Left ventricular hypertrophy and chronic fluid overload in peritoneal dialysis patients

Purpose

Cardiovascular disease is the leading cause of mortality in dialysis patients with left ventricular hypertrophy (LVH) being an important predictor of mortality. We wanted to determine the prevalence of LVH in peritoneal dialysis (PD) patients and factors contributing to it.

Methods

This is a cross-sectional study assessing LVH using echocardiogram in PD patients. Left ventricular mass index (LVMI) was calculated to determine LVH. Chronic fluid overload (overhydration) was assessed using the body composition monitor, and blood pressure (BP) was measured using 24-h ambulatory BP monitoring.

Results

Thirty-one patients (21 females:10 males, 48.97 ± 14.50 years and dialysis vintage 40.0 ± 28.9 months) were studied. More than two-thirds (77.4 %) were hypertensive, and a third (35.5 %) were diabetic. Baseline data included mean serum albumin (37.34 ± 4.43 g/l), weekly Kt/V (2.02 ± 0.23), residual renal function of 68 (0–880) ml and ultrafiltration of 1,606.9 ± 548.6 ml. Majority of patients (80.6 %) had LVH on echocardiogram with LVMI of 136.5 ± 37.8 g/m² and overhydration of 2.23 ± 1.77 l. Average systolic BP, diastolic BP and mean arterial pressure were 141.2 ± 23.3, 90.8 ± 19.7 and 107.6 ± 19.6 mmHg, respectively. Patients with LVH had a lower serum albumin (p = 0.003), were more overhydrated (p = 0.010) and were on higher number of anti-hypertensive agents (p ≤ 0.001). Predictors of LVMI were overhydration (p = 0.002), the presence of diabetes (p = 0.008) and the number of anti-hypertensive agents used (p = 0.026). However, overhydration (p = 0.007) was the main predictor of LVH on multivariate analysis.

Conclusion

Overhydration is strongly associated with LVH in PD patients.     

Cardiovascular disease in pediatric chronic dialysis patients

BACKGROUND: Little information is available regarding cardiac morbidity and mortality in children with end-stage renal disease. We sought to determine the incidence of cardiac morbidity and mortality in pediatric chronic dialysis patients. METHODS: Medicare incident pediatric (0 to 19 years) dialysis patients from 1991 to 1996 were identified from the United States Renal Data System. Study endpoints included development of arrhythmia, valvular heart disease, cardiomyopathy, or cardiac arrest, all causes of death, and cardiac-related death. Statistical analyses were performed using the Poisson regression model and chi-square test. RESULTS: A total of 1454 children were eligible for inclusion, 452 (31.1%) of whom developed a cardiac-related event. Arrhythmia was the most common event (19.6%) compared with valvular disease (11.7%), cardiomyopathy (9.6%), and cardiac arrest (3%). Arrhythmia and valvular heart disease incidence were increased in 15- to 19-year-olds (P < 0.0001 for both), females (P = 0.004, P = 0.03) and blacks (P < 0.0001, P = 0.002). Cardiomyopathy incidence was increased in blacks (P = 0.001) and tended to be increased in females (P = 0.053). The adjusted annual cardiomyopathy rate during the first 3 years increased between 1991 and 1996 (P = 0.003). Death occurred in 107 patients, and 41 (38%) were cardiac deaths. CONCLUSIONS: Cardiovascular disease is a significant cause of morbidity and mortality in pediatric chronic dialysis patients. Cardiomyopathy incidence is increasing. Black, female, and adolescent children have increased risk for cardiovascular disease.     

持续性血液透析患者铁代谢与贫血状况的研究

目的 观察维持性血液透析(maintenance hemodialysis,MHD)患者铁过载的相关情况及其与贫血的相关性.方法 采用单中心、回顾性临床研究.选择2014年6月至2014年12月本院维持血液透析患者120例,按SF水平分为三组.A组(SF≤500 mg/L,n=60),B组(500 mg/L＜ SF≤1000 mg/L,n =35)和C组(SF＞ 1000 mg/L,n =25).调查患者的促红细胞生成素的用量、静脉补铁剂量、血红蛋白的变化、尿素氮、肌酐、全段甲状旁腺激素以及铁调素的水平.结果 C组患者的静脉铁补充剂量、输血量均大于A、B两组(P＜0.05),A组血红蛋白变化量大于B、C两组(P＜0.05),C组铁调素高于A、B两组(P＜0.05).结论 慢性肾衰竭维持血液透析的患者在SF≤500 mg/L,静脉补铁能有效地改善贫血,如补铁过量;SF＞ 1000 mg/L并不能显著的改善贫血及表现出铁代谢紊乱.     

