Transplanted Rat Kidney Research Articles

Hyperbaric Oxygenation Protects Against Ischemia-Reperfusion Injury in Transplanted Rat Kidneys by Triggering Autophagy and Inhibiting Inflammatory Response.

BACKGROUND Ischemia-reperfusion injury (IRI) is a clinically common pathologic process defined as the inability to improve neuronal function. This study aimed to investigate the pathological mechanism of IRI and to explore effects of hyperbaric oxygenation (HBO) on autophagy and inflammatory response in IRI. MATERIAL AND METHODS Ninety Sprague-Dawley (SD) rats were randomly divided into a Sham group, a kidney transplant group (Trans), and a kidney transplant plus HBO treatment group (Trans+HBO). The kidney was harvested from the donor and transplanted to recipient rats according to a previously reported study. Rats were anesthetized using pentobarbital-natrium, and the kidney was resected and fixed in 4% paraformaldehyde. Serum creatinine (Scr) was detected using an automatic biochemical analyzer. The interleukin-6 (IL-6) level was assessed using enzyme-linked immunosorbent assay (ELISA). LC-3 was examined using indirect immunofluorescence assay and immunochemistry assay. LC-3 mRNA levels were analyzed using real-time PCR (RT-PCR). RESULTS The kidney transplant IRI model was successfully established. Scr and IL-6 levels were significantly increased in the Trans group (P<0.05). HBO significantly enhanced Scr and IL-6 levels. Scr was positively correlated with IL-6 levels (r-0.607, P<0.05). HBO increased LC-3 protein and mRNA expression in kidney-transplanted rats compared to the Sham and Trans group (P<0.05). Moreover, immunofluorescence assay also showed that LC-3 protein mainly distributes along renal tubular epithelial cells in a linear manner. CONCLUSIONS Autophagy dysfunction and inflammatory response after renal transplantation play important roles in processes of IRI. HBO treatment protects against the renal injury of IRI in renal tissues at the early stage, which may be triggered by the IL-6 pathway.

Role of combination of l‐arginine and α‐tocopherol in renal transplantation ischaemia/reperfusion injury: a randomized controlled experimental study in a rat model

What's known on the subject? and What does the study add? Renal ischaemia/reperfusion (I/R) injury is an inevitable consequence of kidney transplantation. It contributes to delayed graft function (DGF), acute renal failure and graft rejection. The present study investigates for the first time the impact of a combination of L-arginine and alpha tocopherol on the renal ischemia/reperfusion injury in a rodent model of kidney transplantation. We found that concomitant administration of L-arginine and α-tocopherol has a more protective effect and synergistic antioxidant effect on ischaemia/reperfusion injury in transplanted rat kidneys. To investigate the role of L-arginine and α-tocopherol in ischaemia/reperfusion injury in a kidney transplanted rat model. In total, 40 male Sprague-Dawley rats subjected to renal transplantation received FK506 (tacrolimus) to overcome early acute rejection episodes. Animals were divided randomly into four groups (ten rats each). Group I were treated with FK506 (2 mg/kg/bw/day) and served as the control group. Group II were treated with L-arginine 300 mg/kg/bw. Group III were treated with α-tocopherol 30 mg/kg/bw. Group IV were treated with L-arginine and α-tocopherol. Urine and blood samples were taken at 0 (before operation), 2, 7 and 14 days post-transplantation for estimation of urine sodium, creatinine, fractional excretion of sodium, serum creatinine, sodium and blood urea nitrogen. Histological examination and measurement of malondialdehyde in kidney tissues were also performed. Serum creatinine and blood urea nitrogen significantly decreased in L-arginine and α-tocopherol, as well as combination groups, compared to the control group. Malondialdehyde was significantly decreased in the combination group compared to L-arginine and α-tocopherol alone. Histological examination of the control group showed that acute tubular necrosis was markedly decreased in transplanted kidneys treated with a combination of both L-arginine and α-tocopherol. Concomitant administration of l-arginine and α-tocopherol has a more protective effect and synergistic antioxidant effect on ischaemia/reperfusion injury in transplanted rat kidneys.

