Anderson–Fabry disease: a case-finding study among male kidney transplant recipients in Austria

The diagnosis of Anderson–Fabry disease is often delayed or even missed. As severe renal manifestations are a hallmark of alfa-galactosidase A (AGAL) deficiency, we tested the hypothesis that Anderson–Fabry disease is under-recognized among male kidney transplant recipients. This nation-wide study in Austria enrolled 1306 patients (ca 65% of all kidney transplanted males) from 30 kidney centers. AGAL activity was determined from filter paper dried blood spots by a fluorescence assay. A positive screening test was defined by an AGAL activity below 1.5 nmol/h/ml. In patients with a positive blood spot-screening test, AGAL activity was re-examined in peripheral blood leukocytes. Genetic testing for mutations in the GLA gene was performed by sequencing to confirm the diagnosis of Anderson–Fabry disease. Two previously not recognized cases with Anderson–Fabry disease were identified. Our study is the first showing that a diagnosis of Anderson–Fabry disease can be missed even in patients who undergo kidney transplantation. Case-finding strategies may be considered a useful tool for diagnosis of this rare disease that may be somewhat more prevalent among kidney transplant recipients compared with dialysis populations.     

Chronic renal failure, dialysis, and renal transplantation in Anderson-Fabry disease

Anderson-Fabry disease (AFd) is a rare, inherited, x-linked disease characterized by the deficiency of the lysosomal enzymatic alpha-galactosidase A activity (alpha-Gal-A). The enzyme defect leads to progressive accumulation of glycosphingolipids (GL) in all kinds of cells, tissues, organs, and body fluids. The clinical manifestations are very protean, the residual activity of alpha-Gal-A and/or different gene mutations might explain different phenotypes, but as yet these concepts have not been proven. Usually, patients with AFd show 3 clinical phases, more evident in men than in heterozygous women. The first phase (childhood and adolescence) is characterized by myalgia, arthralgia, acroparesthesia, fever, cutaneous angiokeratomas, and corneal opacities. The second phase is characterized mainly by renal involvement. In the third phase, severe renal impairment and involvement of cerebrovascular and cardiovascular systems are present. The progression to end-stage renal disease (ESRD) is common in hemizygous males (3rd-5th decade of life); usually, death occurs because of cerebral and/or cardiovascular complications in patients undergoing chronic dialysis therapies. The survival of patients with AFd in dialysis is better than in diabetic patients, but it clearly is decreased compared with uremic patients with other nephropathies, despite a lower mean age of uremia (50 versus 60 y). The outcome of kidney transplantation is similar to that found in other patients with ESRD, despite controversial issues published in the past. The use of a kidney donor with normal alpha-Gal-A activity in the control of the metabolic systemic disease is unproven. The recurrence of GL deposits in the kidney graft has been documented rarely. The definitive treatment for AFd is enzyme replacement therapy with purified alpha-Gal-A produced by a genetically engineered human cell line or Chinese hamster oocytes: relatively short-term studies have shown a significant treatment effect on clinical outcome measures.     

Chronic renal failure: an epidemic?

End-stage renal disease affects more than 70,000 persons in France, i.e., 1,1 per 1000 people, of whom 53% are on dialysis and 47% are living with a functioning graft. This prevalence increases about 4% per year. Overall, end-stage renal disease incidence tends to stabilize, except in persons aged 75 years or older and in those with diabetes in whom it continues to rise. About 30% of the patients treated for end-stage renal disease start dialysis on an emergency basis, indicating the persistence and frequency of inadequate care in the advanced stage of chronic kidney disease, whatever the reasons for it. Screening of chronic kidney disease includes measures of both urinary albumin- or protein-to-creatinine ratio and serum creatinine, preferably with an enzymatic assay, and estimation of glomerular filtration rate with new equations such as MDRD. Highest priority for targeted screening include patients with diabetes, hypertension or cardiovascular disease. Screening should also be considered in the elderly, in those obese, exposed to toxic drugs, with family history of chronic kidney disease or with personal history of low birth weight, nephrectomy, kidney or urinary tract cancers or chronic infections. Chronic kidney disease stages 1 to 3 is about 100 times more common than end-stage renal disease, mortality risk at these stages being much higher than to progress to end-stage. In the elderly, chronic kidney disease is extremely common, affecting about one person older than 70 years out of three, but only a fraction, higher in men than women, may have clinically relevant markers requiring appropriate care. Glomerular filtration rate decline with age should be monitored regularly and drug doses adjusted in order to prevent adverse effects.     

