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Background - Quality of life (QOL) is suboptimal in end-stage renal disease. However, studies indicate that QOL is already impaired prior to the initiation of renal replacement therapy, implying that the initial decline originates in the chronic kidney disease (CKD) phase of the renal disease trajectory. Given the significance of QOL as a clinical outcome, there is a paucity of QOL research in CKD. Aims - To measure QOL at three distinct phases (based on creatinine clearance - Ccr) of the disease trajectory in CKD: normal renal function (NRF) with underlying renal disease, moderate CKD, and advanced CKD (Ccr ≥75, 40–60, and ≤30 ml/minute, respectively), and to establish if QOL is different between these groups. Methods - Data was collected from 25 patients from each of the Ccr bands (N=75). We measured self-reported QOL (Schedule for the Evaluation of Individual Quality of Life - SEIQOL), uraemic symptoms (Leicester Uraemic Symptom Scale - LUSS), and laboratory variables. Results - SEIQOL was significantly lower (p<0.001), and symptom number, frequency, and intrusiveness significantly higher (all p<0.001) in the advanced CKD group when compared to the NRF group. Although SEIQOL and symptom intrusiveness did not differ between the advanced and moderate CKD groups, SEIQOL was significantly lower (p<0.05) and symptom intrusiveness significantly higher (p<0.05) in the moderate CKD group when compared to the NRF group. Conclusion - QOL is already impaired in moderate CKD. The significant difference in QOL and symptom intrusiveness between the moderate CKD and NRF groups may denote a causal relationship between symptom intrusiveness and QOL early in CKD. [ABSTRACT FROM AUTHOR]

Background — Quality of life (QOL) is suboptimal in end-stage renal disease. However, studies indicate that QOL is already impaired prior to the initiation of renal replacement therapy, implying that the initial decline originates in the chronic kidney disease (CKD) phase of the renal disease trajectory. Given the significance of QOL as a clinical outcome, there is a paucity of QOL research in CKD. Aims — To measure QOL at three distinct phases (based on creatinine clearance — Ccr) of the disease trajectory in CKD: normal renal function (NRF) with underlying renal disease, moderate CKD, and advanced CKD (Ccr ≥75, 40-60, and ≤30 ml/minute, respectively), and to establish if QOL is different between these groups. Methods — Data was collected from 25 patients from each of the Ccr bands (N=75). We measured self-reported QOL (Schedule for the Evaluation of Individual Quality of Life — SEIQOL), uraemic symptoms (Leicester Uraemic Symptom Scale — LUSS), and laboratory variables. Results — SEIQOL was significantly lower (p<0.001), and symptom number, frequency, and intrusiveness significantly higher (all p<0.001) in the advanced CKD group when compared to the NRF group. Although SEIQOL and symptom intrusiveness did not differ between the advanced and moderate CKD groups, SEIQOL was significantly lower (p<0.05) and symptom intrusiveness significantly higher (p<0.05) in the moderate CKD group when compared to the NRF group. Conclusion — QOL is already impaired in moderate CKD. The significant difference in QOL and symptom intrusiveness between the moderate CKD and NRF groups may denote a causal relationship between symptom intrusiveness and QOL early in CKD. [ABSTRACT FROM AUTHOR]

The role of complement has been studied in the autologous phase of nephrotoxic nephritis (NTN) in rabbits. No reduction in glomerular fibrin deposition, crescent formation or protection from renal failure was observed in either the standard model of NTN when decomplementing doses of cobra venom factor (CNF) were given before the autologous phase or in a telescoped model when CNT was administered before the nephrotoxic antibody. In the latter situation glomerular fibrin deposition and crescent formation were found in the absence of detectable deposition of C3. However, substantial protection was observed when circulating polymorphonuclear leucocytes (PMN) were depleted by antipolymorph serum. These observations establish the existence of' a system of allergic glomerular injury mediated by PMN hut independent of C3. It is postulated that this system may account for the glomerular injury seen in patients with Goodpasture's syndrome in whom glomerular C3 deposition is not found. [ABSTRACT FROM AUTHOR]

