Family History Of Chronic Kidney Disease Research Articles

#382 Unexpected diagnoses of ADTKD-MUC1 with the help of VNtyper

Abstract Background and Aims Autosomal dominant tubulointerstitial kidney disease (ADTKD) due to pathogenic variants in the MUC1 gene is difficult to diagnose since these variants lie in a large variable number tandem repeats (VNTR) and require specialized genetic testing, such as SNaPshot minisequencing. We recently developed a computational pipeline, VNtyper, for easier reliable detection of MUC1 VNTR pathogenic variants and have applied this tool to a large cohort of patients with various phenotypes of kidney disease. The aim of this study is to clinically describe patients in whom MUC1 pathogenic variants were unexpectedly detected with the help of VNtyper. Method We applied a computational pipeline, VNtyper, to a large cohort of patients with suspected hereditary kidney disease referred for genetic testing, regardless of their phenotype. This cohort included patients evaluated from 2017 to 2023 in the Molecular Genetics Department of Necker-Enfants Malades Hospital (Paris, France). Clinical characteristics were collected from patients in whom we detected new MUC1 VNTR pathogenic variants. Results 44 out of 3735 patients tested (1.2%) were newly diagnosed with a MUC1 pathogenic variant. Of these patients, ADTKD was clinically suspected in only 31 out of 44 patients (70%). In 2 patients, there was a pathogenic variant in another gene that could explain the phenotype, in addition to the MUC1 pathogenic variant. In fact, one 52-year-old patient had polycystic kidneys, nephrolithiasis, hematuria and normal kidney function. Her mother also had kidney cysts with absence of chronic kidney disease (CKD). This patient had a pathogenic variant in IFT140 gene (c.2399+1G>T) which could explain her autosomal dominant polycystic kidney disease (ADPKD) phenotype. Whether the MUC1 variant contributes to her disease remains unclear, especially seeing as her kidney function is normal at the age of 52 years. On the other hand, one patient had kidney cysts discovered at 3 days of age. A heterozygous HNF1B deletion was detected which could explain the phenotype. The following detection of a pathogenic MUC1 variant was thus an incidental finding and seemed de novo, although parents declined to get tested. These incidental findings can be challenging, especially when it comes to counselling and follow-up. There was no family history of kidney disease in 7 out of 44 patients (16%), and in one patient, we were able to confirm de novo disease since her parents were tested and were negative. It was unfortunately not possible to get DNA from the parents of the other patients. This is the first case of proven de novo ADTKD-MUC1 described to our knowledge. De novo variants in ADTKD-MUC1 are not surprising since the 7C stretch found in VNTR is a hotspot for mutagenesis. Interestingly, these patients seemed to have a more severe clinical presentation with an early onset of disease (median age at diagnosis 28 years [18, 32]). However, this could be due to a selection bias. In fact, young age of onset of CKD may have prompted clinicians to refer these patients for genetic testing despite negative family history, whereas older patients with possible ADTKD-MUC1 and no family history of kidney disease might be presumed to have another etiology of CKD. One way to confirm this would be to test a large cohort of patients with CKD from unknown etiology with no family history of CKD. Considering the nonspecific clinical manifestations of ADTKD-MUC1 and the phenotypic variability, it has previously been suggested that the most important clue to diagnosis is the presence of CKD in first-degree family. The possibility of de novo cases makes the clinical diagnosis of ADKTD-MUC1 even more challenging. Conclusion With VNtyper, we were able to diagnose new cases of ADTKD-MUC1 in a large cohort of patients with various phenotypes, with a significant prevalence of 1.2%. ADTKD-MUC1 was not suspected in 30% of these patients who would have maybe never been diagnosed otherwise. This is also the first study in which we describe a proven de novo case of ADTKD-MUC1. Pathogenic variants in the MUC1 gene should thus be in the differential diagnosis of all unspecified CKD, even if there is no family history since de novo variants are also possible.

Genomic Testing in Patients with Kidney Failure of an Unknown Cause: a National Australian Study

