“The Renal Foot” - Angiographic Pattern of Patients with Chronic Limb Threatening Ischemia and End-Stage Renal Disease

BackgroundPatients with chronic limb threatening ischemia (CLTI) and end-stage renal disease (ESRD) have greater risk of limb loss compared to those with CLTI alone. We investigated angiographic patterns in patients with CLTI and evaluated for differences based on ESRD status.MethodsWe reviewed lower extremity angiograms of 152 CLTI patients at a single academic medical center from 2011 to 2017 and analyzed them based on the Graziani and Bollinger classification systems. We used these classification systems to evaluate for angiographic patterns and arterial disease severity categorized by the presence or absence of ESRD.ResultsThe analysis included 152 CLTI patients (161 angiograms). Patients' mean age was 63.4 ± 11.3 years and 20 (12.4%) patients had ESRD. In our study population, infrapopliteal arterial disease was more severe than femoropopliteal disease. Disease of the arteries providing direct flow to the plantar arch was more severe in ESRD patients compared to non-ESRD patients, evident by higher Graziani Class VII disease (20% vs. 4.9%, p = .03). ESRD patients also had higher rates of concurrent significant stenosis of the posterior tibial and lateral plantar arteries (70% vs. 23%, p < .0001).ConclusionIn people with CLTI, infrapopliteal arteries are more severely affected than proximal femoropopliteal arteries. ESRD patients exhibit a pattern of arterial disease, we termed the “renal foot,” that frequently involves arteries providing direct flow to the plantar arch.     

Does Peritoneal Protein Transport Increase with Peritoneal Dialysis Therapy Duration and Lead to Extracellular Water Overload in Peritoneal Dialysis Patients?

Faster peritoneal transport status has been associated with adverse outcomes for peritoneal dialysis (PD) patients. Peritoneal protein clearance, through large pores, may be a surrogate marker of local inflammation. We wished to determine whether peritoneal protein transport increased with PD duration or was associated with extracellular water (ECW) expansion. We studied the relationships between 4 h Dialysate (D)/Serum (S) protein and ECW excess, using multifrequency bioelectrical impedance assessments, in 103 PD patients with up to 4 years of prospectively collected peritoneal equilibrium test (PET) results. 4 h PET D/S total protein and creatinine ratios were stable over time (K‐W test, P = 0.063 and P = 0.3357, respectively). The initial PET 4 h D/S creatinine and D/S total protein correlated with ECW excess (r = 0.33, P = 0.003, and r = 0.27, P = 0.019, respectively), but thereafter there was no association. CRP and albumin did not correlate with 4 h D/S creatinine or total protein. Serial 4 h D/S total protein and 4 h D/S creatinine correlated all time points (P < 0.001). At the start of PD therapy, over‐hydration (ECW excess) was observed with higher 4 h D/S creatinine and 4 h D/S total protein ratios, suggesting initial exposure to PD fluids causes faster transport. Thereafter changes in peritoneal creatinine and total protein transport mirrored each other suggesting that similar factors lead to changes in both small and large pore transport, and there was no sustained increase in larger pore transport with therapy time.     

Measuring Kidney Disease–Related Loss in Samples of Predialysis and Dialysis Patients: Validating the Kidney Disease Loss Scale

