A Survey of Chronic Renal Failure in Southeastern Ontario

A survey of all physicians in southeastern Ontario was conducted to determine the potential number of patients with chronic uremia who would be candidates for a chronic dialysis program. Four hundred and sixty-four replies were received from the 1391 physicians who received the questionnaire. With the data provided it was calculated that the period prevalence rate of persons suffering from chronic uremia in the area surveyed ranged from 2.2 to 3.3/100,000 population. On the basis of these figures it was estimated that dialysis facilities might be required for six new patients each year in this area.     

Monitoring haemodialysis using electronic nose and chemometrics

An ever-increasing number of patients have to undergo regular renal dialysis to compensate for acute or chronic renal failure. The adequacy of the treatment has a profound effect on patients’ morbidity and mortality. Therefore, it is necessary to assess the delivered dialysis dose. For the quantification of the dialysis dose, two parameters are most commonly used, namely the K_t/V value (normalised dose of dialysis) and the urea reduction rate, yet the prescribed dialysis dose often differs from the actual delivered dialysis dose. Currently, no interactive process is available to ensure optimal treatment. The aim of this study was to investigate the potential for an “electronic nose” as a novel monitoring tool for haemodialysis. Blood samples were analysed using an electronic nose, comprising an array of 14 conducting polymer sensors, and compared to traditional biochemistry. Principal component analysis and hierarchical cluster analysis were applied to evaluate the data, and demonstrated the ability to distinguish between pre-dialysis blood from post-dialysis blood independent of the method used. It is concluded that the electronic nose is capable of discriminating pre-dialysis from post-dialysis blood and hence, together with an appropriate classification model, suitable for on-line monitoring.     

A nonlinear regression program for small computers

A BASIC computer program for performing weighted nonlinear regression is described and a listing of the program is given. The program, which is small and simple to use, has been designed to be run by users with little knowledge of mathematics or computers. Robust methods of analysis are described which may be applied to data in which experimental errors are not normally distributed, and the program incorporates one such method. It is shown that the program is useful for the analysis of data conforming to the Michaelis-Menten equation, a single exponential, and to binding equations, and other applications are discussed.     

The first 10 years of the dialysis-transplantation program at The Hospital for Sick Children,Toronto. 1: Predialysis and dialysis.

Renal dialysis and transplantation have been used for many years for adults with kidney failure but only recently for children. In May 1967 a renal-dialysis-transplantation program was established at The Hospital for Sick Children, Toronto for patients aged 6 to 18 years living within 240 km of Toronto. In 1973, children aged 1 to 5 years began to be accepted into the program, and by August 1977, 90 children (mean age 11 years) from all parts of Canada had been admitted to the program. The creation of vascular access in very small patients is difficult; the most successful types of access have been central shunts (established above the knee or the elbow) and bovine grafts. Specially made dialysis equipment is necessary for young patients. Young children should only be accepted in a dialysis-transplantation program that has a medical staff expert in meeting the specific needs of such children.     

A flexible new computer program for handling DNA sequence data.

A compact new computer program for handling nucleic acid sequence data is presented. It consists of a number of different subsets, which may be used according to a given code system. The program is designed for the determination of restriction enzyme and other recognition sites in correlation with translation patterns, and allows tabulation of codon frequencies and protein molecular weights within specified gene boundaries. The program is especially designed for detection of overlapping genes. The language, is FORTRAN and thus the program may be used on small computers; it may also be used without any prior computer experience. Copies are available on request.     

Contamination of peritoneal dialysis fluid by filamentous fungi

Peritonitis is a frequent complication in peritoneal dialysis. It may be caused by contamination of the dialysis tubing or by extension of the catheter exit site. Gram-positive bacteria are the most common organism, accounting for 60% of all documented cases of continuous ambulatorial peritonitis dialysis. Fungi are isolated from to 1-15% of cases. Forty-nine out of 490 bottles containing fluid for peritoneal dialysis were randomly selected for microbiological analysis in S?o Paulo, Brazil. In this report the contamination of peritoneal dialysis fluid by Chaetomium globosum and Chrysonilia sitophila is reported.     

