Robert L. Madden

Trough serum vancomycin levels predict the relapse of gram-positive peritonitis in peritoneal dialysis patients.

We reviewed 31 episodes of gram-positive peritonitis that occurred in our peritoneal dialysis population between 1990 and 1993 in an attempt to identify the risk factor(s) for peritonitis relapse. All patients were treated with 4 weekly doses of intravenous vancomycin. Vancomycin doses no. 1 and 2 were based on body weight (15 mg/kg with a 1-g minimum); vancomycin doses no. 3 and 4 were adjusted in an attempt to maintain the trough serum vancomycin level at greater than 12 mg/L. Nine peritonitis episodes complicated by a relapse were identified. Peritonitis episodes preceding a relapse were similar to relapse-free episodes with respect to patient age, diabetes, peritoneal dialysis modality, duration of peritoneal dialysis treatment, residual urea clearance, peritoneal fluid cell count, causative organism, and weekly vancomycin dose. However, cumulative 4-week mean trough vancomycin levels were consistently lower during peritonitis episodes preceding a relapse (7.8 +/- 0.6 mg/L during relapse-prone episodes v 13.7 +/- 0.9 mg/L during relapse-free episodes; P = 0.0004). Furthermore, relapses developed during nine of 14 peritonitis episodes demonstrating a 4-week mean trough vancomycin level less than 12 mg/L compared with zero of 17 episodes with a 4-week trough level greater than 12 mg/L (P < 0.05). The detection of a low initial 7-day trough vancomycin level also was a useful marker for subsequent peritonitis relapse. In 13 peritonitis episodes associated with an initial trough level less than 9 mg/L, nine were complicated by a relapse.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine phosphoribosyltransferase deficiency and renal allograft dysfunction

Adenine phosphoribosyltransferase (APRT) deficiency is a rarely diagnosed cause of renal allograft dysfunction. We report the case of a 42-year-old man who presented in 1996 with idiopathic renal failure. Native kidney biopsy showed extensive microcrystalline interstitial nephritis. The patient subsequently underwent a living-related kidney transplant with excellent early graft function. During the next year, however, he had worsening allograft function, and allograft biopsy showed recurrent interstitial nephritis. Further chemical and spectroscopic analysis showed this lesion to be an annular microcrystalline nephritis consistent with APRT deficiency. This diagnosis was confirmed on erythrocyte assay. Treatment with allopurinol and a low-purine diet led to improvement and stabilization of renal function. APRT is a rare cause of renal allograft dysfunction requiring a high index of suspicion for early diagnosis and treatment. Increased physician awareness in the United States may hasten diagnosis and limit the morbidity associated with this disease.

Effect of a short course of rapamycin, cyclosporin A, and donor-specific transfusion on rat cardiac allograft survival

The interactions of rapamycin (Rapa), CsA, and donor-specific transfusion (DST) were examined in an ACI to Lewis rat heterotopic cardiac allograft model. Survival data were truncated at 175 days for the purpose of statistical comparisons. Vehicle (Veh)-treated animals rejected at a mean of 7.3 +/- 0.2 days. Treatment with a DST on the day before transplantation (d-1) resulted in a decreased survival of 5.5 +/- 0.3 days (P < 0.05). An 8-day course of low-dose CsA (d-1 to d6) in Veh-treated animals prolonged allograft survival to 10.3 +/- 0.5 days (P < 0.05). The addition of a DST d-1 to the Veh/CsA-treated animals resulted in a synergistic prolongation of survival to 45.7 +/- 12.5 days (P < 0.05). Rapa proved to be a potent immunosuppressive agent in this model, with an 8-day course of Rapa (d-1 to d6) at 0.5 mg/kg/day (R1) or 1.5 mg/kg/day (R2), resulting in mean allograft survivals of 24.2 +/- 5.0 and 67.3 +/- 20.9 days, respectively (P < 0.05 vs. Veh or Veh/CsA). Rapa demonstrated synergy with CsA by further prolonging allograft survival to 115.9 +/- 27.9 days (R1/CsA, P < 0.05 vs. Veh/CsA, R1) and 164.6 +/- 10.4 days (R2/CsA, P < 0.05 vs. Veh/CsA). The extended graft survival using a combination of Rapa and DST, compared to Rapa alone, did not prove to be statistically significant. When all three treatments were combined (Rapa/DST/CsA), no significant benefit to survival was seen over Veh/DST/CsA (45.7 +/- 12.5 days vs. R1/DST/CsA, 81.9 +/- 18.4 days; R2/DST/CsA, 98.5 +/- 21.3 days; P > 0.05). If Rapa was withheld until postoperative day 1 (Rapa, 1.5 mg/kg/day on d1 to d6/DST/CsA), enhancement of the DST/CsA effect was seen with a mean survival of 170.2 +/- 4.8 days (P < 0.05). This suggests that the timing of Rapa administration may significantly impact its interaction with DST/CsA treatment and merits further investigation.

