scholarly journals PNPLA3 gene and kidney disease

2020 ◽  
Vol 1 (1) ◽  
pp. 42-50 ◽  
Author(s):  
Alessandro Mantovani ◽  
Chiara Zusi
Keyword(s):  
Kidney Disease ◽  
Association Studies ◽  
Liver Steatosis ◽  
Kidney Injury ◽  
Future Perspective ◽  
Genome Wide Association Studies ◽  
Alcoholic Fatty Liver ◽  
Liver And Kidney ◽  
Stage Renal Disease ◽  
End Stage

Chronic kidney disease (CKD) is a disease regularly seen in clinical practice. At present, CKD is described as a change of kidney structure and/or function and it is classified in relation to cause, values of glomerular filtration rate and albuminuria category. Seeing that CKD is closely linked to the development of end-stage renal disease and other comorbidities, the determination of additional independent predictors for CKD is clinically necessary. At present, there is evidence associating non-alcoholic fatty liver disease (NAFLD) with CKD, thereby suggesting that NAFLD patients may require intensive surveillance to reduce their risk of CKD. In 2008, genome-wide association studies documented an association between the variant rs738409 (C > G p.I148M) in the patatin-like phospholipase domain containing 3 (PNPLA3) gene (mainly implicated in the lipid regulation) and the entire spectrum of NAFLD (i.e., liver steatosis, non-alcoholic steatohepatitis, fibrosis, and hepatocellular carcinoma). In the last years, accumulating epidemiological evidence suggests the existence of a relationship between PNPLA3 rs738409 and risk of CKD, indicating that rs738409 may also contribute to the kidney injury. This is of particular scientific interest, as such association may explain, at least in part, the epidemiological association between liver and kidney disease. In this narrative review, we will discuss the accumulating evidence regarding the association between PNPLA3 rs738409 and risk of CKD, the putative biological mechanisms underpinning such relationship, and the possible future perspective.

scholarly journals Polymorphism in the GATM Locus Associated with Dialysis-Independent Chronic Kidney Disease but Not Dialysis-Dependent Kidney Failure

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 834
Author(s):  
Špela Šalamon ◽  
Sebastjan Bevc ◽  
Robert Ekart ◽  
Radovan Hojs ◽  
Uroš Potočnik
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Kidney Failure ◽  
Association Studies ◽  
Genetic Difference ◽  
Genome Wide Association Studies ◽  
Healthy Controls ◽  
Genome Wide ◽  
Stage Renal Disease ◽  
End Stage

The ten most statistically significant estimated glomerular filtration rate (eGFRcrea)-associated loci from genome-wide association studies (GWAs) are tested for associations with chronic kidney disease (CKD) in 208 patients, including dialysis-independent CKD and dialysis-dependent end-stage renal disease (kidney failure). The allele A of intergenic SNP rs2453533 (near GATM) is more frequent in dialysis-independent CKD patients (n = 135, adjusted p = 0.020) but not dialysis-dependent kidney failure patients (n = 73) compared to healthy controls (n = 309). The allele C of intronic SNP rs4293393 (UMOD) is more frequent in healthy controls (adjusted p = 0.042) than in CKD patients. The Allele T of intronic SNP rs9895661 (BCAS3) is associated with decreased eGFRcys (adjusted p = 0.001) and eGFRcrea (adjusted p = 0.017). Our results provide further evidence of a genetic difference between dialysis-dialysis-independent CKD and dialysis-dependent kidney failure, and add the GATM gene locus to the list of loci associated only with dialysis-independent CKD. GATM risk allele carriers in the dialysis-independent group may have a genetic susceptibility to higher creatinine production rather than increased serum creatinine due to kidney malfunction, and therefore, do not progress to dialysis-dependent kidney failure. When using eGFRcrea for CKD diagnosis, physicians might benefit from information about creatinine-increasing loci.

scholarly journals High Elmo1 expression aggravates and low Elmo1 expression prevents diabetic nephropathy

