Acute thrombosis of the renal transplant artery after a single dose of OKT3.

We present the case of an 18-year-old male who 8 months after a living-related donor, one-haplotype-matched renal transplantation developed acute thrombosis of the renal allograft artery, within 10 h of the first dose of OKT3. The antibody therapy had followed five daily doses of intravenous pulse methylprednisolone for a Banff class 1B acute tubulointerstitial rejection, on a ciclosporin-based immunosuppression protocol. We briefly review the literature on the incidence of vascular thrombosis after transplantation and the procoagulant effects of OKT3, pulse methylprednisolone, and ciclosporin therapy.

Percutaneous renal biopsy in the 1990s: safety, value, and implications for early hospital discharge.

To determine the parameters associated with significant bleeding and to examine the value of performing a renal biopsy, we studied 83 consecutive patients, including 24 renal allograft recipients, who had undergone percutaneous renal biopsy. The patients were stratified into four groups according to the percentage of decline in their hematocrit (Hct) at 24 hours postbiopsy, as follows: 10% or greater (n = 21; 25%) and less than 10% decline (n = 62; 75%). The latter group was further subgrouped into 5% to 10% (n = 22) and less than 5% decline (n = 40). There was a significant decline in Hct postbiopsy, with a linear correlation between the decrease in Hct at 6 and 24 hours (R2 = 0.47; P < 0.0001), suggesting that the former was a predictor of the latter. There was a linear correlation between the number of passes and number of cores obtained for the first four passes, but an inverse correlation when five passes or greater were required. Interestingly, there was no correlation between bleeding (>10% decline in Hct) and the number of passes or cores obtained. Gross hematuria and blood transfusion requirement were each encountered in three patients (3.6%). Importantly, the prebiopsy clinical diagnosis was altered in 18 of 59 native kidney biopsies (33%) and 10 of 24 transplant biopsies (41%). We conclude that percutaneous renal biopsy using an automated spring-loaded gun device coupled with ultrasound guidance is a safe technique and provides essential clinical information. Importantly, patients with a stable Hct at 6 hours were at low risk for bleeding at 24 hours while hospitalized. It remains to be determined if these findings could be extrapolated to early discharge from hospital.

Lupus nephritis in an anti-nuclear antibody-negative young male. The simultaneous presence of class III and class V renal lesions.

We report about a 27-year-old white male, a known case of class III lupus nephritis with a very high anti-nuclear antibody (ANA) titer, who after 10 years of complete clinical and serological remission presented with sudden development of malar rash, proteinuria and an increase in the serum creatinine. Repeated serologic studies were all negative for ANA. A repeat kidney biopsy disclosed the presence of focal segmental glomerulosclerosis lupus nephritis (class IIIc) superimposed with a new membranous lupus nephritis (class V).

Polyarticular pigmented villonodular synovitis in a child.

Pigmented villonodular synovitis is rare in the younger child. Polyarticular involvement in this condition, regardless of patient age, is distinctly uncommon. The authors describe a case of pigmented villonodular synovitis involving multiple joints in a young boy who also had congenital anomalies of the genitourinary tract. Although rare, pigmented villonodular synovitis should be considered in the differential diagnosis of multiple joint swellings in children with congenital anomalies.

Renoprotective effects of the 21-aminosteroid U74389G in ischemia-reperfusion injury and cold storage preservation.

