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The use of 24-h urine protein collections for the assessment of proteinuria in renal transplant patients has been compared with the protein creatinine index (PCI) obtained from spot urine samples. Paired data from 148 patients showed a correlation of 0.77 (P less than 0.001) between 24-h protein excretion and the PCI. A PCI of 750 identified proteinuria of greater than 1.0 g/24 h with a sensitivity of 89% and a specificity of 93%. The predictive value of a positive test was 81% and that of a negative test 96%. Similar performance was observed for the detection of proteinuria of differing severities ranging from 0.5 g/24 h to 2.0 g/24 h. The use of spot testing was popular with both patients and staff, and reduced the sample handling cost to 15% of that of 24-h urine collection. We recommend that PCI be adopted as the standard outpatient test for the assessment of proteinuria following renal transplantation.

The authors have developed a system for volumetric control of continuous haemodialysis. The article describes this system and reports its successful use in providing renal support in the intensive care unit to 10 patients with multiorgan failure. In addition to providing effective treatment of uraemia, it permits the precise control of fluid balance in a prospective manner ("dial-up" fluid balance) while reducing nursing workload.

We detected glomerular anionic sites in fixed, LR Gold-embedded ultra-thin tissue sections using cationic colloidal gold. Manual and computer-assisted quantitation were compared, and the influence of pH and glycosaminoglycan-degrading enzymes on site expression was examined. Both quantitation methods produced similar results. Alteration of pH within a narrow range (pH 2.5-3.0) markedly affected the staining pattern. At pH 2.5, epithelial and endothelial glycocalyx and regular sites restricted to the lamina rara externa were stained. At pH 3.0 and above, glycocalyx was unstained but intracellular and nuclear staining was present; glomerular basement membrane (GBM) and mesangial matrix sites were abundant. After chondroitinase ABC or hyaluronidase digestion, GBM staining was eliminated at pH 2.0 and reduced at pH 7.0 (p less than 0.001), suggesting that degraded sites are associated with chondroitin sulfate or hyaluronic acid. By contrast, prolonged heparitinase I digestion was ineffective at either pH. Digestion of purified substrates revealed crossreactivity of heparitinase towards chondroitin sulfate and of chondroitinase towards hyaluronic acid. Since tissue sites were reduced by chondroitinase but not heparitinase, we suggest that degradation is due to hyaluronidase activity of chondroitinase and the anionic sites are associated with hyaluronic acid. However, the influence of pH indicates that lamina rara externa sites are structurally distinct from other GBM anionic sites.

We monitored urinary aluminium excretion in 60 renal allograft recipients for the first 6 months following transplantation. Plasma and urinary aluminium values steadily decreased during the study period. Patients who suffered two or more bacterial infections during this period excreted more urinary aluminium than those with only one or no infections. Twenty patients experienced a two-fold or greater sudden unexpected increase in urinary aluminium excretion: 14 of these patients (60 per cent) had evidence of infection (10 bacterial and four viral), at this time. Both urinary aluminium and fractional aluminium excretion were greater in the 10 patients with bacterial infection than in the other 10 patients. Thus, patients who suffered bacterial infections had higher base-line urinary aluminium excretion, suggesting a higher body burden of aluminium. In addition, bacterial sepsis was associated with aluminium release from tissue stores with an associated increase in urinary aluminium excretion. This implies that patients with an increased body burden of aluminium are more prone to bacterial sepsis, and that aluminium excretion is increased during sepsis.

Prostacyclin was administered on 20 occasions to 12 patients with fulminant hepatic failure complicated by acute renal failure prior to commencing dialysis at a dose of 5 ng/kg.min. Intracranial pressure was noted to increase during the infusion from a median of 12 mmHg (95% confidence limits 9-14) to 17 mmHg (12-25), p less than 0.01, at the same time the mean arterial blood pressure declined from 79 mmHg (65-82) to 64 (56-70), p less than 0.01, and the cerebral perfusion pressure from 62 mmHg (53-67) to 44 mmHg (41-55), p less than 0.01. The changes were greater for those patients who subsequently died from cerebral edema. Patients with fulminant hepatic and acute renal failure are at risk of dying from cerebral edema. The direct administration of prostacyclin, used for extracorporeal anticoagulation, may cause a further increase in intracranial pressure and reduce cerebral perfusion, thus resulting in patient morbidity and mortality.

