Patients' representations of their end-stage renal disease: relation with mortality.

BACKGROUND: Self-regulation theory explains how patients' illness perceptions influence self-management behaviour (e.g. via adherence to treatment). Following these assumptions, we explored whether illness perceptions of ESRD-patients are related to mortality rates. METHODS: Illness perceptions of 182 patients participating in the NECOSAD-2 study in the period between December 2004 and June 2005 were assessed. Cox proportional hazard models were used to estimate whether subsequent all-cause mortality could be attributed to illness perception dimensions. RESULTS: One-third of the participants had died at the end of the follow-up. Mortality rates were higher among patients who believed that their treatment was less effective in controlling their disease (perceived treatment control; RR = 0.71, P = 0.028). This effect remained stable after adjusting for sociodemographic and clinical variables (RR = 0.65, P = 0.015). CONCLUSIONS: If we consider risk factors for mortality, we tend to rely on clinical parameters rather than on patients' representations of their illness. Nevertheless, results from the current exploration may suggest that addressing patients' personal beliefs regarding the effectiveness of treatment can provide a powerful tool for predicting and perhaps even enhancing survival.

[Estimating renal function based on creatinine clearance: application of different formulas and correction for obese patients]. / Schatting van de nierfunctie op grond van de creatinineklaring: bruikbaarheid van enkele formules en correctie bij obese patiënten.

OBJECTIVE: To determine whether glomerular filtration rate (GFR) is best estimated by the Cockcroft-Gault formula or the formula used in the 'Modification ofdiet in renal disease' (MDRD) study. DESIGN: Descriptive inventory. METHOD: Passing-Bablok regression analysis was performed using the statistics program 'Analyse it' for the estimated GFR derived by both formulas based on 467 patients who had data on height, weight and creatinine clearance entered into the laboratory information system of the Máxima Medical Centre, Veldhoven, the Netherlands, during a 2-year period. The performance of each formula was analysed in different patient groups based on weight. RESULTS: The MDRD formula and the Cockcroft-Gault formula performed similarly in all weight groups with adequate precision, particularly when the corrected Cockcroft-Gault formula was used for patients with a body-mass index (BMI) >25 kg/m2. The fact that outcomes using the BMI-corrected Cockcroft-Gault formula strongly correlated with outcomes calculated using the so-called Salazar-Corcoran formula, which was developed specifically for use in obese patients, confirms the validity of the BMI-corrected approach. CONCLUSION: The Cockcroft-Gault formula and the MDRD formula both provided appropriate estimates of GFR and were also considerably more suitable for screening for renal function than assessment of plasma creatinine concentration. However, the best non-invasive way to determine GFR remains a carefully performed assessment ofcreatinine clearance using plasma and 24-hour urine samples.

[Diagnostic image (352). A man with spots, dyspnoea and lethargy]. / Diagnose in beeld (352). Een man met vlekjes, dyspneu en apathie.

A 54-year-old man with Down's syndrome presented with petechiae, hypoxia and lethargy due to a collum fracture and a secondary fat embolism syndrome.

Idiopathic focal segmental glomerulosclerosis: a favourable prognosis in untreated patients?

BACKGROUND: Patients with focal segmental glomerulosclerosis (FSGS) are considered to have a poor prognosis and spontaneous remissions are seldom reported. However, FSGS is not a single disease entity. Our aim was to describe the clinical course in initially untreated patients with recently diagnosed idiopathic FSGS. METHODS: This was a retrospective study of patients with a diagnosis of FSGS by histology, who fulfilled the following criteria: proteinuria >3.5 g/day, normal renal function, duration of proteinuria or hypertension of less than one year, normal-sized kidneys, no underlying renal disease, and a negative family history. Renal biopsies were reviewed without knowledge of the clinical course. RESULTS: Twenty patients (13 male, 7 female) fulfilled the study criteria. Median age was 49.3 (range 21.8 to 73.0) years, serum creatinine 90 +/- 20 micromol/l, proteinuria 10.0 +/- 5.5 g/day and serum albumin 24 +/- 6 g/l. After a median follow-up of 9.4 (2.1-18.6) years, 13 patients (65%) were in remission of proteinuria. Renal function deterioration occurred in seven patients, and prompted treatment in four of them. The ten-year death-censored renal survival was 89%. Renal function deterioration and remission rate could be predicted by selectivity index, serum albumin at three months after renal biopsy and the percentage of glomeruli with segmental sclerosis. CONCLUSION: Focal glomerulosclerosis is not a single disease. Case definition using strict clinical criteria identifies a subgroup of patients with idiopathic FSGS who have a good prognosis. In the majority of these patients immunosuppressive therapy is not warranted.

