Parathyroidectomy in patients on renal replacement therapy: an epidemiologic study

Secondary hyperparathyroidism is a frequent complication of long-term dialysis treatment, and despite recent advances in medical therapy, surgical parathyroidectomy (PTx) is necessary in a considerable number of uremic patients. A prevalence of PTx of 22% was reported in Europe in 1988 in patients on dialysis from 10 to 15 yr, but no large-scale epidemiologic study has been published since then. The aim of the study was to evaluate the prevalence, incidence, and risk factors for PTx in patients on renal replacement therapy (RRT) in Lombardy and to determine whether the incidence has changed over time. The study involved 14,180 patients included in the Lombardy Registry of Dialysis and Transplantation who received RRT for end-stage renal disease (ESRD) between 1983 and 1996. Cox-proportional hazards regression models were used to evaluate the risk factors of PTx, the explanatory covariates being age on admission to RRT, gender, underlying renal disease (nondiabetic or diabetic nephropathy), and dialysis modality (peritoneal dialysis or hemodialysis). The prevalence of PTx in the 7371 ERSD patients who were alive on December 31, 1996, was 5.5% and increased with the duration of RRT (9.2% after 10 to 15 yr, 20.8% after 16 to 20 yr). Similarly, the incidence of PTx increased from 3.3 per 1000 patient-years in patients who had been on RRT for <5 yr to 30 per 1000 patient-years in those receiving RRT for >10 yr. The Cox regression models showed that the relative risk for PTx was significantly higher in women and lower in elderly and diabetic patients. The relative risk for PTx (adjusted for gender, age, and nephropathy) was higher in the patients on peritoneal dialysis than in those on hemodialysis and decreased after transplantation. During the course of a follow-up of 7 yr, the incidence of PTx in patients who started RRT between 1990 and 1992 was no different from that observed in patients who started RRT between 1983 and 1985. In conclusion, the prevalence and incidence of PTx in patients receiving RRT in Lombardy is lower than that in Europe and Italy as a whole, as reported by the 1988 European Dialysis and Transplantation Association Registry; its frequency has not changed significantly during the past few years. The need for PTx decreases markedly after successful transplantation. The epidemiologic finding that the rate of PTx is greater in women, young patients, and individuals who do not have diabetes suggests the need for a more aggressive medical treatment of secondary hyperparathyroidism particularly in such patients.     

Parathyroidectomy in dialysis patients

Subtotal parathyroidectomy or total parathyroidectomy (PTx) with autotransplantation are surgical procedures considered while the patient is included on the waiting list for renal transplantation. Total PTx alone is based in the possibility that a fragment of tissue (nodular hyperplasia in particular) left in the same pathophysiological environment of long term dialysis would show the same behavior and reproduce in time the same clinicopathological picture. The persistence of uremia induces a continued growth stimulus developing residual hyperplasia and consequently a very high risk of recurrence. We performed total PTx alone in 15 uremic patients excluded for renal transplantation 10 patients with undetectable iPTH serum concentration and were followed up for 37 to 144 months. There was no evidence of clinical bone disease (bone pain or fractures). Bone mineral lumbar spine and hip density was measured at the end of follow-up. The z score data showed that all patients had a bone mass similar than that expected for their age. Bone biopsies performed in four patients showed a uniform picture of low turnover without aluminium staining. Calcification of small arteries (digital and arcade vessels in hands and feet) were evaluated pre and post total PTx alone in nine out of the 10 patients with undetectable PTH levels.The small vessel calcification was present in five patients at the moment of PTx. At the end of the long term follow-up only one patient showed progression. In conclusion, total PTx without autotransplantation is a very effective and adequate treatment for refractory severe hyperparathyroidism in patients excluded for renal transplantation. Aluminium related osteopathy post PTx is a risk to be controlled with aluminium "free" dialysis water and avoiding aluminium containing phosphate binders.     

