Kurt H. Stenzel

Hypertension is Not Adequately Controlled in Hemodialysis Patients

To examine the adequacy of hypertension control, we monitored the blood pressure (BP) of 53 hemodialysis patients who received treatment for hypertension. BP measurement using an ambulatory BP monitor began 1 hour before dialysis and continued every 30 to 60 minutes for 48 hours until the next dialysis. Diet, medications including antihypertensive drugs, and hemodialysis prescription were not changed during this study. Each patient had a mean of 68 BP measurements during the monitoring period. Mean (+/- SD) systolic and diastolic BP levels of all patients over 48 hours were 158.6 +/- 22.7 mm Hg and 88.7 +/- 16.6 mm Hg, respectively, without diurnal variations. In these, BP loads (the percentage of systolic BP exceeding 150 mm Hg and diastolic BP exceeding 90 mm Hg) were 58.4% and 39.4%, respectively, suggesting that hypertension was inadequately controlled for more than half of the study period. Eight patients (15%) maintained BP within normal ranges at all times. All patients lost weight (2.9 +/- 0.9 kg) at the end of dialysis by ultrafiltration. However, only 27 patients (51%) had a greater than 5% decrease in mean arterial BP post-dialysis, which returned to predialysis levels within 12 to 24 hours. Reduction of BP postdialysis was significantly more common among black patients (72%) than white patients (30%) (P less than 0.01). However, there was no difference in age, cause of kidney disease, amount of ultrafiltration, and BP loads between those whose BP decreased and those whose did not. BP monitoring was repeated in eight patients, 2 to 3 months after adjustment of their antihypertensive regimens.(ABSTRACT TRUNCATED AT 250 WORDS)

Regulation of new DNA synthesis in mammalian cells by cyclosporine : demonstration of a transforming growth factor β-dependent mechanism of inhibition of cell growth

Immunosuppressants such as cyclosporine are considered to constrain cell growth by preventing the production of growth stimulatory cytokines (e.g., interleukin-2). The possibility exists, however, that CsA and other immunosuppressants might restrain cell growth by promoting the production of growth-inhibitory cytokines. We have explored herein the hypothesis that CsA stimulates the production of transforming growth factor-beta (TGF-beta), and restrains new DNA synthesis in mammalian cells via a TGF-beta-dependent mechanism. To investigate this new postulate independently of an IL-2-dependent mechanism, we utilized, as probes, two mammalian cell lines, distinguished by their sensitivity to growth inhibition by TGF-beta and resistance to IL-2: CCL-64 mink lung epithelial cells (CCL-64 cells) and A-549 human adenocarcinoma cells (A-549 cells). Our experimental approach revealed the following: (A) CsA and not cyclosporine H, an inactive analogue of CsA, mediates growth inhibition of TGF-beta-sensitive cells, CCL-64 cells, and A-549 cells; (B) CsA stimulates these mammalian cells to secrete TGF-beta; and (C) TGF-beta induced by CsA is biologically active in inducing cell growth inhibition (demonstrated by the reversal of CsA-associated inhibition with anti-TGF-beta monoclonal antibodies). Our observations suggest that CsA can regulate cell growth via a TGF-beta-dependent mechanism. Since the multifunctional cytokine TGF-beta can enhance extracellular matrix accumulation as well as augment endothelin production, our findings also advance a mechanism that links, via TGF-beta, the beneficial (immunosuppression) and the harmful (fibrosis, hypertension) consequences of CsA usage.

Somatomedin and Growth after Renal Transplantation

Extract: Hormonal and metabolic factors which influence growth were studied in nine growth-retarded uremic children who received renal homografts. Post-transplant growth velocity based on bone age (GVBA) became normal in four (88–103%), accelerated in two (127–139%), and remained subnormal in three (18–50%). Serum somatomedin (SM), was very low in all children before transplant (0.39 ± 0.10 U/ml), but rose in each child after transplantation. Post-transplant somatomedin (0.84 ± 0.14 U/ml) was not significantly different from the somatomedin of eight healthy male control subjects matched for bone age (1.03 ± 0.16). Post-transplant GVBA was directly correlated (P < 0.05) with serum somatomedin and creatinine clearance (Ccr), but was not related to stimulated growth hormone response or to other variables of endocrine function. The data suggested that the growth failure in our patients with severe chronic uremia was due, at least in part, to lack of serum somatomedin. However, in four of five patients with persisting moderate azotemia (Ccr 11.8–42.5 ml/min/1.73 m2), subnormal growth continued despite relatively normalized serum somatomedin activity. Three of the four poorly growing azotemic patients had the highest average steroid dosages in the group (prednisolone > 9.1 mg/m2/24 hr).Speculation: If low serum somatomedin activity develops in the course of end stage renal disease in children, growth retardation may be the consequence. After renal transplantation normalization of serum somatomedin activity may be a necessary although not sufficient condition for the resumption of growth.

Hypercalcemia after renal transplantation

Hypercalcemia and hypophosphatemia after renal transplantation are described. Serum and urine calcium, phosphorus, creatinine and serum levels of parathyroid hormone (PTH) were followed in thirty-four patients who received transplants. Hypophosphatemia occurred in nearly all those with successfull transplants and correlated with the administration of oral hydroxide antacids. Clinical effects of phosphorus depletion included weakness, intention tremor, bone pain, pseudofractures and hypercalcemia. Treatment with oral phosphate reversed the abnormalities. The administration of aluminum phosphate gel did not induce hypophosphatemia. Hypercalcemia of 12 to 15 mg per cent necessitated subtotal parathyroidectomy in five patients, two of whom had oliguria and one polyuria due to hypercalcemia. The roles of parathyroid hyperplasia, phosphorus depletion, vitamin D therapy, steroid therapy and magnesium depletion in the evolution of post-transplant hypercalcemia are discussed.

