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Current Opinion in Nephrology and... Nov 2023Despite a strong consensus that treatment of hypertension is fundamental to strategies seeking to slow chronic kidney disease (CKD) progression and reduce the associated... (Review)
Review
PURPOSE OF REVIEW
Despite a strong consensus that treatment of hypertension is fundamental to strategies seeking to slow chronic kidney disease (CKD) progression and reduce the associated risk of cardiovascular events (CVE), controversy persists regarding optimal blood pressure (BP) targets. This article reviews the evidence for different targets, discusses associated controversies and suggests approaches to improve BP control.
RECENT FINDINGS
Landmark clinical trials established the principle that lower BP targets are associated with slower progression of CKD in people with a greater magnitude of proteinuria and previous guidelines recommended a target BP of <130/80 mmHg for those with proteinuria. However, the Systolic Blood Pressure Intervention Trial provided new evidence that a systolic BP target of <120 mmHg was associated with a reduced risk of CVE, though there was no impact on CKD progression and there was concern about an increase in renal adverse events. Nevertheless, 2021 Kidney Disease Improving Global Outcomes guidelines recommended systolic BP <120 mmHg, though other updated guidelines did not follow this trend. All guidelines emphasise the importance of standardised BP measurement and a personalised approach.
SUMMARY
An individualised and shared decision-making approach to BP target setting and management is recommended, guided by standardised BP measurement.
Topics: Humans; Blood Pressure; Consensus; Hypertension; Renal Insufficiency, Chronic; Proteinuria; Antihypertensive Agents
PubMed: 37753643
DOI: 10.1097/MNH.0000000000000920 -
Trials Mar 2024Proteinuria is a modifiable risk factor for chronic kidney disease (CKD) progression in children. Finerenone, a selective, non-steroidal, mineralocorticoid receptor... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Proteinuria is a modifiable risk factor for chronic kidney disease (CKD) progression in children. Finerenone, a selective, non-steroidal, mineralocorticoid receptor antagonist (MRA) has been approved to treat adults with CKD associated with type 2 diabetes mellitus (T2DM) following results from the phase III clinical trials FIDELIO-DKD (NCT02540993) and FIGARO-DKD (NCT02545049). In a pre-specified pooled analysis of both studies (N = 13,026), finerenone was shown to have an acceptable safety profile and was efficacious in decreasing the risk of adverse kidney and cardiovascular outcomes and of proteinuria.
OBJECTIVE
FIONA and the associated open-label extension (OLE) study aim to demonstrate that combining finerenone with an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) is safe, well-tolerated, and effective in sustainably reducing urinary protein excretion in children with CKD and proteinuria.
DESIGN
FIONA (NCT05196035; Eudra-CT: 2021-002071-19) is a randomized (2:1), double-blind, placebo-controlled, multicenter, phase III study of 6 months' duration in approximately 219 pediatric patients. Patients must have a clinical diagnosis of CKD (an eGFR ≥ 30 mL/min/1.73 m if ≥ 1 to < 18 years or a serum creatinine level ≤ 0.40 mg/dL for infants 6 months to < 1 year) with significant proteinuria despite ACEi or ARB usage. The primary objective is to demonstrate that finerenone, added to an ACEi or ARB, is superior to placebo in reducing urinary protein excretion. FIONA OLE (NCT05457283; Eudra-CT: 2021-002905-89) is a single-arm, open-label study, enrolling participants who have completed FIONA. The primary objective of FIONA OLE is to provide long-term safety data. FIONA has two primary endpoints: urinary protein-to-creatinine ratio (UPCR) reduction of ≥ 30% from baseline to day 180 and percent change in UPCR from baseline to day 180. A sample size of 198 participants (aged 2 to < 18 years) in FIONA will provide at least 80% power to reject the null hypothesis of either of the two primary endpoints.
CONCLUSION
FIONA is evaluating the use of finerenone in children with CKD and proteinuria. Should safety, tolerability, and efficacy be demonstrated, finerenone could become a useful additional therapeutic agent in managing proteinuria and improving kidney outcomes in children with CKD.
TRIAL REGISTRATION
ClinicalTrials.gov NCT05196035. Registered on 19 January 2022.
Topics: Adult; Humans; Child; Diabetes Mellitus, Type 2; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Renal Insufficiency, Chronic; Proteinuria; Mineralocorticoid Receptor Antagonists; Diabetic Nephropathies; Naphthyridines
PubMed: 38509517
DOI: 10.1186/s13063-024-08021-z -
Orphanet Journal of Rare Diseases Sep 2023Imerslund-Gräsbeck syndrome (IGS) is a rare autosomal recessive disorder characterized by vitamin B12 malabsorption. Most patients present with non-specific symptoms... (Review)
Review
Imerslund-Gräsbeck syndrome (IGS) is a rare autosomal recessive disorder characterized by vitamin B12 malabsorption. Most patients present with non-specific symptoms attributed to vitamin B12 deficiency, and proteinuria. Patients may if untreated, develop severe neurocognitive manifestations. If recognized and treated with sufficient doses of vitamin B12, patients recover completely. We provide, for the first time, an overview of all previously reported cases of IGS. In addition, we provide a complete review of IGS and describe two new patients.
