Fredric O. Finkelstein

KDIGO Clinical Practice Guideline for Anemia in Chronic Kidney Disease

To the Editor: We have read the letter to the editor by Jerzy Przedlacki1 and the response from the authors2 of the Kidney Disease-Improving Global Outcomes (KDIGO) clinical practice guidelines for bisphosphonate (BP) treatment in chronic kidney disease (CKD), and would like to share our concerns regarding the use of BP treatment of CKD. The kidney is the organ that excretes many drugs, and any change in renal function will affect the pharmacology of these drugs. Existing or residual renal function of the patient will have to be taken into account while prescribing drugs. This is just as important for the patient with CKD 4 or 5, including those with CKD 5 already on peritoneal dialysis or hemodialysis, who may still have residual renal function. Nephrotoxic drugs including nonsteroidal anti-inflammatory drugs can very readily destroy whatever residual renal function patients may still have. Residual renal function is important to preserve as it contributes to less patient morbidity and mortality3 in the dialysis patient. Recently, there have been adverse reports of a certain BP that works by inhibiting osteoclast-mediated bone resorption, thereby slowing the breakdown of bone to reduce the risk of fractures. As of 14 August 2009, there have been 139 post-marketing reports of renal impairment following its use as an infusion worldwide. Many of these occur in patients with pre-existing medical conditions or risk factors (elderly, renal impairment, and/or concurrent dehydration), or in those on nonsteroidal anti-inflammatory drugs or other concurrent exposure to other nephrotoxic agents. There have also been cases requiring dialysis, and occasional fatal outcomes have been reported in patients with pre-existing renal impairment and concomitant risk factors.4, 5, 6, 7

International Society of Nephrology's 0by25 initiative for acute kidney injury (zero preventable deaths by 2025): a human rights case for nephrology

Executive summary Acute kidney injury (AKI) is a major contributor to poor patient outcomes. AKI occurs in about 13·3 million people per year, 85% of whom live in the developing world, and, although no direct link between AKI and death has yet been shown, AKI is thought to contribute to about 1·7 million deaths every year. The course of AKI varies with the setting in which it occurs, and the severity and duration of AKI aff ects outcomes such as dialysis requirement, renal functional recovery, and survival. Recognition is increasing for the eff ect of AKI on patients, and the resulting societal burden from its longterm eff ects, including development of chronic kidney disease and end-stage renal disease needing dialysis or trans plantation. Few systematic eff orts to manage (prevent, diagnose, and treat) AKI have been put in place and few resources have been allocated to inform health-care professionals and the public of the importance of AKI as a preventable and treatable disease. Several factors have contributed to the paucity of information. Most importantly, there have been few population-level epidemiological studies in several regions of the world. Diffi culties in defi nition of the incidence of AKI are especially evident in searches for data from low-income and middle-income countries, where more than 85% of the world’s population resides. No nationwide data collection systems are available, and data are usually from isolated centres and probably largely underestimate the true extent of AKI because they mostly do not include patients with AKI who were not able to reach a hospital for treatment. A recent metaanalysis that included 312 cohort studies and more than 49 million patients shows a scarcity of data from Africa and large parts of southeast Asia. We did an updated meta-analysis that used the most recent KDIGO (Kidney Disease: Improving Global Outcomes) defi nitions, which confi rms the high incidence and resulting outcomes of AKI, particularly in Africa, Asia, and Latin America, for which data were previously absent. The strong relation between the severity of AKI and consequent mortality is reiterated by our fi ndings and is evident across heterogeneous populations and specifi c disease cohorts. However, large gaps remain in knowledge about the factors that aff ect the geographical variation of AKI and poor outcomes. Many diff erences exist in the aetiology, pathophysiology, and management of AKI across the world. In high-income countries, AKI develops mainly in patients in hospitals. In low-income and middle-income countries, AKI occurs mainly in the community setting in acute illness, usually in association with diarrhoeal states and dehydration, infections such as malaria, and toxins (venoms and poisons). Public health issues (eg, contaminated water, poor sanitation, endemic infections such as malaria and dengue fever, venomous snakes, and toxic traditional medicines) and socioeconomic factors (eg, availability of health-care facilities) aff ect the epidemiology of AKI. Additionally availability of trained personnel and access to diagnostic tests and dialysis aff ect practice patterns and impose barriers to care. The extent to which these factors contribute to mortality and non-recovery of renal function has not been quantifi ed. AKI is potentially preventable and treatable with timely intervention, but there continues to be a high human burden. Which specifi c factors account for the poor outcomes and to what extent variations in care delivery contribute are unclear. The ability to provide lifesaving treatments for AKI provides a compelling argument to consider therapy for AKI as much of a basic right as it is to give antiretroviral drugs to treat HIV in low-resource regions, especially because care needs only be given for a Published Online March 13, 2015 http://dx.doi.org/10.1016/ S0140-6736(15)60126-X