Screening for Fabry disease in male patients with end-stage renal disease in western France

ContextFabry disease is a rare X-linked genetic disease due to pathogenic variants in the GLA gene. Classic Fabry disease is characterized by glycosphingolipids accumulation in all organs including the kidney, resulting in end-stage renal disease in a subset of male patients. Fabry disease should therefore be considered in the differential diagnosis of patients with unexplained end-stage renal disease.ObjectiveWe performed a prospective screening study in Western France to determine the prevalence of Fabry disease in a large population of dialyzed and transplanted patients.Patients and methodsPatients meeting the inclusion criteria (males, 18-70 years with end-stage renal disease of unknown or vascular origin) were selected from the REIN® registry and the CRISTAL® database. Screening on filter papers was performed after patient consent was obtained during either a dialysis session or a transplantation follow-up visit.ResultsOne thousand five hundred and sixty-one end-stage renal disease male patients were screened and 819 consented (dialysis: n = 242; transplant: n = 577). One single patient was found with decreased alpha-galactosidase levels <25%. GLA sequencing identified the p.Phe113Leu variant in favor of an unknown superimposed kidney disease responsible for end-stage renal disease since this GLA pathogenic variant is associated with a later-onset cardiac form of Fabry disease with minimal kidney involvement. Family cascade genotyping revealed a previously undiagnosed affected brother.ConclusionThe prevalence of Fabry disease in end-stage renal disease patients was 0.12%, questioning the efficacy of this screening strategy with respect to the low prevalence. However, beside the benefit for the patient and his family, the increased awareness of Fabry disease among participating nephrologists may be of interest for future patients.     

Prise en charge des patients avant l’initiation d’un traitement de suppléance de l’insuffisance rénale chronique terminale en 2013 en France

This study evaluated the management of patients with end-stage renal disease prior to initiation of renal replacement therapy. Among the 51 million national health insurance general scheme beneficiaries (77% of the population), persons 18 years and older, starting dialysis or undergoing preemptive renal transplantation in 2013, were included in this study. Data were derived from the French national health insurance system (SNIIRAM). In this population of 6674 patients (median age: 68 years), 88% initiated renal replacement therapy by haemodialysis, 8% by peritoneal dialysis, and 4% by renal transplantation. During the year preceding initiation of dialysis, 76% of patients had been hospitalised with at least one diagnostic code for renal disease in 83% of cases, 16% had not received any reimbursements for serum creatinine assay and 32% had not seen a nephrologist; 87% were taking at least one antihypertensive drug (60% were taking at least a renin-angiotensin system inhibitor) and 30% were taking a combination of 4 or more classes of antihypertensive drugs. For patients initiating haemodialysis in a haemodialysis centre, 39% had undergone a procedure related to arteriovenous fistula and 10% had been admitted to an intensive care unit. This study, based on the available reimbursement data, shows that, despite frequent use of the health care system by this population, there is still room for improvement of screening and management of patients with end-stage renal disease and preparation for renal replacement therapy.     

