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What's new in nephrology and hypertension
Official reprint from UpToDate® ©2017 UpToDate®
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What's new in nephrology and hypertension
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Mar 2017. | This topic last updated: Apr 18, 2017.

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.


Prophylactic administration of fluids and contrast nephropathy (April 2017)

A single-center randomized trial (AMACING) showed no difference in the rate of contrast nephropathy between groups of patients felt to be at risk for contrast-induced nephropathy who were assigned to receive intravenous 0.9 percent saline or no intravenous fluids prior to contrast administration [1]. Adverse events, including heart failure, hyponatremia, and arrhythmia, were more common in the group receiving intravenous fluid. However, these results are called into question by trial limitations, including low power (while planned for 1300, approximately 600 patients were enrolled) and the low overall rate of contrast nephropathy, which suggests that the patients may not have been at significantly high risk. Pending data from further studies of prophylactic fluid administration in high-risk patients, we administer intravenous isotonic saline for all high-risk patients undergoing procedures involving intravascular contrast administration, if there are no contraindications to volume expansion. (See "Prevention of contrast-induced nephropathy", section on 'Fluid administration'.)

Multitarget therapy and progression of kidney disease in type 2 diabetes (March 2017)

The optimal therapeutic approach to the treatment of diabetic nephropathy may be intensive multifactorial risk factor reduction targeting behavior (ie, counseling on diet, exercise, and smoking cessation), glycemic control, blood pressure, and dyslipidemia. The efficacy of implementing this approach for eight years, compared with usual care, in patients with type 2 diabetes and increased albuminuria was examined in the Steno type 2 trial. At the end of the trial phase, all patients were offered intensive multitarget therapy [2]. After an additional 20 years of follow-up, those who were assigned to intensive multitarget therapy had a significantly lower annual decline in glomerular filtration rate and a higher likelihood of survival without end-stage renal disease (approximately 50 versus 30 percent). (See "Treatment of diabetic nephropathy", section on 'Type 2'.)

Early versus late initiation of dialysis for acute kidney injury (March 2017)

Randomized trials have yielded conflicting results regarding a possible benefit of early initiation of dialysis (ie, before there are clear electrolyte or fluid balance indications) among patients with acute kidney injury (AKI). A meta-analysis of 10 randomized trials showed no benefit of early dialysis initiation on mortality, risk of dialysis dependence, length of hospital stay, or recovery of renal function [3]. The quality of the analysis was low, in part because of heterogeneity due to varying definitions of early versus late initiation. Nevertheless, we do not electively initiate dialysis for AKI unless electrolyte or fluid balance abnormalities have reached a particular threshold. (See "Renal replacement therapy (dialysis) in acute kidney injury in adults: Indications, timing, and dialysis dose", section on 'Timing of elective initiation'.)

Metformin use in patients with diabetes and renal impairment, heart failure, or chronic liver disease (January 2017)

In a systematic review of 17 observational studies comparing diabetes regimens with and without metformin, metformin use was associated with lower all-cause mortality among patients with heart failure, renal impairment, or chronic liver disease with hepatic impairment [4]. In addition, metformin use in patients with renal impairment or heart failure was associated with fewer heart failure readmissions. This study supports a recent US Food and Drug Administration (FDA) labeling revision for metformin, which will increase use in patients with renal impairment. Metformin remains contraindicated in patients with estimated glomerular filtration rate (eGFR) <30 mL/min, concurrent active or progressive liver disease, or unstable or acute heart failure with risk of hypoperfusion and hypoxemia. Recommendations regarding metformin use in patients with an eGFR between 30 and 45 mL/min vary and UpToDate authors individualize decisions about metformin use in such patients. (See "Metformin in the treatment of adults with type 2 diabetes mellitus", section on 'Contraindications'.)

Thrombotic microangiopathy from interferon (October 2016)

Drug-induced thrombotic microangiopathy (DITMA) has been described with a number of chemotherapeutic, immunosuppressive, and other drugs. Unlike thrombotic thrombocytopenic purpura (TTP), DITMA is not associated with severely reduced ADAMTS13 activity, and the principal treatment is drug discontinuation rather than plasma exchange. A new report has provided strong evidence for interferon as a cause of TMA [5]. Patients receiving interferon who develop signs of a TMA should have the drug discontinued promptly before organ failure develops. (See "Drug-induced thrombotic microangiopathy", section on 'Immunosuppressive agents'.)


