Acute renal infarction in sickle cell disease

End organ failure in sickle cell disease has classically been attributed to changes in the microvasculature. A case is reported in which sudden and complete loss of blood flow to the left kidney occurred during a painful crisis in a woman with homozygous SS disease. The findings are most consistent with occlusion of the renal artery.     

Rapid decline in estimated glomerular filtration rate is common in adults with sickle cell disease and associated with increased mortality

We evaluated the prevalence of rapid decline in kidney function, its potential risk factors and influence upon mortality in sickle cell disease (SCD) in a retrospective single-center study. Rapid decline of kidney function was defined as estimated glomerular filtration rate (eGFR) loss of >3·0 ml/min/1·73 m² per year. A multivariable logistic regression model for rapid eGFR decline was constructed after evaluating individual covariates. We constructed multivariate Cox-regression models for rapid eGFR decline and mortality. Among 331 SCD patients (median age 29 years [interquartile range, IQR: 20, 41]; 187 [56·5%] female) followed for median 4·01 years (IQR: 1·66, 7·19), rapid eGFR decline was noted in 103 (31·1%). History of stroke (odds ratio [OR]: 2·91, 95% confidence interval [CI]: 1·25–6·77) and use of angiotensin converting enzyme inhibitors/angiotensin receptor blockers (OR: 3·17, 95% CI: 1·28–7·84) were associated with rapid eGFR decline. The rate of eGFR change over time was associated with mortality (hazard ratio [HR]: 0·99, 95% CI: 0·984–0·995, P = 0·0002). In Cox-regression, rapid eGFR decline associated with mortality (HR: 2·07, 95% CI: 1·039–4·138, P = 0·04) adjusting for age, sex and history of stroke. Rapid eGFR decline is common in SCD and associated with increased mortality. Long-term studies are needed to determine whether attenuating loss of kidney function may decrease mortality in SCD.     

Medical care utilization and mortality in sickle cell disease: a population-based study

The purpose of this study was to evaluate the pattern of medical care utilization and mortality in children and adults with sickle cell disease (SCD) in the state of Tennessee. Rates of hospitalization, emergency department visits, and deaths were measured in a cohort of adults and children with SCD enrolled in TennCare, Tennessee's Medicaid managed health care program, from January 1995 to December 2002. TennCare data linked to Tennessee vital records were used to define the population and identify the outcomes. For children less than 5 years of age, the mortality rate was similar to that of other black Tennessee children (P = 0.71). Among children, the death rate was highest in 10-19 years of age and was 8-fold higher than Tennessee's race- and age-specific rate. Among 20- to 49-year-old patients with SCD, mortality was significantly higher in males than in females (P < 0.001). As compared to the black population without SCD in TennCare, patients with SCD had 7-30 times higher rate of hospitalization and 2-6 times higher rates of emergency department visits (P < 0.001). The death rate in adolescents and young adults with SCD continues to be much higher than population-specific rates. Interventions to prevent morbidity and mortality related to SCD are urgently needed.     

中国终末期肾脏疾病的现状问题和对策

慢性肾脏病(CKD)和终末期肾脏疾病(ESRD)的防治已经成为中国重要的公共卫生问题。文章概括介绍中国CKD和ESRD的现状、危害以及防治中的问题,简述了中华医学会肾脏病学分会做出的工作,提出了今后防治ESRD的对策。目的在于提高社会、政府、公众以及医务人员对防治ESRD迫切性的认识,提高中国ESRD防治水平。     

Cardiac disease in diabetic end-stage renal disease

Summary Little is known about the epidemiology of cardiac disease in diabetic end-stage renal disease. We therefore prospectively followed a cohort of 433 patients who survived 6 months after the inception of dialysis therapy for an average of 41 months. Clinical and echocardiographic data were collected yearly. At baseline, diabetic patients (n = 116) had more echocardiographic concentric left ventricular hypertrophy (50 vs 38 %, p = 0.04), clinically diagnosed ischaemic heart disease (32 vs 18 %, p = 0.003) and cardiac failure (48 vs 24 %, p < 0.00 001) than non-diabetic patients (n = 317). After adjusting for age and sex, diabetic patients had similar rates of progression of echocardiographic disorders, and de novo cardiac failure, but higher rates of de novo clinically diagnosed ischaemic heart disease (RR 3.2, p = 0.0002), overall mortality (RR 2.3, p < 0.0001) and cardiovascular mortality (RR 2.6, p < 0.0001) than non-diabetic patients. Mortality was higher in diabetic patients following admission for clinically diagnosed ischaemic heart disease (RR 1.7, p = 0.05) and cardiac failure (RR 2.2, p = 0.0003). Among diabetic patients older age, left ventricular hypertrophy, smoking, clinically diagnosed ischaemic heart disease, cardiac failure and hypoalbuminaemia were independently associated with mortality. The excessive cardiac morbidity and mortality of diabetic patients seem to be mediated via ischaemic disease, rather than progression of cardiomyopathy while on dialysis therapy. Potentially remediable risk factors include smoking, left ventricular hypertrophy, and hypoalbuminaemia. [Diabetologia (1997) 40: 1307–1312] Received: 25 March 1997 and in final revised form: 23 June 1997     

