Leslie S. T. Fang

Efficacy of Single-Dose and Conventional Amoxicillin Therapy in Urinary Tract Infection Localized by the Antibody-Coated Bacteria Technic

Urine specimens from 61 women with symptoms of cystitis who are infected with amoxicillin-sensitive organisms were examined by the antibody-coated bacteria assay. Patients with negative assays were randomized to receive either a single 3-g oral dose of amoxicillin or 10 days of amoxicillin, 250 mg, given by mouth four times per day (conventional therapy). Patients with positive assays received conventional therapy. All 43 patients without antibody-coated bacteria in the urine, 22 given single-dose therapy and 21 treated conventionally, were cured of their infection. Of 18 patients with antibody-coated bacteria, nine relapsed within one week of completion of conventional therapy. The results of the antibody-coated bacteria assay appear to predict the therapeutic response: both single-dose and conventional amoxicillin therapy are completely successful in patients with negative assays; in contrast, conventional therapy is ineffective in 50 per cent of patients with positive assays.

Atheroembolic renal failure after invasive procedures. Natural history based on 52 histologically proven cases

Atheromatous plaque material containing cholesterol crystals may dislodge and cause distal ischemia. To characterize atheroembolic renal failure, we retrospectively evaluated all patients at the Massachusetts General Hospital from 1981 to 1990 with both renal failure and histologically proven atheroembolism after angiography or cardiovascular surgery. Over the 10-year period, 52 patients were identified. They tended to be elderly men with a history of hypertension (81%), coronary artery disease (73%), peripheral vascular disease (69%), and current smoking (50%). Within 30 days of their procedure, only 50% of patients had cutaneous signs of atheroembolism, and 14% had documented blood eosinophilia. Urinalysis was often abnormal. Hemodynamically unstable patients died shortly after their procedure, yet renal function in the remainder continued to decline over 3 to 8 weeks. Patients who received dialysis had a higher baseline serum creatinine than those who did not (168 +/- 44 mumol/L versus 133 +/- 18 mumol/L, p = 0.02), with dialysis starting a median of 29 days after the procedure. Patients with renal failure due to atheroembolism alone, as opposed to multiple renal insults, were more likely to recover renal function (24% versus 3%, p = 0.03) and had a lower risk of death during the 6 months after their procedure (log-rank p = 0.002). Renal failure due to procedure-induced AE is characterized by a decline in renal function over 3 to 8 weeks. This time course is not consistent with most other iatrogenic causes of renal failure, such as radiocontrast or nephrotoxic medications, which present earlier and often resolve within 2 to 3 weeks after appropriate intervention.(ABSTRACT TRUNCATED AT 250 WORDS)

Evolving Use Of Okt3 Monoclonal Antibody For Treatment Of Renal Allograft Rejection

OKT3, a monoclonal antibody reactive with a surface glycoprotein present on all postthymic T cells, was used to treat the initial acute episode of rejection in 30 recipients of cadaveric donor renal allografts. The first 16 patients received 1–5 mg daily for a period of 10–21 days during which the azathioprine and prednisone dosages were sharply reduced. Circulating T cells were eliminated within minutes after the first OKT3 infusion. T cells reactive with OKT3 remained depressed throughout the period of treatment, although a significant number of cells reactive with other T cell subset reagents became detectable after several days of OKT3 treatment. In all instances, the established rejection episode was reversed in 2–8 days without the addition of other immunosuppressive measures. Recurrent rejection occurred in 12 of 16 patients, but with further conventional immunosuppression, 50% of the renal allografts remain functional 20–44 months after transplantation. Fever, chills, and, in some instances, dyspnea following the first dose of OKT3 were the only side-effects observed. Most patients developed antiidiotypic or antimouse immunoglobulin antibodies without apparent clinical sequelae. In the subsequent 14 patients, modifications in the protocol included a steroid bolus prior to the first OKT3 infusion, limitation of therapy to 10 days, resumption of maintenance levels of azathioprine and prednisone prior to discontinuing OKT3, and addition of 3 i.v. doses of cyclophosphamide at the termination of treatment. Respiratory symptoms after the first infusion of the reagent have been eliminated. Antibody responses to OKT3 have been reduced, occurring in 38% as compared with 73% of patients treated previously. Recurrent rejection episodes observed in 8 of 14 patients have been reversible in all but one case. Allograft survival is 86% at 6–17 months posttransplantation. In the entire series of 30 OKT3-treated patients, only 4 grafts (13%) have been lost because of recurrent episodes of rejection.

Renal artery reconstruction for the preservation of renal function

PURPOSE We reviewed a 13-year experience with an emphasis on long-term survival and renal function response when renal artery reconstruction (RAR) was performed primarily for the preservation or restoration of renal function in patients who had atherosclerotic renovascular disease. METHODS From January 1, 1980, to June 30, 1993, 139 patients underwent RAR for renal function salvage and were retrospectively reviewed. Inclusion criteria were either preoperative serum creatinine level > 2.0 mg/dl (67% of patients) or RAR to the entire functioning renal mass irrespective of baseline renal function. Patient survival was calculated by life-table methods. Cox regression analysis was used to determine relative risk (RR) estimates for the late outcomes of continued deterioration of renal function and late survival after RAR. A logistic regression model was used to evaluate variables associated with perioperative complications. RESULTS Clinical characteristics of the cohort were notable for advanced cardiac (history of congestive heart failure, 27%; angina, 22%; previous myocardial infarction, 19%) and renal disease (serum creatinine level < 2.0 mg/dl, 33%; 2.0 mg/dl to 3.0 mg/dl, 40%, > 3.0 mg/dl, 27%). Cardiac disease was the principle cause of early (6 of 11 operative deaths) and late death. Operative management consisted of aortorenal bypass in 47%, extraanatomic bypass in 45%, and endarterectomy in 8%; 45% of patients required combined aortic and RAR. The operative mortality rate was 8%; significant perioperative renal dysfunction occurred in 10%. Major operative morbidity was associated with increasing azotemia (RR = 2.1; p = 0.001; 95% confidence interval [CI], 1.3 to 4.7 for each 1.0 mg/dl increase in baseline creatinine level). Of those patients who had a baseline creatinine level > or = 2.0 mg/dl, 54% had > or = 20% reduction in creatinine level after RAR. Late follow-up data were available for 87% of operative survivors at a mean duration of 4 years (range, 6 weeks to 12.6 years). Actuarial survival at 5 years was 52% +/- 5%. Continued deterioration in renal function occurred in 24% of patients who survived operation, and eventual dialysis was required in 15%. Deterioration of renal function after RAR was associated with increasing levels of preoperative creatinine (RR = 1.6; 95% CI, 1.2 to 1.8; p = 0.001 for each 1.0 mg/dl increment in baseline creatinine level), and inversely related to early postoperative improvement in creatinine level (RR = 0.41; 95% CI, 0.2 to 0.9; p = 0.04). CONCLUSIONS Intervention before major deterioration in renal function and an aggressive posture toward the frequently associated coronary artery disease are necessary to improve long-term results when RAR is performed for renal function salvage.

Time of flight renal MR angiography: Utility in patients with renal insufficiency

We studied the renal arteries prospectively in 16 patients with renal insufficiency using a combination of two-dimensional and three-dimensional time of flight magnetic resonance angiography (MRA). Results were compared with conventional angiography. All renal arteries were identified by MRA. Accuracy for classifying renal arteries into patent, moderately (30-70%) stenotic, severely (> 70%) stenotic, or occluded was 91%. With regard to the presence or absence of severe occlusive disease (> 70% stenosis or occlusion) the sensitivity was 100%, with a specificity of 93%.

Long-term, low-dose cyclosporine treatment of renal allograft recipients. A randomized trial.

