Transforming growth factor-beta (TGF-β), a cytokine with near omnipresence, is an integral part of many vital cellular processes across the human body. The family includes three isoforms: Transforming growth factor-beta 1, 2, and 3. These cytokines play a significant role in the fibrosis cascade. Diabetic kidney disease (DKD), a major complication of diabetes, is increasing in prevalence daily, and the classical diagnosis of diabetes is based on the presence of albuminuria. The occurrence of nonalbuminuric DKD has provided new insight into the pathogenesis of this disease. The emphasis on multifactorial pathways involved in developing DKD has highlighted some markers associated with tissue fibrosis. In diabetic nephropathy, TGF-β is significantly involved in its pathology. Its presence in serum and urine means that it could be a diagnostic tool while its regulation provides potential therapeutic targets. Completely blocking TGF-β signaling could reach untargeted regions and cause unanticipated effects. This paper reviews the basic details of TGF-β as a cytokine, its role in DKD, and updates on research carried out to validate its candidacy.

Purpose: Diabetic kidney disease (DKD) represents a unique subset of patients with chronic kidney disease (CKD). Acute kidney injury (AKI) is implicated in DKD progression; however, their interplay is not studied well. We studied risk factors for AKI and the effect of AKI on disease progression in a homogeneous group of patients with DKD. Patients and Methods: We conducted a retrospective open cohort study of patients with DKD at a single tertiary care centre between August 2016 – August 2019. Patients with a minimum follow-up of 2 years were included in the study. The incidence, etiology and risk factors for AKI were studied. The primary outcome studied was the effect of AKI on reduction in estimated glomerular filtration rate (eGFR) in DKD. Loss in eGFR by 50% and need for renal replacement therapy or reaching CKD stage V were studied as secondary outcomes. Results: Two hundred and ninety-two DKD patients meeting the study criteria with a follow-up of 29.57 (± 4.3) months were included. The incidence of AKI was 31.1%. Sepsis was the most common etiology (61%). Proteinuria was an independent risk factor for AKI after adjusting for covariates (adjusted OR - 1.158; 95% CI (1.018– 1.316); p=0.025). In patients with AKI, median decline in eGFR was 10.29 mL/min/1.73m²/year (IQR-5.58– 13.84) which was significantly higher compared to patients with no AKI [eGFR 7.25 (IQR 5.06– 11.38); p-0.014]. On subgroup analysis, sepsis-induced AKI (versus non-sepsis AKI; p< 0.001) and higher AKI stage (stage 2/3 versus stage 1; p=0.019) were associated with a faster decline in eGFR. Conclusion: AKI is common in patients with DKD with sepsis being the most common etiology. AKI in diabetic kidney disease is associated with a faster decline in eGFR. Baseline proteinuria is an independent risk factor for AKI.

The role of obesity in the progression of primary glomerular diseases is controversial. A few studies report overweight/obesity as a risk factor for disease progression in immunoglobulin A nephropathy (IgAN), and the real impact of it still remains unclear. The aim of this study was to elucidate the effect of body mass index (BMI) on disease progression and proteinuria in patients with IgAN in Indian population. A cohort of biopsy-proven primary IgAN patients diagnosed between March 2010 and February 2015 who had a follow-up for a minimum of 12 months were included in the study. We defined two groups of patients according to the BMI value at diagnosis: non-obese group (Group N) with BMI 23 Kg/m² as per Asia-Pacific task force criteria. Baseline characteristics were compared between the groups. The estimated glomerular filtration rate (eGFR) and urine protein-creatinine ratio (UPCR) were followed up at entry time, 6 months, 12 months, and at the end of follow-up. Outcomes studied were change in eGFR, proteinuria, and progression to end-stage renal disease. Statistical analysis was done using the Statistical Package for the Social Sciences version 15.0. Of 51 patients, 25 (49%) had BMI 23 kg/m² (Group O) (P = 0.01). The baseline clinical, histopathological, and treatment characteristics of both the groups were comparable. The BMI at the time of diagnosis did not have any significant effect on eGFR (P = 0.41) or proteinuria (P = 0.99) at presentation. At the end of follow-up, both the groups had a similar reduction of proteinuria (UPCR) (P = 0.46) and eGFR (P = 0.20). Two patients in each group have reached chronic kidney disease Stage 5. In the present study, BMI at presentation did not have any impact on eGFR or proteinuria, either at diagnosis or at follow-up. It needs further large multicenter randomized control studies to see the effect of BMI on progression of IgAN.