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.

Antibody response to ChAdOx1 nCoV-19 (Covishield®) vaccine in people on maintenance hemodialysis.

INTRODUCTION: People on renal replacement therapy (RRT) have a high risk of COVID-19 infection and subsequent death. COVID-19 vaccination is strongly recommended for those on RRT. Data are limited on the immune response of the ChAdOx1 nCoV-19/AZD1222 (Covishield®) vaccine in patients on RRT. METHODS: A prospective cohort of adult (age > 18 years), on RRT in the form of hemodialysis were included and received two intramuscular doses of Covishield®. A blood specimen of 5.0 mL was collected at two time points, within a few days before administering the first dose of the vaccine and at 4-16 weeks after the second dose. According to their prior COVID-19 infection status, the participants were grouped as (i) prior symptomatic COVID-19 infection, (ii) prior asymptomatic COVID-19 infection, and (iii) no prior COVID-19 infection. RESULTS: A large proportion (81%) of participants had anti-spike antibodies (ASAb) before vaccination, and a reasonable proportion (30%) also had neutralizing antibodies (NAb). The titer of ASAb was relatively low (207 U/mL) before vaccination. The ASAb titer (9405 [1635-25,000] U/mL) and percentage of NAb (96.4% [59.6-98.1%]) were markedly increased following the administration of two doses of the vaccine. The participants' prior COVID-19 exposure status did not influence the rise in ASAb titer and NAb percentage. Further, administering two doses of the Covishield vaccine helps them achieve a high ASAb titer. CONCLUSION: Two doses of ChAdOx1 nCoV-19/AZD1222 (Covishield®) vaccine, given 12 weeks apart, achieve a high titer of ASAb and a high percentage of NAb in people on hemodialysis.

Clinicopathologic characteristics and outcomes of late onset lupus nephritis: a single centre experience.

Systemic Lupus Erythematosus (SLE) occurs in the reproductive age group. Renal involvement occurs less frequently in late-onset SLE than in reproductive-age SLE patients. Here, we aimed to study the clinical, serological and histopathological characteristics of late-onset lupus nephritis (LN). Late-onset LN was defined as disease onset after 47 years of age, corresponding to the average menopausal age. Records of biopsy proven late-onset lupus nephritis patients diagnosed between June 2000 and June 2020 were reviewed. Late-onset LN constituted 53 of 4420 patients (1.2%) biopsied during the study period. Females represented 90.65% of the cohort. Mean age of the cohort was 49.5 ± 7.05 years at the time of SLE diagnosis while its renal presentation was delayed by median duration of 10 months (IQR 3-48 months). Renal failure was present in 28 patients (52.8%) with acute kidney injury (AKI) (28.3%, n = 15) as the most common presentation. On histopathological analysis, class IV was observed in 23 patients (43.5%), crescents were observed in one-third cases and lupus vasculopathy in 4 patients (7.5%). All patients received steroids. Majority of patients (43.3%; n = 23) received Euro lupus protocol for induction. On median follow up duration of 82 months, renal flares were noted in 9 patients (17%) and 8 patients (15.1%) became dialysis dependent. Among 11 patients (21%) with infectious complications, 7 patients (13.2%) suffered from tuberculosis. Infections caused three-fourth of the deaths. Late-onset lupus nephritis is rare and presents as renal failure in majority. Renal biopsy affects the clinical decision of judicious use of immunosuppression which is imperative due to high rate of infections in this cohort.

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.

"Unconventional" Causes of Acute Kidney Injury: A Critical Nuance of Interpretation and Intervention.

BACKGROUND: Acute kidney injury (AKI) is one of the most common clinical problems encountered by physicians in day-to-day practice which is associated with increased morbidity and mortality. The incidence of AKI is increasing so the right approach for interpretation of clinical clues and investigation may be lifesaving. AIM: The study aimed to document the variety of unusual cases of AKI and suggest a case-based approach for clinical evaluation and investigations to help physicians treat such cases. MATERIALS AND METHODS: This was a retrospective analysis of medical/electronic records of 10 patients who were admitted in medical wards between January 2020 and June 2021 and diagnosed to have AKI. RESULTS: We present the history, clinical findings, and investigations of 10 patients diagnosed with unusual causes of AKI. CONCLUSION: It is important for physicians to recognize unusual causes of AKI. A high index of suspicion and timely diagnosis and treatment interventions may bring complete recovery of renal functions in patients of AKI.

