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J I Shapiro

Publications and source records attributed to J I Shapiro.

At least 73 records · Page 4Linked to original sources
PubMed1989

Contributions of nuclear magnetic resonance to study of acute renal failure.

Nuclear magnetic resonance (NMR) has contributed considerably to our understanding of experimental acute renal failure. Changes in energy metabolism which are caused by ischemia, urinary obstruction, and nephrotoxic drugs have been characterized with NMR spectroscopy. Data from our laboratory and others utilizing 31P NMR have demonstrated that levels of adenosine triphosphate fall rapidly with ischemia, and that the ability of the kidney to regenerate ATP correlates with ultimate functional recovery. Additionally, development of intracellular acidosis appears to occur early with ischemia and may, if severe enough, predict poor functional recovery. Urinary obstruction is associated with the rapid development of a large peak resonating in the phosphodiester region of the P-31 NMR kidney spectrum which is attributable to increases in urinary inorganic phosphate. Nephrotoxic acute renal failure with a variety of nephrotoxins is associated with little to no changes in high energy phosphates. Renal transplant allograft rejection is associated with energy metabolic changes similar to those seen with ischemia; however, the intracellular pH remains normal. These findings allow causes of experimental acute renal failure to be differentiated among each other in both native and transplanted kidneys. With recent advances in NMR software and hardware, the application of this methodology to human acute renal failure is now possible.

Acute Kidney Injury↗
PubMed1989

The role of aluminum in the pathogenesis of anemia in an outpatient hemodialysis population.

Anemia is a well-defined complication of aluminum overload in chronic dialysis patients which may be present before other manifestations of aluminum toxicity are obvious. Causes of anemia in chronic renal failure are multiple, and at the present time there is no marker for aluminum-induced anemia. Deferoxamine (DFO) treatment can correct aluminum-related anemia and microcytosis, but may be associated with side effects. Because of the possible role of aluminum in red blood cells in causing the anemia associated with aluminum overload, we attempted to test red blood cell (RBC) aluminum as a marker for aluminum-associated anemia and to assess the prevalence of aluminum-associated anemia in an outpatient dialysis population. Both random plasma aluminum and RBC aluminum correlated well with the increase in plasma aluminum seen following DFO challenge. However, RBC aluminum was affected less by changes in oral aluminum intake than plasma aluminum. There were strong correlations of RBC and plasma aluminum to corpuscular volume (MCV) in our patients. Moreover, patients within the highest quartile of RBC aluminum had a lower mean MCV (82.1 +/- 1.7 vs 89.6 +/- 1.7, p less than .01) and hematocrit (HCT) (24.3 +/- 4 vs 28.2 +/- 1.5, p less than .05) than those within the lowest quartile. These data suggest that aluminum toxicity is an important cause of microcytic anemia in outpatient hemodialysis patients. Prospective long-term studies are needed to further define the usefulness of RBC aluminum in diagnosing and following hemodialysis patients with aluminum-induced anemia.

Aluminum↗
PubMed1989

Effect of adenosine triphosphate depletion in vivo on renal function in the rat with and without ischemia.

To investigate the importance of renal tissue concentrations of adenosine triphosphate (ATP) in maintaining normal renal functions as well in the recovery from ischemic injury in vivo, fructose was administered without ischemia as well as in the setting of an ischemic insult. In nonischemic as well as kidneys recovering from 30 min of clamp ischemia, fructose caused a 50% reduction in the tissue concentration of ATP which persisted for over 1 h. In nonischemic animals, fructose had no effect on renal function as assessed by inulin clearance and sodium reabsorption and showed no evidence of histologic injury 24 h after administration. In animals subjected to 30 min of ischemia, animals given fructose showed no worsening of functional or histologic injury as compared to controls. We conclude from these data that reductions in the tissue concentration of ATP in the range observed does not adversely affect normal renal functions or recovery from a reversible ischemic insult.

Adenine Nucleotides↗
PubMed1988

Tubular hypermetabolism as a factor in the progression of chronic renal failure.

