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C A Pollock

Publications and source records attributed to C A Pollock.

At least 37 records · Page 2Linked to original sources
PubMed1998

Paracrine stimulation of human renal fibroblasts by proximal tubule cells.

UNLABELLED: Paracrine stimulation of human renal fibroblasts by proximal tubule cells. BACKGROUND: Interstitial fibrosis strongly predicts the degree and progression of renal failure in human renal disorders. Since active fibrosis tends to initially occur in a peritubular distribution, the possibility that human proximal tubule cells (PTC) relay fibrogenic signals to neighboring cortical fibroblasts was examined in vitro. METHODS: Cell proliferation (cell counts and thymidine incorporation), total collagen synthesis (proline incorporation), matrix metalloproteinase (MMP) activity (gelatin zymography), and autocrine secretion of insulin-like growth factor-I (IGF-I) were measured in primary cultures of human cortical fibroblasts cocultured with PTC or exposed to PTC-conditioned media (PTCCM). RESULTS: Cell numbers and thymidine incorporation rates were increased in cortical fibroblasts cocultured with PTC (136.4+/-7.3% and 119.3+/-8.2% of control values, respectively, P < 0.05) or incubated in PTC-CM (114.0+/-5.9%, P < 0.05 and 146.7+/-13.3%, P < 0.05, respectively). PTC-CM stimulated cortical fibroblast collagen synthesis (13.5+/-1.0% vs. 10.8+/-0.7%, respectively, N = 24, P < 0.05) and MMP-2 and MMP-9 secretion. Cortical fibroblast secretion of IGF-I binding protein-3 (IGFBP-3), which in turn modulates the autocrine and paracrine actions of IGF-I, was enhanced in the presence of PTC-CM compared with control (1162.2+/-94.2 vs. 969.1+/-58.9 ng/mg protein/day, P < 0.05), but no change was observed in cortical fibroblast secretion of IGFBP-2 (260.9+/-38.8 vs. 290.9+/-36.6 ng/mg protein/day, P = NS) or IGF-I (56.7+/-6.6 vs. 57.0+/-6.8 ng/mg protein/day, P = NS). Human PTC secreted transforming growth factor-beta1 (TGF-beta1) and the AB heterodimer of platelet-derived growth factor (PDGF-AB) in a time-dependent fashion and the augmentation of cortical fibroblasts mitogenesis, collagen synthesis and IGFBP-3 secretion induced by PTC-CM was replicated by exogenous TGF-beta1 and PDGF. Furthermore, the stimulatory effects of PTC on cortical fibroblasts were potentiated in transiently acidified PTC-CM (which activated latent TGF-beta1), and were abrogated by neutralizing antibodies specifically directed against TGF-beta1 and PDGF-AB. Cortical fibroblasts in turn released a soluble factor(s) into cortical fibroblast-conditioned media that reciprocally stimulated PDGF-AB production by PTC (4.79+/-1.55 vs. 0.78+/-.06 ng/mg protein/day, P < 0.05). CONCLUSIONS: PTC modulate the biological behavior of neighboring cortical fibroblasts in the human kidney through paracrine mechanisms, which include the production and release of PDGF-AB and TGF-beta1. Renal insults that result in proximal tubule injury may perturb this paracrine interaction, thereby culminating in excessive fibroblast proliferation and interstitial fibrosis.

Adult↗
PubMed1998

Renal expression of transforming growth factor-beta inducible gene-h3 (beta ig-h3) in normal and diabetic rats.

