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Angiotensin-converting enzyme inhibitors in native nephropathies reduce proteinuria and delay progression to renal failure. Data in renal transplantation remain limited. A negative effect on glomerular filtration rate was concluded in a recent systematic review.

During the past 2 years a number of studies, meta-analyses and reviews have shown that micronutrient supplementation may be beneficial in critical illness. Selenium is emerging as a particularly important micronutrient. This paper reviews the evidence from trials in the critically ill, putting mechanisms, methods and shortcomings into perspective.

Chronic allograft nephropathy (CAN) is commonly associated with proteinuria. In native nephropathies, proteinuria is linked with proximal renal tubular damage. This study uses regression analysis to link proteinuria with urinary N-acetyl-β-d-glucosaminidase (NAG) as a marker of tubular injury or hyperfunction in renal transplant patients.

This review highlights recent research into the causes and prevention of free radical (particularly reactive oxygen species)-induced surgical complications. Experimental and clinical studies have contributed new understanding of the sources of free radical attack, modalities to counter these and newer approaches developed with the aid of molecular biology.

AbstractThis article critically reviews the role of the laboratory services in assessment, monitoring and management of complications in patients requiring nutritional support. It has broadly been divided into three sections.(i)Assessment of protein and energy status: whilst it is stressed that clinical judgement and anthropometric measurements are the most effective methods of evaluation of nutritional requirements, laboratory tests which can be of use in assessment of protein energy status are discussed in detail, including an appraisal of the value of each test in various clinical situations.(ii)Assessment of micronutrient and electrolyte status: the clinical justification for assessment of the various micronutrients and electrolytes is considered. A few selected examples are discussed in detail including an evaluation of the tests of status available and examples of situations where measurement may be clinically helpful.(iii)Effective use of the laboratory: this section attempts to guide the clinician in the most appropriate use of laboratory tests, firstly in the assessment of requirement for aspects of nutritional support, secondly in the continued monitoring and evaluation of the support provided, and thirdly in prevention and treatment of metabolic complications.It is emphasised that clinical nutrition is a multidisciplinary topic requiring input from the laboratory in conjunction with other specialities to provide the best available patient care.

Assessment of nutritional status is used as both a prognostic indicator and to monitor the adequacy of the different components of nutritional support regimens. Available tests are of variable value, differing in accuracy and precision of measurement.

1. Progression to renal failure may be linked to the degree of proteinuria through tubulo-interstitial mechanisms. However, there are no data in man on the kinetics of proximal renal tubular protein catabolism or markers of tubular injury before and after lisinopril. We developed a method to allow such studies, and found increased tubular catabolism of 99mTc-labelled aprotinin (Trasylol) in patients with nephrotic range proteinuria which was associated with increased ammonia excretion. 2. In this study, 10 patients with mild renal impairment (51Cr-EDTA clearance 63.7 ± 8.3 ml · min−1 · 1.73 m−2) and heavy proteinuria (8.2 ± 2.3 g/24 h) were given lisinopril (10–20 mg) for 6 weeks. Renal tubular catabolism of intravenous aprotinin was measured before and after lisinopril by renal imaging and urinary excretion of the free radiolabel over 26 h. Fractional degradation was calculated from these data. Fresh timed urine collections were also analysed for ammonia excretion every fortnight from 6 weeks before treatment. Total urinary N-acetyl-β-d-glucosaminidase and the more tubulo-specific N-acetyl-β-d-glucosaminidase ‘A2’ isoenzyme were also measured. 3. After lisinopril proteinuria fell significantly as expected (from 9.5 ± 1.6 to 4.5 ± 1.0 g/24 h, P < 0.01). This was associated with a reduction in metabolism over 26 h (from 1.7 ± 0.1 to 1.2 ± 0.1% dose/h, P < 0.01) and in fractional degradation of aprotinin (from 0.08 ± 0.02 to 0.04 ± 0.007/h, P < 0.04). Ammonia excretion also fell significantly (from 1.2 ± 0.1 to 0.6 ± 0.1 mmol/h, P < 0.0001), as did both total urinary N-acetyl-β-d-glucosaminidase (P < 0.0001) and the N-acetyl-β-d-glucosaminidase ‘A2’ isoenzyme (P < 0.015). These observations after lisinopril treatment have not been described previously. There was no significant change in blood pressure nor in glomerular haemodynamics.

