No change in complication rate using spring-loaded gun compared to traditional percutaneous renal allograft biopsy techniques.

The previous methods to biopsy renal allografts at our institution involved the use of the Franklin-Silverman or Tru-Cut needles. Unfortunately they had a significant rate of post biopsy bleeding secondary to deep penetration when excess force was used to penetrate a tough transplant capsule. Although spring loaded biopsy devices have been widely used for native kidney biopsies over the past three years, the complication rate for renal allograft biopsies has not been sufficiently evaluated. We describe our experience using a disposable spring loaded biopsy device on transplanted renal grafts. Fifty-four biopsies were performed with the device, all under ultrasound guidance. The ASAP automatic biopsy system by Medi-tech was used comprising of a spring loaded gun with a 15 cm long 15 GA needle echogenic tip and 17 mm specimen notch. All patients were ultrasounded immediately post biopsy to look for hematomas. Compared to 55 previous biopsies performed using Tru-Cut needles, we conclude that the ASAP automated biopsy system proved equally effective in obtaining adequate tissue for diagnosis with fewer post-biopsy hematomas compared to traditional biopsy methods.

Late withdrawal of cyclosporine in stable renal transplant recipients.

The use of cyclosporine (CsA) in renal transplantation has been associated with an improvement in 1-year graft survival, but has not changed the rate of late graft loss. We sought to determine whether the intent to withdraw CsA late after renal transplantation affects renal transplant survival and whether there is a racial difference in the effect of CsA withdrawal. This retrospective study included 384 consecutive patients receiving a renal transplant during the 1984 to 1991 period who were treated with CsA/azathioprine/prednisone and who had a functioning allograft 6 months following transplantation. Of these, 97 were electively withdrawn from CsA at a median of 22 months following transplantation. Factors significantly associated with the decision to withdraw CsA included white race, older age, and lower serum creatinine. Acute rejection within 6 months of stopping CsA occurred in 12 patients (12.4%), including nine of 78 (11.5%) white patients and three of 19 (15.8%) black patients. For the group of 287 patients who were not withdrawn from CsA, the 6-year graft survival rate was 59% (95% confidence interval, 52%, 66%). For the group of patients taken off of CsA, the 6-year graft survival rate was 84% (95% confidence interval, 76%, 92%). Cox proportional hazard survival analysis indicated that the intent to discontinue CsA was associated with better graft survival, with a hazard ratio of 0.37 (95% confidence interval, 0.20, 0.70), independent of other variables that may affect graft survival. A separate analysis controlling for waiting time bias also favored the CsA withdrawal group. There was no detectable racial difference in the effect of CsA withdrawal on graft survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical and pathologic features of familial focal segmental glomerulosclerosis.

The occurrence of focal segmental glomerulosclerosis (FSGS) in a familial pattern has been rarely reported previously. Over the last 10 years we have treated 31 patients among eight families with familial FSGS. The diagnosis was confirmed by renal biopsy in 18 cases, and each family had at least two members in whom the diagnosis was confirmed histologically. Both males and females were affected, as were both blacks and whites. The mean age at presentation was 28 years, with a range of 8 to 56 years. The mean serum creatinine at presentation was 3.7 mg/dL. Twenty-five of the 31 patients progressed to end-stage renal disease; and treatment with prednisone did not appear to retard the progression to end-stage renal disease. Seven patients received a cadaveric renal transplant and none of them showed evidence of recurrence of disease in the graft. The pattern of inheritance in two families appeared to be autosomal dominant; in the other families the pattern of inheritance was less clear and may have been autosomal recessive, although a familial exposure to an unidentified environmental toxin cannot be excluded. Histologic examination of the renal tissue revealed a variety of changes previously described as occurring in FSGS. We conclude that FSGS may occur in a familial pattern that carries a poor prognosis. Further studies of these families may shed light on the pathogenesis of sporadic FSGS.

Surgical treatment of primary hyperaldosteronism.

OBJECTIVE: A retrospective review of patients with primary hyperaldosteronism treated at the Duke University Medical Center was performed. SUMMARY BACKGROUND DATA: The management of patients with primary hyperaldosteronism has changed dramatically in the past 20 years. The outcome of surgical treatment was examined to optimize the management of these patients. METHODS: All patients who were evaluated for primary hyperaldosteronism before operation and who had adrenal surgery at Duke University Medical Center from 1970 to 1993 were included in the study. RESULTS: A ratio of plasma aldosterone concentration to plasma renin activity greater than 250 was predictive of hyperaldosteronism in 94% of patients. This ratio also predicted the size of the adenoma. Surgical treatment cured hypokalemia in 90% of the patients. Hypertension was cured or greatly improved, with an average decrease of 50.4 mmHg and 25.2 mmHg for systolic and diastolic pressures, respectively. Patients who had hypertension for less than 5 years achieved a satisfactory blood pressure response more often (13 of 14 patients) than did patients who had hypertension for 5 or more years (15 of 20 patients). CONCLUSIONS: Preoperative evaluation of patients with primary hyperaldosteronism using current modes allows a posterior approach to be used in most patients. Adrenalectomy cures hypokalemia and hypertension; however, patients with a history of hypertension for less than 5 years may be more likely to be cured by adrenal resection.

