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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: Sep 2017. | This topic last updated: Oct 19, 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

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 [1]. 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'.)

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 [2]. We do not use RIPC to prevent ischemic ATN. (See "Possible prevention and therapy of ischemic acute tubular necrosis", section on 'Remote ischemic preconditioning'.)

DIALYSIS

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 [3]. 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 [4]. 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 [5]. 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 [6]. 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 [7]. 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'.)

HYPERTENSION

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 [8]. 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'.)

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 [9]. 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 [10]. (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 [11]. 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 [12]. 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) [13]. (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 [14]. 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 [15]. 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 [16]. 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

Transplantation of HCV-infected kidneys into HCV-negative recipients (October 2017)

Transplantation of kidneys from hepatitis C virus (HCV)-infected donors into HCV-negative recipients is generally not performed due to the high risk of HCV transmission, and many high-quality kidneys from HCV-infected deceased donors are discarded each year. However, the availability of direct-acting antiviral agents that can effectively treat HCV could enable HCV-infected kidneys to be transplanted. 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 [17]. 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 [18]. (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 [19]. 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) [20]. 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. Nadkarni GN, Ferrandino R, Chang A, et al. Acute Kidney Injury in Patients on SGLT2 Inhibitors: A Propensity-Matched Analysis. Diabetes Care 2017.
  2. 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.
  3. Zoccali C, Moissl U, Chazot C, et al. Chronic Fluid Overload and Mortality in ESRD. J Am Soc Nephrol 2017; 28:2491.
  4. Lv J, Zhang H, Wong MG, et al. Effect of Oral Methylprednisolone on Clinical Outcomes in Patients With IgA Nephropathy: The TESTING Randomized Clinical Trial. JAMA 2017; 318:432.
  5. 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.
  6. 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.
  7. 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.
  8. Futier E, Lefrant JY, Guinot PG, et al. Effect of Individualized vs Standard Blood Pressure Management Strategies on Postoperative Organ Dysfunction Among High-Risk Patients Undergoing Major Surgery: A Randomized Clinical Trial. JAMA 2017; 318:1346.
  9. 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.
  10. Bress AP, Bellows BK, King JB, et al. Cost-Effectiveness of Intensive versus Standard Blood-Pressure Control. N Engl J Med 2017; 377:745.
  11. 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.
  12. 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.
  13. 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.
  14. 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.
  15. Cheung AK, Mahboob R, Reboussin DM, et al. Effects of intensive BP control in CKD. J Am Soc Nephrol 2017; epub ahead of print.
  16. Bavishi C, Bangalore S, Messerli FH. Outcomes of Intensive Blood Pressure Lowering in Older Hypertensive Patients. J Am Coll Cardiol 2017; 69:486.
  17. Goldberg DS, Abt PL, Blumberg EA, et al. Trial of Transplantation of HCV-Infected Kidneys into Uninfected Recipients. N Engl J Med 2017; 376:2394.
  18. 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.
  19. 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.
  20. 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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