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Biomedical subjects

R G Luke

Publications and source records attributed to R G Luke.

At least 73 records · Page 4Linked to original sources
PubMed1986

Cyclosporin in therapeutic doses increases renal allograft vascular resistance.

In fourteen renal transplant patients converted from cyclosporin to azathioprine for financial reasons renal blood flow was greater and renal vascular resistance lower after conversion. These changes occurred without any change in serum creatinine. This finding suggests that the renal allograft vasoconstriction induced by cyclosporin occurs before evidence of nephrotoxicity and that the vasoconstriction is reversible. Renal allograft recipients had cyclosporin-induced haemodynamic changes even early (2 weeks) after transplantation, when the allograft is still denervated. These findings may explain the increased sensitivity to other nephrotoxic agents and hypertension observed in cyclosporin-treated patients.

Adolescent↗
PubMed1986

Cytomegalovirus glomerulopathy: a controversial lesion.

Seven autopsies performed on immunosuppressed bone marrow transplant recipients who died with documented herpes virus infection were reviewed. The kidneys were studied by light and electron microscopy and revealed no pathological findings, specifically no glomerulopathy or tubular interstitial nephritis. Seven renal biopsies performed on kidney transplant recipients in whom a diagnosis of cytomegalovirus glomerulopathy was entertained were also studied. These patients exhibited clinical parameters suggestive of cytomegalovirus infection. Three patients had subsequent nephrectomies and two showed severe acute vascular rejection. The one kidney without demonstrable acute vascular rejection was negative for cytomegalovirus on culture. Three additional patients improved or stabilized their renal function under therapy for rejection. Light, electron microscopic and immunofluorescent studies, although confirmatory of endothelial cell damage, did not substantiate active cytomegalovirus renal infection in these patients. An additional group of fifteen children with disseminated cytomegalovirus infection revealed no evidence of glomerulopathy. Finally, two kidney transplant recipients with proven cytomegalovirus infection (one with associated tubular interstitial nephritis) also showed no glomerular alterations. It is the author's opinion that the entity that has been considered as cytomegalovirus glomerulopathy probably represents rejection, either a peculiar anti-endothelial type of rejection or a protracted, early, or partially resolved acute vascular rejection without residual or identifiable acute vascular rejection changes in the tissue sampled.

Adolescent↗
PubMed1986

Role of the loop segment in the urinary concentrating defect of hypercalcemia.

Hypercalcemia is associated with impaired urinary concentrating ability. To explore the mechanism(s) by which hypercalcemia impairs chloride transport in the loop of Henle, we carried out in vivo microperfusion of the loop segment in Sprague-Dawley rats rendered acutely hypercalcemic (12.1 +/- 0.1 mg/dliter) by calcium gluconate infusion. Control rats were infused with sodium gluconate and had normal plasma calcium (8.0 +/- 0.2 mg/dliter). Compared to control, fractional chloride reabsorption was decreased (61 +/- 4 to 50 +/- 3%; P less than 0.05) and early distal chloride increased 74 +/- 6 to 98 +/- 3 mEq/liter (P less than 0.001) in hypercalcemia. During hypercalcemia, infusion of verapamil failed to increase fractional chloride reabsorption (49 +/- 4%; P less than 0.05) or decrease early distal chloride (95 +/- 2; P less than 0.05) toward control values. Similarly, indomethacin did not improve fractional chloride reabsorption (48 +/- 4%; P less than 0.05) or distal chloride concentration (93 +/- 7; P less than 0.05). In control rats infused with Ringers HCO3, the addition of calcium 8.0 mEq/liter to the perfusate increased early distal calcium (9.22 to 3.11 mEq/liter) but was associated with no change in fractional chloride reabsorption (-6 +/- 6%) and a slight decrease in early distal chloride (-9 +/- 3 mEq/liter; P less than 0.05). These data are consistent with the hypothesis that an elevated plasma, not luminal calcium, concentration impairs chloride reabsorption in the loop segment, primarily the ADH-stimulated component. This may have an important role in the urinary concentrating defect of hypercalcemia.

Animals↗
PubMed1986

Importance of the kidney in the correction of chloride-depletion alkalosis in the rat.