Ototoxicity Induced by Furosemide

FUROSEMIDE is a diuretic that has achieved wide use because of its great potency as a saluretic agent and its low order of toxicity. We describe here transient ototoxic effects of high-dose furosem...

Effects of ultraviolet irradiation on native and telopeptide-poor collagen

Abstract Effects of ultraviolet light on physical, chemical and immunologic properties of acid-soluble and enzyme (proctase)-treated collagen were studied. Ultraviolet irradiation in air caused an initial increase in viscosity of both collagen preparations, rapidly followed by a loss of viscosity and a loss of negative optical rotation. Ultraviolet irradiation in nitrogen, however, led to a rapid increase in viscosity until a gel formed. With prolonged irradiation, this gel also depolymerized. Enzyme-treated collagen was less sensitive to the effects of ultraviolet irradiation than was acid-soluble collagen. Immunologic reactivity of enzyme-treated collagen was rapidly lost with short exposures to ultraviolet irradiation. Ultraviolet irradiation also inhibited fiber formation. These results suggest that photochemical modifications occur at telopeptide regions or remaining aromatic residues of enzyme-treated collagen during early stages of irradiation. The transition temperature of the melting curve of collagen became broad but there was no loss of negative optical rotation, suggesting that scission of collagen molecules into shorter fragments which retain helical configurations occurred with longer periods of irradiation. Splitting of the polypeptide chain probably occurs between nitrogen and the α-carbon.

Collagen-induced platelet aggregation and release. I effects of side-chain modifications and role of arginyl residues

To investigate the mechanisms governing collagen interaction with blood platelets, the effects of side-chain modifications on collagen-induced platelet aggregation and release of serotonin were studied. Since many chemical modifications alter the ability of collagen to form fibers that, according to current theory, may complicate interpretation of data, we eliminated this possibility by using collagen stabilized in a native-type fibrillar structure by treatment with either glutaraldehyde or ultraviolet irradiation. Acetylation, methylation, succinylation, treatment with 2,4-dinitrofluorobenzene, 2,4,6-trinitrobenzene sulfonic acid or 1,2-cyclohexanedione, and deguanidination with hypobromite were used to modify collagen side-chain reactive groups: amino, carboxyl, hydroxyl and guanidino. Both unmodified monomeric dispersed and fibrillar collagen preparations initiated platelet aggregation and release, although the kinetics and magnitude of the response were different. Monomeric collagen which had been modified by deguanidination, methylation or succinylation, failed to polymerize in physiological conditions and did not induce platelet aggregation and release. However, none of the chemical modifications of stabilized native-type collagen fibers, except treatment with hypobromite or cyclohexanedione, had an effect on collagen-induced platelet aggregation and release. Both hypobromite and cyclohexanedione modified guanidino groups of arginyl residues. Results showed that the ability of a collagen sample to induce platelet aggregation and release of serotonin is dependent on the arginine content of fibrillar collagen. These data demonstrate that manipulation of amino, carboxyl and hydroxyl groups is unimportant as long as the native-type fibrillar structure is maintained, and that arginyl residues are directly involved in collagen-platelet interaction. Moreover, the data suggest that only the arginyl residues in the Y position of the tripeptide unit Gly-X-Y of collagen are responsible.

Pruritus in Dialysis Patients Treated with Parenteral Lidocaine

Pruritus is one of the most disturbing and poorly understood symptoms in patients on chronic hemodialysis,1 2 3 4 its reported prevalence varying from 15 to 86 per cent. Except for a few case repor...

Lupus erythematosus-like disease due to hydrazine

A case of systemic lupus erythematosus-like disease due to occupational exposure to hydrazine is described. The patient had four of the 1982 revised criteria for SLE (malar rash, photosensitivity, antinuclear antibody, and antibody to nDNA) and genetically is a slow acetylator with the HLA DR2,3 phenotype. Many of her healthy family members had antibodies to nuclear constituents. Lymphocytes from the patient and an identical twin sister, but not from three normal control subjects, showed inhibition of pokeweed mitogen-stimulated IgG synthesis after five daily exposures of each subject to hydrazine. Chemicals such as hydrazine in the environment can induce cases of SLE-like disease in predisposed persons.

Urinary calculi in renal transplant recipients

Urinary calculi are an uncommon complication in renal transplant recipients. During a 15-year period, in 544 cases of kidney transplantation with a functioning allograft for more than 3 months, and a long-term follow-up, we have observed 9 cases (1.7%) of urinary calculi. Calculi occurred in 6 male and 3 female patients, 6 patients were recipients of living related and 3 of cadaveric kidneys. Calculi were diagnosed as early as 3 months and as late as 3.5 years after transplantation, but most were detected within the first year. The location of the calculi was the bladder in 4 cases, the transplant in 3, and indeterminant in 2. Crystallographic analysis of retrieved stones revealed calcium oxalate and/or phosphate in 4 cases, triple phosphate in 2, and uric acid in 1. All patients had one or more stone-predisposing factors, such as obstructive uropathy and recurrent urinary tract infection (4 cases), hyperoxaluria (3), or hypercalciuria (2). During long-term follow-up (mean 60 months), only one patient lost the renal graft, 14.5 years after transplantation, primarily from causes unrelated to urinary calculi. One instance of stone recurrence was noted. In conclusion: (1) urinary calculi after renal transplantation are relatively uncommon; (2) predisposing factors and crystallographic composition of the calculi are identical in type, but not frequency, to those of nontransplant patients; and (3) with proper medical and surgical management, post-transplant urolithiasis does not appear to affect graft prognosis.