The role of polymorphonuclear leucocytes (PMN) in the autologous phase of nephrotoxic nephritis (NTN) in the rabbit has been investigated. Depletion of circulating PMN by nitrogen mustard protected renal function and immunofluroescent examination showed reduction in glomerular fibrin deposition. Depletion of circulating PMN using a highly specific goat anti-PMN serum (APS) provided similar protection of renal function. highly significant reduction in proteinuria and histological and immunofluroescent examination showed reduced glomeruIar PMN infiltration, extracapillary cell proliferation and virtual absence of fibrin deposition. Although protection by nitrogen mustard may have been partly due to immunosuppression, no reduction in antibody response was detected in the AN-treated rabbits. The results implicate the polymorph as the principal injurious agent in this model of NTN, responsible directly or indirectly for both proteinuria and glomerular fibrin deposition. [ABSTRACT FROM AUTHOR]

Quantitative studies of the effects of defibrination (with ancrod) have been undertaken in two forms of allergic glomerular damage, nephrotoxic serum nephritis and acute serum sickness in rabbits. No differences in intrarenal fixation of nephrotoxic antibody, complement activation or host antibody response were detected between defibrinated and untreated rabbits with nephrotoxic serum nephritis. Defibrination prevented intraglomerular fibrin deposition in this disease; but some glomerular damage as shown by a rise in blood urea and endothelial proliferation still occurred in defibrinated animals. No differences in immune elimination of BSA, circulating immune complex formation or intrarenal localization of immune complexes were noted in defibrinated animals with acute serum sickness. No intraglomerular fibrin deposition was detected in treated or untreated animals in this disease model. It is concluded that the protective effects of ancrod are directly related to defibrination, and not to any other modification of allergic events. [ABSTRACT FROM AUTHOR]

Mesangial kinetics were studied in six groups of rats. Rats were either sham operated or were subjected to 1 1/3 nephrectomy (4/6 Nx). Each group was either untreated or was treated with enalapril (EN) or the drug regimen of hydralazine, hydrochlorthiazide, and reserpine (HHR). Four weeks after surgery rats were injected with iodinated aggregated bovine serum albumin (I-aggBSA) and mesangial localization quantified 2, 4, or 8 h later. Mesangial kinetics in untreated 4/6 Nx rats were characterized by accumulation of I-aggBSA to 4 h after injection with rapid clearance over the 4–8 h period; i.e. mesangial trafficking was increased following 4/6 Nx. Mesangial trafficking in 4/6 Nx rats treated with EN was reduced by virtue of lesser uptake of I-aggBSA at 4 h and retarded clearance over 4–8 h when compared with untreated 4/6 Nx animals. Treatment of 4/6 Nx rats with HHR maintained the increased trafficking observed in untreated 4/6 Nx rats. At 30 weeks untreated 4/6 Nx rats had severe albuminuria and glomerulosclerosis. Both indices of renal damage were significantly less in 4/6 Nx rats treated with enalapril. Treatment with HHR did not prevent albuminuria and had only limited effectiveness in preventing glomerulosclerosis. The different effects of EN and HHR on mesangial trafficking and glomerulosclerosis provide further evidence for a relationship between mesangial trafficking following partial renal ablation and subsequent development of glomerulosclerosis. [ABSTRACT FROM PUBLISHER]

Mesangial kinetics of aggregated BSA (aggBSA) were studied in rats subjected to 1 1/3 nephrectomy (47sol;6 Nx) fed either a normal (16%) or a low-protein (8%) diet. At 4 weeks postsurgery, ablated rats exhibited modest elevations in blood pressure but had neither significant proteinuria nor evidence of glomerular damage. Following injection of aggBSA into 4/6 Nx rats (16% diet) there was a marked increase in mesangial localization at 4 h compared with control animals, followed by rapid clearance over 4–8 h, in keeping with increased trafficking in this model. The increased trafficking was significantly reduced by dietary protein restriction with 4/6 Nx rats fed an 8% protein diet exhibiting mesangial kinetics not significantly different from control animals. Control animals exhibited identical kinetics irrespective of diet. In separate studies, the 8% protein diet significantly reduced proteinuria and glomerulosclerosis when compared with untreated animals when studied at 30 weeks postsurgery. [ABSTRACT FROM PUBLISHER]

