Renal Function In Chronic Kidney Disease Research Articles

A multi-center randomized controlled trial to investigate potential effects of exercise therapy on renal function stratified by renal disorders and renal pathology: beneficial or harmful effect in immunoglobulin a nephropathy.

The effects of exercise therapy (ET) on renal function in chronic kidney disease (CKD) remain unclear. In a randomized controlled trial (UMIN-CTR number: UMIN000038415), we investigated whether ET affects renal function in CKD; eligible patients had undergone renal biopsy in the past 3months. We stratified patients by disease (immunoglobulin A [IgA] nephropathy, n = 16; diabetic nephropathy, n = 4; benign nephrosclerosis, n = 13; and other CKD types, n = 13) and randomized them to 12weeks' observation and 24weeks' ET comprising home-based aerobic exercise 3×/week and resistance training 2×/week (intervention group) or usual care (non-intervention group). Primary endpoint was creatinine-based estimated glomerular filtration rate (eGFR) or serum cystatin C-based eGFR (eGFRcys). Secondary endpoints included urinary protein and exercise tolerance. Seventy patients were enrolled, 50 fulfilled the inclusion criteria, but 4 discontinued before randomization. No items significantly differed between week 0 to 24 in either group (intervention group, n = 23; non-intervention group, n = 23) or between groups at week 24 (intention-to-treat population) in the total study population. The eGFRcys slope showed no significant intergroup difference in the observation period, but eGFRcys improved significantly in IgA nephropathy patients (n = 16) in the intervention group (stratified comparison; week 0, 48.3 ± 18.2; week 24, 51.6 ± 17.6; p = 0.043). In these patients, urinary protein was significantly worse at week 24 in the non-intervention group (p = 0.046) and worsened significantly less in the intervention group (p = 0.039). ET did not improve renal function overall in CKD patients but might help maintain renal function in patients with IgA nephropathy.

The dynamics of hypertension and renal function in CKD and non-CKD patients affected with COVID-19 – final results of BIRCOV trial

Introduction and aim. There is evidence in the literature about a change in the effectiveness of inhibitors of the renin-angiotensin system (iRAS) in people with COVID-19. Considering different mechanisms of pressure reduction by different iRAS groups, one can expect differences in people with COVID-19 receiving these drugs. The aim of angiotensin-converting enzyme inhibitors (ACEi), angiotensin II receptor blockers (ARB) and direct renin inhibitors (DRi) usage in COVID-19 (BIRCOV study) was to pinpoint clinical and laboratory differences in people with hypertension who received iRAS and suffered coronavirus infection. Material and methods. An open prospective trial of 108 patients was performed in subjects suffering from COVID-19 who have been receiving iRAS: ACEi, ARB or DRi as basic antihypertensive therapy. The disease follow-up was 12 and 24 weeks. A blood pressure (BP) measurement was performed the week before COVID-19 and up to 24 weeks from the disease onset. Subanalysis in patients with chronic kidney disease (CKD) was performed. Results. In patients with COVID-19, a change in the effectiveness of antihypertensive therapy depending on the type of drug in the iRAS group has been documented in the first 4 weeks from the onset of the disease. The use of ACEi had significantly increased the risk of severe hypotension, unlike ARBs that do not cause hypotension. The synchronous decline of estimated glomerular filtration rate (eGFR) and systolic BP was more pronounced in CKD patients followed by albuminuria incidence. The greatest decrease in eGFR was in people taking ACEi. Conclusion. People with grade 1-2 hypertension who are constantly receiving RAS inhibitors suffering from COVID-19 may develop hypotension with ACEi. COVID-19 leads to transient albuminuria and decreased glomerular filtration rate, which is especially dangerous for people with CKD 4-5.

Exploring the interplay between kidney health, vitamin D levels, and mineral/bone disorders in chronic kidney disease (CKD)

Introduction: CKD is associated with a number of problems of mineral and bone metabolism, including vitamin D deficiency and secondary hyperparathyroidism. The relationships between a lack of vitamin D, circulating indicators of mineral and bone diseases (MBD), and renal function in CKD are not well understood. This cross-sectional research included 1,060 individuals with CKD stages 2 to 5 from the Institute of Kidney Disease (IKD), Peshawar. In addition to other indicators of bone metabolism, we evaluated the estimated glomerular filtration rate (eGFR), blood levels of Calcifediol, calcium, phosphate, and intact parathyroid hormone (PTH). The results of interest were blood calcium, phosphate, and PTH levels as well as other indicators of bone metabolism. These markers also included circulating markers of MBD. Results: Higher blood Parathyroid Hormones levels, in addition to lower levels of blood calcium and phosphate, were all associated with vitamin D deficiency and decreased eGFR. Additionally, vitamin D deficiency has been independently linked to lower levels of other bone metabolism indicators, including tartrate-resistant acid phosphatase-5b and bone-specific alkaline phosphatase. In patients with CKD, abnormalities in mineral and bone metabolism, including greater PTH levels and lower calcium and phosphate levels, are independently correlated with reduced eGFR and vitamin D insufficiency.