Topics: Humans; Vitamin B 12 Deficiency; Anemia, Megaloblastic; Proteinuria; Vitamin B 12
PubMed: 37710296
DOI: 10.1186/s13023-023-02889-x -
Journal of Diabetes and Its... Aug 2023In diabetic kidney disease (DKD) patients, early-onset T2DM effects on renal disease severity and outcomes remain uncertain. Herein, we aim to investigate the...
AIMS
In diabetic kidney disease (DKD) patients, early-onset T2DM effects on renal disease severity and outcomes remain uncertain. Herein, we aim to investigate the clinicopathological characteristics and renal outcomes in DKD patients with early-onset T2DM.
METHODS
489 patients with T2DM and DKD were retrospectively recruited and classified as having early (age at onset of T2DM < 40 years) and late (age at onset of T2DM ≥ 40 years) T2DM onset, analyzing the clinical and histopathological data. The predictive value of early-onset T2DM to renal outcomes in DKD patients was analyzed by Cox's regression.
RESULTS
Among 489 DKD patients, 142 and 347 were classified as early and late T2DM onset, respectively. Early-onset T2DM patients exhibited worse glycaemic control (7.36 % ± 1.80 % vs. 6.86 % ± 1.57 %, P = 0.007) and more severe proteinuria (3.69 [1.55 to 7.03] vs. 1.81 [0.50 to 4.33] g/24 h, P < 0.001). Those with early-onset T2DM presented more severe glomerular lesions. In univariable Cox regression, early-onset T2DM showed a significant correlation with renal composite endpoint (HR [95%CI]: 0.56 [0.43 to 0.73], P < 0.001). However, after adjusting for potential confounders, early-onset T2DM was not independently correlated with renal composite endpoint (HR [95%CI]: 0.74 [0.46 to 1.21], P = 0.232).
CONCLUSIONS
In DKD patients with early-onset T2DM, renal clinicopathological manifestations were severe. Age at onset in T2DM was significantly correlated with eGFR slope (r = 0.211, P < 0.001).
Topics: Humans; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Kidney; Proteinuria; Retrospective Studies; Adult; Middle Aged
PubMed: 37311359
DOI: 10.1016/j.jdiacomp.2023.108520 -
Current Opinion in Nephrology and... Mar 2024Kidney function declines with normal aging. But it also declines with the progression of some diseases. This review calls for a more nuanced interpretation of kidney... (Review)
Review
PURPOSE OF REVIEW
Kidney function declines with normal aging. But it also declines with the progression of some diseases. This review calls for a more nuanced interpretation of kidney function in the geriatric population, who may have frailty and comorbidities.
RECENT FINDINGS
GFR declines with healthy aging kidneys. Aging kidney changes include decreased cortical volume, senescent global glomerulosclerosis, and reduced nephron numbers. Yet normal aging is not associated with increased glomerular volume or single-nephron GFR. The prevalence of GFR less than 60 ml/min/1.73 m 2 in the geriatric population is high. However, the decline in GFR with normal aging may not reflect true CKD without albuminuria. Although the risk of ESKD and mortality increases in all age groups when eGFR less than 45 ml/min/m 2 , there is no significant increased relative risk of ESKD and mortality in the geriatric population when eGFR 45-59 ml/min/m 2 in the absence of albuminuria. Innovative approaches are needed to better estimate GFR and define CKD in the geriatric population.
SUMMARY
The expected GFR decline in the geriatric population is consistent with normal aging kidney changes. To avoid CKD overdiagnosis and unnecessary referrals to nephrology for possible CKD, age-adapted definitions of CKD in the absence of albuminuria are needed.
Topics: Aged; Humans; Albuminuria; Kidney; Aging; Glomerular Filtration Rate; Renal Insufficiency, Chronic
PubMed: 37965904
DOI: 10.1097/MNH.0000000000000955 -
Nephrology, Dialysis, Transplantation :... Dec 2023De novo donor-specific antibodies (dnDSAs) may cause antibody-mediated rejection and graft dysfunction. Little is known about the clinical course after first detection...
BACKGROUND
De novo donor-specific antibodies (dnDSAs) may cause antibody-mediated rejection and graft dysfunction. Little is known about the clinical course after first detection of dnDSAs during screening in asymptomatic patients. We aimed to assess the value of estimated glomerular filtration rate (eGFR) and proteinuria to predict graft failure in patients with dnDSAs and their potential utility as surrogate endpoints.
