Nephronophthisis (NPHP) is an autosomal recessive hereditary disease with highly variable clinical characteristics for which 20 genes (NPHP1–20) have been identified. NPHP1 is the major subtype leading to pediatric end-stage renal disease (ESRD). Reports of adult NPHP1 are rare. Here, we report a 27-year-old male from a Chinese intermarriage family who was diagnosed as NPHP from clinical presentations and molecular genetic analysis by whole-exome sequencing. The genetic investigation revealed a novel homozygous nonsense mutation, p. E697X,37 and a novel homozygous missense mutation, p. F691 L, in the NPHP1 gene. His parents and fraternal twin harbored heterozygous mutations of the two loci and had no renal symptoms. His elder sister developed ESRD and died at 23 years of age. The report indicated that adult NPHP should be taken into consideration for adults with ESRD of uncertain cause. The genotype-phenotype correlation requires further investigation.

The immune system is involved in the development of diabetes complications and IgG Fc gamma receptors (FcgRs) are key immune receptors responsible for the effective control of both humoral and innate immunity. We investigated the effects of members of the FcgR superfamily into both the streptozotocin plus high fat-induced type 2 diabetes and high fat diet (HFD) models. FcgRIII^-/- diabetic mice and FcgRIIb^-/- diabetic mice had elevated levels of serum creatinine compared with wildtype (WT) diabetic mice. Renal histology of diabetic FcgRIII knockout and FcgRIIb knockout mice showed mesangial expansion and GBM thickening; the mechanistic study indicated a higher expression of TGF-β1, TNF-α, and p-NFκB-p65 compared with wild type mouse. The HFD mouse with FcgRIII knockout or FcgRIIb knockout had increased biochemical and renal injury factors, but oxLDL deposition was higher than in FcgRIII^-/- diabetic mice and FcgRIIb^-/- diabetic mice. In vitro we further examined the mechanism by which the Fc gamma receptor promoted renal injury and transfected glomerular mesangial cells (GMCs) with FcgRI siRNA attenuated the level of TGF-β1, TNF-α expression. In summary, FcgRI knockdown downregulated kidney inflammation and fibrosis and FcgRIIb knockout accelerated inflammation, fibrosis, and the anomalous deposition of oxLDL whereas FcgRIII deficiency failed to protect kidney from diabetic renal injury. These observations suggested that FcgRs might represent a novel target for the therapeutic intervention of diabetic nephropathy.

Background: Diabetic kidney disease (DKD) is characterized by a sustained pro‐inflammatory response of the immune system, which leads to renal failure progression and related complications. Emerging evidence suggests that gut microbiota dysregulation may be a pathogenic mediator in DKD, while mechanisms remain unclear. This study aimed to identify differences in the gut microbiota of the DKD group and healthy controls (HC). Methods: Gut microbiota composition was determined using shotgun metagenomic sequencing on fecal samples; serum cytokines were measured via ELISA, immune phenotypes were detected using flow cytometry. Results: Significant differences in gut microbiota diversity and richness were observed between patients with DKD and HC, with higher abundances of Enterobacteriaceae, Serratia , and Shigella in the DKD group than in the HC group. Additionally, CD3+ (especially CD4+) T cells were significantly higher in the renal tissue of the DKD group than the HC group. Flow cytometry identified significantly higher circulating levels of NKT cells and CD8+ T cells and lymphocyte ratio in HC than in DKD. CD4+ cells, CD4+ TCM cells, CD8+ TCM cells, and the CD4+/CD8+ cell ratio were significantly higher in the DKD group than in the HC group, as were levels of pro‐inflammatory mediators, including IL‐6, TNF‐α, and sCD14, and expression of the gut barrier dysfunction marker ZO‐1. Conclusions: Gut barrier dysfunction and gut microbiota imbalance may mediate the pro‐inflammatory immune phenotype observed in patients with DKD and thereby contribute to DKD progression. These findings underscore the important role of the microbiota–immune axis in the development of DKD.

Aims. This study investigated the relationship between proteinuria levels, clinicopathological features, and renal prognoses in Chinese patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN). Methods. Three hundred patients with T2DM and biopsy-proven DN were enrolled. Patients were stratified by 24-h proteinuria levels: Group 1:<= 1g/24h); Group 2:1-3g/24h; and Group 3:>= 3g/24h. Renal outcomes were defined as having reached end-stage renal disease (ESRD). The proteinuria level's influence on the renal outcomes was evaluated using Cox regression analysis. Results. Among subgroups stratified by proteinuria levels, systolic blood pressure, serum creatinine, BUN, cholesterol, DR and hypertension incidence, the incidences of patients who progressed to ESRD were the lowest in group 1 (P<0.05). However, eGFR, serum albumin and hemoglobin were highest in group 1. Patients with higher proteinuria levels had much lower five-year renal survival rates. Univariate analyses revealed that higher proteinuria levels were significant clinical predictors of renal prognosis (P0.05). Conclusions. The higher the level of proteinuria, the lower the 5-year renal survival rate of DN patients, but there was no significant correlation between proteinuria level and 5-year renal survival rate. Other factors in the proteinuria group may have more significant effects on the 5-year renal survival rate, such as lower baseline eGFR, serum albumin, hemoglobin and higher cholesterol, higher incidences of DR and more severe lesions.

Obesity is an independent risk factor for the development of diabetic nephropathy (DN). Obesity, type 2 diabetes, and kidney damage interact with each other. Recent studies have shown that adipokines are closely related to the occurrence and development of DN, and are potential targets for treatment and prevention of complications. However, the potential interaction between adipocytokines and renal injury remains unclear. We investigated the mechanisms linking adipose tissue to DN. We assessed fat and renal functions in db/db and wild-type mice, and the effects of adipocyte-conditioned medium on cultured tubular epithelial cells. Mice were used to analyze changes in plasma BUN, creatinine, urine protein, and renal histology. Additionally, tubular epithelial cells were incubated with adipocyte-conditioned medium to investigate the effects on tubular epithelial cell apoptosis.