Background The cause of kidney failure is unknown in approximately 10% of patients with stage 5 chronic kidney disease (CKD). For those who first present to nephrology care with kidney failure, standard investigations of serology, imaging, urinalysis and kidney biopsy are limited differentiators of etiology. We aimed to determine the diagnostic utility of whole-genome sequencing (WGS) with analysis of a broad kidney gene panel in patients with kidney failure of unknown cause. Methods We prospectively recruited 100 participants who reached CKD stage 5 at 50 years of age and had an unknown cause of kidney failure after standard investigation. Clinically-accredited WGS was performed in this national cohort after genetic counselling. The primary analysis was targeted to 388 kidney-related genes with second-tier genome-wide and mitochondrial analysis. Results The cohort was 61% male and the average age of participants at stage 5 CKD was 32 years (9 months to 50 years). A genetic diagnosis was made in 25% of participants. Disease-causing variants were identified across autosomal dominant tubulointerstitial kidney disease (6), glomerular disorders (4), ciliopathies (3), tubular disorders (2), Alport syndrome (4) and mitochondrial disease (1). Most diagnoses (80%) were in autosomal dominant, X-linked or mitochondrial conditions (UMOD; COL4A5; INF2; CLCN5; TRPC6; COL4A4; EYA1; HNF1B; WT1; NBEA; m.3243A>G). Patients with a family history of CKD were more likely to have a positive result (OR 3.29, 95% CI 1.10-11.29). Thirteen percent of participants without a CKD family history had a positive result. In those who first presented in stage 5 CKD, WGS with broad analysis of a curated kidney-disease gene panel was diagnostically more informative than kidney biopsy, with biopsy being inconclusive in 24 of 25 participants. Conclusions In this prospectively ascertained Australian cohort, we identified a genetic diagnosis in 25% of patients with kidney failure of unknown cause.

THE RELATIONSHIP BETWEEN SOFT DRINK CONSUMPTION AND CHRONIC KIDNEY DISEASE IN MUHAMMADIYAH PALEMBANG HOSPITAL

Chronic kidney disease (CKD) has become one of the leading causes of death worldwide. It is one of several non-communicable diseases that have seen an associated increase in mortality over the past two decades. The causes of decreased kidney function are due to several factors, including a history of hypertension, cardiovascular history, family history of CKD, history of drinking preserved beverages, colored beverages, and other chemicals, and older age groups. Consuming soft drinks is associated with diabetes, hypertension, and kidney stones as risk factors for chronic kidney disease. This study aims to analyze the relationship between the frequency of soft drinks and chronic kidney disease at the Muhammadiyah Palembang Hospital. The sample of this study was 47 cases and 47 controls with an analytic observational research design with a case-control approach. This study used questionnaires and medical record data at the Palembang Muhammadiyah Hospital. Sampling used a consecutive sampling technique. The results showed that 61.7% of CKD patients and 55.3% of control subjects consumed soft drinks. The types of soft drinks consumed by CKD patients and control subjects were soft drinks with added sweeteners (100.0%). The results of the Pearson Chi-square test showed a value of p=0.644 (p>0.05). This study concluded that there is no relationship between the frequency of soft drinks and chronic kidney disease.

Out of sight: chronic kidney diseases among diabetic patients attending care and follow up. Findings from pastoralist health facilities of Southern Ethiopia.

In Ethiopia, the prevalence of chronic kidney disease (CKD) among the adult population ranges to 19.1%. The disease's impact has increased in low-resource settings due to a lack of knowledge about the condition and its risk factors. Diabetes is one of the numerous causes of CKD. Despite this, little was known in Ethiopia, particularly in the study area. This study aimed to identify the determinants of CKD among diabetic patients enrolled in care and follow up at pastoralist health facility of Jinka General Hospital (JGH), Southern Ethiopia, 2023. An institutional-based cross-sectional study design was conducted among 626 diabetic patients recruited through a systematic random sampling. Data was collected using a structured interviewer-administered questionnaire and entered into Epi data version 7.2 and then exported to the Statistical Package for Social Sciences (SPSS) version 25 for further analysis. Bivariate and multivariate logistic regression analyses were conducted to find eligible variables for the later analysis. Variables with p < 0.25 at bivariate logistic regression were selected for multivariate logistic regression analysis. The variables with p < 0.05 at the multivariate analysis were taken as statically significant in the final model. The prevalence of CKD was 2.7% (95% CI: 1.12-6.01%). Place of residence (AOR: 4.84; 95% CI: 1.51-15.40), presence of hypertension (AOR: 5.69; 95% CI: 1.58-20.51) and family history of CKD (AOR: 6.20; 95% CI: 1.40-15.49) were factors associated with CKD among diabetes patients. The prevalence found in this study was low when compared with the local studies. Provision of health education to diabetic patients on preventative measures such as physical exercise is cost-effective approach. Factors associated with CKD among diabetics can be significantly mitigated by strengthening the existing NCDs prevention packages in the study area particularly and in Ethiopia generally.

Risk factors for Undiagnosed Kidney Disease among Stable First-Degree Relatives of Chronic Kidney Disease Patients at Nnamdi Azikiwe University Teaching Hospital, Nnewi, South Eastern Nigeria

