Trimethylaminuria (fish malodour syndrome) in chronic renal failure.

Trimethylaminuria (fish malodour syndrome) is a rare genetic metabolic disorder presented with a body odour which smells like a decaying fish. This odour is highly objectionable, that can be destructive for the social, and work life of the patient. Trimethylamine is derived from the intestinal bacterial degradation of foods that are rich of choline and carnitine. Trimethylamine is normally oxidised by the liver to odourless trimethylamine N-oxide which is excreted in the urine, so, uremia may worsen the condition. Uremia itself may cause more or less unpleasant odour. Poor uremic control may worsen the odour. We reported this case because Trimethylaminuria is not usually considered in the differential diagnosis of malodour in chronic renal failure and it is the first case that shown the association with Trimethylaminuria and chronic renal failure in the literature.

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.

Increased use of catheters as vascular access: is it justified by patients' clinical conditions?

BACKGROUND: Over the last years many technical improvements have been made in hemodialysis treatment. Vascular access (VA) still remains an important problem. Although the use of indwelling vascular catheters is discouraged, in Europe there is an increasing use of them. The K/DOQI Guidelines recommend a native arteriovenous fistula (AVF) as VA of choice. As reported by DOPPS, there is considerable geographic variation in the distribution of type of VA used amongst hemodialysis patients. The aim of this study was to evaluate the time patients in four European countries have to wait before undergoing their first surgery for VA (AVF or graft). METHODS: All incident patients admitted to HD clinics located in Turkey, Italy, the UK and Portugal of the European FME clinics network between October 1, 2002 and September 30, 2004 were considered. Data were gained from the Clinical Database EuCliD. RESULTS: 2,152 patients (males 55.9%, mean age 62.5+/-15.7 years, diabetics 27%) were selected. Italy and Portugal had a higher proportion of elderly patients. At time of admission, the proportion of patients starting dialysis with AVF ranged between 23% and 60% from Turkey to Italy respectively. Patients with an indwelling catheter at admission are expected to undergo VA surgery as soon as possible. After 3 months of follow-up, about 75% of all patients had undergone surgery, however in the UK less than 50% of the patients had had a VA procedure. Overall, males have significantly higher probability of undergoing surgery, whilst elderly patients have a lower probability (27% and 14% respectively). CONCLUSION: Significant differences exist between countries in the time interval from referral to creation of VA. Health care system related problems seem to be the major reason to explain such differences. Patients in the UK have longer waiting times than the other countries studied.

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.

Nosocomial hepatitis C virus infection in a renal transplantation center.

Nosocomial hepatitis C virus (HCV) infections were recorded in the renal transplantation unit of the university hospital. There were cases of acute HCV infection with aggressive clinical courses diagnosed from a positive HCV RNA test in the early post-transplantation period and which remained anti-HCV negative. Their anti-HCV seronegativity was attributed to them having acquired HCV under intense immunosuppressive therapy and suggested that the aggressive clinical course could be due to the deficient immune response resulting in an inability to limit viral replication. There were also donors diagnosed as having acute HCV infection in the early post-operative period. Genotyping and sequence analysis for HCV were performed on the isolates of eight of these patients who were consecutively transplanted and of three donors whose recipients were infected with HCV prior to transplantation, and who acquired acute HCV infection after transplantation. Of the eight recipients in the first group three were genotype 1a, three were genotype 1b, one was genotype 3a, and the last one was genotype 4 according to Simmond's classification. Of the three donor-recipient couples both the HCV isolates from one couple were genotyped as 1b and the phylogenetic analysis indicated that the patients were infected with a common variant of HCV, but the genotypes of HCV isolates from the other couples were different. Recipients were genotype 1b and the donors were genotype 1a in these couples. Genotype results of the first group and donor-recipient couples, and sequence analysis of genotype 1b and 1a isolates, showed that the source of infection was not a unique strain and there were multiple breaks in universal precautions while managing these patients.

By reducing TGF beta 1, octreotide lessens the peritoneal derangements induced by a high glucose solution.

