Terminal Chronic Renal Failure Research Articles

Repeated analysis of estimated insulin resistance using the HOMAIR index in nondiabetic patients on peritoneal dialysis and its relationship with cardiovascular disease and mortality.

Terminal chronic renal failure patients show early insulin resistance (IR), characterised by alterations in the hydrocarbon metabolism and hyperinsulinaemia generally associated with dyslipidaemia and a proinflammatory condition. Cardiovascular disease (CVD) is the main cause of mortality in patients on dialysis. There is a strong association between IR, hyperinsulinism and CV disease. The objective of this study was to evaluate the effect of peritoneal dialysis (PD) on IR and its effects on the subsequent CVD morbidity and mortality in nondiabetic uraemic patients. It involved 69 nondiabetic patients on PD, 35 incident patients (≤ 3 months on PD) and 34 prevalent patients (>3 months on PD), with 2 estimated insulin resistance measurements 12 months apart using the insulin resistance index (HOMAIR). The mean HOMAIR value in incident patients was 1.8 ± 1.3 and 2.2 ± 2.1 at baseline situation and at 12 months respectively (not significant [NS]). In prevalent patients these values were 2.3 ± 1.3 and 2.5 ± 2.2 (NS). In our study, the mean glucose, insulin and IR concentrations measured by the HOMAIR and QUICKI indexes (the latter being a quantitative control for insulin sensitivity control) were similar at baseline situation and the following year, in both incident and prevalent patients. We did not find any significant differences in relation to CVD comorbidity, ischaemic heart disease, heart failure or cerebrovascular or peripheral comorbidity neither in the HOMAIR index or insulin levels. To conclude, nondiabetic patients on PD do not display a significant increase in HOMAIR levels and this remains the case over time when on dialysis. This, in turn, suggests that PD is not an IR risk factor. The fact that the IR indexes are not associated with CVD morbidity or mortality seems to suggest that this is a less significant factor in the field of PD.

Impact of Biologics for Induction in Kidney Transplant Patients with a Positive Serology for Hepatitis C

Introduction: Kidney transplantation is the best therapeutic option for HCV-positive patient with terminal chronic renal failure. However, there is limited and contradictory information on the impact that induction therapy with biological agents may have in this risk group. Aim of the study: Analyze the mid-term efficacy and safety of the induction with biologics (lymphocyte-depleting antibodies or anti-CD25 antibodies) in kidney transplant patients with anti-HCV antibodies positive, in terms of patient survival, graft survival and outcome of liver disease. Patients and methods: Retrospective observational study, based on the analysis of the clinical charts of HCV positive kidney recipients (EIA 1,2,3) at the moment of transplantation (TX) receiving a kidney graft in two Spanish units from March 1990 to March 2007, with follow-up until May 2007. 465 patients who met the inclusion criteria (anti-HCV antibodies positive at the moment of transplantation), and none of the exclusion criteria (HBsAg (+), IFN before Tx, previous or simultaneous transplant of a non-kidney graft), 301 did not receive induction therapy (Group I), 117 were treated with ATG, OKT3 or Timoglobuline ® (Group II), and 47 were treated with anti-CD25 antibodies (Group III). Induction therapy is only applied in patients with a high-immunological risk. Results: The induction with biological agents were not identified as an independent risk factor for the death of the patient (OR = 0, 869, 95% CI 0, 552-1, 369, p = 0, 545) being the 3-years patient survival of 91%, 92% and 93% in the three groups respectively (p = 0. 597). No patient died due to liver disease in groups II and III, and only five did so in group I. The death-censored graft survival to 3 years was similar between groups: 83% group I; 76% Group II; 81% Group III respectively (p = 0. 565). In addition, in the multivariate analysis, induction therapy was not an independent risk factor for graft loss among HCV-positive patients (O = 0. 877, CI 95% 0.646-1.192, p = 0. 403). Also, there were no significant differences in the evolution of ALT post-transplant levels, or in the incidence of postransplant severe clinical liver disease. Conclusion: Our data suggest that induction with biologics in HCV-positive kidney transplant patients with high-immunological risk, is related to a favorable mid-term results with regard to the graft survival, patient survival and without a negative impact on the clinical course of liver disease.

Tissue and Organs Transplantation in the Republic of Kazakhstan

In modern surgery it is generally accepted that successful kidney transplantation restores the quality of life for a significant proportion of patients with terminal chronic renal failure and provides them with the medical and social rehabilitation. The first successful kidney transplantation from a asystilic donor in Kazakhstan was accomplished on April 17th, 1979. Total for this period there were more than 600 transplants of donor kidneys accomplished, 46 kidney transplantations accomplished from related donors, 7 - autotransplontation of kidney and more than 40 kidney transplantations at children aged 6 to 18 years. Survival of renal transplant during the first year now stands at 81%, while the number of acute intractable rejection crises tends to decrease and nowadays is 7.8%. In addition to clinical kidney transplantation, NSCS after A.N. Syzganov develops a direction of the heart and liver transplantation in the experiment and in the clinic. The number of patients having terminal chronic renal insufficiency in the country tends to a constant growth in 2011 over a year on renal replacement therapy there are more than 1,800 patients - 65 per 1 million of population, mortality on the transplantation waiting list is 35.4%. With the collapse of the Soviet Union and Kazakhstan gaining its sovereignty, a legislative vacuum arose; including issues of organ and tissue transplantation due to what, along with the solving medical issues, there was a need for a legislative framework for the creation of conditions of work in organ donation. As a result of profound analysis of existing precedents in the world based on the provision on the organ transplantation of the World Health Organization, the draft law regulating the transplantation of organs and tissues in Republic was developed. Code of the Republic has a chapter on “Transplantation of tissues and (or) of (parts of)” c introduced the article “Transplantation of tissues and (or) of organs (parts of organs) and the condition of their withdrawal,” which includes Paragraph: 1. Transplantation donor of organs and tissues can be a person, the corpse of man, and animal. 2. Forced withdrawal of organs and tissues and their transplantation is not allowed. 3. The order of organ and tissue transplantation from one person to another, from the corpse of a man and from animals to humans is established by the Ministry of Health. The source of donor organ for heterotopic allotransplantation in the Republic of Kazakhstan can be living or cadaveric donor, and in the case of using a living donor the legislation of the Republic allows transplantation only from the related donor, and only in public health facilities. The main criterion for a related donation is to guarantee its security and obtaining optimal renal transplant.

Donor Kidney Transplantation in the Republic of Kazakhstan

In modern surgery it is generally accepted that successful kidney transplantation restores the quality of life for a significant proportion of patients with terminal chronic renal failure and provides them with the medical and social rehabilitation. At the same time, not all patients in need can be provided with transplantation due to some limitations, one of the major constraints is the shortage of donor organs. The first successful kidney transplantation from a asystilic donor in Kazakhstan was accomplished on April 17th, 1979. Total for this period there were more than 600 transplants of donor kidneys accomplished, 46 kidney transplantations accomplished from related donors, 7 - autotransplontation of kidney and more than 40 kidney transplantations at children aged 6 to 18 years. Survival of renal transplant during the first year now stands at 81%, while the number of acute intractable rejection crises tends to decrease and nowadays is 7.8%. In addition to clinical kidney transplantation, NSCS after A.N. Syzganov develops a direction of the heart and liver transplantation in the experiment and in the clinic. The number of patients having terminal chronic renal insufficiency in the country tends to a constant growth in 2011 over a year on renal replacement therapy there are more than 1,800 patients - 65 per 1 million of population, mortality on the transplantation waiting list is 35.4%. With the collapse of the Soviet Union and Kazakhstan gaining its sovereignty, a legislative vacuum arose; including issues of organ and tissue transplantation due to what, along with the solving medical issues, there was a need for a legislative framework for the creation of conditions of work in organ donation. As a result of profound analysis of existing precedents in the world based on the provision on the organ transplantation of the World Health Organization, the draft law regulating the transplantation of organs and tissues in Republic was developed. Code of the Republic has a chapter on “Transplantation of tissues and (or) of (parts of)” c introduced the article “Transplantation of tissues and (or) of organs (parts of organs) and the condition of their withdrawal,” which includes Paragraph: 1. Transplantation donor of organs and tissues can be a person, the corpse of man, and animal. 2. Forced withdrawal of organs and tissues and their transplantation is not allowed. 3. The order of organ and tissue transplantation from one person to another, from the corpse of a man and from animals to humans is established by the Ministry of Health. Despite the experience of transplantation services of Republic there are still organizational issues. An important issue for the service of transplantation remains the strengthening of legal framework for donation. One of the important conditions for the service is solidary awareness and unity of health care workers standing at the stage of organ donation and transplantation, as well as to eliminate social tensions of the general public to service.