A new, specific haemolytic assay for C2 is described using EAC43 Antrypol) cells and serum deficient in C4 and C2 from a patient with hereditary angio-oedema. The method is simple and the results in pathological and normal sera correlate well with those obtained using the EA and C2-deficient serum method. [ABSTRACT FROM AUTHOR]

A significant percentage of patients with end-stage renal disease are malnourished and/or muscle wasted. Uremia is associated with decreased protein synthesis and increased protein degradation. Fortunately, nutritional status has been shown to be a modifiable risk factor in the dialysis population. It has long been proposed that exercise could positively alter the protein synthesis-degradation balance. Resistance training had been considered as the only form of exercise likely to induce anabolism in renal failure patients. However, a small, but growing, body of evidence indicates that for some dialysis patients, favourable improvements in muscle atrophy and fibre hypertrophy can be achieved via predominantly aerobic exercise training. Moreover, some studies tentatively suggest that nutritional status, as measured by SGA, can also be modestly improved by modes and patterns of exercise training that have been shown to also increase muscle fibre cross-sectional area and improve functional capacity. Functional capacity tests can augment the information content of basic nutritional status assessments of dialysis patients and as such are recommended for routine inclusion as a feature of all nutritional status assessments.

Objective: To determine the interday reproducibility of peak and submaximal exercise tolerance of patients with end-stage renal disease (ESRD)., Design: Repeated measures., Setting: Day-patient rehabilitation center., Participants: Twelve consecutively presenting, self-selected patients with ESRD., Interventions: All patients performed peak exercise tolerance assessments on a cycle ergometer up to the point of volitional fatigue, with a 1-week interval between the 2 tests., Main Outcome Measures: Cardiopulmonary, hemodynamic, and physical performance parameters were assessed at peak exercise and at the lactate threshold. Standard error of measurement, percentage coefficient of variation (CV%), intraclass correlation coefficient (ICC), and limits of agreement (LOA) were calculated to determine the reproducibility of all variables., Results: CV% (range, 5%-7%) and ICCs (range, .94 - .98) for oxygen uptake and heart rate at peak exercise and lactate threshold indicated highly acceptable levels of group mean reproducibility. LOA analysis revealed satisfactory levels of reproducibility for individual patients., Conclusion: Taken together, these reproducibility data may be applied to clinical work, requiring the quantification of changes in the exercise tolerance of patients with ESRD after short-term interventions (eg, exercise training, therapeutic use of recombinant erythropoietin)., (Copyright 2001 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation)

Background: Poor nutrition is associated with a loss of residual renal function and inferior clinical outcome in peritoneal dialysis (PD) patients. The value of increasing the PD dose in these individuals is unclear., Methods: An open, prospective, longitudinal, "intention to treat" study was performed on a whole PD population. All patients treated during an 18-month recruitment period underwent nutritional assessment and were defined as malnourished if they had a subjective global assessment (SGA) of B or C and were 5% or more below their desirable body weight. These patients received an intended dialysis dose increase of 25% and were reassessed after six months. Dialysis was not increased in the remaining patients, unless dictated by uremic symptoms., Results: Forty-eight of 153 patients were malnourished by the previously mentioned criteria. When compared with well-nourished PD patients, they had evidence of declining nutrition over the previous 12 months, as judged by a loss in body weight and mid-arm circumference (MAC), a reduced creatinine appearance, a reduced appetite for protein and calories, and low plasma albumin. They had been on treatment longer and had less residual renal function, resulting in significantly poorer solute clearances. Their peritoneal membrane function, plasma bicarbonate, comorbid, Karnofsky, Hospital Anxiety and Depression (HAD) scores were not different. Following intervention, their peritoneal Kt/Vurea was increased by 22.5%, and their total Kt/Vurea by 18%, because of a continued loss of residual function. There was also an increase in dialysis-derived calories. Weight and MAC stabilized after an initial deterioration, and creatinine appearance increased. There was no increase in protein intake, as judged by dietetic interview or protein nitrogen appearance. Oral calorie intake improved, as did plasma albumin after an initial decline. Both of these improvements were correlated with the achieved increase in Kt/Vurea. Objective measures of improvement (plasma albumin and protein nitrogen appearance) were significant in those patients without comorbid disease., Conclusions: These results support the existing evidence that malnutrition is acquired on PD in those patients who lose residual renal function. It is feasible to increase the dialysis dose in these individuals without a detrimental effect, and there is evidence of a modest benefit in patients without comorbidity.

