Acute parathyroid hormone response to epinephrine in vivo.

The acute effects of epinephrine, norepinephrine, and isoproterenol on the plasma immunoreactive parathyroid hormone (iPTH) response were studied in 13 550-600 kg cows. Catecholamines were infused for 7.0 min. During epinephrine infusions at 0.08 mumol/min iPTH increased from 0.48+/-0.12 (mean+/-SE, ng/ml) to 1.09+/-0.18 ng/ml (P < 0.02). Small increases in plasma free fatty acids and glucose could be detected with 0.08 mumol/min epinephrine; the iPTH response to epinephrine was as sensitive as the free fatty acid and glucose responses and possibly of physiological importance. Plasma calcium (total and ionized) and magnesium did not change. The responses were more pronounced at 0.8 mumol/min epinephrine with a mean iPTH increase from 0.49+/-0.16 ng/ml to 1.74+/-0.35 ng/ml (P < 0.01). Small decreases in plasma calcium occurred at 0.8 mumol/min epinephrine, but the plasma magnesium remained unchanged. However, when the plasma calcium was lowered with ethylene glycol bis(beta-aminoethyl ether)-N, N'-tetraacetic acid (EGTA), a much more pronounced lowering of the plasma calcium was required to produce comparable increases of the plasma iPTH concentrations than when epinephrine was infused. It appears that epinephrine has a direct effect on the release of iPTH from the parathyroid glands. Simultaneous infusions of calcium and epinephrine suppressed the stimulation by epinephrine. This points towards a common mechanism of the regulation of parathyroid hormone secretion caused by decreases in the extracellular calcium concentration and/or alterations in the distribution of calcium within parathyroid cells following the administration of epinephrine. The iPTH response to epinephrine was suppressed in the presence of propranolol. Isoproterenol was less active in raising iPTH than epinephrine, and norepinephrine was the least active. The stimulation by isoproterenol and the suppression by propranolol suggest beta adrenergic receptor sites within the parathyroid glands.

Human parathyroid hormone. Immunological characterization of antibodies against a glandular extract and the synthetic amino-terminal fragments 1-12 and 1-34 and their use in the determination of immunoreactive hormone in human sera.

Antibodies to a urea-trichloroacetic acid extract [hPTH-(TCA)] of human parathyroid tumors and to the synthetic NH(2)-terminal fragments of human parathyroid hormone hPTH-(1-12) and -(1-34) were developed in goats to characterize immunochemically various PTH preparations and to estimate immunoreactive PTH (iPTH) in human sera. They were quantitated on the basis of their capacity to bind [(131)I]-hPTH-(1-12), [(131)I]hPTH-(1-34) or [(131)I]bovine PTH (bPTH-(1-84)). The quality of the antibodies was assessed by reference to inhibition of their interaction with labeled peptides by synthetic hPTH comprising 34 NH(2)-terminal amino acid residues or fragments thereof [hPTH-(1-12), -(13-34), -(18-34), -(25-34), -(18-24)] or by the Sephadex G-100-purified full-length peptide hPTH-(1-84) [hPTH-(1-84)G-100]. The synthetic peptides used in this work correspond in their structure to the NH(2)-terminal amino acid sequence 1-34, as elucidated by Brewer and collaborators (1972. Proc. Natl. Acad. Sci. U. S. A.69: 3583-3588). Inhibition studies were also carried out with bPTH-(1-34) and bPTH-(1-84). Anti-hPTH-(TCA) exhibited specificities directed to determinants in the COOH-terminal and NH(2)-terminal part of hPTH-(1-84) and exhibited cross-reactivity with bPTH-(1-84). Anti-hPTH-(1-34), on the other hand, showed immunological specificities mainly directed to antigenic determinants located in the COOH-terminal half of hPTH-(1-34). In addition, some reactivity with the NH(2)-terminal hPTH-(1-12) and with the extractive full-length peptides of human and bovine origin was observed. Antibodies to hPTH-(1-12) cross-reacted with hPTH-(1-34) and -(1-84)G-100.IPTH WAS RADIOIMMUNOLOGICALLY DETERMINED IN HUMAN SERA BY THE FOLLOWING SYSTEMS: (a) [(131)I]bPTH-(1-84), anti-hPTH-(TCA) and hPTH-(1-84)G-100 as standard; (b) [(131)I]hPTH-(1-34), anti-hPTH-(1-34) and hPTH-(1-34) as standard. With system (a), COOH-terminal fragments of hPTH-(1-84) having a molecular weight of approximately 7,000 were detected, and there was an almost total discrimination of serum iPTH levels in normal and in hyperparathyroid subjects. With system (b), on the other hand, several molecular species of iPTH were detected, including a component larger than hPTH-(1-84) and others similar to hPTH-(1-84) and to a fragment co-eluting with the NH(2)-terminal fragment hPTH-(1-34). When serum iPTH was assayed in system (b), there was a large overlap of iPTH levels in control subjects and in patients with primary hyperparathyroidism.