Mesenchymal stem cells: A new therapeutic tool for chronic kidney disease.

Chronic kidney disease (CKD) has a major impact on public health, which could progress to end-stage kidney disease (ESRD) and consume many medical resources. Currently, the treatment for CKD has many flaws, so more effective treatment tools are urgently required for CKD. Mesenchymal stem cells (MSCs) are primitive cells with self-renewal and proliferation capacity and differentiation potential. Extensive preclinical and clinical data has shown that cell-based therapies using MSCs can modulate immunity, inhibit inflammatory factors, and improve renal function in CKD, suggesting that MSCs have the potential to be a new, effective therapeutic tool for CKD. In this review, we will describe different kinds of MSCs and MSCs products for the treatment of CKD in experimental models and clinical trials, potential signaling pathways, therapeutic efficacy, and critical issues that need to be addressed before therapeutic application in humans.

Faecalibacterium prausnitzii Attenuates CKD via Butyrate-Renal GPR43 Axis.

Despite available clinical management strategies, chronic kidney disease (CKD) is associated with severe morbidity and mortality worldwide, which beckons new solutions. Host-microbial interactions with a depletion of Faecalibacterium prausnitzii in CKD are reported. However, the mechanisms about if and how F prausnitzii can be used as a probiotic to treat CKD remains unknown. We evaluated the microbial compositions in 2 independent CKD populations for any potential probiotic. Next, we investigated if supplementation of such probiotic in a mouse CKD model can restore gut-renal homeostasis as monitored by its effects on suppression on renal inflammation, improvement in gut permeability and renal function. Last, we investigated the molecular mechanisms underlying the probiotic-induced beneficial outcomes. We observed significant depletion of Faecalibacterium in the patients with CKD in both Western (n=283) and Eastern populations (n=75). Supplementation of F prausnitzii to CKD mice reduced renal dysfunction, renal inflammation, and lowered the serum levels of various uremic toxins. These are coupled with improved gut microbial ecology and intestinal integrity. Moreover, we demonstrated that the beneficial effects in kidney induced by F prausnitzii-derived butyrate were through the GPR (G protein-coupled receptor)-43. Using a mouse CKD model, we uncovered a novel beneficial role of F prausnitzii in the restoration of renal function in CKD, which is, at least in part, attributed to the butyrate-mediated GPR-43 signaling in the kidney. Our study provides the necessary foundation to harness the therapeutic potential of F prausnitzii for ameliorating CKD.

How to determine the prognosis of renal function in CKD?

The presented material raises the most important question in practical nephrology – how to correctly assess kidney function to understand the prognosis and duration of the predialysis period in a particular patient with chronic kidney disease (CKD)? From the standpoint of onto- and phylogenesis, the hierarchy of kidney functions was assessed. It is noted that the existing approaches to such an assessment are convenient for practice, but do not sufficiently take into account individual characteristics and are devoid of a load component that can show kidney reserves. The authors focused on the functional renal reserve (FRR) and the possibility of its detection. The above technique with 0.45 % saline allows revealing the true functional capabilities of the kidneys and understanding the patient's capabilities in the pre-dialysis period. Conclusions are drawn about the convenient use of the KDIGO scale, a more individual approach when using the QxMD calculator, and the possibility of a personalized approach when assessing the FRR.

Shenkang injection protects against renal fibrosis by reducing perforin expression through the STING/TBK1/IRF3 signaling pathways in natural killer cells

BackgroundImmune activation, chronic inflammation, and renal interstitial fibrosis (RIF) are associated with chronic kidney disease (CKD). The herbal formula, Shenkang injection (SKI), has been reported to attenuate RIF. However, the mechanisms by which SKI alleviates renal fibrosis, especially the role of natural killer (NK) cells, are unknown and require exploration. PurposeThis study aimed to determine the mechanisms by which SKI alleviates RIF. MethodsDifferential gene expression between CKD mice and control groups was explored using bioinformatics analysis. To reveal how SKI reduces RIF in CKD, a CKD mouse model was established using folic acid for in vivo studies, and human kidney-2 cells were used for in vitro experiments. The effects of various SKI doses were then determined. Immunohistochemical staining, Enzyme-linked immunosorbent assay, western blotting, and quantitative real-time PCR were used for pathological and molecular expression detection. ResultsWe first investigated the potential immune dysfunction in CKD using bioinformatics analysis. Some differentially expressed genes were enriched in immune-related functions. The expressions of perforin and interferon (IFN)-γ, which are mainly released by NK cells, were significantly higher in patients with CKD (p< 0.05). In vivo experiments showed that SKI alleviated renal fibrosis in a folic acid-induced renal fibrosis model. Serum creatinine and blood urea nitrogen levels were reduced in the high-dose SKI-treated group. Additionally, the mRNA and protein expression levels of type IV collagen and alpha-spinal muscular atrophy were reduced. Biochemical detection showed that SKI could also downregulate the activity of NK cells (by decreasing the expressions of perforin and IFN-γ). Increased levels of stimulator of interferon genes (STING)/TANK-binding kinase 1 (TBK1)/IFN regulatory factor 3 (IRF3), phosphorylation of TBK1, and IRF3 in FA-induced RIF mice were alleviated by SKI treatment, which was consistent with the results of in vitro experiments. ConclusionThese results demonstrated that SKI could decrease the activation of NK cells via the STING/TBK1/IRF3 signaling pathway, thereby alleviating RIF and protecting renal function in CKD. This may provide valuable evidence supporting the clinical use of SKI in the treatment of patients with CKD.

