HIV testing in patients with end stage renal disease.

One hundred and twenty eight British and Irish nephrologists were questioned about their policy for HIV testing of patients with end stage renal failure being considered for renal replacement therapy. A total of 101 (79%) replied. In the case of candidates for dialysis roughly one third of respondents tested only people they considered at risk of infection with HIV and nearly one fifth considered testing unnecessary. In the case of candidates for transplantation routine HIV testing was carried out by 68 of 100 nephrologists; 22 tested only patients "at risk" and 10 did not test. A positive HIV test result was considered by most but not all respondents (63/86) to exclude patients from transplantation. Twenty four of 88 nephrologists considered that HIV positivity should exclude patients from haemodialysis, but only seven of 87 would exclude such patients from peritoneal dialysis. Similar attitudes pertained for patients with end stage renal failure who refused HIV testing. Testing with the patient''s knowledge and consent was the policy of two thirds of nephrologists, but a patient''s signature was obtained by only 24 of 88. There should be a consensus on practice for HIV testing of patients with end stage renal failure.     

Inflammatory markers in chronic kidney disease and end stage renal disease patients

Molecular Biology Reports - Chronic kidney disease (CKD) is condition characterized by a gradual loss of kidney function, patient with CKD suffering from a variety of immune system defects. This...     

Diagnostic value of salivary cortisol in end stage renal disease

OBJECTIVES: Salivary cortisol has been proposed a surrogate marker for free serum cortisol measurements. The aim of this study was to ascertain the diagnostic value of basal and stimulated salivary cortisol for the detection of adrenal insufficiency (AI) in hypotensive end stage renal disease (ESRD) patients. Basal salivary cortisol and basal total serum cortisol were studied in order to determine the accuracy of both biomarkers in predicting AI. PATIENTS AND METHODS: Twenty-nine ESRD patients with sustained hypotension were investigated for possible AI. Salivary cortisol was assessed at baseline and 30min after 25microg ACTH i.m. (LDTs). The dosage of salivary aldosterone was performed in salivary cortisol hypo-responders. Basal blood samples were drawn for steroids, renin and ACTH measurements. RESULTS: A clear separation between patients with normal and impaired adrenal function was obtained through salivary cortisol levels at 30min after ACTH. AI was detected in six cases (21%) through impaired salivary cortisol responses; stimulated salivary aldosterone helped to differentiate primary (n=3) from secondary AI (n=3). ROC curves showed that cutoff values for basal SAF < or =4.4nM and serum cortisol < or =232.0nM suggest AI (sensitivities: 93% and 69%; specificities: 86.4% and 91%, respectively). CONCLUSIONS: We conclude that ACTH stimulated SAF is an accurate biomarker for the diagnosis of AI in hypotensive ESRD patients. Neither basal salivary cortisol nor serum cortisol showed 100% sensitivities for the detection of AI.     

Successful treatment of middle aged and elderly patients with end stage renal disease.

Many patients over the age of 55 with end stage renal disease in the United Kingdom are denied dialysis or transplantation. Although the reasons are complex, anticipation of a poor prognosis for these patients might explain why most British renal units impose an arbitrary age limit on the acceptance of patients for treatment. A study was therefore conducted to examine the prognosis and quality of life of 84 patients (mean age 59.6 years, range 55-72) accepted into our renal replacement programme from the beginning of 1975. The five year survival of the patients was 62.0% with 78.1% of the survivors either having successful transplants or caring for themselves using home haemodialysis or continuous ambulatory peritoneal dialysis. The results show that in terms of survival, economics, and rehabilitation it is both feasible and reasonable to treat middle aged and elderly patients with end stage renal disease. These patients should therefore not be denied dialysis or transplantation on the basis of age alone, and the lack of resources and other factors that allow this state to persist in Britain should be rapidly redressed.     

Evaluation of 25 OH Vitamin D in chronic renal failure and end stage renal disease subjects

Analysis of laboratory samples from chronic renal failure (CRF) and end stage renal disease (ESRD) patients can be problematic. Current HPLC and RIA methods for the determination of 25 OH Vitamin D involve sample extraction. However, the differences between a normal and CRF or ESRD matrix can lead to interference or inaccuracy in non-extracted, automated methods now available. The objective of this study was to assess the accuracy of the non-extracted LIAISON 25 OH Vitamin D assay in the analysis of CRF and ESRD samples as compared against RIA as reference. Samples were collected from regional reference laboratories and analyzed in both the LIAISON 25 OH Vitamin D assay and the DiaSorin 25 OH Vitamin D RIA. By Student's t test, no significant difference was observed between the RIA values and the LIAISON values (P = 0.07 CRF; P = 0.28 ESRD). The linear regression analysis resulted in the equations: CRF: LIAISON = 0.91 (RIA) + 0.6; r = 0.82 and ESRD: LIAISON = 0.93 (RIA) - 0.6; r = 0.78. From these data we conclude that the LIAISON 25 OH Vitamin D assay correctly assesses the 25 OH Vitamin D status of CRF and ESRD patients.     

