Higher pro-inflammatory cytokines IL-6 and IFN-γ are associated with anti-SARS-CoV-2 spike protein-specific seroconversion in renal allograft recipients.

BACKGROUND: Maintenance immunosuppressive regimens are speculated to hamper immunogenic response against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) in renal transplant recipients (RTRs) compared to the healthy population. Healthy people with SARS-CoV-2 infection often develop neutralizing antibodies and secret copious quantities of cytokines, leading to virus clearance and sometimes more severe immune-related complications. METHODS: RTRs, either acquired SARS-CoV-2 infection (infection group, n = 132) or were vaccinated with two vaccine doses (vaccination group, n = 78) against SARS-CoV-2, were recruited in the study. Thirty-five unvaccinated RTRs, without anti-SARS-CoV-2 spike protein-specific antibodies, were also included as control. Cytokines interleukine-6 (IL-6), interferon-γ (IFN-γ), TGF-ß, and IL-10 were measured using ELISA. The SARS-CoV-2 spike protein-specific IgG-titer was measured by chemiluminescent microparticle immunoassay methods. RESULTS: The seroconversion rate in the infection group was 115/132 (87.12%), with a median antibody titer 706.40 au/mL (IQR, 215.45-1844.42), and in the vaccination group was 63/78 (80.76%) with antibody titer 1454.20 au/mL (IQR, 80.52-3838.75). The IL-6, IFN-γ, TGF-ß, and IL-10 levels were significantly higher in both the infection and vaccination group compared to healthy control. In the infection group, pro-inflammatory cytokines IL-6 (55.41 ± 24.30 vs. 31.64 ± 16.98 pg/mL, p < .001) and IFN-γ (91.21 ± 33.09 vs. 61.69 ± 33.28 pg/mL, p = .001) were significantly higher in the seroconverter group as compared to non-seroconverter. Similarly, in the vaccination group, pro-inflammatory cytokines IL-6 (50.31 ± 25.67 vs. 30.00 ± 11.19 pg/mL; p = .002) and IFN-γ (65.70 ± 39.78 vs. 32.14 ± 17.48 pg/mL; p = .001) were significantly higher in the seroconverter group compared to non-seroconverter. In contrast, TGF-ß (820.96 ± 415.78 vs. 1045.57 ± 204.66; p = .046) was higher in non-seroconverter. CONCLUSIONS: Pro-inflammatory cytokines IL-6 and IFN-γ were significantly associated with seroconversion after SARS-CoV-2 infection and vaccination in RTRs.

The adverse effects of high-dose corticosteroid on infectious and non-infectious sequelae in renal transplant recipients with coronavirus disease-19 in India.

INTRODUCTION: The corticosteroid dosing modulation in renal transplant recipients (RTRs) with coronavirus disease-19 (COVID-19) is not well defined. We aimed to analyze the outcomes and infectious and non-infectious sequelae in RTR with COVID-19 with reference to corticosteroid dosing and the first and second pandemic waves of COVID-19. MATERIALS AND METHODS: This study included RTRs admitted during two pandemic waves between March 25, 2020, and July 31, 2021. Patients were categorized into mild, moderate, and severe COVID-19. The outcomes and predictors of survival at 4 weeks were analyzed. The survivors were also followed for 6 months and were studied for mortality, readmission rates, and infectious and non-infectious sequelae with reference to high-dose and standard-dose corticosteroids. RESULTS: A total of 251 RTRs, 104 during the first wave and 147 during the second wave, were treated. Overall mortality was 15.1% (11.5% in the first wave vs. 17.5% in the second wave, p = .23). The use of high-dose steroids was also significantly high in non-survivors (85.8% vs. 11.3%, p = .001). On multivariate analysis, the severity of COVID-19, graft dysfunction, and high dose of corticosteroid therapy were associated with increased odds of mortality. Among survivors, 6-month mortality (17.3% vs. 0.5%, p = .001), readmission rate (91.3% vs. 23.7%, p = .001), fungal infection (30.4% vs. 2.2%, p < .001), and post-COVID lung sequelae (21.7% vs. 4.4%, p = .008) were significantly higher in the high-dose corticosteroid group than in the standard-dose group. CONCLUSION: High-dose corticosteroid dosing in RTRs with COVID-19 was associated with increased infections, particularly fungal infections, and non-infectious sequelae with higher mortality on subsequent follow-up.

Risk of tuberculosis among renal transplant recipients receiving rituximab therapy.