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.

Acute hepatitis C treatment in advanced renal failure using 8 weeks of pan-genotypic daclatasvir and reduced-dose sofosbuvir.

BACKGROUND: Sofosbuvir is not recommended in persons with estimated glomerular filtration rate (eGFR) <30 mL/min. We report the results of treatment with an off-label 8-week regimen of daclatasvir and half-dose sofosbuvir in patients with acute infection with hepatitis C virus ( HCV) and eGFR <30 mL/min. METHODS: Clinic records were searched to identify treatment-naïve, noncirrhotic adults with acute hepatitis C (HCV viremia and a ≥10-fold elevation of serum alanine aminotransferase activity) and eGFR <30 mL/min, who had been treated with a sofosbuvir-based regimen. Treatment response was assessed using serum HCV RNA testing at 4 weeks of treatment, end of the 8-week treatment and 12 weeks after stopping treatment. RESULTS: Of the 31 patients with acute hepatitis C, 27 [median age (range): 36 (18-74) years; 20 (74%) male] were started on treatment with 200 mg sofosbuvir and 60 mg daclatasvir daily for 8 weeks, irrespective of HCV genotype. All the 27 completed the planned 8-week treatment. One patient died 10 weeks after completing the treatment of an unrelated cause. All the 27 patients had undetectable HCV RNA after 4 weeks of and at the end of treatment. At 12 weeks after completion of treatment, only one tested HCV RNA positive and 25 were negative, with sustained virological response rate of 25/27 (92.6%) and 25/26 (96.2%) on intention-to-treat and per-protocol basis, respectively. CONCLUSION: Eight-week course of daclatasvir and half-dose sofosbuvir is effective for acute hepatitis C in patients with eGFR <30 mL/min and could be a useful alternative to costly, kidney-safe anti-HCV oral drugs in resource-constrained settings.

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.

Daclatasvir and reduced-dose sofosbuvir: An effective and pangenotypic treatment for hepatitis C in patients with estimated glomerular filtration rate <30 mL/min.

AIM: Sofosbuvir is a key agent for HCV treatment. It is not recommended for patients with chronic kidney disease (CKD) and estimated glomerular filtration rate (eGFR) <30 mL/min. We report real-life experience of treating a cohort of CKD patients with eGFR <30 mL/min using daclatasvir and half-daily dose of sofosbuvir. METHODS: Adults patients who (i) had eGFR<30 mL/min and detectable HCV RNA and (ii) were treated with interferon and ribavirin free, DAA based regimens were included. All patients were treated with daily doses of daclatasvir 60 mg and sofosbuvir 200 mg. The planned duration of treatment was 12 weeks, except for 24 weeks in those with either clinical evidence of cirrhosis or on immunosuppressive drugs. The end-points of the study were: (i) 12 weeks of follow-up after treatment completion, (ii) treatment discontinuation, or (iii) death or loss to follow-up. RESULTS: Thirty-six (88%) among 41 included patients (median [range] age: 48 [19-75] years; 25 [61%] male; genotype 1/3/4 were 17/ 22/2; cirrhosis 5) completed the treatment, two discontinued and three died during treatment. On an intention-to-treat basis, HCV RNA were undetectable at 4 weeks of treatment, treatment completion and after 12 weeks of follow-up in 40/41 (97.6%), 37/41 (90.2%) and 37/41 (90.2%), respectively. None of the patients had a relapse. CONCLUSIONS: Daclatasvir and half-daily dose of sofosbuvir was effective against genotype 1 and 3 HCV infection in patients with eGFR <30 mL/min. This combination could be a pangenotypic treatment option for such patients.

