Elevated serum alkaline phosphatase levels in a renal transplant patient precede colitis.

An asymptomatic, but highly significant, rise in serum alkaline phosphatase (AP) levels developed in a renal transplant recipient. Investigations ruled out bony or hepatobiliary disease. Subsequent diarrhea and weight loss led to a diagnosis of cytomegalovirus (CMV) colitis, which was confirmed with a positive CMV pp65 antigenemia test and an endoscopic finding of multiple colonic erosions. Intravenous ganciclovir led to complete patient recovery and a swift reduction of serum AP levels to normal. Normally, intestinal AP isoenzymes are cleared quickly from the circulation. However, acute bowel diseases, especially when inflammatory in origin, can produce high serum AP levels. In this presented patient, the rise in serum AP levels preceded symptomatic manifestations of CMV colitis, and fell with successful therapy. Acute CMV disease in solid organ transplant recipients is common, can take many shapes, and needs to be diagnosed quickly. An unexplained rise in serum AP levels should lead to a search for inflammatory bowel disease, specifically CMV colitis, in transplanted patients.

Hepatitis C infection in dialysis patients in Israel.

BACKGROUND: Hepatitis C virus is the major cause of acute and chronic hepatitis in patients with end-stage renal disease receiving replacement therapy. OBJECTIVES: To define the prevalence of HCV RNA in a population of patients on dialysis in Israel, to determine the relative risk of acquiring HCV infection while treated by hemodialysis or chronic ambulatory peritoneal dialysis, and to define the HCV genotypes in this population. METHODS: During 1995 we studied 162 dialysis patients. Information was obtained regarding the mode of dialysis, years of treatment, number of blood transfusions, and results of serological testing for HCV, hepatitis B virus, and human immunodeficiency virus. Anti-HCV antibodies were tested by a third-generation microparticle enzyme immunoassay. HCV RNA was determined by polymerase chain reaction. HCV genotyping was performed by a hybridization assay. RESULTS: HCV RNA was detected in 18% of the HD group and 7% of the CAPD group. The number of HCV RNA-positive patients was significantly higher in the HD than the CAPD group (P < 0.05). HCV RNA-positive HD patients were treated longer than the HCV RNA-negative patients (P < 0.02). CONCLUSIONS: Third-generation immunoassay proved to be highly sensitive (94%) and specific (91%) in identifying HCV RNA positivity. Several HCV subtypes were detected, 1b being the most frequent. Identification and isolation of infected HCV patients may minimize its spread in dialysis units and prevent cross-infection.

Effect of cyclosporin A on DNA repair and cancer incidence in kidney transplant recipients.

Cancer incidence is enhanced in transplant recipients. Decreased DNA repair ability is associated with increased cancer incidence. Transplanted patients with cancer were found to have reduced DNA repair. We hypothesized that immunosuppressive therapy may impair DNA repair and thus contribute to the increased cancer incidence in transplanted patients. The objectives of this study were (1) to investigate the effect of two immunosuppressive treatment protocols on DNA repair in kidney transplant recipients; (2) to evaluate the cancer incidence in these patients; and (3) to study the in vitro effect of cyclosporin A (CsA), azathioprine, and prednisolone-separately and in various combinations-on DNA repair. Three groups were studied: (1) a control group; (2) patients treated with azathioprine and prednisone (double-therapy group); and (3) patients treated with CsA, azathioprine, and prednisone (triple-therapy group). The two patient groups did not differ in age, gender, time on dialysis before transplantation, or kidney function or in the number of acute rejections. However, the interval from transplantation to the DNA repair study was shorter in the triple-therapy group (P <.01). DNA repair was induced in peripheral blood mononuclear cells (PBMCs) by ultraviolet irradiation and expressed as tritiated thymidine uptake by these cells. DNA repair in the triple-therapy group was 679 +/- 64 cpm/10(6) cells, significantly less than that in the control group (1049 +/- 69 cpm/10(6) cells, P <.02). In the double-therapy group, DNA repair was similar to that in the control group. The follow-up period was shorter in the triple-therapy group (116 +/- 19 months vs 174 +/- 29 months, P <.01). Five tumors developed in the triple-therapy group, but only one developed in the double-therapy group (P =.05). The in vitro study showed a dose-dependent reduction in PBMC DNA repair by CsA. Azathioprine and prednisolone reduced DNA repair slightly, but CsA reduced DNA repair significantly more than either one or a combination of them. In summary, triple therapy was associated with impaired PBMC DNA repair and increased cancer incidence. CsA was responsible in large part for the reduction in DNA repair ability found in the in vitro and in vivo studies. This may have partly contributed to the enhanced cancer incidence in the kidney transplant recipients.