2016 ◽  
Vol 113 (8) ◽  
pp. 2218-2222 ◽  
Author(s):  
Catherine K. Hathaway ◽  
Albert S. Chang ◽  
Ruriko Grant ◽  
Hyung-Suk Kim ◽  
Victoria J. Madden ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Transforming Growth Factor ◽  
Association Studies ◽  
Lipid Peroxides ◽  
Transforming Growth Factor Β1 ◽  
Genome Wide Association Studies ◽  
Diabetic Mice ◽  
Stage Renal Disease ◽  
End Stage

Human genome-wide association studies have demonstrated that polymorphisms in the engulfment and cell motility protein 1 gene (ELMO1) are strongly associated with susceptibility to diabetic nephropathy. However, proof of causation is lacking. To test whether modest changes in its expression alter the severity of the renal phenotype in diabetic mice, we have generated mice that are type 1 diabetic because they have the Ins2Akita gene, and also have genetically graded expression of Elmo1 in all tissues ranging in five steps from ∼30% to ∼200% normal. We here show that the Elmo1 hypermorphs have albuminuria, glomerulosclerosis, and changes in the ultrastructure of the glomerular basement membrane that increase in severity in parallel with the expression of Elmo 1. Progressive changes in renal mRNA expression of transforming growth factor β1 (TGFβ1), endothelin-1, and NAD(P)H oxidase 4 also occur in parallel with Elmo1, as do the plasma levels of cystatin C, lipid peroxides, and TGFβ1, and erythrocyte levels of reduced glutathione. In contrast, Akita type 1 diabetic mice with below-normal Elmo1 expression have reduced expression of these various factors and less severe diabetic complications. Remarkably, the reduced Elmo1 expression in the 30% hypomorphs almost abolishes the pathological features of diabetic nephropathy, although it does not affect the hyperglycemia caused by the Akita mutation. Thus, ELMO1 plays an important role in the development of type 1 diabetic nephropathy, and its inhibition could be a promising option for slowing or preventing progression of the condition to end-stage renal disease.

Renal medicine

2021 ◽  
pp. 353-382
Author(s):  
Gopesh K. Modi ◽  
Vivekanand Jha
Keyword(s):  
Kidney Disease ◽  
Renal Disease ◽  
Rapidly Progressive Glomerulonephritis ◽  
Kidney Injury ◽  
Renal Stones ◽  
Renal Diseases ◽  
Acute Glomerulonephritis ◽  
Glomerular Diseases ◽  
Stage Renal Disease ◽  
End Stage

Assessing renal function, Urinalysis, Proteinuria, Hematuria, Chyluria, Imaging in renal disease, Kidney biopsy, Acute Kidney Injury (AKI), Chronic Kidney Disease (CKD), Diabetic Nephropathy, End Stage Renal Disease and Dialysis, Kidney Transplantation, Glomerular diseases, Acute glomerulonephritis, Urinary schistosomiasis (bilharzia), Infections and Kidney Disease, Rapidly Progressive glomerulonephritis, Tubulointerstitial Disease, Urinary Tract Infection, Vesico-ureteric reflux, Renal Stones, Renal Disease in Pregnancy, Renal Artery Stenosis, Renal Mass, Inherited Renal Diseases

Management of acute kidney injury and chronic kidney disease

2017 ◽  
pp. 1087-1096
Author(s):  
Natalie Ebert ◽  
Elke Schaeffner
Keyword(s):  
Older Adults ◽  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Kidney Injury ◽  
Staging System ◽  
Kidney Damage ◽  
The Right ◽  
Stage Renal Disease ◽  
End Stage