BACKGROUND: Rituximab is an anti-CD 20 agent used widely in renal transplant recipients. Its use is associated with various infections; however, its association with tuberculosis (TB) is not well established and has not been studied in post renal transplantation patients. METHODS: This is a single-center, retrospective analysis of 56 renal transplant recipients who received rituximab as a part of desensitization protocol or as rescue therapy for rejections and 287 post-renal transplant patients who did not receive rituximab during the study period from January 2013 to June 2017. The association between use of rituximab and occurance of TB was studied. Other factors associated with TB were also investigated. RESULTS: Baseline characteristics were similar in both the groups. Mean time for occurrence of TB was 18.4 ± 10.6 months after renal transplantation. Rituximab use was not significantly associated with TB or any other infection. Higher number of rejection episodes (60% vs. 32.72%, p = .029) was the only factor associated with greater incidence of TB. However, no specific type of rejection was associated with TB. Use of plasmapheresis in post-transplant period for treatment of humoral rejections was associated with significantly higher incidence of TB (33.33% vs. 13.41%, p = .031); however, when pre-transplant plasmapheresis was also considered, there was no significant difference. The choice of induction agent was not associated with higher incidence of TB. CONCLUSION: Use of rituximab is not associated with higher incidence of TB when compared to other immunosuppressive agents. Routine screening and prophylaxis may not be advisable, especially in a country like India with high prevalence of TB, as it will further delay transplantation and may adversely affect the outcome of the patients.

Delayed onset bleed after percutaneous kidney biopsy: is it the same as early bleed?

BACKGROUND: While the majority of bleeding complications after a percutaneous kidney biopsy (PKB) occur early (≤24 h), delayed onset bleeding complications (>24 h) have been rarely reported and can be catastrophic for the patient. PURPOSE: To describe the incidence, risk factors, and outcomes of delayed bleeding complications after PKB. MATERIAL AND METHODS: We retrospectively studied native and graft kidney biopsies in patients who developed delayed bleeding complications (>24 h) after the biopsy performed in the Department of Nephrology and Renal Transplantation of a tertiary care medical institution in north India between January 2014 to December 2018. RESULTS: Of the 4912 renal biopsies reviewed, 20 patients (16 men, 4 women; 0.40%) had a delayed biopsy bleeding complication. Of these patients, 95% had major bleeding complications requiring blood transfusions and 85% needed intervention like gelfoam/coil embolization. Despite intervention, one patient (5%) had mortality due to complications of bleeding and sepsis. When compared to a control group of patients with early biopsy bleed, patients with the delayed biopsy bleed had similar demographic and clinical profiles except for higher pre-biopsy hemoglobin and lower systolic and diastolic blood pressure. CONCLUSION: A post-PKB delayed onset bleed is not uncommon, and the vast majority of these patients had major bleeding complications requiring blood transfusions and/or intervention like embolization. They had a similar demographic and clinical profile presentation as early bleed patients. Meticulous outpatient monitoring and patient education after discharge may be useful to detect this complication promptly and to intervene early to have good patient outcome.

Midterm eGFR Predicts Pregnancy Outcomes: An Observational Study.

INTRODUCTION: The hemodynamic adjustments during pregnancy play a pivotal role in sustaining the gestation, however, its clinical connotation on midterm renal hyperfiltration and its consequence on maternal and fetal outcomes need a greater appraisal. The present retrospective study looked into the midterm estimated glomerular filtration rate (eGFR) among pregnant females without overt pieces of evidence of chronic kidney disease (CKD) as a surrogate marker for midterm hyperfiltration and its implication on maternal and fetal outcomes. MATERIALS AND METHODS: All pregnancies among females aged 18-50 years with available pregestational baseline serum creatinine were included in the study. Maternal renal hyperfiltration was expressed as the highest eGFR, using the creatinine clearance method. Its association with adverse maternal and fetal outcomes was assessed. RESULTS: A total of 1,045 pregnancies were assessed during the study. According to midterm eGFR, among them, 65% of pregnancies showed midterm eGFR between 120 and 150, however, 4.3% of pregnancies had values more than 150 mL/min per 1.73 m2 . The risk of poor pregnancy outcome was observed for eGFR levels below and above the reference level of 120-150 mL/min per 1.73 m2 (1.97 for values ≥150 mL/min per 1.73 m2 , and 1.72 for 90-120 mL/min per 1.73 m2 ). Pregnancies with eGFR between 60 and 90 mL/min per 1.73 m2 had odds ratios (ORs) of 5.64. CONCLUSION: A distinctive relationship was observed between the midterm eGFR and adverse pregnancy outcomes with the best outcomes for midterm eGFR levels between 120 and 150 mL/min per 1.73 m2 . Despite no apparent functional renal deterioration, a poor maternal hyperfiltration response may play a crucial impact on poor pregnancy outcomes.

