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Advances in Kidney Disease and Health Nov 2023Low-protein diets (LPDs), usually defined as a daily dietary protein intake of 0.6 to 0.8 g/kg body weight, have been recommended for decades as a safe and effective... (Review)
Review
Low-protein diets (LPDs), usually defined as a daily dietary protein intake of 0.6 to 0.8 g/kg body weight, have been recommended for decades as a safe and effective lifestyle modification to ameliorate inflammatory damage and proteinuria, reduce glomerular hyperfiltration, and improve metabolic acidosis control in patients with chronic kidney disease (CKD). The mechanism for this is largely attributed to altered tubuloglomerular feedback and afferent arteriole contraction leading to decreased glomerular pressure. Additionally, low protein intake reduces urea generation, which can help delay dialysis initiation in advanced CKD. LPDs have different types including plant-dominant LPDs that can exert additional kidney protective effects as a result of dietary protein quality in addition to quantity. In addition, strong clinical evidence shows that a new class of diabetes mellitus medications, the sodium-glucose cotransporter 2 inhibitors, reduces albuminuria and slows the estimated glomerular filtration rate decline in CKD, even in patients without diabetes mellitus, especially if significant proteinuria is present. Given prior studies investigating the effect of LPDs used in conjunction with angiotensin pathway modulators, we argue that LPDs have a synergistic role in disease management and are expected to display additive effects when combined with sodium-glucose cotransporter 2 inhibitor usage or other pharmacologic agents. Even with medical therapy, it is prudent to implement tailored LPDs for different types of CKD.
Topics: Humans; Sodium-Glucose Transporter 2 Inhibitors; Diet, Protein-Restricted; Dietary Proteins; Renal Dialysis; Diabetes Mellitus; Renal Insufficiency, Chronic; Proteinuria; Glucose; Sodium
PubMed: 38453269
DOI: 10.1053/j.akdh.2023.12.005 -
Kidney International May 2024The circadian clock influences a wide range of biological process and controls numerous aspects of physiology to adapt to the daily environmental changes caused by...
The circadian clock influences a wide range of biological process and controls numerous aspects of physiology to adapt to the daily environmental changes caused by Earth's rotation. The kidney clock plays an important role in maintaining tubular function, but its effect on podocytes remains unclear. Here, we found that podocytes expressed CLOCK proteins, and that 2666 glomerular gene transcripts (13.4%), including autophagy related genes, had 24-hour circadian rhythms. Deletion of Clock in podocytes resulted in 1666 gene transcripts with the loss of circadian rhythm including autophagy genes. Podocyte-specific Clock knockout mice at age three and eight months showed deficient autophagy, loss of podocytes and increased albuminuria. Chromatin immunoprecipitation (ChIP) sequence analysis indicated autophagy related genes were targets of CLOCK in podocytes. ChIP-PCR further confirmed Clock binding to the promoter regions of Becn1 and Atg12, two autophagy related genes. Furthermore, the association of CLOCK regulated autophagy with chronic sleep fragmentation and diabetic kidney disease was analyzed. Chronic sleep fragmentation resulted in the loss of glomerular Clock rhythm, inhibition of podocyte autophagy, and proteinuria. Rhythmic oscillations of Clock also disappeared in high glucose treated podocytes and in glomeruli from diabetic mice. Finally, circadian differences in podocyte autophagy were also abolished in diabetic mice. Deletion Clock in podocytes aggravated podocyte injury and proteinuria in diabetic mice. Thus, our findings demonstrate that clock-dependent regulation of autophagy may be essential for podocyte survival. Hence. loss of circadian controlled autophagy may play an important role in podocyte injury and proteinuria.
Topics: Mice; Animals; Podocytes; Diabetes Mellitus, Experimental; Sleep Deprivation; Proteinuria; Diabetic Nephropathies; Mice, Knockout; Autophagy
PubMed: 38387504
DOI: 10.1016/j.kint.2024.01.035 -
Pediatric Nephrology (Berlin, Germany) Feb 2024Proteinuria remission is the most significant predictive factor for kidney outcome in childhood IgA nephropathy (c-IgAN). Even if proteinuria remission can be obtained,...
BACKGROUND
Proteinuria remission is the most significant predictive factor for kidney outcome in childhood IgA nephropathy (c-IgAN). Even if proteinuria remission can be obtained, some patients have recurrence of proteinuria in the long-term.