Free radical mediated lipid peroxidation (LPO) has been implicated in the pathogenesis of ischemic-reperfusion injury (IRI). To address the renoprotective effect(s) of LPO inhibition, the efficacy of the 21 aminosteroid U74389G was evaluated in three IRI models. In Model 1 51 unilateral nephrectomized rats that underwent 60 min of warm ischemia followed by a 72-hr reperfusion interval were treated with the test vehicle only, or 3, 6, or 12 mg/kg of U74389G intravenously, 5 min pre- or postischemia. In Model 2 Sprague-Dawley rats underwent sham operation (n=9), or 45 min of warm ischemia and 10 min of reperfusion with U74389G (6 mg/kg; n=10) or test vehicle only (n=10) administered intravenously over 10 min beginning 5 min prior to clamp release. After reperfusion, LPO was determined by assay of snap frozen tissue for thiobarbituric acid (TBA) concentrations (nmol/g tissue weight). In Model 3 domestic lean maid pigs (14-18 kg) underwent left nephrectomy with 30 min of warm ischemia, Collins C-4 flush, and 24 hr of cold storage preservation. Heterotopic autotransplantation and immediate contralateral nephrectomy was then performed in Group A-nonischemic controls (n=4), Group B-ischemic controls (n=5), and Group C-U74389G (6 mg/kg) administered preischemia and at autotransplantation (n=5). In Model 1 maximal renoprotection was demonstrated with the 6 mg/kg dose of U74389G administered after ischemia (ischemic control 72-hr serum creatinine (Cr) = 8.01+/-1.1 mg% vs. 3.32+/-0.96 mg%; ischemic control creatinine clearance = 0.069+/-0.03 ml/min vs. 0.206+/-0.04 ml/min; P<0.05). In Model 2 TBA levels were significantly lower in U74389G treated animals (88.5+/-10.0 vs. ischemic controls = 296.8+/-81.4; P=0.02). In Model 3 graft survivals were 100%, 0%, and 60% respectively. Peak Cr and BUN (mg%) were significantly greater in Group C vs. Group A, (Group A Cr = 8.59+/-0.63 vs. Group C = 12.8+/-1.01; Group A BUN = 64.1+/-2.73 vs. Group C = 104.9+/-12.21)--however, by day 10, thee were no significant differences in renal function: (Group A Cr = 2.15+/-0.3 vs. Group C = 2.10+/-0.06; Group A BUN = 27.0+/-6.0 vs. Group C = 31.1+/-6.4). These results support the beneficial effects of LPO inhibitors in models of ischemia-reperfusion, as well as preservation/transplantation, and suggest that this renoprotection correlates with decreased membrane lipid peroxidation.

Evaluation of the thromboxane A2 synthetase inhibitor OKY-046 in a warm ischemia-reperfusion rat model.

The pathophysiology of ischemia-reperfusion renal injury is mediated, in part, by the generation of the vasoconstricting prostanoid thromboxane A2 (TXA2). This study was undertaken to evaluate the renoprotective effects, as well as the optimal timing and dosage, of a selective thromboxane synthetase inhibitor, OKY-046, in a unilateral nephrectomized, 60 min ischemia, 72 hr reperfusion, rodent model. Forty-one rats were subjected to right nephrectomy only (group A), or right nephrectomy with 60 min of left renal ischemia and treatment with inactive vehicle only (group B), or 2 mg/kg or 4 mg/kg of OKY-046 administered intravenously before (groups C and D) or after (groups E and F) pedicle clamping. Outcome variables included animal survival; change in kidney weight; 0, 24, and 72 hr plasma creatinine (CR); urea nitrogen (BUN); thromboxane B2 (TXB2) and 6-keto prostaglandin F(1alpha) (6 kPGF(2alpha)) levels; creatinine clearance (CRCL); and histologic evidence of renal injury. Animal survival and postperfusion kidney weight were not significantly different among the groups. However, renal functional parameters were significantly improved with the 2 mg/kg dose of OKY-046 administered after renal ischemia. (group B 72 hr Cr= 8.01 +/- 1.1 mg% vs. group E=3.99 +/- 1.5 mg%, and group B 72 hr BUN=241.3 +/- 32.8 mg% vs. group E=52.6 +/- 22.5 mg%). The CRCL was also improved in group E vs. group B, although these results did not reach statistical significance (group B=0.069 ml/min vs. group E=0.194 ml/ min). The 24 hr TXB2 levels were significantly increased in group B (0 hr=754.1 +/- 219.4 pg/ml vs. 24 hr=2055.9 +/- 550.0 pg/ml), and pre- or posttreatment with OKY-046 abrogated this increase (group C 0 hr=517.1 +/- 80.9 pg/ml vs. 24 hr=384.7 +/- 251.5 pg/ml, and group E 0 hr=781.6 +/- 390.4 pg/ml vs. 24 hr=183.0 +/- 81.4 pg/ml). The 24 hr 6 kPGF(1alpha) levels decreased in all groups, whereas 72 hr 6 kPGF(1alpha) levels increased above baseline in groups A, C, and E, but not in group B. These data demonstrate the beneficial effects of thromboxane A2 synthesis inhibition in the setting of ischemia-reperfusion injury and suggest that this renoprotection correlates with late vasodilatory prostanoid synthesis.