Restrictive use of immunosuppressive treatment in patients with idiopathic membranous nephropathy: high renal survival in a large patient cohort.

BACKGROUND: Immunosuppressive treatment initiated at an early stage in patients with idiopathic membranous nephropathy (iMN) improves renal survival. Treatment should ideally be restricted to high-risk patients. AIM: To evaluate the efficacy of a restrictive immunosuppressive treatment strategy for patients with iMN. DESIGN: Prospective cohort study evaluating a predefined treatment protocol. METHODS: From 1988, we adopted a restrictive treatment strategy: immunosuppressive treatment, mainly consisting of cyclophosphamide and steroids, was advised only in patients with renal insufficiency or severe intolerable nephrotic syndrome. We evaluated this strategy in a large patient cohort. To exclude any bias, we included all adult patients with iMN biopsied in the study period with a serum creatinine (Scr) < 135 micromol/l, a proteinuria > or = 3.0 g/day and/or a serum albumin (Salb) < or = 30 g/l at the time of biopsy. Analysis was according to the intention-to-treat principle. RESULTS: We studied 69 patients. At the time of biopsy, mean age was 51 years, Scr 90 micromol/l, Salb 23 g/l and proteinuria 6.7 g/day. Average follow-up was 5.5 years. Thus far 33 (48%) patients have received immunosuppressive therapy, mainly because of renal insufficiency (n = 24). Status at the end of follow-up was: complete remission n = 22 (32%), partial remission n = 24 (35%), nephrotic syndrome n = 15 (22%), persistent proteinuria n = 1 (1.4%), ESRD n = 6 (8.7%), death n = 1 (1.4%; due to bladder carcinoma after cyclophosphamide therapy). Patient survival was 100% at 5 and 7 years. Renal survival was 94% at 5 years and 88% at 7 years. DISCUSSION: In patients with iMN, a restrictive treatment policy assures a favourable prognosis, while preventing exposure to immunosuppressive therapy in >50% of the patients.

Hemolytic uremic syndrome after capnocytophaga canimorsus (DF-2) septicemia.

A 66-year-old man developed a hemolytic uremic syndrome (HUS) with acute renal failure, thrombocytopenia, fragmented red cells in the blood film and elevated serum LDH following a capnocytophaga canimorsus (DF-2) infection after a dog bite. He was treated with antibiotics, plasmapheresis and hemodialysis. Although hematologic values improved, the patient remained hemodialysis-dependent for six months. In the literature several cases of renal failure following capnocytophaga canimorsus septicemia have been described, caused by hypotension or disseminated intravascular coagulation (DIC). In our patient there were no signs of hypotension or extensive DIC. A few case reports described HUS and thrombotic thrombocytopenic purpura (TTP) following DF-2 sepsis.

Combination diuretic therapy in severe congestive heart failure.

Severe congestive heart failure (CHF) is often characterised by fluid retention. A (chronic) state of overhydration has a negative influence on both the quality of life and prognosis of these patients. Therefore, the use of diuretics remains a cornerstone in the treatment of heart failure. However, diuretic resistance, a failure to correct the hydration state adequately with the use of conventional dosages of loop diuretics, is a frequently occurring complication in the treatment of advanced stages of CHF. Several intra- and extrarenal mechanisms may be involved in the development of diuretic resistance. An important pathophysiological mechanism leading to diuretic resistance seen after chronic use of loop diuretics is the functional adaptation of the distal tubule. Studies in animals demonstrate that the sodium reabsorption capacity of this nephron segment increases significantly when the sodium delivery to this segment is augmented, as is the case during administration of loop diuretics. The use of combinations of diuretics acting on different segments of the nephron appears to be an effective option in the treatment of diuretic resistance. Several combinations have been used; however, the combination of a loop diuretic and a thiazide drug acting on the distal tubule appears to be the most effective. However, since the use of this combination may lead to serious adverse effects such as hypokalaemia, metabolic alkalosis and dehydration, careful monitoring of the patient of combination diuretic therapy is necessary.

The influence of bicarbonate supplementation on plasma levels of branched-chain amino acids in haemodialysis patients with metabolic acidosis.