Pancreatitis and duodenitis from sarcoidosis: successful therapy with mycophenolate mofetil.

Sarcoidosis is a chronic granulomatous inflammatory disease that may affect extrapulmonary organs including the kidneys and the gastrointestinal tract (1). The most common renal complication from sarcoidosis is hypercalciuria, which may induce nephrocalcinosis and/or nephrolithiasis (2). Chronic interstitial nephritis with noncaseating granulomas in the renal interstitium may cause mild to end-stage chronic renal failure (2). In addition, glomerular lesions have been reported, including membranous nephropathy, membranoproliferative glomerulonephritis, IgA nephropathy, focal glomerulosclerosis, and rarely, crescentic gomerulonephritis (2). Therapy for glomerular diseases associated with sarcoidosis is anecdotal, and there are no data showing successful, longterm therapy for sarcoidosis associated with crescentic glomerulonephritis. The most common gastrointestinal manifestation of sarcoidosis is acute or chronic hepatitis, but disseminated gastrointestinal sarcoidosis, especially in the small intestine and pancreas, can cause considerable morbidity (1, 3–7). Glucocorticoids and/or surgery are often utilized as therapy, but the long-term outcome of patients with intestinal or pancreatic sarcoidosis has never been reported (8). We describe a patient with sarcoidosis who initially presented with idiopathic crescentic glomerulonephritis successfully treated with prednisone and cyclophosphamide. Subsequently, the patient developed pulmonary, pancreatic, and gastrointestinal sarcoidosis with a severe relapsing course despite therapy with glucocorticoids, cyclosporin, methotrexate or pentoxyphilline. The gastroin-

Transplantation and 2-year follow-up of kidneys procured from a cadaver donor with a history of lupus nephritis.

BACKGROUND Two patients underwent cadaver transplantation with kidneys from a donor with a history of World Health Organization Class IV/V lupus nephritis, and we report their clinical and pathological outcome. METHODS The donor had a diagnosis of lupus nephritis made by renal biopsy 5 years before donation. At the time of donation, a biopsy was performed on the donor and on one of the recipients at 2 months and 1 year after the transplant. RESULTS Both recipients underwent uneventful renal transplantation. On the first postoperative day, the donors final pathological results became available. Although the frozen section seemed to be quite benign, the permanent sections revealed World Health Organization Class II/V lupus nephritis, with full house immunofluorescence and multiple electron dense deposits. Biopsies were performed on recipient #2 at 8 weeks and 1 year after the transplant. These revealed marked diminution followed by complete resolution of all tubular reticular structures and deposits as well as immunofluorescent activity. Both recipients remain with normal renal function and urinalysis at 3 years after the transplant. CONCLUSION Although a history of clinically significant renal disease has been considered an absolute contraindication to kidney donation, with appropriate workup and caution, select patients may still be considered, which would increase the potential donor pool.

Association of post-renal transplant erythrocytosis and microalbuminuria: response to angiotensin-converting enzyme inhibition.

