Gadolinium-based contrast and carbon dioxide angiography to evaluate renal transplants for vascular causes of renal insufficiency and accelerated hypertension

PURPOSE: To evaluate the utility and potential nephrotoxicity of gadolinium-based contrast angiography when used with carbon dioxide angiography in renal transplant patients with suspected vascular causes of renal insufficiency and/or accelerated hypertension. MATERIALS AND METHODS: Thirteen consecutive renal transplant patients with suspected vascular causes of renal insufficiency and/or accelerated hypertension were evaluated with gadolinium-based contrast and CO2 angiography with use of digital subtraction techniques. Stenotic lesions were treated with angioplasty with/or without stent placement. No iodinated contrast agents were used. Serum creatinine levels were obtained before and at 24 and 48 hours after the procedure. An increase in creatinine levels greater than 0.5 mg/dL (44 micromol/L) was considered significant. RESULTS: Nine patients were studied for renal insufficiency, two for accelerated hypertension, and two for both. All 13 studies were considered diagnostic. Significant stenoses were treated in four patients with angioplasty with or without stent placement. Two patients had progression of their renal insufficiency. One of these patients underwent biopsy and was found to have both acute and chronic rejection. The other patient underwent cardiac catheterization 2 days after a transplant renal artery angioplasty. In the remaining nine patients with renal insufficiency (creatinine range, 1.8-3.9 mg/dL [159-345 micromol/L]; mean, 2.7 mg/dL [239 micromol/L]), renal function improved or did not worsen. CONCLUSION: Based on this limited study, gadolinium-based contrast angiography appears to be a promising supplement to CO2 angiography for the diagnosis and treatment of vascular lesions in patients with renal transplant insufficiency and/or accelerated hypertension. Further study is necessary to determine safety, optimal gadolinium dosage, and imaging parameters.     

Detection of anti-lipoarabinomannan antibodies for the diagnosis of active tuberculosis

Patients with acquired cystic kidney disease (ACKD) are at an increased risk of renal neoplasms. Frequent tumors are adenomas and renal cell carcinomas. However, renal oncocytomas may occur in patients with ACKD. Little is known about oncocytomas of the native kidney following renal transplantation. By means of B scan ultrasonography, a solid and echo-inhomogeneous renal mass was incidentically observed in the right native kidney of a 28-year-old female patient with ACKD 4 years following renal transplantation. A nephrectomy was performed. The histological examination revealed a renal oncocytoma. The increased prevalence of neoplasms in the case of ACKD and following renal transplantation requires careful monitoring of the patients concerned. In very rare cases a renal oncocytoma may develop in the native kidney after renal transplantation.     

Performance of a semiautomated Papanicolaou smear screening system: results of a population-based study conducted in Guanacaste, Costa Rica

Cardiovascular disease is one of the most common complications of dialysis and renal transplant patients, and high levels of AGE are present in end-stage renal failure. To address the potential involvement of AGE and growth factors in the pathophysiology of cardiovascular complications, we performed immunostaining using cardiac tissues from autopsy cases of patients on maintenance dialysis (10 cases), long-term surviving renal transplant patients with functioning grafts (8 cases), control subjects with normal renal function (7 cases) and non diabetic subjects with mild renal insufficiency (8 cases). We used two types of AGE-antibodies, 6D12 [monoclonal anti-AGE antibody, recognizing N epsilon-(carboxymethyl) lysine(CML)-modified AGE] (oxidative AGE) and non-CML-PA [polyclonal, not recognizing CML], and antibodies against PDGFs, PDGF receptors and TGF beta. Positive 6D12 staining was observed in the coronary arterial walls and in macrophages. The accumulation of 6D12-reactive AGE in the coronary arterial walls of maintenance dialysis patients was significantly greater than that of control subjects (p < 0.05). Renal transplantation significantly reduced this accumulation (p < 0.05). On the other hand non-CML-PA mainly detected AGE in intracardiac arterioles and neural tissues. There was little difference in the accumulation of non-CML-AGE among the four groups. PDGFs and PDGF receptors were mainly detected in vascular endothelial cells and infiltrating cells of cardiac tissues of renal transplant patients, but not of maintenance dialysis patients. TGF beta was not detected in cardiovascular tissue of transplant patients. Our results indicated that the accumulation of oxidative AGE (CML-AGE) in the cardiac vascular tissue is one of the factors for cardiovascular complications of maintenance dialysis patients, and also that renal transplantation has a reducing effect on CML-AGE accumulation. PDGFs may be involved in the cardiovascular complications after renal transplantation.     