Thus, in summary, we hypothesize that nephron loss by a time-limited insult (eg, an acute immunological insult, surgical removal of five sixths of normal nephrons) may cause events in the tubules of the remaining nephrons that contribute substantially, though not exclusively, to the inexorable progression to ESRD. Specifically, hypermetabolism in the remaining tubules as assessed by oxygen consumption and ATP synthesis rates has been found to occur. This hypermetabolism in residual nephrons appears to be due to the known increased sodium transport per nephron, but nonsodium transport events also appear to be involved. With respect to the latter phenomenon, we propose that an increase in growth factor response per tubule, as a mechanism of renal hypertrophy, activates the DAG----protein kinase C----Na/H antiporter system. We have evidence in support of this sequence of events by the demonstration of a two-fold increase in membrane (particulate) protein kinase C within 24 hours after removal of the contralateral kidney and an increase in intracellular pH as assessed by NMR spectroscopy. Activation of the Na/H antiporter not only leads to proton extrusion and cellular alkalinization, which may activate cellular alkalinization, which may activate cellular enzymes such as phospholipases, but also increases intracellular Na concentration, thereby further increasing Na/K-ATPase, ATP use, and enhancing ATP synthesis. The increase in mitochondrial oxygen consumption, which accompanies the enhanced ATP synthesis, would be expected to be associated with increased oxygen radicle generation. If the tissue scavengers of oxygen radicles are not sufficient to scavenge the increase in oxygen radicles, then lipid peroxidation and tissue damage will occur.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1988

Acidosis and hypoxic medullary injury in the isolated perfused kidney.

The effects of acidosis on renal function and morphology were examined in the isolated perfused rat kidney (IPK). Kidneys were perfused with oxygenated Krebs-Henseleit-albumin medium for 60 minutes at pH 7.4 or pH 7.0. At the lower pH, GFR was reduced by 25%, TRNa by 32% and oxygen consumption by 41% as compared to perfusion at pH 7.4 (all P less than 0.05). In addition, the usual hypoxic injury observed in the medullary thick ascending limb of the Loop of Henle (TAL) in the IPK at pH 7.4 (consisting of nuclear pyknosis and focal fragmentation necrosis) was reduced by acidosis from 62% to 14% of tubules involved (P less than 0.005). This cytoprotection was not the result of improved oxygenation since O2 delivery was actually slighty reduced at pH 7.0 compared to pH 7.4. Furthermore, acidosis was protective even after perfusion with non-oxygenated media (42% tubules damaged at pH 7.0 vs. 95% of tubules damaged at pH 7.4; P less than 0.01), making it very unlikely that the effect of acidosis is to improve TAL oxygenation. Since previous studies indicate that the TAL lesion is transport dependent and prevented in the non-filtering kidney, it was possible that the decrease in GFR associated with acidosis could account for decreased injury. The GFR was manipulated by alterations in perfusion pressure or albumin concentration, and no consistent relationship between the extent of injury and GFR could be shown at either pH over a wide range of GFR values. Therefore, acidosis protected the TAL from hypoxic injury by a mechanism apparently independent of oxygen or solute delivery.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis↗
PubMed1988

31P nuclear magnetic resonance study of renal allograft rejection in the rat.

Phosphorus (31P) nuclear magnetic resonance (NMR) spectroscopy was used to serially evaluate heterotopic renal allograft rejection in the rat. Renal allografts transplanted to the groin of recipient animals were studied using a 1.89 Tesla horizontal bore magnet. The relative intracellular concentrations of phosphorus metabolites such as adenosine triphosphate and inorganic phosphate as well as intracellular pH were determined by 31P NMR on days 4, 7, 10, and 14 following transplantation across a major histocompatibility mismatch. Recipient rats chosen to be rejectors received no immunosuppression while animals chosen to be nonrejectors received cyclosporine during the first 7 days following transplantation. By day 7, all rejector rats could be distinguished from nonrejector rats by their higher relative concentration of inorganic phosphate and their lower relative concentration of adenosine triphosphate. These NMR findings correlated with histologic findings of renal infarction probably related to vascular rejection in the allografts. 31P NMR spectroscopy may have application as a noninvasive tool in the differential diagnosis of posttransplantation renal insufficiency.

Adenosine Triphosphate↗
PubMed1988

Improvement of renal preservation by verapamil with 24-hour cold perfusion in the isolated rat kidney.