Background: Chronic kidney disease (CKD) is a global public health problem and has a major impact on health and cost of health care. In Nigeria, renal replacement therapy (RRT) is funded out of pockets by patients and their relatives unlike in most developed countries. There is a high clustering of the risk factors for CKD in FDRs of CKD patients, making then an ideal population for the screening for and the reversal of the modifiable risk factors that predispose to CKD.&#x0D; Objective: This study determined the risk factors for CKD in the FDRs of patients&#x0D; Methodology: This study involving 300 subjects: 150 FDRs of CKD patients and 150 control subjects without personal or family history of CKD. The study and control subjects were screened for CKD using urine albumin creatinine ratio (uACR) and estimated glomerular filtration rate (eGFR). Prevalence rate of the risk factors for CKD such as hypertension, diabetes mellitus, obesity, dyslipidaemia, hyperuricaemia and life style practices like significant smoking and heavy alcohol consumption were determined for both the FDRs and the control subjects. Data was analyzed with SPSS version 21.0. Mann-Whitney U test was used for comparing the variables between the two study groups for continuous variables that were not normally distributed and Chi square tests for categorical variables.&#x0D; Results: The prevalence rate of dyslipidaemia and hyperuricaemia was significantly higher among the FDRs of CKD patients compared with the control subjects (26% versus 12%; P = 0.003) and (20.7% versus 7.3%; P = 0.001) respectively. The other risk factors for CKD that included hypertension, diabetes mellitus, obesity, significant cigarette smoking, heavy alcohol consumption and herbal medication use were equally more among the FDRs of CKD patients compared with the controls, although not statistically significant.&#x0D; Conclusion: The risk factors for CKD were common among FDRs of CKD patients. Screening for these risk factors at the earliest possible contact with the FDRs of CKD patients and taking appropriate actions to tackle the modifiable ones will prevent the development of CKD and retard the progression of the already existing disease, reduce the alarming global burden of CKD.

COL4A gene variants are common in children with hematuria and a family history of kidney disease.

Inherited kidney diseases are a common cause of chronic kidney disease (CKD) in children. Identification of a monogenic cause of CKD is more common in children than in adults. This study evaluated the diagnostic yield and phenotypic spectrum of children who received genetic testing through the KIDNEYCODE sponsored genetic testing program. Unrelated children < 18years of age who received panel testing through the KIDNEYCODE sponsored genetic testing program from September 2019 through August 2021 were included (N = 832). Eligible children met at least one of the following clinician-reported criteria: estimated GFR ≤ 90ml/min/1.73 m2, hematuria, a family history of kidney disease, or suspected or biopsy confirmed Alport syndrome or focal segmental glomerulosclerosis (FSGS) in the tested individual or family member. A positive genetic diagnosis was observed in 234 children (28.1%, 95% CI [25.2-31.4%]) in genes associated with Alport syndrome (N = 213), FSGS (N = 9), or other disorders (N = 12). Among children with a family history of kidney disease, 30.8% had a positive genetic diagnosis. Among those with hematuria and a family history of CKD, the genetic diagnostic rate increased to 40.4%. Children with hematuria and a family history of CKD have a high likelihood of being diagnosed with a monogenic cause of kidney disease, identified through KIDNEYCODE panel testing, particularly COL4A variants. Early genetic diagnosis can be valuable in targeting appropriate therapy and identification of other at-risk family members. A higher resolution version of the Graphical abstract is available as Supplementary information.

Prevalence of Chronic Kidney Disease Among Diabetes and Hypertensive Patients in a Teaching Hospital in Ekiti State, Southwest Nigeria

Introduction: Chronic kidney disease (CKD) is a growing public health problem associated with enormous economic burdens, reduced quality of life, and untimely deaths, predominantly in developing countries. Aims: The study determines the prevalence and risk factors for CKD among diabetes and hypertensive patients in a teaching hospital in Ekiti State. Methods: Descriptive and cross-sectional research designs were employed using a quantitative strategy. Two hundred (200) randomly selected participants participated in the study. Socio-demographic data, awareness, and risk factors for CKD were determined using a standardized questionnaire, while CKD prevalence was investigated with biophysical measurements and laboratory investigations. Descriptive analyses were used to answer the research questions, while inferential statistics were used to test hypotheses at a significant level of p &lt; 0.05. Results: Findings revealed that 50% and 57.1% of the diabetics and hypertensives were above 60 years, 36.7% of the people with diabetes had comorbidity, while only 2% and 3.1% of diabetics and hypertensives participants had a family history of CKD. The study revealed that the respondents' level of awareness of CKD was inadequate. Major risk factors of CKD identified among the respondents were already diagnosed with diabetes and hypertension, age above 60 years (50% and 57.1%), herbal concoction (77.7% and 73.5%), and NSAID (74.5% and 78.6%). The prevalence of CKD for people with diabetes was 39.8%, while 57.1% for hypertensives. There was a significant relationship between respondents’ level of education and awareness of CKD (X2 =44.20, p=&lt;0.001). The prevalence of CKD among the studied population was high. Conclusion: Efforts should be intensified by nurses and all other stakeholders on awareness and prevention programs for CKD. Furthermore, the promotion of patients’ satisfaction with the quality of healthcare services should be the goal to promote positive health outcomes.

Clinicopathological Study of Chronic Kidney Disease of Unknown Etiology in Odisha.

