High Risk For Kidney Disease Research Articles

Effect of spironolactone wash-out on albuminuria after long-term treatment in individuals with type 2 diabetes and high risk of kidney disease-An observational follow-up of the PRIORITY study.

This study aimed to explore the effect of discontinuation of long-term spironolactone treatment on markers of kidney function in individuals with type 2 diabetes (T2D) at high risk of kidney disease enrolled in the Proteomic prediction and Renin angiotensin aldosterone system Inhibition prevention Of early diabetic nephRopathy In TYpe 2 diabetic patients with normoalbuminuria (PRIORITY) study. An observational study following the nested randomised part of the PRIORITY study was conducted. A total of 115 individuals with T2D and normoalbuminuria but high risk for progression based on urinary proteomics, randomised to daily spironolactone (n = 50) or placebo (n = 65) for a median of 2.5 years, were re-examined approximately 6 weeks after the final visit in the PRIORITY study. Primary endpoint was relative change in geometric mean of urinary albumin-creatinine ratio (UACR) between the final visit in PRIORITY (baseline) and follow-up. Secondary endpoints were change in estimated glomerular filtration rate (eGFR), systolic blood pressure (SBP) and serum potassium. No change in UACR was observed in neither the spironolactone (geometric mean change: 17%; 95% CI -12, 55; p = 0.28) nor the placebo (5%; 95% CI -13, 26; p = 0.63) group at follow-up. No difference in UACR between the groups was observed at follow-up (relative difference in geometric mean: 11%, 95% CI -26, 67; p = 0.60). For eGFR and SBP, an increase after discontinuation of spironolactone was observed, as well as for SBP after placebo discontinuation. Potassium levels were lower after discontinuation of spironolactone, but higher after placebo discontinuation (all p < 0.05). UACR did not change after discontinuation of long-term treatment with spironolactone. However, an increase in eGFR was observed supporting a haemodynamic effect of spironolactone in the kidneys.

Albuminuria Screening in People With Type 2 Diabetes in a Managed Care Organization

Albuminuria-an increased amount of urine albumin, in milligrams, adjusted for grams of urine creatinine-is an early marker of diabetic kidney disease. Several new classes of medications are now available that effectively lower albuminuria levels with the potential to delay or prevent the progression of diabetic kidney disease. However, screening for albuminuria in the U.S. is low in population-based studies (<10% to ∼50% at most). In this study, we examine whether screening for albuminuria was improved in an integrated model of healthcare delivery following the recommendations of the National Committee for Quality Assurance mandate (an umbrella group for the managed healthcare industry) to screen for albuminuria. We examined screening for albuminuria over a 2-year period among people with Type 2 diabetes in a U.S. HMO with an electronic medical record, onto which automated laboratory ordering for albuminuria could be added when a patient appeared at the laboratory (for any reason) if albuminuria testing had not been obtained within the previous 365 days. Participants under this plan received diabetes education at no cost and panel managers to guide their diabetes care. Logistic regression using data from 2020 and 2021, separately, evaluated the relationship between patient characteristics and the likelihood of albuminuria screening. There were 20,688 and 22,487 participants with Type 2 diabetes mellitus in 2020 and 2021, respectively, who were analyzed. Approximately 80% were screened for albuminuria in both years. African American participants and those aged >64 years were more likely to have completed albuminuria screening. Screened individuals had lower HbA1c, blood pressure, and low-density lipoprotein cholesterol levels than those who were not screened. In an integrated healthcare model, it is possible to achieve consistently high rates of albuminuria screening in people with Type 2 diabetes, especially in groups at high risk for kidney disease.

Disruption to routine diabetes care processes during the pandemic: evidence from a large integrated health system in the Southeast United States

IntroductionWe investigated the impact of the COVID-19 pandemic on annual adherence to seven diabetes care guidelines and risk factor management among people with diabetes.Research design and methodsWe included all adults...

Interventions for and experiences of shared decision-making underpinning reproductive health, family planning options and pregnancy for women with or at high risk of kidney disease: a systematic review and qualitative framework synthesis

ObjectiveTo determine intervention effects and synthesise qualitative research that explored women with or at high risk of kidney disease experiences of shared decision-making in relation to their reproductive health, family...

