Clinical and pathological characterization of posttransplantation lymphoproliferative disorders in kidney transplant recipients: single institution experience.
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Adolescent↗
Biomedical subjects
R Correa-Rotter
Publications and source records attributed to R Correa-Rotter.
Acute abdomen requiring emergency surgery in renal allograft recipients during a single center cohort follow-up.
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Abdomen, Acute↗
Histological and subcellular distribution of 65 and 70 kD heat shock proteins in experimental nephrotoxic injury.
The cellular distribution of 65 and 70 kD heat shock proteins (HSPs) was studied in the normal rat kidney and after acute tubular necrosis (ATN) induced by inorganic mercury (HgCl2). In the normal kidney the 65 kD HSP was found in the cytoplasm of podocytes and proximal convoluted tubules, whereas the 70 kD HSP was located in nuclei and cytoplasm of podocytes, cortical convoluted, and collecting tubules. The distribution of both HSPs along ATN changed as a function of time. In the early phase, before evidence of histological damage, both HSPs were found in the pielocaly ceal epithelium and medullary collecting tubules. During the necrotic phase, HSPs coexisted with sites of severe damage (i.e. cortical tubules). With immunoelectron microscopy damaged cells showed an abundance of 65 kD HSP-I in mitochondria, as well as in chromatin and nucleoli, while 70 kD HSP-I was overexpressed in the cytoplasm, mito chondria, lysosomes, cytoskeleton, chromatin, and nucleoli, and coincided with urinary excretion of HSPs. In the postregenerative phase, the distribution of HSPs was similar to that found in the normal kidney. HSPs of 65 and 70 kD were encountered constitutionally and their immunolabeling is correlated with the magnitude of cell injury.
Animals↗
Consistency of the peritoneal equilibration test in a cohort of nonselected Mexican CAPD patients.
The peritoneal equilibration test (PET) is a useful tool in continuous ambulatory peritoneal dialysis (CAPD) prescription. PET D/P ratios are reproducible in the same patient when performed within a short period. However, peritoneal transport consistency in nonselected patients over longer periods of time is debated. The PET was performed twice in 19 randomly selected patients (13 female) from a cohort of 55 patients on CAPD for 32 +/- 24 months, age 44 +/- 18 years. Mean time between the first and second PET was 9.6 +/- 4 months. All patients were peritonitis-free at least 6 weeks before each PET. Fifteen patients did not change transport type between the two PETs: 3 low (L), 8 low-average (LA), 3 high-average (HA), and 1 high (H). Only 4 changed: 1 H to HA, 2 LA to HA, and 1 L to LA. In these 4 patients the change was centripetal (towards the mean) and less than 1 SD and not considered clinically significant. No differences between both groups in peritonitis rate, gender, age, time on dialysis, and diabetes mellitus status were observed. Transport type, as evaluated by the PET, was consistent over time in our group of patients.
Adult↗
Expression of clusterin in human renal diseases.
Clusterin, a glycoprotein with potent cohesive properties, is induced in a wide variety of acute and chronic experimental renal diseases. The purpose of this study was to examine clusterin expression in human renal diseases. Clusterin immunostaining was examined in nephrectomy specimens from patients with autosomal-dominant polycystic kidney disease (N = 5), autosomal-recessive polycystic kidney disease (N = 3), multilocular cyst of the kidney (N = 2), renal hypoplasia/dysplasia (N = 7), Wilms' tumor (nephroblastoma) (N = 6), renal cell carcinoma (N = 9), and acute and/or chronic renal transplant rejection (N = 15). No clusterin staining was detected in normal renal tissue distant from renal cell carcinomas. Increased expression of clusterin was found in epithelial cells lining cysts in all of the cystic disorders studied. Clusterin expression was found in some immature tubules in hypoplastic/dysplastic kidneys and in tubules of rejected renal allografts, but was not a prominent finding in renal neoplasms, although some renal cell carcinomas expressed clusterin in a focal manner. Common features of clusterin induction included exclusively epithelial production of clusterin in cysts, immature nephrons, and injured tubules, heterogeneity of clusterin expression, with only some tubules and/or cysts in a given area staining for clusterin, and uniform clusterin staining of epithelial cells in a given tubule or cyst in most cases. Based on its cohesive properties, we speculate clusterin functions to maintain cell-cell and cell-substratum interactions which become perturbed in the setting of renal injury and cystic diseases.