Background and objectives: Kidney disease–related loss is clinically significant in patients with ESRD and is related to depression and quality of life. The Kidney Disease Loss Scale (KDLS) was recently developed for long-term dialysis patients as a means of studying loss and applying it to clinical practice; however, its validity and usability in the other developmental stages of ESRD—predialysis and early dialysis—remain unknown. This study examined the validity and reliability of the KDLS in the long-term dialysis, early dialysis, and predialysis populations.Design, setting, participants, & measurements: Four groups of participants were recruited from four large university teaching hospitals in the Sydney metropolitan area. Participants were long-term dialysis (n = 151), early dialysis (n = 163), and predialysis (n = 111) patients. An additional independent group of dialysis (n = 50) patients were recruited to measure the test–retest reliability. Multisample confirmatory factor analysis and correlational analysis were used.Results: Results demonstrated good internal consistency and test–retest reliability for KDLS. Multisample confirmatory factor analysis indicated that the factor structure of KDLS was invariant across samples and thus supported its construct validity. The convergent and discriminant validities of KDLS were supported by its correlations with scales that measure health-related quality of life, depression, and positive affect in the expected directions and magnitudes. The KDLS was sensitive to the developmental stages of ESRD.Conclusions: These findings demonstrated that the concept of loss exists in dialysis patients. The KDLS is a reliable measure of loss in ESRD and valid in the developmental stages of ESRD.Loss, conceptualized as cognitive and affective grief responses to individual losses characterized by rumination of and yearning for losses, disbelief, and stunned feelings, is clinically significant in chronic illnesses and ESRD (kidney disease that requires renal replacement therapy) (1–5). Loss has traditionally been studied in relation to death but has been extended to examine the losses that are associated with chronic illnesses and their psychological consequences (6,7). Facing multiple losses, patients with ESRD often experience negative grief responses that may continue for years and affect their mental health (2,5).Loss has special interest in ESRD because of its relationship with depression, which is highly prevalent in this population and associated with other patient outcomes, such as mortality, quality of life (QoL), and treatment adherence (8,9). Loss, a distinct construct from depression (2,5,10), is seen as either a cause or a consequence of depression (11,12). Moreover, it has been identified by both patients with ESRD and health staff as one of the important factors in psychosocial adaptation and QoL (4). Thus, studying loss is important in understanding its contribution to depression and QoL in patients with ESRD as well as providing new insights into potential interventions (2). Loss research has remained limited, partly because of the lack of a measure that is specific for kidney disease–related loss.Recently, with a long-term dialysis sample, the Kidney Disease Loss Scale (KDLS) was developed to measure the level cognitive and affective responses of patients with ESRD to kidney disease– and dialysis-related losses and to identify the most important types of losses (2). Using the KDLS, a recent study found that loss, as a distinct construct, contributes to long-term dialysis patients'' level of depression and indirectly affects their QoL (2).For the KDLS to be widely usable in ESRD, its validity and reliability need to be established in other samples patients with ESRD, especially in two of the four developmental stages of the ESRD life cycle: Patients who have recently commenced dialysis (early dialysis patients) and those who are yet to commence dialysis (predialysis patients) (13,14). Examining the KDLS in these ESRD developmental stages would establish the validity and utility of the KDLS in the ESRD life cycle, and such validation would facilitate further study on loss in ESRD. This study aimed to (1) examine the construct validity of the KDLS by testing the consistency of its factor structure in the three samples long-term dialysis patients, early dialysis patients, and predialysis patients; (2) test its convergent-discriminant validity; and (3) examine its internal consistency and temporal stability.     

Heart Rate Variability in Peritoneal Dialysis Patients: What Is the Role of Residual Renal Function?

Background: The relationship between heart rate variability (HRV) and residual renal function (RRF) has not been elucidated previously. Methods: In this cross-sectional study, HRV was evaluated in 71 peritoneal dialysis patients. Patients were divided into RRF decline group, RRF stable group and anuric group. Results: RRF was negatively correlated with SDNN (r = -0.284, p = 0.017), TP (r = -0.247, p = 0.039), and HF (r = -0.238, p = 0.047). Significant sympathetic nerve activation was found in the RRF decline group (significantly lower SDNN, SDSD, RMSSD, pNN50, LF, HF, TP and higher LF/HF ratio) as compared to the RRF stable and anuric groups. Besides, significantly parasympathetic activation was found in the anuric group (the lowest LF/HF ratio as compared to the other groups (both p < 0.05). Multivariate stepwise regression analysis showed that the status of RRF was an independent factor associated with HRV parameters. Conclusion: This study showed autonomic nervous function in peritoneal dialysis patients was associated with a different status of RRF.     

Should the Metabolic Syndrome Patient with Prediabetes Be Offered Pharmacotherapy?

Impaired fasting glucose and impaired glucose tolerance reflect perturbations in glucose metabolism and define a prediabetic state in which risk for type 2 diabetes mellitus (T2DM) is increased. There is overlap between prediabetes and the metabolic syndrome, which itself increases the risk for T2DM and cardiovascular disease. The utility of medical interventions to prevent progression to diabetes in prediabetic individuals, many of whom also manifest metabolic syndrome, has been examined in several large clinical trials. Intensive lifestyle intervention consistently results in drastic reductions in the incidence of T2DM and reversal of metabolic syndrome. Additionally, pharmacotherapies—including metformin, acarbose, thiazolidinediones, glucagon-like peptide 1 receptor agonists, and renin-angiotensin inhibitors—also reduce diabetes incidence with variable effects on metabolic syndrome components. Taken together, we recommend that prediabetic patients undergo intensive lifestyle intervention, with the addition of pharmacotherapy based on the presence of specific features of the metabolic syndrome, for diabetes prevention.     

