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Effect of human natural xenoantibody depletion and complement inactivation on early pig kidney function.

Preformed xenoreactive natural antibodies (XNA) and complement mediate hyperacute xenograft rejection (HXR) in pig-to-human discordant xenotransplantation. In a pig kidney-human blood xenoperfusion model, we investigated whether XNA depletion and/or human complement inactivation preserved early pig kidney function. Pig kidneys were perfused for 180 min with pig blood (AUTO group, n = 8), human blood (HETER group, n = 6), complement-inactivated human blood (COMi group, n = 5), XNA-depleted human blood (ABd group, n = 5) or complement-inactivated and XNA-depleted human blood (ABd&COMi group, n = 5). HETER kidneys were rejected after 15-30 min and showed vascular microthrombi and interstitial hemorrhages. XNA depletion and/or complement inactivation prevented HXR. The glomerular filtration rate in ABd, COMi and ABd&COMi groups was significantly lower than in the AUTO group. Also, beyond 60 min, the COMi group showed a significantly lower glomerular filtration rate than that observed in ABd and ABd&COMi groups. Kidneys from ABd, COMi and ABd&COMi groups displayed endothelial cell edema, as well as higher soluble P-selectin levels and a higher renal myeloperoxidase content than the AUTO group kidneys. COMi and ABd&COMi groups had a significantly lower renal myeloperoxidase level than the HETER group. Also, in contrast to HETER and ABd groups, these complement-inactivated groups failed to show a positive correlation between P-selectin and renal myeloperoxidase. We also investigated platelet-activating factor (PAF) as possible mediator for these functional and pathologic changes. We found that blood PAF levels were similar in HETER, ABd, COMi and ABd&COMi groups and significantly higher than in the AUTO group. Also, when PAF was added to porcine endothelial cell monolayers, morphological changes due to cytoskeleton contraction were observed, and these changes were prevented by preincubation with a PAF receptor antagonist. In conclusion, although depletion of XNA and/or complement inactivation prevent HXR, the pig kidney function is not preserved at the level of the autologous combination. The PAF overproduction observed in the xenogenic combination, which is independent of the presence of XNA and complement, may be, at least in part, responsible for early endothelial cell morphological changes still present when HXR is prevented.

Animals↗

Long-term effects of spironolactone on proteinuria and kidney function in patients with chronic kidney disease.

Experimental evidence suggests that aldosterone contributes to progressive kidney disease. Angiotensin-converting enzyme inhibitors and angiotensin type 1 receptor antagonists suppress the renin-angiotensin system but they do not effectively reduce plasma aldosterone. Hence, administration of aldosterone receptor antagonists may provide additional renal protection. In the present prospective randomized open-label study, we evaluated the effects of spironolactone (25 mg/day for 1 year) on proteinuria and estimated glomerular filtration rate in 83 patients with chronic kidney disease already treated with angiotensin-converting enzyme inhibitors and/or angiotensin type 1 receptor antagonists. Eighty-two patients were treated with angiotensin-converting enzyme inhibitors and/or angiotensin type 1 receptor antagonists alone and served as controls. After 1 year of therapy, proteinuria decreased from 2.1+/-0.08 to 0.89+/-0.06 g/g creatinine (P<0.001) in patients treated with spironolactone, but it did not change in control patients. Baseline aldosterone levels were significantly correlated with proteinuria (r=0.76, P<0.0001), and predicted the degree of reduction in proteinuria with spironolactone (r=0.42, P<0.0002). Baseline estimated glomerular filtration rate was similar in patients treated with spironolactone and controls (62.4+/-2.4 and 62.2+/-2.1 ml/min/1.73 m(2), respectively). After 1 month of therapy with spironolactone, estimated glomerular filtration rate decreased more in patients treated with spironolactone than in controls. However, by the end of 1 year the monthly rate of decrease in estimated glomerular filtration rate from baseline was lower in patients treated with spironolactone than in controls (0.323+/-0.044 vs 0.474+/-0.037 ml/min/1.73 m(2), P<0.01). Spironolactone caused a significant rise in serum potassium levels (from 4.2+/-0.04 at baseline to 5.0+/-0.05 mEq/l after 12 months of treatment, P<0.001). In conclusion, this study has shown that spironolactone may reduce proteinuria and retard renal progression in chronic kidney disease patients.