Background: Several risk factors for patients treated with peritoneal dialysis (PD) have now been identified. These include age, comorbid disease, nutritional status, loss of residual renal function (RRF) and high peritoneal solute transport. This is not the same, however, as knowing what actually happens to these patients, particularly in the long-term. The purpose of this review was to give as complete a description as is currently possible of the long-term PD patient., Methods: The literature was surveyed for publications that provide longitudinal cohort data of either selected or unselected patient groups. Detailed data from the Stoke PD Study is presented in the context of these studies. Three principle aspects of what really happens to patients were considered: (1) death, both cause and mode of death; (2) technique failure, with reference to peritoneal function and how the cause of technique failure related to patient survival; and (3) evolution of clinically relevant parameters of patients on PD, such as nutrition and peritoneal function., Results: Sudden death and debilitation were the predominant modes of death, with sepsis playing a contributory role. Debilitation was important regardless of co-existent comorbid disease, and time to death was not influenced by the mode of death. Predominant causes for technique failure remain peritonitis and ultrafiltration, the latter becoming more important with time on treatment. Technical failure is associated with poorer survival, particularly when due to multiple peritonitis or failure to cope with treatment. Cox regression demonstrated that whereas low albumin, loss of RRF and high solute transport predicted patient death, only high solute transport predicted technique failure. Longitudinal changes over the first five years of treatment included loss of RRF, increasing solute transport and following an initial improvement in nutritional state, a decline after two years. Patients surviving long-term PD (at least five years, N = 25) were characterized by prolonged RRF, maintained nutrition and lower solute transport in the medium term., Conclusions: Several studies of long-term PD in the literature now complement each other in providing a picture of what really happens to PD patients. The links between loss of solute clearance and poor peritoneal ultrafiltration combining to exacerbate sudden or debilitated death and technique failure are emerging. For PD to be successful as a long-term therapy, strategies that maintain nutrition and preserve peritoneal membrane function must be developed.

26 patients with systemic lupus erythematosus (SLE) induced by treatment with the antihypertensive drug hydralazine were investigated to determine if predisposition to the toxic effect was associated with an HLA-DR antigen. 25 of the 26 patients were slow acetylators. The group was compared with three others (1) 113 healthy subjects, untested for acetylator phenotype, (2) 16 slow-acetylator hypertensive patients treated with hydralazine for more than a year without developing SLE, and (3) 20 patients with idiopathic SLE. The frequency of HLA-DR4 (73%) was significantly higher in the group with hydralazine-induced SLE than in the other groups (respectively 33%, 25%, and 25%). The ratio of women to men affected was 4:1. If the slow acetylators treated with hydralazine were analysed as one group, it was observed that all women with DR4 developed hydralazine-induced SLE; the only men to do so were those with DR2 who were receiving 200 mg hydralazine per day. These observations have led us to suggest guide lines for hydralazine therapy and point to a striking association between an HLA-DR antigen and an adverse reaction to a therapeutic agent. It was also noted that the distribution of DR antigens in the hydralazine-SLE patients was significantly different from that in the group with idiopathic SLE. This supports the view that the syndromes are separate entities.

Five of twenty-three patients with paraproteinaemia (two IgM, three IgG) have been shown to exhibit marked classical pathway complement activation. The mechanisms of hypocomplementaemia proposed for the five patients are cryoglobulinaemia in one and in vivo immunoglobulin aggregation in the other four. Three further patients had a low C1q and three a low C3 unassociated with any other complement abnormality. No association with any particular IgG subclass or obvious clinical abnormality existed in association with hypocomplementaemia.