Rapport REIN 2005 — Synthèse

In 2005, 6,021 patients with end-stage renal disease living in fourteen regions covering 45 millions inhabitants (73% of the French population), started renal replacement therapy (dialysis or preemptive graft): median age was 70 years; 3% had a preemptive graft. The overall crude annual incidence rate of renal replacement therapy for end-stage renal disease was 139 per million population (pmp) in thirteen regions that met exhaustivity, with significant differences in sex and age-adjusted incidence across regions (92 to 171 pmh). At initiation, 48% of the patients had at least one cardiovascular disease and 36% diabetes (89% Type 2 non-insulin-dependent diabetes).On December 31, 2005, 21,813 patients living in these fourteen regions were on dialysis: median age was 69 years. The overall crude prevalence rate of dialysis was 539 pmp in thirteen regions. On December 31, 2005, 19,491 patients were living with a functioning graft : median age was 53 years. The overall crude prevalence rate for these patients was 390 pmp in thirteen regions. The overall crude prevalence rate of renal replacement therapy for end-stage renal disease was 929 pmp in thirteen regions, with significant differences in age-adjusted prevalence across regions (732 to 1009 pmh).In the 2002-05 cohort of 11,632 incident patients, the overall one-year survival rate was 82%, 72% at 2 years and 62% at 3 years. Survival decreased with age, but remained above 50% at 2 years in patients older than 75 at RRT initiation.Among the 5,902 new patients starting dialysis in 2005 in the 14 regions, 7% had a BMI lower than 18,5 kg/m² and 16% a BMI higher than 30. At initiation, 63% had an haemoglobin value lower than 11g/l and 9% an albumin value lower than 25 g/l. The first haemodialysis was started in emergency in 30% of the patients and with a catheter in 46%.On December 31, 2005, 8% treated in the dialysis units of the fourteen regions received peritoneal dialysis, of which 35% were treated with automated peritoneal dialysis. 94% of the patients on haemodialysis had 3 sessions per week, with a median duration of 4 hours.In 2005, 1,911 patients received a renal graft. On December 31, 2005, 4,634 patients were on the waiting list for a renal graft in the transplantation centres of the 14 regions.     

REIN annual report 2005. Renal Epidemiology and Information Network & Agence de la biomédecine

In 2005, 6,021 patients with end-stage renal disease living in fourteen regions covering 45 millions inhabitants (73% of the French population), started renal replacement therapy (dialysis or preemptive graft): median age was 70 years; 3% had a preemptive graft. The overall crude annual incidence rate of renal replacement therapy for end-stage renal disease was 139 per million population (pmp) in thirteen regions that met exhaustivity, with significant differences in sex and age-adjusted incidence across regions (92 to 171 pmh). At initiation, 48% of the patients had at least one cardiovascular disease and 36% diabetes (89% Type 2 non-insulin-dependent diabetes). On December 31, 2005, 21,813 patients living in these fourteen regions were on dialysis: median age was 69 years. The overall crude prevalence rate of dialysis was 539 pmp in thirteen regions. On December 31, 2005, 19,491 patients were living with a functioning graft : median age was 53 years. The overall crude prevalence rate for these patients was 390 pmp in thirteen regions. The overall crude prevalence rate of renal replacement therapy for end-stage renal disease was 929 pmp in thirteen regions, with significant differences in age-adjusted prevalence across regions (732 to 1009 pmh). In the 2002-05 cohort of 11,632 incident patients, the overall one-year survival rate was 82%, 72% at 2 years and 62% at 3 years. Survival decreased with age, but remained above 50% at 2 years in patients older than 75 at RRT initiation. Among the 5,902 new patients starting dialysis in 2005 in the 14 regions, 7% had a BMI lower than 18,5 kg/m2 and 16% a BMI higher than 30. At initiation, 63% had an haemoglobin value lower than 11 g/ l and 9% an albumin value lower than 25 g/l. The first haemodialysis was started in emergency in 30% of the patients and with a catheter in 46%. On December 31, 2005, 8% treated in the dialysis units of the fourteen regions received peritoneal dialysis, of which 35% were treated with automated peritoneal dialysis. 94% of the patients on haemodialysis had 3 sessions per week, with a median duration of 4 hours. In 2005, 1,911 patients received a renal graft. On December 31, 2005, 4,634 patients were on the waiting List for a renal graft in the transplantation centres of the 14 regions.     