Statistical Approach to Planning an Integrated Haemodialysis/Transplantation Programme

A mathematical model has been constructed to assist in planning the future requirements of a combined haemodialysis and transplantation centre. It has been used to predict the number of patients in the dialysis unit, the general wards, and at home on dialysis, as well as providing further information on transplantation rates and overall costs. The model can be adapted for units with different facilities from our own.It can be primed with data from an individual unit or with pooled data from the whole country. The purpose of this paper is to demonstrate the methodology of a particular statistical approach.     

Peritoneal Dialysis in Chronic Renal Failure

The long-term results of intermittent peritoneal dialysis in long-term treatment of renal disease have yet to equal those of intermittent hemodialysis. However, further exploration and refinement of this technique is justified.Performed in acute stages of disease, both peritoneal dialysis and hemodialysis relieve the symptoms of uremia and specifically “buy time” for the patient so that proper medical or surgical therapy may be instituted. In acute situations, peritoneal dialysis is the procedure of choice, and is an important adjunct to more conventional treatment for chronic renal disease. It may be useful sometimes even in chronically hemodialyzed patients—for example, when the hemodialysis cannula for one reason or another is inaccessible because of clots, replacement, or infection. It is especially valuable when the hemorrhagic complications of uremia contraindicate hemodialysis treatment.Its use in chronic uremia remains sharply limited in time, but for brief periods chronic peritoneal dialysis appears to be a reasonably satisfactory means of prolonging life while awaiting homotransplant or decision for maintenance hemodialysis therapy.     

Effect of intraperitoneal furosemide administration on levels of +proteins+ in plasma and signs of their ability to be dialyzed during intermittent peritoneal dialysis]

The study aimed at evaluating an effect of intraperitoneal furosemide on plasma proteins such as albumins, globulins, IgG and IgA and their loss during dialysis. An experiment involved 18 patients with critical renal failure treated with intermittent peritoneal dialyses. Furosemide was administered intraperitoneally with dialysing fluid (40 mg/1) in a total dose of 240 mg. Each patient underwent 2 dialyses of 14 exchanges each. The first dialysis without furosemide served as a control of plasma protein loss during conventional dialysis with a fluid of 369 mOsm/kg at flow rate 2.4 l/hour. Furosemide was given during the second dialysis during three consecutive exchanges. An effect of furosemide on plasma proteins was compared with the results obtained before and after its administration. It was found that furosemide did not change plasma proteins levels and does not increase their loss during exchanges of dialysing fluid containing this drug; during dialysing fluid exchanges without furosemide some indices of IgG and IgA dialysis are significantly decreased due to an increase in ultrafiltration following furosemide cessation. It is important for the increase in intermittent peritoneal dialyses efficiency with the aid of furosemide that its short-term administration does not increase proteins loss during dialysis, if their molecular weight is not exceeding 69,000.     

Effect of dialysis on oxidative stress in uraemia

It has been postulated that dialysis of patients with chronic renal failure (CRF) is associated with increased lipid peroxidation which may contribute to vascular and other complications of the syndrome. In the present study, a specific and precise technique [ferrous oxidation in xylenol orange (FOX) assay] was used to measure plasma lipid hydroperoxides (ROOHs) in three groups of uraemic patients. Patients were either studied before starting dialysis (n = 12) or on continuous ambulatory peritoneal dialysis (CAPD, n = 12) or haemodialysis (HD, n = 36) and compared to healthy controls (n = 20). Plasma ROOHs were markedly elevated in HD patients compared with the controls (7.01 +/- 2.9 microM versus 4.25 +/- 2.05 microM; P < 0.005, Mann-Whitney test). Plasma ROOH concentrations in the CAPD patients were increased but not significantly higher than controls (5.36 +/- 3.56 microM versus 4.25 +/- 2.05 microM). By contrast, no differences in ROOH levels were found between controls and predialysis patients. There was no difference in plasma thiobarbituric acid reactive substances (TBARS) between control and the three CRF groups. Absolute and cholesterol standardised plasma alpha-tocopherol levels were lower in the patients (whether they were on dialysis or not) than in the controls (18.62 +/- 6.88 microM versus 22.73 +/- 5.33 microM; P < 0.01 and 1.99 +/- 1.88 microM/mM versus 5.25 +/- 1.0 microM/mM; P < 0.0005, respectively). This study provides direct evidence that enhanced oxidative stress in CRF patients is related to the dialysis treatment rather than the disease itself. Further studies will be necessary to establish the relationships between plasma measures of oxidative stress and cardiovascular complications in CRF patients under dialysis and whether treatment with antioxidants may reduce oxidative stress or reverse adverse effects associated with dialysis.     