Aftermath of fortnightly universal testing for severe acute respiratory corona virus-2 infection in maintenance hemodialysis patients.

INTRODUCTION: Asymptomatic maintenance hemodialysis patients with acute respiratory corona virus-2 (SARS-COV-2) are missed with pre-dialysis screening without testing. The possible ideal strategy of testing each patient before each shift with reverse transcription polymerase chain reaction (RT-PCR) is not feasible. We aimed to study the effectiveness of fortnightly screening with RT-PCR for SARS-CoV-2 in curbing transmission. METHODS: Between July 1, 2020 and September 30, 2020, all 273 patients receiving hemodialysis were subjected to fortnightly testing for SARS-Cov-2 in the unit to detect asymptomatic patients. The cost and effectiveness of universal testing in preventing transmission were analyzed using susceptible-infectious-removed (SIR) modeling assuming R0 of 2.2. RESULTS: Of 273 MHD patients, 55 (20.1%) found infected with SARS-CoV-2 over 3 months. Six (10.9%) were symptomatic, and 49 (89.1%) asymptomatic at the time of testing. Six (10.9%) asymptomatic patients develop symptoms later, and 43 (78.2%) remained asymptomatic. A total of seven (6.1%) HCWs also tested positive for the virus. Fortnightly universal testing is cost-effective, and SIR modeling proved effective in preventing person-to-person transmission. CONCLUSIONS: Repeated universal testing in maintenance hemodialysis patients detected 89% of asymptomatic SARS-CoV-2 patients over 3 months and appeared to be an effective strategy to prevent person-to-person transmission in the dialysis unit.

Long-term outcomes of lupus nephritis treated with regimens based on cyclophosphamide and mycophenolate mofetil.

INTRODUCTION: Lupus nephritis (LN) has a considerable impact on the morbidity and mortality of systemic lupus erythematosus (SLE) patients. Long-term comparative outcome data from the Indian subcontinent on treatment regimens with cyclophosphamide (CYP) and mycophenolate mofetil (MMF) are sparse. We assessed renal and patient survival for these patients in terms of the types of induction - CYP or MMF - and the two maintenance therapies - MMF or azathioprine (AZA). METHODS: We retrospectively analysed outcomes of 100 LN patients, 67 treated with CYP (26 class III, 25 class IV, 6 class III + V and 10 class IV + V; 40 Euro lupus regimen and 27 National Institutes of Health regimen) and 33 treated with a MMF-based regimen with steroids between July 2008 and June 2018. Data regarding demographic, clinical and histopathological features and the treatment given to all patients were extracted. Outcomes between the two regimens CYP and MMF were compared in terms of remission, dialysis and patient survival. RESULTS: The clinical characteristics were similar in both groups, except that the activity index was higher in CYP patients (6.13 ± 4.48 vs. 4.61 ± 2.80). However, the chronicity index was similar. The overall remission rate was 70% at the end of induction. The rates of complete remission, partial remission and non-responders in the CYP group were 46.2%, 23.9% and 29.9%, respectively. However, in the MMF group, the corresponding rates were 57.6%, 12.1% and 30.3%, respectively. The 1-, 2-, 3-, 4-, 5- and 10-year patient survival rates in the CYP group were 89.5%, 86.2%, 86.2%, 83.8%, 83.8% and 83.8%, respectively. In the MMF induction group, the corresponding rates were 93.9%, 93.9%, 89%, 89%, 89% and 89%, respectively. At the end of the study, rates of end-stage renal disease in the MMF group and CYP group were 7.5% and 12.1%, respectively. The death-censored and non-censored renal survival rates were also similar in the long term. With regard to maintenance therapy, 3/56 (5.3%) in the MMF group and 7/34 (20.5%) in the AZA group experienced doubling of serum creatinine (p = 0.03). CONCLUSIONS: Long-term outcomes in terms of patient and renal survival of LN patients treated with CYP and MMF induction are similar. Doubling of serum creatinine occurred more with AZA-based maintenance therapy than with MMF-based maintenance therapy. Most deaths occurred during induction, and sepsis was the most common cause of death.

Nocardiosis in kidney transplant recipients: A tertiary care center experience.

