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The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.
ACUTE AND CHRONIC KIDNEY DISEASE
Healthy Transitions Program for chronic kidney disease (October 2017)
A randomized trial has shown that an outpatient care management program utilizing nurse care managers supported by a protocol-driven informatics system for patients with late-stage chronic kidney disease (stage 4 to 5 CKD) decreases hospitalization rates, increases the rate at which hemodialysis is begun without a hospitalization, decreases the use of catheters, and increases the selection of peritoneal dialysis . The informatics system provided daily reports for each patient that identified incomplete process steps (including discussions of renal replacement modality, dietary education, medication reconciliation, and home safety). Although the trial was small, these data suggest important benefits of such a program. (See "Overview of the management of chronic kidney disease in adults", section on 'Multidisciplinary chronic kidney disease clinic'.)
Thrombotic microangiopathy due to quinine ingestion (October 2017)
Quinine is a common cause of drug-induced thrombotic microangiopathy (DITMA). A new report illustrates common features among the largest series of individuals (18 women and 1 man) with quinine-associated DITMA . Most of the patients had a prior history of quinine-induced fever, nausea, headache, or confusion. Many reported symptoms within four hours of quinine ingestion. All had acute kidney injury. Eighteen required dialysis, and two underwent renal transplantation. Eighteen had quinine-dependent antibodies. Individuals presenting with thrombotic microangiopathy require specific questioning about quinine ingestion since the source may be a beverage or an over-the-counter tablet. (See "Drug-induced thrombotic microangiopathy", section on 'Quinine'.)
SGLT2 inhibitors and risk of acute kidney injury (October 2017)
In postmarketing reports, sodium-glucose co-transporter 2 (SGLT2) inhibitors used for the treatment of type 2 diabetes have been associated with acute kidney injury, with some patients requiring hospitalization and dialysis. However, a recent analysis of two different cohorts of diabetic patients, including both SGLT2 users and nonusers, did not show an increased risk of acute kidney injury . Nevertheless, renal function should be assessed prior to initiation of SGLT2 inhibitors and monitored during treatment. (See "Sodium-glucose co-transporter 2 inhibitors for the treatment of type 2 diabetes mellitus", section on 'Acute kidney injury'.)
Fibroblast growth factor (FGF) 23 and polycystic kidney disease (October 2017)
Fibroblast growth factor (FGF) 23 plays a key role in phosphorus homeostasis, and blood levels of FGF23 are markedly increased in patients with reduced estimated glomerular filtration rate (eGFR). FGF23 was measured in baseline blood samples from individuals in the Halt Progression of Polycystic Kidney Disease (HALT-PKD) A and B Studies . The highest FGF23 quartile was associated with more rapid decline in the annualized eGFR compared with the lowest FGF23 quartile, even among individuals with preserved eGFR. Higher FGF23 levels were also associated with a greater increase in height-adjusted total kidney volume, which predicts progression of CKD, but adding FGF23 to existing prediction models did not improve the prediction of CKD progression. These data suggest a possible mechanistic role for FGF23 in progression of polycystic kidney disease. (See "Course and treatment of autosomal dominant polycystic kidney disease", section on 'Increased fibroblast growth factor (FGF) 23'.)
Chronic fluid overload and mortality in hemodialysis (October 2017)
The importance of maintaining an accurate dry weight among hemodialysis patients is generally accepted. A large observational study demonstrated striking associations between one-year cumulative fluid overload and increased mortality among outpatient hemodialysis patients, particularly among those with lower blood pressures . The effect of fluid overload was similar in all groups when stratified by age, sex, body mass index, and comorbidities including diabetes and heart disease. However, given the limitations of observational data, this study does not prove a causal relationship between fluid overload and mortality. (See "Patient survival and maintenance dialysis", section on 'Control of fluid balance and hypertension'.)
