Partial Renal Infarction Research Articles

Transplantation of developing metanephroi into adult rats

Transplantation of developing metanephroi into adult hosts has been proposed as a means to augment host renal function. We implanted whole metanephroi from embryonic day 15 (E15) rats subcapsularly in kidneys or into the omentum of non-immunosupressed adult rat hosts. At the time of implantation, some host rats underwent unilateral nephrectomy (UNX) or unilateral nephrectomy and partial contralateral renal infarction (1 1/2 NX). E15 metanephroi contained only metanephric blastema, segments of ureteric bud, and primitive nephrons with no glomeruli. Four to six weeks post-implantation, metanephroi from E15 rats had enlarged, become vascularized, and had formed mature tubules and glomeruli. Ureters of metanephroi transplanted into the omentum were anastomosed to hosts' ureters that remained after UNX. Four weeks following ureteroureterostomy, the contralateral kidney was removed. Inulin clearances of seven metanephroi implanted into UNX hosts averaged 0.11 +/- 0.02 microliters/min/100 g (2.42 +/- 0.70 microliters/min/g kidney wt) and the creatinine clearances averaged 0.65 +/- 0.18 microliters/min/100 g. Metanephroi weighed 71 +/- 15 mg (approximately 4% of the contralateral native kidney). The transplanted metanephroi were vascularized by arteries originating from the omentum. Both weights of transplanted metanephroi (145 +/- 24 mg) and inulin clearances of transplanted metanephroi (30.1 +/- 8.7 microliters/min/g kidney weight) were significantly increased in rats that underwent 1 1/2 NX compared to UNX. In contrast, transplantation of developed kidneys resulted in rejection. Our findings establish that functional chimeric kidneys develop from metanephroi transplanted in adult hosts.

Enhanced renal IGF-I expression following partial kidney infarction

Renal insulin-like growth factor (IGF)-I expression is enhanced in tissue that remains following removal of kidney mass. To characterize the expression of renal IGF-I after reduction of kidney mass by partial unilateral infarction, we measured levels of IGF-I extracted from noninfarcted (remnant) renal tissue that remained after one-half unilateral kidney infarction that was performed without (1/2NX) or with (1 1/2NX) contralateral nephrectomy. Levels of IGF-I extracted from remnant renal tissue after 1/2NX increased significantly, peaking on day 3 after renal mass reduction, and then returned toward baseline. Steady-state levels of IGF-I mRNA were also elevated on day 3, suggesting that the increase in IGF-I results from enhanced synthesis. A similar pattern of increased extracted IGF-I and elevated IGF-I mRNA occurred after 1 1/2NX. Levels of IGF-I extracted from remnant renal tissue 3 days after 1 1/2NX were not higher than levels extracted from remnant tissue 3 days after 1/2NX, and both were higher than levels of IGF-I extracted from contralateral kidneys 3 days after unilateral nephrectomy. Therefore, levels of IGF-I did not correlate with the extent of reduction of renal mass per se. We conclude that partial renal infarction provides a stimulus to enhance IGF-I expression. Increased renal IGF-I must be considered in the interpretation of findings originating from use of remnant kidney models of chronic renal failure.

Dietary Protein Loading and the Oral Adsorbent AST-120 in the Progression of Chronic Renal Failure in the Rat

Excess protein intake enhances the progression of renal failure. The oral carbonaceous adsorbent, AST-120, was found experimentally and clinically to retard the progression of renal failure. This study was designed to determine whether deterioration of renal function by dietary protein loading can be prevented or mitigated by this oral adsorbent. Rats with uremia induced by partial renal infarction were fed a normal or high-protein diet for 70 days with or without AST-120, in which the inorganic phosphate content was adjusted to the same level. The survival rate deteriorated with the high dietary protein, but was improved from 30% to 100% with AST-120. Dietary protein loading reduced renal function, based on creatinine clearance. AST-120 improved renal function and renal histopathology not only in the normal diet group but in the high-protein group as well. The progression of renal failure induced by protein loading is thus shown to be prevented by oral AST-120. The mechanism for its action remains to be clarified.

