摘要:

Vascularized pancreas transplantation has assumed an increasing role in the treatment of diabetes mellitus. Through 1994, over 6000 pancreas transplants had been performed worldwide, with over 80% being combined pancreas-kidney transplants. Overall 1-year patient survival exceeds 90% and graft survival (complete insulin independence) exceeds 70%. Although successful pancreas transplantation achieves euglycemia and complete insulin independence, this occurs at the expense of hyperinsulinemia and chronic immunosup-pression. The net effect of these changes on diabetic complications in the long term remains to be determined. In the short term, improvement in the quality of life and possible prevention of further morbidity associated with diabetes makes pancreas transplantation an important therapeutic option, particularly when combined with a kidney transplant, in appropriately selected diabetic patients.

ISSN:0886-022X    

DOI:10.3109/08860229509037599

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

Small peptide molecules known as low molecular weight growth factor (LMW-GF) have been identified in human serum. They enhance the effect of IGF-1 (insulin-like growth factor) on proteoglycan synthesis. In the present work we investigated the role played by the kidney in the production of LMW-GF, using the pig as an experimental model. Six pigs underwent bilateral nephrectomy followed 24 h later by orthotopic autotransplantation of the kidney. Renal and liver functions were evaluated by measurement of serum creatinine, urea, electrolytes, amino transferases (ASAT, ALAT), proteins, and bilirubin. LMW-GF was measured by bioassay using 11-day-old pelvic chick embryo cartilages. We observed that LMW-GF quickly disappeared from pig serum after nephrectomy and only reappeared when transplantation was successful. Reappearance of LMW-GF can precede improvement of renal function evaluated by plasma creatinine levels. These data appear to demonstrate that the kidney is involved in LMW-GF production.

ISSN:0886-022X    

DOI:10.3109/08860229509037600

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

The changes in kidneys of streptozotocin (STZ)-induced diabetic rats fed a low-zinc (LZ) diet were observed. Calcium deposits were detected in the LZ-diabetic groups from the 2nd to the 8th week. The deposits were mainly detected in the corticomedullary junction, and found in the tubular lumina and epithelial cytoplasm and interstitium. Tubular morphological changes, including luminary distension, epithelial flattening, and paleness of cytoplasm and nuclei, were observed near the calcium deposits in the LZ-diabetic group over the 2nd week. Moreover, at the 8th week, wedge-shaped vasogenic lesions were found on the surface of the renal cortex in the LZ-diabetic group. No changes were detected in the control for the LZ or in the diabetic group fed a standard (SC) diet. When STZ was administered, plasma glucose level in groups fed LZ or SC diet increased in the 1st week, and over the 2nd week, glucose level was maintained at more than 400 mg/dL. Glucose level of the LZ-diabetic group did not differ from that of the SC-diabetic group. However, urinary N-acetyl-β-D-glucosaminidase activity of the LZ-diabetic group at the 8th week was significantly higher than that of the SC-diabetic group. These findings suggested that low-zinc diet hastens renal damages in diabetic rats.

ISSN:0886-022X    

DOI:10.3109/08860229509037601

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

Angiotensin I converting enzyme (ACE) activity was measured in serum, urine, and tissues of rats with acute renal failure (ARF) induced by glycerol. Glycerol-injected rats were subdivided in three groups according to the urinary volume: oliguric, nonoliguric, and polyuric. The damage to the proximal tubule was evident by (a) the histological analysis at light and electron microscopy level, (b) the augmented urinary excretion of the enzymes dipeptidyl aminopeptidase IV and N-acetyl-β-D-glucosaminidase, and (c) the low molecular weight proteinuria pattern. On the other hand, the appearance of the glomeruli at the ultrastructural level was normal. These data suggest that the increased urinary excretion of enzymes and proteins in these rats is a consequence of the tubular injury. ARF was markedly higher in the oliguric rats. Urine ACE activity increased in the rats of the three groups, but statistical significance was reached only in the oliguric rats. Serum ACE activity increased in the oliguric rats and tissue ACE activity did not change. It is concluded that the high urinary ACE in glycerol-treated rats is associated with the damage to the kidney tubules. These data support the contention that urinary ACE may be another marker of injury to the proximal tubule.