The differential effect of animal versus vegetable dietary protein on the clinical manifestations of diabetic kidney disease in humans.

Patients with diabetes are at a high risk for kidney disease and cardiovascular disease (CVD). Inadequate glycemic control or conventional cardiovascular risk factors do not fully explain these vascular complications. Insulin resistance has been established as a powerful and independent risk factor for both CVD and diabetic kidney disease (DKD). The source of dietary protein (animal versus vegetable) largely defines the degree of insulin sensitivity. Animal protein intake activates glucagon secretion and magnifies insulin resistance while vegetable food enhances insulin sensitivity. Reducing animal meat while augmenting vegetable protein has demonstrated definite advantages regarding insulin sensitivity. A comprehensive literature search was conducted on the PubMed database up to December 2021 on the differential effect of animal versus vegetable protein on DKD. Articles written in English concerning human subjects were included. Animal protein is strongly associated with clinical features of DKD (glomerular hyperfiltration, albuminuria and kidney function decline) and CVD. Conversely, plant-sourced protein has a strong beneficial effect on both DKD and CVD. Plant-based diets have demonstrated to be nutritionally safe in subjects from the general population, patients with diabetes, and patients with kidney disease. Available evidence suggests that the dietary potassium load due to plant-sourced food does not usually induce hyperkalemia, although future research is required to establish the effect of meat (and subsequent insulin resistance) and vegetable food on kalemia. Nutritional advice to patients with diabetes should consider the strikingly different effect of animal versus vegetable protein on insulin resistance and its clinical consequences.

Three-Year Clinical Outcomes of the First South Asian Prospective Longitudinal Observational IgA Nephropathy Cohort

IntroductionGlomerular Research And Clinical Experiments—IgA Nephropathy in Indians (GRACE-IgANI) is the first prospective South Asian IgA nephropathy (IgAN) cohort with prespecified objectives, protocolized longitudinal follow-up, and extensive biosample collection. The baseline risk scores predicted high risk of kidney disease progression.MethodsA total of 195 of 201 patients (97%) completed 3-year follow-up in September 2020. All patients received optimized supportive care, and those at high risk of progression were offered systemic corticosteroids.ResultsA total of 76 patients (76 of 193, 39.4%) had rapid progression in 3 years (≥5 ml/min per 1.73 m2 decline in estimated glomerular filtration rate [eGFR] per year). A total of 72 patients (72 of 195, 36.9%) experienced the composite outcome (CO), defined as ≥50% fall in eGFR, eGFR < 15 ml/min per 1.73 m2, commenced kidney replacement therapy or death, in 3 years. At each scheduled follow-up, achievement of proteinuria level < 1 g/d significantly delayed the time to the CO. The receiver operating characteristic curve of average annual decline in eGFR ≥ 5 ml/min per 1.73 m2 had 86% sensitivity and 89% specificity for CO in 3 years and had good discrimination from 1 year onwards (area under the curve 0.8, SE 0.04, 95% CI 0.7–0.9, P < 0.0001). The significant predictors of CO by Cox proportional-hazards model were as follows: baseline MEST-T2 score (hazard ratio [HR] 3.3, 95% CI 1.7–6.5, P < 0.001), along with 24-hour urine protein level ≥ 1 g/d (HR 2.1, 95% CI 1.1–3.9, P = 0.02), eGFR < 60 ml/min per 1.73 m2 (HR 2.9, 95% CI 1.1–7.6, P = 0.03), and rate of eGFR decline ≥ 5 ml/min per 1.73 m2/yr (HR 2.7, 95% CI 1.6–4.8, P < 0.001) all measured at 6 months. Mortality was 11 of 195 (5.6%).ConclusionWe identified longitudinal clinical variables measured at 6 months and ≥5 ml/min per 1.73 m2 annual fall in eGFR after kidney biopsy as important predictors for composite outcome in addition to baseline histology.

