Sindhura Lakshmi Koulmane Laxminarayana

BACKGROUND: Peripheral artery disease is a growing public health problem. We aimed to estimate the global disease burden of peripheral artery disease, its risk factors, and temporospatial trends to inform policy and public measures. METHODS: Data on peripheral artery disease were modelled using the Global Burden of Disease, Injuries, and Risk Factors Study (GBD) 2019 database. Prevalence, disability-adjusted life years (DALYs), and mortality estimates of peripheral artery disease were extracted from GBD 2019. Total DALYs and age-standardised DALY rate of peripheral artery disease attributed to modifiable risk factors were also assessed. FINDINGS: In 2019, the number of people aged 40 years and older with peripheral artery disease was 113 million (95% uncertainty interval [UI] 99·2-128·4), with a global prevalence of 1·52% (95% UI 1·33-1·72), of which 42·6% was in countries with low to middle Socio-demographic Index (SDI). The global prevalence of peripheral artery disease was higher in older people, (14·91% [12·41-17·87] in those aged 80-84 years), and was generally higher in females than in males. Globally, the total number of DALYs attributable to modifiable risk factors in 2019 accounted for 69·4% (64·2-74·3) of total peripheral artery disease DALYs. The prevalence of peripheral artery disease was highest in countries with high SDI and lowest in countries with low SDI, whereas DALY and mortality rates showed U-shaped curves, with the highest burden in the high and low SDI quintiles. INTERPRETATION: The total number of people with peripheral artery disease has increased globally from 1990 to 2019. Despite the lower prevalence of peripheral artery disease in males and low-income countries, these groups showed similar DALY rates to females and higher-income countries, highlighting disproportionate burden in these groups. Modifiable risk factors were responsible for around 70% of the global peripheral artery disease burden. Public measures could mitigate the burden of peripheral artery disease by modifying risk factors. FUNDING: Bill & Melinda Gates Foundation.

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 and the overweight/obese group (Group O) 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 N) and 26 (51%) had BMI >23 kg/m² (Group O) (<i>P</i> = 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 (<i>P</i> = 0.41) or proteinuria (<i>P</i> = 0.99) at presentation. At the end of follow-up, both the groups had a similar reduction of proteinuria (UPCR) (<i>P</i> = 0.46) and eGFR (<i>P</i> = 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.

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/1.73m 2 /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. Keywords: diabetic kidney disease, acute kidney injury, GFR decline, proteinuria, sepsis

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.

We report a series of three patients with end-stage renal disease on maintenance hemodialysis presenting with hemophagocytic lymphohistiocytosis (HLH) as an unusual manifestation of extrapulmonary tuberculosis. All three patients were middle-aged men. They presented with fever, pancytopenia, varying degrees of hepatosplenomegaly, abnormal liver function tests, coagulopathy, increased serum ferritin, and triglycerides. Tests for fever work-up were negative. Bone marrow examination revealed hemophagocytosis and caseating granuloma. Acid fast bacilli were demonstrated in two patients. The HLH-2004 diagnostic criteria suggested by the histiocytic society were followed to arrive at the diagnosis. All of them succumbed to death even before the definitive diagnosis could be made. We suggest that aggressive diagnostic work-up must be done when hemodialysis patients present with fever and pancytopenia. Priority should be toward early diagnosis and appropriate treatment to improve the prognosis.