ISSN:0886-022X    

DOI:10.3109/08860229509037602

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

Angiotensin I converting enzyme (ACE) was measured in urine, serum, and tissues from rats with acute renal failure (ARF) induced by a single subcutaneous injection (15 mg/kg BW) of uranyl nitrate (UN). Urine was collected daily until day 5, when rats were sacrificed by decapitation for the obtention of blood serum and tissues. Other groups of rats were sacrificed on days 1 and 2. These rats showed proteinuria and polyuria. The damage to the kidney proximal tubule was shown by (a) histological analysis at light and electron microscopy levels on days 1, 2, and 5, (b) the increase in urinary excretion of dipeptidyl aminopeptidase IV and N-acetyl-β-D-glucosaminidase on days 1–5, and (c) the low molecular weight proteinuria pattern on day 1. In addition, the histological analysis at the ultrastructural level showed normal glomeruli appearance on days 1 and 2, but structural alterations on day 5. These data suggest that the increased urinary excretion of enzymes and proteins is a consequence of the tubular injury on days 1 and 2, and of tubular and glomerular injury on day 5. ACE activity increased in urine on days 1–5 and in serum on day 5. Tissue ACE activity increased in lung, small intestine, and adrenal glands; and remained unchanged in testis, aorta, brain, kidney, heart, and liver. Our data suggest that: (a) the increase in serum ACE may be secondary to the changes in tissue ACE activity, and (b) the urine ACE increase may be due to the kidney proximal tubule damage. This work supports the contention that an increase in urine ACE may be an indicator of injury to the proximal tubule.

ISSN:0886-022X    

DOI:10.3109/08860229509037603

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

This study was designed to examine if acute systemic blockade of nitric oxide (NO) production by inhibition of nitric oxide synthase (NOS) with N-ω-nitro-L-arginine methyl ester (L-NAME) would worsen the severity of ischemic acute renal failure (ARF). Initially three groups of rats, were studied: 45 min of bilateral renal ischemia (I) alone, Group I; L-NAME (L; 10 mg/kg BW, i.v.) alone, Group L; and L-NAME administered 15 min before renal ischemia, Group L+I. We observed, however, a 60% mortality in Group I+L during the first 4 h of reflow. Captopril, administered acutely 15 min before L-NAME in an attempt to offset any detrimental effects of increased angiotensin II generation in response to renal ischemia, failed to obviate the mortality because 67% of rats in this group (Group C+L+I) also died. Therefore, additional studies were performed in rats instrumented for cardiovascular studies to evaluate the acute hemodynamic responses during the first 90 min of reperfusion following renal ischemia in rats pretreated with L-NAME. As expected, L-NAME injection was accompanied by a 25–30 mm Hg increase in mean systemic arterial pressure (SAP) (p<0.05), a bradycardia (p<0.02), and a decrease in cardiac output (CO) (p<0.02). The increase in SAP was due exclusively to an increase in systemic vascular resistance (SVR) (p<0.01). Ischemia and reflow in the L-NAME-treated rats were attended by a progressive increase in SVR and a progressive decrease in CO such that by the end of 45 min of reperfusion SVR had increased 10-fold and CO had decreased to one third of its initial rate (both p<0.02). Pulmonary artery pressure (PAP) increased promptly following L-NAME injection. Total pulmonary resistance (PRT) increased significantly by the end of reperfusion. L-NAME in combination with renal ischemia and reflow induces a large increase in both SVR and PRT, and is accompanied by a 70% reduction in CO and substantial mortality.

ISSN:0886-022X    

DOI:10.3109/08860229509037604

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

We examined rat kidneys for serial expressions of two major heat-shock proteins (HSPs), HSP73 and HSP90, after 60 min of unilateral renal ischemia up to day 28. Immunohistochemical studies showed that HSP73 and HSP90 were rapidly induced in the cytoplasm of injured epithelial cells of the S3 segment of proximal tubules and were again induced in the cytoplasm of regenerative cells in this segment from day 3. In epithelial cells of the Henle's loops, HSP90 was also induced in the cytoplasm of both injured and regenerative cells, but HSP73 was not induced in this portion. Furthermore, a transient accumulation of HSP73 into the nucleus was observed in epithelial cells of papillary collecting ducts shortly after ischemia. Serial immunoblot analysis of isotonic buffer extractable fractions from ischemic kidneys revealed the induction of both HSP73 and HSP90 in the degenerative and regenerative phases: the maximal inductions in the two phases were at 3–6 h and on days 5–7, respectively. These results demonstrate that HSP73 and HSP90 are induced in injured tubular epithelial cells with a regional heterogeneity during the degenerative and regenerative phases after renal ischemia and suggest that these HSPs are involved in the process of postischemic cellular recovery.