Potential role of PFOB enhanced sonography of the kidney. II. Detection of partial infarction

Aside from its ability to assess flow velocity within vessels, color Doppler and gray-scale sonography cannot distinguish perfused from non-perfused tissues. In this study we evaluated whether Perfluorooctylbromide (PFOB), a sonographic contrast agent given i.v., could aid sonography with this recognition. Partial renal infarction was produced by a 1 mm bead embolized in the right, the left, or both renal arteries of 20 normal rabbits. The sonographer, unaware of rabbit assignment, attempted to diagnose the infarct 24 hours later. All 20 rabbits were studied with gray-scale and color Doppler sonography, 10 before and after PFOB and 10 only after PFOB. Angiography and post-mortem examination were done for confirmation. Of the 20 kidneys evaluated before PFOB, the sonographer was unable to diagnose the 10 partial infarctions. Color Doppler identified five of the ten infarcted kidneys, but accurately localized the infarction in only two. Of the 40 kidneys evaluated after PFOB infusion, 20 scanned before and 20 scanned only after PFOB, all 20 partial infarctions were accurately diagnosed with both gray-scale and color Doppler. PFOB enhanced the echogenicity of perfused renal tissue allowing the easy detection of the unenhanced infarct. Because of the increased signal from vessels after PFOB, color Doppler displayed the entire vascular tree, allowing the detection of the truncated embolized branch. The ability of PFOB to enhance Doppler signals and the echogenicity of perfused tissues improved the diagnostic accuracy of sonography when used to detect partial renal infarctions.

Mechanisms of partial renal infarct hypertension

Contributions of both the renin-angiotensin and immune systems to the aetiology of renal infarct hypertension were examined in Sprague-Dawley rats. Partial renal infarction was produced by ligating and sectioning two out of three branches of the left renal artery. The right kidney remained intact. Renal infarction resulted in rapid development of stable hypertension. One week following infarction, the plasma renin activity (PRA) increased more than threefold. However, PRA returned to control levels 4 weeks after infarction. Chronic immunosuppressive therapy with cyclophosphamide at most only attenuated the development of renal infarct hypertension associated with this transient renin elevation. However, cyclophosphamide prevented the later maintenance phase of the hypertension, and could also completely reverse established infarct hypertension. Activation of the renin-angiotensin system plays a role in the onset of partial renal infarct hypertension, but an intact immune system is required for maintenance of the hypertension. It is hypothesized that immunological reactions against renal tissue maintain renal infarct hypertension.

Effect of varying quantity and quality of dietary protein intake in experimental renal disease in rats.

Dietary protein restriction is known to be beneficial in the preservation of renal function when renal mass is reduced. This study investigates the effects of two different dietary proteins, casein and soya, upon renal function in normal rats and rats subjected to subtotal nephrectomy. The diets were isocaloric, with identical sodium, potassium and phosphorus contents. Normal rats ingesting a 24% soya protein diet demonstrate lower effective renal plasma flow rates and lower glomerular filtration rates than rats ingesting a 24% casein diet. Experimental animals were subjected to a unilateral nephrectomy and contralateral partial renal infarction and were fed either casein or soya, at 24 or 12% levels, for 3 months. Those animals ingesting the soya diets demonstrated improved survival (p less than 0.05), less proteinuria (p less than 0.02), less renal hypertrophy (p less than 0.005) and less renal histological damage. The nature of the dietary protein appears to influence both normal renal function and the progression of experimentally induced renal disease.

Spontaneous Resolution of Bilateral Renal Artery Dissection: A Case Report

We report a case of simultaneous bilateral dissection of the renal arteries with partial renal infarction. Of interest is the fact that the dissection resolved spontaneously during the 1-year followup. The radiology, including angiography, computerized tomography and ultrasonography, findings are described. The etiology and treatment of isolated dissection of the renal artery also are discussed.