INTRODUCTION: Kidney transplant recipients are at increased risk of opportunistic infections, including Nocardia. The incidence of nocardiosis in kidney transplant recipients is 0.4-1.3%. The data regarding its epidemiology and outcomes is limited. METHODS: This was a 10-year retrospective observational study from January 2012 to December 2021 at a tertiary care center in northern India, in which all kidney transplant recipients with Nocardia infection were included and followed. RESULTS: 12 (1.1%) patients had a Nocardia infection among the 1108 kidney transplant recipients. All were living donor kidney transplant recipients, and the mean age at diagnosis was 48.67 ± 12.60 years. Nocardia infection occurred at a median of 26 months (range 4-235) post-transplantation, with 4 (33.1%) of the cases occurring within a year of transplant. Breakthrough infection occurred in 7 (58.3%) patients on cotrimoxazole prophylaxis. 41.7% (n = 5) cases had an episode of rejection in the preceding year of Nocardia diagnosis. Concurrent cytomegalovirus (CMV) infection was present in one (8.3%) case. The lung was the most frequently involved organ. Microscopy was positive in all the cases; while culture was positive in 10 cases, and antimicrobial susceptibility testing (AST) were performed for these isolates. The majority (60%) of isolates were resistant to cotrimoxazole. All tested isolates remained susceptible to Amikacin, Imipenem, and Linezolid. No patients experienced Nocardia recurrence after completion of antibiotic therapy. The mortality at 12 months was 66.7% (n = 4), and only one death was Nocardia-related. CONCLUSION: Nocardia may cause a late-manifesting infection beyond the traditional window. The cotrimoxazole prophylaxis may not be sufficient for Nocardia prevention.

Micro-vascular complications of post-transplant diabetes mellitus in renal transplant recipients- an observational study.

INTRODUCTION: The incidence of post-transplant diabetes mellitus (PTDM) ranges from 2.5% to 20% in kidney transplant recipients. Diabetic retinopathy (DR), diabetic kidney disease (DKD), and distal symmetric polyneuropathy (DSPN) are the microvascular complications frequently seen in both type 1 and 2 diabetes mellitus (DM). However, the data regarding these complications in patients with PTDM is lacking. METHOD: A retrospective and prospective observational study of PTDM conducted at a tertiary care hospital from November 2018 to December 2020. 115 kidney transplant recipients who had PTDM of ≥5 years duration were included and analysed. RESULTS: The mean duration of PTDM was 8.8 ± 3.0 years, and the mean of all available HbA1c values was 7.0 ± 0.9%. while none of the patients had evidence of diabetic retinopathy on direct ophthalmoscopy, 37.4% of patients (n = 43) had DSPN and this was associated with the duration of PTDM and age. The mean estimated glomerular filtration rate (eGFR) was 59.24 ± 21.82 ml/min/1.73m2, and patients had a median proteinuria of 620 mg/day (IQR 1290). Out of 115 patients, 20% of them (n = 23) underwent graft kidney biopsy, and 10 biopsies were diagnosed as de-novo DKD. Patients with biopsy proven DKD had a mean PTDM duration of 143.3 ± 52.4 months; a mean HbA1c level of 7.9 ± 1.3%; a mean eGFR of 44.8 ± 21.8 ml/min; and a median proteinuria of 2653 mg (IQR 2758). An additional analysis of all 23 biopsied patients showed that HbA1c level and degree of proteinuria were significantly associated with de-novo DKD. CONCLUSION: PTDM in transplant patients had milder microvascular complications than usually expected in Type 1/2 diabetes in non-transplant patients. DR was not strongly associated with DKD in PTDM patients. Furthermore, de-novo DKD development was associated with poor glycaemic control and increased proteinuria.

Clinico-epidemiological characteristics of early- versus late-onset cytomegalovirus disease among renal transplant recipients: A two-decade experience.

BACKGROUND: Reactivation of cytomegalovirus (CMV) infection in transplant patients is high because of immunosuppression. We have evaluated the clinical and epidemiological characteristics of early versus late onset of CMV infection among renal transplant recipients. METHODS: A single center retrospective observational study was conducted among renal transplant recipients who underwent kidney transplant between January 2002 and December 2021. CMV disease was classified as early or late depending on its detection prior to or after 90 days post-transplantation. Herein, we reported the differences between early and late onset of CMV disease with respect to clinical symptoms, the use of immunosuppression and the impact on graft outcomes. RESULTS: Out of total 2164 renal transplant recipients, 156 patients (7.2%) were diagnosed with CMV disease. Among these 156 patients, 25 patients (16%) had early CMV while 131 patients (84%) had late CMV. Overall, the two groups did not differ with respect to the induction or maintenance of immunosuppressive agents. However, the proportion of CMV syndrome was greater among early (56.0%) than late (26.7%) CMV groups (p = 0.01). In contrast, tissue invasive disease was more frequent among late (73.3%) in comparison to early (44.0%) CMV groups (p = 0.01). Among clinical symptoms, diarrhea was more frequent in late (63.4%) vs. early (36%) CMV-affected patients (p = 0.01). Graft loss occurred in 4.0% of early CMV group vs. 25.2% of late CMV group (p = 0.03). Neither of the clinical groups differed with respect to occurrence of biopsy-proven allograft rejection post-infection. CONCLUSIONS: Early CMV disease presents more frequently as CMV syndrome while late CMV disease usually manifests itself as tissue invasive disease. Graft loss is more common in patients with late onset of CMV disease.