Association between hemolysis and albuminuria in adults with sickle cell anemia

Studies have questioned whether renal dysfunction in sickle cell disease is linked to hemolysis-associated vasculopathy. We have investigated renal function and markers of hemolysis in a cohort of 424 adult African-British patients with sickle cell disease. While significant associations were found in HbSS and HbSβ(0) (sickle cell anemia) patients with and without controlling for covariates between hemolytic markers and albuminuria, the associations were not significant in patients with HbSC. Estimated glomerular filtration rate, a marker of renal function, correlated significantly with reticulocyte count and bilirubin. Alpha thalassemia, present in 34% of the sickle cell anaemia patients, had a protective effect against albuminuria in this group. Altogether, the incidence of hyperfiltration was 71% and microalbuminuria 37%, making nephropathy a common complication of sickle cell anemia.     

Bone mass density in adults with sickle cell disease

Sickle cell disease (SCD) leads to many complications including osteoporosis and osteopenia. We studied the prevalence and predisposing factors of low bone mass density (BMD) in adults with SCD. In this retrospective study, dual X-ray absorptiometry bone scans were used to determine BMD in the lumbar spine, femoral neck and ultra distal radius of 103 patients (73 females, 30 males, aged 15-80 years). Chart reviews and a patient questionnaire were used to collect patient characteristics, disease course and severity, and low BMD risk factors. The 79.6% of patients (mean age 36.5 +/- 12.5 years) had an abnormal BMD, with a predilection for the lumbar spine (P = 0.001). Analysis by 3 (low BMD versus very low BMD versus normal) or by 2 groups (abnormal versus normal) showed that abnormal BMD was associated with lower body mass index (BMI) (P = 0.003), lower Hb level (P = 0.001) and higher ferritin (P = 0.003). Low BMD patients were more likely to be SS, SC or Sbeta(0)thal than Sbeta(+)thal (P = 0.022). Abnormal BMD was not related to age, sex, menarche, SCD complications, number of crises, iron overload, treatment with hydroxycarbamide or desferal, renal disease, smoking or alcohol. Patients treated with hydroxycarbamide for at least 6 months were more likely to have an abnormal BMD. In this SCD population, abnormal BMD seemed to be independent of sex, age and menopause, whereas BMI, ferritin level, Hb type and level appeared to play a major role.     

Cancer incidence rate and mortality rate in sickle cell disease patients at Howard University Hospital: 1986–1995

The incidence of cancer in patients with sickle cell disease (SCD) is not known. The 10-year follow-up data on 696 patients with SCD was analyzed at our institution in order to determine the cancer incidence and cancer mortality rates. The age range was 18 to 79 years, with a mean age of 28.8 years. There were 377 females and 319 males. The median follow-up was 3 years. Five patients developed cancer during this period. The cancer incidence rate was 5/2,864 or 1.74 per 1,000 patient years. The 95% CI was 0.64 to 4.32 per 1,000 patient years. There were 68 deaths with 3 being due to cancer. The cancer mortality rate was 3/2,873 or 1.04 cases per 1,000 patient years. Our data represent the first published paper that the authors are aware of, where the cancer incidence and mortality rates have been calculated for any group of patients with SCD. Am. J. Hematol. 55:188–192, 1997. © 1997 Wiley-Liss, Inc.     

Survival and specific outcome of sickle cell disease patients after renal transplantation

The prognosis of sickle cell disease (SCD) patients who need dialysis is poor, but experience with kidney transplantation is limited. This study assessed the characteristics of 36 SCD patients undergoing renal transplantation. Immediate post-surgical complications occurred in 25% of cases. Cytomegalovirus and bacterial infections were frequently observed. Twelve patients died after a median follow-up period of 17·4 months. Overall patient survival was significantly lower in SCD than in the control group without significant difference for overall death-censored graft survival. Our data suggest that renal transplantation should be systematically considered in SCD patients with end-stage renal disease.     

