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Biomedical subjects

P Kincaid-Smith

Publications and source records attributed to P Kincaid-Smith.

At least 19 recordsLinked to original sources
PubMed2000

Glomerular size and glomerulosclerosis in Australian aborigines.

We have previously described the prevalence of glomerulomegaly in biopsy specimens from Australian Aborigines with renal disease, a phenomenon documented in a number of other indigenous populations. Many of the biopsy specimens showed variable degrees of focal and segmental glomerulosclerosis (FSGS). Correlations between glomerular size and FSGS have been described in various animal models, as well as studies of humans. The aim of this study is to determine whether a relation exists between glomerular volume and severity of FSGS in biopsy specimens from Australian Aboriginals in the Northern Territory and Aboriginal inhabitants of the Tiwi Islands (Bathurst Island and Melville Island, Northern Territory, Australia). Consecutive clinical biopsy specimens were obtained from 78 non-Tiwi and 72 Tiwi Aboriginals. Glomerular volume was estimated using the stereological method of Weibel and Gomez. FSGS was graded from 0 to 4; 0 indicates no sclerosis and 4 indicates severe sclerosis. A biphasic relationship between glomerular size and severity of FSGS was identified. As the severity of FSGS increased from grade 0 to grade 3, glomerular size also increased. For both populations studied, glomeruli scored as grades 1, 2, and 3 were approximately 50% (P< 0.001), 65% (P< 0.001), and 100% (P< 0.001) larger than normal glomeruli, respectively. However, in glomeruli with grade 4 FSGS, glomerular size decreased to the size of normal glomeruli. These results show a biphasic relationship between severity of FSGS and glomerular size in Australian Aborigines.

Biopsy↗
PubMed1999

Treatment of mesangial immunoglobulin A glomerulonephritis.

Mesangial immunoglobulin A glomerulonephritis does not progress unless microscopic hematuria presents at levels over 100,000/mL, proteinuria presents at levels over 0.5 g in 24 hours, or hypertension is inadequately controlled. Hypertension, microscopic hematuria, and proteinuria all can be controlled; the evidence for control of these three risk factors is reviewed. The evidence for prevention of progression in mesangial immunoglobulin A glomerulonephritis is also reviewed.

Disease Progression↗
PubMed1996

The significance of focal and segmental hyalinosis and sclerosis (FSHS) and nephrotic range proteinuria in IgA nephropathy.

Between 1971 and 1991, 845 patients were diagnosed as having IgA glomerulonephritis on renal biopsy performed. These patients were followed for a mean period of 53 months post biopsy (range 0-336 months). By the end of follow up 147 (17%) of patients have developed chronic renal failure (Cr > 0.2 mmol/l) or end-stage renal failure. Presenting creatinine > 0.12 mmol/l, hypertension, nephrotic range, age > 40 years and male gender, all correlated strongly on univariate analysis with the development of chronic renal failure or kidney disease (all p < 0.0001). However, a number of patients developing chronic renal failure or end-stage renal failure already had renal impairment (creatinine > 0.12 mmol/l at presentation). A separate comparison was performed of patients presenting with creatinine < 0.12 mmol/l and either developing chronic failure or end-stage renal failure within 5 years of biopsy (n = 18) and those with creatinine still < 0.12 mmol/l after 5 years follow up (n = 186). Of the 18 patients who deteriorated 6 (35%) were nephrotic at presentation and 9 (56%) had focal hyalinosis and sclerosis on renal biopsy. This compared with 5 (3%) patients with nephrotic range proteinuria and 16 (10%) patients with focal hyalinosis and sclerosis among the 186 patients who did not deteriorate (p < 0.0001). The sensitivity and specificity of the presence of either or both factors in predicting deterioration was calculated at 65% and 87% respectively. Thus in patients with normal renal function at presentation the presence of nephrotic range or focal hyalinosis and sclerosis are strong predictors of adverse clinical outcome.

Adult↗
PubMed1995

Prevention of preeclampsia with heparin and antiplatelet drugs in women with renal disease.