Experimental Study on Early Protective Effect of Ischemic Preconditioning on Rat Kidney Graft

Objective Our aim was to investigate the mechanisms of early protection by ischemic preconditioning (IPC) of transplanted rat kidneys. Materials and Methods Thirty-six male donor and recipient Sprague-Dawley (SD) rats were randomly divided into 3 groups: sham-operated (A), transplantation (B), and IPC treatment (C) groups. Group A underwent exploratory laparotomy, group B received orthotopic transplantation, and group C, 15 minutes of ischemia followed by 10 minutes of reperfusion before transplantation. We measured the serum creatinine (SCr), blood urea nitrogen (BUN), and degree of kidney graft ischemic/reperfusion injury (IRI) by tumor necrosis factor-alpha (TNF-α) IκB kinase beta (IKK-β) nuclear factor-kappa β (NF-κβ) p65 subunit mRNA expressions. Results The SCr and BUN levels in groups C and B were higher than those in the sham-operated group ( P < .01), without a significant difference between groups C and B at 24 hours after transplantation ( P > .05). The degree of renal graft tubular injury in group C was significantly lower than that in group B ( P < .01). TNF-α transcription levels at 24 hours after transplantation were significantly lower compared with the non-IPC group ( P < .01). However, we failed to note a significant difference in IKK-β or p65 mRNA expressions between groups C and B ( P > .05). Conclusions One cycle of preconditioning (15 min/10 min) attenuated renal graft IRI in the early phase. The inhibiting effects on TNF-α and the positive feedback signaling of TNF-α/NF-KB pathways may play important roles in renal graft protection.

Ischemic Preconditioning Improves Rat Kidney Allograft Function After Ischemia/Reperfusion Injury: The Role of Tumor Necrosis Factor-Alpha

Objective The aim of this study was to investigate the early protection of ischemic preconditioning (IPC) and its mechanisms in transplanted rat kidneys. Materials and Methods Thirty-six male Sprague-Dawley (SD) rat donors and recipients were randomly divided into the following groups: sham-operated group (A; n = 6); untreated transplantation group (B; n = 6); and treatment group (C; n = 6). Group A was subjected to exploratory laparotomy. Group B received orthotopic transplantation. Group C underwent a 15-minute period of ischemia followed by a 10-minute reperfusion before orthotopic transplantation. We assessed the serum creatinine (SCr), blood urea nitrogen (BUN), and to evaluate the degree of kidney graft ischemia/reperfusion injury: tumor necrosis factor-alpha (TNF-α), IκB kinase-beta (IKK-β), and nuclear factor-kappa B (NF-κB) P65 subunit mRNA expressions. Results The levels of SCr and BUN in groups C and B were greater than in the sham-operated group ( P < .01), but there was no significant difference between the C and B groups at 24 hours after transplantation ( P > .05). The degree of renal graft tubular injury in group C was significantly less compared with group B ( P < .01). TNF-α transcription levels at 24 hours after transplantation were significantly less compared with the non-IPC group ( P < .01). However, no significant difference was observed in IKK-β mRNA and P65 mRNA expressions between groups C and B ( P > .05). Conclusions A 1-cycle schedule of preconditioning (15 min/10 min) attenuated renal graft ischemia/reperfusion injury in the early phase. IPC can improve rat kidney allograft function after ischemia/reperfusion injury. The inhibitory effects on TNF-α and on positive feedback signaling of TNF-α/NF-κB pathways may play important roles in renal graft protection in the early stage.

Upregulation of connective tissue growth factor in a rat model of chronic allograft nephropathy

To study the expression of connective tissue growth factor (CTGF) in transplanted rat kidney and its relationship with chronic allograft nephropathy (CAN). Kidney transplantation was performed from Lewis to Fisher 344 allogeneic rat strain, and kidney grafts were harvested at the eighth, 12th and 16th week. The morphological changes were studied, and collagen deposition was determined by Masson trichrome stain. Serum creatinine was examined. The fibrotic process and the CAN grades were evaluated according to Banff 97 schema. The expressions of transforming growth factor beta, CTGF and alpha-smooth muscle actin were detected to assess the development of grafted kidney fibrosis and to discuss their relationships. Spearman correlation was used for correlation study between CTGF expression and development of CAN. Serum creatinine was promoted in a time-dependent manner. Morphological changes suggested that the grafted kidneys were under abnormalities. At the end stage, focal segmental glomerulosclerosis was seen; tubular epithelial cells lost their phenotype and interstitial fibrosis was notable. Masson trichrome stain showed significant collagen accumulation in a time-dependent manner. Immunohistochemistry and western blotting results showed that the transforming growth factor beta, CTGF and alpha-smooth muscle actin expression were markedly promoted compared with the control group. CTGF was mainly expressed in the plasm of proximal tubular epithelial cells based on the severity of CAN. Connective tissue growth factor might play an important role in the pathological changes of CAN after kidney transplantation. The expression of CTGF in epithelial cells could act as a molecular marker of interstitial fibrosis and CAN.

