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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: Apr 2017. | This topic last updated: May 17, 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.


Remote ischemic preconditioning (RIPC) and ischemic acute tubular necrosis (ATN) (May 2017)

Remote ischemic preconditioning (RIPC) is a minimally invasive procedure by which the deliberate induction of transient, nonlethal ischemia of an organ protects against subsequent ischemic injury of another organ. Numerous clinical trials and meta-analyses have examined the effects of RIPC on ischemic acute tubular necrosis (ATN) with conflicting results. A meta-analysis of 28 randomized clinical trials involving over 6500 patients found that RIPC, prior to surgical procedures associated with a high risk of ischemic ATN, had no effect on the serum creatinine, need for dialysis, length of hospital stay, or all-cause mortality [1]. We do not use RIPC to prevent ischemic ATN. (See "Possible prevention and therapy of ischemic acute tubular necrosis", section on 'Remote ischemic preconditioning'.)

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 [2]. 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 [3]. 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 [4]. 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 [5]. 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'.)


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'.)


Targeted-release budesonide and IgA nephropathy (May 2017)

An investigational oral targeted-release formulation of the glucocorticoid budesonide (TRF-budesonide) has been designed to release the drug in the ileocecal region in patients with IgA nephropathy, to target the presumed site of production of aberrantly galactosylated IgA1 while limiting systemic glucocorticoid absorption. The safety and efficacy of TRF-budesonide was evaluated in a randomized trial of 149 patients with IgA nephropathy and persistent proteinuria despite optimized renin-angiotensin system blockade [8]. Treatment with TRF-budesonide, compared with placebo, resulted in a greater reduction in proteinuria from baseline at 9 and 12 months and stabilization of estimated glomerular filtration rate at 9 months. However, adverse events were more frequent in the TRF-budesonide groups, suggesting that the drug has significant systemic absorption. Additional studies, particularly in comparison with oral bioavailable glucocorticoids, are indicated to determine if there is a role for TRF-budesonide in patients with IgA nephropathy. (See "Treatment and prognosis of IgA nephropathy", section on 'Budesonide'.)

Rituximab ineffective for treatment of IgA nephropathy (May 2017)

B cell-depleting therapies such as rituximab have been used in the treatment of autoantibody-mediated renal diseases and could theoretically remove the autoantibodies against aberrantly galactosylated IgA1 (Gd-IgA1) that drive the progression of IgA nephropathy. An open-label randomized trial of 34 patients with IgA nephropathy and proteinuria >1 g/day compared groups assigned to rituximab or no rituximab; all patients were maintained on renin-angiotensin system inhibitors [9]. At 12 months, there was no difference between groups in the change from baseline in proteinuria or change in renal function. Although treatment with rituximab resulted in the successful depletion of B cells, there were also no differences in serum levels of Gd-IgA1 or autoantibodies against Gd-IgA1. We do not routinely use rituximab in the treatment of patients with IgA nephropathy. (See "Treatment and prognosis of IgA nephropathy", section on 'Rituximab'.)

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'.)


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 [11]. 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 [12]. 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 [13]. 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) [14]. 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'.)


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) [15]. 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'.)


Bisphosphonate use in renal transplant recipients (May 2017)

Bone loss occurs rapidly following kidney transplantation and is primarily related to the use of glucocorticoids and other immunosuppressive agents. A 2017 systematic review and meta-analysis evaluated the efficacy and safety of bisphosphonates and other osteoporosis medications among patients with chronic kidney disease, including renal transplant recipients [16]. Treatment with bisphosphonates, compared with treatment without bisphosphonates or with placebo, reduced the loss of lumbar spine bone mineral density (BMD) but did not consistently reduce the loss of femoral neck BMD at 12 to 24 months. There was no significant difference in the risk of vertebral fractures between patients treated with or without bisphosphonate therapy, although the meta-analysis was not sufficiently powered to detect this difference in renal transplant recipients. Recommendations regarding bisphosphonate use in renal transplant patients vary, and UpToDate authors individualize decisions about bisphosphonate use in such patients. (See "Bone disease after renal transplantation", section on 'Bisphosphonates'.)

