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K Solez

Publications and source records attributed to K Solez.

At least 55 records · Page 3Linked to original sources
PubMed1995

A comparison of the effects of rapamycin and cyclosporine on kidney and heart morphology in a rabbit heterotopic heart transplant model.

Rapamycin (RAPA) or cyclosporine (CsA) was administered intravenously, daily for 60 days, to rabbits with heterotopic heart transplants. Groups of 5 rabbits were randomly assigned to receive RAPA at 0.05, 0.1, 0.5 or 1.0 mg/kg/day or CsA at either 5.0, 10.0 or 15 mg/kg/day. Drug vehicle and saline controls were also included. Animals were examined daily and the cervical allografts assessed by palpation for viability/rejection. In those animals in which the heart stopped beating, the heart was removed and processed for light microscopic evaluation. The duration of the study was for 60 days at which time the animals were sacrificed and the transplanted heart and native kidneys removed and processed for light microscopic assessment of rejection and drug toxicity respectively. Biochemical and functional parameters in these animals were previously reported (Transplantation 5: 340-345, 1993). Animals that rejected their grafts were maintained on the drug until the endpoint of the study to assess toxicity in the native kidneys. The rejected hearts from these animals were also harvested for microscopic evaluation. The results of the study revealed that heart rejection in drug treated animals was significantly lower than in corresponding controls but not different among the various drug treated groups. In the kidney, there were no differences in glomerular tuft area or tuft volume density amongst drug-treated or control animals. In contrast, tubule atrophy and interstitial fibrosis were markedly greater in CsA-treated vs RAPA-treated animals (X2 5.00, p < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Dysplastic tubular epithelium in "normal" kidney associated with renal cell carcinoma.

Intratubular epithelial dysplasia (IED) of the renal tubules has not been fully described in human renal cell carcinoma (RCC). This lesion has been found in male Syrian hamsters exposed to estrogens. One article reports IED in human kidney showing nephrosclerosis and RCC. We examined "normal" kidney tissue adjacent to 110 cases of RCC in an attempt to identify possible precursor lesions. There were 73 male and 37 female patients (M/F = 2:1). The ages ranged from 27 to 86 years (median 64 years). IED was identified in 30 cases. The lesions consisted of foci of crowded tubular epithelium with large, vesicular nuclei two to three times the size of nuclei of benign tubular cells with eosinophilic macronucleoli. The tubules were occasionally filled with dysplastic cells mimicking carcinoma in situ. The lesions were predominantly cortical and periglomerular. They either were subtle and focal or, less commonly, involved tubules diffusely. Eighteen of the 73 male patients (24%) had these lesions compared with 12 of 37 female patients (32%). They were more usually seen in the clear cell (21 of 66) and sarcomatoid (three of four) variants of RCC than in the oncocytic/granular cell (four of 25) or tubulopapillary (two of 14) variants. One case of collecting duct RCC showed no evidence of IED. Immunohistochemical assessment of 20 dysplastic and 20 nondysplastic lesions with their adjacent RCC for cytokeratin, vimentin, cathepsin-D, and epidermal growth factor receptors was inconclusive. Our findings suggest that IED associated with RCC might represent previously unrecognized precursor lesions along the spectrum ranging from dysplasia to frank carcinoma. The biological significance of these lesions, their preponderance in women, and the phenotypic and genotypic characteristics require further investigation.

Adult↗
PubMed1994

Immunochemical study of epidermal growth factor in rats with mercuric chloride-induced acute renal failure.

Urine contains high concentrations of epidermal growth factor (EGF), and EGF is a potent growth promoter for proximal tubular cells. In the present study, urinary and whole-kidney EGF levels were investigated in rats with mercuric chloride (HgCl2)-induced acute renal failure (ARF) using a specific radioimmunoassay for rat EGF to clarify changes in EGF after toxic injury. Male Wistar rats were given HgCl2 (2 mg/kg, subcutaneously) or saline. Serum urea nitrogen and creatinine levels were measured for 4 days after toxin administration. Forty-eight hours after toxic injury, urinary immunoreactive EGF levels in HgCl2-treated rats decreased significantly compared with control rats (1.62 +/- 0.15 versus 3.78 +/- 0.21 ng/mg creatinine; p < 0.01). Urinary immunoreactive EGF was at its lowest level 96 h after toxic injury (0.64 +/- 0.06 ng/mg creatinine; p < 0.001). Twenty-four hours after toxic injury, renal immunoreactive EGF levels increased significantly compared with control rats (22.04 +/- 2.12 versus 4.84 +/- 0.70 ng/g wet weight tissue; p < 0.001), and the increase persisted for as long as 48 h (13.36 +/- 1.61 ng/g wet weight tissue; p < 0.05). In summary, urinary immunoreactive EGF levels decreased and renal EGF levels increased in rats with HgCl2-induced ARF. These findings suggest that there is an impairment in the excretion of EGF in rats with HgCl2-induced ARF and that local paracrine production of EGF continues in ARF.

