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Biomedical subjects

A M Brownjohn

Publications and source records attributed to A M Brownjohn.

At least 37 records · Page 2Linked to original sources

Increased plasma leptin/fat ratio in patients with chronic renal failure: a cause of malnutrition?

BACKGROUND: Protein-energy malnutrition occurs in patients with chronic renal failure primarily due to loss of appetite. The ob gene protein, leptin, which is secreted by adipocytes, regulates body composition by lowering food intake. We have measured plasma leptin in undialysed and dialysed patients and in controls and the concentrations have been related to body composition, dietary intake, and biochemistry. METHODS: Plasma leptin was measured by radioimmunoassay in 93 individuals in groups of undialysed, peritoneal dialysed, and haemodialysed patients and controls. Body composition was determined by DEXA. RESULTS: Protein-energy malnutrition was evident in non-dialysed and dialysed patients from low lean or fat tissues, plasma albumin and transferrin. A third of the dialysis patients were eating less than prescribed intakes. Leptin relative to total fat mass (ng/ml/kg) was significantly greater for patients than for controls, particularly the dialysed patients. Leptin was highly correlated with total, arm, leg, and all other fat measurements, e.g. r for leptin vsm % total fat was: undialysed 0.88, PD 0.81, HD 0.93, and controls 0.83 (P < 0.0001 for all). Dialysis patients with the highest leptin/fat mass ratio had low protein intakes and significantly lower lean tissue mass. Leptin/fat ratio correlated inversely with dietary intake e.g. with protein intake in g/day and marginally in g/kg of ideal weight/day. Leptin concentration was unrelated to plasma creatinine or residual renal function or to the protein 'nutritional indices', albumin and transferrin. CONCLUSIONS: Our data suggests that leptin is markedly increased in some patients with chronic renal failure. The association of increased leptin with low protein intake and loss of lean tissue is consistent with leptin contributing to malnutrition but a definitive role cannot be substantiated by this study.

Aged↗

Assessment of renal osteodystrophy in dialysis patients: use of bone alkaline phosphatase, bone mineral density and parathyroid ultrasound in comparison with bone histology.

Bone biopsies were studied in 73 patients to determine if a two-site radioimmunometric assay for serum bone alkaline phosphatase (BAP), total serum alkaline phosphatase (ALP), serum intact parathyroid hormone (iPTH), hand X-rays, regional bone mineral density (BMD) measurements and parathyroid enlargement detected by ultrasonography could accurately predict renal osteodystrophy. In the patients studied 57 had hyperparathyroid bone disease, 4 mixed renal osteodystrophy, 3 adynamic bone disease, 1 osteomalacia and 8 normal histology. Serum BAP, ALP and iPTH correlated positively with mineral apposition rate, osteoblastic, osteoid and eroded surface. In the diagnosis of hyperparathyroid bone disease serum iPTH was the most sensitive investigation, detecting 81% of patients at a level > 100 pg/ml but with a specificity of only 66%. Serum BAP was more sensitive, 70% at a level of > 10 ng/ml, than serum total ALP, 30% at a level of 300 IU/l, with similar specificities, 92 and 100%, respectively. Ultrasound detection of an enlarged parathyroid gland had a sensitivity of 64% and a specificity of 100% for the diagnosis of hyperparathyroid bone disease. Hand X-rays had a poor sensitivity, 47%, but a high specificity, 92%, for the detection of hyperparathyroid bone disease. The majority of patients had regional BMD values within the normal reference range and this test was of poor discriminatory value. The non-invasive markers were unable to distinguish between patients with low turnover, mild hyperparathyroidism and patients with normal histology. In conclusion the measurement of serum iPTH is a useful screening tool for the detection of hyperparathyroid bone disease which can be confirmed by the finding of a raised serum BAP or parathyroid enlargement. For definitive diagnosis, however, the gold standard remains bone biopsy and at present one cannot recommend any non-invasive method as an adequate substitute.

Adult↗

Red cell ferritin, a marker of iron deficiency in hemodialysis patients.