Ultrasound Evaluation of the Shoulder in Patients with Terminal Chronic Renal Failure

This work addresses the evaluation of shoulder condition in patients with terminal chronic renal failure (TCRF), and analyses a possible relation between discovered changes with impairment of calcium-phosphorus metabolism.

Genetic analysis (PKD2) of autosomal dominant polycystic kidney disease

Autosomal dominant polycystic kidney disease is a multi-organic hereditary disorder. It is responsible for 7-10% of cases of end stage renal failure. It is caused by mutations in the genes PKD1 and PKD2. Both polycystic kidney disease's forms have a pathogeny and similar clinic, but in the patients with mutation in PKD2, the clinical manifestations appear later and the progression to end stage renal failure happens 10 years later than in the patients with mutation in PKD1. The diagnosis of this disease can be performed through ultrasounds, but the molecular diagnosis offers some advantages, such as the early detection of asymptomatic individuals who carry this genetic defect, in order to perform a preventive monitoring and genetic counselling. In this work, we present the results of the mutational analysis of the PKD2 gene in 18 patients diagnosed with autosomal dominant polycystic kidney disease. The objectives of this work were to analyze the profitability of the genetic study compared with the radiologic study, and perform an early genetic diagnosis in the descendants of patients who were affected by a mutation in the PKD2 gene, trying to establish a correlation between phenotype and genotype. After the genetic analysis, only one family was diagnosed with a mutation in exon 13 of the PKD2 gene (5.56%), which consists on a substitution of the nucleotide adenosine by cytosine (c.2398A>C), which implies that the amino acid methionine is replaced by leucine (p.800Met>Leu). In our population, contrary to what was published in the literature, the mutation of the gene was clinically significant and did segregate with the disease. All the members with a clinical and ultrasound diagnosis of polycystic renal disease presented the above mentioned mutation. We could not confirm any clinical-genetic correlation. Due to the high prevalence of chronic renal failure and terminal chronic renal failure secondary to polycystic kidney disease in our study, an early genetic diagnosis would involve a better prognosis in connection with a closer clinical monitoring.

Agreement between two routine methods of estimation of glomerular filtration rate in patients with advanced and terminal chronic renal failure

Estimations of glomerular filtration rate (GFR) obtained either by the modification of diet in renal disease study equation (MDRD-GFR) or by classic 24-hour urine collection-based methods (mean of creatinine and urea clearance (Ccr-ur)) are considered to be equivalent in patients with chronic renal failure (CRF). However, the agreement between both methods has been insufficiently studied in patients during the most advanced stages of CRF. We compared 615 estimations of GFR performed by both methods simultaneously in adult (> 18 years) patients with advanced (aCRF) (15 - 30 ml/min/1.73m2) and preterminal (tCRF) (< 15 ml/min/1.73m2) chronic renal failure. We also analyzed the influence of some relevant covariables (demographic characteristics, inflammatory and nutritional markers) with respect to the concordance between both methods. In aCRF, mean GFR were 19.7 +/- 5.5 (MDRD-GFR) and 19.3 +/- 3.7 ml/min/1.73m2 (Ccr-ur) (mean difference 0.4 ml/min/1.73m2, 95% confidence interval CI -0.3/1.1, p = 0.26), with an intraclass correlation coefficient of 0.46. In tCRF, mean GFR was 12.5 +/- 4.2 and 10.4 +/- 2.7 ml/min/1.73m2, respectively (mean difference 2.1 ml/min/1.73m2, 95% CI 1.7/2.4, p < 0.0005), with an intraclass correlation co-efficient of 0.43. Multivariate analysis identified lean body mass, body mass index, protein nitrogen appearance, proteinuria, gender, age, albumin (aCRF) and prealbumin (tCRF) as variables independently correlated with the difference MDRD-GFR minus Ccr-ur. Lean body mass was by far the strongest predictor of deviations between both methods, both in aCRF (R2 = 0.66, p < 0.0005) and tCRF (R2 = 0.49, p < 0.0005). MDRD-GFR and Ccr-ur show an acceptable agreement in advanced stages of chronic renal failure. However, MDRD-GFR produces estimations of GFR systematically higher than those given by the Ccr-ur method, in patients with tCRF. Moreover, this overestimation is particularly marked in some high risk subsets, including elderly patients and those presenting markers of a poor nutritional condition. Until this issue is further clarified, GFR should be estimated using Ccr-ur rather than MDRD-GFR in patients with tCRF, as also in older and malnourished patients with aCRF, as this may represent a more conservative and safer approach at the time of planning initiation of renal replacement therapy.

