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What's new in nephrology and hypertension

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All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jun 2014. | This topic last updated: Jul 14, 2014.

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

Estimated albumin excretion rate (March 2014)

The spot urine albumin-to-creatinine ratio (UACR) is limited in part because of person to person variability in creatinine excretion. The estimated albumin excretion rate (eAER), which can be calculated by multiplying the spot UACR by the expected 24-hour creatinine generation (calculator 1), may more accurately predict the 24-hour urine albumin excretion. An equation to calculate the eAER was derived in a large study of 1693 patients with kidney disease using age, sex, race, and the UACR, and then was evaluated in two other large cohorts of patients with chronic kidney disease or diabetes [1]. The eAER was significantly more accurate and less biased than the UACR in predicting the measured 24-hour albumin excretion. Using the eAER rather than the UACR to estimate albumin excretion may be particularly important in patients who have very large or very small muscle mass (eg, young athletic men and elderly women, respectively). (See "Assessment of urinary protein excretion and evaluation of isolated non-nephrotic proteinuria in adults", section on 'Estimated albumin excretion rate'.)

Low-dose dopamine or nesiritide in cardiorenal syndrome (February 2014)

Therapy to relieve congestion in patients with heart failure frequently worsens renal function. The Renal Optimization Strategies Evaluation (ROSE) trial studied whether the addition of low-dose dopamine or low-dose nesiritide to diuretic therapy would improve urine output and renal function among patients hospitalized with acute heart failure with renal dysfunction [2]. Compared to placebo, neither low-dose dopamine nor low-dose nesiritide improved urine output or renal function. (See "Cardiorenal syndrome: Prognosis and treatment", section on 'Inotropic drugs'.)

DIALYSIS

The role of anticoagulation in AF patients with end stage renal disease (February 2014)

Although the benefit from a reduction in the risk of stroke with anticoagulant therapy outweighs the risk of bleeding in most patients with atrial fibrillation (AF) and chronic kidney disease (CKD), the net benefit in patients with end stage renal disease (ESRD) has not been established. In a well-performed, population-based retrospective cohort study of older AF patients receiving dialysis, there was no reduction in the risk of stroke with warfarin and a significantly higher risk of bleeding [3]. For most AF patients with ESRD, we suggest no anticoagulant therapy. For these patients with very high risk predictors for thromboembolism, such as known atrial thrombus, prosthetic heart valve (particularly in the mitral position), mitral stenosis, and previous transient ischemic attack or stroke, we believe it is reasonable to prescribe warfarin. (See "Management of thromboembolic risk in patients with atrial fibrillation and chronic kidney disease", section on 'Patients on dialysis (stage 5D chronic kidney disease)'.)

GLOMERULAR DISEASE AND VASCULITIS

Anti-PLA2R autoantibody testing for primary membranous nephropathy (July 2014)

Autoantibodies against the phospholipase A2 receptor (anti-PLA2R) are present in the great majority of patients with primary (idiopathic) membranous nephropathy (MN); serologic tests for anti-PLA2R are highly sensitive and specific for a diagnosis of primary MN [4-8]. The US Food and Drug Administration (FDA) has approved two commercially available tests for anti-PLA2R, including an indirect immunofluorescence assay and an enzyme-linked immunosorbent assay

Testing for anti-PLA2R is particularly useful in nephrotic patients who cannot undergo kidney biopsy, since a positive test essentially rules out other causes of nephrotic syndrome (such as minimal change disease or focal segmental glomerulosclerosis). In addition, a positive test in someone diagnosed with MN by kidney biopsy may help distinguish primary from secondary MN. (See "Causes and diagnosis of membranous nephropathy", section on 'Laboratory testing'.)