There is substantial evidence that increased cellular calcium may activate processes that lead to cellular injury and death, and calcium entry blockers (CEB) have been shown to protect against renal ischemic injury. This approach has been used experimentally to enhance kidney preservation during both warm and cold ischemia. In the present study, the effect of the CEB verapamil on kidney function after 24 hr of hypothermic (4-7 degrees C) perfusion was examined and compared with simple cold storage with Eurocollins' solution (4 hr), 4 or 24 hr cold perfusion, without the addition of verapamil. The cold perfusion media consisted of 3% albumin in phosphate-free Krebs-Henseleit saline supplemented with 5 mM glucose. Cold perfusion was performed at 40 mmHg perfusion pressure with either 0 (C) or 5 microM verapamil (V) added to the cold perfusion media. Renal functional parameters of plasma flow (RPF), inulin clearance (Cin), fractional (FRNa+) and net sodium reabsorption (TNa+) were assessed during 60 min of reperfusion at 37 degrees C using 6.7% albumin in Krebs-Henseleit saline supplemented with glucose, inulin, and 20 amino acids. There was no increase in RPF with V (33 +/- 1 vs. 32 +/- 2 ml/min/g,NS) but Cin was significantly higher (271 +/- 30 vs. 168 +/- 20 microliter/min/g P less than 0.01) with V. Preservation of tubular function by V was demonstrated by an increase in FRNa+ (84 +/- 5 vs. 57 +/- 8%, P less than .01), TNa+ (32 +/- 6 vs. 15 +/- 3 mumol/min/g, P less than .01) and renal adenosine triphosphate (ATP) concentration (8.0 +/- 5 vs. 4.7 +/- 1.0 mumol/g dry tissue, P less than .01). Thus, V appears not only to enhance kidney preservation with warm and cold ischemia but also improves renal function, as assessed by glomerular filtration rate (GFR) tubular function, and tissue ATP concentration with 24-hr cold perfusion.

Animals↗
PubMed1988

A new microvascular model for noninvasive nuclear magnetic resonance spectroscopy of the transplanted kidney.

The cellular biology of graft rejection is not well understood. Phosphorus-31 nuclear magnetic resonance (31P NMR) spectroscopy is a new noninvasive technique for the measurement of intracellular pH and relative amounts of phosphorus-containing compounds, such as adenosine triphosphate (ATP), inorganic phosphate, phosphocreatine, and sugar phosphates, in any tissue from which a clear signal can be obtained. Biochemical analysis of such precision, without the need for tissue destruction, represents an unusual opportunity for analysis of in vivo cellular metabolism under varying conditions, including graft rejection. 31P NMR study of intra-abdominal viscera has not been feasible in most laboratories without laparotomy because of signal interference from abdominal wall muscle. In this study, to eliminate this interference, a rat kidney was transplanted to the groin, where it could be serially studied without overlying skeletal muscle. This new vascular technique was successful in 11 of 11 attempts and maintained normal serum creatinines in 10 chronic survivors after removal of both native kidneys. The 31P NMR spectroscopic signal from the groin kidney is clear and highly reproducible. This new microvascular model will make it possible to carry out noninvasive long-term spectroscopic studies that could potentially identify a reliable marker for allograft rejection.

Adenosine Triphosphate↗
PubMed1987

Atrial natriuretic factor (ANF) levels are elevated in rats bearing rejecting heart-lung allografts.

Intra-abdominal heart-lung grafts were transplanted into 8 rats across a major histocompatibility barrier. Four of the 8 rats were treated with Cyclosporin A (CsA) to prevent rejection. Atrial natriuretic factor (ANF) levels measured 6 days after transplantation revealed a significantly (p less than .005) higher mean ANF concentration in rats bearing a rejecting heart-lung allograft (642 +/- 148.0 pg/ml) compared to rats bearing a heart-lung allograft not undergoing rejection (200.8 +/- 13.07 pg/ml). ANF might be a useful noninvasive marker in the diagnosis of rejection in heart and heart-lung transplants.

Animals↗
PubMed1987

31P nuclear magnetic resonance study of acute renal dysfunction in rat kidney transplants.