As atividades lúdicas em unidade de hemodiálise

This paper aimed at knowing the influence of playful activities on the treatment of patients with Terminal Chronic Renal Failure during hemodialysis. A qualitative approach, based on semi-structured interviews, was used. The study was performed with 16 patients in a hemodialysis unit. A category, defined as the individual ability of understanding their experiences, in a positive or negative way was observed. The following subcategories were developed: positive understanding, defined as the great care showed by patients through the playful activities, such as welfare; negative understanding, such as the indifference shown through the playful activities. The results showed that playful activities had a positive influence on most of the patients’ life, causing feelings of welfare. Even those patients indifferent to playful activities assumed that they enjoyed playing. We believe the results reinforce the nursing necessity of pursuing more humanistic actions in dialysis units

Paliación en diálisis

Con el fin de elaborar una guía de cuidados paliativos en enfermería para el paciente con insuficiencia renal crónica terminal en diálisis y sin posibilidad de transplante, se indagaron los conocimientos que tenían los enfermeros que laboran en diferentes unidades renales de Bogotá, sobre los cuidados paliativos que brindaban a los pacientes, y cómo estos los recibían y aplicaban en su propio cuidado para paliar su enfermedad. Esta información fue obtenida por medio de la aplicación de dos cuestionarios semiestructurados que arrojaron un interés general de mejorar la calidad de vida de los pacientes, a través de cuidados sencillos y efectivos que permiten cumplir tal objetivo. Después la información se complementó con la experiencia de la investigadora y la literatura obtenida acerca del tema en los diferentes textos consultados, todo ello con el propósito de agregar nuevos cuidados y optimizar los ya sugeridos por la población en estudio. Luego se elaboró la guía según los patrones funcionales de M. Gordon y los diagnósticos de la Asociación norteamericana de diagnósticos de enfermería, así como las características definitorias, resultados esperados y los cuidados obtenidos durante la investigación con fundamentos científicos.

Long-term follow-up of kidney allografts in patients with sickle cell hemoglobinopathy

Although sickle cell anemia and sickle cell disease produce a variety of functional renal abnormalities they uncommonly cause end stage renal failure. Renal transplantation has been a successful alternative for the treatment of the rare terminal chronic renal failure with outcomes comparable with non-sickle recipients. This approach, however, has not been often described on patients with renal failure associated with SC hemoglobinopathy. Here we report the outcomes of two patients with chronic renal failure due to SC hemoglobinopathies who underwent renal transplantation. At the time of the transplantation they were both severely anemic and had frequent vasoocclosive pain crises. Both patients evolved with good allograft function, near normal hematological parameters, and very rare pain crisis, thirteen and eight years after transplant. These cases illustrate that terminal renal failure due to SC hemoglobinopathy can be successfully managed by renal transplantation and satisfactory long-term results are achievable not only in terms of renal allograft function but also of their hematological condition.

Blink reflex in end-stage-renal disease patients undergoing hemodialysis

This study analyses the blink reflex in 20 adult male patients with terminal chronic renal failure undergoing hemodialysis. Abnormalities were found in ten patients (50%), eight of them with conduction studies showing axonal peripheral neuropathy. Dialysis time was longer for patients with blink reflex alterations (median 55.1 months) than for patients with normal blink reflex (median 36.3 months). Different types of early R1 and late R2 component abnormalities were recorded. The late response abnormalities may indicate subclinical functional or anatomical impairment of the low brainstem reticular formation in patients with chronic renal failure.

A Clinical and Bacteriological Study of Children Suffering from Haemolytic Uraemic Syndrome in Tucmán, Argentina