Adolescent↗
The paradox of the renin-angiotensin system in chronic renal disease.
Despite normal to suppressed levels of renin activity in chronic renal disease, multiple lines of evidence suggest a role for the RAS, especially its intrarenal expression, in several critical aspects of this condition. Alterations in the distribution and control of components of the renal RAS could account for localized areas of activation of this system. Renal scarring may be particularly important as a major stimulus to renin synthesis in the diseased kidney. While both intrarenal and systemic hypertension may depend in part upon actions of the RAS, other non-hemodynamic actions of the RAS may also contribute to the adaptation of residual nephrons as well as their progressive injury.
Animals↗
Abnormalities of coagulation in experimental nephrotic syndrome.
The human nephrotic syndrome is accompanied by important alterations of the coagulation system related proteins. The purpose of the present study was to examine the activity of coagulation- and fibrinolysis-related proteins in plasma and urine of control and puromycin aminonucleoside injected rats on days 2 (prenephrotic stage) and 10 (nephrotic stage). We measured the prothrombin time (PT), the activated partial thromboplastin time (aPTT), and the activities of (1) the coagulation factors (CFs) I, II, V, and VII-XII; (2) the inhibitor of coagulation antithrombin III (ATIII), and (3) the component of the fibrinolytic system alpha 2-antiplasmin (alpha 2-APL). PT and aPTT and the activities of CF, ATIII, and alpha 2-APL were not measurable in the urine of control and puromycin amino-nucleoside injected rats on day 2. On this same day, plasma ATIII and CF VIII decreased. On day 10 (1) PT and aPTT decreased in plasma and were not measurable in urine; (2), plasma CFs I, II, V, VII, VIII, X, and XI increased; (3), plasma ATIII decreased; (4), plasma CFs IX and XII and alpha 2-APL did not change, and (5) ATIII and CFs II, VII, VIII, IX, X, XI, and XII, but not CFs I and V and alpha 2-APL, appeared in urine on day 10. ATIII deficiency was secondary probably to the urinary losses; however, the plasma activity of CFs II, VII, VIII, X, and XI increased and that of CFs IX and XII remained unchanged in spite of their urinary losses which suggests that other mechanisms such as deranged catabolism and altered hepatic synthesis may be involved.(ABSTRACT TRUNCATED AT 250 WORDS)
Albuminuria↗
Serum albumin and body surface area are the strongest predictors of the peritoneal transport type.
The peritoneal equilibration test (PET) is used as a tool for dialysis prescription. In order to establish which parameters can predict peritoneal transport type, we studied 55 patients on continuous ambulatory peritoneal dialysis (CAPD), who were subjected to a standard PET. Clinical data (sex, age, calculated body surface area [BS], average time on dialysis [TD], and presence of diabetes mellitus), laboratory variables, (serum creatinine [SCr] blood urea nitrogen [BUN], serum albumin [SA], and residual renal function), and adequacy parameters (dialysate creatinine clearance [CrCl], weekly clearance of urea normalized to total body water [KT/V], protein catabolic rate, and dialysis index), were obtained and recorded at the time of the PET. The study group was composed of 29 males and 26 females, mean age of 43.5 +/- 16 years, and average TD of 25.2 +/- 18 months. PET results: 13 patients were low, 16 low average, 19 high average, and 7 high peritoneal transporters. According to the logistic regression analysis, the factors significantly associated with the type of peritoneal transport were: BS, SA, dialysate CrCl, and TD (coefficients 7.2, -1.23, 0.72, and -0.03, respectively). Greater BS and lower SA directly correlate with high peritoneal transport, and are the strongest predictors for the model.
Adult↗
Induction of clusterin in acute and chronic oxidative renal disease in the rat and its dissociation from cell injury.
