The role of body protein studies in clinical trials.
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Biomedical subjects
Publications and source records attributed to L S Ibels.
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The nutritional status of 35 patients on continuous ambulatory peritoneal dialysis (CAPD) was assessed by the traditional methods of dietary history and anthropometric measurements, and was compared with simultaneous measurements of dietary protein intake (DPI) calculated from urea generation rate and total-body nitrogen (TBN) assessment by prompt neutron activation analysis (PNAA). DPI as determined by dietary recall was significantly higher than calculated DPI (1.04 +/- 0.42 v 0.84 +/- 0.28 g/kg/d; P less than 0.001). Anthropometric measurements did not differ significantly from the predicted normal values for sex, height, and age. However, PNAA measurements of TBN demonstrated significant nitrogen depletion, being 88.2% of normal for males (P less than 0.001) and 87.5% of normal for females (P less than 0.002); TBN correlated significantly with DPI calculated from urea generation rate (P less than 0.05). Assessment of these 35 patients 17.5 +/- 4.4 months later, demonstrated that patients who died or suffered serious morbidity requiring transfer from CAPD (n = 10) had significantly lower TBN than those who remained on CAPD or underwent successful renal transplantation (n = 25): 80.0% v 93.2% of normal (P less than 0.01). No difference in anthropometric measurements was observed between the two groups of patients. Eleven patients on maintenance home or satellite hemodialysis underwent identical dietary, anthropometric, and TBN assessments and results were similar to those obtained in the CAPD population, although no correlation with calculated DPI and TBN was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Afferent arteriolar C3 deposition was the sole histological abnormality in 79 and the major histological abnormality in an additional 39 of 959 renal biopsies performed over a 10-year period. Of these 79 patients, hematuria was the presenting symptom in 90%, with coincident loin pain in 49%. Urine microscopy of asymptomatic first-degree relatives revealed hematuria in 44% of children and siblings and 54% of parents, suggesting autosomal dominant inheritance. Arteriolar C3 deposition was confirmed by biopsy in four asymptomatic relatives with hematuria. Generalized thinning of glomerular basement membrane (less than 200 nm) was observed in five patients and focal thinning was observed in six patients with coincident afferent arteriolar C3 deposition. Seven other patients were identified as having generalized thinning of glomerular basement membrane in the absence of afferent arteriolar C3 deposition. Renal function was stable and similar in all groups studied over 37.9 +/- 23.7 months. No difference in clinical presentation or urinary abnormalities was evident between the groups. No arteriolar C3 deposition was evident in eight autopsy specimens with no known renal disease. It was concluded that afferent arteriolar C3 deposition is a marker of a distinct hereditary pathological entity, with differentiation from thin basement membrane disease not possible on clinical grounds. The medium- and long-term prognoses with respect to renal function are excellent.
One hundred and thirty-four patients using continuous ambulatory peritoneal dialysis (CAPD) for a mean time of 23.1 +/- 18.3 months (range, 1-76.6) from a single center are reviewed with respect to biochemistry, hematology, parameters of dialysis efficiency, nutrition, and the nature and frequency of complications. Cumulative patient survival was 90%, 86% and 75% at 1, 2 and 3 years, and survival of patients using this technique was 75%, 62% and 40% at corresponding time intervals with no difference demonstrated in diabetic patients or in those older than 50 years. Biochemical and hematologic parameters were well maintained with peritoneal creatinine clearance increasing and peritoneal protein loss remaining stable with ongoing CAPD. Loss of ultrafiltration, however, accounted for 17.7% of permanent transfers to alternative therapy. Low serum albumin and elevated serum triglyceride concentrations correlated with mortality, whereas low serum albumin, low cholesterol, and high phosphate levels correlated with morbidity as assessed by frequency of hospital admissions. Dietary protein intake assessed by urea generation rate was significantly lower than that estimated from a 24-hour dietary recall (0.82 vs. 1.02 g/kg/day, p less than 0.01) and with the exception of body mass index and serum albumin, anthropometric and visceral protein measurements showed few correlations with nutritional adequacy. Bacterial peritonitis remained the major complication, although fungal infections made a significant contribution to morbidity and mortality. Overall, CAPD is confirmed to be a satisfactory form of dialysis for all forms of end-stage renal failure and an integral part of any renal replacement program. However, nutritional adequacy and lowering of complication rates require further investigation.
Five renal transplant recipients were observed to have recurrent infections in association with low serum immunoglobulin levels. They have benefited from parenteral gamma globulin therapy. Following this observation, 110 renal transplant recipients were assessed; 46% had abnormal serum immunoglobulins with 4 patients identified as having monoclonal gammopathies, 8 polyclonal gammopathies, and 39 low levels of 1 or more immunoglobulins. Those with abnormal serum immunoglobulins had been immunosuppressed longer, but maintenance immunosuppression dosage was not different from those with normal immunoglobulins. Respiratory tract infection and skin cancer were more frequent in those with low immunoglobulin levels.