Both acute and chronic states of kidney disease have considerable healthcare impact as they can produce enormous disease burden and costs. To classify chronic kidney disease into the CKD staging system, glomerular filtration rate as an index of kidney function, as well as albuminuria as a marker of kidney damage have to be assessed as correctly as possible. Misclassification is a serious concern due to the difficulties in precise GFR assessment and correct interpretation of results. Differentiating between pure senescence and true disease among older adults can be a delicate issue. To find the right renal replacement option for individuals that progress to end-stage renal disease can be challenging, and some older patients may even benefit from conservative care without dialysis. To prevent acute kidney injury as a frequent and potentially life-threatening complication, clinicians need to develop an understanding of the common vulnerability to kidney damage among older adults.

scholarly journals PROTON PUMP INHIBITORS AND THE RISK OF CHRONIC KIDNEY DISEASES: A CRITICAL REVIEW

2020 ◽  
pp. 11-14
Author(s):  
SHAREEF J. ◽  
SRIDHAR S. B. ◽  
SHARIFF A.
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
End Stage Renal Disease ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Stage Renal Disease ◽  
End Stage

Proton pump inhibitors (PPIs) are most widely used medications for acid related gastrointestinal disorders. Accessible evidence based studies suggest that the increased use of PPI is linked to a greater risk of developing kidney diseases. This review aims to determine the association of kidney disease with the use of proton pump inhibitor with various study designs. PubMed, Scopus and Google Scholar databases as well as a reference list of relevant articles were systematically searched for studies by using the following search terms; ‘proton pump inhibitors’, ‘acute kidney injury’, ‘chronic kidney disease’ and ‘end stage renal disease’. Both observational and randomized controlled trials (RCTs) exploring the association of PPI use with kidney disease were eligible for inclusion. A total of 8 articles, including 9 studies (n = 794,349 participants) were identified and included in the review. Majority of the studies showed a higher risk of kidney outcomes in patients taking PPIs, with effect higher of acute kidney injury (4-to 6-fold) compared with chronic kidney disease and end stage renal disease (1.5-to 2.5-fold). However, the studies suggest that the strength of evidence is weak and could not prove causation. The risk increased considerably with the use of high dose of PPIs and prolonged duration of exposure necessitates the monitoring of renal function. Exercising vigilance in PPI use and cessation of proton pump inhibitor when there is no clear indication may be a reasonable approach to reduce the population burden of kidney diseases.

scholarly journals Microvascular rarefaction and hypertension in the impaired recovery and progression of kidney disease following AKI in preexisting CKD states

2018 ◽  
Vol 315 (6) ◽  
pp. F1513-F1518 ◽  
Author(s):  
Aaron J. Polichnowski
Keyword(s):  
Kidney Disease ◽  
Renal Disease ◽  
Kidney Injury ◽  
Major Complication ◽  
Progression Of Kidney Disease ◽  
Underlying Mechanisms ◽  
Stage Renal Disease ◽  
End Stage ◽  
Progression Of Renal Disease ◽  
Microvascular Rarefaction

Acute kidney injury (AKI) is a major complication in hospitalized patients and is associated with elevated mortality rates. Numerous recent studies indicate that AKI also significantly increases the risk of chronic kidney disease (CKD), end-stage renal disease (ESRD), hypertension, cardiovascular disease, and mortality in those patients who survive AKI. Moreover, the risk of ESRD and mortality after AKI is substantially higher in patients with preexisting CKD. However, the underlying mechanisms by which AKI and CKD interact to promote ESRD remain poorly understood. The recently developed models that superimpose AKI on rodents with preexisting CKD have provided new insights into the pathogenic mechanisms mediating the deleterious interactions between AKI and CKD. These studies show that preexisting CKD impairs recovery from AKI and promotes the development of mechanisms of CKD progression. Specifically, preexisting CKD exacerbates microvascular rarefaction, failed tubular redifferentiation, disruption of cell cycle regulation, hypertension, and proteinuria after AKI. The purpose of this review is to discuss the potential mechanisms by which microvascular rarefaction and hypertension contribute to impaired recovery from AKI and the subsequent progression of renal disease in preexisting CKD states.

