Kidney metabolism during hypothermic perfusion. An experimental study on dog kidney, human kidney and human kidney carcinoma.
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The displacement of kidney was studied by using the combined liver-spleen-kidney scintigraphy and the subsequent subtraction of the kidney scintiphotograph to leave the liver-spleen scintiphotograph alone. A suprarenal mass was shown as cold spot between the liver and right kidney on the combined study. When the liver scintiphotograph and kidney scintiphotograph were over-lapped and the differential diagnosis was difficult, the subsequent subtraction of the kidney scintiphotograph was useful in the diagnosis of the enlarged liver.
Pre- and postoperative kidney size and kidney function were studied in 46 living kidney donors aged 20-74 years. Kidney size was measured by planimetry and by estimation of a renal index. Kidney function was assessed by endogenous creatinine clearance and serum creatinine. Planimetry was superior to the renal index for expressing changes in renal size. Compensatory renal hypertrophy took place in donors up to the age of 74, but the greatest changes in renal size were observed in donors of under 40. Total renal function decreased postoperatively to about 77% of the initial level; this change in renal function was inversely correlated with age, but in all subjects studied the function remained within normal limits.
The relative importance of renal biopsy and cytological studies (fine needle aspiration biopsy and urine sediment examination by phase contrast) in the diagnosis of acute rejection episode was evaluated in 30 patients who received a kidney transplant. All patients underwent these 3 examinations simultaneously during an acute degradation of graft function. Sensitivity of renal biopsy, fine needle biopsy and urine sediment was 0.86, 0.68, 0.43 respectively. The association of fine needle biopsy and urine sediment examination increased the sensitivity up to 0.73. Renal biopsy is indicated to assess the vascular and glomerular status or in the presence of inconclusive cytological studies.
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Specific unresponsiveness inducible in newborn Lewis (Le) rats by injection of bone marrow or kidney cells from (Bu x Le)F1 hybrids was tested in adults by allografting of skin or kidneys from strongly incompatible Buffalo (Bu) strain donors. High doses of bone marrow cells (10(7) or more) proved quite effective in procuring indefinite survival of subsequent Bu kidney allografts, but not Bu skin allografts. Kidney allografts remained fully functional without modulation of their inherent immunogenicity regardless whether skin allografts were acutely rejected before or after kidney grafting on bone marrow-tolerant recipients. Lower doses of bone marrow cells were either near threshold for induction of specific Bu kidney allograft tolerance (5 x 10(6)) or, conversely, led to increased immunity(1-5 x 106). A strikingly different pattern of reactivity was found in adult Le recipients of Bu skin allografts as shown by only a moderate, but stepwise increase in survival times as a function of increasing allogeneic cell dosage at birth. Allogeneic kidney cells at all doses were surprisingly ineffective in inducing tolerance of either kidney or skin allografts, so the existence of kidney-specific transplantation antigens remains problematical. Lymphocytes from kidney allograft-tolerant recipients showed much reduced but still significant antidonor activity in several tests of cell-mediated immunity in vitro and in vivo. Blocking antibody activity was also demonstrable in these animals. Acquired tolerance (i.e., essential nonreactivity) may not only exist in degrees in either T or B cell pathways but may coexist with specific immunoblocking reactions in a dynamic equilibrium. Instead of tolerance versus enhancement, a new concept of selective specific immunoregulation emerges.
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HL-A typing of cadaver kidney cell suspension by fluorochromasia cytotoxicity was successful in 76 out of 124 cases. In the 44 cases with confirmed phenotypes, 24 had identical results for lymphocytes and kidney cells. Twenty kidney cells had HL-A antigens not detected on that donor's lymphocytes, most commonly HL-A7 and HL-A8. In eight of these 20 cases, the additional kidney antigens brought the total to more than two per segregant sereis, in disagreement with an earlier report from this laboratory. The discrepancy was traced to a change in the method of complement preparation. The complement was successfully deprived of the resulting non-specific cytotoxicity for kidney cells by absorption with human red blood cells. Prior to absorption, the complement had rendered kidney cells susceptible to the lytic effect of anti-A and B red cell antibodies. Using the absorbed complement, a patient who had hyperacutely rejected two cadaver kidneys provided sera with an antibody reacting with, and absorbed by, the kidney cells but not the lymphocytes of the donors.