BACKGROUND: Transforming growth factor-beta (TGF-beta) has been implicated in the pathogenesis of a number of kidney diseases characterized by glomerulosclerosis and tubulointerstitial fibrosis. TGF-beta is secreted in a latent form requiring extracellular modification to become biologically active. TGF-beta inducible gene-h3 (beta ig-h3) is a recently identified TGF-beta-induced gene product. The present study sought to examine beta ig-h3 expression in normal and diabetic rats. METHODS: Beta ig-h3, TGF-beta1 and alpha1 (IV) collagen gene expression were assessed by Northern blot analysis and in situ hybridization in 20 Sprague Dawley rats, randomly assigned to receive streptozotocin (diabetic, N = 11) or citrate buffer alone (control, N = 9) and sacrificed eight months later. The effect of exogenous TGF-beta1 on beta ig-h3 expression was also assessed in cultured proximal tubular cells. RESULTS: In situ hybridization localized beta ig-h3 gene expression to the juxtaglomerular apparatus and the pars recta (S3 segment) of proximal tubules in both control and diabetic animals. Kidney TGF-beta 1, beta ig-h3 and alpha1 (IV) collagen mRNA from diabetic rats were increased two- to threefold compared with controls (P < 0.01). There was a significant correlation between TGF-beta1 and beta ig-h3 gene expression in kidneys from diabetic rats (r = 0.73, P = 0.01). In addition, beta ig-h3 mRNA increased in response to exogenous TGF-beta1 in a dose-dependent fashion in cultured proximal tubular cells. CONCLUSION: These findings support the hypothesis that biologically active TGF-beta plays a pathogenetic role in diabetic kidney disease and suggest that beta ig-h3 may be a useful index of TGF-beta1 bioactivity in the kidney.

Animals↗
PubMed1998

TGF-beta 1 dissociates human proximal tubule cell growth and Na(+)-H+ exchange activity.

Stimulation of proximal tubule cell (PTC) growth in a variety of physiological and pathological renal conditions is preceded by increased renal production of transforming growth factor-beta 1 (TGF-beta 1) and by augmented tubular sodium transport via activated sodium hydrogen exchange (NHE). Since TGF-beta 1 has been shown to be an important paracrine and autocrine regulator of PTC growth, the hypothesis that TGF-beta 1 modulates basal and mitogen-stimulated PTC growth via an effect on NHE activity was examined. Confluent, quiescent, human PTC were incubated for 24 hours in serum-free media containing vehicle (control) or 1 ng/ml TGF-beta 1, in the presence or absence of 100 ng/ml insulin-like growth factor-1 (IGF-I). Under basal conditions, TGF-beta 1 inhibited thymidine incorporation (73.5 +/- 7.3% of control, P < 0.05), but exerted no effect on cellular protein content (97.4 +/- 10.7% of control), an index of hypertrophy. There was no significant alteration of NHE activity, measured as ethylisopropylamiloride (EIPA)-sensitive H+ efflux (2.72 +/- 0.50 vs. control 3.26 +/- 0.68 mmol/liter/min) or 22Na+ influx (2.20 +/- 0.23 vs. control 2.19 +/- 0.19 nmol/mg protein/min). When co-incubated with IGF-I. TGF-beta 1 induced significant PTC hypertrophy (116.9 +/- 8.2% of control, P < 0.05), which was not seen with either agent alone. TGF-beta 1 counteracted the stimulatory effect of IGF-I on DNA synthesis (TGF-beta 1 + IGF-I 103.0 +/- 7.3% vs. IGF-I alone 181.2 +/- 30.3% of control, P < 0.05), but did not affect IGF-I-stimulated EIPA-sensitive 22Na+ influx (3.63 +/- 0.63 vs. IGF-I alone 3.67 +/- 0.50 nmol/mg protein/min, P = NS, both vs. control 2.19 +/- 0.19 nmol/mg protein/min, P < 0.05). Similar results were obtained when NHE activity was measured as EIPA-sensitive H+ efflux. Moreover, the kinetics of NHE activation by the combination of TGF-beta 1 and IGF-I (involving an increase in Vmax) were identical to that previously found for PTC exposed to IGF-I alone. The study demonstrates that TGF-beta 1 elicits distinct PTC growth responses in the presence and absence of IGF-I, without modification of NHE activity. The combination of predominant PTC hypertrophy and enhanced proximal tubule Na+ reabsorption found in many conditions that are associated with renal growth is likely to require the integrated actions of both TGF-beta 1 and IGF-I.

Aged↗
PubMed1998

Recognition and management of IgA nephropathy.