Normal and transplanted rat kidneys: diffusion MR imaging at 7 T.

To investigate the feasibility of obtaining reproducible apparent diffusion coefficient (ADC) maps of normal rat kidneys by using respiratory-triggered spin-echo diffusion-weighted magnetic resonance (MR) imaging, to investigate the sensitivity of ADC maps in the evaluation of renal blood flow, and to use this technique to monitor acute graft rejection in transplanted rat kidneys. Spin-echo diffusion-weighted MR imaging measurements were performed in 20 normal rats and nine rats that had undergone transplantation (six rats had received allografts; three had received isografts) at 7 T. To evaluate the effect of alteration in blood flow and water transport function, angiotensin II was infused in six normal rats and a series of spin-echo diffusion-weighted MR images was obtained at five time points. Transplanted kidneys were monitored by obtaining spin-echo diffusion-weighted MR images and gradient-echo MR images every 2 hours for 8 hours on postoperative day 4. Statistical analysis was performed with repeated-measures multivariate analysis of variance and the paired t test. No significant differences in ADC values were observed between right and left kidneys in all three orthogonal directions; however, a small difference was observed between the cortex and medulla. ADC values in the cephalocaudal and mediolateral directions were higher than those in the anteroposterior direction (P <.01 for all). ADC values in the cortex and medulla decreased significantly (by >35%, P <.01) during angiotensin II-induced reduction in renal blood flow. No significant signal intensity change was observed between native and transplanted kidneys on gradient-echo MR images. Allografts exhibited decreased ADC values (P <.01) and isografts exhibited similar ADC values compared with native kidneys. These findings suggest that reproducible renal ADC maps can be obtained in rats by using spin-echo diffusion-weighted MR imaging at 7 T. Spin-echo diffusion-weighted MR imaging may have potential as a noninvasive tool for monitoring early graft rejection after kidney transplantation.

738. Transfection of Decoy Oligonucleotides Using Therapeutic Ultrasound Machine into Transplanted Rat Kidney

738. Transfection of Decoy Oligonucleotides Using Therapeutic Ultrasound Machine into Transplanted Rat Kidney

USPIO-enhanced dynamic MRI: evaluation of normal and transplanted rat kidneys.

To evaluate first-pass renal perfusion with ultrasmall superparamagnetic iron oxide (USPIO) particles by MRI, 40 normal rats (20 Dark Agouti (DA) rats and 20 Brown Norway (BN) rats) and 16 transplanted rats (12 allografts and four isografts) were studied on day 4 post-transplantation with different USPIO doses (3.0-18.1 mg Fe/kg/body weight). All animals underwent 128 consecutive snapshot fast low-angle shot (FLASH) coronal dynamic studies in 43 s. In the normal rats, a larger maximum signal decrease (MSD) in the cortex and the outer medulla is observed with an increasing dose of USPIO particles (P < 0.01). No significant differences were observed between the right and left kidneys at all doses studied. Higher MSD, time of occurrence of MSD (tMSD), and wash-in slope appear with higher doses of USPIO particles. The dynamic curves for DA rats show similar shapes when compared to those for BN rats. In the transplanted rats, allograft kidneys show lower MSD, longer tMSD, and lower wash-in slope compared to those in the normal kidneys. Isograft kidneys show perfusion patterns similar to those of normal kidneys in the cortex and the outer medulla. Histopathology indicates acute vascular rejection in all allografts and normal kidney architecture in all isografts. The results clearly show good agreement between the renal graft perfusion measurements and histopathological changes associated with rejection. This work also introduces a new signal analysis methodology for the automatic detection of transplanted organ rejection. This method compares the dynamics of the intrarenal signal intensities for native and transplanted kidneys. A quantitative measurement to detect significant differences between these signals was developed, and showed that this technique exhibits good performance in identifying renal rejection.

