What's new in nephrology and hypertension

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

Long-term effects of empagliflozin in patients with chronic kidney disease (March 2025)

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to reduce the risk of kidney and cardiovascular events in randomized trials of two to three years' duration, but longer-term outcome data are lacking. After two years of randomized therapy in the Study of Heart and Kidney Protection with Empagliflozin (EMPA-KIDNEY) trial, participants in both treatment groups were entered into an open-label post-trial follow-up for an additional two years, during which time SGLT2 inhibitors could be prescribed at the discretion of the patients' clinicians [1]. The benefits of empagliflozin observed during the full four years of follow-up were similar to those noted during the initial two-year randomization period; effects were similar in patients with and without diabetes, with various levels of baseline albuminuria, and regardless of the estimated glomerular filtration rate (eGFR) at the start of the study. SGLT2 inhibitors provide long-term benefits in patients with chronic kidney disease and albuminuria. (See "Overview of the management of chronic kidney disease in adults", section on 'Patients with albuminuria'.)

APOL1 variants and kidney disease in West African populations (November 2024)

Two different polymorphisms in the apolipoprotein L1 (APOL1) gene, termed G1 and G2, are common in individuals of West African descent, and biallelic inheritance (ie, G1/G1, G1/G2, or G2/G2) is associated with a substantially higher risk of chronic kidney disease (CKD) and focal segmental glomerulosclerosis (FSGS). In a case-control study of over 8300 residents of Ghana and Nigeria, both monoallelic (ie, one APOL1 variant) and biallelic inheritance were associated with a higher risk of CKD (odds ratios 1.18 and 1.25, respectively) and FSGS (1.61 and 1.84, respectively) [2]. If confirmed in other populations, these data suggest that the number of individuals at risk for APOL1-associated CKD and FSGS may be greater than previously recognized. (See "Focal segmental glomerulosclerosis: Genetic causes", section on 'APOL1'.)

DIALYSIS

Beneficial effect of intradialytic exercise on cerebral oxygenation (April 2025)

Among patients on hemodialysis, intradialytic reductions in blood flow may be a risk factor for cognitive impairment. In a crossover trial in which 20 patients on maintenance hemodialysis were assigned to two sequential dialysis regimens in random order, 35 minutes of intradialytic exercise, compared with no intradialytic exercise, led to increased intradialytic cerebral oxygenation as assessed by near-infrared spectroscopy [3]. The physical benefits of exercise in the dialysis population are well established; these data should prompt additional research to delineate potential cognitive benefits. (See "Deconditioning and weakness in patients with chronic kidney disease (including those on dialysis)", section on 'Other benefits'.)

Using medium cutoff dialyzers to preserve residual kidney function (March 2025)

By improving middle molecule clearance in patients on hemodialysis, medium cutoff (MCO) dialyzers may help preserve residual kidney function, which is associated with improved survival, better volume control, and higher health-related quality of life. In a 12-month trial in which 80 patients new to kidney replacement therapy were randomly assigned to hemodialysis with a MCO dialyzer or a conventional high-flux dialyzer, the decrease in glomerular filtration rate (calculated as the mean of 24-hour urine creatinine and urea clearance) was less in the MCO group (-1.0 versus -2.4 mL/min/1.73 m²) [4]. In addition, patients in the MCO group had higher urine volumes at 9, though not 12, months, as well as greater dialysis-mediated reductions in a variety of inflammatory and kidney injury biomarkers. Additional studies are needed to validate these promising results and to examine the effect of MCO dialyzers on patient-centered outcomes. (See "Residual kidney function in kidney failure", section on 'Hemodialysis'.)

Nonpharmacologic treatment of pain for patients on dialysis (January 2025)

Many analgesic agents have adverse effects among patients with impaired kidney function. In a trial in which over 640 patients on maintenance hemodialysis with chronic pain were randomly assigned to 24 weeks of cognitive-behavioral therapy (CBT) or usual care, functional status and quality-of-life metrics were modestly higher and pain intensity, depression, and anxiety scores were modestly lower in the CBT group [5]. These data support the use of nonpharmacologic modalities as first-line therapy for chronic pain among patients on dialysis. (See "Management of chronic pain in advanced chronic kidney disease", section on 'Nonpharmacologic treatment preferred'.)