Long-term kidney function in children with Wilms tumour and constitutional WT1 pathogenic variant

BackgroundWilms tumour (WT) survivors, especially patients with associated syndromes or genitourinary anomalies due to constitutional WT1 pathogenic variant, have increased risk of kidney failure. We describe the long-term kidney function in children with WT and WT1 pathogenic variant to inform the surgical strategy and oncological management of such complex children.MethodsRetrospective analysis of patients with WT and constitutional WT1 pathogenic variant treated at a single centre between 1993 and 2016, reviewing genotype, phenotype, tumour histology, laterality, treatment, patient survival, and kidney outcome.ResultsWe identified 25 patients (60% male, median age at diagnosis 14 months, range 4–74 months) with WT1 deletion (4), missense (2), nonsense (8), frameshift (7), or splice site (4) pathogenic variant. Thirteen (52%) had bilateral disease, 3 (12%) had WT-aniridia, 1 had incomplete Denys-Drash syndrome, 11 (44%) had genitourinary malformation, and 10 (40%) had no phenotypic anomalies.Patient survival was 100% and 3 patients were in remission after relapse at median follow-up of 9 years. Seven patients (28%) commenced chronic dialysis of which 3 were after bilateral nephrectomies. The overall kidney survival for this cohort as mean time to start of dialysis was 13.38 years (95% CI: 10.3–16.4), where 7 patients experienced kidney failure at a median of 5.6 years. All of these 7 patients were subsequently transplanted. In addition, 2 patients have stage III and stage IV chronic kidney disease and 12 patients have albuminuria and/or treatment with ACE inhibitors. Four patients (3 frameshift; 1 WT1 deletion) had normal blood pressure and kidney function without proteinuria at follow-up from 1.5 to 12 years.ConclusionsDespite the known high risk of kidney disease in patients with WT and constitutional WT1 pathogenic variant, nearly two-thirds of patients had sustained native kidney function, suggesting that nephron-sparing surgery (NSS) should be attempted when possible without compromising oncological risk. Larger international studies are needed for accurate assessment of WT1genotype-kidney function phenotype correlation.

Cross-Sectional and Longitudinal Performance of Creatinine- and Cystatin C-Based Estimating Equations Relative to Exogenously Measured Glomerular Filtration Rate in HIV-Positive and HIV-Negative Persons.

Reliable estimates of glomerular filtration rate (GFR) are important in the clinical management of HIV-positive patients. Data on the performance of widely used estimating equations (eGFR) relative to exogenously measured GFR are sparse in this population. We evaluated cross-sectional and longitudinal accuracy and bias of eGFR, based on creatinine and cystatin C, relative to disappearance of infused iohexol from plasma (iGFR) in a cohort of participants followed annually for up to 7 years. A total of 222 HIV-positive and 139 HIV-negative participants contributed 1240 visits with valid iGFR and eGFR measures. Estimated GFR based on both creatinine and cystatin C performed the best. Estimated GFR based on creatinine alone overestimated iGFR by 9 mL·min·1.73 m on average and was significantly less accurate in HIV-positive than HIV-negative individuals. The performance of equations based on either creatinine alone or cystatin C alone were significantly affected by participant factors (eg, non-suppressed HIV RNA, nadir CD4 count, hepatitis C virus coinfection). The average iGFR slope was -4% per year in HIV-positive participants. In both HIV-positive and HIV-negative participants, eGFR slope measures were generally unbiased but inaccurate, with only 60%-74% of observations falling within ±5% points of iGFR slope. Both creatinine and cystatin C have limitations as GFR indices in HIV-positive individuals. Estimated GFR based on both creatinine and cystatin C performed best in our study and may be preferred in HIV-positive persons with kidney disease or comorbidities that place them at high risk for kidney disease.

Use of sodium-glucose co-transporter-2 inhibitors in Asian patients with type 2 diabetes and kidney disease: An Asian perspective and expert recommendations.