Screening for kidney disease in adults with diabetes and prediabetes

PURPOSE OF REVIEW: Worldwide, we are facing an increasing prevalence of diabetes mellitus, the number one cause of end-stage renal disease. It is imperative that chronic kidney disease among adults with diabetes mellitus be detected early when interventions are most effective in preventing end-stage renal disease. RECENT FINDINGS: Screening tools work best when health care providers have a clear understanding of the natural history of the disease process. The use of urine albumin measurement as a screening tool for diabetic nephropathy is based on the well characterized evolution of nephropathy in type 1 diabetes mellitus. However, the evolution of chronic kidney disease among adults with type 2 diabetes mellitus appears to be more heterogeneous. In contrast to type 1 diabetes mellitus, a substantial percentage of adults with type 2 diabetes mellitus have decreased glomerular filtration rate in the absence of increased urine albumin excretion. Focusing solely on urine albumin excretion to screen for chronic kidney disease may miss a substantial number of cases in adults with diabetes mellitus. In addition, up to one-third of adults with newly diagnosed diabetes mellitus already have chronic kidney disease, which may have first developed during the prediabetic state. Screening for chronic kidney disease only after an adult develops diabetes mellitus may miss that 'early' window of opportunity in many patients. SUMMARY: To maximize the effectiveness of our screening programs, we must not only use tests with adequate sensitivity but also implement screening tests early in the disease process to prevent the progression of chronic kidney disease to end-stage renal disease.     

Preventive medical screening is not appropriate for many chronic dialysis patients

Establishing guidelines for the appropriate preventive medical care for chronic dialysis patients requires consideration of many factors. These include the population's underlying risk factors and expected survival, the effectiveness of screening procedures in improving the duration and/or quality of life, and the potential for renal transplantation. Although many nephrologists order and direct routine cancer screening in their dialysis patients, recent studies suggest such screening is not cost effective. Cardiovascular disease is the leading cause of death among end-stage renal disease (ESRD) patients and peripheral vascular disease is a leading cause of morbidity among dialysis patients, but even less is known about the cost-effectiveness of screening for peripheral vascular and cardiovascular disease risks in ESRD patients. Despite a recently reported overall standardized cancer incidence of 1.18 in dialysis patients compared with normal populations, the shortened expected survival of dialysis patients argues against routine cancer screening in this population. Dialysis units and nephrologists should focus cancer screening on individual patients and include specific cancer risk as well as expected survival assessments and transplant candidacy in their decisions to screen a patient for cancer. Routine cancer screening of all dialysis patients is not indicated. Additional study of the benefits and cost-effectiveness of screening ESRD patients for cardiovascular and peripheral vascular disease risk factors is needed.     

Use of digital subtraction fluorography in screening for coronary artery disease in patients with chronic renal failure

The diagnosis of coronary artery disease remains a major problem in patients with end-stage renal disease. Screening with conventional noninvasive techniques is limited by the poor exercise capacity of these patients. This study evaluated the accuracy of digital subtraction fluorography in detecting coronary calcification as a noninvasive, nonexercise screening test for coronary artery disease. Eighty-six patients under evaluation for renal transplantation and considered at increased risk of coronary artery disease were studied by coronary arteriography and digital subtraction fluorography for coronary calcification. Significant coronary disease (greater than or equal to 50% obstruction in at least one vessel) was present in 36 (42%) patients. The detection of coronary calcification by digital subtraction fluorography had a sensitivity of 78% and a specificity of 66%. The probability of disease being present in the absence of coronary calcification in this group was 18%. The detection of coronary calcification by digital subtraction fluorography appears to be a satisfactory and inexpensive screening test in this setting.     

Peritoneal dialysis in Mexico

While Mexico has the thirteenth largest economy, a large portion of the population is impoverished. About 90% of the population is Mestizo, the result of the admixture of Mexican Indians and Spaniards, with the Indigenous peoples concentrated in the southeastern region. Treatment for end-stage renal disease (estimated 268 patients per million population) is largely determined by the limited healthcare system and the individual's access to resources such as private insurance ( approximately 15%) and governmental sources ( approximately 85%). With only 5% of the gross national product spent on healthcare and most treatment providers being public health institutions that are often under severe economic restrictions, it is not surprising that many Mexican patients do not receive renal replacement therapy. Mexico uses proportionately more peritoneal dialysis than other countries; 1% of the patients are on automated peritoneal dialysis, 19% on hemodialysis and 80% on CAPD. Malnutrition and diabetes, important risk factors for poor outcome, are prevalent among the patients in CAPD programs.     