Identification and treatment of depression in a cohort of patients maintained on chronic peritoneal dialysis.

Depression is the most commonly encountered psychological problem in patients with end-stage renal disease (ESRD). Depression has recently been shown to significantly impact on the morbidity and mortality of patients undergoing therapy for ESRD. The present study was designed as a pilot study to evaluate the feasibility of screening a large cohort of patients maintained on chronic peritoneal dialysis (CPD) for depression and then pharmacologically treating those patients assessed to have clinical depression. One hundred thirty-six patients maintained on CPD in our CPD unit were screened for depression using the Beck Depression Inventory (BDI), a self-administered questionnaire. Patients with scores of 11 or greater were referred to a trained psychiatric interviewer for further evaluation to confirm the diagnosis of clinical depression and determine whether the patient was a candidate for antidepressant medication. Sixty-seven patients had BDI scores of 11 or greater, and 60 of these patients were asked to participate in further evaluation and possible therapy. Only 27 patients agreed to further study and were evaluated by a trained psychiatric interviewer for clinical depression. Twenty-three of these patients were assessed to have clinical depression, and 22 patients were eligible for antidepressant medication based on their scores on the Hamilton Depression Scale and psychiatric interview. Eleven patients completed a 12-week course of therapy with antidepressant medication, and their BDI scores decreased from a mean of 17.1 +/- 6.9 (SD) to a mean of 8.6 +/- 3.2. Seven patients were treated with sertraline, 2 patients with bupropion, and 2 patients with nefazodone. It is concluded that (1) depression is commonly present in patients maintained on CPD, (2) the BDI is a useful tool to use to screen for clinical depression, and (3) clinical depression is treatable with medication in this patient population.

A practical approach to the treatment of depression in patients with chronic kidney disease and end-stage renal disease

Depression is a common, under-recognized, and under-treated problem that is independently associated with increased morbidity and mortality in CKD patients. However, only a minority of CKD patients with depression are treated with antidepressant medications or nonpharmacologic therapy. Reasons for low treatment rates include a lack of properly controlled trials that support or refute efficacy and safety of various treatment regimens in CKD patients. The aim of this manuscript is to provide a comprehensive review of studies exploring depression treatment options in CKD. Observational studies as well as small trials suggest that certain serotonin-selective reuptake inhibitors may be safe to use in patients with advanced CKD and ESRD. These studies were limited by small sample sizes, lack of placebo control, and lack of formal assessment for depression diagnosis. Nonpharmacologic treatments were explored in selected ESRD samples. The most promising data were reported for frequent hemodialysis and cognitive behavioral therapy. Alternative proposed therapies include exercise training regimens, treatment of anxiety, and music therapy. Given the association of depression with cardiovascular events and mortality, and the excessive rates of cardiovascular death in CKD, it becomes imperative to not only investigate whether treatment of depression is efficacious, but also whether it would result in a reduction in morbidity and mortality in this patient population.

Health related quality of life and the CKD patient: challenges for the nephrology community

The compromised health-related quality of life (HRQOL) of patients with chronic kidney disease is now well documented. The recent mandate by the Center for Medicare Services in the United States that all dialysis units monitor HRQOL as a condition of coverage has focused attention on the importance of these measures. The challenge for the nephrology care team is understanding how to interpret and utilize the information obtained from these HRQOL measurements. Can HRQOL of these patients be improved? The present review addresses this issue by commenting on strategies that have been used to improve the HRQOL of chronic kidney disease patients. A systematic approach is suggested for nephrology care providers to attempt to evaluate and improve the HRQOL of CKD patients.