Erythropoietin, folic acid deficiency and hyperhomocysteinemia: is there a possible relationship in chronically hemodialyzed patients?

AIMS: To examine the possible relationships between recombinant human erythropoietin (rhEPO) therapy, serum folic acid and homocysteine levels in a cohort of stable, chronically hemodialyzed patients. MATERIAL AND METHODS: The study was cross-sectional in its first phase and consisted of 3 groups of subjects (group 1:6 healthy controls; group 2:7 dialyzed patients not receiving rhEPO; group 3: 14 patients on rhEPO therapy). Hematological and biochemical parameters were taken after an overnight fast in all subjects. The second phase of the study was prospective, and included 8 dialyzed patients, and investigated the effects of a 6-month period of folic acid supplementation (10 mg, 3 times a week) on the same parameters examined in the first phase of the study. RESULTS: In the first part of the study hemoglobin levels were near-normal, or normal, in all patients. No differences in hemoglobin or hematocrit values were observed in the 3 groups. 80% of all hemodialyzed patients had low serum folic acid levels, irrespective of whether they were receiving rhEPO. Serum erythropoietin level was elevated in group 3 (23.3+/-10.4 mIU/ml). In group 2, serum erythropoietin level was not different from that of the healthy controls (13.5+/-11.2 vs. 8.0+/-5.4 mIU/ml, p = n.s.). Total serum homocysteine levels were elevated in all dialyzed patients (group 2: 24.7+/-9.2 micromol/l; group 3: 31.6+/-14.4 micromol/l), with a significant difference seen when comparing controls and those dialyzed patients on rhEPO therapy (8.7+/-2.2 vs. 31.6+/-14.4 micromol/l; p<0.05). Significant correlations (ANOVA) were observed between serum erythropoietin and folic acid levels (r = -0.382; p = 0.049), and between folic acid and homocysteine levels (r = -0.560; p = 0.002). In the second part of the study folic acid supplementation led to a highly significant reduction in homocysteine levels (20.9+/-4.9 vs. 11.9+/-2.5 micromol/l; p<0.0005). Two of 3 patients receiving rhEPO therapy, had rhEPO discontinued after commencing folic acid, as hemoglobin levels remained adequate, even without rhEPO. CONCLUSIONS: In hemodialyzed patients, the presence of a near-normal hemoglobin level, irrespective of rhEPO therapy, implies efficient erythropoiesis. Without adequate folic acid reserves, folic acid deficiency may develop in these patients and this will aggravate already high homocysteine levels. Therefore, folic acid supplementation is warranted in hemodialyzed patients, especially in those patients with hemoglobin levels approaching normal. This treatment is safe and effective in reducing homocysteine levels, especially when given in high doses for prolonged periods of time.

The effect of drug cost on hypertension treatment decision.

The cost of medical care is constantly increasing. Therefore, ways of saving expenses should be considered. The aim of the present study is to evaluate the possibility than an awareness of the cost of drugs for treatment of hypertension may affect physicians' prescription decisions. A questionnaire containing the clinical data of a young and an elderly imaginary patient with moderate hypertension was given to 30 family physicians and 30 hospital physicians together with a list of appropriate drugs (phase I). This was repeated as phase II except that for this stage the cost of the drugs was brought to the participants' attention. Knowing the cost of the drugs caused a decrease in prescription of the more expensive drugs for the younger patients; of 60% (family physicians) and 87% (hospital physicians). For their elderly patients family physicians preferred the less expensive drugs at both phases. 25% of the hospital doctors changed their preference towards less expensive drugs at phase II. For the younger patient, no correlation was found between the number of years of physicians' practice and the cost of the drugs chosen. For the elderly patient, physicians from both groups preferred less expensive drugs at phase II without any relation to their years of practice. The results of this study indicate that a knowledge of the price of the drugs may affect physicians' prescription decisions, a fact that may result in considerable saving by health providing organizations.