Error analysis in equilibrium dialysis: evaluation of adsorption phenomena

Various sources of error in equilibrium dialysis may lead to inaccurate results of binding experiments: (i) the finite time of dialysis; (ii) the Donnan effects; (iii) the adsorption of ligand to the membrane; and (iv) release of contaminating material from dialysis casings. These errors were analyzed for a polynucleotide-oligopeptide model system with particular regard to adsorption phenomena and the underlying mechanisms. Adsorption data were treated according to Freundlich and Langmuir isotherms. The latter turned out to be more appropriate for the consideration of adsorption phenomena with respect to a minimum error propagation. Furthermore, it was shown that the degree of adsorption varies with ionic strength and temperature and could be interpreted in terms of polyelectrolyte theory. The kinetics of both adsorption and of the ligand distribution between the polymer and buffer compartments follow first order at the beginning of dialysis which is in line with a simple diffusion process. After 13-15 h data deviate from first order kinetics indicating an alteration in the transport mechanism. The effects of errors on binding parameters were determined and a detailed protocol for correction is presented allowing one to obtain binding data from equilibrium dialysis experiments with the required degree of accuracy. The fundamental principles and results for the system under investigation generally apply to all protein-ligand systems.     

Effect of chronic renal failure,dialysis and transplantation on motor nerve conduction velocity in children.

Ulnar and peroneal motor nerve conduction volocities (MNCVs) were measured in 47 children in a dialysis-transplantation program. Mean peroneal MNCV was significantly decreased from normal in children with mild renal failure (serum creatinine concentration, 1.5 to 2.9 mg/dl), whereas ulnar MNCV was significantly decreased only when the serum creatinine value was at least 9 mg/dl. Both ulnar and peroneal MNCVs remained unchanged during long-term hemodialysis or peritoneal dialysis; however, after individual dialyses ulnar MNCV increased. After renal transplantation ulnar MNCV returned to normal within a year and peroneal MNCV within 3 years. Before dialysis was required and during long-term dialysis most plasma magnesium values were elevated; ionized calcium activity was decreased in about 50% of determinations. After transplantation and the concentration of divalent cations rapidly returned to normal. These children differed from adults studied in that (a) there was no correlation between severity of renal failure and MNCV, (b) long-term dialysis did not improve MNCV and (c) peroneal velocities did not recover for 3 years after transplantation.     

Effect Modifying Role of Serum Calcium on Mortality-Predictability of PTH and Alkaline Phosphatase in Hemodialysis Patients: An Investigation Using Data from the Taiwan Renal Registry Data System from 2005 to 2012

Predicting mortality in dialysis patients based on low intact parathyroid hormone levels is difficult, because aluminum intoxication, malnutrition, older age, race, diabetes, or peritoneal dialysis may influence these levels. We investigated the clinical implications of low parathyroid hormone levels in relation to the mortality of dialysis patients using sensitive, stratified, and adjusted models and a nationwide dialysis database. We analyzed data from 2005 to 2012 that were held on the Taiwan Renal Registry Data System, and 94,983 hemodialysis patients with valid data regarding their intact parathyroid levels were included in this study. The patient cohort was subdivided based on the intact parathyroid hormone and alkaline phosphatase levels. The mean hemodialysis duration within this cohort was 3.5 years. The mean (standard deviation) age was 62 (14) years. After adjusting for age, sex, diabetes, the hemodialysis duration, serum albumin levels, hematocrit levels, calcium levels, phosphate levels, and the hemodialysis treatment adequacy score, the single-pool Kt/V, the crude and adjusted all-cause mortality rates increased when alkaline phosphatase levels were higher or intact parathyroid hormone levels were lower. In general, at any given level of serum calcium or phosphate, patients with low intact parathyroid hormone levels had higher mortality rates than those with normal or high iPTH levels. At a given alkaline phosphatase level, the hazard ratio for all-cause mortality was 1.33 (p < 0.01, 95% confidence interval 1.27–1.39) in the group with intact parathyroid hormone levels < 150 pg/mL and serum calcium levels > 9.5 mg/dL, but in the group with intact parathyroid hormone levels > 300 pg/mL and serum calcium levels > 9.5 mg/dL, the hazard ratio was 0.92 (95% confidence interval 0.85–1.01). Hence, maintaining albumin-corrected high serum calcium levels at > 9.5 mg/dL may correlate with poor prognoses for patients with low intact parathyroid hormone levels.     