Haemolytic uraemic syndrome (HUS) is a disease with serious consequences for children, such as terminal chronic renal failure. During the last few years there have been numerous studies undertaken to determine whether there is a relationship between this disease and the presence of Shiga toxin-producing bacteria. Escherichia coli (E. coli) O157:H7 is one of the most frequent etiologic agents of HUS. It acts through cytotoxins called Shiga toxin 1 (Stx1) and/or Shiga toxin 2 (Stx2) and carries a 90-Kb plasmid codified for an adhesion fimbria which is part of its pathogenicity. The objectives of this study were to: 1). confirm whether there exists a relationship between severity and clinical presentation of HUS; 2). prove the existence of Stx1 and/or Stx2 in the faeces of HUS patients; and 3). detect the presence of Stx1- and/or Stx2-producing E. coli. Our results did not show any difference in the average age, sex or clinical behavior between children with diarrhea positive (D+) HUS and diarrhea negative (D-) HUS. Male patients were predominant, as was incidence during summer, considering all cases. Nor could we find any relationship between severity and HUS type. E. coli O157:H7 was isolated in 40% of the patients with (D+) HUS and in 50% of patients with (D-) HUS. Another serotype, O55:K59, was also isolated (7%). Stx1 and/or Stx2 were found in all HUS cases. The following virulence factors of E. coli strains isolated from 12 patients were found: Adhesion fimbria (100%), Stx1 (16%), Stx2 (32%), and Stx1 + Stx2 (50%). None of these factors was found in control patients. Sixty-three percent of the HUS cases showed seroconversion for lipopolysaccharides of E. coli O157. We drew the following conclusions: 1). there is no significant relationship between seriousness of HUS and type of disease; 2). an association exists between HUS and the production of Stx1 and Stx2; 3). the incidence of E. coli O157:H7 was high in Tucuman, Argentina; and 4). Stx2 alone or in association with Stx1 was the predominant toxin.

Strong association between malnutrition, inflammation, and atherosclerosis in chronic renal failure

Atherosclerotic cardiovascular disease and malnutrition are widely recognized as leading causes of the increased morbidity and mortality observed in uremic patients. C-reactive protein (CRP), an acute-phase protein, is a predictor of cardiovascular mortality in nonrenal patient populations. In chronic renal failure (CRF), the prevalence of an acute-phase response has been associated with an increased mortality. One hundred and nine predialysis patients (age 52 +/- 1 years) with terminal CRF (glomerular filtration rate 7 +/- 1 ml/min) were studied. By using noninvasive B-mode ultrasonography, the cross-sectional carotid intima-media area was calculated, and the presence or absence of carotid plaques was determined. Nutritional status was assessed by subjective global assessment (SGA), dual-energy x-ray absorptiometry (DXA), serum albumin, serum creatinine, serum urea, and 24-hour urine urea excretion. The presence of an inflammatory reaction was assessed by CRP, fibrinogen (N = 46), and tumor necrosis factor-alpha (TNF-alpha; N = 87). Lipid parameters, including Lp(a) and apo(a)-isoforms, as well as markers of oxidative stress (autoantibodies against oxidized low-density lipoprotein and vitamin E), were also determined. Compared with healthy controls, CRF patients had an increased mean carotid intima-media area (18.3 +/- 0.6 vs. 13.2 +/- 0.7 mm2, P < 0.0001) and a higher prevalence of carotid plaques (72 vs. 32%, P = 0.001). The prevalence of malnutrition (SGA 2 to 4) was 44%, and 32% of all patients had an acute-phase response (CRP > or = 10 mg/liter). Malnourished patients had higher CRP levels (23 +/- 3 vs. 13 +/- 2 mg/liter, P < 0.01), elevated calculated intima-media area (20.2 +/- 0.8 vs. 16.9 +/- 0.7 mm2, P < 0.01) and a higher prevalence of carotid plaques (90 vs. 60%, P < 0.0001) compared with well-nourished patients. During stepwise multivariate analysis adjusting for age and gender, vitamin E (P < 0.05) and CRP (P < 0.05) remained associated with an increased intima-media area. The presence of carotid plaques was significantly associated with age (P < 0.001), log oxidized low-density lipoprotein (oxLDL; P < 0.01), and small apo(a) isoform size (P < 0.05) in a multivariate logistic regression model. These results indicate that the rapidly developing atherosclerosis in advanced CRF appears to be caused by a synergism of different mechanisms, such as malnutrition, inflammation, oxidative stress, and genetic components. Apart from classic risk factors, low vitamin E levels and elevated CRP levels are associated with an increased intima-media area, whereas small molecular weight apo(a) isoforms and increased levels of oxLDL are associated with the presence of carotid plaques.