Prognosis after primary renal transplant failure and the beneficial effects of repeat transplantation: multivariate analyses from the United States Renal Data System

BACKGROUND: Survival of transplant recipients after primary renal allograft failure has not been well studied. METHODS: A cohort of 19,208 renal transplant recipients with primary allograft failure between 1985 and 1995 were followed from the date of allograft loss until death, repeat transplantation, or December 31, 1996. The mortality, wait-listing, and repeat transplantation rates were assessed. The mortality risks associated with repeat transplantation were estimated with a time-dependent survival model. RESULTS: In total, 34.5% (n=6,631) of patients died during follow-up. Of these deaths, 82.9% (n=5,498) occurred in patients not wait-listed for repeat transplantation, 11.9% (n=789) occurred in wait-listed patients, and 5.2% (n=344) occurred in second transplant recipients. Before repeat transplantation, the adjusted 5-year patient survival was 36%, 49%, and 65% for type I diabetes mellitus (DM), type II DM, and nondiabetic end-stage renal disease, respectively (P<0.001; DM vs. nondiabetics). The adjusted 5-year patient survival was lower in Caucasians (57%, P<0.001) compared with African-Americans (67%) and other races (64%). The 5-yr repeat transplantation rate was 29%, 15%, and 19%, whereas the median waiting time for a second transplant was 32, 90, and 81 months for Caucasians, African-Americans, and other races, respectively (P<0.0001 each). Repeat transplantation was associated with 45% and 23% reduction in 5-year mortality for type I DM and nondiabetic end-stage renal disease, respectively, when compared with their wait-listed dialysis counterparts with prior transplant failure. CONCLUSIONS: The loss of a primary renal allograft was associated with significant mortality, especially in recipients with type I DM. Repeat transplantation was associated with a substantial improvement in 5-year patient survival. Recipients with type I DM achieved the greatest proportional benefit from repeat transplantation.     

Mispredicting and misremembering: Patients with renal failure overestimate improvements in quality of life after a kidney transplant.

Objective: People tend to overestimate the impact that future events will have on their quality of life. In the case of a medical treatment like kidney transplant, this should result in biased predictions--overestimates of how much the transplant will benefit quality of life. The authors surveyed kidney transplant patients, both before and after transplant, to test whether they would overestimate the benefits of a successful transplant for their quality of life. Design: The authors interviewed 307 patients on a waiting list for cadaveric renal or renal-pancreatic transplant, and 195 patients one year after a successful transplant. A sub sample of patients were interviewed both before and after transplant. Main Outcome Measures: The survey included measures of quality of life, both in terms of an overall estimate (0-100), and across sub domains, including health, employment, and travel. Results: Cross-sectional results suggested that overall quality of life improved after transplant, but the predictions of pretransplant patients overestimated the magnitude of the improvement (p     

Breast and lung cancers in two cyclosporin-A-treated psoriatic women

We report malignant neoplasms of the breast and lung developed in two psoriatric patients after long-term treatment with low-dose cyclosporin A (CsA). A procarcinogen role of the drug cannot be ignored. Concern regarding the documented evidence from studies of organ transplant patients should be stressed in patients treated with low doses of CsA for chronic cutaneous inflammatory diseases.     

Solitary choroidal metastasis as the first sign of metastatic lung carcinoid

The identification of malignancies associated with transplantation has led to enhanced vigilance and care in these patients, as well as insight into the pathogenesis of select malignancies. We report a case of Merkel cell carcinoma, an uncommon cutaneous malignancy of neuroendocrine origin, diagnosed in a 65-year-old Caucasian man 6 years after renal transplantation. While it is well known that transplant patients are at increased risk for squamous cell carcinomas of the skin, other types may also have an increased frequency. We suggest that Merkel cell carcinoma could have an increased incidence in the transplant population.     

