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What's new in nephrology and hypertension

What's new in nephrology and hypertension
Authors:
John P Forman, MD, MSc
Albert Q Lam, MD
Eric N Taylor, MD, MSc, FASN
Literature review current through: Feb 2023. | This topic last updated: Mar 20, 2023.

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

Detecting tolvaptan-associated liver injury in patients with ADPKD (February 2023)

Due to the risk of drug-associated liver injury, treatment of patients with autosomal dominant polycystic kidney disease (ADPKD) with tolvaptan requires participation in a Risk Evaluation and Mitigation Strategy (REMS) that monitors liver function tests for the duration of therapy, with more frequent testing in the first 18 months. The utility of this REMS was evaluated in a retrospective analysis of data from randomized trials that included over 2900 tolvaptan-treated patients, 2300 of whom had 18 months or more of tolvaptan exposure [1]. Alanine aminotransferase elevations associated with tolvaptan therapy (>3 times the upper limit of normal in approximately 5 percent of patients) most often occurred within 18 months after tolvaptan initiation and normalized after treatment interruption or discontinuation. These data support the current REMS protocol as a way of detecting early liver injury and preventing severe liver injury in tolvaptan-treated patients with ADPKD. (See "Autosomal dominant polycystic kidney disease (ADPKD): Treatment", section on 'Monitoring'.)

Trial of discontinuing ACE inhibitors and ARBs in advanced CKD (December 2022)

In patients with chronic kidney disease (CKD) who take angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) chronically, the question of whether to discontinue these agents when patients progress to advanced CKD is debated. Theoretically, the acute decline in glomerular filtration rate (GFR) occurring after initiation of therapy could be regained when these drugs are stopped, thereby delaying the onset of end-stage kidney disease (ESKD). In a large trial in which over 400 patients with advanced CKD (median estimated GFR 18 mL/min/1.73 m2) on chronic therapy with an ACE inhibitor or ARB were randomly assigned to continue or discontinue therapy with these drugs, patients who discontinued therapy were more likely to develop ESKD at three years, although this was not statistically significant; rates of death and cardiovascular events were similar between the groups [2]. These data support continuing these agents in patients with advanced CKD. (See "Antihypertensive therapy and progression of nondiabetic chronic kidney disease in adults", section on 'Adverse effects'.)

Effect of SGLT2 inhibitors on kidney disease progression (November 2022)

UpToDate recommends therapy with a sodium-glucose co-transporter 2 (SGLT2) inhibitor in both patients with diabetic kidney disease and those with proteinuric nondiabetic kidney disease. A meta-analysis of 13 trials and more than 90,000 participants with and without preexisting chronic kidney disease (including the CREDENCE, DAPA-CKD, and EMPA-KIDNEY trials) examined the effect of SGLT2 inhibitors on kidney disease progression, which was defined as a sustained ≥50 percent decline in estimated glomerular filtration rate (eGFR), need for maintenance dialysis or kidney transplantation, a sustained decline in eGFR to <10 to 15 mL/min/1.73 m2, or death from kidney failure [3]. Compared with placebo, SGLT2 inhibitors reduced the rate of kidney disease progression regardless of whether the patient had diabetes. The data from this large meta-analysis support our current recommendations. (See "Treatment of diabetic kidney disease", section on 'Type 2 diabetes: Treat with additional kidney-protective therapy'.)