BACKGROUND: It has been hypothesized that correction of metabolic acidosis might improve the nutritional state of acidotic haemodialysis (HD) patients partly because of a reduced oxidation of branched-chain amino acids (BCAA). AIM: We investigated whether bicarbonate (Bic) supplementation in acidotic HD patients results in increased plasma levels of BCAA. METHODS: In a longitudinal study (run-in period, 2 months; study period, 6 months), the effect of Bic supplementation on plasma levels of BCAA was studied in 12 acidotic HD patients (7 men, 5 women, mean age 54 +/- 18 years) with a predialysis bicarbonate (Bic) concentration smaller or equal to 22 mmol/l. Bic was supplemented by increasing Bic concentration of the dialysate and by oral Bic supplementation. RESULTS: Predialysis Bic increased significantly during the study period (18.7 +/- 2.7 vs. 23.1 +/- 11.5 mmol/l). There was no change in nutritional parameters. However, plasma levels of the BCAA valine, leucine, and isoleucine increased significantly. CONCLUSIONS: In haemodialysis patients with metabolic acidosis, Bic supplementation over a 6-months period resulted in an increase in plasma levels of BCAA. Further study is needed to elucidate the mechanisms behind, and the clinical importance of the observed changes in plasma BCAA levels.

[Failing diuretics in severe chronic heart failure]. / Falende diuretica bij ernstig chronisch hartfalen.

Three patients with chronic heart failure, men aged 29, 78 and 69 years, developed severe dyspnoea and oedema in spite of reduced sodium and fluid intake and medication including furosemide. Heart failure may become 'resistant to diuretics' due to pharmacokinetic and pharmacodynamic causes. High-dose continuous intravenous administration of a loop diuretic may afford relief in such cases, if necessary in combination with a thiazide derivative, an ACE inhibitor, an inotropic agent or an extracorporal technique. Monitoring and correction of the state of hydration of a patient with chronic heart failure may improve the prognosis and the quality of life.

Combination of high-dose furosemide and hydrochlorothiazide in the treatment of refractory congestive heart failure.

OBJECTIVE: We studied the synergism between high-dose furosemide and hydrochlorothiazide in patients with severe congestive heart failure and impaired renal function showing diuretic resistance to a daily dose of furosemide of at least 250 mg. DESIGN AND SETTING: An open study. A general hospital in The Netherlands. METHODS: In 20 patients with severe congestive heart failure (stage III-IV according to the New York Heart Association) with an oedematous mass of more than 5 kg and a proven diuretic resistance to high-dose furosemide, hydrochlorothiazide (25-100 mg daily) was added to the medication for 3-12 days, leaving the other medication unchanged. After correction of the hydration state, hydrochlorothiazide was withdrawn. Variables included body weight, serum electrolytes, renal function and natriuresis. RESULTS: Addition of hydrochlorothiazide resulted in a mean (+/-standard deviation) body weight reduction of 6.7 +/- 3.3 kg per patient. Mean daily urine volume increased from 1899 +/- 958 ml to 3065 +/- 925 ml (P < 0.001). Fractional sodium excretion increased significantly from 3.5 +/- 3.2% to 11.5 +/- 9.0% (P < 0.001). The most important side effect of this combination therapy appeared to be hypokalaemia. Mean endogenous creatinine clearance decreased (not significantly) from 32.7 +/- 22.5 ml. min-1.1.73 m-2 to 27.6 +/- 22.5 ml. min-1.1.73 m-2. CONCLUSIONS: Addition of hydrochlorothiazide to high-dose furosemide is a powerful diuretic tool, even in patients with a significantly reduced renal function. Because of its potentially dangerous side effects (hypokalaemia), it should be used in a carefully controlled setting.

Vascular reactivity during combined ultrafiltration-hemodialysis: influence of dialysate-derived contaminants.

It has been suggested that hemodynamic instability and impaired vascular reactivity during combined ultrafiltration-hemodialysis are related to bioincompatibility factors such as dialysate-derived contaminants or the dialyzer. The study presented here investigated whether vascular reactivity could be improved by the use of sterile dialysate. Forearm vascular resistance and venous tone (measured by strain-gauge plethysmography) as well as arterial blood pressure (by Dinamap) and heart rate (by electrocardiogram) were measured in ten stable dialysis patients (age range, 28 to 71 yr) during 2 h of combined ultrafiltration-hemodialysis (bicarbonate; ultrafiltration rate 1.0 L/h). In addition, a dialysate sample was obtained for culture and limulus amebocyte lysate testing while blood was withdrawn for the estimation of plasma bactericidal/permeability increasing factor (measured by ELISA) and the soluble tumor necrosis factor receptor p75 (measured by ELISA). Patients served as their own control, comparing dialysis with nonsterile and sterile dialysate. No bacterial growth was observed in sterile dialysate, whereas all samples were positive for Pseudomonas in culture in nonsterile dialysis. All limulus amebocyte lysate tests were negative. Bactericidal/permeability increasing factor tended to increase during nonsterile dialysis (P = 0.063) and remained unchanged during sterile dialysis. In both treatments, tumor necrosis factor receptor p75 increased significantly (P < 0.01). There were no significant differences in hemodynamic parameters between the treatment modalities. Despite use of sterile dialysate, forearm vascular resistance remained unchanged whereas venous tone decreased significantly. These results indicate that vascular reactivity during combined ultrafiltration-hemodialysis is not improved by the use of sterile dialysate.

