Genetic analysis of albuminuria in a cross between C57BL/6J and DBA/2J mice

Chronic kidney disease (CKD) is a growing medical problem and a significant risk factor for the development of end-stage renal disease, cardiovascular disease, and cardiovascular mortality. The genetic basis of CKD is recognized, but knowledge of the specific genes that contribute to the onset and progression of kidney disease is limited, mainly because of the difficulty and expense of identifying genes underlying CKD in humans. Results from genetic studies of CKD in rodents often correspond to findings in humans; therefore, we used quantitative trait locus (QTL) analysis to detect genomic regions affecting albuminuria in a cross between C57BL/6J and DBA/2J mice, strains resistant and susceptible to CKD, respectively. We identified several independent and interacting loci affecting albuminuria, including one QTL on mouse chromosome (Chr) 2 that is concordant with QTL influencing urinary albumin excretion on rat Chr 3 and diabetic nephropathy on human Chr 20p. Because this QTL was identified in multiple mouse crosses, as well as in rats and in humans, we used comparative genomics, haplotype analysis, and expression profiling to narrow the initial QTL interval from 386 genes to 10 genes with known coding sequence polymorphisms or expression differences between the strains. These results support the continued use of multiple cross-mapping and cross-species comparisons to further our understanding of the genetic basis of kidney disease.

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Novel differences in renal gene expression in a diet-induced obesity model

AJP Renal Physiology ◽

10.1152/ajprenal.00345.2017 ◽

2018 ◽

Vol 314 (4) ◽

pp. F517-F530 ◽

Cited By ~ 5

Author(s):

Victoria L. Halperin Kuhns ◽

Jennifer L. Pluznick

Keyword(s):

Renal Cortex ◽

Significant Risk ◽

Significant Risk Factor ◽

Differentially Expressed ◽

Diet Induced Obesity ◽

Transcriptional Changes ◽

Stage Renal Disease ◽

End Stage ◽

Upregulated Genes

Obesity is a significant risk factor for both chronic kidney disease and end-stage renal disease. To better understand disease development, we sought to identify novel genes differentially expressed early in disease progression. We first confirmed that mice fed a high-fat (HF) diet exhibit early signs of renal injury including hyperfiltration. We then performed RNA-Seq using renal cortex RNA from C57BL6/J male mice fed either HF or control (Ctrl) diet. We identified 1,134 genes differentially expressed in the cortex on HF vs. Ctrl, of which 31 genes were selected for follow-up analysis. This included the 9 most upregulated, the 11 most downregulated, and 11 genes of interest (primarily sensory receptors and G proteins). Quantitative (q)RT-PCR for these 31 genes was performed on additional male renal cortex and medulla samples, and 11 genes (including all 9 upregulated genes) were selected for further study based on qRT-PCR. We then examined expression of these 11 genes in Ctrl and HF male heart and liver samples, which demonstrated that these changes are relatively specific to the renal cortex. These 11 genes were also examined in female renal cortex, where we found that the expression changes seen in males on a HF diet are not replicated in females, even when the females are started on the diet sooner to match weight gain of the males. In sum, these data demonstrate that in a HF-diet model of early disease, novel transcriptional changes occur that are both sex specific and specific to the renal cortex.

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

AJP Renal Physiology ◽

10.1152/ajprenal.00419.2018 ◽

2018 ◽

Vol 315 (6) ◽

pp. F1513-F1518 ◽

Cited By ~ 7

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.

