bluuebunny/crossref_metadata_2025 huggingface dataset:
Complete hydatidiform mole in twin pregnancy
Authors: KAA C.A. VAN DE , ROBBEN J.C.M. , HOPMAN A.H.N. , HANSELAAR A.G.J.M. , VOOIJS G.P.
Published: April 2007

Six cases of hydatidiform mole associated with normal chorionic villi and a normal embryo/fetus (in five cases) were investigated with interphase cytogenetic and DNA cytometric analyses for diagnostic purposes. DNA probes specific for the pericentromeric regions of chromosomes 1 and X and for the long arm of chromosome Y were used. In four cases a dizygotic twin pregnancy could be proven. In these cases, the histologically normal chorionic villi showed an XY DNA‐diploid pattern, consistent with a normal male conceptus, and the molar chorionic villi a XX pattern. In the other two cases an identical sex chromosomal pattern was found in the normal and in the molar villi (XX/XX and XY/XY respectively). In all six cases the molar placental tissues showed prominent trophoblastic hyperplasia with DNA‐polyploidy, consistent with a complete hydatidiform mole. In two cases persistent gestational trophoblastic disease developed. It is emphasized that twin pregnancies composed of a normal conceptus and a complete mole have a relatively high risk for the development of persistent trophoblastic disease and therefore, should be carefully differentiated from triploid partial moles with a relatively low risk of persistent gestational trophoblastic disease. These case reports indicate that additional interphase cytogenetic and DNA cytometric analyses are useful in this differential diagnosis.
Mixed tumours of the skin: a histopathological, enzyme‐histochemical and immunohistochemical study
Authors: HARA K.
Published: April 2007

Twenty‐eight cases of mixed tumour of the skin were studied and subclassified into three types: eccrine (1 case), indeterminate (7), and apocrine type (20). The indeterminate type was defined as mixed tumours having tubulo‐alveolar patterns with two layers of epithelium, but without apocrine secretion or pilosebaceous differentiation. Enzyme‐histochemical studies were performed on four cases (one indeterminate, three apocrine): in the indeterminate type the tubular epithelial cells showed eccrine differentiation while in the apocrine type tubules were found showing the direction of differentiation to be toward the apocrine gland, but tubules with eccrine differentiation were intermingled in all three. Immunohistochemically, no differences were observed between the indeterminate and the apocrine type: hints of eccrine features were observed in both groups. Thus, the indeterminate type could be an eccrine tumour and the apocrine type showed direction of differentiation toward both eccrine and apocrine glands. It is concluded that mixed tumours of the skin are fundamentally eccrine neoplasmas, and that the apocrine features may represent apocrine metaplasia.
Localized amyloid deposition in cartilage is glycosaminoglycans‐associated
Authors: ATHANASOU N.A. , WEST L. , SALLIE B. , PUDDLE B.
Published: April 2007

Localized amyloid deposition is known to occur commonly in the articular cartilage of elderly patients. Its pathogenesis is uncertain and it is not known if other cartilage‐containing tissues also contain amyloid deposits. Systemic amyloid deposits are known to contain highly sulphated glycosaminoglycans, a major constituent of cartilage. As the composition of articular cartilage glycosaminoglycans is known to change with age, we sought to identify whether localized amyloid deposition in cartilage was glycosaminoglycan‐related. We examined specimens of articular cartilage over a wide age range and also examined a variety of cartilaginous tumours and tumour‐like lesions for the presence or absence of amyloid deposits. Using mucin histochemistry (alcian blue: MgCl2 critical electrolyte concentration) and immunohistochemistry, we found that highly sulphated glycosaminoglycans (0.9 M and 1 M MgCl2), in particular keratan sulphate, localized to amyloid deposits in both articular cartilage and loose bodies derived from the articular surface. Other cartilaginous lesions (including loose bodies of primary synovial chondromatosis) were negative for amyloid and did not contain highly sulphated glycosaminoglycans. These findings suggest that changes in specific highly sulphated glycosaminoglycans may play a role in localized amyloid deposition in articular cartilage.
Colonic tubular adenomas and intestinal spirochaetosis: an incompatible association
Authors: COYNE J.D. , CURRY A. , PURNELL P. , HABOUBI N.Y.
Published: April 2007

Two cases of tubulovillous adenoma and adjacent colonic mucosa were studied in which intestinal spirochaetosis had heavily colonized the non‐neoplastic but not the neoplastic epithelium. Ultrastructural and histochemical studies were performed and we postulate that the reason for this disparity is the normal microvillous pattern of the non‐neoplastic epithelium which facilitates colonization by the spirochaetes.
Lipoprotein glomerulopathy: A new aspect of lipid induced glomerular injury
Authors: SAITO Takao , SATO Hiroshi , OIKAWA Shinichi
Published: April 2007

Summary: Lipoprotein glomerulopathy is a new type of glomerular disease which is thought to be induced by an abnormality of lipoprotein metabolism. Until the end of 1994, 21 cases had been reported from Japan. However, this disease is not restricted to Japan because two cases with similar features have been described in France and the United States recently. Clinically, the presenting feature in all patients is proteinuria, resulting in a nephrotic syndrome in the majority. Renal biopsy specimens reveal that capillary lumina in the glomerulus are markedly dilated with pale‐stained and mesh‐like substances which are composed of fine granules. Under electron microscopy, it is observed that a combination of granules forms strata as fingerprints. Sudan or oil red‐O staining and immunofluorescence study on snap‐frozen sections show lipid droplets and apolipoproteins (apos) B and E in the capillary lumina, respectively. Accordingly, the intracapillary substances are thought to be lipoprotein thrombi. Lipid and lipoprotein profiles show type III hyperlipoproteinaemia and high level of apo E in plasma. However, the apo E phenotype is usually the heterozygous E2/3 or E2/4, different from the homozygous E2/2 in familial type III hyperlipoproteinaemia. Systemic manifestations characteristic of the previously‐reported lipidoses are not observed.