ISSN:0886-022X    

DOI:10.3109/08860229509037605

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

Removal of extracellular calcium has been demonstrated to improve membrane integrity of rodent myocytes, astrocytes, and renal tubular cells injured by hypoxia. In this study, the effect of extracellular calcium on long-term survival of cultured human proximal tubular epithelial cells (PTEC) subjected to hypoxia was evaluated. In addition, the effect of extracellular calcium on release of arachidonic acid metabolites (AAM) was assessed during and after hypoxia. To induce hypoxic injury, PTEC were incubated in an anaerobic chamber in glucose-free buffer (combined oxygen/glucose deprivation, COGD). Long-term survival was assessed by measuring lactate dehydrogenase (LDH) efflux during COGD and after an additional 24-h“recovery'’period (in routine culture medium in 95% air/5% CO2). To determine if extracellular calcium influenced AAM release from membrane phospholipids, cells were preincubated with [3H]arachidonic acid and the release of AAM was measured during COGD and recovery. With this model system, PTEC exhibited minimal LDH efflux during≤12 h COGD, but LDH efflux increased to 73.9±4.7% by 24 h COGD. With 12–18 h of COGD, the extent of LDH efflux was greater during recovery than during COGD, indicating that, for human PTEC, the extent of membrane damage does not become fully evident by LDH efflux for hours after hypoxia. PTEC exposed to 24 h of COGD in the absence of extracellular calcium exhibited strikingly less LDH efflux during COGD than cells incubated in the presence of extracellular calcium, suggesting that extracellular calcium contributes to membrane damage during COGD. However, upon reexposure of PTEC to extracellular calcium, LDH efflux rapidly increased to control levels. Furthermore, despite allowing cells to recover in oxygen or oxygen and glucose before exposure to calcium-containing medium, a rapid increase in LDH efflux could not be avoided. These results suggest that COGD induces an irreversible injury that ultimately leads to loss of membrane integrity whether or not extracellular calcium is present; however, extracellular calcium accelerates the loss of membrane integrity caused by hypoxia. Extracellular calcium did not alter AAM release, indicating that the effect of extracellular calcium on membrane damage (as indicated by LDH efflux) was not mediated by an increased activity of phospholipases (such as phospholipase A2) that are involved in the release of AAM.

ISSN:0886-022X    

DOI:10.3109/08860229509037606

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

The syndrome of progressive ischemic gangrene (PIG) of the extremities was examined over 3.5 years in patients undergoing maintenance dialysis (MD) in Kuwait and was compared to that in a similar age group (>40 years) in the general population. The incidence of PIG in MD patients was 15.4/1000 person years of observation (PYO) versus 0.086/1000 PYO in the general population. Patients with diabetes mellitus were found to be at particular risk. PIG developed in 41.4/1000 PYO of diabetic patients who received MD, compared to 7.1/1000 in nondiabetic patients on MD and 0.14/1000 in diabetics without renal disease. The clinical, biochemical, radiological, and histological findings in the 8 patients who developed PIG while on maintenance dialysis (MD) are presented. Two patients had severe hyperparathyroidism and their histological findings were consistent with systemic calciphylaxis. Histological examination, in the remaining patients, showed severe calcified atherosclerosis. Intimal hypertrophy was common especially in patients with long duration on dialysis. The three lesions produced a variable degree ofluminal narrowing and were associated with arterial thrombosis. None of the patients showed evidence of iron deposition even in those with systemic calciphylaxis and excessive iron stores. Our study indicated a high incidence of PIG in patients undergoing MD, especially in those with diabetes mellitus. These findings constitute a cogent argument in favor of early parathyroidectomy in selected cases and concern with long-term consequences of atherosclerosis in this patient population.

ISSN:0886-022X    

DOI:10.3109/08860229509037607

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

We investigated the frequency of IgA nephropathy in transplanted kidneys in 2 ethnic groups in New Mexico (USA). A total of 80 renal graft biopsies were obtained from 66 patients when clinically indicated for the differential diagnosis of graft dysfunction. Glomerulonephritis was present in 16 patients, in biopsies obtained after the first posttransplantation month. The frequency of IgAN in allografts was not the same in Native Americans and in Caucasians: Nondonor IgAN was observed in 4/18 biopsies from Native American patients (22.2%) but only in 4/48 biopsies from Caucasians (8.3%) (p<0.01). This study demonstrates that in New Mexico the frequency of IgAN in transplanted kidneys in Native American patients is 2.7 times higher than in Caucasian graft recipients.

ISSN:0886-022X    

DOI:10.3109/08860229509037608

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor