A comparison of the effects of cyclosporine versus antilymphocyte globulin on delayed graft function in cadaver renal transplant recipients.

There has been concern that cyclosporine's nephrotoxicity increases the incidence of delayed graft function (DGF), prolongs periods of oliguria, and reduces graft survival. In order to further study whether CsA should be used in DGF, we conducted a randomized prospective trial of the effect of CsA versus antilymphocyte globulin on the effects of DGF. Between 12/22/85 and 3/11/88, all patients with DGF after an initial 12-24 hr of CsA were randomized to either daily Minnesota ALG and prednisone or lower-dose CsA (10 mg/kg/day) and prednisone. Resolution of DGF was defined as a lack of dialysis dependency and a 25% fall in the serum creatinine (CR). If DGF was not resolved by 2 weeks, transplant renal biopsies were performed to assess the presence of occult rejection. CsA (10 mg/kg/day) was initiated in the ALG group only after resolution of the DGF. Of the 45 patients who recovered graft function, 19 received ALG and 26 received CsA. CsA significantly prolonged the duration of DGF (ALG 9.74 days, CsA 13.69 days, P = 0.035) but did not result in a prolongation of hospitalization. No difference in CR was found between the two groups at 1 month, 3 months, 6 months, or 12 months. Mean CR at 12 months was 1.98 mg/dl for ALG versus 1.96 mg/dl for CsA. Overall graft survival did not differ in the CsA and ALG groups (P = 0.33). CsA does slightly increase the duration of DGF as compared with ALG but has no effect on one-year serum CR or one-year graft survival. Since there appeared to be no harmful long-term effects of the slight lengthening of DGF, a lower-dose of CsA protocol with biopsy surveillance for occult rejection can be used in patients with DGF.

Surgery in the patient with acute or chronic renal failure.

Medical management of the surgical patient with renal dysfunction revolves primarily around the application of sound medical principles used in the care of all patients. In this article, the unique peculiarities associated with renal failure are stressed. Knowledge of these points is vital in securing a favorable outcome for the patient.

Accelerated atherosclerosis in chronic-dialysis patients--another look.

Actuarial statistics of 53 dialysis patients treated between 1965 and 1976 are reviewed. It is suggested that dialysis did not accelerate atherosclerosis over the observed time period. It appears as though a fundamental change in the dialysis population has occurred and there are too few long-term dialysis patients available to establish whether dialysis does accelerate atherosclerosis.

Rifampicin-induced renal failure.

Renal failure is a rare complication associated with the use of rifampicin for the treatment of tuberculosis, usually occurring well into the course of therapy. The following is a report of 2 cases of rifampicin-induced renal insufficiency. In the first case oligo-anuric renal failure occurred on the thirteenth day of treatment, after the patient had taken only 9 doses of medication. The second case occurred in a patient who developed renal failure while on daily therapy in the hospital. A literature review revealed 83 other reported cases of rifampicin-induced renal insufficiency. Intermittent or interrupted therapy appears to be a significant risk factor for the development of this complication.

A retrospective analysis of the effect of indomethacin on adverse reactions to orthoclone OKT3 in the therapy of acute renal allograft rejection.

Orthoclone OKT3 (Ortho Biotech Inc, Raritan, NJ) is a potent immunosuppressive agent effective in the therapy of acute renal allograft rejection. Following the first one or two doses, patients often exhibit a "flu-like" illness ascribed to OKT3-induced release of cytokines. Systemic reactions resulting from the cytokines include pyrexia, pulmonary edema, bronchospasm, photophobia, headache, hypotension, rigors, hypertension, gastrointestinal disturbances, and arthralgias/myalgias. The cyclooxygenase inhibitor indomethacin has been shown to ameliorate the pyrexia associated with OKT3 administration. We conducted a retrospective analysis with the purposes of (1) confirming that indomethacin reduces pyrexia and (2) determining the effect of indomethacin on the other aforementioned adverse side effects. Group 1 patients (n = 28) received indomethacin during the initial 48 hours of OKT3 antirejection therapy. Group 2 patients (n = 28) received OKT3 without indomethacin. The incidence of fever (P < 0.0001), headache (P < 0.030), and gastrointestinal disturbances (P < 0.030), and the number of adverse effects (P < 0.0001) were significantly less in the indomethacin-treated group. There were no differences between the groups in pre- and post-OKT3 serum creatinine levels. The indomethacin was well tolerated. We conclude that the widely available and relatively inexpensive cyclooxygenase inhibitor indomethacin safely and significantly reduces adverse effects associated with OKT3 therapy of acute renal allograft rejection.