Occurrence in several families and recurrence in two transplanted kidneys suggest that the disease may be induced by the hereditary abnormalities of lipoprotein metabolism. On the other hand, it is likely that in situ mechanisms may mediate development of the disease in the glomerulus.
Biochemical characteristics of cyst fluid in undialysed patients with autosomal dominant poiycystic kidney disease
Authors: UEMASU Jiro , MUNEMURA Chishio , FUJIWARA Michihiro , KAWASAKI Hironaka
Published: April 2007

Summary: The biochemical composition of cyst fluid was analysed in 148 cysts obtained from 10 patients with autosomal dominant polycystic kidney disease (ADPKD). Serum creatinine levels ranged from 1.7 to 9.0 mg/dL. No patients were receiving renal replacement therapy. Aspirated cyst volume ranged from 4‐120 mL. There was no significant correlation between cyst volume and cyst sodium concentration ([Na]cyst). Cyst sodium concentration demonstrated a bimodal distribution pattern, with one peak from 10‐20 mEq/L and the other from 140‐150 mEq/L. the ratios of cyst fluid versus serum sodium concen tration ([Na]cyst/serum) were positively correlated with [C1]cyst/serum, while negatively correlated with [K]cyst/serum, [Ca]cyst/serum, [P]cyst/serum and [UA]cyst/serum. Based on the [Nalcyst/serum, the cysts were assigned to three types: proximal (0.8‐1.4), indeterminant (0.4–0.8) and distal (<0.4). the percentage of each type was 54.7, 19.6 and 25.7%, respectively. There were no significant differences in [Na]cyst/serum between the right and left kidney in individual patients. the concentrations of amino acids were higher in the distal type than in the proximal type.

These results indicate the divergent function of the cyst‐lining epithelia in polycystic kidneys.
Modulators of growth in primary culture of rat proximal tubular cells
Authors: NOBES Michael S , POLLOCK Carol A , HENG Pan T , FIELD Michael J
Published: April 2007

Summary: The effects of known growth factors and circulating serum factors in animals following unilateral nephrectomy on cellular hypertrophy and hyperplasia were studied in primary culture of rat proximal tubular cells. the cultured cells were derived from normal rat kidney, as well as from rat kidneys which had undergone compensatory renal hypertrophy. Cellular thymidine incorporation was stimulated with insulin‐like growth factor 1 (IGF‐1; P<0.001), epidermal growth factor (EGF; P<0.01) and additively by the combination of IGF‐1+EGF (P<0.0001). Transforming growth factor β1 (TGF β1) potently inhibited thymidine incorporation in the presence or absence of these growth factors. Cellular protein content was increased in the presence of IGF‐1 (P<0.01). the addition of 10% serum harvested from sham operated (Sx) animals to cell cultures derived from Sx animals significantly increased cell protein content (P<0.02), and stimulated cellular thymidine incorporation (P<0.005). the addition of 10% serum harvested from unilaterally nephrectomized (Nx) animals further enhanced the growth response. In cell cultures derived from Nx rats, a further marked stimulation of thymidine incorporation and cellular protein was observed in the presence of both Sx and Nx serum, indicating an increased sensitivity of these cells to serum‐derived factors. In summary, the growth factors tested have direct effects in regulating rat renal tubular cell growth. Circulating factors stimulating proximal tubular cell growth are present in animals which have undergone nephrectomy. Renal tubular cells derived from animals with compensatory renal hypertrophy are sensitized to the effects of the manipulations which enhance proximal tubular cell growth.
Histocytochemical study of Spot 35‐calbindin‐D28K and Ca2+‐ATPase in rat kidney
Authors: KAZAMA Junichiro J , TAKEDA Tetsuro , KATAGIRI Takashi , KUWANO Ryozo , KUMANISHI Toshiro , OZAWA Hidehiro , ARAKAWA Masaaki
Published: April 2007

Summary: We determined the distribution of Spot 35‐calbindin‐D28K, a vitamin‐D dependent calciumbinding protein, in rat kidney using histochemical methods and compared it with the distribution of Ca2+‐ATPase activity. Spot 35‐calbindin‐D28K immunoreactivity was localized in the cytosol of urinary epithelial cells in distal convoluted tubules (DCT), connecting tubules (CNT) and cortical collecting ducts (CCD), identifying the physiologically confirmed site of active transcellular calcium transport. In the cytosol, the immunoreactivity was clustered near the luminal plasma membrane and around the mitochondria. These findings indicated that Spot 35‐calbindin‐D28K seemed to have a cytosolic calcium buffering effect in the urinary tubular epithelial cells. Enzyme histochemical analysis showed that Ca2+‐ATPase activity was localized at the basolateral plasma membrane of distal nephron segments and was strongest at the cortical thick ascending limb of Henle (CTAL), including the macula densa portion. Ca2+‐ATPase activity was not evident in DCT, CNT or CCD. Strong Ca2+‐ATPase activity and Spot 35‐calbindin‐D28K immunoreactivity did not coexist in a urinary tubular cell.
Mechanisms and significance of proteinuria
Authors: OIKAWA Tsuyoshi , FOGO Agnes
Published: April 2007

