Nodular Regenerative Hyperplasia of the Liver in Rheumatic Disease: Cases and Review of the Literature.

Nodular regenerative hyperplasia (NRH) is a rare disease that is characterized by benign transformation of the hepatic parenchyma into small nodules with little to no fibrosis. Nodular regenerative hyperplasia is a cause of noncirrhotic portal hypertension. Symptoms can range from asymptomatic disease to more serious complications of portal hypertension such as esophageal varices and ascites. Nodular regenerative hyperplasia has been described in association with a variety of different rheumatologic, hematologic, and oncologic diseases, as well as in immune deficiency states and with exposures to certain toxins. Diagnosis is made by histology, and the treatment involves addressing the underlying disease. The first description of this rare disease was actually described in a patient with rheumatoid arthritis, neutropenia, and splenomegaly (Felty's Syndrome). We describe 2 cases of NRH associated with underlying rheumatic disorders, in one of which NRH was actually the presenting feature of the patient's underlying autoimmune condition. Subsequently, we provide a brief review of the literature of NRH in autoimmune disease with respect to epidemiology, cause, clinical manifestations, diagnosis, and treatment.

Implications of Early Decline in eGFR due to Intensive BP Control for Cardiovascular Outcomes in SPRINT.

BACKGROUND: The Systolic BP Intervention Trial (SPRINT) found that intensive versus standard systolic BP control (targeting <120 or <140 mm Hg, respectively) reduced the risks of death and major cardiovascular events in persons with elevated cardiovascular disease risk. However, the intensive intervention was associated with an early decline in eGFR, and the clinical implications of this early decline are unclear. METHODS: In a post hoc analysis of SPRINT, we defined change in eGFR as the percentage change in eGFR at 6 months compared with baseline. We performed causal mediation analyses to separate the overall effects of the randomized systolic BP intervention on the SPRINT primary cardiovascular composite and all-cause mortality into indirect effects (mediated by percentage change in eGFR) and direct effects (mediated through pathways other than percentage change in eGFR). RESULTS: About 10.3% of the 4270 participants in the intensive group had a ≥20% eGFR decline versus 4.4% of the 4256 participants in the standard arm (P<0.001). After the 6-month visit, there were 591 cardiovascular composite events during 27,849 person-years of follow-up. The hazard ratios for total effect, direct effect, and indirect effect of the intervention on the cardiovascular composite were 0.67 (95% confidence interval [95% CI], 0.56 to 0.78), 0.68 (95% CI, 0.57 to 0.79), and 0.99 (95% CI, 0.95 to 1.03), respectively. All-cause mortality results were similar. CONCLUSIONS: Although intensive systolic BP lowering resulted in greater early decline in eGFR, there was no evidence that the reduction in eGFR owing to intensive systolic BP lowering attenuated the beneficial effects of this intervention on cardiovascular events or all-cause mortality.

Acute Kidney Injury in Subjects With Chronic Kidney Disease Undergoing Total Joint Arthroplasty.

BACKGROUND: Chronic kidney disease (CKD) has been associated with higher incidence of complications after total joint arthroplasty (TJA) but the incidence, risk factors and outcomes of acute kidney injury (AKI) in this setting remains insufficiently understood. METHODS: We assessed the impact of baseline CKD on the risk of developing AKI after TJA performed between 1/2012 and 12/2016 in a single-center, retrospective cohort study. CKD was defined by estimated glomerular filtration rate <60 mL/min/1.73 m2 on 2 separate occasions within 3 months prior TJA. AKI was defined using a modified Kidney Disease: Improving Global Outcomes criteria based on serum creatinine (sCr) only to assess the severity of AKI. Complete AKI recovery was defined as the lowest post-AKI sCr within 20% of pre-AKI sCr values and partial recovery if within 30%, all within 90 days after TJA. RESULTS: Twenty-four percent of the 1,212 subjects undergoing TJA had pre-existing CKD. The overall incidence of AKI in the CKD subjects was 30%; of these, 55% had stage-1 AKI, 1% had stage-2 AKI and 44% had stage-3 AKI. AKI was more common in African Americans, those with diabetes or heart failure, requiring perioperative transfusions or receiving diuretics before surgery. While 82% of the AKI subjects achieved complete recovery of kidney function, 4% had only partial recovery and 14% did not reach a post-AKI sCr level within 30% of pre-AKI values. The incidence (P < 0.001) but not the severity (P = 0.202) of AKI correlated with stages of baseline CKD. CONCLUSIONS: The presence of CKD was associated with a high incidence of AKI after TJA. In these subjects, more than half the cases of AKI were of mild degree and had a favorable outcome. However, 18% of them did not have complete recovery of kidney function. Stages of baseline CKD were associated with increased incidence but not severity of AKI after TJA.