MO393: Kidney Echogenicity and Kidney Length as Surrogate Markers of Kidney Function With an Increased Echogenic Pattern Being the Most Predictive of Renal Dysfunction, Particularly in HIV

Abstract BACKGROUND AND AIMS Non-communicable diseases (NCDs) are rapidly emerging as a major cause of chronic kidney disease (CKD) in Africa with a reported prevalence of 10.7% locally. At current, few high-quality studies assessing the epidemiology of CKD in South Africa have been published. Alarmingly, CKD is now at epidemic proportions and is a leading cause of mortality with significant cost implications. This study aims to investigate economic means of predicting renal function in CKD by exploring the association between estimated glomerular filtration rate (eGFR) and renal morphology evaluated by ultrasound (US). METHOD This is a retrospective descriptive chart review conducted at the Department of Nephrology, Inkosi Albert Luthuli Central Hospital (IALCH), Cato Manor, Kwa-Zulu Natal from January 2016 to December 2016. A total of 455 patients who had met the Kidney Disease Improving Global Outcomes (KDIGO) definition of CKD with eGFR (MDRD) and kidney US performed were included. Demographic, clinical, laboratory and kidney morphological data [kidney length (KL), increased echogenicity (IE) and loss of corticomedullary differentiation (LCMD)] on US were collected and analyzed with SPSS software (v. 27). Associations between eGFR, parameters on US and CKD risk factors were determined using logistic regression analysis. RESULTS Black Africans (75.2%; n = 342) and females (56.9%; n = 259) predominated the sample. Whilst, Indians, Whites and Coloreds comprised of 20.4%, 2.42% and 1.98% of the study respectively. The median age was 45.8 ± 14.3 years. Hypertension (34.9%), diabetes (26.8%), HIV (27.5%) and glomerulonephritis 9.89% were the four most frequently reported risk factors, of which Black Africans comprised more than 50% of cases (P &amp;lt; 0.001). A significant proportion of patients 65.7% (n = 307) had end-stage renal disease with a median eGFR of 14.4 ± 12.8mL/min/1.73m2 (P &amp;lt; 0.001). The median right and left KL were short at 8.49 ± 2.16 cm and 8.60 ± 2.20 cm respectively. Black Africans were also found to have significantly shorter KLs and lower eGFRs (P &amp;lt; 0.001). The dual effect of IE and LCMD predisposed to significantly shorter KLs and lower eGFRs than in the presence of one or no abnormality on US (P &amp;lt; 0.001). IE [−9.29 odds ratio (OR); 95% confidence interval (CI) (−13.8 to −4.77); P &amp;lt; 0.001] and KL [right: 5.02 OR; 95% CI (3.44–6.60); P = 0.04; left: 5.11 OR; 95% CI (3.56–6.66); P = 0.04] were found to be significant predictors of eGFR. HIV was the only risk factor found to be negatively associated with all determined measures of renal function, as well as the sole predictor of IE [2.31 OR; 95% CI (0.17–3.15); P = 0.02]. CONCLUSION The CKD epidemic is driven by the complex interplay between communicable (HIV) and NCDs (HPT/DM) and has emerged as important public health and economic threat in Southern Africa. Africans are most vulnerable presenting with an advanced and accelerated disease course. GFR determination and US are inexpensive means of determining renal function, particularly in resource-limited settings. IE and KL are surrogate markers of kidney function with an increased echogenic pattern being most predictive of kidney dysfunction in CKD, particularly in HIV.

Treatment of Chronic Kidney Disease with Extracellular Vesicles from Mesenchymal Stem Cells and CD133+ Expanded Cells: A Comparative Preclinical Analysis.

Chronic kidney disease (CKD) is characterized by structural abnormalities and the progressive loss of kidney function. Extracellular vesicles (EVs) from human umbilical cord tissue (hUCT)-derived mesenchymal stem cells (MSCs) and expanded human umbilical cord blood (hUCB)-derived CD133+ cells (eCD133+) maintain the characteristics of the parent cells, providing a new form of cell-free treatment. We evaluated the effects of EVs from hUCT-derived MSCs and hUCB-derived CD133+ cells on rats with CDK induced by an adenine-enriched diet. EVs were isolated by ultracentrifugation and characterized by nanoparticle tracking analysis (NTA) and electron microscopy. The animals were randomized and divided into the MSC-EV group, eEPC-EV group and control group. Infusions occurred on the seventh and 14th days after CKD induction. Evaluations of kidney function were carried out by biochemical and histological analyses. Intense labeling of the α-SMA protein was observed when comparing the control with MSC-EVs. In both groups treated with EVs, a significant increase in serum albumin was observed, and the increase in cystatin C was inhibited. The results indicated improvements in renal function in CKD, demonstrating the therapeutic potential of EVs derived from MSCs and eCD133+ cells and suggesting the possibility that in the future, more than one type of EV will be used concurrently.