Summary: Glomerular permselectivity is determined by complex interactions of the glomerular basement membrane (GBM) and the endothelial and epithelial cells of the glomerular capillary wall. Proteinuria may result acutely from functional changes in filtration, and be quickly reversible. Chronic structural changes may also contribute to proteinuria in many disease settings by affecting the components of the glomerular capillary wall (GCW). Thus, glomerular epithelial cell abnormalities are prominent in both minimal change disease and focal segmental glomerulosclerosis, whereas altered GBM thickness and composition are major features in diabetic nephropathy and Alport syndrome. A multitude of pathologic stimuli appear to influence proteinuria, including the renin‐angiotensin system and numerous other cytokines. Human and experimental data indicate a heterogeneity of mechanisms in different diseases manifesting proteinuria which are associated with a range of structural appearances from normal morphology to a severely damaged GCW. Current therapeutic trials in progressive human renal diseases have focused on the potential benefits of angiotensin converting enzyme inhibitor (ACEI). Encouraging results indicate amelioration of both functional and structural components of proteinuria, as well as a benefit on sclerosis, although the latter effect has so far only been documented in animal studies. Advances in molecular technologies may allow identification of more specific abnormalities in the GCW which underlie proteinuria. Further understanding of these abnormalities will direct future therapy at the specific defect in each disease setting.
Report of renal failure treatment in Australia and New Zealand from the dialysis and transplant registry (ANZDATA)
Authors: DISNEY* APS
Published: April 2007

Summary: The Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) has recorded 15675 patients resident in Australia and 2909 patients in New Zealand who have been treated by dialysis and transplantation for end‐stage renal failure. the majority of patients have a functioning transplant (51% Australia, 50% New Zealand). Cadaveric organs have been the mainstay of the transplant programme from 1963 to 1993 (91% Australia, 87% New Zealand). In recent years the early graft survival has dramatically improved; the 12 month graft survivals were 74 and 87% in Australia, and 68 and 78% in New Zealand in 1983 and 1992, respectively. A large majority of patients have dialysed at home (49% Australia, 84% New Zealand) or with low level assistance in facilities remote from tertiary level hospital renal units (21% Australia). While most patients use haemodialysis (64% Australia, 41% New Zealand), continuous ambulatory peritoneal dialysis is the predominant form of dialysis in the home (63% Australia, 70% New Zealand). the demographic analysis displays a slight predominance of males (55.5% Australia, 50.4% New Zealand), and a steadily increasing number of patients over 65 years old (31% Australia, 15% New Zealand), and of diabetics (16% Australia, 31% New Zealand). Aborigines, Maoris and Pacific Islanders have a strikingly higher rate of renal failure per million population than the Caucasoid/Europid population. Certain causes of renal failure such as excess analgesic ingestion and malignant hypertension have declined. Glomerulonephritis has been the most common cause of renal failure in Australia (33%), diabetic nephropathy the most common in New Zealand (31%).
Immunosuppression in renal transplantation: Long‐term clinical trial of a double versus triple therapy regimen
Authors: LO CY , CHENG IKP , FANG GX , CHAN MK , WONG KK , LI MK , POON KP
Published: April 2007

Summary: Sixty‐nine renal allograft recipients were randomized to two immunosuppressive regimens: 35 patients received cyclosporine A and prednisolone (PC) while 34 patients received low dose cyclosporine A, prednisolone and short term azathioprine (PCA). the data of 66 patients (34 in PC and 32 in PCA groups) were analysed. the median follow‐up periods were 62 months for the PC group and 60 months for the PCA group. There was no difference in graft survival between the two groups but five patients died in the PC group compared to none in the PCA group (graft survival: 88 vs 90% at 1 year and 82 vs 82% at 5 years, P= not significant at any time point; patient survival: 90 vs 100% at 1 year and 88 vs 100% at 5 years, P= 0.05 at 5 years). There was a trend for patients in the PCA group to develop earlier and more frequent rejections (not significant; P= 0.106 and P= 0.062, respectively). There were also more episodes of acute cyclosporine A nephrotoxicity and cytomegalovirus (CMV) infection in the PC group. the mean serum creatinine at 5 years was significantly higher in the PCA group when compared to the PC group (179.8 ± 76.5 μmol/L vs 154.7 ± 41.0 μmol/L; P=0.05). We found that both therapeutic regimens were effective in preventing renal allograft rejections. However, double therapy was associated with higher patient mortality secondary to infection. Patients on triple therapy, on the other hand, were more prone to develop rejections in the early post‐transplant period and were associated with less favourable renal function in the long run.
Immunohistochemical staining of renal biopsy samples in patients with diabetic nephropathy in non‐insulin dependent diabetes mellitus using monoclonal antibody to advanced glycation end products
Authors: SUZUKI Daisuke , YAGAME Mitsunori , NAKA Raita , JINDE Kiichiro , ENDOH Masayuki , NOMOTO Yasuo , SAKAI Hideto , ARAKI Norie , HORIUCHI Seikoh
Published: April 2007

Summary: Immunohistochemical staining of glomeruli in patients with diabetic nephropathy (DN) in non‐insulin dependent diabetes mellitus (NIDDM) using the monoclonal anti‐advanced glycation end products (AGE) antibody is described. In order to detect the localization of AGE in human renal tissues, we performed immunohistochemical staining using the monoclonal anti‐AGE antibody in the glomeruli of 11 patients with DN and 11 age‐matched patients with diffuse mesangial proliferative glomerulonephritis without IgA deposition (DPGN) as controls.