In a retrospective cohort study of women with renal disease in pregnancy we investigated if: 1. low dose aspirin reduced the prevalence of preeclampsia and improved fetal outcome compared to no anticoagulant therapy. 2. heparin plus low dose aspirin and/or dipyridamole reduced the prevalence of preeclampsia and improved fetal outcome compared to i. no treatment ii. low dose aspirin alone. Women with renal disease were allocated into 3 groups according to the treatment received during their pregnancies: I. no prophylactic heparin or antiplatelet drugs, n = 76 II. prophylactic low-dose aspirin 75(50-150)mg, n = 27 III. prophylactic subcutaneous heparin 10,000 (5000-12,500) IU b.d. combined with low-dose aspirin 50 (50-150)mg and/or dipyridamole 400 (200-400)mg, n = 44. Preeclampsia and fetal outcome was analysed according to treatment group. Preeclampsia was less common in the heparin group (2.3%) compared with 27.6% in the no treatment group [O.R. 0.06 (0.01-0.30)] and 25.9% in the aspirin group [O.R. 0.07 (0.01-0.38)]. Women on aspirin, who developed preeclampsia, delivered later in pregnancy [35.4 (33-38.2) weeks] than preeclamptic women on no treatment [29 (22-38) weeks], p = 0.04. There was a trend to reduced perinatal deaths in the heparin + antiplatelet drug group, [2.3%; O.R., 0.17 (0.02-1.4)] and in the aspirin group [0%, O.R., 0.13 (0.01-2.3)] compared with 11.7% perinatal deaths in the no treatment group. Heparin with anti-platelet drugs may prevent preeclampsia in high risk women with renal disease. Further investigation in a randomized trial is indicated.

Adult↗
PubMed1994

Evaluation of ultrasonographic diagnostic criteria for autosomal dominant polycystic kidney disease 1.

Although ultrasound is commonly used for screening subjects at risk of polycystic kidney disease 1 (PKD1), there has been no evaluation of ultrasonographic diagnostic criteria. We used DNA linkage among subjects from 128 sibships within 18 PKD1 families as the basis for an assessment of ultrasound sensitivity. Positive and negative predictive values were calculated to allow assessment of different diagnostic cut-off points in previously undiagnosed cases. Currently used criteria (bilateral cysts with at least two in one kidney) provided good sensitivity (88.5% at age 15-29 years and 100% at 30 years and above) but performance could be improved by less stringent criteria in subjects aged 15-29 years and more stringent criteria in older family members, in whom simple renal cysts are frequent. The presence of at least two renal cysts (unilateral or bilateral) in individuals at risk and younger than 30 years may be regarded as sufficient to establish a diagnosis; among those aged 30-59 years, the presence of at least two cysts in each kidney may be required, and among those aged 60 years and above, at least four cysts in each kidney should be required.

Adolescent↗
PubMed1994

Hypertension in pregnancy.

From the clinical point of view proteinuric hypertension or preeclampsia is the most important form of hypertension in pregnancy and carries the greatest risks for mother and foetus. The syndrome 'preeclampsia' differs from other types of hypertension and its effects on mother and foetus are not clearly benefited by lowering the blood pressure with drugs. The characteristic morphological changes and altered vascular reactivity which develop in preeclampsia commence at about 14 weeks gestation, long before hypertension or proteinuria appear. Many abnormalities in coagulation mechanisms appear in preeclampsia and some may play an important part in pathogenesis. Increased plasminogen activator inhibitor may play a key role. Antihypertensive drugs used during pregnancy may reduce foetal mortality and the incidence of preeclampsia. Calcium supplementation and aspirin may reduce the incidence of preeclampsia in high risk subjects. Heparin and dipyridamole may reduce the risk of preeclampsia in high risk patients with renal disease.

Antihypertensive Agents↗
PubMed1994

The effects of dietary potassium on vascular and glomerular lesions in hypertensive rats.

The present study examines the effects of dietary potassium (K) on hypertensive glomerular and vascular lesions in deoxycorticosterone acetate and salt induced (DOCA-salt) and two kidney one clip (2K1C) hypertensive as well as normotensive control rats. Animals received a regular (0.28% K), high (1.1% K) or low (0.07% K) potassium diet for 6 weeks. In control rats, low K diet significantly increased systolic blood pressure (SBP) (p < 0.05). In DOCA-salt rats, high K diet did not modify SBP or glomerular and vascular lesions while low K diet significantly increased premature death in these rats. In 2K1C rats, dietary K did not alter the blood pressure, but percentage media area (% media) of intramyocardial arteries, percentage of glomerular lesions, and renal arterial and arteriolar lesion scores were lower in high K diet rats than regular and low K diet rats (p < 0.05). This study is the first demonstration that high K diet can protect against vascular and glomerular lesions in a non salt-loaded hypertensive model. The beneficial effects of dietary K on vascular lesions are at least in part independent of changes in blood pressure, and may be renin related.

Animals↗
PubMed1994

Uterine artery waveform as a predictor of pregnancy outcome in women with underlying renal disease.

