Glomerular Filtration Rate Progression Research Articles

Obstructive sleep apnea in chronic kidney disease patients undergoing hemodialysis. Prevalence, severity, and treatment. A narrative review

Background: Chronic kidney disease (CKD), also known as chronic renal insufficiency (CRI), can be defined by a glomerular filtration rate (GFR) less than 60mL/min/1.73m^2 associated with an albumin-to-creatinine ratio greater than 30mg of albumin per 1g of creatinine. CKD is a significant factor leading to a decline in the quality of life, increased morbidity, and a substantial reduction in life expectancy. Currently, it is estimated that there are 3.9 million patients worldwide on renal replacement therapy for CKD. Recent data indicates that in the United States of America (USA), more than 500,000 people suffer from renal failure or insufficiency. In Brazil, epidemiological data is incomplete and outdated. In 2016, there were 122,825 patients in Brazil on renal replacement therapy. Objectives: This literature review aims to assess the prevalence, severity, and therapeutic recommendations for obstructive sleep apnea (OSA) in patients with CKD undergoing hemodialysis. Methods: A literature review was conducted using PubMed, Web of Science, and SciELO databases with keywords including "Obstructive Sleep Apnea", "Chronic kidney disease", "End-stage renal disease", "sleep disorders", "hemodialysis", "CPAP", "Continuous positive airway pressure", and "Physiotherapy." Only studies published in the last twenty years and in the English language were included. Results: Despite scientific evidence demonstrating a high prevalence of OSA in CKD patients undergoing hemodialysis, there are still a lack of studies examining the effects of Continuous positive airway pressure (CPAP) therapy on the clinical outcomes of these patients. In the scientific literature, only three randomized clinical trials were found that investigated the impact of CPAP therapy on improving kidney function. Consequently, there is a critical need for clinical studies to assess the effects of CPAP therapy in CKD patients undergoing hemodialysis. It is also essential to highlight the role of physiotherapy in managing sleep disorders and aiding in the adaptation and monitoring of patients undergoing CPAP therapy. Conclusion: This literature review concluded that more randomized controlled studies are necessary to better define the optimal therapy for OSA in CKD patients, with the goal of preventing a decline in GFR progression, reducing morbidity and mortality, and enhancing overall quality of life.

Deletion of protein tyrosine phosphatase SHP-1 restores SUMOylation of podocin and reverses the progression of diabetic kidney disease

Both clinical and experimental data suggest that podocyte injury is involved in the onset and progression of diabetic kidney disease (DKD). Although the mechanisms underlying the development of podocyte loss are not completely understood, critical structural proteins such as podocin play a major role in podocyte survival and function. We have reported that the protein tyrosine phosphatase SHP-1 expression increased in podocytes of diabetic mice and glomeruli of patients with diabetes. However, the invivo contribution of SHP-1 in podocytes is unknown. Conditional podocyte-specific SHP-1-deficient mice (Podo-SHP-1-/-) were generated to evaluate the impact of SHP-1 deletion at four weeks of age (early) prior to the onset of diabetes and after 20 weeks (late) of diabetes (DM; Ins2+/C96Y) on kidney function (albuminuria and glomerular filtration rate) and kidney pathology. Ablation of the SHP-1 gene specifically in podocytes prevented and even reversed the elevated albumin/creatinine ratio, glomerular filtration rate progression, mesangial cell expansion, glomerular hypertrophy, glomerular basement membrane thickening and podocyte foot process effacement induced by diabetes. Moreover, podocyte-specific deletion of SHP-1 at an early and late stage prevented diabetes-induced expression of collagen IV, fibronectin, transforming growth factor-β, transforming protein RhoA, and serine/threonine kinase ROCK1, whereas it restored nephrin, podocin and cation channel TRPC6 expression. Mass spectrometry analysis revealed that SHP-1 reduced SUMO2 post-translational modification of podocin while podocyte-specific deletion of SHP-1 preserved slit diaphragm protein complexes in the diabetic context. Thus, our data uncovered a new role of SHP-1 in the regulation of cytoskeleton dynamics and slit diaphragm protein expression/stability, and its inhibition preserved podocyte function preventing DKD progression.

Modeling the impact of obesity on the lifetime risk of chronic kidney disease in the United States using updated estimates of GFR progression from the CRIC study.