Chronic kidney disease (CKD) is emerging as a serious health problem in Odisha, India. A new form of severe CKD affecting adults, not due to traditional risk factors like diabetes, hypertension, glomerulonephritis, has been reported in Sri Lanka, Central America, and Egypt in the last two decades. This has been named CKD of unknown origin (CKDu), and it is fatal due to late recognition and rapid disease progression. The aim of the study was to elucidate the association between different sociodemographic, and biochemical parameters with renal morphology in CKD of unknown origin patients. A cross-sectional study was conducted on 124 consecutive patients with CKD from the period January 2018 to December 2018. Patients in the age group 18-60 years who met clinical criteria for CKD were included. Participants answered a questionnaire. After the necessary history, clinical evaluation, and blood and urine analyses, a kidney biopsy was undertaken. Kidney biopsy was feasible in 51 patients as the rest 61 patients had shrunken kidneys and 12 patients did not give consent. Patients with diabetes mellitus (DM), hypertension, glomerulonephritis, polycystic kidney disease, obstructive kidney disease or any other congenital diseases, snakebite, pregnancy, malignancy, gout, primary hyperparathyroidism, infectious diseases like human immunodeficiency virus (HIV), TB, Hepatitis B and C, malaria, syphilis, leprosy and coagulopathies were excluded. Among the 51 patients, 23 had CKDu, 25 had chronic glomerulonephritis and three biopsies were inconclusive. The mean age of CKDu patients was 36.78 ± 9.85 years. Males (73.9%) were predominantly affected. A family history of CKD was seen in 82.6% of CKDu cases. Hyponatremia and hypokalemia were predominant biochemical abnormalities in our CKDu cases. Binary logistic regression showed rural residence, family history of CKD, exposure to smoke from burning coal, charcoal, or biomass fuels, low socioeconomic status, and low body mass index were strongly associated with CKDu. There was an increased risk of developing CKDu in persons with a family history of CKD [p = 0.003, odds ratio (OR)- 17.58], persons exposed to smoke from burning coal, charcoal or biomass fuels (p = 0.003, OR- 32.4), and patients with low socio-economic status (p = 0.001, OR- 15.87). Interstitial fibrosis (IF), interstitial inflammation with mononuclear infiltration, tubular atrophy (TA), and global glomerulosclerosis (GS) were pertinent histopathological findings in our study. There is no strong evidence for a single cause for CKDu, and multiple environmental, occupational and social factors are probably involved. We need to design consistent and comparative multisite studies to identify etiologies of CKDu, across high-risk populations that may help elucidate the importance of region-specific vs global risk factors.

Knowledge of chronic kidney disease among undergraduate and postgraduate students in a public university in Klang Valley, Malaysia: A cross sectional study.

The prevalence of chronic kidney disease (CKD) risk factors such as diabetes mellitus, hypertension, and obesity among the young Malaysians are increasing. Understanding the factors associated with CKD knowledge could assists healthcare providers to design health education programmes. There are scarce local studies on CKD knowledge and its associated factors among university students. This subpopulation comprises of young people with diverse background and characteristics. This study was aimed to assess the CKD knowledge and its associated factors among university students. A cross-sectional study was conducted among Universiti Kebangsaan Malaysia students from July 2020 to August 2020. A convenience sampling method was applied. All students were invited to complete an online survey using Google Forms that were sent to their email. The survey consisted of questions related to their sociodemographic, socioeconomics, university programme enrolled, medical history, lifestyle characteristics and CKD knowledge. The data were analysed using SPSS Statistics 26.0. Multiple logistic regression analysis was performed to identify the final associated factors after controlling for confounders. A total of 3074 students participated and 32.6% of them had below average CKD knowledge. Students of male gender, enrolment in undergraduate programmes and non-health-related faculties/institutes were more likely to have below average CKD knowledge. Students who are Chinese, from high monthly household income family and with family history of CKD were less likely to have below average CKD knowledge. Almost one-third of the students had below average CKD knowledge. The six associated factors with CKD knowledge were non-modifiable. Of the six factors, three were associated with students being more likely to have below average CKD knowledge; another three were associated with students being less likely to have below average CKD knowledge. Future health education programmes to enhance CKD knowledge should be designed focusing on students who are more likely to have below average CKD knowledge.

Effect of Dietary Phosphorous Restriction on Fibroblast Growth 2 Factor-23 and sKlotho Levels in Patients with Stages 1-2 Chronic Kidney Disease.