Successful intradialytic parenteral nutrition after abdominal "Catastrophes" in chronically hemodialysed patients.

OBJECTIVE: To assess the therapeutic contribution of intradialytic parenteral nutrition (IDPN) in four acutely ill, hypercatabolic, hemodialysed patients. All underwent major surgery, complicated by infection and malnutrition. DESIGN: A retrospective clinical study. SETTING: An in-center hemodialysis unit, at a tertiary referral hospital. PATIENTS: Patient 1: a young woman, with a good renal transplant. Developed gastric lymphoma, which required gastrectomy. After cessation of immunosuppression, "lost" her kidney and returned to hemodialysis. Received IDPN for 4 months and recovered well from severe malnourishment. Patient 2: an elderly, malnourished man, on continuous ambulatory peritoneal dialysis (CAPD). Developed biliary peritonitis and bacteremia. In a 3-month period, the patient had four operations. Maintained on IDPN for 4 months. Patient 3: a young and obese man, who suffered from life-threatening staphylococcal aureus peritonitis, resulting in widespread bowel adhesions. Underwent repeated aspirations of purulent ascites, laparoscopy, and explorative laparotomy. IDPN was administered for 4 months and stopped on the patient's request. Patient 4: a young man, who after cadaveric renal transplantation remained hospitalized for 6 months because of acute rejection and peritoneal and retroperitoneal abscesses. Had major surgery performed seven times. Received IDPN for 6 months, and is now well. RESULTS: All four patients benefited from 4 to 6 months of IDPN, as an integral part of intensive supportive and nutritional treatment. Weight loss was halted, as patient appetite returned and oral nutrition became adequate. Estimated daily protein intake reached 1.2 g/kg, while caloric intake rose to nearly 30 kcal/kg/d (Table 3). Mean serum albumin levels increased from 25.5 g/L +/- 0.9 g/L to 38.0 g/L +/- 1.5 g/L. No adverse side effects were seen from IDPN. CONCLUSION: IDPN is a worthwhile part of treatments used in the catabolic, postoperative hemodialysed patient. It is safe and efficient when used over a 6-month period in trying to attenuate existing, or worsening malnutrition in these patients. It should be commenced at an early stage in these patients, after attempts at oral nutritional support have been deemed inadequate.

Calcium balance during pulse alfacalcidol therapy for secondary hyperparathyroidism in CAPD patients treated with 1.0 and 1.25 mmol/L dialysate calcium.

Hypercalcemia frequently occurs in continuous ambulatory peritoneal dialysis (CAPD) patients treated with calcium carbonate and vitamin D metabolites. To reduce the incidence of this complication, it has been proposed to use dialysate solutions with a low calcium concentration. However, there is concern that these solutions may lead to a negative calcium balance. We measured calcium balance in 13 CAPD patients with secondary hyperparathyroidism who were treated with calcium carbonate and alfacalcidol, 2 microg twice weekly, while using 1.0- (1.0 group) and 1.25-mmol/L (1.25 group) dialysate calcium solutions. Calcium absorption was measured after the administration of Ca47. Results for the 1.0 (n = 6) and 1.25 (n = 7) groups included fractional calcium absorptions of 0.14 (range, 0.09 to 0.27) and 0.08 (range, 0.03 to 0.40; P = not significant [NS]) and calcium absorptions of 380 +/- 92 and 331 +/- 83 mg/d (P = NS). Dialysate calcium losses were 93 +/- 20 and 91 +/- 26 mg/d, and total calcium losses (dialysate and urine) were 106 +/- 16 and 108 +/- 40 mg/d (P = NS). Calcium balance was positive in all patients (274 +/- 92 and 223 +/- 65 mg/d; P = NS). These data suggest that the use of 1.0- and 1.25-mmol/L calcium solutions in conjunction with calcium carbonate and pulse alfacalcidol therapy is associated with a positive calcium balance in CAPD patients.

The femoral artery-femoral vein polytetrafluoroethylene graft: a 14-year retrospective study.