Early onset of type 2 diabetes and a high prevalence of co‐morbidities predispose the Asian population to a high risk for, and rapid progression of, diabetic kidney disease (DKD). Apart from renin‐angiotensin system inhibitors, sodium‐glucose co‐transporter‐2 (SGLT‐2) inhibitors have been shown to delay renal disease progression in patients with DKD. In this review article, we consolidate the existing literature on SGLT‐2 inhibitor use in Asian patients with DKD to establish contemporary guidance for clinicians. We extensively reviewed recommendations from international and regional guidelines, data from studies on Asian patients with DKD, global trials (DAPA‐CKD, CREDENCE and DELIGHT) and cardiovascular outcomes trials. In patients with DKD, SGLT‐2 inhibitor therapy significantly reduced albuminuria and the risk of hard renal outcomes (defined as the onset of end‐stage kidney disease, substantial decline in renal function from baseline and renal death), cardiovascular outcomes and hospitalization for heart failure. In all the cardiovascular and renal outcomes trials, there was an initial decline in the estimated glomerular filtration rate (eGFR), which was followed by a slowing in the decline of renal function compared with that seen with placebo. Despite an attenuation in glucose‐lowering efficacy in patients with low eGFR, there were sustained reductions in body weight and blood pressure, and an increase in haematocrit. Based on the available evidence, we conclude that SGLT‐2 inhibitors represent an evidence‐based therapeutic option for delaying the progression of renal disease in Asian patients with DKD and preserving renal function in patients at high risk of kidney disease.

The Effects of High-Protein Diets on Kidney Health and Longevity.

Although high-protein diets continue to be popular for weight loss and type 2 diabetes, evidence suggests that worsening renal function may occur in individuals with-and perhaps without-impaired kidney function. High dietary protein intake can cause intraglomerular hypertension, which may result in kidney hyperfiltration, glomerular injury, and proteinuria. It is possible that long-term high protein intake may lead to de novo CKD. The quality of dietary protein may also play a role in kidney health. Compared with protein from plant sources, animal protein has been associated with an increased risk of ESKD in several observational studies, including the Singapore Chinese Health Study. Potential mediators of kidney damage from animal protein include dietary acid load, phosphate content, gut microbiome dysbiosis, and resultant inflammation. In light of such findings, adopting current dietary approaches that include a high proportion of protein for weight reduction or glycemic control should be considered with care in those at high risk for kidney disease. Given the possibility of residual confounding within some observational studies and the conflicting evidence from previous trials, long-term studies including those with large sample sizes are warranted to better ascertain the effects of high protein intake on kidney health.

P0842MANAGEMENT OF RENAL RISK PATIENTS AND THERAPEUTIC CHANGES AFTER DIAGNOSIS OF KIDNEY DISEASE IN PRIMARY CARE

Abstract Background and Aims Screening for chronic kidney disease (CKD) is proposed in high risk groups. Whether a new CKD diagnosis in general practice leads to improved patient management, is largely unknown. Method To answer this question and evaluate the kidney disease specific pharmacological care in renal risk patients, a screening study in patients at high risk for kidney disease was performed in the primary care setting in ten general practices in the state of Vorarlberg, Austria. General practitioners were provided with guidelines for the management of CKD with a focus on blood pressure control, RAS inhibition and use of statins. Results In total, 434 patients between age 35 and 77 were included (61% males, mean age 56±7 years, eGFR 86±15 ml/min, body mass index 31±6 kg/m, blood pressure 135±16/83±10 mmHg), of whom 80% had hypertension, 43% had diabetes and 42% were obese. RAS-blockers were already taken by 64% of patients, statins by 39%. A diagnosis of CKD (stage ≥G3 and/or ≥A2) was established in 73 patients (17%), 60% of them had diabetes. Compared to patients without CKD, CKD patients were already treated more often with RAS-blockers (78% vs 61%, p=0.005), whereas statin usage was comparable (44% vs 38%, p=0.3347). After CKD diagnosis, medical therapy was changed in 13 patients (18%). A RAS-blocker was initiated in two out of the 16 patients without a preexisting RAS-blocker (12.5%), the dosage was increased in one patient. Antihypertensive therapy was intensified adding amlodipine in seven patients (10%), and a statin was begun in six (15%) out of 41 statin-naive patients. In those without CKD after the screening, therapy was changed in 40 patients (11%). Compared to patients with CKD, fewer patients started a statin therapy (5% vs 15%, p=0.012) and were additionally treated with amlodipine (3% vs 10%, p=0.021) to optimize blood pressure control. Conclusion This study shows that in the primary care setting a great proportion of CKD patients are already on RAS-blockers, whereas the prescription rate for statins is low. A diagnosis of CKD led to a moderate increase in statin therapy, which leaves further opportunity for improvement. The reasons for this rather low use of statins in CKD patients need to be determined.