The dialysis orders objective structured clinical examination (OSCE): a formative assessment for nephrology fellows.

BACKGROUND: Few quantitative nephrology-specific simulations assess fellow competency. We describe the development and initial validation of a formative objective structured clinical examination (OSCE) assessing fellow competence in ordering acute dialysis. METHODS: The three test scenarios were acute continuous renal replacement therapy, chronic dialysis initiation in moderate uremia and acute dialysis in end-stage renal disease-associated hyperkalemia. The test committee included five academic nephrologists and four clinically practicing nephrologists outside of academia. There were 49 test items (58 points). A passing score was 46/58 points. No item had median relevance less than 'important'. The content validity index was 0.91. Ninety-five percent of positive-point items were easy-medium difficulty. Preliminary validation was by 10 board-certified volunteers, not test committee members, a median of 3.5 years from graduation. The mean score was 49 [95% confidence interval (CI) 46-51], κ = 0.68 (95% CI 0.59-0.77), Cronbach's α = 0.84. RESULTS: We subsequently administered the test to 25 fellows. The mean score was 44 (95% CI 43-45); 36% passed the test. Fellows scored significantly less than validators (P < 0.001). Of evidence-based questions, 72% were answered correctly by validators and 54% by fellows (P = 0.018). Fellows and validators scored least well on the acute hyperkalemia question. In self-assessing proficiency, 71% of fellows surveyed agreed or strongly agreed that the OSCE was useful. CONCLUSIONS: The OSCE may be used to formatively assess fellow proficiency in three common areas of acute dialysis practice. Further validation studies are in progress.

Effects of Intensive Blood Pressure Treatment on Acute Kidney Injury Events in the Systolic Blood Pressure Intervention Trial (SPRINT).

BACKGROUND: Treating to a lower blood pressure (BP) may increase acute kidney injury (AKI) events. STUDY DESIGN: Data for AKI resulting in or during hospitalization or emergency department visits were collected as part of the serious adverse events reporting process of the Systolic Blood Pressure Intervention Trial (SPRINT). SETTING & PARTICIPANTS: 9,361 participants 50 years or older with 1 or more risk factors for cardiovascular disease. INTERVENTIONS: Participants were randomly assigned to a systolic BP target of <120 (intensive arm) or <140mmHg (standard arm). OUTCOMES & MEASUREMENTS: Primary outcome was the number of adjudicated AKI events. Secondary outcomes included severity of AKI and degree of recovery of kidney function after an AKI event. Baseline creatinine concentration was defined as the most recent SPRINT outpatient creatinine value before the date of the AKI event. RESULTS: There were 179 participants with AKI events in the intensive arm and 109 in the standard arm (3.8% vs 2.3%; HR, 1.64; 95% CI, 1.30-2.10; P<0.001). Of 288 participants with an AKI event, 248 (86.1%) had a single AKI event during the trial. Based on modified KDIGO (Kidney Disease: Improving Global Outcomes) criteria for severity of AKI, the number of AKI events in the intensive versus standard arm by KDIGO stage was 128 (58.5%) versus 81 (62.8%) for AKI stage 1, 42 (19.2%) versus 18 (14.0%) for AKI stage 2, and 42 (19.2%) versus 25 (19.4%) for AKI stage 3 (P=0.5). For participants with sufficient data, complete or partial resolution of AKI was seen for 169 (90.4%) and 9 (4.8%) of 187 AKI events in the intensive arm and 86 (86.9%) and 4 (4.0%) of 99 AKI events in the standard arm, respectively. LIMITATIONS: Trial results are not generalizable to patients with diabetes mellitus or without risk factors for cardiovascular disease. CONCLUSIONS: More intensive BP lowering resulted in more frequent episodes of AKI. Most cases were mild and most participants had complete recovery of kidney function. TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCT01206062.

Influence of Baseline Diastolic Blood Pressure on Effects of Intensive Compared With Standard Blood Pressure Control.