Can the Response to Iron Therapy Be Predicted in Anemic Nondialysis Patients with Chronic Kidney Disease?

Background and objectives: Anemia is iron responsive in 30 to 50% of nondialysis patients with chronic kidney disease (CKD), but the utility of bone marrow iron stores and peripheral iron indices to predict the erythropoietic response is not settled. We investigated the accuracy of peripheral and central iron indices to predict the response to intravenous iron in nondialysis patients with CKD and anemia.Design, setting, participants, & measurements: A diagnostic study was conducted on 100 nondialysis patients who had CKD and anemia and were erythropoiesis-stimulating agent and iron naive. Bone marrow iron stores were evaluated by aspiration. Hemoglobin, transferrin saturation index (TSAT), and ferritin were measured at baseline and 1 month after 1000 mg of intravenous iron sucrose. Posttest predictive values for the erythropoietic response (≥1-g/dl increase in hemoglobin) of peripheral and central iron indices were calculated.Results: The erythropoietic response was noted in a higher proportion in bone marrow iron-deplete than in iron-replete patients (63 versus 30%). Peripheral iron indices had a moderate accuracy in predicting response. The positive (PPV) and negative predictive values (NPV) were 76 and 72% for a TSAT of 15% and 74 and 70% for a ferritin of 75 ng/ml, respectively. In the final logistic regression model, including TSAT and ferritin, the chances of a positive response increased by 7% for each 1% decrease in TSAT.Conclusions: Because an erythropoietic response is seen in half of patients and even one third of those with iron-replete stores responded whereas peripheral indices had only a moderate utility in predicting response, the therapeutic trial to intravenous iron seems to be a useful tool in the management of anemia in nondialysis patients with CKD.Iron deficiency is common, and intravenous iron supplementation is a recognized therapy of anemia in long-term hemodialysis patients (HD), especially in those who are treated with epoetin (1–6). Several studies suggested that iron deficiency—evaluated by bone marrow iron examination—is common also in predialysis patients with chronic kidney diseases (CKD). In the reported series, the prevalence of bone marrow iron depletion varied widely from 23 to 90% (7,8). The role of iron supplementation in nondialysis patients with CKD is much less clear than in HD patients, although studies have reported a positive response to intravenous iron even without concomitant epoetin administration in 38 to 68% of patients (9–12).The prediction of erythropoietic response is clinically important, because the conventional markers of iron status—serum ferritin level and transferrin saturation index (TSAT)—although simple and relatively inexpensive, are not highly accurate in predicting response to iron in this population (5,7,8,11), and the safety of intravenous iron is a matter of concern in patients with CKD (13,14). Moreover, there are no published data relating iron stores, peripheral iron indices, and the response to intravenous iron. We conducted a study to investigate the accuracy of peripheral and central iron status indices to predict the response to intravenous iron in nondialysis patients who had CKD and anemia and were erythropoiesis-stimulating agent and iron naive.     

Is Population-Wide Diuretic Use Directly Associated With the Incidence of End-Stage Renal Disease in the United States?: A Hypothesis

BACKGROUND: We introduce the hypothesis that population-wide use of diuretics might be associated with acceleration of the incidence of end-stage renal disease (ESRD). METHODS: Based on the technique of data fusion, pooled-data trends in disease incidence and antihypertensive medication use were examined to determine whether changes in drug use patterns are predictive of disease emergence in the United States. National databases for all-cause cardiovascular disease (CVD) mortality and stroke mortality from the National Vital Statistics Registry, renal failure data obtained from the United States Renal Data Service, and drug information obtained from IMS Health (Fairfield, CT) were examined. RESULTS: A statistically significant inverse relationship was observed between all-cause CVD mortality rates and ESRD incidence rates for the period 1980 to 1998 (r = -0.98948; P < .0001). A statistically significant direct time-lagged relationship was found between both annual changes in diuretic distribution and total diuretic expenditure to annual changes in the ESRD growth rate (r = 0.754, P = .03, r(2) = 0.568, 95% CI for slope = 0.08975 to 1.3010). CONCLUSIONS: Increasing annual diuretic distribution in the US is directly associated with accelerated time-lagged growth rates of ESRD incidence. One potential explanation is that diuretic therapy could promote ESRD expression. A large-scale, randomized, controlled trial to investigate acceleration of ESRD by diuretics would be justifiable. The data invites the hypothesis that reliance on nondiuretic antihypertensive therapies such as calcium channel blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers might attenuate the epidemic rise of ESRD that is prevalent in the United States.     