SGLT2 inhibitors in patients with nondiabetic proteinuric chronic kidney disease (November 2022)

Sodium-glucose co-transporter 2 (SGLT2) inhibitors are recommended in patients with diabetic kidney disease; previously, only one large trial examined their effects in nondiabetic chronic kidney disease. In the EMPA-KIDNEY trial, 6609 patients with estimated glomerular filtration rate (eGFR) 20 to 44 mL/min/1.73 m2 (regardless of albuminuria) or 45 to 89 mL/min/1.73 m2 (if albumin-to-creatinine ratio was at least 200 mg/g) were randomly assigned to empagliflozin 10 mg daily or placebo [4]. At two years, empagliflozin reduced the incidence of end-stage kidney disease, the incidence of a sustained decline in eGFR to <10 mL/min/1.73 m2, and the incidence of a sustained decrease in eGFR of 40 percent or more; the risks of all-cause mortality and nonfatal cardiovascular events were similar between groups. The benefit from empagliflozin was larger in patients with albumin-to-creatinine ratio ≥300 mg/g and substantially less in patients with lower albumin excretion. We now recommend SGLT2 inhibitor therapy in patients with nondiabetic chronic kidney disease and albuminuria. (See "Overview of the management of chronic kidney disease in adults", section on 'Patients with proteinuria'.)

Finerenone in patients with diabetic kidney disease (November 2022)

Sodium-glucose co-transporter 2 (SGLT2) inhibitors and finerenone (a nonsteroidal mineralocorticoid receptor antagonist) prevent important adverse kidney and cardiovascular outcomes in patients with diabetic kidney disease (DKD). The 2022 guidelines from the American Diabetes Association (ADA) and the Kidney Disease: Improving Global Outcomes (KDIGO) on the treatment of patients with DKD advise the use of SGLT2 inhibitors in all patients with DKD; they also advise the use of finerenone in patients who have increased albuminuria despite treatment with an angiotensin inhibitor and an SGLT2 inhibitor [5,6]. We agree with these guidelines and now suggest use of finerenone in patients with albuminuria despite other recommended therapies, except when serum potassium is elevated (serum potassium >4.8 mEq/L or estimated glomerular filtration rate <25 mL/min/1.73 m2). (See "Treatment of diabetic kidney disease", section on 'Type 2 diabetes: Treat with additional kidney-protective therapy'.)

DIALYSIS

Patient decision aids and conservative kidney management (January 2023)

Patient decision aids (PDAs) are tools used to facilitate informed decision-making and have been proposed as a way to promote conservative kidney management (CKM), an underutilized alternative to dialysis for many older patients with end-stage kidney disease (ESKD). In a trial that randomly assigned over 360 patients aged 70 years or older with nondialysis stage 4 or 5 chronic kidney disease to dialysis education with an interactive web-based PDA (Decision-Aid for Renal Therapy [DART]) or to usual care, scores assessing decisional quality and knowledge about ESKD were better in the DART group at three and six months of follow-up [7]. The preference for CKM increased from approximately 12 percent at baseline to 20 percent at six months in the DART group but remained stable for patients in the usual care group; however, differences in CKM preference between groups were not statistically significant. Although additional studies are required, PDAs such as DART may hold promise as a way of increasing the use of CKM. (See "Kidney palliative care: Conservative kidney management", section on 'Timing and content of the discussion'.)

Cool dialysate for patients on hemodialysis (November 2022)

Reduction of dialysate temperature has been proposed as a means of preventing cardiovascular complications and intradialytic hypotension in patients on hemodialysis. In a recent trial in which over 15,400 patients in outpatient hemodialysis units were randomly assigned to dialysis with cooler dialysate (0.5 to 0.9°C below predialysis body temperature; mean temperature 35.8°C) or standard temperature dialysate (36.5°C), rates of the composite outcome of cardiovascular mortality and hospitalization for cardiovascular events were similar between the groups after a median follow-up of 1.8 years [8]. Mean decreases in intradialytic systolic blood pressure were also similar between the groups, although blood pressure data were only analyzed for approximately 1 percent of dialysis treatments. More studies are needed to determine whether cool dialysate may benefit certain subgroups of patients on hemodialysis, such as those with frequent or severe intradialytic hypotension. (See "Intradialytic hypotension in an otherwise stable patient", section on 'Second-line approach'.)

