bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevention and treatment of diabetic nephropathy with blood pressure lowering drugs
Authors: PARVING HANS‐HENRIK , ROSSING PETER , TARNOW LISE , HOMMEL EVA , MATHIESEN ELISABETH
Published: April 2007

Summary: Diabetic nephropathy is a clinical syndrome characterized by persistent albuminuria (>300 mg/24 h), a relentless decline in glomerular filtration rate (GFR), and raised arterial blood pressure. the prevalence of abnormal elevated albumin excretion rate (>30 mg/24 h) is approximately 40% in insulin‐dependent (IDDM) and non‐insulin‐dependent (NIDDM) patients. Diabetes has become the leading cause of end‐stage renal failure in the United States of America and Japan and it remains the second leading cause in Europe. Patients suffering from diabetic nephropathy have an enormous increase in morbidity and mortality from cardiovascular disease in addition to renal death. Elevated blood pressure is an early and frequent phenomenon and furthermore accelerates the course of diabetic nephropathy. Studies in humans suggest that angiotensin‐converting enzyme (ACE) inhibitors postpone and may even prevent progression to clinical overt diabetic nephropathy in normotensive IDDM and NIDDM patients with persistent microalbuminuria. Conventional antihypertensive therapy and ACE inhibition usually combined with a diuretic reduces albuminuria and postpones renal insufficiency in hypertensive IDDM patients with overt nephropathy. A more beneficial effect on the rate of decline in glomerular filtration rate has been demonstrated by ACE inhibitors compared to conventional antihypertensive treatment in IDDM patients with diabetic nephropathy and reduced kidney function (serum creatinine >133 mmol/L). These findings suggest that ACE inhibition causes renal protection (i.e. a beneficial effect on kidney function [structure] above and beyond what would be expected from blood pressure lowering effect alone). Finally, it should be stressed that ACE inhibition and conventional antihypertensive treatment postpone end‐stage renal failure and improve survival in diabetic nephropathy.
Hepatitis C virus infection in patients on renal replacement therapy
Authors: CHAN TM
Published: April 2007

Summary: The hepatitis C virus (HCV) is a major cause of chronic liver disease in patients on renal replacement therapy. Spontaneous clearance of HCV is unusual. Second generation assays for anti‐HCV, which have high sensitivity and specificity, are used conventionally for diagnosis. They are supplemented by the polymerase chain reaction (PCR) assay for HCV RNA. Quantitative HCV RNA assays, although expensive, may be useful in patients receiving anti‐viral therapy. Preliminary data also suggest that the clinical course and response to treatment may vary according to the HCV genotypes. the higher prevalence of HCV infection among haemodialysed patients (approximately 30%), as compared to patients on continuous ambulatory peritoneal dialysis (CAPD; <5%), is largely attributable to their higher transfusion requirement. Yet there is accumulating evidence to incriminate nosocomial transmission. Organ transplantation is another mode of infection, but the incidence remains controversial. Chronic liver disease is demonstrable in around 60% of HCV‐positive patients on renal replacement therapy. Patients can present with prominent elevations in ductal enzyme levels, in addition to abnormalities in parenchymal enzymes. Histologic examination is mandatory to assess the activity and chronicity of liver disease. Liver pathology due to chronic HCV in renal allograft recipients correlates with the dialysis duration and the profile of abnormal liver biochemistry. Although HCV infection does not appear to adversely affect the short‐term graft or patient survival, patients can develop potentially fatal exacerbations of liver disease after renal transplantation. Interferon therapy results in sustained virologic remission in <20% of HCV‐positive dialysis patients, but is associated with a high incidence of symptomatic side effects. In renal allograft recipients, the risk of allograft dysfunction is too high to justify the routine use of interferon, which should be considered only in patients with rapidly deteriorating liver pathology.
Approach to the patient with hyponatraemia: A quantitative and pathophysiologic approach
Authors: HALPERIN ML , GOWRISHANKAR M , KAMEL K
Published: April 2007

Summary: Hyponatraemia is a common electrolyte abnormality that signals an expanded intracellular fluid (ICF) volume in most cases (e.g. absence of hyperglycaemia). the approach to the patient with hyponatraemia that is outlined in this paper is based on its pathophysiology and emphasizes a quantitative analysis. Both the change in ICF volume and the content of sodium (Na) in the extracellular fluid (ECF) are calculated while the volume of ECF is assessed clinically. to perform the calculations, the normal ICF and ECF volumes from body composition are estimated. the next step is to determine the basis for water retention (usually the reason why antidiuretic hormone [ADH] is released) and then the basis for the Na imbalance. Therapy is dictated by the presence or absence of severe symptoms: if the patient is symptomatic, the plasma Na concentration should be raised by 3‐5 mmol/L in 1 h. If not, the aim of therapy is to correct the water surplus and Na deficit slowly (aim for a rise in plasma Na concentration of 6–12 mmol/L per day). Changes in the ICF composition must also be considered. If there is a deficit of potassium (K), therapy with K salts (KCI instead of NaCI) will be required. A case example is provided to illustrate these points.
Free radical release and progression of renal failure
Authors: RODRIGUEZ GILBERTO E , YI ZHU WEN , KRIEG RICHARD J , CHAN JAMES CM
Published: April 2007

Summary: IgA nephropathy, formerly known as Berger's Disease, is now recognized as the world's most common primary nephropathy. the rate of progression has recently been shown to be the same in childhood as well as adulthood (i.e. slightly more than 1/4 of the patients had end‐stage renal disease at follow up of 20 years). the pathogenesis may be associated with free‐radical release as demonstrated in experimental IgA nephropathy and indirectly in leucocytes of these patients. the use of vitamin E and fish oil is discussed.
Rhubarb in preventing progression of chronic renal disease
Authors: LI LEI‐SHI
Published: April 2007