Recurrent Acute Kidney Injury in Tropics-Epidemiology and Outcomes.

BACKGROUND: Acute kidney injury (AKI) is now an established and preventable cause for chronic Kidney disease. Poor outcome of Acute Kidney Injury is influenced by severity and duration of AKI. We hypothesize that recurrent episodes of acute kidney injury are associated with adverse renal and patient related outcome. METHODS: Study was undertaken to look into etiological risk factors for recurrent AKI and its effect on renal and patient related outcome. This retrospective analytical study was conducted at tertiary care health care centre from northern part of India from January 2003 to December 2013. All patients with the diagnosis of "acute renal failure" or "acute kidney injury" as their hospital admission diagnosis was identified and individuals with recurrent Acute Injury were included in the study. RESULTS: Recurrent acute kidney injury was found in 21 (0.56%) of 3698 patients who presented with acute kidney injury during the 10 years period. Topical infections were the most common etiology of recurrent AKI followed by rhabdomyolysis and intravascular hemolysis leading to pigment nephropathy. Acute tubular necrosis was the most common histopathological diagnosis among patients biopsied. As the episodes of AKI increased from 2 to >2 episodes, there was poor immediate as well as late renal outcome. 50% were protienuric and 87.5% were hypertensive at 1 year among patients who had >2 episodes of AKI while it was 15.3% and 7.69% among patients having < 2 episodes respectively. CONCLUSION: Recurrent episodes of AKI are associated with poor patient and renal outcome suggesting that each episode of acute kidney injury needs close evaluation and follow up following hospital discharge with particular attention to renal outcomes.

Safety and effectiveness of response-guided therapy using pegylated interferon and ribavirin for chronic hepatitis C virus infection in patients on maintenance dialysis.

AIM: Treatment of hepatitis C virus (HCV) infection in patients with end-stage renal disease (ESRD) is difficult. Addition of ribavirin to pegylated-interferon (Peg-IFN) may help to improve the treatment response. Further, treatment duration could be shortened using a response-guided treatment (RGT) approach. METHODS: We retrospectively reviewed records of treatment-naïve adult patients with ESRD and chronic HCV infection who had been treated with Peg-IFN and low-dose ribavirin using a RGT approach. Rapid responders (undetectable HCV-RNA at 4 weeks) received treatment for 12 weeks, and slow responders (HCV-RNA detectable at 4 weeks, but undetectable or with >2.0 log10 reduction at week 12) for 24 (genotype 3; GT3) or 48 (genotype 1; GT1) weeks. In those without such reduction (null responders), treatment was discontinued. RESULTS: Of 26 non-cirrhotic patients (GT1 15, GT3 11) treated, four (15%; GT1 3, GT3 1) were null responders. Twenty-two (85%) patients had either rapid (n = 14 (54%); GT1 10, GT3 4) or slow response (n = 8 (31%); GT1 2, GT3 6). Of them, 21 patients had undetectable RNA at the end of treatment; one could not complete the treatment and was lost thereafter. There were no deaths during treatment. Three patients relapsed and three others died in 6 months after stopping treatment. Overall, 15/26 (58%) patients attained SVR24. Fourteen patients underwent transplantation beginning one month after treatment completion, and all were relapse-free after 17 (14-24) months of follow-up. CONCLUSION: RGT using Peg-IFN and ribavirin was effective in ESRD patients on maintenance dialysis. Renal transplant was safely done within one month of completing such treatment.