Sympathetic reinnervation of rat kidney grafts.

Reinnervation occurs in many transplanted tissues and organs. Sympathetic reinnervation in rat kidney grafts was investigated. Rats were syngeneically transplanted with a kidney and bilaterally nephrectomized. Reinnervation was assessed by immunohistochemical staining for neuron-specific protein gene product 9.5 (PGP 9.5) and by tissue norepinephrine measurements in grafts removed 1.5 (n=6), 3 (n=7), 6 (n=8), and 9 (n=7) months after transplantation. PGP 9.5-positive neural structures were significantly reduced in grafts removed 1.5 and 3 months after transplantation compared with native kidneys with slightly increased numbers at 6 and 9 months after transplantation. Median transplant norepinephrine concentrations remained at approximately 3% compared with native kidneys until 9 months after transplantation. In transplanted rat kidneys, some reinnervation occurs in the hilum within 9 months after transplantation. This is not accompanied by a significant recovery of norepinephrine concentration in renal tissue indicating persistent sympathetic denervation.

Expression of TGF-B and PDGF-AA antigens after CMV infection in transplanted rat kidney

Expression of TGF-B and PDGF-AA antigens after CMV infection in transplanted rat kidney

Perfusion quantitation in transplanted rat kidney by MRI with arterial spin labeling

The purpose of this study was to determine the feasibility of using quantitative magnetic resonance imaging (MRI) with non-invasive arterial spin labeling to assess perfusion of transplanted kidneys in rats. MRI studies were performed on five groups of rats: normal Fisher 344 rats, Fisher 344 rats that had received a syngeneic kidney transplant either 3 or seven days prior to study, and Fisher 344 rats that had received an allogeneic kidney (ACI rat as the donor) either three or seven days prior to study. The contralateral native kidney remained in place for comparison. Cortical perfusion was quantitated from a slice through the center of each kidney in anesthetized rats at 4.7 Tesla with a fast gradient-echo MRI sequence following the arterial spin labeling. The spin-lattice relaxation time was measured within the cortex, and the cross sectional area of the kidney was also determined within the same MRI plane. Immediately after the perfusion imaging measurement, transplanted kidneys were removed and scored for rejection using the Banff histological criteria. Renal cortical perfusion in normal kidneys was 7.5 +/- 0.8 ml/g/min (N = 12 rats, 24 kidneys). At the third day post-transplantation, that is, before marked acute rejection, the renal cortical perfusion rate was similar in both syngeneic and allogeneic kidneys [3.3 +/- 1.7 (N = 6) and 3.0 +/- 2.4 ml/g/min (N = 6), respectively]. In contrast, at the seventh day post-transplantation, that is, during severe rejection, the renal cortical perfusion rate in allogeneic kidneys was very low (undetectable) compared to the value in syngeneic kidneys [that is, < or = 0.3 (N = 6) versus 5.2 +/- 2.0 ml/g/min (N = 6), respectively]. Moreover, the renal cortical perfusion rate determined by MRI was significantly (P < 0.05, r = -0.82) correlated with histological rejection. We conclude that the quantitative measurement of renal cortical perfusion by MRI with arterial spin-labeling could provide a non-invasive diagnostic method for monitoring the status of renal transplants without requiring the administration of a contrast agent.

Influence of complement on the allospecific antibody response to a primary vascularized organ graft.