GLOMERULAR DISEASE AND VASCULITIS
Oral glucocorticoids versus supportive therapy in progressive IgA nephropathy (October 2017)
The optimal role of anti-inflammatory therapy in IgA nephropathy is uncertain. A randomized trial evaluated the efficacy and safety of oral methylprednisolone versus placebo in over 250 patients with IgA nephropathy, an estimated glomerular filtration rate (eGFR) of 20 to 120 mL/min/1.73 m2, and proteinuria of >1 g/day after at least three months of supportive therapy (blood pressure control with maximally tolerated renin-angiotensin system blockade); supportive therapy was continued in both groups . The primary renal endpoint (a composite of end-stage renal disease, death due to renal failure, or a 40 percent decrease in eGFR) occurred in fewer patients in the glucocorticoid group. However, the trial was terminated early because of an excess of serious adverse effects (mostly serious infection) in the methylprednisolone arm, and definitive conclusions about the benefits or harms of treatment could not be drawn. We continue to suggest oral glucocorticoids in patients with IgA nephropathy and clinical features indicating active disease and progression. (See "Treatment and prognosis of IgA nephropathy", section on 'Glucocorticoids as sole immunosuppressive/anti-inflammatory therapy'.)
Effects of agalsidase dosing on kidney histology in Fabry disease (July 2017)
The treatment of patients with Fabry disease primarily focuses upon replacing the missing or deficient enzyme (alpha-galactosidase A). In one study of 20 Fabry patients, both lower and higher doses of recombinant alpha-galactosidase A (agalsidase) significantly reduced podocyte accumulation of Gb3 in serial kidney biopsies performed over a mean of 9.4 years, and albuminuria and the rate of renal function decline did not differ between the groups . Histologically, higher cumulative agalsidase doses correlated with increased clearance of podocyte Gb3, and arterial/arteriolar intimal Gb3 inclusions were reduced, compared with baseline, in the higher-dose group. These findings support our dosing recommendations for Fabry patients who initiate therapy with enzyme replacement. (See "Fabry disease: Treatment", section on 'Dosing of ERT'.)
Prevalence of high blood pressure in United States adults under the 2017 revised definition of hypertension (November 2017)
The 2017 American College of Cardiology/American Heart Association (ACC/AHA) guidelines changed the definition of hypertension in adults (now defined as a systolic pressure ≥130 mmHg and/or a diastolic pressure ≥80 mmHg). This has substantially changed the prevalence of hypertension among adults in the United States. According to NHANES data from 2011 to 2014, 46 percent of adults 18 years and older had hypertension . Based upon the size of the adult population, this translates into 103 million adults in the United States with hypertension. (See "The prevalence and control of hypertension in adults", section on 'Prevalence of hypertension'.)
New criteria for hypertension in the 2017 American College of Cardiology/American Heart Association (ACC/AHA) guidelines (November 2017)
The 2017 American College of Cardiology/American Heart Association (ACC/AHA) guidelines, with input from the American Society of Hypertension (ASH) as well as geriatrics, pharmacist, and nursing organizations, provide guidance for the prevention, detection, evaluation, and management of hypertension in adults . Major changes from prior recommendations include a lower threshold for the diagnosis of hypertension based upon office blood pressure readings (hypertension now defined as a blood pressure ≥130 mmHg systolic or ≥80 mmHg diastolic), and a lower blood pressure goal (<130/<80 mmHg). Pharmacologic therapy is recommended for all hypertensive patients with a higher cardiovascular risk, and for lower-risk patients who have a blood pressure ≥140 mmHg systolic or ≥90 mmHg diastolic. Recommendations in UpToDate are broadly consistent with these guidelines. (See "What is goal blood pressure in the treatment of hypertension?" and "Overview of hypertension in adults" and "Blood pressure measurement in the diagnosis and management of hypertension in adults" and "The prevalence and control of hypertension in adults".)