BACKGROUND: In individuals with a low diastolic blood pressure (DBP), the potential benefits or risks of intensive systolic blood pressure (SBP) lowering are unclear. METHODS: SPRINT (Systolic Blood Pressure Intervention Trial) was a randomized controlled trial that compared the effects of intensive (target <120 mm Hg) and standard (target <140 mm Hg) SBP control in 9361 older adults with high blood pressure at increased risk of cardiovascular disease. The primary outcome was a composite of cardiovascular disease events. All-cause death and incident chronic kidney disease were secondary outcomes. This post hoc analysis examined whether the effects of the SBP intervention differed by baseline DBP. RESULTS: Mean baseline SBP and DBP were 139.7±15.6 and 78.1±11.9 mm Hg, respectively. Regardless of the randomized treatment, baseline DBP had a U-shaped association with the hazard of the primary cardiovascular disease outcome. However, the effects of the intensive SBP intervention on the primary outcome were not influenced by baseline DBP level (P for interaction=0.83). The primary outcome hazard ratio for intensive versus standard treatment was 0.78 (95% confidence interval, 0.57-1.07) in the lowest DBP quintile (mean baseline DBP, 61±5 mm Hg) and 0.74 (95% confidence interval, 0.61-0.90) in the upper 4 DBP quintiles (mean baseline DBP, 82±9 mm Hg), with an interaction P value of 0.78. Results were similar for all-cause death and kidney events. CONCLUSIONS: Low baseline DBP was associated with increased risk of cardiovascular disease events, but there was no evidence that the benefit of the intensive SBP lowering differed by baseline DBP. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01206062.

Intensive vs Standard Blood Pressure Control and Cardiovascular Disease Outcomes in Adults Aged ≥75 Years: A Randomized Clinical Trial.

IMPORTANCE: The appropriate treatment target for systolic blood pressure (SBP) in older patients with hypertension remains uncertain. OBJECTIVE: To evaluate the effects of intensive (<120 mm Hg) compared with standard (<140 mm Hg) SBP targets in persons aged 75 years or older with hypertension but without diabetes. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, randomized clinical trial of patients aged 75 years or older who participated in the Systolic Blood Pressure Intervention Trial (SPRINT). Recruitment began on October 20, 2010, and follow-up ended on August 20, 2015. INTERVENTIONS: Participants were randomized to an SBP target of less than 120 mm Hg (intensive treatment group, n = 1317) or an SBP target of less than 140 mm Hg (standard treatment group, n = 1319). MAIN OUTCOMES AND MEASURES: The primary cardiovascular disease outcome was a composite of nonfatal myocardial infarction, acute coronary syndrome not resulting in a myocardial infarction, nonfatal stroke, nonfatal acute decompensated heart failure, and death from cardiovascular causes. All-cause mortality was a secondary outcome. RESULTS: Among 2636 participants (mean age, 79.9 years; 37.9% women), 2510 (95.2%) provided complete follow-up data. At a median follow-up of 3.14 years, there was a significantly lower rate of the primary composite outcome (102 events in the intensive treatment group vs 148 events in the standard treatment group; hazard ratio [HR], 0.66 [95% CI, 0.51-0.85]) and all-cause mortality (73 deaths vs 107 deaths, respectively; HR, 0.67 [95% CI, 0.49-0.91]). The overall rate of serious adverse events was not different between treatment groups (48.4% in the intensive treatment group vs 48.3% in the standard treatment group; HR, 0.99 [95% CI, 0.89-1.11]). Absolute rates of hypotension were 2.4% in the intensive treatment group vs 1.4% in the standard treatment group (HR, 1.71 [95% CI, 0.97-3.09]), 3.0% vs 2.4%, respectively, for syncope (HR, 1.23 [95% CI, 0.76-2.00]), 4.0% vs 2.7% for electrolyte abnormalities (HR, 1.51 [95% CI, 0.99-2.33]), 5.5% vs 4.0% for acute kidney injury (HR, 1.41 [95% CI, 0.98-2.04]), and 4.9% vs 5.5% for injurious falls (HR, 0.91 [95% CI, 0.65-1.29]). CONCLUSIONS AND RELEVANCE: Among ambulatory adults aged 75 years or older, treating to an SBP target of less than 120 mm Hg compared with an SBP target of less than 140 mm Hg resulted in significantly lower rates of fatal and nonfatal major cardiovascular events and death from any cause. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01206062.