Analysis of patients dying within one year of starting renal replacement therapy

BACKGROUND: The annual gross mortality of end-stage renal failure patients remains very high (approximately 15-20%) leading some to question the wisdom of accepting patients with limited prognosis for dialysis. We have reviewed the demographic and clinical characteristics of patients who died within a year of commencing renal replacement therapy (RRT) over a 5-year period to establish whether these patients could be identified at the start of therapy. METHODS: Case notes of patients who died within 1 year of commencing RRT between 1st April, 1991 and 31st March, 1996 were reviewed. Comorbidity at the start of dialysis was used to classify patients into high-, medium- and low-risk groups using two published scales to determine whether either graded a high proportion of deaths as high risk. Factors such as age, social circumstances, cause of death, renal diagnosis and mode of dialysis were also analysed. RESULTS: 17.5% of patients commencing RRT died in the first year. Not all of these patients could be identified as high risk by comorbidity assessment at dialysis initiation - 50% of patients who died were classified by one scale as medium risk. Age did not clearly predict outcome, as 42% of patients who died were less than 65 years old. CONCLUSION: These data suggest that it is difficult to use current risk stratifications to accurately predict outcome on RRT.     

Identification of risk factors on secondary hyperparathyroidism undergoing long-term haemodialysis with vitamin D3

In order to evaluate the clinical outcome as well as the effectof vitamin D3 treatment on secondary hyperparathyroidism (SHPT)in the patients undergoing long-term dialysis therapy, we conducteda long-term follow-up survey on the demographic characteristicsof 425 patients who were observed for more than 3 years. Allpatients were treated with daily 1(OH)D3 treatment after theinitiation of dialysis. Among them the percentage of patientsneeding parathyroidectomy was 4.9% aggravation of SHPT, 11.8%an increase of the parathyroid hormone (PTH) level without radiographicalabnormalities, 17.4% stable, 56.2% and a decrease of the PTHlevel, 9.7% at the final observation. The average PTH levelsincreased year by year irrespective of the difference of originalrenal disease. Gender, age at the start of dialysis, originalrenal disease, duration of dialysis treatment, the decade ofstarting dialysis, the degree of phosphate control, and thePTH level at starting dialysis were analysed as potential riskfactors for SHPT, and assessed by multivariate analysis. Multivariateanalysis revealed that only the terms of duration of dialysisand the PTH level at starting dialysis were the significantrisks for developing overt SHPT. Logistic regression analysisrevealed that the relative risk was significantly higher inthe patients with more than 10 years history of dialysis andin those with the carboxyterminal PTH levels at the start ofdialysis being more than 5 ng/ml. These results suggest thatthe treatment with daily low-dose vitamin D3 administrationafter dialysis initiation is imperfect; therefore some prophylactictherapy from the predialysis stage is necessary to prevent overtSHPT, which will occur after long-term haemodialysis.     

Survival and development of cardiovascular disease by modality of treatment in patients with end-stage renal disease.

Patients undergoing dialysis are at high risk for cardiovascular disease (CVD). The aim of this study was to evaluate the influence of hemodialysis (HD) versus peritoneal dialysis (PD) on survival and the risk of developing de novo CVD. Of the 4191 patients with end-stage renal disease (ESRD) who started renal replacement treatment (RRT) in Lombardy between 1994 and 1997, 4064 (who were on dialysis 30 d after the start of RRT) were considered for survival analysis: 2772 were on HD (mean age 60.9 yr; 21.2% diabetic) and 1292 on PD (mean age 63.6 yr; 16% diabetic). The 3120 patients who were free of CVD at the start of RRT were included in the analysis of the risk of developing de novo CVD. HD and PD were compared by use of a Cox-regression proportional hazard model, stratified by diabetic status; the explanatory covariates were age and gender. The death rate was 13.3 per 100 patient-years (13.0 on HD and 13.9 on PD); 197 (6.3%) of the 3120 patients included in the CVD analysis developed de novo CVD (128 on HD and 69 on PD). After adjustment for age, gender, and established CVD and stratification by diabetic status, there was no significant between-treatment difference in 4-yr survival (relative risk [RR], 0.91; 95% confidence interval [CI], 0.79 to 1.06). The risk of de novo CVD did not differ significantly by treatment modality (RR, 1.06; 95% CI, 0.79 to 1.43). The risk of mortality and de novo CVD for new patients with ESRD assigned to HD or PD was similar in Lombardy in the period 1994 through 1997.     