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 [17]. 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'.)


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 [18]. 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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  1. Menting TP, Wever KE, Ozdemir-van Brunschot DM, et al. Ischaemic preconditioning for the reduction of renal ischaemia reperfusion injury. Cochrane Database Syst Rev 2017; 3:CD010777.
  2. Nijssen EC, Rennenberg RJ, Nelemans PJ, et al. Prophylactic hydration to protect renal function from intravascular iodinated contrast material in patients at high risk of contrast-induced nephropathy (AMACING): a prospective, randomised, phase 3, controlled, open-label, non-inferiority trial. Lancet 2017; 389:1312.
  3. 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.
  4. 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.
  5. 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.
  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.
  7. Block GA, Bushinsky DA, Cheng S, et al. Effect of Etelcalcetide vs Cinacalcet on Serum Parathyroid Hormone in Patients Receiving Hemodialysis With Secondary Hyperparathyroidism: A Randomized Clinical Trial. JAMA 2017; 317:156.
  8. Fellström BC, Barratt J, Cook H, et al. Targeted-release budesonide versus placebo in patients with IgA nephropathy (NEFIGAN): a double-blind, randomised, placebo-controlled phase 2b trial. Lancet 2017.
  9. Lafayette RA, Canetta PA, Rovin BH, et al. A Randomized, Controlled Trial of Rituximab in IgA Nephropathy with Proteinuria and Renal Dysfunction. J Am Soc Nephrol 2017; 28:1306.
  10. Chauvet S, Frémeaux-Bacchi V, Petitprez F, et al. Treatment of B-cell disorder improves renal outcome of patients with monoclonal gammopathy-associated C3 glomerulopathy. Blood 2017; 129:1437.
  11. Qaseem A, Wilt TJ, Rich R, et al. Pharmacologic Treatment of Hypertension in Adults Aged 60 Years or Older to Higher Versus Lower Blood Pressure Targets: A Clinical Practice Guideline From the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med 2017; 166:430.
  12. Chow CK, Thakkar J, Bennett A, et al. Quarter-dose quadruple combination therapy for initial treatment of hypertension: placebo-controlled, crossover, randomised trial and systematic review. Lancet 2017; 389:1035.
  13. Puttnam R, Davis BR, Pressel SL, et al. Association of 3 Different Antihypertensive Medications With Hip and Pelvic Fracture Risk in Older Adults: Secondary Analysis of a Randomized Clinical Trial. JAMA Intern Med 2017; 177:67.
  14. Vidal-Petiot E, Ford I, Greenlaw N, et al. Cardiovascular event rates and mortality according to achieved systolic and diastolic blood pressure in patients with stable coronary artery disease: an international cohort study. Lancet 2016; 388:2142.
  15. Kaddourah A, Basu RK, Bagshaw SM, et al. Epidemiology of Acute Kidney Injury in Critically Ill Children and Young Adults. N Engl J Med 2017; 376:11.
  16. Wilson LM, Rebholz CM, Jirru E, et al. Benefits and Harms of Osteoporosis Medications in Patients With Chronic Kidney Disease: A Systematic Review and Meta-analysis. Ann Intern Med 2017; 166:649.
  17. Thomusch O, Wiesener M, Opgenoorth M, et al. Rabbit-ATG or basiliximab induction for rapid steroid withdrawal after renal transplantation (Harmony): an open-label, multicentre, randomised controlled trial. Lancet 2016; 388:3006.
  18. de Boer IH, Gao X, Cleary PA, et al. Albuminuria Changes and Cardiovascular and Renal Outcomes in Type 1 Diabetes: The DCCT/EDIC Study. Clin J Am Soc Nephrol 2016; 11:1969.
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