We have used machine hemofiltration (MHF) with lactate-buffered hemofiltration replacement solution in the management of four patients with severe hepatorenal failure. Hyperlactatemia developed in all four patients. However, consecutive treatments were associated with increasing blood lactate values postfiltration in the two patients who died and with a fall in the lactates in the two patients who survived. The survivors had lower postfiltration blood lactates 3.2 +/- 0.2 mmol/L (mean +/- SEM) compared to the nonsurvivors, 5.3 +/- 0.5 mmol/L (p less than 0.01). This suggests that the measurement of blood lactate following a lactate challenge may be of prognostic significance in patients with severe hepatorenal failure.

Serum hyaluronic acid was measured in 176 adults and 15 children receiving regular dialysis therapy. Hyaluronic acid was elevated to greater than 80 micrograms/l in more than 90%, with median value 182 micrograms/l (range 39-898 micrograms/l). Concentrations did not correlate with serum creatinine, but showed a significant correlation with duration of dialysis and serum beta 2-microglobulin. Values greater than 400 micrograms/l were frequent in patients whose clinical condition deteriorated, but in others, hyaluronic acid remained stable over 4-15 months. Serum hyaluronic acid is mainly in a high-molecular-weight form, which in the presence of normal hepatic function suggests that there is a metabolic disorder involving connective tissue and/or vascular endothelium that increases with progressive loss of renal function. Hyaluronic acid may also be a biochemical marker of patients whose condition deteriorates despite renal replacement therapy.

Prior to commencing renal replacement therapy, 8 patients with fulminant hepatic failure and acute renal failure were treated with an infusion of prostacyclin, 5 ng/kg/min, for 30 min, administered directly into the femoral vein. During this period, several adverse effects were noted. There was a reduction in mean arterial blood pressure from a median of 82 (range 65-93) to 67 mm Hg (55-80), p less than 0.01; and an increase in intracranial pressure from a median of 14 (6-33) to 17 mm Hg (6-42), p less than 0.05; with a consequent reduction in cerebral perfusion pressure from a median of 63 (43-77) to 43 mm Hg (15-74), p less than 0.05. There was a reduction in arterial oxygen tension from a median of 19 (13-28) to 16 kPa (12-27), p less than 0.05; and no change in cardiac output, from a median of 6.7 (4.9-11.2) to 6.5 l/min/m2 (3.8-11.0), p greater than 0.05). The administration of prostacyclin into this group of critically ill patients, at risk of death due to cerebral oedema/hypoxia, produced both a reduction in cerebral perfusion pressure and a reduction in total cerebral oxygen delivery.

The prevalence of Helicobacter pylori was determined using an ELISA technique for IgG antibodies to H. pylori in 76 patients with end-stage renal failure who were receiving regular haemodialysis and 202 patients with functioning renal transplants. Twenty-seven (34%) of the haemodialysis group and 58 (29%) of the transplant group were positive for H. pylori IgG antibodies, and the prevalence did not differ significantly from that in 247 age-matched healthy controls. In the haemodialysis group, patients positive for H. pylori were older, median age 60 years (range 22-73), compared to those patients without H. pylori antibodies, median age 52 years (range 22-75), p less than 0.05, more suffered from dyspeptic symptoms, 35 vs. 10% (p less than 0.01), yet fewer had been prescribed aluminium-containing antacids, 38 vs. 78% (p less than 0.01). In the transplanted group, those positive for H. pylori were more symptomatic for dyspepsia, 30 vs. 11% (p less than 0.01), and had lower serum creatinine values, 136 +/- 10 mumol/l (mean +/- SEM) vs. 172 +/- 12 mumol/l (p less than 0.05), compared to those without H. pylori antibodies. Almost all the transplant patients with H. pylori antibodies were taking steroids (98%) compared to 84% of those without antibodies (p less than 0.05). The prevalence of antibodies to H. pylori in this study was increased in symptomatic dyspeptic subjects and reduced in those patients prescribed aluminium-containing phosphate binders.