High prevalence and correlates of low bone mineral density in young adults with sickle cell disease

Sickle cell disease (SCD) is a prevalent genetic disorder in which sickle hemoglobin leads to tissue hypoxia and adverse effects on bone. Published studies suggest that children with SCD often have undiagnosed osteopenia or osteoporosis. Minimal data exist on the prevalence of low bone mineral density (BMD) in adults. Our objective was to describe the prevalence of osteopenia and osteoporosis in adults with SCD and to identify patient or disease characteristics associated with low BMD. We conducted a cross-sectional study of adults with SCD. Through questionnaires, we collected data about disease course and osteoporosis risk factors. Patients underwent dual X-ray absorptiometry (DXA) measurement of BMD at the hip, spine, and forearm and sampling of blood and urine for markers of bone turnover, sickle cell disease severity, and secondary causes of osteoporosis. Our main outcome measure was prevalence of osteopenia and osteoporosis as defined by WHO criteria. Of 32 adults with SCD (14 men and 18 women) with a mean age of 34 years, 72% (95% confidence interval 53-86%) had low BMD at one or more anatomic sites. Thirteen patients were classified as osteoporotic and 10 as osteopenic. The prevalence of low BMD was greatest in the lumbar spine (66% of patients). Significant correlates of decreased BMD included low BMI (P < 0.01), male sex (P = 0.02), and low serum zinc concentrations (P < 0.01). The prevalence of osteopenia and osteoporosis in young adults with SCD is extremely high. Further research is needed to address fracture risk and therapeutic interventions.     

Frequent and prolonged hospitalizations: a risk factor for early mortality in sickle cell disease patients

A subset of patients with sickle cell disease (SCD) has frequent and prolonged hospitalizations. Clinical outcomes for this subset of patients are not known. We analyzed mortality data in 71 such patients enrolled in a case management study. Adult patients (mean age 32 years) with SCD and > or = 50 hospitalization days/year or > or = 6 admissions/year were enrolled. Clinical and psychosocial data were obtained. During a mean 24-month follow up, 11 of 71 patients died (15.5%). Patients who died had a higher mean number of hospitalization days in the year before study entry (116 vs. 40, P < 0.000008) and were also more depressed than those who survived (mean score 17.8 vs. 11.9, P = 0.031). Frequent and prolonged hospitalizations are a risk factor for early mortality in patients with SCD.     

Pancreatic-type hyperamylasemia in end-stage renal disease

Pancreatic-type isoamylase (P-type) and salivary-type isoamylase (S-type) activities were determined by the wheat protein inhibitor method in 29 patients with end-stage renal disease and in 38 healthy volunteers. Serum levels of total amylase (322±43 units/liter) and P-type (212±39 units/liter) in ESRD were significantly higher than those of controls (total: 142±7 units/liter,P<0.01; P-type: 52±4 units/liter,P<0.01). There was no significant difference between S-type activities in ESRD (110±16 units/liter) and in controls (90±6 units/liter). The ratios of amylase clearance to creatinine clearance (C_am/C_cr) and S-type clearance to creatinine clearance (C_s-amy/C_cr) rose significantly in ESRD(C_am/C_cr: 5.7±0.6%; C_s-amy/C_cr: 4.3±0.55%) compared to controls (C_am/C_cr: 3.2±0.24%,P<0.01; C_s-amy/C_cr: 2.1±0.17%,P<0.01). The ratio of P-type clearance to creatinine clearance (C_p-amy/C_cr) revealed no significant difference between ESRD (5.5±0.54%) and controls (5.6±0.42%). The renal excretion of P-type appeared to be more impaired than that of S-type in ESRD.     

Delayed haemolytic transfusion reaction in adults with sickle cell disease: a 5‐year experience

Delayed haemolytic transfusion reactions (DHTR) are potentially life‐threatening complications in patients with sickle cell disease (SCD). Between 1 August 2008 and 31 December 2013, 220 of 637 adult patients in our centre had at least one red blood cell (RBC) transfusion in 2158 separate transfusion episodes. Twenty‐three DHTR events occurred in 17 patients (13 female) including 15 HbSS, one HbSC and one HbSβ⁰ thalassaemia, equating to a DHTR rate of 7·7% of patients transfused. Mean interval from RBC transfusion to DHTR event was 10·1 ± 5·4 d, and typical presenting features were fever, pain and haemoglobinuria. Twenty of the 23 (87·0%) DHTR episodes occurred following transfusion in the acute setting. Notably, 11/23 (47·8%) of DHTRs were not diagnosed at the time of the event, most were misdiagnosed as a vaso‐occlusive crisis. 16/23 DHTRs had ‘relative reticulocytopenia’, which was more common in older patients. Seven of 23 episodes resulted in alloantibody formation, and three caused autoantibody formation. DHTRs are a severe but uncommon complication of RBC transfusion in SCD and remain poorly recognized, possibly because they mimic an acute painful crisis. Most of the DHTRs are triggered by RBC transfusion in the acute setting when patients are in an inflammatory state.     