Correction of chloride-depletion alkalosis (CDA) may involve renal as well as extrarenal mechanisms. To determine the relative contribution of these mechanisms in a rat model of CDA produced by peritoneal dialysis (PD), we studied six groups of anesthetized Sprague-Dawley rats after PD. Groups II-IV and IIa were subjected to functional bilateral nephrectomy, and groups I and Ia were sham-operated. Groups I, Ia, II, and IIa were infused with isotonic fluid containing 70 mM Cl- and 40 mM HCO3-; the infusate in group III was 140 mM Cl- and in group IV, 70 mM neutral PO4 was substituted for Cl-. Groups I and Ia were infused at 0.5 ml . h-1 X 100 g body wt-1 and groups II, IIa, III, and IV at 0.25 ml . h-1 X 100 g-1. After 3 h of infusion, early partial correction with reciprocal changes in plasma Cl (+6.1 +/- 1.9 mmHg) and total CO2 (-6.0 +/- 0.8 meq/liter) occurred (P less than 0.01) only in group I. Hypokalemia (3.1 +/- 0.1 meq/liter) also occurred only in group I. The responses of groups Ia and IIa studied at 5 h were similar to those of groups I and II. These data suggest that the kidney, and not extrarenal mechanisms, is primarily responsible for the correction of CDA during infusion of chloride.

Alkalosis↗
PubMed1986

Effect of dietary NaCl on chloride uptake in rat collecting duct segment.

To explore further the mechanism of the effect of dietary NaCl intake on collecting duct (CDS) chloride uptake, we compared late distal chloride delivery to and urinary 36Cl recovery (the latter as an index of unidirectional efflux) from the CDS in four groups of male Sprague-Dawley rats. Groups were prepared for 7-10 days as follows: group 1, drinking 0.15 M NaCl; group 2A, regular diet; group 2B, regular diet plus deoxycorticosterone (2 mg im) (at 24 and 2 h before micropuncture); and group 3, low-NaCl diet. To increase tubule fluid flow rate and produce natriuresis without chloruresis, 0.15 M NaHCO3 at 5% body wt/h was infused in all groups except group 3, in which an infusion of 150 mM Na+, 55 mM Cl-, and 85 mM HCO3- was required to maintain a plasma chloride concentration equal to that in other groups. Plasma chloride concentration and arterial pH did not differ between groups before infusion. Urinary 36Cl recovery increased in parallel with dietary NaCl content (P = 0.0001). By analysis of multiple covariances, neither tubule fluid chloride concentration nor chloride delivery to the CDS correlated with urinary 36Cl recovery within any of the groups or for all animals studied. High doses of mineralocorticoid did not alter chloride uptake in group 2. These data suggest that progressive restriction of dietary NaCl enhances chloride uptake in the CDS of the rat unrelated to changes in plasma chloride concentration or chloride delivery from the superficial late distal tubules.

Animals↗
PubMed1985

Benefits of removal of native kidneys in hypertension after renal transplantation.

To find out whether diseased native kidneys can be the cause of hypertension in patients whose allograft otherwise seems to function well, six such hypertensive renal transplant patients were investigated before and 4.5 +/- 1.5 (+/- SD) months after removal of their native kidneys. After nephrectomy mean arterial pressure fell considerably yet renal (allograft) plasma flow increased by 77% and vascular resistance of the allograft fell by 55%. Mean transverse cardiac diameter and electrocardiogram voltage measurements of left ventricular hypertrophy both improved significantly. Since the rise in renal plasma flow could be induced by giving captopril, an inhibitor of angiotensin II formation, to patients who had not had their native kidneys removed, the native kidneys seem to exert their effect on the allograft via the renin-angiotensin system. The improvement in allograft plasma flow after nephrectomy was maintained for more than 1 1/2 years. Administration of captopril after native nephrectomy did not further change allograft plasma flow. The findings suggest that in many carefully selected patients with post-transplantation hypertension native kidney nephrectomy offers tangible benefits.

Adult↗
PubMed1985

Effect of reduced chloride reabsorption on renin release in the isolated rat kidney.

To investigate the relationship between tubular reabsorption of chloride and renal renin release in the isolated perfused rat kidney, perfusate renin activity was measured during substitution of either nitrate or thiocyanate for varying amounts of perfusate chloride but with maintained perfusate sodium concentration. Renin rose significantly as perfusate chloride fell; there was a sevenfold increase between perfusion with normal chloride and almost complete substitution of chloride by nitrate. With a normal perfusate chloride the addition of furosemide 10(-4) M to the perfusate also led to an increase in renin and a reduction in tubule chloride reabsorption. For all these experiments there was a significant negative correlation between renin and absolute tubular reabsorption of chloride (r = -0.68, P less than 0.001), but no such relationship with absolute sodium reabsorption. Renin release in a nonfiltering kidney, produced by elevating perfusate albumin concentration, increased approximately 40-fold. Thus increasing plasma oncotic pressure elevates renin by mechanisms additional to cessation of tubular chloride absorption. However, substitution of chloride in the perfusate by nitrate in this nonfiltering kidney did not further elevate renin release. We conclude that renin release is influenced by a signal dependent on, and inversely proportional to, chloride reabsorption in the thick ascending limb of the Loop of Henle.

