Diabetes, cyclosporin nephrotoxicity, and serum creatinine concentration.
Explore the source record for details and available documents.
Creatinine↗
Biomedical subjects
J Walls
Publications and source records attributed to J Walls.
Acute renal failure associated with haematological malignancies: a review of 10 years experience.
Patients with ARF and haematological malignancy (excluding myeloma), presenting to a single unit over 10 years were analyzed to see if patients likely to benefit from intensive renal supportive therapy could be identified. 31 episodes of ARF were identified in 29 patients (mean age 51 +/- 2.9 yr): 19 were associated with acute leukaemia (13 AML, 6 ALL); 10 with lymphoma. Acute tubular necrosis (ATN) was identified as the cause of ARF in 26 cases, with sepsis (96%) and exposure to nephrotoxic drugs (88%), especially aminoglycosides, being the commonest precipitating factors. Toxic levels of the latter were commonly documented. Patient survival was 45%. Requirement for mechanical ventilation resulted in a universally fatal outcome; age greater than 55 yr and the presence of CNS symptoms or signs were also significantly associated with a poor outcome. Non-ATN causes (urate nephropathy or obstruction) carried a better prognosis. However, only 4 patients (14%) lived for more than 6 months following ARF. Thus, although a subgroup of patients more likely to benefit from treatment can be identified, the overall prognosis is poor and limited by that of the underlying disease. The potential benefit of avoiding nephrotoxic drugs, especially aminoglycosides, in these patients is highlighted by this study.
Acute Kidney Injury↗
High prevalence of systemic disease and mortality in Asian subjects with systemic lupus erythematosus.
All patients with systemic lupus erythematosus (SLE) (American Rheumatism Association criteria with positive antinuclear antibody titre) and who attended any of the three general hospitals in Leicester over a 10 year period were ascertained using several complementary sources. Eighty seven subjects (26 Asian, 61 white) were identified. The estimated prevalence of SLE in Leicester is 0.4/1000 for Asian and 0.2/1000 for white subjects. Mean age of onset of the disease was 24 years in Asian and 31 years in white subjects, with both groups showing a female preponderance. Proteinuria (greater than 1 g/24 h) was noted in 15 (58%) Asian and 21 (35%) white subjects; neuropsychiatric disease in 10 (38%) Asian and 8 (13%) white subjects; myalgic symptoms with raised muscle enzymes in 9 (35%) Asian and 3 (5%) white subjects. Nineteen (73%) Asian subjects were positive for extractable nuclear antigens as well, at some stage of their disease, compared with 6 (10%) white subjects. Immunosuppressive treatment was required in 12 (46%) Asian and 12 (20%) white subjects, and deaths of seven Asian and five white subjects were attributed to SLE. These findings show that Asian subjects have a higher prevalence of SLE with greater systemic disease and mortality.
Adult↗
Cholesterol feeding following unilateral nephrectomy in the rat leads to glomerular hypertrophy.
Experimental glomerulosclerosis is associated with hyperlipidaemia and the deposition of lipid in glomeruli. Glomerulosclerosis is typically preceded by glomerular hypertrophy. To investigate a possible pathogenic role of lipids in glomerulosclerosis, glomerular structure and cellular composition were studied in rats fed either a control diet or one supplemented with 4% cholesterol and 1% cholic acid for 21 weeks following unilateral nephrectomy. On the cholesterol diet there were significant increases in glomerular cross-sectional area (13.11 +/- 0.39 x 10(3) vs. 11.13 +/- 0.44 x 10(3) mu 2, p less than 0.01) and mesangial area (1.81 +/- 0.07 x 10(3) vs. 1.50 +/- 0.08 x 10(3) mu 2, p less than 0.02). These changes were significantly correlated with proteinuria, which was significantly greater on the cholesterol diet (mean area under curve for duration of diet = 3.11 +/- 0.38 vs. 1.42 +/- 0.35 g, p less than 0.02). There was a significant increase in glomerular leukocytes on the cholesterol diet (4.10 +/- 0.44 vs 2.86 +/- 0.25 OX-1 positive cells/10(4) mu 2, p less than 0.05). Mesangial foam cells, derived from macrophages, were associated with adhesions to Bowman's capsule. These results demonstrate that hyperlipidaemia exacerbates the development of glomerular hypertrophy and that this may be mediated by factors released during the phagocytosis of lipoprotein deposits by macrophages.