Hyperphosphatemia has emerged as an independent risk factor for cardiovascular disease (CVD) and excess mortality in chronic kidney disease (CKD). The study evaluates the effect of dietary phosphorus (Ph) restriction (DPhR) at an early stage as a therapeutic strategy for delaying CKD progression and preventing CVD. Methods: This was a one-year interventional study conducted on 79 stage 1 and 2 CKD patients. The dietary phosphorus intake (DPhI), fibroblast growth factor-23 (FGF-23), sKlotho and serum phosphorous (SP) levels were analyzed. Patients were categorized into two groups based on their DPhI, recommended DPhI (RPhI) with <1000 mg/day of dietary phosphorous (dietary counselling) and high DPhI (HPhI) with >1000 mg/day (dietary intervention). For comparisons of differences between the two groups, independent t-test; for correlation analysis, Pearson correlation; for identifying the significant associated risk factors for CKD, binary logistic regression analysis and for comparing the means across the three visits, repeated measures ANOVA were used for statistical analysis. Results: The mean age and glomerular filtration rate (GFR) of CKD patients were 38 ± 12 years and 82.95 ± 16.93 mL/min/1.73 m2. FGF-23, SP, dietary protein and DPhI were significantly higher and sKlotho was significantly lower in HPhI group than RPhI group. In HPhI group; GFR, sKlotho, SP and FGF-23 correlated significantly with DPhI. Risk factors with a statistical bearing on the progression of CKD were animal-based diet, family history of CKD and hypertension. In HPhI group; GFR, DPhI, SP and FGF-23 levels significantly improved within the intervention period whereas a significant increase in sKlotho levels was observed in both the groups. Conclusion: Restricting DPhI emerged as a favorable therapeutic strategy for CKD patients for improving renal function and controlling hyperphosphatemia. The results of the present study may serve as the basis for future interventional studies with dietary phosphate restriction in the initial stages of CKD that would preserve renal function. Highlights: Early restriction of dietary phosphorus prevents decline in eGFR, elevation in FGF23 and increases Klotho levels.

A BRIEF REPORT TO STUDY RISK ASSESMENT OF CKD IN TYPE-II DIABETIC AND HYPERTENSIVE PATIENTS

Chronic kidney disease (CKD) is a long-term pathological condition with loss of function over several months to years. In the present study the CKD risk assessment in diabetic, hypertension is assessed using CKD assessment questionnaire, GFR and other biochemical parameters. In the present study 1270 patients were identified with risk of CKD in which 250 patients were dropped due to various reasons, 1020 patients data was studied and analyzed as per our objectives. The findings suggest that the CKD risk is more in elder patients than younger patients with diabetics and hypertension. Females are at more risk to CKD when compared to males. When BMI was analyzed the Female Obese patients are 90% significant risk to CKD followed by obese male. 95% significant risk was observed for CKD in house wives, Govt employees followed by Private employees with sedentary life style. Family history of CKD in diabetic and hypertension was analyzed then there is no significant difference among them. When education status was analyzed in hypertension and diabetes patients then there is no significant difference among them. when GFR was analyzed then 95% significant risk was observed in stage-1 vs stage-3A, 95% significant risk was observed in stage-1 Vs stage-3B and 99% significant risk was observed between stage-1 Vs stage-5. It is concluded that increased age are at more risk, in Gender Females are more risk than males, in BMI higher BMI are more risk, Family history was Independent ,in Occupation house wives are more risk , in GFR – Stage 5 are more risk and in Social history was Independent. KEY WORDS: Age, Gender, BMI, GFR, Social history, family history, Occupation

Risk Factors and Complications of Chronic Kidney Disease: Narrative Review

Chronic kidney disease (CKD) is associated with several adverse clinical outcomes, such as cardiovascular events, kidney failure requiring renal replacement therapy, mortality, and poor quality of life for survivors in general. CKD is a slow and progressive loss of kidney function over several years and may ultimately lead to the development of kidney failure. CKD has become a serious public health issue. Although cardiovascular disease, family history of CKD, and certain ethnic and racial backgrounds are important predictors of CKD risk, they do not contribute significantly beyond the scope of diabetes, hypertension, and older age. The number of CKD patients will continue to rise, reflecting the growing elderly population and increasing numbers of patients with diabetes and hypertension. As the number of CKD patients increases, primary care practitioners will be confronted with the management of the complex medical problems unique to patients with chronic renal impairment. As well documented in the literature, the nephrologist rarely manages the medical needs of CKD patients until renal replacement therapy is required. Whereas the symptoms of CKD in diabetes are few, many risk factors and biomarkers can be used to identify individuals at high risk for developing this condition. This article highlights the effect of risk factors and complications associated with chronic kidney disease at its various stages.

Limited Public Knowledge of Chronic Kidney Disease in a Resource-Limited Setting: A Cross-Sectional Study.

