Chronic renal failure (CRF) is both a risk factor for, and a consequence of, peripheral arterial disease. There is also increasing evidence that patients with CRF have a higher mortality rate following arterial reconstruction, but it is not known whether this is different for aneurysmal or occlusive disease.

Proteinuria is well described in atherosclerotic renovascular disease (ARVD), but the prevalence is unknown, and the pathogenesis may vary between patients. Substantial proteinuria (> 2 g/day) however, would be regarded by many as atypical of ARVD. We studied 94 patients (52 male) with ARVD, median age 67 years (range 49-87). Digital subtraction angiography was performed on all patients. Protein was assayed in 24-h urine samples and GFR derived using the Cockroft-Gault formula. Forty-nine patients (52%) had proteinuria < 0.5 g/24 h. Proteinuria increased with worsening renal function. Biopsies from seven non-diabetic patients with substantial proteinuria showed: minimal changes (1); glomerular sclerosis with marked ischaemic changes (3); focal glomerulosclerosis (2); and athero-emboli (1). Proteinuria, rather than being indicative of other pathology, is often a marker of severity of parenchymal disorder in atherosclerotic nephropathy, which itself is the major determinant of renal dysfunction in patients with ARVD.

An Asian man, now 54 years old, under the care of our hospital since 1968, developed progressive renal impairment over 10 years. His previous medical history suggested a number of likely causes including longstanding rheumatoid arthritis previously treated with gold, penicillamine, sulphasalazine, and non-steroidal anti-inflammatory drugs; type 2 diabetes, treated with diet, sulphonylureas, then insulin; and hypertension, treated with nifedipine and later enalapril. Clinic records showed that his creatinine concentration was last normal over 10 years ago and had gradually increased to 250–300 μmol/L (creatinine clearance: 29 mL/min) and did not change after starting enalapril. He was first found to have low-grade proteinuria (0·5 g/24 h) 8 years after the decline in renal function started, in the absence of infection or haematuria. Ultrasound showed a small (8·4cm) right and normal-sized (10 cm) left kidney with no stones or obstruction. A 99M Technetium mereaproacetyl glycine glycine glycine (MAG3) scan showed that the larger kidney contributed 63% of renal function, a proportion unchanged after captopril. Diabetic control was good (HbA1c<7%) since starting on insulin, there were no microvascular complications. Other previous investigations included a normal blood count with occasional mild eosinophilia, intermittently raised erythrocyte sedimentation rate (ESR) (assumed due to rheumatoid disease activity), normal liver function, calcium and phosphate, fasting total cholesterol never more than 5·2 mmol/L and triglycerides less than 1·0mmol/L. On examination, there were ???, indicating peripheral vascular disease in the absence of symptoms. Angiography showed stenosis of one of two arteries to the small (right) kidney and diffuse aortic atheromatous disease. At this stage the cause of his renal impairment was uncertain.

Key words: renal artery stenosis; polycystic kidney acute tubular necrosis in the presence of adult polycystic kidney disease.disease His creatinine reached a nadir of 182 mmol/l a year later.Over the next 5 years the creatinine rose slowly to

BACKGROUND:HDL is present in the urine of patients with the nephrotic syndrome. The amount of HDL is directly related to the protein selectivity and therefore to the renal prognosis. Urinary HDL may therefore be involved in the pathogenesis of progressive renal impairment in proteinuric renal disease.METHODS:LLC-PK1 cells were grown as orientated monolayers on filters. Uptake of HDL and permeability to inulin were measured. The influence of HDL in the growth medium on monolayer resistance, protein content, and sodium dependent glucose transport was studied. The effects of tetranitromethane (TNM) nitrosylation of HDL and of albumin, mevalonate, or simvastatin were investigated.RESULTS:Confluent LLC-PK1 monolayers took up fluorescently labelled HDL from either epithelial surface and formed a significant diffusion barrier to inulin. Monolayers incubated in 300 micrograms/ml HDL achieved a protein content and plateau of resistance equal to those in 10% fetal calf serum (FCS); 30-1000 micrograms/ml HDL applied to the apical surface of confluent monolayers maintained a plateau of resistance as well as 10% FCS and significantly better than serum-free medium. Sodium-dependent glucose transport was preserved in monolayers exposed to HDL. Simvastatin completely, and nitrosylation partially, removed the stimulatory properties of HDL. These were partly reproduced by albumin or mevalonate.CONCLUSIONS:HDL can enter renal epithelial cells from the apical surface. HDL added to this surface at confluence, reproducing the conditions found in the nephrotic syndrome, had a measurable positive effect on monolayer resistance. Results with nitrosylated HDL and HMG-CoA blockade suggest that these effects may be mediated via receptors and this enzyme system.