Administration, Oral↗
Phosphoinositide hydrolysis is not enhanced by ciclosporin.
Explore the source record for details and available documents.
Animals↗
Nifedipine does not inhibit ciclosporin A uptake into human cultured proximal tubular cells.
Explore the source record for details and available documents.
Biological Transport, Active↗
The role of omentectomy in continuous ambulatory peritoneal dialysis.
Long-term survival of the peritoneal catheter is essential for successful CAPD. In our unit, all CAPD catheters are now placed by an open surgical technique, which in some cases has included performing a partial omentectomy. The aim of this study was to assess the influence of omentectomy on CAPD catheter survival. Three hundred consecutive CAPD catheters inserted over a 5-year period were analyzed. Omentectomy was performed in 113 cases (38%). Data relating to a number of potentially significant risk/benefit factors were analyzed using multiple regression analysis (proportional hazards method of Cox). Performing a partial omentectomy at the time of catheter insertion was found to significantly improve CAPD catheter survival (p = 0.0002).
Adolescent↗
The role of continuous ambulatory peritoneal dialysis in end-stage renal failure due to multiple myeloma.
A study in 10 patients (eight male, two female; mean age 61.9 +/- 10.7 years) suffering from multiple myeloma (MM) and end-stage renal failure (ESRF) is detailed. Continuous ambulatory peritoneal dialysis (CAPD) was the preferred mode of chronic dialysis in all the patients. Survival after diagnosis was 32.2 +/- 23.9 months. Survival after starting dialysis was 24.6 +/- 20.6 months. All patients on CAPD were adequately dialyzed and in good fluid control. Peritonitis was the main problem on CAPD (one episode per 5.6 patient-months). The majority of peritonitis episodes responded to intraperitoneal antibiotic therapy. One patient with Staphylococcus aureus peritonitis, septicemia, and neutropenia secondary to chemotherapy, died. Recommendations for prophylaxis and treatment of peritonitis are given. Three patients were transferred to hemodialysis. The use of subclavian vein catheters during hemodialysis was associated with a high incidence of gram-positive septicemia. Alkylating agent-based chemotherapy resulted in hematological responses in five patients. Survival after diagnosis in those responders was 47.4 +/- 25.6 months, compared with 17.0 +/- 7.2 months in the nonresponders (P less than 0.05). All responders subsequently relapsed. Four patients died with progressive myeloma. Bone marrow suppression resulted in a high blood transfusion requirement, neutropenia, and thrombocytopenia associated with bleeding into the gastrointestinal tract and central nervous system. Uremic myeloma patients can be adequately dialyzed using CAPD. Those patients who do not have an initial hematological response have a poor prognosis.
Adult↗
Effect of nifedipine on renal haemodynamics in an animal model of cyclosporin A nephrotoxicity.
1. This study investigates the effect of nifedipine on cyclosporin A nephrotoxicity in the spontaneously hypertensive rat. 2. Cyclosporin A, administered daily by subcutaneous injection at 25 mg/kg body weight for 14 days, induced a significant reduction in glomerular filtration rate (35.3%) and effective renal plasma flow (45.0%), and an increase in renal vascular resistance (219%). Using this regimen, tubular, glomerular or vascular morphological damage was not evident on light microscopy. 3. The administration of nifedipine simultaneously with cyclosporin A from day 1 prevented the characteristic decline in renal function and increase in renal vascular resistance. However, the administration of nifedipine to spontaneously hypertensive rats previously exposed to cyclosporin A for 7 days failed to improve renal haemodynamics. 4. This study suggests that the beneficial effect conferred by nifedipine on cyclosporin A nephrotoxicity is present only when treatment is initiated simultaneously with cyclosporin A.
Animals↗
The effect of nifedipine on renal function in normotensive cyclosporin-A-treated renal allograft recipients.
Intrarenal vasoconstriction is a characteristic feature of CsA nephrotoxicity. The influence of nifedipine, a dihydropyridine calcium channel blocker and potent renal vasodilator, on renal haemodynamics was investigated in 11 cyclosporin A (CsA)- and 9 azathioprine (Aza)-treated normotensive long-term renal allograft recipients. Baseline Cr51-EDTA clearance and effective renal plasma flow (ERPF) were similar in both groups. Nifedipine 20 mg twice daily for 28 days significantly increased Cr51-EDTA clearance (+14.8%) in the CsA group; however, ERPF, renal vascular resistance (RVR), and filtration fraction did not change. Nifedipine did not influence renal haemodynamics in the azathioprine group. The increase in Cr51-EDTA clearance in the CsA group did not correlate with baseline renal function, CsA dose or whole blood levels, donor age, duration of graft, or renal functional reserve capacity. This study suggests that nifedipine confers a beneficial effect on renal haemodynamics in long-term CsA-treated renal allograft recipients and appears to improve renal function by a non-haemodynamic mechanism.