Intravenous calcimimetic for secondary hyperparathyroidism in hemodialysis patients (February 2017)

The first intravenous calcimimetic, etelcalcetide, was compared with placebo and with oral cinacalcet in three randomized trials of treatment for secondary hyperparathyroidism in patients receiving hemodialysis [6,7]. Etelcalcetide was more effective than placebo and cinacalcet in reducing parathyroid hormone. However, etelcalcetide led to more gastrointestinal side effects and prolonged the QTc interval compared with placebo and increased the risk of hypocalcemia compared with cinacalcet. Longer-term studies to evaluate the effects of etelcalcetide on cardiovascular events and mortality are required before its use can be recommended. Etelcalcetide is not yet widely available. (See "Management of secondary hyperparathyroidism and mineral metabolism abnormalities in dialysis patients", section on 'Etelcalcetide'.)

Regional anesthesia for hemodialysis arteriovenous fistula creation (November 2016)

Regional anesthesia during the creation of hemodialysis arteriovenous fistulas causes arterial and venous dilation, which may improve early fistula patency. In a trial that randomly assigned 126 adults receiving primarily radiocephalic or brachiocephalic fistulas to brachial plexus block or local anesthesia, brachial plexus block resulted in a higher rate of primary fistula patency and a trend toward a higher rate of functional patency at three months [8]. Based upon these findings, we suggest brachial plexus block for the creation of arteriovenous fistulas, rather than using local anesthesia alone. (See "Creating an arteriovenous fistula for hemodialysis", section on 'Type of anesthesia'.)

Predialysis education and choice of modality (November 2016)

Predialysis education regarding different dialysis modalities may increase the number of patients who opt for peritoneal dialysis. In a systematic review and meta-analysis, structured educational interventions were associated with a twofold increase in the odds of choosing peritoneal dialysis compared with standard care [9]. (See "Dialysis modality and patient outcome", section on 'Selection of dialysis modality'.)


Chemotherapy for C3 glomerulopathy with monoclonal gammopathy (March 2017)

C3 glomerulopathy with monoclonal gammopathy is a form of monoclonal gammopathy of renal significance (MGRS), a group of kidney disorders caused by a monoclonal immunoglobulin that is secreted by a nonmalignant or premalignant B cell or plasma cell clone. A retrospective analysis compared renal outcomes among 50 patients with C3 glomerulopathy with monoclonal gammopathy who were treated with or without chemotherapy directed against the underlying plasma or B cell clone [10]. Treatment with clone-directed chemotherapy was associated with a higher rate of renal response and improved renal survival at a median of 24 months. Importantly, renal survival was significantly higher among patients who achieved a hematologic response with chemotherapy. We typically treat patients who have C3 glomerulopathy with monoclonal gammopathy using chemotherapy based upon the isotype of the circulating monoclonal protein detected in the serum or urine. (See "Diagnosis and treatment of monoclonal gammopathy of renal significance", section on 'Patients with C3 glomerulopathy with monoclonal gammopathy'.)

Durability of remission in idiopathic membranous nephropathy (November 2016)

Among patients with idiopathic membranous nephropathy (MN), the durability of remission (spontaneous or treatment-associated) is associated with improved renal survival. In a prospective study of 376 patients with idiopathic MN who achieved complete or partial remission of nephrotic-range proteinuria, persistent remission at 3, 6, 12, and 24 months, compared with disease relapse at those time points, was associated with a lower risk of the primary endpoint (end-stage renal disease or 50 percent reduction in estimated glomerular filtration rate) [11]. (See "Treatment of idiopathic membranous nephropathy", section on 'Prognosis'.)


ACP/AAFP guidelines for hypertension treatment in older adults (March 2017)

The American College of Physicians/American Academy of Family Physicians (ACP/AAFP) have issued guidelines for pharmacologic treatment of hypertension in older adults, addressing targets for blood pressure [12]. These guidelines depart from our recommendations and from other recent guidelines (the 2016 Canadian Hypertension Education Program [CHEP] guidelines and the 2016 National Heart Foundation of Australia guidelines) released after publication of the SPRINT trial. The ACP/AAFP suggest a goal systolic pressure of <150 mmHg in adults 60 years of age and older, with consideration of a goal <140 mmHg in patients at high cardiovascular risk. However, we continue to recommend lower goals for such patients, consistent with guidelines from other groups. (See "What is goal blood pressure in the treatment of hypertension?", section on 'Recommendations of others'.)