Angiotensin II Type 1 Receptor Blockers↗

Ureteroarterial fistula in a patient with a single functioning kidney.

A rare case is reported of a fistula between the left internal iliac artery and the left ureter in a patient whose left kidney was the only functioning kidney. Internal iliac artery embolization was initially successful in stopping the bleeding, but the fistula recurred when the ureteral stent was removed. Even after embolization, the tissue surrounding a fistula remains very fragile, so the fistula may easily recur as a result of slight injury or inflammation.

Aged↗

[Serum lipids in diminished kidney function, during hemodialysis and after kidney transplantation].

Lipids have been investigated in three groups of patients with chronic renal insufficiency. 19 patients were on conservative treatment (no dialysis), 52 patients were on regular hemodialysis, and 27 patients had been transplanted. The results were compared with those obtained from control subjects of the same age and sex. Hyperlipoproteinemia was found in 25% of the uremic patients, 55% of hemodialysis patients, and 85% of transplant recipients. The predominant lipid abnormalities were hyperlipoproteinemia of Type IV in both uremic (5 out of 19) and hemodialysis patients (17 ou of 52). Hyperlipoproteinemia of Type II was mainly observed after transplantation (IIb: 13, IIa: 5 out of 27).

Adult↗

Functional and morphologic maturation of the superficial nephrons. Relationship to total kidney function.

The functional and morphologic pattern of superficial nephron development was studied in guinea pigs ranging in age between 2 h and 38 days. Concomitent measurements of total kidney function and glomerular counts were also performed. Superficial nephron glomerular filtration rate was found to increase from 0.92 to 19.32 nl/min. The filtration rate of the entire kidney rose from 0.19 to 1.31 ml/min. During the first 15 days of life the average rate of increase in glomerular filtration rate per nephron (0.48 nl/min.day), obtained by dividing the increase in total kidney glomerular filtration rate by glomerular number, was more than twice the observed rate of increase in the superficial nephrons (0.21 nl/min.day). During the remainder of the first month, the increase in superficial nephron glomerular filtration rate (0.97 nl/min.day) was greater than the average increase for all nephrons (0.71 nl/min.day). Thus, the initial increase in total kidney glomerular filtration rate was primarily a consequence of the activity of the deep nephrons, whereas during the ensuing period the superficial nephrons appeared to be the sole contributors to the change in total kidney glomerular filtration rate.The increase in superficial nephron glomerular filtration rate was found to correlate closely with the increase in proximal tubular length. Functional glomerulotubular balance was maintained throughout the entire period of renal maturation.

Aging↗

Percutaneous transluminal renal angioplasty in the patient with a solitary functioning kidney.

Since the introduction of percutaneous transluminal renal angioplasty, it has become established as an effective treatment for the correction of renovascular hypertension or the preservation of renal function. However, there has been a general reluctance to use it or other interventional procedures in any patient with a solitary functioning kidney. We attempted renal angioplasty in 11 patients each of whom had a solitary functioning kidney. All 11 had had either a previous contralateral nephrectomy or an autonephrectomy from chronic arterial occlusion. The patients ranged in age from 42 to 81 years. In nine of the 11 patients, a catheter was negotiated across the stenosis, and the lesion was dilated successfully. In two, the lesion could not be crossed. In the group of nine patients whose lesions were dilated successfully, clinical follow-up (2-180 weeks) revealed that hypertension was cured in four and improved in five. Of the two patients in whom angioplasty was not possible, one required emergency renal bypass surgery and the other had no change in renal status. Renal function test results after the procedure were variable and did not correlate with decreases in blood pressure. We conclude that percutaneous renal angioplasty is a satisfactory alternative to surgery for the treatment of renovascular hypertension or the preservation of renal function in a patient with a solitary functioning kidney.

Adult↗

Level of kidney function as a risk factor for atherosclerotic cardiovascular outcomes in the community.