BACKGROUND: Clusterin is a glycoprotein incriminated in diverse biologic processes including complement regulation, cell death, and tissue remodelling. Induction of clusterin occurs in renal and other tissue injuries. EXPERIMENTAL DESIGN: The purpose of this study was to determine the effect of prooxidant states, one acute (glycerol-induced acute renal failure) and the other chronic (vitamin E and selenium deficiency) on renal clusterin expression, and to attempt to delineate the signals which in these in vivo models can elicit expression of clusterin in vitro. RESULTS: In glycerol-induced acute renal failure, a model of rhabdomyolysis, clusterin mRNA was markedly increased 24 hours after injection of glycerol (control 97 +/- 21 versus glycerol 3644 +/- 134 optical density units; p < 0.001). Immunohistochemical clusterin was also increased in glycerol-treated rats with tubules in both cortex and medulla staining for clusterin. In vitamin E and selenium deficiency, clusterin mRNA was increased 9 weeks after initiation of the deficient diet (control 97 +/- 13 versus deficient 1137 +/- 403 optical density units; p < 0.04) as were the number of tubules staining for clusterin. Since renal injury is instigated in the glycerol model by muscle damage, we tested the effect of muscle extract on clusterin expression in vitro. A homogenate of skeletal muscle induced clusterin mRNA and this induction was not associated with disruption of cell membranes and was not inhibited by cycloheximide treatment, but was blocked by actinomycin D. Since increased generation of hydrogen peroxide is a pivotal biochemical lesion in both in vivo models, we tested the effect of peroxide to induce clusterin in vitro; no such induction occurred. CONCLUSIONS: Renal tubular clusterin expression was increased in both acute glycerol-induced renal failure and chronic vitamin E and selenium deficiency, two in vivo models of oxidant injury to the kidney. In vitro induction of clusterin can occur and can be dissociated from cell injury.
Acute Disease↗
Death risk in CAPD patients. The predictive value of the initial clinical and laboratory variables.
The characteristics, survival rate and risk factors associated with death in patients with end-stage renal failure treated with chronic ambulatory peritoneal dialysis (CAPD) were studied. This is a retrospective study of a cohort of 206 patients, from which the follow-up was complete in 190 patients (92%). Only 16 patients (8%) were lost. The study group is composed of 118 males and 88 females, with a mean age of 39 +/- 15 years. The origin of the renal disease was: unknown in 90 patients (44%); diabetes mellitus in 50 (24%); systemic lupus erythematosus in 16 (8%); obstructive uropathy in 15 (7%); glomerulonephritis in 14 (7%), and miscellaneous in 21 (10%). The average follow-up was 12 +/- 11 months. At the end of study, 66 patients were dead (32%). CAPD was discontinued in 12 (6%). Thirty-eight patients (18%) received kidney transplantation. The survival rate for the whole group was 67 and 48% at 1 and 3 years, respectively. Multivariate survival analysis according to the Cox proportional-hazard model showed that the most powerful predictor associated with high risk of death was low serum albumin levels. According to the Cox model other independent variables significantly associated with increase in the probability of death while on CAPD were advancing age, low serum creatinine concentrations and elevated serum cholesterol levels. These results indicate that the risk factors associated with death in CAPD patients are similar to those observed for hemodialysis patients and suggest that using simple laboratory measurements at the enrollment in CAPD the relative risk of death for each patient can be estimated.
Adolescent↗
Clusterin: an enigmatic protein recruited by diverse stimuli.
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Animals↗
Renin and angiotensinogen gene expression in experimental diabetes mellitus.
The renin-angiotensin system may play a role in the initiation and progression of diabetic kidney disease. In this study, the local intrarenal renin-angiotensin system was examined in streptozotocin-treated rats maintained moderately hyperglycemic by daily low-dose insulin injection. Four weeks after induction of diabetes, plasma renin activity was significantly lower in the diabetic compared to a non-diabetic control group (diabetes: 2.30 +/- 0.30 vs. control: 6.93 +/- 1.36 ng Al/ml/hr; P less than 0.01). Renal tissue renin content (diabetes: 1.81 +/- 0.46 vs. control: 2.05 +/- 0.27 micrograms Al/mg protein/hr; P less than 0.05) and renal renin mRNA (diabetes: 2.32 +/- 0.16 vs. control: 1.89 +/- 0.12 pg/micrograms RNA; P = NS) were not different between diabetic and control rats. Renal and liver angiotensinogen mRNA were lower in the diabetic group. Glomerular renin mRNA was not different between the diabetic and sham group. The dissociation between systemic renin activity (a decrease), and in renal renin content or mRNA in the diabetic rats (no change), suggests a post-translational alteration in renin processing and/or renin secretion.