BackgroundThe general public’s awareness and knowledge of chronic kidney disease (CKD) and its risk factors remains low, which may contribute to the development of CKD and undiagnosed disease. Therefore, the current study aimed to assess public knowledge of CKD in the Ethiopian community using a validated tool.MethodsA community-based cross-sectional study was conducted in Ethiopia’s capital, Addis Ababa. For administrative purposes, the city is divided into ten sub-cities; proportional numbers of study participants were drawn from each sub-city based on their total population size. This study’s target population was the general public, and health professionals were excluded. SPSS version 26 was used to analyze the data, and frequencies, tables, percentages, mean, and standard deviation were used to describe the responses of the participants. To identify factors associated with public knowledge of CKD, an independent T-test and one-way ANOVA statistics were used.ResultsA total of 350 people were approached, with 301 of them completing and returning the questionnaire, yielding an 86% response rate. The mean (S.D.) knowledge score of participants in this study was 11.12 (±4.21), with a minimum of 0 and a maximum of 22. In terms of the distribution of the CKD knowledge score, half of the respondents have a score of 11 or less. One-way ANOVA revealed that respondents with a degree educational background and family history of CKD had higher knowledge scores. An independent t-test was also performed, but it found no link between socio-demographic characteristics and knowledge score.ConclusionThe Ethiopian population has a low level of general knowledge about CKD and its risk factors. Non-communicable diseases, such as diabetes and hypertension, are currently a public health concern and one of the major risk factors for CKD.

Histologic characterization and risk factors for persistent albuminuria in adolescents in a region of highly prevalent end-stage renal failure of unknown origin.

ABSTRACTBackgroundEnd-stage renal failure of unknown origin (ESRD-UO) is a public health problem in Mexico and many regions of the world. The prevalence of ESRD-UO in Aguascalientes, Mexico, is one of the highest worldwide, particularly in adults between 20 and 40 years of age. Our aim was to screen adolescents for chronic kidney disease (CKD) to identify risk factors and histologically characterize adolescents with persistent albuminuria.MethodsThis was a cross-sectional, observational and comparative study of adolescents in whom serum creatinine and the albumin:creatinine ratio (ACR) were determined when screening for CKD. A clinical evaluation and risk factor survey were conducted. Patients with an abnormal ACR (≥30 mg/g) or a low glomerular filtration rate (GFR) (≤75 mL/min/1.73 m2) were re-evaluated and a renal ultrasound (US) was obtained. A kidney biopsy was performed in patients with persistent albuminuria.ResultsA total of 513 students were included; 19 had persistent albuminuria and 494 were controls. The prevalence of persistent albuminuria was 3.7% [95% confidence interval (CI) 2.1–5.3]. Only one patient had a decreased GFR. None of the patients with persistent albuminuria had anatomical abnormalities of the urinary tract by renal US. Patients with persistent albuminuria had a decreased total renal volume compared with the control group (150 versus 195 mL/m2; P < 0.01). Eighteen kidney biopsies were performed; 72% had glomerulomegaly and only one patient had mild fibrosis. Podocyte abnormalities were evident on electron microscopy, including partial fusion (100%), microvillous degeneration (80%) and increased organelles (60%). Risk factors for persistent albuminuria were: homestead proximity to maize crops, the use of pesticides at the father’s workplace, a family history of CKD and blood pressure abnormalities. The body mass index and breastfeeding were protective factors.ConclusionsThe prevalence of persistent albuminuria in adolescents in Aguascalientes is high and histologic compromise is characterized by podocyte injury in the absence of fibrosis. The renal volume of persistent albuminuria patients was decreased, suggesting oligonephronia. Exposure to environmental toxins such as pesticides, even prenatally, may be responsible for this pathological entity. Screening programs in adolescents by determining ACR are necessary in this setting.

Use of SGLT-2 Inhibitors in Patients with Chronic Kidney Disease.

• Chronic kidney disease (CKD) is common, occurring in 1 of 7 adults in the United States. • 9 out of 10 adults with CKD are unaware of it. • People with CKD have the same risk for cardiovascular (CV) death as people with known atherosclerotic heart disease. • The risk for CV events and death increases with worsening albuminuria and estimated glomerular filtration rate (eGFR). • Patients with risk factors for CKD (hypertension, diabetes, family history of CKD, or advancing age) should be screened by measuring both eGFR and urinary albuminto-creatinine ratio. • Sodium-glucose cotransporter-2 inhibitors are first-line agents for treatment of patients with type 2 diabetes mellitus and CKD or a history of atherosclerotic CV disease. • Dapagliflozin has demonstrated equivalent efficacy for reducing kidney events in patients with CKD irrespective of diabetes status, and a similar, ongoing trial with empagliflozin may provide potential confirmation.