Absorption↗
PubMed1985

Hypertension after successful renal transplantation.

Thirty-three renal allograft recipients who had high blood pressure (mean arterial pressure more than 105 mm Hg) at least one year after their successful transplant operation were compared with 23 normotensive kidney transplant recipients (mean arterial pressure less than 105 mm Hg) at the General Clinical Research Center. The patients with higher blood pressure had markedly and significantly higher (96 percent) renal vascular resistance and significantly lower (41 percent) renal plasma flow. Responses to salt loading and restriction were suggestive of marked activity of the renin-angiotensin system as were plasma renin activity measurements. Subsequent follow-up has revealed chronic rejection or renal artery stenosis as a probable cause of hypertension for 11 of the 33 patients. The remaining 22 patients had increased renal vascular resistance and decreased renal plasma flow indistinguishable from that in the 11 patients in whom follow-up revealed a cause for their persistent hypertension; however, 21 of these 22 patients have their native kidneys in place.

Adult↗
PubMed1985

Mechanisms of posttransplant hypertension.

Posttransplant hypertension is an important risk factor for cardiovascular mortality and graft function. We performed metabolic studies in 35 hypertensive patients with well-maintained graft function on maintenance immunosuppressive drugs and in 17 normotensive control transplant recipients. The group of hypertensive recipients were characterized by increased peripheral plasma renin activity, lack of change in blood pressure in response to salt loading and restriction, and by increased peripheral and renal resistance. In contrast, on the same protocol in a group of patients with essential hypertension, blood pressure fell significantly on a low-salt intake. Peripheral resistance in hypertensive transplant recipients fell in response to saline loading, in contrast to the effects in normotensive transplant recipients. Hypertensive patients with retained native kidneys as compared to those who had these removed prior to transplant, but were still hypertensive, differed only with regard to reduced renal plasma flow in the former group. These data are consistent with a predominantly renin-dependent hypertension in these renal transplant recipients. When bilateral nephrectomy or repair of graft renal artery stenosis is being considered, response to captopril may offer a means of selection; acute renal failure on captopril suggests functionally significant renal artery stenosis.

Adult↗
PubMed1985

Effect of urinary pH and diatrizoate on Bence Jones protein nephrotoxicity in the rat.

Both low urinary pH and radiocontrast agents may intensify myeloma nephrotoxicity. To study the effects of these factors, we determined inulin clearances (CIn) before and after infusions of human Bence Jones protein (BJP) in male Sprague-Dawley rats in a dose previously shown to be nephrotoxic. Rats that drank 0.15 M NaHCO3 for 48 hr before study had no change in CIn (+3 +/- 20%) after BJP unlike those that drank 0.15 M NH4Cl (-33 +/- 14%, P less than 0.05); urinary pH differed (7.6 +/- 0.1 vs. 6.2 +/- 0.1, P less than 0.05), but urinary flow rates did not. The acidifying regimen was used in all subsequent groups. Infusion of diatrizoate (DTZ) after BJP produced a further decrease in CIn (-85 +/- 8%, P less than 0.05). In contrast, infusion of albumin, which raised plasma protein concentration to that seen in BJP-infused rats, did not change CIn (+39 +/- 17%). Infusion of beta-lactoglobulin also led to a greater decrease in CIn after DTZ (-35 +/- 9 vs. -67 +/- 8%, P less than 0.05), but myoglobin did not (-58 +/- 7 vs. -54 +/- 12%). Urinary pH and flow rate did not differ between any DTZ-infused group and its appropriate control. These data suggest that aciduria independent of urinary flow rate increases the nephrotoxicity of BJP. In this setting, DTZ further intensifies the nephrotoxicity of BJP as well as some but not all filterable proteins.

Acute Kidney Injury↗
PubMed1985

Effect of potassium depletion on chloride transport in the loop of Henle in the rat.