Angiotensinogen↗
Intrarenal distribution of clusterin following reduction of renal mass.
Clusterin is a multifunctional protein isolated from a number of tissues in several different species. In a variety of renal diseases, clusterin appears in the glomerulus and tubules in association with the membrane attack complex of complement. It is also transiently expressed after several forms of acute renal injury. In this study, we examined the expression and intrarenal distribution of clusterin following subtotal renal ablation. Male rats were subjected to either 1-1/3 nephrectomy (1-1/3 NX), uninephrectomy (UNX) or sham operation (SHAM). Two weeks after surgery, clusterin mRNA was elevated in the 1-1/3 NX group (1-1/3 NX: 1215 +/- 88; UNX: 208 +/- 11; SHAM: 207 +/- 19 OD units; P less than 0.001). Clusterin mRNA increased between 3 and 24 hours after 1-1/3 NX, plateaued, and remained elevated for at least seven weeks. The increased clusterin mRNA in 1-1/3 NX was localized to the tissue adjacent to the infarctive scar (scar 858 +/- 173 vs. non-scar 98 +/- 27 OD units; P less than 0.001). Clusterin protein followed a similar pattern of localization, being increased in most tubules and some peritubular capillaries in the peri-infarct zone. Only occasional tubules were positive for clusterin in the renal tissue distant from the scar or in the kidneys of sham operated rats. Co-localization of clusterin and C5b-9 was not detected. Evidence for apoptosis was found in the peri-infarct zone but not elsewhere in 1-1/3 NX kidney or in the normal kidney following sham operation. Infarction of 1/3 of the left kidney without contralateral nephrectomy, a maneuver which eliminates the compensatory growth, and uremia seen with 1-1/3 NX still resulted in increased clusterin mRNA in the infarcted left kidney compared to the intact right kidney (LK: 790 +/- 112 vs. RK: 128 +/- 25 OD units; P less than 0.001), although the amount of clusterin mRNA was less than that found following 1-1/3 NX. In conclusion, persistently increased clusterin mRNA and protein was seen in the peri-infarct zone following 1-1/3 NX. This increased expression of clusterin may be playing a role in the ischemia-related apoptosis present in the scar-adjacent tissue.
Animals↗
Effect of dietary protein on renin and angiotensinogen gene expression after renal ablation.
High dietary protein increases renin mRNA and likely contributes to the increased plasma renin activity (PRA) in the normal rat. In experimental renal ablation, dietary protein influences renal growth and injury. This study was undertaken to examine the effect of dietary protein on the renin-angiotensin system after reduction of renal mass. Male Sprague-Dawley rats were subjected to 1 1/3 nephrectomy (1 1/3 NX) and maintained for 7 days on a low-protein (6%) diet, at which time they were stratified according to serum creatinine to either continue on the low-protein diet or were switched to a high-protein (40%) diet. Two weeks after stratification renal renin mRNA was higher on the 40% compared with the 6% protein diet, angiotensinogen mRNA was lower in the high-protein group, and no change occurred in renal actin mRNA. The magnitude of this dietary protein-induced increase in renin mRNA with high-protein diet was greater in the 1 1/3 NX group compared with that observed in sham-operated rats (320 vs. 60%). PRA and tissue renin activity were also elevated on the high-protein diet after 1 1/3 NX. When three levels of dietary protein intake were examined after 1 1/3 NX, the high-protein (40%) diet was associated with increased renal renin mRNA compared with both the intermediate-protein (20%) and low-protein (6%) diets. In conclusion, a high-protein diet induced activation of the renin-angiotensin system. This activation may explain some of the detrimental effects of dietary protein on the course of chronic renal failure.
Angiotensinogen↗
Relationship between renin, angiotensinogen and histone H2b messenger ribonucleic acid in the maturing rat kidney.
