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.     

Mortality risk in hemodialysis patients according to anemia control and erythropoietin dosing

There is no consensus about the toxicity of erythropoiesis‐stimulating agents among hemodialysis patients. We aimed to calculate the risk of death according to anemia control and erythropoietin (EPO) dosing among end‐stage renal disease patients undergoing hemodialysis. We retrospectively studied 156 end‐stage renal disease patients on hemodialysis from a single renal unit during 12 months. Participants were classified according to anemia control into four groups: excellent (A), good (B), moderate (C) and bad (D) control. They were also classified according to EPO dosing into two groups: usual and high EPO dosing. The Cox proportional hazards regression model, adjusted for the difference in age, sex, time on dialysis, comorbidity, albumin, and Kt/V index, was performed to calculate the risk of death according to anemia control and EPO dosing profiles. Multivariate analysis by backward stepwise logistic regression was used to calculate the risk of death according to the variables that differed in the comparison between survivors and nonsurvivors. The hazard ratio of death was not significant according to anemia control profile C/D vs. A/B, but hazard ratio was 2.967 (95% confidence interval [CI] = 1.132–7.777; P = 0.027) for high EPO dosing profile patients. The multivariate analysis showed comorbidity (odds ratio [OR] = 8.958; 95% CI = 2.843–26.223; P < 0.001], high EPO dosing profile (OR = 5.172; 95% CI = 1.663–16,081; P = 0.005), age (OR = 1.056; 95% CI = 1.020–1.094; P = 0.002), and mean hemoglobin (OR = 0.435; 95% CI = 0.267–0.709; P = 0.001) to be predictive of death. Even though we cannot conclude that mortality risk is due to EPO toxicity, hemodialysis patients using high EPO dosing must be seen as at risk.     

Factors affecting anemia management in hemodialysis patients: a single-center experience

The difficulty maintaining hemoglobin (Hgb) within the targets recommended by KDOQI is widely recognized. While factors responsible for erythropoietin resistance have been widely studied, factors responsible for the marked fluctuations and the inability to maintain Hgb within the target range have only begun to be investigated. This study was a cross-sectional review of anemia management in hemodialysis patients. The purpose was to evaluate factors responsible for Hgb decreases of 0.5 or 1.0 g/dL and to determine the primary factors responsible for Hgb decreases below 11 g/dL. Hgb values and clinical events were extracted from patient management databases between January 1, 2005 and November 30, 2006. Isolated events were defined as events that occurred at least 30 days after any previous event and had Hgb measurements within 2 weeks before and after the event. Increasing hospital length of stay and surgical access intervention were the most common events that resulted in a decrease in Hgb. The most common factor present in patients with Hgb decreases below 11 g/dL was the withholding of recombinant human erythropoietin (rHuEPO) within the preceding 2 months. This was the only explanation for the decrease in Hgb to <11 g/dL in 38.5% of such events. The ability to maintain dialysis patients' Hgb in the target range is complicated by intervening acute events that require hospitalization or surgical access interventions. The withholding of rHuEPO appears to be a major factor in Hgb decreases below 11 g/dL.     

Tuberculosis in end-stage renal disease patients on hemodialysis

Recent studies have shown that there is an increase in the incidence of mycobacterium tuberculosis (MBT). This is more prevalent among immune compromised patients (those on dialysis) and recipients of organ transplants. Furthermore, extra-pulmonary presentation appears to be more common and difficult to diagnose. We aimed in this study to assess and evaluate the presentation of MBT in a retrospective study conducted among 256 hemodialysis (HD) patients where 18 of them were diagnosed and managed for tuberculosis over a 10-year period between 1990 and 2000. The mean age of the patients was 38 years (21-75 years). The mean interval between the onset of HD and the time of diagnosis was about 24 months (1-120 months). The diagnosis of tuberculosis was made either by isolation of acid-fast bacilli (AFB), the typical caseating granuloma on biopsy, or by recovery of tubercle bacilli from the culture of the biopsy material. Extra-pulmonary tuberculosis was more common (77.8%) than pulmonary tuberculosis (22.2%). The various extra-pulmonary tuberculosis sites noted were cervical lymphadenitis (16.7%), gastrointestinal (16.7%), genitourinary (11.1%), peritonitis (11.1%), pleural effusion (5.6%), pericardial effusion (5.6%), miliary tuberculosis (5.6%), and pyrexia of unknown origin (5.6%). None of the patients with extra-pulmonary tuberculosis had evidence of pulmonary tuberculosis. The atypical presentation with insidious onset was quite common. Anergy to tuberculin skin test was noticed in 56% of cases. All of our patients received modified antituberculosis treatment for 1 year with adequate response, and without undue side effects. We conclude that a high index of suspicion is required especially in the diagnosis of extra-pulmonary tuberculosis, and when there is a high percentage of anergy to tuberculin skin test. Tissue biopsy both for characteristic histology and demonstration of MTB, either by staining or culture, remains the main criteria for the diagnosis of extra-pulmonary tuberculosis.     

