Impact of body mass index on adverse kidney events in diabetes mellitus patients: A systematic-review and meta-analysis.

BACKGROUND: The incidence of chronic kidney disease among patients with diabetes mellitus (DM) remains a global concern. Long-term obesity is known to possibly influence the development of type 2 diabetes mellitus. However, no previous meta-analysis has assessed the effects of body mass index (BMI) on adverse kidney events in patients with DM. AIM: To determine the impact of BMI on adverse kidney events in patients with DM. METHODS: A systematic literature search was performed on the PubMed, ISI Web of Science, Scopus, Ovid, Google Scholar, EMBASE, and BMJ databases. We included trials with the following characteristics: (1) Type of study: Prospective, retrospective, randomized, and non-randomized in design; (2) participants: Restricted to patients with DM aged ≥ 18 years; (3) intervention: No intervention; and (4) kidney adverse events: Onset of diabetic kidney disease [estimated glomerular filtration rate (eGFR) of < 60 mL/min/1.73 m2 and/or microalbuminuria value of ≥ 30 mg/g Cr], serum creatinine increase of more than double the baseline or end-stage renal disease (eGFR < 15 mL/min/1.73 m2 or dialysis), or death. RESULTS: Overall, 11 studies involving 801 patients with DM were included. High BMI (≥ 25 kg/m2) was significantly associated with higher blood pressure (BP) [systolic BP by 0.20, 95% confidence interval (CI): 0.15-0.25, P < 0.00001; diastolic BP by 0.21 mmHg, 95%CI: 0.04-0.37, P = 0.010], serum albumin, triglycerides [standard mean difference (SMD) = 0.35, 95%CI: 0.29-0.41, P < 0.00001], low-density lipoprotein (SMD = 0.12, 95%CI: 0.04-0.20, P = 0.030), and lower high-density lipoprotein (SMD = -0.36, 95%CI: -0.51 to -0.21, P < 0.00001) in patients with DM compared with those with low BMIs (< 25 kg/m2). Our analysis showed that high BMI was associated with a higher risk ratio of adverse kidney events than low BMI (RR: 1.22, 95%CI: 1.01-1.43, P = 0.036). CONCLUSION: The present analysis suggested that high BMI was a risk factor for adverse kidney events in patients with DM.

High-dose HOOK effect in urinary DcR2 assay in patients with chronic kidney disease.

BACKGROUND: Urinary DcR2 (uDcR2) is a biomarker for the early detection the tubulointerstitial injury (TII) in patients with chronic kidney disease (CKD), but the high-dose hook effect may lead to falsely low or even negative results when using an enzyme-linked immunosorbent assay (ELISA). This study aimed to investigate if the high-dose hook effect exists with ELISA testing, and to uncover a potential approach for reducing this effect. METHODS: 72 CKD patients were recruited and categorized into four groups based on TII scores. uDcR2 was measured in undiluted and serially diluted (two-, four-, eight- and 16-fold dilutions) urine using an ELISA kit. The results from the assay were normalized to urinary creatinine. We evaluated the correlation between uDcR2/cre levels at different dilutions and renal histological parameters. Receiver operating characteristic (ROC) curves were generated to examine the value of uDcR2/cre for predicting TII. RESULTS: uDcR2/cre levels in the undiluted urine were significantly higher in patients with CKD than those in the control. However, higher TII scores did not yield higher levels of uDcR2/cre in the undiluted urine. After serial dilution, uDcR2/cre levels were highest with the four-fold dilution. A positive correlation was found between uDcR2/cre levels at different dilutions and TII scores, with the highest correlation coefficient and the largest AUC being observed at the four-fold dilution. CONCLUSIONS: The high-dose hook effect was apparent during ELISA testing of uDcR2 in CKD patients, yet dilution of the urine samples neutralized this effect. However, the use of a four-fold dilution of urine for uDcR2/cre testing may eliminate the high-dose hook effect and make it possible to effectively monitor the severity of TII in CKD patients.

Urinary DcR2 is a novel biomarker for tubulointerstitial injury in patients with diabetic nephropathy.

Tubulointerstitial injury (TII) plays a crucial role in the progression of diabetic nephropathy (DN), but lack of specific and sensitive biomarkers for monitoring TII in DN management. This study is to investigate whether urinary decoy receptor 2 (uDcR2) could serve as a novel noninvasive biomarker for assessing TII in DN. We recruited 311 type 2 diabetics and 139 DN patients who were diagnosed by renal biopsy. uDcR2 levels were measured by ELISA, and renal DcR2 expression was detected immunohistochemically. Associations between uDcR2 and renal DcR2 and renal functional parameters were evaluated. Receiver operating characteristics (ROC) curve analyzed area under the curve (AUC) of uDcR2 for assessing TII. Double staining was undertaken for renal DcR2 with proximal and distal tubular markers; senescent markers p16, p21, and senescence-associated ß-galactosidase (SA-ß-gal); and fibrotic markers collagen I and IV. We found DcR2 was primarily expressed in renal proximal tubules; uDcR2 levels were elevated per albuminuria stratum and correlated with renal functional parameters in diabetics and were associated with percentage of tubular DcR2 and TII score in DN. The uDcR2 had an AUC of 0.909 for assessing TII in DN by ROC analysis. Almost all tubular DcR2 was coexpressed with p16 and p21, and nearly more than one-half of tubular DcR2 was positive for SA-ß-gal, primarily in collagen I- and IV-positive regions of DN. Our results indicate uDcR2 could potentially serve as a novel biomarker for TII and may reflect senescence of renal proximal tubular cells in DN pathogenesis.