Value of adding the renal pathological score to the kidney failure risk equation in advanced diabetic nephropathy

金沢大学医薬保健研究域医学系Background There have been a limited number of biopsy-based studies on diabetic nephropathy, and therefore the clinical importance of renal biopsy in patients with diabetes in late-stage chronic kidney disease (CKD) is still debated. We aimed to clarify the renal prognostic value of pathological information to clinical information in patients with diabetes and advanced CKD. Methods We retrospectively assessed 493 type 2 diabetics with biopsy-proven diabetic nephropathy in four centers in Japan. 296 patients with stage 3–5 CKD at the time of biopsy were identified and assigned two risk prediction scores for end-stage renal disease (ESRD): the Kidney Failure Risk Equation (KFRE, a score composed of clinical parameters) and the Diabetic Nephropathy Score (D-score, a score integrated pathological parameters of the Diabetic Nephropathy Classification by the Renal Pathology Society (RPS DN Classification)). They were randomized 2:1 to development and validation cohort. Hazard Ratios (HR) of incident ESRD were reported with 95% confidence interval (CI) of the KFRE, D-score and KFRE+D-score in Cox regression model. Improvement of risk prediction with the addition of D-score to the KFRE was assessed using c-statistics, continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Results During median follow-up of 1.9 years, 194 patients developed ESRD. The cox regression analysis showed that the KFRE,D-score and KFRE+D-score were significant predictors of ESRD both in the development cohort and in the validation cohort. The c-statistics of the D-score was 0.67. The c-statistics of the KFRE was good, but its predictive value was weaker than that in the miscellaneous CKD cohort originally reported (c-statistics, 0.78 vs. 0.90) and was not significantly improved by adding the D-score (0.78 vs. 0.79, p = 0.83). Only continuous NRI was positive after adding the D-score to the KFRE (0.4%; CI: 0.0–0.8%). Conclusions We found that the predict values of the KFRE and the D-score were not as good as reported, and combining the D-score with the KFRE did not significantly improve prediction of the risk of ESRD in advanced diabetic nephropathy. To improve prediction of renal prognosis for advanced diabetic nephropathy may require different approaches with combining clinical and pathological parameters that were not measured in the KFRE and the RPS DN Classification. © 2018 Yamanouchi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

The features of bone articular lesions in dialysis-related amyloidosis (DRA) and criteria for the clinical diagnosis of DRA

Abstract We introduced criteria for the clinical diagnosis of dialysis-related amyloidosis (DRA) from the Amyloidosis Research Group study supported by a Grant-in-Aid from the Ministry of Health, Labour and Welfare of Japan. DRA exhibits various kinds of bone articular lesions, such as carpal tunnel syndrome, trigger finger, destructive spondyloarthropathy, spinal canal stenosis, and joint pains. These bone articular lesions, excluding destructive spondyloarthropathy, are observed in non-dialysis patients or dialysis patients without DRA. We carefully compared these lesions between DRA and non-DRA patients and summarized the differences between them. The incidence age, male to female ratio, and coincidence rate were distinct between these groups of patients. Biopsies from bone articular lesions are invasive and burdensome for dialysis patients; therefore, a precise clinical diagnosis is required for DRA. We discussed the validity and availability of our proposed criteria

Glycated albumin and hemoglobin A1c levels and cause-specific mortality by patients’ conditions among hemodialysis patients with diabetes: a 3-year nationwide cohort study

Introduction Differences in mortality and cause-specific mortality rates according to glycated albumin (GA) and hemoglobin A1c (HbA1c) levels among dialysis patients with diabetes based on hypoglycemic agent use and malnutrition status remain unclear. Here, we examine these associations using a nationwide cohort.Research design and methods We examined 40 417 dialysis patients with diabetes who met our inclusion criteria (female, 30.8%; mean age, 67.3±11.2 years; mean dialysis duration, 5.4±4.6 years). The Global Leadership Initiative on Malnutrition criteria were used to assess malnutrition. Adjusted HRs and 95% confidence limits were calculated for 3-year mortality after adjustment for 18 potential confounders. HRs and subdistribution HRs were used to explore cause-specific mortality.Results We found a linear association between 3-year mortality and GA levels only in patients with GA ≥18% and not in patients with low GA levels, with a U-shaped association between HbA1c levels and the lowest morality at an HbA1c 6.0%–6.3%. This association differed based on patient conditions and hypoglycemic agent use. If patients using hypoglycemic agents were malnourished, mortality was increased with GA ≥24% and HbA1c ≥8%. In addition, patients with GA ≥22% and HbA1c ≥7.6% had significantly higher infectious or cardiovascular mortality rates. On the other hand, an inverse association was found between GA or HbA1c levels and cancer mortality. Patients with GA ≤15.8% had a higher risk of cancer mortality, especially those not using hypoglycemic agents (HR 1.63 (1.00–2.66)).Conclusions Target GA and HbA1c levels in dialysis patients may differ according to hypoglycemic agent use, nutritional status, and the presence of cancer. The levels may be higher in malnourished patients than in other patients, and a very low GA level in dialysis patients not taking hypoglycemic agents may be associated with a risk of cancer.Trial registration number UMIN000018641