Myocardial toxoplasmosis complicating cardiac transplant.

The increase in numbers of immunocompromised patients has been reflected by an increasing frequency of opportunistic infections. Of these, Toxoplasma gondii has been reported as a significant human pathogen following cardiac transplantation. In this setting, quiescent toxoplasma myocardial cysts may become active after implantation into a therapeutically immunosuppressed host. The consequences of infection are significant and carry a high morbidity and mortality. We present the clinical and pathologic characteristics of a patient with toxoplasma infection complicating cardiac transplant and review previously reported cases of this entity.

Experimental ureteral obstruction in the fetal opossum: histologic assessment.

In the North American opossum, Didelphis virginiana unilateral complete ureteral obstruction (ECO) and partial unilateral (EPO) ureteral obstruction were created during the early metanephric stage of kidney development in pups attached to the teat (approximately 4.5 cm. long, 20 days old). At 70 days of pouch life (full-term equivalent in the human) some completely obstructed ureters were unobstructed with reanastomosis in the bladder (RECO). Other pups underwent unilateral complete ureteral ligation at this full-term equivalent (70 days of pouch life) and constituted the late obstruction (LCO) group. Unoperated animals constituted the control (C) group. All animals were harvested when full grown (.7 to 2.2 kg.), and paraffin sections of the kidneys were stained with hematoxylin and eosin and Masson's Trichrome. In each a semiquantitative assessment of 24 histologic features was made and a digital score assigned. All experimental groups except EPO demonstrated significant epithelial and mesenchymal alterations. The changes can be broadly categorized as those secondary to obstruction of urine flow (dilation and cystic changes), those affecting epithelial differentiation in both cortex and medulla and those affecting mesenchymal differentiation. The EPO group demonstrated significantly fewer glomerular generations than did control kidneys. For all other characteristics studied, the EPO group did not differ from control. The ECO group demonstrated significant changes when compared with control for most parameters studied. Medullary dysplasia was more prominent in kidneys obstructed early. Reanastomosis (RECO) at a full-term equivalent did ameliorate the changes of medullary dysplasia and cortical atrophy. More collecting duct hyperplasia, cortical and medullary aplasia were present in the LCO group compared with the ECO. The LCO group also had less primitive duct formation and less medullary dysplasia than the ECO group. Renal blastema, previously unreported in experimental obstruction, was present in 41% of experimental kidneys.

Acquired essential fatty acid depletion in the remnant kidney: amelioration with U-63557A.

Previous studies have demonstrated an association between renal cortical fatty acid composition and experimental models of renal injury. The present study was designed to extend these observations to the remnant kidney and to investigate the hypothesis that increased endogenous turnover of arachidonic acid metabolites results in the depletion of progenitor fatty acids. Remnant kidney cortex demonstrated a relative reduction of the essential fatty acids, linoleate and arachidonate (20 +/- 7.2% and 11 +/- 0.3%, respectively), nine weeks after subtotal nephrectomy. In addition, the monounsaturated fatty acid, oleate, was increased (48 +/- 10.6%) while its saturated progenitor, stearate, was decreased (13 +/- 4.3%). Serial evaluation of dienoic prostanoids revealed a significant increase in the renal excretion of TXB2 in rats with remnant kidneys (27 +/- 3.0, 29 +/- 1.1, and 34 +/- 3.3 ng/day vs. 21 +/- 0.8, 20 +/- 1.5, and 22 +/- 3.3 ng/day in control rats, at 3, 6, and 9 weeks, respectively). Moreover, TXB2 excretion inversely correlated with dienoic progenitor fatty acids [18:2(n-6), r2 = 0.76; 20:4(n-6), r2 = 0.79], suggesting that these events are biochemically coupled. Endogenous turnover of precursor fatty acids, confirmed by an increase in renal TXB2 excretion, preceded overt depletion of essential fatty acids by several weeks. Importantly, blockade of endogenous synthesis of TXA2 with the specific TXA2 synthase antagonist, U-63557A, restored the essential fatty acid composition to normal and ameliorated progressive glomerular destruction. Moreover, the ancillary fatty acid disturbances were attenuated by administration of U-63557A.(ABSTRACT TRUNCATED AT 250 WORDS)