Renal autotransplantation for the loin pain-hematuria syndrome: long-term followup of 26 cases

PURPOSE: We review the long-term results of renal autotransplantation as a form of nephron sparing renal denervation for patients with the loin pain-hematuria syndrome. MATERIALS AND METHODS: From 1985 to 1997, after exclusion of other urological, nephrological and psychiatric causes for severe intractable flank pain and recurrent hematuria, 22 patients with severe debility and heavy narcotic dependency underwent 26 renal autotransplantations for pain control. Postoperative pain relief, narcotic use, level of function in daily activities and status of the autograft were assessed. RESULTS: Median and mean followup was 78.5 and 84.7 months (range 30 to 138), respectively. There were 2 technical failures. Pain recurred within 2 years after 6 procedures, of which 3 resulted in transplant nephrectomy and 3 were managed with a reduced analgesic requirement. Of the 16 patients with minimum 5 years of followup 12 (75%) were pain-free after surgery with 3 additional patients pain-free after transplant nephrectomy. Overall, 18 of the 26 autotransplant procedures (69.2%) resulted in pain relief, in some cases beyond 10 years, with patients returning to normal daily activities. CONCLUSIONS: Renal autotransplantation results in durable narcotic-free favorable results in the majority of meticulously screened loin pain-hematuria syndrome patients. Although some failures, which usually occur within 2 years after surgery, can be expected, autotransplantation is justified as a nephron sparing denervation therapy for select loin pain-hematuria syndrome patients.     

Cyclosporine therapy after cardiac transplantation causes hypertension and renal vasoconstriction without sympathetic activation

BACKGROUND: Hypertension frequently complicates the use of cyclosporine A (CyA) therapy, and it has been suggested that sympathoexcitation may be the underlying mechanism in this form of hypertension. METHODS AND RESULTS: To further investigate the possibility of a neurogenic mechanism for this hypertensive effect, we studied the effects of CyA on renal blood flow (n = 11), forearm blood flow (n = 8), and sympathetic nervous system activity, assessed by renal and whole-body radiolabeled norepinephrine plasma kinetics and muscle sympathetic nerve firing (using microneurography) in cardiac transplant recipients receiving CyA and a reference group of healthy age-matched control subjects (n = 17). In 11 cardiac transplant patients (2 hours after cyclosporine dose), renal blood flow was significantly lower than that in 8 control subjects (680 +/- 88 vs 1285 +/- 58 mL/min, P < .001). In 5 of these transplant patients, renal blood flow was measured before and for 2 hours after oral cyclosporine and fell progressively over this period, by 37% (P < .01). Total body and renal norepinephrine spillover rates in transplant patients were similar to those in control subjects (3070 +/- 538 vs 2618 +/- 313 pmol/min and 579 +/- 124 vs 573 +/- 95 pmol/min, respectively), and there was no progressive effect in the 2 hours after cyclosporine dosing. Forearm blood flow was increased 2 hours after CyA administration (1.74 +/- 0.31 to 3.12 +/- 0.50 mL x 100 mL-1 x min-1, P < .001), whereas mean arterial blood pressure and noninvasively determined cardiac output (indirect Fick method) were unchanged. Muscle sympathetic nerve discharge rates recorded in 6 of these transplant patients were not different from those in 9 healthy control subjects (37.9 +/- 10.1 vs 41.3 +/- 2.3 bursts per 100 beats per minute). During 90 to 120 minutes of recording after cyclosporine dosing, nerve firing rates remained unchanged. CONCLUSIONS: CyA therapy causes acute renal vasoconstriction without accompanying systemic hemodynamic effects. These renal effects are nonneural, not being attributable to sympathoexcitation.     

Outcome of renal replacement therapy in antineutrophil cytoplasmic antibody-associated systemic vasculitis

Antineutrophil cytoplasmic antibody-associated systemic vasculitis (AASV) frequently leads to end-stage renal disease (ESRD). Potentially fatal disease activity can continue after the onset of ESRD in both dialysis and transplant patients, despite the immunosuppressive effects of uremia and rejection prophylaxis, leading to concerns that such patients have greater morbidity and mortality. To assess the outcome of AASV patients receiving renal replacement therapy, a retrospective analysis of 59 patients from our unit who received chronic dialysis, renal transplantation, or both, was performed. The survival of AASV patients with ESRD was comparable to national registry controls, as were both graft and patient survival after renal transplantation. Ther is no evidence that standard immunosuppressive protocols should be altered for AASV patients receiving renal transplants. The rate of relapse of vasculitis for patients on chronic dialysis and after transplantation was 0.09 and 0.02 per patient per year, respectively. These rates are lower than those of other series and support the contention that continued immunosuppression after ESRD, as practiced in our unit, is warranted. Relapses usually responded to cyclophosphamide and high-dose prednisolone treatment. Significantly, vasculitic flare-ups in dialysis patients were sometimes initially misdiagnosed as dialysis complications, leading to fatal delays in effective treatment. Follow-up by physicians experienced in the diagnosis and treatment of vasculitis activity should continue in these patients.     