The Error of Estimated GFR in Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus represents 30–50% of the cases of end stage renal disease worldwide. Thus, a correct evaluation of renal function in patients with diabetes is crucial to prevent or ameliorate diabetes-associated kidney disease. The reliability of formulas to estimate renal function is still unclear, in particular, those new equations based on cystatin-C or the combination of creatinine and cystatin-C. We aimed to assess the error of the available formulas to estimate glomerular filtration rate in diabetic patients. We evaluated the error of creatinine and/or cystatin-C based formulas in reflecting real renal function over a wide range of glomerular filtration rate (from advanced chronic kidney disease to hyperfiltration). The error of estimated glomerular filtration rate by any equation was common and wide averaging 30% of real renal function, and larger in patients with measured glomerular filtration rate below 60 mL/min. This led to chronic kidney disease stages misclassification in about 30% of the individuals and failed to detect 25% of the cases with hyperfiltration. Cystatin-C based formulas did not outperform creatinine based equations, and the reliability of more modern algorithms proved to be as poor as older equations. Formulas failed in reflecting renal function in type 2 diabetes mellitus. Caution is needed with the use of these formulas in patients with diabetes, a population at high risk for kidney disease. Whenever possible, the use of a gold standard method to measure renal function is recommended.

Methods and reporting of kidney function: a systematic review of studies from sub-Saharan Africa.

Globally, chronic kidney disease (CKD) is an emerging public health challenge but accurate data on its true prevalence are scarce, particularly in poorly resourced regions such as sub-Saharan Africa (SSA). Limited funding for population-based studies, poor laboratory infrastructure and the absence of a validated estimating equation for kidney function in Africans are contributing factors. Consequently, most available studies used to estimate population prevalence are hospital-based, with small samples of participants who are at high risk for kidney disease. While serum creatinine is most commonly used to estimate glomerular filtration, there is considerable potential bias in the measurement of creatinine that might lead to inaccurate estimates of kidney disease at individual and population level. To address this, the Laboratory Working Group of the National Kidney Disease Education Program published recommendations in 2006 to standardize the laboratory measurement of creatinine. The primary objective of this review was to appraise implementation of these recommendations in studies conducted in SSA after 2006. Secondary objectives were to assess bias relating to choice of estimating equations for assessing glomerular function in Africans and to evaluate use of recommended diagnostic criteria for CKD. This study was registered with Prospero (CRD42017068151), and using PubMed, African Journals Online and Web of Science, 5845 abstracts were reviewed and 252 full-text articles included for narrative analysis. Overall, two-thirds of studies did not report laboratory methods for creatinine measurement and just over 80% did not report whether their creatinine measurement was isotope dilution mass spectroscopy (IDMS) traceable. For those reporting a method, Jaffe was the most common (93%). The four-variable Modification of Diet in Renal Disease (4-v MDRD) equation was most frequently used (42%), followed by the CKD Epidemiology Collaboration (CKD-EPI) equation for creatinine (26%). For the 4-v MDRD equation and CKD-EPI equations, respectively, one-third to one half of studies clarified use of the coefficient for African-American (AA) ethnicity. When reporting CKD prevalence, <15% of studies fulfilled Kidney Disease: Improving Global Outcomes criteria and even fewer used a population-based sample. Six studies compared performance of estimating equations to measured glomerular filtration rate (GFR) demonstrating that coefficients for AA ethnicity used in the 4-v MDRD and the CKD-EPI equations overestimated GFR in Africans. To improve on reporting in future studies, we propose an ‘easy to use’ checklist that will standardize reporting of kidney function and improve the quality of studies in the region. This research contributes some understanding of the factors requiring attention to ensure accurate assessment of the burden of kidney disease in SSA. Many of these factors are difficult to address and extend beyond individual researchers to health systems and governmental policy, but understanding the burden of kidney disease is a critical first step to informing an integrated public health response that would provide appropriate screening, prevention and management of kidney disease in countries from SSA. This is particularly relevant as CKD is a common pathway in both infectious and non-communicable diseases, and multimorbidity is now commonplace, and even more so when those living with severe kidney disease have limited or no access to renal replacement therapy.