Adult↗
The role of lipids in the pathogenesis of glomerulosclerosis in the rat following subtotal nephrectomy.
Similarities between atherosclerosis and glomerulosclerosis suggest that hyperlipidaemia may contribute to glomerular injury. Dietary supplementation with 4% cholesterol + 1% cholic acid was administered to rats 4 weeks after 1 1/3 nephrectomy and continued for 7 weeks. There was a significant increase in serum cholesterol (peak = 11.52 +/- 1.09 mmol l-1 vs. 4.73 +/- 0.31 on control diet, P less than 0.001) and triglyceride concentrations (peak = 2.31 +/- 0.27 mmol l-1 vs. 1.41 +/- 0.29, P less than 0.05) and a marked increase in beta-migrating lipoproteins. The severity of hypercholesterolaemia was significantly correlated with proteinuria (control diet: r = 0.600, cholesterol diet: r = 0.672, P less than 0.0001) as was hypertriglyceridaemia (control diet: r = 0.544, cholesterol diet: r = 0.678, P less than 0.0001). The percentage of glomeruli containing lipid deposits was increased from 21% to 60% (P less than 0.05). The kidney total cholesterol content was increased from 29.2 +/- 0.8 to 47.7 +/- 3.3 mumols g-1 dry weight (P less than 0.0001), with esterified cholesterol increasing from 7.5 +/- 0.4% to 14.5 +/- 2.1% of total (P less than 0.01). Serum cholesterol concentration was significantly correlated with both glomerular lipid deposition (rs = 0.7195, P less than 0.0001) and tissue total cholesterol content (rs = 0.6053, P less than 0.001). Lipid vacuolation was prominent in the paramesangium and within mesangial cells. Despite these changes hypertension, uraemia, proteinuria and glomerulosclerosis were not significantly increased on the cholesterol diet. Cholesterol deposition in the glomeruli occurs secondary to hyperlipidaemia in rats following subtotal nephrectomy but over 7 weeks no exacerbation of glomerulosclerosis is detectable.
Animals↗
Acute renal failure associated with a labetalol overdose.
A case of acute renal failure in association with a deliberate labetalol overdose is described. The possible pathogenetic mechanisms behind the deterioration in renal function are discussed. Treatment of beta-blockade overdose, with special emphasis on the place of glucagon in such poisoning, is reviewed.
Acute Kidney Injury↗
A clinical audit of thallium-technetium subtraction parathyroid scans.
Eighty six consecutive thallium-technetium subtraction parathyroid scans performed over a three year period for hypercalcaemia have been evaluated. Twelve had chronic renal failure, 11 had hypercalcaemia due to non-hyperparathyroid causes and in 10 the imaging study was technically inadequate. The remaining 53 technically adequate studies performed for hypercalcaemia clinically thought to be possibly due to hyperparathyroidism have been analysed. Of 20 (38%) positive scans, 13 came to surgery (10 correctly localized parathyroid adenomas, 2 with multiple gland hyperplasia, and 1 papillary carcinoma of the thyroid). Of 33 (62%) negative scans, 9 had surgical exploration on the basis of strong clinical grounds and all had parathyroid adenomas. Multiple biochemical parameters have been assessed in relation to a positive outcome on scan. The adjusted calcium-phosphate product and the ratio of the adjusted calcium-phosphate product to creatinine (Ca x P/Cr) were both significantly lower in the scan positive group (P less than 0.01). The scan positive group had a significantly higher mean level of PTH (P less than 0.001) and lower mean level of phosphate (P less than 0.001). The present experience shows that parathyroid imaging is useful in localizing parathyroid adenomas in 50% of cases (10 out of 19). This figure is at the lower end of the range of previously published results. It is less effective in demonstrating multiple gland hyperplasia. The decision as to whether to undertake surgical exploration when the scan is negative has been based successfully on clinical judgement. We feel that an analysis of this nature is important, as it gives insights into the practical relevance of parathyroid imaging in the context of routine clinical work.