Carotid atherosclerosis in renal transplant recipients

BACKGROUND: Cardiovascular accidents are the major cause of morbidity and mortality in renal transplant recipients. However, there is little information concerning carotid atherosclerotic wall changes in renal transplant recipients, their relationship with cardiovascular accidents and their possible association with cardiovascular risk factors in such patients. METHODS: Between April 1991 and December 1997, we prospectively assessed cardiovascular accidents in 79 renal transplant recipients who had received a transplant at our institution before January 1, 1986. Carotid morphology by B-mode ultrasonography, relevant clinical and laboratory cardiovascular risk factors, including lipid abnormalities and total homocyst(e)ine, were determined at the start of the follow-up period. Seventeen healthy subjects matched for age and sex with renal transplant recipients served as controls who volunteered for ultrasonographic examination of carotid arteries. RESULTS: Nine patients experienced cardiovascular events during the period of follow-up. Compared with healthy, age- and sex-matched control subjects (n = 17), the frequency of carotid plaques was higher in renal transplant recipients with cardiovascular events (n = 9), but not in those without such events (n = 70). The frequency of cardiovascular accidents was related to the number of carotid plaques (4, 17 and 24% for no plaque, one plaque and > 1 plaque respectively, P < 0.04). However, by multivariate analysis, serum total cholesterol [odds ratio (OR) of 1.8 for each 1.0 mM, P < 0.07) and the presence of diabetes mellitus (OR of 28.4 for presence, P < 0.01) were the only predictors of cardiovascular events in such patients, whereas the presence of carotid plaques was not. Moreover, neither serum lipoprotein (a) nor total homocyst(e)ine concentrations could be identified as risk factors. CONCLUSIONS: This prospective study shows that although a close association exists between asymptomatic carotid atherosclerosis and cardiovascular accidents in renal transplant recipients with long-term follow-up and relatively good renal function, other potentially modifiable risk factors appear to be better predictors of cardiovascular events. Consequently, the assessment of carotid atherosclerosis may not be clinically useful for the systematic identification of renal transplant recipients with an increased risk of developing cardiovascular events.     

Hypernephroma in the solitary kidney: experience with 20 cases and review of the literature

Twenty patients with renal cell carcinoma in anatomically or functionally solitary kidneys were treated and followed for up to 18 years. Factors pertinent to management and survival of these patients and 66 other well documented similar patients reported in the literature are analyzed. Most of the patients were unusually young and a significant number had had nephrectomy for contralateral renal cell carcinoma. Survival was closely related to the earlier presence of malignant disease in the other kidney, the duration of the interval between detection of the 2 neoplasms and the stage of the lesion in the solitary kidney. Partial nephrectomy has been the most successful treatment. The mean survival in the Mayo Clinic series has been 6 years for patients still alive and 2.4 years for those dead at the time of this analysis. Results in this and other series emphasize the importance of thorough long-term followup after nephrectomy for hypernephroma and of aggressive therapy when the remaining kidney becomes involved. It is foolhardy to abandon hope merely because there is a malignant tumor in a solitary kidney.     

Health related quality of life outcomes in patients treated for metastatic kidney cancer: a pilot study