METHODS
All 400 kidney transplant recipients with dnDSAs at our centre (1 March 2000-31 May 2021) were included in this retrospective study. The dates of graft loss, rejection, doubling of creatinine, ≥30% eGFR decline, proteinuria ≥500 mg/g and ≥1000 mg/g were registered from the first dnDSA appearance.
RESULTS
During 8.3 years of follow-up, graft failure occurred in 33.3% of patients. Baseline eGFR and proteinuria correlated with 5-year graft loss (area under the receiver operating characteristics curve 0.75 and 0.80, P < .001). Creatinine doubled after a median of 2.8 years [interquartile range (IQR) 1.5-5.0] from dnDSA and the time from doubling creatinine to graft failure was 1.0 year (IQR 0.4-2.9). Analysing eGFR reduction ≥30% as a surrogate endpoint (148/400), the time from dnDSA to this event was 2.0 years (IQR 0.6-4.2), with a positive predictive value (PPV) of 45.9% to predict graft loss, which occurred after 2.0 years (IQR 0.8-3.2). The median time from proteinuria ≥500 mg/g and ≥1000 mg/g to graft failure was identical, 1.8 years, with a PPV of 43.8% and 49.0%, respectively. Composite endpoints did not improve PPV. Multivariable analysis showed that rejection was the most important independent risk factor for all renal endpoints and graft loss.
CONCLUSIONS
Renal function, proteinuria and rejection are strongly associated with graft failure in patients with dnDSA and may serve as surrogate endpoints.
Topics: Humans; Retrospective Studies; Kidney Transplantation; Isoantibodies; Creatinine; Graft Rejection; Graft Survival; Biomarkers; Proteinuria; Tissue Donors; HLA Antigens; Transplant Recipients
PubMed: 37410616
DOI: 10.1093/ndt/gfad149 -
Clinical and Experimental Nephrology Mar 2024The association between proteinuria, which is also an indicator of chronic kidney disease (CKD), and coronavirus disease 2019 (COVID-19) severity is unclear.
BACKGROUND
The association between proteinuria, which is also an indicator of chronic kidney disease (CKD), and coronavirus disease 2019 (COVID-19) severity is unclear.
METHODS
We selected 342 hospitalized patients with COVID-19 diagnosed via polymerase chain reaction testing between February 2020 and October 2022 and who had at least one urinalysis 14-365 days before admission.
RESULTS
Proteinuria before admission was associated neither with oxygen administration nor developing pneumonia in multivariate analysis (odds ratio [OR] 1.03; 95% confidence interval (CI) 0.44-2.40, p = 0.95 and OR 1.01; 95% CI 0.47-2.17, p = 0.98, respectively). Proteinuria on admission was associated both with oxygen administration and developing pneumonia in multivariate analysis (OR 3.29; 95% CI 1.37-7.88, p < 0.01 and OR 3.81; 95% CI 1.68-8.62, p < 0.01, respectively). The percentage of patients with proteinuria on admission was significantly higher than those before admission (37.4% vs. 17.8%; p < 0.01). In the subgroup analysis, proteinuria on admission among patients with eGFR ≥ 60 mL/min/1.73 m was associated with both oxygen administration and developing pneumonia (OR 4.86; 95% CI 1.22-19.38, p = 0.03, OR 3.65; 95% CI 1.06-12.58, p = 0.04, respectively). In contrast, proteinuria on admission among patients with eGFR < 60 mL/min/1.73 m was associated with developing pneumonia (OR 6.45; 95%CI 1.78-23.35, p = 0.01), not with oxygen administration (OR 3.28; 95% CI 0.92-11.72, p = 0.07).
CONCLUSIONS
Although underlying proteinuria before admission was not associated with COVID-19 severity, proteinuria on admission was associated with oxygen demand and developing pneumonia.
Topics: Humans; COVID-19; Proteinuria; Pneumonia; Renal Insufficiency, Chronic; Oxygen; Risk Factors
PubMed: 37962747
DOI: 10.1007/s10157-023-02428-9 -
Clinical Journal of the American... Mar 2024In a phase 3 study of adults with active lupus nephritis, addition of voclosporin to mycophenolate mofetil (MMF) and low-dose glucocorticoids led to significant... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
In a phase 3 study of adults with active lupus nephritis, addition of voclosporin to mycophenolate mofetil (MMF) and low-dose glucocorticoids led to significant improvements in the proportion of participants achieving complete and partial renal response as well as sustained reduction in proteinuria. This analysis examined the efficacy and safety of voclosporin in a subgroup of the phase 3 study with proliferative lupus nephritis and high levels of proteinuria.