Lowering risk of cardiac arrhythmias among patients on hemodialysis (January 2025)

Lower potassium dialysate may contribute to the high rate of sudden cardiac arrest among patients on hemodialysis. In a trial in which nearly 90 hyperkalemic patients on three-times-weekly maintenance hemodialysis were randomly assigned to eight weeks of either 2 mEq/L potassium dialysate or 3 mEq/L potassium dialysate plus an oral potassium-lowering agent (sodium zirconium cyclosilicate [SCZ]) on nondialysis days, followed by treatment crossover for another eight weeks, the rate of clinically significant cardiac arrhythmias was lower (6.8 versus 10.2 per person-year) in the higher potassium dialysate/SCZ group [6]. Although the optimal approach to managing moderate hyperkalemia in this patient population remains uncertain, these data suggest that minimizing dialysis-mediated decreases in serum potassium may be beneficial. (See "Overview of the hemodialysis apparatus", section on 'Components of the dialysate'.)

FLUID, ELECTROLYTES, AND ACID-BASE BALANCE

Estimation of free calcium using albumin-adjusted calcium formulas (March 2025)

Albumin-adjusted calcium formulas are often used to estimate free calcium when albumin is abnormal, but none appears to be universally acceptable when compared with ionized calcium. In a new cross-sectional study that included 17,500 patients who had simultaneous testing of albumin, total calcium, and ionized calcium, very few (≤0.3 percent) patients with an albumin <3 g/dL and hypercalcemia by ionized calcium were misclassified as normocalcemic by a commonly used calcium correction formula [7]. However, the formula misclassified 44 percent with hypocalcemia by ionized calcium as normocalcemic, and 6.8 percent with normocalcemia by ionized calcium were misclassified as hypercalcemic. If reliable measurement of ionized calcium is not available, the total calcium may be corrected for any abnormalities in albumin, but the accuracy of the estimate may be poor in a variety of populations. (See "Diagnostic approach to hypercalcemia", section on 'Verify elevated calcium' and "Relation between total and ionized serum calcium concentrations".)

Association of hyponatremia correction rates with in-hospital mortality (December 2024)

In patients with severe, chronic hyponatremia (ie, serum sodium <120 mEq/L), the goal of initial therapy is to raise the serum sodium level slowly to avoid overcorrection. This recommendation was challenged by a meta-analysis of retrospective cohort studies that found that rapid correction of severe hyponatremia in hospitalized patients was associated with lower in-hospital mortality compared with slow correction [8]. However, the major limitation of this study is its analysis of all-cause in-hospital mortality rather than death from cerebral edema (the cause of death potentially caused by slower correction). Thus, the findings were likely confounded by the fact that severely ill patients, who are at high risk for in-hospital mortality, have hyponatremia that is more recalcitrant and less likely to correct without hypertonic saline; conversely, patients with acute hyponatremia or less severe underlying disease (and a lower risk of in-hospital mortality) are more likely to correct quickly when the cause of hyponatremia is eliminated. We continue to suggest slow correction in patients with severe, chronic hyponatremia. (See "Overview of the treatment of hyponatremia in adults", section on 'Goal rate of correction'.)

GLOMERULAR DISEASE AND VASCULITIS

Antibody-negative granulomatosis with polyangiitis (January 2025)

Some patients with granulomatosis with polyangiitis (GPA) lack antineutrophil cytoplasmic autoantibodies (ANCA), but the significance of this finding has not been clear. In a cohort study that compared clinical features and outcomes among 110 patients with ANCA-negative GPA and 110 with ANCA-positive GPA, patients with ANCA-negative GPA had milder disease and less pulmonary and kidney involvement than those with ANCA-positive GPA [9]. They also had lower remission rates (75 versus 89 percent) and lower relapse rates (9 versus 22 percent) at 60 months, which may reflect the tendency to use conventional immunosuppression (eg, methotrexate, azathioprine) to treat mild GPA. These findings suggest that patients with ANCA-negative GPA experience a more benign course than those with ANCA-positive disease. (See "Clinical spectrum of antineutrophil cytoplasmic autoantibodies", section on 'Granulomatosis with polyangiitis'.)

Avacopan for necrotizing granuloma in granulomatosis with polyangiitis (January 2025)

A randomized trial in over 330 patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) previously found comparable rates of remission with avacopan (an oral complement inhibitor) or a prednisone taper when used with standard remission induction therapy; whether avacopan is effective for the necrotizing granulomatous lesions of GPA (which typically affect the ear, nose, and throat [ENT] and lung) is less clear. In a post-hoc analysis of this trial that included 144 patients with ENT manifestations and 142 patients with lung manifestations, remission rates at 26 and 52 weeks were similar among those treated with avacopan or a prednisone taper [10]. At 52 weeks, patients with lung manifestations receiving avacopan had a lower relapse rate than those receiving prednisone. These findings imply that avacopan can be used in lieu of glucocorticoids to manage the necrotizing granulomatous manifestations of GPA. (See "Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy", section on 'Avacopan'.)