Effect of having a functioning cadaveric renal transplant on cardiovascular mortality risk in patients on renal replacement therapy

Our aim was to estimate the effect of having a functioning cadavericrenal transplant on the risk of cardiovascular and total mortalityin patients on renal replacement therapy (RRT). We retrospectivelystudied (by the Cox proportional hazards regression model) 195subjects who began RRT with maintenance dialysis in our centrefrom 1 January 1978 to 31 December 1991. Out of this number,76 patients received a cadaveric kidney transplant. Cardiovascular abnormalities at the onset of RRT were the principalindependent determinant of both total and cardiovascular mortalityrisk. As compared to patients on dialysis with the same durationof RRT, patients with a functioning renal transplant for morethan 1 year had a significantly lower total mortality risk (meanrelative risk (RR): 0.48 (0.25–0.91) (95% confidence limitsin parentheses), P=0.03), an effect whose significance disappearedafter adjustment for pretreatment conditions (RR=0.62 (0.30–1.30),P>0.3). However, the beneficial effect of a functioning renaltransplant for more than 1 year on cardiovascular mortalityrisk was significant, both before (RR=0.21 (0.06–0.74),P=0.02) and after the adjustment for pretreatment conditions(RR=0.32 (0.11–0.90), P=0.035). During the first yearafter a successful transplantation the beneficial effect ofhaving a functioning transplant on cardiovascular mortalityrisk was only weakly attenuated. During RRT a functioning cadaveric renal transplant decreasescardiovascular mortality risk partially independently of thebetter pretreatment status of the patients selected for transplantation.     

Renal survival and prognostic factors in patients with PR3-ANCA associated vasculitis with renal involvement

BACKGROUND: Severe renal disease is a feature of anti-neutrophil cytoplasmic antibodies (ANCA)-associated small-vessel vasculitis. We evaluated patient and renal survival and prognostic factors in patients with PR3-ANCA associated vasculitis with renal involvement at diagnosis during long-term follow-up. METHODS: Eighty-five patients were diagnosed between 1982 and 1996 and followed until 2001 allowing >or=5 years of follow-up. All patients were treated with prednisolone and cyclophosphamide. Univariate and multivariate analyses with patient and renal survival as dependent variables were performed. RESULTS: Of the 85 patients in this study, 17 (20%) died within one year after diagnosis. Of the 25 patients (29%) who were dialysis dependent at diagnosis, two remained dependent and two again became dialysis dependent after less than one year; nine died early without renal recovery. Risk factors for death occurring within one year in univariate analysis (RR, 95% CI) were age>65 years (6.5, 1.6-13.7) and dialysis dependency at diagnosis (3.6, 1.0-13). Twenty patients died beyond one year during the long-term follow-up. Male gender (4.7, 1.6-10) and developing dialysis dependency during follow-up (4.1, 1.4-12) were associated with poor outcome. Risk factor for renal failure within one year was dialysis dependency at diagnosis (29, 3.6-229). Of 64 patients dialysis independent one year after diagnosis, 12 patients became dialysis dependent during follow-up. A renal relapse was strongly associated with development of renal failure in long-term follow-up (17, 3.5-81). CONCLUSIONS: Early death and failure to recover renal function in PR3-ANCA associated vasculitis is associated with age> 65 years and dialysis dependency at diagnosis. Long-term renal survival is determined by renal relapses during follow-up only. Slow, progressive renal failure without relapses is rarely observed in this group.     

Why do patients known to renal services still undergo urgent dialysis initiation? A cross-sectional survey.

BACKGROUND: Unplanned, urgent initiation of renal replacement therapy (RRT) is associated with poorer outcomes than planned initiation. However, in many services worldwide, substantial numbers of patients still do not begin treatment electively. The aim of this study was to identify numbers of and possible risk factors for, patients starting unplanned RRT despite being known to renal services for > or =4 months. METHODS: A retrospective survey of electronic and medical records was conducted of patients starting RRT in a large regional UK renal network in 2003. Data extracted included information on demographic, biochemical and treatment factors. Patients were classified as known acute (starting dialysis urgently yet known to renal services > or =4 months) or elective (starting RRT in a planned manner with a fistula or peritoneal dialysis catheter). Urgent dialysis was defined as starting either with a haemodialysis catheter or as an inpatient. Logistic regression was used to identify factors predicting an urgent dialysis start. RESULTS: Data from 109 of the 126 eligible patients were included; 60 elective, 49 known acute. Reasons for presenting as known acute were illness (21), service (24) and patient related (17). More than one reason was identified for 11 patients. The known acute group had more severe anaemia and lower glomerular filtration rates. Fewer known acute patients had attended dedicated predialysis clinics (90% increased odds of known acute start for non-attendance, P = 0.001) and patient dialysis information sessions (P = 0.020). Dialysis counselling had begun sooner in elective patients (P = 0.003). Odds of an urgent dialysis start increased by 4% with each year of age (P = 0.024). CONCLUSIONS: Early dialysis education and predialysis clinic attendance were associated with greater likelihood of elective dialysis initiation. Further studies are required to determine the cost effectiveness of these interventions, but services that initiate RRT urgently in a high proportion of patients should consider improving predialysis clinic attendance and early dialysis education.     