The use of the immuno-suppressant cyclosporine A (CsA) after transplantation has been associated with less favorable plasma lipid profiles, which may contribute to the high incidence of cardiovascular morbidity and mortality in transplant recipients. Recent studies have suggested that oxidative modification of LDL plays an important role in the initiation and progression of atherosclerosis. It has also been demonstrated that CsA may facilitate lipid peroxidation in vitro and in vivo. Therefore, we determined several parameters of LDL oxidizability in renal transplant recipients who were switched from CsA to azathioprine (AZA)-based immunosuppressive treatment. The susceptibility of LDL to in vitro oxidation, LDL particle size, plasma titers of IgG and IgM antibodies against oxidized LDL and plasma LDL subclass patterns in 19 renal transplant recipients were determined during CsA treatment and 16 weeks after these patients were converted to AZA treatment. In addition, mean arterial pressure was recorded, and glomerular filtration rate and renal blood flow were estimated from the clearance of radiolabeled thalamate and hippurate. After conversion, the plasma concentrations of total cholesterol, LDL cholesterol and triglyceride decreased, while plasma HDL cholesterol did not change. During CsA therapy plasma LDL was significantly more susceptible to in vitro oxidation than during AZA, as reflected by a longer lag phase during in vitro oxidation (98.9 +/- 24.3 vs. 114.7 +/- 17.3 min, P = 0.031). In addition, the LDL size increased (236.5 +/- 7.3 vs. 240.7 +/- 6.8 nm, P = 0.00001), and the titers of IgM- and IgG-autoantibodies against oxidized LDL decreased significantly after patients were converted from CsA to AZA. The more atherogenic LDL subclass pattern B was present in 13 out of 19 patients during CsA. In five patients, pattern B changed into pattern A after conversion. The subclass B pattern was maintained in eight patients and subclass A pattern in six patients. In all patients the lag time of in vitro LDL oxidation increased, although the biggest changes were found in those patients in whom the LDL subclass changed from pattern B to pattern A. Mean arterial pressure decreased and renal function improved significantly after conversion. No correlation between parameters of lipid peroxidation and changes in blood pressure or renal function upon conversion, underlying renal disease, time since transplantation, or antihypertensive treatment was found. Our study demonstrates that treatment with CsA increases the susceptibility of LDL to in vitro oxidation, and also enhances the oxidation of LDL in vivo. In addition, conversion to AZA results in a more favorable lipid profile, which in combination with a lower arterial pressure and better renal function may decrease the risk for atherosclerosis. These factors may account for the cardiovascular complications during CsA treatment after organ transplantation, and also when CsA is used for other diseases.     

Inhibition of epithelial Na+ currents by intracellular domains of the cystic fibrosis transmembrane conductance regulator

Mucormycosis historically has caused substantial morbidity with high mortality in renal transplant patients with disseminated and/or rhinocerebral infection and in patients with gastrointestinal illness regardless of predisposing conditions. We report the first successful treatment of gastric mucormycosis in a renal transplant recipient and review presumed pathogenic mechanisms of mucormycosis in renal transplant recipients as well as historical data.     

Tetanus immunization and its association to hepatitis B vaccination in patients with chronic renal failure

A defect in the immune response of patients with chronic renal failure leads to low response rates and insufficient antibody concentrations following a number of highly recommended vaccinations. This has been shown before for immunization against hepatitis B and influenza. Few data are available concerning the efficacy of vaccination with tetanus toxoid in these patients. In a prospective, controlled study we vaccinated seronegative patients with chronic renal failure not on dialysis, patients on chronic intermittent hemodialysis, and patients after kidney transplantation with tetanus toxoid. The results were compared with those of a control group consisting of 13 age-matched patients with mild essential hypertension and normal kidney function. Only 11 of 20 (55%) patients in the chronic renal failure group and 16 of 23 (69%) in the dialysis group had a protective antibody response after triple vaccination. In contrast, all the patients in the control group and six of seven transplant patients seroconverted. The response to tetanus toxoid was highly associated with the response to a previously administered vaccination against hepatitis B. Responders to this vaccination also had a better response rate to tetanus toxoid. The antibody concentrations after vaccination were lower in all patient groups compared with the controls; the lowest titers were found in the transplant patients. Therefore, renal patients will need revaccination much earlier, and tetanus toxoid antibody levels should be checked if a patient is injured and potentially requires vaccination.     

