Jhoong S. Cheigh

Accumulation of Normeperidine, an Active Metabolite of Meperidine, in Patients with Renal Failure or Cancer

Concentrations of meperidine and its active metabolite, normeperidine, were measured in plasma of patients receiving the drug for analgesia. Meperidine levels in cancer patients were 0.10 to 0.55 microng/ml 1 h after a dose and were 0.05 to 0.14 in patients in the oliguric period after renal transplantation. Normeperidine levels were 0.05 to 0.28 microng/ml in the cancer patients and 0.13 to 0.36 in the renal failure patients. The ratio of normeperidine to meperidine levels was always higher in the renal failure patients than in the cancer patients. Additionally, two patients receiving multiple doses of meperidine had high normeperidine levels and very high normeperidine/meperidine ratios when they showed signs of central nervous system excitation. These data indicate that normeperidine can contribute to the excitatory effects seen after multiple doses of meperidine and suggest that patients with renal failure are particularly susceptible to this problem.

Hypertension is Not Adequately Controlled in Hemodialysis Patients

To examine the adequacy of hypertension control, we monitored the blood pressure (BP) of 53 hemodialysis patients who received treatment for hypertension. BP measurement using an ambulatory BP monitor began 1 hour before dialysis and continued every 30 to 60 minutes for 48 hours until the next dialysis. Diet, medications including antihypertensive drugs, and hemodialysis prescription were not changed during this study. Each patient had a mean of 68 BP measurements during the monitoring period. Mean (+/- SD) systolic and diastolic BP levels of all patients over 48 hours were 158.6 +/- 22.7 mm Hg and 88.7 +/- 16.6 mm Hg, respectively, without diurnal variations. In these, BP loads (the percentage of systolic BP exceeding 150 mm Hg and diastolic BP exceeding 90 mm Hg) were 58.4% and 39.4%, respectively, suggesting that hypertension was inadequately controlled for more than half of the study period. Eight patients (15%) maintained BP within normal ranges at all times. All patients lost weight (2.9 +/- 0.9 kg) at the end of dialysis by ultrafiltration. However, only 27 patients (51%) had a greater than 5% decrease in mean arterial BP post-dialysis, which returned to predialysis levels within 12 to 24 hours. Reduction of BP postdialysis was significantly more common among black patients (72%) than white patients (30%) (P less than 0.01). However, there was no difference in age, cause of kidney disease, amount of ultrafiltration, and BP loads between those whose BP decreased and those whose did not. BP monitoring was repeated in eight patients, 2 to 3 months after adjustment of their antihypertensive regimens.(ABSTRACT TRUNCATED AT 250 WORDS)

Impact of renal donation. Long-term clinical and biochemical follow-up of living donors in a single center

Forty-six renal donors who responded to a questionnaire and two additional donors with nephrotic syndrome and renal insufficiency were studied. The mean age was 46 +/- 2.0 years (mean +/- SE). Duration of follow-up was 6 +/- 0.5 years. Serum creatinine levels increased from 1.0 +/- 0.03 mg/dl before donation to 1.2 +/- 0.04 mg/dl at follow-up. The incidence of proteinuria (more than 150 mg over 24 hours) was 39 percent. The serum creatinine level was 1.0 +/- 0.08 mg/dl and 1.2 +/- 0.06 mg/dl in the proteinuric and nonproteinuric groups, respectively. The incidence of hypertension was 31 percent with a serum creatinine level of 1.1 +/- 0.11 mg/dl and 1.2 +/- 0.07 mg/dl in the hypertensive and normotensive groups, respectively. One patient with nephrotic syndrome had proliferative glomerulonephritis. It is concluded that renal donation is associated with a minimal but statistically significant increment in serum creatinine levels. The incidence of mild hypertension and proteinuria is increased, but impact on renal function is minimal as assessed by serum creatinine determination.