BACKGROUND: The use of the femoral vessels for permanent haemodialysis access has been neglected during the last two decades. Since 1981 femoral artery-vein loop polytetrafluoroethylene grafts have been constructed in our chronic haemodialysis patients. This study examines results obtained in patients with this particular graft over the last 14 years. METHODS: This clinical study is retrospective in nature. Overall 35 patients, with 37 femoral grafts, are included. Inclusion and exclusion criteria for this type of graft are given and the surgical procedure detailed. RESULTS: Seven patients had femoral grafts used as primary dialysis access. Twenty-eight patients had femoral grafts used after multiple access failures. There was no perioperative mortality. Immediate thrombotic non-function of the graft occurred in three patients. In the long term no patient death was related to the femoral grafts. Twenty-seven (73%) grafts had no long-term complications. The leading cause for graft 'loss' was patient death; in the first year 10 grafts were lost, eight because of patient death. All eight patients died with functioning grafts. Median graft survival was 21 months in all patients and 28 months in non-diabetic patients. Twenty-seven (73%) grafts were patent at the end of the first year, 33% of grafts were still patent after 5 years. Worsening claudication occurred in four patients; one diabetic required foot amputation. Four patients had late graft thrombosis; only two patients had bacteraemia originating from the femoral graft. Urea reduction ratio greater than 60% was measured in 87.5% of patients. CONCLUSION: The femoral artery vein graft is a good primary and secondary haemodialysis access. Both infection and thrombosis rates are low and graft survival is comparable, if not superior to, that of upper-limb grafts. The graft is easy to cannulate, can be used early, is easily protected, and is cosmetically acceptable.

Postoperative rhabdomyolysis in patients with end-stage renal failure.

Four patients with end-stage renal failure on intermittent hemodialysis in whom rhabdomyolysis developed after major surgery are described. This possibly underdiagnosed complication was manifested by extreme hyperphosphatemia, hypocalcemia, and elevated creatine phosphokinase levels. Serum myoglobin levels further supported the diagnosis. The metabolic abnormalities reached a peak on the fourth postoperative day. The possible precipitating factors included opiates used for anesthesia and postoperative pain control, anesthetic agents, and surgical position. The preferred treatment option is increasing dialysis to control hyperphosphatemia and hypocalcemia.

Hypercalcemia during pulse vitamin D3 therapy in CAPD patients treated with low calcium dialysate: the role of the decreasing serum parathyroid hormone level.

Oral pulse therapy with vitamin D is effective in suppressing parathyroid hormone (PTH) secretion in continuous ambulatory peritoneal dialysis patients with secondary hyperparathyroidism (2'hpt). However, this treatment often leads to hypercalcemia. The goals of the study were: (1) to examine whether the incidence of hypercalcemia decreases when dialysate calcium is reduced from 1.25 to 1.0 mmol/L; (2) to determine the relative role of the factors involved in the pathogenesis of hypercalcemia; and (3) to study the efficacy of a low oral pulse dose of alfacalcidol in preventing the recurrence of 2'hpt. Fourteen continuous ambulatory peritoneal dialysis patients with 2'hpt were treated with pulse oral alfacalcidol and calcium carbonate and dialyzed with a 1.0-mmol (n = 7) or a 1.25-mmol (n = 7) dialysate calcium. The response rate (87%) and the incidence (71%) and severity of hypercalcemia were similar in both groups. In the early response stage, PTH decreased by 70% in both groups, and serum ionized calcium (iCa) increased from 1.18 +/- 0.02 to 1.27 +/- 0.04 mmol/L (P < 0.005) in the 1.0 group and from 1.19 +/- 0.02 to 1.29 +/- 0.02 mmol/L in the 1.25 group (P < 0.005). Nine of the 12 responders had a further decrease in serum PTH, which was associated with an additional increase in iCa from 1.28 +/- 0.02 to 1.47 +/- 0.04 (P < 0.005). Multivariate analysis showed that the early increase in iCa was positively correlated with alfacalcidol dosage (r = 0.69). In contrast, the late increase in iCa was mostly accounted for by the decrease in serum PTH (r = -0.93). This occurred while calcium carbonate, alfacalcidol dosage, and serum 1,25 hydroxy D3 remained unchanged compared with the early response stage. Finally, an alfacalcidol dose of 1 microg twice weekly was unable to maintain serum PTH at an adequate level in the long term. These data show that a reduction in dialysate calcium from 1.25 to 1.0 mmol does not reduce the occurrence of hypercalcemia and suggest that lowering serum PTH reduces the ability of the bone to handle a calcium load within a few weeks, thus causing hypercalcemia.