Antiproteinuric therapy and Fabry nephropathy: factors associated with preserved kidney function during agalsidase-beta therapy.

BACKGROUND: Nephropathy is an important feature of classical Fabry disease, which results in alpha-galactosidase A deficiency and cellular globotriaosylceramide accumulation. We report the safety and efficacy of antiproteinuric therapy with ACE inhibitors or angiotensin II receptor blockers (ARBs) in a study of classical Fabry patients receiving recombinant agalsidase-beta therapy. METHODS AND DESIGN: The goal was maintenance of urine protein to creatinine ratio (UPCR) <0.5 g/g or a 50% reduction in baseline UPCR for 24 patients at eight study sites. The change in estimated glomerular filtration rate (eGFR) was assessed over 21 months of treatment. RESULTS: 18 out of 24 patients achieved the UPCR goal with eGFR slopes that were significantly better than six patients who did not achieve the UPCR goal (-3.6 (-4.8 to -1.1) versus -7.0 (-9.0 to -5.6) mL/min/1.73 m(2)/year, respectively, p=0.018). Despite achieving the UPCR goal, 67% (12/18 patients) still progressed with an eGFR slope <-2 mL/min/1.73 m(2)/year. Regression analysis showed that increased age at initiation of agalsidase-beta therapy was significantly associated with worsened kidney outcome. Hypotension and hyperkalaemia occurred in seven and eight patients, respectively, which required modification of antiproteinuric therapy but was not associated with serious adverse events. CONCLUSIONS: This study documents the effectiveness of agalsidase-beta (1 mg/kg/2 weeks) and antiproteinuric therapy with ACE inhibitors and/or ARB in patients with severe Fabry nephropathy. Patients had preservation of kidney function if agalsidase-beta treatment was initiated at a younger age, and UPCR maintained at or below 0.5 g/g with antiproteinuric therapy. TRIAL REGISTRATION NUMBER: NCT00446862.

Interdisciplinary care clinics in chronic kidney disease.

The burden of chronic kidney disease (CKD) is substantial, and is associated with high hospitalization rates, premature deaths, and considerable health care costs. These factors provide strong rationale for quality improvement initiatives in CKD care. The interdisciplinary care clinic (IDC) has emerged as one solution to improving CKD care. The IDC team may include other physicians, advanced practice providers, nurses, dietitians, pharmacists, and social workers--all working together to provide effective care to patients with chronic kidney disease. Studies suggest that IDCs may improve patient education and preparedness prior to kidney failure, both of which have been associated with improved health outcomes. Interdisciplinary care may also delay the progression to end-stage renal disease and reduce mortality. While most studies suggest that IDC services are likely cost-effective, financing IDCs is challenging and many insurance providers do not pay for all of the services. There are also no robust long-term studies demonstrating the cost-effectiveness of IDCs. This review discusses IDC models and its potential impact on CKD care as well as some of the challenges that may be associated with implementing these clinics.

High sodium:potassium intake ratio increases the risk for all-cause mortality: the REasons for Geographic And Racial Differences in Stroke (REGARDS) study.

Increased dietary Na intake and decreased dietary K intake are associated with higher blood pressure. It is not known whether the dietary Na:K ratio is associated with all-cause mortality or stroke incidence and whether this relationship varies according to race. Between 2003 and 2007, the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort enrolled 30 239 black and white Americans aged 45 years or older. Diet was assessed using the Block 98 FFQ and was available on 21 374 participants. The Na:K ratio was modelled in race- and sex-specific quintiles for all analyses, with the lowest quintile (Q1) as the reference group. Data on other covariates were collected using both an in-home assessment and telephone interviews. We identified 1779 deaths and 363 strokes over a mean of 4·9 years. We used Cox proportional hazards models to obtain multivariable-adjusted hazard ratios (HR). In the highest quintile (Q5), a high Na:K ratio was associated with all-cause mortality (Q5 v. Q1 for whites: HR 1·22; 95 % CI 1·00, 1·47, P for trend = 0·084; for blacks: HR 1·36; 95 % CI 1·04, 1·77, P for trend = 0·028). A high Na:K ratio was not significantly associated with stroke in whites (HR 1·29; 95 % CI 0·88, 1·90) or blacks (HR 1·39; 95 % CI 0·78, 2·48), partly because of the low number of stroke events. In the REGARDS study, a high Na:K ratio was associated with all-cause mortality and there was a suggestive association between the Na:K ratio and stroke. These data support the policies targeted at reduction of Na from the food supply and recommendations to increase K intake.

