INCREASED SENSITIVITY TO ENDOTHELIN-1 IN ISOLATED KREBS-PERFUSED KIDNEYS OF STREPTOZOTOCIN-DIABETIC RATS

1. Vascular responses to endothelin-1 (ET-1) and noradrenaline (NA) were measured in isolated Krebs'-perfused kidneys of 2 week old streptozotocin-diabetic and non-diabetic rats. 2. Bolus injections of either ET-1 or NA caused dose-dependent increases in perfusion pressure. Responses to ET-1 (10-60 ng/g kidney), but not to NA (0.001-10 micrograms/g kidney), were significantly potentiated in kidneys of diabetic rats compared with non-diabetics. 3. Indomethacin significantly attenuated responses to NA (0.3-10 micrograms/g kidney) in kidneys of both diabetic and non-diabetic rats. 4. Neither indomethacin (1 mumol/L) nor the cyclo-oxygenase/lipoxygenase inhibitor BW755C (1 mumol/L) had any significant effect on the log dose-response curve to ET-1 in either group of kidneys. 5. Perfusion with N-nitro-L-arginine (NOLA; 10 mumol/L) had no effect on basal perfusion pressures, but potentiated responses to ET-1 in both groups of kidneys. However, the difference in responses to ET-1 between kidneys from diabetic and non-diabetic rats remained significant in the presence of NOLA. 6. ET-1 responses were inhibited in Ca(2+)-free Krebs' solution (plus 1 mmol/L EGTA). 7. The results of the present study indicate an increased sensitivity to ET-1 in isolated Krebs'-perfused kidneys of diabetic rats. Responses to ET-1 were unaffected by cyclo-oxygenase and/or lipoxygenase inhibitors, but were potentiated by an endothelium-derived relaxing factor (EDRF) synthesis inhibitor.     

Genetically engineered kidneys

We review the available methods of creating genetically engineered kidneys. These include transgenic technology to introduce novel genes or delete existing genes and methods of gene transfer into the post-natal or adult kidney. The use of such technology has provided insights into renal development and growth and created new animal models of human diseases. Although some of these techniques are of potential use for introducing therapeutically useful gene products into the diseased kidney, many problems remain to be solved before this aim is attained.     

Nephroblastoma and end-stage renal failure with bilateral cystic kidneys

A child of 10 years 5 months presenting with chronic renal failure had bilateral cystic kidneys. Biopsy of a right lower-pole solid mass revealed nephroblastoma. At bilateral nephrectomy, both kidneys were both replaced by variable-sized cysts with a unifocal nephroblastoma on the right. Renal failure with nephroblastoma is uncommon and is usually either a manifestation of the Drash syndrome or a complication of chemotherapy. The need to assess both kidneys in a child with any other renal abnormality in addition to a renal mass should always be considered.     

Sonographic evaluation of the nonfunctioning kidney.

The results of B-mode ultrasound examinations in 113 consecutive patients with unilateral renal nonfunction or severe azotemia were reviewed. The causes of nonfunction included the following: hydronephrosis; renal parenchymal disease; renal agenesis; atrophy or dysplasia; multicystic, medullary cystic, and polycystic kidneys; renal arterial or venous occlusive disease; extensively infiltrating neoplasm. The sonographic findings were consistent with the final diagnosis in 92 percent of the cases. A coronal view of the kidney for diagnosing hydronephrosis is described. This view demonstrates the dilated calyces in continuity with the renal pelvis and, when combined with transverse views, improves the reliability of the sonographic diagnosis of hydronephrosis. In cases where the renal landmarks appear totally normal, obstruction can be excluded as a cause of nonfunction, and retrograde pyelography may be avoided. The sonographic manifestations of other parenchymal abnormalities associated with nonfunction, such as cystic renal disease, glomerulonephritis, and renal transplant rejection, are also discussed.     

Effect of contrycal on activity of dehydrogenases and their isozymes in muscles and organs of animals with developing granulation tissue

The effect of contrycal on the state of the enzyme systems of the muscles, liver, kidneys, and heart was investigated in rats with developing granulation tissue. This protease inhibitor was found to stimulated lactate and malate dehydrogenase activity and also the isozyme spectrum of these enzymes. The action of the inhibitor was manifested as a change in the state of the enzyme systems both at the site of injury (granulations and underlying tissue) and in certain internal organs (liver and kidneys).Presented by Academician of the Academy of Medical Sciences of the USSR A. A. Vishnevskii [deceased].Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 82, No. 7, pp. 807–810, July, 1976.     

Deferoxamine Reduces Cold-Ischemic Renal Injury in a Syngeneic Kidney Transplant Model

In cell-culture models, addition of deferoxamine (DFO) to University of Wisconsin Solution (UW solution) reduces cold-storage injury. The efficacy of DFO was therefore tested in a kidney transplantation model employing inbred Wistar Furth rats. Donor left kidneys, cold stored for 18 h in UW solution with or without 0.125 mM or 0.625 mM DFO were transplanted to the recipients' left renal fosse. Deferoxamine dose-dependently and significantly increased glomerular filtration rate (GFR) and renal blood flow (RBF), and suppressed renal F2-isoprostanes (vasoactive lipid peroxidation products) and apoptotic and necrotic injury 3 days post-transplantation. In a second set of similar experiments, the remaining native kidneys of the recipient rats were removed on day 7 of transplantation. Transplanted kidneys' function assessed by serum creatinine was 75% higher in the cold-stored transplanted kidneys treated with DFO compared with untreated kidneys. Moreover, the DFO treatment was attended by a significant reduction in apoptotic and necrotic tubular injury. Thus, our consistent findings from two sets of studies in a transplant model suggest that a simple strategy of including DFO in the cold-storage solution reduces cold ischemia-associated renal transplant damage and improves renal function. Our findings have potentially important ramifications for cold preservation of kidneys, and possibly other organs, in clinical transplantation.     

Is prolonged cold ischemia a contraindication to using kidneys from acute kidney injury donors?

To determine the impact of prolonged cold ischemia time (CIT) on the outcome of acute kidney injury (AKI) renal grafts, we therefore performed a single‐center retrospective analysis in adult patients receiving kidney transplantation (KT) from AKI donors. Outcomes were stratified according to duration of CIT. A total of 118 patients receiving AKI grafts were enrolled. Based on CIT, patients were stratified as follows: (i) <20 hours, 27 patients; (ii) 20‐30 hours, 52 patients; (iii) 30‐40 hours, 30 patients; (iv) ≥40 hours, nine patients. The overall incidence of delayed graft function DGF was 41.5%. According to increasing CIT category, DGF rates were 30%, 42%, 40%, and 78%, respectively (P = .03). With a mean follow‐up of 48 months, overall patient and graft survival rates were 91% and 81%. Death‐censored graft survival (DCGS) rates were 84% and 88% for patients with and without DGF (P = NS). DCGS rates were 92% in patients with CIT <20 hours compared to 85% with CIT >20 hours (P = NS). In the nine patients with CIT >40 hours, the 4‐year DCGS rate was 100%. We conclude that prolonged CIT in AKI grafts may not adversely influence outcomes and so discard of AKI kidneys because of projected long CIT is not warranted when donors are wisely triaged.