Normalisation des appareils d'épuration extrarénale

Various medical devices and sterile/non pyrogenic solutions for injection are used to performed haemodialysis, which is the most used method for renal replacement therapy in patients with terminal chronic renal failure. This paper reviews the European standard for hemodialysis systems (dialysis machines and dialysers) with respect to medical practice. Experience shows that dialysis machines in bad working conditions or those which are misused could result in hazards for patients, even with medical devices carrying the CE marking — which are supposed to comply with the essential requirements. State of the art practices dictate comprehensive maintenance protocol of dialysis systems associated with good medical practices, which should be implemented in every dialysis unit in order to provide a high degree of safety to patients. Réaliser une épuration extrarénale par hémodialyse ou par dialyse péritonéale nécessite l'utilisation de dispositifs médicaux variés et de produits pharmaceutiques divers. L'objet de cet article est de faire l'état des lieux dans le domaine de l'hémodialyse, méthode la plus utilisée dans le traitement de l'insuffisance rénale, et d'apporter des éléments de réflexion soulevés par l'expérience. Bien que les dispositifs médicaux portant la marque CE répondent à des exigences essentielles du moment, la confrontation des normes à la pratique médicale montre des cas où des dérives et/ou une utilisation inappropriée de l'appareil peuvent aboutir à des incidents. Seul, un suivi régulier du bon fonctionnement de l'appareil par une maintenance prospective, aidée en cela par la matériovigilance, complément naturel de la normalisation, et une application rigoureuse des bonnes pratiques cliniques peuvent apporter au patient un haut degré de sécurité en rapport avec l'état de l'art.

Serum immunoreactive leptin concentration and its relation to the body fat content in chronic renal failure.

Leptin, secreted from fat cells, functions as a lipostat mechanism through modulation of satiety signals. The role of leptin in humans has been only partly revealed. However, obese patients have markedly elevated levels of this hormone, and in both normal-weight and obese subjects there is a direct correlation between serum leptin levels and the percentage of body fat. The aim of the present study was to investigate the role of leptin and its relation to body fat content in chronic renal failure (CRF), a disorder associated with decreased appetite. Serum leptin levels and body composition (dual-energy x-ray absorptiometry) were measured in a cohort of 59 patients with terminal CRF (creatinine clearance rate, 8 +/- 1 ml/min). Sixteen of the patients were re-evaluated after 12 mo of peritoneal dialysis treatment, and eight patients were re-evaluated after 12 mo of hemodialysis treatment. The mean serum leptin concentrations were markedly higher (mean +/- SEM) in patients with CRF than in healthy control subjects matched for gender and body mass index (25.7 +/- 5.2 ng/ml versus 8.4 +/- 0.9 ng/ml; P < 0.001). Patients with ongoing signs of inflammation (C-reactive protein > 10 mg/L) demonstrated higher serum leptin levels (41.9 +/- 13.7 ng/ml versus 18.6 +/- 4.2 ng/ml; P < 0.05) than patients with normal C-reactive protein. A strong positive correlation (rho = 0.83; P < 0.0001) was found between serum leptin concentrations and the percentage of body fat. After 12 mo of peritoneal dialysis, the amount of body fat increased markedly (19.0 +/- 1.5 to 25.1 +/- 2.2 kg; P < 0.001), and the changes in serum leptin concentrations correlated significantly (rho = 0.69; P < 0.01) to the changes in the body fat content. In contrast, no significant changes in either body fat content or serum leptin levels were recorded in the eight patients that were re-evaluated after 12 mo of hemodialysis. Serum leptin concentrations are approximately three times higher in patients with CRF compared with healthy control subjects with a similar body mass index. In this study, it is also demonstrated that serum leptin is a good marker for the body fat content in CRF patients and correlates strongly to changes in body fat during 12 mo of peritoneal dialysis. These findings suggest that serum leptin could serve as a valuable clinical marker for the body fat content in patients with CRF. Further studies are needed to verify the hypothesis that increased serum leptin concentrations may contribute to uremic anorexia.

Ofloxacin Pharmacokinetics in Chronic Renal Failure and Dialysis

Data on the pharmacokinetics of ofloxacin in chronic renal failure, in patients who were not dialysed or were receiving haemodialysis or continuous ambulatory peritoneal dialysis (CAPD), are reviewed. In addition, a large pool of data obtained in patients with a wide range of renal dysfunction is provided. The good absorption of ofloxacin after oral administration is not influenced by renal failure. Total plasma clearance (CL) is largely dependent on renal elimination of the drug, and renal clearance (CLR) and urinary recovery are reduced in parallel with reductions in renal function. Consequently, the serum half-life progressively increases when creatinine clearance decreases. Although there is wide variation in the published absolute values for the CL and CLR of ofloxacin, all studies show a similar pattern in the pharmacokinetic behaviour of the drug in chronic renal failure. A proposed protocol for ofloxacin dosage adjustment in chronic renal failure is reported which differs slightly but significantly from that recommended by the manufacturer. This new dosage regimen was derived from the pharmacokinetic results after single and multiple oral administration of the drug to patients with chronic renal failure. Since no clinically relevant losses of ofloxacin occur during haemodialysis or continuous ambulatory peritoneal dialysis (CAPD), the same protocol should be followed in these patients as in undialysed patients with terminal chronic renal failure.