Diagnosis and Management of Fabry Disease in High-Risk Renal Disease Patients in Taiwan: A Single Center Study

BackgroundFabry disease (FD) is an X-linked inborn error of lysosomal storage disorder, a deficiency in lysosomal hydrolase α-galactosidase A activity due to pathogenic variants in the GLA gene. Accumulation of globotriaosylceramide in multiple organs contributes to end-stage kidney disease, heart failure, and cerebrovascular accidents.MethodsWe began the FD screening program by involving male patients older than 20 years of age who were on chronic dialysis, had a post-kidney transplantation, and were part of the Pre-End Stage Renal Disease Program in our hospital. α-galactosidase A activity was detected through an initial dried blood spots screen assay, followed by levels of lyso-globotriaosylceramide and sequencing of the GLA gene when screening patients with suspected FD to confirm their diagnosis.ResultsA total of 1812 patients had been FD screened, with the prevalence of FD being approximately 0.16 % (3/1812) up until June 2022. Interestingly, we confirmed a family cluster (2 sons and their mother) of having the c.936+919G>A mutation (designated GLA IVS4) with hypertrophic cardiomyopathy in Taiwan and another with the mutation c.644A>G (p.Asn215Ser), a more common later-onset variant reported in people of European or North American descent. Two patients were confirmed with cardiomyopathy through a cardiac biopsy, with their cardiac function later reversed after enzyme replacement therapy.ConclusionsThe FD screening test detects chronic kidney disease due to an unknown etiology and prevents other organ complications. Early detection of FD is crucial for reversing target organ damage with enzyme replacement therapy.     

Network and epidemiologic information in nephrology: Kidney report 2009

In 2009, 8,560 patients with end-stage renal disease living in 20 regions (Alsace, Auvergne, Bourgogne, Bretagne, Centre, Champagne-Ardenne, Corse, Haute-Normandie, Ile de France, la Réunion, Languedoc-Roussillon, Limousin, Lorraine, Midi- Pyrénées, Nord-Pas de Calais, Pays de Loire, Picardie, Poitou- Charentes, Provence-Alpes C?te d'Azur and Rh?ne-Alpes) covering 57 million inhabitants (89% of the French population), started renal replacement therapy (dialysis or preemptive graft): median age was 70,2 years ; 3,4% had a preemptive graft. The overall crude annual incidence rate of renal replacement therapy for end-stage renal disease was 150 per million population (pmp), with significant differences in sex and age-adjusted incidence across regions (99 to 389 pmh). At initiation, more than one patient out of two had at least one cardiovascular disease and 41% diabetes (92% Type 2 non-insulin-dependent diabetes). On December 31, 2009, 33,558 patients living in the above 20 regions were on dialysis : median age was 70,5 years. On December 31, 2009, 29,181 patients were living with a functioning graft : median age was 54,8 years. In these 20 regions, the overall prevalence of dialysis was 588 pmp, that of renal graft, 510 pmp and the overall rate of renal replacement therapy for end stage renal disease, 1,098 pmp with significant differences in age-adjusted prevalence across regions (809 to 2,709 pmh). In the 2002-2009 cohort of 43,433 incident patients, the overall one-year survival rate was 83%, 45% at 6 years. Survival decreased with age, but remained above 50% at 2 years in patients older than 75 at RRT initiation. Among the 8,688 new patients starting dialysis in 2009 in 23 regions (the 20 regions mentioned above, plus Aquitaine, Pays de Loire and Guadeloupe), 5% had a BMI lower than 18,5 kg/m2 and 20% a BMI higher than 30. At initiation, 66% had a haemoglobin value lower than 11 g/l and 10% an albumin value lower than 25 g/l. The first haemodialysis was started in emergency in 33 % of the patients and with a catheter in 54 %. On December 31, 2009, 7 % treated in the dialysis units of the 22 regions (the 20 regions mentioned above, plus Aquitaine and Pays de Loire) received peritoneal dialysis, of which 40% were treated with automated peritoneal dialysis. 95% of the patients on haemodialysis had 3 sessions per week, with a median duration of 4 hours. In the 2002-2009 cohort of incident patients in 18 regions under 60 years, the probability to be at least once on the waiting list for a renal graft is 50% at 15,6 months. In 2009, 2,750 patients received a renal graft. On December 31, 2009, 7,272 patients were on the waiting list for a renal graft in the transplantation centres of the 22 regions. The analysis of the flows between treatments indicates that the proportion of the transplanted patients among RTT patients is increasing. The main source for transplantation is the outcenter patients.     

