Indications for therapy, biopsy findings, number of PE/DFPP sessions, laboratory data, medications, complications as well as graft and patient survivals were recorded. RESULTS: Overall mean age of subjects was 34.1 ± 8.8 years and 55% were female. Sixteen patients underwent 95 DFPP sessions and 42 underwent 215 PE sessions. Indications for therapy were acute humoral rejection (n = 39), recurrent focal segmental glomerulosclerosis (FSGS; n = 8), thrombotic microangiopathy (n = 6), and chronic humoral rejection (n = 5). Responses to therapy were 24/39 for acute humoral rejection, 1/5 for chronic rejection, 4/8 for FSGS, and 3/6 for thrombotic microangiography. No complication was observed in any patient. CONCLUSION: PE/DFPP is a safe and successful method for treatment of acute humaral rejection as less so for recurrent FSGS and thrombotic microangiopathy. The outcomes among subjects with chronic humoral rejection were not satisfactory.

The acquisition time of infection: a determinant of the severity of hepatitis C virus-related liver disease in renal transplant patients.

BACKGROUND: The aim of this study was to compare the clinical and histopathological course of HCV infection acquired before and during or after renal transplantation. METHODS: According to HCV status, 197 RT patients were divided into three groups. At the time of RT, anti-HCV antibody was positive in 47 patients (pre-RT HCV group). In 27 patients, in whom anti-HCV negative at the time of RT, anti-HCV and/or HCV RNA was found to be positive following an ALT elevation episode after RT (post-RT HCV group). Both anti-HCV and HCV RNA were negative at all times in remaining 123 patients (control group). RESULTS: Liver biopsy was performed in 31 of 47 patients in pre-RT and 24 of 27 in post-RT HCV group after RT. Duration of follow-up was similar in all groups with a mean of 7.1 +/- 4.0 yr. Ascites and encephalopathy were seen in only post-RT HCV group (22%). Histological grade (6.5 +/- 2.7 vs. 4.1 +/- 1.4) and stage (2.0 +/- 1.5 vs. 0.8 +/- 0.8) was significantly severe in post-RT HCV group (p < 0.01). Three patients died due to liver failure in post-RT HCV group. CONCLUSIONS: HCV infection acquired during or after RT shows a severe and rapidly progressive clinicopathological course, which is significantly different from pre-transplant anti-HCV positive patients.

Is "zero-hour" biopsy of the transplanted kidney risky?

"Zero-hour" renal allograft biopsy provides valuable diagnostic information for comparison to subsequent kidney material. However, the invasive nature of the biopsy procedure tends to limit its widespread use in many centers. We undertook this retrospective study to examine the rate and clinical importance of complications in our series of patients routinely undergoing zero-hour biopsies performed between 1994 and 2001. Two hundred thirty-six zero-hour biopsies included only one sample performed with a 14G needle from lower posterior part of kidney by using a manual tru-cut technique. Doppler ultrasonography was performed after first 5 days. An average of 34 +/- 19 glomeruli were obtained in the biopsies. The biopsy specimens were adequate for diagnosis in 77% of the procedures. Ten (4%) patients experienced complications of intraparenchymal arteriovenous fistula (n = 4), which regressed spontaneously; perirenal hematoma (n = 4); intraparenchymal hematoma (n = 2); and a minimal perirenal collection (n = 41). We conclude that zero-hour biopsy is a safe diagnostic method. The rate of complications is low, as well as generally mild and self-limiting.

Intima media thickness as a predictor of atherosclerosis in renal transplantation.

It has been reported that an increase in carotid artery intima-media thickness (IMT), a sign of early atherosclerosis, has a predictive value for future cardiovascular (CV) events. There are limited data about IMT measurements in renal transplant patients who display a high rate of CV mortality. In this study carotid artery IMT was measured by high resolution B-mode ultrasonography in 102 randomly selected RT patients to assess the relationship between IMT and CV disease and risk factors. A positive correlation was found between IMT and age, triglyceride level, and hematocrit. IMT was significantly higher among patients who were diabetic (0.68 +/- 0.27 vs 0.50 +/- 0.2) or had CV disease (0.88 +/- 0.28 vs 0.53 +/- 0.21). An increased IMT was associated with a longer duration of ESRD, higher lipid level, lower serum albumin, and presence of previous CMV disease. CV disease was more frequent among patients with increased IMT. Considering its relation to CV risk factors, it is concluded that the measurement of carotid artery IMT is an easy, reliable and non-invasive method to be used to assess atherosclerotic disease in renal transplant patients.

Comparison of tacrolimus and cyclosporin in renal transplantation by the protocol biopsies.