Emergence of AGE in the mesangial area was more marked in the glomeruli of patients with severe mesangial expansion than in those with mild expansion. AGE in the extraglomerular arteriolar walls was also observed. In contrast, there was no positive staining using the same antibody in renal tissue obtained from DPGN.

These data support the concept that deposition and/or formation of AGE in the mesangial area might be associated with the progression of diabetic nephropathy.
Bacterial biofilms on devices used in nephrology
Authors: REID Gregor , TIESZER Christina , BAILEY Ross R
Published: April 2007

Summary: Prosthetic devices are commonly used in nephrological and urological practice for the management of urinary and peritoneal dialysis flow, haemodialysis and drainage of renal calculi after laser or lithotripsy treatment. Many different types of materials are used and a number of complications arise, yet the fundamental interactions which occur at these biomaterial surfaces have been little studied. Recent information has shown that host conditioning films are deposited onto materials upon implantation, and that dense bacterial biofllms can form and resist conventional therapy. In order to better manage patients with prostheses, it will be imperative to understand the processes arising in the host and, using scientific data, to select the optimal interventions.
Modulators of growth in primary culture of rat proximal tubular cells II
Authors: NOBES Michael S , POLLOCK Carol A , HENG Pan T , FIELD Michaelj
Published: April 2007

Summary: The present studies assessed the effects of manipulating extracellular sodium (Na) concentration and Na transport on cellular hypertrophy and hyperplasia in primary culture of rat proximal tubular cells. A concentration‐dependent effect on thymidine incorporation and protein content was observed with cell culture media Na concentration of 130, 140 and 150 mmol/L. This effect was independent of osmolality (matched with mannitol) and no stimulatory effect occurred if choline was substituted for Na. Cells derived from sham‐operated (Sx) animals exposed to a higher media concentration of Na (150 vs 140 mmol/L) had both stimulated thymidine incorporation to 186.8 ± 35.41% (P<0.05) and enhanced cell protein content to 134.7 ± 135% (P<0.05). This effect was more pronounced in cell cultures derived from unilaterally nephrectomized (Nx) animals, being 212.8 ± 31.5% (P<0.01) for thymidine incorporation (P<0.05 vs cells from sham‐operated animals grown in high Na media) and 114.4 ± 3.2% (P<0.001) for protein content (P=0.11 vs sham‐operated cells grown in similar conditions). the addition of 10−4 mmol/L ethylisopropyl amiloride hydrochloride (EIPA) to Nx cells in a normal or high Na concentration media resulted in a decrease in cellular protein content to 82.6 ± 6.8% (P<0.05) and 85.5 ± 0.2% (P<0.0001) compared to respective controls. 10−4 mol/L EIPA in media supplemented with insulin‐like growth factor (IGF‐1) blocked the proliferative response normally seen in response to this growth factor from 156.6 ± 13.7 to 27.5 ± 3.1% (P<0.0001) compared to control. However, the presence of EIPA did not abrogate the hypertrophic response elicited by IGF‐1 (cell protein content 128.1 ± 13.1% of control with IGF‐1 vs 124.9 ± 12.5 with IGF‐1 and EIPA; P= n.s.). Addition of 10−4 mol/L EIPA to 10% serum derived from either Sx or Nx animals blocked the growth response to the sera, limiting the cellular protein content to 76.6 ± 5.5% (P<0.0001) and 89.7 ± 4.4% (P<0.0001) and thymidine incorporation to quiescent levels of 0.2 ± 0.1% (P<0.0001) and 0.4 ± 0.1% (P<0.0001) compared to respective controls. In summary, rat renal proximal tubular cell growth is influenced by Na concentrations in the cell culture environment and inhibited in the presence of EIPA. This supports a role for altered epithelial transport in the cellular growth response to a number of stimuli.
Low incidence of malignancies following renal transplantation in India
Authors: SAKHUJA Vinay , JHA Vivekand , GHOSH Amit K , SINGH Shrawan K , CHUGH Kirpal S
Published: April 2007

Summary: Renal transplant recipients have an increased incidence of certain malignancies. the nature of these malignancies varies with the geographic location and the nature of immunosuppressive therapy. There are no reports on the incidence and spectrum of cancers in renal transplant recipients from India. In a retrospective analysis of 294 patients followed up for more than 6 months after transplantation at our centre, we noted six malignancies in four patients, giving an incidence of 2%. Among 157 of those who were followed up for more than 2 years, the incidence was 3.8%. the mean duration of follow up was 5.8 years (range 6 months to 18.5 years). Cyclosporine was given for the first year after transplantation in 168 patients and 126 patients received only azathioprine and steroids. the interval between transplantation and development of malignancies varied from 24 to 169 months. the tumours included extranodal non‐Hodgkin's lymphoma (NHL) involving the central nervous system and small bowel and carcinoma of the tongue in one case each. the fourth patient, who survived for 14 years after transplantation, developed three squamous cell malignancies during this period: carcinoma of the cervix, perianal region and nasopharynx. Both patients with NHL died despite surgical excision of the tumour. None of the patients developed a cutaneous malignancy. In conclusion, renal transplant recipients living in a tropical environment have alow incidence of malignancies compared to those in temperate zones. This discrepancy can be explained by an absence of malignant tumours of the exposed skin in our patients. the absence of any tumours within the first 2 years is also unusual.
Attenuating effect of castration or oestrogen administration on glomerular injury in adriamycin‐induced nephropathy of rats
Authors: OHTSUKA Noriaki , SAKEMI Takanobu , TOMIYOSHI Yoshiyuki , MORITO Fumitake
Published: April 2007