Case report: severe hyponatremia after water intoxication: a potential cause of rhabdomyolysis.

A 28-year-old woman, treated for schizophrenia, developed severe hypotonic hyponatremia (serum Na: 109 mEq/L) after several days of compulsive water drinking. The patient was admitted in a coma and required intensive supportive therapy. Rhabdomyolysis quickly followed with high serum creatine phosphokinase levels and myoglobinuria. A high volume alkaline diuresis was initiated. Renal failure or compartment syndrome did not complicate the clinical picture. The mechanisms causing water intoxication and hyponatremia are discussed as are the possible pathogenetic explanations behind acute hyponatremia and rhabdomyolysis.

Acute necrotizing pancreatitis, lactic acidosis and prolonged hypoglycemia in a hemodialysed patient--a logical but unfortunately fatal combination.

A hemodialysed patient with abdominal pain, severe lactic acidosis and prolonged hypoglycemia is described. The diagnosis of acute necrotizing pancreatitis was delayed and the patient died from both systemic and peripancreatic complications of the acute pancreatitis. The article deals with the problem of diagnosing acute pancreatitis in an end-stage renal failure (ESRF) patient; on the possible surgical options open to the physician in the management of acute pancreatitis and on a pathophysiological explanation behind both the lactic acidosis and hypoglycemia in this patient.

Twenty-four-hour blood pressure monitoring during treatment with extended-release felodipine versus slow-release nifedipine: cross-over study.

The lack of comparative studies of nifedipine and felodipine using 24-h blood pressure (BP) monitoring in the same patients led to the present study evaluating the antihypertensive efficacy and side effects of treatment with slow-release (SR) nifedipine (20 mg twice daily) and extended-release (ER) felodipine (10 mg once daily). In the double-blind study, subjects were randomly assigned to one of two treatment groups: 6 weeks of nifedipine SR (20 mg twice daily) followed by 6 weeks of felodipine (ER) (10 mg once daily with evening matched placebo), or vice versa. Twenty-four-hour ambulatory BP monitoring showed no significant differences in systolic BP (SBP) during the day. There were no significant differences in diastolic BP (DBP) throughout the 24 h, although the frequency of DBP recordings > 90 mm Hg was greater during nifedipine (33.1%) than felodipine (27.75%) treatment. The most common side effects were flushing, palpitations, headaches, and ankle edema; there were no adverse effect on lipid profile or glucose level.

Adenocarcinoma at ureterosigmoidostomy junction in a renal transplant recipient 15 years after conversion to ileal conduit.

In recent years, adenocarcinoma of the colon mucosa has become a recognized complication of ureterosigmoidostomy and in most cases the tumor arises at the site of ureterocolonic anastomosis. We report a case of a 29-year-old renal transplant recipient who developed two colonic carcinomas at the site of ureterosigmoidostomy 25 years after the urinary diversion and 15 years after conversion to an ileal conduit. This case emphasizes the need for a careful life-long follow-up of all patients who undergo ureterosigmoidostomy.

Effect of nifedipine on the renal functional reserve in cyclosporine-treated renal-transplant recipients.

Cyclosporine decreases renal perfusion and impairs the renal hemodynamic response to a protein load. High-dose nifedipine has been shown to elevate renal plasma flow (RPF). We measured the renal functional reserve of 6 cyclosporine-treated renal-transplant recipients following intravenous administration of an amino acid solution, before and 2 weeks after therapy with high-dose nifedipine (up to 120 mg/day). Pretreatment renal functional reserve was nil Following administration of nifedipine, RPF increased by 22% (p < 0.01), filtration fraction decreased by 14% (p < 0.005) and renal vascular resistance declined by 39% (p < 0.005). Renal functional reserve remained unchanged. High-dose nifedipine increases renal perfusion but does not restore renal functional reserve in cyclosporine-treated renal-transplant recipients.