Adenoma↗
Receptor-mediated endocytosis of low-density lipoprotein by cultured human glomerular cells.
Lipoproteins might be involved in the pathogenesis of glomerular damage. Uptake of low-density lipoprotein (LDL) by cultured human glomerular cells has been studied using LDL, labelled with the fluorescent probe 1,1'-dioctadecyl-3,3,3'3'-tetramethyl-indocarbocyanine perchlorate (diI). Cells have been characterised using phase-contrast microscopy, monoclonal antibodies and lectins. Differentiated glomerular epithelial cells, epithelial-like cells and mesangial cells all took up diI-LDL. Uptake was specific for LDL, of high affinity and inhibited by excess unlabelled LDL, heparin and preloading the cells with cholesterol. Binding of diI-LDL to the cell surface was restricted to discrete areas which were arranged in linear arrays on mesangial cells. Endocytosis of surface-bound diI-LDL occurred within 3 min and breakdown of internalised diI-LDL within 30 min. These results indicate that cultured human glomerular cells take up LDL by receptor-mediated endocytosis.
Cells, Cultured↗
Metabolic role of acidosis in uraemia.
Explore the source record for details and available documents.
Acidosis↗
Maintaining nutrition in CAPD patients.
Explore the source record for details and available documents.
Diet↗
Systemic vasculitis in the 1980s--is there an increasing incidence of Wegener's granulomatosis and microscopic polyarteritis?
Thirty-six cases of Wegener's granulomatosis (WG) and microscopic polyarteritis (MPA) presenting to the nephrology service in Leicester between 1980 and 1989 were reviewed. Apart from the diagnostic respiratory tract lesions seen in WG, cases of MPA and WG could not be distinguished by age and sex, range and severity of organ involvement, response to treatment (oral prednisolone and cyclophosphamide), mortality or renal outcome. The combined incidence of WG and MPA in 1980-86 was 1.5/million/year. Following the introduction in January 1987 of an assay for anti-neutrophil cytoplasmic antibody (ANCA), the incidence of WG and MPA increased in 1987-89 to 6.1/million/year (p less than 0.0001). Cases seen during these two periods did not differ by any clinical parameter except that later cases had less severe renal disease at referral and improved renal outcome. Median serum creatinine was significantly lower at presentation in 1987-89 (p less than 0.02). Of those surviving 3 months from presentation only 1/20 in 1987-89 had end stage renal failure compared with 4/10 in 1980-86 (p less than 0.02). These findings may reflect increasing diagnostic awareness of WG and MPA among physicians since the introduction of ANCA.
Adult↗
The prevalence and risk factors associated with the onset of diabetic nephropathy in juvenile-onset (insulin-dependent) diabetics diagnosed under the age of 17 years in Leicestershire 1930-1985.
The prevalence of diabetic nephropathy was studied in a population of 847 juvenile-onset (insulin-dependent) diabetics diagnosed under the age of 17 years who attended diabetic clinics in Leicestershire between 1930 and 1985. Seven hundred and eighty-nine patients (93.2 per cent) were traced. Eight patients with non-diabetic proteinuria and four classified as maturity-onset diabetics of the young were excluded from further analysis. The mean age at onset was 9.3 +/- 4.2 years (mean +/- SD) and the mean duration of diabetes 17.0 +/- 10.6 years (range 3-63 years). Overall, 28 patients (3.6 per cent) developed persistent proteinuria and 39 patients (five per cent) intermittent proteinuria. End-stage renal failure developed in eight patients. In patients with diabetes of 20 years duration (n = 254) the prevalence of persistent proteinuria was 9.1 per cent and of intermittent proteinuria, 7.9 per cent. Systolic and diastolic blood pressures were elevated in diabetics with persistent proteinuria compared to patients without proteinuria (154/89 +/- 27/15 vs 123/76 +/- 15/9 mm Hg mean +/- SD; p less than 0.001). Systolic blood pressure was also raised in patients with intermittent proteinuria (133/77 +/- 17/12, p less than 0.005). In addition, proteinuria (intermittent and persistent) was significantly associated with the use of once-daily insulin therapy in childhood and poor clinic attendance. This study suggests that twice-daily insulin therapy from diagnosis in childhood and regular contact with the diabetic clinic decreased the prevalence of diabetic nephropathy in this population.
Adolescent↗