Prophylactic anticoagulation in membranous nephropathy (May 2014)

The decision to administer prophylactic anticoagulation to patients with nephrotic syndrome due to membranous nephropathy depends upon balancing the risks of thromboembolism and anticoagulation-associated bleeding. An online tool was created that estimates thromboembolism and bleeding risk using data from two large glomerular disease cohorts [9]. In patients with membranous nephropathy and nephrotic syndrome who do not have a contraindication to anticoagulation, the potential benefits of prophylactic anticoagulation are likely to outweigh the potential harms in those with a low bleeding risk and a serum albumin <3.0 mg/dL (30 g/L); and in those with an intermediate bleeding risk and a serum albumin <2.0 mg/dL (20 g/L). In contrast, the potential harms are likely to outweigh the benefits in patients who have a high bleeding risk, regardless of the serum albumin. (See "Renal vein thrombosis and hypercoagulable state in nephrotic syndrome", section on 'Approach to prophylactic anticoagulation'.)

Lack of an association between suPAR and primary FSGS (April 2014)

Although the soluble urokinase plasminogen activating receptor (suPAR) can induce focal segmental glomerulosclerosis (FSGS) lesions in mice, the role of suPAR in primary FSGS in humans is not clear. Three large cohorts totalling 1151 patients (including 212 patients with biopsy proven primary FSGS) measured serum suPAR using a commercially-available assay [10-12]. Levels of suPAR did not discriminate between primary FSGS and other causes of renal disease (eg, minimal change disease, membranous nephropathy, and IgA nephropathy). The major predictor of suPAR was the degree of kidney impairment; suPAR was consistently higher among those with reduced estimated glomerular filtration rate. (See "Epidemiology, classification, and pathogenesis of focal segmental glomerulosclerosis", section on 'suPAR'.)

Rituximab as maintenance therapy in ANCA-associated vasculitis (April 2014)

Several earlier retrospective single-center cohort studies examined a variety of protocols for rituximab use as maintenance therapy for ANCA-associated vasculitis. The recent and largest cohort study evaluated rituximab as maintenance therapy in 170 patients who had achieved remission with induction therapy [13]. Rituximab (usually one intravenous dose of 1000 mg) was given every four months for a median of two years. Relapse occurred in 25 patients and responded to either a short course of glucocorticoids or addition of another immunosuppressive drug. Infection requiring hospitalization, late-onset neutropenia, and hypogammaglobulinemia occurred in 12, 10, and 10 percent, respectively. (See "Maintenance immunosuppressive therapy in granulomatosis with polyangiitis and microscopic polyangiitis", section on 'Rituximab'.)

HYPERTENSION

ACE inhibitors and ARBs in diabetic patients (May 2014)

A meta-analysis of 48 trials in patients with diabetes that compared angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) with either placebo or another antihypertensive drug found that ACE inhibitors, but not ARBs, significantly reduced mortality compared with placebo [14]. However, differences in patient populations may explain some of these findings; the overall mortality in the trials comparing ARBs with placebo was substantially lower than trials comparing ACE inhibitors with placebo. Both ACE-inhibitors and ARBs had similar, nonsignificant benefits on mortality when compared with another antihypertensive drug, and both agents had significant benefits on heart failure. Other meta-analyses in both diabetic and nondiabetic patients have reported that ACE inhibitors and ARBs have identical effects on mortality and kidney disease. (See "Treatment of hypertension in patients with diabetes mellitus", section on 'Overall approach to selecting a therapy'.)

Failure of renal denervation in resistant hypertension (April 2014)

The utility of catheter-based radiofrequency ablation of renal sympathetic nerves (also known as renal denervation) in patients with resistant hypertension has not been established. Although several unblinded studies suggested that renal denervation could substantially lower blood pressure in patients with resistant hypertension, a blinded randomized trial (SYMPLICITY-HTN-3) failed to demonstrate benefit [15]. In SYMPLICITY-HTN-3, 535 patients with treatment-resistant hypertension (systolic pressure >160 mmHg despite three or more antihypertensive medications, including a diuretic) were assigned to renal denervation or a sham procedure; blood pressure decreased to a similar degree in both groups at six months and there was no difference in the incidence of serious adverse events. Due to the lack of benefit, a larger ongoing international trial (SYMPLICITY-HTN-4) was stopped early. (See "Treatment of resistant hypertension", section on 'Catheter-based radiofrequency ablation of renal sympathetic nerves'.)