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P1009RENAL OUTCOMES IN DIABETIC KIDNEY PATIENTS TREATED WITH GLP1 AGONIST RECEPTORS VS SGLT2 INHIBITORS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p1009 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Alba Maroto ◽

Maria Marques Vidas ◽

Ignacio Sanz ◽

Paula López ◽

Jose' M Portoles

Keyword(s):

Kidney Disease ◽

Renal Disease ◽

Renal Outcomes ◽

Arterial Blood ◽

Gastrointestinal Intolerance ◽

Progression Of Kidney Disease ◽

Risk Patients ◽

Stage Renal Disease ◽

End Stage

Abstract Background and Aims End stage renal disease of diabetic cause is an increasing issue worldwide. Both GLP1 antagonist receptors (GLP1ar) and the sodium-glucose co-transporter 2 inhibitors (SGLT2i) have shown promising results in preventing or ameliorating the progression of renal disease, however there is no data comparing the effect of both drugs on renal outcomes. Method Here we present the result of a retrospective study analyzing the main renal outcomes of 98 T2DM patients treated with GLP1ar (25% dulaglutide, 25% liraglutide, 50% semaglutide) or SLGT2 (46.9% dapagliflozin, 21% empagliflozin, 32.1% canagliflozin). All participants were on ACEi/ARB on maximally tolerated dose and patients that have been on both treatments at any time during observation period were excluded. Mean follow-up was 1,9 years, (SD 1,1). Results Main descriptive data are shown on the table: in summary, patients on SGLT2i had higher eGFR (64,7 SD 22,7 vs 43,7 SD 13,5) ml/min/1,73m2 (p<0.001), lower BMI (30,2 SD 4,8 vs 35,0 SD 4,0 p<0,001) and were more frequently free from previous cardiovascular events (60% vs 29,4%, p 0,02)Incident kidney disease defined as drop of eGFR below 60 ml/min/1,73m2 and/or new onset albuminuria occurred on 18 (39,1%) and 7 (87,5%) of patients on SGLT2i and GLP1ar respectively (p 0,01), however, nor SGLT2i or GLP1ar treated patients suffered significant decrease on eGFR along the study period (2.5% change in eGFR-SGLT2i and 5% in GLP1ar). We found no significant differences on arterial blood pressure or glycemic control along the study period and BMI decrease was only significative on GLP1ar patients (-7,7%, p<0.001)6,7% and 15,8% of patients treated with GLP1ar and SGLT2i respectively suffered one CV event along the follow-up period (p ns) with 6,7% deaths on both groups (0.03 death/patient-year). Adverse events were similar on both groups though discontinuation rate was higher on SGLT2i (16,7% gastrointestinal intolerance, 58% “others”) Conclusion We conclude that both GLP1ar and SGLT2i prevent progression of kidney disease in T2DM patients. Though GLP1ar patients showed higher rates of incident kidney disease, when initiated on already decreased GFR this treatment achieved similar results to SGLT2i in preventing progression of kidney disease even in high cardiovascular risk patients.

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Social Environmental Stressors, Psychological Factors, and Kidney Disease

Journal of Investigative Medicine ◽

10.2310/jim.0b013e31819dbb91 ◽

2009 ◽

Vol 57 (4) ◽

pp. 583-589 ◽

Cited By ~ 59

Author(s):

Marino A. Bruce ◽

Bettina M. Beech ◽

Mario Sims ◽

Tony N. Brown ◽

Sharon B. Wyatt ◽

...

Keyword(s):

Risk Factors ◽

Health Disparities ◽

Kidney Disease ◽

Renal Disease ◽

End Stage Renal Disease ◽

Social Epidemiology ◽

Disease Risk ◽

Progression Of Kidney Disease ◽

Stage Renal Disease ◽

End Stage

Kidney disease is one of the most striking examples of health disparities in American public health. Disparities in the prevalence and progression of kidney disease are generally thought to be a function of group differences in the prevalence of kidney disease risk factors such as diabetes, hypertension, and obesity. However, the presence of these comorbidities does not completely explain the elevated rate of progression from chronic kidney disease (CKD) to end-stage renal disease among high-risk populations such as African Americans. We believe that the social environment is an important element in the pathway from CKD risk factors to CKD and end-stage renal disease. This review of the literature draws heavily from social science and social epidemiology to present a conceptual frame specifying how social, economic, and psychosocial factors interact to affect the risks for and the progression of kidney disease.