Summary: To clarify the role of sex‐related factors in the development of focal segmental glomerulosclerosis (FSGS) we investigated the effect of castration or oestrogen administration in adriamycin (ADR)‐induced nephropathy of Sprague‐Dawley rats. At 6 weeks of age, group 1 (control group) and group 3 were shamoperated and group 2 was castrated. Adriamycin 2 mg/kg was administered intravenously to all rats at 8 weeks of age twice at a 20‐day interval. Group 3 was administered 0.2 mg oestrogen subcutaneously once a month. Bodyweight (BW) and urinary protein were measured every 4 weeks (mm 15 to 23 weeks of age. Blood pressure and serum constituents were measured at 15 and 23 weeks of age. Each group was studied morphologically at 23 weeks of age. Adriamycin induced massive proteinuria in group 1, whereas castration or oestrogen significantly attenuated proteinuria, accompanied by a significant reduction of urinary sex‐related low molecular weight (LMW) protein. the glomerulosclerosis index was significantly higher in the control group than in the castrated group or oestrogen‐treated group. Attenuation in glomerular injury was more associated with reduction of urinary sex‐related LMW protein than the reduction of serum testosterone. These observations suggest that sex‐related factors, such as a sex‐related LMW protein, influenced by castration or oestrogen administration may play a contributory role in the development of glomerulosclerosis in ADR‐induced nephropathy.
Detection of monocyte chemoattractant protein‐1 (MCP‐1) and its receptors in mesangial proliferative glomerulonephritis
Authors: YAMAUCHI Fumio , KASHEM Abul , ENDOH Masayuki , NOMOTO Yasuo , SAKAI Hideto
Published: April 2007

Summary: There are many reports suggesting that tissue damage in chronic glomerulonephritis (CGN) might be related to macrophages, and that a variety of chemotactic factors (intercrine or chemokine) activate macrophages. Monocyte chemoattractant protein‐1 (MCP‐1), a chemotactic cytokine, has been suggested to be both an important monocyte chemotaxin and activator in renal inflammation. Here, we studied the expression of MCP‐1 and its receptors, both common (CKR‐1), as well as specific (MCP‐la and MCP‐1b) in human renal tissues at mRNA levels by reverse transcriptase polymerase chain reaction (RT‐PCR) assay. Total RNA was extracted from renal tissues that were obtained from 40 patients. Separation of the glomeruli was performed in 17 patients. There was stronger MCP‐1 mRNA expression in the whole renal tissue samples than in the isolated glomeruli. the expression of MCP‐1 receptor was also greater in the whole tissue than in the glomeruli. Moreover, the expression of MCP‐1 mRNA was correlated with the levels of serum creatinine, creatinine clearance (Ccr) and interstitial tissue damage. Finally, our study shows the infiltration of macrophages was strongly demonstrated in the interstitium by monoclonal antibody (CD68) using the ABC method, and it has a correlation with the frequency of MCP‐1 positive group. We concluded that MCP‐1 might be connected with the pathogenesis of mesangial proliferative glomerulonephritis (mesPGN) and that interstitial events might be related to the progression of mesPGN.
The changing pattern of severe acute renal failure
Authors: BELLOMO Rinaldo , RONCO Claudio
Published: April 2007

Summary: The pattern of severe acute renal failure has changed considerably over the past 2 decades. Severe acute renal failure is now most commonly seen in the intensive care unit and is just one of the manifestations of the multi‐organ dysfunction syndrome. the pathogenesis of severe acute renal failure is complex involving decreased renal perfusion, humorally mediated renal vasoconstriction and local migration and activiation of inflammatory cells. the initial final common pathway to renal injury seems to be outer medullary ischaemia. Protection from renal dysfunction in critically ill patients must therefore be directed toward sufficient haemodynamic resucitation to avoid inadequate medullary perfusion. Such perfusion is highly dependent on the maintenance of optimal intravascular filling, adequate cardiac output and, importantly, adequate renal perfusion pressure. In these patients, such renal perfusion pressure can often only be maintained if vasopressor agents are used and titrated to keep the mean arterial pressure at the highest effective and safe level (mean arterial pressure of approximately 80–85 mmHg in most septic patients). If severe acute renal failure develops despite full medical support, renal replacement therapy becomes necesary. There is now a growing worldwide trend toward the use of continuous haemofiltration techniques as the preferred mode of renal replacement therapy. Such techniques provide important practical advantages and, in many cases, are the only form of renal replacement therapy that the patient is able to tolerate. Continous haemofiltration also appears to provide not only outstanding haemodynamic stability but also some membrane adsorption and removal of the humoral mediators of sepsis. This makes continuous haemofiltration a particularly attractive approach to renal support and is responsible for this treatment now being the leading form of acute renal replacement therapy in Australia. After a relatively static period, the area of acute renal failure management is rapidly evolving and offering some promise of a level of support able to match the illness severity associated with it.
The prospects for renal xenotransplantation
Authors: Van DENDEREN Bryce JW , PEARSE Martin J , D'APICE Anthony JF
Published: April 2007