Renal replacement therapy in the elderly.

BACKGROUND AND METHODS: In a retrospective study the medical records of 122 patients aged over 65 years at the start of renal replacement therapy (RRT) in our dialysis centre were analysed. RESULTS: The mean age at the start of RRT was 72.7 +/- 5.7 years (range 65.0-90.3). Seventy-six percent were treated with haemodialysis, 21% with haemofiltration and 3% with continuous ambulatory peritoneal dialysis. There was no significant difference in survival between the different modes of treatment. The median survival was 23.8 months, the actuarial survival rates at 2, 5 and 7 years were 50, 27 and 18%, respectively. Patients aged between 65 and 75 years had a median survival of 36.4 months, patients above 75 years of 12.5 months (P = 0.009). Patients with tubulo-interstitial nephritis had a significantly longer survival than patients with other renal diseases. When chronic obstructive pulmonary disease or peripheral vascular disease was present, there was a significantly shorter survival. There was no difference in survival between patients with malignancy, cardiac diseases, diabetes mellitus or cerebrovascular diseases before the start of RRT and others. After the start of RRT there was a significant increase of infectious and psychiatric disease. During the study period 70% died, most frequently from cardiovascular causes (28%), discontinuation of dialysis treatment (28%) or infection (19%). CONCLUSIONS: We think that both survival and quality of life in elderly patients during RRT are acceptable, and that neither age nor comorbidity should be a contraindication to RRT.

Diuretic efficacy of high dose furosemide in severe heart failure: bolus injection versus continuous infusion.

OBJECTIVES: The efficacy of high dose furosemide as a continuous infusion was compared with a bolus injection of equal dose in patients with severe heart failure. BACKGROUND: The delivery rate of furosemide into the nephron has been proved to be a determinant of diuretic efficacy in healthy volunteers. METHODS: In a randomized crossover study we compared the efficacy of a continuous infusion of high dose furosemide (mean daily dosage 690 mg, range 250 to 2,000) versus a single bolus injection of an equal dose in 20 patients with severe heart failure. The patients received an equal dosage, either as a single intravenous bolus injection or as an 8-h continuous infusion preceded by a loading dose (20% of total dosage). RESULTS: Mean (+/- SEM) daily urinary volume (infusion 2,860 +/- 240 ml, bolus 2,260 +/- 150 ml, p = 0.0005) and sodium excretion (infusion 210 +/- 40 mmol, bolus 150 +/- 20 mmol, p = 0.0045) were significantly higher after treatment with continuous infusion than with bolus injection, despite significantly lower urinary furosemide excretion (infusion 310 +/- 60 mg every 24 h, bolus 330 +/- 60 mg every 24 h, p = 0.0195). The maximal plasma furosemide concentration was significantly higher after bolus injection than during continuous infusion (infusion 24 +/- 5 micrograms/ml, bolus 95 +/- 20 micrograms/ml, p < 0.0001). Short-term, completely reversible hearing loss was reported only after bolus injection in 5 patients. CONCLUSIONS: We conclude that in patients with severe heart failure, high dose furosemide administered as a continuous infusion is more efficacious than bolus injection and causes less ototoxic side effects.

Chronic intermittent haemofiltration and haemodialysis in end stage chronic heart failure with oedema refractory to high dose frusemide.

OBJECTIVE: To assess the benefits and problems of chronic intermittent treatment with haemofiltration or haemodialysis or both in patients with severe chronic heart failure (New York Heart Association class III or IV) and oedema refractory to pharmacological treatment. DESIGN AND SETTING: A retrospective case-cohort study. A general hospital in The Netherlands. PATIENTS: The results of chronic intermittent treatment with haemofiltration (n = 10) or haemodialysis (n = 2) were analysed in patients with severe chronic heart failure, predominantly due to coronary heart disease, and oedema refractory to a pharmacological regimen including high dose frusemide. INTERVENTION: Patients had an average of 25 (SD 38) treatments. RESULTS: There was improvement of NYHA class IV to III in seven patients. However, this was not reflected in a decrease in hospital admission: only two patients could be managed as outpatients. The median survival after start of the treatment was 24 days (varying from 0 to 393 days). In four patients the treatment was discontinued after discussion with the patient and family. CONCLUSIONS: The use of chronic intermittent haemofiltration and haemodialysis is of limited value in end stage chronic heart failure with oedema, refractory to maximal conventional treatment.