Management of hypertension in hemodialysis patients

The relationship of hypertension with adverse outcomes is uncertain in the hemodialysis population. If hypertension is an etiologically significant cardiovascular risk factor in hemodialysis patients, the first step would be to assess the level of BP accurately. BP obtained at home over a week and averaged using a validated oscillometric automatic device can prove valuable. To the extent BP lowering influences cardiovascular outcomes, home BP of 150/90 mm Hg would warrant therapy, since it correlates with target organ damage and hypertension diagnosed by ambulatory BP monitoring. To manage hypertension, limiting dietary sodium intake and individualizing dialysate sodium delivery would be first steps. The magnitude of reduction in BP with dietary sodium restriction and the whether dialysate sodium can be safely limited in those who are hypotension-prone is unclear. Antihypertensive drug therapies can effectively reduce BP and are needed by the vast majority of hemodialysis patients. Whether control of hypertension translates into better outcomes is not known, but collective evidence suggests that hypertension should be controlled in hemodialysis patients.     

Associations of microvascular dysfunction with cardiovascular outcomes: The cardiac,endothelial function and arterial stiffness in ESRD (CERES) cohort

Introduction: Patients with end‐stage renal disease (ESRD) have reduced endothelial function, but whether macro‐ and microvascular endothelial function correlate with baseline risk factors and cardiovascular outcomes in this population is not well understood. Methods: Among 146 participants of the Cardiac, Endothelial Function and Arterial Stiffness in ESRD (CERES) study, we evaluated macro‐ and microvascular endothelial dysfunction as flow‐mediated dilation (FMD) and velocity time integral (VTI), respectively. We examined cross‐sectional correlations of baseline characteristics, inflammatory and cardiac markers with FMD and VTI. We followed participants for the composite outcome of cardiovascular hospitalization or all‐cause death over fourteen months. Cox survival analyses were adjusted for demographics, comorbidities, medications, systolic blood pressure, inflammation, high‐sensitivity troponin T (hs‐TnT), and N‐terminal pro B‐type natriuretic peptide (NT‐proBNP). Findings: Impaired VTI was associated with older age and Black race (P < 0.05), as well as female gender, atherosclerosis, and hemodialysis (as opposed to peritoneal dialysis) (P < 0.2). Myocardial injury, measured as hs‐TnT, inflammatory markers and NT‐proBNP correlated with impaired VTI. In unadjusted analyses, VTI was significantly associated with the composite outcome (HR per SD VTI 0.65 [95%CI 0.45, 0.95]), but FMD was not (HR per SD FMD 0.97 [95%CI 0.69, 1.4]). When VTI was calculated as the ratio of (hyperemic VTI‐baseline VTI)/baseline VTI, its association with the outcome persisted after multivariable adjustment. Discussion: Microvascular function was associated with higher rates of cardiovascular hospitalizations and all‐cause mortality among individuals with ESRD on dialysis. Further research is needed to learn whether novel therapies that target microvascular endothelial function could improve outcomes in this high‐risk population.     

Disseminated tuberculosis: A neglected entity in immunocompromised hemodialysis patients

End‐stage renal disease is considered a factor predisposing to increased risk of tuberculosis with frequent extrapulmonary localization. Although extrapulmonary tuberculosis has been observed for decades, disseminated tuberculosis, a major cause of morbidity and mortality in immunocompromised hosts, remains rather neglected. We report an unusual case of an immunocompromised patient with a late diagnosis and delayed treatment of genitourinary tuberculosis that subsequently led to the diagnosis of vertebral and miliary tuberculosis (disseminating tuberculosis). Therefore, increased awareness is warranted from physicians dealing with hemodialysis patients in order to avoid delays in diagnosis and treatment initiation.     