FC 064A RENAL-CARDIO INFLAMMATORY AXIS MEDIATES CARDIAC DYSFUNCTION IN CKD VIA IL-33-ST2: A NOVEL MECHANISM

Abstract Background and Aims We developed a swine model of chronic kidney disease (CKD) that also display cardiac abnormalities associated with heart failure (HF). Inflammation contributes to progressive renal dysfunction and increases cardiovascular mortality of patients with CKD. Interleukin (IL)-33 is a tissue-derived nuclear cytokine from the IL family. IL-33 constitutively expressed but upregulated and released after cellular damage or necrotic cell death, acting as a pro-inflammatory cytokine. We hypothesize that IL-33 plays a prominent mechanistic role in renal-cardio pathophysiology in CKD. Method We induced CKD in 10 pigs via bilateral renovascular disease and dyslipidemia. We developed a renally-targeted biopolymer-fused peptide inhibitor of nuclear-factor kappa (NF-k)B (ELP-p50i) and show it blocks NFkB activity in vitro and in vivo. NF-kB is a key pro-inflammatory transcription factor upregulated in CKD and closely interacts with IL-33. Pigs were observed for 6 weeks, renal (multi-detector CT) and cardiac structure and function (echo) were quantified, then randomized to single intra-renal ELP-p50i or placebo (n=5 each), and studies repeated 8 weeks later. Blood was collected to measure circulating TNF-α, IL-33 and its specific decoy receptor soluble (s) ST2 (ELISA). Heart weights were measured after euthanasia, and renal and cardiac expression of ST2 and morphometric analyses were performed. Results Loss of renal function in CKD was accompanied by increased heart weight, left ventricular (LV) hypertrophy, diastolic dysfunction, abnormal LV strain, renal/cardiac fibrosis, circulating TNF-α, IL-33 but unchanged sST2, and increased renal/cardiac ST2 expression. Most of these changes were improved after intra-renal ELP-p50i and accompanied by augmented sST2, suggesting that inhibition of renal inflammation can attenuate cardiac abnormalities via augmented clearance of IL-33 (Figure). Conclusion Our study supports a prominent role for renal inflammation as a driving force for precursors of HF in CKD, proposing a renal-cardio inflammatory axis possibly mediated by NF-kB-TNF-α-IL-33/ST2 interactions. TNF-α can stimulate IL-33 as IL33 can activate NF-kB and TNF-α, extending this inflammatory loop in both the kidney and heart. We show that a translational renal anti-inflammatory strategy via targeted inhibition of renal NFkB inhibits this axis and improves renal and cardiac function, which may guide to new treatments targeting renal inflammation in CKD.

Protective effect of miRNA-containing extracellular vesicles derived from mesenchymal stromal cells of old rats on renal function in chronic kidney disease

IntroductionMesenchymal stromal cells (MSCs) play an important role in the prevention of cell and tissue fibrosis. Senescence may decrease the function of MSCs during recovery from tissue and organ damage. Extracellular vesicles (EVs) released from MSCs contribute to the repair of kidney injury. We explored the influence of senescence on EVs derived from MSCs (MSC-EVs) and detected the protective effects of MSC-EVs expressing low levels of miR-294/miR-133 derived from old rats against chronic kidney disease (CKD).MethodsThe effects of MSC-EVs derived from 3-month-old and 18-month-old male Fisher 344 rats on renal fibrosis were explored in a unilateral ureteral obstruction (UUO) model. pLV-miR-294/pLV-miR-133 mimic/inhibitor were injected into young and old rats before UUO to detect the effects of miR-294/miR-133, which were decreased in MSC-EVs and sera from old rats, on renal function in CKD. Transforming growth factor-β1 (TGF-β1)-induced human renal proximal tubular epithelial (HK2) cells were used to imitate the pathological process of renal fibrosis in vitro. Western blotting was used to assess the expression of epithelial/mesenchymal markers and phosphorylation of proteins in HK2 cells.ResultsThe inhibition of UUO-induced CKD by MSC-EVs was weaker in old rats than in young rats. Downregulation of miRNAs (miR-294 and miR-133) in both MSC-EVs and sera from old rats obviously attenuated UUO-induced renal injury in old rats. miR-294 and miR-133 overexpression mitigated TGF-β1-mediated epithelial-mesenchymal transition (EMT) in HK2 cells, and the obvious increase in the phosphorylation of both SMAD2/3 and ERK1/2 induced by TGF-β1 was prevented in miR-294- and miR-133-overexpressing HK2 cells.ConclusionsThe ability of MSC-EVs to inhibit renal fibrosis decreased with age. miR-294/miR-133 in MSC-EVs and sera had an important effect on renal fibrosis in old rats and on EMT in HK2 cells. Furthermore, miR-294/miR-133 overexpression prevented SMAD2/3 and ERK1/2 phosphorylation in HK2 cells during TGF-β1-mediated EMT. These findings show that miR-294/miR-133 may be therapeutic in renal fibrosis and related renal dysfunction in elderly individuals.