Angiotensin-converting enzyme (ACE) inhibitor therapy has recently been shown to be effective in the treatment of post-renal transplant erythrocytosis (PTE). In an attempt to assess the effect of drug treatment on serum erythropoietin level, glomerular filtration rate, and urinary protein excretion, we prospectively evaluated 8 consecutive cadaveric renal transplant recipients with PTE treated with ACE inhibitor therapy for 3 months. In response to ACE inhibition, the mean hematocrit (HCT) value decreased from 53.7 +/- 0.6% before treatment to 42.7 +/- 2.2% at the conclusion of the study (p = 0.03). However, 1 patient failed to respond to ACE inhibition (HCT > 50%), and 2 patients with PTE developed anemia (HCT < 35%) while maintained on drug treatment. Although the mean serum erythropoietin level decreased during ACE inhibition (from 22.8 +/- 8.4 to 9.4 +/- 5.3 mU/ml; p = 0.06), a consistent change in individual erythropoietin levels was not identified. At the conclusion of the study, the serum erythropoietin levels were undetectable in 4 patients, decreased in 1, unchanged in 2, and increased in the only patient with PTE who failed to respond to drug treatment. All patients tolerated the ACE inhibitor therapy without developing cough or hyperkalemia. In addition, serum creatinine levels, 125I-iothalamate clearances, and mean arterial blood pressures were unchanged throughout the study. Microalbuminuria (spot urinary albumin/creatinine ratio between 30 and 200 mg/g) developed in 5 patients with PTE and coincided with the onset of erythrocytosis (25.2 +/- 7 mg/g before PTE and 76.3 +/- 36.7 mg/g at the time of PTE detection).(ABSTRACT TRUNCATED AT 250 WORDS)

Early small bowel obstruction complicating hand-assisted laparoscopic donor nephrectomy: an uncommon etiology.

Laparoscopic donor nephrectomy is gaining widespread acceptance as a minimally invasive technique for kidney donation. Although it has been associated with decreased patient morbidity and more rapid recovery, it exposes patients to possible complications inherent in its transperitoneal route. We report a case of a small bowel obstruction secondary to midjejunal intussusception occurring on the third postoperative day after a hand-assisted laparoscopic donor nephrectomy. The intus-susception proved to be idiopathic since no lead point was identified. The patient recovered without significant sequela after reduction of the intussusceptum. Postoperative ideopathic intussusception is an uncommon cause of bowel obstruction in adults. Surgeons that perform laparoscopic donor nephrectomy will need to remain vigilant for complications that can be associated with the intraperitoneal route of this technique.

Experience with cryo-preserved cadaveric femoral vein allografts used for hemodialysis access

The purpose of this study was to review the patency and complications of cryopreserved vein allografts used for hemodialysis access, and to compare them to a group with polytetrafluoroethylene (PTFE) grafts. Patients without adequate vasculature for native fistula were implanted with vein allografts or PTFE grafts at the surgeons discretion. Only cryopreserved (CRY) veins were used until January 2001, when decellularized, cryopreserved Synergraft (SYN) veins became available. The CRY group had 48 patients; the SYN group, 42 patients; the PTFE group, 100 patients, who were selected from billing records listing PTFE graft insertion. Patient demographics were similar. Primary and secondary patencies were not significantly different at 1 or 2 years between groups. Complications in PTFE versus CRY and SYN groups were as follows: infection, 10 % vs. 0% (p < 0.01); aneurysm, 2% vs. 18% (p < 0.001); and steal syndrome, 12% vs. 12% (p = NS). Significantly more vein allograft patients lost their accesses to aneurysm (p < 0.01) and multiple stenoses (p < 0.05), whereas PTFE patients lost significantly more accesses to infection (p < 0.01) and recurrent thrombosis (p < 0.05). We conclude that cadaver vein allografts have similar patency to PTFE grafts. These allografts are more resistant to infection but significantly more susceptible to aneurysms. When used, vein allografts should be monitored aggressively for the development of aneurysms.