31P NMR spectroscopy was used to study renal allografts in rats subjected to allograft rejection, cyclosporine toxicity, ischemia, and ureteral obstruction. Parameters of relative peak areas and intracellular pH were accurately distinguished among the different causes of graft dysfunction. Ureteral obstruction was clearly identified by elevations in the phosphodiester/urine phosphate peak. Ischemia and rejection were both associated with increases in inorganic phosphates and phosphomonesters and decreases in the beta-phosphate peak of adenosine triphosphate but were distinguishable from each other by differences in intracellular pH which was normal in rejected allografts (7.33 +/- 0.07, n = 3) but low in ischemic allografts (7.00 +/- 0.05, n = 3, P less than 0.05). Grafts insulted with cyclosporine toxicity were not distinguishable from normal allografts by any of the parameters studied. These data suggest that 31P NMR spectroscopy may have potential clinical application in differentiating among the causes of graft failure of human renal allografts.

Animals↗
PubMed1987

Comparison of the natriuretic response to atriopeptin III and loop diuretic in the isolated perfused rat kidney.

1. Isolated rat kidneys were perfused at a constant perfusion pressure of 90 mmHg to study the natriuretic effects of atriopeptin III (AP-III) and to compare these effects with those of frusemide. AP-III (1 microgram) or frusemide (1 mg) were added to the perfusate (100 ml) after two 15 min control collection periods. 2. Compared with the control group, AP-III and frusemide increased urinary sodium excretion (UNa V, 5.6 +/- 1.1 and 4.6 +/- 0.6 vs control 1.8 +/- 0.3 mumol min-1 g-1, mean +/- SEM, P less than 0.01 and P less than 0.05, respectively), fractional sodium excretion (FENa, 4.8 +/- 1.1 and 6.7 +/- 0.8 vs control 2.0 +/- 0.2%, P less than 0.05 and P less than 0.001, respectively) and potassium excretion (UKV, 3.2 +/- 0.3 and 3.0 +/- 0.3 vs control 1.5 +/- 0.3 mumol min-1 g-1, both P less than 0.01). However, AP-III, but not frusemide, increased glomerular filtration rate (820 +/- 55 vs 590 +/- 24 microliter min-1 g-1, P less than 0.01) and urine flow rate (V 97.5 +/- 8.0 vs 44.1 +/- 5.2 microliter min-1 g-1, P less than 0.001). Calculated distal delivery of sodium (CNa +/- CH2O, 76.6 +/- 6.8 vs 30.7 +/- 3.8 microliter min-1 g-1, P less than 0.005) as well as fractional distal delivery of sodium [(CNa +/- CH2O)/CIn, 9.4 +/- 0.9 vs 5.1 +/- 0.6%, P less than 0.01] were increased by AP-III, but not frusemide.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

P-31 nuclear magnetic resonance spectroscopic evaluation of heterotopic cardiac allograft rejection in the rat.

P-31 nuclear magnetic resonance (NMR) spectroscopy was used to evaluate heterotropic cardiac allograft rejection in the rat. To enable optimal application of NMR spectroscopy for the in vivo study of myocardial metabolism in the transplanted organ, an accessory heart transplantation to groin in the rat was used. The allografts were studied in a 1.89 Tesla horizontal bore magnet. Each spectrum was obtained by Fourier transform of 512 scans using 60-degree pulses with 2-sec delays. Changes in phosphocreatine (PCr), adenosine 5-triphosphate (ATP), and inorganic phosphate (Pi) and intracellular pH as determined by P-31 NMR were compared with rejection process as judged by histological studies. Allografts treated with cyclosporine (CsA) did not show any rejection (NR) and had relatively high levels of PCr, and low levels of Pi. Allografts that did not receive any CsA revealed both vascular and cellular rejection. These rejected allografts (R) had relatively low levels of PCr and high levels of Pi. It is concluded that P-31 NMR spectroscopy may have potential application to the clinical diagnosis of cardiac allograft rejection.

Adenosine Triphosphate↗
PubMed1987

In vitro and in vivo protective effect of atriopeptin III on ischemic acute renal failure.