Cost benefits of low dose subcutaneous erythropoietin in patients with anaemia of end stage renal disease.

OBJECTIVE--To assess the cost benefits of low dose subcutaneous recombinant human erythropoietin in correcting the anaemia of end stage renal disease. DESIGN--Three year retrospective study. SETTING--Subregional nephrology service serving a mixed urban and rural population of 800,000. SUBJECTS--60 patients with symptoms of anaemic end stage renal disease treated with erythropoietin (43 receiving haemodialysis; 11 receiving continuous ambulatory peritoneal dialysis; two with predialysis end stage renal disease; four with failing renal transplants). MAIN OUTCOME MEASURES--Costs and savings of achieving and maintaining a haemoglobin concentration of 85-105 g/l with erythropoietin. RESULTS--All patients treated with erythropoietin achieved the target haemoglobin concentration at median induction doses of 97 (95% confidence interval 95 to 108) units/kg/week, and this was maintained with 79 (75 to 95) units/kg/week at an average annual cost per patient of 2260 pounds. Admissions related to anaemia were virtually eliminated (246 v 1 inpatient days for 12 months before and after starting erythropoietin). 54 patients required no blood transfusions after starting erythropoietin, and the total requirements fell from 230 to 21 units in the 12 months before and after starting erythropoietin. Iron stores were maintained with oral or intravenous iron. All patients reported increased wellbeing, appetite, and exercise capacity. Hypertension developed or worsened in 30 patients, resulting in hospital admissions in five patients, one of whom had seizures. CONCLUSION--Low dose subcutaneous erythropoietin restores haemoglobin concentrations sufficiently to abolish blood transfusion requirements and reduce morbidity. The net cost of erythropoietin prescribed in this way (2260 pounds/patient/year) was largely offset by savings in costs of hospital admissions. The true annual cost to the NHS was around 1200 pounds per patient.     

Incidence of advanced chronic renal failure and the need for end stage renal replacement treatment.

OBJECTIVE--To determine the age related incidence of advanced chronic renal failure in two areas of England. DESIGN--Prospective study of patients newly identified as having advanced chronic renal failure within a two year period; subsequent monitoring of patients'' clinical course for a further 26 months. SETTING--Devon and Blackburn. SUBJECTS--Those patients in a population of 708,997 who developed advanced chronic renal failure (serum creatinine concentration greater than 500 mumol/l) for the first time during a two year period. MAIN OUTCOME MEASURES AND RESULTS--210 Patients (148 per million population per year) developed advanced chronic renal failure, 117 (51%) of whom were over 70. The age related incidence rose from 58 per million per year in those aged 20-49 to 588 per million per year in those aged 80 or over. Only 54% (113) of patients were referred to a nephrologist; 120 patients (57%) needed dialysis or died within three months of presenting without receiving dialysis, and 187 (89%) died or needed dialysis within three years. After those unsuitable for further treatment had been excluded, 78 patients per million population per year aged under 80 needed to start long term renal replacement treatment. CONCLUSIONS--Many patients suitable for renal replacement treatment are still not referred for nephrological opinion and are denied treatment. If the treatment rate in the United Kingdom rose from the 1988 rate of 55.1 per million per year to 78 per million per year then the number of patients receiving treatment would rise to about 800 per million. This is double the present number and has considerable but predictable resource implications for the NHS.     

Male microchimerism at high levels in peripheral blood mononuclear cells from women with end stage renal disease before kidney transplantation

Patients with end stage renal diseases (ESRD) are generally tested for donor chimerism after kidney transplantation for tolerance mechanism purposes. But, to our knowledge, no data are available on natural and/or iatrogenic microchimerism (Mc), deriving from pregnancy and/or blood transfusion, acquired prior to transplantation. In this context, we tested the prevalence of male Mc using a real time PCR assay for DYS14, a Y-chromosome specific sequence, in peripheral blood mononuclear cells (PBMC) from 55 women with ESRD, prior to their first kidney transplantation, and compared them with results from 82 healthy women. Male Mc was also quantified in 5 native kidney biopsies obtained two to four years prior to blood testing and in PBMC from 8 women collected after female kidney transplantation, several years after the initial blood testing. Women with ESRD showed statistically higher frequencies (62%) and quantities (98 genome equivalent cells per million of host cells, gEq/M) of male Mc in their PBMC than healthy women (16% and 0.3 gEq/M, p<0.00001 and p = 0.0005 respectively). Male Mc was increased in women with ESRD whether they had or not a history of male pregnancy and/or of blood transfusion. Three out of five renal biopsies obtained a few years prior to the blood test also contained Mc, but no correlation could be established between earlier Mc in a kidney and later presence in PBMC. Finally, several years after female kidney transplantation, male Mc was totally cleared from PBMC in all women tested but one. This intriguing and striking initial result of natural and iatrogenic male Mc persistence in peripheral blood from women with ESRD raises several hypotheses for the possible role of these cells in renal diseases. Further studies are needed to elucidate mechanisms of recruitment and persistence of Mc in women with ESRD.     

