Version May 2024
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
APOL1 variant reduces risk of kidney disease in individuals with high-risk APOL1 genotypes (October 2023)
Two different polymorphisms in the apolipoprotein L1 (APOL1) gene, termed G1 and G2, are common in individuals of West African descent and confer a high risk of chronic kidney disease (CKD) and end-stage kidney disease (ESKD) when inherited in an autosomal recessive fashion (ie, G1/G1, G1/G2, or G2/G2). In a study of over 150,000 individuals of African ancestry in one primary and two replication cohorts, the increased risk of CKD and ESKD associated with high-risk APOL1 genotypes was completely abrogated in those who also had a different APOL1 mutation, p.N264k [1]. In addition, in vitro functional studies in cell models showed that APOL1 p.N264k reduced toxicity of high-risk APOL1 genotypes. These data contribute to our understanding of the epidemiology of kidney disease and support ongoing research into novel drugs that mimic the activity of APOL1 p.N264k. (See "Epidemiology of chronic kidney disease", section on 'Apolipoprotein L1 in African Americans'.)
DIALYSIS
Severe hypocalcemia with denosumab therapy in dialysis-treated patients (February 2024)
Denosumab use is not restricted in individuals with osteoporosis who have advanced kidney disease. However, concerns remain regarding the risk of severe hypocalcemia in such patients. In a cohort study of 2804 female patients (aged ≥65 years) undergoing dialysis, severe hypocalcemia (serum calcium <7.5 mg/dL [1.9 mmol/L] or hypocalcemia requiring emergency care) occurred in a higher proportion of patients who initiated denosumab compared with those who initiated an oral bisphosphonate (12-week weighted cumulative incidence 41.1 versus 2 percent, respectively) [2]. Denosumab also was associated with a higher incidence of very severe hypocalcemia (serum calcium <6.5 mg/dL [1.6 mmol/L]). A boxed warning about risk of severe hypocalcemia in individuals with advanced kidney disease has been added for brand name denosumab (Prolia) [3], underscoring the need for greater caution and increased monitoring during treatment. (See "Denosumab for osteoporosis", section on 'Hypocalcemia'.)
Taurolidine catheter locks for the prevention of hemodialysis catheter-related bloodstream infections (December 2023)
Catheter-related bloodstream infections (CRBSIs) are an important cause of morbidity and mortality in patients on hemodialysis. In a randomized trial of nearly 800 patients on maintenance hemodialysis via a tunneled central venous catheter, a catheter lock solution containing taurolidine, an antimicrobial agent, plus heparin reduced the incidence of CRBSI compared with a heparin control lock solution (2 versus 8 percent) over a mean of 200 days [4]. No trial participants used chlorhexidine-coated catheter caps, which are commonly used to reduce the risk of CRBSI. Based on these results, taurolidine lock solutions are a reasonable alternative to chlorhexidine-coated catheter caps to help prevent CRBSIs in select patients. (See "Tunneled hemodialysis catheter-related bloodstream infection (CRBSI): Management and prevention", section on 'Methods we use'.)
Tenapanor for refractory hyperphosphatemia in patients on dialysis (November 2023)
Despite adequate dialysis, dietary restriction, treatment of hyperparathyroidism, and phosphate binders (PBs), hyperphosphatemia is common among patients on dialysis and associated with adverse outcomes. In a trial in which nearly 170 patients on hemodialysis with hyperphosphatemia despite PB therapy were randomly assigned to PBs plus either tenapanor (an inhibitor of intestinal sodium/hydrogen exchanger 3) or placebo for eight weeks, serum phosphorus levels were 1.76 mg/dL lower in the tenapanor group [5]. Diarrhea was more frequent among patients receiving tenapanor but was mild or moderate in all cases. These data, in conjunction with prior trial data, support our approach of using tenapanor as add-on therapy in patients on dialysis who have an inadequate response to PBs. (See "Management of hyperphosphatemia in adults with chronic kidney disease", section on 'Refractory hyperphosphatemia'.)
Residual kidney function and survival in patients on dialysis (October 2023)
In patients on dialysis, greater residual kidney function (RKF) is associated with improved survival; however, whether this benefit is apparent over a wide range of RKF values or is limited to a reduction in death from cardiovascular causes is uncertain. In a longitudinal study of over 39,000 patients starting hemodialysis whose RKF was assessed by renal urea clearance, greater RKF was associated in a dose-dependent fashion with lower rates of sudden cardiac death (SCD), non-SCD cardiovascular death, and non-cardiovascular death [6]. The broad-based benefit of RKF observed in this study highlights the importance of taking specific measures to preserve RKF in patients starting dialysis. (See "Residual kidney function in kidney failure", section on 'Survival'.)