Effect of renal denervation on blood pressure in hypertensive patients without resistant hypertension (October 2017)
Catheter-based renal denervation is a potential therapy in patients with resistant hypertension. Previously, only unblinded studies showed a benefit from this procedure. In a small blinded trial of 80 patients without resistant hypertension (24-hour systolic pressure 140 to 170 mmHg on no antihypertensive medications), renal denervation reduced ambulatory blood pressure by 5 mmHg systolic/4 mmHg diastolic compared with a sham procedure . While this study provides proof of principle, establishing the benefit of renal denervation will require a large blinded trial of patients with resistant hypertension. (See "Treatment of resistant hypertension", section on 'Catheter-based radiofrequency ablation of renal sympathetic nerves'.)
Intraoperative blood pressure management in patients at increased risk for postoperative complications (September 2017)
Whether intraoperative management of systolic blood pressure (SBP) should be based on individualized targets or standard care was evaluated in a randomized trial conducted in nearly 300 patients undergoing major abdominal surgery who were at risk for postoperative complications due to hypertension or other risk factors . In the intervention group, SBP was maintained within 10 percent of the patient’s resting baseline value, with norepinephrine infusion as needed, while the control group received standard care (treatment to maintain the SBP ≥80 mmHg or to prevent a 40 percent or greater decrease from baseline SBP). The primary composite outcome (systemic inflammatory response syndrome with renal, respiratory, cardiovascular, or neurologic dysfunction) occurred less frequently in the intervention group. This study supports individualizing intraoperative management to maintain the blood pressure close to the patient’s baseline in patients at high risk of postoperative complications due to chronic hypertension, age, or other factors. (See "Anesthesia for adult patients with hypertension", section on 'Determination of target blood pressure values'.)
Cost-effectiveness of intensive antihypertensive treatment (August 2017)
Although intensive blood pressure lowering reduces cardiovascular events and mortality, it requires a higher burden of antihypertensive therapy and more frequent monitoring. A modeling study that used data from SPRINT projected that intensive blood pressure lowering cost between $28,000 and $47,000 per quality-adjusted life year, well below current thresholds used to determine if an intervention is cost-effective . (See "What is goal blood pressure in the treatment of hypertension?", section on 'Benefit according to overall cardiovascular risk'.)
Effect of intensive blood pressure lowering on patient-reported quality of life (August 2017)
Intensive blood pressure lowering in patients at high cardiovascular risk reduces cardiovascular events and mortality, but whether intensive therapy adversely affects patients' assessments of their quality of life is unknown. In a secondary analysis of the SPRINT trial comparing outcomes of higher and lower blood pressure targets in nondiabetic patients with hypertension and increased cardiovascular risk, there were no differences between treatment groups in terms of physical and mental health-related quality of life, symptoms of depression, or satisfaction with care . These results suggest that the benefits from intensive blood pressure lowering are not diminished by any effect on quality of life. (See "What is goal blood pressure in the treatment of hypertension?", section on 'Benefit according to overall cardiovascular risk'.)
Long-term risk of hypertension in women with pregnancy-associated hypertension (August 2017)
For women with a history of gestational hypertension, preeclampsia, eclampsia, or HELLP syndrome, at least annual lifelong measurement of blood pressure is important due to their increased risk for chronic hypertension. In a long-term population-based study, the rate of hypertension in the first decade postpartum for primiparous women in their 20s with pregnancy-associated hypertension was 14 percent, compared with 4 percent for those without pregnancy-associated hypertension . For primiparous women in their 40s, the rates were 32 and 11 percent, respectively. The risk of chronic hypertension in this population may be reduced by adherence to a beneficial lifestyle (eg, achieving/maintaining a healthy weight, salt restriction, exercise, limited alcohol intake) . (See "Management of hypertension in pregnant and postpartum women", section on 'Long-term prognosis of women with hypertension during pregnancy'.)
Goal blood pressure in patients with CKD (June 2017, Modified June 2017)
The appropriate goal blood pressure in nondiabetic patients with chronic kidney disease (CKD) is debated. Several recent papers support improved outcomes for a more intensive blood pressure target in patients with CKD:
●A meta-analysis of nine goal blood pressure trials and over 8000 patients reported no effect of more intensive versus standard blood pressure lowering on CKD progression, cardiovascular events, or mortality at 3.3 years of follow-up . However, long-term (post-trial) follow-up of those patients with proteinuria revealed a benefit from more intensive treatment on the incidence of end-stage renal disease. (See "Antihypertensive therapy and progression of nondiabetic chronic kidney disease in adults", section on 'Meta-analyses'.)