Malignancy in patients with sickle cell disease

Malignancy in patients with sickle cell disease (SCD) has been previously reported, but the types of cancer and its incidence remain undefined. With the advent of hydroxyurea therapy, there is concern about increasing the cancer risk for patients with SCD. The International Association of Sickle Cell Nurses and Physician Assistants identified 52 cases of cancer (49 patients) among 16,613 patients with SCD followed at 52 institutions. The median age at malignancy diagnosis was 34 years (range, 14 months-62 years). Twenty-one cases (40%) occurred in pediatric patients, primarily leukemia (n = 7) or Wilms' tumor (n = 5), with 15 children surviving. Most adults had solid tumors, especially carcinomas, and only nine were known to be alive. Three patients received hydroxyurea before the diagnosis of malignancy. These data provide essential baseline information for the accurate interpretation of future reports of malignancy in patients with SCD, especially those receiving hydroxyurea therapy.     

Current developmental screening practices in young children with sickle cell disease

Despite recent developmental screening guidelines, rates of neurodevelopmental disorders (NDDs) remain lower than expected in children with sickle cell disease (SCD). A retrospective chart review identified 276 eligible patients; 214 charts were available for developmental screening and 207 charts for autism-specific screening. Developmental surveillance/screening was conducted in 70% of charts and autism-specific screening in 19% of charts. Validated tools were used in 32% of developmental screenings and 92% of autism-specific screenings. Many children (57%) were screened outside recommended ages. In conclusion, children with SCD are not regularly receiving appropriate developmental screening and surveillance by their healthcare providers.     

Consequences of late referral of patients with end-stage renal disease

OBJECTIVES: The aim of the present retrospective single centre study of patients entering renal replacement therapy (RRT), was to evaluate the effects of different referral patterns on morbidity, choice of therapy, and duration of hospitalization in patients with chronic renal failure. SUBJECTS: A total of 242 patients with chronic renal failure starting their first RRT between 1984 and 1998, were divided into three groups. Group 1 (n=80): RRT started 1984-88, group 2 (n=73): RRT started 1989-93 and group 3 (n=89): RRT started 1994-98. Patients were classified as early referrals (ER) or late referrals (LR) depending on whether they started first RRT more than or less than 3 months after first referral to a nephrologist. RESULTS: The proportion of LR was 27.3% (21 patients) in group 1, 27.4% (20 patients) in group 2 and 28.1% (25 patients) in group 3. In the ER, 35 patients (14.5%) received a predialytic kidney transplant, none in the LR. Comparing clinical details, the LR's in group 3 were significantly older than ER [median age 72 (53-81) vs. 56 (15-81) years, P < 0.0001], had a lower serum-albumin [median 33.0 (19.0-42.0) vs. 39 (19.0-48.0) g L-1, P < 0.0001], and serum-calcium [median 2.0 (1.4-2.6) vs. 2.3 (1.8-2.7) mmol L-1, P < 0.0001]. The ER had a significantly higher use of antihypertensive drugs, calcitriol, phosphate binders, and bicarbonate. Of the patients starting RRT on haemodialysis, all LR started on a temporary vascular access. About 43% of the ER started on a functioning arteriovenous fistula (P < 0.0001). The duration of hospital stay in connection with start of dialysis was 31 days (7-73) in the LR as compared with 7 (1-59) days in the ER (P < 0.0001). CONCLUSIONS: We conclude that in our centre, early referral to nephrologist is associated with lower age, a higher likelihood of predialytic transplantation, better metabolic status at start of RRT, a higher proportion starting haemodialysis on a functioning arteriovenous fistula, and a shorter duration of the initial hospital stay. Further research on health care delivery is warranted.     

Pulmonary hypertension in patients with sickle cell disease: a longitudinal study

Although pulmonary hypertension (PHT) is a common complication in patients with sickle cell disease (SCD), the rate of development of PHT and the factors that affect disease progression are unknown. We observed 93 patients over a median follow-up period of 2.6 years (range 0.2-5.1 years). Data were censored at the time of death or loss to follow-up. Pulmonary hypertension was associated with an increased risk of death (relative risk, 9.24; 95% confidence interval: 1.2-73.3; P = 0.01). There was no difference in the risk of death when patients with different degrees of PHT were compared. Lactate dehydrogenase and blood urea nitrogen were significantly associated with PHT in a logistic regression model. Higher levels of fetal haemoglobin and treatment with hydroxycarbamide were observed more frequently in patients without PHT. Thirteen per cent of patients with no previous evidence of PHT developed PHT following 3 years of observation. In conclusion: (1) PHT, regardless of severity, is associated with an increased risk of death in SCD patients; (2) haemolysis is strongly associated with PHT in SCD; (3) high levels of fetal haemoglobin and hydroxycarbamide therapy may decrease the occurrence of PHT; (4) screening for PHT is indicated for SCD patients in their non-crisis, steady states.