Corticosteroids pulse therapy and oral corticosteroids therapy for IgA nephropathy patients with advanced chronic kidney disease: results of a multicenter, large-scale, long-term observational cohort study

Abstract Background Corticosteroids are widely used to reduce the urine protein levels of patients with immunoglobulin A nephropathy (IgAN). However, their potential preventive effects on end-stage kidney disease (ESKD) are unclear. Methods We previously performed a large-scale, long-term multicenter cohort study of patients with biopsy-proven IgAN treated between 1981 and 2013 (n = 1923). Based on the results, we reported that corticosteroids pulse therapy was potentially effective for the treatment of patients with an eGFR ≥30 ml/min/1.73m2 and a urine protein amount of ≥1 g/gCr. In the present study, we extracted 766 patients with chronic kidney disease (CKD), stage G3–G4 (15 ≤ estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73m2) from the same cohort. We divided these patients into a steroid pulse (SP) group, oral steroid (OS) group, and no steroid (NS) group, and analyzed the risk of end-stage kidney disease (ESKD) stratified by eGFR and urine protein (UP) amounts. Results Over the median long-term follow-up of 70 ± 115 months, 37.1% of the patients with UP ≥1.0 g/day and 11.2% of the patients with UP < 1.0 g/day reached ESKD. Among the patients with UP ≥1 g/gCr, the SP group showed significantly better renal outcome (p < 0.001) than the OS and NS groups. In patients with UP < 1 g/gCr, there were no differences in renal survival among the treatment groups. These trends appeared even in the CKD stage G4 patients, and were also apparent in patients taking renin-angiotensin system inhibitors. The unprecedented long-term observation period in this study may have been necessary to reveal the favorable effect of corticosteroids on ESKD progression. Conclusions In our long-term multicenter study, Corticosteroids pulse therapy was associated with better renal outcomes in IgAN patients with higher UP values, even if their eGFR values were low

Developing an HbA(1c)-based equation to estimate blood glucose in maintenance hemodialysis patients.

ObjectiveHemoglobin A1c (HbA(1c)) has been widely used as a clinically important assessment tool for outcome analyses related to glycemic control. However, because of special conditions in dialysis patients, including the uremic milieu, there is no HbA(1c) blood glucose (BG) equation specific for patients on dialysis. In this study, we sought to develop HbA(1c)-BG equation models for hemodialysis patients.Research design and methodsWe examined associations between HbA(1c) and random serum BG over time in a contemporary cohort of diabetic patients with hemodialysis treated in DaVita dialysis clinics. We identified 11,986 patients (63 ± 12 years old and 49% male) with 69,764 paired measurements of HbA(1c) and BG over the course of 5 years (2001-2006). Bootstrapping method was used to estimate average BG and corresponding HbA(1c) levels. The association was adjusted by patient factors using linear regression.ResultsLinear regression analyses yielded the following three regression equations: BG = 59.2 + 29.4 × HbA(1c) - 20.8 × Alb (R(2) = 0.483); BG = 104.8 + 29.7 × HbA(1c) - 18.4 × Alb - 4.7 × Hb (R(2) = 0.486); and BG = 82.9 + 30.7 × HbA(1c) - 16.5 × Alb - 5.4 × Hb + 0.3 × age + race (R(2) = 0.491). All our models showed stronger association than previous equation models (R(2) = 0.468 in the Diabetes Control and Complications Trial and A1c-Derived Average Glucose equations).ConclusionsThe association between HbA(1c) and BG in hemodialysis patients is different than that of patients with normal kidney function. Our analysis suggests that equations including serum albumin or hemoglobin are better for hemodialysis patients

Developing an HbA(1c)-based equation to estimate blood glucose in maintenance hemodialysis patients.

ObjectiveHemoglobin A1c (HbA(1c)) has been widely used as a clinically important assessment tool for outcome analyses related to glycemic control. However, because of special conditions in dialysis patients, including the uremic milieu, there is no HbA(1c) blood glucose (BG) equation specific for patients on dialysis. In this study, we sought to develop HbA(1c)-BG equation models for hemodialysis patients.Research design and methodsWe examined associations between HbA(1c) and random serum BG over time in a contemporary cohort of diabetic patients with hemodialysis treated in DaVita dialysis clinics. We identified 11,986 patients (63 ± 12 years old and 49% male) with 69,764 paired measurements of HbA(1c) and BG over the course of 5 years (2001-2006). Bootstrapping method was used to estimate average BG and corresponding HbA(1c) levels. The association was adjusted by patient factors using linear regression.ResultsLinear regression analyses yielded the following three regression equations: BG = 59.2 + 29.4 × HbA(1c) - 20.8 × Alb (R(2) = 0.483); BG = 104.8 + 29.7 × HbA(1c) - 18.4 × Alb - 4.7 × Hb (R(2) = 0.486); and BG = 82.9 + 30.7 × HbA(1c) - 16.5 × Alb - 5.4 × Hb + 0.3 × age + race (R(2) = 0.491). All our models showed stronger association than previous equation models (R(2) = 0.468 in the Diabetes Control and Complications Trial and A1c-Derived Average Glucose equations).ConclusionsThe association between HbA(1c) and BG in hemodialysis patients is different than that of patients with normal kidney function. Our analysis suggests that equations including serum albumin or hemoglobin are better for hemodialysis patients