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      Insights into the Role of Renal Biopsy in Patients with T2DM: A Literature Review of Global Renal Biopsy Results

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          Abstract

          Introduction

          Renal biopsy performed in patients with type 2 diabetes mellitus (T2DM) for atypical or suspected diabetic kidney disease (DKD) reveals one of three possibilities: diabetic nephropathy (DN, pathological diagnosis of DKD), nondiabetic kidney disease (NDKD) and DN plus NDKD (mixed form). NDKD (including the mixed form) is increasingly being recognized worldwide. With the emerging concept of DKD and the complexity of routine application of renal biopsy, the identification of “clinical indicators” to differentiate DKD from NDKD has been an area of active research.

          Methods

          The PubMed database was searched for relevant articles mainly according to the keyword search method. We reviewed prevalence of the three types of DKD and different pathological lesions of NDKD. We also reviewed the clinical indicators used to identify DKD and NDKD.

          Results

          The literature search identified 40 studies (5304 data) worldwide between 1977 and 2019 that looked at global renal biopsy and pathological NDKD lesions. The overall prevalence rate of DN, NDKD and DN plus NDKD is reported to be 41.3, 40.6 and 18.1%, respectively. In Asia, Africa (specifically Morocco and Tunisia) and Europe, the most common isolated NDKD pathological type is membranous nephropathy, representing 24.1, 15.1 and 22.6% of cases, respectively. In contrast, focal segmental glomerulosclerosis is reported to be the primary pathological type in North America (specifically the USA) and Oceania (specifically New Zealand), representing 22% and 63.9% of cases, respectively. Tubulointerstitial disease accounts for a high rate in the mixed group (21.7%), with acute interstitial nephritis being the most prevalent (9.3%), followed by acute tubular necrosis (9.0%). Regarding clinical indicators to differentiate DKD from NDKD, a total of 14 indicators were identified included in 42 studies. Among these, the most commonly studied indicators included diabetic retinopathy, duration of diabetes, proteinuria and hematuria. Regrettably, indicators with high sensitivity and specificity have not yet been identified.

          Conclusion

          To date, renal biopsy is still the gold standard to diagnose diabetes complicated with renal disease, especially when T2DM patients present atypical DKD symptoms (e.g. absence of diabetic retinopathy, shorter duration of diabetes, microscopic hematuria, sub-nephrotic range proteinuria, lower glycated hemoglobin, lower fasting blood glucose). We conclude that renal biopsy as early as possible is of great significance to enable personalized treatment to T2DM patients.

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          Most cited references79

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          Diabetic kidney disease

          The kidney is arguably the most important target of microvascular damage in diabetes. A substantial proportion of individuals with diabetes will develop kidney disease owing to their disease and/or other co-morbidity, including hypertension and ageing-related nephron loss. The presence and severity of chronic kidney disease (CKD) identify individuals who are at increased risk of adverse health outcomes and premature mortality. Consequently, preventing and managing CKD in patients with diabetes is now a key aim of their overall management. Intensive management of patients with diabetes includes controlling blood glucose levels and blood pressure as well as blockade of the renin-angiotensin-aldosterone system; these approaches will reduce the incidence of diabetic kidney disease and slow its progression. Indeed, the major decline in the incidence of diabetic kidney disease (DKD) over the past 30 years and improved patient prognosis are largely attributable to improved diabetes care. However, there remains an unmet need for innovative treatment strategies to prevent, arrest, treat and reverse DKD. In this Primer, we summarize what is now known about the molecular pathogenesis of CKD in patients with diabetes and the key pathways and targets implicated in its progression. In addition, we discuss the current evidence for the prevention and management of DKD as well as the many controversies. Finally, we explore the opportunities to develop new interventions through urgently needed investment in dedicated and focused research. For an illustrated summary of this Primer, visit: http://go.nature.com/NKHDzg.
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            CKD in diabetes: diabetic kidney disease versus nondiabetic kidney disease

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              Prevalence of Diagnosed Diabetes in Adults by Diabetes Type — United States, 2016