The mechanism for the high lactate production during hypothermic kidney perfusion has not been clarified previously. The metabolism of lactate and acetate was studied in 23 dog kidneys during continuous hypothermic perfusion. The perfusions were performed in a Gambro machine with a perfusate based on human serum albumin. With a perfusate containing fatty acid extracted albumin, which was almost free of fatty acids, the glucose uptake of the kidney was more pronounced than during perfusion with a fatty acid-rich perfusate. The high glucose uptake under this perfusion condition was associated with a lower lactate production and a higher glucose oxidation rate. In perfusions with a perfusate containing lactate at a concentration of 2.5 mmol/l a considerable lactate uptake of the kidney was shown. By isotope dilution technique the production and uptake rate of lactate was estimated at 4.4 and 8.0 mumol/g kidney and day in two experiments. The labeled lactate carbon was recovered in CO2, and glucose in the perfusate indicating a continuous oxidation and gluconeogenesis. Acetate was used by the kidney both for oxidation and for gluconeogenesis. Addition of acetate to the ordinary fatty acid-rich perfusate caused an enhanced lactate production from the perfused kidney. The results indicate that the high lactate production during hypothermic perfusion of kidneys is mainly dependent on a metabolic blockade at the level of pyruvate dehydrogenase.
Single injection of a high dose of folic acid causes a proliferation of the kidney with an increase of the 3H-thymidine incorporation into the DNA of kidney cortex slices in rats. An aqueous extract from rat kidneys inhibits the increase of 3H-thymidine incorporation. The inhibition begins after 4 hours. The maximum effect is observed between 11 and 17 hours after injection of the kidney extract. The kidney extract also inhibits the increase of the DNA content per kidney after folic acid injection. Heart, lung, spleen and liver extracts and bovine serum albumin do not lead to inhibition of the 3H-thymidine incorporation into the DNA of kidney cortex sclices.
Nearly one-third of the global population is affected by cardio-kidney-metabolic (CKM) diseases; however, the molecular mechanisms underlying CKM diseases are poorly understood. Here we show that tissue proteomics provide critical insights not captured by tissue gene expression or blood proteomics information by performing whole-genome and RNA sequencing and proteomics analysis of human kidney samples (n = 337), and we generated a publicly available database. Via Bayesian co-localization and Mendelian randomization analyses of kidney protein quantitative trait loci and 36 CKM genome-wide association studies, we prioritized 89 proteins for CKM traits. We prioritized relationships that could underlie the interconnectedness of CKM traits and discovered multiple and targetable mechanisms for CKM diseases, including the potential role of kidney angiopoietin-like protein 3 (ANGPTL3) in serum lipid levels and kidney function as well as the role of charged multivesicular body protein 1A in kidney function and hypertension. Notably, we identify pathways with confluence of evidence from genetic loci, tissue gene expression and protein levels for CKM traits. In summary, our large-scale kidney proteomics study uncovers proteins and targetable mechanisms prioritized for CKM diseases.
A method of graded sieving for counting of glomeruli in removed kidneys is described. The number of nephrons (glomeruli) in six normal kidneys deriving from sutopsies of three children 22-73 months of age was 1.82 plus or minus 0.35 times 10-6. The results give a little higher number than most previous studies with which they are compared. In the kidneys of two 10- and 15-month-old patients with the congenital nephrotic syndrome of the Finnish type the mean number of nephrons was 3.17 plus or minus 0.52 times 10-6 which is on the average 73% higher than in the normal kidneys studied. The number of nephrons in kidneys of five other patients showed an average of at least 3.42 plus or minus 0.30 times 10-6 the counting method being a little different. The unusually high number of nephrons in CNF kidneys seems to be fully evident.
3 patients with renal transplantation who developed polycythemia presented normalization of the hemoglobin levels immediately after nephrectomy of the native kidneys. This observation induced the authors to study the role of the native kidneys in the genesis of polycythemia in recipients of renal allografts. Comparison was made among 32 patients submitted to renal transplantation, with maintenance of native kidneys (group I) and among 31 under the same conditions, but without the native kidneys (group II). Both groups were comparable according to age, sex, rejection crisis incidence and immunosuppressive therapy. It was observed that the hemoglobin levels of group I were significantly higher (p less than 0.05 to p less than 0.005) than those observed in group II, from the 3rd to the 30th posttransplantation month, becoming comparable from the 36th to the 54th months. The hemoglobin production, measured by the kinetics of labeled iron (59Fe), was higher in patients of group I. The authors concluded that the native kidneys are responsible for the observed polycythemia after a kidney transplantation.
