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Biomedical subjects

R G Walker

Publications and source records attributed to R G Walker.

At least 19 recordsLinked to original sources
PubMed1992

Phenotype and genotype heterogeneity in autosomal dominant polycystic kidney disease.

It is now clear that mutations of at least two genetic loci can lead to autosomal dominant polycystic kidney disease (ADPKD). We have compared the clinical features of ADPKD caused by mutations at the PKD1 locus (linked to the alpha-globin complex on chromosome 16) with those of disease not linked to the locus (non-PKD1). We identified 18 families (285 affected members) with mutations at PKD1 and 5 families (49 affected individuals) in which involvement of this locus could be dismissed. Non-PKD1 patients lived longer than PKD1 patients (median survival 71.5 vs 56.0 years), had a lower risk of progressing to renal failure (odds ratio 0.35, 95% CI 0.13-0.92), were less likely to have hypertension (odds ratio adjusted for age and family of origin 0.29, 0.11-0.80), were diagnosed at an older age (median 69.1 vs 44.8 years), and had fewer renal cysts at the time of diagnosis. Although most of the PKD1 families were ascertained through clinics treating patients with renal impairment, no non-PKD1 family was identified through this source. Non-PKD1 ADPKD has a much milder phenotype than that linked to PKD1. Partly as a result of this difference in severity, the reported prevalence of this genotype is probably an underestimate.

Adolescent↗
PubMed1992

Spontaneous renal allograft rupture: a disappearing phenomenon in the cyclosporine era?

Spontaneous renal allograft rupture occurred in six patients in a series of 384 consecutive renal transplants performed between July 1983 and December 1990. All cases occurred in patients treated with Azathioprine and Prednisolone, and none occurred in patients immunosuppressed with Cyclosporine. Acute allograft rejection was the underlying cause of rupture. All patients underwent urgent operation and repair of the ruptured transplant. Four patients had good renal function 74-84 months after repair, while two returned to dialysis 3 and 65 months after repair because of irreversible rejection.

Adult↗
PubMed1992

Endothelial cell antigens recognized by IgA autoantibodies in patients with IgA nephropathy: partial characterization.

Antibodies directed against endothelial cells (AECA) have been described in IgA nephropathy. We have previously measured AECA of the IgA subclass (AECA-IgA) in the sera of patients with glomerulonephritis by an ELISA method, and have shown that patients with IgA nephritis (IgA N) and lupus nephritis (LN) had significantly greater AECA-IgA activity compared with normal controls [1]. In the current study, on Western blotting of the EC membrane components, 6 of 18 (33%) IgA N sera positive for AECA-IgA bound to molecules of 135 and 116 kDa and 10 of 18 (56%) to a molecule of 205 kDa. These EC membrane components recognized by AECA-IgA may be of importance in the pathogenesis of IgA nephropathy.

Autoantibodies↗
PubMed1992

Randomized study of peritonitis with conventional versus O-set techniques in continuous ambulatory peritoneal dialysis.

We performed a prospective randomized trial, comparing the incidence of peritonitis between a flush-disconnect (O-System, Baxter, Deerfield, IL) (OS) and a conventional (System II, Baxter) (CS) continuous ambulatory peritoneal dialysis (CAPD) method. Sixty consenting patients with no significant physical disabilities who commenced CAPD after May 1987 were entered and followed for a minimum of 12 months. Thirty were placed on the OS system and 30 were placed on CS. Age, gender, and time for training did not differ significantly. The period of observation for OS was 375 months; CS was observed for 430 months. OS patients experienced 28 episodes of peritonitis (13.4 months/patient/episode) compared with 88 (4.9 months/patient/episode) in CS (p less than 0.005). By 6 months, 32% of OS patients had had at least one episode of peritonitis, compared with 62% of CS patients; at 12 months, these figures rose to 48% for OS and 91% for CS (p less than 0.01) patients (Life Table Analysis). The median survival time to first peritonitis episode was 5.1 months in CS and 9.7 months in OS (p less than 0.01). Exit-site infections occurred in 14/30 (46%) of patients on OS and in 13/30 (43%) of CS patients. We conclude that the OS was associated with a significant reduction in the incidence of peritonitis.

Catheters, Indwelling↗
PubMed1991

Perceptions of genetic risk in individuals with a one in two chance of developing autosomal dominant polycystic kidney disease.

OBJECTIVE: To determine the level of understanding of personal genetic risk in people born with a one in two risk of having autosomal dominant polycystic kidney disease (ADPKD). DESIGN: Consenting individuals, contacted through affected family members, were asked standard questions about their knowledge of their own genetic risk. These questions were incorporated into a study investigating the use of DNA diagnostic techniques in ADPKD which was an opportunity to interview a substantial number of Australians at risk of inheriting this condition. SETTING: Interviews were conducted in the individuals' homes, or at the Royal Melbourne Hospital Renal Clinic or the Royal Children's Hospital Genetics Clinic. PATIENTS: Three hundred and eighty-seven individuals aged 15 years or more, born with a one in two risk but who had remained undiagnosed up until the time of study were identified within 46 families. Sixty-six were excluded from the study either because they resided too far away or they declined involvement. The remaining 321 were assessed clinically, 304 of whom were also interviewed about their understanding of their risk of having inherited this condition. RESULTS: Thirty per cent knew their risk at birth was one in two. Nine per cent were unaware that ADPKD was an inherited condition. Forty-one per cent were aware that ADPKD was inherited but had no opinion about their personal risk. Three per cent thought that they had no chance of having the condition, 3% thought that they were definitely affected, 8% considered their risk lay from 1%-49% and 6% thought their risk lay from 51%-99%. CONCLUSION: Within this group of people with a high risk of having an inherited condition with preventable and treatable components, the majority has a poor understanding of their genetic risk.