Can we improve early mortality in patients receiving renal replacement therapy?

BACKGROUND: Approximately one in eight patients with end-stage renal disease (ESRD) die within the first three months of starting renal replacement therapy (RRT). We investigated which factors might improve this early mortality. METHODS: We performed a prospective nationwide study of all patients commencing RRT for ESRD in Scotland over one year. Patients were classified according to how they presented to start RRT, their burden of comorbid diseases, access prepared for dialysis, and duration of care by a nephrologist prior to commencing RRT. Those factors most strongly associated with death within 90 days of commencing treatment were determined by logistic regression analysis. RESULTS: Patients with an acute unexpected element to their presentation for RRT had early mortality rates between 6.0 and 8.9 times greater than those who commenced RRT electively after a period of care from a nephrologist. Patients in high and medium comorbidity risk groups had early mortality rates of 4.7 and 2.2 times greater than those in the low-risk group. Low serum albumin had a significant association with early death. Patients who progressed steadily to ESRD, who had a planned start to dialysis, and who had mature access were 3.6 times more likely to survive beyond three months than those with no access; they were, however, also younger with less comorbidity. CONCLUSIONS: The factors principally associated with early mortality are nonelective presentation for RRT, comorbid illness, and low serum albumin. Patients cared for by a nephrologist before requiring RRT who have mature access have better short-term survival than those without access. They are also younger with less comorbidity. It may be possible to improve short-term survival in this "unplanned" group if referred early to facilitate reducing cardiovascular risk factors and preparation for RRT.     

Ten-years trends in renal replacement therapy for end-stage renal disease in mainland France: Lessons from the French Renal Epidemiology and Information Network (REIN) registry

BackgroundThe incidence rate of renal replacement therapy (RRT) for end-stage renal disease (ESRD) is decreasing in several countries, but not in France. We studied the RRT trends in mainland France from 2005 to 2014 to understand the reasons for this discrepancy and determine the effects of ESRD management changes.MethodsData were extracted from the French Renal Epidemiology and Information Network registry. Time trends of RRT incidence and prevalence rates, patients’ clinical and treatment characteristics were analysed using the Joinpoint regression program and annual percentage changes. Survival within the first year of RRT was analysed using Kaplan-Meier estimates for 4 periods of time.ResultsThe overall age- and gender-adjusted RRT incidence rate increased from 144 to 159 individuals per million inhabitants (pmi) (+0.8% per year; 95% CI: 0.5–1.2) and the prevalence from 903 to 1141 pmi (+2.4% per year; 95% CI: 2.2–2.7). This increase concerned exclusively ESRD associated with type 2 diabetes (+4.0%; 3.4–4.6) and mostly elderly men. Despite patient aging and increasing comorbidity burden and a persistent 30% rate of emergency dialysis start, the one-year survival rate slightly improved from 82.1% (81.4–82.8) to 83.8% (83.3–84.4). Pre-emptive wait listing for renal transplantation and the percentage of wait-listed patients within one year after dialysis start strongly increased (from 5.6% to 15.5% and from 29% to 39%, respectively).ConclusionKidney transplantation and survival significantly improved despite the heavier patient burden. However, the rise in type 2 diabetes-related ESRD and the stable high rate of emergency dialysis start remain major issues.     