Iron overload and mobilization in long-term hemodialysis patients

Iron overload from repeated transfusions of RBCs in long-term hemodialysis patients is a problem of increasing clinical significance. We report on the prevalence of and diagnostic criteria for identification of hemodialysis patients with iron overload. In 150 unselected hemodialysis patients, 62 (41%) had ferritin levels greater than 2,000 ng/mL (normal = 10 to 360 ng/mL). In 16 of these patients, accurate transfusion histories were obtained and ferritin levels correlated with calculated transfusional iron burden (r = 0.553, P less than .05). These patients could be divided into two distinct groups on the basis of their response to a single dose (2 g, IV) of deferoxamine: "high" responders had twice the level of feroxamine (the chelated product of deferoxamine and iron) of the "low" responders (P less than .001). High responders also had significantly higher prevalence of the "hemochromatosis" alleles A3, B7, and B14 than a large group of dialysis patients awaiting transplantation (71% v 37%, P less than .001). In two patients with iron overload and clinically significant bone disease, bone histology revealed prominent iron staining at the calcification front. We conclude that transfusional iron overload is a significant clinical problem in long-term hemodialysis patients, that may also be associated with bone pathology.     

Acquired cystic disease of kidney in chronic dialysis patients

Eight cases of acquired cystic disease of the kidney (ACDK) associated with chronic renal failure and hemodialysis are described. No patient had a family history or clinical evidence of congenital adult polycystic kidney disease (CAPKD). Glomerulonephritis was the cause of renal failure in 6, and pyelonephritis in 2. Massive renal and perirenal hemorrhage necessitated 3 nephrectomies in 2 patients. Single kidney weights did not exceed 280 Gm., a major feature in the distinction of ACDK from CAPKD. Morphologically, in addition to the usual stigmata of end-stage kidneys, 40 to 80 per cent of the renal parenchyma was replaced by small cysts. Continuity of cysts with tubules was established by nephron dissection.     

Clinical and histologic features of iron-related bone disease in dialysis patients

Forty-eight dialysis patients undergoing bone biopsy were analyzed for clinical history, blood biochemical values, bone histologic findings, bone aluminum content (BAC), bone iron content (BIC), bone iron stores, and histochemical staining of bone aluminum and bone iron. Four patients had significant trabecular bone iron staining alone; eight patients had significant bone iron and bone aluminum staining; 13 patients had significant bone aluminum staining alone; and 23 patients showed no significant bone aluminum or iron staining. Patients with significant bone iron staining were younger (37.4 +/- 5.3 years v 53.2 +/- 2.3 years, P less than 0.01, mean +/- SEM) and were more likely to be anephric (P less than 0.001) and to have a history of prior renal transplantation (P less than 0.10). The 12 patients with significant bone iron staining had received more blood transfusions than those without bone iron staining (96 +/- 22.8 U v 22 +/- 5.8 U, P less than 0.005). Patients with bone iron accumulation had higher levels of serum ferritin (3,594 +/- 1,138.4 micrograms/L [ng/mL] v 265 +/- 60.1 micrograms/L, P less than 0.01) and lower levels of immunoreactive parathyroid hormone (iPTH) (349 +/- 150 microLEq/mL v 1,801 +/- 397 microLEq/mL [386 +/- 166 pmol/L v 1,990 +/- 439 pmol/L], P less than 0.005). BIC was also higher in these patients (1,008 +/- 149 micrograms iron/g bone v 300 +/- 46.5 micrograms iron/g bone, P less than 0.001) and higher than normal BIC (256 +/- 44.2 micrograms iron/g bone, eight normals). Bone marrow iron stores were positively related to serum ferritin levels (P less than 0.01) and trabecular bone iron staining (P less than 0.10). All 13 patients with osteomalacia demonstrated significant bone aluminum staining; seven of these patients demonstrated concomitant significant iron staining. Fourteen of 15 patients with severe hyperparathyroidism showed no significant iron or aluminum staining. Our data indicate that iron will probably not accumulate within bone until all other storage sites (eg, bone marrow) are fully saturated. The presence of lower levels of iPTH in iron-overloaded patients raises the possibility that iron overload may induce a state of relative hypoparathyroidism. The most important determinant for the presence of osteomalacia seems to be the presence of significant aluminum staining. No specific bone histologic finding was related to the presence of bone iron staining, but the rarity of isolated significant bone iron staining makes it difficult to evaluate bone histologic diagnoses that might be solely attributable to iron.     

Effect of calcitonin on bone lesions in chronic dialysis patients.