METHODS
This is a retrospective analysis of 312 cases of proteinuria remission among 538 consecutive children with biopsy-proven IgAN from 1976 to 2013. To elucidate the incidence and factors related to recurrence of proteinuria in c-IgAN, we compare clinical and pathological findings between patients with and without recurrence of proteinuria.
RESULTS
Among 312 patients with remission of proteinuria, 91 (29.2%) had recurrence of proteinuria within the observation period (median 8 years). Using a multivariate Cox regression analysis, significant factors associated with recurrence of proteinuria were onset age (HR 1.13 [95%CI: 1.05-1.22], P = 0.002) and presence of hematuria after proteinuria remission (HR 2.11 [95%CI: 1.30-3.45], P = 0.003). The Kaplan-Meier analysis showed significant differences in CKD G3a-G5-free survival between the patients with no-recurrence of proteinuria, recurrence of proteinuria and non-proteinuria remission (P < 0.0001, log-rank test). Kidney survival was 100% in no-recurrence of proteinuria, 92.2% in recurrence of proteinuria, and 65.6% in non-proteinuria remission at 15 years. Cox analyses adjusted by proteinuria remission showed that recurrence of proteinuria (HR 03.10e [95%CI: NA], P = 0.003) was a significant factor associated with progression to CKD G3a-G5 in all patients with c-IgAN.
CONCLUSIONS
Approximately 30% of patients with proteinuria remission had recurrence of proteinuria regardless of treatment. Both remission and recurrence of proteinuria are significant prognostic factors for kidney outcome. A higher resolution version of the Graphical abstract is available as Supplementary information.
Topics: Child; Humans; Glomerulonephritis, IGA; Retrospective Studies; Immunoglobulin A; Proteinuria; Kidney Failure, Chronic
PubMed: 37594578
DOI: 10.1007/s00467-023-06116-4 -
The Pediatric Infectious Disease Journal Mar 2024We aimed to determine the prevalence and severity of glomerular and tubular renal dysfunction by means of urinalysis in infants and toddlers with congenital...
BACKGROUND
We aimed to determine the prevalence and severity of glomerular and tubular renal dysfunction by means of urinalysis in infants and toddlers with congenital cytomegalovirus infection (cCMV) and their association with cCMV disease, viruria and antiviral treatment.
METHODS
This cross-sectional study was done using the Spanish Registry of Congenital Cytomegalovirus Infection. First-morning urine samples were collected from January 2016 to December 2018 from patients <5 years old enrolled in Spanish Registry of Congenital Cytomegalovirus Infection. Samples were excluded in case of fever or other signs or symptoms consistent with acute infection, bacteriuria or bacterial growth in urine culture. Urinary protein/creatinine and albumin/creatinine ratios, urinary beta-2-microglobulin levels, hematuria and CMV viruria were determined. A 0.4 cutoff in the urinary albumin/protein ratio was used to define tubular (<0.4) or glomerular (>0.4) proteinuria. Signs and symptoms of cCMV at birth, the use of antivirals and cCMV-associated sequelae at last available follow-up were obtained from Spanish Registry of Congenital Cytomegalovirus Infection.
RESULTS
Seventy-seven patients (37 females, 48.1%; median [interquartile range] age: 14.0 [4.4-36.2] months) were included. Symptom-free elevated urinary protein/creatinine and albumin/creatinine ratios were observed in 37.5% and 41.9% of patients, respectively, with tubular proteinuria prevailing (88.3%) over glomerular proteinuria (11.6%). Proteinuria in the nephrotic range was not observed in any patients. In multivariate analysis, female gender was the only risk factor for tubular proteinuria (adjusted odds ratio = 3.339, 95% confidence interval: 1.086-10.268; P = 0.035). cCMV disease at birth, long-term sequelae, viruria or the use of antivirals were not associated with urinalysis findings.
CONCLUSIONS
Mild nonsymptomatic tubular proteinuria affects approximately 40% of infants and toddlers with mostly symptomatic cCMV in the first 5 years of life.
Topics: Infant, Newborn; Infant; Humans; Female; Adolescent; Child, Preschool; Cross-Sectional Studies; Cytomegalovirus; Creatinine; Cytomegalovirus Infections; Proteinuria; Antiviral Agents; Kidney; Albumins
PubMed: 38063508
DOI: 10.1097/INF.0000000000004176 -
Kidney International Mar 2024Clinical studies suggest that non-alcoholic steatohepatitis (NASH) is an independent risk factor for chronic kidney disease (CKD), but causality and mechanisms linking...