Sex and IgA vasculitis outcomes (January 2025)

IgA vasculitis (IgAV) is more common in males, but the impact of sex on disease presentation and outcomes has been unclear. A recent retrospective analysis of 164 males and 95 females with IgAV found that while baseline rates of cutaneous, joint, gastrointestinal, and kidney involvement were similar, males had more severe kidney disease (ie, lower glomerular filtration rate, higher proteinuria) than females [11]. Males were also more likely to develop refractory disease (30 versus 13 percent). These findings suggest that sex may be an important prognostic factor in IgAV, particularly in predicting kidney disease severity and response to treatment. (See "IgA vasculitis (Henoch-Schönlein purpura): Management", section on 'Prognosis'.)

Avacopan-associated drug-induced liver injury (January 2025)

Avacopan, an oral complement inhibitor used for the treatment of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), has been associated with reversible increases in liver function tests in clinical trials; however, the risk of drug-induced liver injury (DILI) may be higher in some populations. In an observational study of 22 Japanese patients with GPA or MPA who were treated with avacopan, nine (41 percent) developed DILI; eight improved after discontinuation of avacopan and other medications, and one developed vanishing bile duct syndrome resulting in death [12]. These findings suggest that patients of Japanese descent may be at increased risk of avacopan-associated DILI and may benefit from closer monitoring. (See "Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy", section on 'Avacopan'.)

Cutaneous and noncutaneous manifestations of IgA vasculitis (January 2025)

The relationship between the cutaneous and noncutaneous manifestations of immunoglobulin A (IgA) vasculitis is not well understood. In a retrospective study of 489 patients with IgA vasculitis, 7 percent of patients had a persistent rash (ie, lasting for longer than one month) and 29 percent had a rash that affected the trunk, arms, or face [13]. Patients with a persistent rash were more likely to develop glomerulonephritis, while patients with lesions above the level of the buttocks were more likely to develop gastrointestinal or genital tract involvement. These results imply that the cutaneous manifestations of IgA vasculitis may be helpful to predict outcomes in patients with this diagnosis. (See "IgA vasculitis (Henoch-Schönlein purpura): Management", section on 'Prognosis'.)

HYPERTENSION

Blood pressure measurement using a cuffless blood pressure device (March 2025)

The diagnosis and management of hypertension is based on standardized blood pressure (BP) measurement using cuff-based BP monitors, but studies are evaluating the accuracy of cuffless devices that estimate BP indirectly through measurements of photoplethysmography, pulse wave analysis, and other techniques. In a single-center observational study of 51 patients, the seven-day average daytime systolic BP obtained from the cuffless monitor was similar to that obtained by 24-hour ambulatory blood pressure monitoring (ABPM) [14]. However, the cuffless BP device consistently reported higher nocturnal systolic and diastolic BP compared with ABPM (mean difference 12.5 mmHg and 4.1 mmHg, respectively). Further validation and specific implementation guidelines are needed before cuffless devices can be recommended for clinical use. (See "Hypertension in adults: Blood pressure measurement and diagnosis", section on 'Cuffless blood pressure monitors'.)

Intensive blood pressure lowering in patients with type 2 diabetes mellitus (January 2025)

We suggest intensive blood pressure (BP) lowering (eg, systolic blood pressure [SBP] <125 mmHg using standardized methods) for patients with type 2 diabetes based on goal BP trials that included diabetic patients and indirect data from the SPRINT trial, although one trial found no significant benefit to this approach. In a randomized trial in over 12,800 patients with type 2 diabetes, hypertension, and other cardiovascular risk factors, patients assigned to a target SBP of <120 mmHg had a lower incidence of a cardiovascular composite of nonfatal stroke, nonfatal myocardial infarction, heart failure, and cardiovascular death at a median of 4.2 years, compared with patients assigned to a target SBP of <140 mmHg [15]. The algorithm for follow-up and antihypertensive therapy was similar to that used in the SPRINT trial. These data, combined with previous studies, support a strong recommendation for intensive BP lowering in patients with diabetes mellitus. (See "Goal blood pressure in adults with hypertension", section on 'Patients with diabetes mellitus'.)