Summary: Rhubarb (Rheum Officinale), a chinese herb that had been used as a laxative for many years during ancient times is now found to be of value in preventing progression of chronic renal disease. In animal experimentation it suppresses the hypermetabolic states of the severely damaged kidney and retards the progression of chronic renal failure. Controlled clinical trials also have proved that the extract of Rhubarb is effective in preventing the progression of chronic renal disease and the therapeutic results seemed to be better than that with an angioconvertirig‐enzyme (ACE) inhibitor.
Impact of new connectology in reducing peritonitis
Authors: CHURCHILL DAVID N
Published: April 2007

Summary: A computer initiated literature search for publications addressing the association between connectology and peritonitis in continuous peritoneal dialysis patients identified 23 relevant articles. These publications used one of four basic clinical research designs (before‐after; single centre prospective cohort; multi‐centre prospective cohort and randomized clinical trial). the methodologic weaknesses inherent in the first two designs significantly impaired the validity of their conclusions. the two multi‐centre cohort studies and the five randomized clinical trials have external and internal validity, respectively. Combined, they suggest that the Y connector‐disinfectant system and the twin bag systems are associated with less peritonitis than standard, ultraviolet and possibly the Y set without disinfectant. the effect is entirely due to decreased infection with Staphylococcus epidermidis and other organisms associated with touch contamination. Peritonitis due to these organisms does not cause significant loss of peritoneal dialysis catheters or transfer to haemodialysis. the decreased hospitalization due to fewer episodes of peritonitis will become less important with more outpatient antibiotic treatment of these mild infections. Significant improvement in the morbidity associated with peritoneal dialysis related infection will require effective strategies for prevention of infection due to Staphylococcus aureus and gram‐negative organisms.
Peritoneal defence in peritoneal dialysis
Authors: TOPLEY NICHOLAS , DAVENPORT ANDREW , LI FU‐KEUNG , FEAR HUW , WILLIAMS JOHN D
Published: April 2007

Summary: Over the past 20 years the use of peritoneal dialysis as a renal replacement therapy has increased dramatically. Its use has identified that infection and long‐term loss of function of the peritoneal membrane as a dialysing organ are the major problems associated with this form of therapy. This has led, over the last decade, to research into the importance of peritoneal host defence mechanisms in the control of infection and more recently to studies on the contribution of the resident peritoneal cell populations (peritoneal macrophages; PMO) and the cells of the peritoneal membrane (mesothelial cells and peritoneal fibroblasts) to the ‘peritoneal cytokine network’. It is widely accepted that PMO represent the first line of cellular defence against peritoneal infection. Recently it has become clear that the cells of the peritoneal membrane, and the mesothelial cell in particular, are primary responders in the inflammatory cascade. Evidence suggests that the initial activation of inflammation occurs on the peritoneal membrane and that the mesothelium and PMO interact directly (via adhesion molecule/integrin binding) and indirectly via the secretion of pro‐/anti‐ and immuno‐modulatory mediators to initiate, amplify and resolve inflammatory episodes. In vitro studies of peritoneal cell inflammatory function have been paralleled by ex vivo observations of the peritoneal inflammatory cascade. These have identified the temporal sequence of inflammatory events (cytokine and prostaglandin synthesis) that occur in vivo. These observations demonstrate that local (intra‐peritoneal) generation of inflammatory mediators and confirm the importance of the various peritoneal cell populations and the cross‐talk between them in the evolution of the inflammatory response. the initial activation appears to occur on the mesothelial cell surface driven by the pro‐inflammatory products of the PMO (IL‐1 and tumour necrosis factor; TNF). This results in the amplification of the inflammatory cascade and the generation of chemotactic cytokines (IL‐8 and MCP‐i) responsible for the recruitment of inflammatory leucocytes (neutrophils, macrophages and lymphocytes) into the peritoneal cavity. This process is facilitated by the simultaneous up‐regulation of adhesion molecules (intercellular adhesion molecule‐1; ICAM‐1 and vascular cell adhesion molecule‐1; VCAM‐1) on the mesothelial cell surface which facilitate the transmigration of leucocytes across the peritoneal membrane. Taken together these data suggest that both leucocyte and peritoneal membrane cell populations, interact and play pivotal roles in the control of peritoneal defence during continuous ambulatory peritoneal dialysis.
Highly permeable membranes in dialysis: Optimal therapy design
Authors: LEDEBO INGRID
Published: April 2007

Summary: Considering the removal potential of diffusion and convection in relation to the size of uraemic toxins, it is evident that we should not rely solely on diffusion to purify the blood, as is the case in the most common form of dialysis, haemodialysis with low‐flux membranes. In order to remove more of the larger uraemic toxins, we need to use more convective transport in dialysis therapy. the use of high‐flux membranes is increasing and approximately 25% of all dialysis treatments are performed with these membranes. They are characterized by high permeability to water, but for good convective transport they should also have generous and stable sieving properties. the convective transport provided by these membranes when used in a haemodialysis set‐up is limited to the desired weight loss and the uncontrolled ultrafiltration which is compensated by backfiltration. to better use the potential of a high‐flux membrane, the ultrafiltration should be greatly increased, as in haemodiafiltration (HDF) and haemofiltration (HF). the large volumes of fluid, free from bacteria and pyrogen, which are required for these therapies can be provided by special multi purpose treatment systems. On‐line preparation of bicarbonate‐containing fluid that can be used for substitution is a safe, practical and cost‐effective method. In addition to high clearance of solutes over a wide molecular weight range, the convective therapies provide good haemodynamic stability in response to fluid removal during dialysis.
Approaches to the management of renal bone disease
Authors: RITZ EBERHARD
Published: April 2007