Inhibition by anticoagulant drugs of the progressive hypertension and uremia associated with renal infarction in rats

We confirmed our previously reported findings that subcutaneous administration of heparin (200 U q 12 hr) in rats with experimental partial renal infarction prevents the development of progressive renal failure and hypertension, as well as the glomerular abnormalities which occur in the remaining viable renal tissue. In the present study, heparin, in the dosage used to prevent progressive renal failure, caused a marked and sustained prolongation of the activated partial thromboplastin time and prothrombin time, as well as a transient prolongation of the bleeding time. Administration of coumadin at doses which caused a significant prolongation of the prothrombin time and bleeding time also inhibited the development of progressive hypertension and uremia in rats with experimental partial renal infarction. These findings indicate that inhibition of blood coagulation effectively protects rats with experimentally decreased renal mass from the development of progressive renal failure and hypertension and support the concept that the glomerular thrombosis plays an important role in the pathogenesis of these complications.

Unilateral Small Kidney

Common Chronic pyelonephritis Obstructive renal atrophy Renal artery stenosis with ischemia (eg, arteriosclerosis, thromboembolism, fibromuscular hyperplasia, congenital stenosis) Uncommon Congenital hypoplastic kidney Partial nephrectomy Radiation therapy Renal infarction (late) Tuberculosis Diagnosis Chronic pyelonephritis. Comment The excretory urogram demonstrates a poorly functioning, right kidney and a normal left kidney (Fig 1). A selected view from the early arterial phase of an aortogram shows reduced vascularity of the right kidney (Fig 2). Capillary phase of the aortogram shows indentations on the outline of the right kidney with clear demarcation of cortex and medulla (Fig 3). Unilateral kidney, as seen here, may result from a number of causes. First, however, the small kidney must be defined. In general, renal size is proportional to body size. In children 1 1/2 to 14 years of age, the average kidney length corresponds to

Pathogenesis of the glomerulopathy associated with renal infarction in rats

The present studies were designed to characterize the extent and pathogenesis of the glomerular lesions which occur in the viable portion of the kidney following partial renal infarction in rats. Control rats with two normal kidneys had a mean blood pressure of 112 mm Hg, minimal proteinuria and no glomerular pathology on light (LM), electron (EM) or immunofluorescence microscopy (IFM). Rats with two-thirds infarction of one kidney (stage II) became hypertensive, although less than 4% of the glomeruli from either kidney were abnormal. Rats with two-thirds infarction of one kidney and contralateral nephrectomy (stage III) developed proteinuria and hypertension whether fed a normal, low or high Na+ diet. By light microscopy 37% of glomeruli were abnormal 28 days after partial infarction and contralateral nephrectomy and thereafter the percent of abnormal glomeruli increased. Detectable amounts of immunoglobulin and complement (C3) were present in kidneys of stage II or III rats but were always accompanied by more extensive albumin and fibrin deposits. Basement membrane deposits characteristic of immune complexes were not seen on EM. Administration of antihypertensive medication to stage III rats significantly lowered blood pressure and reduced the number of abnormal glomeruli on LM; however, IFM abnormalities remained prominent. Platelet thrombi seen by EM and abundant glomerular fibrin deposits seen on IFM suggested that coagulation mechanisms may be prominent in the pathogenesis of the renal lesion. Heparin-treated stage III rats had significantly lower blood urea nitrogen concentrations, blood pressures and proportion of abnormal glomeruli although glomerular deposition of serum proteins was still present on IFM. These observations suggest that this glomerulopathy is initiated by an unknown agent(s) which increased capillary permeability. This lesion progresses via thrombotic mechanisms which are prevented by heparin administration.

Malignant Hypertension Following Renal Artery Branch Obstruction

Occlusion of a renal artery branch with subsequent partial renal infarction resulted in high renin production from the ischemic part of the kidney and malignant hypertension. Absence of overall ischemia from the affected kidney prevented development of a pattern of increased concentration of nonabsorbable solutes (ie, creatinine and para-aminohippuric acid), although total urine flow was decreased by reduction of renal excretory mass. Renin activity was at least tenfold higher in the ischemic area than in the normal kidney and manifested itself clinically by a 1.7 to 1 difference in the preoperative renal vein renin values between the affected and nonaffected kidneys. Removal of the affected kidney resulted in a cure of the malignant hypertension.

On the mechanism of the splay in the glucose titration curve in advanced experimental renal disease in the rat.