Estimation of red cell ferritin (RCFer) may give a good indication of iron supply to the erythron and it may therefore be clinically useful for the detection of functional iron deficiency. In a cross-sectional study of hemodialysis patients on erythropoietin (EPO) therapy and regular oral iron we have compared the RCFer levels with conventional indicators of iron status. The patients studied, 19 female, 48 male, mean age 62 +/- 3.6 years (range 20-83 years) were characterized by the following mean parameters: aluminum 1.24 +/- 0.12 mumol/L, PTH 115.7 +/- 39 pg/mL, vitamin B12 626 +/- 71.2 ng/L, serum folate 18.8 +/- 2.2 micrograms/L, and hemoglobin 9.8 +/- 0.3 g/dL (range 7.3-12.4). The median serum ferritin (SF), RCFer, total iron binding capacity (TIBC), transferrin saturation (TS), and serum iron were 68 micrograms/L, 14.1 ag ferritin/red cell, 57 mumol/L, 20% and 11.5 mumol/L, respectively. Eleven patients had a reduced RCFer (< 7 ag ferritin/red cell), 5 had a SF of < 15 micrograms/L and 22 a TS of < 16%. The occurrence of functional iron deficiency was suggested by the presence of 10 subjects with reduced RCFer despite normal SF levels (15-240 micrograms/L). Four patients with reduced SF showed acceptable levels of RCFer, suggesting that some patients may maintain an adequate iron supply despite diminished iron stores. Despite oral iron therapy, a significant number of patients (63%) on regular hemodialysis remain relatively iron deficient with a serum ferritin of less than 100 micrograms/L. It has previously been proposed that oral iron provides adequate supplementation during increased demand caused by EPO stimulation. The present study has demonstrated overt iron deficiency in five subjects and suggests functional iron deficiency in a further seven (22% of total patients). We therefore conclude that oral iron therapy cannot maximize the response to EPO.

Administration, Oral↗

Whole body and regional body composition in patients with chronic renal failure.

BACKGROUND: Nutritional state is a powerful prognostic factor in chronic renal failure (CRF). Techniques for the assessment of nutrition have limitations which are often most marked in the presence of renal disease. We have used techniques of body composition analysis to assess the nutritional state of groups of patients with CRF. METHODS: Body composition was measured in groups of patients with advanced CRF on conservative treatment, peritoneal dialysis, and haemodialysis and the results compared with a healthy control group. The selection criteria for the CRF patients ensured that they were "stable' with no recent intercurrent illness, and dialysis adequacy was satisfactory according to currently accepted targets. RESULTS: Whole body dual energy X-ray absorptiometry (DEXA) found significant reduction in lean tissue in haemodialysis patients and female peritoneal dialysis patients. Regional analysis with DEXA showed reduction in limb (especially arm), lean tissue in CRF patients, with arm lean tissue being reduced in all three CRF groups for females and both dialysis groups for males. Limb/trunk lean tissue ratios were significantly reduced for all CRF groups. Bioelectrical impedance showed reductions of fat-free mass in the same groups who had reduced whole body lean tissue with DEXA, but skinfold anthropometry failed to detect any significant reduction in fat-free mass. CONCLUSIONS: We conclude that even in "healthy' groups of CRF patients receiving adequate dialytic and dietary management, lean tissue depletion is a common problem. Regional analysis by DEXA, with measurement of limb lean tissue mass is a more sensitive method for the detection of lean tissue depletion than measurement of whole body lean tissue in patients with CRF.

Absorptiometry, Photon↗

The clinical and biochemical features of acute renal failure due to rhabdomyolysis.

Rhabdomyolysis caused 28 out of 903 (3.1%) of cases of severe acute renal failure (ARF) treated at Leeds General Infirmary over a 14-year period (1980-1993). The commonest cause of rhabdomyolysis was muscle compression, usually due to drug- or alcohol-induced coma. Other causes included fits, infection, acute limb ischemia, trauma, and heat stroke. Prognosis was relatively good, with a 78.6% survival rate and recovery of renal function to normal in all survivors who were followed up. The creatinine/urea ratio was higher in ARF due to rhabdomyolysis than in an unselected group of patients with other causes of ARF but not when the comparison was with sex- and age-matched controls with ARF. This suggests that this previously described feature of rhabdomyolysis simply reflects the increased muscle mass of a younger group of patients, rather than a specific effect of muscle damage. Clinical features of muscle damage were often absent and so the possibility of rhabdomyolysis should be considered in appropriate settings if the diagnosis is to be made early enough to administer treatment that may prevent ARF and the consequences of the compartment syndrome.

Acute Kidney Injury↗

Acute renal failure in patients with type 1 diabetes mellitus.