Clinical studies suggest that non-alcoholic steatohepatitis (NASH) is an independent risk factor for chronic kidney disease (CKD), but causality and mechanisms linking these two major diseases are lacking. To assess whether NASH can induce CKD, we have characterized kidney function, histological features, transcriptomic and lipidomic profiles in a well-validated murine NASH model. Mice with NASH progressively developed significant podocyte foot process effacement, proteinuria, glomerulosclerosis, tubular epithelial cell injury, lipid accumulation, and interstitial fibrosis. The progression of kidney fibrosis paralleled the severity of the histologic NASH-activity score. Significantly, we confirmed the causal link between NASH and CKD by orthotopic liver transplantation, which attenuated proteinuria, kidney dysfunction, and fibrosis compared with control sham operated mice. Transcriptomic analysis of mouse kidney cortices revealed differentially expressed genes that were highly enriched in mitochondrial dysfunction, lipid metabolic process, and insulin signaling pathways in NASH-induced CKD. Lipidomic analysis of kidney cortices further revealed that phospholipids and sphingolipids were the most significantly changed lipid species. Notably, we found similar kidney histological changes in human NASH and CKD. Thus, our results confirm a causative role of NASH in the development of CKD, reveal potential pathophysiologic mechanisms of NASH-induced kidney injury, and established a valuable model to study the pathogenesis of NASH-associated CKD. This is an important feature of fatty liver disease that has been largely overlooked but has clinical and prognostic importance.
Topics: Humans; Animals; Mice; Non-alcoholic Fatty Liver Disease; Disease Models, Animal; Fibrosis; Renal Insufficiency, Chronic; Phospholipids; Proteinuria; Liver
PubMed: 38159678
DOI: 10.1016/j.kint.2023.12.009 -
BMC Pregnancy and Childbirth Nov 2023Although the majority of pregnancies with preeclampsia are characterised by elevated blood pressure, preeclampsia is often associated with nephrotic syndrome with...
BACKGROUND
Although the majority of pregnancies with preeclampsia are characterised by elevated blood pressure, preeclampsia is often associated with nephrotic syndrome with similar symptoms such as high proteinuria and bilateral lower limb oedema. In this study, we compared the maternal-foetal outcomes of pregnant women with preeclampsia in a population with nephrotic syndrome and explored the factors that contribute to the corresponding outcomes and disease development.
METHODS
A total of 90 pregnant women were included in this study, of whom 30 had nephrotic syndrome and were diagnosed with preeclampsia during pregnancy, and 60 had nephrotic syndrome alone. Descriptive statistical analyses of baseline data were performed to analyse the effect of combined preeclampsia on maternal and foetal pregnancy outcomes using unadjusted and adjusted logistic regression models.
RESULTS
In this study, the baseline data of the two study populations demonstrated no differences except for the history of caesarean section and 24-h proteinuria results, which were significantly different (P < 0.05). The risk of preterm birth in the nephrotic syndrome with preeclampsia group was 8.25 (95% CI:3.041-22.084 P < 0.05); for a low birth weight, the risk was 6.00 (95% CI:2.302-15.638 P < 0.05); for foetal distress,the risk was 5.667 (95% CI:2.070-15.514 P < 0.05); and the risk of foetal birth restriction was 7.429 (95% CI: 2.642-20.885 P < 0.05). A risk-based analysis of adverse maternal outcomes yielded a risk of miscarriage of 2.200 (95% CI: 0.584-8.291; P > 0.05). After adjusting the model for each outcome, significant risks of preterm labour, foetal birth restriction, and low birth weight were revealed (P < 0.05).
CONCLUSION
Combined preeclampsia has a significantly higher risk of adverse pregnancy outcomes for the foetus.Therefore, the prevention and control of eclampsia in pregnant women should be improved to ensure maternal and neonatal health.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Pre-Eclampsia; Premature Birth; Nephrotic Syndrome; Cesarean Section; Pregnancy Outcome; Proteinuria
PubMed: 37936071
DOI: 10.1186/s12884-023-06073-8 -
Pediatric Nephrology (Berlin, Germany) Jun 2024IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide. While studies have primarily focused on identifying risk factors for disease progression, very...
BACKGROUND
IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide. While studies have primarily focused on identifying risk factors for disease progression, very few data exist on the likelihood of achieving complete recovery from the disease.