IgA (immunoglobulin A) nephropathy is the most common form of primary glomerulonephritis worldwide. It generally has a good prognosis, with 15-year rates of kidney survival from the apparent onset of disease usually well in excess of 70%. Progression, when it occurs, is usually a slow, indolent process, and spontaneous remission of disease activity occurs in 7% of patients. It is possible to predict, from the initial presenting features and laboratory findings, renal biopsy and clinical course during follow-up, which patients are likely to have progressive renal disease. Identification of the factors likely to be associated with progression is of importance in helping to establish which patients will benefit from specific therapeutic intervention. For all patients, attention should be directed toward general health issues in an endeavour to reverse factors that are likely to have an adverse impact on renal function. This should include early detection and tight control of hypertension (present in 50% of all patients with IgA nephropathy during the course of their disease), along with utilisation of antihypertensive agents that have specific renoprotective effects, namely ACE inhibitors or calcium antagonists. Such therapy should also be considered in normotensive patients with heavy proteinuria, as a reduction of proteinuria is often achieved by this means. Other aims should include maintenance of desirable bodyweight, correction of hyperlipidaemia, cessation of smoking, participation in an active exercise programme, avoidance of exposure to nephrotoxins and maintenance of a high fluid intake. A low protein/low phosphate diet together with phosphate binder therapy should be commenced early in the course of renal impairment. Corticosteroid and/or cytotoxic drug therapy should be considered in the small percentage of patients with heavy proteinuria or a rapid decline in renal function. Such therapeutic endeavours are likely to delay the onset of renal failure in patients with progressive IgA nephropathy.

Antihypertensive Agents↗
PubMed1997

Human renal fibroblasts modulate proximal tubule cell growth and transport via the IGF-I axis.

To determine the paracrine interactions involved in the tubulointerstitial response to progressive renal disease, the role of insulin-like growth factor-I (IGF-I) and its binding proteins (IGFBPs) in in vitro interactions between human proximal tubule cells (PTC) and renal cortical fibroblasts (CF) were studied in primary cell culture. PTC growth and transport were increased in the presence of CF-conditioned media (CF-CM), as shown by increased thymidine incorporation, cellular protein content and sodium-hydrogen exchange (NHE) activity, to 185 +/- 31% (P < 0.01), 150 +/- 18% (P < 0.05) and 195 +/- 27% (P < 0.01) of the control values, respectively. IGF-I was produced by cultured CF at a rate of 64.6 +/- 7.5 ng/mg protein/day. Exogenous IGF-I applied to PTC provoked similar enhancement of growth and NHE activity as CF-CM and the stimulatory effect of CF-CM was blocked by specific immunoneutralization of IGF-I receptors. These receptors were threefold more abundant on PTC basolateral versus apical membranes. IGF binding proteins (IGFBP)-2 and IGFBP-3 were secreted by CF at rates of 694 +/- 88 and 1769 +/- 45 ng/mg/day, with the release of IGFBP-3 being enhanced in the presence of PTC-CM (120.0 +/- 9.7% of control, P < 0.01). Moreover, the addition of CF-CM to PTC increased cell-associated IGFBP-3 on PTC surfaces, without changes in IGF-I receptor numbers or affinity and without changes in PTC mRNA for IGFBP-3. Des(1-3)IGF-I, an analog that binds to the IGF-I receptor but not to IGFBPs, provided a less potent stimulus for PTC growth compared with IGF-I, indicating that cell-associated IGFBP-3 facilitates the action of IGF-I on PTC. The results support important paracrine roles for both IGF-I and IGFBPs in the interstitial regulation of proximal tubule growth and transport.

Antibodies↗
PubMed1997

Insulin-like growth factor I stimulates apical sodium/hydrogen exchange in human proximal tubule cells.