Incidence and Risk Factors of Persistent Hyperparathyroidism After Kidney Transplantation

Persistent hyperparathyroidism after kidney transplantation is related to graft function, but pre-transplantation risk factors of persistent hyperparathyroidism have not been evaluated in detail. We enrolled 86 patients who had undergone kidney transplantation between 2008 and 2014. Nine patients showed persistent hyperparathyroidism characterized by the following: 1) serum parathyroid hormone levels >65 pg/mL and serum calcium levels >10.5 mg/dL at 1 year after kidney transplantation; 2) parathyroidectomy after kidney transplantation; and 3) reintroduction of cinacalcet after kidney transplantation. Compared with other patients, these 9 patients had significantly longer duration of dialysis therapy (186 ± 74 mo vs 57 ± 78 mo) and more frequent treatment with cinacalcet during dialysis (89% vs 12%). Multivariate analysis showed that dialysis vintage, calcium phosphate products, and cinacalcet use before kidney transplantation were independent risk factors of persistent hyperparathyroidism after kidney transplantation. A receiver operating characteristic curve showed 72 months as the cutoff value of dialysis vintage and 55 as the cutoff value of calcium phosphate products. In conclusion, dialysis vintage >6 years, calcium phosphate products >55 (mg/dL)², and cinacalcet use before kidney transplantation are strong predictors of persistent hyperparathyroidism. High-risk patients should be evaluated for parathyroid enlargement, and parathyroidectomy must be considered before kidney transplantation.     

Agalsidase therapy in patients with Fabry disease on renal replacement therapy: a nationwide study in Italy.

BACKGROUND: In Fabry disease, end-stage renal disease (ESRD) and severe neurologic and cardiac complications represent the leading causes of late morbidity and mortality. A comprehensive Italian nationwide survey study was conducted to explore changes in cardiac status and renal allograft function in Fabry patients on renal replacement therapy (RRT) and enzyme replacement therapy (ERT). METHODS: This study was designed as a cross-sectional survey study with prospective follow-up. Of the 34 patients identified via searches in registries, 31 males and 2 females who received RRT and ERT (agalsidase beta in 30 patients, agalsidase alpha in 3) were included. Left ventricular mass index (LVMI), interventricular septal thickness at end diastole (IVSD), left ventricular posterior wall thickness (LVPWT) and renal allograft function were assessed at ERT baseline and subsequently at yearly intervals. RESULTS: The patients in the dialysis and transplant groups had been started on dialysis at age 42.0 and 37.1 years (mean), respectively, and patients in the transplant group received their renal allograft at age 39.8 years (mean). The mean age at the start of ERT was similar, 44.1 and 44.6 years, respectively. The mean RRT follow-up was 61.1 and 110.6 months for dialysis and transplant patients, respectively, whereas the ERT duration was 45.1 and 48.4 months, respectively. Cardiac parameters increased in dialysis patients. In transplant patients, mean LVMI seemed to plateau during agalsidase therapy at a lower level as compared to baseline. Decline in renal allograft function was relatively mild (-1.92 ml/min/year). Agalsidase therapy was well tolerated. Serious ERT-unrelated events occurred more often in the dialysis group. CONCLUSIONS: Kidney transplantation should be the standard of care for Fabry patients progressing towards ESRD. Transplanted Fabry patients on ERT may do better than patients remaining on maintenance dialysis. Larger, controlled studies in Fabry patients with ESRD will have to demonstrate if ERT is able to change the trajectory of cardiac disease and can preserve graft renal function.     

Time trends in initiation and dose of dialysis in end-stage renal disease patients in The Netherlands.

BACKGROUND: The guidelines published by the NKF-Dialysis Outcomes Quality Initiative (DOQI) in 1997 advocate an earlier start of dialysis in ESRD patients and a higher dialysis dose than usual. We studied the possible influence of the increasing emphasis on adequate dialysis on the management of ESRD patients in The Netherlands in 1993-2000. METHODS: The NECOSAD study on the adequacy of dialysis started in 1993. This prospective multi-centre study included ESRD patients older than 18 years who started HD or PD as the first RRT. We analysed the distribution of age, gender, primary renal disease and co-morbidity, the mean residual renal function and the mean dialysis-Kt/V(urea) at 3 months in 1569 consecutive patients by calendar year of initiation dialysis. RESULTS: Age, gender, primary renal disease and number of co-morbid conditions at the start of dialysis remained stable over time between 1993 and 2000. The mean renal Kt/V(urea) at 3 months increased from 0.5 in 1993 to 0.8 per week in 2000 (P<0.01). An upward trend remained after adjustment for patient characteristics and dialysis centre. The total Kt/V(urea) at 3 months increased from 3.3 in 1993 to 3.7 per week in 2000 in HD (P<0.01) and from 2.0 in 1993 to 2.3 per week in 1999 in PD patients (P<0.01). An upward trend in the dialysis-Kt/V(urea) was found after adjustment for renal Kt/V(urea) (HD: +0.3 per week, P=0.06; PD, +0.2 per week, P<0.05). CONCLUSIONS: These results indicate a tendency towards earlier introduction of RRT and higher doses of dialysis in The Netherlands. Possible effects of this development on mortality, morbidity, quality of life and the balance between costs and benefits need further investigation.     

