摘要:

The burgeoning literature on glomerulosclerosis makes frequent review of the literature necessary. At this stage, the key processes involved have surely been defined. It is now appropriate to make deductions about possible therapies and to plan experiments and trials.

ISSN:0886-022X    

DOI:10.3109/08860229409044883

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

Diabetes mellitus is now the most common cause of end-stage renal disease (ESRD) in the U.S., and the percentage of ESRD patients with diabetes is increasing yearly. One-year survival in such patients is poorer than in those with other etiologies of ESRD but has improved from 64% to 74% over the past decade. However, overall 5-year survival on dialysis is still less than 20% in this population. It is controversial whether hemodialysis or peritoneal dialysis (CAPD, CCPD) is the best choice. Advantages of hemodialysis include its ready-availability and convenience for patients, who are frequently incapacitated by blindness, cerebrovascular disease, and/or amputations. However, patients may tolerate dialytic ultrafiltration poorly due to autonomic neuropathy. Maintenance of vascular access is difficult, which may contribute to inadequate dialysis in some patients. Cardiovascular disease remains the most common cause of death. Management of coronary artery disease is difficult because of the high prevalence of silent ischemia. Control of blood pressure is of paramount importance in preventing cardiovascular complications. Improved survival in diabetics who were dialyzed in a more intensive than usual fashion has been reported recently. In addition, much of the difference in survival rates between diabetics and nondiabetics can be accounted for by the poorer nutritional status in the former group. Thus attention to the dose of dialysis administered and assurance of adequate nutrition should result in improved survival of the diabetic patient on hemodialysis.

ISSN:0886-022X    

DOI:10.3109/08860229409044884

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

Nitric oxide (NO) is involved in the regulation of renal perfusion and glomerular hemodynamics under basal conditions. We examined the hypothesis that L-arginine-derived NO modifies ischemic acute renal failure (ARF) in the rat. After a basal period ischemia was induced by clamping of both renal arteries (40 min). Thereafter, in the reperfusion period, we intravenously infused L-arginine (Arg, 300 mg/kg/60 min), or L-monomethylarginine (MeArg, 30 mg/kg/60 min), or Arg + MeArg (300 mg/kg/60 min, 30 mg/kg/60 min, resp.). Besides monitoring of urinary flow rate and arterial blood pressure, and determination of sodium excretion, glomerular filtration rate (GFR, mL/ min/100 g) was estimated at the end of the infusion period and again after another 30 and 120 min by inulin clearance (fluorescene-marked inulin). In the basal period GFR showed no differences between the groups (Arg:0.86±0.07, MeArg:0.92±0.06, Arg + MeArg:0.89±0.08, control:0.84±0.07). At 180 min after the beginning of the reperfusion period, GFR was 0.13±0.02 in the control group. After administration of Arg, a remarkable and persistent increase in GFR was observed (0.28±0.03), whereas infusion of MeArg showed no significant effects (0.13±0.04). Combined administration of Arg + MeArg revealed a moderate increase of GFR (0.19±0.05), ranging between the Arg and the control group. Also, 60 and 90 min after the beginning of the reperfusion period, the highest values for GFR were obtained in the Arg group. We conclude that in this model of ischemic ARF in the rat, L-arginine-derived NO is capable of improving renal function. These data underline the regulatory role of the L-Arg-NO pathway for renal function, not only under normal conditions, but also in ARF.

ISSN:0886-022X    

DOI:10.3109/08860229409044885

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

The first part of this study evaluates a new paired microinjection technique for studying single-nephron permeability (in this case to calcium) following injection of 5–10 nL of a Ringer solution into a superficial proximal tubule. The mean difference in fractional45Ca recovery from two identical microinjections into the same nephron site was 2.2±0.2% for 89 paired microinjections. Individual nephrons therefore normally show differences in calcium permeability with time. However, moment-to-moment variations in ion transport in any one nephron are in a random direction; differences cancel one another out if enough experiments are performed. The technique thus appears well suited to studies where comparisons are made between the acute nephron responses to two test solutions. It specifically overcomes problems of nephron heterogeneity seen in some other micropuncture techniques. The second part of this study uses the new technique to investigate the effects of a raised intratubular d-glucose concentration on single-nephron calcium transport. Urinary45Ca recoveries from late proximal microinjections were significantly higher when d- (as opposed to L-) glucose was included in the injectate (6.87±0.88 vs. 5.24±0.50%; p<.02). The ability of d-glucose to depress tubular calcium reabsorption at distal nephron sites may contribute to the observed hypercalciuria following systemic d-glucose loading. It may also be relevant to the acute renal failure accompanying renal stone disease, where a relationship between hyper-calciuria, urolithiasis, and the consumption of refined carbohydrates has been proposed.