Parathyroid hormone responses to catecholamines and to changes of extracellular calcium in cows.

Modifications of the plasma level of immunoreactive parathyroid hormone (PTH) in cattle were induced by changes of the plasma concentrations of epinephrine, isoproterenol, or calcium. During abrupt hypocalcemia, PTH, obtained by infusions with ethylene glycol-bis (beta-aminoethylether) N, N'-tetraacetate (EGTA), increased during the first 4-8 min. After a transient decline, the hormone levels rose again and remained elevated. Infusions of calcium suppressed the hypocalcemia-induced augmentation of PTH levels within a few minutes. Prolonged epinephrine (and isoproterenol) infusions also rapidly increased PTH levels, however, in this case, they returned to basal concentrations after 50-60 min. Additional epinephrine infusions could not further raise PTH values. Moreover, three short-lasting infusions of epinephrine (7 min each), given at 30-min intervals, increased PTH levels to the same extent, whereas additional infusions were much less effective. The PTH response to epinephrine was completely restored, when the interval after a prolonged epinephrine infusion had been prolonged to > 100 min. During moderate hypocalcemia, occurring at the end of EGTA infusions and lasting for 90 min, the PTH response to a short-lasting epinephrine infusion (7 min) was more pronounced than in normocalcemic animals. During severe hypocalcemia, in which superimposed short-lasting infusions of EGTA (7 min) led to an additional abrupt fall of plasma calcium concentrations but not to a corresponding additional rise of the PTH levels, epinephrine rapidly and further increased PTH concentrations. On the other hand, at the end of prolonged infusions of epinephrine, when additional infusions of epinephrine were ineffective in raising PTH levels, EGTA-induced hypocalcemia consistently increased PTH concentrations. The EGTA-induced augmentation of PTH levels was enhanced by epinephrine and isoproterenol but not by propranolol. The present findings indicate, that variations of the extracellular calcium concentrations and beta-adrenergic agonists modify PTH levels by two different and independent mechanisms. On the other hand, it appears that the magnitude of change of the PTH levels to either stimulus is partially modulated by exposure to the other.

Pneumocystis carinii pneumonia during immunosuppressive therapy for antineutrophil cytoplasmic autoantibody-positive vasculitis.

We describe two human immunodeficiency virus-negative patients who developed Pneumocystis carinii pneumonia (PCP) during immunosuppressive therapy for antineutrophil cytoplasmic autoantibody-positive vasculitis and review the literature regarding the pathogenesis and frequency of PCP. The recent application of DNA amplification techniques suggests that PCP developing in immunocompromised individuals does not necessarily result from reactivation of a dormant focus, but may arise as de novo infection after exposure to an exogenous source of P carinii. In addition, several reports about clusters of PCP cases raise concern about the risk of a nosocomial transmission of P carinii. Therefore, PCP should be added to the list of bronchopulmonary complications in patients with antineutrophil cytoplasmic autoantibody-positive vasculitis who are receiving long-term steroid therapy.

Rapidity of plasma 1,25-dihydroxyvitamin D responses to hypo- and hypercalcemia in steers.

Experiments were designed to study the rapidity of changes in plasma 1,25-dihydroxyvitamin D [1,25-(OH)2D] levels in response to hypercalcemia and hypocalcemia induced by 10-h infusions of CaCl2 or EGTA in steers. In response to CaCl2 infusions, 1,25-(OH)2D was decreased within 4 h (P less than 0.05) and remained lower (P less than 0.05) than preinfusion concentrations for up to 14 h after termination of the infusions. PTH and inorganic phosphate (Pin) transiently decreased in response to the CaCl2 infusions, whereas total magnesium (Mg) continuously fell for up to 24 h after the start of the infusions. In response to infusions with EGTA, on the other hand, 1,25-(OH)2D continuously increased and was raised significantly (P less than 0.05) between 12 and 24 h after the start of the infusions. PTH increased within 2 h (P less than 0.05) and remained elevated (P less than 0.05) for up to 2 h after the end of the EGTA infusions, whereas Pin and Mg were not significantly changed. During and after 10-h control infusions of sodium chloride, the levels of 1,25-(OH)2D, PTH, Ca, Ca++, Pin, and Mg remained unaltered. In conclusion, plasma levels of 1,25-(OH)2D were lowered in response to hypercalcemia within 4 h and increased in response to hypocalcemia within 12 h. After termination of the infusions with CaCl2 or EGTA, levels of 1,25-(OH)2D remained decreased or elevated for at least 14 h, even though Ca, Ca++, and PTH levels were normalized. The slow changes in 1,25-(OH)2D contrast with the rapid responses of PTH to hyper- and hypocalcemia.

Relation of cyclosporine blood levels to adverse effects on lipoproteins.

Hyperlipidemia is common in renal allograft recipients. To elucidate the role of cyclosporine in posttransplant hyperlipidemia, we measured lipids, lipoprotein lipids, and apolipoproteins of thirty-five renal allograft recipients and evaluated their relation to trough cyclosporine blood levels. All patients were on a triple immunosuppressive regimen with equal doses of prednisone and azathioprine, and had stable graft function. Cyclosporine blood levels were significantly correlated to total plasma cholesterol (P = 0.028), low-density lipoprotein cholesterol (P = 0.022), apolipoprotein B (P = 0.017), and the cholesterol/high-density lipoprotein cholesterol ratio (P < 0.002), but not to plasma triglycerides. Significant inverse correlations were found between cyclosporine blood levels and high-density lipoprotein cholesterol (P = 0.034), high-density lipoprotein3 cholesterol (P = 0.025), and apolipoprotein A-1 (P = 0.047), but not high-density lipoprotein2 cholesterol. The independent relation of cyclosporine blood levels to each of the measured lipid parameters was investigated by a stepwise regression model including age, body mass index, interval from transplantation, diabetes mellitus, plasma creatinine, and intake of diuretics and beta-blockers. After correction for these 7 variables, cyclosporine blood levels remained significantly associated with high-density lipoprotein cholesterol, high-density lipoprotein3 cholesterol, apolipoprotein A-1, apolipoprotein B, low-density lipoprotein cholesterol, and the cholesterol/high-density lipoprotein cholesterol ratio. These data suggest that cyclosporine causes atherogenic dyslipidemia.

Immunogenicity of a hepatitis B subunit vaccine in hemodialysis and in renal transplant recipients.

A hepatitis B subunit vaccine was given to 59 medical staff members, 106 hemodialysis patients and 28 renal allograft recipients. The vaccine consisted of formalin-inactivated hepatitis Bsurface antigen (HBsAg) and was given in 3 doses (times 0, 1 and 6 months) of 20-40 micrograms. Some of the vaccinees received anti-HBs antibodies together with the first vaccine dose (active/passive vaccination). One month after the last infection, 93% of the medical staff members who had received active/passive immunisation and 97% of those who had received active immunisation had detectable anti-HBs antibodies with mean titers ranging from 1:512 to 1:1024. In the group of hemodialysis patients antibodies were detectable in 63-65% of the individuals who had received active or passive/active immunisation in mean titers between 1:32 and 1:64. Finally, only 32% of the renal allograft patients developed measurable anti-HBs antibodies, the titers of responders being still lower than in the hemodialysis patients. Side effects occurred following 10% of all vaccine injections and were always mild in nature. Within the 12 months observation period period following the first vaccination, 3 HBV events occurred in the 193 individuals: One aclinical case detected by a transient seroconversion against the hepatitis B core antigen, one anicteric and one icteric hepatitis case. The data illustrate the difficulties for active immunisation against hepatitis B of hemodialysis patients or of renal transplant recipients.