OBJECTIVES: The goal of this study was to determine whether the level of kidney function is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) outcomes in the Atherosclerosis Risk in Communities (ARIC) study, a prospective cohort study of subjects aged 45 to 64 years. BACKGROUND: The level of kidney function is now recognized as a risk factor for ASCVD outcomes in patients at high risk for ASCVD, but it remains unknown whether the level of kidney function is a risk factor for ASCVD outcomes in the community. METHODS: Cox proportional-hazards regression was used to evaluate the association of glomerular filtration rate (GFR) with ASCVD after adjustment for the major ASCVD risk factors in 15,350 subjects. We searched for nonlinear relationships between GFR and ASCVD. RESULTS: During a mean follow-up time of 6.2 years, 965 (6.3%) of subjects had ASCVD events. Subjects with GFR of 15 to 59 ml/min/1.73 m(2) (n = 444, hazard ratio 1.38 [1.02, 1.87]) and 60 to 89 ml/min/1.73 m(2) (n = 7,665, hazard ratio 1.16 [1.00, 1.34]) had an increased adjusted risk of ASCVD compared with subjects with GFR of 90 to 150 ml/min/1.73 m(2). Each 10 ml/min/1.73 m(2) lower GFR was associated with an adjusted hazard ratio of 1.05 (1.02, 1.09), 1.07 (1.01, 1.12), and 1.06 (0.99, 1.13) for ASCVD, de novo ASCVD, and recurrent ASCVD, respectively. A nonlinear model did not fit the data better than a linear model. CONCLUSIONS: The level of GFR is an independent risk factor for ASCVD and de novo ASCVD in the ARIC study.

Arteriosclerosis↗

Rabbit kidney function in vitro: the effect of colloids, energy substrate, a vasodilator, perfusion pressure, and bovine serum albumin.

An in vitro perfusion system at 37 degrees C for the assessment of rabbit kidney function is described. The purpose of this assay system is to evaluate the effects of cryobiological manipulation on kidney function. The effect of the colloids dextran (MW = 70,000, 80,000, and 180,000) in the perfusate at 110 mm Hg were compared to a reduced perfusion pressure, colloid-free perfusate. Better function was obtained at lower perfusion pressure with the colloid-free perfusate. Less damage was noted histologically on light and electron microscopy. Investigation of energy substrates on rabbit kidney function demonstrated that butyrate, or lactate, in addition to glucose resulted in increased sodium and glucose reabsorption over glucose alone. Substrate-free perfused kidneys exhibited depressed Na transport. Lactate, and to some extent butyrate, decreased net glucose utilization. An alpha-adrenergic blocking agent, isoxsuprine, in the initial flush solution did not appear to be beneficial. An increase of perfusion pressure from 50 to 75 mm Hg resulted in an increase in GFR. Tubular function was enhanced by inclusion of small amounts of BSA in the perfusate.

Animals↗

Kidney function in domestic fowl with chronic occlusion of the ureter and caudal renal vein.

A previously published technique for producing renal insufficiency in chicks involves ligating the caudal renal vein together with the ureter near the midpoint of the kidney. This ligation occludes the normal route (caudal renal vein) by which blood exits the medial and posterior kidney divisions. The present study was conducted to evaluate kidney function following chronic caudal renal vein and ureter occlusion. The ureters and caudal renal veins of 2 to 3-week-old chicks were clamped with hemostatic clips (Clamp Group), and kidney function evaluations were conducted when the birds reached 14 weeks of age. Plasma values [osmolality, Na, K, Ca, inorganic P (Pi)] of control, sham, and clamp groups did not differ significantly. Plasma uric acid concentrations did not differ when the control and clamp groups were compared. Clamping the ureter near the midpoint of the kidney caused a significant reduction in the number of filtering glomeruli per kidney, but due to compensatory hypertrophy the kidney weights of the groups did not differ significantly. Kidney function comparisons (urine flow rates, glomerular filtration rates, renal plasma flow rates, urine pH, fractional excretion of Na, K, Ca, Pi, and uric acid) revealed a significant reduction in Na and K excretion by the clamp group, but other renal function parameters did not differ significantly. These experiments demonstrate that chickens have a remarkable capacity to survive significant reductions in renal mass and to adapt to major disruptions of blood flow patterns.

Animals↗