Effect of Daily Hemodialysis on Depressive Symptoms and Postdialysis Recovery Time: Interim Report From the FREEDOM (Following Rehabilitation, Economics and Everyday-Dialysis Outcome Measurements) Study

BACKGROUND Clinical depression and postdialysis fatigue are important concerns for patients with kidney failure and can have a negative impact on quality of life and survival. STUDY DESIGN The FREEDOM (Following Rehabilitation, Economics and Everyday-Dialysis Outcome Measurements) Study is an ongoing prospective cohort study investigating the clinical and economic benefits of daily (6 times per week) hemodialysis (HD). In this interim report, as part of an a priori planned analysis, we examine the long-term impact of daily HD on depressive symptoms, measured using the Beck Depression Inventory (BDI) survey, and postdialysis recovery time, measured using a previously validated questionnaire. SETTING & PARTICIPANTS Adult patients initiating daily HD with a planned 12-month follow-up. OUTCOMES & MEASUREMENTS The BDI survey and postdialysis recovery time question were administered at baseline, and changes were assessed at months 4 and 12. RESULTS 239 participants were enrolled (intention-to-treat cohort) and 128 completed the study (per-protocol cohort). Mean age was 52 years, 64% were men, 55% had an arteriovenous fistula, and 90% transitioned from in-center HD therapy. In the per-protocol cohort, there was a significant decrease in mean BDI score over 12 months (11.2 [95% CI, 9.6-12.9] vs 7.8 [95% CI, 6.5-9.1]; P<0.001). For robustness, the intention-to-treat analysis was performed, yielding similar results. The percentage of patients with depressive symptoms (BDI score>10) significantly decreased during 12 months (41% vs 27%; P=0.03). Similarly, in the per-protocol cohort, there was a significant decrease in postdialysis recovery time over 12 months (476 [95% CI, 359-594] vs 63 minutes [95% CI, 32-95]; P<0.001). The intention-to-treat analysis yielded similar results. The percentage of patients experiencing prolonged postdialysis recovery time (>or=60 minutes) also significantly decreased (81% vs 35%; P=0.001). LIMITATIONS Observational study with lack of control arm. CONCLUSIONS Daily HD is associated with long-term improvement in depressive symptoms and postdialysis recovery time.

Epidemiology, Diagnosis, and Management of Depression in Patients With CKD

A 58-year-old Hispanic man who has been dialysis dependent for 2 years because of diabetic nephropathy reports depressive symptoms during dialysis rounds. For the past 6 weeks, he has had reduced energy and difficulty sleeping and concentrating. He reports a loss of interest in his usual hobbies and family activities and notes an increasing sense of feeling worthless and guilty. He denies suicidal ideation. Medical history includes diabetic retinopathy and neuropathy, coronary artery disease treated with 4-vessel coronary artery bypass grafting 3 years ago, ischemic cardiomyopathy with an ejection fraction of 30%, and cerebrovascular disease. His wife recently has been given a diagnosis of breast cancer. His medications are aspirin, metoprolol, lisinopril, simvastatin, sevelamer, and epoetin alfa. His blood pressure is 130/75 mm Hg, pulse is 65 beats/min, and cardiac and pulmonary examination results are unremarkable. He is interviewed by the social worker in the dialysis unit, who diagnoses clinical depression by using standard Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) (DSM IV) criteria. The patient refuses to discuss his problems with the social worker and declines further psychiatric evaluation. His nephrologist discusses a trial of antidepressant medication, but the patient refuses to use additional medication. During the next month, the patient presents with greater interdialytic weight gains and begins to come late for dialysis sessions. He then presents to a dialysis session reporting dyspnea and orthopnea and is found to have a 10-kg weight gain. On physical examination, blood pressure is 196/96 mm Hg and he has increased jugular venous pressure and bibasilar crackles. He is admitted to the hospital with a diagnosis of congestive heart failure.

The identification and treatment of depression in patients maintained on dialysis.