The effect of atriopeptin III (AP-III) on ameliorate ischemic acute renal failure was first examined in the isolated perfused kidney. Isolated rat kidneys were clamped for 1 h and reperfused for 30 min without therapy and then perfused with either 0 (control) or 100 micrograms/dl AP-III. In this system AP-III significantly improved renal plasma flow (39.6 +/- 2.4 vs. 32.2 +/- 2.1 ml/min per g; P less than 0.05) inulin clearance (182.6 +/- 49.2 vs. 24.6 +/- 6.2 microliters/min per g; P less than 0.05), urine flow (52.9 +/- 12.1 vs. 7.1 +/- 0.8 microliters/min per g, P less than 0.01), and net tubular sodium reabsorption (21.2 +/- 6.6 vs. 2.9 +/- 0.9 mumol/min per g, P less than 0.05) as compared with control. A second series of in vivo studies experiments were performed using 1 h of bilateral renal artery clamping followed by an intravenous infusion of either saline alone (control) or AP-III (0.20 microgram/kg per min) for 60 min. The results demonstrated that inulin clearance (244.4 +/- 25.1 vs. 15.8 +/- 8.2 microliters/min per 100 g; P less than 0.01), urine flow (23.1 +/- 5.9 vs. 1.1 +/- 0.5 microliters/min per 100 g; P less than 0.01), and net tubular sodium reabsorption (38.9 +/- 4.7 vs. 4.3 +/- 1.6 mumol/min per 100 g; P less than 0.01) were significantly higher in AP-III-treated rats than controls during the hour of AP-III infusion. In 1 h posttreatment study this significant protective effect of AP-III was documented to persist. In more chronic studies animals treated acutely with AP-III had lower serum creatinine concentration at 24 h (1.8 +/- 0.3 vs. 3.3 +/- 0.4 mg/dl; P less than 0.01) and 48 (1.0 +/- 0.2 vs. 2.4 +/- 4.0 mg/dl; P less than 0.01) after the 60 min of ischemia than controls. Renal adenosine triphosphate regeneration as assessed by P-31 nuclear magnetic resonance during reflow was also significantly improved in AP-III-treated animals at 1 h (3.03 +/- 0.30 vs. 1.45 +/- 0.40 mumol/g dry wt; P less than 0.05) and 2 h (3.98 +/- 0.46 vs. 1.80 +/- 0.05 mumol/g dry wt; P less than 0.01) or reflow as compared with control rats. Thus, AP-III significantly ameliorates ischemic acute renal failure both in vitro and in vivo in the rat.

Acute Kidney Injury↗
PubMed1987

P-31 nuclear magnetic resonance spectroscopic study of obstructive uropathy in the rat.

P-31 nuclear magnetic resonance (NMR) spectroscopy of the rat kidney with ureteral ligation resulted in a rapid and major increase in a peak resonating at 7096.63 +/- 0.65 Hz from the reference frequency of phosphorus (32.60 MHz). This corresponded to an increase in the concentration of the substance responsible for peak X from 0.34 +/- 0.04 mumol/g wet weight in normal kidneys to 1.45 +/- 0.27 mumol/g wet weight in unilaterally obstructed kidneys and 2.00 +/- 0.34 mumol/g wet weight in bilaterally obstructed kidneys at 3 h (P less than 0.01). Further NMR studies performed with in vivo kidneys and tissue extracts revealed that inorganic phosphate in the urine, resonating at a lower frequency due to the acid pH environment, was responsible for the increase in this peak. These findings may prove to be of fundamental interest as well as potential clinical significance.

Adenosine Triphosphate↗
PubMed1987

Effects of adenosine triphosphate depletion in the isolated perfused rat kidney.

Glycerol or fructose (40 mM) was added to the control perfusate and renal function was observed in the isolated perfused rat kidney during nonischemic perfusions or perfusions following 30 min of clamp ischemia. Addition of glycerol or fructose resulted in lowering adenosine triphosphate (ATP) levels to 62 and 35%, respectively, of levels achieved with control perfusate under nonischemic conditions (p less than 0.01). Total adenine nucleotides (TAN) were also lowered to 67% with glycerol and 61% with fructose of control values under nonischemic conditions (p less than 0.05). However, physiologic parameters of renal plasma flow and inulin clearance were essentially unaffected by either glycerol or fructose. Following ischemia, glycerol and fructose reduced ATP levels to 51 and 37% and TAN levels to 67 and 65%, respectively, of values seen with control perfusate. However, recovery of renal plasma flow and inulin clearance were uneffected by the addition of either glycerol or fructose. Thus, a 33-65% reduction in renal tissue ATP by glycerol or fructose does not appear to have a deleterious effect on organ function in the basal state or during recovery from an ischemic insult in the isolated perfused rat kidney.

Adenine Nucleotides↗