Occupational risk factors for chronic kidney disease in Andhra Pradesh: 'Uddanam Nephropathy'.

BACKGROUND: CKD of unknown etiology (CKDu) has been reported in several countries including India. We previously showed a prevalence of CKD in India to be 17.2% and we found a CKD epidemic in Andhra Pradesh (AP) to be 46.8%. We conducted this study to further explore the unexplained CKD epidemic in AP. METHODS: We recruited 1201 adult participants through systematic random sampling from eight administrative divisions. Demographic, medical, and detailed occupational history was collected. Anthropometric measurements and blood pressure were taken and blood and urine samples were collected. Poisson regression model was used to identify potential predictors for CKD. RESULTS: We analyzed data for 1184 individuals with mean age of 44.6 ± 14.0 years, of whom 44% were male. Prevalence of CKD was 32.2%. Working as a farmer had 20% more prevalence of CKD compared to non-farmers in the fully adjusted model (PR 1.2, 95% CI 1.01-1.42). Age, alcohol consumption, and chewing tobacco were also independent predictors of CKD. Gender, hypertension, and diabetes were not associated with CKD. CONCLUSIONS: The prevalence of CKD in AP is 32.2%. Occupational exposure among farmers could play a potential role in this epidemic. Large longitudinal epidemiologic research studies are needed to trace the causes of this problem.

What do we know about chronic kidney disease in India: first report of the Indian CKD registry.

BACKGROUND: There are no national data on the magnitude and pattern of chronic kidney disease (CKD) in India. The Indian CKD Registry documents the demographics, etiological spectrum, practice patterns, variations and special characteristics. METHODS: Data was collected for this cross-sectional study in a standardized format according to predetermined criteria. Of the 52,273 adult patients, 35.5%, 27.9%, 25.6% and 11% patients came from South, North, West and East zones respectively. RESULTS: The mean age was 50.1 ± 14.6 years, with M:F ratio of 70:30. Patients from North Zone were younger and those from the East Zone older. Diabetic nephropathy was the commonest cause (31%), followed by CKD of undetermined etiology (16%), chronic glomerulonephritis (14%) and hypertensive nephrosclerosis (13%). About 48% cases presented in Stage V; they were younger than those in Stages III-IV. Diabetic nephropathy patients were older, more likely to present in earlier stages of CKD and had a higher frequency of males; whereas those with CKD of unexplained etiology were younger, had more females and more frequently presented in Stage V. Patients in lower income groups had more advanced CKD at presentation. Patients presenting to public sector hospitals were poorer, younger, and more frequently had CKD of unknown etiology. CONCLUSIONS: This report confirms the emergence of diabetic nephropathy as the pre-eminent cause in India. Patients with CKD of unknown etiology are younger, poorer and more likely to present with advanced CKD. There were some geographic variations.

Identification of the novel allele, HLA-B*44:256, in an individual from West Bengal in Eastern India.

Next generation sequencing based HLA typing has led to the identification of a novel allele HLA-B*44:256. The novel allele HLA-B*44:256 differs from B*44:02:01:01 by eight nucleotides in exon 3.

SARS-CoV-2 Infection in Kidney Transplant Recipients: A Single-Centre Study of 20 Cases from India.

INTRODUCTION: The second wave of COVID-19 has spread across India causing unprecedented misery to people since March 2021. Kidney transplant recipients (KTRs) are at an increased risk of severe infection. Their outcomes appear to be worse than those in the general population. There is no robust evidence or consensus to support any form of treatment protocol or modification of immunosuppression in KTRs with COVID-19. There is a need to develop effective and safe therapeutic protocols for this frail population. Remdesivir is the only approved antiviral drug in COVID-19 till now. METHODS: We describe clinical features, role of HRCT, therapeutic protocols, and mortality rate of 20 KTRs with SARS-CoV-2 infection. RESULTS: Complete recovery was seen in 8 (40%) patients monitored at home. 12 (60%) patients with HRCT scores more than 8/25 were hospitalized. 11 (55%) had hypoxia, of these 8 (40%) had mild hypoxia, 1 (5%) required NIV, and 2 (10%) needed mechanical ventilation. Immunosuppression was modified in all the patients. Remdesivir and dexamethasone were administered to the hospitalized patients. 1 (5%) patient had AKI requiring RRT. 1 (5%) patient expired, and 1 still hospitalized. 10 of the hospitalized patients recovered. Out of the total 20 patients, 18 (90%) recovered completely within two weeks of infection. CONCLUSION: Clinical presentation of COVID-19 in KTRs was similar to nontransplant patients. Early hospitalisation and assessing the severity by HRCT were important. Continuing tacrolimus and administering remdesivir and dexamethasone reduced the incidence of renal failure and improved survival rates.

Severe Acute Respiratory Syndrome Corona Virus-2 Infection in a Pediatric Kidney Transplant Recipient: A Case Report from India.