scholarly journals Clinical Presentation, Renal Histopathological Findings, and Outcome in Patients with Monoclonal Gammopathy and Kidney Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Gaetano Alfano ◽  
Alice Delrio ◽  
Francesco Fontana ◽  
Giacomo Mori ◽  
Silvia Cazzato ◽  
...  
Keyword(s):  
Kidney Disease ◽  
End Stage Renal Disease ◽  
Monoclonal Gammopathy ◽  
Kidney Biopsy ◽  
Clinical Manifestations ◽  
Kidney Injury ◽  
M Protein ◽  
Monoclonal Gammopathies ◽  
Stage Renal Disease ◽  
End Stage

Monoclonal gammopathies are associated with acute and chronic kidney injury. Nephrotoxicity of the secreted monoclonal (M)-protein is related to its biological properties and blood concentration. Little is known about epidemiology, clinical manifestations, and outcome of monoclonal gammopathies in patients with kidney disease. We retrospectively collected data about demographics, clinical manifestations, and renal histological lesions of all patients (n = 1334) who underwent kidney biopsy between January 2000 and March 2017. Monoclonal gammopathy was detected in 174 (13%) patients with a mean age of 66.4 ± 13.1 years. The spectrum of monoclonal gammopathies comprised monoclonal gammopathy of undetermined significate (MGUS) (52.8%), multiple myeloma (MM) (25.2%), primary amyloidosis (AL) (9.1%), smoldering MM (SMM) (4%), non-Hodgkin lymphoma (NHL) (6.8%), and Hodgkin lymphoma (HL) (1.7%). Monoclonal gammopathy of renal significance (MGRS) accounted for 6.5% in patients with MGUS and 14.2% in patients with SMM. Evaluation of kidney biopsy revealed that M-protein was directly involved in causing kidney injury in MM (93.1%). MM was the only gammopathy significantly associated with an increased risk of kidney injury (odds ratio [OR] = 47.5, CI 95%, 13.7–164.9; P ≤ 0.001 ). While there were no significant differences in the progression toward end-stage renal disease or dialysis P = 0.776 , monoclonal gammopathies were associated with a different risk of death P = 0.047 at the end of the follow-up. In conclusion, monoclonal gammopathy was a frequent finding (13%) in patients who underwent kidney biopsy. M-protein was secreted by both premalignant (56.8%) and malignant (43.2%) lymphoproliferative clones. Kidney biopsy had a key role in identifying MGRS in patients with MGUS (6.5%) and SMM (14.2%). Among monoclonal gammopathies, only MM was significantly associated with biopsy-proven kidney injury. The rate of end-stage renal disease or dialysis was similar among monoclonal gammopathies, whereas NHL, MM, and SMM showed a higher rate of deaths.

scholarly journals Urine Osmolarity and Risk of Dialysis Initiation in a CKD Cohort

2015 ◽  
Vol 66 (Suppl. 3) ◽  
pp. 14-17 ◽  
Author(s):  
Lise Bankir ◽  
Max Plischke ◽  
Nadine Bouby ◽  
Martin Haas
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Association Studies ◽  
Experimental Studies ◽  
Dialysis Initiation ◽  
Hazards Model ◽  
Baseline Creatinine ◽  
Stage Renal Disease ◽  
End Stage ◽  
Disease Stages

Background: Several experimental studies in rats and a few association studies in humans suggest that the antidiuretic action of vasopressin may accelerate the progression of chronic kidney disease. We undertook a retrospective analysis in a monocentric cohort of 273 patients with chronic kidney disease stages 1-4, focusing on a strong variable of interest, urinary osmolarity, and a strong endpoint, dialysis initiation. Data was analyzed in a multivariate proportional sub-distribution hazards model for competing risk data with appropriate co-variates. Main Results: Over a median follow-up period of 92 months, dialysis was initiated in 105 patients. After adjustments for baseline creatinine clearance, and other confounding factors, a higher risk for initiation of dialysis was found in patients with higher urinary osmolarity. After 72 months, the estimated adjusted cumulative incidence probability for dialysis initiation was 15, 24, and 34% in patients with baseline urinary osmolarity of 315, 510, and 775 mosm/l, respectively (p = 0.033). Key Messages: In this retrospective, longitudinal study, a higher baseline urinary osmolarity was strongly associated with a higher risk of end-stage renal disease (after appropriate adjustments). Further, prospective studies are required to evaluate the possible benefit of interventions aiming at reducing urinary osmolarity as a potential treatment for slowing chronic kidney disease progression.