Timing of nephrology referral: a study of its effects on the likelihood of transplantation and impact on mortality

SUMMARY: Delayed referral of patients with end-stage renal disease (ESRD) to a nephrologist is associated with considerable early morbidity and increased mortality. the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) has collected data regarding the timing of referral to a nephrologist for all patients beginning renal replacement therapy (RRT) since 1 April 1995. We examined survival and likelihood of transplantation for patients who started RRT between 1 April 1995 and 31 December 1998, with follow-up until 31 March 2000 (up to 5 years follow-up). of 4886 patients starting RRT, 1277 (26.1%) were in the late referral (LR) group and 3609 (73.9%) were not (NLR). In a multivariate analysis, predictors of LR were age 0–44 years and the presence of two or more comorbidities. Ninety days after referral, 60% of patients in the LR group were on haemodialysis compared with 55% of patients in the NLR group; 40% of patients in each group were receiving peritoneal dialysis at this time. Patients in the LR group were significantly less likely to receive a transplant in the first year after referral and throughout the duration of the study compared with the NLR group. Mortality rates were 19 and 13 persons per 100 patient years in the LR and NLR groups, respectively. In conclusion, delayed referral to a nephrologist was associated with increased mortality which continued for up to 5 years, even after adjustment for known predictors of mortality including age, sex, comorbidities and primary renal disease.     

Serum erythropoietin and erythropoiesis in primary and secondary hyperparathyroidism: effect of parathyroidectomy.

Primary as well as secondary hyperparathyroidism may be associated with anemia, and parathyroidectomy (PTx) may improve or even heal it. The precise link between the two conditions is still matter of discussion. The purpose of the present study was to investigate possible effects of PTx on serum immunoreactive erythropoietin (iEPO) in secondary (group I, n = 23), and primary (group II, n = 16) hyperparathyroidism patients, and in 3 patients undergoing cervicotomy for thyroid mass removal (group III). In group I patients, circulating iEPO levels rose from 23.1 +/- 4.8 mU/ml before PTx to 28.2 +/- 5.0 and 245 +/- 125 mU/ml (mean +/- SEM) at day 7 (p = NS) and 14 after PTx (p less than 0.003), respectively. Reticulocyte count increased 2 weeks after PTx: from 61,000 +/- 13,317 to 86,533 +/- 13,462/mm3 (p less than 0.05, n = 23). In 4 of these patients serum iEPO levels could be measured again 12-24 months after PTx. They were slightly higher than those determined before PTx: 37.0 +/- 8.4 versus 31.8 +/- 13.5 mU/ml. Their hematocrits were also higher than before PTx: 12.8 +/- 0.9 versus 11.0 +/- 0.9 g/dl. In group II patients, serum iEPO levels remained unchanged after PTx: 17.5 +/- 2.0 mU/ml before PTx and 20.0 +/- 3.0 mU/ml 14 days PTx. The reticulocyte count, however, increased significantly 2 weeks after PTx: from 25,103 +/- 3,000 to 40,827 +/- 4,080/mm3 (p less than 0.01). In group III patients, serum iEPO, reticulocyte count, and hemoglobin remained stable after surgery. Since all group I patients had received vitamin D supplementation after PTx, we studied an additional group of 14 chronic dialysis patients (group IV) who received either calcitriol (1 micrograms/day, n = 7) or placebo (n = 7) during 14 days. The patients on calcitriol treatment, but not those on placebo, had a significant decrease of serum iEPO: 18.6 +/- 4.9 versus 16.0 +/- 4.2 mU/ml (p less than 0.03). In conclusion, PTx led to a striking increase of serum iEPO and blood reticulocytes in uremic patients with secondary hyperparathyroidism, and an increase of reticulocyte count, but not of iEPO, in patients with primary hyperparathyroidism. Marked changes of circulating PTH, extra-or intracellular calcium and phosphorus concentrations as well as of tissue sensitivity to EPO after PTx could all be responsible. In contrast, the surgical procedure and the therapeutic increase in plasma calcitriol do not appear to be involved.     