P0736A NOVEL MODEL OF CHRONIC KIDNEY DISEASE AND HEART FAILURE WITH PRESERVED EJECTION FRACTION

Abstract Background and Aims Patients with chronic kidney disease (CKD) have a significantly higher cardiovascular risk that non-CKD patients, and over 50% of CKD patients die of cardiovascular events. We recently developed a model of CKD that displays major pathological features of clinical CKD: GFR of about 60 ml/min (stage 2-3a), significant renal inflammation, fibrosis, microvascular dysfunction and remodeling, and hypertension. The current study aims to define the cardiac phenotype of this model and, if cardiac abnormalities are present, the potential pathological traits involved. Method CKD was induced in 6 pigs via bilateral renovascular disease and dyslipidemia and observed for 14 weeks. After 14 weeks, renal hemodynamics (RBF, GFR) were quantified using multi-detector CT and echocardiographic assessment (morphology and function) performed using ultrasound-doppler. Mean arterial pressure (MAP) was continuously measured by telemetry. Blood was collected to measure circulating inflammatory cytokines (TNF-α, MCP-1, IL-6) and biomarkers of heart failure (ANP, BNP, NT-proBNP). Animals were then euthanized and kidneys and hearts collected for ex vivo studies. Normal pigs were used as time-matched controls. Results Loss of renal function in CKD was accompanied by left ventricular hypertrophy, left atrial dilatation, diastolic dysfunction (E/A ratio) with preserved ejection fraction (pEF), elevated ANP, BNP, and NT-proBNP, and hypertension (average MAP of 131.2 mm/Hg, p&amp;lt;0.05 vs. normal). CKD also increased renal (but not cardiac) mRNA expression of TNF-α, MCP-1, IL-6, accompanied by increased circulating inflammatory cytokines (Figure). Conclusion This study shows that CKD in the swine model leads to cardiac hypertrophy and diastolic dysfunction (with pEF) and increased biomarkers of heart failure, meeting the criteria for a potential novel model of heart failure with pEF (HFpEF). Our data also suggest that hypertension and inflammatory mediators (possibly originated in the kidney) target the heart and may contribute to HFpEF pathophysiology. HFpEF is considered the largest unmet need in cardiology with no specific treatments and associates with CKD in about 50% of cases. Thus, our study offers a promising new experimental platform to increase our understanding of CKD-HFpEF and to test new treatments in a translational fashion.

Prevalence of Mineral Bone Disease in Chronic Kidney Disease Patients using Biochemical Markers

Introduction: Chronic Kidney Disease (CKD), a condition characterised by a gradual loss of renal function over the time, has emerged as a major public health concern with 17% prevalence in Indian population. Decrease in renal function in CKD leads to progressive metabolic derangements of mineral and bone homeostasis which in turn makes them susceptible to bone related and cardiovascular complications. Aim: To calculate the prevalence of Mineral Bone Disease (MBD) in CKD patients by estimation of biochemical markers Calcium (Ca), Phosphorus (P), Alkaline Phosphatase (ALP) and intact Parathyroid Hormone (iPTH) and to analyse their prevalence across different stages of CKD. Materials and Methods: This was a hospital based cross-sectional study conducted at Medanta-the Medicity hospital in 2300 previously diagnosed CKD cases who visited the Nephrology OPD for their follow-up visits, from October 2017 to December 2018. Serum levels of Ca, P, ALP and iPTH were estimated in VITROS 4600 and ARCHITECT I system automated analysers using commercially available kits. Stage-wise and overall prevalence of deranged levels of these markers was calculated and based on this the prevalence of MBD was calculated. Statistical analysis was done using SPSS version 24.0. Descriptive analysis of quantitative parameters was expressed as means and standard deviation. The analysis for comparison among three or more categories was done using one-way ANOVA. Categorical data was analysed using Chi square test for proportions and data was expressed as absolute number and percentage in a contingency table along with the chi square and p-values. The p-value &lt;0.05 was considered statistically significant. Results: Prevalence of MBD in overall CKD patients was 81.6%; the stage-wise prevalence being 63.4% (stage 3), 76.9% (stage 4), 87.6% (stage 5) and 91.3% (stage 5D). The overall prevalence of hypocalcaemia, hyperphosphatemia, high ALP and secondary hyperparathyroidism was 27.8%, 48.3%, 26.5% and 75.6%, respectively. Conclusion: The present study reports an alarmingly high prevalence of MBD in CKD cases; the disease burden being maximum in stage 5 and 5D. This was despite the administration of relevant medications and supplements to prevent MBD. Thus, there needs to be some change in treatment protocol to reduce the prevalence of MBD to improve the quality of life and reduce mortality rate in CKD patients.