Irreversibility of cyclosporine-induced renal function impairment in heart transplant recipients.

The use of cyclosporine therapy for heart transplant recipients has been associated with a significant improvement of graft survival. Renal function impairment is a frequent finding in patients chronically treated with cyclosporine. The purpose of this prospective randomized study was to establish renal function in a group of heart transplant recipients receiving chronic cyclosporine treatment and to test the hypothesis of reversibility of cyclosporine-induced nephropathy by late reduction of cyclosporine. A total of 28 patients who underwent operation at least 18 months before this study began were randomly assigned to either group A (n = 14), in which the whole-blood polyclonal cyclosporine target trough level was reduced from 400 to 600 micrograms/L to 200 to 400 micrograms/L, and group B (n = 14), in which the level was maintained at 400 to 600 micrograms/L. Renal and cardiac function were assessed by paraaminohippuric acid, inulin and lithium clearances and heart catheterization, respectively, at entry and 4 months later. Cellular rejection in the transplanted heart was monitored by at least four endomyocardial biopsies every 14 days with the histologic Texas scale (grading: 0 to 10). In heart recipients renal blood flow (592 +/- 202 ml/min/1.73 m2) and glomerular-filtration rate (74 +/- 33 ml/min/1.73 m2) were significantly lower (p < 0.01), and mean arterial blood pressure (109 +/- 13 mm Hg) and renal vascular resistance (22.4 +/- 9 mm Hg/dl/min/1.73 m2) were significantly higher than the corresponding values in normal controls (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Recurrent and de novo membranous glomerulonephritis in renal cadaver allotransplants.

Significant glomerular changes occur in a substantial number of renal cadaver allotransplants. Transplant glomerulopathy and recurrent glomerulonephritis account for most of the lesions whereas the development of de novo glomerulonephritis is a rare event. Only a few cases of membranous glomerulonephritis in the graft have been documented. The four patients presented all developed heavy proteinuria of 11.5 to 14 g/day 5 months to 1 year after transplantation. Three cases of de novo membranous glomerulonephritis were transplanted because of renal failure due to chronic pyelonephritis, chronic glomerulonephritis and medullary sponge kidney. One patient has recurrent membranous glomerulonephritis. Transplant biopsy revealed only minimal glomerular changes by light microscopy in all cases. Immunofluorescence and electron microscopy demonstrated typical membranous glomerulonephritis.

Differential use of cardiac troponin T versus I in hemodialysis patients.

BACKGROUND: Cardiac troponin T (cTnT) is frequently elevated in asymptomatic hemodialysis (HD) patients and predicts increased cardiovascular morbidity and mortality. Compared to cTnT, cardiac troponin I (cTnI) has a shorter half-life. How this influences its diagnostic reliability in chronic HD patients is only partially known. PATIENTS AND METHODS: First, in a cross-sectional study cardiac troponins were measured in 31 asymptomatic HD patients. A third-generation cTnT assay was used. The rate of false positive tests and the intraindividual variability were determined. Second, in a retrospective analysis over 12 months all acute events with clinical suspicion for acute coronary syndrome (ACS) were analysed in the same patients to determine the diagnostic power of cTnT by receiver-operating curve (ROC) plot. RESULTS: Cross-sectional study: 9 of 52 (17%) cTnT and 0/52 cTnI (0%) tests were positive in asymptomatic HD patients with a low intraindividual variability. Retrospective analysis: 16 acute clinical events with determination of cTnT were recorded, and in 4/16 an ACS was diagnosed. Using a cut-off level of 0.1 microg/l, the cTnT test reached a sensitivity of 100%, a specificity of 42%, a positive predicitive value of 36% and a negative predictive value of 100%, using a cut-off level of 0.2 microg/l the corresponding values were 75%, 58%, 38% and 88%. CONCLUSIONS: Cardiac TnT, but only rarely cTnI, is elevated in a significant number of asymptomatic HD patients. For diagnosis of ACS in HD patients, a combination of cTnT and cTnI may be used, since the former has higher sensitivity and the latter higher specificity. A higher threshold value for cTnT in HD patients could further increase its diagnostic accuracy.