Revascularization in high-risk patients with renal artery stenosis (March 2014)

Randomized trials of renal artery revascularization in patients with renal artery stenosis did not include many patients with high-risk factors such as flash pulmonary edema, resistant hypertension, and progressive kidney disease. In a prospective cohort study, 467 patients with renal artery stenosis, treated according to patient and physician preferences with either revascularization or medical therapy alone, were followed for a median of 3.8 years [16]. Revascularization was independently associated with a lower risk of death in patients who presented with flash pulmonary edema (58 versus 76 percent) and in patients who presented with both resistant hypertension and progressive kidney function decline (9 versus 65 percent). Revascularization was also associated with fewer cardiovascular events among patients with both resistant hypertension and progressive kidney function decline (27 versus 60 percent). In contrast, revascularization was not associated with such benefits in patients without these high-risk factors. (See "Treatment of unilateral atherosclerotic renal artery stenosis", section on 'Revascularization versus medical therapy alone'.)

NEPHROLITHIASIS

Alpha blocker therapy to facilitate kidney stone passage (May 2014)

Several medical interventions have been used to increase the passage rate of ureteral stones, including antispasmodic agents, calcium channel blockers, and alpha blockers. In a meta-analysis of 32 trials that enrolled 5864 patients, ureteral stone passage occurred more frequently with alpha blocker therapy versus conservative treatment alone (77 versus 52 percent); in addition, stone passage occurred an average of three days faster with alpha blocker therapy [17]. In four trials that compared tamsulosin (an alpha blocker) with nifedipine (a calcium channel blocker), the stone passage rate was significantly higher with tamsulosin. We suggest treatment with tamsulosin (0.4 mg once daily) for four weeks to facilitate spontaneous stone passage in patients with stones ≤10 mm in diameter. (See "Diagnosis and acute management of suspected nephrolithiasis in adults", section on 'Facilitating stone passage'.)

PEDIATRIC NEPHROLOGY

Rituximab for relapsing or steroid-dependent nephrotic syndrome (July 2014)

A randomized trial has confirmed previous observational findings that rituximab, a chimeric anti-CD20 monoclonal antibody that depletes B-cell lymphocytes, is effective in prolonging remission in children with severe nephrotic syndrome [18]. In this study of 48 children with frequently relapsing or steroid-dependent nephrotic syndrome, compared with placebo, four weekly doses of rituximab (375 mg/m2) increased median duration of remission and decreased average daily prednisolone dose. Although rituximab decreased relapse at one year, all patients in both groups relapsed by 19 months. Rituximab has been associated with serious complications, including some that resulted in death. Outside of clinical trials, use of rituximab for nephrotic syndrome should be restricted to children with frequent relapses and significant medication-related adverse effects. (See "Treatment of idiopathic nephrotic syndrome in children", section on 'Rituximab'.)

Prophylactic antibiotics for children with vesicoureteral reflux (May 2014)

The results of the Randomized Intervention for Vesicoureteral Reflux (RIVUR) trial help to clarify treatment options for children with vesicoureteral reflux (VUR). Earlier studies evaluating the effectiveness of prophylactic antibiotics in preventing recurrent urinary tract infection (UTI) or renal scarring have had inconsistent findings and/or were methodologically limited. The RIVUR trial compared daily treatment with trimethoprim-sulfamethoxazole (TMP-SMX) or placebo in 607 children (two months to six years) with grade I to IV VUR diagnosed after a febrile or symptomatic UTI [19]. At the two-year follow-up, the risk of renal scarring was similar, but TMP-SMX reduced the risk of recurrent febrile or symptomatic UTI by 50 percent. These findings support our approach to VUR management. For children with grade III or higher VUR, who are more likely to have recurrent UTI (even with prophylaxis) and renal scarring, we provide prophylactic antibiotics or surgical treatment. For children with grade I or II VUR, who are more likely to have spontaneous resolution, we discuss the risks and benefits of antibiotic prophylaxis versus observation with the family. (See "Management of vesicoureteral reflux", section on 'Intervention versus surveillance/placebo trials'.)

