Glomerular Hyperfiltration Research Articles

Molecular Insight into Obesity-Associated Nephropathy: Clinical Implications and Possible Strategies for its Management.

Obesity is a significant health concern due to its rapid increase worldwide. It has been linked to the pathogenic factors of renal diseases, cancer, cardiovascular diseases, hypertension, dyslipidemia, and type 2 diabetes. Notably, obesity raises the likelihood of developing chronic kidney disease (CKD), leading to higher adult mortality and morbidity rates. This study explores the molecular mechanisms that underlie obesity-associated nephropathy and its clinical implications. Obesity-Associated Nephropathy (OAN) develops and worsens due to insulin resistance and hyperinsulinemia, which promote renal sodium reabsorption, glomerular hyperfiltration, and hypertension, leading to progressive kidney damage. Renal damage is further aggravated by persistent inflammation and redox damage, mediated by adipokines and proinflammatory cytokines, such as TNF-α and IL-6. Furthermore, stimulation of the sympathetic nervous system and the renin-angiotensin- aldosterone system (RAAS) intensifies glomerular hypertension and fibrosis. These elements cause glomerular hyperfiltration, renal hypertrophy, and progressive kidney damage. Clinical manifestations of obesity-associated nephropathy include proteinuria, reduced glomerular filtration rate (GFR), and ultimately, CKD. Management strategies currently focus on lifestyle modifications, such as weight loss through diet and exercise, which have been effective in reducing proteinuria and improving GFR. Pharmacological treatments targeting metabolic pathways, including GLP-1 receptor agonists and SGLT2 inhibitors, have shown renoprotective properties. Additionally, traditional RAAS inhibitors offer therapeutic benefits. Early detection and comprehensive management of OAN are essential to prevent its progression and lessen the burden of CKD.

SGLT2i and GLP1-RA exert additive cardiorenal protection with a RAS blocker in uninephrectomized db/db mice.

Diabetic Kidney Disease (DKD) is the main cause of end-stage renal disease in the developed world. The current treatment of the DKD with renin-angiotensin system (RAS) blockade does not totally halt the progression to end stage kidney disease. Currently, several drugs have shown to delay DKD progression such as sodium-glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like-1 receptor agonists (GLP-1RA). We hypothesized that by combining several drugs that prevent DKD progression on top of RAS blockade a synergistic effect would be achieved in terms of cardiorenal protection. In the present study, we analysed if the combination of a RAS blocker (ramipril) with a SGLT2i (empagliflozin) and/or GLP-1RA (semaglutide) in a type 2 diabetic mouse model could have add-on effects in kidney and heart protection. Male and female uninephrectomized type 2 diabetic db/db mice were treated with empagliflozin and/or semaglutide on top of ramipril during 8weeks. During the study body weight, water and food intake were weekly monitored, glycaemia biweekly and albuminuria and glomerular filtration rate (GFR) before and after the treatment. At the end of the experiment, kidney and heart were isolated for histological and gene expression studies as well as for intrarenal RAS state assessment. Semaglutide combined with ramipril and/or empagliflozin significantly decreased albuminuria but only when combined with both compounds, semaglutide further decreased blood glucose, glomerular hyperfiltration in male mice and glomerular mesangial matrix expansion. In kidney, only the triple treatment with empagliflozin, semaglutide and ramipril reduced the expression of the proinflammatory and profibrotic genes ccl2 and TGFß1. In addition, the combination of empagliflozin and semaglutide on top of RAS blockade was superior in decreasing cardiomyocyte hypertrophy and heart fibrosis in db/db mice. Our results suggest that the combination of SGLT2i with GLP-1RA is superior in cardiorenal protection in DKD than the drugs administered alone on top of RAS blockade.

Peripheral dopamine suppression and elevated cystatin C in early diabetic nephropathy in spontaneously diabetic rats.