Peritoneal dialysis-related drain pain (August 2023)
Pain that occurs during the draining phase of peritoneal dialysis (PD), or drain pain, is an underreported complication of PD. An international study of over 1600 patients on PD reported that 28 percent had drain pain, 35 percent of whom rated their pain as severe [7]. Among patients with drain pain who were on automated PD, only a minority (39 percent) used tidal PD, which often reduces or resolves drain pain. Because drain pain is common and may lead to cessation of PD, clinicians should ask their patients about drain pain and offer appropriate interventions. (See "Noninfectious complications of continuous peritoneal dialysis", section on 'Drain pain'.)
GLOMERULAR DISEASE AND VASCULITIS
Sibeprenlimab for IgA nephropathy (December 2023)
A Proliferation-Inducing Ligand (APRIL) is critical for mucosal B cell survival, maturation, and proliferation and has been implicated in the pathogenesis of IgA nephropathy (IgAN). The efficacy and safety of sibeprenlimab, an investigational monoclonal antibody against APRIL, were evaluated in a phase II trial in which over 150 patients with IgAN and persistent proteinuria despite optimized supportive care were randomly assigned to intravenous sibeprenlimab (2, 4, or 8 mg/kg body weight) or placebo once monthly for 12 months [8]. At 12 months, patients receiving sibeprenlimab had a greater, dose-dependent reduction in proteinuria; rates of serious adverse events were similar among the treatment groups. A larger phase III trial is in progress. (See "IgA nephropathy: Treatment and prognosis", section on 'Investigational agents'.)
Sparsentan in patients with IgA nephropathy (December 2023)
Patients with IgA nephropathy (IgAN) generally receive a renin-angiotensin system (RAS) inhibitor to reduce proteinuria, but proteinuria may persist despite maximally tolerated therapy. The efficacy and safety of sparsentan, a dual angiotensin II receptor and endothelin-1 receptor antagonist, were evaluated in a phase 3 trial in which over 400 adults with IgAN and persistent proteinuria despite three months of optimized supportive care were randomly assigned to sparsentan or irbesartan once daily [9,10]. At week 110, patients receiving sparsentan had a greater reduction in proteinuria and a smaller decline in two-year estimated glomerular filtration rate (eGFR) chronic slope; while rates of serious adverse events were similar between the groups, hypotension, dizziness, and acute kidney injury were more frequent with sparsentan. We consider sparsentan as an alternative option to reduce proteinuria in patients with IgAN and persistent proteinuria ≥1 g/day despite optimal treatment with an RAS inhibitor and a sodium-glucose cotransporter 2 (SGLT2) inhibitor for at least three to six months. (See "IgA nephropathy: Treatment and prognosis", section on 'Dual endothelin angiotensin receptor antagonists'.)
Trial of sparsentan in focal segmental glomerulosclerosis (December 2023)
Patients with focal segmental glomerulosclerosis (FSGS) are commonly treated with renin-angiotensin system (RAS) inhibitors to reduce proteinuria and stabilize kidney function. In a phase 3 trial in which over 370 patients with an FSGS lesion on kidney biopsy or a genetic variant associated with FSGS were randomly assigned to sparsentan, a dual endothelin receptor and angiotensin II receptor antagonist, or to the angiotensin II receptor antagonist irbesartan, sparsentan-treated patients had a greater reduction in proteinuria at 36 and 108 weeks, but there was no significant difference between the groups in estimated glomerular filtration rate (eGFR) slope at 108 weeks [11]. The discrepancy between sparsentan's effects on proteinuria and eGFR may reflect the enrollment of a heterogeneous mix of patients with primary, secondary, and genetic FSGS, who have a fundamentally different pathogenesis and disease course. Based on these findings, we do not use sparsentan in patients with an FSGS lesion. (See "Focal segmental glomerulosclerosis: Treatment and prognosis", section on 'Investigational therapies'.)
TRF-budesonide in patients with IgA nephropathy (September 2023)
In a phase 3 trial in patients with immunoglobulin A nephropathy (IgAN) and persistent proteinuria despite optimized renin-angiotensin system blockade, an oral targeted-release formulation of the glucocorticoid budesonide (TRF-budesonide) reduced proteinuria from baseline and slowed decline of kidney function at nine months compared with placebo [12]. Benefits were maintained at two years [13]. While rates of serious adverse effects were similar between the groups, hypertension, edema, muscle spasms, and acne were more frequent in the TRF-budesonide group, possibly suggesting a systemic glucocorticoid effect. For patients with IgAN at high risk of disease progression, we continue to suggest initial therapy with oral systemic glucocorticoids plus supportive care; TRF-budesonide is an alternative for those who cannot tolerate or do not wish to take oral systemic glucocorticoids. (See "IgA nephropathy: Treatment and prognosis", section on 'Other regimens'.)