Investigations of glomerular anionic charge status in human renal biopsies have previously been restricted, by the techniques and markers used, to staining of sites in pre-embedded tissue. The introduction of a novel marker, cationic colloidal gold, which demonstrates fixed anionic sites in hydrophilic resin (LR Gold)-embedded, ultrathin tissue sections, has now enabled glomerular charge to be evaluated in routine biopsy material. The cationic gold marker detects components which express anionic charge under different pH conditions. The patterns of staining in tissue showing minor glomerular pathology and low proteinuria, together with enzyme-digestion studies indicate that anionic sites are normally associated with heparan sulphate proteoglycans, glycocalyx sialoproteins, hyaluronic acid, and other GBM components which have not yet been characterised. Several charge aberrations involving different pathological mechanisms have been identified using cationic gold. These aberrations may be categorised according to the pathological basis of the charge pattern defect, rather than glomerular disease classification, as a prelude to the precise identification of the anionic sites and their functional importance in relation to the glomerular charge selectivity barrier. The categories which have been defined are: (1) 'Normal', (2) interrupted, (3) neutralised, (4) structurally disorganised, and (5) depleted. As sites are further characterised sub-categorisation is likely. We anticipate that this approach will help to elucidate both the participation of charged components in disease pathogenesis and their role in relation to glomerular proteinuria.

Serum tumour necrosis factor (TNF) was measured by both bioassay and immunoassay (ELISA) during routine cuprophane acetate haemodialysis in 17 asymptomatic patients. In 14 (82%) there was no change in the serum values during haemodialysis. TNF was found to increase, using both assays, in three patients, the responders. These patients differed from the others in terms of body mass index, mean index 16.8 kg/m2 (range 14.8-18.2), compared to the non-responders, mean 24.1 kg/m2 (range 19.6-33.1), P less than 0.05, and had an increased serum calcium, mean 2.9 mmol/l (range 2.6-3.2) compared to the non-responders, mean 2.4 mmol/l (range 1.7-2.8), P less than 0.05. Two of the TNF responders subsequently died of cachexia and respiratory infection. The third underwent a successful parathyroidectomy, and when retested after an increase in body-weight with a normal serum calcium concentration no longer showed an increase in TNF during haemodialysis.

We have investigated the effect of an exogenous lactate load given during machine haemofiltration treatment in 22 patients with acute renal failure and 12 patients with chronic renal failure, without any overt evidence of liver disease. Hyperlactataemia occurred in all patients, but the expected changes in acid base status, an increase in bicarbonate and a reduction in arterial hydrogen ions were observed in less than 40% of the treatments in the acute renal failure group. Ultrafiltrate losses of lactate and bicarbonate could not alone explain the changes in acid-base status. There was a positive correlation between the increase in arterial lactate and hydrogen ion concentrations, r = 0.52, p less than 0.01. Lactate accumulation in patients at, or close to, their threshold for lactate utilisation may result in further depression of cardiac function and peripheral lactate utilisation. Hyperlactataemia due to use of lactate-based dialysis/haemofiltration solutions in critically ill patients may result in a worsening of the acid-base status, and arterial pH should be monitored so that bicarbonate solutions can be substituted if the changes are progressive.

We measured the effect of posture on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in eight patients admitted with grade 4 hepatic coma due to fulminant hepatic failure complicated by renal failure. Upward head elevation greater than 20 degrees did not consistently reduce ICP; instead, ICP increased in three patients who later died of cerebral edema. CPP was reduced significantly by elevation greater than 20 degrees, falling to less than 50 mm Hg in those patients who subsequently died of cerebral edema. Our study does not support the current practice of nursing patients with hepatic coma, who are at risk of dying from cerebral edema, in head-upright postures greater than 20 degrees.

We examined the localization of a glomerular mesangial antigen with a Thy-1.1 monoclonal antibody by epipolarization microscopy (EPI) of silver-enhanced, immunogold-stained renal tissue embedded in LR Gold and Lowicryl K4M, and compared the attributes of these hydrophilic resins. Antigen was well preserved in tissue embedded in both resins. LR Gold-embedded tissue demonstrated excellent immunostaining properties, sectioned more easily, and showed better durability during staining than K4M. Lowicryl K4M-embedded tissue, however, displayed a phenomenon of self-illumination when counterstained with eosin which was not seen with LR Gold. This enabled immunostaining to be precisely related to tissue morphology without the necessity of simultaneous transillumination, which can be problematic when used in combination with EPI because of reflection of incident illumination from sub-stage optical surfaces.

