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What's new in nephrology and hypertension

What's new in nephrology and hypertension
John P Forman, MD, MSc
Albert Q Lam, MD
Eric N Taylor, MD, MSc, FASN
Literature review current through: Nov 2022. | This topic last updated: Dec 30, 2022.

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.


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 [1]. 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 [2]. 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 [3]. 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 [4,5]. 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'.)

Individual-level differences between estimated and measured GFR (August 2022)

UpToDate recommends using the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation to calculate estimated glomerular filtration rate (eGFR) in most clinical settings. In an analysis of more than 3000 participants from four cohorts in the United States, although the median difference between eGFR and measured GFR (mGFR) was only 0.6 mL/min per 1.73 m2, the individual-level differences were often large, and CKD staging based upon eGFR varied from staging based upon mGFR in as many as one-third of individuals [6]. Clinicians should therefore be aware that individual-level differences between eGFR and mGFR can be clinically relevant; in addition, differences between eGFR and mGFR can be large enough to impact CKD staging. (See "Assessment of kidney function", section on 'eGFR from creatinine (primary approach)'.)


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 [7]. 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 [8]. 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'.)


Rituximab for adults >75 years old with ANCA-associated vasculitis (August 2022)

Rituximab has been shown to be efficacious in patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA), but randomized trials included few patients who were 75 years or older. An observational study of 93 adults aged >75 years with GPA or MPA found that rituximab for induction and/or maintenance therapy was associated with remission in most patients and low rates of relapse [9]. However, rates of serious infection were high (46.6 per 100 patient-years) among patients receiving rituximab for induction therapy. These findings support the use of rituximab in patients 75 years old but highlight the risk of serious infections in this patient population. (See "Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy", section on 'Induction therapy'.)

Oral tacrolimus versus intravenous cyclophosphamide for lupus nephritis (August 2022)

Calcineurin inhibitors (CNIs) in combination with mycophenolate (MMF) have been used for initial therapy for lupus nephritis (LN) as an alternative to cyclophosphamide, but the efficacy of CNIs without MMF remains unclear. In a trial that randomly assigned over 300 patients with LN to oral tacrolimus or intravenous cyclophosphamide for 24 weeks, the rate of complete response was higher in the tacrolimus group (50 versus 36 percent) [10]. Rates of serious treatment-emergent adverse events were lower in the tacrolimus group; however, patients receiving tacrolimus had an increase in serum creatinine that was sustained for the duration of the trial. Although additional longer-term studies are needed to confirm these findings, we continue to suggest glucocorticoids in combination with MMF or cyclophosphamide alone for initial therapy of focal or diffuse LN. (See "Lupus nephritis: Initial and subsequent therapy for focal or diffuse lupus nephritis", section on 'Calcineurin inhibitors plus mycophenolate'.)

Risk of arterial and venous thromboembolism in nephrotic syndrome (July 2022)

Patients with the nephrotic syndrome are at increased risk for venous and arterial thrombosis compared with the general population. In a large Danish registry study that followed nearly 4000 adults with first-time nephrotic syndrome for 10 years, the 10-year absolute risks of arterial and venous thromboembolism were 14 and 8 percent, respectively, compared with 9 and 3 percent, respectively, in age- and sex-matched controls without the nephrotic syndrome [11]. The risks of ischemic stroke and myocardial infarction were higher than those of other types of thromboembolism. These findings support those of prior studies and highlight the long-term risk of thromboembolic disease among patients with the nephrotic syndrome. (See "Hypercoagulability in nephrotic syndrome", section on 'Epidemiology'.)


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) [12]. 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 [13]. 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'.)

Remote monitoring of self-measured blood pressure and blood pressure control (July 2022)

Self-measurement of blood pressure (at home) may improve blood pressure control in patients with hypertension, especially if integrated with other supportive interventions. In a meta-analysis of 18 randomized trials, blood pressure self-measurement combined with mobile or web-based telemonitoring led to greater decreases in systolic and diastolic blood pressure compared with usual care,, possibly due to increased patient engagement and adherence [14]. Patients who are interested in self-monitoring should be provided with adequate training in the machine's use, and the device should be checked for accuracy approximately once yearly. (See "Out-of-office blood pressure measurement: Ambulatory and self-measured blood pressure monitoring", section on 'Possible improvement in blood pressure control with SMBP'.)