TRANSPLANTATION

Risk of ESRD among kidney donors (February 2014)

A large cohort study reported an increased risk of end stage renal disease (ESRD) among over 90,000 kidney donors compared with over 20,000 healthy matched controls from a US database [20]. The risk of ESRD was highest among black donors compared with Hispanic and white donors, but for every group and every age studied, the risk was higher among donors compared with nondonors. The absolute risk of ESRD among both donors and nondonors was quite low (90 per 10,000 donors and 14 per 10,000 healthy nondonors). The risk of ESRD may have been underestimated in the nondonor group, which would impact the study findings. (See "Evaluation of the living kidney donor and risk of donor nephrectomy", section on 'End-stage renal disease (ESRD)'.)

IDSA guidelines for vaccination of immunocompromised hosts (January 2014)

The Infectious Diseases Society of America has published new guidelines for vaccination of immunocompromised hosts, including hematopoietic cell transplant recipients, solid organ transplant recipients, as well as patients with cancer, asplenia, primary immunodeficiency disorders, chronic inflammatory conditions, HIV infection, and chronic inflammatory diseases receiving immunosuppressive agents [21]. The document includes recommendations about the appropriate use (and avoidance) of specific vaccines in immunocompromised hosts. (See "Immunizations in hematopoietic cell transplant candidates and recipients" and "Immunizations in solid organ transplant candidates and recipients" and "Immunizations in patients with cancer" and "Prevention of sepsis in the asplenic patient".)

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REFERENCES

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  2. Chen HH, Anstrom KJ, Givertz MM, et al. Low-dose dopamine or low-dose nesiritide in acute heart failure with renal dysfunction: the ROSE acute heart failure randomized trial. JAMA 2013; 310:2533.
  3. Shah M, Avgil Tsadok M, Jackevicius CA, et al. Warfarin use and the risk for stroke and bleeding in patients with atrial fibrillation undergoing dialysis. Circulation 2014; 129:1196.
  4. Debiec H, Ronco P. PLA2R autoantibodies and PLA2R glomerular deposits in membranous nephropathy. N Engl J Med 2011; 364:689.
  5. Qin W, Beck LH Jr, Zeng C, et al. Anti-phospholipase A2 receptor antibody in membranous nephropathy. J Am Soc Nephrol 2011; 22:1137.
  6. Hofstra JM, Beck LH Jr, Beck DM, et al. Anti-phospholipase A₂ receptor antibodies correlate with clinical status in idiopathic membranous nephropathy. Clin J Am Soc Nephrol 2011; 6:1286.
  7. Hofstra JM, Debiec H, Short CD, et al. Antiphospholipase A2 receptor antibody titer and subclass in idiopathic membranous nephropathy. J Am Soc Nephrol 2012; 23:1735.
  8. Kanigicherla D, Gummadova J, McKenzie EA, et al. Anti-PLA2R antibodies measured by ELISA predict long-term outcome in a prevalent population of patients with idiopathic membranous nephropathy. Kidney Int 2013; 83:940.
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  14. Cheng J, Zhang W, Zhang X, et al. Effect of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on all-cause mortality, cardiovascular deaths, and cardiovascular events in patients with diabetes mellitus: a meta-analysis. JAMA Intern Med 2014; 174:773.
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  18. Iijama K, Sako M, Nozu K, et al. Rituximab for childhood-onset,complciated, frequently relapsing nephrotic syndrome or steroid-dependent nephrotic syndrome: a multicentre, double-blind, randomised, placebo-controlled trial. Lancet 2014.
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