We have investigated lactate intolerance in nine patients with acute hepatorenal failure during 21 machine haemofiltration treatments using a lactate based replacement solution. In all cases hyperlactataemia occurred, the mean arterial lactate increased from 1 +/- 0.2 mmol/l (mean +/- SEM) prior to treatment to 3.2 +/- 0.3 mmol/l at 1 h (P less than 0.01), 4.2 +/- 0.4 mmol/l at 2 h (P less than 0.01), 4.2 +/- 0.4 mmol/l at 3 h (P less than 0.01) and 3.9 +/- 0.4 mmol/l (P less than 0.01) post-treatment. There were correlations between the maximum increase in blood lactate and both the change in arterial hydrogen ion concentration (r = 0.71, P = 0.001) and the mean arterial blood pressure prior to starting treatment (r = -0.57, P = 0.007). During eight of the treatments (38%), the arterial hydrogen ion concentration increased. This group showed increased lactate intolerance in association with a lesser pretreatment mean arterial pressure. The administration of exogenous lactate to patients with hepatorenal failure who are at, or near to, the threshold of their own endogenous lactate metabolism can result in an increase in hydrogen ion concentration rather than the expected decrease, and therefore lactate-based dialysate solutions are best avoided.

We measured the intracranial pressure (ICP), using a subdural catheter in nine patients admitted with grade 4 hepatic encephalopathy due to fulminant hepatic failure complicated by oliguric renal failure. Six patients received daily machine haemofiltration and four patients were treated with continuous arteriovenous haemofiltration (CAVHF). The mean ICP increased during the first hour of machine haemofiltration from 9 +/- 1.4 mmHg to 13 +/- 1.8 mmHg (P less than 0.05), and there was a reduction in the mean arterial pressure from 92.4 +/- 2.7 mmHg to 81 +/- 3.2 mmHg (P less than 0.05) resulting in a reduction in cerebral perfusion pressure of up to 30%. The group treated by CAVHF, although having a greater mean ICP prior to treatment (19 +/- 4.8 mmHg) and a lower mean arterial pressure (66 +/- 3.6 mmHg) and consequently a lower cerebral perfusion pressure, did not show any increase in ICP or reduction in mean arterial or cerebral perfusion pressure. There was a significant reduction in serum osmolality during the first hour of treatment in the machine haemofiltration group (314 +/- 4 mOsm/kg to 309 +/- 4 mOsm/kg, P less than 0.05), whereas there was no corresponding change in the CAVHF group. This suggests that CAVHF is to be preferred for the treatment of acute renal failure in such patients who are at considerable risk of developing cerebral oedema.

We have investigated the effect of the direction of the dialysate flow during continuous arteriovenous haemodialysis. Under similar conditions countercurrent flow was more efficient than concurrent flow in terms of both urea clearance (mean +/- SEM), 23.5 +/- 0.5 compared to 18.4 +/- 0.4 ml/min (p less than 0.001) and creatinine clearance, 21.1 +/- 0.5 compared to 15.6 +/- 0.4 ml/min (p less than 0.001). There was a greater drop in pressure along the blood compartment of the haemodiafilter during countercurrent flow, 16 +/- 0.8 compared to 13 +/- 0.3 mm Hg (p less than 0.05) during concurrent flow, and this was associated with a greater ultrafiltration rate, 7.2 +/- 0.6 compared to 6.0 +/- 0.5 ml/min. The differences in diffusion, back diffusion and convection between the two systems resulted in a net gain of lactate/bicarbonate and a net loss of chloride during countercurrent dialysate flow, and a net loss of lactate/bicarbonate with a gain of chloride during concurrent flow. These losses would have to be corrected in the clinical setting of patients who had been continuously treated by these systems for several days.

We infused prostacyclin into 11 critically ill patients for 30 min at a rate of 5 ng/kg.min, prior to commencing prostacyclin haemodialysis. All patients had combined respiratory and renal failure and required intropic support. Despite the previous correction of hypovolaemia, prostacyclin produced a decrease in mean arterial pressure, pulmonary and systemic vascular resistances and cardiac filling pressures. There was no compensatory increase in cardiac output and due to an increase in pulmonary ventilation/perfusion mismatch an overall decrease in tissue oxygen delivery from a median of 560 ml/min.m2 to 370 ml/min.m2 was noted p less than 0.05, with a corresponding reduction in tissue oxygen uptake from 140 ml/min.m2 to 125 ml/min.m2. This was associated with an increase in both arterial hydrogen ion and lactate concentrations in 8 of the 11 patients studied, suggesting a deterioration in tissue oxygen supply/oxygen requirement. Prostacyclin should not be infused directly into patients unless monitored to assess the therapeutic/adverse effects on an individual patient basis.