MO427SAFE USE OF ALLOPURINOL TO TREAT ACUTE URIC ACID NEPHROPATHY IN PREGNANCY: A CASE REPORT

Abstract Introduction Acute uric acid nephropathy (UAN) is characterized by acute kidney injury (AKI) due to uric acid crystal precipitation within the distal tubules and collecting ducts. We present a young woman, with a history of hyperuricaemia, who was treated with allopurinol for acute UAN during her first pregnancy. She also continued allopurinol treatment during her second pregnancy for prevention of further acute UAN. To the author’s knowledge, this is the first case report of biopsy-confirmed acute UAN during pregnancy. Case report A 20 year old woman, who was 13 weeks pregnant, was admitted with AKI. Past medical history included chronic kidney disease (CKD) and gout since the age of 17. She had an extensive family history of CKD and gout (without diagnosis, despite genetic testing). She had been on daily allopurinol 300mg, but this was stopped 8 weeks prior by her rheumatology team due to concerns about teratogenicity. At that time serum creatinine was at her baseline of 100 μmol/L (normal range 50-120 μmol/L) and serum uric acid had been 740 μmol/L (normal range 140-360 μmol/L). On admission, she felt well and was euvolemic. Serum creatinine was now 352 μmol/L and her serum uric acid level was 1720 μmol/L, with an elevated urine uric acid to creatinine ratio of 1.1. She underwent renal biopsy, which showed significant deposition of uric acid crystals in the renal tubules, confirming a diagnosis of acute UAN. She was given intravenous fluids. The uncertainties of allopurinol use in pregnancy were discussed with her, and she was restarted on allopurinol 200 mg daily. Over the next 3 weeks, serum uric acid decreased to 470 μmol/L and serum creatinine to 116 μmol/L. She was maintained on allopurinol during her pregnancy and delivered a healthy baby girl. She was advised against further pregnancies due to increased risk of maternal and fetal complications. However, three years later she presented at 15 weeks’ gestation. After a discussion regarding the potential teratogenic effects of allopurinol versus the risk of recurrent severe AKI due to acute UAN if it was again discontinued, she chose to continue allopurinol. The pregnancy proceeded without complication. Her daughters are now 8 and 5 years old. They do not have any congenital malformations, though both have mild to moderate learning difficulties. Discussion Allopurinol is approved for the treatment of hyperuricaemia outside of pregnancy, but given it interrupts purine synthesis there is a biologically plausible concern regarding teratogenicity. However, in our patient with long-standing hyperuricaemia it was the discontinuation of allopurinol that precipitated AKI due to the resultant crystal formation when serum uric acid reached very high levels. Biopsy confirmation of acute UAN was vital in this case, given the possibility of missing an alternative diagnosis and the risks of giving empirical allopurinol therapy. Once the diagnosis for her severe AKI was confirmed, it was clear our patient would benefit from uric acid lowering therapy. Our patient had two healthy girls despite using allopurinol from week 16 in her first pregnancy and throughout her second pregnancy. Unfortunately, both girls have mild to moderate learning needs, though it is unprovable whether allopurinol was causative as no study has followed up long term outcomes after foetal exposure during pregnancy.

Awareness of Chronic Kidney Disease among Tamil Nadu Population- ACross-sectional Study

Introduction: Chronic kidney failure in India and around the world is a significant health problem. The most effective and affordable treatment may require screening for early detection,intervention and prevention. Public awareness is a key determinant to overcome the burden of Chronic Kidney Disease(CKD). However, there is a lack of information on CKD among South Indian people. Aim: To assess the awareness and knowledge of CKD among the South Indian population. Materials and Methods: A questionnaire-based cross-sectional study was conducted through an online form; the questions were generally based on the physiological role of kidney and awareness questions related to CKD. The sample size was 500 participants, of age &gt;18 years and snowball sampling method was implemented. Among the study population, 68 participants had a family history of CKD and they were excluded. The data were analysed through Pearson Chi-Square test. Results: The mean knowledge score was 13 (SD±5.0), with values ranging from 0 to 22. The mean age of the population was 47.80±8.5 years. Multiple regression on demographic data and knowledge yielded statistically negligible results.The study population included 432 participants and the result showed the realms that most responded incorrectly were physiology of kidney, CKD symptoms, risk factors and the domain of testing and diagnosis. Conclusion: The participants had ample knowledge of the risk factors, signs and symptoms of CKD and insufficient knowledge of the physiological function of the kidney and the diagnosis of CKD. Therefore, efforts are necessary to create awareness and educate people about the early detection and prevention of CKD.

Characteristics of Asymptomatic Bacteriuria in Patients with Chronic Kidney Disease: A Tertiary Care Hospital Experience from a Developing Country.

Asymptomatic bacteriuria (ASB) is the isolation of bacteria in a urine sample from individuals who do not have any symptoms of a urinary tract infection (UTI). The outcomes of ASB in chronic kidney disease (CKD) patients are poorly understood in Pakistan. This study aimed to determine the characteristics of ASB and antibiotic susceptibility pattern among patients with CKD. A cross-sectional retrospective survey was administered to perform this study in a tertiary care hospital, to include all CKD patients. The study included all those patients with a diagnosis of CKD with no signs and symptoms of UTI present, and showing the growth of an organism in urine culture. A total of 175 urine cultures were observed retrospectively meeting the inclusion criteria through nonprobability consecutive sampling. Out of 175 urine cultures observed, mean age of 58.56 ± 16.81, 71% of them were females, 55% were diabetic, and 22% had a family history of CKD. Escherichia coli, Enterococcus, Klebsiella, Pseudomonas, Enterobacter, and streptococcal species were the most often isolated microbes. A total of 17 subjects got dual bacterial growth in their cultures which were having Enterococcus species as the most common organism. Twenty-three cultures were identified as pandrug resistant (13.14%), only sensitive to colomycin/polymyxin B. The susceptibilities of these organisms were contrasting to traditional antibiotics known to treat UTIs empirically, hence demanding further screening and treatment protocols to be defined for minimizing the irrational choice of antibiotics.