To determine whether insulin-like growth factor I (IGF-I) stimulated apical sodium/hydrogen exchange (NHE), confluent primary human proximal tubule cells (PTC) were incubated for 48 h in serum-free media in the presence or absence of 100 ng/ml IGF-I. Cells incubated in IGF-I demonstrated significant increases in thymidine incorporation (181.2 +/- 30.3% of control values; n = 12, P = 0.01) and in resting intracellular pH (pHi) (7.52 +/- 0.08 vs. 7.30 +/- 0.06; n = 20, P < 0.05), as determined by 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein quantitative microspectrofluorometry. Following intracellular acid loading, ethylisopropylamiloride (EIPA)-inhibitable H+ efflux and 22Na+ influx after 1 min were both significantly enhanced in IGF-I-treated cells compared with controls (8.78 +/- 1.69 vs. 3.03 +/- 0.72 mM/min and 3.47 +/- 0.49 vs. 1.55 +/- 0.35 nmol x mg protein(-1) x min(-1), respectively). 22Na+ uptake studies in PTC grown on permeable supports demonstrated preferential stimulation of apical vs. basolateral NHE. The 50% inhibitory concentrations (IC50) in IGF-I-treated and control cells for EIPA (0.5 and 1.1 microM, respectively) and for HOE-694 (4.0 and 10.0 microM, respectively) were also consistent with predominant activation of apical, rather than basolateral, NHE activity. Kinetic analysis revealed an increase in maximal transport velocity (Vmax, 15.50 +/- 1.50 vs. 7.26 +/- 3.07 mM/min; n = 10, P < 0.05), without a significant change in antiporter affinity for extracellular Na+. Incubation of PTC with 100 ng/ml IGF-I produced an acute, reversible, and EIPA-inhibitable pHi increase of 0.05 +/- 0.01 pH units (n = 5, P < 0.05). The results suggest that IGF-I may contribute to the metachronous stimulation of apical NHE and PTC growth observed in many physiological and pathological conditions involving the human kidney.

Adult↗
PubMed1997

Protein intake in renal disease.

The dietary protein intake (DPI) of 766 patients (aged 7 to 88 yr) was determined from 24-h urinary urea and protein excretion by urea kinetic modelling. Five hundred sixty-five patients had a normal serum creatinine concentration, and of these 565, 385 patients had no dietary modification advised and 180 were advised to follow a low-protein diet. The remaining 201 patients had an increased serum creatinine concentration; 148 of these 201 patients had been advised to restrict their DPI. Patients with a normal serum creatinine concentration who had no dietary restriction had a significantly higher DPI than those advised to restrict their protein intake (1.08 +/- 0.01 versus 0.96 +/- 0.02 g/kg per day (mean +/- SEM), P < 0.01). Similarly, patients with abnormal renal function who were advised to follow a low-protein diet had a reduced DPI (0.93 +/- 0.01 versus 0.87 +/- 0.02 g/kg per day; P < 0.05). A lower DPI correlated with level of renal dysfunction, independent of dietary advice (P < 0.0001). In the overall population, DPI correlated with body mass index (BMI; P < 0.0001) and serum albumin (P < 0.0001), and inverse correlations were evident between age (P < 0.0001), blood glucose level (P < 0.01), serum cholesterol level (P < 0.0001), and triglyceride levels (P < 0.0001) independently of renal function. Fifty-two patients were assessed within the 3 months before the commencement of dialysis, and 47 were reassessed within 3 months after the commencement of dialysis. Despite advice regarding an increase in dietary protein after the commencement of dialysis, this increase failed to occur within the 3 months of commencement of dialytic therapy (0.79 +/- 0.04 versus 0.82 +/- 0.03 g/kg per day); P = 0.64). However, 6 to 9 months after the commencement of dialysis, a significant increase in protein intake was evident (1.04 +/- 0.04 g/kg per day; P < 0.005 versus both prior measurements). Hence a low DPI in renal impairment occurs independently of dietary advice, but compliance with such advice is evident because patients advised to consume a low-protein diet had significantly lower protein intake than did patients receiving no dietary advice. Adaptation to a high-protein diet after instigation of dialysis is unsuccessful in the short term, irrespective of whether or not advice is given regarding a low-protein diet before dialysis is initiated. However, 6 to 9 months after the commencement of dialysis, a significant increase in protein intake occurs, which in the hemodialysis population correlates with dialysis delivery.

Adolescent↗
PubMed1996

Transferable circulating factors and epithelial sodium transport after unilateral nephrectomy in the rat.