Fulminant ruptured septic aneurysm complicating the catheter related blood stream infection in a patient on maintenance hemodialysis: A case report.

Metastatic infections can complicate catheter-related blood stream infections (CRBSI) in dialysis dependent patients. However, an infected/septic aneurysm involving the aorta or its branches as a direct complication of CRBSI without an underlying infective endocarditis is not reported so far in the literature. We report a 43-year female, who presented with CRBSI 2 weeks following a tunneled dialysis catheter (TDC) insertion. Due to the lack of defervescence after 72 h of antibiotics given as per the culture sensitivity reports, the TDC was removed. Blood cultures grew Pseudomonas aeruginosa. After a catheter free interval of 4 days, a TDC was reinserted, an antibiotic course was completed, and she was discharged in stable condition. Five days later, she presented with acute abdominal pain and fever. A tender, firm, and pulsatile mass was noted in the hypogastrium with a bruit. Contrast-enhanced CT revealed a pseudoaneurysm of the aorta, and left common iliac artery at the site of origin. She was started on IV antibiotics and planned for an endovascular prosthesis but had a sudden collapse during her hospital stay due to a ruptured aneurysm. CRBSI due to certain pathogens such as Pseudomonas might require prolonged and dual antibiotic therapy to prevent fulminant complications.

Divergent manifestations and outcomes of diffuse crescentic immunoglobulin A nephropathy and pauci-immune crescentic glomerulonephritis on long-term.

BACKGROUND: Diffuse crescentic IgAN (CIgAN) is an uncommon phenotype of IgAN, which presents as rapidly progressive renal failure, similar to patients with pauci-immune crescentic glomerulonephritis(PCGN). There are limited data on outcomes comparisons between the two. METHODS: In this single-center, retrospective cohort study, we compared the clinical features, pathological presentation, and renal outcomes of 52 patients with CIgAN and 42 patients with renal-limited PCGN from January 2007 to December 2019. RESULTS: The CIgAN patients were younger (30.5 ± 13.8 years) than PCGN patients (46.1 ± 11.8 years) (P = 0.001). The CIgAN patients had a higher prevalence of hypertension (86.5% Vs. 41.3%, P = 0.001); and degree of proteinuria (4.2 ± 2.7 g/24 h Vs. 2.3 ± 1.16 g/24 h; P = 0.001) than PCGN patients. The chronicity in terms of global glomerulosclerosis, interstitial fibrosis, and tubular atrophy was higher in the CIgAN group than in the PCGN group. The remission rate with immunosuppression was significantly higher in the PCGN group than in the CIgAN group (P = 0.016). The end-stage renal disease (ESRD) or death within 1 year of diagnosis was significantly more in the CIgAN group (62.3% Vs. 39.1%) than PCGNgroup. For patients who were dialysis-dependent at presentation, the primary outcome of ESRD or death within one year was seen in 90.9% of patients of CIgAN and 44.1% in the PCGN group (P = 0.001). The long-term death non-censored renal survival is poor in the CIgAN group than in PCGN patients. However, patient survival is poor in PCGN patients. CONCLUSION: CIgAN is a different form of RPGN compared to PCGN and carries a poor prognosis despite similar immunosuppressive therapy in the long term.

Non-Diabetic Kidney Disease in Type 2 Diabetes Mellitus: A Changing Spectrum with Therapeutic Ascendancy.

