Search PubMed⌕ Search

Biomedical subjects

R G Walker

Publications and source records attributed to R G Walker.

At least 91 records · Page 5Linked to original sources

The treatment of mesangial IgA nephropathy with cyclophosphamide, dipyridamole and warfarin: a two-year prospective trial.

Of 52 patients with mesangial IgA nephropathy, 25 were allocated to treatment with cyclophosphamide (6 months), and dipyridamole and warfarin (2 years) and 27 to no treatment in a randomized prospective 2-year study. At entry, the treated and untreated groups of patients did not differ in mean serum creatinines, urinary protein excretions, quantitative urinary erythrocyte counts or blood pressure readings. At the end of the trial mean (+/- SEM) serum creatinine values had gone from 0.12 +/- 0.01 to 0.13 +/- 0.01 mmol/l (p less than 0.05) in untreated patients and from 0.10 +/- 0.01 to 0.12 +/- 0.01 mmol/l (p less than 0.05) in treated patients. Mean (+/- SEM) log values of urinary erythrocyte (rbc) counts had not changed significantly from 5.47 +/- 0.09 to 5.21 +/- 0.14 log rbc/ml in untreated patients, from 5.45 +/- 0.11 to 5.49 +/- 0.19 log rbc/ml in treated patients. However, in treated patients, mean (+/- SEM) urinary protein excretions decreased from 1.67 +/- 0.35 to 1.15 +/- 0.31 g/24 h (p less than 0.01) whereas in untreated patients urinary protein was unchanged between initial values of 1.76 +/- 0.34 and follow-up at 1.89 +/- 0.45 g/24 h. No significant changes in blood pressure occurred in either group. This study supports the observation that treatment of IgA nephropathy with cyclophosphamide, dipyridamole and warfarin is associated with a reduction of urinary protein excretion but a significant effect on preservation of renal function, at least as determined by serum creatinine values, could not be confirmed over this two-year study.

Adult↗

Mesangiocapillary glomerulonephritis type II (dense-deposit disease): clinical features of progressive disease.

Twenty-seven patients presenting to the Royal Melbourne Hospital between 1968 and 1988 with mesangiocapillary glomerulonephritis type II with intramembranous dense deposits (dense-deposit disease, DDD) are analyzed. Patients were divided into two groups on the basis of whether renal function deteriorated (14 patients) or remained stable (13 patients). At presentation or during the course of the disease, heavy proteinuria, macroscopic hematuria, and high quantitative urinary red cell or white cell counts characterized patients with progressive disease. Patients with crescents on their initial renal biopsy or with large numbers of polymorphs in glomerular capillaries corresponding with sterile pyuria were more likely to have deterioration of renal function. The average time from onset of symptoms to development of end-stage renal disease was over 16 years. The patient's clinical course could not be anticipated by serum complement profiles, the presence of C3 nephritic factor, or partial lipodystrophy. Pregnancy did not affect the course of the disease. Six patients underwent renal transplantation and the disease recurred on renal biopsy in four. However, only two individuals lost renal allografts due to recurrent DDD.

Adolescent↗

Treatment of IgA nephropathy with eicosapentanoic acid (EPA): a two-year prospective trial.

Thirty-seven patients with biopsy proven mesangial IgA nephropathy were prospectively allocated to either two years of treatment with eicosapentanoic acid (EPA) 10 g per day or no treatment. At entry treated and untreated patients with renal dysfunction (Group A) or patients with normal serum creatinine less than 0.12 mmol/l (Group B) did not differ in serum creatinine, creatinine clearance, urinary protein excretion, or quantitative urinary red cell counts. Compliance with EPA therapy was excellent as assessed by plasma fatty acid profiles. At the end of the trial creatinine clearance in treated patients had gone from 80 +/- 16 to 57 +/- 17 ml/min (p less than 0.05) and in untreated patients from 76 +/- 18 to 55 +/- 14 (p less than 0.05). There were no beneficial effects in either Group A or Group B patients. The only two patients who had improvement in renal function were in the EPA treatment group. Although no side effects of treatment were noted, EPA does not alter the course of established mesangial IgA nephropathy.

Adult↗

Low red cell arachidonic acid in cyclosporine-treated patients.

Red blood cell phospholipid arachidonic acid concentration was determined in 38 renal transplant recipients on cyclosporine-azathioprine-prednisolone therapy and in a comparable group of 20 patients on azathioprine-prednisolone alone. Samples also were obtained from 18 normal controls and 30 patients with "classical" hemolytic uremic syndrome (HUS). The arachidonic acid content was estimated as the percentage relative to the five principal fatty acids in red blood cell phospholipids (C16:0, C18:0, C18:1 omega 9, C18:2 omega 6, C18:3 omega 6) and quoted as mean value +/- standard deviation. There was a highly significant difference between patients on cyclosporine (14.7 +/- 2.9) and non-cyclosporine-treated transplant recipients (17.1 +/- 2.5; p less than 0.002). This difference was even more significant when patients who had been on cyclosporine for less than 3 months were excluded (14.1 +/- 2.7; p less than 0.001). The mean arachidonic acid content in non-cyclosporine recipients also was significantly less than that in normal controls (19.2 +/- 1.5; p less than 0.005) whilst the HUS patients (11.2 +/- 3.6) had significantly reduced values when compared with all the other groups. Cyclosporine often causes nephrotoxicity and in some cases HUS may develop in cyclosporine-treated transplant recipients. We have found a significant negative correlation between serum creatinine levels and red blood cell phospholipid arachidonic acid levels (r = -0.45; p less than 0.01). We propose that the decreased concentration of arachidonic acid in the cyclosporine-treated group may be related to the development of nephrotoxicity in the long term and may be a useful marker in predicting the early development of nephrotoxicity in these patients.