Intrarenal dopamine plays a protective role against the development of diabetic nephropathy during the early stages of the disease. In streptozotocin-induced diabetic mice with renal-specific catechol-O-methyl transferase knockout, intrarenal dopamine was found to suppress glomerular hyperfiltration, reduce oxidative stress and inflammation, and inhibit fibrosis. However, although dopamine activation in streptozotocin-induced diabetic models has been shown to provide renal protection, the role of dopamine in models of naturally induced diabetes mellitus is still unclear. In the present study, we orally administered 10 mg/kg benserazide, a peripheral decarboxylase inhibitor, to spontaneously diabetic Torii rats daily to investigate the activation of the renal dopaminergic system during the progression of diabetic nephropathy. Our findings show that peripheral dopamine decreased urinary 8-iso-prostaglandin F2α and suppressed increases in plasma cystatin C levels. This study demonstrates that a reduction in peripheral dopamine can exacerbate renal dysfunction, even in the early stages of diabetic nephropathy characterized by glomerular hyperfiltration, thereby clarifying the pivotal role of endogenous peripheral dopamine in modulating oxidative stress and kidney performance.NEW & NOTEWORTHY By administering a peripheral decarboxylase inhibitor, we revealed that peripheral dopamine inhibits both the increase in urinary 8-iso-prostaglandin F2α, an oxidative stress marker, and the increase in plasma cystatin C, an early renal dysfunction marker, even in the early stages of diabetic nephropathy characterized by glomerular hyperfiltration. By visualizing renal dopamine precursor distribution, we highlighted the role of endogenous renal dopamine in oxidative stress and renal function following the onset of glomerular hyperfiltration.

High Protein Diets and Glomerular Hyperfiltration in Athletes and Bodybuilders: Is Chronic Kidney Disease the Real Finish Line?

Several observational and experimental studies in humans have suggested that high protein intake (PI) causes intraglomerular hypertension leading to hyperfiltration. This phenomenon results in progressive loss of renal function with long-term exposure to high-protein diets (HPDs), even in healthy people. The recommended daily allowance for PI is 0.83g/kg per day, which meets the protein requirement for approximately 98% of the population. A HPD is defined as a protein consumption > 1.5g/kg per day. Athletes and bodybuilders are encouraged to follow HPDs to optimize muscle protein balance, increase lean body mass, and enhance performance. A series of studies in resistance-trained athletes looking at HPD has been published concluding that there are no harmful effects of HPD on renal health. However, the aim of these studies was to evaluate body composition changes and they were not designed to assess safety or kidney outcomes. Here we review the effects of HPD on kidney health in athletes and healthy individuals with normal kidney function.

Dietary protein intake and the tubular handling of indoxyl sulfate.

Chronic kidney disease (CKD) patients are advised to limit their protein intake. A high protein diet is known to induce glomerular hyperfiltration, as well as hypertrophy of the remnant kidney, and glomerulosclerosis. Whether the diet causes changes in kidney tubule transport via gut microbiome metabolites is still unknown. We hypothesized that protein intake affects not only the intestinal generation and absorption, but also the kidney disposal of microbial amino acid metabolites. We combined data from animal models and human studies. 5/6th nephrectomy rats were administered a high (HP) or low-protein (LP) diet for 7 weeks. Plasma and urine concentration of the uremic toxins (UTs) indoxyl sulfate (IS), p-cresyl sulfate (PCS), and p-cresyl glucuronide (PCG) were measured. Their fractional excretion (FE) was calculated. The expression of kidney membrane transporters OAT1, OAT3, BCRP, OCT2 and MRP4 was analyzed. Differences in FE of UTs between individuals with higher and lower protein intake in two CKD cohorts were sought. CKD rats on an HP diet showed increased plasma levels of PCS and PCG but not IS compared to rats on a LP diet. Conversely, urinary excretion and FE of IS were higher in the HP CKD group. BCRP, MRP4 and OCT2 were not influenced by the diet. OAT1 and OAT3 were upregulated in the HP CKD group. In two independent cohorts of CKD patients, individuals with a high dietary protein intake showed a significantly higher FE of IS. A HP diet leads to a higher generation and/or absorption of aminoacid-derived UT precursors in CKD rodent models and humans, most likely via gut microbiome modulation. We demonstrate that dietary protein intake modulates transcription and expression of OAT1 and OAT3, corroborating the existence of the remote sensing and signaling hypothesis. Dietary protein intake influences kidney physiology beyond glomerular filtration.