An angiotensin converting enzyme haplotype predicts survival in patients with end stage renal disease

The renin-angiotensin system is implicated in the development of a variety of human diseases. Many studies have sought to characterize the clinical implications of polymorphisms in the angiotensin converting enzyme (ACE) gene. Given the high mortality rate of individuals on chronic hemodialysis (HD), we sought to investigate whether genetic diversity in the ACE gene correlates with mortality in this population. We assembled a racially diverse cohort of prevalent individuals on chronic outpatient HD, and followed it prospectively for a mean of 2.1 years. Subjects were genotyped for seven single nucleotide polymorphisms (SNPs) in the ACE gene. Haplotype probabilities were calculated using an expectation–maximization algorithm. Cox proportional hazards regression was used to determine associations between haplotype and time to mortality from initiation of HD. There was strong linkage disequilibrium (LD) across the ACE gene, with three tagging SNPs found to account for all seven-SNP haplotypes that had a frequency of greater than 4%. After adjustment for age, race, gender, and diabetes status, a three-locus haplotype was associated with a 72% risk reduction in mortality (P = 0.004). The majority of this association was captured by the TT genotype of A-239T promoter polymorphism. The TGG (non-wild-type) haplotype, consisting of three tagging SNPs in the ACE gene, is associated with significantly decreased risk of all-cause mortality in HD patients independent of age, race, gender, and diabetic status. This “protective” haplotype may encompass loci with functional significance in the ACE gene.Electronic Supplementary Material Supplementary material is available to authorised users in the online version of this article at .     

Heart and lung transplantation in patients with end stage lung disease.

Combined heart and lung transplantation was used to treat seven patients with end stage lung disease. All were severely disabled, and their disease carried a poor prognosis. Six patients were well four to 33 months after transplantation. One patient died after 44 days from a primary cytomegalovirus pneumonia transmitted from the donor. All the survivors had normal exercise tolerance and greatly improved lung function. It is concluded that heart and lung transplantation is a suitable treatment for selected patients with end stage chronic lung disease.     

Accumulation of plasma N-methyl-2-pyridone-5-carboxamide in patients with chronic renal failure

Intracellular catabolism of NAD in mammalian cells occurs mainly via reaction catalyzed by poly(ADP-ribose) polymerase (PARP) with the release of nicotinamide, which is then metabolized predominantly to N-methyl-2-pyridone-5-carboxamide (2PY). PARP could be activated by binding to broken DNA and is known to be involved in DNA repair mechanisms, cell stress response and regulation of apoptosis. 2PY may accumulate under disease conditions resulting in accelerated DNA damage and retention of catabolic products. Our hypothesis was that chronic renal failure would lead to elevation of 2PY and potentially to inhibition of PARP and related physiological mechanisms. In the present study we: (a) compared plasma 2PY concentration in healthy subjects and in patients with chronic renal failure (CRF); (b) evaluated the relationship between plasma 2PY concentration and the severity of CRF; (c) evaluated the effect of hemodialysis treatment and kidney transplantation on 2PY concentration.We found that the plasma 2PY concentration in healthy subjects is 0.83 ± 0.18 M but it could increase up to 40 M in patients with CRF. A significant correlation was found in CRF between plasma 2PY and creatinine concentration. A single hemodialysis treatment was associated with significant reduction of plasma 2PY concentration after the hemodialysis, but it increased rapidly 48 h after the end of treatment. Successful kidney transplantation was associated with return of 2PY concentration to the normal range.In conclusion, our results indicated significant production of 2PY in humans. In healthy subjects 2PY is cleared from the plasma by excretion in the urine. Altered excretion by the kidney leads to increase in plasma concentration of 2PY. It is possible that 2PY may play a significant role in the development of uremic toxemia, especially as an inhibitor of poly(ADP-ribose)polymerase.     

Decrease of serum chemerin concentration in patients with end stage renal disease after successful kidney transplantation

Chemerin is an adipokine associated with metabolic syndrome, systemic inflammation and innate immune system. It has been suggested recently that the decrease in renal function may cause an increase in serum chemerin concentration. In this paper we investigated the effect of kidney transplantation on elevated serum chemerin concentration in dialyzed patients with end stage renal disease (ESRD). Twenty five ESRD patients were tested before and 3months after the kidney transplantation. The control group was comprised of twenty one healthy subjects. Serum chemerin concentrations were measured using commercial ELISA kit, and were related to clinical status, and biomarkers of renal function. We have shown that the kidney transplantation resulted in the decrease of the serum chemerin concentration. Concomitantly, serum creatinine, blood urea nitrogen, phosphate and C-reactive protein concentrations were significantly reduced, while estimated glomerular filtration rate (eGFR), calcium and hemoglobin substantially increased. Univariate regression analysis showed that serum chemerin concentration was positively correlated with serum creatinine and phosphate concentrations and negatively correlated with eGFR. The results presented here indicate that the serum chemerin concentration in patients with ESRD normalizes after the kidney transplantation, and provide additional evidence that serum chemerin concentration is related to renal function.