ISSN:0886-022X    

DOI:10.3109/08860229409044886

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

Acute tubular necrosis induced by aminoglycoside antibiotics and various other nephrotoxins is followed by a regenerative process which leads to the restoration of damaged tubules. Several lines of evidence indicate that tubular regeneration is mediated by polypeptide growth factors such as epidermal growth factor (EGF). Previous studies devoted to cisplatin nephrotoxicity have shown that this agent causes tubular cystic degeneration possibly related to an impairment of renal tissue repair. Thus, we examined on a comparative basis the time course of the regenerative response subsequent to tubular damage induced by tobramycin or cisplatin, particular attention being paid to renal EGF and its receptor. Female Sprague-Dawley rats (160–180 g body weight) were treated during 4 consecutive days with daily doses of 200 mg/kg tobramycin i.p. (BID) or 2 mg/kg cisplatin (once a day). Sham-treated rats were given 0.9% NaCl i. p. following the same protocol. Groups of experimental animals (n = 5–10) were terminated at increasing time intervals (1, 4, 7,14, 21, 60 days) after cessation of treatment. One hour prior to sacrifice, each individual received i.p. 200 mg/kg 5-bromo-2'-deoxyuridine (BrdU)for the immunohisto-chemical demonstration of cell proliferation. Blood was collected at the time of sacrifice in order to assess glomerular filtration rate by measuring serum creatinine and BUN levels. Kidneys were analyzed with respect to total EGF determined by RIA in renal tissue homogenates, and soluble EGF was assayed in extracts prepared by centrifugation. Renal tissue was processed for the immunohistochemical detection of S-phase cells, of EGF, of EGF receptors, and of the intermediate filament vimentin, the latter being used as a marker of epithelium dedifferentiation. In absence of nephrotoxic alterations, EGF was immunolocalized in distal tubules, whereas EGF receptor immunostaining was seen in proximal tubules cells. Vimentin immunostaining was confined to glomeruli and blood vessels. Tobramycin and cisplatin caused acute tubular necrosis in proximal convoluted tubules and proximal straight tubules, respectively. Tissue damage was accompanied by renal dysfunction reflected by an elevation of serum creatinine and BUN levels. Tubular necrosis was followed by a proliferative response indicative of tubular regeneration. Regenerative hyper-plasia was associated with a reduction of total immunoreactive EGF due to a decrease of tissue-bound proEGF. Tubules undergoing regenerative repair were characterized by a disappearance of EGF receptors and the presence of immunoreactive vimentin. In tobramycin-treated rats, renal dysfunction lasted for 4–7 days and was fully reversible, as indicated by the return of serum markers to normal values. Accordingly, tubular regeneration had led to the restoration of tubular epithelium in approximately 7–14 days. Moreover, the reduction of proEGF in renal tissue, and the loss of EGF receptors and vimentin expression in regenerating tubules occurred as a sequence of transient events so that kidneys had resumed a normal appearance by 14 days. In contrast with what was observed after exposure to tobramycin, cisplatin administration induced a protracted renal impairment probably related to a defective tissue repair. Kidneys of treated animals displayed a persistent depletion of immunoreactive proEGF. In addition, cystic tubules developing in the long term after exposure to cisplatin remained devoid of EGF receptors and exhibited continuous vimentin expression. The current study suggests that renal tubules damaged by cisplatin cannot undergo normal regeneration and probably remain in a dedifferentiated state.

ISSN:0886-022X    

DOI:10.3109/08860229409044887

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

Lipid profile and postheparin lipolytic activity (PHLA) were investigated in 21 patients with acute renal failure (ARF), 24 with chronic renal failure (CRF), and 23 healthy volunteers. Plasma triglycerides were significantly elevated in ARF (155.19±72.39 mg/dL) as well as CRF (166.79±72.36 mg/dL), as compared to controls (89.91±23.41 mg/dL, p<.001). PHLA was determined at 5, 10, 30, and 60 min after intravenous heparin (100 U/kg) and was observed to be reduced in ARF (7.82±1.41µmol FFA/mL/h) as well as CRF (8.44±1.68µmol FFA/mL/h) at 10 min, as compared to the values in the control subjects (12.03±2.43µmol FFA/mL/h, p<.01). No correlation was found between PHLA and plasma triglycerides in ARF or CRF. In 15 patients in each group, PHLA subfractions, hepatic triglyceride lipase (HTGL), and lipoprotein lipase (LPL) were determined at similar time intervals after heparin. Both fractions were found to be reduced significantly (p<.01) in ARF as well as in CRF versus controls. These findings indicate that the lipid alterations in acute and chronic renal failure share common features including hyper-triglyceridemia and reduced PHLA and its subfractions HTGL and LPL.