Urinary aluminium was measured in 48 patients with primary graft function for 14 days following renal transplantation. The plasma aluminium prior to transplantation was greater in those prescribed aluminium-containing phosphate binders (1.7 +/- 0.2 vs 0.6 +/- 0.2 mumol/L, P less than 0.05) and correlated with the duration of dialysis therapy (r = 0.42, P less than 0.008). After an initial reduction the plasma aluminium returned to pre-transplant values by the fifth day. The 24 h urinary aluminium excretion, aluminium clearance and fractional aluminium excretion all increased during the first week to a maximum around the sixth postoperative day, thereafter returning to values obtained during the first postoperative days, suggesting an early 'wash-out' of a readily accessible aluminium pool followed by a lower steady state determined by the rate of release of aluminium from tissue stores. For the whole group, aluminium excretion, at this steady state, was five times that of urinary aluminium excretion in normal subjects. Acute allograft rejection was diagnosed in 25 patients, who were treated with pulsed methyl prednisolone. Apart from improving graft function, no additional effect was observed on aluminium excretion, suggesting that the readily accessible aluminium pool does not come from lysosomal release, but probably from aluminium bound to small molecular weight protein.

The natural killer (NK) cell activity of human peripheral blood lymphocytes falls following major surgical procedures including renal transplantation but in non-immunosuppressed individuals returns to normal levels within the first 72 hr after operation. In renal allograft recipients, if this early postoperative fall is excluded from the analysis, NK cell function appears to follow changes in allograft function, suggesting that in vivo, as has been reported in vitro, NK activity is generated during activation of the alloreactive process. In an additional group of patients whose grafts were functioning for between 3 and 102 months after cadaveric renal transplantation using conventional immunosuppression, NK function was depressed in comparison with that of control subjects. However, some patients who were more than 48 months post-transplant had normal NK cell activity. Collectively, these results suggest that NK cell function may recover despite the continued administration of conventional immunosuppressive agents.

Biochemical, radiological and histological indicators of dialysis bone disease were studied before, 6 months (58 patients) and 12 months (48 patients) after starting treatment with 1 alpha-OH D3. Radiographic healing of subperiosteal erosions was seen after 6 months in 60% and after 12 months in 77% of affected patients. Radiographic improvement, however, was not significantly related to reductions in resorptive surfaces seen on quantitative bone histology, nor to changes in plasma concentrations of immunoreactive parathyroid hormone. Metastatic calcification appeared or increased in 43% of patients after 6 months and 52% after 12 months. Periosteal new bone developed or increased in 14% of patients after 6 months and 17% after 12 months. Both metastatic calcification and periosteal new bone formation were associated with high plasma phosphate concentrations, but not with plasma calcium, alkaline phosphatase or parathyroid hormone concentrations. Treatment with 1 alpha-OH D3 produces radiological improvement in the majority of patients with dialysis bone disease, but the lack of correlation with histological changes confirms the need for regular radiographic examination. Metastatic calcification and periosteal new bone formation probably represent toxicity of 1 alpha-OH D3 but may be minimised by phosphate restriction.

After successful renal transplantation there is continuing malabsorption of calcium and phosphorus. This is due in part to impaired glomerular filtration rate, and in part to the action of steroid on calcium and phosphorus absorption. The effect of steroids is most marked over the first 18 months after transplantation and causes significant malabsorption of calcium and phosphorus even though good graft function is established. Calcium and phosphorus malabsorption can be improved by exogenous 1,25-dihydroxy vitamin D (oral 1 alpha-OH D3 or 1,25-[OH]2D3).

Nine consecutive patients with both fulminant hepatic failure and acute oliguric renal failure were treated either by daily machine haemofiltration (MHF), or by continuous arterio-venous haemofiltration (CAVHF). Six patients received a total of twenty treatments by MHF and four CAVHF, mean duration of treatment 56 hours, range 24-160. Intracranial pressure (ICP) was measured using a subdural catheter. During treatment with MHF, the mean ICP increased from 8.9 +/- 1.4 mmHg at the start of filtration to 14.8 +/- 2.1 mmHg at the end of treatment (p less than 0.05), whereas there was no corresponding increase during the same period of time with CAVHF treatment, the mean ICP fell, but not significantly from 19.4 +/- 4.8 mmHg to 11.2 +/- 2.3 mmHg. The mean ICP increased to greater than 25 mmHg on eleven occasions during treatment with MHF, requiring treatment with bolus mannitol or propofol, during the same period of treatment with CAVHF no such surges in ICP were recorded. This suggests that continuous haemofiltration is to be preferred to intermittent machine haemofiltration in the management of patients with acute hepatorenal failure.

The enhanced in vitro proliferative response of peripheral mononuclear cells (PMNC) when pre-cultured for 24 hours prior to the addition of Concanavalin-A has been used as an indirect parameter of suppressor cell activity in healthy subjects and in patients undergoing chronic haemodialysis. The proliferative response of PMNC from haemodialysis patients is lower than that of control subjects when Con-A is added at the initiation of culture but approximates to that of normal subjects when the addition of Con-A was deferred for 24 hours. The Suppressor Indices of PMNC from haemodialysis patients were at least as great and sometimes greater than those of control subjects but the absolute T-cell counts were lower in haemodialysis patients than in controls. These results suggest that the relative energy of haemodialysis patients is partly attributable to T-cell depletion but this is accompanied by retention, and in some cases augmentation, of suppressor cell activity.

Imposil iron-dextran is an inert tracer that has been used to study mesangial uptake and clearance of macromolecular material from the glomerular circulation. Such a tracer may be a useful marker of altered mesangial function in animals with some forms of glomerulonephritis. We have studied mesangial handling of intravenously injected Imposil (50 mg/100 g body weight) in normal rats by light, immunofluorescence and electron microscopy for up to 3 months. Mesangial cell uptake was maximal at 48-54 h. Extrusion and drainage of tracer to the vascular pole and distal tubule was evident at 3 days but iron was still present in mesangial cells at 3 months. Possible functional renal impairment resulting from persistent mesangially sequestered tracer was examined by measuring daily urine protein and iron excretion. A possible relationship between failure of mesangial cells to eliminate inert tracer and increasing glomerular permeability is demonstrated, suggesting that Imposil and similar inert macromolecules cannot be used for long-term studies of mesangial function.

Twenty patients with rheumatoid arthritis developing proteinuria when being treated with penicillamine have been studied. In 5 the proteinuria was mild and resolved rapidly. Eleven of the remaining patients have undergone renal biopsy. One was found to have amyloidosis, and in the other 10 there was evidence of an immune complex type of injury, manifested by a granular immunoglobulin deposition within glomerular capillary walls associated with subepithelial deposits, found on electron microscopy. The proteinuria associated with this was mild (mean 2.6 g per 24 h) and occurred on average some eight months after commencing therapy (range 6 weeks to 60 months).

Nineteen patients presenting with late renal failure due to prostatic outflow obstruction (mean age 68.7 years; mean serum creatinine concentration 1158 mumol/l) were identified from the admission records of two renal units. As late renal failure secondary to prostatic enlargement is preventable case records were analysed retrospectively in an attempt to identify aspects of management in which preventive efforts might be of value. Delays in referral were common, with a mean of 2.8 years between the onset of prostatic symptoms and time of referral, six patients being referred who had had symptoms for more than three years. Four of five patients who had had a prostatectomy were known to be in renal failure at the time of operation but were not referred until 2-13 years later, when prostatic symptoms had recurred and there was evidence of progressive nephropathy with dilatation of the upper urinary tract. Two patients died on admission and eight (47% of survivors) required long term dialysis, most patients (80%) requiring some dialysis support during the initial period. These findings suggest that progressive nephropathy caused by prostatic outflow obstruction might, in part, be averted by more adequate screening of renal function in men with untreated prostatism and closer follow up of patients with uraemia at the time of prostatectomy.

The role of the renin-aldosterone system in predicting the hypotensive effect of beta-blockade is controversial. We have measured blood pressure, heart rate, plasma active renin, prorenin and aldosterone in 44 hypertensive patients before and after 18 weeks treatment with either nadolol or metoprolol in a double blind randomized study. Prorenin increased and active renin decreased with treatment, total renin and aldosterone remaining unchanged. After beta-blockade the correlation between active renin and prorenin improved from p less than 0.025 to p less than 0.001, and both variables attained a correlation with aldosterone. There was a weak correlation between the reduction in diastolic pressure and both pretreatment active renin and pretreatment prorenin (p less than 0.05). However, using a multiple regression analysis there was a highly significant correlation between the combination of the pretreatment values of active renin, prorenin and aldosterone and the reduction in diastolic pressure with both nadolol (p less than 0.001) and metoprolol (p less than 0.003). This indicates that the combination of active renin with prorenin and aldosterone is a reliable guide to the hypotensive effects of beta-blockade and that the failure to detect this in previous studies is most likely due to errors in the measurement of renin.

