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Biomedical subjects

R G Luke

Publications and source records attributed to R G Luke.

At least 55 records · Page 3Linked to original sources
PubMed1989

Successful renal allografts in recipients with crossmatch-positive, dithioerythritol-treated negative sera. Race, transplant history, and HLA-DR1 phenotype.

Graft survival was examined in 15 renal allograft recipients from a group of 20 patients with IgM autolymphocytotoxic antibody that could be removed in a crossmatch assay using a reducing agent, dithioerythritol (DTE). The significant differences in this group of 20 patients compared with end-stage renal disease (ESRD) patients lacking autolymphocytotoxic antibodies included an increased frequency of black patients (P = 0.002), a lack of previous transplants (P = 0.003), and an increased frequency of the HLA-DR1 phenotype (P = 0.0001). Sex and the number of transfusions did not appear significant, whereas the cause of ESRD was primarily systemic lupus erythematosus. Fifteen of the 20 patients were transplanted against a positive donor crossmatch. Eleven were recipients of cadaveric kidneys, nine of which are still functioning for periods ranging from 0.5 to 40 months. Two fo the cadaveric recipients died with functional grafts. Four received living-related donor transplants, one of which was lost to acute rejection one month posttransplant, while the remaining three have survived 1.5, 9, and 21 months, respectively. Fourteen patients had immediate allograft function with no hyperacute rejection and only one case of acute tubular necrosis (ATN) was found. In summary, a negative crossmatch using DTE-treated, autologous reactive recipient sera may identify a group of patients who can be transplanted with minimal concern for hyperacute rejection or ATN. In addition to cause of ESRD, race, transplant history, and HLA-DR phenotype may further define this group of transplant candidates having IgM autolymphocytotoxic antibody. Extrapolation of these conclusions to transplant candidates lacking autolymphocytotoxic antibodies is not warranted.

Absorption↗
PubMed1989

Superficial distal and deep nephrons in correction of metabolic alkalosis.

Chloride is necessary and sufficient to correct alkalosis induced by dialysis vs. 0.15 M NaHCO3. To determine the contribution of the cortical (SC) distal convolution (DCT) and juxtamedullary (JM) nephrons to correction, we examined Cl and total CO2 (tCO2) transport in alkalotic Sprague-Dawley rats infused with 5% dextrose (group DM) or with 5% dextrose and 80 mM Cl (group CC); in papillary studies in alkalotic Munich-Wistar rats, 6% albumin was added to the infusate. In cortical studies, changes in plasma Cl and tCO2 were 4.9 +/- 0.7 vs. 0.7 +/- 0.9 and -6.0 +/- 0.8 vs. 0.4 +/- 0.9 meq/l and in tCO2 excretion (133 +/- 28 vs. -8 +/- 10 mueq/min) in groups CC and DM, respectively; results in papillary studies were similar. Delivery of tCO2 out of late SC DCT (CC 146 +/- 20 and DM 146 +/- 23 pmol/min) and Henle's loop (CC 145 +/- 18 and DM 202 +/- 56 pmol/min) and reabsorption within DCT (CC 15 +/- 24 and DM 45 +/- 19 pmol/min) did not differ. During correction of chloride-depletion alkalosis, the increment in bicarbonate excretion does not emanate from DCT of SC nephrons or JM nephrons but rather from the collecting duct.

Alkalosis↗
PubMed1988

On the mechanism by which chloride corrects metabolic alkalosis in man.

To determine whether administration of chloride corrects chloride-depletion metabolic alkalosis (CDA) by correction of plasma volume contraction and restoration of glomerular filtration rate or by an independent effect of chloride repletion, CDA was produced in normal men by the administration of furosemide and maintained by restriction of dietary sodium chloride intake. Negative sodium balance (-112 +/- 16 meq) and reduced plasma volume (2.53 versus 2.93 liters, p less than 0.05) developed. The cumulative chloride deficit of 271 +/- 16 meq was then repleted by oral potassium chloride (267 +/- 19 meq) over 36 hours with continued serial measurements of glomerular filtration rate, effective renal plasma flow, plasma volume, body weight, and plasma renin and aldosterone levels. CDA was corrected, even though body weight, plasma volume, glomerular filtration rate, and renal plasma flow all remained reduced and plasma aldosterone was elevated; urinary bicarbonate excretion increased during correction. Administration of an identical potassium chloride load to similarly sodium-depleted but not chloride-depleted normal subjects produced no change in acid-base status. It is concluded that chloride repletion can correct CDA by a renal mechanism without restoring plasma volume or glomerular filtration rate or by altering sodium avidity.