Temporal association between the incidence of foot ulceration and the start of dialysis in diabetes mellitus.

BACKGROUND: The aim of this study was to seek a temporal association between the start of renal replacement therapy (RRT) and the first recorded foot ulcer in diabetes. METHODS: Details of all patients with diabetes who had received RRT were extracted from the renal database and were cross-checked with the database held in the specialist foot clinic. The date of onset of first registered foot ulcer was taken and compared with the date of onset of RRT. The self-controlled case-series method was used to establish any significant temporal association between the start of RRT and first recorded foot ulcer in diabetes. RESULTS: Of 466 patients with diabetes dialysed at our hospital since 1976, 94 (20.2%) were recorded as having at least one foot ulcer, with 15 of these undergoing major amputation. Incidence ratios (IRs) were calculated for 90 patients in whom complete data were available. A close temporal association was observed between the start of RRT and the first recorded foot ulceration: IR (95% CI) in the first and between the second and fifth years of dialysis were 3.35 (95% CI: 1.59-7.04), and 4.56 (2.19-9.50), respectively, relative to the time before dialysis. The IR for major amputation was 31.98 (2.09-490.3) in the first year and 34.01 (1.74-666.2) in the second to fifth years. CONCLUSION: These results reveal a close relationship between the onset of RRT in diabetes and the onset of foot ulceration, and confirm the high incidence of amputation in those on dialysis. Urgent steps should be taken to coordinate all aspects of diabetes foot care before and after the start of RRT.     

Cardiovascular disease determinants in chronic renal failure: clinical approach and treatment.

INTRODUCTION: Cardiovascular disease (CVD), as the leading cause of morbidity and mortality in patients on renal replacement therapy (RRT), has a central role in everyday nephrological practice. METHODS: Consensus was reached on key points relating to the clinical approach and treatment of the main cardiovascular risk factors in RRT patients (hypertension, anaemia, hyperparathyroidism, dyslipidaemia, new emerging risk factors). In addition, the role of convective treatments on cardiovascular outcomes was examined. RESULTS: Hypertension should be managed by aiming at blood pressure values of < or =140/90 mmHg (< or =160/90 mmHg in the elderly), firstly by ensuring target dry body weight is achieved. No single class of drug has proved superior to others in RRT patients, provided that the blood pressure target is achieved, although ACE inhibitors have shown specific organ protection in high-risk patients (HOPE study) and are well tolerated. Anaemia should be managed by using erythropoietin and iron supplements, aiming at haemoglobin levels of 12 g/dl and keeping serum ferritin levels < 500 ng/ml. The management of hyperparathyroidism is currently unsatisfactory, as calcium supplements have the potential to increase cardiovascular calcification. While awaiting new calcium- and aluminium-free phosphate binders, it is essential to ensure dialysis adequacy. Clinical studies are in progress to assess the real impact of lipid-lowering drugs in RRT. In the meantime, serum LDL-cholesterol < 160 mg/dl and triglycerides < 500 mg/dl may be desirable targets. The impact of new emerging risk factors (inflammation and chronic infection, hyperhomocysteinaemia, metabolic waste-product accumulation) and their proper management are still under research. Convective dialysis treatments may confer some degree of protection from dialysis-related amyloidosis and mortality, but clinical data on this important issue are still controversial and no definitive conclusions can be drawn at present. CONCLUSION: CVD prevention and treatment is a great challenge for the nephrologist. Achieving evidence-based consensus can help in encouraging the implementation of best clinical practice in line with the progress of current knowledge.     

