ABO Incompatible Kidney Transplant in a Patient With Atypical Hemolytic Uremic Syndrome: Case Report.

Kidney transplant (KT) or renal transplant is 1 of the preferred treatment options for patients with end-stage renal disease, but the presence of atypical hemolytic uremic syndrome (aHUS) further increases the risk of reoccurrence with graft rejection, and poor outcomes. ABO incompatibility further adds to the rejection risk. Here, we present a case of a young adult with a history of aHUS undergoing a successful ABO-incompatible (ABOi) renal transplant. ABO incompatibility desensitization was carried out, and the antibody titer was reduced to nullify the risk of rejection. Graft acceptance was facilitated by triple immunosuppression (steroid, tacrolimus, and mycophenolate mofetil), and 4-month serum creatinine follow-up indicated the absence of antibody-mediated rejection and recurrence of aHUS. This case demonstrates that in patients with aHUS, ABOi renal transplant can be performed successfully.

Kidney Transplant Outcomes in Patients with Atypical Hemolytic Uremic Syndrome.

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a rare disorder with a high probability of recurrence after a kidney transplant and can adversely affect the graft outcome. Our objective was to assess the transplant outcome of patients with aHUS who had undergone a kidney transplant. METHODS: We retrospectively included patients who had undergone a kidney transplant and been diagnosed with aHUS based on an anti-complement factor H (AFH) antibody level >100 AU/mL and the presence of a genetic abnormality in complement factor H (CHF) or CHF-related (CFHR) genes. Data were analyzed with descriptive statistics. RESULTS: Among 47 patients with AFH antibody levels >100 AU/mL, 5 (10.6%) had undergone a kidney transplant. The mean age was 24.2 years, and all were male. Atypical hemolytic uremic syndrome was diagnosed before transplant in 4 (80.0%) cases, whereas 1 was diagnosed after transplant owing to disease recurrence in the transplanted graft. Genetic analysis of all cases revealed one or more abnormalities in CFH and CFHR genes 1 and 3. With an average of 5 sessions of plasma exchange and the use of rituximab in 4 cases, there was a reduction in the disease severity with no recurrences in the post-transplant period. At the latest follow-up of 223 days, the mean serum creatinine level was 1.89 mg/dL, indicating good graft function. CONCLUSIONS: Among patients diagnosed with aHUS, the use of pre-transplant plasma exchange and rituximab can be beneficial in terms of preventing graft dysfunction and reducing disease recurrence in the post-transplant period.

Profile and Post-Kidney Retrieval Outcomes in Asymptomatic Kidney Donors With Genetic Mutations in Complement Factors-Related Genes.

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a rare disorder triggered by various stressors. Most of the time, stressors may not be identified in patients with aHUS. The disease may remain quiescent without manifestation throughout life. BACKGROUND: To assess the outcome of an asymptomatic carrier of genetic mutations of patients with aHUS who had undergone donor kidney retrieval surgery. METHODS: We retrospectively included the patients diagnosed with a genetic abnormality in complement factor H (CHF) or CHF-related (CFHR) genes without manifestation of the aHUS and who had undergone donor kidney retrieval surgery. The data were analyzed with descriptive statistics. RESULTS: Among patients who were the kidney recipients from the prospective donors, 6 donors were screened for genetic mutations in CFH and CFHR genes. Four donors showed positive mutation for CFH and CFHR. The mean age was 54.5 years (range, 50-64 years). After over a year since donor kidney retrieval surgery, all prospective mother donors are alive without aHUS activation and with a normal kidney function on a single kidney. CONCLUSION: Asymptomatic carriers of genetic mutations in CFH and CFHR can be the prospective donors for their first-degree family member who have active aHUS. A genetic mutation in an asymptomatic donor should not be a contraindication for refuting the prospective donor.

CYP3A5 Polymorphism in Renal Transplantation: A Key to Personalized Immunosuppression.

BACKGROUND: Tacrolimus is essential for the maintenance of immunosuppression after a kidney transplant. CYP3A5 is the gene that metabolizes tacrolimus, and polymorphism in this gene affects the metabolizing status. AIM: To assess the genetic polymorphism status of patients undergoing kidney transplantation and determine its impact on graft function and complications in the post-transplant period. METHODS: We retrospectively included the patients who had undergone a kidney transplant and had positive genetic polymorphism of the CYP3A5 gene. Based on loss of alleles, patients were categorized as non-expresser (loss of both alleles), intermediate expresser (loss of one allele), and expresser (no loss of allele) denoted by CYP3A5*3/*3, CYP3A5*1/*3, and CYP3A5*1/*1, respectively. Data were analyzed with descriptive statistics. RESULTS: Of 25 patients, 60%, 32%, and 8% were non-expressers, intermediate-expressers, and expressers, respectively. The mean tacrolimus trough concentration to dose ratio after 6 months of the transplant was higher in non-expressers than intermediate-expressers and expressers (213 vs 85 and 46 ng/mL/mg/kg/d, respectively). The graft function was normal in all 3 groups except for graft rejection 1 patient in the expresser group. Compared with expressers, urinary tract infections (42.9% and 62.5%) and new-onset diabetes after transplantation (28.6% and 12.5%) were more frequent in non-expresser and intermediate expressers, respectively. The proportion of patients developing new-onset diabetes after transplantation was lower with the pre-transplant diagnosis of CYP3A5 polymorphism (16.7% vs 23.1%). CONCLUSION: Genotype-based dosing of tacrolimus helps achieve the desired therapeutic concentrations that can help to optimize graft outcomes and reduce the tacrolimus-related adverse effects. Pre-transplant evaluation of CYP3A5 can be more helpful in planning treatment strategies for optimized outcomes after kidney transplantation.