Summary: The major, although not the exclusive, factors in the pathogenesis of renal bone disease are: (i) inappropriate renal production of calcitriol; (ii) variable resistance to the action of calcitriol, both abnormalities eliciting; (iii) secondary hyperparathyroidism with increased hormonal secretion and in the long‐term parathyroid hyperplasia: first polyclonal and then monoclonal; and (iv) variable resistance to parathyroid hormone (PTH) on the receptor and also the post receptor level altering the relationship between PTH concentration and bone turnover. Unresolved in pathogenesis issues concern the role of phosphate (direct or indirect stimulatory action on the parathyroid and the quantitative contribution to parathyroid stimulation of changes in calcaemia (altered Ca sensor‐mediated signal to the parathyroid?). Unresolved practical problems concern: (i) optimal time of administration of calcitriol (prophylactic vs therapeutic); (ii) the dose of calcitriol (recent evidence showing that very low levels are both safe with respect to hypercalcaemia and efficaceous); (iii) the mode of administration (continuous vs intermittent; intravenous [i.v.] vs per oral; [p.o.]); and (iv) the choice of dialysate Ca concentration (low concentration permitting higher CaCO3 and calcitriol dosage, but exposing to the risk of negative Ca balance). Recent controlled studies have shed some light on these issues. Very low doses of calcitriol (0.125 μg/day) prevent a further rise of 1,84 PTH without causing hypercalcaemia, hypercalciuria or hyperphosphataemia. A controlled head‐on comparison failed to show a significant difference between i.v. and p.o. calcitriol with respect to PTH response or side effects. Because of the high prevalence of monoclonal growth in advanced nodular parathyroid hyperplasia there is an increasing tendency to advocate early parathy‐roidectomy or alternative procedures (injection of alcohol in the parathyroids).
The influence of recipient age on kidney transplant outcome
Authors: OPELZ GERHARD
Published: April 2007

Summary: The influence of recipient age on kidney transplant outcome was analyzed in more than 80 000 adult recipients of primary renal cadaver transplants and 10 000 recipients of related donor transplants. Elderly recipients showed only a modest decrease in graft survival when compared to young patients. However, the patient survival rate was significantly associated with recipient age. the 10 year patient survival rate in 16‐40‐year‐old cadaver transplant recipients was nearly 50% higher than that in 66–70‐yearold recipients (81 ± 1%vs 34 ± 6%, P < 0.0001). A similar age effect on the patient survival rate was noted among related donor transplant recipients. the rate of functioning grafts is similar in young and elderly adults; however, elder transplant recipients are exposed to a much higher risk of death after transplantation.
Renal replacement modalities for childhood end‐stage renal failure
Authors: BALFE JW
Published: April 2007

Summary: An overview is presented of the current management of children with end‐stage renal disease (ESRD), focusing on specific therapies such as haemodialysis, peritoneal dialysis and renal transplantation. Also discussed is the overall management of such children, with attention directed at growth, nutrition and development.
Relation of glycaemic control and hypertension to progression of glomerular lesions in non‐insulin dependent diabetes mellitus
Authors: KANAUCHI Masao , SHIIKI Hideo , FUJII Yoshihiro , DOHI Kazuhiro
Published: April 2007

Summary: We investigated the influence of glycaemic control and hypertension on the progression of renal structural changes in 18 patients with non‐insulin dependent diabetes mellitus (NIDDM) who had undergone sequential renal biopsies. Renal biopsies were performed after median interval of 6.0 years (range 2‐11 years). the severity of glomerular diffuse lesions was graded on a 5‐point scale according to Gellman's criteria. Subjects were divided into two groups: (i) patients who showed progression of glomerular diffuse lesions (n= 12); and (ii) patients who showed no change in histological grade (n= 6). Mean arterial blood pressure was significantly higher in group 1. There was no significant difference in the HbA1c between the two groups. These findings suggest that the mean arterial blood pressure is closely related to the progression of glomerular morphological changes regardless of the status of glycaemic control.
Zinc and testicular hormone profiles before and after renal transplantation
Authors: SWAMINATHAN S , KANAGASABAPATHY AS , SELVAKUMAR R , SESHADRI MS , SHASTRY JCM
Published: April 2007

Summary: Data on zinc status in Indian patients with chronic renal failure is lacking. There are conflicting data in the literature on plasma and erythrocyte zinc levels in renal failure patients and the effect of haemodialysis on zinc status. of the multiple factors believed to be involved in the pathogenesis of uraemic impotence, attention has been focused on the possible role of zinc depletion and hyperprolactinaemia. We report a longitudinal study on 27 patients with end‐stage renal disease (ESRD). Plasma and erythrocyte zinc, serum prolactin and serum total testosterone were studied at diagnosis, 4 weeks after haemodialysis, and 3 and 6 months after successful renal transplantation. Zinc status and hyperprolactinaemia are both normalized within 6 months after renal transplantation. While there was a significant positive correlation between plasma zinc and serum testosterone, there was no correlation between serum prolactin and testosterone. This observation suggests that plasma zinc may be a more important determinant of normal gonadal function than prolactin in renal transplant recipients.
Outcome of live related and live unrelated renal transplants
Authors: GULATI Sanjeev , GUPTA Sandeep , KHER Vijay , GUPTA Amit , AHLAWAT Rajesh , ARORA Pradeep
Published: April 2007