To investigate the use of uterine artery flow velocity waveforms in predicting gestational hypertension (GH), preeclampsia (PE) and intrauterine growth retardation (IUGR), Colour Doppler ultrasound of the uterine arteries was performed at 19-24 weeks gestation in 51 women with known renal disease. On four consecutive waveforms, peak systolic (A), end-diastolic (B) and early diastolic (C) velocities were measured. Resistance index (RI) was calculated as (A-B)/A, and the severity of the waveform notch expressed as the AC ratio (A/C). Gestational hypertension was defined as a blood pressure (BP) > or = 140/90 mmHg with an increase of at least 15 mmHg in diastolic BP. PE included women with gestational hypertension and proteinuria > 300 mg/24 h or a doubling of early gestation protein excretion. IUGR was defined as a birthweight less than the 10th percentile for gestation. RI and/or AC ratio in 14 women (27%) exceeded the 90th percentile for gestational age of our low risk control population. Of the women with an abnormal test, 11 (79%) developed complications, 8 (57%) developed GH or PE, 3 (21%) IUGR alone, 2 (14%) GH and IUGR, and in one women intrauterine fetal death of an IUGR infant occurred, and 3 (21%) had an uncomplicated pregnancy. Of the women with a normal test, 34 (92%) had an uncomplicated pregnancy, and only 3 (8%) developed GH or IUGR. In summary, uterine artery waveform indices at 19-24 weeks gestation may be useful for the prediction of pregnancy complications in woman with underlying renal disease.

Adult↗
PubMed1994

Effect of dietary calcium on the development of hypertension and hypertensive vascular lesions in DOCA-salt and two-kidney, one clip hypertensive rats.

OBJECTIVE: To examine the effect of modest changes in dietary calcium on systolic blood pressure (SBP) and myocardial and renal vascular lesions in Sprague-Dawley rats. DESIGN: Regular- (0.4%, by weight), high- (0.8%) or low-calcium (0.24%) diets were fed to normotensive control, deoxycorticosterone acetate (DOCA)-salt and two-kidney, one clip (2-K, 1C) hypertensive rats for 8 weeks. METHODS: Tail-cuff SBP and metabolic balance were measured once a week. At the end of the study the kidneys and hearts were collected for histological study. RESULTS: Dietary calcium had no effect on SBP in the DOCA-salt rats, but loading with calcium accelerated the rise in SBP in 2-K,1C rats (P < 0.01, high- versus regular-calcium diet). The high-calcium diet reduced the percentage medial area of intramyocardial arteries in the DOCA-salt and 2-K,1C hypertensive rats. The DOCA-salt rats on the low-calcium diet had a higher renal vascular lesions score than those on the regular- or high-calcium diet (P < 0.05). CONCLUSIONS: A high-calcium diet appears to prevent intramyocardial vascular wall thickening in DOCA-salt and 2-K,1C hypertensive rats, and a low-calcium diet aggravates renal vascular lesions in DOCA-salt hypertensive rats. These effects are not related simply to changes in blood pressure.

Animals↗
PubMed1994

Uterine artery Doppler flow velocity waveforms in the second trimester for the prediction of preeclampsia and fetal growth retardation.

OBJECTIVE: To determine the optimal method of measuring uterine artery waveforms with Doppler ultrasound when screening healthy nulliparas for subsequent development of preeclampsia and fetal growth retardation (FGR). METHODS: Color Doppler ultrasound was used to obtain uterine artery waveforms at 19-24 weeks' gestation in 458 nulliparas. In each uterine artery, the resistance index (RI), the ratio between peak systolic (A) and early diastolic (C) blood flow velocities (AC ratio) (a measure of the early notch in the uterine artery waveform), and placental position were recorded. The predictive values of these uterine artery Doppler measurements were evaluated for pregnancy complications. The major end points were preeclampsia and small for gestational age (SGA) infants. RESULTS: The best screening test for preeclampsia and SGA infants was the placental-side uterine artery RI or AC ratio above the 90th percentile for gestational age when the placenta was located on the left or right, and the highest RI or AC ratio when the placenta was midline. This method identified 51% of women with subsequent preeclampsia or SGA infants and had a positive predictive value of 29%. The test detected women with severe disease requiring delivery before 37 weeks with a sensitivity of 83% and specificity of 88%. However, the results were similar if the placental-side uterine artery RI was above an arbitrary cutoff of 0.56 or the AC ratio was above 2.05. A normal test predicted an uncomplicated pregnancy. CONCLUSIONS: Although abnormal uterine artery Doppler is associated with an increased risk of preeclampsia and FGR, the positive predictive values do not support its introduction as a routine screening test in nulliparous women.