High prevalence of subclinical hypothyroidism and nodular thyroid disease in patients on hemodialysis

Chronic kidney disease has been known to affect thyroid hormone metabolism. Low serum levels of T3 and T4 are the most remarkable laboratorial findings. A high incidence of goiter and nodules on thyroid ultrasonography has been reported in patients with end‐stage renal disease (ESRD). Our objective is to evaluate the prevalence of laboratorial and morphologic alterations in the thyroid gland in a cohort of patients with ESRD on hemodialysis (HD). Sixty‐one patients with ESRD on HD were selected and compared with 43 healthy subjects matched by age, gender, and weight. Patients were submitted to thyroid ultrasonography. T3, free T4 (FT4), thyroid‐stimulating hormone, antithyroglobulin, and antithyroperoxidase antibodies were measured. The mean age of patients with ESRD was 47.4 ± 12.3 and 61% were women. ESRD was mainly caused by hypertensive nephrosclerosis and diabetic nephropathy. Mean thyroid volume, as determined by ultrasonography, was similar in both groups. Patients with ESRD had more hypoechoic nodules when compared with the control group (24.1% vs. 7.9%, P = 0.056). Mean serum FT4 and T3 levels were significantly lower in patients with ESRD, and subclinical hypothyroidism was more prevalent in patients with ESRD (21.82% vs. 7.14% control group, P = 0.04). Titers of antithyroid antibodies were similar in both groups. ESRD was associated with a higher prevalence of subclinical hypothyroidism and lower levels of T3 and FT4. Almost a quarter of patients showed thyroid nodules >10 mm. Periodic ultrasound evaluation and assessment of thyroid function are recommended in patients with ESRD on HD.     

Clinical and psychosocial factors predicting health‐related quality of life in hemodialysis patients

Many patients with end‐stage renal disease have significant impairment in health‐related quality of life (HRQoL). Most previous studies have focused on clinical factors; however, quality of life can also be affected by psychosocial factors. The aim of this study was to identify the possible predictors of HRQoL among clinical and psychosocial factors in hemodialysis (HD) patients. The study included 101 patients who were undergoing HD. Psychosocial factors were evaluated using the Hospital Anxiety and Depression Scale, Multidimensional Scale of Perceived Social Support, Montreal Cognitive Assessment, and Pittsburgh Sleep Quality Index. We also assessed laboratory and clinical factors, including albumin, Kt/V as a marker of dialysis adequacy, normalized protein catabolic rate, and duration of HD. The Euro Quality of Life Questionnaire 5‐Dimensional Classification (EQ‐5D) was used to evaluate HRQoL. The mean EQ‐5D index score was 0.704 ± 0.199. The following variables showed a significant association with the EQ‐5D index: age (P < 0.001), depression (P < 0.001), anxiety (P < 0.001), support from friends (P < 0.001), cognitive function (P < 0.001), duration of HD (P = 0.034), triglyceride (P = 0.031), total iron‐binding capacity (P = 0.036), and phosphorus (P = 0.037). Multiple regression analysis showed that age (95% confidence interval [CI] ?0.008 to ?0.002), anxiety (95% CI ?0.025 to ?0.009), and support from friends (95% CI 0.004 to 0.018) were independent predictors of impaired HRQoL. This study explored determinants of impaired HRQoL in HD patients. We found that impaired HRQoL was independently associated with age, anxiety, and support from friends. We should consider psychosocial as well as clinical factors when evaluating ways to improve HRQoL in HD patients.     

N‐acetylcysteine may improve residual renal function in hemodialysis patients: A pilot study

Clinical outcomes in chronic dialysis patients are highly dependent on preservation of residual renal function (RRF). N‐acetylcysteine (NAC) may have a positive effect on renal function in the setting of nephrotoxic contrast media administration. In our recent study, we showed that NAC may improve RRF in peritoneal dialysis patients. The aim of the present study was to investigate the effect of NAC on RRF in patients treated with chronic hemodialysis. Prevalent chronic hemodialysis patients with a residual urine output of at least 100 mL/24 hours were included. The patients were administered oral NAC 1200 mg twice daily for 2 weeks. Residual renal function was assessed at baseline and at the end of treatment using a midweek interdialytic urine collection for measurement of urine output and calculation of residual renal Kt/V and glomerular filtration rate (GFR). Residual GFR was measured as the mean of urea and creatinine residual renal clearance. Each patient served as his own control. Twenty patients were prospectively enrolled in the study. Administration of NAC 1200 mg twice daily for 2 weeks resulted in significant improvement in RRF: urine volume increased from 320 ± 199 to 430 ± 232 mL/24 hours (P < 0.01), residual renal Kt/V increased from 0.19 ± 0.12 to 0.29 ± 0.14 (P < 0.01), and residual GFR increased from 1.6 ± 1.6 to 2.4 ± 2.3 mL/minute/1.73 m² (P < 0.01). N‐acetylcysteine may improve RRF in patients treated with chronic hemodialysis.     

Bilateral quadriceps and triceps tendon rupture in a hemodialysis patient

This paper presented a 58‐year‐old hemodialysis patient who had bilateral quadriceps and triceps tendon rupture, whereby the role of rehabilitation in functional parameters has been highlighted.     