Acute and chronic lesion scores on renal allograft protocol biopsies may predict long-term graft function. The aim of this study was to compare the effects of tacrolimus (Tac) and cyclosporine microemulsion (CsA) based immunosuppressive protocols using protocol biopsies from well-functioning renal allografts. 35 consecutive renal transplant patients were randomized to Tac (n: 17) versus CsA (n: 18) treatment arms. Patient age and sex, donor type and age, histocompatibility, cold ischemia time and prior delayed graft function were similar between the two groups. Treatment protocol consisted of prednisolone, azathioprine and Tac or CsA. Biopsies performed on the third, sixth and twelfth months were blindly evaluated by the same pathologist. The incidences of acute rejection (AR) episodes among CsA vs Tac groups were 33% vs 29%, respectively (NS). The Creatinine level was lower in Tac than CsA, although it was not significant (Table). Subclinical AR and subclinical chronic allograft nephropathy were detected on protocol biopsies in 3 (2 CsA, 1 Tac) and 12 (7 CsA, 5 Tac) patients, respectively. Acute lesion score at the third month PBx was significantly lower in the Tac group (p < 0.05). Chronic lesion scores in all biopsies were lower in the Tac group, although not significantly. The protocol biopsy findings suggest that graft injury may be less pronounced among the Tac group.

Does enalapril prevent peritoneal fibrosis induced by hypertonic (3.86%) peritoneal dialysis solution?

OBJECTIVE: Peritoneal fibrosis (PF) is one of the most serious causes of failure in continuous ambulatory peritoneal dialysis (PD). Although the underlying mechanism responsible for the genesis of PF is still unknown, transforming growth factor beta (TGFbeta1) has been shown to be associated with PF. Angiotensin converting enzyme inhibitors have been shown to prevent the stimulating effect of growth factors. The aim of the present study was to investigate the effect of enalapril on peritoneal function and morphology in a rat model of experimental PF. METHODS: Twenty-one albino Wistar rats were divided into three groups: (1) the control group (C) received 10 mL isotonic saline intraperitoneally (i.p.), (2) the dextrose (Dx) group 10 mL 3.86% dextrose PD solution i.p., and (3) the enalapril-treated group (ENA) 10 cc 3.86% dextrose PD solution i.p. plus 100 mg/L enalapril in drinking water. After 4 weeks, a 1-hour peritoneal equilibration test was performed with 20 mL 2.27% dextrose PD solution. Dialysate-to-plasma urea ratio (D/P urea), glucose reabsorption (D1/D0 glucose), ultrafiltration (UF) volume, and levels of dialysate protein, TGFbeta1, and cancer antigen 125 (CA125) were determined. The parietal peritoneum was evaluated histologically by light microscopy. RESULTS: Administration of enalapril resulted in preserved UF (-0.2 +/- 0.7 mL vs 1.7 +/- 0.3 mL, p < 0.05), protein loss (2.3 +/- 0.5 g/L vs 1.6 +/- 0.2 g/L, p > 0.05), and peritoneal thickness (77 +/- 7 microns vs 38 +/- 5 microns, p < 0.001). D/P urea increased significantly in the Dx group (p< 0.05). Both higher levels of TGFbeta1 (undetectable vs 298 +/- 43 pg/mL, p < 0.001) and lower levels of CA125 in dialysate effluent (0.94 +/- 0.5 U/L vs 0.11 +/- 0.1 U/L, p > 0.05) were determined in the Dx group. CONCLUSION: These findings show that peritoneal morphology and function tests were dramatically deranged in the Dx group. The same properties were partially preserved in the ENA group. The production of TGFbeta1 was significantly reduced but peritoneal thickness was not completely inhibited. In conclusion, by inhibiting the production of TGFbeta1, enalapril can preserve peritoneal histology, peritoneal function, and remodeling of mesothelial cells.

Strict volume control normalizes hypertension in peritoneal dialysis patients.