Association of dietary sodium and potassium intakes with albuminuria in normal-weight, overweight, and obese participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study.

BACKGROUND: Among obese adults, sodium intake has been associated with cardiovascular disease. Few data are available on sodium intake and albuminuria, a marker of kidney damage and risk factor for cardiovascular disease. OBJECTIVE: We examined the relation between dietary sodium and potassium intakes and the ratio of sodium to potassium (Na/K) with albuminuria by BMI in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study (n = 30,239 adults aged ≥45 y). DESIGN: A modified Block 98 food-frequency questionnaire was used for dietary assessment in 21,636 participants, and nutritional variables were categorized by sex-specific quintiles. Normal weight, overweight, and obese were defined as BMI (in kg/m(2)) categories of 18.5-24.9, 25-29.9, and ≥30, respectively. Albuminuria was defined as a ratio (mg/g) of urinary albumin to creatinine of ≥30. RESULTS: The prevalences of albuminuria were 11.5%, 11.6%, and 16.0% in normal-weight, overweight, and obese participants, respectively. The multivariable-adjusted ORs for albuminuria in a comparison of the highest with the lowest quintile of Na/K intake (≥1.12 to <0.70 for men and ≥1.07 to <0.62 for women) were 0.89 (95% CI: 0.65, 1.22), 1.08 (95% CI: 0.85, 1.36), and 1.28 (95% CI: 1.02, 1.61) in normal-weight, overweight, and obese participants, respectively. The highest quintile of dietary sodium was associated with an increased OR for albuminuria in obese participants (OR: 1.44; 95% CI: 1.00, 2.07) but not in normal-weight or overweight participants. Dietary potassium was not associated with albuminuria. CONCLUSION: In obese adults, higher dietary Na/K and sodium intakes were associated with albuminuria.

Impact of chronic kidney disease on activities of daily living in community-dwelling older adults.

BACKGROUND: Although chronic kidney disease (CKD) is associated with poor physical function, less is known about the longitudinal association between CKD and the decline of instrumental activities of daily living (IADL) and basic activities of daily living (BADL) among community-dwelling older adults. METHODS: Participants were part of the prospective observational University of Alabama at Birmingham Study of Aging (n = 357). CKD was defined as an estimated glomerular filtration rate less than 60 mL/min/1.73 m(2) using the Modification of Diet in Renal Disease equation. Primary outcomes were IADL and BADL decline defined as an increase in the number of activities for which participants reported difficulty after 2 years. Forward stepwise logistic regression was used to determine associations of baseline CKD and functional decline. RESULTS: Participants had a mean age of 77.4 (SD = 5.8) years, 41% were African American, and 52% women. IADL decline occurred in 35% of those with CKD and 17% of those without (unadjusted odds ratio, 2.62, 95% confidence intervals [95% CI], 1.59-4.30, p < .001). BADL decline occurred in 20% and 7% of those with and without CKD, respectively (unadjusted odds ratio, 3.37; 95% CI, 1.73-6.57; p < .001). Multivariable-adjusted odds ratio's (95% CI's) for CKD-associated IADL and BADL decline were 1.83 (1.06-3.17, p =.030) and 2.46 (1.19-5.12, p = .016), respectively. CKD Stage ≥3B (estimated glomerular filtration rate <45 mL/min/1.73 m(2)) was associated with higher multivariable-adjusted odds of both IADL (3.12, 95% CI, 1.38-7.06, p = .006) and BADL (3.78, 95% CI, 1.36-9.77, p = .006) decline. CONCLUSION: In community-dwelling older adults, CKD is associated with IADL and BADL decline.

Hypokalemia and outcomes in patients with chronic heart failure and chronic kidney disease: findings from propensity-matched studies.