Acute Kidney Injury↗
PubMed1994

The anemia of acute renal failure: association with oliguria and elevated blood urea.

Anemia is very frequent in patients with acute failure but the nature of the relationship between the two conditions has remained unclear. We studied all patients with well-documented acute renal failure seen in consultation by our nephrology division during 1991. Fifty-three of the 56 patients had at least mild anemia (hematocrit < 35%) at some point during their hospital stay. Forty-three of the patients had a hematocrit below 30% and 14 had a hematocrit below this level on admission. Twenty-four of the patients underwent major operations and all of these patients required blood transfusions. In this group there was a significant correlation between maximum serum urea and lowest hemoglobin (r = 0.4, p < .05) but no similar correlation between maximum creatinine and lowest hemoglobin. Oliguric patients had a mean lowest hemoglobin of 7.3 +/- 0.4 g/dL, which was significantly lower than the value for nonoliguric patients, 9.0 +/- 0.4 g/dL. This study confirms the presence of anemia in 91% of patients with acute renal failure and shows it to be related to rise in urea and presence of oliguria. Clearly, however, the anemia is multifactorial, since in one-quarter of the patients it precedes onset of renal failure.

Acute Kidney Injury↗
PubMed1994

International standardization in renal allograft biopsy reporting: a model for a new approach to renal pathology.

As we prepare to enter a new century it is reasonable to ask whether our current classification system of renal pathology and descriptive approach to renal biopsy interpretation will be appropriate to the medicine of the future. Assessment of that special category of acute renal failure represented by early post-transplant biopsies is becoming much more quantitative, therapy-oriented, and pathogenesis-based. It would be highly beneficial to the field if similar changes occurred in our approach to native kidney biopsies. We need to provide tighter linkage between exciting new developments in the research laboratory and the clinical practice of renal pathology. In a field largely limited to traditional empirical therapies, we need to be developing new pathogenesis-oriented therapeutic approaches to native kidney disease based on the results of enlightened renal pathology research.

Biopsy↗
PubMed1994

Glomerular endothelial cell detachment in paired cadaver kidney transplants: evidence that some cadaver donors have pre-existing endothelial injury.

Poor initial function is common in cadaveric renal transplantation, and is usually attributed to acute tubular necrosis (ATN) brought about by ischemia during harvesting/implantation. However, this is often an assumption rather than a specific diagnosis. Recently, in 4 kidneys from 2 cadaver donors, we found evidence of severe endothelial injury, prior to exposure to cyclosporine or other known endothelial toxins. The biopsies at the time of completion of the transplant revealed apparent loss of glomerular endothelial cells on light microscopy, corresponding on electron microscopy to shrinkage of the endothelial cells away from the basement membranes of the capillary loops. Extensive microvascular thrombi were present. All 4 grafts displayed impaired initial function, which partially recovered with time. The finding of these unusual lesions in both kidneys from each of 2 donors suggested donor factors, although the only factor common to both donors was massive brain disruption. Thus, in the differential diagnosis of poor initial function in kidneys transplanted from cadaver donors, one should consider renal endothelial injury, which could lead to microthrombus formation, abnormal vasomotion, and functional impairment in the transplant.

Adult↗
PubMed1994

International standardization of criteria for histologic diagnosis of chronic rejection in renal allografts.

