The path to a paradigm shift in hemodialysis

About 1 out of 4 American conventional dialysis patients die in the first year and 3 out of 5 die within 5 years with no favorable trend in sight. Largely ignored in practice is the evidence accumulated over decades that longer, more frequent dialysis can immediately slash this grim result in half or more. Pierratos has called for a paradigm shift—a disruptive change—in dialysis practice from conventional treatment to daily nocturnal dialysis, performed at home, to realize this dramatic improvement. We examine here how such a paradigm shift might be brought about and suggest that changes in 3 perspectives must occur. First, new dialysis guidelines must be recast from the old goal of minimally adequate to a new goal of best possible . Second, the body of dialysis research must be interpreted through the lens of best possible patient survival and well being, and the near-impossibility of demonstrating dialysis survival advantage through randomized clinical trials must be acknowledged. Finally, dialysis modality must be seen as, most importantly, a survival and well-being choice, not merely a Lifestyle choice; hence, it must be the nondelegatable responsibility of the physician, not dialysis center personnel, to advise and prescribe. Many old perspectives, which might stand in the way of this sorely needed paradigm shift are also examined. These old perspectives make up a fabric of excuses that has delayed—and, if not discarded, will continue to delay—progress toward a survival and well-being outlook for dialysis patients just as favorable as might be achieved through kidney transplant.     

Modification of cardiovascular risk in hemodialysis patients: an evidence-based review

Cardiovascular disease accounts for 40% to 50% of deaths in dialysis populations. Overall, the risk of cardiac mortality is 10-fold to 20-fold greater in dialysis patients than in age and sex-matched controls without chronic kidney disease. The aim of this paper is to review critically the evidence that cardiac outcomes in dialysis patients are modified by cardiovascular risk factor interventions. There is limited, but as yet inconclusive controlled trial evidence that cardiovascular outcomes in dialysis populations may be improved by antioxidants (vitamin E or acetylcysteine), ensuring that hemoglobin levels do not exceed 120 g/L (especially in the setting of known cardiovascular disease), prescribing carvedilol in the setting of dilated cardiomyopathy, and by using cinacalcet in uncontrolled secondary hyperparathyroidism. Similarly, there are a number of negative controlled trials, which have demonstrated that statins, high-dose folic acid, angiotensin-converting enzyme inhibitors, multiple risk factor intervention via multidisciplinary clinics, and high-dose or high-flux dialysis are ineffective in preventing cardiovascular disease. Although none of these studies could be considered conclusive, the negative trials to date should raise significant concerns about the heavy reliance of current clinical practice guidelines on extrapolation of findings from cardiovascular intervention trials in the general population. It may be that cardiovascular disease in dialysis populations is less amenable to intervention, either because of the advanced stage of chronic kidney disease or because the pathogenesis of cardiovascular disease in dialysis patients is different from that in the general population. Large, well-conducted, multicenter randomized-controlled trials in this area are urgently required.     

Spontaneous retroperitoneal hemorrhage due to acquired cystic kidney disease

A patient with end-stage renal disease on maintenance hemodialysis developed sudden severe abdominal pain and distension. He suffered a decline in his hematocrit and subsequent abdominal imaging revealed a large left-sided retroperitoneal hemorrhage in the setting of atrophic, severely cystic kidneys. He underwent selective left renal artery angiography and embolization due to continued hemorrhage with stabilization in his condition. However, he became paraparetic within hours of the embolization procedure due to spinal cord infarct. Acquired cystic kidney disease is a very common entity in patients with chronic kidney disease. Complications include cystic hemorrhage or infection, erythrocytosis, and renal cell carcinoma. Screening of patients for cystic disease and malignant transformation remains a controversial topic; however, most advocate abdominal imaging after 3 to 5 years on dialysis.     

Ventricular arrhythmia in dialysis patients: A link with higher hemoglobin levels?

We investigated the frequencies and associated risk factors of cardiac arrhythmias and heart rate variability (HRV) in hemodialysis (HD) patients. One hundred fifty prevalent HD patients underwent 48-hour Holter monitoring. Holter monitoring was analyzed in 4 phases: early post-HD phase (12 hours), late post-HD phase (20 hours), pre-HD phase (12 hours), and HD phase (4 hours). Echocardiography was applied to measure the left ventricular mass index in a subgroup of patients (n: 52). Patients with ventricular premature contraction (VPC) were significantly older, had a longer HD duration, and higher hemoglobin (Hb) levels. Left ventricular mass index was significantly correlated with the frequency of VPC, during the HD and pre HD phases (r: 0.435, 0.312, respectively). In logistic regression analysis, patients with Hb level >11.9 g/dL (high tertile) had a 4.5-fold increased risk of VPC compared with those with Hb levels <10.8 g/dL (P: 0.04). In HRV analysis, age (P<0.001), and diabetes (P: 0.03) were found to be independent predictors of low standard deviation of all mean normal-to-normal RR intervals. Increased left ventricular mass index is associated with a high frequency of VPC in the pre-HD and HD periods. The occurrence of VPC is predicted by older age, longer dialysis duration, and higher Hb levels, while older age and diabetes are the determinants of HRV. The relation between higher Hb levels and the frequency of VPC might provide a clue for the explanation of the detrimental effect of higher Hb levels on HD patients.     