1. In order to investigate the role of circulating serum factors in the altered renal haemodynamics and enhanced renal tubular transport observed in renal growth, micropuncture experiments were performed on normal animals infused with 20% plasma derived from animals in whom unilateral nephrectomy had been performed 3 days previously. 2. When animals infused with plasma from uninephrectomized animals (NxP) were compared with those infused with control plasma, the former had a higher tubular fluid flow rate measured at both the late proximal (LP; 26.7 +/- 1.6 vs. 18.4 +/- 1.4 nl min-1; P < 0.001) and early distal (ED; 14.9 +/- 1.0 vs. 7.8 +/- 1.0 nl min-1; P < 0.0001) sites, which was reflected in the final urine flow rate (16.1 +/- 3.4 vs. 5.1 +/- 0.8 microliter min-1; P < 0.005). 3. The single nephron glomerular filtration rate (SNGFR) was higher in animals infused with NxP as determined from samples taken at the LP (45.8 +/- 2.8 vs. 35.7 +/- 2.3 nl min-1; P < 0.01) and at the ED (34.5 +/- 2.5 vs. 28.1 +/- 1.8 nl min-1; P = 0.05) sites. However, this increase was not reflected in the whole kidney GFR (1.04 +/- 0.06 vs. 0.89 +/- 0.06; P = 0.07), suggestive of a preferential increase in filtration in the outer cortical nephrons. 4. Tubular Na+ transport was higher in the animals infused with NxP as evidenced by a decrease in the fractional delivery of Na+ at the ED site (4.5 +/- 0.4 vs. 6.5 +/- 0.6% of the filtered load; P < 0.05). However, in the final urine there was a significant increase in the urinary sodium excretion in animals infused with NxP (0.67 +/- 0.14 vs. 0.29 +/- 0.09%; P < 0.05) indicating that natriuresis and probably diuresis was a result of inhibition of Na+ and water transport in the late distal tubule and collecting duct. 5. In conclusion, these experiments demonstrate that circulating factors induced by a reduction in renal mass significantly alter glomerular filtration and tubular Na+ transport.

Angiotensin II↗
PubMed1996

Deliberate overdose of uranium: toxicity and treatment.

A case is described of deliberate ingestion of 15 g of uranium acetate which resulted in acute renal failure requiring dialytic therapy for 2 weeks, refractory anaemia, rhabdomyolysis, myocarditis, liver dysfunction with a disproportionate coagulopathy and paralytic ileus. Despite significant elevations in plasma uranium levels, treatment with both calcium EDTA and calcium DTPA were ineffective in promoting uranium excretion. Six months later the initial significant renal impairment exists with a persistent incomplete Fanconi syndrome. Future options for management of this unusual cause of acute renal failure are discussed.

Acute Kidney Injury↗
PubMed1996

Dialysis adequacy and nutrition determine prognosis in continuous ambulatory peritoneal dialysis patients.

Peritoneal membrane function was assessed in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) using parameters derived from urea kinetic modeling and the peritoneal equilibration test (PET). Their relationships with other nutritional markers and overall morbidity were determined. Data regarding the patients' nutritional status as determined by total body nitrogen (TBN) measurements, hospital admissions, and infectious complications within the last 12 months were reviewed. Total dialysate clearance (Kt/V) delivered was highly dependent on residual renal function (P < 0.0001). Kt/V derived from peritoneal clearance diminished with increasing age (P < 0.05). A higher delivered total Kt/V was associated with higher normalized protein catabolic rates (P < 0.002), which in turn were associated with improved TBN (P < 0.05). Hospital admissions decreased with improved normalized protein catabolic rates (P < 0.05), and higher serum albumin and total protein levels (P < 0.01 and P < 0.002, respectively). Infectious complications correlated positively with time on dialysis (P < 0.01), and correlated negatively with TBN measurements (P = 0.05). No correlations were found between infectious complications and serum albumin level or peritoneal protein loss. However, the total duration of hospitalization was shortened with higher serum albumin and total protein levels (P < 0.0001 and P < 0.002, respectively). Although Kt/V determinations did not correlate with clearances determined by the PET, the PET-determined creatinine transport rate correlated with TBN (P < 0.05) but not with infectious complications. In conclusion, nutritional parameters correlate with outcome on continuous ambulatory peritoneal dialysis. An integral relationship exists between nutritional status and dialysis delivery, which is best assessed by urea kinetic modeling.

Aged↗
PubMed1995

Total body nitrogen as a prognostic marker in maintenance dialysis.