Acute renal failure (ARF) is a serious condition which still carries a mortality of around 50%. People with diabetes may be at increased risk of developing ARF, either as a complication of diabetic ketoacidosis or hyperosmolar coma, increased incidence of cardiovascular disease, or due to increased susceptibility of the kidney to adverse effects in the presence of underlying diabetic renal disease. During the period 1956-1992, 1,661 cases of ARF have been treated at Leeds General Infirmary. Of these, we have identified 26 patients also having type 1 diabetes. ARF due to diabetic ketoacidosis is surprisingly uncommon (14 cases out of 23 patients whose notes were reviewed). All cases of ARF complicating ketoacidosis in the last decade have been associated with particularly severe illness requiring intensive care unit support, rather than otherwise 'uncomplicated' ketoacidosis. We discuss the conditions that may result in ARF in patients with diabetes and the particular difficulties that may be encountered in management.

Acute Kidney Injury↗

Nocturnal intermittent peritoneal dialysis.

Automated methods of peritoneal dialysis have developed as alternative methods of treatment to CAPD. We review our experience of 47 patients treated with nocturnal intermittent peritoneal dialysis (NIPD). Patients receive a nocturnal exchange of 15-25 litres of dialysate with the peritoneum left dry during the day. If biochemical control is inadequate, 1 litre of dialysate is left in during the day. Indications for NIPD included social reasons and CAPD failure due to poor ultrafiltration or problems related to raised intra-abdominal pressure. Some features of biochemical control were less good with NIPD compared with CAPD with higher phosphate (2.18 mmol/l versus 1.83 mmol/l, P < 0.001); creatinine (1256 mumol/l versus 1085 mumol/l, P < 0.001); and potassium (4.92 mmol/l versus 4.64 mmol/l, P = 0.056) in patients changing between CAPD and NIPD. Overall peritonitis rate on NIPD was one episode per 47.1 months compared with a rate of one episode per 17.5 months for patients commencing CAPD over the same period. Conversion from CAPD to NIPD was successful in all six cases for problems related to raised intra-abdominal pressure on CAPD and in six of nine patients transferred due to poor ultrafiltration. NIPD is a useful form of treatment and we believe that the increased cost is offset by the reduced peritonitis rate.

Adult↗

Complement activation during CAPD.

Complement activation was monitored in 20 CAPD patients and 20 normal individuals using markers of the alternative (Bb fragment), classical (C4d fragment), common (iC3b) and terminal pathways (SC5b-9, the soluble form of the membrane attack complex, MAC), together with C3, C4 and factor B. CAPD plasma SC5b-9 was higher than normal although this was not due to increased complement activation in the plasma. The calculated cleavage for C3, C4 and factor B to iC3b, C4d and Bb respectively, due to spontaneous activation, was similar in both groups. C3, C4 and factor B in dialysate were less than 1% of plasma concentration, consistent with vascular leakage, whereas iC3b, Bb and SC5b-9 were at higher concentrations, suggesting generation in the peritoneum by the alternative pathway. 2.4% C4d is consistent with leakage of this small molecule but may indicate slight classical activation. It is concluded that complement activation occurs in the peritoneum during CAPD. MAC and the anaphylatoxins which are also generated may contribute to an increased risk of infection and other inflammatory complications.

Blood↗

Infarction of the tongue in Wegener's granulomatosis.

Wegener's granulomatosis is a form of systemic vasculitis. Untreated, it has a 90% two year mortality, but complete remission can be obtained in 93% of patients following treatment with cyclophosphamide (usually in combination with steroids). There is early and major involvement of the respiratory tract. Renal involvement adversely affects prognosis.

Acute Kidney Injury↗

Erythropoietin deficiency in acute renal failure.

Erythropoietin (Epo) was sequentially measured by radioimmunoassay in 11 patients with acute renal failure (ARF) of varied aetiology. Epo rapidly decreased to a level inappropriately low for the haemoglobin, the reduced Epo value persisting throughout the oliguric phase and for up to 2 weeks after the restoration of apparently normal renal function. Epo values found in ARF were: at referral 18.2 +/- 9.5, mid-oliguria 14.4 +/- 6.8, diuresis 15.6 +/- 5.8, and recovery 25.1 +/- 15.8 mU/ml. Results are compared with 34 patients with end-stage chronic renal failure, 42 with non-renal anaemia, and 96 normal subjects. Epo deficiency alone is an inadequate explanation of the rapid reduction in haemoglobin at the onset of ARF, but would appear to be an important factor in the maintenance of anaemia in prolonged ARF and accounts for the slow increase in haemoglobin following recovery.

Acute Kidney Injury↗