Randomized, placebo-controlled trial on the renal and systemic hemodynamic effects of empagliflozin

IntroductionSodium-glucose cotransporter 2 inhibitors (SGLT2i) improve renal outcomes in type 2 diabetes (DM2) and chronic kidney disease (CKD). A decrease in renal blood flow (RBF) with attenuation of glomerular hyperfiltration may contribute. We examined renal and systemic hemodynamic effects of SGLT2i in relevant patient categories. MethodsUsing a double-blind placebo controlled cross-over design we randomized patients with DM2 and estimated glomerular filtration rate (eGFR) >60 ml/min/1.73m2 (n=16), patients with DM2 and eGFR 20-60 ml/min/1.73m2 (n=17) and patients with non-diabetic CKD and eGFR 20-60 ml/min/1.73m2 (n=16) to empagliflozin 10 mg daily or placebo for four weeks and crossed over to the opposite treatment after two-week washout. RBF was measured with 82Rubidium-positron emission-tomography/computed-tomography, GFR with 99mTechnetium-diethylene-triamine-pentaacetate-clearance. 24-hour blood pressure (BP) and total vascular resistance (TVR) were recorded using a Mobil-O-graph. ResultsCompared to placebo empagliflozin reduced RBF by 6% in the DM2-CKD group (p<0.001) with non-significant decreases of 4% in the DM2 group and 1% in the CKD group (p=0.29 and 0.72). Empagliflozin reduced GFR, BP and TVR in all groups, while renal vascular resistance (RVR) remained unchanged ConclusionEmpagliflozin reduced RBF in patients with DM2 and CKD, whereas GFR, BP and TVR were reduced in all groups. This pattern, together with a lack of reduction in RVR, suggests SGLT2i protect the glomerulus through combined pre-glomerular and post-glomerular effects.

Prevalence and Consequences of Glomerular Hyperfiltration (HF) in Pediatric Solid-Organ Transplant (SOT) Recipients

Prevalence and Consequences of Glomerular Hyperfiltration (HF) in Pediatric Solid-Organ Transplant (SOT) Recipients

Abstract 03: Glomerular Hyperfiltration Promotes Chronic Kidney Disease through Interleukin 17A-Mediated Inflammation

Impaired renal autoregulation in obesity, diabetes and hypertension (HTN) causes elevated glomerular capillary pressure and glomerular hyperfiltration, initiating progressive glomerulosclerosis (GS), nephron loss and chronic kidney disease (CKD). Increased renal perfusion pressure drives renal T cell infiltration. T helper (Th) 17 cells promote vascular stiffening in HTN and renal interstitial fibrosis post AKI, but their roles in GS and CKD are poorly understood. We hypothesized that glomerular hyperfiltration promotes CKD through Th17-mediated GS and tested the hypothesis in 129S6 mice using the reduced kidney mass model (RKM) induced by uninephrectomy and partial renal artery ligation in the remaining kidney (functional renal mass reduced by ~ 5/6). BP (radiotelemetry) and GFR (FITC-sinistrin) of RKM mice were identical to sham controls at baseline (BL, n=4-6). Immediately after the RKM procedure, GFR dropped to 22% of BL, consistent with the extent of renal mass ablation. Mean BP increased by 29 mmHg first week after 5/6 ablation (144 ± 8 vs BL 112 ± 2 mmHg, p&lt;0.05, 2-way ANOVA) and remained elevated through week 12, exposing the remnant nephrons to increased renal perfusion pressure. Serum creatinine, BUN and urinary albumin were significantly elevated after 5/6 ablation. In RKM mice, GFR gradually increased to 38% of BL at day 3, 57% at week 1 and 68% at week 2, suggesting that systemic HTN and impaired renal autoregulation may have caused substantial single-nephron hyperfiltration in the remnant kidney. GFR plateaued at ~ 70% of BL in week 3-4 then declined to 48% at week 8 when glomerular, interstitial, and microvascular fibrosis developed as evidence by Periodic Acid Schiff and Picro Sirius Red staining. Importantly, the early adaptive increase of GFR in the first 2 weeks post 5/6 ablation was accompanied by a striking increase of renal interleukin (IL)-17A+ T cells, which preceded the late infiltration of CD11b+ myeloid cells, F4/80+ monocyte/macrophages, and T regulatory cells. Anti-IL17A antibodies (eBioMM17F3, 100 μg i.p. twice weekly) attenuated the early hyperfiltration, abolished aortic/renal inflammation, and prevented GFR decline and GS at week 8 in male but not female RKM mice, likely due to the anti-hypertensive and anti-inflammatory effects of IL-17A neutralization. We conclude that glomerular hyperfiltration causes progressive nephron loss and kidney fibrosis in CKD, at least in part, through IL-17A mediated renal inflammation.