Renal biopsy diagnosis of acute lymphocytic leukemia.

Hyperuricemia, due to inborn errors of metabolism, dehydration, or tumor lysis, may cause renal insufficiency. Hyperuricemia from tumor lysis syndrome in malignancy is usually associated with electrolyte disturbances such as hyperkalemia, hyperphosphatemia or hyper or hypocalcemia. Tumor infiltration into the kidneys can occur, yet this accounts for renal insufficiency in only 1% of patients. This infiltration of tumor cells into the kidneys is usually associated with evidence of malignancy elsewhere as identified by physical exam, radiographic studies, and examination of the peripheral smear or bone marrow. We report an unusual presentation of a child with acute lymphocytic leukemia presenting with acute renal failure, nephromegaly and hyperuricemia without electrolyte disturbances or systemic evidence of tumor elsewhere. We stress the importance of kidney biopsy in order to identify the etiology of the renal failure and hyperuricemia.

Pathology of renal transplantation.

Renal transplantation is the most appropriate form of treatment for end-stage renal disease in all age groups. We present the experience of two hospitals in the pathology of kidney allograft. Renal biopsy is the most adequate method for the follow-up of these patients, because it permits the differential diagnosis of acute and chronic rejection, transplant glomerulopathy, recurrent and "de novo" glomerulonephritis and immunosuppression nephrotoxicity, mainly by cyclosporine A. We present the pathology features of all these entities, and study the representativity of the biopsy for diagnosis of rejection. The actuarial survival of the graft is 82% and 71% at 1 and 5 years, respectively.

Fetal nephrotoxicity.

Investigation of fetal nephrotoxicity by maternally administered nephrotoxins is hampered by many constraints, including the maternal effects of the nephrotoxin, the ability of the nephrotoxin to cross the placenta and the difficulties associated with direct fetal intervention. In the pouch young of the North American opossum, Didelphis virginiana, we describe the toxic effects of a heavy metal on the immature metanephric kidneys. Varying doses of uranyl nitrate, a heavy metal salt, were administered to opossum pups in the pouch approximately 20 days after birth and the kidneys were harvested 3 to 12 days later for histological analysis. Group 1 consisted of 4 untreated and 5 saline treated pups. Group 2 (9 pups) received 10 to 15 mg./kg. intraperitoneal uranyl nitrate. Group 3 (6 pups) were given a uranyl nitrate dose of 25 mg./kg. Group 4, the high dose group, received either 58 mg./kg. (3 pups) or 87 mg./kg. (3 pups) of intraperitoneal uranyl nitrate. Group 1 kidneys demonstrated no pathological changes except for some mild renal tubular vacuolization seen in the saline treated animals. In group 2 tubular dilatation and necrosis were present 3 days after treatment; tubular regeneration could be seen by day 7. In group 3 glomerular cystic changes, interstitial fibrosis and tubular regeneration were present by day 7. Some restoration of normal architecture occurred by day 12 with fibrosis apparent. Group 4 animals demonstrated much more pronounced cystic changes of glomeruli and tubules as early as day 5 with marked interstitial fibrosis and prominent tubular regeneration. By day 12 group 4 pups continued to demonstrate significant and severe glomerular and tubular cystic changes with marked interstitial fibrosis. Inflammation, although present in all groups (except control), was never prominent. This first description of the effect of heavy metal toxicity on the immature metanephric kidney could provide an insight into the mechanisms of disordered kidney growth.