COVID-19 vaccination and relapse of glomerular disease (September 2023)
Despite their increased risk of severe COVID-19, many patients with glomerular disease are reluctant to vaccinate against COVID-19 because of the potential risk of vaccine-associated disease relapse. In a prospective cohort study of over 2000 patients with biopsy-proven minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, or IgA nephropathy, COVID-19 vaccination was not associated with worsening of glomerular disease activity (defined by an increase in proteinuria) or with a decrease in estimated glomerular filtration rate (eGFR) [14]. These results support our practice of administering COVID-19 vaccinations to most patients with glomerular disease, though our specific recommendations depend on disease type and the temporal relationship between prior COVID-19 vaccination and disease activity. (See "COVID-19: Issues related to acute kidney injury, glomerular disease, and hypertension", section on 'COVID-19 vaccine-associated glomerular disease'.)
Daratumumab for lupus nephritis resistant to standard therapy (August 2023)
Lupus nephritis (LN) that is resistant to standard therapies is associated with high morbidity and mortality, and treatment options are limited. The efficacy of daratumumab, an anti-CD38 monoclonal antibody, was evaluated in a case series of six patients who received this agent over 12 months; all patients had LN resistant to mycophenolate- and/or cyclophosphamide-based regimens, as well as other therapies such as rituximab and belimumab [15]. At 12 months, five patients had an improvement in mean proteinuria, mean serum creatinine, and a systemic lupus erythematosus disease activity index; one patient had no response after six months and discontinued therapy. While these results are promising, further studies are needed to evaluate the potential role for daratumumab in treatment of LN resistant to standard therapy. (See "Overview of the management and prognosis of systemic lupus erythematosus in adults", section on 'Agents under investigation'.)
HYPERTENSION
Novel aldosterone synthase inhibitor in the treatment of hypertension (October 2023)
Aldosterone synthase inhibitors may have the same antihypertensive benefit as mineralocorticoid receptor antagonists (such as spironolactone) without the associated hormonal adverse effects. Lorundrostat, an aldosterone synthase inhibitor, was tested in a trial of over 160 patients with a suppressed plasma renin activity and uncontrolled hypertension despite antihypertensive drug therapy (at least two medications) [16]. Compared with placebo, lorundrostat reduced automated office systolic blood pressure at eight weeks by 1.5 to 9.6 mmHg, depending upon the lorundrostat dose. Aldosterone synthase inhibitors such as lorundrostat may become useful in the treatment of resistant hypertension. (See "Treatment of resistant hypertension", section on 'Novel medications'.)
NEPHROLITHIASIS
Tranexamic acid to reduce bleeding after percutaneous nephrolithotomy (December 2023)
Postoperative bleeding can occur after percutaneous nephrolithotomy (PNL) for kidney stone removal; most bleeding is venous in origin and can be managed with conservative measures. A recent meta-analysis of 10 randomized trials found that use of tranexamic acid (TXA), an antifibrinolytic agent used to reduce bleeding in other clinical settings, may reduce the risk of blood transfusion after PNL [17]. Most trials were conducted in low- to middle-income settings in populations that were younger than those in higher-income settings; whether these findings are generalizable to practice in higher-income settings is uncertain. Pending additional data, we do not routinely use TXA after PNL. (See "Kidney stones in adults: Surgical management of kidney and ureteral stones", section on 'Bleeding'.)
PEDIATRIC NEPHROLOGY
Serial amnioinfusions for bilateral renal agenesis (January 2024)
Bilateral renal agenesis (BRA) is incompatible with extrauterine life because prolonged oligohydramnios results in pulmonary hypoplasia, leading to postnatal respiratory failure. A prospective study (RAFT) assessed use of serial amnioinfusions to treat 18 cases of BRA diagnosed at <26 weeks of gestation [18]. Of the 17 live births, 14 survived ≥14 days and had placement of dialysis access, but only 6 survived to hospital discharge. Of the 4 children alive at 9 to 24 months of age, 3 had experienced a stroke and none had undergone transplant. These findings show that serial amnioinfusions for BRA mitigates pulmonary hypoplasia and increases short-term survival and access to dialysis; however, long-term outcome remains poor with no survival to transplantation. Serial amnioinfusions remain investigational and should be offered only as institutional review board-approved research. (See "Renal agenesis: Prenatal diagnosis", section on 'Investigative role of therapeutic amnioinfusion'.)
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