scholarly journals Found in Translation: Reasons for Optimism in the Pursuit to Prevent Chronic Kidney Disease After Acute Kidney Injury

2019 ◽  
Vol 6 ◽  
pp. 205435811986874
Author(s):  
Samuel A. Silver ◽  
Casimiro Gerarduzzi
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Animal Models ◽  
Kidney Injury ◽  
Narrative Review ◽  
Sources Of Information ◽  
Stage Renal Disease ◽  
End Stage ◽  
Injury Progression

Purpose of review: The current review will discuss on the progress of studying the transition phase between acute kidney injury (AKI) and chronic kidney disease (CKD) through improved animal models, common AKI and CKD pathways, and how human studies may inform different translational approaches. Sources of information: PubMed and Google Scholar. Methods: A narrative review was performed using the main terms “acute kidney injury,” “chronic kidney disease,” “end-stage renal disease,” “animal models,” “review,” “decision-making,” and “translational research.” Key findings: The last decade has shown much progress in the study of AKI, including evidence of a pathophysiological link between AKI and CKD. We are now in a phase of redesigning animal models and discovering mechanisms that can replicate the pathological conditions of the AKI-to-CKD continuum. Translating these findings into the clinic is a barrier that must be overcome. To this end, current efforts include prediction of AKI onset and maladaptive repair, detecting patients susceptible to the progression of chronic maladaptive repair, and understanding shared signaling mechanisms between AKI and CKD. Limitations: This is a narrative review of the literature that is partially influenced by the knowledge, perspectives, and experiences of the authors and their research background. Implications: Overall, this new knowledge from the AKI-to-CKD continuum will help bridge the discontinuity that exists between animal models and patients, resulting in more effective translational biomarkers and therapeutics to test in known AKI pathologies thereby preventing the chronicity of kidney injury progression.

scholarly journals The genetic architecture of NAFLD among inbred strains of mice

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Simon T Hui ◽  
Brian W Parks ◽  
Elin Org ◽  
Frode Norheim ◽  
Nam Che ◽  
...  
Keyword(s):  
Hepatic Steatosis ◽  
Association Studies ◽  
Inbred Mouse ◽  
Liver Steatosis ◽  
Inbred Strains ◽  
Mouse Strains ◽  
Genome Wide Association Studies ◽  
Alcoholic Fatty Liver ◽  
Genetic And Environmental Factors

To identify genetic and environmental factors contributing to the pathogenesis of non-alcoholic fatty liver disease, we examined liver steatosis and related clinical and molecular traits in more than 100 unique inbred mouse strains, which were fed a diet rich in fat and carbohydrates. A >30-fold variation in hepatic TG accumulation was observed among the strains. Genome-wide association studies revealed three loci associated with hepatic TG accumulation. Utilizing transcriptomic data from the liver and adipose tissue, we identified several high-confidence candidate genes for hepatic steatosis, including Gde1, a glycerophosphodiester phosphodiesterase not previously implicated in triglyceride metabolism. We confirmed the role of Gde1 by in vivo hepatic over-expression and shRNA knockdown studies. We hypothesize that Gde1 expression increases TG production by contributing to the production of glycerol-3-phosphate. Our multi-level data, including transcript levels, metabolite levels, and gut microbiota composition, provide a framework for understanding genetic and environmental interactions underlying hepatic steatosis.

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