An out-of-hours emergency biochemistry service, which allows access by all medical practitioners of varying experience within a hospital, can lead to overuse or even abuse of limited and costly facilities. When the workload increases, problems of staffing a voluntary (but paid) working rota may emerge. An industrial dispute involving medical laboratory scientific officers (MLSOs) caused the role of the emergency service to be examined and alternative regulating mechanisms to be tested.Experience at Glasgow Royal Infirmary between 1974 and 1981 has been reviewed. From 1977 to 1979, when clinicians (usually junior) arranged analyses directly with the MLSOs, test numbers increased by about 26% per annum. This was not associated with any concomitant increase in the range of analyses offered. During a five-week period in 1980, consultant clinicians had to contact a consultant clinical biochemist to arrange all emergency analyses, and test numbers were reduced to 13% of the previous levels. Subsequently, all requests for emergency analyses were made by clinicians to laboratory medical staff, and test numbers fell to approximately 60% of 1979 levels. This requesting system is now firmly established.Continued vigilance is required to maintain the reduced level of requesting, but too great a limitation on emergency requests may cause less efficient patient management. Senior clinical staff should be encouraged to take greater responsibility for the use of emergency laboratory services.

Weight loss and impaired nutritional status are associated with increased complications following surgery. This study aimed to assess the effect of nutritional status on the magnitude of the acute phase protein response, and determine if this is associated with changes in the magnitude of the related cytokine responses. Nineteen patients (10 wellnourished, 9 malnourished on the basis of body composition) undergoing major abdominal surgery were studied by frequent blood sampling in the early postoperative period. There was a significant reduction in the plasma C- reactive protein response in the malnourished group, but no difference between the groups in the responses of α1-antitrypsin, α1-acid glycoprotein, or in the trace elements iron or zinc, which reflect induction of ferritin and metallothionein. There was an early increase in IL-6, soluble receptors of TNF, and in IL-1 receptor antagonist in both groups, but no detectable increase in plasma IL-1 or TNF. There was no difference between the wellnourished and malnourished group for any of these markers of activation of the cytokine network. Weight loss is therefore associated with a reduction in aspects of the acute phase response, but this is due to impaired effectiveness rather than reduced magnitude of the cytokine response.

During the past year, two important large-scale studies have been published that demonstrate that preoperative parenteral nutritional support improves the clinical outcome of severely malnourished patients. Both trials highlighted the importance of targeting the use of total parenteral nutrition on those patients most likely to benefit. With regard to the composition of parenteral nutrition solutions, our knowledge of lipid emulsions, particularly regarding their effects on the immune system, has expanded significantly. The infusion of a mixture of medium-chain triglycerides and long-chain triglycerides rather than long-chain triglycerides alone may be beneficial in certain circumstances. More evidence has accumulated in favor of the addition of glutamine to parenteral nutrition solutions, and it appears that free glutamine may, after all, be safely added to parenteral nutrition solutions. From a practical point of view, advances in the prevention of thrombophlebitis have enabled peripheral parenteral nutrition to increase in popularity.

A 27-month-old girl with microvillous atrophy who was maintained on long-term home parenteral nutrition presented with regression of walking skills. She was found to have a tender skeletal myopathy affecting both legs only. Plasma selenium level was <0.05 μmol/L (0.4 μg/dl) (normal 0.8–1.6 μmol/L: 6.3–12.6 μg/dl). red blood cell glutathione peroxidase was undetectable, and plasma glutathione peroxidase was 6 U/L (normal 90–350 U/L). Electromyography was abnormal, muscle biopsy showed a nonspecific myopathy, and muscle selenium was 0.23 μg/g dry weight (normal 0.45–1.05 μg/g dry weight). Following replacement with intravenous sodium selenite, there was a rapid improvement with complete disappearance of muscle pain and tenderness within 1 week. Crawling and walking skills were regained within 6 weeks, in dicating that selenium deficiency was the cause of her symptoms. It is suggested that selenium be monitored and supplemented in children on long-term total parenteral nutrition particularly if cntcral absorption is deficient.

A 27-month-old girl with microvillous atrophy who was maintained on long-term home parenteral nutrition presented with regression of walking skills. She was found to have a tender skeletal myopathy affecting both legs only. Plasma selenium level was <0.05 µmol/L (0.4 µg/dl) (normal 0.8–1.6 µmol/L: 6.3–12.6 µg/dl). red blood cell glutathione peroxidase was undetectable, and plasma glutathione peroxidase was 6 U/L (normal 90–350 U/L). Electromyography was abnormal, muscle biopsy showed a nonspecific myopathy, and muscle selenium was 0.23 µg/g dry weight (normal 0.45–1.05 µg/g dry weight). Following replacement with intravenous sodium selenite, there was a rapid improvement with complete disappearance of muscle pain and tenderness within 1 week. Crawling and walking skills were regained within 6 weeks, in dicating that selenium deficiency was the cause of her symptoms. It is suggested that selenium be monitored and supplemented in children on long-term total parenteral nutrition particularly if cntcral absorption is deficient.