Microperfusion of the superficial loop segment (latest proximal to earliest distal tubule) was performed in potassium-depleted and control rats. Potassium depletion was confirmed by analysis of muscle content (control 45 +/- 2, potassium depletion 33.5 +/- 0.9 meq/100 g dry solids). During perfusion at 20 nl/min net chloride absorption was decreased (66 +/- 3 vs. 77 +/- 2%, P less than 0.01) and early distal chloride concentration increased (70 +/- 5 vs. 50 +/- 4 meq/liter, P less than 0.01) in the potassium-depleted rats. In separate paired experiments in potassium-depleted rats, indomethacin infusion increased net chloride absorption (P less than 0.05) and lowered early distal chloride concentration (P less than 0.05) toward, but not to, normal. A similar effect of indomethacin to decrease early distal chloride concentration was seen in rats ingesting a normal diet and in control rats. We conclude that in potassium-depleted rats there is impaired net chloride absorption in the loop segment, most likely in the thick ascending limb, and that this effect is not produced by an altered response to prostaglandins. This defect in chloride transport may be responsible, at least in part, for the impaired concentrating capacity seen in potassium-depleted rats.

Animals↗
PubMed1985

Effect of ADH on chloride reabsorption in the loop of Henle of the Brattleboro rat.

Both in vivo superficial loop segment microperfusion and in vitro perfusion of isolated medullary thick ascending limb segments were used to assess the effect of vasopressin on loop of Henle chloride absorption in the Brattleboro rat. Superficial loop segments were perfused between the latest proximal and earliest distal tubule in vivo at 19.2 +/- 0.4 nl/min (mean +/- SE) with an artificial tubule fluid. Under control conditions, absolute chloride reabsorption was 1,596 +/- 61 pmol/min and increased to 1,876 +/- 102 after intravenous infusion of vasopressin (P less than 0.005). Distal tubule fluid chloride concentration decreased 4.6 +/- 1.5 meq/liter (P less than 0.05), and fractional chloride reabsorption increased 4.8 +/- 2.0% (P less than 0.05). For in vitro perfusion, medullary thick ascending limb segments were bathed and perfused (9-15 nl/min) with phosphate-buffered solutions at 38 degrees C. Under control conditions, transepithelial voltage was +2.4 +/- 0.3 mV, lumen positive, and the net chloride flux was 147 +/- 24 pmol X min-1 X mm-1 in the absorptive direction. Addition of vasopressin to the bathing solution increased net chloride reabsorption to 342 +/- 56 pmol X min-1 X mm-1 (P less than 0.02) and transepithelial voltage to 3.0 +/- 0.3 mV (P less than 0.002). An additional group of tubules was examined under identical conditions; however, vasopressin was removed from the bathing medium during a subsequent recovery period. In these experiments, net chloride flux and transepithelial voltage significantly increased compared with the control period and returned to control values upon removal of vasopressin from the bath.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1984

The effect of pretransplant stored donor-specific blood transfusion on renal allograft survival in one-haplotype living-related transplant recipients.

The effect of pretransplant stored donor-specific blood transfusions (DSBTs) on renal allograft survival in 108 consecutive one-haplotype living-related donor (LRD) transplant recipients (group A) was compared with a similar consecutive series of 40 one-haplotype LRD recipients (group B) who did not receive DSBTs. All transplant recipients in both groups received identical immunosuppressive protocols using azathioprine and prednisone. One hundred twenty-eight patients received pretransplant stored DSBTs. Twelve of these patients (9%) developed cytotoxic antibodies to their respective donors and those transplants were not performed. Eight patients who had negative final crossmatches with their prospective donor experienced delay or cancellation of their transplants due to late donor withdrawal, or illness of the donor or recipient. Actuarial graft survival for group A and group B patients was compared at 6, 12, 18, and 24 months. Group A graft survival was 94, 90, 90, and 85% and Group B 73, 68, 63, and 63% at the comparison periods. This experience suggests that stored DSBTs are convenient, associated with a low frequency of recipient sensitization, and improved the prospects of success in one-haplotype LRD renal transplantation.

Adolescent↗
PubMed1984

Segmental chloride and fluid handling during correction of chloride-depletion alkalosis without volume expansion in the rat.