Survival on renal replacement therapy in Europe: is there a 'centre effect'?

OBJECTIVE: Survival is the ultimate outcome measure in renal replacement therapy (RRT) and may be used to compare performance among centres. Such comparison, however, is meaningless if the influences of comorbidity, age and early deaths are not considered. We therefore studied survival rates on RRT in seven centres in Europe after taking into account the influence of age, early deaths, primary renal diagnoses, and comorbidity. DESIGN: A retrospective survival analysis was carried out on 1407 patients who commenced RRT in seven centres across five European countries during a 7-year period. Patients were stratified into low-, medium- and high-risk groups based mainly on comorbidity and to a lesser extent on age at commencement of RRT. Kaplan-Meier survival and Cox's proportional hazards model were used to compare survival. RESULTS: Before risk stratification overall 2-year survival across the seven centres ranged from 60.2 to 85.3% (69.3-89.9%) after excluding early deaths) masking a range of survivals of 27.4% for the high-risk group with the worst survival to 100% in the low-risk group with the best survival. After excluding early deaths 2-year survival in the low risk groups (n=622) was greater than 90% in all centres. Multivariate analysis showed that the mortality risk increased four fold from low- to medium- and a further 1.6-fold from medium- to high-risk group. However, despite this adjustment for comorbidity and age there still remained a significant difference in survival among some centres, i.e. a 'centre effect' which ranked the centres. CONCLUSION: Risk stratification diminishes the variance in survival between centres but a centre effect remains despite adjusting for age and comorbidity. Multicentre prospective studies are urgently required to identify the reasons for this apparent centre effect.

The Gracz arteriovenous fistula evaluated. Results of the brachiocephalic elbow fistula in haemodialysis angio-access.

OBJECTIVES: To assess fistula patency and complication rates in braciocephalic elbow fistulas of both the Gracz and the side-to-side configuration. DESIGN: Retrospective clinical study. METHODS: Life table patency and complications of 50 Gracz fistulas and 23 side-to-side elbow fistulas created between 1988 and 1993 were reviewed. RESULTS: The cumulative patency for the elbow fistulas was 84% after 1 year and 78% after 3 years. No difference was found between the Gracz fistula and the side-to-side elbow fistula. Stenosis was the most frequent indication for revision and thrombosis was the most frequent cause of fistula failure. CONCLUSION: The elbow fistula has a long patency with few complications and performs as well as wrist fistulas and better than the graft fistulas reported in the literature. The Gracz elbow fistula has results as good as the side-to-side elbow fistula. Graft fistulas should be reserved for tertiary procedures only.

Differences between anti-myeloperoxidase- and anti-proteinase 3-associated renal disease.

We performed a retrospective study of the clinical features, the pattern of the pre-treatment renal function loss, the renal morphology and the outcome in 92 patients with anti-neutrophil cytoplasmic autoantibodies directed against proteinase 3 (aPR3; N = 46) or myeloperoxidase (aMPO; N = 46). Patients with aMPO had a higher median age than patients with a PR3 (63 and 56 years; P < 0.05). The mean (+/- SD) number of affected organs in the aPR3 group exceeded that of the aMPO group (3.9 +/- 1.4 and 2.2 +/- 1.1; P < 0.01). The prevalence of renal involvement did not differ between patients with aPR3 and aMPO (83% and 67%, respectively; NS). Pre-treatment renal function deteriorated significantly faster in aPR3- than in aMPO-associated renal disease. The kidney biopsies from patients with aPR3 showed a higher activity index (10.2 +/- 3.8 and 7.3 +/- 3.2; P < 0.03) and a lower chronicity index (4.5 +/- 2.6 and 7.0 +/- 3.1; P < 0.02) than biopsies from patients with aMPO. The kidney survival at two years was 73% in patients with aPR3- and 61% in patients with aMPO-associated renal disease (NS). We conclude that renal function generally deteriorates faster in aPR3- than in aMPO-associated renal disease. This goes together with more active renal lesions in patients with aPR3 and more chronic renal lesions in patients with aMPO. Despite these differences, there is no difference in outcomes between both antibody groups.