Deciphering the kidney hemodynamic effects of SGLT2 inhibition: translating insights from rats to humans in type 2 diabetes

The attenuation of glomerular hyperfiltration is posited to be a principal mechanism underlying the kidney protective effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors in diabetic kidney disease. Notably, the impact of SGLT2 inhibitors on kidney hemodynamic function has been posited to vary between type 1 and type 2 diabetes. The study by Wada etal. documents that in an animal model of type 2 diabetes, SGLT2 inhibitors mitigate glomerular hyperfiltration predominantly through afferent arteriolar constriction, a process mediated by the adenosine/A1 receptor pathway. This observation is consistent with mechanisms identified in type 1 diabetes, arguing for similar methods in type 1 and 2 diabetes.

Prediabetes and CKD: Does a causal relationship exist.

The relationship between diabetes and the development of kidney complications is well known, but the understanding of prediabetes and insulin resistance with impaired kidney function has been scarcely assessed. Various factors could explain this phenomenon, from the lack of standardization in the definitions of prediabetes, to the erratic and inconsistent evidence in large-scale epidemiological and cohort studies. It seems that the pathophysiological pathway of prediabetes could be related to inflammation and neurohormonal hyperactivation, factors present even before the onset of diabetes, which might be the main drivers of glomerular hyperfiltration, albuminuria, and impaired glomerular filtration rate. It is possible that existing treatments for the management of diabetes, as metformin or SGLT2 inhibitors may also be useful in patients with prediabetes with evidence of functional and structural kidney damage. The purpose of this review is to summarize the evidence regarding the relationship between prediabetes (preDM) and the development of CKD.

Finerenone's Impact on Major Adverse Cardiovascular Events in Chronic Kidney Disease and Type 2 Diabetes Mellitus: A Systematic Review.

Chronic kidney disease (CKD) impacts about 10% of adults globally and substantially elevates the risk of major adverse cardiovascular events (MACE), such as heart attacks, strokes, cardiovascular-related deaths, and hospital admissions due to heart failure. The interplay between CKD and cardiovascular disease (CVD) leads to poor health outcomes. Nevertheless, there is a scarcity of systematic reviews focusing on the effectiveness of finerenone, a new non-steroidal mineralocorticoid receptor antagonist (MRA), in lowering these risks. In this systematic review, we aim to evaluate the impact of finerenone on reducing MACEin individuals with CKDand type 2 diabetes mellitus (T2DM). CKD pathophysiology involves hyperglycemia, hypertension, and dyslipidemia, leading to glomerular hyperfiltration, inflammation, and fibrosis. Traditional treatments, including angiotensin-converting enzyme inhibitors (ACEi), angiotensin II receptor blockers (ARBs), and sodium-glucose cotransporter-2 inhibitors (SGLT2i), often fall short in preventing cardiovascular events. Steroidal MRAs like spironolactone and eplerenone, while effective in reducing proteinuria, are limited by hyperkalemia risks. Finerenone offers a more selective mechanism, reducing sodium retention, inflammation, and fibrosis, with a lower risk of hyperkalemia. We searched five electronic databases comprehensively, identifying studies consistently demonstrating that finerenone significantly reduces MACE and improves renal outcomes by reducing albuminuria and slowing the fall in estimated glomerular filtration rate (eGFR). However, limitations include study heterogeneity, short follow-up periods, and potential publication bias. In conclusion, finerenone shows promise as a therapeutic option for CKD and T2DM, reducing MACE and improving renal outcomes. Further research is needed to understand its long-term benefits and safety across diverse populations.

Caffeine intake and cardiometabolic risk factors in adolescents in the United States.