ISSN:0886-022X    

DOI:10.3109/08860229409044888

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

Seven patients with histologically proven IgA nephropathy and modest impairment of renal function, and 2 patients with IgA nephropathy and nephrotic syndrome were investigated, compared to a control group of 9 healthy individuals, to study the effects of amino acids on glomerular and tubular function, and to evaluate renal functional reserve in IgA nephropathy with different clinical course. Inulin and PAH clearances were used to evaluate glomerular filtration rate (GFR) and effective renal plasma flow (ERPF); proximal and distal tubular fluid delivery and reabsorption were measured by lithium clearance, before and after submission of a standardized amino acid solution. GFR and ERPF increased significantly during amino acid load in healthy individuals and patients without nephrotic syndrome, while filtration fraction (GFR/ERPF) remained constant. Lithium clearance (CLi) and fractional lithium excretion (CLi/GFR) rose significantly in both groups, whereas the reabsorbed volume of fluid in the proximal tubule did not change. In the distal tubule, fractional volume excretion decreased significantly during amino acid load whereas the reabsorbed volume significantly increased. Baseline values of the two groups did not differ significantly. Two patients with nephrotic course of IgA nephropathy showed a distinct decrease in glomerular and tubular function, and a loss of renal functional reserve after amino acid load. Conclusions: Despite distinct alterations in renal biopsy, IgA nephropathy without nephrotic course presents with a still adequately preserved kidney function and renal functional reserve. A single determination of renal function with noninvasive functional tests does not give valid prognostic information concerning glomerular and tubular function. Therefore, a repeated measurement of renal function at defined intervals might reveal clinical progression of renal disease. The results of the lithium clearance might indicate an increase in tubular function after amino acid load, indicating a tubular adaptation in state of hyperfiltration.

ISSN:0886-022X    

DOI:10.3109/08860229409044889

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

Clinical variables and laboratory and histologic findings were evaluated in 53 children with IgA nephropathy, of whom 44 were followed for a mean period of 6,2 years (range 1.2–14). At the end of the follow-up 8 patients (18.2%) had had no urinary anomalies for at least 1 year (stage A disease), 28 (63.6%) had microscopic hematuria with proteinuria1 g/m2/day (stage C), and 3 (6.8%) had chronic renal insufficiency (stage D). None of the patients in apparent remission presented with elevated serum IgA levels at disease onset. Gross or microscopic hematuria at onset correlated with stage A/B disease at the end of follow-up (p.05). Presenting features of gross or microscopic hematuria without or with proteinuria (<0.5 g/m2/day) correlated (p<. 001) with minimal glomerular abnormalities at biopsy, whereas patients with nephritic syndrome had more severe histologic pictures. The presence of proliferative glomerulonephritis with crescents correlated (p<. 0001) with poor outcome. The results demonstrate that the prognosis of IgA nephropathy in childhood must be viewed with caution and that outcome correlates with mode of onset and severity of the renal pathology.

ISSN:0886-022X    

DOI:10.3109/08860229409044890

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

We prospectively measured lipid peroxidation following reperfusion during 44 renal allograft transplant operations. Twenty-four (55%) recipients were taking nifedipine pre- and then postoperatively, and 20 (45%) were not. There were no differences between the groups in terms of recipient or donor status. Plasma malondlaldehyde (MDA), mean 2.2 (0.2)µmol/L (SEM) vs. 1.73 (0.1) was greater in the group not prescribed nifedipine, p<. 05, as were cholesterol; 5.89 (0.3) mmol/L vs. 5.58 (0.3) and triglycerides; 2.19 (0.2) mmol/L vs. 1.82 (0.2). Following allograft reperfusion there was a significant increase in the ratio of MDA/cholesterol (±IO3) (MDA corrected for changes in plasma volume) from 0.33 (0.03) in the nifedipine group to 0.38 (0.02) at 30 min after reperfusion and 0.38 (0.03) at 60 min, p<. 01, and similarly from 0.4 (0.04) to 0.48 (0.03) at 30 min and 0.47 (0.05) after 60 min in the other group, p<.01. There was no difference in the percentage change in MDA/cholesterol ratio between the groups; 27 (5)% vs. 19 (6) at 30 min and 20 (8) vs. 15 (8) at 60 min for the nifedipine and no-nifedipine groups, respectively. There was no difference in postoperative renal function between the groups. This study suggests that the oral administration of nifedipine may not prevent the production of lipid peroxides, as measured by changes in plasma malondialdehyde, following renal allograft reperfusion and that it does not affect renal function in the early postoperative period.

ISSN:0886-022X    

DOI:10.3109/08860229409044891

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

Studies were performed to reexamine the response of erythropoietin (Epo) production to acute hypoxic stimuli in patients with end-stage renal disease (ESRD). In the absence of acute bleeding or hypoxia, the serum Epo level in ESRD was similar to that of normal subjects despite severe anemia. In 11 dialysis patients with acute bleeding, the decrease in the Hb level from 8.9 to 5.8 g/dL provoked a significant increase in serum Epo up to 52.2 times the normal value. The increase in serum Epo was associated with a significant increase in corrected reticulocyte. Systemic hypoxemia (PaO2<65 mm Hg) in 8 dialysis patients provoked a significant elevation in the serum Epo level up to 24.6 times the normal level. There was an inverse relationship between serum Epo and arterial PaO2(r = -0.715). The serum Epo level in these patients declined to or near the normal value after recovery from acute hypoxic stress. These data suggest that the ability of the Epo production is well preserved in ESRD, indicating that acute hypoxic stimuli provoke a significant increase in serum Epo.

ISSN:0886-022X    

DOI:10.3109/08860229409044892

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor