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Type 2 diabetes mellitus (DM) is the most common single cause of end-stage renal disease. Albuminuria is the most commonly used marker to predict onset of diabetic nephropathy (DN) without enough sensitivity and specificity to detect early DN. This is the first study to identify urinary cyclophilin A (CypA) as a new biomarker for early DN.We recruited DM outpatients and healthy control subjects from January 2014 to December 2014. In this cross-sectional study, patients’ urine samples were collected to determine the expression of urinary CypA. We also treated mesangial (MES-13) and tubular (HK-2) cells with glucose or free radicals to observe the expression of secreted CypA in Western blot analysis.A total of 100 DN patients and 20 healthy control subjects were enrolled. All variables were matched. In univariate analysis, the concentration of urinary CypA correlated well with the progression of renal function. A significant increase in urinary CypA was noted in stage 2 DN and persisted in later stages. We could diagnose stage 2 DN using urinary CypA with a sensitivity of 90.0% and specificity of 72.7%. The area under curve was up to 0.85, indicating a good discriminatory power. In cellular models, MES-13 and HK-2 cells can both release CypA.Urinary CypA is a good biomarker for early DN detection in humans and it can be released from either mesangial or tubular cells. The underlying molecular mechanisms still need further clarification in cellular and animal studies.

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Renal biopsy remains the golden standard diagnosis of renal function deterioration. The safety in native kidney biopsy is well defined. However, it is a different story in allograft kidney biopsy. We conduct this retrospective study to clarify the safety of allograft kidney biopsy with indication.All variables were grouped by the year of biopsy and they were compared by Mann–Whitney U test (for continuous variables) or Chi-square test (for categorical variables). We collected possible factors associated with complications, including age, gender, body weight, renal function, cause of uremia, status of coagulation, hepatitis, size of needle, and immunosuppressants.We recruited all renal transplant recipients undergoing allograft biopsy between January of 2009 and December of 2014. This is the largest database for allograft kidney biopsy with indication. Of all the 269 biopsies, there was no difference in occurrence among the total 14 complications (5.2%) over these 6 years. There were only 3 cases of hematomas (1.11%), 6 gross hematuria (2.23%), 1 hydronephrosis (0.37%), and 2 hemoglobin decline (0.74%). The outcome of this cohort is the best compared to all other studies, and it is even better than the allograft protocol kidney biopsy. Among all possible factors, patients with pathological report containing “medullary tissue only” were susceptible to complications (P < 0.001, 1.8 of relative risk).In modern era, this study demonstrates the safety of allograft kidney biopsy with indication. Identifying the renal capsule before biopsy to avoid puncture into medulla is the most important element to prevent complications.

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Background: The effect of glucose control, especially variability of glycated hemoglobin (HbA1c), on estimated glomerular filtration rate (eGFR) decline in type 2 diabetes is still debatable. Methods: We used tertiles of coefficient of variation (CV) to determine the variability of HbA1c (HbA1c_CV). Mixed model repeated measures (MMRM) were used to evaluate the annual eGFR decline rate. Results: In 1383 type 2 diabetic patients, we found the greater the HbA1c_CV, the greater the eGFR decline ( p = 0.01, −0.99 in low, −1.73 in mid, and −2.53 ml/min/1.73 m2/year in high HbA1c_CV). Regardless of eGFR (⩾60 or <60 ml/min/1.73 m2), the same result holds ( p = 0.019 and p = 0.007, respectively). In subgroup analysis of baseline HbA1c (%) (HbA1c < 7, 7 ⩽ HbA1c < 9, and HbA1c ⩾ 9), tertiles of HbA1c_CV showed similar effects on annual decline of eGFR ( p = 0.193, 0.300, 0.182, respectively), although a trend for a steeper decline in renal function in the highest HbA1c_CV tertile was observed for all HbA1c strata, and even for HbA1c < 7%. A similar behavior was observed in patients with macroalbuminuria or normoalbuminuria ( p = 0.219, and 0.109, respectively), with a significant trend in those with microalbuminuria ( p = 0.019). Even in patients with HbA1c < 7, high HbA1c_CV also predicts rapid eGFR decline. Before macroalbuminuria, minimizing HbA1c_CV also has renal benefit. Conclusions: HbA1c variability is an independent risk factor for deterioration of renal function. Even with well-controlled HbA1c levels (<7%), patients with high HbA1c_CV still experienced faster eGFR decline. Early minimization of glycemic variability (before macroalbuminuira) can curb deterioration of renal function. Monitoring and lowering of HbA1c_CV is highly recommended for diabetic care.

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