Chronic kidney disease: whom to screen and how to treat, part 1: definition, epidemiology, and laboratory testing.
South Med J. 2010 Feb;103(2):140-6
Authors: Brosnahan G, Fraer M
Chronic kidney disease has become a major public health problem due to its high prevalence, its exorbitant cost, and large reductions in life expectancy and quality of life of affected people. Seventy percent of cases of end-stage renal disease are due to diabetes and hypertension, conditions which are usually managed by primary care providers. Other risk factors are cardiovascular disease, obesity, smoking, family history of kidney disease, and age greater than 55 years. Patients with these risk factors should be evaluated for the presence of chronic kidney disease during their primary care visits, because effective treatments for slowing progression are available, particularly if instituted early. Chronic kidney disease can be diagnosed by simple blood and urine tests, as recommended in guidelines issued by the National Kidney Foundation. This article begins with a case vignette, representing a common clinical scenario from a general internist’s practice. We then review the definition and classification of chronic kidney disease, the epidemiology, etiology, and interconnections with cardiovascular disease. We discuss the guidelines for screening and laboratory testing, as well as the limitations of current assessment tools. A subsequent article will review evidence-based management of chronic kidney disease.
PMID: 20065899 [PubMed - indexed for MEDLINE]
…more
Polygenic risk variants for type 2 diabetes susceptibility modify age at diagnosis in monogenic HNF1A diabetes.
Diabetes. 2010 Jan;59(1):266-71
Authors: Lango Allen H, Johansson S, Ellard S, Shields B, Hertel JK, Raeder H, Colclough K, Molven A, Frayling TM, Njølstad PR, Hattersley AT, Weedon MN
OBJECTIVE: Mutations in the HNF1A gene are the most common cause of maturity-onset diabetes of the young (MODY). There is a substantial variation in the age at diabetes diagnosis, even within families where diabetes is caused by the same mutation. We investigated the hypothesis that common polygenic variants that predispose to type 2 diabetes might account for the difference in age at diagnosis. RESEARCH DESIGN AND METHODS: Fifteen robustly associated type 2 diabetes variants were successfully genotyped in 410 individuals from 203 HNF1A-MODY families, from two study centers in the U.K. and Norway. We assessed their effect on the age at diagnosis both individually and in a combined genetic score by summing the number of type 2 diabetes risk alleles carried by each patient. RESULTS: We confirmed the effects of environmental and genetic factors known to modify the age at HNF1A-MODY diagnosis, namely intrauterine hyperglycemia (-5.1 years if present, P = 1.6 x 10(-10)) and HNF1A mutation position (-5.2 years if at least two isoforms affected, P = 1.8 x 10(-2)). Additionally, our data showed strong effects of sex (females diagnosed 3.0 years earlier, P = 6.0 x 10(-4)) and age at study (0.3 years later diagnosis per year increase in age, P = 4.7 x 10(-38)). There were no strong individual single nucleotide polymorphism effects; however, in the combined genetic score model, each additional risk allele was associated with 0.35 years earlier diabetes diagnosis (P = 5.1 x 10(-3)). CONCLUSIONS: We show that type 2 diabetes risk variants of modest effect sizes reduce the age at diagnosis in HNF1A-MODY. This is one of the first studies to demonstrate that clinical characteristics of a monogenic disease can be modified by common polygenic variants.
PMID: 19794065 [PubMed - indexed for MEDLINE]
…more
GAD antibody positivity predicts type 2 diabetes in an adult population.
Diabetes. 2010 Feb;59(2):416-22
Authors: Lundgren VM, Isomaa B, Lyssenko V, Laurila E, Korhonen P, Groop LC, Tuomi T,
OBJECTIVE: To evaluate the significance of GAD antibodies (GADAs) and family history for type 1 diabetes (FH(T1)) or type 2 diabetes (FH(T2)) in nondiabetic subjects. RESEARCH DESIGN AND METHODS: GADAs were analyzed in 4,976 nondiabetic relatives of type 2 diabetic patients or control subjects from Finland. Altogether, 289 (5.9%) were GADA(+)-a total of 253 GADA(+) and 2,511 GADA(-) subjects participated in repeated oral glucose tolerance tests during a median time of 8.1 years. The risk of progression to diabetes was assessed using Cox regression analysis. RESULTS: Subjects within the highest quartile of GADA(+) (GADA(+)(high)) had more often first-degree FH(T1) (29.2 vs. 7.9%, P < 0.00001) and GADA(+) type 2 diabetic (21.3 vs. 13.7%, P = 0.002) or nondiabetic (26.4 vs. 13.3%, P = 0.010) relatives than GADA(-) subjects. During the follow-up, the GADA(+) subjects developed diabetes significantly more often than the GADA(-) subjects (36/253 [14.2%] vs. 134/2,511 [5.3%], P < 0.00001). GADA(+)(high) conferred a 4.9-fold increased risk of diabetes (95% CI 2.8-8.5) compared with GADA(-)-seroconversion to positive during the follow-up was associated with 6.5-fold (2.8-15.2) and first-degree FH(T1) with 2.2-fold (1.2-4.1) risk of diabetes. Only three subjects developed type 1 diabetes, and others had a non-insulin-dependent phenotype 1 year after diagnosis. GADA(+) and GADA(-) subjects did not clinically differ at baseline, but they were leaner and less insulin resistant after the diagnosis of diabetes. CONCLUSIONS: GADA positivity clusters in families with type 1 diabetes or latent autoimmune diabetes in adults. GADA positivity predicts diabetes independently of family history of diabetes, and this risk was further increased with high GADA concentrations.
PMID: 19864397 [PubMed - indexed for MEDLINE]
…more