SAT-244 High prevalence and low awareness of proteinuria in the community setting: lessons from the Kidney Disease Screening and Awareness Program (KDSAP)

Chronic kidney disease (CKD) is one of the major global burdens of diseases. However, the awareness of CKD is low in the general population, creating challenges for early intervention. Albuminuria as part of the CKD diagnostic criteria independently predicts adverse clinical outcomes. Therefore, screening for proteinuria and raising awareness of CKD are crucial to public health. Currently, there is no effective strategy to improve awareness of proteinuria. Kidney Disease Screening and Awareness Program (KDSAP) aims for early detection of CKD risk factors by providing free community health screening. Data collected from October 2011 to May 2018 through KDSAP was analyzed. The awareness of proteinuria was assessed by two questions (1) Have you ever had protein in the urine? (2) Do you have kidney disease? (Do not include kidney stones, bladder infections, or incontinence) The diagnosis of proteinuria is based on a cross-sectional measurement of urine dipstick. The awareness of proteinuria is defined as participants with trace or more protein on urine dipstick who answered “yes” to either of the two questions. 2,304 out of 2,432 KDSAP participants with available urine analysis results were analyzed. In this ethnically diverse population (54.1% Asian, 18.5% African American, 14.5% White, and 9.7% Hispanic), 44.2% of participants were non-English speaking. Participants with proteinuria were younger, more likely to be male, African American, and smoker; had hypertension, diabetes, family history of kidney disease, higher body mass index (BMI) and microscopic hematuria. The rate of proteinuria was 20%. Alarmingly, the awareness of mild proteinuria (trace or 1+) and heavy proteinuria (2+ or above) were only 10% and 39.5% respectively. Although the older participants tended to have higher awareness, the overall awareness of proteinuria was low (15.8%). There was no significant difference in insurance coverage and access to care between proteinuria and non-proteinuria group. KDSAP participants had more than two-fold higher prevalence of proteinuria compared with previous studies. Most KDSAP participants with proteinuria were unaware of the condition. Efforts are needed to promote early detection of proteinuria, improve awareness, and modify risk factors to improve outcomes. We proposed that KDSAP is an effective model to identify the population with high risk of kidney disease and low awareness at the community level.

SAT-191 WHOLE GENOME ANALYSIS OF ABORIGINAL AUSTRALIANS REVEALS VARIANTS ASSOCIATED WITH KIDNEY DISEASE

Indigenous Australians in remote areas are up to 20 times more likely to develop end stage renal disease than non-Indigenous Australians. Remote communities in Western Australia and Northern Territory are experiencing an escalating renal disease epidemic, such as the Tiwi people who are at a high risk of kidney disease, significantly reducing their life expectancy. Genetic factors are though to affect 36-75% of kidney function and chronic kidney disease (CKD) progression. Population-scale genomic studies have established that the frequencies of specific disease-associated alleles vary substantially between populations, and identifying these alleles can offer insights useful for preventing, diagnosing, and treating these diseases in a population-specific manner. The Tiwi people have participated in a 25 year longitudinal study of chronic disease incidence, progression, treatments, and outcomes, offering a wealth of biochemical and physical phenotyping data. We have previously shown that there is a strong genetic component to kidney disease among the Tiwi people, but the exact alleles involved remained uncertain. In the present study, we conducted a whole genome sequencing (WGS) analysis of 120 individuals from the Tiwi islands and identified several genetic loci associated with traits linked to kidney disease, including serum creatinine, EGFR, and uric acid levels. Study participants were categorized as cases (n=60) or controls (n=60) for kidney disease, based on albumin creatinine ratio and estimated glomerular filtration rate. We sequenced the whole genomes of 120 participants at 30x coverage using HiSeq X Series, aligned reads to the reference human genome using the BWA tool, and then employed the GATK pipeline to identify genetic variants. Six computational approaches were used to assess the functional impact of genetic variants (SIFT, Polyphen2, MutationTaster2, LRT, FATHMM, and PROVEAN), and we probed the association of identified variants with kidney disease using the ClinVar, GAD, and GWAS databases. MAF (Minor Allele Frequency) analysis was carried out using VCFtools and in-house scripts. Notably, we utilized a customized database of genes associated with kidney disease curated from literature sources and currently available diagnostic gene panels. We identified 12,507,010 variants, of which 19,899 were predicted to be deleterious. We observed an at least 2-fold allelic difference between cases and controls for 569 polymorphic variants, of which 16% were present in the 1000 Genome data (<=1 MAF), and 73% were not present in the 1000G dataset. Further focused kidney disease gene analysis showed that 8 variants were associated with kidney disease. We observed a remarkably high frequency (3-fold) in alleles associated with Alport syndrome in cases relative to controls. Our results suggest population-specific CKD risk alleles exist in the Tiwi people that were not detected by previous lower coverage population genomics studies, and we are collecting samples to validate these findings. These novel variants offer a potential means of screening individuals in this population to identify those at risk of kidney disease. The combination of these genomic data with the available 25 years of compiled longitudinal clinical data represents an invaluable resource that can be harnessed to improve health among all Indigenous Australian populations.