P. vivax Malaria presenting as Thrombotic Microangiopathy.

INTRODUCTION: Acute kidney injury (AKI) is reported to occur in patients with falciparum malaria but not uncommon with vivax malaria. AKI, anemia, thrombocytopenia and jaundice is a recurrent finding in severe malaria and can mimic as thrombotic microangiopathy (TMA). Relationship of malaria with TMA is unclear till date however evidences suggest their association. METHODS & MATERIAL: We reviewed our electronic database to evaluate relationship of malaria with TMA, of cases of malaria, jaundice and AKI. RESULTS: 4 patients found to have P. vivax malaria and histopathologically confirmed TMA. All had fever, oliguria, jaundice at presentation. The time between onset of symptoms and admission ranged from 7 to 14 days. All had parasitemia at presentation so were treated with Artesuanate. Hemodialysis and Plasmapheresis was done in all patients. On follow-up all patients recovered and asymptomatic urinary abnormality persisting in one patient. CONCLUSION: High index of suspicion should be kept for TMA in a patient who has nonrecovering AKI with persistent anemia and thrombocytopenia even after clinical and laboratory evidences of recovery from malaria, as response to plasmapheresis seems excellent in this subset of malarial AKI. There could be a pathogenetic link between P.vivax and TMA though yet to be confirmed in larger studies.

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.

The Unusual Adverse Effects of Antituberculosis Therapy in Kidney Patients.

BACKGROUND: Chronic kidney disease (CKD) patients are at a high risk of tuberculosis (TB), with a relative risk of developing active TB of 10%-25%. Similarly, glomerular disease increases the risk of TB due to diminished glomerular filtration rate, proteinuria, and immunosuppression use. Further, the first-line anti-TB drugs are associated with acute kidney injury (AKI) even in patients with normal kidney functions. METHODS: We retrospectively identified 10 patients hospitalized with unusual adverse effects of antituberculosis therapy (ATT) from 2013 to 2022. RESULTS: We found three cases of AKI caused by rifampicin: acute interstitial nephritis, crescentic glomerulonephritis, and heme pigment-induced acute tubular necrosis. We observed rifampicin-induced accelerated hypertension and thrombocytopenia in two patients on maintenance hemodialysis. Isoniazid caused pancreatitis and cerebellitis in two CKD patients, respectively. In a CKD patient, we detected acute gout secondary to pyrazinamide-induced reduced uric acid excretion. We also observed cases of drug rash with eosinophilia and systemic symptoms and hypercalcemia due to immune reconstitution inflammatory syndrome in patients with glomerular disease on ATT. Immediate discontinuation of the offending drug, along with specific and supportive management, led to a recovery in all cases. CONCLUSION: The adverse effects of ATT may be unusually severe and varied in kidney patients due to decreased renal elimination. Early recognition of these adverse effects and timely discontinuation of the offending drug is essential to limit morbidity and mortality.

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.

Rapidly Progressive Renal Failure in Type 2 Diabetic versus Non-diabetic Patients: Changing Trends, Natural History, and Outcome in an Indian Tertiary Care Center.

Rapidly progressive renal failure (RPRF) is not typical of diabetic nephropathy and suggests non-diabetic kidney disease (NDKD). We conducted an analysis of the data of RPRF patients (28 diabetic and 88 non-diabetic patients) with doubled creatinine over 2 weeks to 3 months and/or presented with >4 mg serum creatinine without prior renal disease to ascertain the types of lesions and compare the patients' histopathology. The primary outcome was dependence on dialysis at 1 year. Anti-neutrophilic cytoplasmic antibody-associated pauci-immune glomerulonephritis was the most common cause of RPRF in both groups. No particular lesion was more frequent in either group. Dependence on dialysis at 1 year was similar in both groups and was associated with dependence on dialysis at presentation but not diabetes. Crescentic glomerulonephritis was the most common in non-diabetic patients (57.9 vs. 25%, P = 0.002), and acute tubular necrosis (ATN) was seen in diabetic patients (21.4 vs. 11.4%, P = 0.179). Both factors were associated with adverse renal outcomes. Diffuse global glomerulosclerosis at presentation suggested a poor outcome in both groups. Diabetic nephropathy was seen in 14.29%, and its presence did not affect the outcome. The etiology of RPRF in diabetic patients has changed and is similar to that in non-diabetic patients, with no specific lesions predominating. Diabetic nephropathy does not alter the outcome for those with RPRF. Diffuse global glomerulosclerosis, being on dialysis at presentation, and ATN in a diabetic patient indicate a poor outcome and need close follow-up. Diabetic retinopathy should not prevent us from investigating for NDKD.