METHODS
We conducted a single-center retrospective study on all consecutive patients with biopsy-proven IgAN diagnosed between 1986 and 2018 in our pediatric center. Biopsies were classified according to the MEST-C Oxford classification score. "Complete clinical remission" was defined as the absence of proteinuria, hematuria, and hypertension in patients with normal kidney function who had been off therapy for more than 2 years.
RESULTS
Overall, 153 patients with age at onset of 10.6 ± 4 years were enrolled in the study. Of these, 41 achieved "complete clinical remission." The estimated probability of complete clinical remission at 10 years was 43% (95%CI 33-54). However, seven patients relapsed within 10 years. Multivariable analysis showed that higher age at onset (HR 0.89, 95%CI 0.80-0.98, p = 0.017) and segmental glomerulosclerosis lesions (HR 0.28, 95%CI 0.10-0.79, p = 0.017) decreased significantly the chances of achieving complete clinical remission. Immunosuppressive therapy was not significantly associated with clinical outcomes.
CONCLUSIONS
Approximately one-third of patients with pediatric-onset IgAN achieve prolonged remission, in particular, very young children at disease onset without sclerotic glomerular lesions. Longer term follow-up is needed to assess if these patients have achieved permanent remission.
Topics: Humans; Child; Child, Preschool; Adolescent; Glomerulonephritis, IGA; Retrospective Studies; Glomerular Filtration Rate; Kidney Glomerulus; Glomerulosclerosis, Focal Segmental; Proteinuria; Kidney
PubMed: 38225439
DOI: 10.1007/s00467-023-06259-4 -
BMC Nephrology Dec 2023Focal segmental glomerulosclerosis (FSGS) is one of the leading causes of nephrotic syndrome in adults. This epidemiological study describes a renal centre's 20-year... (Observational Study)
Observational Study
INTRODUCTION
Focal segmental glomerulosclerosis (FSGS) is one of the leading causes of nephrotic syndrome in adults. This epidemiological study describes a renal centre's 20-year experience of primary FSGS.
METHODS
Patients were identified with a diagnosis of primary FSGS after exclusion of known secondary causes. In this retrospective observational study, data was collected for baseline demographics, immunosuppression and outcomes. A two-step cluster analysis was used to identify natural groupings within the dataset.
RESULTS
The total cohort was made up of 87 patients. Those who received immunosuppression had lower median serum albumin than those who did not- 23g/L vs 40g/L (p<0.001) and higher median urine protein creatinine ratios (uPCR)- 795mg/mmol vs 318mg/mmol (p <0.001). They were more likely to achieve complete remission (62% vs 40%, p=0.041), but relapsed more 48.6% vs 22% (p=0.027). Overall 5 year mortality was 10.3% and 5 year progression to RRT was seen in 17.2%. Complete remission was observed in 49.4%. The 2-step cluster analysis separated the cohort into 3 clusters: cluster 1 (n=26) with 'nephrotic-range proteinuria'; cluster 2 (n=43) with 'non-nephrotic-range proteinuria'; and cluster 3 (n=18) with nephrotic syndrome. Immunosuppression use was comparable in clusters 1 and 3, but lower in cluster 2 (77.8% and 69.2% vs 11.6%, p<0.001). Rates of complete remission were greatest in clusters 1 and 3 vs cluster 2: 57.7% and 66.7% vs 37.2%.
CONCLUSION
People who received immunosuppression had lower serum albumin and achieved remission more frequently, but were also prone to relapse. Our cluster analysis highlighted 3 FSGS phenotypes: a nephrotic cluster that clearly require immunosuppression; a cohort with preserved serum albumin and non-nephrotic range proteinuria who will benefit from supportive care; and lastly a cluster with heavy proteinuria but serum albumin > 30g/L. This group may still have immune mediated disease and thus could potentially benefit from immunosuppression.
TRIAL REGISTRATION
This study protocol was reviewed and approved by the 'Research and Innovation committee of the Northern Care Alliance NHS Group', study approval number (Ref: ID 22HIP54).
Topics: Adult; Humans; Nephrotic Syndrome; Glomerulosclerosis, Focal Segmental; Neoplasm Recurrence, Local; Proteinuria; Retrospective Studies; Serum Albumin
PubMed: 38072955
DOI: 10.1186/s12882-023-03405-w -
Endocrinology, Diabetes & Metabolism Nov 2023Low serum Vitamin D levels have been associated with diabetic nephropathy (DN). Our study aimed to analyse the serum levels of vitamin D in patients suffering from DN... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIM
Low serum Vitamin D levels have been associated with diabetic nephropathy (DN). Our study aimed to analyse the serum levels of vitamin D in patients suffering from DN and the subsequent changes in serum vitamin D levels as the disease progresses.