Coexpression of May-Hegglin anomaly and hereditary nephritis in a family.

In three generations of a family investigation for coexpression of May-Hegglin anomaly and hereditary nephritis was done by routine studies, as well as electron microscopy of renal tissue and blood cells, platelet aggregation studies, audiograms, and ophthalmologic evaluations. The propositus had typical May-Hegglin anomaly and a mild form of hereditary nephritis. One son had May-Hegglin anomaly and possible hereditary nephritis, and one daughter had May-Hegglin anomaly and probable hereditary nephritis. A grandson had May-Hegglin anomaly but no evidence of hereditary nephritis at age 23. The mild form of hereditary nephritis described here was atypical for Alport's syndrome, but together with similar reports, suggests that a combination of May-Hegglin anomaly and mild hereditary nephritis may be a distinct disorder.

Clinical and pathologic features of polyarteritis nodosa and its renal-limited variant: primary crescentic and necrotizing glomerulonephritis.

This study supports the concept that primary necrotizing and crescentic glomerulonephritis is a kidney-limited form of polyarteritis nodosa. Thirty-four patients with necrotizing and crescentic glomerulonephritis were divided into three groups based on the presence or absence of systemic vasculitis as determined by clinical or histologic criteria. Laboratory studies demonstrated elevated erythrocyte sedimentation rates, anemia, mild eosinophilia, hematuria, and proteinuria in patients in each group; there were no significant differences in these data between the groups, however. Complement levels and antinuclear antibody screens were normal. Mean serum creatinine levels were markedly elevated but fell by a factor of two following therapy. There was a higher morbidity in the patients with kidney-limited disease. This was attributable to a higher percentage of these patients' having no symptoms and presenting for medical care only after they were in chronic renal failure. Most patients not experiencing chronic renal failure were treated with cyclophosphamide and prednisone, which seemed effective in this retrospective study.

Juxtaglomerular apparatus tumor: a rare but curable cause of secondary hypertension.

We have reported our experience at Duke University Medical Center with juxtaglomerular apparatus tumor, a rare but remediable cause of significant hypertension. Our three cases illustrate markedly different clinical courses and diagnostic difficulties. Results of the usual diagnostic studies, including intravenous pyelogram and renal angiogram with selective renal vein renin assessment, may be normal, but abdominal CT with contrast can show even small lesions. Thus we propose the addition of CT in evaluating all cases of high-renin hypertension when renal artery stenosis has been excluded. Periodic reevaluation of these patients is mandatory to increase diagnostic accuracy and avoid unnecessary morbidity and mortality. Local resection, rather than total nephrectomy, should be considered because the tumors have low invasive potential.

DIgital intravenous subtraction angiography for investigating renovascular hypertension: comparison with hypertensive urography.

We used digital intravenous subtraction angiography (DSA) to evaluate 105 patients with suspected renovascular hypertension. Unilateral renal artery stenoses were identified in 14 patients, two of whom had previously had contralateral nephrectomy. In addition, one of three renal transplant recipients was found to have stenosis of the nutrient artery. Bilateral renal artery stenosis was demonstrated by DSA in three patients. Of the 88 patients who had concomitant minute sequence (hypertensive) urography (HIVP) delayed excretion suggested a renal artery lesion in only 8 patients. In the group of 88 patients, HIVP was able to detect renal artery stenosis in only 50% (eight of the 16) of patients whose stenosis was detected by DSA. When the patients with a single kidney are excluded, HIVP showed 62% (eight of 13) of the lesions detected by DSA. There were no significant complications in the patients examined by either modality. DSA has replaced HIVP as the screening examination for renovascular causes of hypertension in our institution.

Treating the patient with mild hypertension and renal insufficiency.

The Hypertension Detection and Follow-up Program (HDFP) first demonstrated that treatment of patients with mild hypertension (90 to 104 mm Hg diastolic) could reduce morbidity and mortality in coronary heart disease (CHD). Previous studies had already shown the beneficial effect of blood pressure reduction on renal disease, heart failure, and cerebrovascular disease. When uncontrolled, mild hypertension in the patient with renal disease will lead to further deterioration of renal function. To prevent this and other complications (such as atherosclerosis) of hypertension, whether primary or secondary, one should place these patients on antihypertensive therapy. However, standard stepped-care therapy with diuretic drugs and beta-blocking agents is now under reevaluation in view of the potential adverse effect of these agents on serum lipids and renal function. Beta-blocking drugs, furthermore, tend to increase peripheral resistance, a hemodynamic effect opposite to that desired in these patients. Other drugs, acting centrally or peripherally on the nervous system, also have some undesirable features in addition to troublesome side effects. Prazosin, a vasodilator and effective antihypertensive agent with a different mechanism of action, has no adverse action on lipids and renal function, lowers peripheral resistance, and does not cause many of the side effects that limit use of the other drugs. It therefore appears to be a good choice for initial therapy in mild to moderate hypertension with associated renal insufficiency.