Arteries↗
PubMed1994

Pregnancy-related complications in women with reflux nephropathy.

Three hundred and forty-five pregnancies in 137 women with reflux nephropathy have been studied. All pregnancies took place after 1971. Overall foetal loss was 48 (14%) of which only 6 (2%) were therapeutic abortions. Maternal complications (urine infection, hypertension, proteinuria, oedema, deterioration in renal function, hematuria or renal stones) occurred alone or in combination in 39% of pregnancies. Fifty-two pregnancies took place in women with plasma creatinine (P.Cr > 0.11 mmol/l) prior to conception. Foetal loss after 12 weeks gestation (excluding therapeutic abortions) was 18% compared with 8% in the 104 pregnancies where maternal P.Cr was known to be < or = o.11 per/l at conception (p < 0.05). Maternal complications were also more common in the impaired renal function group (p < 0.001). Comparison of pregnancies in women with unilateral versus bilateral renal scarring revealed no significant difference in foetal loss but an increased incidence of over 50% maternal complications in the bilateral renal scar group (p < 0.01). The incidence of pre-eclampsia was higher in women with bilateral renal scars, 50 (24%) than in women with unilateral scars 8 (7%) (p < 0.001). Persistent vesicoureteric reflux was not associated with increased foetal loss or maternal risk. Impaired renal function prior to conception is associated with increased foetal and maternal complications in pregnancy. Bilateral renal scarring is associated with increased maternal complications during pregnancy.

Abortion, Spontaneous↗
PubMed1993

Reflux nephropathy: the glomerular lesion and progression of renal failure.

Reflux nephropathy is the cause of 5%-10% of dialysed end-stage renal failure. Once scarring has occurred, the prognosis depends on the severity of initial damage and the presence of proteinuria, which reflects the development of glomerulosclerosis. It is independent of ongoing reflux or infection. Histological appearances highly suggestive of reflux nephropathy can occur in radiologically normal kidneys. Duplex Doppler scans of ureteric orifices suggest these patients may have lateral insertion, suggesting past reflux. Glomerular hypertrophy correlates well with reduced renal function and severe renal scarring, but poorly with focal and segmental glomerulosclerosis, which correlates with proteinuria. Increasing attention is being paid to the tubulo-interstitium and the relationships between the cellular infiltrates (mainly T4 cells) and glomerular, tubular and vascular damage. Control of hypertension, hyperphosphataemia and a low-protein diet are the only currently widely accepted treatments for slowing progression.

Age Factors↗
PubMed1993

Clinicopathologic associations of anti-endothelial cell antibodies in immunoglobulin A nephropathy and lupus nephritis.

Sera from 45 patients with lupus nephritis (LN), 63 patients with immunoglobulin A nephropathy (IgA N), and 71 glomerulonephritic controls (including 44 mesangial proliferative glomerulonephritis cases, 14 membranous glomerulonephritis cases, and 13 focal segmental glomerular sclerosis cases), and from 33 normal control subjects were tested by a cellular enzyme-linked immunoabsorbent assay for their anti-endothelial cell antibody (AECA) activity. Compared with normal controls, AECAs of the IgG subtype (AECA-IgG) were detected in LN (P < 0.001) and AECAs of the IgA subtype (AECA-IgA) were detected in both IgA N and LN (P = 0.018 and P < 0.001, respectively). Binding activity of AECA to endothelial cells was inhibited by endothelial cell lysate and fibroblast lysate but not by lymphocyte lysate, double stranded-DNA, or bovine serum albumin. Anti-endothelial cell antibody-positive sera also reacted with fibroblasts. In IgA N, associations were found between the presence of AECA and younger age (P = 0.036), proportion of crescents greater than 10% (P = 0.016), fibrin crescents (P = 0.016), and focal and segmental necrotizing lesions (P = 0.047). In LN, inverse associations were found between the presence of AECA and the duration of disease (P = 0.021), elevated serum creatinine levels (P = 0.020), decreased creatinine clearance (P = 0.043), and frequency of chronic renal failure (P = 0.036). Positive associations were observed between the presence of AECA and active lupus (P = 0.017), anti-nuclear antibodies (P = 0.015), and anti-DNA antibodies (P = 0.041). Our results suggest that AECA may be linked with the pathogenesis of LN and IgA N.

Adult↗