Prevention of renal failure: the Malaysian experience

Renal replacement therapy in Malaysia has shown exponential growth since 1990. The dialysis acceptance rate for 2003 was 80 per million population, prevalence 391 per million population. There are now more than 10,000 patients on dialysis. This growth is proportional to the growth in gross domestic product (GDP). Improvement in nephrology and urology services with widespread availability of ultrasonography and renal pathology has improved care of renal patients. Proper management of renal stone disease, lupus nephritis, and acute renal failure has decreased these as causes of end-stage renal disease (ESRD) in younger age groups. Older patients are being accepted for dialysis, and 51% of new patients on dialysis were diabetic in 2003. The prevalence of diabetes is rising in the country (presently 7%); glycemic control of such patients is suboptimal. Thirty-three percent of adult Malaysians are hypertensive and blood pressure control is poor (6%). There is a national coordinating committee to oversee the control of diabetes and hypertension in the country. Primary care clinics have been provided with kits to detect microalbuminuria, and ACE inhibitors for the treatment of hypertension and diabetic nephropathy. Prevention of renal failure workshops targeted at primary care doctors have been launched, opportunistic screening at health clinics is being carried out, and public education targeting high-risk groups is ongoing. The challenge in Malaysia is to stem the rising tide of diabetic ESRD.     

Study on malignancy of end-stage aristolochic acid nephropathy patients in Wenzhou area

Objective To investigate the features of malignancy in end-stage aristolochic acid nephropathy (AAN) patients undergoing renal replacement therapy in the First Affiliated Hospital of Wenhou Medical University. Methods One hundred and two patients diagnosed as end-stage AAN during 2004 to 2013 were enrolled in the study, and separately udergoing hemodialysis, peritoneal dialysis and renal transplantation, to study the features of the malignancy and its risk factors. Results (1) There were totally 42 AAN patients suffering from malignancy, and 39 of them had urinary cancer. Eight cases of urinary cancer had metastasis, and 11 cases of bladder cancer had repeated recurrences. Patients suffering from malignancy had an increased mortality compared to patients without malignancy(13/42 vs 7/60, P=0.022). (2) Thirteenmalignacy cases were diagnosed before the end-stage of AAN, the rest cases appeared in 1-13 years[(4.62±3.31) years] after renal replacement. (3) A further logistic regression analysis of the 29 maligancy patients after renal replacement showed that, the dose of aristolochic acid (counted by Mutong) was the only risk factor of malignancy (P=0.091), compared with the dose of Mutong less than 60 g, the patients with an accumulated dose of Mutong more than 200 g had a 4.26 folds（95%CI 1.02, 17.83）higher risk of malignancy. There was no statistic difference of the malignancy risk among different renal replacement therapies, which however might influence the pathogenic sites of the urinary cancer. The simple bladder cancer was the most common malignancy among the hemodialysis patients (72.72%), and the upper urinary tract cancer among the peritoneal dialysis patients (66.67%), while the complex of both were dominant among the renal transplantation patients(40.00%). Conclusions Among the end-stage of AAN patients undergoing renal replacement therapy in Wenzhou area, the incidence of urinary cancer is high, with a character of complex, multiple and repeated recurrences. The occurence of malignancy seems to be separated from the renal function, but turns out obviously dose-dependent. There was no statisticaldifference of cancer risk among hemodialysis, peritoneal dialysis, and renal transplantation, which may induce different pathogenic sites of the urinary cancer.     