Plasma norepinephrine in the evaluation of baroreceptor function in humans.

The value of plasma norepinephrine measurement in assessing baroreceptor-mediated changes in sympathetic vasomotor activity was studied in seven healthy normotensive volunteers. Blood pressure was decreased by graded steady-state infusions of sodium nitroprusside (25-100 micrograms/min) and increased by infusions of phenylephrine (25-100 micrograms/min) at rates producing a 10% to 20% change in diastolic blood pressure. Sodium nitroprusside produced significant decreases in diastolic blood pressure (p less than 0.01) and calculated mean arterial blood pressure (p less than 0.005), and increases in heart rate (p less than 0.001) and plasma norepinephrine (p less than 0.001). Phenylephrine administration produced increases in systolic (p less than 0.005), diastolic (p less than 0.005), and mean blood pressure (p less than 0.001). Heart rate (p less than 0.001) and plasma norepinephrine (p less than 0.05) fell. The absolute changes in diastolic and mean pressure and heart rate were not significantly different for the two drugs, but were of opposite sign; however, the increase in plasma norepinephrine during hypotension was greater than the decrease during hypertension (p = 0.02). We conclude that plasma norepinephrine changes appropriately in response to altered blood pressure and that the response is greater to a given fall than to a rise in blood pressure, consistent with known changes in sympathetic vasomotor outflow.

Blood pressure response to a single daily dose of a clonidine-chlorthalidone combination.

A single evening dose of a clonidine-chlorthalidone combination (Combipres) was compared with the usual twice-daily schedule in 11 patients with essential hypertension. No significant difference was found between the blood pressures recorded on the two regimens or between morning and afternoon pressures on the once-daily schedule. Only one patient did not maintain adequate blood pressure control. We suggest that some patients with essential hypertension can be adequately treated with a single daily dose of a combination of clonidine and chlorthalidone.

Parathyroid transplantation: fate of a long-term allograft in man.

Previously our group reported clinical, histological, and biochemical evidence of parathyroid allograft survival in a patient transplanted sequentially with renal and parathyroid tissues from the same donor. After 30 months of function, both grafts were concomitantly rrjected. The prolonged parathyroid allograft survival described in certain experimental animals has been attributed to the tissue's being "immunologically privileged." Our current clinical observations do not support this hypothesis.

Regulation of function of transplanted parathyroid glands in man.

The results of studies performed in nine patients who had undergone successful parathyroidectomy and gland transplantation are presented. Transplantation of parathyroid tissue to the forearm, performed for therapeutic reasons, provided a unique opportunity to sample parathyroid gland effluent and to assess secretory function in vivo. The relationship of calcium to immunoreactive parathyroid hormone (iPTH) release was studied during calcium and ethylenediamine tetraacetic acid (EDTA) infusions as well as dialysis against a low calcium bath (low calcium dialysis) in patients with chronic renal failure. Calcium infusions caused an abrupt decrease in hormone release down to a persistent base line within 30 minutes, whereas EDTA infusion caused a sharp increase which peaked between 30 to 60 minutes and returned towards base line despite continuation of the hypocalcemic stimulus. Low calcium dialysis caused an irregular release of hormone which appeared to deplete gland reserves during the period of the stimulus. Ready access to the venous effluent of the transplanted tissue makes this an excellent model for studying parathyroid physiology in man.

Long-term results with forty-five living related renal allograft recipients genotypically identical for HLA.

During the past decade 45 living related renal allografts have been performed between siblings genotypically identical for HLA. In each case all available family members were serotyped and haplotype analysis was performed. Immunosuppressive therapy consisted of standard azathioprine and prednisone regimens. Only one instance of HLA-D incompatibility was documented. HLA-A, -B haplotypes were identical in each case. Histopathological evaluation by light, immunofluorescence, and electron microscopy was completed. Four patients experienced acute cellular rejection with mild long-term impaired renal function. Five patients had acute cellular rejection but subsequently experienced long-term normal renal function. Twenty-three patients had little or no rejection documented and half of these patients are being maintained without steroid therapy. Five patients had histologically proven acute humoral rejection and, of these, three subsequently lost their allografts whereas two regained relatively normal renal function. Recurrent glomerulonephritis was documented in six cases. One was lobular, one crescentic, and one dense-deposit membranoproliferative glomerulonephritis. Three cases of IgA nephropathy were diagnosed. In each case the recurrent glomerulonephritis reflected the same histopathology and clinical course as the disease realized in the host kidneys. Eighty-seven percent of the 40 surviving patients have been rehabilitated completely and are fully employed.