Adolescent↗
PubMed1991

Treatable complications in undiagnosed cases of autosomal dominant polycystic kidney disease.

In a study to determine the proportion of unrecognised cases and the prevalence of treatable complications of autosomal dominant polycystic kidney disease (ADPKD), 46 probands were identified through genetics and renal clinics in Melbourne, Australia. 321 offspring of the probands who were older than 15 years and had not been previously diagnosed as having ADPKD were identified. 68 (21%) had ultrasound evidence of polycystic kidney disease. Of this previously undiagnosed group, 25 (37%) had one or more treatable complications at the time of diagnosis. The complications included 20 cases of hypertension (diastolic blood pressure 95 mm Hg or above), 7 cases of impaired renal function (serum creatinine 0.12 mmol/l or above), and 4 cases of bacterial urinary tract infection. 8 people had several complications. ADPKD has an important treatable component which is not being treated in a substantial proportion of affected individuals, because the disease is not being diagnosed despite the presence of a positive family history.

Adolescent↗
PubMed1991

Recurrent haemolytic uraemic syndrome in a transplant recipient on orthoclone (OKT 3).

Recurrence of haemolytic-uraemic syndrome (HUS) after renal transplantation may occur in both cyclosporin A (CyA) and non-CyA-treated patients, and in patients receiving anti-lymphocyte globulin. We report a case of recurrent HUS in an 8-year-old boy who received Orthoclone (OKT3) combined with prednisolone and azathioprine therapy on receipt of his first cadaveric renal allograft. Despite avoidance of CyA therapy irreversible HUS occurred.

Antibodies, Monoclonal↗
PubMed1991

Morphology of renal parenchymal culture in collagen gels.

Explants of rabbit renal parenchyma have been grown in primary tissue culture suspended within hydrated collagen gels. Light and phase contrast microscopic analysis of the first 17 days in culture is described. Pieces of NZW rabbit renal parenchyma were suspended in collagen gels and bathed in supplemented RPMI 1640 medium and incubated at 37 degrees C in 5% CO2 in air. Tubules demonstrated a fine granularity by phase contrast microscopy and glomeruli appeared as red spheres. Blebs formed at the sides and ends of the explant and a monolayer outgrowth of tightly packed polygonal cells occurred from day 4. Histologically an immediate phase of necrosis was followed by regeneration whereby tubules became lined with a confluent epithelium composed of a single layer of flat to cuboidal-shaped cells sitting on an intact tubular basement membrane (TBM). Intraluminal casts of organized cellular debris as well as material presumed to be Tamm Horsfall protein were present. Glomeruli demonstrated collapsed capillary loops. The interstitium became widened by eosinophilic material. The tissue surface contained epithelial cells arranged in places into sac-like structures enclosing a space.

Animals↗
PubMed1990

IgA affinity to ssDNA or endothelial cells and its deposition in glomerular capillary walls in IgA nephropathy.

Autoantibodies to glomerular components may be pathogenetic in IgA nephropathy. We studied sera from 32 IgA nephropathy patients, 35 normal controls and 102 patients controls with other forms of glomerulonephritis for IgA isotype affinity to endothelial cells, denatured DNA (ssDNA), murine laminin, and cardiolipin measured by ELISA. Compared to the normal controls, patients with IgA nephropathy had significantly elevated IgA with affinity to endothelial cells (P = 0.01) and ssDNA (P = 0.04), but not to murine laminin or cardiolipin. Furthermore, serum IgA with affinity to ssDNA, but not to endothelial cells, was associated with the presence of IgA deposited in the glomerular capillary walls (P = 0.011), an indicator of poor prognosis in patients with IgA nephropathy. Therefore, IgA with affinity to ssDNA may represent an autoantibody with pathogenetic significance in IgA nephropathy.

Adult↗
PubMed1990

The effect of treatment of corticosteroid-resistant idiopathic (primary) focal and segmental hyalinosis and sclerosis (focal glomerulosclerosis) with ciclosporin.

Nine patients with biopsy-proven primary focal and segmental hyalinosis and sclerosis (FSHS) and steroid-resistant nephrotic syndrome were randomly allocated to either a period of 4-6 months of treatment (ciclosporin; (CS); 5-8 mg/kg/24 h and warfarin) or to a control period (warfarin alone) and then crossed over to the alternative for a further 4-6 months. Serum creatinine levels increased at a similar rate during treatment and control periods of observation. Serum albumin levels increased (p less than 0.05) and urinary protein excretion decreased (p less than 0.01) in association with the CS therapy compared to the control period of observation. No patient had complete resolution of the nephrotic syndrome. In primary FSHS, CS treatment is unlikely to produce complete resolution of nephrotic-range proteinuria but does significantly decrease urinary protein excretion.

Adolescent↗
PubMed1990

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↗
PubMed1989

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↗