Urinary PGE2 in rats with chronic partial unilateral ureteral obstruction.

Urinary prostaglandin E2 (PGE2) was measured in Munich-Wistar rats with surgically created chronic partial unilateral ureteral obstruction (UUO). Mean values of bladder urine PGE2 were higher in sham than in UUO (24.5 +/- 14.4 vs 12.9 +/- 8.2 ng/mg creatinine, respectively, P less than 0.05). Following diuresis, both ureters were cannulated and urine was collected. PGE2 excretion was increased in sham (66.5 +/- 34.4 and 70.1 +/- 44.5 ng/mg creatinine, left and right, respectively). But in UUO, the obstructed kidney excreted less PGE2 than the contralateral kidney (32.1 +/- 6.0 vs 62.3 +/- 40.4 ng/mg creatinine, obstructed vs contralateral, respectively, P = 0.08). PGE2 synthesis was then determined in separated renal medullary and cortical slices. Renal medullary slices from kidneys with severe obstruction synthesized less PGE2 than the contralateral unobstructed side (3.30 +/- 1.22 vs 10.52 +/- 3.23 ng/mg wet wt-30 min, respectively, P less than 0.05) and failed to respond to arachidonic acid stimulation with any significant increase in PGE2 synthesis (3.30 +/- 1.22 vs 4.47 +/- 1.04 ng/mg wet wt-30 min, baseline vs stimulated). In contrast, contralateral unobstructed kidney slices responded with a significant increase in PGE2 synthesis (10.52 +/- 3.23 vs 21.10 +/- 2.50 ng/mg wet wt-30 min, baseline vs stimulated, P less than 0.05). We conclude that chronic partial UUO in the Munich-Wistar rats resulted in significantly less PGE2 elaboration.

Experimental ureteral obstruction in the fetal opossum. I. Renal functional assessment.

The North American opossum Didelphis virginiana was used as a model for fetal urinary obstruction. In this animal the fetus develops on a teat in a pouch and, therefore, it is accessible to surgical intervention. Unilateral ureteral obstruction was created at a mid trimester developmental equivalent in 8 pups, late ureteral obstruction was created in a similar fashion in 6 pups at a full-term equivalent and unobstruction of 9 pups was accomplished with a ureteroneocystostomy at a full-term equivalent. After early intervention 6 pups were found to have only partial ureteral obstruction as measured by mild dilatation and probe patency of the ureter. The control group consisted of 11 unoperated animals. The animals were maintained until adulthood when they were harvested after obtaining creatinine clearances from both kidneys. All dilated urinary systems were cultured for bacteria and they were sterile.

Induced renal dysplasia in the young pouch opossum.

Using the North American opossum, Didelphis virginiana, we have developed a new model for studying the effects of early fetal urinary obstruction on subsequent renal development. We have successfully induced renal dysplasia in the marsupial that has a typically mammalian kidney.

Glomerulosclerosis in obstructive uropathy.

Obstructive uropathy is said to result in populations of remnant nephrons subject to hyperfiltration. We studied all obstructed renal tissue removed at our pediatric institution during a 10-year period for focal segmental glomerulosclerosis, which is the histological hallmark of hyperfiltration. Over-all, the histological specimens from 20 patients with ureteropelvic junction obstruction, 14 who underwent heminephrectomy for duplication anomalies and 5 with posterior urethral valves who underwent native nephrectomy were studied. Focal segmental glomerulosclerosis was one of the most common histological findings in these obstructed kidneys but it almost always was found in association with intense interstitial and periglomerular inflammation. We conclude that although focal segmental glomerulosclerosis is common in obstructive uropathological conditions it results from the inflammatory response within the renal parenchyma and not from the hyperfiltration of remnant nephron populations.