BACKGROUND: Chronic peritoneal dialysis may eventually result in peritoneal fibrosis, which progressively reduces dialytic efficacy. Although the pathogenesis has not been elucidated, it has been proposed that transforming growth factor beta-1 (TGF beta 1) plays a central role in the onset of peritoneal fibrosis. METHODS: Rats were divided into three groups and given saline, hypertonic peritoneal dialysis solution alone, a hypertonic peritoneal dialysis solution plus octreotide intraperitoneally. After four weeks, a one-hour peritoneal equilibration test was done. Dialysate-to-plasma urea ratio, glucose reabsorption, ultrafiltration volume and levels of dialysate protein, TGF beta 1 and cancer antigen 125 (CA 125) were determined. The peritoneal membrane was examined histologically by light microscopy. RESULTS: Compared to the saline group, peritoneal function tests (ultrafiltration volume 6 (5-7) vs 0.0 ml, dialysate-to-plasma urea ratio 0.51 vs 0.76, glucose reabsorption 0.54 vs 0.40 and morphology (thickness 4.5 vs 75.5 microns) were dramatically deranged in hypertonic peritoneal dialysis solution-treated rats, which also had a higher level of TGF beta 1 and undetectable CA 125. In contrast, in hypertonic peritoneal dialysis solution plus octreotide rats' peritoneal function was protected (ultrafiltration volume 3 mL, dialysate-to-plasma urea 0.60, glucose reabsorption 0.51) but peritoneal thickening (37.7 microns) was not so markedly reduced although the production of TGF beta 1 was significantly inhibited. CONCLUSION: These data show that by inhibiting the production of TGF beta 1, octreotide can preserve peritoneal function and remodeling of the mesothelial cell. Although the production of TGF beta 1 was significantly inhibited, peritoneal thickening cannot be completely prevented.

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.

How can we standardize peritoneal thickness measurements in experimental studies in rats?

OBJECTIVE: The various methods of measuring peritoneal thickness in experimental studies in rats have yielded conflicting results. Also, no standard method exists to assess histologic findings in peritoneal morphology. We therefore undertook the present study to create a reproducible and standard method for assessing rat peritoneal histology in experimental studies. METHODS: Parietal peritoneal samples from 61 Wistar albino rats were used in the study. Excepting the skin, the whole abdominal wall from each rat was cut two-dimensionally (longitudinally and horizontally), fixed in formalin, and processed routinely for light microscopy. Slides were divided into two groups according to the direction of the inner abdominal muscle fibers in the sections. Longitudinal and horizontal sections of abdominal muscle were evaluated. For every section, one histopathology image was captured from a light microscope to an IBM-compatible computer. Peritoneal thickness (mean of the maximum and the minimum) and submesothelial area (SMA) were drawn on the image. A computer program then automatically performed measurements. Two different measurement methods were compared, based on the same sections. RESULTS: The mean peritoneal thickness was 91 +/- 8 microm in the longitudinal sections and 75 +/- 7 microm in the horizontal sections (p < 0.05). Measurements of the SMA were found to be 47,762 +/- 4,374 microm2 for the longitudinal sections and 40,389 +/- 3,631 microm2 for the horizontal sections (p < 0.05). In both types of sections, a positive correlation (96% for longitudinal and 90% for horizontal) was found between the SMA and the peritoneal thickness (p < 0.01). The SMA measurements correlated significantly with functional properties [ratio of the dialysate concentration of glucose initially and after a 1-hour dwell (D1/D0 glucose), ultrafiltration, and protein loss; p < 0.01]. CONCLUSION: Peritoneal thickness can be measured as a mean of the minimum and maximum values. That measurement strongly correlates with submesothelial area. Both types of sections can be used, but the horizontal and longitudinal sections show systematic differences. All samples in a study should be taken using the same section pattern, either longitudinal or horizontal.

Clinicopathological features of rapidly progressive hepatitis C virus infection in HCV antibody negative renal transplant recipients.