BACKGROUND AND OBJECTIVES: Owing to changing epidemiology and therapeutic practices, a change in the spectrum of renal involvement in Type-2 diabetes mellitus (T2DM) has also been noted. The treatment of non-diabetic kidney disease (NDKD) differs from diabetic kidney disease (DKD) and the reversibility of NDKD in many cases to normal, prompts biopsy for rapid and accurate diagnosis. Data are scarce on kidney biopsy findings in T2DM. STUDY DESIGN & SETTING: In this observational study, we prospectively collected the data of kidney biopsies of patients aged ≥ 18 years with T2DM admitted between 1 August 2005 and 31 July 2022. The clinical, demographic and histopathological data were evaluated. The spectrum of kidney involvement in the form of DKD and/or NDKD was studied. The impact of these findings with the use of drugs retarding disease progression was also analyzed. RESULTS: A total of 5485 biopsies were performed during the study period and of these 538 patients had T2DM. The mean age of the study population was 56.9 ± 11.5 years and 81% were males. The mean duration of DM was 6.4 ± 6.1 years. Diabetic retinopathy (DR) was noted in 29.7%. The most common indication for biopsy was an acute rise in creatinine (147, 27.3%). Amongst the 538 diabetic patients who underwent biopsy, histological features only of DKD were noted in 166 patients (33%), NDKD alone in 262 (49%) and NDKD with DKD lesions in 110 (20%). On multivariate analysis, duration of DM less than 5 years, absence of CAD, absence of DR, oliguria at presentation, an acute rise in creatinine and low C3 were associated with NDKD. CONCLUSIONS: The prevalence of NDKD among diabetics and ATIN in particular might be on an increasing trend in the current era of changing T2DM epidemiological patterns. The use of anti-pro-teinuric agents was associated with lesser degrees of histopathological chronicity in T2DM.

Clinicopathologic Manifestations of Immunoglobulin A Nephropathy in a Northern Indian Cohort: A Mute Assassin with Delayed Diagnosis.

Introduction: Immunoglobulin A nephropathy (IgAN) is the most common glomerulonephritis worldwide, but there is a marked geographic difference in its prevalence and prognosis. IgAN is known to have an aggressive course in Asians. However, its exact prevalence and clinicopathologic spectrum in North India are not well documented. Materials and Methods: The study included all patients aged above 12 years with primary IgAN on kidney biopsy from January 2007 to December 2018. Clinical and pathological parameters were noted. Two histopathologists independently reviewed all kidney biopsies, and MEST-C score was assigned as per the Oxford classification. Results: IgAN was diagnosed in 681 (11.85%) out of 5751 native kidney biopsies. The mean age was 32 ± 12.3 years, and the male to female ratio was 2.5:1. At presentation, 69.8% had hypertension, 68% had an estimated glomerular filtration rate (eGFR) of less than 60 ml/min, 63.2% had microscopic hematuria, and 4.6% had gross hematuria. The mean proteinuria was 3.61 ± 2.26 g/day, with 46.8% showing nephrotic range proteinuria and 15.2% showing nephrotic syndrome manifestation. Histopathologically, 34.4% of patients had diffuse global glomerulosclerosis. Oxford MEST-C scoring revealed M1 in 67%, E1 in 23.9%, S1 in 46.9%, T1/T2 in 33%, and crescents in 19.6% of biopsies. The mean serum creatinine was significantly higher in cases with E1, T1/2, and C1/2 scores (P < 0.05). Hematuria and proteinuria were significantly higher (P < 0.05) with E1 and C1/2 scores. Coexisting C3 was associated with higher serum creatinine at presentation (P < 0.05). Conclusion: IgAN patients with late presentation and advanced disease became less amenable to immunomodulation in our cohort. The implementation of point-of-care screening strategies, early diagnosis, and retarding disease progression should be prioritized in the Indian strategy.

Protocol and Methods: Role of Levothyroxine on the Progression of Chronic Kidney Disease in Subclinical Hypothyroid Populations (LP-CKD) - A Multicenter Randomized Controlled Trial.

Introduction: Subclinical hypothyroidism (SCH) is highly prevalent and associated with chronic kidney disease (CKD). However, it is still unanswered whether the restoration of euthyroid status in these patients will be beneficial in retarding a decline in glomerular filtration rate in early CKD patients. We aim to evaluate the efficacy of levothyroxine therapy versus placebo in slowing estimated glomerular filtration rate (eGFR) decline among CKD patients (stage 2-4) with SCH. Methods: This study will be a multicentric, double-blind, randomized, parallel-group, placebo-controlled study. A total of 500 CKD patients, 250 patients in the treatment group and 250 patients in the placebo group, will be randomized. The randomization between the treatment arm and placebo arm will be performed as per the computer-generated random number table in a 1:1 ratio. The sample size was calculated based on the assumed reduction in eGFR after 1-year follow-up in the treatment and placebo groups of 10% and 25%, respectively, at a minimum two-sided 99% confidence interval and 90% power of the study and considering 20% loss on follow-up. Each patient will be followed every 3 months for at least 1 year after randomization. Individuals completing 1-year follow-up visits will be considered for analysis. The baseline and follow-up data will be compared between the treatment and placebo groups. The study will evaluate the efficacy and safety of levothyroxine therapy versus placebo in slowing eGFR decline among CKD patients (stage 2-4) with SCH. The primary endpoint will be the end of follow-up of the patients, reduction of eGFR by ≥50% from a baseline of that patient, or development of ESKD or death of the patients. The secondary endpoint will be any cardiovascular event or arrhythmia after the institution of the drug.