Chronic kidney disease in children: problems of arterial hypertension

The review contains materials on the course of chronic kidney disease (CKD) in children with arterial hypertension (AH). The relationship between CKD and AH was shown, where hastening of CKD progression to end-stage renal failure in the presence of AH was established. The regulation of AH in children is necessary for the treatment of CKD, because AH is not established on time, is not well controlled and is often masked. Impaired vascular regulation, fluid overload, increased cardiac output, and peripheral vascular resistance, alone or in combination, can lead to hypertension in CKD. The use of modern methods for monitoring and controlling blood pressure is crucial to improve the management of AH and prevent damage to target organs in children. 24-hour blood pressure measurements are an important tool in determining the prognosis and treatment of children with CKD. To identify impaired renal function in CKD, a large number of biomarkers are used. Glomerular filtration rate (GFR), serum creatinine and cystatin C are currently used as biomarkers for renal failure. Recently, biomarkers, including KIM-1, LFABP, NGAL, and IL-18 have been proposed as markers of acute kidney injury, and they may be useful in the future for early detection of CKD progression in children. In newborns and children of early and older age, hypertension occurs due to renovascular and parenchymal diseases.AH is considered a marker of CKD severity and is a risk factor for progressive deterioration of kidney function, as well as thedevelopment of cardiovascular diseases. Sympathetic hyperactivity, excessive formation of free radicals, reduced bioavailability of nitric oxide (NO) and excessive production of angiotensin II leads to an increase in blood pressure. Obesity or an increase in body mass index (BMI) is currently considered as a risk factor not only for cardiovascular diseases and diabetes but also for CKD. Hyperuricemia and CKD are closely related, as the accumulation of uric acid is associated with hypertension, metabolic syndrome and microalbuminuria, which are also risk factors for the progression of CKD. AH has a detrimental effect on target organs, including the kidneys, eyes, and heart. Lifestyle modifications, weight control, healthy eating, reduced sodium intake, maintenance exercises and basic drug therapy using angiotensin-converting enzyme inhibitors (ACE inhibitors), angiotensin receptor blockers can slow the progression of CKD in children.

Mesenchymal stromal cells (Cyto-MSC) are well-tolerated and associated with renal function improvement in patients with chronic kidney disease: an observational retrospective study

Background & Aim Background Microvascular disease and structural damage are hallmarks of chronic kidney disease (CKD). We have demonstrated previously that mesenchymal stromal cells (MSCs) could differentiate into mesangial cells in animal models of glomerular injury. We further demonstrated that MSCs promoted angiogenesis in diabetic patients with critical limb ischemia. Given the ability to improve vascularity and structure, MSCs may potentially improve renal function in CKD. Objective In this study, we evaluated the safety, tolerability and renal function of patients with CKD who had participated in MSC-related clinical trials. Methods, Results & Conclusion Methodology There were 4 clinical trials approved at the National University Malaysia in collaboration with Cytopeutics (Cyberjaya, Malaysia) which provided the mesenchymal stromal cells (Cyto-MSC) for treatment of acute stroke, heart failure, diabetes with critical limb ischemia and severe deforming osteoarthritis. All patients received 65-130 × 106 Cyto-MSC intravenously. Severity of chronic kidney disease is based on baseline estimated glomerular filtration rate (eGFR) and serum creatinine which are markers of renal dysfunction. These and other blood tests including fasting blood sugar (FBS) and Hba1c (marker of glycemic control) were measured at baseline and 12 months post infusion. Results 82 patients (53 men, 29 women; age 38-92 years) with different CKD stages (stage 3, n=65; stage 4, n=5; stage 5, n=12) were identified. 33 patients have type 2 diabetes. All patients tolerated the treatment well. There was significant improvement in serum creatinine (170±148 vs. 144±123 μmol/L; p=0.013) and eGFR values (37±17 vs. 41±18 mL/min/1.73m2; p=0.001). Patients with stage 3 CKD have the most significant eGFR value improvement (45±9 vs. 50±10 mL/min/1.73m2; p=0.006). Among diabetic patients, improvements were observed in creatinine (167±138 vs. 145±115 μmol/L, p=0.011), eGFR (37±15 vs. 41±16, p=0.05), HbA1c (7.4±2.1 vs. 6.2±1.4 %, p=0.011) and FBS (7.1±1.1 vs. 6.8±0.8 mmol/L %, p=0.021). There was also modest positive correlation between FBS with urea (p=0.001) and eGFR (p=0.016). Conclusion Cyto-MSC appears to be safe and well-tolerated by patients with moderate-severe CKD and associated with improvement in renal function particularly for moderate CKD patients. Further randomized prospective studies are warranted.