Urinary Tract Infection in Children

Urinary tract infections (UTI) are common among children. In the past 20 years, a number of key trials have substantially changed practice, in addition to clarifying the natural history of children managed expectantly. It is now clear that among children with normal kidneys at presentation, chronic kidney disease and hypertension are rare. Improved antenatal ultrasound now detects most significant abnormalities of the kidney and urinary tract, particularly severe hypodysplasia, which is often associated with high-grade vesico-ureteric reflux (VUR). This review aims to summarize the evidence-based treatment of UTI in children. There is no difference in symptomatic, microbiologic, or renal outcomes between intravenous and oral antibiotics in treating acute, febrile infection. Long-term antibiotic prophylaxis results in a statistically but not clinically significant reduction in recurrence among young children, with or without VUR. Trials to-date have failed to demonstrate that the surgical correction of VUR confers any additional benefit, which may be because the natural history of VUR is to resolution with time and/or that other factors are more important determinants of outcome. A more conservative approach to the management of UTI is warranted for most children. Antibiotic prophylaxis, voiding cystourethrography, and surgery for VUR are not indicated following an initial or infrequent UTI. These measures may have a role in selected subgroups of children at high risk of kidney disease, but this remains a hypothesis pending the results of ongoing trials.

Gene for preeclampsia

Health Preeclampsia is a serious complication of pregnancy that often presents as an increase in maternal blood pressure. The disorder is more prevalent and severe in women with African ancestry, most likely because of genetic factors. Reidy et al. have been investigating a variant of the gene encoding apolipoprotein L1 ( APOL1 ), which was previously shown to confer a high risk of kidney disease in black Americans. Studying two independent populations of pregnant black women, they found that preeclampsia was associated with the APOL1 high-risk genotype. Interestingly, it was the genotype of the fetus, not the mother, that mattered. The fetal APOL1 high-risk genotype may be linked to one in eight cases of preeclampsia in black women. Am. J. Hum. Genet. 103 , 367 (2018).

High Baseline Levels of Tumor Necrosis Factor Receptor 1 Are Associated With Progression of Kidney Disease in Indigenous Australians With Diabetes: The eGFR Follow-up Study.