Long-term improvement in renal function after cyclosporine reduction in renal transplant recipients with histologically proven chronic cyclosporine nephropathy

BACKGROUND: Chronic cyclosporine (CsA) nephropathy, which has been unequivocally documented in recipients of heart, heart-lung, liver, or bone marrow transplants, as well as in nontransplant situations, usually results in a progressive deterioration of renal function. In this study, we assessed the potential reversibility of chronic CsA nephropathy in renal transplant recipients. PATIENTS AND METHODS: Twenty-three renal transplant patients with biopsy-proven CsA nephropathy associated with long-term CsA administration (27+/-4 months) were followed up for more than 2 years after CsA reduction (18/23 patients) or withdrawal (5/23 patients) and addition of azathioprine. Changes in effective renal plasma flow and glomerular filtration rate were assessed before and 2 years after CsA reduction, whereas serum creatinine, proteinuria, blood pressure, and CsA concentrations were monitored up to 5 years. RESULTS: At 2-year follow-up, glomerular filtration rate increased from 40+/-3 to 47+/-4 (P<0.05) and effective renal plasma flow from 217+/-23 to 244+/-24 ml/min/1.73 m2 (NS). Mean arterial pressure significantly decreased from 98.7+/-2.9 to 93.1+/-2.7 mmHg (P<0.05). There was no significant change in renal vascular resistance, filtration fraction, or albumin excretion. A significant decrease in serum creatinine was also observed during the whole follow-up (73+/-6.5 months). CsA reduction was followed by only one episode of acute reversible rejection; chronic rejection developed in three patients 2 years or later after CsA reduction. CONCLUSIONS: These data suggest that CsA nephropathy participates in graft dysfunction in a small group of renal transplant recipients. In addition, graft dysfunction may be reversible when CsA dosage is reduced early after diagnosis of chronic CsA nephropathy.     

Membranous glomerulonephritis associated with hepatitis C virus infection in renal transplant patients

BACKGROUND: Hepatitis C virus (HCV) infection has been described in association with various types of glomerular diseases, usually type I membranoproliferative glomerulonephritis and rarely membranous glomerulonephritis (MGN). In this article, we describe the first series of MGN exhibited in renal transplant patients and associated with HCV infection. METHODS: From January 1980 to December 1994, 2045 kidney transplantations were performed in our renal transplant units. A retrospective analysis demonstrated an overall 20% prevalence of HCV virus-positive patients; 409 transplanted patients were HCV positive (ELISA and RIBA). RESULTS: Fifteen patients developed an allograft MGN (3.66%) 24 months after renal transplantation. MGN appeared in the form of significant proteinuria (>1.5 g/24 h) with stable renal function. In all cases, graft biopsy demonstrated a thickening of the capillary wall, subepithelial electron-dense deposits, and IgG and C3 diffuse granular deposits along the basal membrane. Ten cases were considered de novo, two cases were considered recurrent MGN, and three cases were considered undetermined because the primary renal disease was chronic glomerulonephritis. All patients showed negative antinuclear antibodies and cryoglobulins, normal complement, and negative rheumatoid factors. During follow-up (an average of 2 years), 12 patients developed a progressive worsening of renal function, with increased serum creatinine and persistent proteinuria; 8 of the 12 patients returned to dialysis. Of the remaining three cases, two patients showed partial remission of nephrotic syndrome after high doses of steroids, and one patient persisted with stable renal function and proteinuria (<2 g/24 h.). CONCLUSIONS: In summary, HCV is preferentially associated with MGN in renal transplant patients, rather than with membranoproliferative glomerulonephritis as in the normal adult population. MGN associated with HCV infection has a similar clinical picture and outcome to posttransplant idiopathic de novo MGN, with persistent massive proteinuria and progressive deterioration of renal function.     

Bone mineral recovery after parathyroidectomy in patients with primary and renal hyperparathyroidism