BACKGROUND: Little is known about the effects of hypokalemia on outcomes in patients with chronic heart failure (HF) and chronic kidney disease. METHODS AND RESULTS: Of the 7788 patients with chronic HF in the Digitalis Investigation Group trial, 2793 had chronic kidney disease, defined as estimated glomerular filtration rate <60 mL/min per 1.73 m(2). Of these, 527 had hypokalemia (serum potassium <4 mEq/L; mild) and 2266 had normokalemia (4 to 4.9 mEq/L). Propensity scores for hypokalemia were used to assemble a balanced cohort of 522 pairs of patients with hypokalemia and normokalemia. All-cause mortality occurred in 48% and 36% of patients with hypokalemia and normokalemia, respectively, during 57 months of follow-up (matched hazard ratio when hypokalemia was compared with normokalemia, 1.56; 95% CI, 1.25 to 1.95; P<0.0001). Matched hazard ratios (95% CIs) for cardiovascular and HF mortalities and all-cause, cardiovascular, and HF hospitalizations were 1.65 (1.29 to 2.11; P<0.0001), 1.82 (1.28 to 2.57; P<0.0001), 1.16 (1.00 to 1.35; P=0.036), 1.27 (1.08 to 1.50; P=0.004), and 1.29 (1.05 to 1.58; P=0.014), respectively. Among 453 pairs of balanced patients with HF and chronic kidney disease, all-cause mortality occurred in 47% and 38% of patients with mild hypokalemia (3.5 to 3.9 mEq/L) and normokalemia, respectively (matched hazard ratio, 1.31; 95% CI, 1.03 to 1.66; P=0.027). Among 169 pairs of balanced patients with estimated glomerular filtration rate <45 mL/min per 1.73 m(2), all-cause mortality occurred in 57% and 47% of patients with hypokalemia (<4 mEq/L; mild) and normokalemia, respectively (matched hazard ratio, 1.53; 95% CI, 1.07 to 2.19; P=0.020). CONCLUSIONS: In patients with HF and chronic kidney disease, hypokalemia (serum potassium <4 mEq/L) is common and associated with increased mortality and hospitalization.

Mild hyperkalemia and outcomes in chronic heart failure: a propensity matched study.

BACKGROUND: Compared with serum potassium levels 4-5.5 mEq/L, those <4 mEq/L have been shown to increase mortality in chronic heart failure (HF). Expert opinions suggest that serum potassium levels >5.5 mEq/L may be harmful in HF. However, little is known about the safety of serum potassium 5-5.5 mEq/L. METHODS: Of the 7788 chronic HF patients in the Digitalis Investigation Group trial, 5656 had serum potassium 4-5.5 mEq/L. Of these, 567 had mild hyperkalemia (5-5.5 mEq/L) and 5089 had normokalemia (4-4.9 mEq/L). Propensity scores for mild hyperkalemia were used to assemble a balanced cohort of 548 patients with mild hyperkalemia and 1629 patients with normokalemia. Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for association between mild hyperkalemia and mortality during a median follow-up of 38 months. RESULTS: All-cause mortality occurred in 36% and 38% of matched patients with normokalemia and mild hyperkalemia respectively (HR, 1.07; 95% CI, 0.90-1.26; P=0.458). Unadjusted, multivariable-adjusted, and propensity-adjusted HRs for mortality associated with mild hyperkalemia were 1.33 (95% CI, 1.15-1.52; P<0.0001), 1.16 (95% CI, 1.01-1.34; P=0.040) and 1.13 (95% CI, 0.98-1.31; P=0.091) respectively. Mild hyperkalemia had no association with cardiovascular or HF mortality or all-cause or cardiovascular hospitalization. CONCLUSION: Serum potassium 4-4.9 mEq/L is optimal and 5-5.5 mEq/L appears relatively safe in HF. Despite lack of an intrinsic association , the bivariate association of mild-hyperkalemia with mortality suggests that it may be useful as a biomarker of poor prognosis in HF.

Mineralocorticoid receptor blockers and chronic kidney disease.

The increasing prevalence of chronic kidney disease (CKD) and the public health initiatives for detection and slowing its progression have placed special emphasis on controlling proteinuria and the renin-angiotensin-aldosterone system (RAAS). In addition to the traditional blockers of angiotensin-converting enzyme and angiotensin receptors, mineralocorticoid receptor blockers (MRBs) have come into focus as anti-proteinuric agents with moderate anti-hypertensive effects. The beneficial effects of MRBs on mortality in patients with cardiac disease have been well described. We review the role of aldosterone in end-organ damage, the rationales for using MRBs as adjuncts to angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in treating CKD, and the adverse effects that may occur when these agents are used in combination. Suggestions are included for avoiding serious adverse events in CKD patients treated with MRBs. There is a clearly defined need for prospective outcome studies focused on cardiovascular mortality as well as progression of CKD in patients treated with MRBS and other inhibitors of the RAAS.