Humoral Response After Two Doses of COVISHIELDTM Vaccine in Patients Undergoing Maintenance Hemodialysis.

OBJECTIVES: Maintenance hemodialysis (MHD) patients are at increased risk of contracting coronavirus disease 2019 (COVID-19). Vaccine against COVID-19 offers the benefit of protection from severe illness. In this study, we assessed the humoral response after two doses of the COVISHIELDTM vaccine in MHD patients. MATERIALS AND METHODS: In a prospective cohort study, the humoral response with two doses of the COVISHIELDTM vaccine was assessed after 14 ± 2 days of the second dose. The COVIPROTECT antibody titers against the spike protein were measured using the electrochemiluminescence immunoassay (ELECSYS, Roche Diagnostics International Ltd.). Data were analyzed to determine the predictors of antibody response. RESULTS: Between February and October 2021, 50 MHD patients were assessed. The mean age was 55.8 ± 10.8 years, and 72% were males. A total of 48 (96%) MHD patients have seropositivity. The median level of spike protein antibody was 579 U/mL [interquartile range (IQR25-75) 166-1852.75]. Compared to patients with no COVID-19 infection history, the median levels of antibodies were significantly higher in those with a history of COVID-19 (1047 vs 297 U/mL, p = 0.011). The antibody titers did not differ by age (p = 0.269), presence of comorbidities such as hypertension (p = 0.341), diabetes mellitus (p = 0.719) or ischemic heart disease (IHD) (p = 0.695), dialysis vintage (p = 0.660), and timing of diagnosis of COVID-19 in relation to vaccination (p = 0.261). Adverse events (AEs) occurred in one-third of patients that were mild and self-limiting. No serious AEs were observed in any patient. CONCLUSION: In MHD patients, two doses of the COVISHIELDTM vaccine induced a substantial humoral response. Prior history of COVID-19 resulted in a higher antibody response. Thus, the COVISHIELDTM vaccine is efficacious and safe for use in patients with MHD. How to cite this article: Balwani MR, Pasari AS, Bawankule C, et al. Humoral Response After Two Doses of COVISHIELDTM Vaccine in Patients Undergoing Maintenance Hemodialysis. J Assoc Physicians India 2023;71(9):56-60.

Current Practice of Hypertension in India: Focus on Blood Pressure Goals.

INTRODUCTION: Recommended Blood Pressure (BP) goals in elderly and those with co-morbid conditions like Diabetes Mellitus (DM) and Chronic Kidney Disease (CKD) vary in different Hypertension (HTN) management guidelines. AIM: To understand currently followed BP goals and practices among the physicians involved in management of HTN in India. MATERIALS AND METHODS: A cross-sectional, observational survey was conducted at 66th annual conference of Cardiological Society of India (CSICON-2014, Hyderabad). A structured questionnaire related to the BP goals and HTN practices was provided and responses from voluntarily participating physicians were collected. Data was analysed with descriptive statistics. RESULTS: Two-hundred sixty physicians completed this survey. In their routine clinical practice, physicians most frequently referred to Joint National Committee (JNC) guidelines (63.85%) followed by Indian guidelines on HTN (14.23%). In patients aged 60 years and above, BP goal <140/90mmHg and <150/90mmHg was aimed by 43.46% and 33.85% of the physicians respectively. In HTN with Type 2 DM (T2DM), most physicians (61.92%) had a BP goal of <130/80mmHg. A target BP <130/80mmHg was aimed by 48.08% physicians in CKD without proteinuria and 68.85% physicians in CKD with proteinuria. In newly diagnosed hypertensives, treatment modification was practiced after 15, 20 and 30 days by 37.31%, 16.15% and 35.77% of the physicians respectively. Beta-blockers were considered as third-line agents in HTN without co-morbidities by 45% physicians. Ambulatory BP Monitoring (ABPM) is practiced only in few patients (<5%) by most (71.93%) physicians. CONCLUSION: In practice, Indian physicians follow lower BP goals when compared to the recommendations from the most referred JNC guidelines. Increasing physicians' awareness to the changes in recommendations is the need.

Strategies to combat antimicrobial resistance.

The global burden of antimicrobial resistance is rising and is associated with increased morbidity and mortality in clinical and community setting. Spread of antibiotic resistance to different environmental niches and development of superbugs have further complicated the effective control strategies. International, national and local approaches have been advised for control and prevention of antimicrobial resistance. Rational use of antimicrobials, regulation on over-the-counter availability of antibiotics, improving hand hygiene and improving infection prevention and control are the major recommended approaches. Thorough understanding of resistance mechanism and innovation in new drugs and vaccines is the need. A multidisciplinary, collaborative, regulatory approach is demanded for combating antimicrobial resistance.