Postnatal nephrogenesis and growth of the rat kidney is greatest during the first 10 days of life. The renin-angiotensin system has important growth-promoting effects. To explore the relationship between postnatal renal development and the renin-angiotensin system, we examined the steady-state levels of messenger ribonucleic acid (mRNA) for renin, angiotensinogen, histone H2b (a marker of DNA synthesis) and the structural protein actin. The pattern of expression for renin and histone H2b were similar, with maximal levels of both mRNAs occurring during the first 10 days of life, the time of most marked postnatal nephrogenesis and kidney growth. A different pattern was seen for angiotensinogen mRNA, with low to undetectable levels during the first 15 days of life, and for actin mRNA, with fairly stable expression at the time points examined, providing evidence that the increase in renin and histone H2b mRNA was not due to a nonspecific increase in mRNA in the newborn kidney. In conclusion, the increase in renal histone H2b mRNA during the early postnatal period is consistent with this being a time of increased DNA synthesis. The similar time course for renin mRNA, histone H2b mRNA and previously defined changes in postnatal nephrogenesis suggests a role for the renin-angiotensin system in postnatal nephron formation.
Age Factors↗
Renin expression in renal ablation.
To determine whether expression of the renin-angiotensin system (RAS) is influenced by the degree of renal ablation, male Sprague-Dawley rats underwent uninephrectomy, 1 1/3 nephrectomy, or sham operation. Renin and angiotensinogen messenger RNA (mRNA) were not different among the three groups 2 weeks after surgery. The time course of expression of renin mRNA after 1 1/3 nephrectomy showed no difference versus controls at 2 and 4 weeks and a decrease at 6 weeks after surgical ablation. Because nephrons adjacent to the infarcted area in the 1 1/3 nephrectomy may be hypoperfused and a source of increased renin synthesis, intrarenal distribution of tissue renin content, renin mRNA, and immunostainable renin were examined in separate groups of rats subjected to 1 1/3 nephrectomy. The kidney was divided into two pieces, one containing the scar and scar-adjacent tissue and the other portion the tissue distant from the scar. Tissue renin content, renin mRNA, and immunostainable renin were significantly greater in the scar-adjacent tissue compared with the nonscar tissue. Immunoreactive renin was seen in the juxtaglomerular apparatuses as well as in vascular elements proximal to the juxtaglomerular apparatus and within mesangial cells of some glomeruli of the scar-adjacent tissue. In conclusion, immunostainable renin, tissue renin content, and renin mRNA were increased in scar-adjacent tissue after 1 1/3 nephrectomy. We speculate that this unique scar-associated redistribution of renin may play a pathophysiological role in the progression of renal disease.
Analysis of Variance↗
Interaction of complement and clusterin in renal injury.
Clusterin is a heterodimeric glycoprotein that has been associated with such diverse biologic functions as reproduction, cell regression, cell aggregation, and regulation of the cytolytic activity of the membrane attack complex of complement. Clusterin is a component of glomerular immune deposits in the kidney, and increased clusterin expression occurs in a number of renal injury states. To further explore the interaction between clusterin and complement, the requirement for an intact complement system for renal clusterin induction in an acute (folic acid nephropathy) and a chronic (subtotal renal ablation) model of renal injury was examined. After it was first demonstrated that folic acid increased renal clusterin mRNA in the rat, a species in which renal clusterin was highly inducible by other stimuli, the effects of folic acid (250 mg/kg ip) on clusterin mRNA and immunoreactivity were examined in mice sufficient and deficient for the fifth component of complement. Similar increases in clusterin mRNA and immunoreactivity were seen in both the C5-sufficient and C5-deficient mice compared with their respective vehicle-injected control groups. Renal clusterin mRNA was also increased to a similar extent in the remaining kidney of both C5-sufficient and C5-deficient mice 10 days after subtotal nephrectomy. In conclusion, the induction of clusterin after folic acid administration or subtotal nephrectomy was independent of the presence of an intact complement system, because similar increases in clusterin expression were observed in C5-sufficient and C5-deficient mice.
Acute Disease↗
Loading and transfer control for Northern hybridization.
We report a simple and inexpensive method to quantitate loading and transfer of RNA and to examine RNA integrity for use with Northern hybridization. This technique involves quantitation by computer-assisted video densitometry of a negative photograph of 28S and 18S rRNA from ethidium bromide-stained RNA fixed to nylon membranes. This method eliminates the issue of variability of expression of "housekeeping" genes and the need for a second round of hybridization to quantitate control probes.
Animals↗