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What's new in nephrology and hypertension
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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: Aug 2017. | This topic last updated: Sep 15, 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.

ACUTE AND CHRONIC KIDNEY DISEASE

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 nephropathy associated with angiography", 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'.)

DIALYSIS

Fish oil does not reduce thrombosis of hemodialysis arteriovenous fistulas (March 2017)

Fish oil may reduce intimal hyperplasia, which is an important cause of hemodialysis arteriovenous (AV) access failure. The majority of trials evaluating the effectiveness of fish oil for reducing AV access failure have been performed in the setting of AV grafts. Now, a multicenter trial has specifically evaluated AV fistulas. In this trial, over 500 patients with newly created AV fistulas were randomly assigned to receive fish oil (4 g/day) or placebo for 12 weeks [5]. At 12 months follow-up, no significant differences between the groups were observed for the primary composite outcome of fistula failure, or for any of the individual outcomes (fistula thrombosis, fistula abandonment, cannulation failure). We do not administer fish oil to individuals with AV fistulas for the sole purpose of preventing AV fistula failure; however, the administration of fish oil may be indicated for other clinically relevant cardiovascular benefits, particularly among individuals with coronary heart disease and its risk equivalents. (See "Overview of hemodialysis arteriovenous graft maintenance and thrombosis prevention".)

GLOMERULAR DISEASE AND VASCULITIS

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 [6]. 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 "Treatment of Fabry disease", section on 'Dosing of ERT'.)

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 [7]. 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 [8]. 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 [9]. 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'.)

HYPERTENSION

Poor medication adherence in patients with resistant hypertension (September 2017)

Adherence to prescribed antihypertensive therapy in a large cohort of patients with resistant hypertension was determined by performing mass spectrometry of blood samples collected from participants enrolled in a trial of renal denervation [10]. Complete nonadherence or poor adherence was detected in 80 percent of all patients. Overall, participants took an average of two antihypertensive medications despite being prescribed an average of four medications. (See "Definition, risk factors, and evaluation of resistant hypertension", section on 'Apparent, true, and pseudoresistant hypertension'.)

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 [11]. (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 [12]. These results suggest that the benefits from intensive blood pressure lowering are not mitigated by a reduction in 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 [13]. 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) [14]. (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 [15]. 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 [16]. 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 [17]. 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'.)

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 [18]. 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 [19]. 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'.)

TRANSPLANTATION

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 [20]. (See "Evaluation of the living kidney donor candidate", section on 'Introduction'.)

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 [21]. 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'.)

OTHER NEPHROLOGY

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) [22]. 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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REFERENCES

  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. Irish AB, Viecelli AK, Hawley CM, et al. Effect of Fish Oil Supplementation and Aspirin Use on Arteriovenous Fistula Failure in Patients Requiring Hemodialysis: A Randomized Clinical Trial. JAMA Intern Med 2017; 177:184.
  6. Skrunes R, Tøndel C, Leh S, et al. Long-Term Dose-Dependent Agalsidase Effects on Kidney Histology in Fabry Disease. Clin J Am Soc Nephrol 2017; 12:1470.
  7. 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.
  8. 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.
  9. 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.
  10. de Jager RL, de Beus E, Beeftink MM, et al. Impact of Medication Adherence on the Effect of Renal Denervation: The SYMPATHY Trial. Hypertension 2017; 69:678.
  11. Bress AP, Bellows BK, King JB, et al. Cost-Effectiveness of Intensive versus Standard Blood-Pressure Control. N Engl J Med 2017; 377:745.
  12. Berlowitz DR, Foy CG, Kazis LE, et al. Effect of Intensive Blood-Pressure Treatment on Patient-Reported Outcomes. N Engl J Med 2017; 377:733.
  13. Behrens I, Basit S, Melbye M, et al. Risk of post-pregnancy hypertension in women with a history of hypertensive disorders of pregnancy: nationwide cohort study. BMJ 2017; 358:j3078.
  14. Timpka S, Stuart JJ, Tanz LJ, et al. Lifestyle in progression from hypertensive disorders of pregnancy to chronic hypertension in Nurses' Health Study II: observational cohort study. BMJ 2017; 358:j3024.
  15. Tsai WC, Wu HY, Peng YS, et al. Association of Intensive Blood Pressure Control and Kidney Disease Progression in Nondiabetic Patients With Chronic Kidney Disease: A Systematic Review and Meta-analysis. JAMA Intern Med 2017; 177:792.
  16. Cheung AK, Mahboob R, Reboussin DM, et al. Effects of intensive BP control in CKD. J Am Soc Nephrol 2017; epub ahead of print.
  17. Bavishi C, Bangalore S, Messerli FH. Outcomes of Intensive Blood Pressure Lowering in Older Hypertensive Patients. J Am Coll Cardiol 2017; 69:486.
  18. 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.
  19. 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.
  20. Lentine KL, Kasiske BL, Levey AS, et al. KDIGO Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors. Transplantation 2017; 101:S1.
  21. 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.
  22. Mann JFE, Ørsted DD, Brown-Frandsen K, et al. Liraglutide and Renal Outcomes in Type 2 Diabetes. N Engl J Med 2017; 377:839.
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