In order to assess long-term nutritional adequacy, 154 patients on maintenance dialysis (78 on hemodialysis (HD), 76 on continuous ambulatory peritoneal dialysis (CAPD)) underwent measurement of total body nitrogen (TBN) with concurrent recording of dietary history, anthropometrics, and serum albumin. Seventy-one patients were reassessed 23.3 +/- 2.2 (5 to 76) months later. In cross-sectional analyses, anthropometric measurements and dietary intake remained stable over time in all patients. However, a significant fall in TBN occurred in the HD population with increasing time on dialysis (P < 0.05). In the prospective analyses, CAPD patients (N = 26) had a significant increase in TBN (P < 0.02). In contrast, longitudinal measurements of TBN in HD patients (N = 36) tended to fall but did not reach significance (P = 0.18). TBN correlated with total caloric intake estimated from the dietary history (P < 0.05), but not with estimated protein intake. During follow-up, 38 patients died. These patients were older (P < 0.05), and in the CAPD population, they had been on dialysis for a longer time (P < 0.05). Those who died had a lower TBN expressed both as grams per kilogram lean body mass (P < 0.005) and as the nitrogen index (P < 0.05). The probability of death within 12 months in the patients with a nitrogen index (ratio of the measured nitrogen to the predicted nitrogen for a sex-, age-, and height-matched control) less than 80% of the predicted normal value was 48%. The relative risk of death in this population was 4.1.(ABSTRACT TRUNCATED AT 250 WORDS)

Anthropometry↗
PubMed1995

Time- and concentration-dependent biphasic effect of ochratoxin A on growth of proximal tubular cells in primary culture.

Ochratoxin A (OTA) leads to trophic and functional changes in the proximal tubule of the kidney. We investigated the effects of micromolar and nanomolar concentrations of OTA on cell growth, cell viability and transepithelial transport in rat proximal tubular cells in primary culture. Micromolar concentrations of OTA exerted a hypotrophic and hypoplastic effect after 24 hr, but a hypertrophic and hypoplastic effect after 72 hr. These effects could be abolished in a concentration-dependent manner by the addition of albumin to the medium. In parallel, micromolar concentrations reduced cell viability, monolayer integrity and abolished the formation of transepithelial gradients of Na+ and K+. Nanomolar concentrations of OTA had neither hypotrophic nor hypertrophic effects, but stimulated DNA synthesis and cell division, leading to hyperplasia. At the same time, nanomolar concentrations did not reduce cell viability or the formation of electrolyte gradients. Lowering extracellular pH to 6.8 abolished the effect of nanomolar concentrations of OTA on DNA synthesis and cell number as well as the effect of micromolar concentrations on cellular protein. Cellular alkalinization (pH 7.7) also stimulated proliferation, but did not act additively with nanomolar concentrations of OTA. From these results, we conclude that OTA exerts a time-dependent biphasic effect on cellular protein content and a concentration-dependent biphasic effect on DNA synthesis. The stimulatory effect is independent of its toxic action. Modulation of both effects by extracellular pH suggests that cellular pH-homeostasis may be involved in the action of OTA.

Animals↗
PubMed1994

Proximal tubular cell electrolytes during volume expansion in the rat.

1. Proximal tubular intracellular elements were measured by electron microprobe X-ray analysis (a) in rats volume-expanded with albumin-saline in which peritubular oncotic pressure remained normal and (b) in rats in which the renal artery was snared before volume expansion (the early snare model). Glomerular filtration rate and urine Na+ excretion were measured in addition to intracellular Rb+ following a 30 s infusion of RbCl as a marker for K+ transport. 2. In albumin-saline volume-expanded rats, intracellular levels of Na+ ([Na+]i) at 21.5 +/- 0.6 mmol (kg wet wt)-1, Cl- ([Cl-]i) at 18.0 +/- 0.4 mmol (kg wet wt)-1 and Rb+ ([Rb+]i) at 9.4 +/- 0.4 mmol (kg wet wt)-1 were significantly higher (P < 0.0001) than the levels in non-expanded rats ([Na+]i, [Cl-]i and [Rb+]i at 17.7 +/- 0.4, 14.6 +/- 0.3 and 4.7 +/- 0.4 mmol (kg wet wt)-1, respectively; means +/- S.E.M.). The data are consistent with Na+ pump inhibition in the proximal tubule, although this cannot be directly derived from intracellular element measurements. 3. In an early snare model of volume expansion, [Na+]i, intracellular K+ ([K+]i) and [Rb+]i remained unchanged (16.1 +/- 0.4, 131.0 +/- 2.0 and 5.2 +/- 0.3 mmol (kg wet wt)-1, respectively) compared to non-expanded snared kidneys (15.9 +/- 0.6, 131.3 +/- 1.8 and 4.8 +/- 0.3 mmol (kg wet wt)-1, respectively). [Cl-]i at 18.3 +/- 0.5 mmol (kg wet wt)-1 increased (P < 0.0008) compared to controls at 15.8 +/- 0.5 mmol (kg wet wt)-1. Thus, in these rats, evidence for an inhibition of the Na+ pump was no longer observed. This points to a major intrinsic mechanism within the kidney for mediating natriuresis, since circulating factors were identical to those in the unsnared kidney, where significant natriuresis occurred.