The induction of antibody responses against T cell-dependent antigens has been reported to be influenced by complement. We therefore asked if the primary induction of alloantibodies against transplantation antigens, an important determinant of transplant outcome, is complement sensitive and whether this has functional implications. We transplanted rat kidney allografts into fully major histocompatibility complex-mismatched recipients, in which complement activation was inhibited by daily injection of soluble recombinant human complement receptor type 1 (sCR1). Control allograft recipients were injected with saline. Animals in the control group showed a marked antibody response against donor-specific antigens and an increase in the proportion of activated B and T splenocytes by day 5 after transplantation. Complement-inhibited rats showed a reduced level of antibody binding on target cells sharing the same histocompatibility antigens as the donor strain (p < 0.001), and a reduced level of activated splenic B (p < 0.01) and T (p < 0.01) cells. In a functional assay, the plasma of complement-inhibited rats showed reduced cytotoxic activity against donor-specific cells, and their grafts contained less bound antibody than controls. Analysis beyond 6 days was obscured due to the development of antibodies against sCR1. We conclude that complement activation facilitates the induction of the alloantibody response. Sparing of vascular injury and prolongation of graft survival, previously reported in complement-inhibited rats (Pratt J. R. et al., Am. J. Path. 1996, 149: 2055), could therefore be due to down-regulation of the B cell response as well as reduced complement-dependent cytotoxicity. Inhibition of complement may provide an ancillary approach to the prevention of allospecific antibody formation and the prolongation of allograft survival in primary kidney grafting.

The effects of surgery and acute rejection on glomerular hemodynamics in the transplanted rat kidney.

The effects of surgery and acute rejection on glomerular hemodynamics in the transplanted rat kidney are examined. Kidneys were transplanted from Munich-Wistar (MW) rats to syngeneic controls and MHC-incompatible PVG strain recipients. We report on 4 groups of animals: (1) two-kidney control MW rats; (2) unilaterally nephrectomized MW rats (UNX); (3) renal transplantation from MHC-identical MW littermates and removal of native kidneys (SYN); and (4) transplantation from MW donors to MHC-incompatible PVG rats and removal of native kidneys (ALLO). Glomerular filtration rate (GFR), single-nephron (SN)GFR, and glomerular capillary pressure (PGC) in SYN kidneys were depressed as compared to those in UNX (GFR, 1.41 +/- 0.08 vs. 0.80 +/- 0.08 ml/min; SNGFR, 67.2 +/- 4.8 vs. 44.7 +/- 6.6 nl/min; and PGC, 67 +/- 2 vs. 48 +/- 4 mmHg, UNX vs. SYN, respectively, P < 0.05). GFR and SNGFR in ALLO kidneys, however, were depressed even further (GFR, 0.40 +/- 0.05 ml/min; SNGFR, 13.8 +/- 1.8 nl/min; P < 0.05 for UNX vs. ALLO and SYN vs. ALLO). Afferent arteriolar resistance (RA) was increased greater than 4-fold (UNX, 1.01 +/- 0.15 10(10) dyn.sec.cm-5; SYN, 1.37 +/- 0.36 10(10) dyn.sec.cm-5; ALLO, 4.76 +/- 0.74 10(10) dyn.sec.cm-5 [P < 0.05, UNX vs. ALLO and SYN vs. ALLO]). This led to a precipitous fall in initial capillary flow rate in ALLO rats. These studies reveal the presence of moderate reductions in SNGFR and PGC in the nonrejecting transplanted kidney, which may relate to as yet unidentified consequences of the transplant surgery. More significantly, the principal mechanism leading to the reduced GFR characteristic of acute allograft rejection is identified as severe preglomerular vasoconstriction.

Reversible compensatory hypertrophy in transplanted Brown Norway rat kidneys

Recently we described methods for optimizing the function of transplanted rat kidneys. In unilaterally nephrectomized recipients, one week after surgery, the left transplanted kidney was identical to the right native kidney with respect to wet weight and the clearances of inulin and para-aminohippuric acid (PAH). The goals of the present experiments were first, to extend the post-surgery period to three weeks (sufficient to allow hypertrophic changes), and second, to study function of transplanted hypertrophied kidneys. Genetically identical Brown Norway rats were used as donor and recipients. Three weeks after transplanting a normal kidney into a unilaterally-nephrectomized recipient, the transplanted kidney had a normal plasma flow and was identical to the contralateral native kidney with respect to wet weight and the clearances of inulin and PAH. Three weeks after transplanting a normal kidney into a bilaterally-nephrectomized recipient, the wet weight, inulin and PAH clearances, and plasma flow of the transplanted kidney were all higher than control, and not significantly different from those observed in unilaterally-nephrectomized control rats. Thus, transplanted and native kidneys exhibited the same degree of compensatory hypertrophy. Hypertrophied donor kidneys (that is, the donor rat had been unilaterally-nephrectomized three weeks previously) remained hypertrophied in bilaterally-nephrectomized recipients, but in unilaterally-nephrectomized recipients, they regressed towards normal (that is, the values of wet weight, inulin and PAH clearances and plasma flow were significantly less than those in rats with only one kidney) while the contralateral native kidney remained normal (values of wet weight and inulin and PAH clearances were not different from control).(ABSTRACT TRUNCATED AT 250 WORDS)