Effects of alpha 2u-globulin accumulating agents on alpha 2u-globulins in rat kidneys were examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting analysis. Treatment of male animals with decalin (150 mg/kg), 2,2,4-trimethylpentane (50 mg/kg), isophorone (150 mg/kg), d-limonene (150 mg/kg) or 1,4-dichlorobenzene (150 mg/kg) by gavage for 14 consecutive days in each case resulted in a marked intensification of a protein band corresponding to kidney-type-alpha 2u-globulin, with a molecular mass calculated to be approximately 16 kDa. However, intraperitoneal treatment with leupeptin and E-64 (two times 0.07 mmol/kg, for each), well known cystein protease inhibitors, while only slightly increasing this kidney-type-alpha 2u-globulin band, caused the intensification of a approximately 19-kDa molecular mass protein band which was revealed to be a native-type-alpha 2u-globulin by SDS-PAGE and immunoblotting. These results indicated that at least two types of alpha 2u-globulin can be increased in male rat kidney by chemical treatment. Moreover, cystein protease(s) appear(s) to play an important role in the degradation of alpha 2u-globulin and particularly in the conversion of native-type-alpha 2u-globulin to kidney-type-alpha 2u-globulin in rat kidneys.
The size of the renal body in convoluted parts of proximal and distal nephrons has been studied in normal dogs and after section and ligation of the efferent lymphatic vessels in 4 series of experiments (85 dogs). Observations have been made 12 h, 3 and 10--150 days after the operation. Histological, histochemical and morphometric methods have been applied; the level of residual nitrogen has been estimated. In early days of the experiment, the disturbance in lymph drainage has been found to result in edema and albuminous saturation of the connective tissue stroma, granular distrophy of the epithelium in the convoluted tubules of the kidney. After 40--150 days of the experiment, diffuse sclerosis of the connective tissue stroma of the medullar substance and of the pyramids develops. Alterations and disorders in the organ's function on nitrogen discharge are especially pronounced when lymph drainage is disturbed in one kidney, and the other kidney is removed. In such a case, the processes of compensatory hypertrophy are delayed. Morpho-functional alterations are less pronounced after lymph drainage disorders in the compensatory hypertrophic kidney.
BACKGROUND: Access to, and experience of, chronic kidney disease (CKD) care is inequitable-with barriers to accessing quality care for marginalised groups. We conducted an exploratory study employing qualitative approaches to understand the factors that influence access to, and experience of, healthcare services for marginalised people with CKD and at risk of CKD. METHODS: An exploratory study employing qualitative approaches was conducted as a cross-sector collaboration between kidney care services and an activist, antiracist community-based research and social justice organisation (Mabadiliko Community Interest Company (CIC)). Two groups were recruited: 1) those with risk factors for CKD or early-stage CKD, and 2) people who presented late to kidney care services. Semi-structured interviews were co-designed with people with lived experience and conducted by Mabadiliko CIC. Thematic analysis was undertaken, with themes refined by participants. RESULTS: Twenty interviews were undertaken with a diverse cohort of participants. Knowledge and awareness of CKD was limited, and compounded by a lack of delivery of accessible, culturally congruent information. Significant barriers to accessing kidney care exist for marginalised people, including people who are from global majority ethnic backgrounds, Disabled people, and/or people experiencing material hardship. These barriers are compounded by interpersonal discrimination and paternalistic power dynamics within healthcare interactions. CONCLUSION: This study captures the experiences of marginalised people at different stages of their journey with CKD, in accessing and engaging with kidney care services. Participants faced a complex array of challenges, highlighting opportunities for multi-level intervention. We outline recommendations to address these issues, co-developed with participants.
Tubule-like cells were found lining an artery and several arterioles and within the capillaries of infarcted glomeruli in one block of kidney from one of 54 cases of end-stage/dialysis kidneys. Three other blocks showed tubule-like structures within infarcted glomeruli and adjacent arterioles. Squamous metaplasia of remaining tubule epithelium was found in sections from four blocks of the same kidney. In two of these blocks, infarcted glomeruli had capillaries which were occupied by squamous cells. These findings are discussed as examples of metaplasia of the endothelium or alternatively as epithelial growth and invasion. The use of special stains and multiple blocks for this study seem to have been justified. These changes offer further evidence that the end-stage kidney after dialysis has unique alterations.
Two cases of so-called multilocular cyst of the kidney are presented. Although both cases satisfied all of the criteria which characterize the multilocular cyst of the kidney, one had cystic lesions and neoplastic lesions (nephroblastoma-like lesions) and the other had only cystic lesions and was complicated with hamartoma. We prefer the term "cystic partially differentiated nephroblastoma" as the diagnostic term for the former and "multilocular cyst of the kidney" for the latter. A study of 40 reported cases of multilocular cystic lesions of the kidney revealed that cases having only cystic lesions were distributed in all ages from 4.5 months to 71 years and that cases having neoplastic lesions were seen in infants from 4 months to 2 years.