BACKGROUND: Hepatitis C virus (HCV) infection acquired during dialysis treatment generally shows a relatively benign course after renal transplantation (RTx). However, less is known about the course of HCV infection acquired during or after RTx. METHODS: Clinical and histopathological assessment of 15 renal transplant recipients who acquired HCV infection during or after RTx. RESULTS: Alanine aminotransferase levels rose for the first time 1-19 weeks after RTx. HCV RNA was found positive in all patients, but anti-HCV became positive in only nine of them. During a mean follow-up of 21 +/- 12 months, jaundice appeared in 12 patients while ascites and/or hepatic encephalopathy occurred in six. Azathioprine was stopped in all patients. Cyclosporin was also stopped in four patients and in two of them prednisolone was also interrupted for a period of 3-7 weeks. Following this, ascites, hepatic encephalopathy and biochemical disturbances improved, while no deterioration was seen in graft function. Nine of the 15 patients had undergone two consecutive liver biopsies (LB). The first LB revealed cirrhosis in three and chronic hepatitis in six patients; the second LB showed cirrhosis in seven patients. The histological activity index (Knodell's score) progressed from 11.8 +/- 3.5 to 13.8 +/- 3.8. CONCLUSIONS: The results suggest that HCV infection acquired during or after RTx may run an unusual and rapidly progressive clinical and histopathological course at least in some of these patients. Decrease or withdrawal of immunosuppressive drugs may improve early hepatic failure without detrimental effect on graft function during that period.

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.

Renal side-effects of long-term lithium treatment.

The beta 2-Mg (beta 2-microglobulin) and GAG (glycosaminogyclan) excretions in 107 patients with bipolar disorder who had been on lithium treatment for 1-15 years were compared with 29 matched psychiatric control patients. 24-h urine volume, urine beta 2-Mg, GAG values were significantly higher, and maximal urinary osmolality was significantly lower in patients on lithium than in controls. No relationship was found between creatinine clearances and duration of illness, duration of lithium treatment and daily lithium dosages. Duration of lithium treatment was not related to the concentrating capacity. The beta 2-Mg excretion rates were significantly higher in patients with manifest polyuria and with severe concentration defect.

Cryptosporidiosis and blastocystosis in renal transplant recipients.

Some intestinal parasitic infections are frequently seen in renal transplant recipients. Parasites such as Cryptosporidium spp. and Blastocystis hominis are often asymptomatic or responsible for limited infections in normals, but may cause prolonged and heavy infections with gastrointestinal complaints, mainly diarrhea, in immunocompromised patients. Such infections can often not be detected by routine diagnostic procedures, but special concentration and staining methods are needed. We investigated 115 fecal specimens from 69 renal transplant recipients and 42 fecal specimens from 42 control cases. Of the 69 recipients, 27 (39.1%) had B. hominis and 13 (18.8%) had Cryptosporidium spp. in at least one fecal specimen. Prevalence of symptomatic Cryptosporidium infections was significantly higher in the renal transplant recipients, when compared with the control group (p < 0.05). Special parasitological procedures must be performed in immunocompromised patients with chronic gastrointestinal complaints. Disappearance of symptoms after antiparastic drugs in some of 16 symptomatic patients are described, suggesting that these infections are more pathogenic in transplant recipients.

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.

Lipid-lowering effects of simvastatin and gemfibrozil in CAPD patients: a prospective cross-over study.

We compared the lipid-lowering effects of simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, and gemfibrozil, a fibric acid derivative, in 22 continuous ambulatory peritoneal dialysis patients whose serum total cholesterol and/or triglyceride levels were > or = 220 mg/dL after a standard diet for six months. The study group was first treated with gemfibrozil (600 mg/b.i.d.) for three months (stage 1). After a wash-out period of two months, during which no treatment was given, all of the patients became hyperlipidemic again and, therefore, were given simvastatin (10 mg/day) for three months (stage 2), which was followed by another two-month wash-out period. A control group, which served to evaluate the natural progression of pharmacologically untreated dyslipidemia, was followed during the same period. Blood determinations of triglyceride, total cholesterol, and high-density lipoprotein (HDL) cholesterol were performed after each step. Low-density lipoprotein (LDL) cholesterol and HDL ratio were calculated from the measured values. Both gemfibrozil and simvastatin improved all parameters of the lipid profile, but the effect of simvastatin was better than that of gemfibrozil (-69 vs -39 mg/dL for triglyceride and -95 vs -64 mg/dL for cholesterol), while their actions on LDL and HDL cholesterol were of equal magnitude. Two months after discontinuation of simvastatin, significant decreases of total cholesterol (-46 mg/dL) and triglyceride (-60 mg/dL) were still present, while these values had returned to pretreatment levels after stopping gemfibrozil. The HDL ratio remained markedlyhigher (p < 0.05) during the wash-out period after simvastatin, while it decreased to pretreatment values after gemfibrozil was stopped. The lipid profile of the control group did not change during the follow-up. Both drugs were well tolerated, and no serious side effects occurred.