METHODS
PubMed, Embase, SCOPUS and Web of Science were searched using keywords such as '25 hydroxyvitamin D' and 'diabetic nephropathy'. We included observational studies that reported the association between the serum 25 hydroxy vitamin D levels and diabetic nephropathy without restriction to age, gender, and location. R Version 4.1.2 was used to perform the meta-analysis. The continuous outcomes were represented as mean difference (MD) and standard deviation (SD) and dichotomous outcomes as risk ratios (RR) with their 95% confidence interval (CI).
RESULTS
Twenty-three studies were included in our analysis with 7722 patients. Our analysis revealed that vitamin D was significantly lower in diabetic patients with nephropathy than those without nephropathy (MD: -4.32, 95% CI: 7.91-0.74, p-value = .0228). On comparing diabetic patients suffering from normoalbuminuria, microalbuminuria, or macroalbuminuria, we found a significant difference in serum vitamin D levels across different groups. Normoalbuminuria versus microalbuminuria showed a MD of -1.69 (95% CI: -2.28 to -1.10, p-value = .0002), while microalbuminuria versus macroalbuminuria showed a MD of (3.75, 95% CI: 1.43-6.06, p-value = .0058), proving that serum vitamin D levels keep declining as the disease progresses. Notwithstanding, we detected an insignificant association between Grade 4 and Grade 5 DN (MD: 2.29, 95% CI: -2.69-7.28, p-value = .1862).
CONCLUSION
Serum Vitamin D levels are lower among DN patients and keep declining as the disease progresses, suggesting its potential benefit as a prognostic marker. However, on reaching the macroalbuminuria stage (Grades 4 and 5), vitamin D is no longer a discriminating factor.
Topics: Humans; Diabetic Nephropathies; Vitamin D; Albuminuria; Diabetes Mellitus
PubMed: 37743677
DOI: 10.1002/edm2.453 -
Arthritis & Rheumatology (Hoboken, N.J.) Jul 2024We describe the demographics, clinical features, disease course, and survival of polyarteritis nodosa (PAN) through an international collaboration (GLOBAL-PAN). (Observational Study)
Observational Study
OBJECTIVE
We describe the demographics, clinical features, disease course, and survival of polyarteritis nodosa (PAN) through an international collaboration (GLOBAL-PAN).
METHODS
Patients with PAN were recruited between 1990 and 2020 from observational cohorts of nine countries across Europe, Japan, and North America. Eligibility was retrospectively defined using the European Medicines Agency classification algorithm. Patients with PAN related to hepatitis B virus (n = 12) and two monogenic diseases mimicking PAN, deficiency of adenosine deaminase 2 enzyme (n = 16) or familial Mediterranean fever (n = 11), were excluded. Data regarding organ involvement, relapse, disease-related damage, and survival were analyzed.
RESULTS
Three hundred fifty-eight patients (female:male ratio 174:184), including those with systemic PAN (sPAN, n = 282) and cutaneous PAN (n = 76), were included. Twenty-five were pediatric onset. Mean ± SD age at diagnosis was 44.3 ± 18.1 years. Constitutional symptoms (71.5%), cutaneous involvement (70.5%), musculoskeletal findings (69.1%), and neurologic features (48.0%) were common manifestations. Among patients with sPAN, gastrointestinal involvement and proteinuria over 400 mg/day were reported in 52.2% and 11.2%, respectively. During a median (interquartile range) 59.6 (99.5) months of follow-up, relapse occurred in 48.5% of patients. One, 5- and 10-year survival rates for sPAN were 97.1%, 94.0%, and 89.0%, respectively. Predictors of death for sPAN included age ≥65 years at diagnosis, serum creatinine at diagnosis >140 μmol/L, gastrointestinal manifestations, and central nervous system (CNS) involvement.
CONCLUSION
The spectrum of PAN remains a complex, multifaceted disease. Relapse is common. Age ≥65 years and serum creatinine >140 μmol/L at diagnosis, as well as gastrointestinal and CNS involvement, are independent predictors of death in sPAN.
Topics: Humans; Polyarteritis Nodosa; Male; Female; Adult; Middle Aged; Retrospective Studies; Europe; Aged; North America; Japan; Young Adult; Proteinuria; Recurrence; Survival Rate
PubMed: 38343337
DOI: 10.1002/art.42817