Summary: Xenotransplantation of non‐human organs into human recipients has long been proposed as a possible strategy to overcome the acute shortage of donor organs. However, vascular organ transplants to humans from phylogenetically disparate species such as the pig are not currently possible due to a rapid rejection process termed hyperacute rejection. This process is initiated by the binding of host pre‐formed ‘natural antibodies’ to the donor vascular endothelium, activation of the host complement system and activation or injury of the donor endothelial cells, leading to intravascular coagulation and loss of the graft due to ischaemic necrosis within minutes to hours of engraftment. Prevention of natural antibody binding and complement activation is viewed as paramount to preventing hyperacute rejection. Even if hyperacute rejection can be prevented, further barriers to successful discordant xenografts such as delayed xenograft rejection and a donor‐directed cell‐mediated rejection process will still represent major obstacles. This review examines recent advances being made in the various areas of xenograft research and the potential clinical application of pig‐to‐human xenografts that these strategies may bring.
Ultrasonic ureteric jet study: A comparison with the voiding cystourethrogram for the detection of vesico‐ureteric reflux in children
Authors: MARSHALL Janicel , de CAMPO Margaret P , CARLIN John B , JOHNSON Neil D
Published: April 2007

Summary: The ultrasonic ureteric jet study is a non‐invasive method of measuring the distance between the midline of the bladder and the ureteric orifice (MOD). Statistical comparison with the results of single cycle voiding cystourethrograms (VCU) indicates that a normal MOD measurement on the ureteric jet study is a good predictor of the absence of vesico‐ureteric reflux (VUR). For ureters of children less than 4 years of age, a MOD ≤8mm has a negative predictive value of 83% (95% confidence interval; 74‐93%). For ureters of children aged 4‐10 years, a MOD ≤9mm has a negative predictive value of 91% (95% confidence interval; 86–97%). the ureteric jet study has the potential to identify children who do not have reflux, thus sparing them an unpleasant, invasive procedure.
Haemostasic markers in amyloid vs non‐amyloid uraemic patients on maintenance haemodialysis
Authors: HAZNEDAROǦLU İRbrahim C , ERDEM Yunus , ÇELIK İRsmail , DÜNDAR Semra , ÇAǦLAR ŞLali , KIRAZLI Serafettin
Published: April 2007

Summary: Haemostatic disturbances effect the prognosis in end‐stage renal disease. Several biological markers of blood coagulation and fibrinolysis have been described for quantitative determination of in vivo coagulation, including plasmin‐α2‐antiplasmin complex (PAP), D‐dimer, prothrombin fragment1+2 (PF 1.2) and thrombin‐antithrombin III complex (TAT). to investigate the influence of uraemia and/or amyloidosis on haemostatic system, eight patients (aged 31 ± 6 years) with systemic amyloidosis and 12 non‐amyloid patients (aged 36 ± 7 years) with end‐stage renal disease and 11 healthy volunteers (aged 36 ± 10 years) with normal renal functions as controls, constituted the study group. Mean plasma PAP concentration has been found to be elevated significantly in uraemic amyloid patients, when compared to that of non‐amyloids and normal subjects. In the uraemic patient group (amyloid vs non‐amyloid) mean plasma concentrations of Ddimer, PF 1.2 and TAT were not statistically different whereas these values were significantly higher than that of healthy controls. It is concluded that elevated in vivo coagulation markers (D‐dimer, PF 1.2 and TAT) favours an increased risk of thrombosis in uraemia, and PAP (the biomarker of active fibrinolysis) may indicate an additional risk of haemorrhagic tendency in amyloid patients in end‐stage renal failure.
Anaemia and endoscopic gastroduodenitis in pre‐dialysis patients
Authors: TAN Chorh C , KANG Jin Y , HO Khek Y , MANJIT K , van der STRAATEN Jane , LEE Evan JC
Published: April 2007

Summary: The extent of pre‐dialysis anaemia in Asian patients and the contribution of gastrointestinal blood loss to anaemia are unknown. of 76 new dialysis patients in our unit in 1994, 7.9% of patients had a haemoglobin (Hb)<6 g/dL; 53.9% had Hb≤6−<8 g/dL; 28.9% had an Hb≤8−<10 g/dL and 9.2% had Hb≤10 g/dL in the 2 months before dialysis. Gastroduodenoscopy in 38 patients 2 months pre‐dialysis (excluding 1 patient each with chronic duodenal ulcer and overt haemorrhagic gastritis), showed that 16.7% were normal, while the rest had mucosal erythema, erosions or petechiae alone or in combination. Haemoglobin was significantly lower in patients with endoscopic petechiae (n=23, Hb 7.24±1.28 g/dL) compared with those without (n=13, Hb 8.35±1.29 g/dL), although preceding blood transfusions were similar. No differences in Hb were noted in patients with or without endoscopic erythema or erosions, respectively. It is possible that occult blood loss associated with gastroduodenal petechiae exacerbates anaemia in chronic renal failure (CRF).
Renal disease in the Australian Aboriginal population: A pathological study
Authors: MOORE Lynette , LLOYD Megan S , PUGSLEY David J , SEYMOUR Anthony E
Published: April 2007