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Chronic Kidney Disease: Highlights for the General Pediatrician

International Journal of Pediatrics ◽

10.1155/2012/943904 ◽

2012 ◽

Vol 2012 ◽

pp. 1-5 ◽

Cited By ~ 1

Author(s):

Raymond Quigley

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Pediatric Population ◽

Critical Role ◽

Vitamin D Metabolism ◽

General Pediatrician ◽

Organ Systems ◽

Progression Of Kidney Disease ◽

Stage Renal Disease ◽

End Stage

Chronic kidney disease in the pediatric population has been increasing. Early detection and treatment can slow down the progression of kidney disease and help prevent the development of end stage renal disease. In addition, as the kidney function declines, there are many pathophysiologic interactions with other organ systems that need to be monitored and treated. In particular, because of impaired vitamin D metabolism, calcium and phosphorus homeostasis is dysregulated and results in secondary bone disease. Anemia is common due to a number of factors including impaired erythropoietin production. Growth is often impacted by chronic kidney disease but can be improved by proper treatment. Complications of chronic kidney disease can be minimized by proper monitoring and treatment of these parameters. The general pediatrician plays a critical role in this process.

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PREVALENCE OF ANEMIA IN CHRONIC KIDNEY DISEASE PATIENTS

International Journal of Medical and Biomedical Studies ◽

10.32553/ijmbs.v5i2.1742 ◽

2021 ◽

Vol 5 (2) ◽

Author(s):

Asma Ismail Alismail

Keyword(s):

Chronic Kidney Disease ◽

Standard Deviation ◽

Kidney Disease ◽

Significant Risk ◽

Public Health Problem ◽

Premature Death ◽

Significant Risk Factor ◽

The Mean ◽

End Stage ◽

Prevalence Of Anemia

Background: Chronic kidney disease (CKD), defined as renal damage with persistent and usually progressive deterioration of ultrafiltration, is a worldwide public health problem. Is considered as a significant risk factor for end-stage renal disease, anemia, cardiovascular disease, and premature death. The aging of the population and the generally increasing rates of obesity, hypertension, and diabetes worldwide suggest that the incidence and prevalence of CKD will rise over the next decades. Materials and Method: The data will consider all patients visiting outpatient’s department at the primary health center attached to King Faisal University in Al-Ahsa between 1st January 2010 and 31st December 2011. From the patients` files, we was record the age, gender, GFR, stages of CKD and state of anemia. Results: In this study, 49.3% of participants were male, and 50.7% was female—only 2.6% of participants on hemodialysis. The prevalence of anemia among the participants in our study was 55.5%. According to the results of the participants in this research, the mean age was 57.82, with a standard deviation of 17.067. The mean Hemoglobin of the participants was 11.775, with a standard deviation of 2.5334. The mean results of the participants by using CKD-EPI formula, to calculate GFR was 74.496 with a standard a deviation of 36.6787, which was the lowest mean of GFR. In Quadratic EGFR formula that was used to calculate GFR, the mean was 84.47 with a standard deviation of 35.677, which was the highest mean of GFR. DMRD formula was also used in this research to calculate the GFR, with a mean of 78.84 with a standard deviation of 50.371. Conclusions: In our data analysis, 100% of patients in the end stage of CKD had anemia although we used three different formulas to calculate GFR; however, the result was the same regarding patients in the end-stage. A surprising fact was found looking to other stages of CKD, and it is a correlation with anemia, the analysis of the data in this study did not show an increasing number of anemic patients to the stage of CKD in a stepwise manner. Keyword: Anemia, CKD, Al-Ahsa

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Urinary Protein and Peptide Markers in Chronic Kidney Disease

International Journal of Molecular Sciences ◽

10.3390/ijms222212123 ◽

2021 ◽

Vol 22 (22) ◽

pp. 12123

Author(s):

Natalia Chebotareva ◽

Anatoliy Vinogradov ◽

Valerie McDonnell ◽

Natalia V. Zakharova ◽

Maria I. Indeykina ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Renal Disease ◽