In adults, caffeine has protective effects against kidney dysfunction and type 2 diabetes mellitus (T2DM) but increases the risk of acute blood pressure (BP) elevation and dyslipidemia. These relationships are unclear in adolescents. This study aimed to determine the association between caffeine intake and markers of childhood cardiometabolic risk, hypothesizing that higher caffeine intake would be associated with elevated BP and dyslipidemia but improved kidney function and insulin sensitivity. Adolescents ages 13-17 who participated in the National Health and Nutritional Examination Survey (NHANES) from 2011 to 2018 and completed 24-h dietary recalls were included. Logistic and linear regression models were used to analyze cross-sectional associations between caffeine and cardiometabolic risk factors. The mean participant age was 15.0 years, with a sex distribution of 49.9% male and 50.1% female. In fully adjusted regression models, higher caffeine intake was not associated with any changes in BP (OR = 0.78, 95%CI [0.52,1.16], p = 0.21), dyslipidemia (OR = 0.91, 95%CI [0.65,1.27], p = 0.57), glomerular hyperfiltration (OR = 1.01, 95%CI [0.60,1.71], p = 0.96), albuminuria (OR = 0.94, 95%CI [0.45,1.98], p = 0.87), or insulin resistance (OR = 1.15, 95%CI [0.85,1.56], p = 0.36). Contrary to its cardiometabolic effects in adults, caffeine intake was not associated with an increased or reduced risk of kidney dysfunction, T2DM, hypertension, or dyslipidemia in adolescents. Although the effects of caffeine intake on cardiometabolic risk have been well defined in adults, data exploring its impact on adolescent cardiovascular and metabolic function is limited. The goal of this study was to understand the relationship between caffeine intake and markers of childhood cardiometabolic risk. Unlike its established effects in adults, caffeine consumption showed no association with markers of cardiometabolic disease, such as kidney dysfunction, type 2 diabetes mellitus, blood pressure, dyslipidemia, or hyperuricemia in adolescents. These findings offer novel insight into the effects of caffeine on cardiometabolic function in adolescents, which may guide clinical recommendations for at-risk patients.

Advances in the diagnosis and poor prognosis of diabetic hyperfiltration

Glomerular hyperfiltration(GHF), as an early manifestation of prediabetes and diabetic kidney disease, occurs mainly by the mechanism of glomerular-tubular feedback and hemodynamic alterations, and the risk of hyperfiltration can be elevated in younger patients, shorter duration of the disease, poor glycemic control, and high-protein, low-salt diet. Currently, there is no recognized standard for the definition of GHF, GHF lacks typical clinical manifestations, imaging diagnostic criteria are unclear, and GHF-related laboratory markers need to be further studied. Hyperfiltration, if not diagnosed and intervened in time, can accelerate the damage of nephron and the rate of nephropathy progression, and increase the risk of complications and death. Sodium-glucose cotransporter 2 inhibitor(SGLT2i), glucagon-like peptide-1 receptor agonist(GLP-1RA)and so on can effectively reverse the hyperfiltration state. Clinical attention should be paid to the diagnosis of diabetic hyperfiltration and the prevention of its poor prognosis.

Changes in glomerular filtration rate in patients with body mass index≥35kg/m2 treated with metabolic and bariatric surgery versus GLP-1 agonist at 1-year follow-up.

Metabolic and bariatric surgery (MBS) reduces glomerular hyperfiltration. The renoprotective effects of GLP-1 analogs were derived from clinical studies in type 2 diabetes (T2D). The objective of this study was to evaluate the changes in glomerular filtration rate (GFR) over time associated with weight loss in patients with a BMI ≥ 35kg/m2 treated with liraglutide compared with patients treated with MBS. A longitudinal study derived from a retrospective cohort of patients with BMI≥35kg/m2 treated with either MBS or liraglutide 3mg/day, with follow-up ≥1year. Clinical variables, baseline GFR, and 1-year GFR were analyzed. A generalized estimating equation (GEE) model was used to compare changes in GFR between both groups while controlling for confounding variables. A total of 159 patients were included in the analysis. Of these, 129 patients underwent MBS (median age 60.5years [IQR 51.8-66.6], body mass index (BMI) 40.9kg/m2 [IQR 0.68-0.89]), and 30 patients were treated with liraglutide (median age 56years [IQR 46-62], BMI 37.4kg/m2 [IQR 0.69-0.93]). No difference in baseline GFR or at 12months of follow-up was found between the two interventions. GEE analysis revealed an increase of 0.32mL/min/1.73m2 per month of follow-up. Factors associated with a greater increase in GFR were the percentage total weight loss (%TWL) (0.12mL/min/1.73m2, p=0.023) and baseline GFR (0.69mL/min/1.73m2, p>0.001) for both interventions, independent of a history of T2D. In patients with BMI≥35kg/m2, changes in GFR are related to %TWL and baseline GFR, regardless of the presence of diabetes or the type of intervention used.