Adult↗
PubMed1988

Hypertension in cyclosporine-treated renal transplant recipients is sodium dependent.

PURPOSE: Physicians increasingly prescribe cyclosporine as an immunosuppressive agent for both organ-transplant and non-organ-transplant recipients. Investigators have reported a high incidence of drug-induced hypertension even when clinical nephrotoxicity was not present. We wanted to determine the reason. PATIENTS AND METHODS: A comparison was made of hypertension in 15 cyclosporine-treated transplant recipients with that in a similar group of 15 azathioprine-treated transplant recipients. RESULTS: Hypertension in the cyclosporine group responded differently from that seen in the azathioprine group and from previously described forms of post-transplantation hypertension. Hypertensive cyclosporine-treated patients show a sodium acquisitive renal state that responds to sodium restriction. Unlike rat models, which suggest cyclosporine-induced stimulation of the renin-angiotensin system, or previous forms of post-transplant hypertension in humans, plasma renin levels were not elevated and blood pressure did not respond to a test dose of captopril. CONCLUSION: Hypertension in cyclosporine-treated patients is an iatrogenic form of hypertension that may be associated with an early, subtle, renal defect in sodium excretion, a genesis of hypertension that is consistent with Guyton's view of essential hypertension.

Adult↗
PubMed1988

A comparison of OKT3 monoclonal antibody and corticosteroids in the treatment of acute renal allograft rejection.

The monoclonal antibody OKT3 (Ortho Pharmaceutical, Raritan, NJ) was utilized in two separate protocols for treatment of acute renal allograft rejection in patients receiving cyclosporine, azathioprine, and prednisone for maintenance immunosuppression. In Group I, 54 patients received steroids for primary treatment of acute rejection with OKT3 used for resistant rejections and second rejection episodes. In Group II, 34 patients received OKT3 as primary treatment of acute rejection while steroids were used for rescue and second rejection episodes. OKT3 successfully reversed 82% of initial acute rejection episodes in Group II as compared with a 63% reversal with steroids in Group I. Rescue treatment was required in only 15% of Group II patients compared with 33% of Group I patients. Overall patient survival was 96% and 94%, respectively, for steroid primary and OKT3 primary treatments. Allograft survival at 3 months was identical, 74% in both groups. Based on allograft survival data, OKT3 is equally effective either as primary treatment for allograft rejection, or for rescue therapy if initial corticosteroid treatment fails.

Acute Disease↗
PubMed1988

Important risk factors of allograft survival in cadaveric renal transplantation. A study of 426 patients.

Multiple risk factors contribute to the allograft survival of patients who have cadaveric renal transplantation. A retrospective review of 19 such factors in 426 patients identified race, DR match, B + DR match, number of transplants, and preservation time to have a significant influence. The parametric analysis confirmed the effect to be primarily in the early phase, i.e., first 6 months. All patients received cyclosporine with other methods of immunosuppression resulting in an overall 1-year graft survival rate of 66%. The overall 1-year graft survival rate in the white race was 73% and in the black race was 57% (p = 0.002). Allograft survival and DR match showed white recipients with a 1 DR match to have 75% survival at 1 year compared with 57% in the black patient (p = 0.009). If HLA B + DR match was considered, the white recipient allograft survival increased to 76%, 84%, and 88% for 1, 2, and 3 match kidneys by parametric analysis. Patients receiving first grafts had better graft survival (68%) than those undergoing retransplantation (58%) (p = 0.05). Organ preservation less than 12 hours influenced allograft survival with a 78% 1-year survival rate compared with 63% for kidneys with 12-18 hours of preservation. Despite the benefits of B + DR typing, short preservation time, and first transplants to the white recipient, the allograft survival in the black recipient remained uninfluenced by these parameters.

Adolescent↗
PubMed1988

Abnormal captopril renogram with a technetium-99m-labeled hippuran analog.

