Steroid withdrawal after long-term medication for immunosuppressive therapy in renal transplant patients: adrenal response and clinical implications

Background. Withdrawal of steroids should be attempted after organ transplantation because of their adverse cardiovascular and metabolic effects. However, immunological, haemodynamic and symptomatic complications may occur due to the suppression of endogenous corticoid hormone synthesis under exogenous steroid intake. We have examined the effect of chronic steroid medication on adrenocortical function, and of steroid withdrawal, in immunologically stable renal transplant patients. Methods. Sixty-three patients under long-term prednisone therapy (mean±SD 36±47 months) were assessed regarding basal fasting cortisol concentration and adrenocortical stimulation by the low-dose Synacten test both prior to and after stepwise prednisone withdrawal. Renal graft function (determined as the calculated glomerular filtration rate according to the Cockroft-Gault formula), mean arterial blood pressure and clinical status were evaluated concomitantly. Results. Basal fasting cortisol concentration was clearly suppressed in 14% of patients under long-term steroid medication, and adrenocortical stimulation by the low-dose Synacten test was impaired in 31% after steroid withdrawal. About a third of all patients were symptomatic with fatigue (60%), arthralgias (60%), muscular weakness (20%), loss of appetite (20%), hypotension (15%) or headaches (5%). The incidence of symptoms was much higher in patients with low basal fasting cortisol concentration prior to steroid withdrawal, and after >2 years of steroid medication. Renal graft function, determined as glomerular filtration rate, decreased only slightly overall by ∼5%, and was more pronounced in symptomatic vs asymptomatic patients (−7 vs −2 ml/min, respectively), as was the fall in mean arterial pressure (−10 vs −4.2 mmHg, respectively). Conclusions. Adrenal function is impaired in renal transplant patients receiving long-term steroid medication as part of their immunosuppressive regimen. This may lead to mainly symptomatic complications when steroids are withdrawn. The slight decrease in glomerular filtration rate probably can be ascribed mostly to the effect of steroids on systemic renal haemodynamics. It is recommended to consider cessation of steroid medication within 48 months of therapy, and after determination of basal cortisol to identify patients with potential complication

Time trends in the epidemiology of renal transplant patients with type 1 diabetes mellitus over the last four decades

Background. Diabetes mellitus (DM) type 1 is an important contributor to end-stage renal disease (ESRD) among younger transplant recipients. However, little is known about the changes in epidemiological characteristics of this population. Especially, time to reach ESRD may have changed in type 1 diabetic patients referred for transplantation, resulting in higher age at time of grafting. Such time trends may allow anticipating future developments regarding the demand for organ replacement in this patient group. Methods. We retrospectively analysed 173 patients with type 1 DM undergoing renal transplantation at our institution, stratified into four groups according to year of reaching ESRD (A = 1973-1983, B = 1984-1990, C = 1991-1995 and D = 1996-2002). For each group we determined age at diagnosis of DM, age at time of reaching ESRD and age at time of transplantation. From these data, the interval from diagnosis of DM to ESRD and from ESRD to transplantation was calculated. The results were analysed in relation to gender, year of and age at onset of diabetes. Results. Patients reaching ESRD in more recent years (group D) tended to be both younger at diagnosis of DM and older when reaching ESRD, resulting in higher mean age at transplantation (35.0, 37.5, 39.6 and 41.0 years in groups A, B, C and D, respectively). Accordingly, median duration to ESRD has significantly been prolonged over the last five decades in patients with type 1 DM undergoing renal transplantation (group A: 21.0, B: 20.7, C: 22.3 and D: 28.5 years; P<0.0001), this finding being more pronounced in female patients. Conclusions. The results of our analysis are compatible with a change in epidemiology in patients undergoing kidney transplantation. Older age at time of reaching ESRD may impact significantly on the demand for renal grafts, as patients are already clearly older nowadays when being transplanted. From our data it cannot be concluded whether this development is due to a change in the progression of diabetic nephropathy or may simply reflect a change in the selection of type 1 diabetic patients referred for transplantatio

CHONDROCALCINOSIS AND OSTEOPOROSIS IN A PATIENT WITH RENAL TUBULAR DISORDER

ABSTRACT We report the case of a 50-year old male patient presenting with a combination of chondrocalcinosis and osteoporosis related to a renal tubular disorder. Laboratory studies revealed hypokalemia, hypomagnesemia, hypocalcemia with renal wastage and metabolic alkalosis, compatible with a renal tubular transport disorder with similarities to Bartter&apos;s and Gitelman&apos;s syndrome. Calcifications of the menisci and cartilage on X-rays of knee joints suggested chondrocalcinosis, which has been associated with Gitelman&apos;s syndrome. Radiologically suspected osteopenia was confirmed by a bone density scan that revealed osteoporosis of the vertebral column. An association of osteoporosis with hypercalciuria, which commonly occurs in Bartter&apos;s syndrome patients, has been reported. Upon treatment of the renal tubular disorder with spironolactone and a thiazide diuretic in combination with calcium and magnesium supplementation, the electrolyte abnormalities resolved and arthralgias disappeared. Our case demonstrates a renal tubular dysfunction with features of both Bartter&apos;s and Gitelman&apos;s syndrome along with concurrent chondrocalcinosis and osteoporosis. Furthermore, the occurrence of osteoporosis in this relatively young patient, in the absence of other risk factors, demonstrates that renal tubular disorders should be suspected in presenile osteoporosis. Vice versa, since osteoporosis usually is asymptomatic before fracturing, patients with renal tubular disorders should be examined for osteoporosis