Summary: This study compares the outcomes of 229 renal transplants, of which 156 were live related renal transplants done at our centre and 73 unrelated transplants done at other centres but followed up at our centre. All the patients were on triple immunosuppression for periods varying between 9 months and 1 year. Patient characteristics, rejections, infections and 1 and 5 years patient and graft survival were analyzed in the two groups. the outcome of patients who continued on cyclosporine beyond 1 year was compared to those who discontinued cyclosporine at 1 year. Males predominated (191 vs 38) in both groups, while younger patients (<50 years) predominated in live related group (152 vs four). There was no difference in the incidence of infection, rejection, graft dysfunction, graft loss or death between the two groups. the 1 and 5 year patient survival in the related and unrelated group, (93.7% and 71.4%vs and 85% and 66%) and graft survival (90.4% and 69.4%vs 83.3% and 65.4%) were similar. However, in the unrelated group, patients who discontinued cyclosporine had a higher incidence of rejections (38%vs 14%) and graft loss (43%vs 11.8%), while in the related group no such difference was found. It is concluded that 1 and 5 year patient and graft survival is comparable between live related and live unrelated transplantation. However, in the unrelated group it is necessary to continue cyclosporine beyond 1 year in order to achieve comparable results.
The kidney in heart failure: Vasodilator‐natriuretic systems
Authors: AKAMA Hiroyoshi , McGRATH Barry P
Published: April 2007

Summary: Congestive heart failure (CHF) is a complex clinical syndrome in which the kidney has a central pathophysiological role. an imbalance between vasoconstrictor‐antinatriuretic and vasodilator‐natriuretic forces is a key feature of the pathophysiology of CHF. This review summarizes current understanding of disturbances in vasodilator‐natriuretic systems in CHF. the key vasodilator systems involved are: the natriuretic peptide family atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), urodilatin, dopamine (DA), endothelium‐derived relaxing factors and prosraglandins. Renal responses to ANP are blunted in CHF, under the influence of haemodynamic, neuro‐humoral, receptor and post‐receptor events. BNP, secreted in response to left ventricular load, may circulate in high concentrations in CHF, with similar effects to ANP. Urodilatin is a newly discovered peptide of renal origin whose physiological role is under investigation. Neural endopeptidase inhibitors have shown some promise in the treatment of human CHF, particularly when combined with ACE inhibition or angiotensin II receptor blockade. the renal DA system is influenced by sodium intake and DA metabolism is altered in CHF. the place of orally active DA prodrugs and DA agonist in the management of patients with CHF is still undecided. In CHF, basal release of nitric oxide may be preserved or even enhanced. However, stimulated release of nitric oxide may be reduced. Renal effects of nitric oxide or arginine in CHF have yet to be defined. Renal prostaglandins play an important role in offsetting renal and systemic vasoconstriction and fluid retention in CHF. the recent availability of specific receptor antagonist should lead to clearer definition of the relative roles of renal angiotensin II inhibition and bradykinin potentiation in the benefical responses to angiotensin converting enzyme (ACE‐1) in CHF. Prostaglandin‐E1 (PG‐E1) and prostaglandin‐E2 (PG‐E2) infusion may have some benefit for the treatment of severe CHF. Adrenomedullin, a vasodilator‐natriuretic peptide closely related to the calcitonin gene‐related peptide family, is present in high concentrations in the kidney. Plasma concentrations of adrenomedullin are increased after acute cardiac injury and in CHF. Its roles in renal physiology and in the pathophysiology of CHF are under investigation. Overall, there is considerable potential to exploit these vasodilator‐natriuretic systems in management strategies for CHF.
Haemodialysis with low dialysate flow rates: A comparison of high performance membranes and conventional membranes
Authors: PARK Kyun I , TOMOYOSHI Tadao
Published: April 2007

Summary: We performed experimental studies to examine the effects of low dialysate flow rates on the clearance of small molecular weight substances, a middle molecular weight substance and a low molecular weight protein using a high performance membrane (HPM) and a conventional membrane (CVM). the blood flow rate was 200 mL/min and the diasylate flow rate varied between 300 and 500 mL/min. Clearance of urea and creatinine, representing small molecular weight substances, clearance of vitamin B12 representing a middle molecular weight substance, and clearance of myoglobin, representing a middle molecular weight substance, and clearance of myoglobin, representing a low molecular weight protein were measured. Lowering the dialysate flow rate from 500 to 300 mL/min in the HPM decreased the clearance of urea, creatinine, vitamin B12 and myoglobin by 7.2%, 8.6%, 8.4%, and 2.4%, respectively. Lowering the dialysate flow rate from 500 to 300 mL/min in the CVM decreased the clearance of urea, creatinine, and vitamin B12 by 8.7%, 10.9%, and 10.4%, respectively. Changes in the clearance of creatinine with reduced dialysate flow rate in the HPM were significantly lower than those in the CVM (P<0.05). Clearance of urea, creatinine, and vitamin B12 in the HPM at a dialysate flow rate of 300 mL/min were higher than those of in the CVM at a dialysate flow rate of 500 mL/min. These results suggest that dialysate flow rates can be reduced and water can be effectively saved by combining a dialysate flow rate of 300 mL/min with a HPM during water shortages due to natural disasters or climate changes.
Autosomal dominant polycystic kidney disease: A genetic perspective
Authors: HARRIS Peter C
Published: April 2007