Rhabdomyolysis Associated with Concomitant Use of Atorvastatin and Cyclosporine

OBJECTIVE: To describe a case of rhabdomyolysis in a cadaveric renal transplant (CRT) patient receiving atorvastatin and cyclosporine. CASE SUMMARY: A 40-year-old Asian woman with a history of systemic lupus erythematosus (SLE) presented with bilateral lower-extremity weakness and elevated concentrations of creatine kinase (CK), aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and alkaline phosphatase after two months of concomitant therapy with atorvastatin and cyclosporine. Her other medications were not known to cause rhabdomyolysis; neither was there evidence of an SLE flare. After atorvastatin was discontinued, her CK concentrations declined dramatically and her symptoms resolved. DISCUSSION: Rhabdomyolysis has been reported in patients treated with other 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors when used in combination with cyclosporine. Atorvastatin, a relatively new HMG-CoA reductase inhibitor, has not been reported to cause rhabdomyolysis when used concomitantly with cyclosporine. However, its pharmacologic and pharmacokinetic properties make an interaction with cyclosporine possible. CONCLUSIONS: Similar to other members of the HMG-CoA reductase inhibitor class, atorvastatin may interact with cyclosporine and potentially result in rhabdomyolysis. Clinicians should be aware of this possible drug interaction and carefully monitor patients receiving these two drugs concomitantly.

Systemic Lupus Erythematosus in Patients with End-Stage Renal Disease: Long-Term Follow-Up on the Prognosis of Patients and the Evolution of Lupus Activity

We studied the clinical course of 59 lupus patients with end-stage renal disease (ESRD) to determine their long-term prognosis and delineate the evolution of their lupus activity. The study population was predominantly female (86%) and young (mean age, 27.4 years), and they were observed for a mean of 6.5 years from the inception of dialysis. At the time dialysis was initiated, only 21 patients (35.6%) had clinically active systemic lupus erythematosus (SLE). The remaining patients progressed to ESRD despite the absence of clinical lupus activity. Lupus activity was clinically apparent in 55.4% of patients in the first year, 6.5% in the fifth, and none in the tenth year. In 45% of patients, lupus activity was clinically inactive at entry to ESRD and remained inactive throughout the observation period. Serological activity declined proportionally, but to a lesser extent than clinical activity. Cumulative patient survival was 81.1% and 74.6% at the fifth and tenth year, respectively, from the inception of dialysis treatment; similarly it was 78% at the fifth and tenth year after the transplantation. Graft survival was 60.4% at the fifth and 45.5% at the tenth year. No one had recurrence of clinical lupus nephritis in the graft for up to 16 years of follow-up. Fourteen patients died from either infectious or cardiovascular complications, but none from SLE per se. This long-term study with a large number of lupus patients confirms our previous findings that the progression of renal disease to ESRD may be mediated by nonimmunologic mechanisms, as well as immunologic insults.(ABSTRACT TRUNCATED AT 250 WORDS)

Pruritus in Dialysis Patients Treated with Parenteral Lidocaine

Pruritus is one of the most disturbing and poorly understood symptoms in patients on chronic hemodialysis,1 2 3 4 its reported prevalence varying from 15 to 86 per cent. Except for a few case repor...

Focal Segmental Glomerulosclerosis in Renal Transplants

This is a study of the incidence and clinicopathological significance of focal segmental glomerulosclerosis (FSG) in 154 renal allografts (22 biopsies, 128 nephrectomies and four necropsies) from 137 cadaveric and 17 living-related donors. FSG was identified in 18 grafts (11.7%) from 16 patients: six as recurrent FSG in four patients (two developed FSG in two consecutive transplants) and 12 as de novo FSG. The incidence of recurrent FSG in patients who had FSG as their original kidney disease was 30.8% whereas that of de novo FSG in patients who had renal diseases other than FSG was 8.7%. Histologically, recurrent FSG was characterized by mild degrees of obliterative arteriopathy of rejection and preferential involvement of the juxtamedullary glomeruli. Whereas, in de novo FSG, the occlusive vascular changes of rejection were severe and the glomeruli in the outer cortical region were mostly involved. Clinically, however, the differences between them were less clear, although nephrotic syndrome tends to occur more often and earlier in patients with recurrent FSG. Obliterative arteriopathy of chronic rejection and consequent glomerular ischemia appeared to be of major importance in the pathogenesis of de novo FSG in renal allografts.