Patients with Fabry disease on dialysis in the United States.

BACKGROUND.: Fabry disease results from an X-linked deficiency of lysosomal alpha-galactosidase A and is a rare cause of end-stage renal disease. Little is known about the characteristics of patients with Fabry disease that initiate dialysis in the United States, although data from Europe suggests these individuals have a poor survival. METHODS.: Using the United States Renal Disease System database, we first studied in detail 42 Fabry patients who initiated dialysis between April 1995 (following the introduction of the new detailed HCFA 2728 form) and July 1998. To examine crude survival in a larger cohort, 95 Fabry patients were studied who initiated dialysis between 1985 and 1993, similar to the European Registry. Diabetic and non-diabetic controls matched by age, gender, race, year of dialysis initiation, and initial dialysis modality were examined for comparison. RESULTS.: During the years 1995 to 1998, the mean age of Fabry patients that initiated dialysis was 42 years, 83% were Caucasian, and 10% were African American. Despite the X-linked inheritance of Fabry disease, 12% of Fabry patients on dialysis were female. At initiation of dialysis mean serum albumin and creatinine were significantly higher and mean body mass index was significantly lower among Fabry patients, but mean glomerular filtration rate was similar to controls. Fabry patients tended to have a lower three-year survival compared to non-diabetic controls, but the results were not significantly different. In a larger cohort of Fabry patients who initiated dialysis between 1985 and 1993, the three-year survival of Fabry patients was significantly lower than non-diabetic controls: 63% (95% CI, 50 to 75%) versus 74% (95% CI, 67 to 80%; P=0.03). CONCLUSION.: End-stage renal disease is associated with significant morbidity and mortality among patients with Fabry disease. Recent evidence that progression of Fabry disease may be attenuated by enzyme replacement therapy necessitates increased awareness of Fabry disease and its comorbidities.     

Estrogen replacement therapy: implications for postmenopausal women with end-stage renal disease

Little information is available about either the potential beneficial or harmful effects of estrogen replacement therapy in postmenopausal women with end-stage renal disease. Although evidence supports a role for estrogen replacement therapy in postmenopausal women in the prevention of cardiovascular disease and bone loss, possible improvement in cognitive function, and the relief of menopausal symptoms, these conclusions may not be applicable to patients with end-stage renal disease, since these studies have generally excluded such women. This issue is of considerable importance since cardiovascular causes account for more than 50% of the all-cause mortality in patients with end-stage renal disease. However, estrogen replacement therapy may also have untoward effects in patients with the disease, including an increased risk of dialysis access thrombosis and potentially worsening coronary artery disease in postmenopausal patients. Furthermore, dosing of estrogens needs to be done carefully since renal excretion is important for the elimination of estrogen metabolites. Low dose or alternate day dosing in addition to monitoring estrogen levels may be warranted when prescribing estrogen replacement therapy to women with end-stage renal disease. In this review, it is our objective to analyze the evidence published in the literature so far and to weigh the risks and benefits of estrogen therapy in postmenopausal women with end-stage renal disease.     