Ninety-two adult renal allograft recipients, receiving baseline immunosuppression with CsA and prednisone, were assigned randomly to one of the following regimens. CsA was discontinued (D/C group) in 47 recipients who were then maintained on Aza and prednisone; or Aza was added to continued low-dose CsA and prednisone (triple drug [TD] group) in 45 patients. Entry into the study required an absence of rejection and a stable creatinine for at least four months prior to randomization. The mean month of randomization was 8.34 +/- 2.9 for the D/C group, and 7.2 +/- 3.2 for the TD group. Following randomization, a significantly greater rate of rejection (P less than .01) was observed in the D/C group (40%) than in the TD group (13%). With a mean follow-up of 30 months, 41/47 of D/C allografts (87.2%) and 39/45 TD allografts (86.6%) were functioning. Nevertheless, rejection had a persistent adverse effect on allograft function, in both the D/C and TD groups, up to 36 months following randomization. Parameters such as donor-type and rejection prior to randomization did not identify recipients at risk for rejection following randomization. Therefore, although the CsA withdrawal regimen might be ideal, the opportunity to select appropriate candidates remained elusive. In contrast, the safety of the TD regimen became apparent. Neither significant nephrotoxicity nor hypertension was observed, and the opportunity for less daily prednisone was evident. Despite its additional cost, the TD regimen utilizing indefinite low-dose CsA, is preferred.

Pharmacokinetics of intravenous amdinocillin in healthy subjects and patients with renal insufficiency.

Five healthy volunteers and 31 patients with various degrees of renal impairment received a 10-mg/kg intravenous dose of amdinocillin by infusion over 15 min to establish the disposition profile of the drug in plasma and urine. Both clearance from plasma and elimination rate constant showed a linear relationship with creatinine clearance. It was noted that in subjects with creatinine clearances of greater than 50 ml/min, the elimination half-life remained relatively constant; however, as the creatinine clearance decreased from 50 to 5 ml/min, there was a progressive rise in the elimination half-life. Despite the removal of the drug by hemodialysis (32 to 72% of the dose), concentrations of amdinocillin in plasma remained in the therapeutic range. In patients undergoing peritoneal dialysis, less than 4.0% of the infused dose was removed by dialysis during the hourly exchanges over a 14- to 18-h period. Although the clearance from plasma and the half-life of amdinocillin were altered up to fourfold in patients with creatinine clearances of less than 15 ml/min, the amdinocillin dosage per se may not need to be reduced for these patients if the frequency of dosing is reduced from six to three or four times daily. This is based on drug accumulation estimates of 56% from a regimen of 10 mg/kg every 8 h in these patients as compared with less than 10% from a regimen of 10 mg/kg every 4 h in subjects with normal renal function. In addition, supplemental doses may not be necessary during or at the end of hemodialysis for patients undergoing hemodialysis.

Clinical Management of Urinary Tract Infection

The clinical management of urinary tract infection has changed considerably over the last two decades due to the recognition of several important factors:

Fibrillary/Immunotactoid Glomerulopathy With Cardiac Involvement

A 44-year-old woman with end-stage renal disease due to fibrillary/immunotactoid glomerulopathy presented with progressive symptoms of heart failure. An echocardiogram showed a dilated left ventricle with diffuse hypokinesis. An endomyocardial biopsy revealed patchy fibrosis. Immunofluorescence demonstrated interstitial staining with immunoglobulin G and complement component C3. Electron microscopy (Figure 1) revealed deposition of fibrils with diameters ranging from 8.0 to 12.4 nm that were negative on Congo red staining and …

The selective use of antilymphocyte serum for cyclosporine treated patients with renal allograft dysfunction.

Eighty-seven adult renal allograft recipients were initially treated with cyclosporine-prednisone immunosuppression. Thirty patients experienced no episode of rejection. Antilymphocyte antibody therapy (ALS) was administered to 21 of the 68 recipients of cadaveric donor allografts for either primary allograft dysfunction or acute rejection, and to 6 of 19 recipients of haploidentical, living-related allografts because of steroid-resistant rejection. The cumulative allograft and patient survival for the entire series (follow-up 9-36 months) was 84% and 95%, respectively. This improvement in the rate of successful transplantation can be attributed to the selective addition of ALS therapy to recipients with specific instances of renal allograft dysfunction. In this report, the indications for the use of ALS preparations following prophylactic CsA immunosuppression are reviewed. Experience with the protocols of the ALS administration is also discussed. In selected cases, the administration of either ATG or OKT3 can significantly benefit CsA recipients who experience either primary allograft nonfunction or an epidose of acute rejection.