Single-pill quadruple antihypertensive therapy (March 2017)

Single-pill dual antihypertensive therapy is commonly used and, compared with monotherapy, may increase both patient compliance and the likelihood that target blood pressures are achieved. One small trial (21 patients) examined the effects of single-pill quadruple therapy, with each agent given at one quarter the normal starting dose [13]. Compared with placebo, quadruple therapy reduced 24-hour systolic pressure by 19 mmHg and increased the proportion attaining goal blood pressure (100 versus 33 percent). No adverse events were reported. Further studies of this concept are indicated that include a larger study population and an active comparator, to determine if this approach has merit. (See "Choice of drug therapy in primary (essential) hypertension", section on 'Combination therapy with more than two agents'.)

Effect of antihypertensive drug class on fracture rates (January 2017)

Thiazide diuretics stimulate distal tubular reabsorption of calcium, leading to a decrease in urinary calcium excretion and a possible benefit on bone mineral density. The rates of hip or pelvic fractures among patients treated with thiazide-like diuretics, angiotensin converting enzyme (ACE) inhibitors, or calcium channel blockers were compared in a post-hoc analysis of the ALLHAT trial [14]. At approximately five years, those randomly assigned chlorthalidone had fewer hip or pelvic fractures as compared with those assigned to either lisinopril or amlodipine. Thus, if monotherapy is appropriate in a patient with hypertension and osteoporosis, thiazide-like diuretics may have advantages over ACE inhibitors, angiotensin receptor blockers (ARBs), and calcium channel blockers. (See "Choice of drug therapy in primary (essential) hypertension", section on 'Thiazide diuretics'.)

J-shaped relationship between blood pressure and cardiovascular outcomes (November 2016)

There may be a blood pressure threshold below which tissue perfusion is reduced and risk is increased for cardiovascular and renal events and mortality (a J-shaped curve between blood pressure and event rate). In a large international prospective observational study of patients with stable coronary artery disease and treated hypertension, achieved diastolic pressures below 70 and above 80 mmHg were independently associated with increased risk for adverse outcomes (figure 1) [15]. Similarly, achieved systolic pressures below 120 and above 140 mmHg were independently associated with increased risk for adverse outcomes (figure 2). However, these data are observational, and other evidence disputes the importance of these J-shaped curves, particularly for systolic pressure. Based upon the available evidence and the physiology of coronary perfusion, we generally try to avoid lowering the diastolic blood pressure to a value of <60 mmHg in most patients. (See "What is goal blood pressure in the treatment of hypertension?", section on 'J-shaped diastolic curve'.)

Outcomes in severe asymptomatic hypertension (hypertensive urgency) (November 2016)

There is no proven benefit from rapid reduction of blood pressure in patients with severe asymptomatic hypertension (systolic blood pressure ≥180 mmHg and/or diastolic blood pressure ≥110 mmHg). In one retrospective study of over 59,000 patients who presented in the ambulatory setting with severe asymptomatic hypertension, there was no difference in major adverse cardiovascular events, or prevalence of uncontrolled hypertension six months later, for patients sent to the emergency department or sent home from the office for outpatient blood pressure management [16]. Hospitalization rates were higher for those sent to the emergency department. This cohort study suggests that most patients with asymptomatic hypertensive urgency who present in the ambulatory setting can be managed as outpatients. (See "Management of severe asymptomatic hypertension (hypertensive urgencies) in adults", section on 'Rapidity of blood pressure lowering'.)

Angioplasty in renal artery stenosis (November 2016)

In patients with atherosclerotic renal artery stenosis, a meta-analysis of trials comparing percutaneous transluminal renal angioplasty (PTRA) with stent placement plus medical therapy with medical therapy alone found no benefit from PTRA on mortality, end-stage renal disease, major cardiovascular events, or blood pressure control [17]. One or more major periprocedural complications occurred in 7.1 percent of patients who underwent PTRA. Thus, in patients with renal artery stenosis and clinical characteristics similar to those enrolled in these trials, we suggest not revascularizing and instead treating with medical therapy alone. (See "Treatment of unilateral atherosclerotic renal artery stenosis", section on 'Revascularization versus medical therapy alone'.)


Dietary protein and the risk of kidney stones (November 2016)

Different types of dietary protein may have different effects on the risk of kidney stones. Earlier studies have found an association between high animal protein intake and an increased incidence of stone disease, at least in men, while vegetable protein intake has not been associated with stone risk. A new study suggests that the risk of stones may vary depending upon whether the source of the animal protein is dairy or nondairy [18]. Higher nondairy animal protein intake was associated with a trend toward an increase in stone risk, whereas higher dairy protein intake in young women was associated with a lower risk of stone disease. (See "Risk factors for calcium stones in adults", section on 'Protein'.)