Timing of preoperative hemodialysis and postoperative mortality in patients with end-stage kidney disease (November 2022)

For patients on maintenance hemodialysis, a dialysis treatment is usually performed on the day before or the day of an elective surgical procedure. In a retrospective cohort study of approximately 350,000 patients with end-stage kidney disease on hemodialysis, day-long intervals between dialysis and surgery of zero (ie, dialysis on the same day of surgery), one, two, and three days were associated with 90-day postoperative mortality risks of 4.0, 4.2, 4.7, and 5.2 percent, respectively [9]. These data support the current practice of scheduling maintenance hemodialysis on the day before or the day of a surgical procedure when practical. (See "Medical management of the dialysis patient undergoing surgery", section on 'Routine dialysis prior to surgery'.)

FLUID, ELECTROLYTES, AND ACID-BASE BALANCE

Diabetes insipidus terminology change (February 2023)

Confusion between diabetes insipidus and diabetes mellitus has led to occasional medication errors resulting in patient-safety concerns; in addition, the name "diabetes insipidus" does not reflect the underlying pathophysiology of disease. As a result, the Endocrine Society, European Society of Endocrinology, Pituitary Society, Society for Endocrinology, European Society for Paediatric Endocrinology, Endocrine Society of Australia, Brazilian Endocrine Society, and Japanese Endocrine Society all proposed to change the names of these disorders [10]. Arginine vasopressin deficiency (AVP-D) is the new name for central diabetes insipidus, and arginine vasopressin resistance (AVP-R) is the new name for nephrogenic diabetes insipidus. (See "Arginine vasopressin deficiency (central diabetes insipidus): Clinical manifestations and causes" and "Arginine vasopressin deficiency (central diabetes insipidus): Treatment" and "Arginine vasopressin resistance (nephrogenic diabetes insipidus): Clinical manifestations and causes" and "Arginine vasopressin resistance (nephrogenic diabetes insipidus): Treatment".)

GLOMERULAR DISEASE AND VASCULITIS

Novel investigational therapy for patients with FSGS and two APOL1 variants (March 2023)

Patients with gain-of-function APOL1 variants are at increased risk of proteinuric chronic kidney disease including focal segmental glomerulosclerosis (FSGS); however, specific therapies for these patients are lacking. The efficacy and safety of inaxaplin, an investigational oral small molecule inhibitor of APOL1 channel function, were evaluated in a single-arm phase 2a study in 16 adults with two APOL1 variants and biopsy-proven FSGS who received the drug for 13 weeks along with standard care [11]. At 13 weeks, patients had a mean reduction in urine protein-to-creatinine ratio of nearly 50 percent compared with baseline; adverse events were experienced by nearly all patients but were mostly mild or moderate in severity. While these findings are promising, additional controlled studies are needed to determine longer-term efficacy and safety. (See "Focal segmental glomerulosclerosis: Treatment and prognosis", section on 'Investigational therapies'.)

Mycophenolate mofetil for progressive IgA nephropathy (March 2023)

For patients with IgA nephropathy (IgAN) who are at high risk for disease progression, mycophenolate mofetil (MMF) is an alternative immunosuppressive therapy for those unable to receive oral glucocorticoids, but supportive data have come from trials that included limited patient populations. In a recent trial in which 170 patients with IgAN and persistent proteinuria after three months of supportive therapy were randomly assigned to treatment with MMF plus supportive care or supportive care alone, fewer patients in the MMF group experienced a doubling of serum creatinine (7 versus 21 percent); rates of end-stage kidney disease and death due to cardiovascular cause were low and not significantly different between the groups [12]. During posttrial follow-up, patients who discontinued MMF had an accelerated annual loss of kidney function compared with those who continued MMF. For patients with high-risk IgAN who cannot tolerate or who do not wish to receive high-dose glucocorticoids, MMF is our preferred alternative option. (See "IgA nephropathy: Treatment and prognosis", section on 'Other regimens'.)

