Warren B. Shapiro

Cinacalcet HCl and Concurrent Low-dose Vitamin D Improves Treatment of Secondary Hyperparathyroidism in Dialysis Patients Compared with Vitamin D Alone: The ACHIEVE Study Results

BACKGROUND AND OBJECTIVES Patients with chronic kidney disease (CKD) receiving dialysis often develop secondary hyperparathyroidism with disturbed calcium and phosphorus metabolism. The National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (KDOQI) was established to guide treatment practices for these disorders. The ACHIEVE study was designed to test two treatment strategies for achieving KDOQI goals. DESIGN, SETTING, PARTICIPANTS, MEASUREMENTS Individuals on hemodialysis treated with vitamin D sterols were enrolled in this 33-week study. Subjects were randomly assigned to treatment with either cinacalcet and low-dose vitamin D (Cinacalcet-D) or flexible vitamin D alone (Flex-D) to achieve KDOQI-recommended bone mineral targets. ACHIEVE included a 6-week screening phase, including vitamin D washout, a 16-week dose-titration phase, and an 11-week assessment phase. RESULTS Of 173 subjects enrolled, 83% of Cinacalcet-D and 67% of Flex-D subjects completed the study. A greater proportion of Cinacalcet-D versus Flex-D subjects had a >30% reduction in parathyroid hormone (PTH) (68% versus 36%, P < 0.001) as well as PTH <300 pg/ml (44% versus 23%, P = 0.006). The proportion of subjects simultaneously achieving targets for intact PTH (150-300 pg/ml) and calcium-phosphorus product (Ca x P) (<55 mg2/dl2) was also greater (21% versus 14%), but this was not statistically significant. This was attributable to 19% of Cinacalcet-D subjects with a PTH value below the KDOQI target range. CONCLUSIONS Achievement of KDOQI targets was difficult, especially with Flex-D. Maintaining calcium and phosphorus target values precluded the use of vitamin D doses necessary to lower PTH to within the narrow target range and highlighted limitations inherent to the KDOQI treatment algorithm.

The Use of Tissue Plasminogen Activator to Declot Arteriovenous Accesses in Hemodialysis Patients

Thrombosis is the most common complication of arteriovenous (A-V) access, resulting in malfunction or total failure. We describe the first use of the thrombolytic agent tissue plasminogen activator (t-PA) to declot the A-V access in 15 hemodialysis patients (14 A-V grafts and one fistula). The t-PA was infused directly into the A-V access in 10-mg doses, at 2-hour intervals, to a maximum of 30 mg. As determined by angiography, t-PA infusion resulted in a dramatic decrease in clot volume in all cases and complete lysis, with return of bruit and thrill, in 10 patients. Eight of the 10 were able to be treated with hemodialysis via the A-V access the following day. In these patients, angiography demonstrated stenosis at the venous end of the A-V access in eight of nine A-V grafts (the one fistula did not have a venous stenosis). Three patients reclotted within 24 hours, and one had bleeding 5 days later after dialysis requiring compression of the A-V access, which resulted in reclotting. Five patients had functioning A-V grafts 1 to 15 months after t-PA treatment (with angioplasty of the venous stenosis required in three of these), and one patient was lost to follow-up. All five patients in whom t-PA infusion was only partially successful had venous stenosis. One patient died before surgery (unrelated to t-PA). Thus, venous stenosis was present in 13 of 15 A-V accesses studied, the highest incidence reported to date.(ABSTRACT TRUNCATED AT 250 WORDS)

The Incidence and Epidemiology of Human Immunodeficiency Virus Infection in 320 Patients Treated in an Inner-City Hemodialysis Center