Weekly low-dose treatment with intravenous iron sucrose maintains iron status and decreases epoetin requirement in iron-replete haemodialysis patients

Background. Haemodialysis patients need sustained treatment with intravenous iron because iron deficiency limits the efficacy of recombinant human epoetin therapy in these patients. However, the optimal intravenous iron maintenance dose has not been established yet. Methods. We performed a prospective multicentre clinical trial in iron-replete haemodialysis patients to evaluate the efficacy of weekly low-dose (50 mg) intravenous iron sucrose administration for 6 months to maintain the iron status, and to examine the effect on epoetin dosage needed to maintain stable haemoglobin values in these patients. Fifty patients were enrolled in this prospective, open-label, single arm, phase IV study. Results. Forty-two patients (84%) completed the study. After 6 months of intravenous iron sucrose treatment, the mean ferritin value showed a tendency to increase slightly from 405 ± 159 at baseline to 490 ± 275 µg/l at the end of the study, but iron, transferrin levels and transferrin saturation did not change. The haemoglobin level remained stable (12 ± 1.1 at baseline and 12.1 ± 1.5 g/dl at the end of the study). The mean dose of darbepoetin alfa could be reduced from 0.75 to 0.46 µg/kg/week; epoetin alfa was decreased from 101 to 74 IU/kg/week; and the mean dose of epoetin beta could be reduced from 148 to 131 IU/kg/week at the end of treatment. Conclusions. A regular 50 mg weekly dosing schedule of iron sucrose maintains stable iron stores and haemoglobin levels in haemodialysed patients and allows considerable dose reductions for epoetins. Low-dose intravenous iron therapy may represent an optimal approach to treat the continuous loss of iron in dialysis patient

Pregnancy-associated plasma protein-A is an independent short-time predictor of mortality in patients on maintenance haemodialysis

Aims Mortality of maintenance haemodialysis (HD) patients is very high due to polymorbidity, mostly from metabolic and cardiovascular disease. In order to identify patients with high risk for life-threatening complications, reliable prognostic markers would be helpful. Pregnancy-associated plasma protein-A (PAPP-A) has been shown to predict cardiovascular events and death in patients with stable coronary artery disease as well as in acute coronary syndrome in patients with normal renal function. It was the aim of this study to evaluate PAPP-A as a marker for death in patients on maintenance HD. Methods and results PAPP-A serum levels were measured in 170 patients participating in the monitor! trial, a prospective dynamic dialysis cohort multicenter study in Switzerland. Patients were followed up for a median time of 17 months after measuring PAPP-A, and evaluated for death of any cause. Survivors and non-survivors were compared with regard to baseline PAPP-A concentrations. A multivariate logistic regression analysis for death was performed including PAPP-A, age, sex, number of comorbidities, dialysis vintage, Kt/V, IL-6, C-reactive protein, parathyroid hormone (PTH), Ca × PO4 product, and total serum cholesterol. A cut-off value for PAPP-A was calculated for discrimination between patients with low and high mortality risk, respectively. A total of 23 deaths occurred during follow-up, equalling an incidence rate of 0.1. Baseline median PAPP-A levels were 40% higher in non-survivors vs. survivors (P = 0.023). In a multivariate analysis, only PAPP-A, age, and Ca × PO4 product were independent predictors of mortality. A cut-off value of 24 mIU/L discriminates significantly (P = 0.015) between patients at low or high risk for death with a negative predictive value of 91%. Conclusion PAPP-A is a novel and independent short-time predictor of mortality in a maintenance HD population. The pathogenetic relevance of PAPP-A, particularly in the development of cardiovascular disease, remains to be further elucidate

Beneficial effect of early initiation of lipid-lowering therapy following renal transplantation

Background. Renal transplant recipients have a significantly reduced life expectancy, largely due to premature cardiovascular disease. The aim of the current analysis was to investigate the importance of time of initiation of therapy after transplantation, on the benefits of statin therapy. Methods. 2102 renal transplant recipients with total cholesterol levels of 4.0-9.0 mmol/l were randomly assigned to treatment with fluvastatin (n = 1050) or placebo (n = 1052) and followed for a mean time of 5.1 years. The end-points were major cardiac events. The average median time from transplantation to randomization was 4.5 years (range: 0.5-29 years). Results. In patients starting treatment with fluvastatin 6 years, respectively. The risk reduction for patients initiating therapy with fluvastatin at years 0-2 (compared with >6 years) following transplantation was 59% (RR: 0.41; 95% CI: 0.18-0.92; P = 0.0328). This is also reflected in total time on renal replacement therapy: in patients in the first quartile (120 months) (P = 0.033). Conclusions. Our data support an early introduction of fluvastatin therapy in a population of transplant recipients at high risk of premature coronary heart diseas