Percutaneous transluminal dilation in renal transplant arterial stenosis.

Twelve hypertensive patients underwent percutaneous transluminal dilation (PTD) for relief of arterial stenosis complicating renal allotransplantation. Two patients underwent repeat PTD for recurrent stenosis and hypertension. Six patients had end to end anastomosis of the donor renal artery to the recipient hypogastric artery; four of six PTDs were successful. Six patients had end to side anastomosis of the donor renal artery to the recipient external iliac artery; seven of eight PTDs, including one of two repeat PTDs, were successful. Prior to PTD, all patients were using several antihypertensive medications. Following successful PTD, the mean blood pressure dropped from 184 ± 15/118 ± 9 to 133 ± 13/89 ± 11 mm Hg (P < 0.001) and remained at that level for up to 15 months (average followup 9 months) with decreased or no antihypertensive medications. Since surgical correction of arterial stenosis occurring after renal transplantation is difficult and may endanger the graft, PTD should be the first interventional therapy.

Urinary calculi in renal transplant recipients

Urinary calculi are an uncommon complication in renal transplant recipients. During a 15-year period, in 544 cases of kidney transplantation with a functioning allograft for more than 3 months, and a long-term follow-up, we have observed 9 cases (1.7%) of urinary calculi. Calculi occurred in 6 male and 3 female patients, 6 patients were recipients of living related and 3 of cadaveric kidneys. Calculi were diagnosed as early as 3 months and as late as 3.5 years after transplantation, but most were detected within the first year. The location of the calculi was the bladder in 4 cases, the transplant in 3, and indeterminant in 2. Crystallographic analysis of retrieved stones revealed calcium oxalate and/or phosphate in 4 cases, triple phosphate in 2, and uric acid in 1. All patients had one or more stone-predisposing factors, such as obstructive uropathy and recurrent urinary tract infection (4 cases), hyperoxaluria (3), or hypercalciuria (2). During long-term follow-up (mean 60 months), only one patient lost the renal graft, 14.5 years after transplantation, primarily from causes unrelated to urinary calculi. One instance of stone recurrence was noted. In conclusion: (1) urinary calculi after renal transplantation are relatively uncommon; (2) predisposing factors and crystallographic composition of the calculi are identical in type, but not frequency, to those of nontransplant patients; and (3) with proper medical and surgical management, post-transplant urolithiasis does not appear to affect graft prognosis.

Systemic lupus erythematosus in patients with chronic renal failure

The clinical courses of 36 patients with systemic lupus erythematosus (SLE) in whom chronic renal failure developed and who required dialysis for more than three months were studied. At the time dialysis was initiated, 14 of 36 patients (38.9 percent) had clinically active SLE, but only three of 24 (12.5 percent) had activity in subsequent years while receiving dialysis therapy. In the majority of patients, however, renal disease progressed to end-stage despite clinical quiescence of SLE. During the follow-up period (mean +/- SD, 36 +/- 39.8 months), eight patients died--six from infections and two from cardiac disease. Actuarial survival rates at one, two, and five years after dialysis treatment were 91.1, 78.8, and 68.9 percent, respectively. This study suggests that the progression of renal disease to end-stage in patients with SLE may be mediated by nonimmunologic mechanisms as well as SLE-related immunologic insults. In most of these patients undergoing long-term dialysis, SLE remains clinically inactive despite persistent serologic abnormalities. Survival of the patients undergoing dialysis is comparable with that of the general dialysis population.