COVID-19 pandemic affected millions of people across India. COVID-19 cases are fewer in children with less severity and better outcomes than in adults. However, a small proportion develop severe illness and succumb to the disease. Clinical manifestations and optimal management of COVID-19 in immunocompromised children are not clearly known. Remdesivir was shown to be efficient in reducing the recovery time in COVID-19 patients requiring supplemental oxygen. Remdesivir is approved for use in children with severe COVID-19, but there are no guidelines in patients with risk factors like recent solid organ transplantation. We report a case of a 10-year-old kidney transplant recipient (KTR) infected with severe acute respiratory syndrome corona virus-2, 2.5 months after the transplantation. Unlike most children, he presented with high fever, cough, and vomiting. His inflammatory markers were elevated. In this case report, we discussed management and clinical outcomes of this patient. In view of recent kidney transplantation and the severity of infection with emergent oxygen requirement, we gave him remdesivir. We continued prednisolone and tacrolimus and stopped mycophenolate. He recovered completely in 7 days. We feel that severely immunosuppressed KTR children with COVID-19 will benefit with remdesivir administration. Monitoring tacrolimus trough levels is essential for maintaining adequate immunosuppression.

Chronic Kidney Disease of Unknown Etiology in India: What Do We Know and Where We Need to Go.

Chronic kidney disease (CKD) not associated with known risk factors has been reported from parts of India and is presumed to be similar to CKD of unknown etiology (CKDu) that has been described from Central America. The reports from India have been fragmented without clear description of the disease phenotype or its determinants. This paper summarizes the current state of knowledge around CKDu in India based on a review of literature, multi-stakeholder consultation, and a survey of Indian nephrologists. We also contacted individual research groups to solicit data. Our findings suggest that that CKDu is reported from most regions in India; however, it is interpreted differently from the phenotype described from Central America and Sri Lanka. The differences include lack of a clear demographic or occupation group, older age of affected participants, and presence of mild hypertension and low-grade proteinuria. Well-designed prospective field studies with appropriate diagnostic workup are needed to establish the disease burden and identify etiologies, along with socioeconomic and health consequences, the intersection with the environment, and the public health response. Community-based research should phenotype the entire CKD population rather than be restricted to cases with presumed CKDu based on predefined criteria. Guidelines are needed for clinical evaluation, referral, management, and harmonization of clinical documentation and health records. More data are needed to support the existence of a unique CKDu phenotype in India.

High Prevalence of CKD of Unknown Etiology in Uddanam, India.

INTRODUCTION: There were concerns raised regarding a high prevalence of chronic kidney disease (CKD) in Uddanam, a fertile subtropical low-altitude territory in the southern Indian state of Andhra Pradesh. The present study was undertaken to ascertain the prevalence of CKD, disease characteristics, and risk factor profile in this area. METHODS: We selected 2210 subjects (age >18 years) using multistage sampling. After obtaining demographic and anthropometric data, urinary protein-creatinine ratio, serum creatinine, and blood glucose were measured in all the subjects. Glomerular filtration rate was estimated (eGFR) using the Modification of Diet in Renal Disease equation. RESULTS: Mean age of the subjects was 43.2 ± 14.2 years (range: 18-98), 44.3% were men and 55.7% were women. Mean eGFR of subjects was 94.3 ± 33.4. Low eGFR (<60 ml/min per 1.73 m2) was seen in 307 (13.98%) patients with a mean eGFR of 34.8 ± 16.6. The prevalence of subjects having low eGFR and with proteinuria (CKD) was 18.23%. Major risk factors, such as diabetes, long-standing hypertension, and significant proteinuria, were absent in 73% of patients with CKD, implying that a significant proportion of the population is afflicted with the entity "CKD of unknown etiology (CKDu)." CONCLUSION: The prevalence of CKD and CKDu in Uddanam is much higher than other earlier studies in either rural or urban communities in India. We suggest that there is a dire need to review health policies and allocate resources for prevention and treatment of CKD in the Uddanam region.

Noninvasive detection of renal allograft inflammation by measurements of mRNA for IP-10 and CXCR3 in urine.

BACKGROUND: We explored the hypothesis that measurements of mRNA encoding interferon-inducible protein-10 (IP-10) or the chemokine receptor CXCR3 in urinary cells offer a noninvasive means of elucidating cellular traffic causing acute rejection of human renal allografts. METHODS: We obtained 63 urine specimens from 58 renal allograft recipients who underwent 63 allograft biopsies to resolve the basis for graft dysfunction, and 27 additional urine samples from 24 other patients with stable allograft function. Twenty-seven of the 63 biopsies were classified as acute rejection, 20 as other, and 16 as chronic allograft nephropathy. We measured the levels of transcripts for IP-10 and CXCR3, and a constitutively expressed gene 18S rRNA in the urine specimens and correlated transcript levels with renal allograft diagnosis. RESULTS: mRNA levels of IP-10 (P < 0.0001) or CXCR3 (P < 0.0001) but not the levels of 18S rRNA (P= 0.56) predicted intragraft cellular traffic causing acute rejection. Receiver-operating characteristic curve analysis demonstrated that acute rejection can be predicted with a sensitivity of 100% and a specificity of 78% using the (log-transformed) cutoff value of 9.11 copies of IP-10, and with a sensitivity of 63% and a specificity of 83% using the cutoff value of 11.59 copies of CXCR3. Immunohistologic analysis of allograft biopsies showed exuberant expression of IP-10 and CXCR3 during acute rejection whereas both were absent in grafts with stable function. CONCLUSION: Our investigation demonstrates that intragraft cellular events associated with acute rejection of human renal allografts can be noninvasively identified by measurements of mRNA for IP-10 and CXCR3 in urinary cells.