Summary:Important advances in understanding the common genetic disease, autosomal dominant polycystic kidney disease (ADPKD), have been made in last 3 years through the identification and characterization of the major genes,PKDIandPKD2.thePKDIandPDK2genes map to the chromosomal regions, 16p13.3 (within a complex reiterated area) and 4q21‐23, respectively, and encode transcripts of over 14kb (PKDI) and 5 kb (PKD2). the predicted PKD1 protein, polycystin, is 4302/3 aa with a calculated molecular mass of approximately 460 kDa. Polycystin has a large extracellular region containing motifs involved in protein‐protein and protein‐carbohydrate interactions, and is attached to the membrane with multiple transmembrane regions. PKD2 is a small integral membrane protein (110 kD) with cytoplasmic N and C termini, 6 transmembrane domains and a region of homology with polycystin. Similarity of PKD2 to voltage‐gated ion channels and an area of homology between polycystin and a receptor for egg jelly protein, which is thought to regulate ion channels, suggests a role for the ADPKD proteins in ion transport. thePKD1andPKD2genes are expressed in most tissues and polycystin has been localised to tubular epithelial structures in the fetal and adult kidney. A Western product of approximately 400 kDa has been detected in membrane fractions of renal tissue and strong polycystin expression has been noted in PKD1 cystic epithelia. the mutations detected atPKD1andPKD2suggest that these germline changes are inactivating. A specific syndrome due to a deletion ofPKD1and the adjacentTSC2gene is associated with early onset polycystic kidney disease and tuberous sclerosis. Recent evidence of somatic mutation in cystic epithelia suggests that PKD1 is recessive at the cellular level, although this appears a odds with the continued polycystin expression noted in these cells. Further studies to determine the precise mutational mechanism and the normal role of the ADPKD proteins is required.
Short term follow up of childhood focal segmental glomerulosclerosis in India
Authors: GULATI S , KHER V , JAIN M , MITTAL S , ARORA P , GUPTA A , GUPTA RK
Published: April 2007

Summary: A retrospective analysis of 67 biopsy proven cases of focal segmental glomerulosclerosis (FSGS) in children was performed. After a mean duration of disease of 48.5 ± 44 months, 20 patients (30%) achieved sustained remission (SR), 23 (34%) had frequent relapses (FR) and 24 (36%) were steroid non‐responders (NR). the NR group had a significantly higher mean age of onset 9.1 ± 1.01 years (P= 0.003) and had higher number of females (P= 0.0009). They also had a significantly higher prevalence of microhaematuria as compared to FR and SR groups (P= 0.002). the initial steroid response category (P<0.00001) and the percentage of glomeruli with segmental sclerosis on histopathology (P= 0.001) correlated with the subsequent outcome. During this period six children developed progressive renal failure and all of them belonged to NR group (25%). There were four deaths and all of them were non‐responders (16.6%). Features predictive of a poor therapeutic outcome in childhood FSGS are age of onset more than 9 years, female sex, microhaematuria, renal dysfunction at onset, initial non‐response to steroids and percentage of glomeruli with segmental sclerosis on histopathology.
Modification of mesangial cell function by ambient chloride is absent in Dahl salt sensitive rat
Authors: OHARA Mamiko , OKUDA Toshihiro , INISHI Yoji , KUROKAWA Kiyoshi
Published: April 2007

Summary: We previously reported that the normally present modification of mesangial cell function by ambient chloride concentration ([Cl]) and insulin was lacking in mesangial cells obtained from spontaneously hypertensive rats (SHR). This aberrant modification of the mesangial cell might be related to the development of hypertension. In this study, we examined if a similar aberrant modification of mesangial cell function by [Cl] and insulin was present in Dahl salt sensitive (DS) rats, which develop hypertension in a NaCl dependent manner. Similar to our previous reports on mesangial cells from normal rats, pre‐treatment with low [Cl] apparently attenuated Ca responses induced by angiotensin II and vasopressin in mesangial cells cultured from Dahl salt resistant (DR) rats. In contrast, this attenuation of vasoactive agents‐induced Ca signal was absent in the DS rat derived‐mesangial cells. Also, the enhancement of prostaglandin E2 production caused by decrease in [Cl] was not observed in the DS rat mesangial cells, while prostaglandin E2 production by DR rat mesangial cell was stimulated when [Cl] was decreased. In contrast, vasopressin‐induced Ca signal by insulin was attenuated in both DR and DS rat mesangial cells. Thus, in DS rat mesangial cells, modification of mesangial cell function by [Cl] was absent, but it was different from SHR mesangial cells because insulin was maintained.
Increased enzymuria in diabetic children without persistent minimal albuminuria
Authors: SCHWITZGEBEL Valerie M , LANFRANCHINI Francesco M , WIESMANN Uuuch N , MULLIS Primus E , PEHEIM Edgar , BIANCHETI Mario G
Published: April 2007

Summary: The urinary activity of the enzyme N‐acetyl‐β‐glucosaminidase is a useful, early marker of renal tubular damage in various conditions. Consequently, it is tempting to presume that the excretion of this enzyme might recognize subclinical renal damage long before elevation of urinary albumin excretion. the urinary N‐acetyl‐β‐glucosaminidase activity was therefore assessed in a group of 77 diabetic patients (37 girls and 40 boys, aged 2.9‐20 years) without persisting minimal albuminuria. Circulating glycosylated haemoglobin and fructosamine were significantly higher in the 24 patients with persistently increased urinary N‐acetyl‐β‐glucosaminidase compared with the remaining patients. It is concluded that raised urinary N‐ acetyl‐β‐glucosaminidase might be the earliest detectable abnormality of renal damage in chronic diabetes mellitus.
Polymorphism of renin‐angiotensin system genes in progressive IgA nephropathy
Authors: YOSHIDA Hiroaki , KAWAMURA Tetsuya , ICHIKAWA Iekuni , SAKAI Osamu
Published: April 2007