Impact of Early versus Late Referral to Nephrologists on Outcomes of Chronic Kidney Disease Patients in Northern India.

Background: CKD patients are often asymptomatic in the early stages and referred late to nephrologists. Late referred patients carry a poor prognosis. There is a lack of data on outcomes associated with referral patterns in CKD patients from northern India. Methods: In this observational cohort study, all CKD patients who visited the nephrology OPD of the institute between Nov 1, 2018, and Dec 31, 2020, were classified as early referral (ER) if their first encounter with a nephrologist occurred more than one year before initiation of dialysis and education about dialysis (from a nurse or nephrologist). The remaining others were considered late referrals (LRs). The outcomes impact of early and late referrals was analyzed. Results: A total of 992 (male 656) CKD patients (ER, n = 475 and LR, n = 517) were enrolled. Patients referred early were older and diabetic and had higher BMI, better education, occupation, and socioeconomic status as compared to those referred late. The mean eGFR at first contact with the nephrologist was (25.4 ± 11.5 ml/min) in ER and 9.6 ± 5.7 ml/min in the LR group and had a higher comorbidity score. The CKD-MBD parameters, hemoglobin, and nutritional parameters were worse in LR. Only a few patients had AVF, and the majority required emergency dialysis in the LR group. A total of 91 (9.2%) patients died, 17 (1.7% ER and 74 (7.5%) patients in the LR group patients. There was significantly lower survival at 6 months (ER 97.1% vs. LR 89.7%), 12 months (ER 96.4% vs. LR 85.7%), 18 months (ER 96.4% vs. LR 85.7%), and 24 months (ER 96.4% vs. LR 85.7%) in late referral group as compared to early referral group (P=0.005). Conclusions: LR to nephrologists has the risk of the emergency start of dialysis with temporary vascular access and had a higher risk of mortality. The timely referral to the nephrologist in the predialysis stage is associated with better survival and reduced mortality.

Psycho-social health and quality of life among kidney donors following transplantation.

INTRODUCTION: Living kidney donation is a complex psychological experience for donors. The present study examined the psychosocial impact of kidney donation on donors. METHODS: The retrospective study included 506 donors who donated a kidney between 2010 and 2018 at a transplant centre in India. These donors responded via a donor insight questionnaire about their hospital anxiety, and their possible level of depression. The information included socio-demographic form with multiple information. The health survey was used periodically evaluate the psychosocial impact among donors following donation, including the transplant outcomes. RESULTS: The majority of donors were females (79.4%). There was a significant improvement in the quality of life among donors (SF-36) following the donation of a kidney, especially among those donors who maintained good graft functions themselves as well as those who were informed about good kidney function in transplanted recipients. These donors showed a lesser degree of depressive and anxiety scores (HAD score 3.5 and BDI II 4.8) than donors who had problems themselves and/or whose donated kidneys did not function well. Most living donors (89.1%) felt that the act of donation had a positive impact on their lives and those donors would encourage others to donate a kidney. Overall, the graft outcomes impacted the donor's state of mind. CONCLUSION: The study showed a very positive impact of the acknowledgment of the donor by the recipient, especially those donors whose kidney transplants were well functioning. The state of depression, anxiety, and psycho-social outcomes correlated with the graft outcomes. Donors showed positive insight towards donation, with inner conscience still conclusively willing to donate and encourage others.

Evanescing renal allograft cortical necrosis from living donor renal transplantation: A lesson learned over two decades.