Journal Article Renal arteriopathy associated with FK 506 therapy following liver transplantation Get access J. O. Connolly, J. O. Connolly 1Renal Unit, Kings College Hospital (Dulwich)London Correspondence and offprint requests to Dr J. 0 Connolly, Renal Administration, Renal Unit, Kings College Hospital (Dulwich), East Dulwich Grove, London SE22 8PT, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar E. Gane, E. Gane 2Institute of Liver StudiesLondon Search for other works by this author on: Oxford Academic PubMed Google Scholar R. M. Higgins, R. M. Higgins 1Renal Unit, Kings College Hospital (Dulwich)London Search for other works by this author on: Oxford Academic PubMed Google Scholar P. J. O'Donnell, P. J. O'Donnell 3Dept. of Histopathology, Kings College HospitalLondon Search for other works by this author on: Oxford Academic PubMed Google Scholar J. Devlin, J. Devlin 2Institute of Liver StudiesLondon Search for other works by this author on: Oxford Academic PubMed Google Scholar J. E. Scoble, J. E. Scoble 1Renal Unit, Kings College Hospital (Dulwich)London Search for other works by this author on: Oxford Academic PubMed Google Scholar R. Williams R. Williams 2Institute of Liver StudiesLondon Search for other works by this author on: Oxford Academic PubMed Google Scholar Nephrology Dialysis Transplantation, Volume 9, Issue 7, 1994, Pages 834–836, https://doi.org/10.1093/ndt/9.7.834 Published: 01 January 1994 Article history Published: 01 January 1994 Received: 12 January 1994 Accepted: 12 January 1994

Atherosclerotic renovascular disease (ARD) is an increasingly important cause of renal failure. However, important features of the clinical presentation are not fully described, and the outcome after intervention by angioplasty remains controversial. Ninety-four patients with ARD diagnosed at angiography were reviewed. Twenty-four patients were diabetic. Thirty-nine patients had unilateral renal artery stenosis or occlusion (group A), 28 had bilateral stenosis (group B), and 27 had unilateral occlusion plus contralateral occlusion or stenosis (group C). Two years after presentation, actuarial patient survival was 96%, 74.3% and 47.1% in groups A, B and C, respectively (p < 0.001 for all differences); actuarial renal survival in surviving patients was 97.3%, 82.4% and 44.7%, respectively (p < 0.001 for all differences). Percutaneous transluminal balloon angioplasty (PCTA) was performed in 74 patients. Renal function improved in only a minority of cases, but was stable in 73% of nondiabetic patients 12 months after PCTA. Angioplasty was less effective in diabetic subjects, with only 53.3% having stable renal function at 12 months follow-up. Renal and patient survival were strongly related to the initial angiographic findings. In non-diabetic subjects, PCTA resulted in stabilization of renal function for at least one year in nearly three-quarters of cases, which suggests a benefit from intervention in this disease whose natural history is otherwise of progression.

Journal Article Malignant hypertension and renal failure: scleroderma renal crisis or renal artery stenosis? Get access K. Morris, K. Morris 1Renal Unit, Kings College Hospital (Dulwich)London Correspondence and offprint requests to: Dr John Connolly, Renal Unit, Dulwich Hospital, East Dulwich Grove, London SE228PT, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar J. O. Connolly, J. O. Connolly 1Renal Unit, Kings College Hospital (Dulwich)London Search for other works by this author on: Oxford Academic PubMed Google Scholar P. J. O'Donnell, P. J. O'Donnell 2Dept. of Histopathology, King's College Hospital London Search for other works by this author on: Oxford Academic PubMed Google Scholar J. E. Scoble J. E. Scoble 1Renal Unit, Kings College Hospital (Dulwich)London Search for other works by this author on: Oxford Academic PubMed Google Scholar Nephrology Dialysis Transplantation, Volume 9, Issue 10, 1994, Pages 1489–1491, https://doi.org/10.1093/ndt/9.10.1489 Published: 01 January 1994 Article history Published: 01 January 1994 Received: 05 May 1994 Accepted: 05 May 1994