Renal pathology and premortem clinical presentation of Caucasian patients with AIDS: an autopsy study from the era prior to antiretroviral therapy.

PRINCIPLES: Renal disease in patients with HIV infection is becoming increasingly frequent. A particular form of HIV-associated nephropathy (HIVAN) has been found in patients of predominantly African-American and Hispanic origin. However, only limited data are available on renal pathology and premortem clinical presentation of kidney disease in Caucasian patients with AIDS. METHODS: To determine the prevalence, clinical presentation and aetiology of renal disease in Caucasian patients with AIDS at the time of death we have performed a prospective autopsy study with 239 patients who died of AIDS between 1981 and 1989. None of these patients had received HIV-specific antiretroviral therapy. Autopsies and histological analyses were performed on the basis of a standardised protocol. Clinical and laboratory data were gathered according to a uniform questionnaire. RESULTS: 95% of patients were of Caucasian race. 75% of all patients had extended AIDS (stage IV). Clinical signs of nephropathy prior to death were found in 36% of patients, including proteinuria (18%), abnormal urinary sediment (19.5%), and renal insufficiency (11%). Histopathological lesions were present in 43% of the autopsies, with two or more distinct structural lesions in 12.5% of patients. Of the pathological findings 28% were glomerular or vascular, 33% were non-glomerular, and 29% were combined lesions. The remaining 10% were renal infiltrations of infectious agents or neoplastic tissue. The most common findings were ischaemic changes and vascular scars (18% of patients), as well as pyelo- and interstitial nephritides (12.2%). Importantly, FSGS was present in only 1.7% of patients, and only a single African patient had classical HIVAN. CONCLUSIONS: Renal involvement in HIV disease is very common at the time of death among patients of Caucasian origin. However, classical HIV-associated nephropathy is absent in this population. These findings suggest that kidney disease affects all races and supports the hypothesis that HIVAN is specifically related to non-Caucasian ethnicity. The results reflect renal disease unaffected by HIV-specific antiretroviral therapy.

[Sonography in the evaluation of reduced function of kidney transplants (author's transl)]. / Die Sonographie bei Funktionseinschränkung von Nierentransplantaten.

Sonography of 58 kidney transplants has been performed in 56 patients and morphological alterations have been registrated. These results have been compared with clinical examination, blood samples and histological evaluation whenever possible. It is our opinion that certain sonographical phenomena exist, which make the rejection of kidney transplants most probable and even allow for differentiation of different degrees. We found a correlation of right results between sonography and final pathological diagnosis in more than 80% of our patients. Moreover sonography permits the diagnosis of ureteral obstruction or leakage.

Is heparin therapy necessary in CAPD peritonitis?