Parathyroidectomy rates among United States dialysis patients: 1990-1999

BACKGROUND: Medical therapy for secondary hyperparathyroidism (SHPTH) has evolved considerably during the past decade. It is not known how changes in medical therapy might impact the parathyroidectomy (PTX) rate among dialysis patients. Relatively low parathyroid hormone (PTH) levels have been found among elderly dialysis patients and those with diabetes. Clinical factors associated with differing PTX rates among United States dialysis patients have not been reported. We report PTX rates in the United States from 1990 to 1999 among persons with end-stage renal disease, accounting for changes in patient characteristics. METHODS: Data from the United States Renal Database were utilized. Patients insured by Medicare or Medicaid and receiving renal replacement therapy between January 1, 1990, and December 31, 1999 were considered for analysis. PTX was determined by ICD-9 procedure codes. Multivariate Poisson models were used to estimate adjusted PTX rates. RESULTS: The overall observed PTX rate in the study sample was 7.16 per 1000 person-years at risk. After a slight rise during the early 1990s, adjusted PTX rates declined by approximately 30% between 1995 and 1999. Adjusted PTX rates were higher among patients who were younger, female, nondiabetic, receiving peritoneal dialysis, and those with a longer cumulative duration of dialysis. CONCLUSION: PTX rates have recently decreased in the United States, independent of changes in patient characteristics. The effectiveness of medical therapy in targeting secondary hyperparathyroidism may be improving. Younger, nondiabetic patients with a longer cumulative dialysis burden are at particularly high risk for PTX.     

Demographics of blood pressure and hypertension in children on renal replacement therapy in Europe

Hypertension is a well-known complication in children on renal replacement therapy and an important risk factor for cardiovascular disease in later life. In order to define the prevalence of and risk factors for hypertension among children, we enrolled 3337 pediatric patients from 15 countries in the ESPN/ERA-EDTA Registry of whom 464 were on hemodialysis, 851 on peritoneal dialysis, and 2023 had received a renal allograft. Hypertension was defined as either systolic or diastolic blood pressures in the 95th percentile or greater for age, height, and gender or use of antihypertensive medication. Analyses were adjusted for age, gender, duration, and modality of renal replacement therapy. In 10 countries in which information on the use of antihypertensive medication was available, hypertension was present in over two-thirds of hemodialysis, peritoneal dialysis, or transplant patients. Blood pressure values above the 95th percentile were significantly more prevalent in very young patients (under 3 years) compared to 13- to 17-year olds (odds ratio 2.47), during the first year compared to over 5 years of renal replacement therapy (odds ratio 1.80), and in patients on hemodialysis compared to transplant recipients or those on peritoneal dialysis (odds ratios of 2.48 and 1.59, respectively). Over time, mean blood pressures decreased in both hemodialysis and transplant patients, but not in peritoneal dialysis patients. Hence, our findings highlight the extent of the problem of hypertension in children with end-stage renal disease in Europe.     

Gonadal dysfunction in men with chronic kidney disease: clinical features, prognostic implications and therapeutic options

Gonadal dysfunction is a frequent finding in men with chronic kidney disease and with end-stage renal disease. Testosterone deficiency, usually accompanied by elevation of serum gonadotropin concentrations, is present in 26-66% of men with different degrees of renal failure. Uremia-associated hypogonadism is multifactorial in its origin, and rarely improves with initiation of dialysis, although it usually normalizes after renal transplantation. Experimental and clinical evidence suggests that testosterone may have important clinical implications with regards to kidney disease progression, derangements in sexual drive, libido and erectile dysfunction, development of anemia, impairment of muscle mass and strength, and also progression of atherosclerosis and cardiovascular disease. Additionally, low testosterone levels in hemodialysis patients have been associated with increased mortality risk in some studies. Currently, we count with available therapeutic options in the management of uremic hypogonadism, from optimal delivery of dialysis and adequate nutritional intake, to hormone replacement therapy with different testosterone preparations. Other potential options for treatment include the use of antiestrogens, dopamine agonists, erythropoiesis-stimulating factors, vitamins, essential trace elements, chorionic gonadotropin and renal transplantation. Potential adverse effects of androgen replacement therapy in patients with kidney disease comprise, however, erythrocytosis, prostate and breast cancer growth, reduced fertility, gynecomastia, obstructive sleep apnea and fluid retention. Androgen preparations should be used with caution with stringent monitoring in uremic men. Although there are encouraging data suggesting plausible benefits from testosterone replacement therapy, further studies are needed with regards to safety and effectiveness of this therapy.