An accurate diagnosis of acute rejection in renal allografts can be made histologically by quantitating specific morphologic changes observed on biopsy. The Banff Schema, an internationally standardized system of renal allograft biopsy assessment published in the August 1993 issue of Kidney International (1) has been shown to be highly reproducible and clinically valid for acute rejection. The schema also includes quantitation of the lesions of chronic rejection: fibrous intimal thickening, chronic transplant glomerulopathy, interstitial fibrosis, tubular atrophy. Biopsies that demonstrate these lesions are assigned the noncommittal term "chronic transplant nephropathy," as other conditions such as cyclosporine toxicity, hypertension, infection, and reflux can generate these lesions as well. In certain clinical settings, some lesions probably are specific for chronic rejection, such as fibrous intimal thickening with fragmentation of the elastic lamina, but because of their extreme focality they are infrequently seen on biopsy. It is possible that chronic rejection involves a specific pattern of scarring and peritubular capillary injury, but these changes have yet to be fully characterized. Late allograft biopsies in ongoing clinical trials of new immunosuppressive agents will help to further define the specific pathologic changes of chronic rejection.

Atrophy↗
PubMed1994

New approaches to renal biopsy assessment in acute renal failure: extrapolation from renal transplantation.

Although frequently considered synonymous with acute tubular necrosis, acute renal failure may be brought about by primary disease in any of the four histologic components of the kidney: glomerular, tubular, interstitial, or vascular. It is reasonable to ask whether our current classification system of renal pathology and descriptive approach to renal biopsy interpretation in this setting is optimal. Assessment of renal transplant biopsies performed in the setting of acute dysfunction is becoming much more quantitative, therapy-oriented, pathogenesis-based, and standardized. It would be highly beneficial to the field if similar changes occurred in the approach to native kidney biopsies in acute renal failure. Tighter linkage should be established between promising new developments in the research laboratory and the clinical practice of renal pathology with creation of therapy-oriented classifications which employ standardized quantitative lesion assessment. In a field largely limited to traditional empirical therapies, new pathogenesis-oriented therapeutic approaches to native kidney acute renal failure and allied conditions should be developed based on the products of enlightened renal pathology research.

Acute Kidney Injury↗
PubMed1993

Morphology of ischemic acute renal failure, normal function, and cyclosporine toxicity in cyclosporine-treated renal allograft recipients.

To characterize morphologic changes in the early post-transplant period in cyclosporine-treated renal allograft recipients, we examined biopsies from three groups of cyclosporine-treated patients: normal function (N = 9), ischemic acute renal failure or "acute tubular necrosis" (N = 12), and cyclosporine toxicity (N = 7). Groups were compared with each other and with previously studied groups of azathioprine-treated patients and native kidney patients. The interstitial infiltrate commonly observed in normally functioning azathioprine-treated grafts was not observed in normally functioning cyclosporine-treated grafts, but two of nine such grafts had a significant venulitis, a change also seen in three of the patients with cyclosporine nephrotoxicity. "Acute tubular necrosis" (ATN) in cyclosporine-treated graft recipients was characterized by focal necrosis of complete tubular cross sections, a finding normally rare in other types of ATN, and by shedding into the tubular lumen of tubular cells with non-pyknotic nuclei, a finding supporting our previous observation of detachment of viable tubular cells in ATN but not in the normal kidney. Hyaline arteriolar thickening was the only morphologic finding on biopsy which distinguished patients with cyclosporine nephrotoxicity from other groups. In summary, the morphologic changes observed in cyclosporine-treated renal allograft recipients with ATN or normal function are quite different from those observed in azathioprine-treated patients. Cyclosporine appears to enhance the tubular injury observed in ATN. Hyaline arteriolar thickening is the main distinguishing feature of cyclosporine nephrotoxicity.

Adult↗
PubMed1993

International standardization of criteria for the histologic diagnosis of renal allograft rejection: the Banff working classification of kidney transplant pathology.