The effects of synthetic salmon CT, administered subcutaneously and intermittently (1 MRC U/kg/day for 15 days/month over 6 months) were investigated in 15 uremic patients on regular dialysis treatment (RDT), all presenting various degrees of osteodystrophy. Clinically, osteoarticular pain disappeared in 8 out of 10 cases; 1 patient with rib fractures had a rapid calcification of the bone fracture repair tissue. No significant changes were found in serum calcium and PTH levels. Phosphotemia showed a significant decrease within the first 20 days. The varying individual hypophosphatemic response proved to be related to the initial level of phosphatemia. The alkaline phosphatase, when increased, showed a decrease to the normal range. A significant decrease in osteoclastic hyperactivity (active resorption surface, osteoclast index) and a slight increase in osteoblastic pool (active osteoid surface) were documented. No change was noted when osteomalacia predominated. Side effects included: anorexia, nausea, vomiting, face flushing. Our data suggest that salmon CT may be usefully employed in chronic uremic patients on RDT, when secondary hyperparathyroidism predominates.     

Deferoxamine test and bone disease in dialysis patients with mild aluminum accumulation

Aluminum bone disease is a frequent complication of dialysis patients. The deferoxamine (DFO) test has been advocated as a noninvasive procedure for the diagnosis of AI bone lesion. However most of these studies have been performed in symptomatic patients with significant AI bone disease. Whether this test may provide similar data at an earlier stage of AI toxicity is not known. The present study evaluates prospectively 28 patients with mild AI load. Patients studied ranged in age from 21 to 65 years; duration of dialysis was 5.6 +/- 3.2 years; deferoxamine, 40 mg/kg body weight, was infused at the end of dialysis. Serum AI was measured before DFO administration and before the next dialysis treatment. Bone biopsies were performed in all patients. Cortical bone AI was determined biochemically; trabecular and cortical bone AI were also determined histochemically. Mean basal serum AI (43.2 +/- 30.8 micrograms/L) and cortical bone AI (25.7 +/- 35.2 micrograms/g) were moderately increased. Basal serum AI correlated (r = 0.77) with the increment in serum AI after DFO infusion. After DFO, stainable trabecular and cortical bone AI correlated in a similar manner with both basal serum AI and increment in serum AI. Only biochemically determined cortical bone AI was not significantly related to basal serum AI. Nineteen of the 28 patients had evidence of osteitis fibrosa on bone biopsy. Stained AI surfaces but not trabecular AI were different in patients with low and patients with high bone formation rates. The bone findings, assessed as bone formation rates and resorption surfaces, did not correlate with biochemically or histochemically determined bone AI.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fatigue in chronic dialysis patients

Fatigue is common in chronic hemodialysis (HD) patients and impacts on daily living, impairs significantly the quality of life, increases the risk of cardiovascular events and negatively influences survival. Although numerous social, demographic, clinical, and laboratory variables have been associated with fatigue, the causes of this symptom are often unclear. In the absence of an underlying, treatable disorder, the results of therapeutic intervention are typically frustrating. So far, none of the drugs tested can be recommended for preventing and treating fatigue in chronic HD patients. There is some evidence that exercise may significantly improve fatigue in dialysis patients; however, this requires confirmation through large, prospective, randomized studies.     

Adynamic bone in patients with chronic kidney disease

Adynamic bone in patients with chronic kidney disease (CKD) is a clinical concern because of its potential increased risk for fracture and cardiovascular disease (CVD). Prevalence rates for adynamic bone are reportedly increased, although the variance for its prevalence and incidence is large. Differences in its prevalence are largely attributed to classification and population differences, the latter of which constitutes divergent groups of elderly patients having diabetes and other comorbidities that are prone to low bone formation. Most patients have vitamin D deficiency and the active form, 1,25-dihydroxyvitamin D, invariably decreases to very low levels during CKD progression. Fortunately, therapy with vitamin D receptor activators (VDRAs) appears to be useful in preventing bone loss, in part, by its effect to stimulate bone formation and in decreasing CVD morbidity, and should be considered as essential therapy regardless of bone turnover status. Future studies will depend on assessing cardiovascular outcomes to determine whether the risk/reward profile for complications related to VDRA and CKD is tolerable.     

Non-invasive prediction of aluminum bone disease in hemo- and peritoneal dialysis patients.