Summary: Clinical studies revealed that angiotensin converting enzyme (ACE) inhibitor reduces proteinuria and attenuates progressive decline in renal function in IgA nephropathy. Recent studies by us and others have demonstrated that the homozygote of the D allele (DD) of the ACE insertion/deletion (I/D) polymorphism is a potential risk factor for poor prognosis in IgA nephropathy, and that this deletion polymorphism predicts the therapeutic efficacy of ACE inhibition on proteinuria and, potentially, on progressive deterioration of renal function in patients with the nephropathy.
Treatment of IgA nephritis in Singapore
Authors: WOO Keng‐Thye
Published: April 2007

Summary: Any form of therapy for IgA nephritis must be rational and practical. the least toxic agent should be chosen with a view to even life long therapy for patients with bad prognostic indices. Patients with IgA nephritis have evidence of platelet involvement and low‐grade intravascular coagulation, with a tendency for increased thrombogenicity within the kidneys. the use of dipyridamole (an anti‐platelet agent) and warfarin (an anti‐thrombotic agent) has been successful in two separate trials in patients with IgA nephritis. the relative lack of side‐effects and their low cost allow their long‐term use for treatment in these patients. the indications for combination therapy with dipyridamole and low dose warfarin are the presence of any one of the following parameters: proteinuria < 1 g m/day, hypertension, renal impairment, glomerulosclerosis < 20% on renal biopsy, presence of even a single crescent, medial hyperplasia of blood vessels on biopsy. Treatment of patients with IgA nephritis with asymptomatic haematuria and proteinuria consist of control of systemic hypertension, use of ACE inhibitor for glomerular hyperfiltration, dipyridamole and low dose warfarin, low protein diet (0.8 g/kg per body weight/day) and control of serum cholesterol to prevent lipid induced glomerulosclerosis. Patients with IgA nephritis who have the nephrotic syndrome with selective proteinuria, should be treated with prednisolone. Those who do not respond to steroids can be given a course of cyclophosphamide. Patients with IgA nephritis with predominantly tubular interstitital lesions not in proportion to the degree of glomerular sclerosis should be treated with a low dose steroid regimen. While there is no cure for IgA nephritis such therapeutic measures serve to retard the progression to end‐stage renal failure (ESRF). Future therapeutic strategies lie in immunomodulation using inhibitors of cytokines and possibly gene therapy.
Steroid therapy in progressive IgA nephropathy: A 10 year follow‐up study
Authors: KOBAYASHI Yutaka , HIKI Yoshiyuki , KOKUBO Tohru , SANO Takashi , HASHIXUME Kenjiro , TATENO Sumio
Published: April 2007

Summary: This study was undertaken in order to evaluate the effect of steroid therapy on the long‐term clinical course in progressive IgA nephropathy with persistent massive proteinuria of ≤ 1.0 g/day. From 1972 to 1986, 109 patients with persistent massive proteinuria who were continuously followed up during a 10 year period. Seventy‐seven of these patients had moderate proteinuria of 1‐2 g/day and the remaining 32 patients had heavy proteinuria of more than 2 g/day. the 109 patients were divided into three groups according to the grade of renal function and histological severity: group 1 (58 cases), preserved renal function (creatinine clearance rate [Ccr] ≤ 70 mL/min) and moderate to severe histology (total score ≤ 7); group 2 (35 cases), decreased renal function (Ccr >70 mL/min) and moderate to severe histology; and group 3 (16 cases), preserved renal function and mild histology (total score ≥ 6). Fifty‐five patients received steroid therapy for 2 years, followed by an anti‐platelet drug therapy until the completion of the study. Fifty‐four patients were treated with only an anti‐platelet drug therapy for the duration of the study. There were no significant differences in renal function and renal survival rates over the 10 year period between the steroid‐treated and the non‐steroidtreated groups. Among the moderately proteinuric patients of group 1, the 20 steroid‐treated patients showed significantly favourable clinical courses compared to the 26 non‐steroid‐treated patients of the same group. the 12 heavily proteinuric, steroid‐treated patients of the group 1 also showed significantly favourable courses compared to those 26 moderately proteinuric, non‐steroid patients. However, all but one patient in group 2, (with and without steroid therapy) went into end‐stage renal failure within the 10 year follow‐up period. These results indicate that corticosteroid treatment has a long‐term beneficial effect for the stabilization of renal function in progressive IgA nephropathy with massive proteinuria ≤ 1.0 g/day, when patients have preserved renal function of 70 mL/min or more in initial Ccr values.
New therapeutic strategies of molecular intervention in glomerulonephritis
Authors: IMAI Enyu , ISAKA Yoshitaka , AKAGI Yoshitaka , ANDO Yutaka , ARAI Makoto , KANEKO Tetsuya , TAKENAKA Masaru , MORIYAMA Toshiki , YAMAUCHI Atsushi , HORIO Masaru , ANDO Akio , ORITA Yoshimasa , UEDA Naohiko
Published: April 2007