Preventative dental practices and cardiometabolic health in adolescents.

The aim of this study was to identify the relationship between preventative dental practices and cardiometabolic health in adolescents. Analysis included children aged 13-17 years enrolled in the National Health and Nutrition Examination Survey (NHANES) from 2011-2018 who completed an Oral Health Examination and Questionnaire. Deferred dental care was defined as not having a dental visit in the past year. Financial barriers to seeking dental care (vs. no financial barriers) were assessed among those with deferred dental care in the past year. Primary cardiometabolic outcomes included obesity, elevated blood pressure and hypertensive blood pressure. Secondary outcomes included dyslipidemia, glucose intolerance, uric acid, glomerular hyperfiltration, and albuminuria. Regression models adjusted for age, sex, ethnicity, household income, food insecurity, health insurance status, household education, and body mass index z-score examined associations using complex survey design procedures. Of 2,861 adolescents, 17.6% (SE 0.9%) did not receive dental care in the past year and 20.2% (SE 1.9%) had a financial barrier to accessing dental care. In adjusted regression models, adolescents with deferred dental care had higher odds of dyslipidemia (OR= 1.51, 95% CI 1.07, 2.11 p = 0.020). Having a financial barrier was associated with a lower odd of dyslipidemia (OR=0.35, 95% CI 0.14, 0.89 p = 0.03). Financial barriers were associated with lower non-HDL (b=-7.95, 95% CI -14.87, -1.05 p=0.03) and higher HDL (b=3.06, 95% CI 0.37, 5.75 p=0.03) in adjusted models. Deferred dental care and financial barriers were not associated with any other cardiometabolic parameters. In this nationally representative cohort of adolescents, there was an association between lack of preventative dental care and the cardiometabolic health marker of dyslipidemia. However, financial barriers to dental care were surprisingly associated with higher HDL levels and lower odds of dyslipidemia.

Dulaglutide and Glomerular Hyperfiltration, Proteinuria, and Albuminuria in Youth With Type 2 Diabetes: Post Hoc Analysis of the AWARD-PEDS Study.

To examine changes in glomerular hyperfiltration and other measures of kidney function in youth with type 2 diabetes treated with dulaglutide or placebo. Post hoc analysis was performed on kidney laboratory data from 154 youths (age 10-18 years) with type 2 diabetes enrolled in a completed placebo-controlled glycemic control trial of dulaglutide. Mean estimated glomerular filtration rate (eGFR) decreased from baseline to 26 weeks in participants treated with dulaglutide versus placebo (-5.8 vs. -0.1 mL/min/1.73 m2; P = 0.016). Decreases in eGFR were observed primarily in participants with baseline glomerular hyperfiltration. At 26 weeks, the prevalence of both glomerular hyperfiltration and proteinuria increased with placebo but decreased with dulaglutide (P = 0.014 and 0.004 vs. placebo, respectively). Dulaglutide was associated with attenuated glomerular hyperfiltration and proteinuria in youth with type 2 diabetes. The impact of these changes on the risk of diabetic kidney disease is unclear.

Relevance of repeated analyses of albuminuria and glomerular filtration rate in African children with sickle cell anaemia.

Glomerular hyperfiltration and albuminuria are frequent kidney abnormalities in children with sickle cell anaemia (SCA). However, little is known about their persistence in African SCA children. This prospective study included 600 steady-state SCA children aged 2-18 years from the Democratic Republic of Congo. Participants were genotyped for apolipoprotein L1 (APOL1) risk variants (RVs) and haem oxygenase-1 (HMOX1) GT-dinucleotide repeats. Kidney abnormalities were defined as albuminuria, hyperfiltration or decreased estimated creatinine-based glomerular filtration rate (eGFRcr). At baseline, 247/600 (41.2%) participants presented with kidney abnormalities: 82/592 (13.8%) with albuminuria, 184/587 (31.3%) with hyperfiltration and 15/587 (2.6%) with decreased eGFRcr. After a median follow-up of 5 months, repeated testing was performed in 180/247 (72.9%) available participants. Persistent hyperfiltration and persistent albuminuria (PA) were present in 29.2% (38/130) and 39.7% (23/58) respectively. eGFR normalized in all participants with a baseline decreased eGFRcr. Haemoglobinuria (p = 0.017) and male gender (p = 0.047) were significantly associated with PA and persistent hyperfiltration respectively. APOL1 RVs (G1G1/G2G2/G1G2) were borderline associated with PA (p = 0.075), while HMOX1 long repeat was not associated with any persistent kidney abnormality. This study reveals that a single screening can overestimate the rate of kidney abnormalities in children with SCA and could lead to overtreatment.