Association of bioimpedance spectroscopy‐based volume estimation with postdialysis hypotension in patients receiving hemodialysis

Clinical examination to determine the dry weight of patients on hemodialysis (HD) has been problematic, with studies showing discordance between physician assessment and objective measures of volume status.We studied the association between predialysis bioimpedance spectroscopy (BIS)‐based estimates of fluid overload and postdialysis hypotension in 635 patients in the United States Renal Data System ACTIVE/ADIPOSE (A Cohort study To Investigate the Value of Exercise/Analyses Designed to Investigate the Paradox of Obesity and Survival in ESRD) study receiving HD in 2009–2011. We recorded predialysis and postdialysis weight and blood pressures over 3 consecutive HD sessions and performed BIS before a single session. Using a previously reported method of estimating normohydration weight, we estimated postdialysis fluid overload (FO_post) in liters. We used logistic regression with extracellular water/total body water (ECW/TBW) or estimated FO_post as the primary predictor and 1 or more postdialysis systolic blood pressures less than 110 mmHg as the dependent variable. Models were adjusted for age, sex, race, ultrafiltration rate per kilogram of body weight, end‐stage renal disease vintage, diabetes mellitus, heart failure, and albumin. Higher ECW/TBW was associated with lower odds of postdialysis hypotension (odds ratio [OR] 0.35, 95% confidence interval [CI] 0.15–0.84 per 0.1, P = 0.02). Every liter of FO_post was associated with lower adjusted odds of postdialysis hypotension (OR 0.86, 95% CI 0.79–0.95, P = 0.003). Prospective studies are needed to determine whether this application of BIS could improve current clinical efforts to minimize episodes of postdialysis hypotension without leading to volume overload.     

Association between depression and inflammatory/anti‐inflammatory cytokines in chronic kidney disease and end‐stage renal disease patients: A review of literature

Depression is a common psychiatric disorder in patients with advanced chronic kidney diseases (CKDs). Strong correlation has been reported between depression and patients' morbidity and mortality among dialysis patients. On the contrary, chronic inflammation may be a major contributor to morbidity and mortality in these patients. Elevated plasma levels of proinflammatory cytokines, especially C‐reactive protein and interleukin (IL)‐6, have been correlated with cardiovascular events, hospitalization, and all‐cause and cardiovascular‐associated mortality in dialysis patients. Studies suggested that inflammation‐mediated atherosclerotic cardiovascular diseases are the possible reasons for depression‐induced mortality among patients without renal diseases. Several studies found significant elevations in circulating levels of proinflammatory cytokines, particularly IL‐6 and tumor necrosis factor‐α, in patients with major depression. Furthermore, depressive mood and behaviors, including sadness and suicidal ideation, were observed in patients who received repeated injections of recombinant cytokines. A thorough literature review indicates that while depressive symptoms and elevated inflammatory cytokine levels coexist in CKD and dialysis patients, their association is uncertain. Depression seems to be more associated with elevated serum levels of IL‐6 than other cytokines in these patients. Further studies are needed to clarify the possibility of a causal relationship between inflammation and depressive symptoms in CKD and dialysis patients.     

Genetic polymorphisms and the risk of progressive renal failure in elderly Hungarian patients

The relationship between renal disease progression and genetic polymorphism of enzymes influencing endothelial function remains incompletely understood. We genotyped three cohorts of elderly Hungarian patients: 245 patients with end‐stage renal disease (ESRD) on chronic hemodialysis (HD), 88 patients with mild chronic kidney disease (CKD), and 200 healthy controls. The underlying diagnoses of renal diseases were primary glomerulonephritis, interstitial nephritis, hypertension, diabetic nephropathy, and hereditary diseases. We examined genetic polymorphisms of eight candidate genes associated with endothelial function: endothelial constitutive nitric oxide synthase (ecNOS) T‐786C, endothelin‐1 G5727T, methylenetetrahydrofolate reductase (MTHFR) C677T, paraoxonase‐1 Q192R and M55L, angiotensinogen M235T, angiotensin‐converting enzyme (ACE) I/D and angiotensin II type 1 receptor A1166C gene. Six gene polymorphisms were detected by real‐time polymerase chain reaction with melting‐point analysis, and two via allele‐specific amplification and gel electrophoresis. Control group patients were in Hardy‐Weinberg equilibrium for all tested genotypes. In ESRD patients attributed to hypertension, the endothelin gene G5727T GG genotype occurred significantly less but GT genotype more frequently (P < 0.01 for both). In ESRD patients attributed to primary glomerulonephritis, more ACE DD and less ID genotypes were found (P < 0.02 for both) than in the controls. The underlying diagnosis may modify the association of genetic polymorphism and dialysis‐dependent ESRD.