The prevention of micronutrient deficiency alone is no longer an adequate objective in micronutrient provision. New research indicates that many micronutrients are involved in other aspects of cell metabolism, especially in preventing cell damage caused by free radicals produced as part of oxidative metabolism. Clinical trials of micronutrient supplements are now becoming available, so that biochemical changes can be related to physiological, immunological, and clinical endpoints.

This review describes the place of trace elements in the management of critically ill injured patients. There has been a growing interest in trace elements as a result of their essential role in endogenous antioxidant defence mechanisms and in immunity. Burns and trauma are associated with increased free radical production and negative trace element balances, which contribute to the imbalance in endogenous antioxidant capacity and the extension of primary lesions. Supplementation trials have shown that early provision of large amounts of trace elements improve recovery after major burns and brain injury.

Markers of renal tubular injury are difficult to interpret in patients with proteinura. The 24-hour urinary N-acetyl-β-D-glucosaminidase (NAG) concentration was measured in 167 patients with dissimilar renal disease, function, and proteinuria. NAG isoenzymes were also separated in 69 patients, using a modified fast protein liquid chromatography technique. The ‘A2’ isoenzyme predominated at all levels of renal function and in all diagnostic groups. Urinary NAG and proteinuria were well correlated at all levels of renal function, as was NAG ‘A2’ isoenzyme. Proteinuria and urinary NAG were similarly correlated in patients with different glomerulonephritides, hypertensive nephrosclerosis, and chronic pyelonephritis, but not in those with diabetic nephropathy.

SummaryMorphine in therapeutic dosage has been shown to impair the plasma 11-hydroxy corticosteroid response to the stress of insulin-induced hypoglycaemia. Nalorphine in similar dosage produced no impairment of the response to hypoglycaemia.

The excretion of the amino acid 3-methylhistidine in urine has been shown to be correlated with protein catabolism in skeletal muscle. In rats, 3-methylhistidine is partly acetylated (N-acetyl-3-methylhistidine) and it has been proposed that the relative amounts of 3-methylhistidine and N-acetyl-3-methylhistidine in urine is age dependent. In this experiment, the effect of dietary protein quality on urine excretion of 3-methylhistidine and N-acetyl-3-methylhistidine was studied. Six groups of rats (mean weight 80 g) were fed diets containing 10% protein of different quality, the net protein utilization ranging from 76.7 for egg albumin to 28.9 for wheat gluten. The excretion of non-acetylated 3-methylhistidine was not dependent on the diet. There was, however, a good correlation between protein quality and total urine 3-methylhistidine (3-methylhistidine plus N-acetyl-3-methylhistidine), the higher the protein quality, the greater being the excretion of total 3-methylhistidine. The relative amounts of 3-methylhistidine and N-acetyl-3-methylhistidine correlated with the mean body weight, but not the age, of the animals. This study therefore demonstrates that a relationship exists between the nutritive quality of the dietary protein and the urinary excretion of 3-methylhistidine in rats.

The individual benefits of dietary therapy for hyperlipidaemia are known to be unpredictable. Variants at the lipoprotein lipase gene have been shown to associate with atherogenic lipoprotein phenotypes and the delayed clearance of triglyceride-rich lipoproteins. Together with variants of the closely homologous hepatic lipase gene, these may influence the extent of amelioration of plasma lipoprotein concentrations seen in dyslipidaemic patients treated with a low saturates/low cholesterol diet.We correlated the lipid changes seen following an 8-week diet in 83 subjects with primary hypercholesterolaemia (fasting plasma cholesterol >6·5mmol/L) with alleles of three restriction polymorphisms (LPL-Hind III and Pvu II; HL-Msp I). Although dietary changes produced a significant improvement in fasting lipids [total cholesterol falling by 5·2% (range −27·9% to +24·3%) and low-density lipoprotein cholesterol reduced by 6·0% (−30·5% to +29·3%)], no significant difference in response between different genotypes could be detected.