Cardiovascular risk in patients with granulomatosis with polyangiitis and microscopic polyangiitis (February 2023)

Patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) have an increased risk of cardiovascular events, although data on long-term outcomes are limited. In a large cohort study that examined cardiovascular events among over 2300 patients with GPA or MPA and nearly 7000 control patients over a median of 9.5 years, a diagnosis of GPA or MPA was associated with an increased risk of ischemic heart disease, heart failure, myocardial infarction, atrial fibrillation, ventricular arrhythmia/defibrillator implantation, ischemic stroke, percutaneous coronary intervention, and in-hospital cardiac arrest [13]. These findings highlight the importance of monitoring and preventing cardiovascular disease in this patient population. (See "Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy", section on 'Prognosis and other outcomes'.)

Targeted-release budesonide for IgA nephropathy (February 2023)

An oral targeted-release formulation of the glucocorticoid budesonide (TRF-budesonide) has been designed to release the drug in the distal ileum in patients with immunoglobulin A nephropathy (IgAN) to target the presumed site of production of aberrantly galactosylated IgA1 while limiting systemic glucocorticoid absorption. The efficacy and safety of this agent were evaluated in a randomized phase 3 trial of 199 patients with IgAN and persistent proteinuria despite optimized renin-angiotensin system blockade [14]. Treatment with TRF-budesonide, compared with placebo, resulted in a greater reduction in proteinuria from baseline and a slower rate of estimated glomerular filtration rate decline at nine months; while rates of adverse effects were similar between the groups, rates of adverse events leading to treatment discontinuation were higher in the TRF-budesonide group. Pending data on longer-term outcomes with TRF-budesonide, we continue to suggest initial therapy with oral systemic glucocorticoids plus supportive care for patients with IgAN at high risk for disease progression. (See "IgA nephropathy: Treatment and prognosis", section on 'Other regimens'.)

HYPERTENSION

Therapeutic inertia in older adults with uncontrolled blood pressure (March 2023)

Therapeutic inertia, defined as the failure by clinicians to intensify antihypertensive treatment when blood pressure rises or remains above therapeutic goals, is an important contributor to low rates of hypertension control in the population. A large population-based study examined rates of antihypertensive initiation (or antihypertensive intensification) in older adults in the United States who had an ambulatory care visit in which their blood pressure was above goal (according to the American College of Cardiology/American Heart Association guidelines) [15]. In 2018, appropriate initiation of antihypertensive medication among untreated individuals occurred in less than 20 percent of visits, and appropriate addition of another antihypertensive agent among those already treated occurred in less than 10 percent of visits, representing a decrease in prescribing compared with data from 2008. These findings indicate that therapeutic inertia continues to be a major impediment to attaining hypertension control. (See "The prevalence and control of hypertension in adults", section on 'Methods to improve control rates'.)

Renal denervation in untreated patients with hypertension (March 2023)

Denervation of the renal sympathetic nerves lowers blood pressure in patients with hypertension. In a sham-controlled trial of over 200 patients with hypertension taking no antihypertensive therapy, ultrasound-based renal denervation lowered 24-hour ambulatory blood pressure by 6/4 mmHg at two months compared with the sham procedure and increased the rate of attaining goal blood pressure [16]. These findings, as well as those of other trials, demonstrate that renal denervation can be used to lower blood pressure in patients with hypertension. (See "Treatment of resistant hypertension", section on 'Renal denervation'.)

Ultrasound renal denervation in patients with resistant hypertension (January 2023)

Denervation of the renal sympathetic nerves reduced blood pressure in patients with resistant hypertension in one sham-controlled trial. In a second sham-controlled trial (RADIANCE-HTN TRIO), 136 patients with resistant hypertension despite treatment with a three-drug single-pill combination were randomly assigned to renal denervation or sham procedure [17,18]. At two months, renal denervation produced a larger decrease in daytime ambulatory systolic pressure; thereafter, medication adjustment was permitted and, at six months, the daytime ambulatory systolic pressures were similar between the groups. Patients in the denervation group were prescribed less antihypertensive medication at six months, but this difference was not statistically significant. These data suggest that renal denervation might reduce the number of medications needed to control blood pressure in patients with resistant hypertension. (See "Treatment of resistant hypertension", section on 'Renal denervation'.)