To examine the association between soluble tumor necrosis factor receptor 1 (sTNFR1) levels and kidney disease progression in Indigenous Australians at high risk of kidney disease. This longitudinal observational study examined participants aged ≥18 years recruited from >20 sites across diabetes and/or kidney function strata. Baseline measures included sTNFR1, serum creatinine, urine albumin-to-creatinine ratio (uACR), HbA1c, C-reactive protein (CRP), waist-to-hip ratio, systolic blood pressure, and medical history. Linear regression was used to estimate annual change in estimated glomerular filtration rate (eGFR) for increasing sTNFR1, and Cox proportional hazards were used to estimate the hazard ratio (HR) and 95% CI for developing a combined renal outcome (first of a ≥30% decline in eGFR with a follow-up eGFR <60 mL/min/1.73 m2, progression to renal replacement therapy, or renal death) for increasing sTNFR1. Over a median of 3 years, participants with diabetes (n = 194) in the highest compared with the lowest quartile of sTNFR1 experienced significantly greater eGFR decline (-4.22 mL/min/1.73 m2/year [95% CI -7.06 to -1.38]; P = 0.004), independent of baseline age, sex, eGFR, and uACR. The adjusted HR (95% CI) for participants with diabetes per doubling of sTNFR1 for the combined renal outcome (n = 32) was 3.8 (1.1-12.8; P = 0.03). No association between sTNFR1 and either renal outcome was observed for those without diabetes (n = 259). sTNFR1 is associated with greater kidney disease progression independent of albuminuria and eGFR in Indigenous Australians with diabetes. Further research is required to assess whether TNFR1 operates independently of other metabolic factors associated with kidney disease progression.

Measured GFR in Routine Clinical Practice-The Promise of Dried Blood Spots.

Accurate determination of glomerular filtration rate (GFR) is crucial for the diagnosis of kidney disease. Estimated GFR (eGFR) calculated by serum creatinine and/or cystatin C is a mainstay in clinical practice and epidemiologic research but lacks precision and accuracy until GFR <60mL/min/1.73m2. Furthermore, eGFR may not precisely and accurately represent changes in GFR longitudinally. The lack of precision and accuracy is of concern in populations at high risk for kidney disease, as the dissociation between changes in eGFR and GFR may lead to missed diagnoses of early kidney disease. Therefore, improved methods to quantify GFR are needed. Whereas direct measures of GFR have been too cumbersome for screening and ambulatory care, a practical method of measuring GFR by iohexol clearance using dried capillary blood spots exists. In this review, we examine the current literature and data addressing GFR measurements by dried capillary blood spots and its potential application in high-risk groups.

P092 APOL1 genotyping: Can it aid in donor selection?

Aim Apolipoprotein L1 (APOL1) is capable of killing Trypanosoma brucei brucei . In populations with recent African ancestry, 2 APOL1 coding variants (G1, G2) confer resistance to T. brucei rhodesiense, a leading cause of African sleeping sickness. G1 is a pair of non-synonymous single nucleotide polymorphisms (SNPs; S342G and I384M). G2 is an in-frame deletion of 2 amino acid residues, N388 and Y389. People with one G1 or G2 variant are resistant to T. b. rhodesiense , but those with 2 copies of G1 and/or G2 are at high risk for kidney disease. Knowledge of APOL1 renal-risk genotypes may aid physicians in allocation of deceased donor kidneys and suitability of living donors, potentially improving outcomes for recipients and donors. This study aimed to evaluate the feasibly of performing rapid genotyping in an “on call” situation. Methods Using a MicroAmp® Optical 96-well Reaction Plate, 2 μl of DNA is added to 3 wells. A cocktail containing TaqMan® Genotyping Master Mix plus Custom TaqMan® SNP Genotyping Mix is made for each of the 3 SNP’s (rs73885319 [G1a], rs60910145 [G1b], rs143830837 [G2]) then added to the appropriate wells. The tray is sealed, placed into a Thermo-Fisher ViiA7 TM and run using a predefined program. Based on intensity data, risk is assigned based on the homozygous presence of the nucleotide guanine at both of the sites in G1 or homozygosity of deletion at G2. Alternatively, risk can be assigned via the combination of heterozygous mutations at both G1 and G2. Results To date, nearly 100 African American deceased donors and 10 potential living donors have been tested. Utilizing Real-time PCR techniques, it was feasible to perform APOL1 testing in an afterhours situation, adding no more than 30 min to the time required for HLA typing. Conclusions APOL1 genotyping may assist in determining risk for chronic kidney disease. We conclude that rapid APOL1 testing is feasible to perform alongside our normal histocompatibility testing, even in on call situations. B.I. Freeman: Grant/Research Support; Company/Organization; Novartis Pharmaceuticals. Consultant; Company/Organization; Ionis Pharmaceuticals. Other (Identify); Company/Organization; Wake Forest University Health Sciences and Dr. Barry Freedman have applied for a patent related to APOL1 genetic testing.