Summary: End‐stage renal failure and clinical evidence of renal disease are more frequent in Australian Aboriginals than in the non‐Aboriginal Australian population. to investigate the lesions responsible for this excess a systematic study of renal biopsy findings in a series of Aboriginal patients in South Australia and the Northern Territory was performed and the data on these patients were compared with a consecutive series of renal biopsy findings in non‐Aboriginal patients. Histological and morphometric comparison was made between biopsies from 206 Aboriginal and 690 non‐Aboriginal patients. the distribution of glomerular lesions was found to differ significantly between the Aboriginal and non‐Aboriginal groups: diabetic glomerulosclerosis, idiopathic glomerular enlargement (glomerulomegaly), mesangiocapillary glomeru‐lonephritis (MCGN), and non‐IgA mesangiopathic glomerulonephritis (GN) were found more frequently in the Aboriginal population, whereas there were fewer than expected examples of thin membrane nephropathy, minimal change disease and membranous GN. Diabetic glomerulosclerosis was significantly more frequent, and the lesions more severe, in Central Australia (where diabetes is more prevalent) and glomerulomegaly was especially common in Bathurst Island. These two conditions accounted for one third of the series and evidence is presented to suggest that a substantial proportion of renal disease in Aboriginals may be the consequence of conversion to a Western life style. of the 206 Aboriginal patients, 23 presented with chronic renal failure, suggesting either late presentation or unusually aggressive renal lesions, and 10 had end‐stage renal disease on biopsy.
24R, 25‐Dihydroxyvitamin D3 ameliorates the high‐turnover bone diseases without suppressing parathyroid function in chronic renal failure in rats
Authors: KAZAMA Junichiro J , WA Masafumi FUKAGAWA , YI Hung , KUMAGAI Miki , YAMATO Hideyuki , TANIGUCHI Nobuyuki , GEJYO Fumitake , ARAKAWA Masaaki , OZAWA Hidehiro , KUROKAWA Kiyoshi
Published: April 2007

Summary: To evaluate the effect of 24R,25‐dihydroxyvitamin D3 (24,25D) on uraemic bone disease, we treated the model rats of mild renal failure either with 0.5 μg/kg bodyweight (BW) of 24,25D, or with 5 μg/kg BW of 24,25D, or with 0.01 μg/kg BW of 1,25‐dihydroxyvitamin D3 (1,25D), or with 0.01 μg/kg BW of 1,25D and 0.5 μg/kg BW of 24,25D, or with vehicle alone, given orally for 16 weeks. the examination of bone histology revealed extreme acceleration of bone turnover and decreased trabecular bone volume with elevated serum parathyroid hormone (PTH) level in vehicle‐treated uraemic rats compared with those of sham‐operated rats. Treatment with 24,25D (5 μg/kg BW) not only ameliorated high‐turnover bone disease as with 1,25D, but also prevented the reduction of trabecular bone volume without any changes of serum PTH levels, suggesting the possible direct effect of 24,25D on the bone. Our data suggest 24,25D may be another useful agent for the treatment of high‐turnover bone disease caused by secondary hyperparathyroidism in chronic renal failure, with less suppression of parathyroid function.
Delayed‐type hypersensitivity mediates Bowman's capsule rupture in Tamm—Horsfall protein‐induced tubulointerstitial nephritis in the rat
Authors: SONG Qing , NIKOLIC‐PATERSON David J , ATKINS Robert C , BACHER Michael , BUCALA Richard , LAN Hui Y
Published: April 2007

Summary: It is generally thought that disruption of Bowman's capsule, a feature of progressive forms of glomerulonephritis, is mediated by leucocytes which accumulate within Bowman's space. However, we have recently shown that periglomerular T cell and macrophage accumulation is associated with Bowman's capsule rupture irrespective of crescent formation in rat crescentic glomerulonephritis. Thus, to determine whether periglomerular leucocytes can mediate rupture of Bowman's capsule, we have examined Bowman's capsule integrity in a model of immune cell‐mediated interstitial nephritis which is devoid of glomerular inflammation. Tubulointerstitial nephritis was induced in rats by repeated immunization with autologous Tamm‐Horsfall protein (THP) or adjuvant alone (control) and groups of animals were killed on weeks 26, 30 and 34. All animals immunized with autologous THP developed a humoral immune response to the antigen as measured by serum antibodies. In addition, a cellular immune response to autologous THP was demonstrated by a skin delayed‐type hypersensitivity (DTH) response and prominent interstitial T cell and macrophage infiltration around THP+ tubules. Marked periglomerular leucocyte infiltration developed around some glomeruli in association with granular THP deposition and increased local expression of intercellular adhesion molecule‐1 (ICAM‐1) and the classic DTH associated cytokine macrophage migration inhibitory factor. On week 26 of the disease, disruption of Bowman's capsule was evident in 5.5 ± 2.8% of glomeruli and this increased to 9.5 ± 4.8% of glomeruli by week 34. Disruption of Bowman's capsule integrity was invariably associated with THP deposition and a significant periglomerular infiltrate of T cells and macrophages, whereas glomeruli with little periglomerular infiltration retained an intact Bowman's capsule. Strong lysozyme staining of macrophage‐like cells at sites of rupture suggest that degradation of Bowman's capsule was mediated by macrophages through the production of proteolytic enzymes. In conclusion, these results demonstrate that periglomerular leucocytes can cause Bowman's capsule rupture through a DTH mechanism.
Tubulointerstitial injury in glomerulonephritis
Authors: ATKINS ROBERT C , NIKOLIC‐PATERSON DAVID J , LAN HUI Y
Published: April 2007