Importance of blood pressure control in hemodialysis patient survival

BACKGROUND: In the general population, hypertension is the leading cause of cardiovascular mortality. In dialysis patients, however, the relationship between blood pressure (BP) and mortality is controversial. We analyzed this relationship in hemodialysis (HD) patients. METHODS: The study population included 405 patients who had survived at least two years on HD. The observation period was initiated at the beginning of the third year. Predialysis BP measurements of all the dialysis treatments performed during the second year of HD was collected as the baseline data. Mean systolic BP (SBP) and mean diastolic BP (DBP) were calculated. Demographic and comorbidity data were collected at the start of the observation period (beginning of third year of HD). Mortality was analyzed at the end of the follow-up (death or December 31, 1998; total mortality), during the first two years of follow-up (years 3 and 4 of HD; early mortality) and after the second year of follow-up (> or = 5 years of HD; late mortality). RESULTS: In the multivariate analysis, SBP and DBP were significantly associated with death. The adjusted total mortalities were U shaped. When early mortality was analyzed, only low BP (DBP <74.5 mm Hg) was significantly associated with mortality. When late mortality was analyzed, only high BP (SBP> 160 mm Hg) was significantly associated with mortality. In the early deaths, a cardiac cause was significantly less frequent, while withdrawal and malignancy were more frequent than in late deaths. CONCLUSIONS: This study confirms that hypertension is a risk factor for mortality in HD patients, and shows the importance of the length of the follow-up time to demonstrate this relationship. The low frequency of a cardiac cause in the early death group suggests that the association between hypotension and mortality in HD patients is not related to cardiovascular causes, and only reflects the association between hypotension and other severe medical conditions.     

Effects of a parathyroidectomy on the immune system and nutritional condition in chronic dialysis patients with secondary hyperparathyroidism

BACKGROUND: Parathyroid hormone (PTH) has an adverse effect on the immune system and may cause immunologic disorders in patients with chronic renal failure. The in vivo effects of a parathyroidectomy on the immunologic parameters was examined. METHODS: Thirty-four patients under dialysis therapy received a parathyroidectomy (PTx) for secondary hyperparathyroidism (HPT). They were prospectively studied regarding serum immunoglobulins, complements, CD markers, and serum soluble IL-2 receptor (sIL-2R) until 12 months after PTx. RESULTS: The serum levels of IgG, IgA and IgM showed significant increase until 12 months after PTx (P<0.001, respectively). C3, C4, and CH50 also indicated significant increase at 12 months after PTx. In cellular immunity, only serum sIL-2R showed significant increase 2 weeks after PTx (P = 0.028). The hematocrit and serum albumin also improved significantly at 12 months. CONCLUSIONS: PTx showed beneficial effects on humoral immunological markers. The effects are probably due to the remarkable PTH reduction and partly improved nutritional state after PTx.     

Natural history of claudication: Long-term serial follow-up study of 1244 claudicants

OBJECTIVE: The purpose of this study was to delineate the natural history of claudication and determine risk factors for ischemic rest pain (IRP) and ischemic ulceration (IU) among patients with claudication. METHODS: We prospectively collected data on 1244 men with claudication during a 15-year period, including demographics, clinical risk factors, and ankle-brachial index (ABI). We followed these patients serially with ABIs, self-reported walking distance (WalkDist), and monitoring for IRP and IU. We used Kaplan-Meier and proportional hazards modeling to find independent predictors of IRP and IU. RESULTS: Mean follow-up was 45 months; statistically valid follow-up could be carried out for as long as 12 years. ABI declined an average of 0.014 per year. WalkDist declined at an average rate of 9.2 yards per year. The cumulative 10-year risks of development of IU and IRP were 23% and 30%, respectively. In multivariate analysis using several clinical risk factors, we found that only DM (relative risk [RR], 1.8) and ABI (RR, 2.2 for 0.1 decrease in ABI) predicted the development of IRP. Similarly, only DM (RR, 3.0) and ABI (RR, 1.9 for 0.1 decrease in ABI) were significant predictors of IU. CONCLUSION: This large serial study of claudication is, to our knowledge, the longest of its kind. We documented an average rate of ABI decline of 0.014 per year and a decline in WalkDist of 9.2 yards per year. Two clinical factors, ABI and DM, were found to be associated with the development of IRP and IU. Our findings may be useful in predicting the clinical course of claudication.