Intermittent protein restriction before but not after the onset of diabetic kidney disease attenuates disease progression in mice.

High dietary protein intake exacerbates proteinuria in individuals with diabetic kidney disease (DKD). However, studies on the impacts of low protein diet (LPD) on DKD have yielded conflicting results. Furthermore, patient compliance to continuous protein restriction is challenging. The current study aims to investigate the effects of intermittent protein restriction (IPR) on disease progression of DKD. Diabetic KK-Ay mice were used in this study. For the IPR treatment, three consecutive days of LPD were followed by four consecutive days of normal protein diet (NPD) within each week. For early intervention, mice received IPR before DKD onset. For late intervention, mice received IPR after DKD onset. In both experiments, age-matched mice fed continuous NPD served as the control group. Kidney morphology, structure and function of mice in different groups were examined. Intermittent protein restriction before DKD onset ameliorated pathological changes in kidney, including nephromegaly, glomerular hyperfiltration, tubular injuries and proteinuria, without improving glycemic control. Meanwhile, IPR initiated after DKD onset showed no renoprotective effects despite improved glucose homeostasis. Intermittent protein restriction before rather than after DKD onset protects kidneys, and the impacts of IPR on the kidneys are independent of glycemic control. IPR shows promise as an effective strategy for managing DKD and improving patient compliance.

Transforming growth factor-β1: relation between its single-nucleotide genetic variants and sickle cell nephropathy

BackgroundSickle cell nephropathy is a complication of sickle cell disease characterized by functional abnormalities of the kidney and glomeruli. Our study aimed to investigate the single-nucleotide genetic variants in TGF-β-1-related genes as an early predictor of sickle cell nephropathy (SCN) risk.MethodsTwo hundred participants, 100 patients with SCD, and 100 age and sex-matched control. The study included full history taking, clinical examination, and laboratory evaluation. Renal function tests (serum urea and creatinine, microalbuminuria, albumin/ creatinine ratio, and e-GFR). Genotyping for TGF-β1 genetic variants rs1800469 and rs1800471.ResultsTwenty-one percent of patients had glomerular hyperfiltration, while 31% had reduced e-GFR. Microalbuminuria was present in 14%, and none had macroalbuminuria or edema. TGF-β1 genotyping revealed a statistically significant difference in the rs 1800471 C allele, which was more common in the control group (p 0.028). No significant correlation between the result of TGF‐ β genotyping and the albumin-to-creatinine ratio, creatinine, and e-GFR.ConclusionTGF-β1 rs1800469 and rs1800471 genetic variants were not associated with the risk of sickle nephropathy in children with sickle cell disease.

Obesity and kidney disease

The obesity epidemic has led to an increased prevalence of obesity-related glomerulopathy (ORG). This disease is characte-rized by proteinuria, glomerulomegaly, progressive glomerulosclerosis and a decline in renal function. Individuals with obesity frequently display arterial hypertension and diabetes mellitus, exacerbating renal damage. The pathogenesis involves overactivation of the RAAS (Renin-Angiotensin-Aldosterone System), glomerular hyperfiltration, an inflammatory state with oxidative stress, hyperinsulinemia-induced hemodynamic alterations and lipotoxicity. Additionally, obesity represents a significant risk factor for kidney stone formation, further contributing to renal damage. The management of obesity-induced nephropathy primarily involves weight reduction strategies and optimized control of blood pressure and metabolic factors. Early detection is crucial to counteract the progression of kidney disease. Noteworthy, obesity significantly complicates the implementation of renal replacement procedures, including kidney transplantation, and increases the rate of complications. In summary, there are many reasons why obesity should gain attention in the field of nephrology.