Removal of small, asymptomatic kidney stones and risk of relapse (August 2022)

In patients undergoing surgical removal of kidney or ureteral stones, the benefits of simultaneously removing small, asymptomatic stones are uncertain. In a trial that randomly assigned 73 adults scheduled for endoscopic stone removal surgery and with small (<6 mm) asymptomatic (secondary) stones on preoperative computed tomography to removal of both primary and secondary stones (treatment group) or primary stones alone (control group), rates of stone relapse were lower in the treatment group after a median of four years [15]. Removing secondary stones added a median of 25 minutes to overall surgery time, and rates of adverse events were similar between the groups. These findings support our approach of routinely removing ipsilateral asymptomatic stones when removing an obstructing or symptomatic stone by endoscopic methods. (See "Kidney stones in adults: Surgical management of kidney and ureteral stones", section on 'Removal of secondary stones'.)


Five-year graft survival for recipients of HCV-RNA-positive donor kidneys (August 2022)

Transplantation of hepatitis C virus (HCV) ribonucleic acid (RNA)-positive donor kidneys into HCV RNA-negative recipients, combined with direct-acting antiviral (DAA) therapy, has been shown to be safe and efficacious, but data on long-term patient and graft outcomes have been lacking. An analysis of nearly 76,000 adult deceased-donor kidney transplant recipients from 2016 to 2021 found that five-year graft survival was similar between recipients of HCV RNA-positive versus HCV RNA-negative donor kidneys (72 versus 69 percent) [16,17]. These findings add to the growing evidence that transplantation of HCV RNA-positive kidneys into HCV RNA-negative recipients in the era of DAA therapy can provide well-functioning allografts and increase organ supply. (See "Kidney transplantation in adults: Hepatitis C virus infection in kidney donors", section on 'Among HCV-seronegative recipients'.)

  1. Bhandari S, Mehta S, Khwaja A, et al. Renin-Angiotensin System Inhibition in Advanced Chronic Kidney Disease. N Engl J Med 2022; 387:2021.
  2. 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.
  3. EMPA-KIDNEY Collaborative Group, Herrington WG, Staplin N, et al. Empagliflozin in Patients with Chronic Kidney Disease. N Engl J Med 2022.
  4. 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.
  5. Rossing P, Caramori ML, Chan JCN, et al. Executive summary of the KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease: an update based on rapidly emerging new evidence. Kidney Int 2022; 102:990.
  6. Shafi T, Zhu X, Lirette ST, et al. Quantifying Individual-Level Inaccuracy in Glomerular Filtration Rate Estimation : A Cross-Sectional Study. Ann Intern Med 2022; 175:1073.
  7. MyTEMP writing committee. Personalised cooler dialysate for patients receiving maintenance haemodialysis (MyTEMP): a pragmatic, cluster-randomised trial. Lancet 2022; 400:1693.
  8. 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.
  9. Thietart S, Karras A, Augusto JF, et al. Evaluation of Rituximab for Induction and Maintenance Therapy in Patients 75 Years and Older With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis. JAMA Netw Open 2022; 5:e2220925.
  10. Zheng Z, Zhang H, Peng X, et al. Effect of Tacrolimus vs Intravenous Cyclophosphamide on Complete or Partial Response in Patients With Lupus Nephritis: A Randomized Clinical Trial. JAMA Netw Open 2022; 5:e224492.
  11. Vestergaard SV, Birn H, Darvalics B, et al. Risk of Arterial Thromboembolism, Venous Thromboembolism, and Bleeding in Patients with Nephrotic Syndrome: A Population-Based Cohort Study. Am J Med 2022; 135:615.
  12. 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.
  13. Mackenzie IS, Rogers A, Poulter NR, et al. Cardiovascular outcomes in adults with hypertension with evening versus morning dosing of usual antihypertensives in the UK (TIME study): a prospective, randomised, open-label, blinded-endpoint clinical trial. Lancet 2022; 400:1417.
  14. Kalagara R, Chennareddy S, Scaggiante J, et al. Blood pressure management through application-based telehealth platforms: a systematic review and meta-analysis. J Hypertens 2022; 40:1249.
  15. Sorensen MD, Harper JD, Borofsky MS, et al. Removal of Small, Asymptomatic Kidney Stones and Incidence of Relapse. N Engl J Med 2022; 387:506.
  16. Molnar MZ, Azhar A, Tsujita M, et al. Transplantation of Kidneys From Hepatitis C Virus-Infected Donors to Hepatitis C Virus-Negative Recipients: One-Year Kidney Allograft Outcomes. Am J Kidney Dis 2021; 77:739.
  17. Schaubel DE, Tran AH, Abt PL, et al. Five-Year Allograft Survival for Recipients of Kidney Transplants From Hepatitis C Virus Infected vs Uninfected Deceased Donors in the Direct-Acting Antiviral Therapy Era. JAMA 2022; 328:1102.
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