To determine whether chloride-depletion metabolic alkalosis (CDA) can be corrected by provision of chloride without volume expansion or intranephronal redistribution of fluid reabsorption, CDA was produced in Sprague-Dawley rats by peritoneal dialysis against 0.15 M NaHCO3; controls (CON) were dialyzed against Ringer's bicarbonate. Animals were infused with isotonic solutions containing the same Cl and total CO2 (tCO2) concentrations as in postdialysis plasma at rates shown to be associated with slight but stable volume contraction. During the subsequent 6 h, serum Cl and tCO2 concentrations remained stable and normal in CON and corrected towards normal in CDA; urinary chloride excretion was less and bicarbonate excretion greater than those in CON during this period. Micropuncture and microinjection studies were performed in the 3rd h after dialysis. Plasma volumes determined by 125I-albumin were not different. Inulin clearance and fractional chloride excretion were lower (P less than 0.05) in CDA. Superficial nephron glomerular filtration rate determined from distal puncture sites was lower (P less than 0.02) in CDA (27.9 +/- 2.3 nl/min) compared with that in CON (37.9 +/- 2.6). Fractional fluid and chloride reabsorption in the proximal convoluted tubule and within the loop segment did not differ. Fractional chloride delivery to the early distal convolution did not differ but that out of this segment was less (P less than 0.01) in group CDA. Urinary recovery of 36Cl injected into the collecting duct segment was lower (P less than 0.01) in CDA (CON 74 +/- 3; CDA 34 +/- 4%). These data show that CDA can be corrected by the provision of chloride without volume expansion or alterations in the intranephronal distribution of fluid reabsorption. Enhanced chloride reabsorption in the collecting duct segment, and possibly in the distal convoluted tubule, contributes importantly to this correction.

Absorption↗
PubMed1984

Volume-independent reductions in glomerular filtration rate in acute chloride-depletion alkalosis in the rat. Evidence for mediation by tubuloglomerular feedback.

We have recently described reduced superficial nephron glomerular filtration rate (SNGFR) in chloride-depletion alkalosis (CDA) without volume depletion. To elucidate the mechanism of this phenomenon, we studied three degrees of increasing severity of CDA (groups CDA-1, 2, and 3) produced by one or two peritoneal dialyses against 0.15 M NaHCO3 and electrolyte infusions of different Cl and HCO3 content in Sprague-Dawley rats; control rats (CON) were dialyzed against and infused with Ringers-HCO3. Extracellular fluid (ECF) volume was assessed by blood pressure, hematocrit, plasma protein concentration, and 125I-albumin space; none of these variables differed among the four groups. Micropuncture of the latest proximal and earliest distal convolutions was carried out. As CDA intensified from CON to CDA-3 (plasma tCO2 25 +/- 1 to 43 +/- 1 meq/L; P less than 0.01), distally determined SNGFR declined progressively (40.9 +/- 1.7 to 28.3 +/- 1.8 nl/min; P less than 0.01), while in early distal tubule fluid, flow rate (8.6 +/- 0.7 to 3.4 +/- 0.6 nl/min) and Cl concentration (36 +/- 2 to 19 +/- 3 meq/L) decreased and osmolality (110 +/- 5 to 208 +/- 12 mosmol/kg) increased (P less than 0.01), and, in the loop segment, Cl reabsorption decreased progressively (2,009 +/- 112 to 765 +/- 128 peq/min; P less than 0.01). In early distal tubule fluid, Cl concentration correlated positively and osmolality negatively with distally determined SNGFR (P less than 0.05). Proximally determined SNGFRs did not differ among the four groups. Proximal tubule stop-flow pressure responses to increasing rates of orthograde perfusion of the loop segment from 0 to 40 nl/min did not differ between groups CON and CDA-2. We interpret these data to show that reductions in SNGFR in CDA in the rat can occur by tubuloglomerular feedback (TGF) in the absence of differences in ECF volume or of alterations in TGF sensitivity during metabolic alkalosis. Of the proposed signals for TGF sensed by the macula densa, distal tubule fluid osmolality or some related variable is the signal most compatible with our data.

Alkalosis↗
PubMed1983

Remission of essential hypertension after renal transplantation.

Six patients in whom "essential hypertension" led to nephrosclerosis and kidney failure received kidney transplants from normotensive donors. After an average follow-up of 4.5 years, all were normotensive and had evidence of reversal of hypertensive damage to the heart and retinal vessels. These six patients, all of whom were black, and six control subjects matched for age, sex, and race were admitted to the General Clinical Research Center for 11 days for observation of their blood pressure and their responses to salt deprivation and salt loading. Mean arterial pressure (+/- S.E.M.) among the patients who had previously had essential hypertension was similar to that of the normal controls (92 +/- 1.9 vs. 94 +/- 3.9; P not significant), and both groups had similar responses to salt deprivation and salt loading. Thus, essential hypertension in human beings is shown to be similar to the hypertension seen in spontaneously hypertensive rats in that both can be corrected by transplantation of a kidney from a normotensive donor. This observation supports the concept of the primary of the kidney in causing essential hypertension.

Adult↗