Selective interaction of ethidium derivatives with quadruplexes: an equilibrium dialysis and electrospray ionization mass spectrometry analysis

The telomeric G-rich single-stranded DNA can adopt in vitro an intramolecular quadruplex structure, which has been shown to directly inhibit telomerase activity. The reactivation of this enzyme in immortalized and most cancer cells suggests that telomerase is a relevant target in oncology, and telomerase inhibitors have been proposed as new potential anticancer agents. In this paper, we have analyzed the selectivity of four ethidium derivatives and ethidium itself toward different G-quadruplex species, with electrospray mass spectrometry and competitive equilibrium dialysis and evaluated their inhibitory properties against telomerase. A selectivity profile may be obtained through electrospray ionization mass spectrometry (ESI-MS), which is in fair agreement with competitive equilibrium dialysis data. It also provides unambiguous data on the number of binding sites per nucleic acid (maximal number of two ethidium derivatives per quadruplex, in agreement with external stacking). Our experiments also demonstrate that one compound (4) is the most active and selective G-quadruplex ligand within this series and the most selective telomerase inhibitor in a modified TRAP-G4 assay.     

A framework for structural equation models in general pedigrees

Background/Aims: Structural Equation Modeling (SEM) is an analysis approach that accounts for both the causal relationships between variables and the errors associated with the measurement of these variables. In this paper, a framework for implementing structural equation models (SEMs) in family data is proposed. Methods: This framework includes both a latent measurement model and a structural model with covariates. It allows for a wide variety of models, including latent growth curve models. Environmental, polygenic and other genetic variance components can be included in the SEM. Kronecker notation makes it easy to separate the SEM process from a familial correlation model. A limited information method of model fitting is discussed. We show how missing data and ascertainment may be handled. We give several examples of how the framework may be used. Results: A simulation study shows that our method is computationally feasible, and has good statistical properties. Conclusion: Our framework may be used to build and compare causal models using family data without any genetic marker data. It also allows for a nearly endless array of genetic association and/or linkage tests. A preliminary Matlab program is available, and we are currently implementing a more complete and user-friendly R package.     

Home peritoneal dialysis: 3 years' experience in Toronto.

From November 1972 to November 1975, 52 males and 39 females aged 11 to 71 years were trained for home peritoneal dialysis. Dialysis was performed through a permanent catheter 4 nights a week. The first 11 patients used the manual system, exchanging 2 / of dialysate solution every 50 to 60 minutes. Subsequently 73 patients used the automatic cycler and commercially available dialysate and 7 patients used Tenckhoff''s reverse osmosis peritoneal dialysis machine. The average duration of training was 15, 11.6 and 15 dialysis days, respectively, for the three methods. For the 83 patients followed up, the average duration of home dialysis was 8.3 months (range, 0.5 to 33 months); the total number of dialyses at home was 10 571. Ten received a transplant, 20 were transferred to hospital peritoneal dialysis or hemodialysis, 8 died and 48 continued with home dialysis. Twenty-three patients had a total of 33 episodes of peritonitis, an incidence of 27.7% among the patients in the program for up to 3 years or 0.3% among all the dialyses. By November 1975, 46 patients had returned to their predialysis lifestyle, 18 were working part-time, 10 were able to work but were not doing so, and 9 were unable to work or care for themselves.     