Adolescent↗

Haemolytic-uraemic syndrome after treatment with metronidazole.

This paper describes the clinical features of six children who developed the haemolytic-uraemic syndrome after treatment with metronidazole. These children were older and were more likely to have undergone recent bowel surgery than are other children with this condition. While the involvement of metronidazole in the aetiology of the haemolytic-uraemic syndrome is not established firmly, the action of this drug in sensitizing tissues to oxidation injury and the reported evidence of oxidation changes in the haemolytic-uraemic syndrome suggest a possible link between metronidazole treatment and some cases of the haemolytic-uraemic syndrome.

Adolescent↗

Paediatric cadaveric renal transplantation. Initial experience with a triple therapy immunosuppressive regimen.

Since June 1985 ten consecutive paediatric cadaveric renal transplant recipients (aged from 7 to 15 years) have been studied prospectively to evaluate a triple immunosuppressive regime of low-dose cyclosporin A (CyA), azathioprine (AZA) and prednisolone (PNL) with the aim of eliminating PNL from the regime within 6 months. Follow-up has been over 6-18 months. Patient and graft survival are both 100%. Median (range) serum creatinine values at 6 months were 0.09 (0.05-0.14) mmol/l (n = 10) and 0.09 (0.06-0.16) mmol/l (n = 5) at 12 months. Readily reversible acute rejection episodes occurred in five patients (50%); two of these episodes occurred soon after cessation of PNL. Six months post-transplantation, PNL had been discontinued in six patients (60%). After 12 months, three of five patients were still not receiving PNL. Complications included hypertension (seven patients), cytomegaloviral infections (three patients), labial herpes simplex (one patient), leucopenia (two patients), marked hirsutism (four patients) and transient CyA nephrotoxicity (one patient). Following transplantation, all children had growth velocities greater than 5 cm/year and seven have growth patterns which suggest that "catch-up growth" may be occurring. This preliminary study shows that a triple immunosuppressive regime of low-dose CyA, AZA and PNL allows excellent patient survival, graft survival and graft function and has been associated with few complications, including a low incidence of CyA nephrotoxicity. Growth rates are very encouraging and in a high proportion of children it has been possible to discontinue PNL completely.

Adolescent↗

Exaggerated responsiveness of immunoreactive atrial natriuretic peptide to saline infusion in chronic renal failure.

Plasma levels of immunoreactive alpha human atrial natriuretic peptide (IR-ANP) were measured in nine patients with chronic renal failure before and after removal of 1.3-3.7 litres of fluid by ultrafiltration and again during volume repletion with intravenous sodium chloride solution (150 mmol/l: saline). Baseline levels of IR-ANP were elevated but fell by 22% during ultrafiltration. Saline infusion induced a rapid and steep rise in IR-ANP levels which were 150% of baseline while body weight was still 2% below baseline. Changes in plasma renin, angiotensin II, aldosterone and vasopressin during the study were slight compared with the change in IR-ANP, but noradrenaline levels rose threefold during ultrafiltration. There was a significant positive relationship between arterial pressure and IR-ANP levels before and after ultrafiltration. These results lend support to the suggestion that atrial peptides are of physiological importance, especially in states of chronic fluid overload such as chronic renal failure.

Arginine Vasopressin↗

Chronic progressive renal lesions induced by lithium.

New Zealand white rabbits, eight fed lithium (Li) (50 to 250 mmole LiCl/kg food) and seven controls (C) had sequential open renal biopsies at zero, one, three, six, and 12 months. A distinctive histological lesion, consisting of cytoplasmic vacuolation and accumulation of glycogen in cells lining distal convoluted tubules and collecting ducts, was present in Li (one, three, six, and 12 months), but was absent in Li prior to lithium (zero months) and in C (zero, one, three, six, and 12 months). Histological changes of chronic focal interstitial nephropathy namely, interstitial fibrosis, (quantitated by point counting), tubular atrophy and cast formation (quantitated by digitization), and glomerular sclerosis (determined as the percent of sclerosed glomeruli) showed significant differences between Li and C from as early as one month (interstitial fibrosis, P less than 0.02; tubular atrophy, P less than 0.05; casts, P less than 0.05), and up to 12 months (glomerular sclerosis, P less than 0.05). Distal tubular dilatation and microcyst formation, (quantitated by digitization) was also marked in Li compared with C from one month (P less than 0.05). The degree of distal tubular dilatation and other changes of interstitial nephropathy tended to progress with duration of lithium exposure. Macroscopically, Li kidneys (12 months) were pale, granular, and exhibited microcysts. Raised blood urea (P less than 0.02) and serum creatinine levels (P less than 0.05) were also late features (12 months) of lithium-induced nephropathy. The data support the view that lithium induces chronic renal lesions. The precise relationship between the distinctive distal tubular lesion, distal tubular dilatation and focal interstitial nephropathy remains speculative.

Animals↗