METHODS
Participants were randomized to oral voclosporin (23.7 mg twice daily) or placebo for 12 months; all participants received MMF and low-dose glucocorticoids. This analysis includes participants with class III or IV (±class V) lupus nephritis and baseline urine protein-creatinine ratio (UPCR) ≥3 g/g. Efficacy end points included complete renal response (UPCR ≤0.5 g/g with stable eGFR, low-dose glucocorticoids, and no rescue medication), partial renal response (≥50% reduction from baseline UPCR), and UPCR over time. Safety outcomes were also assessed.
RESULTS
A total of 148 participants were in the voclosporin ( n =76) and control ( n =72) arms. At 12 months, 34% and 11% of participants in the voclosporin and control arms, respectively, achieved a complete renal response (odds ratio, 4.43; 95% confidence interval [CI], 1.78 to >9.99; P = 0.001). A partial renal response was achieved by 65% of the voclosporin arm and 51% of the control arm at 12 months (odds ratio, 1.60; 95% CI, 0.8 to 3.20; P = 0.18). More voclosporin- than control-treated participants achieved UPCR ≤0.5 g/g (51% versus 26%), and voclosporin-treated participants met this end point significantly earlier (hazard ratio, 2.07; 95% CI, 1.19 to 3.60; P = 0.01). The incidence of adverse events was similar between the arms; mean eGFR values remained stable and within normal range in both arms.
CONCLUSIONS
Addition of voclosporin to MMF and low-dose glucocorticoids resulted in a significantly higher proportion of participants with proliferative lupus nephritis achieving complete and partial renal responses as well as earlier reductions in proteinuria, with no evidence of worsening kidney function.
Topics: Adult; Humans; Lupus Nephritis; Immunosuppressive Agents; Cyclosporine; Mycophenolic Acid; Proteinuria; Glucocorticoids; Treatment Outcome
PubMed: 38110196
DOI: 10.2215/CJN.0000000000000297 -
Journal of Obstetrics and Gynaecology :... Dec 2023Proteinuria during pregnancy is closely related to the occurrence of adverse pregnancy outcomes. One hundred and forty-two women with proteinuria during pregnancy and...
Proteinuria during pregnancy is closely related to the occurrence of adverse pregnancy outcomes. One hundred and forty-two women with proteinuria during pregnancy and followed between January 2018 and December 2020 were evaluated. Based on the 24-h proteinuria value, they were divided as mild ( = 76, 300-1000 mg/day), moderate ( = 39, 1000-3500 mg/day) and severe ( = 27, >3500 mg/day) proteinuria. The rates of prematurity, low birth weight and neonatal asphyxia were significantly higher in the severe proteinuria group than in the mild and moderate groups, while the rates of foetal growth restriction and neonatal intensive care unit admission were significantly higher in the severe compared with the mild proteinuria group (all < .05). Logistic regression analysis showed that moderate proteinuria (OR = 97.2, 95%CI: 7.1-1334.2, = .001) and severe proteinuria (OR = 34.0, 95%CI: 1.6-711.0, = .023) were associated with adverse perinatal outcomes. Compared with mild proteinuria, moderate and severe proteinuria are associated with adverse pregnancy outcomes in perinatal infants.Impact Statement The production of proteinuria is closely related to the filtration function of the glomerulus, the reabsorption and secretion function of the renal tubules. For women with normal renal function before pregnancy, such physiological changes are less likely to cause adverse symptoms; however, for women with chronic kidney disease before pregnancy, especially those with significantly impaired renal function, the kidneys often cannot compensate for these physiological changes, which can lead to serious complications for both mother and infant. In our study, logistic regression analysis showed that the severity of proteinuria was independently associated with adverse perinatal outcomes. The ROC curve showed that 24-h proteinuria had a predictive value for adverse perinatal outcomes. Therefore, for patients with urine protein quantification ≥0.3 g/24 h, regular 24-h urine protein quantification during pregnancy could help predict adverse perinatal outcomes and improve prognosis. Proteinuria quantification can be used as one of the factors predicting adverse pregnancy outcomes. Thus, monitoring of urinary protein quantification in women during pregnancy should be strengthened for early detection of renal impairment, then interventions be used to improve maternal and infant outcomes.
Topics: Pregnancy; Infant, Newborn; Infant; Female; Humans; Pre-Eclampsia; Retrospective Studies; Pregnancy Outcome; Infant, Premature; Proteinuria
PubMed: 36178502
DOI: 10.1080/01443615.2022.2126299 -
Kidney International Aug 2023
Topics: Humans; Glomerulosclerosis, Focal Segmental; Apolipoprotein L1; Proteinuria; Kidney; Nephrotic Syndrome
PubMed: 37224918
DOI: 10.1016/j.kint.2023.04.022