A group of renal pathologists, nephrologists, and transplant surgeons met in Banff, Canada on August 2-4, 1991 to develop a schema for international standardization of nomenclature and criteria for the histologic diagnosis of renal allograft rejection. Development continued after the meeting and the schema was validated by the circulation of sets of slides for scoring by participant pathologists. In this schema intimal arteritis and tubulitis are the principal lesions indicative of acute rejection. Glomerular, interstitial, tubular, and vascular lesions of acute rejection and "chronic rejection" are defined and scored 0 to 3+, to produce an acute and/or chronic numerical coding for each biopsy. Arteriolar hyalinosis (an indication of cyclosporine toxicity) is also scored. Principal diagnostic categories, which can be used with or without the quantitative coding, are: (1) normal, (2) hyperacute rejection, (3) borderline changes, (4) acute rejection (grade I to III), (5) chronic allograft nephropathy ("chronic rejection") (grade I to III), and (6) other. The goal is to devise a schema in which a given biopsy grading would imply a prognosis for a therapeutic response or long-term function. While the clinical implications must be proven through further studies, the development of a standardized schema is a critical first step. This standardized classification should promote international uniformity in reporting of renal allograft pathology, facilitate the performance of multicenter trials of new therapies in renal transplantation, and ultimately lead to improvement in the management and care of renal transplant recipients.

Graft Rejection↗
PubMed1993

Pathology of kidney transplant rejection.

In the past year there has been considerable progress in defining the morphologic characteristics of the normally functioning renal allograft in the cyclosporine era. Based on these characteristics and knowledge of clinically validated important changes in rejection, internationally agreed upon standardized terms and criteria have been developed for the histologic diagnosis of acute and chronic rejection and allied conditions. Chronic changes observed in normally functioning grafts at 2 years posttransplantation have been shown to predict the presence of renal functional impairment for 4 years. Important new rejection changes have been identified in the peritubular capillaries. Various alternatives to core biopsy have been explored, but no technique as yet has sufficient sensitivity and specificity for general use in rejection diagnosis. The accurate distinction of chronic rejection from other conditions remains a challenge for the future.

Biopsy, Needle↗
PubMed1992

The significance of the anti-class I response. II. Clinical and pathologic features of renal transplants with anti-class I-like antibody.

Although the ability of preformed anti-class I antibodies to mediate hyperacute rejection is well established, their pathogenic role in acute rejection remains ill-defined. We set out to identify patients with anti-class I against donor cells and to define the clinical and pathological features of such patients. We collected sera pretransplant and in the first 3 months posttransplant from 64 renal transplant recipients (59 cadaver donors and 5 one-haplotype matched living-related donors). We assayed the sera for class I-like antibody against donor T cells in complement-dependent microcytotoxicity, with crossmatches against autologous T cells to exclude auto-antibodies. All pretransplant sera were negative against donor T cells. Of the 797 sera tested posttransplant, 131/195 sera from 13 patients were positive, and 602 sera from 51 patients were negative. All patients who formed anti-class I underwent rejections compared with only 41% of patients with no anti-class I detected (P less than 0.0005). More rejections in patients with anti-class I were classed as severe (12/15 [80%] compared with 9/28 [32%] P less than 0.005), and graft loss was significantly higher (5/13 vs. 2/51; P less than 0.002). Rejections associated with anti-class I occurred earlier; more frequently developed oliguria (35% versus 10%) and required dialysis (40% versus 10%) and biopsies (10/13 vs. 6/28); and had a higher rate of rise in serum creatinine (249 versus 79 microns/L in the first 48 hr). Biopsies during anti-class I positive rejections more frequently displayed endothelial injury in the microcirculation, neutrophils in the glomeruli and/or peritubular capillaries, and fibrin deposition in glomeruli or blood vessels. The biopsies in anti-class I negative rejection episodes tended to have tubulitis, interstitial infiltration, and blasts, suggesting that these lesions reflect T-cell-mediated mechanisms. We conclude that patients with antibody against donor class I had more severe rejection, probably because anti-class I injuries the endothelium of small blood vessels of the graft, leading to rapid functional deterioration. We believe that anti-class I may be a major factor in some severe rejection episodes.

Adolescent↗
PubMed1991

Dissociation of tubular cell detachment and tubular cell death in clinical and experimental "acute tubular necrosis".