Summary: Recent progress of genetic engineering allows us to create animal models expressing the new genetic phenotype and also indicates a sure future for clinical use of gene therapy. We applied HVJ‐liposome method for manipulation of transforming growth factor (TGF)‐β gene expression in anti‐Thy‐1 experimental glomerulonephritis. Either the glomerular introduction of TGF‐β antisense oligodeoxynucleotides or transfection of gene for decorin, a natural inhibitor of TGF‐β, into the skeletal muscle could suppress the extracellular matrix (ECM) expansion in glomerulonephritis. Thus, these results may suggest the potential of gene therapy as a novel treatment for fibrotic diseases caused by TGF‐β.
THE IMPORTANCE OF FAILURE MODE IN FATIGUE–CREEP INTERACTIONS
Authors: PLUMBRIDGE W. J. , DEAN M. S. , MILLER D. A.
Published: April 2007

Abstract— The present work emphasizes the need to understand the processes involved in fatigue–creep interactions before reliable life predictions may be sensibly made. In particular, the simultaneous interaction involving a strain controlled cycle with a dwell period at maximum tensile strain is analysed and the accumulation of fatigue–creep damage computed in terms of strain range, extent of dwell and microstructure. Dominant failure modes are thus identified and the findings are used to explain the apparently different failure mechanisms previously reported for a 1Cr–Mo–V alloy steel and a Type 316 stainless steel. Due to lack of data overall mapping of regimes of dominance is not possible, but in cases where a single mechanism prevails throughout the duration of dwell accurate lifetime prediction may be achieved.
FATIGUE STRENGTH OF A ROTOR STEEL SUBJECTED TO TORSIONAL LOADING SIMULATING THAT OCCURRING DUE TO CIRCUIT BREAKER RECLOSING IN AN ELECTRIC POWER PLANT
Authors: Tanaka K. , Matsuoka S. , Kouzu F. , Nagata K.
Published: April 2007

Abstract—The fatigue strength of notched specimens of a rotor steel was examined under variable torsional loading which simulates turbine‐generator oscillations resulting from the high speed reclosing of transmission‐line circuit breakers. The local stress‐strain response at a notch root was analysed using Neuber's rule and the resulting complex strain sequences applied to smooth specimens. Using the rain flow analysis and the linear summation rule, fatigue lives of the smooth specimens were successfully predicted from constant amplitude fatigue life data in association with the cyclic stress‐strain curve obtained by the incremental step method. Experimental crack initiation lives for notched specimens subjected to variable torsional loading were in excellent agreement with the theoretical curves derived from results on smooth specimens. According to the view that fatigue damage is equated to crack length, the propagation life of a mode II crack along the notch root was predicted to be actually coincident with the life to crack initiation at the notch root denned in this study, i.e. the life at the stage of finding a continuous circumferential crack.
A FINITE ELEMENT ANALYSIS OF A CRACK GROWING UNDER CYCLIC LOADING
Authors: Wästberg Stig
Published: April 2007

Abstract—Crack growth under cyclic loading has been studied by the finite element method. The calculation was made for plane stress conditions. The crack tip zone was modelled as a cohesive zone.

The displacement of the free crack surface during unloading was found to be governed by the surrounding continuum and was independent of the details in the fracture zone. This means that crack closure upon unloading is directly related to the ultimate separation, of the cohesive zone, which in turn controls the residual plastic deformation left in the wake of the growing crack.

If the distance over which closure takes place is rather small, closure may be very difficult to detect by the compliance technique.
CLOSURE BEHAVIOUR OF SURFACE CRACKS
Authors: Fleck N. A. , Smith I. F. C. , Smith R. A.
Published: April 2007

Abstract— The fatigue crack closure response was investigated for a surface crack in BS4360 50B structural steel, subjected to (1) constant amplitude loading and (2) constant amplitude loading interrupted by a single peak overload. A variety of compliance techniques was employed to determine closure behaviour. The crack mouth gauge measured the bulk, plane strain closure load, while the near tip strain gauge indicated the surface, plane stress closure response. For constant amplitude loading it was found that the surface regions of a surface crack are closed for a greater portion of the load cycle than the maximum depth point. A single peak overload caused different closure and growth rate transients at the surface of the thumbnail crack and at the maximum depth point. For growth rates above 10‐6 mm/cycle, such behaviour agrees with the response of a through crack when subjected to constant amplitude loading, and a single peak overload.
THE EFFECT OF ENVIRONMENT ON CRACK CLOSURE AND FATIGUE THRESHOLD*
Authors: Ruppen J. A. , Salzbrenner R.
Published: April 2007

Abstract— The threshold value for fatigue crack growth of a medium carbon steel was increased when the test‐environment was changed from air to an aggressive H2S‐containing brine. This increase in fatique threshold was shown to be caused by corrosion product‐induced crack closure. Further, the fatigue threshold and crack closure level were shown to be dependent on the growth rate history in approaching threshold. The differences in fatigue crack growth rate and fatigue threshold resulting from test procedure and growth rate history were significantly reduced by employing the effective stress intensity concept.
THE INFLUENCE OF AGE‐HARDENING ON FATIGUE CRACK PROPAGATION BEHAVIOUR IN 7075 ALUMINIUM ALLOY IN VACUUM
Authors: Lafarie‐Frenot M. C. , Gasc C.
Published: April 2007