BACKGROUND: Renal graft cortical necrosis (GCN) is a catastrophic cause of graft failure. We evaluated the incidence, causes, management, and outcome of GCN across two decades from our center. METHODS: This is a retrospective analysis of transplant patients who had biopsy-proven GCN transplanted between 2000 and 2020. The clinical details, immunological workup, induction, maintenance regimen, causes of cortical necrosis, and the outcomes were compared between the first period 2000-2012, and the second period 2013-2020, when Flow cytometric and Luminex based crossmatch were included in the workup plan. RESULTS: Among 2333 live ABO-compatible renal transplants, 37 (0.015%) patients (36 patients between 2000 and 2012 and 1 between 2013 and 2020) developed GCN (60% had diffuse and 40% patchy GCN) at a median of 8 days after transplantation.Twenty-six (60%) received ATG, 4 received plasmapheresis and ATG (10.8%) as antirejection therapy. The cyclosporine-based regimen was associated with a higher risk of GCN (RR 2.54; 95% CI 1.26 to 5.12, p = 0.009), whereas tacrolimus-based therapy had a lower risk (RR 0.39; 95% CI 0.19 to 0.79, p = 0.009). The introduction of flow cytometry and DSA assay has significantly decreased the incidence of acute rejection and GCN. Only one patient had GCN during the 2013-2020 period because of graft's mucormycosis. Twenty-five (67.56%) patients had no recovery, and 12 (32.43%) had partial recovery of graft function. CONCLUSION: GCN is mainly associated with rejection, and cyclosporin-based maintenance regimen had a higher incidence. The remarkable decrease in GCN after 2012 onwards could be attributed to the use of Flowcytometry, Luminex-based DSA assays, and tacrolimus-based regimens.

Health-Related Quality of Life Score and Outcomes in Living Donor Renal Transplant Recipients With COVID-19.

OBJECTIVES: Renal transplant recipients with severe COVID-19 may have sequelae that can affect their quality of life and can have poor patient and graft outcomes. MATERIALS AND METHODS: We conducted a prospective, observational study between April 1, 2020, and December 31, 2020, to assess patient and graft outcomes and quality of life using the EQ-5D quality of life survey score at baseline and at follow-up of at least 12 weeks. RESULTS: Of the 3100 renal transplant recipients with follow-up, 104 patients had COVID-19. Of these patients, 75 (72.1%) had mild-moderate disease and 29 (27.9%) had severe disease. In addition, 78 patients (75.0%) were hospitalized, with 43 patients (41.3%) in the intensive care unit. Remdesivir was used in 46 of the 78 hospitalized patients (58.9%) without any mortality benefitin the severe group. Sixteen patients (17.5%) were rehospitalized with opportunistic infection (n = 7), persistent graft dysfunction (n = 6), pulmonary sequelae (n = 2), and angina (n = 1). Thirteen patients (12.5%) died. On follow-up, the overall EQ-5D score was significantly lower, particularly the pain and anxiety/depression scores in patients with mild-moderate disease, whereas all components of the EQ-5D score were significantly affected in patients with severe COVID-19. CONCLUSIONS: Renal transplant recipients with severe COVID-19 are at high risk of mortality, acute graft dysfunction, and residual disability, severely affecting their quality of life score and requiring rehabilitation.

Two Decades Outcomes of Posttransplant Immunoglobulin A Nephropathy in Live Donor Renal Transplantation.

Background: The data on long-term outcomes of posttransplant immunoglobulin A nephropathy (IgAN) are confounding and vary with geography and ethnicity worldwide. We aimed to study the long-term graft outcomes of patients with posttransplant IgAN in the northern Indian cohort. Methods: The long-term graft outcomes of 51 live donor renal transplant recipients with biopsy-proven posttransplant IgAN (recurrence/de novo) were analyzed. The risk factors for graft failure in the posttransplant IgA groups were analyzed using the Cox regression analysis. Results: Out of the total of 51 patients who had posttransplant IgAN, 40 patients had a biopsy-proven native kidney IgAN. The mean duration of the clinical presentation of posttransplant IgAN was 62.4 months (5.2 years) posttransplant. Proteinuria at the time of biopsy was 3.03 ± 2.2 g/day, and 41.2% had proteinuria of more than 3 g/day at the time of biopsy. The estimated 1, 5, 10, and 20 years patient survival was 98%, 95.4%, 75.9%, and 25.2%, respectively, and the estimated 1, 5, 10, and 20 years graft survival was 98%, 88.5%, 44.6%, and 11.9%, respectively, in patients who had posttransplant IgA. Many of the traditional risk factors associated with progression in native kidney IgAN, such as the degree of proteinuria, Oxford MEST (mesangial and endocapillary hypercellularity, segmental sclerosis, and interstitial fibrosis/tubular atrophy) scoring, recipient's age, and sex were not predictive of early graft failure among patients with posttransplant IgAN. In our cohort, the only significant graft failure predictor was serum creatinine at 5 years. Chronic antibody-mediated rejection (ABMR) was seen in 21.6% of patients with posttransplant IgAN. Whether this coexistence of chronic ABMR is an incidental finding or posttransplant IgAN predisposes to chronic ABMR requires further investigation. Conclusion: Posttransplant IgAN is associated with poor long-term graft outcomes in live donor renal transplants. Proteinuria and MEST scoring were not predictive of graft failure in living donor posttransplant IgAN.