OBJECTIVE: Heparin therapy in continuous ambulatory peritoneal dialysis (CAPD) peritonitis seems well established; it is costly due to the necessity of hospitalization. There are no clinical studies that show a benefit of such a treatment. The aim of this study was to investigate whether heparin therapy in CAPD peritonitis is necessary. DESIGN AND PATIENTS: 194 samples of peritoneal dialysates were collected from 17 patients over a period of 24 months. Samples were subdivided into three groups: those without peritonitis (< 100 leukocytes/microL), those with mild peritonitis (100-499 leukocytes/microL), and those with severe peritonitis (> or = 500 leukocytes/microL). MEASUREMENTS: The number of leukocytes per microL dialysate and total protein concentrations were determined. Furthermore, dialysate concentrations of thrombin-antithrombin III- (TAT-) complexes (indicator of thrombin formation), D-dimers (indicator of fibrinolysis), and plasminogen activator inhibitor 1 (PAI-1) were measured. RESULTS: The dialysate protein concentration progressively increased from no peritonitis to mild and severe inflammation. In parallel, dialysate TAT-complex and D-dimer concentrations increased. Thrombin-antithrombin III-complex and D-dimer concentrations correlated strongly in 179 cases (r = 0.76; 62 samples showing peritonitis, 117 samples with no evidence of peritonitis). In the remaining 15 samples of 3 patients, high PAI-1 levels (> 40 ng/mL) and low D-dimer concentrations were found. Eleven of the 15 samples showed evidence of peritonitis. In these 11 samples with evidence of peritonitis, high levels of TAT-complexes were detected, while D-dimer concentrations were found to be very low, pointing to a blocked fibrinolysis. The PAI-1 levels were not related to leukocyte counts or protein concentrations in the dialysates. CONCLUSIONS: Based on our findings, the routine intraperitoneal administration of heparin in CAPD peritonitis is not necessary. In rare cases an imbalance between coagulation and fibrinolysis due to high PAI-1 levels exists (15 of 194 dialysate samples, 11 of the 15 samples showing peritonitis). These cases--which do require heparinization--can be identified by demonstrating low D-dimer levels in CAPD dialysate at times of peritonitis.

[Lymphocele following renal transplantation]. / Lymphocelen nach Nierentransplantation

Lymphoceles as seen after renal transplantation are cystic swellings filled with lymph, situated beneath the lower end of the transplant on the iliac vessels. It seems that the lymph originates from lymphatics cut during operation. 5 such cases have been seen in our series of 268 renal allotransplantations. Symptoms arose 1 to 6 months after transplantation. According to our own experience and to 39 cases of the literature, deterioration of renal function because of compression of the ureter is the most common symptom. Therefore, intravenous pyelography is the main diagnostic means. Some cysts can be visualized by lymphangiography. Marsupialisation to the peritoneal cavity is the treatment of choice.

[Urinary infection and vesicorenal reflux after renal transplant (author's transl)]. / Harnwegsinfekt und vesiko-renaler reflux nach nierentransplantation.

Worldwide experience shows that a urinary infection can endanger a renal transplant. Our experience with vesicorenal reflux and its possible complications led gave us to check randomly selected patients with renal transplant. In 3 out of 4 patients with chronic or relapsing infections, reflux was found. Four out of 23 patients with no reflux had a chronic urinary infection. In our opinion a ureter implantat with antireflux mechanism in the bladder should be given closest attention.

[Does the primary disease recur in kidney transplantation?]. / Rekurriert die Grundkrankheit im Nierentransplantat?

Improved graft survival is accompanied by complications which interfere with the long-term function of the allograft. Recurrence of the primary renal disease in the graft is well recognized and is found in 10 to 20% of all recipients; however, graft loss due to recurrent disease is reported in less than 5% of all cases. The most frequent cause of recurrence is glomerulonephritis: Membrano-proliferative GN type II, IgA nephritis and focal sclerosis are frequently observed. Among metabolic disorders linked to graft disease, diabetic nephropathy has to be mentioned first. Primary oxalosis is a rare disorder, but it is related to a very high risk of recurrent disease in the transplant. Combined kidney-liver transplantation seems to offer a valuable alternative for these patients. The high risk of recurrence of certain diseases, i.e. membrano-proliferative GN type II, focal-segmental glomerulosclerosis, primary oxalosis, should prevent living donation. In addition, there are some reports suggesting that living-related donation might increase the recurrence rate of hemolytic-uremic syndrome, membranous GN and Schönlein-Henoch purpura. Recurrent disease might not only affect the outcome of the transplant, but can provide insight into the nature and pathogenesis of the primary disease. Currently there are no conclusive reports indicating that chronic immunosuppression, especially cyclosporin-A treatment, reduces recurrence rates; however the clinical course might be ameliorated.

[Kidney replacement therapy 1993]. / Nierenersatztherapie 1993.

The continuous rise in the number of patients treated for chronic renal failure is due to improved technique, demand for treatment and an increased incidence of certain renal diseases in the elderly. Preventive measures and a discussion of socio-ethical problems are needed.