End-stage renal disease patients on hemodialysis: a study from a tertiary care center in a developing country

The exact number of patients with chronic renal failure requiring renal replacement therapy in developing world is not known. Unlike the developed world, most developing countries lack renal registries. This study was initiated to know demographic and clinical data of end-stage renal disease (ESRD) patients presenting to maintenance hemodialysis (MHD) at a government funded tertiary care centre in a developing country. A prospective analysis of all new ESRD patients attending to hemodialysis at our centre from 2004 to 2007 had been done. There were 237 new hemodialysis patients during a three-year period. Males were 153 and females were 84, with the mean age 44.92 years. Diabetes mellitus (31.22%) was the most common cause of ESRD. Only 29.95% of patients had education on renal replacement therapy. 65.40% patients had emergency hemodialysis. Internal jugular catheter was the most common form of vascular access at initiation of hemodialysis. Arteriovenous fistula was secured in 29.95% of patients at presentation. Catheter-related infection appeared in 13.55% of patients on catheter. The most common infection in dialysis patients was urinary tract infection (37.14%). Renal transplantation was opted by 9.7% patients and continuous ambulatory peritoneal dialysis in 20.25% and 103 (43.45%) were lost to follow up. The rest (8.86%) continued on MHD. There were 42 (17.72%) deaths over a three-year period. The present study provided the information of the practice of hemodialysis, its population characteristics and outcomes from a developing country.     

Clinical characteristics and outcomes of new uremic patients with extreme azotemia in southern Taiwan

Serum creatinine (SCr) had been considered to be an important predictor of mortality in end-stage renal disease (ESRD) patients at the start of renal replacement therapy (RRT). However, the data were limited about initially extreme azotemia (EA), exclusively defined as blood urea nitrogen (BUN) > or = 300 mg/dL, SCr > or = 30 mg/dL, or both. This retrospective study was conducted to clarify the characteristics and outcome in our EA patients. We had 1682 new ESRD patients from July 1988 to December 1996. With frequency match for age, gender, and starting RRT in the same period, 20 EA patients and 60 controls were included. Fifty percent of our EA patients had unknown etiology. The EA patients had significantly lower prevalence of underlying diabetic nephropathy, and comorbid hypertension. All the EA patients had late referral to nephrologists within 4 weeks before the initiation of RRT, and 90% of them had taken Chinese herbals. The EA group had significantly higher BUN, SCr, and iron storage as well as a higher prevalence of severe anemia, hyperkalemia, hypocalcemia, and acidemia. However, the similar prevalence of cardiomegaly and left ventricular hypertrophy as well as the similar early mortality rate and long-term survival were noted. Age over 40 years, comorbid diabetes mellitus, and hypoalbuminemia were independent predictors of poor survival. Our EA patients had different initial presentations from other uremic ones at the start of RRT. However, the short-term and long-term mortality rates were similar. The lower prevalence of underlying diabetic nephropathy and comorbid hypertension among the EA patients might contribute to their fair outcome.     

Clinical epidemiology of parathyroidectomy in hemodialysis patients: the USRDS waves 1, 3, and 4 study

Despite advances in the medical management of secondary hyperparathyroidism, parathyroidectomy remains necessary in some end-stage renal disease patients. Observational studies may help with the design of intervention trials. We linked the retrospective Waves 1, 3, and 4 Dialysis Morbidity and Mortality Study datasets to Medicare claims data to identify incident parathyroidectomy in 10,588 Medicare patients receiving hemodialysis in the United States on December 31, 1993. The mean age was 60.0 years, and the mean follow-up 3.6 years. De novo parathyroidectomy incidence was 14.2/1000 patient-years. Considered as quintiles (Q), higher levels of standard bone metabolism variables were associated (p<0.0001) with parathyroidectomy stepwise, such that adjusted hazards ratios (AHR) for Q5 (vs. Q1) were, for calcium (>10.3 mg/dL), 5.09 (3.64-7.10); for phosphorus (>7.5 mg/dL), 2.92 (2.06-4.15); for calcium-phosphorus product (>71 mg2/dL2), 3.32 (2.27-4.85); and for parathyroid hormone (PTH; >480 pg/mL), 13.81 (7.47-25.55). Other antecedent associations included younger age, lower hemoglobin, and longer dialysis vintage, while transplantation, as a time-dependent covariate, was associated with lower hazards ratios. Using interval Poisson analysis, parathyroidectomy was associated with higher mortality risk ratios in the first year, and progressively lower risk ratios subsequently. Demographic variables may modify the risk of parathyroidectomy. Younger patients on long-term hemodialysis may be at a special risk. Parathyroidectomy risk increases stepwise with alterations in bone metabolism variables, suggesting that a single-threshold management approach may not be ideal.     

Doppler echocardiograph evaluation of pulmonary hypertension in patients undergoing hemodialysis

Pulmonary hypertension (PH) has been reported in hemodialysis (HD) patients, but data regarding its incidence and mechanisms are scarce. The aims of this study was to evaluate the prevalence of unexplained PH in long-term HD patients, and to examine some possible etiologic factors for its occurrence. The prevalence of PH was estimated by Doppler echocardiography in a cohort of 86 stable patients on HD via arteriovenous access for more than 12 months. All the patients underwent full clinical evaluation, chest radiography, and a standard 12-lead echocardiograph. Laboratory investigation included a mean of 12 months (serum calcium, phosphorus, parathormone (PTH), alkaline phosphatase, lipids, and hemoglobin). Pulmonary hypertension was defined as pulmonary artery systolic pressure >35 mmHg as determined by Doppler echocardiography using the modified Bernoulli equation. Pulmonary hypertension was detected in 23 patients (26.74%). Of those with PH, left ventricular hypertrophy was seen in 13 patients (56.52%), and valvular calcifications in 6 patients (26.08%). There were no significant differences between both groups with regard to age, sex, duration of dialysis, shunt location, and all the biological parameters of the study. The presence of PH was not related to the level of PTH, or the severity of other metabolic abnormalities. This study demonstrates a high prevalence of PH among patients with ESRD receiving long-term HD via surgical arteriovenous access. The role of the vascular access, anemia, or secondary hyperparathyroidism as the etiology of PH in HD patients did not hold in this study.