Autonomic Nervous System in Haemodialysis

Fifty-two patients with terminal chronic renal failure on haemodialysis were assessed for the existence of autonomic neuropathy using the Valsava index. The values in the patients were lower than in the controls. Only a few symptoms could be related to the autonomic neuropathy. No correlation was found between Valsalva index and orthostatic or intradialysis hypotension, motor-nerve conduction velocity or plasma intact parathyroid hormone. Having demonstrated the existence of autonomic neuropathy, eight healthy subjects and ten patients on haemodialysis were studied to locate the segment of the autonomic reflex are affected. Heart rate and intraarterial pressure were monitored during the following tests: phenylephrine; hyperventilation; cold pressor; atropine; tyramine and adrenaline. An alteration was observed in baroreceptors, together with adrenergic hyperexcitability (reflected in the hypersensitivity of the sympathetic efferent pathway) and a greater response to the stimulus for the release of extra-adrenal adrenaline. The lower response to atropine is indicative of vagal alteration.

Laser Microprobe Mass Analysis (LAMMA) to Verify the Aluminon Staining of Bone

Triammonium aurin tricarboxylate (aluminon) has been used to localize aluminum in 2 micron sections of undecalcified, methyl methacrylate embedded bone obtained from patients with terminal chronic renal failure. Aluminum appeared in four cases as bright red lines at the mineralized-bone boundary. In two cases, however, purplish lines were found and one patient showed red as well as purplish lines. Laser microprobe mass analysis (LAMMA) identified aluminum at the location of the red lines and both aluminum and iron at the purplish lines. Furthermore, both iron and aluminum were found in histiocytic bone marrow cells, which showed brownish aluminon staining. It appears that when aluminum and iron occur together, aluminon staining may yield aberrant results. This study shows that LAMMA can be used for the identification of elements sought by histochemical methods and thus permits the evaluation of their staining effects.

Survival in Elderly Patients Presenting with Uraemia

A retrospective study was made of 93 patients aged 60 years or greater presenting with renal failure between 1976 and 1981 to assess survival and analyse the factors influencing it. Two-year survival of 28 patients with acute renal failure was 50 per cent and of 65 patients with chronic renal failure it was 40 per cent. Higher initial plasma urea and creatinine values and increasing age had a significantly adverse effect on survival. Patients requiring dialysis likewise fared less well although only one patient succumbed as a direct result of the dialysis procedure. The study reveals a worthwhile survival in both acute and chronic renal failure even though during the period under consideration long-term dialysis of patients in this age group with terminal chronic renal failure was rarely undertaken.

Drug-induced Renal Disease

The clinical manifestations of drug-induced renal disease may include all the manifestations attributed to natural or spontaneous renal diseases such as acute renal failure, chronic renal failure, acute nephritic syndrome, renal colic, haematuria, selective tubular defects, obstructive nephropathy, etc. It is therefore vital in any patient with renal disease whatever the clinical manifestations might be, to obtain a meticulous drug and toxin inventory. Withdrawal of the offending drug may result in amelioration or cure of the renal disorder although in the case of severe renal failure it may be necessary to utilise haemodialysis or peritoneal dialysis to tide the patient over the period of acute renal failure. Analgesic nephropathy is an important cause of terminal chronic renal failure and it is therefore vital to make the diagnosis as early as possible. The pathogenesis of some drug-induced renal disorders appears to be immunologically mediated. There are many other pathogenetic mechanisms involved in drug-induced renal disorders and some drugs may under appropriate circumstances be responsible for a variety of different nephrotoxic effects. For example, the sulphonamides have been incriminated in examples of crystalluria, acute interstitial nephritis, acute tubular necrosis, generalised hypersensitivity reactions, polyarteritis nodosa and drug-induced lupus erythematosus.