Summary: It is now widely accepted that tubulointerstitial lesions correlate with renal function in glomerulonephritis and that the severity of such lesions predicts disease progression. Interstitial leucocytic infiltration is a prominent feature of tubulointerstitial lesions which also correlates with renal function and outcome in human glomerulonephritis, while intervention studies in animal disease models have demonstrated a causal role of these cells in progressive tubulointerstitial injury. This paper focuses on two aspects of immune‐mediated tubulointerstitial injury. First, the development of interstitial leucocytic infiltration and the relationship between periglomerular leucocytes and Bownman's capsule integrity, and second, the concept that tubular cells are not only passive targets of injury in glomerulonephritis, but that they actively participate in the immune/inflammatory process.
Clinical correlates with microalbuminuria in non‐insulin dependent diabetes: Preliminary results of the appropriate blood pressure control in diabetes trial
Authors: SCHRIER ROBERT W , ESTACIO RAYMOND O
Published: April 2007

Summary: Clinical correlates associated with urinary albumin excretion (UAE) in non‐insulin dependent diabetes (NIDDM) are less well known than in insulin dependent diabetes (IDDM). We therefore performed a cross sectional study examining the relationships of clinical risk factors and diabetic complications with UAE in 950 NIDDM patients. the UAE status was classified into the following categories: (i) no albuminuria (<20 μmg/min), (ii) microalbuminuria (20–200 μg/min); and (iii) overt albuminuria (>200 μg/min). Univariate and miltivariate analyses were initially performed evaluating the associations between clinical risk factors and UAE. Univariate and multivariate analyses were then performed examining the relationships between UAE and the diabetic complications (retinopathy, neuropathy and cardiovascular disease). Using multivariate logistic regression analyses controlling for diabetes duration, glycosylated haemoglobin, gender and race, the most significant predictors of microalbuminuria and overt albuminuria were systolic hypertension, increased body mass index (BMI), decreased high‐density lipoprotein (HDL) cholesterol, insulin use and smoking pack years. Univariate and multivariate analyses evaluating the associations between UAE and diabetic complications revealed that UAE was a strong predictor of retinopathy (odds ratio [OR]=1.31:95% confidence interval [CI]=1.05,1.66), neuropathy (OR=1.47; CI=1.19,19.83), and cardiovascular diseases (OR=1.28; CI=1.05,1.52). Thus, in the present study increases in UAE were associated with retinopathy, neuropathy and cardiovascular disease. Urinary albumin excretion may therefore be a marker of diffuse vascular disease in NIDDM. Aggressive treatment of smoking, cholesterol and hypertension may not only diminish UAE but may also play a significant role in decreasing the other NIDDM vascular complications.
Neurohormonal factors in the pathogenesis of essential hypertension
Authors: NICHOLLS M GARY , RICHARDS A MARK
Published: April 2007

Summary: The level of arterial pressure in an individual is dictated by many interacting factors including neurohormonal systems. Heightened activity of pressor systems could contribute to the pathogenesis of essential hypertension; evidence for this is strongest for sympathetic overactivity in some young patients. Inadequacy of vasodilator systems, especially natriuretic peptides or nitric oxide, has also been suggested as central to the pathogenesis of essential hypertension although evidence is far from definitive. the existence of authentic ouabain in human plasma, let alone its pathophysiological importance in hypertension, is now in doubt. Information is awaited regarding the role of the endothelins and adrenomedullin in physiology and in essential hypertension.
Hepatitis C and glomerulonephritis
Authors: EKNOYAN GARABED
Published: April 2007

Summary: Several systemic viral infections have been associated with the development of glomerular lesions. of the viruses that cause liver disease hepatitis B was the first to be recognized. the recent availability of serologic tests for the hepatitis C virus (HCV) has uncovered an association between HCV infection and renal disease. the principal glomerular lesion that develops is that of a membranoproliferative glomerulonephritis (MPGN), usually in association with antigenaemia and circulating immune complexes that have the characteristics of mixed cryoglobulinaemia represented by polyclonal IgG and monoclonal IgM with rheumatoid factor activity. the presence of a very high percentage of anti‐HCV seropositivity in cryoglobulinaemic forms of MPGN suggests that the virus plays an important role in the pathogenesis of the associated immune complex glomerulonephritis. Precipitates containing HCV‐RNA and circulating anti‐HCV IgG and IgM have been found in the majority of such cases. the course of the renal disease that develops is progressive. Treatment with interferon alpha appears to attenuate the progression of the renal lesions, and the response to treatment appears to be closely related to the clearance of hepatitis C viraemia. Renal lesions also occur in the absence of clinical evidence of liver disease or mixed cryoglobulinaemia. In addition to MPGN, membranous glomerulonephropathy, IgA nephropathy and focal segmental glomerulosclerosis have been reported in these cases of HCV infection. the prevalence of glomerular lesions in patients with HCV infection remains to be determined. the available serologic tests for HCV are still in evolution. In the meantime, all patients presenting with glomerular disease should be screened for HCV.
Approach to the patient with metabolic acidosis: Newer concepts
Authors: HALPERIN ML , KAMEL K
Published: April 2007

Summary: A new classification for patients with metabolic acidosis is provided: a pathophysiological classification. to recognize an overproduction of acids which results in a hydrogen ion (H+) gain the number of new anions retained in the body is added to those excreted in the urine when the cation accompanying them was not H+ or ammonium (NH4+). the first tools are to recognize new anions that were added during the overproduction of acids. the nature of these anions can be recognized by assessing their fractional excretion. the second set of tools focuses on an assessment of NH4+ in the urine using urine anion and osmolar gaps. the clinical approach suggested focuses on detecting an emergency (severity of H+ accumulation, toxic alcohols and/or dyskalaemias). the second step analyzes the expected responses to acidaemia; here the focus is on the PCO2 in vital organs and the rate of excretion of ammonium. the principles used for diagnosis and treatment of metabolic acidosis are illustrated by a case example.