Between October 1987 and October of 1989, we conducted a prospective study to evaluate non-invasive test strategies for predicting aluminum bone disease (ABD) in a group of largely unselected dialysis patients based on their deferoxamine (DFO) test alone, or the combined results of their DFO test and intact 1-84 parathyroid hormone (PTH) levels. These test parameters were evaluated against the pathological diagnosis of ABD based on bone biopsy ("gold standard"). A total of 445 patients in three dialysis centers in Toronto were serially followed for their clinical, laboratory and risk parameters for renal osteodystrophy during the study, and 259 (142 PD and 117 HD) patients underwent a series of investigations which included the DFO test, measurement of intact 1-84 PTH levels, and an iliac crest bone biopsy. Serum aluminum ([Al]) level greater than or equal to 3700 nM (or 100 micrograms/liter) had a positive predictive value (PPV) of 75% for ABD in our PD and 88% in our HD patients, but its sensitivity was low (10 and 37%). Delta [Al] (that is, incremental rise of serum [Al] from baseline post-DFO) was useful in predicting ABD in our PD but not HD patients. Test combination based on delta [Al] greater than or equal to 5550 nM (or 150 microgram/liter) and PTH levels less than 20 pM (or 200 pg/ml) yielded the best PPV greater than or equal to 95% for ABD in both PD and HD patients. This test cut-off would remain highly predictive of ABD even if the prevalence of ABD decreases to as low as 5% for the PD patients and 10% for the HD patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acquired cystic kidney disease: occurrence in patients on chronic peritoneal dialysis

Acquired cystic kidney disease (ACKD) is a well-known complication of long-term hemodialysis. To the best of our knowledge, only six patients on continuous ambulatory peritoneal dialysis have been reported to develop this disease. We herein report two such cases, and concluded that the morphology of ACKD seems to be independent of the type of dialysis and that hemodialysis is not necessary for the development of ACKD.     

Psoas abscess in chronic dialysis patients

We report 4 cases of nontuberculous psoas abscess occurring in patients with end stage renal disease. Fever and pain were the presenting symptoms but diagnosis was delayed. A computerized tomography scan of the abdomen was the critical test that led to the correct diagnosis. Therapy involved drainage and antibiotics, and was successful in 3 of the 4 patients.     

Beta-blockade in chronic dialysis patients.

Approximately 50% of the mortality in chronic dialysis patients is due to cardiovascular diseases (CVD). Cardiomyopathy, coronary artery disease, and arrhythmia are all common conditions and predispose to sudden death, which accounts for 60% of all cardiac deaths in this population. Despite advances in dialysis therapy, the mortality from CVD remains substantially unchanged, partly due to the lack of evidence-based strategies for improving the outcome of cardiac diseases in this population. Activation of the sympathetic adrenergic system is well documented in chronic dialysis patients and is likely involved in the pathogenesis of myocardial hypertrophy, coronary artery disease, heart failure, and arrhythmia. Given the proven benefit of beta-blockers in patients with normal kidney function with similar cardiac comorbidities, beta-blockers would seem to be attractive agents to reduce cardiovascular morbidity and mortality in the patient population with advanced chronic kidney disease. However, the value of beta-blockade in patients on chronic dialysis remains unclear. This uncertainty surrounding the efficacy is compounded by the risk of side effects to these patients, such as hypotension, bradycardia, and hyperkalemia. In addition, numerous studies have suggested suboptimal usage of beta-blockers in the dialysis population; this is seen even in high risk patients, such as those with established coronary artery disease. In this review, we will focus on sympathetic nervous system activation in kidney disease and highlight the benefit and risks of beta-blockers usage in the chronic dialysis patient population.     

Aluminum-associated bone disease in chronic renal failure: high prevalence in a long-term dialysis population

Twenty-seven asymptomatic patients treated with hemodialysis longer than 8 years (mean 12.9 +/- 3.1 years) underwent bone biopsy to determine the prevalence of aluminum-associated bone disease. None had excess aluminum exposure from the dialysate. Ten patients (37%) had aluminum-associated bone disease as defined by a bone formation rate (BFR) below normal in the presence of stainable bone aluminum that covered more than 25% of the trabecular surface. The predominant type of bone histology in this group was the aplastic lesion characterized by low bone turnover, a decreased number of osteoblasts, and lack of excess unmineralized osteoid. Osteoblastic osteoid was highly correlated with stainable surface bone aluminum (r = -.82, p less than .001). Among the dynamic bone parameters, the double-tetracycline labeled surface was a more sensitive indicator of impaired bone function than was the bone apposition rate (BAR), since half of the patients with aluminum-associated bone disease had a normal BAR. In all of the biopsies the extent of double-labeled surfaces was inversely proportional to the amount of stainable aluminum on the bone surface (r = -.71, p less than .001), whereas stainable bone aluminum did not correlate with BAR. In seven of the patients with aluminum-associated bone disease, amino-terminal PTH levels were in the normal range while only one patient had a normal plasma mid-region PTH. PTH correlated directly with osteoblastic osteoid, BFR, and double-labeled surfaces. These results indicate that long-term oral aluminum intake in hemodialysis patients results in a high prevalence of aluminum-associated bone disease.(ABSTRACT TRUNCATED AT 250 WORDS)