Abstract— The influence of age‐hardening on the middle and low crack growth rates of a 7075 Al alloy is studied in vacuum. A transition in fracture surfaces morphology and crack growth curves is observed with the T 651 and T 7351 treatments in the near‐threshold regime. Measurements of crack closure show its dependance on surfaces roughness and explain the lack of dependance of ΔKth with load ratio, except for the T 7351 alloy. An equation of crack growth rate to the fourth power of ΔKeff is in good agreement only with the crack propagation curves obtained for microstructure with an homogeneous deformation mode.
A CRITICAL STUDY OF THE CRACK CLOSURE EFFECT ON NEAR‐THRESHOLD FATIGUE CRACK GROWTH
Authors: Minakawa K. , Newman J. C. , McEvily A. J.
Published: April 2007

Abstract—Crack closure in the near‐crack‐tip region has been considered to be an important contribution to the development of a crack‐growth threshold for macroscopic cracks. Recent analytical work, however, has suggested that closure well back of the tip may be the controlling factor. In order to check on this possibility, material has been machined away far behind the crack tip in order to eliminate long‐range closure. Removal of this material did not eliminate the threshold, but did lower the threshold level by approx. 10% for tests conducted on 6.3 mm‐thick X7090‐T6 powder metallurgy aluminum alloy.
ON THE OVERLOAD INDUCED FATIGUE CRACK PROPAGATION BEHAVIOR IN ALUMINUM AND STEEL ALLOYS
Authors: Vecchio, R. S. , Hertzberg R. W. , Jaccard R.
Published: April 2007

The overload induced fatigue crack propagation behavior of several aluminum and steel alloys was examined as a function of the baseline stress intensity factor range (δKb). In order to gain a clearer understanding of the parameters which influence the cyclic delay phenomenon, under both plane strain and plane stress conditions, tests were conducted at δKbvalues ranging from the near threshold regime to high δKlevels approaching fast fracture. Large amounts of overload induced cyclic delay (˜100,000 cycles) were observed at both high and low δKlevels (provided the plastic zone size/thickness ratio and plastic zone size/grain size ratio approached unity, respectively) with significantly less delay occurring at intermediate δKvalues. All alloys examined exhibited this type of delay behavior which can be described by a “U‐shaped” plot. The delay phenomenon at high δKblevels under plane stress conditions was attributed to increased crack closure associated with large tensile displacements in the wake of the advancing crack. At low δKblevels increasing cyclic delay was attributed to an increasedeffectiveoverload ratio as δKapproached δKth.
INFLUENCE OF ADIABATIC SHEAR BANDS ON THE FATIGUE STRENGTH OF A TITANIUM ALLOY
Authors: Timothy S. P. , Hutchings I. M.
Published: April 2007

An experimental investigation is reported of the possible effects of adiabatic shear bands, caused by projectile impact, on the fatigue strength of a titanium alloy (Ti‐6%A1‐4%V). No significant reduction in fatigue strength due to the presence of adiabatic shear bands was found, nor did the fatigue cracks initiate from the bands. The results are relevant to the problem of foreign object impact damage to compressor blades in gas turbine aeroengines.
FATIGUE CRACK GROWTH LAWS FOR BRITTLE AND DUCTILE MATERIALS INCLUDING THE EFFECTS OF STATIC MODES AND ELASTIC‐PLASTIC DEFORMATION
Authors: Chell G. G.
Published: April 2007

A fatigue crack growth damage accumulation model is used to derive laws for the fatigue crack growth rates of brittle and ductile materials. The damage accumulated during cyclic loading is assumed to be proportional to the cyclic change in the plastic displacement in the crack tip yielded zone. The static mode contribution to the fatigue damage is assumed to be proportional to some power of the crack tip displacement. The laws are applicable in either the small or large scale yielding regimes provided that the stress ratio remains positive. Static modes are assumed to be controlled by the fracture toughness value in brittle materials, and by the gradient of the crack growth resistance curve in ductile materials. In the analysis of ductile materials it is assumed that the crack growth resistance of the material is not significantly altered by fatigue crack growth.

The growth rate equations are expressed in terms of the near field value of theJ‐integral, i.e. the value which would be calculated from assuming the material deformed in a non‐linear elastic manner during the increasing load part of the fatigue cycle. Examples are given of the predictions of the growth law for ductile materials. It is predicted that after the initiation of stable tearing the crack growth rate, when expressed in terms of the cyclic change in the stress intensity factor, depends on both the structural geometry and the degree of crack tip plastic deformation. In both brittle and ductile materials the fatigue crack growth rate is predicted to accelerate as the failure criteria relevant to static crack instability are approached.
CREEP‐FATIGUE STUDIES UNDER A BIAXIAL STRESS STATE AT ELEVATED TEMPERATURE
Authors: Hamada Naomi , Sakane Masao , Ohnami Masateru
Published: April 2007

In order to study creep‐fatigue interactions under multiaxial stress states, both push‐pull and reversed torsion low‐cycle fatigue tests were carried out using an austenitic stainless steel, SUS 304, at 923 K in air. From the tests, it is concluded that the hold‐times introduced at the peak strain reduce low‐cycle fatigue lives in the push‐pull mode, but in the torsional mode they were not so harmful. This difference in the hold‐time effect is discussed from considerations of crack formation and propagation and the stress amplitude applied to the specimen.

Both maximum principal strain range, Δε1, and the von Mises' equivalent strain range, Δεeq, provide a nearly adequate comparison base for the assessment of biaxial low‐cycle fatigue lives in tests without strain hold‐time but are inadequate for hold‐time tests. An equivalent stress range, Δσ*, which includes the effect of the stress parallel to the fatigue crack and which was previously proposed by the authors for no hold‐time tests, is applied to the hold‐time tests in the biaxial stress state. It is found that Δσ* is a good parameter for the correlation of biaxial low‐cycle fatigue data in both no hold‐time and hold‐time tests.