Rationale & objectiveAs the prevalence of obesity continues to rise in the United States, it is important to understand its impact on the lifetime risk of chronic kidney disease (CKD).Study designThe CKD Health Policy Model was used to simulate the lifetime risk of CKD for those with and without obesity at baseline. Model structure was updated for glomerular filtration rate (GFR) decline to incorporate new longitudinal data from the Chronic Renal Insufficiency Cohort (CRIC) study.Setting and populationThe updated model was populated with a nationally representative cohort from National Health and Nutrition Examination Survey (NHANES).OutcomesLifetime risk of CKD, highest stage and any stage.Model, perspective, & timeframeSimulation model following up individuals from current age through death or age 90 years.ResultsLifetime risk of any CKD stage was 32.5% (95% CI 28.6%–36.3%) for persons with normal weight, 37.6% (95% CI 33.5%–41.7%) for persons who were overweight, and 41.0% (95% CI 36.7%–45.3%) for persons with obesity at baseline. The difference between persons with normal weight and persons with obesity at baseline was statistically significant (p<0.01). Lifetime risk of CKD stages 4 and 5 was higher for persons with obesity at baseline (Stage 4: 2.1%, 95% CI 0.9%–3.3%; stage 5: 0.6%, 95% CI 0.0%–1.1%), but the differences were not statistically significant (stage 4: p = 0.08; stage 5: p = 0.23).LimitationsDue to limited data, our simulation model estimates are based on assumptions about the causal pathways from obesity to CKD, diabetes, and hypertension.ConclusionsThe results of this study indicate that obesity may have a large impact on the lifetime risk of CKD. This is important information for policymakers seeking to set priorities and targets for CKD prevention and treatment.

Soluble Tumor Necrosis Factor Receptor 1 Is Associated with Glomerular Filtration Rate Progression and Incidence of Chronic Kidney Disease in Two Community-Based Cohorts of Elderly Individuals

Objective: We aimed to explore and validate the longitudinal associations between soluble tumor necrosis factor receptor 1 (sTNFR1), glomerular filtration rate (GFR) progression, and chronic kidney disease (CKD) incidence in two independent community-based cohorts of elderly individuals with prespecified subgroup analyses in individuals without prevalent diabetes. Research Design and Methods: Two community-based cohorts of elderly individuals were used with 5-year follow-up data on estimated GFR: the Uppsala Longitudinal Study of Adult Men (ULSAM; n = 437 men; mean age: 78 years) and the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; n = 703; mean age: 70 years; 51% women). GFR categories were defined as ≥60, 30-60, and <30 ml/min/1.73 m². Results: In longitudinal multivariable logistic regression models adjusted for inflammatory markers and established cardiovascular risk factors, higher serum sTNFR1 was significantly associated with an increased risk to progress to a lower GFR category in both ULSAM and PIVUS [odds ratio (OR) per standard deviation (SD) increase 1.28 (95% CI 1.03-1.60) and OR 1.56 (95% CI 1.30-1.87), respectively]. Also, in subgroup analyses in individuals with a GFR ≥60 ml/min/1.73 m² at baseline, higher sTNFRs were associated with incident CKD after 5 years in both cohorts [ULSAM: OR per SD increase 1.49 (95% CI 1.16-1.9) and PIVUS: OR 1.84 (95% CI 1.50-2.26)]. Associations were similar in individuals without diabetes. Conclusions: Higher circulating sTNFR1 independently predicts the progression to a worse GFR category and CKD incidence in elderly individuals even in the absence of diabetes. Further studies are warranted to investigate the underlying mechanisms, and to evaluate the clinical relevance of our findings.

Longitudinal Progression Trajectory of GFR Among Patients With CKD

The traditional paradigm of glomerular filtration rate (GFR) progression in patients with chronic kidney disease (CKD) is a steady nearly linear decline over time. We describe individual GFR progression trajectories over 12 years of follow-up in participants in the African American Study of Kidney Disease and Hypertension (AASK). Longitudinal observational study. 846 AASK patients with at least 3 years of follow-up and 8 GFR estimates. Longitudinal GFR estimates from creatinine-based equations. Patient demographic and clinical features. Probability of a nonlinear trajectory and probability of a period of nonprogression calculated for each patient from a Bayesian model of individual estimated GFR (eGFR) trajectories. 352 (41.6%) patients showed a > 0.9 probability of having either a nonlinear trajectory or a prolonged nonprogression period; in 559 (66.1%), the probability was > 0.5. Baseline eGFR > 40 mL/min/1.73 m2 and urine protein-creatinine ratio < 0.22 g/g were associated with a higher likelihood of a nonprogression period. 74 patients (8.7%) had both a substantial period of stable or increasing eGFR and a substantial period of rapid eGFR decrease. Clinical trial population; absence of direct GFR measurements. In contrast to the traditional paradigm of steady GFR progression over time, many patients with CKD have a nonlinear GFR trajectory or a prolonged period of nonprogression. These findings highlight the possibility that stable kidney disease progression can accelerate and, conversely, provide hope that CKD need not be relentlessly progressive. These results should encourage researchers to identify time-dependent factors associated with periods of nonprogression and other desirable trajectories.