ADA guidelines for hypertension treatment in individuals with diabetes (January 2023)

Hypertension management is a cornerstone of cardiovascular risk reduction in patients with diabetes, but society guidelines have been discordant in their recommended treatment targets for medical therapy. In its recently published guidelines, the American Diabetes Association (ADA) recommends treatment targets for systolic and diastolic blood pressures of <130 mmHg and <80 mmHg, respectively, for most patients with diabetes [19]. These treatment targets should be implemented only if they can be achieved safely, and treatment goals should be individualized based on cardiovascular risk, patient preferences, and possible adverse effects of therapy. These ADA guidelines are now consistent with those of the American College of Cardiology/American Heart Association and support our current recommendations for medical management of hypertension in patients with diabetes. (See "Overview of general medical care in nonpregnant adults with diabetes mellitus", section on 'Blood pressure control' and "Goal blood pressure in adults with hypertension", section on 'Patients with diabetes mellitus'.)

Chlorthalidone versus hydrochlorothiazide on cardiovascular outcomes (January 2023)

Thiazide-like diuretics such as chlorthalidone have greater antihypertensive efficacy than hydrochlorothiazide (HCTZ), and we suggest using a thiazide-like diuretic rather than HCTZ in patients with hypertension. In a trial that compared the effects of these agents on cardiovascular outcomes, over 13,000 older male veterans with uncontrolled hypertension despite taking HCTZ 25 mg daily with or without other antihypertensive agents were randomly assigned to continue HCTZ or switch to chlorthalidone 12.5 mg daily [20]. At 2.4 years, rates of all-cause mortality, stroke, myocardial infarction, and hospitalization for heart failure were the same in each group; blood pressure was also similar between the groups and remained uncontrolled throughout the trial. This trial had multiple limitations that diminish the usefulness of the findings, and we continue to prefer thiazide-like diuretics (eg, chlorthalidone) over HCTZ for hypertension treatment. (See "Choice of drug therapy in primary (essential) hypertension", section on 'Patients selected for initial monotherapy'.)

Long-term results of renal denervation in patients with resistant hypertension (November 2022)

Renal denervation lowers blood pressure in patients with untreated and treated hypertension, although the usefulness of the procedure in patients with resistant hypertension was unclear. In the SYMPLICITY HTN-3 trial, renal denervation, compared with a sham-control procedure, did not significantly improve ambulatory blood pressure at six months. However, renal denervation produced a larger decrease in ambulatory systolic blood pressure at 12 months (-7.5 versus -0.1 mmHg) and 36 months (-15.6 versus -0.3 mmHg) [21]. These data suggest that renal denervation can effectively lower blood pressure in patients with resistant hypertension. (See "Treatment of resistant hypertension", section on 'Renal denervation'.)

Morning versus bedtime dosing of once-daily antihypertensive medications (October 2022)

The best time of day to take once-daily antihypertensive medications was previously controversial, and some studies found that bedtime dosing lowered nocturnal blood pressure and improved cardiovascular outcomes. In the largest and most rigorous trial (ie, the Treatment In the Morning or Evening [TIME] study), more than 21,000 adults with hypertension were randomly assigned to take their antihypertensive medications in the morning or the evening [22]. At approximately five years, rates of cardiovascular outcomes were similar between the groups, as were adverse events. This study indicates that patients can take their once-daily antihypertensive medications at a time that they find most suitable. (See "Choice of drug therapy in primary (essential) hypertension", section on 'Bedtime versus morning dosing'.)