The aim of this study is to investigate whether normal blood pressure (BP) can be achieved in patients with hypertension on continuous ambulatory peritoneal dialysis (CAPD) therapy by strict volume control without the use of antihypertensive drugs. Of the 78 patients in our center, 47 persons had hypertension and/or were on antihypertensive drug therapy. After discontinuing these drugs, a strong dietary salt restriction was imposed by repeatedly explaining the need for it to patients and families. If this approach did not result in sufficient BP decrease, ultrafiltration (UF) was added by increased use of hypertonic (3.86% glucose) peritoneal dialysis solution. Cardiothoracic index (CTI) on the chest radiograph was also used as a measure of volume control. With salt restriction alone or combined with UF, body weight decreased by a mean of 2.8 +/- 0.5 kg, and BP decreased from a mean of 158.2 +/- 17.0/95.7 +/- 10.3 to 119.7 +/- 16.0/77.9 +/- 9.7 mm Hg in 37 patients, accompanied by a decrease in CTI from 48.0% +/- 5.6% to 42.9% +/- 4.5%. In 19 patients who had residual renal function, 24-hour urine volume decreased to 28% of the pretreatment volume, accompanied by a mean decrease in Kt/V urea from 2.06 +/- 0.5 to 1.85 +/- 0.4. In 7 of the remaining patients who did not respond to the applied treatment, BP decreased from 158.8 +/- 23.2/111.6 +/- 9.8 to 113.5 +/- 14.3/76.4 +/- 6.2 mm Hg after administration of an angiotensin-converting enzyme (ACE) inhibitor. Their CTI was 41.2% +/- 1.3%, indicating the absence of hypervolemia. In 3 patients, the desired results could not be reached because of noncompliance. Our findings show that normal BP can be achieved by severe salt restriction combined with increased UF in the majority of CAPD patients. This is accompanied by a decrease in CTI from upper limits into the normal range, but also by a decrease in residual renal function and Kt/V index. In most of the remaining patients, normal BP can be reached by the use of ACE inhibitors.

Tuberculosis in renal transplant recipients.

BACKGROUND: Tuberculosis is an important cause of morbidity and mortality in renal transplant recipients, but there are insufficient data regarding the efficacy and complications of therapy and of INH prophylaxis. METHODS: This study is a retrospective review of the records of 880 renal transplant recipients in two centers in Turkey. RESULTS: Tuberculosis developed in 36 patients (4.1%) at posttransplant 3-111 months, of which 28 were successfully treated. Eight patients (22.2%) died of tuberculosis or complications of anti-tuberculosis therapy. Use of rifampin necessitated a mean of 2-fold increase in the cyclosporine dose, but no allograft rejection occurred due to inadequate cyclosporine levels. Hepatotoxicity developed in eight patients during treatment, two of whom died due to hepatic failure. No risk factor, including age, gender, renal dysfunction, hepatitis C, or past hepatitis B infection, was found to be associated with development of hepatic toxicity. A subgroup of 36 patients with a past history of or radiographic findings suggesting inactive tuberculosis, was considered to be at high risk for developing active disease, of whom 23 were given isoniazid (INH) prophylaxis. None versus 1 of 13 (7.7%) of cases with and without INH prophylaxis, respectively, developed active disease (P>0.05). None of the patients receiving INH had hepatic toxicity or needed modification of cyclosporine dose. CONCLUSIONS: These data show that tuberculosis has a high prevalence in transplant recipients, that it can effectively be treated using rifampin-containing antituberculosis drugs with a close follow-up of serum cyclosporine levels, and that INH prophylaxis is safe but more experience is needed to define the target population.

Treatment of hypertension in dialysis patients by ultrafiltration: role of cardiac dilatation and time factor.

We retrospectively analyzed the blood pressure (BP) and cardiothoracic index (CTi) of 67 hemodialysis patients with hypertension who could be followed up for at least 8 months. A new treatment policy was adopted, aimed at strict volume control. Dietary salt restriction was strongly emphasized. Ultrafiltration (UF) was applied during regular dialysis sessions and sometimes in additional sessions, as long as BP and CTi remained at greater than normal values. All antihypertensive drugs were discontinued at the beginning of treatment. Average BP decreased from 173 +/- 17/102 +/- 9 to 139 +/- 18/86 +/- 11 mm Hg after 6 months and to 118 +/- 12/73 +/- 6 mm Hg after 36 months. Corresponding values for CTi were 52% +/- 4%, 47% +/- 3%, and 42% +/- 4%, respectively. Conventional relatively short dialysis (three times weekly for at least 4 hours) can achieve normal BPs with prolonged effort in most patients, whereas improvement in heart condition facilitates this.

Regression of left ventricular hypertrophy in haemodialysis patients by ultrafiltration and reduced salt intake without antihypertensive drugs.