Oral sodium bicarbonate (NaHCO3) is widely used to treat acidosis in patients with renal failure. However, no data are available in man on the effects on proximal renal tubular protein catabolism or markers of tubular injury. We have developed methods to allow such studies, and both increased tubular catabolism of 99mTc-labelled aprotinin (Apr*), as well as tubular damage were found in association with increased ammonia (NH3) excretion in patients with nephrotic range proteinuria.We now examine the effects of reducing renal ammoniogenesis, without altering proteinuria, using oral NaHCO3 in 11 patients with mild/moderate renal impairment and proteinuria. Renal tubular catabolism of Apr* was measured before and after NaHCO3 by renal imaging (Kidney uptake, K % of dose) and urinary excretion of free 99mTcO4 (metabolism, Met % of dose/h) over 26 h. Fractional degradation (Frac) was calculated from Met/K (/h). Fresh urine was also analyzed for NH3 excretion every fortnight from 6/52 before treatment. Total urinary N-acetyl-β-D-glucoseaminidase (NAG) and the more tubulo-specific NAG “A2” were measured. 51CrEDTA clearance and 99mTc- MAG 3 TER were also assessed.After NaHCO3 Met over 26 h was significantly reduced (from 1.3 ± 0.2 % of dose/h to 0.9 ± 0.1 % dose/hrp <0.005), as was Frac of Apr* (from 0.06 ± .006/h to 0.04 ± 0.005/hrp <0.003). NH3 excretion also fell significantly (from 0.9 ± 0.2 mmol/h to 0.2 ± 0.05 mmol/hp <0.007), as did both total urinary NAG (from 169 μmol/24 h, 74-642 μmol/24 h to 79 μmol/ 24 h, 37-393 μmol/24 hp <0.01), and the NAG 'A2' isoenzyme (from 81.5 μmol/24 h, 20-472 μmol/24 h to 35.0 μmol/24 h, 6-388 μmol/24 hp <0.001). Proteinuria remained unaltered, and there was no change in blood pressure nor in glomerular haemodynamics. Oral NaHCO3 may thus pro-tect the proximal renal tubule and help delay renal disease progression.

A comparison of paraprotein estimation by immunoturbidimetry (IT) and electrophoresis followed by scanning densitometry (EFD) showed significant differences in concentration for IgG, IgA, and IgM paraproteins. Overestimation of IgM paraproteins by IT was particularly marked. Our data suggest that both techniques should be used for IgG and IgA paraproteins but for IgM paraproteins IT was found to be unsuitable and EFD is the method of choice.

Background Severe hypertriglyceridaemia (HTG) is uncommon but most prevalent in subjects with type 2 diabetes mellitus (T2DM) and excess ethanol intake.Case presentation We describe a case of a middle age male (53 y) presenting to the emergency room with acute atypical central chest pain and severe HTG in the absence of evidence of overt ischaemic heart disease (IHD). Admission ECG and EET (exercise tolerance test) were negative for reversible ischaemic changes. His admission glucose was 12.2 mmol/l, triglycerides (TG) were 103 mmol/l, total cholesterol 37 mmol/l. Cardiac Troponin T could not be measured on three occasions but CK MB mass was normal at 3 μg/l. The patient was started on Bezafibrate 400 mg OD, Simvastatin 20 mg nocte, Omacor (Omega-3 fish oil) 1 gm bd and Metformin 500 mg tds. Four weeks after admission, lipid and liver profiles showed remarkable improvement, TG 2.9 mmol/l, Tchol 6.3 mmol/l and HDLc 1.5 mmol/l, ALAT and GGT were normal.Conclusion A case report of severe hypertriglyceridaemia with atypical presentation demonstrate the role of combined lipid modifying agents in lowering triglycerides and cholesterol as well as improving liver enzymes.

Introduction Nosocomial pneumonia is a major source of morbidity and mortality after severe burns. Burned patients suffer trace element deficiencies and depressed antioxidant and immune defences. This study aimed at determining the effect of trace element supplementation on nosocomial or intensive care unit (ICU)-acquired pneumonia.Methods Two consecutive, randomised, double-blinded, supplementation studies including two homogeneous groups of 41 severely burned patients (20 placebo and 21 intervention) admitted to the burn centre of a university hospital were combined. Intervention consisted of intravenous trace element supplements (copper 2.5 to 3.1 mg/day, selenium 315 to 380 μg/day, and zinc 26.2 to 31.4 mg/day) for 8 to 21 days versus placebo. Endpoints were infections during the first 30 days (predefined criteria for pneumonia, bacteraemia, wound, urine, and other), wound healing, and length of ICU stay. Plasma and skin (study 2) concentrations of selenium and zinc were determined on days 3, 10, and 20.Results The patients, 42 ± 15 years old, were burned on 46% ± 19% of body surface: the combined characteristics of the patients did not differ between the groups. Plasma trace element concentrations and antioxidative capacity were significantly enhanced with normalisation of plasma selenium, zinc, and glutathione peroxidase concentrations in plasma and skin in the trace element-supplemented group. A significant reduction in number of infections was observed in the supplemented patients, which decreased from 3.5 ± 1.2 to 2.0 ± 1.0 episodes per patient in placebo group (p < 0.001). This was related to a reduction of nosocomial pneumonia, which occurred in 16 (80%) patients versus seven (33%) patients, respectively (p < 0.001), and of ventilator-associated pneumonia from 13 to six episodes, respectively (p = 0.023).Conclusion Enhancing trace element status and antioxidant defences by selenium, zinc, and copper supplementation was associated with a decrease of nosocomial pneumonia in critically ill, severely burned patients.