A case of renovascular hypertension is presented in which the [131I]hippuran renogram was initially normal, but became strikingly abnormal upon administration of the angiotensin converting enzyme (ACE) inhibitor captopril. The patient presented with fibromuscular dysplasia of the renal arteries, which was shown by hippuran renography to be functionally significant on the right side. She became normotensive after angioplasty of the right renal artery. Hypertension recurred a year later, at which time the renogram was normal without captopril, but showed functionally significant left renal artery stenosis with captopril challenge. Both the conventional agent, [131I]hippuran, and an experimental new 99mTc-labeled hippuran analog, [99mTc]MAG3, were used. Angiography confirmed progression of disease on the left side, which was successfully treated by angioplasty. Functionally significant unilateral renal artery stenosis was thus demonstrated first on the right side and then, 1 yr later, on the left side, using hippuran and [99mTc]MAG3. Anatomic progression of disease was documented by angiography.

Adult↗
PubMed1987

Systemic hypertension and the kidney in black patients.

Hypertension occurs more frequently in U.S. blacks than whites and is more severe. Blacks represent a disproportionate percentage of patients receiving dialysis treatment. This disproportion raises the question of whether the renal circulation of blacks is more sensitive to the damaging effects of elevated intraarterial pressure or whether it is structurally different in ways that would render it more prone to damage. The first part of the question has not been conclusively answered although some data support the hypothesis. For the second part, it is clear that malignant nephrosclerosis of blacks is different from that of whites in an absence of fibrinoid necrosis of arterioles and glomeruli and the presence of musculomucoid intimal hyperplasia of small arteries. Whether this is a genetically determined reaction to damage has not been determined. It is a widely held belief that the kidney is the cause of much essential hypertension. In fact 6 cases of essential hypertension in blacks have been "cured" by renal transplantation, strongly supporting the belief. Also blacks differ from whites in 2 ways that could be relevant for their increased prevalence of hypertension: they excrete sodium loads more slowly and have a markedly lower urinary kallikrein. The former could be responsible for the predominance of salt-dependent hypertension in blacks and the latter could reflect a racial deficiency in a naturally occurring vasodilator system.

Adolescent↗
PubMed1987

Importance of chloride for the correction of chronic metabolic alkalosis in the rat.

To determine whether chloride repletion without sodium could correct chronic chloride depletion metabolic alkalosis (CDA) in Sprague-Dawley rats without volume expansion and without increasing glomerular filtration rate (GFR), CDA was generated by peritoneal dialysis (PD) against 0.15 M NaHCO3 and maintained for 7-10 days by a chloride-restricted diet supplemented with sodium and potassium salts. Control animals were dialyzed against Ringer bicarbonate. The maintenance period of chronic CDA, compared with control, was characterized by hypokalemic metabolic alkalosis (serum TCO2 31.9 +/- 0.6 vs. 23.1 +/- 0.5 meq/l, P less than 0.05), volume contraction (plasma volume 3.76 +/- 0.08 vs. 4.19 +/- 0.22 ml/100 g body wt, P less than 0.05), decreased GFR (838 +/- 84 vs. 1045 +/- 45 microliters.min-1.100 g body wt-1, P less than 0.05), increased plasma renin activity (PRA) (63 +/- 13 vs. 12 +/- 3 ng.ml-1.h-1, P less than 0.05), but unchanged plasma aldosterone concentrations (PAC) (4.1 +/- 1.0 vs. 3.4 +/- 1.6 ng/dl, P = NS). Complete correction of chronic CDA was accomplished by 24 h of ingestion of choline chloride drink, and despite negative sodium balance, neutral potassium balance, continued bicarbonate ingestion, and persistent volume contraction (plasma volume 3.76 +/- 0.08 vs. 3.73 +/- 0.12 ml/100 g body wt pre- and postcorrection, P = NS), GFR remained decreased (659 +/- 87 vs. 1,045 +/- 45 microliters.min-1.100 g body wt-1, P less than 0.05), PRA decreased (63 +/- 13 vs. 33 +/- 5 ng.ml-1.h-1, P less than 0.05), but PAC did not change (4.1 +/- 1.0 vs. 6.1 +/- 1.6 ng/dl, P = NS) after correction of CDA.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗
PubMed1987

Effects of chloride and extracellular fluid volume on bicarbonate reabsorption along the nephron in metabolic alkalosis in the rat. Reassessment of the classical hypothesis of the pathogenesis of metabolic alkalosis.