BACKGROUND: Left ventricular hypertrophy (LVH) is very frequent in haemodialysis patients. Only few investigations have reported its regression, and only by the use of antihypertensive drugs. Because volume load is at least as important as pressure load, we investigated whether persistent strict volume control by ultrafiltration alone may be effective in improving LVH METHODS: Using blood pressure (BP) and cardiac dimensions as a guide, we treated all hypertensive patients in our dialysis unit during the 3 times weekly dialysis sessions for 4 h per session with as much ultrafiltration as they could stand. If they gained too much weight an extra isolated ultrafiltration (UF) session was applied. Special attention was given to dietary salt restriction. The study group of all 15 patients in whom echocardiographic assessment had been made at least 1.5 years previously was selected retrospectively, and we acknowledge that important confounding factors might not have been controlled for. Cardiothoracic index (CTI) was estimated on the chest X-ray. Diameters of left atrium (LA), left ventricle systolic (LVS) and diastolic (LVD), interventricular septum (IVS), posterior wall (PW), and left ventricular mass index (LVMI) were estimated by standard echocardiographic methods. RESULTS: Mean arterial pressure of the study group had been lowered by UF before the first echocardiogram from predialysis 136+/-11 to 101+/-14 and from postdialysis 119+/-8 to 92+/-12 mmHg. During a mean follow-up period of 37+/-11 months LVMI decreased from 175+/-60 to 105+/-11 g/m2. CTI decreased further from 48+/-3 to 43+/-4%, while significant decreases of LA (22.5+/-3 to 19.9+/-4 mm/m2), LVS (18.7+/-4 to 15.9+/-3 mm/m2) and LVD (28.3+/-4 to 24.0+/-3 mm/m2) were seen in all patients. There also was a further decrease in both pre- and postdialysis BP to 116+/-12/73+/-7 and 105+/-7/65+/-3 mmHg respectively. CONCLUSION: The results of this uncontrolled retrospective study suggest that good long-term BP control and a decrease of LVM can be achieved by continuous efforts to control hypervolaemia. The decrease in volume may be even more important than pressure reduction to achieve this goal.

Disappearance of mitral and tricuspid regurgitation in haemodialysis patients after ultrafiltration.

BACKGROUND: Doppler echocardiography has recently revealed frequent occurrence of valvular (in particular mitral) regurgitation in dialysis (HD) patients. We hypothesized that this may be in part 'functional' and related to the cardiac dilatation which is also frequently present. Thus it would be possible to improve it by ultrafiltration. METHODS: Mitral and tricuspid regurgitation was detected in 21 haemodialysis patients who had cardiomegaly but no manifest cardiac failure. They were treated by intensified ultrafiltration sessions, as much as they could tolerate, while all antihypertensive drugs were stopped. Doppler echocardiograms were then repeated. RESULTS: Mitral regurgitation disappeared in 13 and tricuspid regurgitation in 14 patients, while lesser degrees of either of them persisted in seven. This was accompanied by decreases of body weight (5.4 +/- 2.7 kg) mean arterial pressure (125 +/- 15 to 95 +/- 11 mmHg), cardiothoracic index (from 0.57 to 0.47), and left atrial (28 +/- 4 to 22 +/- 3 mm/m2), left ventricular systolic (25 +/- 5 to 21 +/- 55 mm/m2) and left ventricular diastolic (31 +/- 5 to 27 +/- 5 mm/m2), and mitral annular diameters (19.4 +/- 2 to 16.6 +/- 2 mm/m2). Ejection fraction increased but remained below 50% in 11 patients. CONCLUSION: Most of the mitral and tricuspid regurgitations seen in HD patients are partly or completely functional, due to dilatation of the mitral annulus which is related to volume overload. A more aggressive approach, while discontinuing antihypertensive drugs can correct or improve many of them and also ameliorate cardiac function.

The efficiency of fractionated parenteral iron treatment in CAPD patients.

Some chronic renal failure patients respond poorly to recombinant human erythropoietin (rHuEPO). In continuous ambulatory peritoneal dialysis (CAPD) patients, such a poor response may indicate inadequate dialysis or low body iron stores. To correct iron deficiency, once-a-week intravenous iron supplementation is recommended. However, hemodialysis patients receive iron supplements three times a week. This study was designed to compare the efficacy of iron supplementation between once-weekly and twice-weekly regimens. In both groups, rHuEPO doses were similar. Seventeen CAPD patients were studied. All had hemoglobin levels less than 10 g/dL. Ten patients were given 100 mg intravenous iron once weekly, and 7 were given 50 mg intravenous iron twice weekly until a total iron dose of 600 mg was achieved (stage I). The patients were crossed over to receive another 600 mg iron (stage II). Hematocrit increased significantly in patients receiving twice-a-week iron supplementation (+3.8% and 6%) compared to those receiving once-a-week iron supplementation (+1.3% and 1.4%) during stages I and II. The ferritin levels were not different between the groups. In conclusion, rHuEPO is more effective when administered with intravenous iron.