Familial Aggregation of CKD and Heritability of Kidney Biomarkers in the General Population: The Lifelines Cohort Study

Chronic kidney disease (CKD) has a heritable component. We aimed to quantify familial aggregation of CKD in the general population and assess the extent to which kidney traits could be explained by genetic and environmental factors. Cross-sectional 3-generation family study. Data were collected at entry into the Lifelines Cohort Study from a sample of the general population of the northern Netherlands, composed predominantly of individuals of European ancestry. Family history of CKD. The primary outcome was CKD, defined as estimated glomerular filtration rate (eGFR)<60mL/min/1.73m2, where GFR was estimated using the CKD Epidemiology Collaboration creatinine equation. Among a subsample for which urinary albumin concentration was available (n=59,943), urinary albumin excretion was expressed as the rate of urinary albumin excretion (UAE) per 24 hours or urinary albumin-creatinine ratio (UACR). Familial aggregation of CKD was assessed by calculating the recurrence risk ratio (RRR), using adapted Cox proportional hazards models. Heritability of continuous kidney-related traits was estimated using linear mixed models and defined as the ratio of the additive genetic variance to total phenotypic variance. All models were adjusted for age, sex, and known risk factors for kidney disease. Among 155,911 participants with available eGFR data, the prevalence of CKD was 1.19% (1,862 cases per 155,911). The risk of CKD in those with an affected first-degree relative was 3 timeshigher than the risk in the total sample (RRR, 3.04 [95% CI, 2.26-4.09). In those with an affected spouse, risk of CKD was also higher (RRR, 1.56 [95% CI, 1.20-1.96]), indicative of shared environmental factors and/or assortative mating. Heritability estimates of eGFR, UAE, and UACR were 44%, 20%, and 18%, respectively. For serum urea, creatinine, and uric acid, estimates were 31%, 37%, and 48%, respectively, whereas estimates for serum electrolytes ranged from 22% to 28%. Use of estimated rather than measured GFR. UAE data only available in a subsample. In this large population-based family study, a positive family history was strongly associated with increased risk of CKD. We observed moderate to high heritability of kidney traits and related biomarkers. These results indicate an important role of genetic factors in CKD risk.

Risk factors and knowledge assessment of general public for chronic kidney disease in Taif Region, Saudi Arabia

Introduction: Chronic kidney disease (CKD) is a worldwide public health problem since the rapid increasing prevalence of relevant risk factors, like diabetes, hypertension, unhealthy diet, low to no physical activity and metabolic syndrome. The current study aimed at assessing the risk factors and the general public awareness of CKD in Taif region, Saudi Arabia. Method: We conducted a cross-sectional study during the period of September 2019 to March 2020. For risk factors assessment data regarding CKD cases were collected from the department of nephrology at AL-Hada Military hospital in Taif. An online-based questionnaire was distributed to the general public for knowledge assessment of CKD. 6th year pharmacy student at Taif University and nephrologists from the hospital were also invited to answer the questionnaire. Results: The data of 456 CKD patients with 600 non-CKD individuals were compared for assessment of the most common risk factors. 99% of participants were CKD stage III-V patients. The majority, n=371(81.57%), of the participants were &gt;50 years old. N=328(71.93%) had type 2 diabetes mellitus (Risk ratio= 2.32, CI= 2.03-2.65; Odd ratio=5.7, CI= 4.36-7.45), n=396(86.84%) had hypertension (Risk ratio =9.65,CI-7.46-12.48; Odd ratio: 66.73, CI=45.19-98.54) and n=264(57.89%) had a history of heart diseases (Risk ratio= 3.62, CI=2.96-4.42; Odd ratio= 7.22, CI= 5.42-9.62). In CKD groups, 28.07% of them had low physical activity. In contrast with the control group, only 4% had low physical activity level in their daily routine (p&lt;0.00001). In the general public (n=1419), 919 (64.7%) had poor knowledge, 273 (19.22%) had fair knowledge, and 227 respondents (16.01%) had good knowledge of CKD. Conclusion: The finding suggests that age &gt;50 years, low educational attainment, family history of CKD, diabetes, hypertension, history of kidney stone, CVD and high BMI were significantly associated with CKD progression. We also found that the majority of the general public had poor knowledge of CKD compared to pharmacy graduates and nephrologists. These findings warrant the need for the development of awareness initiatives and programs designed to increase the level of knowledge of the general public of CKD.