Correlation of Ultrasound Parameters with Serum Creatinine in Renal Parenchymal Disease

Introduction: Chronic kidney disease (CKD) is common cause of renal failure. It involves a progressive loss in the structure and function of the kidneys over the course of months, with or without decreased glomerular filtration rate (GFR). CKD can be diagnosed by its pathological abnormalities, changes in the levels of renal function markers in the blood or urine, or by imaging investigations (E.g. USG etc).&#x0D; Objectives: The purpose of our study is 1) To correlate renal echogenicity with serum creatinine in order to determine the significance of renal echogenicity for identifying the progression of chronic kidney disease (CKD) and for the sonographic grading of CKD, 2) To study association of blood pressure, renal cortical cysts and renal size with grade of chronic renal disease.&#x0D; Methods: This hospital based cross sectional study was carried out at National Kidney Centre, Banasthali Kathmandu. Two hundred patients above 20 years, diagnosed with CKD according to the guidelines of the National Kidney Foundation and referred for USG, were included in the study. Patients with kidney transplant, on dialysis, with liver disease and renal tumors were excluded. Ultrasound of kidneys was performed by senior consultant radiologist who was blind to the patients’ serum creatinine levels. The relationship between grade of CKD with serum creatinine, kidney size, blood pressure and cortical cysts were assessed. Statistical analysis was performed by Kruskal wallis test using SPSS version 17. P values less than 0.05 were considered statistically significant.&#x0D; Results: Mean serum creatinine was 1.7 mg/dl for Grade 1 (range: 1.1- 4.7 mg/dl, STD 0.44), 2.38 mg/dl for Grade 2 (range: 1.8-3.9 mg/dl STD 0.40), 4.18 mg/dl for Grade 3 (range: 2.6-6.0 mg/dl, STD 0.88), and 5.65 mg/dl for Grade 4 (range: 3.1-12 mg/dl, STD 2.0.&#x0D; Conclusion: Renal echogenicity and its grading correlates better with serum creatinine in CKD than other sonographic parameters. Hence, renal echogenicity is a better parameter than serum creatinine for estimating renal function in CKD, and has the added advantage of irreversibility.

Urotensin II in the development and progression of chronic kidney disease following ⅚ nephrectomy in the rat.

New Findings What is the central question of this study? Urotensin II is upregulated in patients in the later stages of chronic kidney disease (CKD), particularly in individuals requiring dialysis. Could treatment with a urotensin II receptor antagonist slow progression of renal disease? What is the main finding and its importance? In the rat, expression of urotensin II and its receptor increased, extending into cortical structures as CKD progressed towards end‐stage renal failure. Subchronic treatment with a urotensin receptor antagonist slowed but did not prevent progression of CKD. This suggests that urotensin II contributes to the decline in renal function in CKD. Elevated serum and urine urotensin II (UII) concentrations have been reported in patients with end‐stage chronic kidney disease (CKD). Similar increases in UII and its receptor, UT, have been reported in animal models of CKD, but only at much earlier stages of renal dysfunction. The aim of this study was to characterize urotensin system expression as renal disease progresses to end‐stage failure in a ⅚ subtotal nephrectomy (SNx) rat model. Male Sprague–Dawley rats underwent SNx or sham surgery and were killed at 8 weeks postsurgery [early (E)] or immediately before end‐stage renal failure [30 ± 3 weeks postsurgery; late (L)]. Systolic blood pressure, urinary albumin:creatinine ratio and glomerulosclerosis index were all increased in SNx‐E rats compared with sham‐E by 8 weeks postsurgery. These changes were associated with an increase in renal immunoreactive UII staining but little change in UT expression. As CKD progressed to end‐stage disease in the SNx‐L group, markers of renal function deteriorated further, in association with a marked increase in immunoreactive UII and UT staining. Subchronic administration of a UT antagonist, SB‐611812, at 30 mg kg−1 day−1 for 13 weeks, in a separate group of SNx rats resulted in a 2 week delay in the increase in both systolic blood pressure and urinary albumin:creatinine ratio observed in vehicle‐treated SNx but did not prevent the progression of renal dysfunction. The urotensin system is upregulated as renal function deteriorates in the rat; UT antagonism can slow but not prevent disease progression, suggesting that UII plays a role in CKD.

Sitagliptin and shock wave-supported peripheral blood derived endothelial progenitor cell therapy effectively preserves residual renal function in chronic kidney disease in rat—role of dipeptidyl peptidase 4 inhibition