              Currently 23 million U.S. adults have been diagnosed with diabetes ( 1 ). The two most common forms of diabetes are type 1 and type 2. Type 1 diabetes results from the autoimmune destruction of the pancreas’s beta cells, which produce insulin. Persons with type 1 diabetes require insulin for survival; insulin may be given as a daily shot or continuously with an insulin pump ( 2 ). Type 2 diabetes is mainly caused by a combination of insulin resistance and relative insulin deficiency ( 3 ). A small proportion of diabetes cases might be types other than type 1 or type 2, such as maturity-onset diabetes of the young or latent autoimmune diabetes in adults ( 3 ). Although the majority of prevalent cases of type 1 and type 2 diabetes are in adults, national data on the prevalence of type 1 and type 2 in the U.S. adult population are sparse, in part because of the previous difficulty in classifying diabetes by type in surveys ( 2 , 4 , 5 ). In 2016, supplemental questions to help distinguish diabetes type were added to the National Health Interview Survey (NHIS) ( 6 ). This study used NHIS data from 2016 to estimate the prevalence of diagnosed diabetes among adults by primary type. Overall, based on self-reported type and current insulin use, 0.55% of U.S. adults had diagnosed type 1 diabetes, representing 1.3 million adults; 8.6% had diagnosed type 2 diabetes, representing 21.0 million adults. Of all diagnosed cases, 5.8% were type 1 diabetes, and 90.9% were type 2 diabetes; the remaining 3.3% of cases were other types of diabetes. Understanding the prevalence of diagnosed diabetes by type is important for monitoring trends, planning public health responses, assessing the burden of disease for education and management programs, and prioritizing national plans for future type-specific health services. NHIS is an annual, cross-sectional household interview survey conducted by CDC that gathers health-related data in a nationally representative sample of the civilian, noninstitutionalized U.S. population ( 6 ). The 2016 NHIS Sample Adult Core consisted of 33,028 adults aged ≥18 years, with a final response rate of 54.3%. Each respondent was randomly selected among all adults aged ≥18 years in each household. During face-to-face interviews, respondents were asked whether a doctor or health care professional had ever told them that they had diabetes, other than during pregnancy. Among those who said they had diabetes, questions were asked regarding age at diagnosis and insulin and oral hypoglycemic medication use. In 2016, respondents were also asked to report whether they had type 1, type 2, or another type of diabetes. Virtually all patients with type 1 diabetes require insulin to survive, and very few persons who use insulin do not report using it ( 5 ). Previous studies have found that self-reported diabetes type alone is not a valid method for classifying diabetes type in surveys because some patients are not aware of their diabetes type ( 5 , 7 ). Therefore, for this analysis, type 1 diabetes was defined as current insulin use and self-report of type 1 diabetes. Adults who reported having type 1 diabetes but reported not using insulin were classified as having type 2 diabetes, as were persons who reported type 2 diabetes, unknown diabetes type, or who would not report diabetes type. Respondents who reported having another diabetes type were classified as having “other type.” Crude prevalence estimates of diagnosed diabetes by type and 95% confidence intervals (CIs) were calculated for the overall population and by selected sociodemographic characteristics. P values were calculated from chi-squared tests and were considered significant at High school 0.48 (0.39–0.61) 6.89 (6.47–7.34) 0.27 (0.19–0.38) Abbreviation: CI = confidence interval. * Overall crude prevalence of diagnosed diabetes = 9.44% (95% CI = 9.01–9.88). † Type 1 diabetes was defined as self-report of type 1 diabetes and current insulin use. Respondents who self-reported other diabetes types were classified as having “other type” diabetes. All remaining cases were classified as type 2 diabetes. § Estimates are weighted percentages and 95% CIs. CIs were based on a logit transformation and might be asymmetric about the point estimate. ¶ Estimate might be unreliable because of large relative standard error (>30%); data not shown. Estimated crude prevalence of type 1 diabetes among U.S. adults did not significantly vary by age group (p = 0.54) or education (p = 0.14) (Table). The prevalence of type 1 diabetes was higher among men (0.64%) than among women (0.46%) (p<0.05) and higher among non-Hispanic whites (whites) (0.67%) than among Hispanics (0.22%) (p<0.01). By age group, the prevalence of type 2 diabetes was highest among adults aged ≥65 years and lowest among adults aged 18–29 years (p<0.001), and by race/ethnicity, was higher among non-Hispanic blacks (11.52%) than among non-Hispanic Asians (6.89%), whites (7.99%), and Hispanics (9.07%) (p<0.001) (Table). The prevalence of type 2 diabetes decreased with higher levels of educational attainment (p<0.001). Discussion In 2016, the estimated prevalences of diagnosed type 1 and type 2 diabetes were 0.55% (corresponding to 1.3 million U.S. adults) and 8.6% (corresponding to 21.0 million U.S. adults), respectively. Type 1 and type 2 diabetes accounted for approximately 6% and 91% of all cases of diagnosed diabetes, respectively. Because the prevalence of type 2 diabetes is so much higher than that of type 1, current diabetes surveillance data that do not distinguish diabetes type are more reflective of persons with type 2 diabetes. Recent analysis of diagnosed diabetes prevalence indicates a plateauing among adults aged 20–79 years ( 8 ), but it is not known whether this trend might differ for type 1 diabetes. Because the etiology, treatment, and outcomes of diabetes vary by type, it is important to distinguish between them. There is no reference standard for classifying prevalent type 1 diabetes or type 2 diabetes cases in public health surveillance. The presence of autoantibodies against the beta cells of the pancreas and the lack of endogenous insulin secretion are biologic markers of type 1 diabetes. However, beta cell autoantibodies disappear with time and might even be absent at the time of type 1 diabetes diagnosis ( 2 ). Insulin secretion tests are difficult to perform and interpret, making these tests unsuitable for use in cross-sectional surveys. In administrative health databases and electronic medical records, adults with diabetes frequently have International Classification of Diseases codes for both type 1 and type 2 diabetes. For this reason, disease coding has been combined with other information (e.g., current prescriptions for insulin or oral hypoglycemic medication) when estimating diabetes type in these data ( 9 , 10 ). Using type 1 diabetes self-report and current insulin use to classify diabetes type, the percentage of all diabetes cases that were type 1 diabetes fell reasonably within the range of results from other studies (approximately 5%–10%) ( 3 – 5 , 9 ). The findings in this report are subject to at least three limitations. First, the data were self-reported and underestimate the total number of adults with diabetes. Second, data were not validated, which could have led to misclassification of diabetes type. Adults with self-reported type 1 diabetes who did not report insulin use were reclassified as having type 2 diabetes, which might have resulted in misclassification if they actually used insulin but did not report use. However, self-reported use of insulin is highly specific: <0.02% of persons who reported insulin in a medication log failed to report using it when asked ( 5 ). Some insulin users with type 2 diabetes might have incorrectly reported type 1 diabetes, assuming that taking insulin meant they had type 1 diabetes ( 5 ). In addition, because self-reported cases of unknown type were reclassified as type 2 diabetes, the prevalence of type 2 diabetes might have been overestimated. However, according to a Canadian survey-based algorithm to distinguish diabetes types, 99% of adults who self-reported unknown type would have been classified as type 2 diabetes ( 7 ). Finally, the small sample size of some subgroups limited precision. Despite these limitations, this first study to estimate the prevalence of diagnosed type 1 and type 2 diabetes based on self-report and current insulin use among U.S. adults provides information to track prevalence of diabetes by type to monitor trends and assess the burden of disease for education and prevention programs. Knowledge about national prevalences of type 1 and type 2 diabetes might facilitate assessment of the long-term cost-effectiveness of public health interventions and policies aimed at improving diabetes management and help to prioritize national plans for future type-specific health services. Summary What is already known about this topic? The two most common forms of diabetes are type 1 and type 2. Previous national diabetes prevalence estimates did not distinguish between types among U.S. adults. What is added by this report? New data allowed estimation of diagnosed diabetes by type. In 2016, the prevalence of diagnosed type 1 diabetes was 0.55%, representing 1.3 million U.S. adults; the prevalence of diagnosed type 2 diabetes was 8.6%, representing 21.0 million U.S. adults. Non-Hispanic white adults had a higher prevalence of diagnosed type 1 diabetes than did Hispanic adults. Non-Hispanic blacks had the highest prevalence of diagnosed type 2 diabetes. Diagnosed type 2 diabetes prevalence estimates increased with age and decreased with increasing levels of educational attainment. What are the implications for public health practice? Knowledge about national prevalence of diagnosed diabetes by type might be helpful in monitoring trends, assessing the burden of disease for education and management programs, and guiding and prioritizing national plans for future type-specific health services.
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                Author and article information

                Contributors
                yb8203@126.com
                Journal
                Diabetes Ther
                Diabetes Ther
                Diabetes Therapy
                Springer Healthcare (Cheshire )
                1869-6953
                1869-6961
                5 August 2020
                5 August 2020
                September 2020
                : 11
                : 9
                : 1983-1999
                Affiliations
                [1 ]GRID grid.412635.7, ISNI 0000 0004 1799 2712, Department of Nephrology, , First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, ; Tianjin, China
                [2 ]GRID grid.412125.1, ISNI 0000 0001 0619 1117, Department of Internal Medicine and Nephrology, , King Abdulaziz University, ; Jeddah, Saudi Arabia
                Article
                888
                10.1007/s13300-020-00888-w
                7434810
                32757123
                ea89d76f-57bd-46eb-8a43-704333f2dec0
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 17 June 2020
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                Review
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                © The Author(s) 2020

                Endocrinology & Diabetes
                type 2 diabetes mellitus,renal biopsy,diabetic kidney disease,nondiabetic kidney disease,clinical indicators

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