●Among the nearly 3000 patients 50 years and older from SPRINT with CKD at baseline, more versus less intensive blood pressure lowering (target <120 versus <140 mmHg) produced a significant decrease in all-cause mortality and a nonsignificant reduction in cardiovascular events . Although more patients in the intensive group had a 30 percent or larger decline in estimated glomerular filtration rate, this appeared to be an acute hemodynamic effect; rates of end-stage renal disease or a 50 percent decline in kidney function were similar between the groups. (See "Antihypertensive therapy and progression of nondiabetic chronic kidney disease in adults", section on 'SPRINT CKD'.)
Together these analyses support a more intensive blood pressure goal in patients with CKD.
Goal blood pressure in older adults (May 2017)
Goal blood pressure in older hypertensive adults is controversial. A meta-analysis of over 10,000 hypertensive adults 65 years or older combined results from the older subgroup in the SPRINT trial with three other large randomized trials evaluating goal blood pressure . At three-year follow-up, compared with less intensive therapy, more intensive blood pressure lowering reduced the rates of major adverse cardiovascular events, cardiovascular mortality, and heart failure. In general, UpToDate recommends a systolic blood pressure goal of 125 to 135 mmHg if standard manual blood pressure measurements are used or 120 to 125 mmHg if unattended automated oscillometric measurements are used. If attaining goal blood pressure proves difficult or burdensome for the patient, the systolic blood pressure that is reached with two or three antihypertensive agents (even if above target) may be a reasonable interim goal. (See "Treatment of hypertension in the elderly patient, particularly isolated systolic hypertension", section on 'Goal blood pressure'.)
Transplantation of HCV-infected kidneys into HCV-negative recipients (October 2017)
Kidneys from hepatitis C virus (HCV)-infected donors generally are not transplanted into HCV-negative recipients due to the high risk of HCV transmission, and many high-quality kidneys from HCV-infected deceased donors are discarded each year. However, direct-acting antiviral agents that can effectively treat HCV are available and may enable transplantation of HCV-infected kidneys. In a pilot trial of 10 patients, transplantation of HCV genotype 1-infected kidneys into HCV-negative recipients, followed by direct-acting antiviral therapy, resulted in well-functioning allografts at six months and a sustained virologic response in all patients . Additional studies are required to assess longer-term graft and patient outcomes. (See "Hepatitis C virus infection in kidney donors", section on 'Among HCV-negative recipients'.)
KDIGO guidelines on the evaluation of living kidney donors (September 2017)
The 2017 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors provides a framework for donor candidate evaluation that is grounded in simultaneous consideration of the combined impact of a candidate's profile of demographic (ie, age, sex, and race) and health characteristics (eg, kidney function, blood pressure, body mass index, smoking status) on the risk of serious adverse outcomes (most notably kidney failure) after donation . (See "Evaluation of the living kidney donor candidate", section on 'Introduction'.)
Liraglutide and renal outcomes in type 2 diabetes (September 2017)
In an earlier report of a randomized trial comparing liraglutide with placebo in patients with type 2 diabetes and coexisting cardiovascular disease, liraglutide reduced the incidence of the composite cardiovascular endpoint. In a separate analysis of the secondary microvascular endpoints in the trial, liraglutide reduced the incidence of the renal outcome (a composite of new-onset persistent macroalbuminuria, persistent doubling of the serum creatinine level, end-stage renal disease, or death due to renal disease) . The results were driven by a lower incidence of new-onset persistent macroalbuminuria. Trials of longer duration with primary microvascular outcomes and in patients who are not at high cardiovascular risk are required in order to better understand the microvascular effects of GLP-1 receptor agonists. (See "Glucagon-like peptide-1 receptor agonists for the treatment of type 2 diabetes mellitus", section on 'Microvascular outcomes'.)
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