Effects of diabetes mellitus in patients with heart failure and chronic kidney disease: a propensity-matched study of multimorbidity in chronic heart failure.

BACKGROUND: Chronic kidney disease (CKD) and diabetes mellitus (DM) are common comorbidities in heart failure (HF) and each is associated with poor outcomes. However, the effects of multimorbidity related to having both CKD and DM compared to CKD alone have not been well studied in a propensity-matched population of chronic HF patients. METHODS: Of the 7788 ambulatory chronic HF patients in the Digitalis Investigation Group trial, 3527 had CKD, of whom 1095 had DM. Based on the absence or presence of DM, patients were categorized CKD-only and CKD-DM, respectively. Propensity scores for CKD-DM were calculated for each patient and were used to match 987 pairs of CKD-only and CKD-DM patients. Hazard ratios (HR) and 95% confidence intervals (CI) comparing CKD-DM patients with CKD-only patients were estimated using matched Cox regression models. RESULTS: All-cause mortality occurred in 47.0% (rate, 1783/10,000 person-years of follow-up) of CKD-DM patients and 39.6% (rate, 1414/10,000 person-years) of CKD-only patients (HR when CKD-DM is compared with CKD-only, 1.25; 95%-CI, 1.07-1.46; p=0.006). All-cause hospitalization occurred in 75.4% (rate, 5710/10,000 person-years) and 67.8% (rate, 4213/10,000 person-years) of CKD-DM and CKD-only patients respectively (HR, 1.32; 95%-CI, 1.15-1.52; p<0.0001). Respective HR and 95%-CI for other outcomes were: cardiovascular mortality (1.27; 1.06-1.52; p=0.009), HF mortality (1.34; 1.04-1.72; p=0.025); cardiovascular hospitalization (1.29; 1.12-1.49; p=0.001) and HF hospitalization (1.37; 1.16-1.63; p<0.0001). CONCLUSIONS: Compared with comorbidity due to CKD alone, multimorbidity with CKD and DM was associated with poor outcomes in chronic HF patients.

Multimorbidity due to diabetes mellitus and chronic kidney disease and outcomes in chronic heart failure.

Diabetes mellitus (DM) and chronic kidney disease (CKD) are common in patients with chronic heart failure (HF) and are associated with poor outcomes. However, the impact of multimorbidity due to DM and CKD on outcomes, relative to co-morbidity due to DM alone, has not been well studied in these patients. Of the 7,788 patients with chronic HF in the Digitalis Investigation Group trial, 2,218 had DM. We categorized these patients into those with DM alone (DM-only n = 1,123) and those with both DM and CKD (DM-CKD n = 1,095). Propensity scores for DM-CKD, calculated for each of the 2,218 patients, were used to match 699 pairs of patients with DM-only or DM-CKD. Matched Cox regression models were used to estimate associations between DM-CKD and outcomes. All-cause mortality occurred in 44% (rate 1,648/10,000 person-years) of patients with DM-CKD and 39% (rate 1,349/10,000 person-years of follow-up) of patients with DM-only (hazard ratio when DM-CKD was compared with DM-only 1.34, 95% confidence interval [CI] 1.11 to 1.62, p = 0.003). All-cause hospitalization occurred in 76% (rate 5,799/10,000 person-years) and 73% (rate 4,909/10,000 person-years) of patients with DM-CKD and DM-only, respectively (hazard ratio 1.16, 95% CI 0.99 to 1.36, p = 0.064). Respective hazard ratios for other outcomes were cardiovascular mortality 1.33 (95% CI 1.07 to 1.66, p = 0.010), HF mortality 1.41 (95% CI 1.02 to 1.96, p = 0.040), cardiovascular hospitalization 1.17 (95% CI 0.99 to 1.39, p = 0.064), and HF hospitalization 1.26 (95% CI 1.03 to 1.55, p = 0.026). In conclusion, compared with co-morbidity due to DM alone, the presence of multimorbidity due to DM and CKD was associated with increased mortality and morbidity in patients with chronic HF.