KIDNEY TRANSPLANTS IN CYCLOSPORINE-TREATED SPRAGUE-DAWLEY RATS

Previous studies by others have shown that transplanted rat kidneys have abnormally low clearances of paraaminohippuric acid, inulin, and creatinine, due to rejection and/or to warm-ischemia-induced injury. In the present studies, randomly bred Sprague-Dawley rats were used as donors and recipients. The left kidneys of recipients were removed, and the right kidneys were left intact. Donor kidneys were flushed with an ice-cold hypertonic solution (150 mM NaCl, 200 mM mannitol, pH 6.4), and the kidneys were kept cold during surgery. Renal function was assessed 1 week later. The left transplanted kidneys in untreated recipients exhibited morphologic evidence of rejection, and the clearances of PAH and inulin were approximately 50% of those of the right native kidneys. CsA-treated rats did not reject the transplants, and the PAH and inulin clearances of the left transplanted kidneys were identical to those of the right native kidneys. Untreated and CsA-treated rats with both native kidneys intact served as controls. The amount of CsA given during the 7-day period produced no measurable change in renal function. This is the first demonstration of virtually normal hemodynamics in transplanted rat kidneys when randomly bred animals are used as donors and recipients. Moreover, the results indicate that if both rejection and warm ischemia are avoided, the presence of a functioning native kidney does not have a detrimental effect on the function of a transplanted kidney.

Influence of different preservation solutions and intentional hemodilution of recipient on viability of preserved and transplanted rat kidneys

A total of 81 rat kidney grafts, flushed out and cold stored in either Sacks' or University of Wisconsin (UW) solution, were transplanted into hemodiluted (Hct = 30% +/- 4%) or untreated (Hct = 43% +/- 3%) recipients. The cold ischemia times (CIT) used were 24 and 36 h. One week after transplantation, the surviving recipients (n = 67) were contralaterally nephrectomized. The experiment was terminated after a total period of 4 weeks, and the percentage of surviving animals was determined for each treatment. Data was pooled and the results show that grafts cold stored in UW solution were viable to a significantly greater extent and after longer CIT than grafts cold stored in Sacks' solution (47% vs 23%; P less than 0.05). Recipient hemodilution did not improve graft viability (39% vs 32%; NS). Kidneys cold stored for 24 h were viable to a greater extent than kidneys with a CIT of 36 h (50% vs 15%; P less than 0.01).

Influence of different preservation solutions and intentional hemodilution of recipient on viability of preserved and transplanted rat kidneys

Abstract. A total of 81 rat kidney grafts, flushed out and cold stored in either Sacks' or University of Wisconsin (UW) solution, were transplanted into hemodiluted (Hct = 30%± 4%) or untreated (Hct = 43%± 3%) recipients. The cold ischemia times (CIT) used were 24 and 36 h. One week after transplantation, the surviving recipients (n= 67) were contralaterally nephrectomized. The experiment was terminated after a total period of 4 weeks, and the percentage of surviving animals was determined for each treatment. Data was pooled and the results show that grafts cold stored in UW solution were viable to a significantly greater extent and after longer CIT than grafts cold stored in Sacks' solution (47% vs 23%; P< 0. 05). Recipient hemodilution did not improve graft viability (39% vs 32%; NS). Kidneys cold stored for 24 h were viable to a greater extent than kidneys with a CIT of 36 h (50% vs 15%; P < 0. 01).

Indomethacin inhibits renal functional adaptation to nephron loss.