Animals↗
PubMed1994

Effects of erythropoietin therapy on the lipid profile in end-stage renal failure.

To evaluate the effects of erythropoietin (EPO) therapy on the lipid profile in end-stage renal failure, we undertook a prospective study in patients on both hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD). One hundred and twelve patients (81 HD, 31 CAPD) were enrolled into the study. Lipid parameters [that is, total cholesterol and the LDL and HDL subfractions, triglycerides, lipoprotein (a), apoproteins A and B], full blood count, iron studies, B12, folate, blood urea, aluminium and serum parathyroid hormone were measured prior to commencement of EPO therapy. Ninety-five patients were reassessed 5.2 +/- 0.3 (mean +/- SEM) months later and 53 patients underwent a further assessment 13.1 +/- 0.6 months after the commencement of EPO, giving an overall follow-up of 10.0 +/- 0.6 months in 95 patients. As expected, EPO treatment was associated with an increase in hemoglobin (7.7 +/- 0.1 vs. 9.9 +/- 0.2 g/dl; P < 0.001) and a decrease in ferritin (687 +/- 99 vs. 399 +/- 69 micrograms/liter; P < 0.01). A significant fall in total cholesterol occurred (5.8 +/- 0.1 vs. 5.4 +/- 0.2 mmol/liter; P < 0.05) in association with a fall in apoprotein B (1.15 +/- 0.04 vs. 1.04 +/- 0.06; P < 0.05) and serum triglycerides (2.26 +/- 0.14 vs. 1.99 +/- 0.21; P < 0.05) during the course of the study. Other lipid parameters did not change, although there was a trend towards improvement.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Hyperlipidemia in renal transplant recipients: natural history and response to treatment.

The lipid profiles of 192 patients with functioning renal transplants and their etiologic associations and response to therapy, in particular simvastatin, were assessed. Hypercholesterolemia was present in 71.3% of patients within 3 years following transplantation. There were independent associations of serum cholesterol with prednisone dosage (p < 0.05), renal function (p < 0.05), and smoking (p < 0.05) in the early posttransplant period (up to 3 months posttransplant). Those patients whose immunosuppression included cyclosporin had lower serum cholesterol levels than those receiving azathioprine and prednisone (p < 0.02). Plasma triglyceride levels reflected a marked interindividual variation, and no independent correlations were observed. The presence of diabetes mellitus, hypertension (or the use of antihypertensive agents), or the form or duration of prior dialysis did not independently influence the lipid profiles. During the study period 22 patients died, 54.5% due to vascular causes. Those who died of vascular causes had higher serum cholesterol levels than those who died of other causes, which reached statistical significance at 3 years posttransplant (7.74 +/- 0.4 versus 5.5 +/- 0.52 mmol/L; p < 0.02). Cholestyramine was introduced in 30 patients, only 2 of whom continued with therapy beyond 3 months. Simvastatin was used in 43 patients, 20 of whom were receiving cyclosporin, resulting in a mean reduction in serum cholesterol of 16.5% (p < 0.001) and in serum triglycerides of 21% (p < 0.05). No clinical or biochemical evidence of muscle, liver, or renal toxicity occurred in 15.4 +/- 0.9 months of follow-up.

Adolescent↗