From January 1, 1986 through June 30, 1989, 320 maintenance hemodialysis patients treated at The Brookdale Hospital Medical Center were tested for the presence of antibody to the human immunodeficiency virus (HIV) using the enzyme-linked immunosorbent assay (ELISA) and Western blot assays. Thirty-nine patients (12%) tested positive for HIV antibody (HIV+) with both the ELISA and Western blot, 24 (62%) of whom were known intravenous drug abusers (IVDA). Of the remaining non-IVDA patients, unanticipated HIV+ results were found in 10 (25%). Thirty-four (87%) of the 39 HIV+ patients were asymptomatic at the start of the study, while two had acquired immunodeficiency syndrome (AIDS) and three others, AIDS-related complex (ARC). Four patients subsequently developed AIDS 20 +/- 4.9 weeks (range, 12 to 32) after testing, three of whom initially had ARC. One patient developed ARC 7 months after testing. Sixteen HIV+ patients died, including five of the six with AIDS, one with ARC, and two others from Mycobacterium tuberculosis. The eight other deaths were from causes unrelated to HIV disease and occurred 12 +/- 2.3 months (range, 1 to 24) after testing. Two HIV+ patients were lost to follow-up. Twenty-one HIV+ patients (54%) are alive and 20 (51%) asymptomatic 15 +/- 2.4 months (range, 1 to 42) after HIV testing. Thus, despite HIV positivity, 28 patients (72%) had an asymptomatic period lasting 14 +/- 1.9 months (range, 1 to 42). Seventy-two of the 281 HIV-negative (HIV-) patients died during the study. None of the HIV- patients manifested ARC or AIDS, confirming that there was no false-negative HIV test.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodynamic effects of peritoneovenous shunts in hemodialysis patients with ascites

Ascites in hemodialysis patients has been reported in association with systemic diseases, such as cirrhosis or congestive heart failure, and as an idiopathic form. Regardless of the etiology, these patients often are refractory to treatment with intradialytic ultrafiltration because of recurrent hypotensive episodes. In this report we describe the hemodynamic effects of peritoneovenous shunts (PVSs) in three hemodialysis patients with ascites refractory to conventional treatment. One patient had idiopathic ascites and the other two had associated liver disease. Patients were monitored for lowest blood pressure, number of intradialytic hypotensive episodes, number of grams of albumin infused to treat hypotensive episodes, interdialytic weight gain, and hemodynamic stability (defined as the difference between the predialysis mean arterial pressure and the lowest intradialytic mean arterial pressure). In all three patients the hemodynamic parameters stabilized after PVS placement despite equal or greater ultrafiltration during dialysis (due to a significant increase in the lowest measured intradialytic blood pressure). The total number of hypotensive episodes decreased from 219 prior to PVS placement to zero after shunt placement. The need for albumin infusion during hemodialysis (for blood pressure support) decreased (significantly in two patients), as did the volume of ascites in all three patients. One patient required PVS replacement secondary to infection, which was the only complication. We believe that refractory ascites in end-stage renal disease patients can be successfully treated by placement of a PVS, which often results in relief of the ascites and significant improvement in intradialytic hemodynamic stability.

Retroperitoneal fibrosis presenting as spontaneously reversible renal failure.

Three patients are reported who presented with severe oliguric renal failure due to retroperitoneal fibrosis and obstructive uropathy in whom spontaneous diuresis and recovery of renal function took place, a course resembling acute tubular necrosis. There were, however, several clinical and laboratory findings that provided clues to the presence of obstructive uropathy. Two of the three patients had low back or abdominal pain. All three patients presented with anemia and significant hyperkalemic, hyperchloremic metabolic acidosis with only a small increase in anion gap and two of the patients had an inappropriately high urine pH. Neither tubular cell casts nor pigmented granular casts were identified in the urine in any of the patients. In all three patients the urine output increased from oliguric levels to 1400 - 2000 ml/day within 1 day associated with rapidly improving renal function. This report demonstrates and reinforces the need to rule out obstruction in all patients with renal failure of unknown etiology and adds retroperitoneal fibrosis to the list of diseases associated with renal failure and spontaneous recovery.