Immediately after unilateral nephrectomy, the glomerular filtration rate (GFR) and urinary excretion rate increase in the remaining transplanted rat kidney. In a previous study, we found that GFR in a transplanted kidney was reduced through an activation of the tubuloglomerular feedback control. Excision of the rat's own remnant kidney then reduced feedback sensitivity and thereby allowed GFR to rise. The present study aimed at investigating whether prostaglandins are involved in this functional adaptation. Clearance and micropuncture experiments were performed before and after administration of indomethacin and after subsequent unilateral nephrectomy. GFR and the urinary excretion rate of electrolytes and water were measured. From proximal tubular stop-flow pressure (PSF) measurements the feedback characteristics were determined as the maximal stop-flow pressure response (delta PSF) to an increase in distal flow and the turning point (TP), i.e. the end proximal flow rate that caused 50% reduction of delta PSF. The results showed that following nephrectomy the tubuloglomerular feedback sensitivity was decreased, with an increased TP and reduced delta PSF. Pretreatment with indomethacin (2 mg/kg BW) prevented not only the change in feedback sensitivity at nephrectomy but also the rise in GFR. These results suggest that the prostaglandins play a possible role as one link in the chain of adaptive events occurring immediately after nephron loss.

The glomerular filtration rate of isogeneically transplanted rat kidneys

The glomerular filtration rate (GFR) was determined in rats with an isogeneic kidney transplant and compared with that of unilaterally nephrectomized rats. Experiments were carried out in adult rats, 3 months of age, weighing approximately 300 g, as well as in juvenile rats, 6 to 8 weeks of age, weighing approximately 170 g. All donor kidneys were taken from adult rats. The GFR was measured regularly, using a chromium 51-EDTA clearance technique which permitted repeated measurements to be taken in the same animals, during a 15-week followup period. After unilateral nephrectomy the GFR per 100 g body weight (BW) increased compared with that of a single normal kidney. Adult transplant recipients had a GFR per 100 g BW of about 80% of that of unilaterally nephrectomized rats. There was no statistical difference in the GFR when comparing adult recipients of either a normal or a hyperfunctional kidney. When isografts were transplanted to juvenile recipients, there was an initial decrease in the absolute GFR compared with the donor value in the case of a normal adult donor kidney. This decrease was even more pronounced when a hyperfunctioning kidney was transplanted to a juvenile recipient. However, when related to BW the GFR was, as in the adult recipients, about 80% of that of unilaterally nephrectomized juvenile rats. During the followup period the systolic blood pressure was measured regularly by tail plethysmography, in order to detect any blood pressure elevations, which are a frequent complication in adult and pediatric human renal transplantation. However, no hypertension was observed after isogeneic kidney transplantation in the various groups. These results show that the GFR of isogeneically transplanted rat kidneys amounts to about 80% of the maximally attainable level. Isogeneic transplantation of an adult kidney to a juvenile recipient results in a rapid adaptation of the GFR to the smaller size of the body and does not cause an increase in blood pressure.

Effects of cold ischemia on the preserved and transplanted rat kidney. Structural changes of the loop of Henle, distal tubule and collecting duct.

The effects of cold ischemia on the loop of Henle, distal tubule and collecting duct of the rat kidney were studied by light and electron microscopy in vitro and also in vivo after transplantation. The duration of cold ischemia was chosen so that after transplantation the function of the kidneys was normal (2 h of ischemia), greatly reduced (12 h) and almost abolished (16 h). The results showed that the cold ischemia led to alterations in the thin loop of Henle and distal tubule in vitro which were reversible, judging from the fine-structural appearance. In the thick ascending limb of the loop of Henle and the collecting duct there were alterations in some cells that could have been signs of irreversible cell damage, but probably were fixation artifacts. In vivo 24 h after transplantation of kidneys exposed to 12 and 16 h of cold ischemia extensive necrotic areas comprising loops of Henle and collecting ducts were seen in the inner stripe of the outer zone of the medulla, and to some extent in the inner zone of the medulla. In segments with viable cells the only changes were proteinaceous casts and cell debris in the lumina and a moderate number of intracellular absorption droplets, especially in the medullary part of the collecting duct. It seems probable that the functional impairment in these groups was caused by the widespread necrotic areas in the inner stripe and inner zone, which were presumably the result of an unsatisfactory reflow of blood to these regions after transplantation, a “no reflow” phenomenon.