Is Valvular Calcification a Part of the Missing Link between Residual Kidney Function and Cardiac Hypertrophy in Peritoneal Dialysis Patients?

Background and objectives: Residual renal function (RRF) predicts survival and shows an important inverse relation with cardiac hypertrophy in peritoneal dialysis (PD) patients. We hypothesized that valvular calcification and the calcification milieu may be part of the process linking loss of RRF and cardiac hypertrophy.Design, setting, participants, & measurements: A cross-sectional study was conducted by performing two-dimensional echocardiography on 230 PD patients to assess valvular calcification and left ventricular (LV) mass and collecting 24-h urine for estimation of RRF.Results: Patients having valvular calcification had lower RRF than those without. Patients with no RRF showed higher calcium-phosphorus product (Ca × P) and C-reactive protein (CRP). Using multiple logistic regression analysis, every 1-ml/min per 1.73 m² increase in residual GFR was associated with a 28% reduction in the risk for valvular calcification. The association was lost after additional adjustment for Ca × P and CRP. Using multiple linear regression analysis, loss of RRF showed significant association with increased LV mass index, but this association was lost after additional adjustment for CRP, Ca × P, and valvular calcification. Patients with all three calcification risk factors, namely inflammation, high Ca×P, and no RRF, showed the highest prevalence of valvular calcification and had the most severe cardiac hypertrophy.Conclusions: The association among loss of RRF, valvular calcification, and cardiac hypertrophy was closely linked to increased inflammation and high Ca × P in PD patients. These data suggest that valvular calcification and the calcification milieu are part of the processes linking loss of RRF and worsening cardiac hypertrophy in PD.Left ventricular hypertrophy (LVH) is one of the major cardiovascular complications in patients with ESRD and an important determinant of survival (1). Many factors are responsible for the development of LVH in patients with ESRD, including advanced age, hypertension, poor extracellular volume control, anemia, and hypoalbuminemia (2,3). A previous study showed that LVH was inversely related to residual renal function (RRF) in long-term peritoneal dialysis (PD) patients (4). Although the exact mechanisms for this association require further elucidation, our study suggested that worsening anemia, uremia, hypoalbuminemia, and increasing arterial pulse pressure with decline in RRF all may contribute to the link between RRF and cardiac hypertrophy in PD patients (4).Conversely, patients with ESRD are at a heightened risk for developing vascular and valvular calcification. As shown previously, cardiac valvular calcification is strongly associated with inflammation (5) and predicts mortality in PD patients (6); however, the relationship between RRF and valvular calcification, if any, in PD patients has so far not been reported. C-reactive protein (CRP) is an important predictor of mortality and cardiovascular disease in patients with ESRD (7,8) and is linked to LVH in PD patients (9). An elevated CRP was observed with decline in RRF in both predialysis (10) and PD patients (11) and was partly explained by reduced renal clearance of CRP and inflammatory cytokines (12) as well as increased inflammatory response secondary to uremia.In this study, we aimed first to test the hypothesis that loss of RRF is associated with valvular calcification. Second, we evaluated whether valvular calcification may represent part of the process that links loss of RRF and LVH—that is, whether the calcification risk profile may increase in association with loss of RRF and may additively contribute to LVH in long-term PD patients.     

Hemoglobin A1c in Patients on Peritoneal Dialysis: How Should We Interpret It?

Almost half the patients on peritoneal dialysis are diabetic and glycemic control is essential to improve both patient and technique survival. Hemoglobin A1c (HbA1c) is widely used in the general population for diabetes diagnosis and monitoring as it highly correlates with blood glucose levels and outcomes. Its use has been extrapolated to the peritoneal dialysis population, despite HbA1c being commonly underestimated. In renal failure patients, HbA1c is influenced by variables affecting not only glycemia but also hemoglobin and the time of interaction between the two. Importantly, the impact of these variables differs in peritoneal dialysis compared to non‐dialysis chronic kidney disease and hemodialysis patients. Although HbA1c in peritoneal dialysis patients is less directly associated with blood glucose levels than in the general population, studies have confirmed its association with patient mortality. In this paper we review the variables that can influence HbA1c value emphasizing their impact in peritoneal dialysis patients. By providing clinicians with a comprehensive understanding of HbA1c results, we provide them with tools for a better patient management care and potential improved outcomes of peritoneal dialysis patients.