"Acute tubular necrosis" in humans is often characterized histologically by tubular cell loss and nonreplacement rather than by frank cellular necrosis. It has been assumed that tubular cells detach from the tubular basement membrane after the occurrence of irreversible cell injury and/or cell death. We examined voided urine from patients with native kidney and transplant kidney "acute tubular necrosis" and found significant tubular cell shedding with up to 100% viability of voided tubular cells, as determined by exclusion of trypan blue. Histochemical stains for the brush border enzyme gamma-glutamyl transpeptidase and electron microscopy of cell isolates demonstrated that 30 to 100% of the voided cells were of proximal tubule origin. Moreover, epithelial cell cultures were readily established from noncontaminated voided specimens, and more than 80% of the cells in monolayers expressed gamma-glutamyl transpeptidase activity in vitro. Electron microscopy of cell monolayers confirmed proximal tubular differentiation in the majority of cells in the monolayer, with the remainder having an appearance more consistent with distal origin. In rabbit models of acute ischemic (pedicle clamp) and toxic (HgCl2 and glycerol-induced) injury, tubular cell shedding was also significant, with a mean of 25 to 30% of the voided cells viable. Epithelial cells were successfully cultured and passed from animals with ischemic renal injury. In vitro studies were carried out in cultured human proximal tubular cells to assess suitability of this system for more direct study of the phenomenon of cell detachment in response to injury. We found significant changes in cell shape in response to exposure to anoxia and HgCl2 in these cultures, with extensive cell rounding and retraction at times when cell viability remained high. This in vitro system could prove useful for defining mechanisms of renal tubular cell detachment in response to injury and for examining potential interventions to prevent epithelial disruption and loss of functional integrity. These strategies may ultimately have clinical relevance in patients with "acute tubular necrosis".

Acute Kidney Injury↗
PubMed1991

Ideas in pathology. Exfoliation of renal tubular cells.

"Acute tubular necrosis" is characterized histologically by tubular cell loss and nonreplacement. There is new evidence that tubular cells may be shed from the tubular basement membrane while still viable. This phenomenon is described in both clinical and experimental acute renal failure. Exfoliation of tubular cells may contribute importantly to the pathogenesis of acute renal failure due to tubular cell injury.

Acute Kidney Injury↗
PubMed1990

Progressive renal failure due to renal invasion and parenchymal destruction by adult T-cell lymphoma.

A 43-year-old patient of occult adult T-cell lymphoma (ATL) presenting with systemic illness and progressive renal failure due to lymphomatous infiltration of kidneys is described. The striking feature observed was destructive infiltration of the kidneys, by malignant CD4 cells, virtually replacing the normal renal architecture. The diagnosis of lymphoma was made by renal biopsy. Clinical features typical of ATL were hypercalcemia, lytic bone lesions, and profound wasting and inanition. The patient died rapidly despite attempted therapy. The case illustrates the potential of ATL for direct renal parenchymal destruction.

Adult↗
PubMed1990

The significance of the anti-class I antibody response. I. Clinical and pathologic features of anti-class I-mediated rejection.

In renal transplantation, preformed cytotoxic antibody against donor HLA class I antigens causes hyperacute rejection of renal allografts, but its pathogenic significance when it develops in the posttransplant period is unknown. In the present studies we describe the clinical and pathologic features of patients with rejection associated with anti-class I. In the course of 400 consecutive cadaveric renal transplants, 7 patients were identified who had antibody against donor class I HLA antigens in association with atypical but distinctive patterns of rejection. All 7 were presensitized. In 3 patients, the transplant had been inadvertently performed with a positive donor-specific T cell crossmatch. In the remaining 4, the T cell crossmatch on current sera was negative but became positive posttransplant. The clinical picture was deterioration of graft function with rapid onset of oliguria, apparently due to acute tubular necrosis, but with persistence of blood flow demonstrable by radioisotope scan studies. Renal histology showed that the typical lesions observed in cell-mediated rejection, such as tubulitis and interstitial infiltration, were absent. Granular complement deposition (6), polymorphonuclear infiltration (6), and endothelial injury in the microvasculature (6) were common, and mononuclear infiltrates were absent (2) or not prominent (4). In 3 patients the glomerular changes resembled a picture of hemolytic uremic syndrome, with capillary fibrin thrombi and widening of the subendothelial space. IgG staining was negative. The pathologic features suggest that anti-class I antibody appearing or persisting in the early posttransplant period injures the endothelium of the microvasculature, with the clinical presentation different from that of hyperacute rejection. Particularly in sensitized patients, rapid deterioration in function, leading to a picture of acute tubular necrosis, with pathologic features of endothelial injury in the microcirculation, should suggest the diagnosis of anti-class I-mediated rejection.

Adult↗