Potassium Balance and Acid-Base Changes in Patients Undergoing Regular Haemodialysis Therapy

Serial measurements of total body potassium in 21 patients with chronic renal failure being treated with three 10-hour periods of dialysis per week, against a dialysate fluid containing 1·5 mEq of potassium per litre, showed no evidence of potassium depletion. Mild hyperkalaemia was found in some patients before dialysis, correlated with the pre-dialysis hydrogen ion concentration. Hypokalaemia occurred during dialysis in almost half of the studies made; the plasma potassium concentration, however, rose to normal levels within two to four hours of stopping dialysis. A delay in the movement of potassium from the cells into the extracellular fluid is suggested as a cause for the observed hypokalaemia.In all but one patient the pre-dialysis blood pH was normal, but rose to alkalaemic levels during dialysis. A pronounced degree of hypocapnia was noted before dialysis, and this was not altered by a rising blood pH during dialysis. It is suggested that a stimulus to respiration other than the hydrogen ion gradient between the brain cells and cerebral spinal fluid may produce the observed hypocapnia.     

Does Erythropoietin Cause Hemoglobin Variability- Is It ‘Normal’?

Hemoglobin variability (Hb-var) in patients with chronic kidney disease has been stipulated to be a result of exogenous treatment with erythropoiesis stimulating agents (ESA) and has been related to mortality in dialysis patients. We hypothesized the existence of Hb-var independent of ESA administration and compared it to that in healthy adults using data from the Scripps-Kaiser and NHANES III databases. We studied the Hb-var in 1571 peritoneal dialysis patients which included 116 patients not requiring treatment with erythropoietin. We systematically studied the differences between the groups that needed ESA therapy and those who did not. White race and male sex were significant predictors of need for erythropoietin therapy. We found peritoneal dialysis patients to exhibit significantly increased Hb-var independent of treatment with exogenous erythropoietin (0.99 gm/dL vs. 1.17 gm/dL, p-value<0.001). We found age to be a significant determinant of Hb-var in the ESA treated group. Hb-var in younger patients (<30 years) was increased by 50% compared to young healthy adults. The Hb-var in elderly (>60 years) peritoneal dialysis patients was similar to that seen in healthy elders, suggesting similarity with anemia of aging. We conclude that exogenous ESA administration does not explain Hb-var entirely but may enhance it. Intrinsic factors affecting erythropoiesis including age may be the major determinants of Hb-var.     

Identification of linked regions using high-density SNP genotype data in linkage analysis

MOTIVATION: With the knowledge of large number of SNPs in human genome and the fast development in high-throughput genotyping technologies, identification of linked regions in linkage analysis through allele sharing status determination will play an ever important role, while consideration of recombination fractions becomes unnecessary. RESULTS: In this study, we have developed a rule-based program that identifies linked regions for underlined diseases using allele sharing information among family members. Our program uses high-density SNP genotype data and works in the face of genotyping errors. It works on nuclear family structures with two or more siblings. The program graphically displays allele sharing status for all members in a pedigree and identifies regions that are potentially linked to the underlined diseases according to user-specified inheritance mode and penetrance. Extensive simulations based on the chi(2) model for recombination show that our program identifies linked regions with high sensitivity and accuracy. Graphical display of allele sharing status helps to detect misspecification of inheritance mode and penetrance, as well as mislabeling or misdiagnosis. Allele sharing determination may represent the future direction of linkage analysis due to its better adaptation to high-density SNP genotyping data. AVAILABILITY: http://paed.hku.hk/uploadarea/yangwl/html/index.html     

An application of multivariate ratio methods for the analysis of a longitudinal clinical trial with missing data.

This paper presents an analysis of a longitudinal multi-center clinical trial with missing data. It illustrates the application, the appropriateness, and the limitations of a straightforward ratio estimation procedure for dealing with multivariate situations in which missing data occur at random and with small probability. The parameter estimates are computed via matrix operators such as those used for the generalized least squares analysis of catetorical data. Thus, the estimates may be conveniently analyzed by asymptotic regression methods within the same computer program which computes the estimates, provided that the sample size is sufficiently computer program which computes the estimates, provided that the sample size is sufficiently large.