Thirty-eight peritoneal biopsies from 37 patients with normal renal function or with end-stage renal failure without replacement therapy or utilizing continuous ambulatory peritoneal dialysis (CAPD), haemodialysis (HD) or a functioning transplant were examined histologically. No abnormality in peritoneal membrane morphology was observed in uraemia in the absence of dialysis. Significant abnormalities of peritoneal membrane morphology were observed in association with CAPD, the predominant finding being the development of peritoneal fibrosis which had a deleterious effect on membrane function. Abnormal peritoneal morphology was less commonly observed in patients on maintenance HD and with functioning transplants but may have implications regarding the future use of CAPD in these patients.
In patients utilizing continuous ambulatory peritoneal dialysis (CAPD), Staphylococcus epidermidis is the most prevalent organism isolated from peritoneal and exit site infections [1] although clinically significant systemic infection is unusual. We report 2 patients undergoing CAPD who developed generalized lymphadenopathy following peritonitis and exit site infection with S. epidermidis isolated from the excised lymph nodes. We conclude that catheter-related S. epidermidis infection may result in generalized lymphadenopathy due to dissemination of the infective focus.
Beta-2 microglobulin (B2M) handling in continuous ambulatory peritoneal dialysis (CAPD) was characterized in acute and chronic clinical studies. Average clearance rate was 0.7 mL/min and mean mass transfer coefficient, KoA, was calculated to be 0.95 cm2/min; these values are in the range expected from extrapolation of published data for other large solutes. In chronic studies with both anuric and oliguric populations, CAPD was shown to be much more effective than conventional hemodialysis in removing B2M and, in fact, CAPD removal rates were equivalent to those reported for high flux dialysis therapies. However, this greater extraction was not associated with any clinically significant reduction in circulating plasma concentrations. These trends remained valid in both the anuric and oliguric subsets of the study population.
Fifteen patients on long-term continuous ambulatory peritoneal dialysis (CAPD) were assessed with respect to net ultrafiltration capacity. Eight patients were defined as having good and seven as having poor ultrafiltration on the basis of net ultrafiltrate obtained/mmol glucose infused. Subsequently, dialysate was sampled at times 0, 1, 15, 30, 60, 90, 120, 180, and 240 min. No difference in residual volume was observed between the groups. A significantly greater decrease in dialysate sodium during the initial dialysis period in those patients with good as compared to those with poor ultrafiltration occurred, reflecting a greater transcapillary movement of electrolyte poor ultrafiltrate. In those with good ultrafiltration, glucose transfer was normal in five and rapid in three, suggesting the latter had low rates of lymphatic reabsorption. Five of seven patients with poor ultrafiltration had no fall in dialysate sodium in association with a high rate of glucose transfer, suggesting a low rate of transcapillary water movement and normal to high lymphatic absorption. Two patients with low ultrafiltration had an initial fall in dialysate sodium with a normal glucose transfer and thus net ultrafiltration is low due to elevated lymphatic reabsorption. We thus propose that the relative contribution of transcapillary water movement and lymphatic reabsorption can be determined by assessing net ultrafiltration and dialysate sodium concentration in conjunction with solute transfer.
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Thirty-eight Sydney Harbour Bridge workers were assessed for possible lead intoxication. Forty-seven per cent were found to have significant lead intoxication as assessed by calcium disodium edetate chelation (Ca EDTA) testing and were subsequently effectively and safely treated with Ca EDTA. The prevalence of neurological, constitutional, gastrointestinal and musculoskeletal symptoms was significantly greater in those with, than those without, lead toxicity. Although blood lead levels and, to a lesser extent, hematological parameters were of some use in diagnosis, they were not sufficiently sensitive and thus should not be used in screening workers at risk of lead intoxication. Ca EDTA testing remains the diagnostic method of choice. Patients exposed to lead dust and fumes, in whom symptoms of lead intoxication are present, should undergo such testing and if a positive result is obtained, then EDTA chelation therapy should be instituted.
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Renal disease in association with lymphoma is more prevalent than generally recognized. Glomerulonephritis may occur as a paraneoplastic phenomenon. We report a patient who presented with acute renal failure due to focal necrotizing glomerulonephritis in association with non-Hodgkin's lymphoma in whom the acute renal failure and glomerulonephritis resolved on clinical, biochemical and histological grounds with treatment of the lymphoma. Focal necrotizing glomerulonephritis is extremely uncommon in association with lymphoma and, to our knowledge, this association with follow-up and histological resolution of glomerulonephritis has not previously been reported.
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Twenty patients with necrotizing glomerulonephritis were seen at a general teaching hospital over a 6-year period. These patients represented 5.2% of the histologically verified glomerulonephritis population. Twelve patients had an associated systemic illness (vasculitis in 6, Wegener's granulomatosis in 2, Goodpasture syndrome in 2, infective endocarditis in 1, pulmonary renal syndrome in 1). The clinical course was variable, with equal numbers of patients having rapidly progressive and indolent courses. Four patients (20%) had less than 10% normal glomeruli on renal biopsy and developed end-stage renal failure. Although immunosuppressive and anticoagulant therapy was associated with an improvement in renal function, 6 patients (30%) had died after a mean follow-up period of 25 months.
Acute renal failure following retrograde pyelography is a rare occurrence. The mechanisms reported have focused upon urinary tract obstruction either at an intrarenal or ureteric level. This report describes the first biopsy-proven case of acute tubular necrosis complicating retrograde pyelography. We propose the etiology to be direct tubular toxicity resulting from pyelolymphatic reflux of contrast.