Skeletal uptake of diphosphonate was measured by emission tomography in 30 patients on chronic dialysis treatment. In 19 patients mean plasma aluminium concentrations, measured over the preceding 12 months, were 'high' (greater than 1.0 mumol/l, and in the other 11 were 'low' (less than 1.0 mumol/l). There was a strong correlation between serum alkaline phosphatase and skeletal uptake of diphosphonate in each group, but no difference in diphosphonate uptake between the groups. Additionally, when six patients with positive desferrioxamine tests were matched for serum alkaline phosphatase with six patients from the 'low' aluminium group there was no significant difference in uptake of diphosphonate (median and range 7.2; 5.2-16.5 and 5.9; 2.7-10.8 respectively). We conclude that skeletal uptake of diphosphonate is not suppressed in patients with moderate aluminium loading, but reflects bone turnover as indicated by serum alkaline phosphatase. Quantitative bone scintigraphy is not a useful discriminator for early aluminium osteomalacia.

Penicillamine has been successfully reintroduced and continued for a minimum of 13 months in 5 patients who developed proteinuria during the first course of the drug. The daily maintenance dose during the second course was 150--250 mg taken midway between 2 meals. Proteinuria did not recur; no significant excretion of fibrin degradation products occurred; complement, urea, creatinine, and serum albumin remained within normal limits. Urine microscopy showed no abnormality.

Serum vitamin A, retinol binding protein, prealbumin and transferrin have been studied in chronic renal failure patients receiving maintenance haemodialysis and after renal transplantation. Vitamin A and retinol binding protein were uniformly raised in haemodialysis patients and this was unrelated to the period on dialysis. There was a molar excess of retinol binding protein to both vitamin A and prealbumin as compared with normal individuals. Renal transplantation significantly reduces serum vitamin A and retinol binding protein concentrations but has no effect on prealbumin concentrations. The reduction in vitamin A and retinol binding protein is variable in individual patients and cannot be predicted either by the allograft function or time since transplantation. Several years after transplantation, with normal serum creatinine, both serum vitamin A and retinol binding protein levels may still be greatly increased. Despite the very high vitamin A and retinol binding protein concentrations, the close correlation between the two seen in normal individuals is well maintained. The continuing high vitamin A and retinol binding protein levels in patients with satisfactorily functioning transplants is unexplained.

We report the results of a survey within the United Kingdom of the importance of persistent systemic infection in patients with unexplained renal disease who undergo renal biopsy. Twenty-two units participated. Overall 1.7 per cent of patients undergoing biopsy had an infection but there was large variation between units. Interstitial nephritis and amyloid deposits were more common in patients with infection, and minimal change nephropathy was less common than in patients undergoing biopsy but without infection. The respiratory tract was the most common site of infection but was rarely associated with glomerulonephritis of which the most common cause was infective endocarditis. Drug treatment may have caused the renal lesion in 16 per cent of patients. Amyloid deposits, present in 13.6 per cent of patients, was the most common cause of progressive renal failure. Most other patients had some improvement in renal function once the putative cause, whether infection or antibiotic, was removed.

Five patients with perioral dermatitis are described. They were all renal transplant recipients maintained on long-term oral corticosteroids and azathioprine (13 months to 7 years). They all responded satisfactorily to oral doxycycline.

We report on a patient with systemic lupus erythematosus (SLE) who suffered catastrophic haemorrhage following rupture of an intrahepatic aneurysm. The association between hepatic artery aneurysm and SLE has not been recorded previously, but we have found evidence from the literature that there may be an association between autoagressive disorders and this surgical emergency.

Two patients with profound dialysis-induced hypotension were seen, in both of whom sequential ultrafiltration and haemodialysis failed to alleviate their symptoms; in one bicarbonate dialysis similarly produced no improvement. The hypotension was frequently severe enough to necessitate premature termination of the dialysis. Haemofiltration was associated with almost total resolution of symptoms, adequate biochemical control of uraemia, and satisfactory removal of weight gain between dialysis sessions. Profound hypotension during dialysis may become more common as older patients enter dialysis programmes; haemofiltration is a valuable technique in such cases.