During a 6 year period 60 patients with atherosclerotic renovascular disease were followed by a single renal unit. Angiotensin converting enzyme inhibitors were being taken by 22% of patients at the time of diagnosis of the atherosclerotic renovascular disease. Intervention to revascularize renal tissue by surgery or angioplasty was performed in 32 patients. Revascularization was not undertaken because of unilateral disease, patient preference, poor operative risk or renal size. The mean age for the nonintervention group was 66.9 years and 63.4 years for the intervention group. Peripheral vascular, disease was common in both groups (96% nonintervention group versus 86% intervention group). There was a statistically significant difference in improvement in renal function in the intervention group (34.4% versus 10.7%) in spite of more patients being dialysis dependent in the intervention group (28.1% versus 14.3%). There was no statistically significant difference in survival between the two groups although the trend was for better survival in the group with intervention. Patients presenting with impaired renal function and atherosclerotic renovascular disease can have useful improvement in renal function with revascularization without any detriment to survival.

We report here for the first time that human renal proximal tubular cells secrete endothelin, clear evidence of de-novo endothelin synthesis by these cells and the effect of cyclosporin A (CsA) on endothelin synthesis both in short-term (24 h) and medium-term (5-day) culture. Human renal cortical epithelial cells were cultured and shown to possess proximal tubular characteristics. These cells produced endothelin in culture in a time-dependent manner, as measured by radioimmunoassay (291.6 +/- 51.4 pg/well/24 h). Furthermore, endothelin production by these cells was significantly decreased by up to 80% by cycloheximide (1051.8 +/- 54.9 pg/mg cell protein/24 h versus 253.2 +/- 12.6 pg/mg cell protein/24 h), showing that these cells actively synthesize endothelin. In short-term culture (24 h), CsA significantly inhibited endothelin synthesis at a medium concentration of 10,000 micrograms/l. No change in endothelin synthesis was seen at lower CsA concentrations. In contrast, over a 5-day period, a non-significant increase in endothelin synthesis was observed at CsA concentrations of 2000 micrograms/l (152.5 +/- 20.4%); however, cell growth was significantly decreased at this concentration (71.33 +/- 6.39%). Using a newly developed two-site immunoradiometric assay specific for endothelin-1 (ET-1), we demonstrate that ET-1 is the major endothelin isoform produced by human renal proximal tubular cells.

Journal Article Progression of occlusive renal vascular disease and axillofemoral bypass grafts Get access C. Streather, C. Streather King's College Hospital (Dulwich), Royal Free Hospital, Greenwich HospitalLondon, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar Z. C. Wlodarczyk, Z. C. Wlodarczyk King's College Hospital (Dulwich), Royal Free Hospital, Greenwich HospitalLondon, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar F. Sneddon, F. Sneddon King's College Hospital (Dulwich), Royal Free Hospital, Greenwich HospitalLondon, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar D. Robson, D. Robson King's College Hospital (Dulwich), Royal Free Hospital, Greenwich HospitalLondon, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar A. Phillips, A. Phillips King's College Hospital (Dulwich), Royal Free Hospital, Greenwich HospitalLondon, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar G. Hamilton, G. Hamilton King's College Hospital (Dulwich), Royal Free Hospital, Greenwich HospitalLondon, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar J. E. Scoble J. E. Scoble King's College Hospital (Dulwich), Royal Free Hospital, Greenwich HospitalLondon, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar Nephrology Dialysis Transplantation, Volume 8, Issue 10, 1993, Pages 1186–1187, https://doi.org/10.1093/ndt/8.10.1186 Published: 01 January 1993

Changes in renal function caused by angiotensin-converting-enzyme (ACE) inhibitors can be detected on 99mTc-DTPA renography so that DTPA scanning before and after a single dose of captopril can be used to screen for renovascular disease. We have performed captopril-DTPA scans with renal arteriography on 104 patients, of whom 27 had renal artery stenosis, all due to atheroma. Using a 5% fall in divided function or a delay of greater than 15 min in time to peak activity on one side after captopril, or the finding of greater than 90% divided function on one side before captopril as criteria for a positive scan, a sensitivity of 93% and specificity of 70% was achieved. The negative predictive value of the test in our population was 93%. Bilateral improvement in renographic function after captopril was seen in patients with accelerated phase hypertension. The presence of bilateral renal artery disease did not reduce the sensitivity of the test, but sensitivity was reduced (75%) in patients with renal impairment. Clinical characteristics in our patients most strongly associated with renal artery stenosis were abdominal bruit, recurrent left ventricular failure, and peripheral vascular disease. In view of the well-publicized risks of ACE inhibitor therapy, care should be exercised in the use of these agents in such patients.