Perioperative management of renin-angiotensin system inhibitors (November 2024)

The optimal perioperative management strategy of renin-angiotensin system inhibitors (RASIs) is unclear. In a trial of over 2000 patients who had been on RASIs for at least three months and were undergoing major noncardiac surgery, intraoperative hypotension was more common in patients randomly assigned to RASI continuation compared with discontinuation 48 hours prior to surgery (54 versus 41 percent), although composite rates of all-cause mortality and major postoperative complications were equivalent in both groups [16]. In patients on RASIs undergoing major noncardiac surgery, management is individualized; discontinuation of RASIs may be favored in patients at higher risk of intraoperative hypotension. (See "Perioperative medication management", section on 'ACE inhibitors and angiotensin II receptor blockers'.)

TRANSPLANTATION

Epstein-Barr virus serostatus and risk of posttransplant lymphoproliferative disorder (April 2025)

Posttransplant lymphoproliferative disorders (PTLD) are a serious complication among solid organ or hematopoietic cell transplant recipients, with most cases being caused by Epstein-Barr virus (EBV)-positive B cell proliferation. Prior studies have found an increased risk for PTLD in cases where the donor is EBV seropositive and the recipient is EBV seronegative (EBV D+/R-). In a recent retrospective cohort study of over 100 EBV D+/R- and over 300 matched EBV-seropositive recipients (with any donor status), biopsy-proven PTLD occurred in 22 percent of EBV D+/R- recipients at a median of 202 days posttransplant, while none of the EBV seropositive recipients developed PTLD [17]. These findings confirm that EBV serostatus is a risk factor for PTLD and suggest that the incidence of PTLD in kidney transplant recipients may be higher than previously estimated. (See "Epidemiology, clinical manifestations, and diagnosis of post-transplant lymphoproliferative disorders", section on 'EBV serostatus'.)

FAT1 as a target antigen in de novo membranous nephropathy after kidney transplantation (January 2025)

Membranous nephropathy (MN) can occur as recurrent or de novo disease following kidney transplantation. While recurrent MN is frequently associated with antibodies against the target antigen phospholipase A2 receptor (PLA2R), most patients with de novo MN are PLA2R negative, and the target antigen in such patients has been unknown. A recent study identified protocadherin FAT1 as a target antigen in more than one-half of patients with de novo MN who have concomitant antibody-mediated rejection [18]. Additional studies are needed to further characterize the clinical features and outcomes of patients with FAT1-associated de mono MN. (See "Membranous nephropathy and kidney transplantation", section on 'Pathogenesis'.)

Kidney transplantation from donors with HIV (November 2024)

For persons with HIV and end-stage kidney disease who are candidates for kidney transplantation, there has been increased interest in the use of kidney donors with HIV given the limited supply of organs. In a report of nearly 200 persons with HIV undergoing kidney transplantation, the rates of overall patient survival and rejection at one and three years were similar with HIV-positive and HIV-negative donors [19]. Although the incidence of HIV breakthrough infection was higher among recipients of donors with HIV versus those without HIV, virologic control was regained in all cases. These findings are consistent with other studies and support the use of donor kidneys from persons with HIV in an effort to increase access to donor organs. (See "Kidney transplantation in patients with HIV", section on 'Donors with HIV'.)

OTHER NEPHROLOGY

Updated microscopic hematuria guidelines from the American Urologic Association (March 2025)

The American Urologic Association (AUA) has released a 2025 update to its guidelines for the diagnosis, evaluation, and follow-up of microscopic hematuria [20]. The amended guidelines include a revised risk stratification system and risk-based evaluation algorithm as well as updated guidance on the use of urine-based tumor markers and cytology. Our approach to the evaluation of microscopic hematuria in adults is largely consistent with these revised guidelines. (See "Evaluation of hematuria in adults", section on 'Asymptomatic patients'.)

Kidney function and rheumatoid arthritis disease activity (February 2025)

The impact of rheumatoid arthritis (RA) disease activity on estimated glomerular filtration rate (eGFR) has been unknown. In an observational study of over 31,000 patients with RA, those with mild disease activity had an additional decline in their annual eGFR of 0.1 mL/min/1.73 m² compared with patients with RA in remission [21]. Patients with moderate or severe disease activity had an additional annual eGFR decline of 0.2 mL/min/1.73 m². This study implies that tight control of disease activity may help preserve kidney function among patients with RA, but further studies are needed. (See "Overview of the systemic and nonarticular manifestations of rheumatoid arthritis", section on 'Kidney disease'.)