NEPHROLITHIASIS

Hydrochlorothiazide and prevention of recurrent kidney stones (March 2023)

Thiazide therapy can lower urinary calcium excretion and has been shown in prior randomized trials to reduce the risk of kidney stone recurrence in patients with calcium stones. A recent trial in over 400 patients with recurrent calcium kidney stones found that once daily hydrochlorothiazide (HCTZ; 12.5, 25, or 50 mg), compared with placebo, did not reduce the risk of a composite of symptomatic or radiologic stone recurrence over a median of three years [23]. However, there was a reduction in the rates of radiologic stone recurrence in patients receiving higher doses of HCTZ. For patients with recurrent calcium oxalate stones and higher than desired urine calcium, we continue to suggest treatment with a thiazide diuretic to lower urinary calcium excretion. (See "Kidney stones in adults: Prevention of recurrent kidney stones", section on 'High urine calcium'.)

TRANSPLANTATION

No benefit of sodium bicarbonate for kidney transplant recipients with metabolic acidosis (March 2023)

Metabolic acidosis is common among kidney transplant recipients and associated with graft loss and mortality. While correction of metabolic acidosis with alkali therapy (eg, sodium bicarbonate) has been shown to slow the decline of kidney function in nontransplant patients with chronic kidney disease, a similar benefit in kidney transplant recipients has not been demonstrated. In a recent trial in nearly 250 long-term kidney transplant recipients with stable graft function and metabolic acidosis, treatment with oral sodium bicarbonate, compared with placebo, increased serum bicarbonate levels but did not slow the decline of estimated glomerular filtration rate over two years [24]. Based on these results, sodium bicarbonate should not be given to preserve graft function in kidney transplant recipients with metabolic acidosis. (See "Kidney transplantation in adults: Overview of care of the adult kidney transplant recipient", section on 'Metabolic acidosis'.)

Machine perfusion versus hypothermia for deceased-donor kidney recovery (February 2023)

Among kidney transplant recipients, ex situ kidney hypothermic machine perfusion and therapeutic hypothermia during deceased-donor kidney retrieval have each been shown to reduce the risk of delayed graft function (DGF; defined as need for dialysis in the first week after transplant), but direct comparative data have been lacking. In a recent trial in which 1349 kidneys from 725 brain-dead donors were randomly assigned to machine perfusion, therapeutic hypothermia, or both before transplantation, the incidence of DGF was lower with machine perfusion than with hypothermia (19 versus 30 percent), with no additional benefit from the combination [25]. Rates of one-year allograft survival were similar among groups. Although machine perfusion adds significant expense to kidney retrieval, the reduction in DGF would mitigate this cost. (See "Deceased- and living-donor kidney allograft recovery", section on 'Pulsatile perfusion'.)

OTHER NEPHROLOGY

Comparison of the EKFC and CKD-EPI equations for estimating glomerular filtration rate (March 2023)

To calculate estimated glomerular filtration rate (eGFR), we and others recommend using the 2021 Chronic Kidney Disease Epidemiology (CKD-EPI) equation. Other equations have been developed using standardized serum creatinine assays, such as the European Kidney Function Consortium (EKFC) equation, which was developed predominantly in White populations and uses a race-specific Q value. In one study, the EKFC creatinine equation was slightly more accurate than the 2021 CKD-EPI creatinine equation in both White and Black populations [26]. However, because this equation takes race into account, we continue to recommend using the 2021 CKD-EPI creatinine equation. (See "Assessment of kidney function", section on 'eGFR from creatinine (primary approach)'.)