Ranitidine-induced acute interstitial nephritis with epithelial cell foot process fusion.

Although acute interstitial nephritis has been well described with the histamine H2-receptor antagonist cimetidine, we found only one previous case report of ranitidine-induced interstitial nephritis in the literature. We describe an additional patient who developed acute interstitial nephritis after taking ranitidine. Electron microscopy showed focal fusion of the epithelial cell foot processes that was not described in the previous report of ranitidine-induced interstitial nephritis.

Dialysis-induced hypoxemia: membrane dependent and membrane independent causes.

Hypoxemia during hemodialysis may result from several differing processes. We initially studied patients undergoing standard acetate hemodialysis. At 15 minutes of dialysis, leukopenia (primarily neutropenia), a decline of platelet count, and hypoxemia occurred, but without a significant change in mean minute ventilation. Complement activation (V/A ratios of C5a greater than 1.0) persisted throughout dialysis. Leukocyte count returned to baseline by one hour. To separate the effects of solute and/or gas fluxes from those of blood-membrane interaction we studied changes in Po2, WBC, C5a, TxB2, and PGI2 during a period of blood membrane interaction without dialysis, and during subsequent acetate dialysis. Patients were studied with both polyacrylonitrile (PAN) and cuprophan membranes containing different priming solutions during membrane contact alone. Despite leukopenia and complement activation, hypoxemia failed to occur during membrane contact alone. At 15 minutes of subsequent acetate dialysis, significant hypoxemia occurred with both membranes. However, the degree of hypoxemia was twice as great with a cuprophan membrane primed with acetate (18.6 +/- 3.3 mm Hg) compared with air or bicarbonate (9.1 +/- 1.4 and 7.0 +/- 2.0 mm Hg, respectively), or compared with PAN (8 +/- 2.8 mm Hg). Changes in thromboxane B2, PGI2, and C5a did not correlate with changes in Po2. We conclude that there are two major components to dialysis related hypoxemia. One is membrane independent, and may relate to the metabolic effects of acetate or to dialyzer CO2 loss. The remaining portion is membrane dependent, occurring with cuprophan, but not with PAN, and is conditioned by an acetate dependent interaction between blood and membrane.

Elevated plasma histamine in chronic uremia. Effects of ketotifen on pruritus.

A role for histamine in the pathogenesis of uremic pruritus was investigated in maintenance hemodialysis patients. Venous plasma histamine levels, as determined by radioenzymatic assay, were significantly higher (p less than 0.05) in hemodialysis patients with pruritus (368 +/- 103 pg/ml [mean +/- SEM], n = 6) than in those without pruritus (146 +/- 22 pg/ml, n = 5) and in normal controls (142 +/- 16, n = 5). Arteriovenous fistula histamine levels (202 +/- 52 pg/ml, n = 6) were significantly lower (p less than 0.05) than simultaneously drawn venous samples. Markedly elevated histamine-degrading enzyme (histaminase) activities were found in both hemodialysis patients with (2.95 +/- 0.18 pg histamine degraded/minute) and without (2.44 +/- 0.28) pruritus, but was undetectable in normal controls. Histaminase activities did not significantly differ in simultaneously drawn venous and fistula samples. With hemodialysis, histaminase activities fell significantly (p less than 0.01), whereas plasma histamine did not change. We further examined the effects of ketotifen, a putative mast cell stabilizer, on severe uremic pruritus. Five of five patients had significant (p less than 0.01) reductions in pruritus, as judged on a six-point pruritus index, after 8 weeks of drug (x = 2.3), as compared to conventional therapy (x = 5.9). Despite these improvements, no significant differences were noted in pre- versus post-drug plasma histamine levels, histaminase activities, or the histamine content per gram of skin biopsy specimen. These data support prior hypotheses that mast cell activation contributes to the pruritus of uremia.