In patients with type 1 diabetes and new-onset microalbuminuria the development of advanced chronic kidney disease may not require progression to proteinuria

Perkins, Bruce A.; Ficociello, Linda H.; Roshan, Bijan; Warram, James H.; Królewski, Andrzej S.

doi:10.1038/ki.2009.399

Cited by 251 publications

(197 citation statements)

References 41 publications

(46 reference statements)

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“…In Pima Indians with type 2 diabetes, RFD occurs frequently before the onset of macroalbuminuria, as it does in type 1 diabetes (3)(4)(5). Progression to ESRD, however, is strongly dependent on progression to macroalbuminuria.…”

Section: Discussionmentioning

confidence: 98%

“…The risk of progressing to ESRD is greatest in patients with macroalbuminuria and intermediate in those with microalbuminuria relative to normal ACR (1). Identifying which patients with microalbuminuria are most likely to develop more advanced kidney disease is difficult, because many patients with microalbuminuria regress to normal urinary albumin excretion during follow-up (1,2), and progression of kidney disease may not depend on progression to macroalbuminuria (3).…”

Section: Introductionmentioning

confidence: 99%

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Early Renal Function Decline in Type 2 Diabetes

Pavkov

Knowler

Lemley

et al. 2012

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives Early decline in GFR may reflect progressive kidney disease in type 1 diabetes, but its predictive value in type 2 diabetes is uncertain.Design, setting, participants, & measurements In this longitudinal study, GFR was measured serially over approximately 4.0 years in 195 Pima Indians with type 2 diabetes. Renal function decline (RFD) was defined during this initial period by an average GFR loss $3.3%/yr, as defined previously in type 1 diabetes. Subsequently, participants were followed for up to 17.8 years to ESRD onset, death, or December 31, 2010, whichever came first.Results RFD prevalence during the initial period was 32% in 68 participants with normal baseline albuminuria (albumin/creatinine ratio [ACR] , 30 mg/g), 42% in 88 with microalbuminuria (ACR 30 to ,300 mg/g), and 74% in 39 with macroalbuminuria (ACR $300 mg/g; P,0.001). The cumulative incidence of ESRD 10 years after the initial period was 41% in those with RFD and 15% in those without (P,0.001); 41 of the 49 ESRD cases (83.7%) occurred in participants who had or developed macroalbuminuria during the initial period. When adjusted for age, sex, diabetes duration, and hemoglobin A1c, the ESRD hazard rate was 4.78 times (95% confidence interval, 2.39-9.58) as high in those with RFD as in those without; further adjustment for albuminuria attenuated this association (hazard ratio, 1.79; 95% confidence interval, 0.82-3.91).Conclusions In type 2 diabetes, loss of GFR often occurs before the onset of macroalbuminuria, but a decline predictive of ESRD is strongly dependent on progression to macroalbuminuria.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Early Renal Function Decline in Type 2 Diabetes

Pavkov

Knowler

Lemley

et al. 2012

Clinical Journal of the American Society of Nephrology

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“…Assessments of cardiac autonomic nerve function were performed for a subset of 370 (29%) patients during the last 12 months of the 2-year accrual period and are the focus of the current study. According to AER, the study cohort was divided into three distinct subgroups: 204 of 834 (24%) patients with long-standing normoalbuminuria, 27 of 109 (25%) patients with new-onset microalbuminuria, and 139 of 312 (45%) patients with prevalent microalbuminuria (22,23). Compared with those not examined by HRV, participants in this analysis did not differ according to age, diabetes duration, sex, systolic BP, hemoglobin A1c (HbA1c), lipid profile, or AER.…”

Section: Selection Of Study Participantsmentioning

confidence: 99%

Cardiac Autonomic Neuropathy and Early Progressive Renal Decline in Patients with Nonmacroalbuminuric Type 1 Diabetes

Orlov

Cherney

Pop‐Busui

et al. 2015

Clinical Journal of the American Society of Nephrology

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Background and objectives Cardiac autonomic neuropathy predicts future adverse renal outcomes in the general population. This study sought to determine its relationship with early progressive renal decline in type 1 diabetes.Design, setting, participants, & measurements A subset of participants with normoalbuminuria (n=204) or microalbuminuria (n=166) from the First Joslin Kidney Study underwent assessment for cardiac autonomic neuropathy using heart rate variability during baseline visits performed from January 1991 to April 1992. Cardiac autonomic neuropathy was defined as an R-R variation (mean circular resultant) ,20. Participants also had baseline and follow-up measurement of eGFR. Early progressive renal decline was evaluated according to two definitions: early GFR loss (slope of eGFR estimated by cystatin C ,23.3%/year) and incident advanced CKD (stage $3, defined by eGFR [calculated by Modification of Diet in Renal Disease method] ,60 ml/min per 1.73 m 2 ). Association with baseline cardiac autonomic neuropathy was assessed by adjusted logistic regression and Cox proportional hazards.Results Among the 370 participants, 47 (13%) had baseline cardiac autonomic neuropathy, 51 (14%) had early GFR loss, and 68 (18%) had incident advanced CKD over a median 14-year follow-up. Early GFR loss occurred in 15 (32%) of the 47 patients with baseline autonomic neuropathy and in 32 (10%) of the 323 without baseline autonomic neuropathy (P,0.001). Baseline autonomic neuropathy was strongly associated with odds of early GFR loss (adjusted odds ratio, 4.09; 95% confidence interval, 1.65 to 10.12; P=0.002). Incident advanced CKD was observed in 22 (47%) of those with baseline autonomic neuropathy and 46 (14%) of those without baseline autonomic neuropathy (P,0.001). Autonomic neuropathy was independently associated with incident advanced CKD (adjusted hazard ratio, 2.76; 95% confidence interval, 1.44 to 5.30; P=0.002).Conclusions Cardiac autonomic neuropathy was a strong independent predictor of the long-term risk of early progressive renal decline in type 1 diabetes. Future research should explore the mechanisms by which autonomic neuropathy may be associated with renal function loss.

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“…2 Data from several longitudinal studies reported in the 2000s, including several from our group, [3][4][5] began to show that the true evolution of diabetic nephropathy differs from this model. In fact, it has been shown that patients with albuminuria can frequently revert to normoalbuminuria.…”

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confidence: 99%