Volume expansion has been considered essential for the correction of chloride-depletion metabolic alkalosis (CDA). To examine the predictions of this hypothesis, rats dialyzed against 0.15 M NaHCO3 to produce CDA and controls, CON, dialyzed against Ringer-HCO3 were infused with either 6% albumin (VE) or 80 mM non-sodium chloride salts (CC) added to 5% dextrose (DX) and studied by micropuncture. CDA was maintained in rats infused with DX. VE expanded plasma volume (25%), maintained glomerular filtration rate (GFR), but did not correct CDA despite increased fractional delivery of total CO2 (tCO2) out of the proximal tubule (36 +/- 2%) as compared with VE/CON (24 +/- 4%; P less than 0.05). In contrast, CC corrected CDA despite volume contraction (-16%) and lower GFR than CC/CON; proximal tCO2 delivery in CC/CDA (29 +/- 4%) did not differ from VE/CDA. CC was associated with an increment in tCO2 excretion. The data strongly suggest that maintenance and correction of CDA are primarily dependent upon total body chloride and its influences on intrarenal mechanisms and not on the demands of sodium or fluid homeostasis.

Absorption↗
PubMed1987

Predictive value of bedside effective renal plasma flow for renal recovery in severe acute renal failure.

Single injection, single blood sample, effective renal plasma flow (ERPF) estimated by 131I-orthoiodohippurate can be performed accurately and conveniently without urine collection at the bedside. The purpose of this study was to determine if ERPF early in the course of severe acute renal failure (ARF) predicts recovery of renal function in hemodynamically stable patients. Over 18 months, ERPF was determined in 33 such patients with ARF in whom an etiologic diagnosis could be established. Eight patients died within 2 months of onset and while on dialysis, did not have an autopsy, and were not considered further. Six patients (Group A) either remained on dialysis after at least 6 months follow-up or had irreversible renal disease at autopsy. In Group B (19 patients, 13 of whom were dialyzed), serum creatinine returned to less than 2.0 mg/dL (n = 16) or was decreasing without dialysis. Peak serum creatinine (Group A 11.2 +/- 1.4; Group B 10.1 +/- 1.3 mg/dL) did not differ between groups. Oliguria was present in 75% of Group A patients and in 25% of Group B patients. Initial ERPFs differed (p less than 0.001) between Group A (90 +/- 11) and Group B (204 +/- 20 mL/min). Initial ERPF was greater than 125 mL/min in 15 Group B patients but in no Group A patients; the false-positive rate was 21% and the false-negative rate was 0%.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1987

Influence of race on renal allograft survival in the pre- and postcyclosporine era.

In conclusion we find that white cadaveric recipients of renal allografts have clearly benefited from the use of CsA. Matching for the major histocompatibility antigens, especially HLA-B + DR, is also associated with improved allograft survival in whites. For black cadaveric recipients there was no significant improvement in allograft survival with the use of CsA nor with matching for HLA. In contrast, for recipients of LRD kidneys both races appear to benefit from the use of CsA over conventional therapy. Consequently, it is clear that with the excellent allograft survival in LRD black recipients that matching can have a significant beneficial effect. However, the differences in survival between the races of cadaveric recipients suggest that for blacks the use of CsA cannot overcome the inherent genetic or physiologic differences that may exist. These results suggest that blacks should be targeted for concentrated study, the benefits of which would be to increase our understanding of potential factors influencing allograft survival in a group that comprises an increasingly larger proportion of candidates on waiting lists throughout the United States. 1. Overall renal allograft survival in CsA-treated black recipients is significantly lower than in comparable white recipients. The major period of allograft loss is in the first 6 months after which the rates of allograft loss for blacks and whites are similar. 2. There was a 12% increase in allograft survival in CsA-treated cadaveric recipients compared to pre-CsA-treated recipients. Allograft survival in white recipients has increased 15% whereas for black recipients there was only a 5% improvement over the azathioprine-prednisone treatment group. 3. Overall, there was a significantly improved graft survival for primary transplants compared to retransplants. Renal allograft survival in black CsA-treated recipients of primary transplants was significantly lower than in comparable whites, whereas there was no significant difference in graft survival between black and white recipients of retransplants. 4. Allograft survival rates in black and white recipients of kidneys from living-related donors were not significantly different from each other in either the non-CsA or the CsA immunotherapy group. 5. Overall there was improved allograft survival with increased matching for HLA-DR or B + DR compared to a zero match in CsA-treated recipients. Significantly, the effect of matching for HLA-DR or B + DR was seen only in white recipients.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