  1. Alpers DH, Lewis JH, Hunt CM, et al. Clinical Pattern of Tolvaptan-Associated Liver Injury in Trial Participants With Autosomal Dominant Polycystic Kidney Disease (ADPKD): An Analysis of Pivotal Clinical Trials. Am J Kidney Dis 2023; 81:281.
  2. Bhandari S, Mehta S, Khwaja A, et al. Renin-Angiotensin System Inhibition in Advanced Chronic Kidney Disease. N Engl J Med 2022; 387:2021.
  3. Nuffield Department of Population Health Renal Studies Group, SGLT2 inhibitor Meta-Analysis Cardio-Renal Trialists' Consortium. Impact of diabetes on the effects of sodium glucose co-transporter-2 inhibitors on kidney outcomes: collaborative meta-analysis of large placebo-controlled trials. Lancet 2022; 400:1788.
  4. The EMPA-KIDNEY Collaborative Group, Herrington WG, Staplin N, et al. Empagliflozin in Patients with Chronic Kidney Disease. N Engl J Med 2023; 388:117.
  5. de Boer IH, Khunti K, Sadusky T, et al. Diabetes management in chronic kidney disease: a consensus report by the American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2022; 102:974.
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  7. Ladin K, Tighiouart H, Bronzi O, et al. Effectiveness of an Intervention to Improve Decision Making for Older Patients With Advanced Chronic Kidney Disease : A Randomized Controlled Trial. Ann Intern Med 2023; 176:29.
  8. MyTEMP writing committee. Personalised cooler dialysate for patients receiving maintenance haemodialysis (MyTEMP): a pragmatic, cluster-randomised trial. Lancet 2022; 400:1693.
  9. Fielding-Singh V, Vanneman MW, Grogan T, et al. Association Between Preoperative Hemodialysis Timing and Postoperative Mortality in Patients With End-stage Kidney Disease. JAMA 2022; 328:1837.
  10. Arima H, Cheetham T, Christ-Crain M, et al. Changing the Name of Diabetes Insipidus: A Position Statement of the Working Group for Renaming Diabetes Insipidus. J Clin Endocrinol Metab 2022; 108:1.
  11. Egbuna O, Zimmerman B, Manos G, et al. Inaxaplin for Proteinuric Kidney Disease in Persons with Two APOL1 Variants. N Engl J Med 2023; 388:969.
  12. Hou FF, Xie D, Wang J, et al. Effectiveness of Mycophenolate Mofetil Among Patients With Progressive IgA Nephropathy: A Randomized Clinical Trial. JAMA Netw Open 2023; 6:e2254054.
  13. Nygaard L, Polcwiartek C, Nelveg-Kristensen KE, et al. Long-term cardiovascular outcomes and temporal trends in patients diagnosed with ANCA-associated vasculitis: a Danish nationwide registry study. Rheumatology (Oxford) 2023; 62:735.
  14. Barratt J, Lafayette R, Kristensen J, et al. Results from part A of the multi-center, double-blind, randomized, placebo-controlled NefIgArd trial, which evaluated targeted-release formulation of budesonide for the treatment of primary immunoglobulin A nephropathy. Kidney Int 2023; 103:391.
  15. Chiu N, Chiu L, Aggarwal R, et al. Trends in Blood Pressure Treatment Intensification in Older Adults With Hypertension in the United States, 2008 to 2018. Hypertension 2023; 80:553.
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  18. Azizi M, Mahfoud F, Weber MA, et al. Effects of Renal Denervation vs Sham in Resistant Hypertension After Medication Escalation: Prespecified Analysis at 6 Months of the RADIANCE-HTN TRIO Randomized Clinical Trial. JAMA Cardiol 2022; 7:1244.
  19. ElSayed NA, Aleppo G, Aroda VR, et al. 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes-2023. Diabetes Care 2023; 46:S158.
  20. Ishani A, Cushman WC, Leatherman SM, et al. Chlorthalidone vs. Hydrochlorothiazide for Hypertension-Cardiovascular Events. N Engl J Med 2022; 387:2401.
  21. Bhatt DL, Vaduganathan M, Kandzari DE, et al. Long-term outcomes after catheter-based renal artery denervation for resistant hypertension: final follow-up of the randomised SYMPLICITY HTN-3 Trial. Lancet 2022; 400:1405.
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