Acute kidney injury in critically ill children (November 2016)

Children cared for in intensive care units (ICUs) are at increased risk of acute kidney injury (AKI). In a large prospective multicenter study of patients 3 months to 25 years of age cared for in over 30 pediatric ICUs worldwide, approximately 27 percent developed AKI and 12 percent developed severe AKI (stage 2 or 3 AKI) (table 1) [19]. Severe AKI was independently associated with an increased risk of death, and increasing severity was associated with increasing risk of death. These data reinforce the need to identify patients at risk for AKI or with mild AKI so that interventions to prevent further injury can be implemented. (See "Acute kidney injury in children: Clinical features, etiology, evaluation, and diagnosis", section on 'Critically-ill children'.)


Basiliximab versus rATG for rapid glucocorticoid withdrawal in low-risk kidney transplant recipients (January 2017)

Basiliximab is an interleukin-2 (IL-2) receptor antibody that interferes with T cell proliferation. In a multicenter trial, 615 low-risk kidney transplant recipients were randomly assigned to basiliximab induction with long-term maintenance glucocorticoids, basiliximab induction with rapid glucocorticoid withdrawal (within eight days of transplant), or rabbit antithymocyte globulin (rATG) induction with rapid glucocorticoid withdrawal [20]. All patients received low-dose tacrolimus and mycophenolate mofetil as maintenance immunosuppression. At 12 months, all three groups had similar rates of biopsy-proven acute rejection, patient and graft survival, infection, and malignancy. Based upon the findings of this study and other randomized trials, we now recommend the use of either rATG or basiliximab as induction therapy in low-risk kidney transplant recipients. (See "Induction immunosuppressive therapy in renal transplantation in adults", section on 'Approach to induction in low-risk patients'.)

Screening for cardiovascular disease before kidney transplantation (October 2016)

Cardiovascular disease is the leading cause of mortality in kidney transplant recipients. Although pretransplant cardiac evaluation is recommended for potential transplant candidates, the optimal screening strategy has not yet been identified. In a prospective study comparing clinical risk factor assessment with coronary artery calcium (CAC) scores among 138 pretransplant patients, CAC scores were not superior to risk factor assessment in identifying patients who would benefit from noninvasive testing for coronary heart disease (CHD) [21]. Both clinical risk factor assessment and CAC scores had a poor positive predictive value but a high negative predictive value for identifying patients with CHD. (See "Evaluation of the potential renal transplant recipient", section on 'Coronary heart disease'.)


Prognostic implications of albuminuria remission in type 1 diabetes (December 2016)

In patients with type 1 diabetes who have moderately increased albuminuria (formerly "microalbuminuria"), progression and stabilization of albuminuria are associated with high and intermediate risks, respectively, for a decline in glomerular filtration rate (GFR), but whether remission of albuminuria can further improve chronic kidney disease risk has not been known. Among patients with type 1 diabetes in the DCCT study who developed moderately increased albuminuria, the risk of GFR decline at 18 years was the same for those whose albuminuria persisted compared with those whose albuminuria remitted [22]. These data suggest that moderately increased albuminuria is an important risk marker for progression of kidney disease, even if remission of albuminuria can be achieved. (See "Moderately increased albuminuria (microalbuminuria) in type 1 diabetes mellitus", section on 'Regression to normoalbuminuria'.)

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  2. Oellgaard J, Gæde P, Rossing P, et al. Intensified multifactorial intervention in type 2 diabetics with microalbuminuria leads to long-term renal benefits. Kidney Int 2017; 91:982.
  3. Bhatt GC, Das RR. Early versus late initiation of renal replacement therapy in patients with acute kidney injury-a systematic review & meta-analysis of randomized controlled trials. BMC Nephrol 2017; 18:78.
  4. Crowley MJ, Diamantidis CJ, McDuffie JR, et al. Clinical Outcomes of Metformin Use in Populations With Chronic Kidney Disease, Congestive Heart Failure, or Chronic Liver Disease: A Systematic Review. Ann Intern Med 2017; 166:191.
  5. Kavanagh D, McGlasson S, Jury A, et al. Type I interferon causes thrombotic microangiopathy by a dose-dependent toxic effect on the microvasculature. Blood 2016; 128:2824.
  6. Block GA, Bushinsky DA, Cunningham J, et al. Effect of Etelcalcetide vs Placebo on Serum Parathyroid Hormone in Patients Receiving Hemodialysis With Secondary Hyperparathyroidism: Two Randomized Clinical Trials. JAMA 2017; 317:146.
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