This study tested whether sitagliptin and shock wave (SW)-assisted circulatory-derived autologous endothelial progenitor cell (EPC) therapy would effectively preserve residual renal function in chronic kidney disease (CKD) induced by 5/6 left-nephrectomy/remove right kidney plus daily feeding high-protein diet (HPD) in rat. Adult-male SD rats (n = 40) were categorized into group 1 (sham-operated control with HPD), group 2 (HPD-CKD), group 3 [HPD-CKD + EPC (1.2 × 106 cell)/intra-vessel administration by day 14 after CKD-induction], group 4 [HPD-CKD + SW (0.12 mJ/mm2/180 shorts) at days 14/21/28 after CKD-induction by ultrasound-guided application] and group 5 [HPD-CKD + SW + EPC + sitagliptin (Sita; 600 mg/kg/day since day 14 after CKD induction)]. All animals were euthanized by day 60. By day 60, renal blood flow (RBF) was highest in group 1 and progressively increased from groups 2 to 5, whereas the levels of creatinine/BUN/proteinuria exhibited an opposite pattern of RBF among the five groups (all p < 0.001). The circulating levels of GLP-1/SDF-1α and protein levels of angiogenesis (VEGF/SDF-1α/CXCR4) and GLP-1R in kidney were progressively increased from groups 1 to 5, whereas circulating DPP4 activity exhibited an opposite pattern of SDF-1α among the groups (all p < 0.0001). The protein expressions of oxidative-stress (NOX-1/NOX-2/oxidized protein), apoptosis (Bax/caspase-3/PARP), fibrosis (Smad3/TGF-ß) and inflammation (TNF-α/NF-κB/MMP-2) and kidney injury score displayed an opposite pattern, whereas the protein expressions of TMP2, endothelial-cell markers (CD31/eNOS) and podocyte integrity biomarkers (podocin/ZO-1/synaptopodin) exhibited an identical pattern of RBF among the groups (all p < 0.001). In conclusion Sita associated SW-assisted EPC effectively protected residual renal function in CKD.

Serum Trimethylamine-N-Oxide Is Strongly Related to Renal Function and Predicts Outcome in Chronic Kidney Disease.

BackgroundThe microbial metabolite Trimethylamine-N-oxide (TMAO) has been linked to adverse cardiovascular outcome and mortality in the general population.ObjectiveTo assess the contribution of TMAO to inflammation and mortality in chronic kidney disease (CKD) patients ranging from mild-moderate to end-stage disease and 1) associations with glomerular filtration rate (GFR) 2) effect of dialysis and renal transplantation (Rtx) 3) association with inflammatory biomarkers and 4) its predictive value for all-cause mortality.MethodsLevels of metabolites were quantified by a novel liquid chromatography/tandem mass spectrometry-based method in fasting plasma samples from 80 controls and 179 CKD 3–5 patients. Comorbidities, nutritional status, biomarkers of inflammation and GFR were assessed.ResultsGFR was the dominant variable affecting TMAO (β = -0.41; p<0.001), choline (β = -0.38; p<0.001), and betaine (β = 0.45; p<0.001) levels. A longitudinal study of 74 CKD 5 patients starting renal replacement therapy demonstrated that whereas dialysis treatment did not affect TMAO, Rtx reduced levels of TMAO to that of controls (p<0.001). Following Rtx choline and betaine levels continued to increase. In CKD 3–5, TMAO levels were associated with IL-6 (Rho = 0.42; p<0.0001), fibrinogen (Rho = 0.43; p<0.0001) and hsCRP (Rho = 0.17; p = 0.022). Higher TMAO levels were associated with an increased risk for all-cause mortality that remained significant after multivariate adjustment (HR 4.32, 95% CI 1.32–14.2; p = 0.016).ConclusionElevated TMAO levels are strongly associated with degree of renal function in CKD and normalize after renal transplantation. TMAO levels correlates with increased systemic inflammation and is an independent predictor of mortality in CKD 3–5 patients.

Correlation of ultrasonographic parameters with serum creatinine in chronic kidney disease.

Objective:The purpose of our study is to correlate renal echogenicity with serum creatinine in order to determine the significance of renal echogenicity when it comes to identifying the progression of chronic kidney disease (CKD) and for the sonographic grading of CKD.Materials and Methods:Sixty patients above 30 years of age who had been diagnosed with CKD according to the guidelines of the National Kidney Foundation were included in the study. Patients on kidney replacement therapy or with fatty liver findings on ultrasonography were excluded. Ultrasounds of kidneys were performed by two radiologists who were blind to the patients’ serum creatinine levels. Renal cortical echogenicity was compared with serum creatinine. Statistical analysis was performed using one-way ANOVA followed by Scheffe's test. The relationship between serum creatinine and sonographic features was assessed by correlation coefficient analysis. A P value less than 0.05 was considered statistically significant.Results:Mean serum creatinine was 2.80 mg/dl for Grade 1 (range: 0.9-9.2 mg/dl), 3.69 mg/dl for Grade 2 (range: 1.2-10.3 mg/dl), 3.86 mg/dl for Grade 3 (range: 1.1-6.5 mg/dl), and 7.90 mg/dl for Grade 4 (range: 3.1-11.4 mg/dl). The grades being determined by cortical echogenicity on imaging A statistically significant, positive correlation was observed between serum creatinine and grading based on cortical echogenicity (P = 0.004).Conclusion:Renal echogenicity and its grading correlates better with serum creatinine in CKD than other sonographic parameters such as longitudinal size, parenchymal thickness, and cortical thickness. Hence, renal echogenicity is a better parameter than serum creatinine for estimating renal function in CKD, and has the added advantage of irreversibility.