Glucose titration studies were performed in rats with unilateral chronic pyelonephritis before and after removal of the contralateral control kidneys. Identical studies were performed in animals with unilateral partial renal infarction in which the experimental kidneys had a marked reduction in nephron population but no anatomic deformation in the surviving nephrons. In the initial studies, both groups of animals were free of clinical and chemical abnormalities of uremia. In the follow-up studies uremic abnormalities were present. Minimal splay was observed in the titration curves in the initial studies; marked splay was present in the group data from the same kidneys in the subsequent studies. Thus a marked reduction in the nephron population was associated with the evolution of splay in both groups of animals. In association with the increase in splay, the mean values for maximal glucose transport increased; thus a defect in glucose transport can be excluded as the basis of the splay. Glomerular filtration rate increased proportionately more than the maximal transport of glucose; hence the ratios of glomerular filtration rate to maximal glucose transport increased consistently. The possibility of asymmetric hypertrophy of glomerular and tubular functions among the nephron population imposed by scar tissue or other anatomic deformities was considered, but the results in the animals with partially infarcted kidneys militate against this explanation. The splay also could reflect an asymmetric alteration in the distribution of glomerulotubular balance among the residual units initiated by functional adaptations. Finally, the splay could relate to an alteration in the kinetics of glucose transport without any change in the level of functional homogeneity. The possible nature of these has been considered in the text.

Functional characteristics of the separate kidneys in hypertensive man

1.1. Functional studies of the separate kidneys were undertaken in 165 hypertensive patients who had previously undergone excretory urography. Of these, 150 had isotope renography and 147 had renal arteriography. Complications consisted of acute or recurrent pyelonephritis in 4 patients; all responded promptly to appropriate chemotherapy.2.2. In 17 hypertensive patients with dominantly unilateral atrophie pyelonephritis, mean values revealed markedly diminished urine volume (54%), clearances of inulin and paraaminohippuric acid (PAH) (65 and 62%), and reabsorption of filtered sodium (1.5%) and water (1.6%) for the diseased kidney. Concentrations of sodium, PAH, and inulin and osmolality of the urine from the diseased side were usually slightly to moderately diminished. In two patients data on urine volume and sodium concentration met criteria for a positive Howard test.3.3. Patients with apparent essential hypertension had only minor differences between the kidneys in all parameters studied. The range of differences in those with essential hypertension and aberrant arteries was somewhat greater; however, mean differences were minimal except for greater clearances of inulin and PAH which correlated well with greater renal mass.4.4. Of 102 patients with stenosing lesions of the renal arteries, 53 had unilateral and 49 had bilateral obstruction. In patients with unilateral severe renal artery stenosis urine volume and sodium concentration were diminished along with usually diminished clearances of inulin and PAH on the involved side (mean values − 79, − 53, − 47 and − 47%, respectively). Urine osmolality was usually increased as were concentrations of inulin and PAH, the latter two usually by more than 100 per cent. The percentage reabsorption of filtered sodium and water was markedly increased on the involved side (mean values 3.1 and 2.6%, respectively).Patients with unilateral severe renal artery stenosis and aberrant renal arteries differed only in that the mean value for sodium concentration in the urine was only slightly diminished on the involved side (6%). Patients with unilateral renal artery stenosis and partial renal infarction usually could not hyperconcentrate urine on the involved side. Urine volume, sodium concentrations, and osmolality were diminished; however, inulin and PAH concentrations were slightly but consistently increased.When stenosis was severe on one side and mild on the other, functional characteristics were similar to those observed with unilateral stenosis, except for more variable sodium concentrations and osmolality. When stenosis was bilateral and equally severe, significant differences in functional characteristics were seldom observed.Patients with mild or moderate stenosis (less than 50% narrowing of the renal artery) seldom had more than slight differences in functional characteristics.5.5. With arteriographically demonstrated renal artery stenosis, (a) increased reabsorption of filtered sodium and water by 1 per cent or more on the involved side, a positive Howard test, and increased osmolality characterized functionally significant lesions and were not seen in essential hypertension; (b) differences in inulin and PAH concentrations largely reflected differences in water reabsorption; and (c) when sodium concentrations were greater on the involved side (negative Howard test), a high incidence of either a branch artery lesion, multiple arteries to the involved kidney, bilateral main artery stenosis, or partial renal infarction was observed.