Significant Risk ◽

Significant Risk Factor ◽

Diagnostic Tools ◽

Renal Disease Progression ◽

Safe Alternative ◽

Stage Renal Disease ◽

Analytical Approaches

Chronic kidney disease (CKD) is a non-specific type of kidney disease that causes a gradual decline in kidney function (from months to years). CKD is a significant risk factor for death, cardiovascular disease, and end-stage renal disease. CKDs of different origins may have the same clinical and laboratory manifestations but different progression rates, which requires early diagnosis to determine. This review focuses on protein/peptide biomarkers of the leading causes of CKD: diabetic nephropathy, IgA nephropathy, lupus nephritis, focal segmental glomerulosclerosis, and membranous nephropathy. Mass spectrometry (MS) approaches provided the most information about urinary peptide and protein contents in different nephropathies. New analytical approaches allow urinary proteomic–peptide profiles to be used as early non-invasive diagnostic tools for specific morphological forms of kidney disease and may become a safe alternative to renal biopsy. MS studies of the key pathogenetic mechanisms of renal disease progression may also contribute to developing new approaches for targeted therapy.

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A Case Report of Neurotoxicity After Prolonged Doses of Acyclovir in a Patient With Renal Dysfunction

Journal of Pharmacy Practice ◽

10.1177/0897190018825033 ◽

2019 ◽

Vol 33 (2) ◽

pp. 217-221 ◽

Cited By ~ 1

Author(s):

Godsfavour O. Umoru ◽

Punit J. Shah ◽

Farheen Tariq

Keyword(s):

Renal Dysfunction ◽

Viral Infections ◽

Clinical Symptoms ◽

Plasma Concentrations ◽

Significant Risk ◽

Significant Risk Factor ◽

Serum Levels ◽

Drug Induced ◽

Stage Renal Disease ◽

End Stage

Renal dysfunction is a significant risk factor for acyclovir-induced neurotoxicity and altered mentation and myoclonic movements are the most common clinical symptoms observed. In majority of reported cases, neurological sequelae associated with acyclovir-induced neurotoxicity often mimic viral infections of the central nervous system and makes diagnosis of the former challenging. Although plasma concentrations of the drug may not always correlate with neurotoxic symptoms, obtaining serum levels of acyclovir may be helpful in confirming drug-induced neurotoxicity. Hemodialysis has been shown to significantly improve altered mentation in patients with suspected or confirmed acyclovir-induced neurotoxicity. Here, we report a definite case of acyclovir-induced neurotoxicity in a patient with end-stage renal disease. Clinical improvements in neurologic symptoms were observed following discontinuation of the drug and hemodialysis.

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Synopsis of Sweet! Mouse Models of Diabetic Kidney Disease

Toxicologic Pathology ◽

10.1177/0192623318799995 ◽

2018 ◽

Vol 46 (8) ◽

pp. 970-975 ◽

Cited By ~ 1

Author(s):

Kathleen M. Heinz-Taheny ◽

Shannon M. Harlan ◽

Zhonghua Qi ◽

Josef G. Heuer

Keyword(s):

Kidney Disease ◽

Mouse Models ◽

Diabetic Kidney Disease ◽

Standard Of Care ◽

Developed Countries ◽

Current Standard ◽

Diabetic Kidney ◽

Progression Of Kidney Disease ◽

Stage Renal Disease ◽

End Stage

Diabetes mellitus (types 1 and 2) is the leading cause of glomerular disease and end-stage renal disease in most developed countries, with estimates that one-third of people living with diabetes will develop diabetic kidney disease (DKD). The current standard of care medications slow but do not arrest progression of kidney disease, and therefore, therapy for DKD is a highly unmet medical need for patients. To discover and test novel and durable new therapies, it is necessary to develop animal models of human DKD, which authentically recapitulate the human disease state and provide translatable efficacy to human patients. Here, we review selected mouse models of human DKD, which demonstrate many of the features of type 2 human DKD.

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