Patients with hyperparathyroidism (HPT) generally display reduced bone mass due to excessive PTH activity. The effect of parathyroidectomy on bone mass changes in different types of HPT, however, is not well understood. Bone mineral density (BMD) was measured in the distal radius, total body, femoral neck, and lumbar spine by dual energy x-ray absorptiometry in four groups of patients with different hyperparathyroid conditions: primary symptomatic HPT (n = 54), primary asymptomatic (mild) HPT (n = 24), HPT associated with hemodialysis (n = 20), and HPT associated with renal transplant (n = 30). Subsets of patients with primary symptomatic HPT (n = 52), HPT associated with hemodialysis (n = 19), and HPT associated with renal transplant (n = 15) underwent parathyroidectomy, and bone density was measured longitudinally for 3 yr. Patients with primary asymptomatic (mild) HPT did not undergo surgery and were followed prospectively. Before surgery, all groups showed a greater reduction of bone mineral density in cortical bone (distal radius) than in predominantly trabecular bone (lumbar spine). In primary symptomatic HPT, the BMD z-score of the distal radius was -1.80 +/- 0.21 (+/-SEM), and the corresponding figures for the total body, femoral neck, and lumbar spine were -0.60 +/- 0.15, -0.54 +/- 0.14, and -0.53 +/- 0.18 compared with those of an age- and sex-matched reference group. In renal HPT BMD z-scores were -2.51 +/- 0.38 (hemodialysis patients) and -2.83 +/- 0.43 (renal transplant patients) for the distal radius and between -0.81 and -1.46 for the other measured sites. After parathyroidectomy, BMD increased by 1-8% at all sites in patients with primary symptomatic HPT and HPT associated with renal transplant. The largest increase in bone mass was observed in patients with HPT associated with hemodialysis, in whom the improvement amounted to 7-23%. In patients with primary HPT and HPT associated with hemodialysis, this increase in bone density resulted in virtual recovery from their preoperative bone loss. The majority of patients with asymptomatic primary HPT disease (n = 21) maintained their bone density during the follow-up period and have not shown evidence of increases in serum calcium or PTH levels, but three patients followed conservatively underwent parathyroidectomy due to progressive deterioration of BMD. We conclude that, regardless of the etiology, a large proportion of HPT patients show reduced bone density. In patients with primary symptomatic HPT and patients with HPT associated with hemodialysis, bone density increases after parathyroidectomy to an extent that largely restores the preoperative bone loss. However, no anabolic effect of parathyroidectomy on bone mass was observed in patients with HPT associated with renal transplant, probably because of their immunosuppressive therapy.     

The use of pamidronate in three children with renal disease

The successful use of pamidronate, a bisphosphonate, for the treatment of hypercalcemia and/or osteopenia is reported in three children with renal failure or following renal transplant. Patient 1 was an 11-year-old post renal transplant male who received a single dose of i.v. pamidronate (0.5 mg/kg) for the treatment of acute hypercalcemia associated with a pathological fracture and subsequent immobilization. Prompt resolution of the hypercalcemia was seen. He received a second course of pamidronate (0.5 mg/kg per day for 3 days) for the treatment of osteopenia and has had a subsequent 15% increase in lumbar spine bone mineral content (BMC). Patient 2, a 14-year-old male on peritoneal dialysis, presented with symptomatic hypercalcemia associated with tertiary hyperparathyroidism. A single dose of i.v. pamidronate (0.4 mg/kg) was given with prompt resolution and prolonged control of his hypercalcemia. The third patient was a 16-year-old female, also in renal failure on peritoneal dialysis. Her course had been complicated by marked osteopenia. I.v. pamidronate (0.5 mg/kg per dose) was given on 3 successive days before and after renal transplant in an attempt to stabilize her bone mineral density (BMD) around the time of renal transplantation, when additional glucocorticoid was necessary. Her total body BMC and BMD remained stable pre and post transplant. The treatment was effective and well tolerated in all three patients. Hence pamidronate is safe and effective for the management of hypercalcemia and osteopenia in children with renal failure and/or renal transplant.     

Effects of cyclosporin A withdrawal on renal function and renal stimulation in liver transplant patients treated with triple-drug immunosuppression for over 2 years

The influence of CsA withdrawal on the glomerular filtration rate (GFR) and the effective renal plasma flow (ERPF) was prospectively studied in nine stable liver transplant recipients. Before CsA withdrawal (test 1), and 6 months thereafter (test 2) the renal function was determined by measuring GFR and the ERPF with 125I-iothalamate and 131I-hippuran respectively. The renal function was also stimulated with dopamine, with an amino-acid infusion and a combination of both. After CsA withdrawal the GFR increased, median from 74 ml min-1 to 90 ml min-1, (P < 0.04). The ERPF also increased, median from 310 ml min-1 to 380 ml min-1, (P < 0.03). In test 1 as well as in test 2 the renal function could be stimulated, especially with dopamine. GFR and ERPF improved, even after more than 2 years of CsA treatment. These results suggest that long-term CsA treatment impairs the renal function, though in these liver transplant patients CsA treatment did not prevent afferent and efferent arteriolar vasodilatation after renal stimulation. This reversible intrarenal vasoconstriction during CsA treatment may predict renal improvement after CsA withdrawal.