The high incidence of depression in end‐stage renal disease (ESRD) patients is well documented. Our group and others have estimated that 20–30% of ESRD patients experience major depression. Several recent studies have emphasized the relationship between depressive symptoms and mortality and morbidity in both hemodialysis (HD) and peritoneal dialysis (PD) patients. We screened 380 PD patients for depression using the Beck Depression Inventory (BDI). The mean patient age was 59.9 ± 14.1 (SD) years, 55% were Caucasian, 51% were male, and 39% had diabetes. The mean BDI score was 12.1 ± 7.7; 49% had a score of 11 or greater. Fifty‐five percent refused further assessment to confirm the diagnosis of major depression, while 45% of patients eligible for treatment agreed to further assessment. Their mean BDI was 18.8 ± 6.2. Eighty‐four percent were diagnosed with major depression on direct interviews and offered pharmacologic treatment, 16% did not meet the criteria for a diagnosis of depression, and 50% successfully completed 12 weeks of pharmacologic treatment. The BDI score of these patients at the start of treatment was 17.4 ± 6.6, and at completion of treatment it was 8.4 ± 3.0. Thirty‐eight percent of treatment failures were in those who were also diagnosed with a DSM‐IV personality disorder. Major depression is common in PD patients, and is potentially treatable with pharmacologic therapy. However, there are major problems providing a depression assessment and treatment program to such patients. Problems include refusal to complete depression assessment and patients with axis 2 personality disorders who have difficulty complying with treatment. Although depression treatment can improve depressive symptoms, it is unclear whether such therapy will improve medical outcomes.

Serum Potassium and Outcomes in CKD: Insights from the RRI-CKD Cohort Study

BACKGROUND AND OBJECTIVES The relationship between serum potassium (S(K)) and mortality in chronic kidney disease (CKD) has not been systematically investigated. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We examined the predictors and mortality association of S(K) in the Renal Research Institute CKD Study cohort, wherein 820 patients with CKD were prospectively followed at four US centers for an average of 2.6 years. Predictors of S(K) were investigated using linear and repeated measures regression models. Associations between S(K) and mortality, the outcomes of ESRD, and cardiovascular events in time-dependent Cox models were examined. RESULTS The mean age was 60.5 years, 80% were white, 90% had hypertension, 36% had diabetes, the average estimated GFR was 25.4 ml/min per 1.73 m(2), and mean baseline S(K) was 4.6 mmol/L. Higher S(K) was associated with male gender, lower estimated GFR and serum bicarbonate, absence of diuretic and calcium channel blocker use, diabetes, and use of angiotensin-converting enzyme inhibitors and/or statins. A U-shaped relationship between S(K) and mortality was observed, with mortality risk significantly greater at S(K) < or = 4.0 mmol/L compared with 4.0 to 5.5 mmol/L. Risk for ESRD was elevated at S(K) < or = 4 mmol/L in S(K) categorical models. Only the composite of cardiovascular events or death as an outcome was associated with higher S(K) (> or = 5.5). CONCLUSIONS Although clinical practice usually emphasizes greater attention to elevated S(K) in the setting of CKD, our results suggest that patients who have CKD and low or even low-normal S(K) are at higher risk for dying than those with mild to moderate hyperkalemia.

Prevalence of chronic kidney disease in an urban HIV infected population.

Background:The prevalence of chronic kidney disease in an HIV-infected population during the highly active antiretroviral era has not been fully evaluated. Methods:A retrospective chart review of HIV-infected patients seen in 2004 was conducted to determine the prevalence of chronic kidney disease (CKD), using the 2004 National Kidney Foundations CKD staging criteria. Glomerular filtration rate (GFR) was calculated, using the Modification of Diet in Renal Disease formula. Univariate analyses were performed comparing individuals with normal kidney function and those with CKD. Multivariate analysis was conducted including all variables with a value of P < 0.1. Results:We found evidence of CKD in 24% of the patients. Forty patients (10%) had stage 1 CKD, 19 patients (4%) stage 2, 29 patients (7%) stage 3, 4 patients (1%) stage 4, and 8 patients (2%) stage 5. Patients with CKD are more likely to be African American (AA), older, have AIDS, lower CD4 counts and higher HIV viral loads. Patients with CKD were also more likely to have hypertension (HTN), diabetes mellitus (DM), or both. Indinavir or tenofovir exposure was associated with CKD. In multivariate analysis HTN, AA race, or HTN and DM were the only significant predictors of CKD. Physicians did not identify CKD in 74% of patients. Renal biopsies were done in 10 patients; 5 had HIV-associated nephropathy. Conclusions:Substantial minorities of HIV-infected patients have CKD. AA race or the presence of HTN or HTN and DM is associated with CKD. Clinicians often do not note the presence of CKD in this population.